Is bone marrow edema syndrome a precursor of hip or knee osteonecrosis? Results of 49 patients and review of the literature

PURPOSEDiagnosis of bone marrow edema syndrome (BMES) can be challenging. There is sometimes uncertainty about the correct diagnosis of BMES on morphologic magnetic resonance imaging (MRI), since subchondral findings like lines and spots can be misinterpreted as "beginning" or "possible" avascular osteonecrosis (AVN). The aim of our study was to systematically assess the temporal course of BMES from first diagnosis on MRI until the end of clinical symptoms and the full disappearance of bone marrow edema (BME) to determine whether subchondral lines and spots detected in these patients can develop into osteonecrosis.METHODSIn a combined retrospective and prospective study, we retrieved serial MRI scans of hips and knees with BME from the hospital database. According to clinical and imaging data, all patients with degenerative, infectious/inflammatory, rheumatic, neoplastic conditions and those showing typical osteonecrosis were excluded. We collected all available MRI examinations from first detection of BME until its disappearance. In case edema had not fully resolved in the last available MRI scan, we performed an MRI with an additional dynamic contrast-enhanced (DCE-MRI) sequence. For each MRI scan, we recorded the severity of edema, the presence of subchondral hypointense lines and the presence of subchondral focal hypointense zones on T1-weighted images by two independent readers. The DCE-MRI scans were used to calculate parameter maps to assess the perfusion characteristics.RESULTSThe study comprised 49 patients aged 22–71 years. In total, 171 morphologic and 5 DCE-MRI scans were evaluated. In 44 patients (89.8%), the BMES completely healed without remnants. In 18 of 49 patients (36.7%), a subchondral line was present in the first MRI exam. Nine patients (18.4%) developed a subchondral line within 1–5 months after the first MRI. In total, 27 out of 49 patients (55.1%) had subchondral lines (12 knees, 15 hips) during the timeframe of the study. All subchondral lines disappeared in the timeframe of the study. Subchondral focal hypointense zones were present in 14 out of 49 patients (28.6%): in 9 cases, subchondral focal hypointense zones disappeared after a median of 5.5 months (range, 1–85 months), while in 5 cases, subchondral focal lesions persisted until the end of the study (up to more than 85 months) without edema in the surrounding bone. All persisting subchondral focal lesions were hyperperfused. These 5 patients had associated meniscal lesions. CONCLUSIONOur study shows that subchondral lines and spots found in patients with BMES do not develop into AVN. Subchondral lines, which resemble subchondral insufficiency fractures, are associated with BMES. Subchondral focal T1-hypointense zones do not represent AVN; most probably these areas represent reparative processes within the subchondral bone, where tensile and shear force overload is present due to altered biomechanics

Sulfated Polysaccharides from Macroalgae Are Potent Dual Inhibitors of Human ATP-Hydrolyzing Ectonucleotidases NPP1 and CD39

Extracellular ATP mediates proinflammatory and antiproliferative effects via activation of P2 nucleotide receptors. In contrast, its metabolite, the nucleoside adenosine, is strongly immunosuppressive and enhances tumor proliferation and metastasis. The conversion of ATP to adenosine is catalyzed by ectonucleotidases, which are expressed on immune cells and typically upregulated on tumor cells. In the present study, we identified sulfopolysaccharides from brown and red sea algae to act as potent dual inhibitors of the main ATP-hydrolyzing ectoenzymes, ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) and ecto-nucleoside triphosphate diphosphohydrolase-1 (NTPDase1, CD39), showing nano- to picomolar potency and displaying a non-competitive mechanism of inhibition. We showed that one of the sulfopolysaccharides tested as a representative example reduced adenosine formation at the surface of the human glioblastoma cell line U87 in a concentration-dependent manner. These natural products represent the most potent inhibitors of extracellular ATP hydrolysis known to date and have potential as novel therapeutics for the immunotherapy of cancer

Collaborative nowcasting of COVID-19 hospitalization incidences in Germany

Real-time surveillance is a crucial element in the response to infectious disease outbreaks. However, the interpretation of incidence data is often hampered by delays occurring at various stages of data gathering and reporting. As a result, recent values are biased downward, which obscures current trends. Statistical nowcasting techniques can be employed to correct these biases, allowing for accurate characterization of recent developments and thus enhancing situational awareness. In this paper, we present a preregistered real-time assessment of eight nowcasting approaches, applied by independent research teams to German 7-day hospitalization incidences during the COVID-19 pandemic. This indicator played an important role in the management of the outbreak in Germany and was linked to levels of non-pharmaceutical interventions via certain thresholds. Due to its definition, in which hospitalization counts are aggregated by the date of case report rather than admission, German hospitalization incidences are particularly affected by delays and can take several weeks or months to fully stabilize. For this study, all methods were applied from 22 November 2021 to 29 April 2022, with probabilistic nowcasts produced each day for the current and 28 preceding days. Nowcasts at the national, state, and age-group levels were collected in the form of quantiles in a public repository and displayed in a dashboard. Moreover, a mean and a median ensemble nowcast were generated. We find that overall, the compared methods were able to remove a large part of the biases introduced by delays. Most participating teams underestimated the importance of very long delays, though, resulting in nowcasts with a slight downward bias. The accompanying prediction intervals were also too narrow for almost all methods. Averaged over all nowcast horizons, the best performance was achieved by a model using case incidences as a covariate and taking into account longer delays than the other approaches. For the most recent days, which are often considered the most relevant in practice, a mean ensemble of the submitted nowcasts performed best. We conclude by providing some lessons learned on the definition of nowcasting targets and practical challenges

Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease

Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higher CSF levels of tau, but we lack knowledge of systems-wide changes of CSF protein levels that accompany AD. Here, we present a highly reproducible mass spectrometry (MS)-based proteomics workflow for the in-depth analysis of CSF from minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins by AD status (> 1,000 proteins, CV < 20%). Proteins with previous links to neurodegeneration such as tau, SOD1, and PARK7 differed most strongly by AD status, providing strong positive controls for our approach. CSF proteome changes in Alzheimer's disease prove to be widespread and often correlated with tau concentrations. Our unbiased screen also reveals a consistent glycolytic signature across our cohorts and a recent study. Machine learning suggests clinical utility of this proteomic signature

Reference Values of Flexion and Supination in the Elbow Joint of a Cohort without Shoulder Pathologies

Background After surgery of the long head of the biceps tendon, the examination of the biceps brachii muscle function and strength is common clinical practice. The muscle strength is usually compared with the uninjured contralateral side or with a matched pair group assuming that the uninjured side can be used as an appropriate reference. Hypothesis/Purpose The purpose of this study was to define reference values of the supination and flexion strength in the elbow joint and to investigate the influence of the arm positions and various anthropometric factors. Methods 105 participants without any shoulder pathologies were enrolled. A full medical history was obtained and a physical examination was performed. The bilateral isometric testing included the supination torque in various forearm positions and elbow flexion strength with a custom engineered dynamometer. Multiple linear regression analysis was used to investigate the correlation of the strength and anthropometric factors. Results Only age and gender were significant supination and flexion strength predictors of the elbow. Hence, it was possible to calculate a gender-specific regression line for each forearm position to predict the age-dependent supination torque. The supination strength was greatest with the arm in 90° elbow flexion and the upper arm in full pronation

Prolonged Cannabidiol Treatment Lacks on Detrimental Effects on Memory, Motor Performance and Anxiety in C57BL/6J Mice

The Cannabis plant contains more than 100 currently known phytocannabinoids. Regarding the rising consumption of the non-psychotropic phytocannabinoid cannabidiol (CBD) in people’s everyday life (e.g., beauty products, food and beverages), the importance of studies on the influence of CBD on healthy humans and rodents is evident. Therefore, the behavioral profile of CBD was investigated with a battery of behavioral tests, including motor, anxiety, and memory tests after prolonged CBD treatment. Adult C57Bl/6J wildtype (WT) mice were daily intraperitoneally injected with 20 mg/kg CBD for 6 weeks starting at two different points of ages (3 months and 5 months) to compare the influence of prolonged CBD treatment with a washout period (former group) to the effects of long term CBD treatment (current group). Our results show that CBD treatment does not influence motor performance on an accelerating Rotarod test, while it also results in a lower locomotor activity in the open field (OF). No influence of CBD on spatial learning and long term memory in the Morris Water Maze (MWM) was observed. Memory in the Novel Object Recognition test (NORT) was unaffected by CBD treatment. Two different anxiety tests revealed that CBD does not affect anxiety behavior in the Dark-Light Box (DLB) and OF test. Although, anxiety is altered by current CBD treatment in the Elevated Plus Maze (EPM). Moreover, CBD-treated C57Bl/6J mice showed an unaltered acoustic startle response (ASR) compared to vehicle-treated mice. However, current CBD treatment impairs prepulse inhibition (PPI), a test to analyze sensorimotor gating. Furthermore, prolonged CBD treatment did not affect the hippocampal neuron number. Our results demonstrate that prolonged CBD treatment has no negative effect on the behavior of adult C57Bl/6J mice

Circulating Adaptive Immune Cells Expressing the Gut Homing Marker α4β7 Integrin Are Decreased in COVID-19

Background Infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide range of symptoms including gastrointestinal manifestations, and intestinal epithelial cells are a target of the virus. However, it is unknown how the intestinal immune system contributes to systemic immune responses in coronavirus disease 2019 (COVID-19). Methods We characterized peripheral blood lymphocytes from patients with active COVID-19 and convalescent patients as well as healthy controls by flow cytometry. Results The frequency and absolute number of circulating memory T and B cells expressing the gut homing integrin α4β7 integrin was reduced during COVID-19, whether gastrointestinal symptoms were present or not. While total IgA-expressing B cells were increased, gut-imprinted B cells with IgA expression were stable. Conclusion COVID-19 is associated with a decrease in circulating adaptive immune cells expressing the key gut homing marker α4β7 suggesting that these cells are preferentially recruited to extra-intestinal tissues independently of α4β7 or that the systemic immune response against SARS-CoV-2 is at least numerically dominated by extraintestinal, particularly pulmonary, immune cell priming

Insights into early animal evolution from the genome of the xenacoelomorph worm Xenoturbella bocki

The evolutionary origins of Bilateria remain enigmatic. One of the more enduring proposals highlights similarities between a cnidarian-like planula larva and simple acoel-like flatworms. This idea is based in part on the view of the Xenacoelomorpha as an outgroup to all other bilaterians which are themselves designated the Nephrozoa (protostomes and deuterostomes). Genome data can provide important comparative data and help understand the evolution and biology of enigmatic species better. Here, we assemble and analyze the genome of the simple, marine xenacoelomorph Xenoturbella bocki, a key species for our understanding of early bilaterian evolution. Our highly contiguous genome assembly of X. bocki has a size of ~111 Mbp in 18 chromosome-like scaffolds, with repeat content and intron, exon, and intergenic space comparable to other bilaterian invertebrates. We find X. bocki to have a similar number of genes to other bilaterians and to have retained ancestral metazoan synteny. Key bilaterian signaling pathways are also largely complete and most bilaterian miRNAs are present. Overall, we conclude that X. bocki has a complex genome typical of bilaterians, which does not reflect the apparent simplicity of its body plan that has been so important to proposals that the Xenacoelomorpha are the simple sister group of the rest of the Bilateria

Roadmap on chalcogenide photonics

Alloys of sulfur, selenium and tellurium, often referred to as chalcogenide semiconductors, offer a highly versatile, compositionally-controllable material platform for a variety of passive and active photonic applications. They are optically nonlinear, photoconductive materials with wide transmission windows that present various high- and low-index dielectric, low-epsilon and plasmonic properties across ultra-violet, visible and infrared frequencies, in addition to an, non-volatile, electrically/optically induced switching capability between phase states with markedly different electromagnetic properties. This roadmap collection presents an in-depth account of the critical role that chalcogenide semiconductors play within various traditional and emerging photonic technology platforms. The potential of this field going forward is demonstrated by presenting context and outlook on selected socio-economically important research streams utilizing chalcogenide semiconductors. To this end, this roadmap encompasses selected topics that range from systematic design of material properties and switching kinetics to device-level nanostructuring and integration within various photonic system architectures

Luminous Type II Short-Plateau Supernovae 2006Y, 2006ai, and 2016egz: A Transitional Class from Stripped Massive Red Supergiants

The diversity of Type II supernovae (SNe II) is thought to be driven mainly by differences in their progenitor's hydrogen-rich (H-rich) envelope mass, with SNe IIP having long plateaus ($\sim100$ days) and the most massive H-rich envelopes. However, it is an ongoing mystery why SNe II with short plateaus (tens of days) are rarely seen. Here we present optical/near-infrared photometric and spectroscopic observations of luminous Type II short-plateau SNe 2006Y, 2006ai, and 2016egz. Their plateaus of about $50$--$70$ days and luminous optical peaks ($\lesssim-18.4$ mag) indicate significant pre-explosion mass loss resulting in partially-stripped H-rich envelopes and early circumstellar material (CSM) interaction. We compute a large grid of MESA+STELLA single-star progenitor and light-curve models with various progenitor zero-age main-sequence (ZAMS) masses, mass-loss efficiencies, explosion energies, $^{56}$Ni masses, and CSM densities. Our model grid shows a continuous population of SNe IIP--IIL--IIb-like light-curve morphology in descending order of H-rich envelope mass. With large $^{56}$Ni masses ($\gtrsim0.05\,M_\odot$), short-plateau SNe II lie in a confined parameter space as a transitional class between SNe IIL and IIb. For SNe 2006Y, 2006ai, and 2016egz, our findings suggest high-mass red supergiant (RSG) progenitors ($M_{\rm ZAMS} \simeq 18$--$22\,M_{\odot}$) with small H-rich envelope masses ($M_{\rm H_{\rm env}} \simeq 1.7\,M_{\odot}$) that experience enhanced mass loss ($\dot{M} \simeq 10^{-2}\,M_{\odot}\,{\rm yr}^{-1}$) for the last few decades before the explosion. If high-mass RSGs result in rare short-plateau SNe II, then these events might ease some of the apparent under-representation of higher-luminosity RSGs in observed SN II progenitor samples.Comment: 26 pages, 16 figures, submitted to Ap