Serratamolide is a hemolytic factor produced by Serratia marcescens

Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use. © 2012 Shanks et al

Knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in Tanzania

Many factors have been mentioned as contributing to under-diagnosis and under-reporting of zoonotic diseases particularly in the sub-Sahara African region. These include poor disease surveillance coverage, poor diagnostic capacity, the geographical distribution of those most affected and lack of clear strategies to address the plight of zoonotic diseases. The current study investigates the knowledge of medical practitioners of zoonotic diseases as a potential contributing factor to their under-diagnosis and hence under-reporting. The study was designed as a cross-sectional survey. Semi-structured open-ended questionnaire was administered to medical practitioners to establish the knowledge of anthrax, rabies, brucellosis, trypanosomiasis, echinococcosis and bovine tuberculosis in selected health facilities within urban and rural settings in Tanzania between April and May 2005. Frequency data were analyzed using likelihood ratio chi-square in Minitab version 14 to compare practitioners' knowledge of transmission, clinical features and diagnosis of the zoonoses in the two settings. For each analysis, likelihood ratio chi-square p-value of less than 0.05 was considered to be significant. Fisher's exact test was used where expected results were less than five. Medical practitioners in rural health facilities had poor knowledge of transmission of sleeping sickness and clinical features of anthrax and rabies in humans compared to their urban counterparts. In both areas the practitioners had poor knowledge of how echinococcosis is transmitted to humans, clinical features of echinococcosis in humans, and diagnosis of bovine tuberculosis in humans. Knowledge of medical practitioners of zoonotic diseases could be a contributing factor to their under-diagnosis and under-reporting in Tanzania. Refresher courses on zoonotic diseases should be conducted particularly to practitioners in rural areas. More emphasis should be put on zoonotic diseases in teaching curricula of medical practitioners' training institutions in Tanzania to improve the diagnosis, reporting and control of zoonotic diseases. Veterinary and medical collaboration should be strengthened to enable more effective control of zoonotic diseases in Tanzania

Sequence Diversities of Serine-Aspartate Repeat Genes among Staphylococcus aureus Isolates from Different Hosts Presumably by Horizontal Gene Transfer

BACKGROUND: Horizontal gene transfer (HGT) is recognized as one of the major forces for bacterial genome evolution. Many clinically important bacteria may acquire virulence factors and antibiotic resistance through HGT. The comparative genomic analysis has become an important tool for identifying HGT in emerging pathogens. In this study, the Serine-Aspartate Repeat (Sdr) family has been compared among different sources of Staphylococcus aureus (S. aureus) to discover sequence diversities within their genomes. METHODOLOGY/PRINCIPAL FINDINGS: Four sdr genes were analyzed for 21 different S. aureus strains and 218 mastitis-associated S. aureus isolates from Canada. Comparative genomic analyses revealed that S. aureus strains from bovine mastitis (RF122 and mastitis isolates in this study), ovine mastitis (ED133), pig (ST398), chicken (ED98), and human methicillin-resistant S. aureus (MRSA) (TCH130, MRSA252, Mu3, Mu50, N315, 04-02981, JH1 and JH9) were highly associated with one another, presumably due to HGT. In addition, several types of insertion and deletion were found in sdr genes of many isolates. A new insertion sequence was found in mastitis isolates, which was presumably responsible for the HGT of sdrC gene among different strains. Moreover, the sdr genes could be used to type S. aureus. Regional difference of sdr genes distribution was also indicated among the tested S. aureus isolates. Finally, certain associations were found between sdr genes and subclinical or clinical mastitis isolates. CONCLUSIONS: Certain sdr gene sequences were shared in S. aureus strains and isolates from different species presumably due to HGT. Our results also suggest that the distributional assay of virulence factors should detect the full sequences or full functional regions of these factors. The traditional assay using short conserved regions may not be accurate or credible. These findings have important implications with regard to animal husbandry practices that may inadvertently enhance the contact of human and animal bacterial pathogens

Unanesthetized Auditory Cortex Exhibits Multiple Codes for Gaps in Cochlear Implant Pulse Trains

Cochlear implant listeners receive auditory stimulation through amplitude-modulated electric pulse trains. Auditory nerve studies in animals demonstrate qualitatively different patterns of firing elicited by low versus high pulse rates, suggesting that stimulus pulse rate might influence the transmission of temporal information through the auditory pathway. We tested in awake guinea pigs the temporal acuity of auditory cortical neurons for gaps in cochlear implant pulse trains. Consistent with results using anesthetized conditions, temporal acuity improved with increasing pulse rates. Unlike the anesthetized condition, however, cortical neurons responded in the awake state to multiple distinct features of the gap-containing pulse trains, with the dominant features varying with stimulus pulse rate. Responses to the onset of the trailing pulse train (Trail-ON) provided the most sensitive gap detection at 1,017 and 4,069 pulse-per-second (pps) rates, particularly for short (25 ms) leading pulse trains. In contrast, under conditions of 254 pps rate and long (200 ms) leading pulse trains, a sizeable fraction of units demonstrated greater temporal acuity in the form of robust responses to the offsets of the leading pulse train (Lead-OFF). Finally, TONIC responses exhibited decrements in firing rate during gaps, but were rarely the most sensitive feature. Unlike results from anesthetized conditions, temporal acuity of the most sensitive units was nearly as sharp for brief as for long leading bursts. The differences in stimulus coding across pulse rates likely originate from pulse rate-dependent variations in adaptation in the auditory nerve. Two marked differences from responses to acoustic stimulation were: first, Trail-ON responses to 4,069 pps trains encoded substantially shorter gaps than have been observed with acoustic stimuli; and second, the Lead-OFF gap coding seen for <15 ms gaps in 254 pps stimuli is not seen in responses to sounds. The current results may help to explain why moderate pulse rates around 1,000 pps are favored by many cochlear implant listeners

A case for increased private sector involvement in Ireland's national animal health services

Non-regulatory animal health issues, such as Johne's disease, infectious bovine rhinotracheitis (IBR) and mastitis will become increasing important, with ongoing globalisation of markets in animals and animal products. In response, Ireland may need to broaden the scope of its national animal health services. However, there have been concerns about the respective roles and responsibilities (both financial and otherwise) of government and industry in any such moves. This paper argues the case for increased private sector involvement in Ireland's national animal health services, based both on theoretical considerations and country case studies (the Netherlands and Australia). The Dutch and Australian case studies present examples of successful partnerships between government and industry, including systems and processes to address non-regulatory animal health issues. In each case, the roles and responsibilities of government are clear, as are the principles underpinning government involvement. Furthermore, the roles and responsibilities (financial and otherwise) of the Dutch and Australian industry are determined through enabling legislation, providing both legitimacy and accountability. There are constraints on the use of EU and national government funds to support non-regulatory animal health services in EU member states (such as Ireland and the Netherlands)

A copula model for marked point processes

The final publication (Diao, Liqun, Richard J. Cook, and Ker-Ai Lee. (2013) A copula model for marked point processes. Lifetime Data Analysis, 19(4): 463-489) is available at Springer via http://dx.doi.org/10.1007/s10985-013-9259-3Many chronic diseases feature recurring clinically important events. In addition, however, there often exists a random variable which is realized upon the occurrence of each event reflecting the severity of the event, a cost associated with it, or possibly a short term response indicating the effect of a therapeutic intervention. We describe a novel model for a marked point process which incorporates a dependence between continuous marks and the event process through the use of a copula function. The copula formulation ensures that event times can be modeled by any intensity function for point processes, and any multivariate model can be specified for the continuous marks. The relative efficiency of joint versus separate analyses of the event times and the marks is examined through simulation under random censoring. An application to data from a recent trial in transfusion medicine is given for illustration.Natural Sciences and Engineering Research Council of Canada (RGPIN 155849); Canadian Institutes for Health Research (FRN 13887); Canada Research Chair (Tier 1) – CIHR funded (950-226626

Impact of a workplace 'sit less, move more' program on efficiency-related outcomes of office employees.

BACKGROUND: Few studies have examined the impact of 'sit less, move more' interventions on workplace performance. This study assessed the short and mid-term impacts of and patterns of change within, a 19-week workplace web-based intervention (Walk@WorkSpain; W@WS; 2010-11) on employees´ presenteeism, mental well-being and lost work performance. METHODS: A site randomised control trial recruited employees at six Spanish university campuses (n = 264; 42 ± 10 years; 171 female), assigned by worksite and campus to an Intervention (IG; used W@WS; n = 129; 87 female) or an active Comparison group (A-CG; pedometer, paper diary and self-reported sitting time; n = 135; 84 female). A linear mixed model assessed changes between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for the IG versus A-CG on (i) % of lost work productivity (Work Limitations Questionnaire; WLQ); (ii) three scales for presenteeism (WLQ) assessing difficulty meeting scheduling demands (Time), performing cognitive and inter-personal tasks (Mental-Interpersonal) and decrements in meeting the quantity, quality and timeliness of completed work (Output); and (iii) mental well-being (Warwick-Edinburgh Mental Well-being Scale). T-tests assessed differences between groups for changes on the main outcomes. In the IG, a multivariate logistic regression model identified patterns of response according to baseline socio-demographic variables, physical activity and sitting time. RESULTS: There was a significant 2 (group) × 2 (program time points) interaction for the Time (F [3]=8.69, p = 0.005), Mental-Interpersonal (F [3]=10.01, p = 0.0185), Output scales for presenteeism (F [3]=8.56, p = 0.0357), and for % of lost work performance (F [3]=10.31, p = 0.0161). Presenteeism and lost performance rose significantly in both groups across all study time points; after baseline performance was consistently better in the IG than in the A-CG. Better performance was linked to employees being more active (Time, p = 0.041) and younger (Mental-interpersonal, p = 0.057; Output, p = 0.017). Higher total sitting time during nonworking days (Mental-interpersonal, p = 0.019) and lower sitting time during workdays (WLQ Index, p = 0.013) also improved performance. CONCLUSION: Versus an active comparison condition, a 'sit less, move more` workplace intervention effectively reduced an array of markers of lost workday productivity. TRIAL REGISTRATION: NCT02960750 ; Date of registration: 07/11/2016

The effects of aging of scientists on their publication and citation patterns

The average age at which U.S. researchers get their first grant from NIH has increased from 34.3 in 1970, to 41.7 in 2004. These data raise the crucial question of the effects of aging on the scientific creativity and productivity of researchers. Those who worry about the aging of scientists usually believe that the younger they are the more creative and productive they will be. Using a large population of 13,680 university professors in Quebec, we show that, while scientific productivity rises sharply between 28 and 40, it increases at a slower pace between 41 and 50 and stabilizes afterward until retirement for the most active researchers. The average scientific impact per paper decreases linearly until 50-55 years old, but the average number of papers in highly cited journals and among highly cited papers rises continuously until retirement. Our results clearly show for the first time the natural history of the scientific productivity of scientists over their entire career and bring to light the fact that researchers over 55 still contribute significantly to the scientific community by producing high impact papers.Comment: 12 pages, 4 figure

Conditioned Pain Modulation Is Associated with Common Polymorphisms in the Serotonin Transporter Gene

BACKGROUND: Variation in the serotonin transporter (5-HTT) gene (SLC6A4) has been shown to influence a wide range of affective processes. Low 5-HTT gene-expression has also been suggested to increase the risk of chronic pain. Conditioned pain modulation (CPM)--i.e. 'pain inhibits pain'--is impaired in chronic pain states and, reciprocally, aberrations of CPM may predict the development of chronic pain. Therefore we hypothesized that a common variation in the SLC6A4 is associated with inter-individual variation in CPM. Forty-five healthy subjects recruited on the basis of tri-allelic 5-HTTLPR genotype, with inferred high or low 5-HTT-expression, were included in a double-blind study. A submaximal-effort tourniquet test was used to provide a standardized degree of conditioning ischemic pain. Individualized noxious heat and pressure pain thresholds (PPTs) were used as subjective test-modalities and the nociceptive flexion reflex (NFR) was used to provide an objective neurophysiological window into spinal processing. RESULTS: The low, as compared to the high, 5-HTT-expressing group exhibited significantly reduced CPM-mediated pain inhibition for PPTs (p = 0.02) and heat-pain (p = 0.02). The CPM-mediated inhibition of the NFR, gauged by increases in NFR-threshold, did not differ significantly between groups (p = 0.75). Inhibition of PPTs and heat-pain were correlated (Spearman's rho = 0.35, p = 0.02), whereas the NFR-threshold increase was not significantly correlated with degree of inhibition of these subjectively reported modalities. CONCLUSIONS: Our results demonstrate the involvement of the tri-allelic 5-HTTLPR genotype in explaining clinically relevant inter-individual differences in pain perception and regulation. Our results also illustrate that shifts in NFR-thresholds do not necessarily correlate to the modulation of experienced pain. We discuss various possible mechanisms underlying these findings and suggest a role of regulation of 5-HT receptors along the neuraxis as a function of differential 5-HTT-expression