Image-guided lymph node core-needle biopsy predicts survival in mycosis fungoides and Sézary syndrome.

BACKGROUND: The prognosis of Sézary syndrome (SS) and mycosis fungoides (MF) depends on lymph node (LN) involvement. The usefulness of LN image-guided core-needle biopsies (CNBs), instead of surgical sampling, has been poorly evaluated. OBJECTIVES: To determine the prognostic value of LN CNB in MF/SS. METHODS: A retrospective search was conducted to identify all LN biopsy specimens of MF/SS between 2008 and 2019. Biopsies were staged according to the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer (ISCL/EORTC) criteria. We performed immunolabelling and determined the tumour clone frequency (TCF) by high-throughput sequencing of the T-cell receptor beta locus. RESULTS: We included 119 consecutive biopsies from 100 patients, 45 with MF and 55 with SS. N1, N2 and N3 stages were diagnosed in 34 (29%), 26 (22%) and 59 (49%) cases, respectively. The TCF, Ki67 index, and percentage of cells positive for thymocyte selection-associated high mobility group box protein (TOX), programmed cell death protein 1 (PD1), killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) and cluster of differentiation (CD)30 were all positively correlated with the N stage. Median overall survival (OS) for N1/N2 vs. N3 patients was 42 months (range 26-not reached) vs. 14 months (range 5-30), respectively (P < 0·001). In univariate analyses, an age > 75 years, LN short-axis diameter > 15 mm, N3 stage, presence of large-cell transformation, TOX > 60%, PD1 > 25%, Ki67 > 30%, KIR3DL2 > 15%, CD30 > 10% and TCF > 25% were identified as adverse prognostic factors. In multivariate analyses, only an age > 75 years and Ki67 index > 30% were associated with reduced OS. We developed a new prognostic index associating the N stage and the Ki67 index, which better discriminates N3 patients with poor prognosis. CONCLUSIONS: CNB allows an objective assessment of the LN involvement in MF/SS, relevant for staging and prognosis.

Chronic unpredictable stress shifts rat behavior from exploration to exploitation.

Chronic stress evokes wide-ranging behavioral alterations, including risk avoidance, increased motoric output, and reduced consummatory behaviors. These are often interpreted as dysfunctions, but they may subserve adaptations for coping with existential threats. We tested this in a cohort of rats previously exposed to mild unpredictable stress for 5 weeks. Previously stressed rats exhibited the typically increased avoidance of open field and altered responses to predator odor, suggesting enhanced sensitivity to threatening contexts and cues. Interestingly, these animals collected rewards at a higher rate than controls, because they locomoted faster, spent less time in off-task (exploratory) behavior, and committed fewer licks at feeders. Further, they were not impaired in flexibly shifting choice as reward probabilities changed among feeders, suggesting that behavioral adaptations are not simply of transference to behavioral control to neural systems insensitive to reward (e.g. habits). These data add to a small but growing body of evidence indicating that stress shifts responses away from exploration and toward exploitation of resources, possibly to reduce threat exposure.HighlightsRats with a history of stress collected reward at a higher rate than controls on an operant task, owing to increase locomotion speed, reduced off-task behavior, and reduced time licking at feeders.Previously stressed rats exhibited increased win-stay responses than controls, suggesting the involvement of neural circuits related to goal-directed responding.Previously stressed rats performed equally to controls on a task requiring a shift of preferences based on reward probability, suggesting that they are not simply relying more on habit-based neural systems.

Concentrations of Cefuroxime in Brain Tissue of Neurointensive Care Patients.

Effective concentrations of antibiotics in brain tissue are essential for antimicrobial therapy of brain infections. However, data concerning cerebral penetration properties of antibiotics for treatment or prophylaxis of central nervous system infections are rare. Six patients suffering subarachnoid hemorrhage and requiring cerebral microdialysis for neurochemical monitoring were included in this study. Free interstitial concentrations of cefuroxime after intravenous application of 1,500 mg were measured by microdialysis in brain tissue, as well as in plasma at steady-state (n = 6) or after single-dose administration (n = 1). At steady state, free area under the concentration-time curve from 0 to 24 h (AUC0-24) values of 389.0 ± 210.3 mg/liter·h and 131.4 ± 72.8 mg/liter·h were achieved for plasma and brain, respectively, resulting in a brain tissue penetration ratio (AUC0-24 brain/AUC0-24 free plasma) of 0.33 ± 0.1. Plasma and brain tissue concentrations at individual time points correlated well (R = 0.59, P = 0.001). At steady-state time over MIC (t>MIC) values of >40% of dosing interval were achieved up to an MIC of 16 mg/liter for plasma and 4 mg/liter for brain tissue. Although MIC90 values could not be achieved in brain tissue for relevant bacteria, current dosing strategies of cefuroxime might be sufficient to treat pathogens with MIC values up to 4 mg/liter. The activity of cefuroxime in brain tissue might be overestimated when relying exclusively on plasma levels. Although currently insufficient data after single dose administration exist, lower brain-plasma ratios observed after the first dose might warrant a loading dose for treatment and perioperative prophylaxis.

Establishment of a Mucin Secreting Cell Line Cx-03 from an Uterine Carcino Sarcoma.

PURPOSE: The identification of novel cell lines which combine the most important properties of mucosal membranes in terms of drug absorption, transmembrane transport and mucus secretion can help to establish improved and meaningful test systems for pharmacological and infectiological studies. METHODS: We have established a novel mucus secreting tumor cell line (Cx-03) derived from a female patient who underwent radical hysterectomy after diagnosis of a large malignant carcino sarcoma (Muellerian mixed tumor). Via xenotransplantation in SCID beige mice, recultivation and subcloning a stable cell line was established from primary tumor cells. RESULTS: Human origin and novelty of the cell line was determined by karyotype analysis and STR fingerprint. During growth cells produce considerable amounts of a PAS positive viscoelastic mucus. Immunostaining revealed expression of mucins and the mucin modifier CLCA1. We demonstrate in initial electrophysiological experiments that confluent, polarized monolayers of Cx-03 are formed (on PCF-filter supports) that exhibit stable electrical resistance (> 600 Ω cm2). Confluent Cx-03 monolayers express barrier-forming tight junction proteins claudin-1 and -4 which co-localize with zonula occludens protein-1 (ZO-1) at cell-cell contacts. CONCLUSIONS: Mucus secretion is a rare property among mammalian cell lines. In combination with its ability to form polarized monolayers Cx-03 might contribute as a novel cell based model for drug absorption, transport and barrier studies.

Endovascular stroke therapy in Austria: a nationwide 1-year experience.

BACKGROUND AND PURPOSE: Based on a tight network of stroke units (SUs) and interventional centres, endovascular treatment of acute major intracranial vessel occlusion has been widely implemented in Austria. Documentation of all patients in the nationwide SU registry has thereby become mandatory. METHODS: Demographic, clinical and interventional characteristics of patients who underwent endovascular treatment for acute ischaemic stroke in 11 Austrian interventional centres between 1 October 2013 and 30 September 2014 were analysed. RESULTS: In total, 301 patients (50.5% women; median age 70.5 years; median National Institutes of Health Stroke Scale score 17) were identified.193 patients (64.1%) additionally received intravenous thrombolysis. The most frequent vessel occlusion sites were the M1 segment of the middle cerebral artery (n = 161, 53.5%), the intracranial internal carotid artery (n = 60, 19.9%) and the basilar artery (n = 40, 13.3%). Stent retrievers were used in 235 patients (78.1%) and adequate reperfusion (modified Thrombolysis in Cerebral Infarction scores 2b and 3, median onset to reperfusion time 254 min) was achieved in 242 patients (81.4%). Symptomatic intracranial haemorrhage occurred in 7%. 43.8% of patients (n = 132) had good functional outcome (modified Rankin Scale score 0-2) and the mortality rate was 20.9% (n = 63) after 3 months. Compared to the anterior circulation, vertebrobasilar stroke patients had higher mortality. Patients with secondary hospital transportation had better outcomes after 3 months than in-house treated patients. CONCLUSION: Our results document nationwide favourable outcome and safety rates of endovascular stroke treatment comparable to recent randomized trials. The ability to provide such data and the need to further optimize such an approach also underscore the contribution of respective registries.

Cerebral and Peripheral Metabolism to Predict Successful Reperfusion After Cardiac Arrest in Rats: A Microdialysis Study.

BACKGROUND: In clinical practice, monitoring of the efficacy of resuscitation can be challenging. The prediction of cerebral and overall outcome in particular is an unmet medical need. Microdialysis is a minimally invasive technique for the continuous determination of metabolic parameters in vivo. Using this technique, we set out to establish a model allowing for concomitant determination of cerebral and peripheral metabolism in a cardiac arrest setting in rodents. METHODS: Microdialysis settings were optimized in vitro and then used in male Sprague-Dawley rats. Probes were implanted into the CA1 region of the right hippocampus and the right femoral vein. With a time interval of 8 min, glucose, lactate, pyruvate, and glutamate levels were determined during baseline conditions, untreated ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation (CPR), reperfusion, and death. RESULTS: In 16 rodents, restoration of spontaneous circulation was achieved in seven animals. Characteristic metabolic changes were evident during cardiac arrest and reperfusion with both probes. Ischemic patterns in peripheral compartments were delayed and more variable compared to the changes in cerebral metabolism highlighting the importance of cerebral metabolic monitoring. Microdialysis allowed distinguishing between survivors and non-survivors 8 min after termination of CPR. Cerebral glutamate showed a trend toward higher levels in non-survivors during CPR. CONCLUSIONS: We established a new rodent model for research in hypoxic ischemic encephalopathy. This setting allows to investigate the impact of resuscitation methods on cerebral and peripheral metabolism simultaneously. The present model may be used to evaluate different resuscitation strategies in order to optimize brain survival in future studies.

Descriptive epidemiology and risk factors of primary central nervous system tumors: Current knowledge.

Although comparisons are difficult due to differences in methodologies, the annual incidence rates of central nervous system (CNS) tumors range from 8.5 to 21.4/100,000 population according to cancer registries, with a predominance of neuroepithelial tumors in men and meningiomas in women. An increase in the incidence of CNS tumors has been observed during the past decades in several countries. It has been suggested that this trend could be due to aging of the population, and improvements in diagnostic imaging and healthcare access, but these factors do not explain differences in incidence by gender and histological subtypes. Several etiological hypotheses related to intrinsic (sociodemographic, anthropometric, hormonal, immunological, genetic) and exogenous (ionizing radiation, electromagnetic fields, diet, infections, pesticides, drugs) risk factors have led to analytical epidemiological studies to establish relationships with CNS tumors. The only established environmental risk factor for CNS tumors is ionizing radiation exposure. However, for other risk factors, studies have been inconsistent and inconclusive due to systematic differences in study design and difficulties in accurately measuring exposures. Thus, the etiology of CNS tumors is complex and may involve several genetic and/or environmental factors that may act differently according to histological subtype.

Moxifloxacin is not anti-inflammatory in experimental pneumococcal pneumonia.

OBJECTIVES: Anti-inflammatory functions of antibiotics may counteract deleterious hyperinflammation in pneumonia. Moxifloxacin reportedly exhibits immunomodulatory properties, but experimental evidence in pneumonia is lacking. Therefore, we investigated moxifloxacin in comparison with ampicillin regarding pneumonia-associated pulmonary and systemic inflammation and lung injury. METHODS: Ex vivo infected human lung tissue and mice with pneumococcal pneumonia were examined regarding local inflammatory response and bacterial growth. In vivo, clinical course of the disease, leucocyte dynamics, pulmonary vascular permeability, lung pathology and systemic inflammation were investigated. In addition, transcellular electrical resistance of thrombin-stimulated endothelial cell monolayers was quantified. RESULTS: Moxifloxacin reduced cytokine production in TNF-α-stimulated, but not in pneumococci-infected, human lung tissue. In vivo, moxifloxacin treatment resulted in reduced bacterial load as compared with ampicillin, whereas inflammatory parameters and lung pathology were not different. Moxifloxacin-treated mice developed less pulmonary vascular permeability during pneumonia, but neither combination therapy with moxifloxacin and ampicillin in vivo nor examination of endothelial monolayer integrity in vitro supported direct barrier-stabilizing effects of moxifloxacin. CONCLUSIONS: The current experimental data do not support the hypothesis that moxifloxacin exhibits potent anti-inflammatory properties in pneumococcal pneumonia.

Prospective assessment and validation of rhythmic and periodic pattern detection in NeuroTrend: A new approach for screening continuous EEG in the intensive care unit.

BACKGROUND: NeuroTrend is a computational method that analyzes long-term scalp EEGs in the ICU according to ACNS standardized critical care EEG terminology (CCET) including electrographic seizures. At present, it attempts to become a screening aid for continuous EEG (cEEG) recordings in the ICU to facilitate the review process and optimize resources. METHODS: A prospective multicenter study was performed in two neurological ICUs including 68 patients who were subjected to video-cEEG. Two reviewers independently annotated the first minute of each hour in the cEEG according to CCET. These segments were also screened for faster patterns with frequencies higher than 4 Hz. The matching annotations (2911 segments) were then used as gold standard condition to test sensitivity and specificity of the rhythmic and periodic pattern detection of NeuroTrend. RESULTS: Interrater agreement showed substantial agreement for localization (main term 1) and pattern type (main term 2) of the CCET. The overall detection sensitivity of NeuroTrend was 94% with high detection rates for periodic discharges (PD = 80%) and rhythmic delta activity (RDA = 82%). Overall specificity was moderate (67%) mainly because of false positive detections of RDA in cases of general slowing. In contrast, a detection specificity of 88% for PDs was reached. Localization revealed only a slight agreement between reviewers and NeuroTrend. CONCLUSIONS: NeuroTrend might be a suitable screening tool for cEEG in the ICU and has the potential to raise efficiency of long-term EEG monitoring in the ICU. At this stage, pattern localization and differentiation between RDA and general slowing need improvement. This article is part of a Special Issue entitled "Status Epilepticus".

Prevalence of biofilms on surgical suture segments in wounds of dogs, cats, and horses.

The formation of biofilms on surgical implants is thought to play a major role in chronic infection and wound-healing disorders and has been rarely described in veterinary medicine. Due to poor and unreliable results from bacterial culturing, histology may be an economic tool for the detection of biofilms. In this study, the prevalence of biofilms on surgical suture materials and swabs with chronic wound-healing complications in dogs, cats, and horses was assessed by histologic examination using hematoxylin and eosin, Gram, and Giemsa stains, as well as periodic acid-Schiff reaction. Of the 91 tissue samples with intralesional suture material or swab residues associated with inflammation, only 2 contained bacterial colonies arranged in an extracellular polymeric matrix consistent with a biofilm. The results of this study suggest that biofilms on suture material may occur in veterinary medicine.

Assessment of Parental Understanding of Positive Newborn Screening Results and Carrier Status for Cystic Fibrosis with the use of a Short Educational Video.

Many children are identified as unaffected carriers for cystic fibrosis (CF) through newborn screening (NBS) programs. The aim of this study was to improve parental understanding of positive NBS results using an educational video in addition to genetic counseling. One hundred parents of infants identified as CF carriers through NBS were randomly assigned by household to either a genetic counseling only group or a genetic counseling and video group. All participants completed a knowledge-based questionnaire before, immediately after, and six weeks following genetic counseling. This included questions about resources accessed before and after the appointment. Seventy-two percent of participants accessed resources on their own prior to genetic counseling; these participants scored significantly higher on the pre-counseling questionnaire (p = 0.03). Post-counseling knowledge scores for both groups significantly improved after genetic counseling (p < 0.001). Post-counseling scores were significantly higher in the video group compared to the non-video group (p = 0.02). Knowledge was retained six weeks following genetic counseling. This study demonstrates the effectiveness of an educational video and reinforces the importance of genetic counseling following positive NBS results for CF.

Toltrazuril does not show an effect against pigeon protozoal encephalitis.

The protozoan parasite Sarcocystis calchasi causes a severe neurologic disease in domestic pigeons (Columba livia f. dom.) named pigeon protozoal encephalitis. Recently, the parasite has also been reported in psittacines causing a virtually identical disease with fatal outcome. So far, an etiological treatment of S. calchasi infections in pigeons or psittacines is unknown. The present study evaluates the effectiveness of the anticoccidian drug toltrazuril against S. calchasi and the influence of the timepoint of treatment. Therefore, nine domestic pigeons were inoculated with 400 S. calchasi sporocysts and treated with toltrazuril (25 mg/kg) in groups of three pigeons each at dpi 10/11 and dpi 40/41 and on two consecutive days at the onset of neurologic signs. After euthanasia at dpi 73, tissue samples including brain and skeletal muscles were examined by histology and S. calchasi-specific real-time PCR. All pigeons independent of the group developed neurologic signs from dpi 49 onwards. Histology identified sarcocysts in the skeletal muscles and a granulomatous encephalitis in the brains. The relative amount of S. calchasi DNA was on a comparable level in all pigeons. Consequently, toltrazuril was demonstrated to be not effective against S. calchasi with the applied treatment regime. Longer treatment periods or agents other the toltrazuril may be considered for further investigations. So far, preventive measures like roofing of aviaries for prevention of infection and regular disinfection remain the most important factor in the control of S. calchasi infections.

Electroencephalographic evaluation of the effectiveness of blunt trauma to induce loss of consciousness for on-farm killing of chickens and turkeys.

Euthanasia of small numbers of birds in case of injury or other illness directly on the farm may be necessary for welfare reasons. This should be done without transportation of the moribund animals in order to minimize pain and distress. Blood loss has to be avoided to minimize the risk of contaminating the environment. Cervical dislocation in combination with a blunt trauma may be an appropriate way to achieve this aim but the bird's age and body weight may influence the practicability of this method in the field. In this study, we evaluated broilers, broiler breeders, and turkeys of different age groups and weights up to nearly 16 kg for the efficacy of blunt trauma to induce unconsciousness, allowing subsequent killing of the bird without pain. The effect of blunt trauma on the brain was determined by electroencephalography (EEG). Auditory evoked potentials (AEPs) were recorded for each animal. Convulsions or tonic seizures were observed in all investigated animals after blunt trauma, including strong wing movements, torticollis, and stretching of legs. The EEG results demonstrate that the blunt trauma induced by a single, sufficiently strong hit placed in the frontoparietal region of the head led to a reduction or loss of the AEP in all groups of birds. These results clearly indicate a loss of sensibility and induction of unconsciousness, which would allow painless killing of the birds immediately after the induction of the blunt trauma.

[Chronic myofacial pain. Reduced pain through psychoeducation and physiotherapy]. / Chronische Kiefer- und Gesichtsschmerzen. Verringerte Schmerzen durch Psychoedukation und Physiotherapie.

BACKGROUND: Psychological factors are associated with the emergence and persistence of pain perception. The aim of this pilot study was to assess the psychological factors relating to pain perception in patients with chronic myofacial pain and to investigate the influence of patient information, education and physiotherapy on pain perception and functional jaw opening examined over a 6-month period. PATIENTS AND METHODS: In accordance with the research diagnostic criteria for temporomandibular disorders (RDC/TMD), 40 patients (31 females and 9 males, mean age 38.6 years) with chronic myofacial pain were assessed at 3 time points: on admission (T1), after 3 months (T2) and 6 months (T3). The study included a structured interview and five psychological questionnaires. At all time points patients were informed about the development of pain and the relationship between chronification of pain and psychological risk factors. RESULTS: After 6 months significant improvements in jaw function and quality of life, as well as a decrease in psychological parameters, such as fear and depression were found. Improvement was related to the severity of pain chronification. CONCLUSION: The results show the necessity of early identification of patients with severe pain chronification and the need for psychological pain therapy.

Weigners fixative-an alternative to formalin fixation for histology with improved preservation of nucleic acids.

Formalin fixation and paraffin embedding (FFPE) is the standard method for tissue storage in histopathology. However, FFPE has disadvantages in terms of user health, environment, and nucleic acid integrity. Weigners fixative has been suggested as an alternative for embalming cadavers in human and veterinary anatomy. The present study tested the applicability of Weigners for histology and immunohistochemistry and the preservation of nucleic acids. To this end, a set of organs was fixed for 2 days and up to 6 months in Weigners (WFPE) or formalin. WFPE tissues from the skin, brain, lymphatic tissues, liver, and muscle had good morphologic preservation, comparable to formalin fixation. The quality of kidney and lung samples was inferior to FFPE material due to less accentuated nuclear staining and retention of proteinaceous interstitial fluids. Azan, Turnbull blue, toluidin, and immunohistochemical stainings for CD79a, cytokeratin, vimentin, and von Willebrand factor led to comparable results with both fixates. Of note, immunohistochemical detection of CD3 was possible after 6 months in WFPE but not in FFPE tissues. mRNA, miRNA, and DNA from WFPE tissues had superior quality and allowed for amplification of miRNA, 400-bp-long mRNA, and 1000-bp-long DNA fragments after 6 months of fixation in WFPE. In summary, Weigners fixative is a nonhazardous alternative to formalin, which provides a good morphologic preservation of most organs, a similar sensitivity for protein detection, and a superior preservation of nucleic acids. Weigners may therefore be a promising alternative to cryopreservation and may be embraced by people affected by formalin allergies.

[Measles surveillance in Germany. From sentinel to mandatory surveillance]. / Masern-Surveillance in Deutschland. Vom Sentinel zur Meldepflicht.

From September 1999 to March 2011, sentinel surveillance of measles was conducted by a self-selected sample of private physicians in Germany. From 2001, when mandatory surveillance for measles was established, two surveillance systems worked in parallel. The aim of this article is to summarize the strengths and limitations of sentinel versus mandatory surveillance. Active monthly reporting included case-based questionnaires on patients with (suspected) measles or zeroreporting. For confirmation of measles, the diagnostic patient specimens were sent to regional laboratories for serological tests or to the National Reference Laboratory (NRC). In the NRC in addition to serological tests measles-virus (MV) detection by PCR in urine, throat swabs, and oral fluid (since 2003) as well as MVgenotyping was offered. From January 2000 to December 2010, 934 out of 1,488 participating sentinel-practices did not see any measles case, while 554 reported 3,573 suspected cases. Measles was confirmed by laboratory testing in 801 cases, excluded in 473 cases, and the diagnosis remained uncertain in 215 cases. Of 3,100 analyzed cases, 2,712 (87 %) were unvaccinated, 217 (7 %) and 32 (1 %) were vaccinated with one or two doses, respectively, and for 139 (4 %) cases the vaccination status was unknown. The main reason for not being vaccinated against measles was refusal (n = 1,383). The confirmation rate was lower in the vaccinated than in the unvaccinated patients (19 % vs. 63 %). Since 2006, sentinel-cases have differed from notified cases by region and age. The proportion of sentinel cases from all NRC-investigated cases decreased from more than 50 % (2002) to less than 5 % (since 2007). Sentinel surveillance allowed for the detection of trends, delivered additional information for measles prevention, and played a major role in measles diagnostics. Since mandatory surveillance was established and sentinel surveillance no longer reflected the epidemiologic situation, the latter was abandoned in April 2011.

[Disturbances of water metabolism in two dogs and one cat with central nervous system disorders]. / Störungen des Wasserhaushaltes bei zwei Hunden und einer Katze mit ZNS-Erkrankungen.

Hypernatremia due to different pathophysiological mechanisms results in a rise in plasma osmolality. Dependent on its severity and on the speed of its development hyperosmolality can be life-threatening. This article describes 2 dogs and 1 cat with central nervous system disorders (adenoma of the pituitary gland, cerebral trauma). All patients developed normovolemic hypernatremia due to pituitary gland and hypothalamus dysfunction, respectively. Plasma sodium concentrations ranged from 163 to 185 mmol/l. Neurological examinations revealed lethargy, disturbances of consciousness, and ataxia, respectively. The dogs had to be euthanased due to the grave prognosis, the cat with cerebral trauma survived.

Le développement d'une hypenatrémie peut avoir plusieurs mécanismes patho-physiologiques. Dans ces cas, il se produit toujours une élévation de l'osmolarité du plasma. Selon l'importance de l'hypernatrémie et la vitesse de l'apparition, une hyperosmolarité peut mettre la vie en danger. Dans le présent article, on décrit des affections du système nerveux central chez deux chiens (adénome de l'hypophyse) et un chat (trauma crânien) ayant développé une hypernatrémie normovolémique suite à un dysfonctionnement de l'hypophyse ou de l'hypothalamus. Les concentrations plasmatiques de sodium étaient comprises entre 163 et 185 mmol/l. Les animaux présentaient de la léthargie, des troubles de la conscience et de l'ataxie. Vu le mauvais pronostic, les chiens ont dû être euthanasiés, le chat victime d'un traumatisme crânien a survécu.

Isolated effects of footwear structure and cushioning on running mechanics in habitual mid/forefoot runners.

The true differences between barefoot and shod running are difficult to directly compare because of the concomitant change to a mid/forefoot footfall pattern that typically occurs during barefoot running. The purpose of this study was to compare isolated effects of footwear structure and cushioning on running mechanics in habitual mid/forefoot runners running shod (SHOD), barefoot (BF), and barefoot on a foam surface (BF+FOAM). Ten habitually shod mid/forefoot runners were recruited (male = 8, female = 2). Repeated measures ANOVA (α = 0.05) revealed differences between conditions for only vertical peak active force, contact time, negative and total ankle joint work, and peak dorsiflexion angle. Post hoc tests revealed that BF+FOAM resulted in smaller vertical active peak magnitude and instantaneous vertical loading rate than SHOD. SHOD resulted in lower total ankle joint work than BF and BF+FOAM. BF+FOAM resulted in lower negative ankle joint work than either BF or SHOD. Contact time was shorter with BF than BF+FOAM or SHOD. Peak dorsiflexion angle was smaller in SHOD than BF. No other differences in sagittal joint kinematics, kinetics, or ground reaction forces were observed. These overall similarities in running mechanics between SHOD and BF+FOAM question the effects of footwear structure on habituated mid/forefoot running described previously.

Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma.

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate.