Immune responses upon experimental Erysipelothrix rhusiopathiae infection of naïve and vaccinated chickens.

Erysipelas, a disease caused by Erysipelothrix rhusiopathiae (ER), is an increasing problem in laying hens housed in cage-free systems. This study aimed to monitor immune responses during ER infection of naïve chickens and chickens vaccinated intra muscularly with a commercial inactivated ER vaccine. Chickens were infected intra muscularly with ER at 30 days of age and blood leukocyte counts, serum levels of mannose binding lectin (MBL) and ER-specific IgY were monitored until the experiment was terminated at day 15 after infection. ER was detected in blood from more chickens and at higher bacterial counts in the naïve group (day 1: 1 of 7 chickens; day 3: 6 of 6 chickens) than in the vaccinated group (day 1: 0 of 7 chickens; day 3: 1 of 6 chickens). During the acute phase of infection transient increases in circulating heterophil numbers and serum MBL levels were detected in all ER infected chickens but these responses were prolonged in chickens from the naïve group compared to vaccinated chickens. Before infection IgY titers to ER in vaccinated chickens did not differ significantly from those of naïve chickens but vaccinated chickens showed significantly increased IgY titers to ER earlier after infection compared to chickens in the naïve group. In conclusion, the ER infection elicited prompt acute innate responses in all chickens. Vaccinated chickens did not have high IgY titers to ER prior to infection but did however show lower levels of bacteraemia and their acute immune responses were of shorter duration.

Optimising healthy and safe fish intake recommendations: a trade-off between personal preference and cost.

Individuals may perceive personalised dietary advice as more relevant and motivational than national guidelines. Personal preference and food cost are factors that can affect consumer decisions. The objective of this study was to present a method for modelling and analysing the trade-off between deviation from preference and food cost for optimised personalised dietary recommendations. Quadratic programming was applied to minimise deviation from fish preference and cost simultaneously with different weights on the cost for 3016 Danish adults (whose dietary intake and body weight were recorded in a national dietary survey). Model constraints included recommendations for EPA, DHA and vitamin D and tolerable levels for methyl mercury, dioxins and dioxin-like polychlorinated biphenyls. When only minimising deviation from preference, 50 % of the study population should be recommended to increase fish intake, 48 % should be suggested to maintain current consumption and 2 % should be suggested to decrease fish consumption. When only minimising cost, the vast majority (99 %) should be recommended to only consume herring, which is the least-expensive fish species. By minimising deviation from preference and cost simultaneously with different weights on the cost, personalised optimal trade-off curves between deviation from fish intake preference and fish cost could be generated for each individual in our study population, except for twenty-two individuals (0·7 %) whose contaminant background exposure was too high. In the future, the method of this paper could be applied in the personal communication of healthy and safe food recommendations that fit the preferences of individual consumers.

Use of Mathematical Optimization Models to Derive Healthy and Safe Fish Intake.

Background: Recommended fish intake differs substantially from observed fish intake. In Denmark, ∼15% of the population consumes the state-recommended fish intake. How much fish individuals eat varies greatly, and this variation cannot be captured by considering the fish intake of the average population. Objective: We developed a method intended to provide realistic and achievable personalized dietary recommendations based on an individual's body weight and current fish intake. The objective of the study was to propose specific fish intake levels for individuals that meet the recommendations for eicosapentaenoic acid, docosahexaenoic acid, and vitamin D without violating the permitted intake recommendations for methyl mercury, dioxins, and polychlorinated biphenyls. Methods: Two mathematical optimization models were developed that apply quadratic programming to model personalized recommended fish intake, fulfilling criteria on nutrients and contaminants, while simultaneously deviating as little as possible from observed individual intake. A recommended intake for 8 fish species was generated for each individual in a group of 3016 Danes (1552 women and 1464 men, aged 18-75 y), whose fish intakes and body weights were known from a national dietary survey. Results: Individual, personal dietary recommendations were successfully modeled. Modeled fish intake levels were compared to observed fish intakes. For women, the average proposed increase in fish intake was 14 g/wk for lean fish and 63 g/wk for fatty fish; and for men these numbers were 12 and 55 g/wk, respectively. Conclusions: Using fish intake as an example, we show how quadratic programming models may be used to advise individual consumers how to optimize their diet, taking both benefits and risks into account. This approach has the potential to increase compliance with dietary guidelines by targeting the individual consumers and minimizing the need for large and ultimately unrealistic behavior changes.

Personalised fish intake recommendations: the effect of background exposure on optimisation.

National dietary guidelines are directed at the general population. However, these guidelines may be perceived as unrealistic by a substantial part of the population, as they differ considerably from individual consumption patterns and preferences. Personalised dietary recommendations will probably improve adherence, and it has been shown that these recommendations can be derived by mathematical optimisation methods. However, to better account for risks and benefits of specific foods, the background exposure to nutrients and contaminants needs to be considered as well. This background exposure may come from other foods and supplements, and also from environmental sources like the air and the sun. The objective of this study was therefore to analyse the effect of including individual variation in background exposure when modelling personalised dietary recommendations for fish. We used a quadratic programming model to generate recommended fish intake accounting for personal preference by deviating as little as possible from observed individual intake. Model constraints ensure that the modelled intake meets recommendations for EPA, DHA and vitamin D without violating tolerable exposure to methyl mercury, dioxins and dioxin-like polychlorinated biphenyls. Several background exposures were analysed for 3016 Danish adults, whose food intakes and body weights were reported in a national dietary survey. We found that the lower nutrient constraints were critical for the largest part of the study population, and that a total of 55% should be advised to increase their fish intake. The modelled fish intake recommendations were particularly sensitive to the vitamin D background exposure.

Diagnostic colposcopic accuracy by the gynocular and a stationary colposcope.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of sensitivity and specificity of cervical lesions by the low-cost, portable Gynocular colposcope and a stationary colposcope, in women referred for colposcopy with abnormal cervical cytology. METHODS: A randomized cross-over clinical trial for evaluating the diagnostic accuracy in detecting cervical lesions by the Gynocular and a stationary colposcope. The Swede score systematic colposcopy system was used for evaluation of colposcopic abnormalities. Directed punch biopsy and excisional cone biopsy were used as the "gold-standard" by histologically confirmed high grade cervical lesions CIN2+ (CIN2, CIN3, CIN3+). In total, 123 women referred for colposcopy due to abnormal cervical cytology were recruited at the Department of Obstetrics and Gynecology, Danderyd Hospital, Stockholm, Sweden. The percentage agreement and the kappa statistic were calculated for Swede score by the Gynocular and a stationary colposcope. Swede scores were compared with the results from directed punch biopsy and excisional cone biopsy. RESULTS: The Gynocular and the stationary colposcope had a high agreement of Swede scores with a Kappa statistic of 0.947, p < .0001. Punch biopsy diagnosed CIN2+ (CIN2, CIN3, and invasive cancer) in 44 (35.7 percent) women while cytology detected CIN2+ in 34 (27.6 percent) women. There were no significant differences of the sensitivity and specificity for different Swede scores by the Gynocular or a stationary colposcope in detecting CIN 2+. CONCLUSIONS: There were no significant differences in sensitivity or specificity in detecting cervical lesions by the Gynocular or stationary colposcope. The Gynocular is as accurate in diagnosing cervical lesions as a stationary colposcope.

Speech recognition in noise using bilateral open-fit hearing aids: the limited benefit of directional microphones and noise reduction.

OBJECTIVE: To investigate speech recognition performance in noise with bilateral open-fit hearing aids and as reference also with closed earmolds, in omnidirectional mode, directional mode, and directional mode in conjunction with noise reduction. DESIGN: A within-subject design with repeated measures across conditions was used. Speech recognition thresholds in noise were obtained for the different conditions. STUDY SAMPLE: Twenty adults without prior experience with hearing aids. All had symmetric sensorineural mild hearing loss in the lower frequencies and moderate to severe hearing loss in the higher frequencies. RESULTS: Speech recognition performance in noise was not significantly better with an omnidirectional microphone compared to unaided, whereas performance was significantly better with a directional microphone (1.6 dB with open fitting and 4.4 dB with closed earmold) compared to unaided. With open fitting, no significant additional advantage was obtained by combining the directional microphone with a noise reduction algorithm, but with closed earmolds a significant additional advantage of 0.8 dB was obtained. CONCLUSIONS: The significant, though limited, advantage of directional microphones and the absence of additional significant improvement by a noise reduction algorithm should be considered when fitting open-fit hearing aids.

Tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator AZD1656, after single ascending doses in healthy subjects during euglycemic clamp.

OBJECTIVES: AZD1656 is a novel glucokinase activator with a postulated dual mechanism of action by activating glucokinase in both the pancreas and the liver, and with the potential to deliver effective glucose-lowering in Type 2 diabetes mellitus. Here, we present the tolerability, pharmacokinetics and pharmacodynamics of AZD1656 in two single-blind, randomized, placebo-controlled studies, one with Western and the other with Japanese healthy adult male subjects. METHODS: Both studies evaluated oral single ascending doses of AZD1656 of up to 180 mg, administered during euglycemic clamp conditions to explore a wide dose range without risking hypoglycemia. Safety, pharmacokinetics and effects on serum insulin and glucose infusion rate were assessed. A population pharmacokinetics analysis was also conducted. RESULTS: AZD1656 was well tolerated in single doses up to 180 mg in both populations. AZD1656 was rapidly absorbed, and a dose-proportional increase in total exposure was observed for AZD1656 and the equipotent metabolite, AZD5658. Taking differences in body weight into account, there were no differences in pharmacokinetic parameters between Western and Japanese subjects. A dose-dependent blood glucose lowering effect was indirectly demonstrated by the increased glucose infusion rate required to maintain euglycemia, which was of similar magnitude in both populations. Dose-dependent increases in insulin secretion were also observed. CONCLUSIONS: No safety concerns were raised. AZD1656 displayed uncomplicated pharmacokinetics and dose-dependent pharmacodynamics effects were observed. The results suggest no ethnic differences in AZD1656 tolerability, pharmacokinetics or pharmacodynamics.

A qualitative study on health care providers' experiences of providing comprehensive abortion care in Cox's Bazar, Bangladesh.

BACKGROUND: Humanitarian settings are characterised by limited access to comprehensive abortion care. At the same time, humanitarian settings can increase the vulnerability of women and girls to unintended pregnancies and unsafe abortions. Humanitarian actors and health care providers can play important roles in ensuring the availability and accessibility of abortion-related care. This study explores health care providers' perceptions and experiences of providing comprehensive abortion care in a humanitarian setting in Cox's Bazar, Bangladesh and identifies barriers and facilitators in service provision. METHOD: In-depth interviews (n = 24) were conducted with health care providers (n = 19) providing comprehensive abortion care to Rohingya refugee women and with key informants (n = 5), who were employed by an organisation involved in the humanitarian response. Data were analysed using an inductive content analysis approach. RESULTS: The national menstrual regulation policy provided a favourable legal environment and facilitated the provision of comprehensive abortion care, while the Mexico City policy created organisational barriers since it made organisations unable or unwilling to provide the full comprehensive abortion care package. Supplies were available, but a lack of space created a barrier to service provision. Although training from organisations had made the health care providers confident and competent and had facilitated the provision of services, their knowledge of the national abortion law and menstrual regulation policy was limited and created a barrier to comprehensive abortion services. Even though the health care providers were willing to provide comprehensive abortion care and had acquired skills and applied strategies to communicate with and provide care to Rohingya women, their personal beliefs and their perceptions of Rohingya women influenced their provision of care. CONCLUSION: The availability and accessibility of comprehensive abortion care was limited by unfavourable abortion policies, a lack of privacy, a lack of knowledge of abortion laws and policies, health care providers' personal beliefs and a lack of cultural safety. To ensure the accessibility and availability of quality services, a comprehensive approach to sexual and reproductive health and rights is needed. Organisations must ensure that health care providers have knowledge of abortion policies and the ability to provide quality care that is woman-centred and non-judgmental.

Detection and quantification of Erysipelothrix rhusiopathiae in blood from infected chickens - addressing challenges with detection of DNA from infectious agents in host species with nucleated red blood cells.

PURPOSE: The present study aimed to establish pretreatment protocols as well as real-time and droplet digital polymerase chain reaction (PCR) methodologies to detect and quantify Erysipelothrix rhusiopathiae (ER) DNA in blood samples from infected chickens, as tools for routine diagnostics and monitoring of experimental infections. Chicken blood is a problematic matrix for PCR analysis because nucleated erythrocytes contribute large amounts of host DNA that inhibit amplification. METHODOLOGY: Using artificially spiked samples of fresh chicken blood, as well as blood samples from three experimental infection studies, the performance of pretreatment protocols, including choice of blood stabilization agent, centrifugation speeds and Ficoll gradient separation, was evaluated. The results were compared with those from traditional culture-based protocols combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).Results/Key findings. Simple preparations producing cell-free samples performed well on artificial spike-in samples, providing high sensitivity. However, performance was poor in clinical samples or artificial samples where the bacteria were incubated for 4 h or more in fresh blood prior to DNA extraction. In these samples, a Ficoll separation protocol that creates samples rich in lymphocytes, monocytes and thrombocytes prior to DNA extraction was far more effective. CONCLUSIONS: Our results indicate that ER bacteria undergo rapid phagocytosis in chicken blood and that analysis of a blood fraction enriched for phagocytic cells is necessary for reliable detection and quantification. The presented results explain the poor performance of PCR detection reported in previously published experimental ER infection studies, and the proposed solutions are likely to have broader implications for PCR-based veterinary diagnostics in non-mammalian host species such as poultry and fish.

Experience of using MOSFET detectors for dose verification measurements in an end-to-end 192Ir brachytherapy quality assurance system.

PURPOSE: Establishment of an end-to-end system for the brachytherapy (BT) dosimetric chain could be valuable in clinical quality assurance. Here, the development of such a system using MOSFET (metal oxide semiconductor field effect transistor) detectors and experience gained during 2 years of use are reported with focus on the performance of the MOSFET detectors. METHODS AND MATERIALS: A bolus phantom was constructed with two implants, mimicking prostate and head & neck treatments, using steel needles and plastic catheters to guide the 192Ir source and house the MOSFET detectors. The phantom was taken through the BT treatment chain from image acquisition to dose evaluation. During the 2-year evaluation-period, delivered doses were verified a total of 56 times using MOSFET detectors which had been calibrated in an external 60Co beam. An initial experimental investigation on beam quality differences between 192Ir and 60Co is reported. RESULTS: The standard deviation in repeated MOSFET measurements was below 3% in the six measurement points with dose levels above 2 Gy. MOSFET measurements overestimated treatment planning system doses by 2-7%. Distance-dependent experimental beam quality correction factors derived in a phantom of similar size as that used for end-to-end tests applied on a time-resolved measurement improved the agreement. CONCLUSIONS: MOSFET detectors provide values stable over time and function well for use as detectors for end-to-end quality assurance purposes in 192Ir BT. Beam quality correction factors should address not only distance from source but also phantom dimensions.

Osteogenic Differentiation of Human Mesenchymal Stem cells in a 3D Woven Scaffold.

Fiber-based scaffolds produced by textile manufacturing technology offer versatile materials for tissue engineering applications since a wide range of crucial scaffold parameters, including porosity, pore size and interconnectivity, can be accurately controlled using 3D weaving. In this study, we developed a weavable, bioactive biodegradable composite fiber from poly (lactic acid) (PLA) and hydroxyapatite powder by melt spinning. Subsequently, scaffolds of these fibers were fabricated by 3D weaving. The differentiation of human mesenchymal stem cells (hMSCs) in vitro was studied on the 3D scaffolds and compared with differentiation on 2D substrates having the same material composition. Our data showed that the 3D woven scaffolds have a major impact on hMSCs proliferation and activation. The 3D architecture supports the differentiation of the hMSCs into osteoblast cells and enhances the production of mineralized bone matrix. The present study further confirms that a 3D scaffold promotes hMSCs differentiation into the osteoblast-lineage and bone mineralization.

Can patients at elevated risk of stroke treated with anticoagulants be further risk stratified?

BACKGROUND AND PURPOSE: Patients with atrial fibrillation have a varied risk of stroke, depending on age and comorbid conditions. The objective of this study was to assess the predictive value of stroke risk classification schemes and to identify patients with atrial fibrillation who are at substantial risk of stroke despite optimal anticoagulant therapy. METHODS: Seven recognized classification schemes-the American College of Chest Physicians 2001, American College of Chest Physicians 2004, Stroke Prevention in Atrial Fibrillation (SPAF), Atrial Fibrillation Investigators, Framingham, van Walraven, and CHADS(2)-were compared for their ability to predict ischemic stroke in patients receiving anticoagulant therapy. Data came from the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III and V trials, which compared the efficacy of adjusted-dose warfarin and the direct thrombin inhibitor ximelagatran (36 mg twice daily) in preventing thromboembolic events in 7329 patients with chronic or paroxysmal nonvalvular atrial fibrillation who were at moderate or high risk of ischemic stroke. The main outcome measure was ischemic stroke, as determined by a central event adjudication committee. RESULTS: During 11 245 patient-years of follow-up, 159 patients had an ischemic stroke (1.4%/year). As indicated by c statistics and hazard ratios, 3 of the classification schemes predicted stroke significantly better than chance: Framingham (c=0.64), CHADS(2) (c=0.65), and SPAF (c=0.61). CONCLUSIONS: In a large cohort of atrial fibrillation patients at moderate or high risk of ischemic stroke treated with warfarin or ximelagatran, the CHADS(2), SPAF, and Framingham schemes had greater predictive accuracy than chance. This predictive ability may allow clinicians to target high-risk patients for more aggressive intervention.

Large variation in lipid content, SigmaPCB and delta13C within individual Atlantic salmon (Salmo salar).

Many studies that investigate pollutant levels, or use stable isotope ratios to define trophic level or animal origin, use different standard ways of sampling (dorsal, whole filet or whole body samples). This study shows that lipid content, SigmaPCB and delta(13)C display large differences within muscle samples taken from a single Atlantic salmon. Lipid- and PCB-content was lowest in tail muscles, intermediate in anterior-dorsal muscles and highest in the stomach (abdominal) muscle area. Stable isotopes of carbon (delta(13)C) showed a lipid accumulation in the stomach muscle area and a depletion in tail muscles. We conclude that it is important to choose an appropriate sample location within an animal based on what processes are to be studied. Care should be taken when attributing persistent pollutant levels or stable isotope data to specific environmental processes before controlling for within-animal variation in these variables.

Biomagnification and polychlorinated biphenyl congener distribution in an aquatic predator-prey, host-parasite system.

Biomagnification and polychlorinated biphenyl (PCB) congener distribution was examined in a predator-prey, host-parasite system, in which Atlantic salmon (Salmo salar) preyed upon sprat (Sprattus sprattus). Eubothrium crassum was an intestinal parasite in salmon that also "preyed upon" sprat, because the parasites gained access to foodstuffs via the host (salmon) gut. Salmon contained significantly higher concentrations of total PCBs compared to both parasites and prey (sprat), but no difference in PCB concentration was found between sprat and E. crassum. Salmon biomagnified several PCB congeners from their diet (sprat), whereas parasites did not, despite the fact that both salmon and their parasites ingested the same prey. Differences in nutrient uptake mechanisms between the host and their parasites, in addition to the lack of a gastrointestinal tract in the cestode, may explain the lack of biomagnification in E. crassum. No difference was found in PCB congener distribution between parasites, salmon, and sprat, and none of the animal types showed a preference for accumulating more or less lipophilic congeners (congeners with a high or low octanol/water partition coefficient [K(ow)]). Biomagnification factors for individual congeners in salmon did not increase with K(ow); rather, they were constant, as shown by a linear relationship for congener concentration in prey and predator.

Polychlorinated biphenyl load, aryl hydrocarbon receptor, and cytochrome P4501A1 induction in a wild population of Atlantic salmon (Salmo salar) from the Baltic Sea.

The toxicity induced by several environmental pollutants is mediated by the aryl hydrocarbon receptor (AHR), which controls the expression of many biotransformation genes, such as cytochrome P4501A1 (CYP1A1). Previous studies have indicated that fish populations can evolve tolerance to persistent chlorinated pollutants by down-regulating the AHR pathway. Here, we measure to what extent tissue loads of polychlorinated biphenyl (PCB) congeners and AHR genotypes contribute to biotransformation capacity in wild, foraging Atlantic salmon (Salmo salar L.) from the Baltic Sea. In muscle, the sum of the 21 most common PCB congeners (ZPCB) was correlated with three extracted AHR agonists (PCBs 77/110, 118/123/149, and 105/132/153). Both the AHR agonists as well as sigmaPCB were correlated with lipid content. The sigmaPCB, controlled for the effects of sex and lipid content in muscle tissue, did not predict mRNA transcript levels of the measured AHRs (AHR2alpha, AHR2gamma, and AHR2delta) or CYP1A1 in liver. However, all AHR2 mRNA transcript levels were positively correlated with CYP1A1 level. In turn, the CYP1A1 level was negatively correlated with concentration of the muscle-tissue antioxidant astaxanthin, suggesting that astaxanthin is depleted when biotransformation processes (CYP1A1) are activated. No correlation was found between ethoxyresorufin-O-deethylase activity and sigmaPCB, CYP1A1, or antioxidant levels. In 5'-flanking regions of the AHR2 genes, we identified multiple allelic variants that were used for genotyping. The mRNA transcript level of AHR2alpha was significantly associated with the AHR2alpha 5'-flanking region genotype and with the interaction of the genotype and individual PCB level. These results suggest that in wild Atlantic salmon from the Baltic Sea, active production of AHR2 mRNA by means of PCB exposure may be affected by genetic polymorphisms at the AHR2 loci.

Serological patterns of Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Pasteurella multocida and Streptococcus suis in pig herds affected by pleuritis.

BACKGROUND: Respiratory illness is traditionally regarded as the disease of the growing pig, and has historically mainly been associated to bacterial infections with focus on Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. These bacteria still are of great importance, but continuously increasing herd sizes have complicated the scenario and the influence of secondary invaders may have been increased. The aim of this study was to evaluate the presence of A. pleuropneumoniae and M. hyopneumoniae, as well as that of the secondary invaders Pasteurella multocida and Streptococcus suis by serology in four pig herds (A-D) using age segregated rearing systems with high incidences of pleuritic lesions at slaughter. RESULTS: Pleuritic lesions registered at slaughter ranged from 20.5 to 33.1 % in the four herds. In herd A, the levels of serum antibodies to A. pleuropneumoniae exceeded A450 > 1.5, but not to any other microbe searched for. The seroconversion took place early during the fattening period. Similar levels of serum antibodies to A. pleuropneumoniae were also recorded in herd B, with a subsequent increase in levels of antibodies to P. multocida. Pigs seroconverted to both agents during the early phase of the fattening period. In herd C, pigs seroconverted to P. multocida during the early phase of the fattening period and thereafter to A. pleuropneumoniae. In herd D, the levels of antibodies to P. multocida exceeded A450 > 1.0 in absence (A450 < 0.5) of antibodies to A. pleuropneumoniae. The levels of serum antibodies to M. hyopneumoniae and to S. suis remained below A450 < 1.0 in all four herds. Pigs seroconverted to M. hyopneumoniae late during the rearing period (herd B-D), or not at all (herd A). CONCLUSION: Different serological patterns were found in the four herds with high levels of serum antibodies to A. pleuropneumoniae and P. multocida, either alone or in combination with each other. Seroconversion to M. hyopneumoniae late during the rearing period or not at all, confirmed the positive effect of age segregated rearing in preventing or delaying infections with M. hyopneumoniae. The results obtained highlight the necessity of diagnostic investigations to define the true disease pattern in herds with a high incidence of pleuritic lesions.

Dose specification for ¹9²Ir high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-to-medium-in-medium.

Dose calculation in high dose rate brachytherapy with (192)Ir is usually based on the TG-43U1 protocol where all media are considered to be water. Several dose calculation algorithms have been developed that are capable of handling heterogeneities with two possibilities to report dose: dose-to-medium-in-medium (Dm,m) and dose-to-water-in-medium (Dw,m). The relation between Dm,m and Dw,m for (192)Ir is the main goal of this study, in particular the dependence of Dw,m on the dose calculation approach using either large cavity theory (LCT) or small cavity theory (SCT). A head and neck case was selected due to the presence of media with a large range of atomic numbers relevant to tissues and mass densities such as air, soft tissues and bone interfaces. This case was simulated using a Monte Carlo (MC) code to score: Dm,m, Dw,m (LCT), mean photon energy and photon fluence. Dw,m (SCT) was derived from MC simulations using the ratio between the unrestricted collisional stopping power of the actual medium and water. Differences between Dm,m and Dw,m (SCT or LCT) can be negligible (<1%) for some tissues e.g. muscle and significant for other tissues with differences of up to 14% for bone. Using SCT or LCT approaches leads to differences between Dw,m (SCT) and Dw,m (LCT) up to 29% for bone and 36% for teeth. The mean photon energy distribution ranges from 222 keV up to 356 keV. However, results obtained using mean photon energies are not equivalent to the ones obtained using the full, local photon spectrum. This work concludes that it is essential that brachytherapy studies clearly report the dose quantity. It further shows that while differences between Dm,m and Dw,m (SCT) mainly depend on tissue type, differences between Dm,m and Dw,m (LCT) are, in addition, significantly dependent on the local photon energy fluence spectrum which varies with distance to implanted sources.

Minor Cytological Abnormalities and up to 7-Year Risk for Subsequent High-Grade Lesions by HPV Type.

OBJECTIVE: Diagnoses of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are common, but the corresponding risk of disease varies by human papillomavirus (HPV) status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with ASCUS/LSIL by age, HPV status, and genotype(s). METHODS: A total of 314 women with ASCUS/ LSIL were followed for a median of 3.8 years. Baseline HPV status was determined by reflex testing and women with histologically confirmed CIN2+ were identified through linkage to the Swedish National Quality Register for Cervical Cancer Prevention. Cumulative incidence and hazard ratios were estimated to explore differences between index data and associations with CIN2+. RESULTS: In total, 89 women (28.3%) developed CIN2+. High-risk (HR) HPV-positive women developed significantly more CIN2+ than HR-HPV-negative women (cumulative incidence 3.5 years after the index test: 42.2%, 95% CI: 32.5-53.5 for HPV16/18; 36.2%, 95% CI: 28.3-45.4 for other HR-HPV types; and 2.0%, 95% CI: 0.5-7.8 for HR-HPV-negative women; p<0.0001). CONCLUSION: HPV status was of greatest importance in determining the risk of CIN2+. The risk was low among HPV-negative women during the first years of follow-up, suggesting these women could be followed less intensively. HPV16/18-positive women may need intensified follow-up as they showed the highest risk of CIN2+.

Osteoclasts in the interface with electrospun hydroxyapatite.

Electrospinning is a method to produce lightweight, resorbable and bioinspired scaffolds for tissue engineering. Here we investigated the influence of electrospun hydroxyapatite fibers (HA) on macrophages and osteoclasts. A mouse macrophage cell line (RAW 264.7) and human bone marrow derived primary osteoclasts (hOC) were cultured with electrospun HA fibers embedded in Matrigel. Cell morphology and the secretion of pro-inflammatory cytokines (IL-6 and TNF-α) were analyzed using macrophages. Both fluorescent microscopy and scanning electron microscopy indicated that the cell morphology differed on the various materials (HA fibers on Matrigel, pure Matrigel and a glass control). Control macrophages were activated with bacterial lipopolysaccharide (LPS) but electrospun HA did not provoke an inflammatory response. Cytokine secretion detected with enzyme-linked immunosorbent assay (ELISA) also supported this observation. LPS, but not HA fibers, stimulated TNF-α and IL-6 secretion by macrophages at the 2 day time point. After 4 days in culture there was an increasing trend in cytokine secretion in the HA fiber samples. Human bone marrow myeloid precursor cells were able to fuse and differentiate on the fibrous mineral scaffold to form functional multinuclear osteoclasts that were able to resorb the HA nanofibers. This indicates that osteoclasts do not necessarily need a continuous bone surface but osteoclast ruffled border membranes can form a resorption interface with a fibrous mineral scaffold.

Triage of HR-HPV positive women with minor cytological abnormalities: a comparison of mRNA testing, HPV DNA testing, and repeat cytology using a 4-year follow-up of a population-based study.

OBJECTIVE: Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology. METHODS: Liquid-based (PreservCyt) cell samples were obtained from HR-HPV-positive women diagnosed with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within the framework of the population-based cervical cancer screening program in Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene-Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the index cytology via medical and laboratory records, and the Stockholm Oncology Center. RESULTS: Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%) women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade 2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity was insufficient (<50%). HPV16 DNA testing and repeat cytology were more specific than APTIMA. CONCLUSION: The results of this population-based study with comprehensive follow-up support the use of APTIMA as a triage test for women with ASCUS. More focused investigation is required for women with LSIL.