There are few studies on sick building syndrome (SBS) including clinical measurements for atopy and fractional exhaled nitric oxide (FeNO). Our aim was to study associations between SBS symptoms, selected personal factors, office characteristics and indoor office exposures among office workers from a university in Malaysia. Health data were collected by a questionnaire (n=695), skin prick test (SPT) (n=463) and FeNO test (n=460). Office settled dust was vacuumed and analyzed for endotoxin, (1,3)-β-glucan and house dust mites (HDM) allergens group 1 namely Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1). Office indoor temperature, relative air humidity (RH), carbon monoxide (CO) and carbon dioxide (CO2) were measured by a direct reading instrument. Associations were studied by two-levels multiple logistic regression with mutual adjustment and stratified analysis. The prevalence of weekly dermal, mucosal and general symptoms was 11.9%, 16.0% and 23.0% respectively. A combination of SPT positivity (allergy to HDM or cat) and high FeNO level (≥25 ppb) was associated with dermal (p=0.002), mucosal (p<0.001) and general symptoms (p=0.05). Der f1 level in dust was associated with dermal (p<0.001), mucosal (p<0.001) and general (p=0.02) symptoms. Among those with allergy to D. farinae, associations were found between Der f 1 levels in dust and dermal (p=0.003), mucosal (p=0.001) and general symptoms (p=0.007). Office-related symptoms were associated with Der f 1 levels in dust (p=0.02), low relative air humidity (p=0.04) and high office temperature (p=0.05). In conclusion, a combination of allergy to cat or HDM and high FeNO is a risk factor for SBS symptoms. Der f 1 allergen in dust can be a risk factor for SBS in the office environment, particularly among those sensitized to Der f 1 allergen.
Eighty-four strains of Vibrio cholerae O1, O139 and non-O1/non-O139 from clinical and environmental sources were investigated for the presence of the toxin co-regulated pilus gene, tcpA, the virulence cassette genes ctxA, zot, ace and cep and also for their ability to elaborate haemolysin and protease. The ctxA and zot genes were detected using DNA-DNA hybridization while the ace, cep and tcpA genes were detected using PCR. Production of haemolysin and protease was detected using mammalian erythrocytes and an agar diffusion assay respectively. Analysis of their virulence profiles showed six different groups designated Type I to Type VI and the major distinguishing factor among these profiles was in the in vitro production of haemolysin and/or protease. Clinical O1, O139 and environmental O1 strains were similar with regard to presence of the virulence cassette genes. All environmental O1 strains with the exception of one were found to possess ctxA, zot and ace giving rise to the probability that these strains may actually be of clinical origin. One strain which had only cep but none of the toxin genes may be a true environmental isolate. The virulence cassette and colonization factor genes were absent in all non-O1/non-O139 environmental strains but production of both the haemolysin and protease was present, indicating that these may be putative virulence factors. These findings suggest that with regard to its pathogenic potential, only strains of the O1 and O139 serogroup that possess the tcpA gene which encodes the phage receptor, have the potential to acquire the CTX genetic element and become choleragenic.
Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.