Expression of transforming growth factor-beta isoforms and their receptors in chronic tendinosis

Chronic tendon lesions are degenerative conditions and may represent a failure to repair or remodel the extracellular matrix after repeated micro-injury. Since TGF-ß is strongly associated with tissue repair, we investigated the expression of TGF-ß isoforms (ß1, ß2 and ß3) and their 2 signalling receptors (TGF-ßRI and TGF-ßRII) in normal and pathological Achilles tendons. In all tissues, all 3 TGF-ß isoforms and the 2 receptors were present at sites of blood vessels. Cells in the matrix showed no staining for TGF-ß1 or ß3, while TGF-ß2 was associated with cells throughout the normal cadaver tendon. Tissue from tendons with pathological lesions showed an increase in cell numbers and percentage TGF-ß2 expression. TGF-ßRII showed a wide distribution in cells throughout the tissue sections. As with TGF-ß2, there was an increase in the number of cells expressing TGF-ßRII in pathological tissue. TGF-ßRI was restricted to blood vessels and was absent from the fibrillar matrix. We conclude that despite the presence and upregulation of TGF-ß2, TGF-ß signalling is not propagated due to the lack of TGF-ßRI. This might explain why chronic tendon lesions fail to resolve and suggests that the addition of exogenous TGF-ß will have little effect on chronic tendinopathy

Ciprofloxacin reduces the stimulation of prostaglandin E2 output by interleukin-1 in human tendon-derived cells

Fluoroquinolone antibiotics such as ciprofloxacin can induce tendon pathology and have various effects on tendon-derived cells in culture. We are investigating whether ciprofloxacin modifies signalling responses in tendon cells. Human Achilles tendon-derived cells were preincubated with or without ciprofloxacin (50?µg/ml) and were then challenged with interleukin-1ß (IL-1ß, 1?ng/ml) for up to 48?h. Prostaglandin E2 (PGE2) output was assayed by ELISA. The expression of cyclooxygenase-2 (COX-2) was examined by Western blotting. IL-1ß stimulated a substantial and prolonged increase in the output of PGE2. Preincubation with ciprofloxacin reduced IL-1ß-induced PGE2 output at all times tested; the reduction at 48?h was 69% (99% confidence interval 59–79%; 15 experiments). Norfloxacin and ofloxacin also reduced PGE2 output. However, ciprofloxacin did not affect the induction of COX-2 by IL-1ß, measured at 4 or 48?h. Ciprofloxacin reduces IL-1ß-induced PGE2 output in tendon-derived cells. The reduction in PGE2 output could modulate various cellular activities of IL-1ß, and may be implicated in fluoroquinolone-induced tendinopathy

Solar Disinfection of MODS Mycobacterial Cultures in Resource-Poor Settings

INTRODUCTION: Safe disposal of TB culture material in which the infectious burden of clinical samples has been greatly amplified is an important challenge in resource-limited settings. The bactericidal capacity of solar cookers has been demonstrated previously for conventional bacteria and contaminated clinical waste. We investigated the use of a simple solar cooker for the sterilization of mycobacterial broth cultures from the microscopic observation drug susceptibility assay (MODS). METHODS: Simulated TB culture materials were prepared by inoculating 24-well MODS plates with 500 microL of a known concentration of Mycobacterium bovis BCG. In a series of experiments, samples were simultaneously placed inside a box-type solar cooker and control box and removed at timepoints between 15 minutes and 6 hours. Quantitative cultures were performed using retrieved samples to determine sterilization effect. RESULTS: All cultures from the control box were positive at or within 1-4 logs of inoculation concentration. Simulated culture plates at concentrations from 10(3) colony-forming-units (CFU)/ml to 10(7) CFU/ml were completely sterilized after only one hour of cooker exposure, at temperatures between 50-102 degrees C. At 10(9) CFU/ml (far in excess of diagnostic cultures), it was only possible to recover mycobacterial growth in plates removed after 15 minutes. By 30 minutes all plates were effectively sterilized. DISCUSSION: Solar disinfection provides a very effective, safe and low-cost alternative to conventional equipment used for disposal of mycobacterial culture material. Effect of climatic conditions and optimal operating procedure remain to be defined

Potential for airborne transmission of infection in the waiting areas of healthcare premises: stochastic analysis using a Monte Carlo model

BACKGROUND: Although many infections that are transmissible from person to person are acquired through direct contact between individuals, a minority, notably pulmonary tuberculosis (TB), measles and influenza are known to be spread by the airborne route. Airborne infections pose a particular threat to susceptible individuals whenever they are placed together with the index case in confined spaces. With this in mind, waiting areas of healthcare facilities present a particular challenge, since large numbers of people, some of whom may have underlying conditions which predispose them to infection, congregate in such spaces and can be exposed to an individual who may be shedding potentially pathogenic microorganisms. It is therefore important to understand the risks posed by infectious individuals in waiting areas, so that interventions can be developed to minimise the spread of airborne infections. METHOD: A stochastic Monte Carlo model was constructed to analyse the transmission of airborne infection in a hypothetical 132 m3 hospital waiting area in which occupancy levels, waiting times and ventilation rate can all be varied. In the model the Gammaitoni-Nucci equation was utilized to predict probability of susceptible individuals becoming infected. The model was used to assess the risk of transmission of three infectious diseases, TB, influenza and measles. In order to allow for stochasticity a random number generator was applied to the variables in the model and a total of 10000 individual simulations were undertaken. The mean quanta production rates used in the study were 12.7, 100 and 570 per hour for TB, influenza and measles, respectively. RESULTS: The results of the study revealed the mean probability of acquiring a TB infection during a 30-minute stay in the waiting area to be negligible (i.e. 0.0034), while that for influenza was an order of magnitude higher at 0.0262. By comparison the mean probability of acquiring a measles infection during the same period was 0.1349. If the duration of the stay was increased to 60 minutes then these values increased to 0.0087, 0.0662 and 0.3094, respectively. CONCLUSION: Under normal circumstances the risk of acquiring a TB infection during a visit to a hospital waiting area is minimal. Likewise the risks associated with the transmission of influenza, although an order of magnitude greater than those for TB, are relatively small. By comparison, the risks associated with measles are high. While the installation of air disinfection may be beneficial, when seeking to prevent the transmission of airborne viral infection it is important to first minimize waiting times and the number of susceptible individuals present before turning to expensive technological solutions

The influence of the atmospheric boundary layer on nocturnal layers of noctuids and other moths migrating over southern Britain

Insects migrating at high altitude over southern Britain have been continuously monitored by automatically-operating, vertical-looking radars over a period of several years. During some occasions in the summer months, the migrants were observed to form well-defined layer concentrations, typically at heights of 200-400 m, in the stable night-time atmosphere. Under these conditions, insects are likely to have control over their vertical movements and are selecting flight heights which are favourable for long-range migration. We therefore investigated the factors influencing the formation of these insect layers by comparing radar measurements of the vertical distribution of insect density with meteorological profiles generated by the UK Met. Office’s Unified Model (UM). Radar-derived measurements of mass and displacement speed, along with data from Rothamsted Insect Survey light traps provided information on the identity of the migrants. We present here three case studies where noctuid and pyralid moths contributed substantially to the observed layers. The major meteorological factors influencing the layer concentrations appeared to be: (a) the altitude of the warmest air, (b) heights corresponding to temperature preferences or thresholds for sustained migration and (c), on nights when air temperatures are relatively high, wind-speed maxima associated with the nocturnal jet. Back-trajectories indicated that layer duration may have been determined by the distance to the coast. Overall, the unique combination of meteorological data from the UM and insect data from entomological radar described here show considerable promise for systematic studies of high-altitude insect layering

Measurement error and timing of predictor values for multivariable risk prediction models are poorly reported

Objective Measurement error in predictor variables may threaten the validity of clinical prediction models. We sought to evaluate the possible extent of the problem. A secondary objective was to examine whether predictors are measured at the intended moment of model use. Methods A systematic search of Medline was used to identify a sample of articles reporting the development of a clinical prediction model published in 2015. After screening according to a predefined inclusion criteria, information on predictors, strategies to control for measurement error, and intended moment of model use were extracted. Susceptibility to measurement error for each predictor was classified into low and high risks. Results Thirty-three studies were reviewed, including 151 different predictors in the final prediction models. Fifty-one (33.7%) predictors were categorized as high risk of error; however, this was not accounted for in the model development. Only 8 (24.2%) studies explicitly stated the intended moment of model use and when the predictors were measured. Conclusion Reporting of measurement error and intended moment of model use is poor in prediction model studies. There is a need to identify circumstances where ignoring measurement error in prediction models is consequential and whether accounting for the error will improve the predictions

Inactivation of Poxviruses by Upper-Room UVC Light in a Simulated Hospital Room Environment

In the event of a smallpox outbreak due to bioterrorism, delays in vaccination programs may lead to significant secondary transmission. In the early phases of such an outbreak, transmission of smallpox will take place especially in locations where infected persons may congregate, such as hospital emergency rooms. Air disinfection using upper-room 254 nm (UVC) light can lower the airborne concentrations of infective viruses in the lower part of the room, and thereby control the spread of airborne infections among room occupants without exposing occupants to a significant amount of UVC. Using vaccinia virus aerosols as a surrogate for smallpox we report on the effectiveness of air disinfection, via upper-room UVC light, under simulated real world conditions including the effects of convection, mechanical mixing, temperature and relative humidity. In decay experiments, upper-room UVC fixtures used with mixing by a conventional ceiling fan produced decreases in airborne virus concentrations that would require additional ventilation of more than 87 air changes per hour. Under steady state conditions the effective air changes per hour associated with upper-room UVC ranged from 18 to 1000. The surprisingly high end of the observed range resulted from the extreme susceptibility of vaccinia virus to UVC at low relative humidity and use of 4 UVC fixtures in a small room with efficient air mixing. Increasing the number of UVC fixtures or mechanical ventilation rates resulted in greater fractional reduction in virus aerosol and UVC effectiveness was higher in winter compared to summer for each scenario tested. These data demonstrate that upper-room UVC has the potential to greatly reduce exposure to susceptible viral aerosols. The greater survival at baseline and greater UVC susceptibility of vaccinia under winter conditions suggest that while risk from an aerosol attack with smallpox would be greatest in winter, protective measures using UVC may also be most efficient at this time. These data may also be relevant to influenza, which also has improved aerosol survival at low RH and somewhat similar sensitivity to UVC

Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional biomarkers of meat and fish intake

Purpose Meat and fish consumption are associated with changes in the risk of chronic diseases. Intake is mainly assessed using self-reporting, as no true quantitative nutritional biomarker is available. The measurement of plasma fatty acids, often used as an alternative, is expensive and time-consuming. As meat and fish differ in their stable isotope ratios, δ13C and δ15N have been proposed as biomarkers. However, they have never been investigated in controlled human dietary intervention studies. Objective In a short-term feeding study, we investigated the suitability of δ13C and δ15N in blood, urine and faeces as biomarkers of meat and fish intake. Methods The dietary intervention study (n = 14) followed a randomised cross-over design with three eight-day dietary periods (meat, fish and half-meat–half-fish). In addition, 4 participants completed a vegetarian control period. At the end of each period, 24-h urine, fasting venous blood and faeces were collected and their δ13C and δ15N analysed. Results There was a significant difference between diets in isotope ratios in faeces and urine samples, but not in blood samples (Kruskal–Wallis test, p < 0.0001). In pairwise comparisons, δ13C and δ15N were significantly higher in urine and faecal samples following a fish diet when compared with all other diets, and significantly lower following a vegetarian diet. There was no significant difference in isotope ratio between meat and half-meat–half-fish diets for blood, urine or faecal samples. Conclusions The results of this study show that urinary and faecal δ13C and δ15N are suitable candidate biomarkers for short-term meat and fish intake