Outcomes of CEM43 in Predicting Thermal Damage Induced by Focal Laser Ablation in Controlled Ex Vivo Experiments: A Comparison to Histology and MRI.

BACKGROUND: Focal laser ablation (FLA) serves as a targeted therapy for prostate cancer (PCa). Clinical studies have demonstrated significant variations in ablation volumes with consistent fiber configurations. Consequently, a prediction model is needed for the safe application of FLA in treating PCa. OBJECTIVE: This study aimed to evaluate the reproducibility of FLA-induced temperature profiles in controlled ex vivo experiments using clinical laser treatment protocols. Additionally, it sought to examine the effectiveness of the CEM43 model in predicting the zone of irreversible damage (ZID) and to compare these findings with outcomes derived from the Arrhenius model. METHODS: Freshly excised postmortem human prostate and porcine liver specimens were used for controlled ex vivo ablation. Tissues were secured in a Perspex sample holder for precise placement of the laser fiber and thermocouples. FLA was conducted with a 1064-nm Nd:YAG laser at 3 W in continuous-wave mode for 10 min. Pre- and post-FLA 3D T1-weighted 7 T MRI scans were obtained to assess the treatment area. Whole-mount hematoxylin and eosin histological slides were prepared and digitized. On histology, the ZID was defined as the total of vaporized, carbonized, and coagulated tissue. A 2D thermal development map was created from temperature data, using bi-cubic interpolation. The cumulative equivalent thermal isoeffect dose at 43°C in minutes (CEM43) model was applied to predict the ZID, with 240 equivalent minutes (240-CEM43) used as the damage threshold. Additionally, the Arrhenius thermal model was used for comparison of CEM43 results. Predicted ZIDs were compared to MRI and histology. RESULTS: FLA treatment was performed on ex vivo human prostate samples (n = 2) and porcine liver specimens (n = 5). For human prostate tissue, FLA did not result in an identifiable ZID upon histological macroscopic examination or a lesion on MRI. Ex vivo porcine liver samples showed a clearly demarcated oval-shaped hyperintense lesion surrounding the laser fiber tip on post-FLA MRI. The MRI lesion (range 1.6-2.1 cm2) corresponded with the shape and location of the ZID on histology, but was smaller (median 1.7 vs. 3.2, p = 0.02). Histological examination of porcine liver samples revealed ZIDs ranging from 2.1 to 4.1 cm2, whereas 240-CEM43-predicted ZIDs ranged from 3.3 to 3.8 cm2. Although the median 240-CEM43-predicted ZID was not significantly larger than the histology ZID (3.8 vs. 3.2 cm2, p = 0.22), it tended to overpredict the histological results in most experiments. The median Arrhenius-predicted ZID was similar to the histological ZID (3.2 vs. 3.2 cm2, p = 0.56), but varied in size when comparing individual experiments (range 2.5-3.2 cm2). CONCLUSION: FLA on ex vivo human prostate showed no thermal damage on histopathology or MRI. Ex vivo porcine liver FLA resulted in identifiable ZID on histology and lesions on MRI. 240-CEM43 generally overestimated the ZID and had less variability compared to histology. Results from the Arrhenius model were in better agreement with the histology findings, but still did not predict the individual FLA-induced histological thermal damage. Inter-experiment ZID variability underlines the need for developing a more comprehensive predictive dosimetry model for FLA in PCa treatment.

BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer.

BACKGROUND: The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab. METHODS: From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups. RESULTS: BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36-4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25-0.80) and BCSS (aHR 0.46, 95% CI 0.24-0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes. CONCLUSIONS: In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.

De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study.

BACKGROUND: Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline. METHODS: In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed. FINDINGS: 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group. INTERPRETATION: In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline. FUNDING: Dutch Cancer Society. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

Postoperative microcirculatory perfusion and endothelial glycocalyx shedding following cardiac surgery with cardiopulmonary bypass.

We investigated microcirculatory perfusion disturbances following cardiopulmonary bypass in the early postoperative period and whether the course of these disturbances mirrored restoration of endothelial glycocalyx integrity. We performed sublingual sidestream dark field imaging of the microcirculation during the first three postoperative days in patients who had undergone on-pump coronary artery bypass graft surgery. We calculated the perfused vessel density, proportion of perfused vessels and perfused boundary region. Plasma was obtained to measure heparan sulphate and syndecan-1 levels as glycocalyx shedding markers. We recruited 17 patients; the mean (SD) duration of non-pulsatile cardiopulmonary bypass was 103 (18) min, following which 491 (29) ml autologous blood was transfused through cell salvage. Cardiopulmonary bypass immediately decreased both microcirculatory perfused vessel density; 11 (3) vs. 16 (4) mm.mm-2 , p = 0.052 and the proportion of perfused vessels; 92 (5) vs. 69 (9) %, p < 0.0001. The proportion of perfused vessels did not increase after transfusion of autologous salvaged blood following cardiopulmonary bypass; 72 (7) %, p = 0.19 or during the first three postoperative days; 71 (5) %, p < 0.0001. The perfused boundary region increased after cardiopulmonary bypass; 2.2 (0.3) vs. 1.9 (0.3) µm, p = 0.037 and during the first three postoperative days; 2.4 (0.3) vs. 1.9 (0.3) µm, p = 0.003. Increased plasma heparan sulphate levels were inversely associated with the proportion of perfused vessels during cardiopulmonary bypass; R = -0.49, p = 0.02. Plasma syndecan-1 levels were inversely associated with the proportion of perfused vessels during the entire study period; R = -0.51, p < 0.0001. Our study shows that cardiopulmonary bypass-induced acute microcirculatory perfusion disturbances persist in the first three postoperative days, and are associated with prolonged endothelial glycocalyx shedding. This suggests prolonged impairment and delayed recovery of both microcirculatory perfusion and function after on-pump cardiac surgery.

Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats.

BACKGROUND: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. METHODS: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. RESULTS: CPB immediately impaired microcirculatory perfusion [5 (4-8) vs 10 (7-12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8-25) vs 7 (1-12) µg g-1, P=0.04] and lung [and 23 (13-60) vs 6 (4-16) µg g-1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6-28) µg g-1vs 23 (13-60) µg g-1, P=0.04], but not in kidney [10 (3-23) vs 12 (8-25) µg g-1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. CONCLUSIONS: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.

Young male sex workers are at high risk for sexually transmitted infections, a cross-sectional study from Dutch STI clinics, the Netherlands, 2006-2012.

BACKGROUND: Male sex workers (MSW) are particularly exposed to sexually transmitted infections (STI) including HIV. In the Netherlands, data about STI among MSW are scarce. We estimated chlamydia, gonorrhoea, syphilis and HIV diagnoses among MSW attending STI clinics and determined associated factors to guide prevention policies. METHODS: Using 2006-2012 cross-sectional national surveillance data from Dutch STI clinics, we calculated the proportion of consultations with a positive test for any of three bacterial STI or HIV among MSW. Associated factors were determined by using Poisson logistic regression with robust variance. RESULTS: We identified 3,053 consultations involving MSW, of which 18.1 % included at least one positive bacterial STI test and 2.5 % a positive HIV test. Factors associated with bacterial STI and/or HIV diagnoses were respectively age groups < 35 y.o. and self-reporting homo- or bisexual preferences (aRR = 1.6; 95 % CI: 1.3-2.1), and age group 25-34 y.o. (aRR = 2.7; 95 % CI: 1.2-6.5) and self-reporting homo- or bisexual preferences (aRR = 24.4; 95 % CI: 3.4-176.9). Newly diagnosed and pre-existing HIV infection were associated with an increased risk for bacterial STI (aRR = 2.7, 95 % CI: 1.7-2.6 and aRR = 2.1, 95 % CI: 2.2-3.4 respectively). MSW with no history of HIV screening were more likely to be tested positive for HIV compared to those with a previous HIV-negative test (aRR = 2.6, 95 % CI: 1.6-4.3). CONCLUSION: Health promotion activities should target MSW who are young, homo- or bisexual, those who are HIV-infected or who have never been tested for HIV, to increase early diagnosis, prevention and treatment.

Allergic disorders and socio-economic status: a study of schoolchildren in an urban area of Makassar, Indonesia.

BACKGROUND: In urban centres of developing countries, there is great variation in socio-economic status (SES) and lifestyle; however, little information is available on allergic disorders in groups with high- or low-SES within the same urban area. OBJECTIVE: To determine the prevalence of allergic disorders and investigate risk factors related to them among high- and low-SES schoolchildren in Makassar, the capital city of South Sulawesi, Indonesia. METHOD: This cross-sectional study was performed in 623 children originating from high- (N = 349) and low-SES (N = 274) schools. Information on reported allergic symptoms and potential factors associated with allergic disorders was obtained by questionnaire. Specific IgE and skin prick test (SPT) reactivity were determined against aeroallergens [Dermatophagoides pteronyssinus (HDM) and cockroach]. Total IgE and helminth infections were also assessed. RESULT: The prevalence of SPT to any aeroallergens was significantly higher in high-SES than in low-SES school (25% vs. 8%, P < 0.001, respectively). However, specific IgE against cockroach and total IgE were significantly lower in high- than in low-SES children. Allergic symptoms were reported more often in low- compared to high-SES children. Specific IgE to aeroallergens significantly increased the risk of SPT positivity to the same aeroallergen in the high-, but not in the low-SES children. In the high- but not in low-SES, there was a significant positive association between SPT to HDM and wheeze. Similarly, cockroach skin reactivity and elevated BMI increased the risk of eczema in the high-SES children only. CONCLUSION AND CLINICAL RELEVANCE: Skin prick test is higher in high-SES, whereas IgE and allergic symptoms are higher in low-SES children. Specific IgE is a risk factor for being SPT-positive, and SPT positivity is a risk factor for allergic symptoms but only in children of high- and not low-SES school. Therefore, the socio-economic status of a child might affect the diagnosis of allergic disease in a developing country.

Initial evaluation of use of an online partner notification tool for STI, called 'suggest a test': a cross sectional pilot study.

OBJECTIVES: Partner notification is crucial for sexually transmitted infection (STI) control. We developed Suggestatest.nl (SAT), an internet-based notification system for verified diagnoses of STI/HIV. METHODS: SAT uses email, short message service, postal letter or a gay dating site to notify sexual contacts. SAT was piloted at the Public Health STI clinics in two major cities in the Netherlands. We evaluated SAT from March to July 2012 by analysing SAT notifications linked with epidemiological data. Determinants for SAT use were assessed using multivariable logistic regression analysis. RESULTS: Of 988 index clients receiving a SAT code, overall 139 (14%) notified through SAT, sending 505 notifications (median 2), 84% by text messaging and 15% by email; 88% non-anonymously. Of those intending to use SAT, 23% notified with SAT. Intention to use SAT was the only independent determinant of SAT use in heterosexuals and men who have sex with men. Among the 67 SAT users in Rotterdam, 56% (225/402) of their partners at risk were contactable, and 95% (213/225) of those were notified using SAT. 58% of SAT-notified partners accessed the SAT-website and 20% of them subsequently consulted the STI clinics. STI positivity in partners was lower in those notified by SAT (28% (32/116)) than in those with contact cards (45% (68/152); p<0.001). CONCLUSIONS: Although the challenges posed by non-contactable partners are not solved by SAT, it is a valuable novel tool for notification of verified STI diagnoses by index patients and providers. In addition to current standard partner notification practice it suits a small number of clients, especially those reporting more than one partner.

Poly(trimethylene carbonate) and biphasic calcium phosphate composites for orbital floor reconstruction: a feasibility study in sheep.

In the treatment of orbital floor fractures, bone is ideally regenerated. The materials currently used for orbital floor reconstruction do not lead to the regeneration of bone. Our objective was to render polymeric materials based on poly(trimethylene carbonate) (PTMC) osteoinductive, and to evaluate their suitability for use in orbital floor reconstruction. For this purpose, osteoinductive biphasic calcium phosphate (BCP) particles were introduced into a polymeric PTMC matrix. Composite sheets containing 50 wt% BCP particles were prepared. Also laminates with poly(D,L-lactide) (PDLLA) were prepared by compression moulding PDLLA films onto the composite sheets. After sterilisation by gamma irradiation, the sheets were used to reconstruct surgically-created orbital floor defects in sheep. The bone inducing potential of the different implants was assessed upon intramuscular implantation. The performance of the implants in orbital floor reconstruction was assessed by cone beam computed tomography (CBCT). Histological evaluation revealed that in the orbital and intramuscular implantations of BCP containing specimens, bone formation could be seen after 3 and 9 months. Analysis of the CBCT scans showed that the composite PTMC sheets and the laminated composite sheets performed well in orbital floor reconstruction. It is concluded that PTMC/BCP composites and PTMC/BCP composites laminated with PDLLA have osteoinductive properties and seem suitable for use in orbital floor reconstruction.

Serogroup distribution of urogenital Chlamydia trachomatis in urban ethnic groups in The Netherlands.

The prevalence of Chlamydia trachomatis varies between ethnic groups in The Netherlands. It is, however, unknown whether this is associated with specific serogroups. The objective of this study was to determine whether serogroup distribution is associated with ethnic origin in the region of The Hague, The Netherlands. Serogroups of 370 microbiologically confirmed C. trachomatis-positive samples were analysed. The samples were obtained from 247 women and 123 men between January and October 2008, of self-reported Dutch Caucasian, Dutch Antillean, Surinamese, N. African/Turkish or other descent. We observed a difference in serogroup distribution comparing Dutch Caucasian women to Dutch Antillean women (χ2 for distribution P = 0·035). Serogroup C was more common in Dutch Antillean women, whereas serogroup B was less common (P = 0·03). This difference was not observed for Dutch Antillean men. The observed difference in distribution of C. trachomatis serogroups between ethnic groups is relevant for further transmission studies.

Viable Legionella pneumophila bacteria in natural soil and rainwater puddles.

AIMS: For the majority of sporadic Legionnaires' disease cases the source of infection remains unknown. Infection may possible result from exposure to Legionella bacteria in sources that are not yet considered in outbreak investigations. Therefore, potential sources of pathogenic Legionella bacteria--natural soil and rainwater puddles on roads--were studied in 2012. METHODS AND RESULTS: Legionella bacteria were detected in 30% (6/20) of soils and 3·9% (3/77) of rainwater puddles by amoebal coculture. Legionella pneumophila was isolated from two out of six Legionella positive soil samples and two out of three Legionella positive rainwater samples. Several other species were found including the pathogenic Leg. gormanii and Leg. longbeachae. Sequence types (ST) could be assigned to two Leg. pneumophila strains isolated from soil, ST710 and ST477, and one strain isolated from rainwater, ST1064. These sequence types were previously associated with Legionnaires' disease patients. CONCLUSIONS: Rainwater and soil may be alternative sources for Legionella. SIGNIFICANCE AND IMPACT OF THE STUDY: The detection of clinically relevant strains indicates that rainwater and soil are potential sources of Legionella bacteria and future research should assess the public health implication of the presence of Leg. pneumophila in rainwater puddles and natural soil.

Force-field perturbations and muscle vibration strengthen stability-related foot placement responses during steady-state gait in healthy adults.

Mediolateral gait stability can be maintained by coordinating our foot placement with respect to the center-of-mass (CoM) kinematic state. Neurological impairments can reduce the degree of foot placement control. For individuals with such impairments, interventions that could improve foot placement control could thus contribute to improved gait stability. In this study we aimed to better understand two potential interventions, by investigating their effect in neurologically intact individuals. The degree of foot placement control can be quantified based on a foot placement model, in which the CoM position and velocity during swing predict subsequent foot placement. Previously, perturbing foot placement with a force-field resulted in an enhanced degree of foot placement control as an after-effect. Moreover, timed muscle vibration enhanced the degree of foot placement control whilst the vibration was applied. Here, we replicated these two findings and further investigated whether Q1) timed muscle vibration leads to an after-effect and Q2) whether combining timed muscle vibration with force-field perturbations leads to a larger after-effect, as compared to force-field perturbations only. In addition, we evaluated several potential contributors to the degree of foot placement control, by considering foot placement errors, CoM variability and the CoM position gain (ßpos) of the foot placement model, next to the R2 measure as the degree of foot placement control. Timed muscle vibration led to a higher degree of foot placement control as an after-effect (Q1). However, combining timed muscle vibration and force-field perturbations did not lead to a larger after-effect, as compared to following force-field perturbations only (Q2). Furthermore, we showed that the improved degree of foot placement control following force-field perturbations and during/following muscle vibration, did not reflect diminished foot placement errors. Rather, participants demonstrated a stronger active response (higher ßpos) as well as higher CoM variability.

Isolation of Legionella pneumophila from pluvial floods by amoebal coculture.

Viable Legionella pneumophila bacteria were isolated by amoebal coculture from pluvial floods after intense rainfall and from water collected at sewage treatment plants. Several isolated L. pneumophila strains belonged to sequence types that have been previously identified in patients.

In vivo behaviour of a biodegradable poly(trimethylene carbonate) barrier membrane: a histological study in rats.

The aim of the present study was to evaluate the response of surrounding tissues to newly developed poly(trimethylene carbonate) (PTMC) membranes. Furthermore, the tissue formation beneath and the space maintaining properties of the PTMC membrane were evaluated. Results were compared with a collagen membrane (Geistlich BioGide), which served as control. Single-sided standardized 5.0 mm circular bicortical defects were created in the mandibular angle of rats. Defects were covered with either the PTMC membrane or a collagen membrane. After 2, 4 and 12 weeks rats were sacrificed and histology was performed. The PTMC membranes induced a mild tissue reaction corresponding to a normal foreign body reaction. The PTMC membranes showed minimal cellular capsule formation and showed signs of a surface erosion process. Bone tissue formed beneath the PTMC membranes comparable to that beneath the collagen membranes. The space maintaining properties of the PTMC membranes were superior to those of the collagen membrane. Newly developed PTMC membranes can be used with success as barrier membranes in critical size rat mandibular defects.

The value of frozen section biopsy in diagnosing necrotizing fasciitis: proposal of a new grading system.

GOALS AND OBJECTIVES: Necrotizing fasciitis is a serious disease entity, with only limited pathognomic features. PURPOSE: In necrotizing fasciitis a rapid diagnosis is necessary in order to reduce morbidity and mortality. In this study the investigation focused on specific features in the frozen section biopsy for diagnosing necrotizing fasciitis. METHODS: A total of ten patients are described with final pathological examination of resected tissue. RESULTS: A new grading system is suggested for frozen section biopsy in patients with necrotizing fasciitis. In the herein reported study it was found that granulocytes were present in both the frozen section biopsy and in the definitive paraffin coupes, in the subcutis and fascia layer. CONCLUSION: Frozen section biopsy could be useful in diagnosing necrotizing fasciitis.

The effect of external lateral stabilization on ankle moment control during steady-state walking.

External lateral stabilization can help identify stability control mechanisms during steady-state walking. The degree of step-by-step foot placement control and step width are known to decrease when walking with external lateral stabilization. Here, we investigated the effect of external lateral stabilization on ankle moment control in healthy participants. Ankle moment control complements foot placement, by allowing a corrective center-of-pressure shift once the foot has been placed. This is reflected by a model predicting this center-of-pressure shift based on the preceding foot placement error. Here, the absolute explained variance accounted for by this model decreased when walking with external lateral stabilization. In other words, we found a reduction in the contribution of step-by-step ankle moment control to mediolateral gait stability when externally stabilized. Concurrently, foot placement error and the average center-of-pressure shift remained unchanged.

Differential effects of ankle constraints on foot placement control between normal and split belt treadmills.

Mediolateral ankle moment control contributes to gait stability. Ankle moments can be constrained by walking with a shoe with a ridge underneath the sole, narrowing the mediolateral support surface. In our previous study, such ankle moment constraints resulted in an increased step width and a decrease in the degree of foot placement control, as defined by the percentage of variance in foot placement that can be explained by CoM state. However, since our previous study was performed on a split-belt treadmill and the narrow ridge could fit inside the gap between the belts, it is not evident whether these effects can be attributed to the constrained ankle moment control or to avoidance of this gap. Therefore, we investigated if the effects of ankle moment constraints are dependent on whether participants walk on a normal treadmill or a split-belt treadmill. We included fourteen healthy young adults. Walking with constrained ankle moment control resulted in a wider step width on both treadmills. Yet, the increase in step width was larger on the split-belt treadmill compared to on the normal treadmill. We only found a decreased degree of foot placement control on the split-belt treadmill, whilst the degree of foot placement control increased on the normal treadmill. We conclude that the effects of ankle moment constraints reported in our previous study were confounded by the use of a split-belt treadmill. For future research, we recommend using a normal treadmill whenever possible, because the gap in a split-belt treadmill might affect gait parameters.

Can foot placement during gait be trained? Adaptations in stability control when ankle moments are constrained.

Accurate coordination of mediolateral foot placement, relative to the center of mass kinematic state, is one of the mechanisms which ensures mediolateral stability during human walking. Previously, we found that shoes constraining ankle moments decreased the degree of foot placement control with respect to the center of mass kinematic state. As such, ankle moment constraints can be seen as a perturbation of foot placement. Direct mechanical perturbations of the swing leg trajectory can improve the degree of foot placement control as an after-effect. Here, we asked whether constrained ankle moments could have a similar effect. If confirmed, this would offer a simple training tool for individuals with impaired foot placement control. Participants walked in three conditions; normal (baseline) while wearing shoes constraining ankle moments (training) and normal again (after-effects). The degree of foot placement control was calculated as the percentage of variance in foot placement that could be predicted based on the center of mass kinematic state in the preceding swing phase. During training, the degree of foot placement control decreased initially compared to baseline, but it gradually improved over time. In the after-effect condition, it was higher than during baseline, yet not significantly so. During training, we observed increased step width, decreased stride time and reduced local dynamic stability. In conclusion, constraining ankle moment control deteriorates the degree of foot placement control. A non-significant trend towards an improved degree of foot placement control after prolonged exposure to constrained ankle moments, allows for speculation on a training potential.

Dynamic Contrast-enhanced and Diffusion-weighted Magnetic Resonance Imaging for Response Evaluation After Single-Dose Ablative Neoadjuvant Partial Breast Irradiation.

Purpose: We aimed to evaluate changes in dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) scans acquired before and after single-dose ablative neoadjuvant partial breast irradiation (NA-PBI), and explore the relation between semiquantitative MRI parameters and radiologic and pathologic responses. Methods and Materials: We analyzed 3.0T DCE and DW-MRI of 36 patients with low-risk breast cancer who were treated with single-dose NA-PBI, followed by breast-conserving surgery 6 or 8 months later. MRI was acquired before NA-PBI and 1 week, 2, 4, and 6 months after NA-PBI. Breast radiologists assessed the radiologic response and breast pathologists scored the pathologic response after surgery. Patients were grouped as either pathologic responders or nonresponders (<10% vs ≥10% residual tumor cells). The semiquantitative MRI parameters evaluated were time to enhancement (TTE), 1-minute relative enhancement (RE1min), percentage of enhancing voxels (%EV), distribution of washout curve types, and apparent diffusion coefficient (ADC). Results: In general, the enhancement increased 1 week after NA-PBI (baseline vs 1 week median - TTE: 15s vs 10s; RE1min: 161% vs 197%; %EV: 47% vs 67%) and decreased from 2 months onward (6 months median - TTE: 25s; RE1min: 86%; %EV: 12%). Median ADC increased from 0.83 × 10-3 mm2/s at baseline to 1.28 × 10-3 mm2/s at 6 months. TTE, RE1min, and %EV showed the most potential to differentiate between radiologic responses, and TTE, RE1min, and ADC between pathologic responses. Conclusions: Semiquantitative analyses of DCE and DW-MRI showed changes in relative enhancement and ADC 1 week after NA-PBI, indicating acute inflammation, followed by changes indicating tumor regression from 2 to 6 months after radiation therapy. A relation between the MRI parameters and radiologic and pathologic responses could not be proven in this exploratory study.

Analyses of multiple-site and concurrent Chlamydia trachomatis serovar infections, and serovar tissue tropism for urogenital versus rectal specimens in male and female patients.

OBJECTIVES: The aims of this study were: to determine the incidence of concurrent infections on a serovar level; to determine the incidence of multiple anatomical infected sites on a detection and genotyping level and analyse site-specific serovar distribution; to identify tissue tropism in urogenital versus rectal specimens. METHODS: Chlamydia trachomatis-infected patients in two populations were analysed: 75 visiting the outpatient department of obstetrics and gynaecology of the MC Haaglanden, and 358 visiting the outpatient sexually transmitted disease clinic, The Hague, The Netherlands. The PACE 2 assay (Gen-Probe) was used to detect C trachomatis from urethral, cervical, vaginal, oropharyngeal and anorectal swabs. C trachomatis genotyping was performed on all C trachomatis positive samples, using the CT-DT genotyping assay. RESULTS: Samples from 433 patients (256 female and 177 male) with confirmed C trachomatis infection were analysed. In 11 patients (2.6%), concurrent serovars in one anatomical sample site were present. In 62 (34.1%) female and four (9.3%) male patients, multiple sample site infections were found. A substantial percentage of women tested at the cervical/vaginal and rectal site were found to be positive at both sites (36.1%, 22/61). In men, D/Da and G/Ga serovars were more prevalent in rectal than urogenital specimens (p=0.0081 and p=0.0033, respectively), while serovar E was more prevalent in urogenital specimens (p=0.0012). CONCLUSIONS: The prevalence of multiple serovar infections is relatively low. Significant differences in serovar distribution are found in rectal specimens from men, with serovar G/Ga being the most prominent, suggesting tissue tropism.