A turning point: Head and neck cancer patients' exercise preferences and barriers before and after participation in an exercise intervention.

This study examined the exercise barriers and preferences of head and neck cancer (HNC) survivors in relation to exercise experience. Participants (n = 22; 46.8% response rate) completed retrospective self-report questionnaires on demographic and medical information, exercise barriers and preferences. A subset of participants then completed semi-structured interviews (n = 18). Participants had previously engaged in the ENHANCE trial during, or immediately following, radiation treatment, an average of 22.1 ± 5.8 months before. Retrospective questionnaires revealed that before ENHANCE participation, lack of interest and time were the primary exercise barriers. After participation, there was a significant decrease in typical barriers including lack of interest (p = .008), exercise not a priority (p = .039) and exercise not in routine (p = .004). Number of barriers experienced after ENHANCE participation was negatively correlated with age, quality of life and minutes of resistance exercise training per week. After ENHANCE participation, significant increases were found in preference for exercising at a cancer centre (p = .031) and with other cancer survivors (p = .016). Four higher order themes emerged inductively from interview data analysis pertaining to preferences (i.e., class format) and three higher order themes regarding barriers (physical, psychological and external). By investigating participants' perspectives after ENHANCE participation, key factors for effective HNC exercise programme design were identified.

Adenoid cystic carcinoma of head and neck: clinical predictors of outcome from a Canadian centre.

OBJECTIVES: Adenoid cystic carcinoma (acc) is often treated with surgery, with or without adjuvant radiation therapy (rt). We evaluated disease characteristics, treatments, and potentially prognostic variables in patients with acc. METHODS: Our retrospective analysis considered consecutive cases of acc presenting at a tertiary care hospital between 2000 and 2014. Factors predictive of overall survival (os) and disease-free survival (dfs) were identified by univariate analysis. RESULTS: The 60 patients analyzed had a mean age of 58 years (range: 22-88 years), with a 2:1 female:male ratio. Tumour locations included the major salivary glands (40% parotid, 17% submandibular and sublingual), the oro-nasopharyngeal cavity (27%), and other locations (16%). Of the 60 patients, 35 (58%) received surgery with adjuvant rt; 12 (20%), rt only; 13 (22%), surgery only. Of 18 patients (30%) who experienced a recurrence within 5 years, 3 (5%) developed local recurrence only, and the remaining 15 (25%), distant metastasis. The 5-year os and dfs were 64.5% [95% confidence interval (ci): 45.9% to 78.1%] and 46.2% (95% ci: 29.7% to 61.2%) respectively. In patients without recurrence, 5-year os was 77% (95% ci: 52.8% to 89.9%), and in patients with recurrence, it was 42.7% (95% ci: 15.8% to 67.6%). Patients treated with rt only had a 5-year os of 9.2%. Predictors of 5-year dfs were TNM stage, T stage, nodal status, treatment received, and margin status; age, nodal status, treatment received, and margin status predicted 5-year os. CONCLUSIONS: Despite surgery and rt, one third of patients with acc experience distant recurrence. Patients whose tumours are not amenable to surgery have a poor prognosis, indicating a need for alternative approaches to improve outcomes.

Angiographic factors associated with haemorrhagic presentation of brain arteriovenous malformation in a Chinese paediatric population.

OBJECTIVE: To identify specific angiographic factors associated with haemorrhagic presentation of brain arteriovenous malformation in Chinese paediatric patients. DESIGN: Retrospective cross-sectional observational study. SETTING: Four locoregional tertiary neurosurgical centres in Hong Kong: Queen Elizabeth Hospital, Tuen Mun Hospital, Kwong Wah Hospital, and Pamela Youde Nethersole Eastern Hospital. PATIENTS: Patients aged 18 years or younger who underwent pretreatment digital subtraction angiography for brain arteriovenous malformation between 1 January 2005 and 31 July 2013 were included. Patients were divided into haemorrhagic and non-haemorrhagic groups based on the initial presentation. Pretreatment digital subtraction angiographies were independently reviewed by two experienced neuroradiologists. MAIN OUTCOME MEASURES: The following parameters were evaluated for their association with haemorrhagic presentation by univariate and multivariate analyses: nidus location, nidus size, nidus morphology (diffuse or compact); origin and number of arterial feeders; venous drainage; number of draining veins; presence of aneurysms, venous varices, and venous stenosis. RESULTS: A total of 67 children and adolescents (28 male, 39 female) with a mean age of 12 years were included. Of them, 52 (78%) presented with haemorrhage. Arteriovenous malformation size (P=0.004) and morphology (P=0.05) were found to be associated with haemorrhagic presentation by univariate analysis. Small arteriovenous malformation nidus size and diffuse nidal morphology were identified as independent risk factors for haemorrhage by multivariate analysis. CONCLUSION: Smaller arteriovenous malformation size and diffuse nidal morphology are angiographic factors independently associated with haemorrhagic presentation. Bleeding risk is important in determining the therapeutic approach (aggressive vs conservative) and timeframe, particularly in paediatric patients.

Paediatric vesicoureteric reflux imaging: where are we? Novel ultrasound-based voiding urosonography.

Vesicoureteric reflux is an important association of paediatric urinary tract infection. Fluoroscopic micturating cystourethrography and radionuclide cystography have been employed for detecting and grading vesicoureteric reflux. However, both modalities involve ionising radiation, which can pose significant radiation risk to growing children. They also have a lower detection rate due to intermittent fluoroscopic technique in micturating cystourethrography, and lower spatial resolution in radionuclide cystography. Therefore, newer radiation-free ultrasound-based contrast-enhanced voiding urosonography has been developed in Europe for 15 years. This article aimed to summarise the current literature and discuss the first local pilot study in our institution on detection of vesicoureteric reflux by contrast-enhanced voiding urosonography. Contrast-enhanced voiding urosonography is a valid alternative to micturating cystourethrography in assessing vesicoureteric reflux, based on its superior diagnostic performance, reliability, safety, feasibility, and radiation safety for children. Therefore, it should be incorporated in the guideline for investigating paediatric urinary tract infection.

Anti-allergic action of anti-malarial drug artesunate in experimental mast cell-mediated anaphylactic models.

BACKGROUND: Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi-synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti-malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti-allergic effects of artesunate in animal models of IgE-dependent anaphylaxis. METHODS: Anti-allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin-induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of artesunate was examined in RBL-2H3 mast cell line and in mature human cultured mast cells. Anti-allergic signaling mechanisms of action of artesunate in mast cells were also investigated. RESULTS: Artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, artesunate suppressed ovalbumin-mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration-dependently blocked IgE-mediated degranulation of RBL-2H3 mast cells and human culture mast cells. Artesunate was found to inhibit IgE-induced Syk and PLCγ1 phosphorylation, production of IP(3) , and rise in cytosolic Ca(+2) level in mast cells. CONCLUSIONS: We report here for the first time that artesunate possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders.

The significance of chloride in the inhibitory action of disodium cromoglycate on immunologically-stimulated rat peritoneal mast cells.

BACKGROUND: The microelectrode array (MEA) was used to investigate the pharmacological relevance of chloride (Cl-) ions in antigen-dependent mast cell activation and the inhibitory effect of disodium cromoglycate (DSCG) on mast cell activation. METHODS: The movements of ions across the cellular membrane and the potential relationship between Cl- channels and DSCG during immunological activation were investigated using the MEA. The results were then subsequently compared with the amount of histamine released from anti-IgE activated peritoneal mast cells. RESULTS: The inclusion of charybdotoxin (ChTX) in Cl--free buffer showed that the measured field potentials during antigen-stimulated peritoneal mast cell were a combination of Cl- influx and K+ efflux. The delayed onset time of Cl- influx indicated the presence of a delayed outwardly-rectifying Cl- current in the antigen-stimulated peritoneal mast cells. The use of 5-nitro-2-(3-phenylpropylamino) benzoic acid demonstrated that the activated mast cell membrane potential can be stabilised, thereby reducing the amount of histamine released from the anti-IgE activated mast cells. The correlation between the results of the histamine release assay and the electrophysiological measurements demonstrated the importance of Cl- to anti-IgE dependent mast cell activation. The inhibitory effect of DSCG on anti-IgE activated cells, however, did not correlate with the presumed influx of Cl-. CONCLUSIONS: The MEA data suggest that Cl- influx is crucial to IgE-dependent mast cell degranulation. GENERAL SIGNIFICANCE: While the MEA cannot yield information about single channel properties, it is convenient to use and can provide information on the global changes in electrophysiological responses of non-excitable cells.

Hospitalisation associated with the 2009 H1N1 pandemic and seasonal influenza in Hong Kong, 2005 to 2010.

Reliable estimates of the morbidity burden caused by the 2009 pandemic influenza (pH1N1) are important for assessing the severity of the pandemic. Poisson regression models were fitted to weekly numbers of cause-specific hospitalisation in Hong Kong from 2005 to 2010. Excess hospitalisation associated with the 2009 pandemic and seasonal influenza was derived from the model by incorporating the proxy variables of weekly proportions of specimens positive for the pandemic influenza A(H1N1)pdm09, seasonal influenza A (subtypes H3N2 and H1N1) and B viruses. Compared with seasonal influenza, pH1N1 influenza was associated with higher hospitalisation rates for acute respiratory disease (ARD) among children younger than 18 years and adults aged between 18 and 64 years, but among the elderly aged 65 years and older the hospitalisation rates were lower for pH1N1 than for seasonal H3N2 and H1N1 influenza. Hospitalisation rates for chronic diseases associated with pH1N1 influenza were generally higher than those associated with seasonal influenza. The reported hospitalised cases with laboratory-confirmed pandemic infections accounted for only 16% of pH1N1 influenza-associated hospitalisations for ARD in the age group 75 years and older, and 5‒66% of hospitalisations for chronic diseases in those older than 40 years. The 2009 H1N1 influenza pandemic was associated with a dramatically increased risk of hospitalisation among children and young adults. The morbidity burden of pandemic was underreported in old people and in those with chronic conditions.

Comparative evaluation of the INNO-LIA syphilis score and the MarDx Treponema pallidum immunoglobulin G Marblot test assays for the serological diagnosis of syphilis.

We evaluated the performance of two immunoblot assays: the INNO-LIA Syphilis Score (LIA) and the MarDx T. pallidum IgG Marblot Test (TWB), as compared with that of the Murex ICE Syphilis enzyme immunoassay (EIA), the Serodia Treponema pallidum particle agglutination (TPPA) assay and the fluorescent treponemal antibody-absorption (FTA-abs) assay, for the serological diagnosis of syphilis using serum samples of 135 attendees of the social hygiene clinics of the Department of Health in Hong Kong newly diagnosed with syphilis and provided with clinical stages (39 in primary, 20 in secondary, 18 in early latent and 58 in latent of unknown duration) and of 43 normal healthy subjects between October and December 2004. The differences in the overall sensitivities of the LIA assay and the EIA/TPPA/FTA-abs assays were not statistically significant (P > 0.05) whereas the overall sensitivity of the TWB assay was significantly lower (P < 0.05) than the overall sensitivities of the EIA, the TPPA and the FTA-abs assays. The LIA assay had an overall sensitivity of 94.1% (95% CI 88.7-97.0%) whereas the TWB assay 65.2% (95% CI 56.8-72.7%). Both the LIA and the TWB assays have a specificity of 100%. When consensus results were derived from the most predominant results of the EIA, the TPPA and the FTA-abs assays, the LIA assay had a positive agreement with the consensus results of 98.5% (95% CI 94.5-99.6%) whereas the TWB assay 68.2% (95% CI 59.8-75.6%). Therefore, the LIA assay performed significantly better (P < 0.05) than the TWB assay. The LIA assay can be considered to be a valid alternative confirmatory test for the serological diagnosis of syphilis.

Infantile cortical hyperostosis (Caffey disease): a possible misdiagnosis as physical abuse.

Infantile cortical hyperostosis (Caffey disease) is a rare self-limiting inflammatory bony disease of early infancy. We report a 1-month-old Chinese boy with Caffey disease who presented with painful swelling over his shins bilaterally. Physical abuse was initially suspected, but the radiological findings of periosteal thickening over multiple bones (particularly the mandible), symmetrical involvement, diaphyseal involvement with sparing of the epiphysis, made Caffey disease a likely diagnosis. This report highlights that infantile cortical hyperostosis is an important differential diagnosis for children suspected of being abused, and clinicians should have a high index of suspicion to avoid misdiagnosis.

The role of biofilms and protozoa in Legionella pathogenesis: implications for drinking water.

Current models to study Legionella pathogenesis include the use of primary macrophages and monocyte cell lines, various free-living protozoan species and murine models of pneumonia. However, there are very few studies of Legionella spp. pathogenesis aimed at associating the role of biofilm colonization and parasitization of biofilm microbiota and release of virulent bacterial cell/vacuoles in drinking water distribution systems. Moreover, the implications of these environmental niches for drinking water exposure to pathogenic legionellae are poorly understood. This review summarizes the known mechanisms of Legionella spp. proliferation within Acanthamoeba and mammalian cells and advocates the use of the amoeba model to study Legionella pathogenicity because of their close association with Legionella spp. in the aquatic environment. The putative role of biofilms and amoebae in the proliferation, development and dissemination of potentially pathogenic Legionella spp. is also discussed. Elucidating the mechanisms of Legionella pathogenicity development in our drinking water systems will aid in elimination strategies and procedural designs for drinking water systems and in controlling exposure to Legionella spp. and similar pathogens.

Myocardial rupture associated with bolus injection of contrast medium during computed tomographic study in a patient with acute myocardial infarction: a rare but lethal complication.

Well-documented potential cardiovascular complications associated with the use of contrast media include bradycardia, hypotension, arrhythmia, and conduction disturbances. Rupture of the myocardium after acute myocardial infarction is a known cause of death, but has yet to be recognised as a potential complication of the use of a bolus injection of contrast medium. On the contrary, contrast-enhanced computed tomographic studies have been performed widely for the diagnosis and evaluation of myocardial infarction. We report a case of complicated myocardial rupture after a single bolus injection of contrast medium during a computed tomographic study in an elderly woman with acute myocardial infarction, which led to cardiac tamponade and rapid death. Although rare, this should alert us to the need for cautious use of contrast medium in patients with acute myocardial infarction.

Gab2 antisense oligonucleotide blocks rat basophilic leukemic cell functions.

Adapter molecule Grb2-associated binder-like protein 2 (Gab2) plays a critical role in FcepsilonRI-induced mast cell degranulation and activation. The present study aimed to investigate the pharmacological effects of an antisense oligonucleotide (ASO) targeted at Gab2 on the immune responses of rat basophilic leukemic (RBL)-2H3 cells. Gab2 ASOs were rationally designed and transfected into RBL-2H3 cells. Gab2 mRNA and protein knockdown was confirmed by real-time RT-PCR and immunoblotting, respectively. Effects of Gab2 ASO on FcepsilonRI-induced release of histamine and beta-hexosaminidase was measured by EIA and an enzymatic assay, respectively; signaling events by immunoblotting; and cytokine mRNA expression by RT-PCR. Effects of Gab2 ASO on cell adhesion and migration were performed on fibronectin-coated 96-well plate and transwells cell culture chambers, respectively. We have characterized a phosphorothioate-modified ASO targeted at Gab2 mRNA that was able to knockdown Gab2 mRNA and protein in RBL-2H3 cells. Gab2 ASO significantly blocked IgE-mediated mast cell release of beta-hexosaminidase and histamine; phosphorylation of Akt, p38 mitogen-activated protein kinase and PKCdelta; and up-regulation of cytokine mRNA levels (e.g. IL-4, -6, -9 and -13, and TNF-alpha). In addition, Gab2 ASO markedly prevented mast cell adhesion to fibronectin-coated plates and restrained random migration of RBL-2H3 cells in cell culture chambers. Our findings show that Gab2 knockdown in RBL-2H3 cells by ASO strategy can suppress many aspects of the mast cell functions and, therefore, a selective Gab2 ASO may have therapeutic potential for mast cell-dependent allergic disorders.

In vitro cytotoxicology model of oligo-chitosan and n, o-carboxymethyl chitosan using primary normal human epidermal keratinocyte cultures.

Chitosan (beta-1, 4-D-glucosamine) is a deacetylated form of chitin with excellent biological properties in wound management. The natural properties of chitosan have the physical and chemical limitations to be widely used in biomedical fields. The improvement of the physical and chemical properties of chitosan with some additional chemicals will alter its biocompatibility. Therefore, the biological attribute of the modified chitosan must be evaluated. In this study, the cytotoxicity of oligo-chitosan (OC) and N, O- carboxymethyl-chitosan (NO-CMC) derivatives (O-C 1%, O-C 5%, NO-CMC 1% and NO-CMC 5%) was evaluated using primary normal human epidermal keratinocyte (pNHEK) cultures as an in vitro toxicology model at standardized cell passages (fourth passages). 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl tetrazolium bromide (MTT) was used as a cell viability assay. The O-C 1% is one of the most compatible chitosan derivatives because it steadily sustained >70% of viable cells until 72 hr post-treatment. This was followed by O-C 5%, NO-CMC 5% and NO-CMC 1%. Therefore, oligo-chitosan had the ideal properties of a biocompatible material compared to N, O- carboxymethyl-chitosan in this study.

Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms.

Despite extensive effort, there has been limited progress in the development of direct RAS inhibitors. Targeting isoprenylcysteine carboxylmethyltransferase (ICMT), a unique enzyme of RAS post-translational modification, represents a promising strategy to inhibit RAS function. However, there lacks direct genetic evidence on the role of ICMT in RAS-driven human cancer initiation and maintenance. Using CRISPR/Cas9 genome editing, we have created Icmt loss-of-function isogenic cell lines for both RAS-transformed human mammary epithelial cells (HME1) and human cancer cell lines MiaPaca-2 and MDA-MB-231 containing naturally occurring mutant KRAS. In both in vitro and in vivo tumorigenesis studies, Icmt loss-of-function abolishes the tumor initiation ability of all major isoforms of mutant RAS in HME1 cells, and the tumor maintenance capacity of MiaPaca-2 and MDA-MB-231 cells, establishing the critical role of ICMT in RAS-driven cancers.

Buffy coat preparation is a convenient source of progenitors for culturing mature human mast cells.

Mast cells are unique immune cells that release a spectrum of chemical mediators contributing to the inflammatory symptoms of allergic disorders. Mature mast cells have recently been cultured from CD34(+) progenitors isolated from fresh umbilical cord blood and adult peripheral blood. In the current study, we investigated whether buffy coat preparations, which are readily available from blood banks, could be used as a convenient and more abundant source of progenitors for culturing human mast cells. We were able to culture a homogeneous population of human mast cells from progenitor cells isolated from human buffy coat. Morphologically, our cultured mast cells contained abundant cytoplasmic granules which stained positively using antibodies against human mast cell tryptase and, to a lesser extent, with those against human mast cell chymase. Functionally, these cultured mast cells responded to anti-human-IgE by releasing histamine in a dose-dependent manner after sensitization with human IgE. Taken together, buffy coat preparations can be a convenient source for culturing human mast cells which are predominantly tryptase positive only and express functional high-affinity IgE receptors.

Re-purposing bridging flocculation for on-site, rapid, qualitative DNA detection in resource-poor settings.

Developing molecular diagnostics in resource-poor settings is challenging. As such, we purpose-built a novel bridging flocculation assay for qualitative evaluation of isothermally amplified DNA by naked eye. The flocculation assay was dependent on pH, DNA polymer amounts and lengths. The method was first applied to the rapid and sensitive detection of important plant pathogens and subsequently extended to other pathogens across the animal kingdom to demonstrate the wide applications of our approach.

Characterization of prostanoid receptors mediating inhibition of histamine release from anti-IgE-activated rat peritoneal mast cells.

1. Prostanoid receptors mediating inhibition of anti-IgE induced histamine release from rat peritoneal mast cells have been characterized pharmacologically. PGD2 and the specific DP receptor agonists BW 245C and ZK 118182 were the most potent inhibitors with half-maximal concentrations of 0.26, 0.06 and 0.02 microM respectively. The maximum inhibition attainable was 60-65% with 10(-5) M BW 245C and ZK 118182. 2. Among several EP receptor agonists investigated, only PGE2 and the EP2/EP3 receptor agonist misoprostol induced significant inhibition (46.8 +/- 4.7% at 10(-4) M and 18.7 +/- 6.8% at 10(-5) M respectively). The IP receptor agonists cicaprost and iloprost were both less potent than the DP agonists in inhibiting histamine release (45.2 +/- 3.3% and 35.1 +/- 2.5% inhibition respectively at 10(-5) M), whereas PGF2 alpha and the TP receptor agonist U-46619 were only marginally effective. 3. The EP4/TP receptor antagonist AH 23848 failed to affect the inhibitory actions of PGD2 or PGE2 even at 10(-5) M, whereas the DP/EP1/EP2 receptor antagonist AH 6809 slightly enhanced the effect of PGD2 at 10(-6) M. 4. At concentrations of 3 x 10(-6) to 10(-5) M, the putative DP receptor antagonist ZK 138357 dose-dependently suppressed the inhibitory activities of the DP agonists, PGE2 and cicaprost. The antagonism of ZK 138357 against the DP receptor agonists appeared to be competitive with pA2 values of around six. 5. In conclusion, these data support our earlier proposal that an inhibitory DP receptor is the predominant prostanoid receptor in rat peritoneal mast cell. The properties of this receptor in relation to putative DP receptor subtypes reported in the literature are discussed.

Seven fractions of twice daily high dose-rate brachytherapy for node-negative carcinoma of the mobile tongue results in loss of therapeutic ratio.

From June 1989 to December 1993, a Phase I/II protocol using high dose-rate (HDR) interstitial brachytherapy for early stage node-negative squamous cell carcinoma of the mobile tongue was undertaken to assess the toxicity and efficacy of this modality. A total of 27 patients were treated: T1-10 patients, T2-15 patients, and T3-two patients. Seven fractions x 6.5 Gy of HDR brachytherapy were given on a twice daily schedule, with a minimum interval time of 6 h, over a period of 3.5 days. The actuarial tumor control probability after HDR brachytherapy was 53% at 5 years. Local control rates for the T1 and T2 tumors were lower than comparable historical controls treated at our institution using low dose-rate (LDR) radium or cesium needle implants and iridium wire implants. This is despite the fact that the HDR schedule was calculated by the linear quadratic formula to have equal tumor killing effects as 60 Gy in 6 days of LDR radiation. In addition, there was a trend towards higher incidence of severe complications for the HDR patients compared to historical controls treated with LDR. We would caution against the use of this schedule of HDR brachytherapy until further studies are done.