The Relationship between Nociceptive Detection Thresholds and Pressure- and Electrical Pain Thresholds: An Explorative Study in Rheumatoid Arthritis Patients.

Recently, methods have been developed enabling the characterization of the nociceptive function at the detection threshold level by measuring nociceptive detection thresholds (NDTs), rather than at the level of the pain threshold via pain threshold (PT) measurements. Both NDT and PT measurements aim to characterize (parts of) the nociceptive system. To date it is unclear if, and if so to what extent, the two outcomes relate to one another. In this study, the primary aim is to explore the relationship between the two measures in patients with rheumatoid arthritis (RA). As secondary aim, we explore differences in NDT between these RA patients with age- and sex-matched healthy controls (HC) from a readily existing dataset. In total 46 RA patients have been recruited, whereby the pressure- (PPT; bilaterally at two locations) and electrical (EPT) pain threshold were evaluated, as well as the NDTs. Significant, positive correlations were found between the EPT and PPT (R=0.54-0.60), but not with the NDTs (R≤0.25). As compared to HC, higher NDTs were found in the RA group. As the presence of a statistically significant weak relationship can only be evaluated using a larger sample size, our results indicate that there is no moderate or stronger relation between PT and NDT outcomes. This implicates that the two outcomes are not strongly driven by the same (nociceptive) mechanism(s). Future research into NDTs and what factors and/or mechanisms affect the outcome, could yield relevant insights into how to use and interpret the results of this relatively new method.Clinical Relevance - The evaluation of nociceptive detection thresholds, in isolation or together with conventionally evaluated pain thresholds, might provide valuable and complementary insights into nociceptive (dis)function in man.

Rotary Bend Fatigue of Nitinol to One Billion Cycles.

Nitinol implants, especially those used in cardiovascular applications, are typically expected to remain durable beyond 108 cycles, yet literature on ultra-high cycle fatigue of nitinol remains relatively scarce and its mechanisms not well understood. To investigate nitinol fatigue behavior in this domain, we conducted a multifaceted evaluation of nitinol wire subjected to rotary bend fatigue that included detailed material characterization and finite element analysis as well as post hoc analyses of the resulting fatigue life data. Below approximately 105 cycles, cyclic phase transformation, as predicted by computational simulations, was associated with fatigue failure. Between 105 and 108 cycles, fractures were relatively infrequent. Beyond 108 cycles, fatigue fractures were relatively common depending on the load level and other factors including the size of non-metallic inclusions present and the number of loading cycles. Given observations of both low cycle and ultra-high cycle fatigue fractures, a two-failure model may be more appropriate than the standard Coffin-Manson equation for characterizing nitinol fatigue life beyond 108 cycles. This work provides the first documented fatigue study of medical grade nitinol to 109 cycles, and the observations and insights described will be of value as design engineers seek to improve durability for future nitinol implants.

Acceptance and Commitment Therapy Group Intervention for Parents of Children with Disabilities (Navigator ACT): An Open Feasibility Trial.

Parents of children with autism spectrum disorder and other disabilities report high levels of distress, but systematically evaluated interventions are few. This study aimed to evaluate the feasibility of a novel, manualized Acceptance and Commitment Therapy group intervention (Navigator ACT) in a sample of 94 parents of children with disabilities. Feasibility was measured by treatment completion, credibility, and satisfaction, and preliminary outcomes by using self-rating scales administered at the baseline, post-intervention, and follow-up. The results imply the intervention is feasible in the context of Swedish outpatient habilitation services. A preliminary analysis of the outcome measures suggests that parents experienced significant improvements in well-being. The results indicate that the treatment is feasible and should be evaluated in a randomized controlled trial.

The effect of the acute phase of infection on absorption of and exposure to orally administered antibiotics in non-critically ill, hospitalized patients.

OBJECTIVES: During the acute phase of infection, IV antibiotics are preferred to ensure adequate systemic exposure. To assess whether adequate exposure may also be achieved with oral antibiotics, we investigated exposure to oral antibiotics and PTA during the acute phase of infection and after defervescence. METHODS: We enrolled hospitalized, non-critically ill febrile patients treated with IV antibiotics other than amoxicillin or ciprofloxacin. The study consisted of two visits: when patients had received <24 h IV treatment; and when patients had become afebrile. On both visits, patients received one additional dose of 750 mg amoxicillin, or 500 mg ciprofloxacin, depending on the presumed infection, after which serial blood samples were obtained. The primary endpoint was the ratio of the AUC during the febrile and the afebrile phase. The AUCs were considered to be equivalent when the ratio of the mean AUCs and its 90% CI was contained within the acceptance interval of 80%-125%. The secondary endpoint was PTA. RESULTS: Forty-four patients (15 amoxicillin, 29 ciprofloxacin) completed both study visits. The median time between the two study visits was 65.8 h (range 33.8-427.4). The ratio of the mean AUCs (study visit 1/study visit 2) was 97% (90% CI of 80%-117%) for amoxicillin and 112% (90% CI of 108%-116%) for ciprofloxacin. The PTA for amoxicillin and ciprofloxacin did not differ between the two phases and was adequate to treat common pathogens. CONCLUSIONS: The acute phase of infection in non-critically ill febrile patients does not influence the exposure to, or PTA of, orally administered amoxicillin and ciprofloxacin. This might justify earlier IV-to-oral switching.

Gut Commensal Bacteroidetes Encode a Novel Class of Vitamin B12-Binding Proteins.

Human gut commensal Bacteroidetes rely on multiple transport systems to acquire vitamin B12 and related cobamides for fitness in the gut. In addition to a set of conserved transport proteins, these systems also include a diverse repertoire of additional proteins with unknown function. Here, we report the function and structural characterization of one of these proteins, BtuH, which binds vitamin B12 directly via a C-terminal globular domain that has no known structural homologs. This protein is required for efficient B12 transport and competitive fitness in the gut, demonstrating that members of the heterogeneous suite of accessory proteins encoded in Bacteroides cobamide transport system loci can play key roles in vitamin acquisition. IMPORTANCE The gut microbiome is a complex microbial community with important impacts on human health. One of the major groups within the gut microbiome, the Bacteroidetes, rely on their ability to capture vitamin B12 and related molecules for fitness in the gut. Unlike well-studied model organisms, gut Bacteroidetes genomes often include multiple vitamin B12 transport systems with a heterogeneous set of components. The role, if any, of these components was unknown. Here, we identify new proteins that play key roles in vitamin B12 capture in these organisms. Notably, these proteins are associated with some B12 transport systems and not others (even in the same bacterial strain), suggesting that these systems may assemble into functionally distinct machines to capture vitamin B12 and related molecules.

Diffuse vertebral marrow changes at MRI: Multiple myeloma or normal?

Five MRI patterns of marrow involvement (diffuse, focal, combined diffuse and focal, variegated, and normal) are observed in patients with a marrow proliferative disorder including MM. The wide range of marrow involvement patterns in monoclonal plasma cell proliferative disorders mirrors that of their natural histories that can vary from indolent to rapidly lethal. MRI of the axial bone marrow contributes to stage these disorders, but it should not be obtained for disease detection and characterization because of its limited specificity and sensitivity. At MRI, diffuse benign hematopoietic marrow hyperplasia and marrow heterogeneities in elderly patients mimic the diffuse and variegated patterns observed in MM patients. Careful analysis of fat- and fluid-sensitive MR images and quantitative marrow assessment by using MRI and FDG-PET can contribute in differentiating these changes from those associated with neoplastic marrow infiltration, with some residual overlapping findings.

Transition to marine ice cliff instability controlled by ice thickness gradients and velocity.

Portions of ice sheets grounded deep beneath sea level can disintegrate if tall ice cliffs at the ice-ocean boundary start to collapse under their own weight. This process, called marine ice cliff instability, could lead to catastrophic retreat of sections of West Antarctica on decadal-to-century time scales. Here we use a model that resolves flow and failure of ice to show that dynamic thinning can slow or stabilize cliff retreat, but when ice thickness increases rapidly upstream from the ice cliff, there is a transition to catastrophic collapse. However, even if vulnerable locations like Thwaites Glacier start to collapse, small resistive forces from sea-ice and calved debris can slow down or arrest retreat, reducing the potential for sustained ice sheet collapse.

Neuronal architecture of the second-order CO2 pathway in the brain of a noctuid moth.

Many insects possess the ability to detect fine fluctuations in the environmental CO2 concentration. In herbivorous species, plant-emitted CO2, in combination with other sensory cues, affect many behaviors including foraging and oviposition. In contrast to the comprehensive knowledge obtained on the insect olfactory pathway in recent years, we still know little about the central CO2 system. By utilizing intracellular labeling and mass staining, we report the neuroanatomy of projection neurons connected with the CO2 sensitive antennal-lobe glomerulus, the labial pit organ glomerulus (LPOG), in the noctuid moth, Helicoverpa armigera. We identified 15 individual LPOG projection neurons passing along different tracts. Most of these uniglomerular neurons terminated in the lateral horn, a previously well-described target area of plant-odor projection neurons originating from the numerous ordinary antennal-lobe glomeruli. The other higher-order processing area for odor information, the calyces, on the other hand, was weakly innervated by the LPOG neurons. The overlapping LPOG terminals in the lateral horn, which is considered important for innate behavior in insects, suggests the biological importance of integrating the CO2 input with plant odor information while the weak innervation of the calyces indicates the insignificance of this ubiquitous cue for learning mechanisms.

Anti-inflammatory and immune properties of the peltatoside, isolated from the leaves of Annona crassiflora Mart., in a new experimental model zebrafish.

Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-ß-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 µg) and dexamethasone (25 µg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 µg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.

Development of osteoarthritis in patients with degenerative meniscal tears treated with exercise therapy or surgery: a randomized controlled trial.

OBJECTIVE: To evaluate progression of individual radiographic features 5 years following exercise therapy or arthroscopic partial meniscectomy as treatment for degenerative meniscal tear. DESIGN: Randomized controlled trial including 140 adults, aged 35-60 years, with a magnetic resonance image verified degenerative meniscal tear, and 96% without definite radiographic knee osteoarthritis. Participants were randomized to either 12-weeks of supervised exercise therapy or arthroscopic partial meniscectomy. The primary outcome was between-group difference in progression of tibiofemoral joint space narrowing and marginal osteophytes at 5 years, assessed semi-quantitatively by the OARSI atlas. Secondary outcomes included incidence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis, medial tibiofemoral fixed joint space width (quantitatively assessed), and patient-reported outcome measures. Statistical analyses were performed using a full analysis set. Per protocol and as treated analysis were also performed. RESULTS: The risk ratios (95% CI) for progression of semi-quantitatively assessed joint space narrowing and medial and lateral osteophytes for the surgery group were 0.89 (0.55-1.44), 1.15 (0.79-1.68) and 0.77 (0.42-1.42), respectively, compared to the exercise therapy group. In secondary outcomes (full-set analysis) no statistically significant between-group differences were found. CONCLUSION: The study was inconclusive with respect to potential differences in progression of individual radiographic features after surgical and non-surgical treatment for degenerative meniscal tear. Further, we found no strong evidence in support of differences in development of incident radiographic knee osteoarthritis or patient-reported outcomes between exercise therapy and arthroscopic partial meniscectomy. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01002794).

MRI detection of radiographically occult fractures of the hip and pelvis in the elderly: Comparison of T2-weighted Dixon sequence with T1-weighted and STIR sequences.

PURPOSE: To compare the diagnostic performance of T2-weighted Dixon, T1-weighted and Short-Tau Inversion Recovery (STIR) MR images for the detection of radiographically occult fractures (ROF) of the hip and pelvis in elderly patients after low-energy trauma. MATERIALS AND METHODS: A total of 22 patients older than 50 years with suspected ROF after low-energy trauma was prospectively included. There were 9 men and 13 women, with a mean age of 80.9 years±12.5 (SD) (range: 52-100 years). T2-weighted Dixon, T1-weighted and STIR MR images were analyzed by 3 independent radiologists blinded to the clinical data and the results of other imaging examinations. Readers separately assessed each series of images for the presence of fractures on a per bone analysis. Diagnostic performance of each reader was compared for Dixon and non-Dixon sequences using contingency tables and McNemar test. Interobserver agreement was evaluated according to the Fleiss-Cuzick's kappa statistics. RESULTS: The sensitivity of the Dixon sequence in the detection of ROF ranged from 90.9% (20/22; 95% CI: 70.8-98.9%) to 100% (22/22; 95% CI: 84.6-100%). The sensitivities of the non-Dixon sequences in the detection of ROF ranged from 95.5% (21/22; 95% CI: 77.2-99.9%) to 100% (22/22; 95% CI: 84.6-100%). For each reader, there were no statistical differences between combined Dixon and combined non-Dixon images for the detection of ROF (P=0.12, 0.99 and 0.99). Interobserver agreement with T2-weighted Dixon water-only images was significantly lower than that with the STIR sequence (0.70-0.79 vs. 0.87-0.93). CONCLUSION: T2-weighted Dixon may be a second-rate alternative to T1-weighted and STIR sequences for the detection of ROF of the hip and pelvis in elderly patients.

Analysis Of Nociceptive Evoked Potentials During Multi-Stimulus Experiments Using Linear Mixed Models.

Neural processing of sensory stimuli can be studied using EEG by estimation of the evoked potential using the averages of large sets of trials. However, it is not always possible to include all stimulus parameters in a conventional analysis, since this would lead to an insufficient amount of trials to obtain the evoked potential by averaging. Linear mixed models use dependencies within the data to combine information from all data for the estimation of the evoked potential. In this work, it is shown that in multi-stimulus EEG data the quality of an evoked potential estimate can be improved by using a linear mixed model. Furthermore, the linear mixed model effectively deals with correlation between parameters in the data and reveals the influence of individual stimulus parameters.

Can we assess healing of surgically treated long bone fractures on radiograph?

PURPOSE: To determine the frequency and causes for limitations in the radiographic evaluation of surgically treated long bone fractures. MATERIALS AND METHODS: Six readers separately scored 140 sets of antero-posterior (AP) and lateral radiographs of surgically treated long bone fractures, using a radiographic union score (RUS). We determined the rate of assessability of the fracture edges at each of the four cortical segments (n=560) seen tangentially on the two radiographs and the causes for non-assessability. The rate of feasibility of the RUS (more than two fracture edges assessable per fracture) was determined and compared according to different parameters. RESULTS: Fracture edges were visible in 71% to 81% of the 560 cortical segments. Metal hardware superimposition was the most frequent cause for non-assessability (79-95%). RUS values could be calculated in 58% to 75% of fractures. Scoring was statistically significantly less frequently calculable in plated (31-56%) than in nailed fractures (90-97%), in distal (47-61%) than in proximal (78-89%) bones and in upper (27-49%) than in lower (76-91%) limb bones (P≤0.01). CONCLUSIONS: The type of stabilization hardware is the main limiting factor in the radiographic assessment of surgically treated long bone fractures. Scoring was feasible in only 31% to 56% of plated fractures.

3D Printed Surgical Simulation Models as educational tool by maxillofacial surgeons.

INTRODUCTION: The aim of this study was to evaluate whether inexpensive 3D models can be suitable to train surgical skills to dental students or oral and maxillofacial surgery residents. Furthermore, we wanted to know which of the most common filament materials, acrylonitrile butadiene styrene (ABS) or polylactic acid (PLA), can better simulate human bone according to surgeons' subjective perceptions. MATERIALS AND METHODS: Upper and lower jaw models were produced with common 3D desktop printers, ABS and PLA filament and silicon rubber for soft tissue simulation. Those models were given to 10 blinded, experienced maxillofacial surgeons to perform sinus lift and wisdom teeth extraction. Evaluation was made using a questionnaire. RESULTS: Because of slightly different density and filament prices, each silicon-covered model costs between 1.40-1.60 USD (ABS) and 1.80-2.00 USD (PLA) based on 2017 material costs. Ten experienced raters took part in the study. All raters deemed the models suitable for surgical education. No significant differences between ABS and PLA were found, with both having distinct advantages. CONCLUSION: The study demonstrated that 3D printing with inexpensive printing filaments is a promising method for training oral and maxillofacial surgery residents or dental students in selected surgical procedures. With a simple and cost-efficient manufacturing process, models of actual patient cases can be produced on a small scale, simulating many kinds of surgical procedures.

Magnetic resonance imaging (MRI) of the knee: Identification of difficult-to-diagnose meniscal lesions.

This article characterizes common meniscal pathologies, reviews magnetic resonance imaging (MRI) diagnostic criteria for meniscal tears, and identifies difficult-to-detect tears and fragments and the best MRI sequences and practices for recognizing these lesions. These difficult-to-diagnose meniscal lesions that radiologists should consider include tears, meniscocapsular separation lesions, and displaced meniscal fragments. Meniscus tears are either vertical, which are generally associated with traumatic injury, horizontal, which are associated with degenerative injury, or combinations of both. MRI has a high sensitivity for tears but not for fragments; MRI performance is also better for medial than lateral meniscal lesions. Fragment detection can be improved by recognizing signs secondary to migration, especially signs of epiphyseal irritation and mechanical impingement. Radial and peripheral tears, as well as those close to the posterior horn insertion, have been traditionally difficult to detect, but improvements in arthroscopic knowledge, identification of common lesion patterns, and selection of the proper MRI sequence and plane for each lesion type mean that, when properly used, MRI is an invaluable tool in detecting all types of meniscal tears.

Fused micro-computed tomography (µCT) and histological images of bone specimens.

OBJECTIVES: To describe a stepwise process to obtain fused images from micro-computed tomography (µCT) and histological images of bone specimens. MATERIAL AND METHODS: Four surgically resected human femoral heads from four patients who had total hip replacement were imaged at a spatial resolution of 12-microns by using µCT. Histological sections of four focal bone lesions including bone cyst in osteoarthritis (n=2) and subchondral bone plate fracture in osteonecrosis (n=2) were prepared and digitized. µCT images were reformatted and adjusted to match the histological images using a landmark-based visual co-registration. Fused µCT and histological images were displayed in a cine-loop video mode with a gradual transition from one image to the other. RESULTS: µCT images of the four focal bone lesions could be successfully fused with the corresponding histological images with a near perfect match of the bone trabeculae. CONCLUSION: We present a stepwise process to obtain fused images from histological and reformatted µCT images of human femoral heads.

Fat suppression at three-dimensional T1-weighted MR imaging of the hands: Dixon method versus CHESS technique.

PURPOSE: To compare the effectiveness of fat suppression and the image quality of the Dixon method with those of the chemical shift-selective (CHESS) technique in hands of normal subjects at non-enhanced three-dimensional (3D) T1-weighted MR imaging. MATERIALS AND METHODS: Both hands of 14 healthy volunteers were imaged with 3D fast spoiled gradient echo (FSPGR) T1-weighted Dixon, 3D FSPGR T1-weighted CHESS and 3D T1-weighted fast spin echo (FSE) CHESS sequences in a 1.5T MR scanner. Three radiologists scored the effectiveness of fat suppression in bone marrow (EFSBM) and soft tissues (EFSST) in 20 joints per subject. One radiologist measured the signal-to-noise ratio (SNR) in 10 bones per subject. Statistical analysis used two-way ANOVA with random effects (P<0.0083), paired t-test (P<0.05) and observed agreement to assess differences in effectiveness of fat suppression, differences in SNR and interobserver agreement. RESULTS: EFSBM was statistically significantly higher for the 3D FSPGR T1-weighted Dixon than for the 3D FSPGR T1-weighted CHESS sequence and the 3D FSE T1-weighted CHESS sequence (P<0.0001). EFSST was statistically significantly higher for the 3D FSPGR T1-weighted Dixon than for the 3D FSPGR T1-weighted CHESS sequence (P<0.0011) and for the 3D FSE T1-weighted CHESS sequence in the axial plane (P=0.0028). Mean SNR was statistically significantly higher for 3D FSPGR T1-weighted Dixon sequence than for 3D FSPGR T1-weighted CHESS and 3D FSE T1-weighted CHESS sequences (P<0.0001). CONCLUSION: The Dixon method yields more effective fat suppression and higher SNR than the CHESS technique at 3D T1-weighted MR imaging of the hands.

Application of a three-dimensional graft of autologous osteodifferentiated adipose stem cells in patients undergoing minimally invasive transforaminal lumbar interbody fusion: clinical proof of concept.

BACKGROUND: The authors applied a scaffold-free osteogenic three-dimensional (3D) graft made of adipose-derived mesenchymal stem cells (AMSCs) in patients undergoing minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). METHODS: Three patients (two patients and one patient with 1 and 2 levels, respectively) with degenerative spondylolisthesis underwent MI-TLIF with 3D graft made of AMSCs. To obtain the AMSCs, fatty tissue was collected from the abdomen by lipoaspiration and differentiated afterwards in our Cell/Tissue bank. Clinical outcomes, including the Oswestry Disability Index (ODI) and visual analog scale (VAS) as well as fusion status were assessed preoperatively and up to 12 months postoperatively. RESULTS: At 12 months, all four operated AMSC levels could be assessed (n = 4). Grade 3 fusion could be confirmed at two levels out of four. Mean VAS score improved from 8.3 to 2 and ODI also improved from 47 to 31%. No donor site complication was observed. The final AMSC osteogenic product was stable, did not rupture with forceps manipulation, and was easily implanted directly into the cage with no marked modification of operating time. CONCLUSIONS: A scaffold-free 3D graft made of AMSCs can be manufactured and used as a promising alternative for spinal fusion procedures. Nevertheless, further studies of a larger series of patients are needed to confirm its effectiveness.

[The willingness of the Dutch to pay for mental health care]. / De betalingsbereidheid voor de geneeskundige geestelijke gezondheidszorg.

BACKGROUND: How much are the Dutch prepared to pay for mental health care? Nearly every year the content of the basic health insurance package alters as a results of new insights and scientific and medical progress. Up till now, the government of the Netherlands has largely ignored the wishes of its people regarding which services should be included in or dropped from the basis health care package.
AIM: To describe a method for measuring the Dutch population's willingness to pay (wtp) for the inclusion of mental health care in the basic health insurance package and, at the same time, to present the first empirical findings obtained by this method.
METHOD: Data were collected in 2013 via a printed questionnaire on which the respondent was asked to declare how much he or she would be prepared to pay for the inclusion of mental health care in the basic health care package.
RESULTS: The average per capita amount that the Dutch were prepared to pay for the inclusion of mental health care was found be € 25.90 per month.
CONCLUSION: The average amount that a Dutch national was prepared to pay for having mental health care included in the basic package was higher that the actual per capita amount paid for mental health care. In 2013 these costs were € 15.80 per capita per month.