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Before antibiotic therapy is administered, the patient must be informed about the possibility of a Jarisch-Herxheimer reaction. In cases of a syphilis infection, a collegial cooperation with the venereologists is always recommended so that an effective and comprehensive diagnosis and therapy can be carried out.Pathologic fractures secondary to metastatic disease are an increasingly prevalent problem. Such patients require multidisciplinary collaboration to optimize clinical outcomes. An established algorithm for clinical, laboratory, and radiographic work-up will ensure that each patient achieves the best outcome while avoiding catastrophic complications. Metastatic disease to the region of the knee is less commonly encountered than in other regions of the body, but it presents unique difficulties that merit discussion. Part one of this two-part article series will discuss the appropriate work-up of patients with suspected or impending pathologic fracture of the distal femur, highlight biopsy principles, address perioperative nonsurgical treatments that will optimize patient outcomes, and discuss available surgical treatment modalities.Resin composites are one of the most commonly used materials in restorative dentistry. To improve their handling and facilitate restoration sculpting, clinicians began to lubricate modeling instruments with various substances like alcohol, unfilled resins, or even bonding agents. Although the technique is commonly present in daily clinical practice, it has not been precisely described in the literature and both application methods and lubricating materials vary across the available studies. This study aims to summarize the currently available knowledge about influence of instrument lubrication on properties of dental composites. Literature selection was conducted within MEDLINE, SCOPUS, and EBSCO databases. Instrument lubrication seems not to be indifferent for composite mechanical and optical properties. Moreover, various lubricants can differently affect the composite material, so the choice of lubricating agent should be deliberate and cautious. Available in vitro studies suggest possible incorporation of lubricant into the composite structure. Unfilled resins based on bisphenol A-glycidyl methacrylate (Bis-GMA) seem to be the best choice for the lubricant, as bonding agents containing hydrophilic molecules and alcohols carry a bigger risk of altering the composite properties. Further research is necessary to evaluate lubricants' influence in clinical practice conditions.This study examined the validity and compared the precision and accuracy of a distance-time linear model (DTLM), a power law and a nomogram to predict the distance running performances of female runners. Official rankings of French women ("senior" category between 23 and 39 years old) for the 3000-m, 5000-m, and 10,000-m track-running events from 2005 to 2019 were examined. Performances of runners who competed in the three distances during the same year were noted (n=158). Mean values and standard deviation (SD) of actual performances were 11.28±1.33, 19.49±2.34 and 41.03±5.12 for the 3000-m, 5000-m, and 10,000-m respectively. Each performance was predicted from two other performances. Between the actual and predicted performances, only DTLM showed a difference (p0.895). Bias and 95% limits of agreement were acceptable because, whatever the method, they were≤-3.7±10.8% on the 3000-m, 1.4±4.3% on the 5000-m, and -2.5±7.4% on the 10,000-m. The study confirms the validity of the three methods to predict track-running performance and suggests that the most accurate and precise model was the nomogram followed by the power law, with the DTLM being the least accurate.Drug design targeting protein-protein interactions (PPIs) associated with the development of diseases has been one of the most important therapeutic strategies. Besides interrupting the PPIs with PPI inhibitors/blockers, increasing evidence shows that stabilizing the interaction between two interacting proteins may also benefit the therapy, such as the development of various types of molecular glues/stabilizers that mostly work by stabilizing the two interacting proteins to regulate the downstream biological effects. However, characterizing the stabilization effect of a stabilizer is usually hard or too complicated for traditional experiments since it involves ternary interactions [protein-protein-stabilizer (PPS) interaction]. Thus, developing reliable computational strategies will facilitate the discovery/design of molecular glues or PPI stabilizers. Here, by fully analyzing the energetic features of the binary interactions in the PPS ternary complex, we systematically investigated the performance of molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) methods on characterizing the stabilization effects of stabilizers in 14-3-3 systems. The results show that both MM/PBSA and MM/GBSA are powerful tools in distinguishing the stabilizers from the decoys (with area under the curves of 0.90-0.93 for all tested cases) and are reasonable for ranking protein-peptide interactions in the presence or absence of stabilizers as well (with the average Pearson correlation coefficient of ~0.6 at a relatively high dielectric constant for both methods). Moreover, to give a detailed picture of the stabilization effects, the stabilization mechanism is also analyzed from the structural and energetic points of view for individual systems containing strong or weak stabilizers. This study demonstrates a potential strategy to accelerate the discovery of PPI stabilizers.Sleep is an essential behavior that supports brain function and cognition throughout life, in part by acting on neuronal synapses. The synaptic signaling pathways that mediate the restorative benefits of sleep are not fully understood, particularly in the context of development. Endocannabinoids (eCBs) including 2-arachidonyl glycerol (2-AG) and anandamide (AEA), are bioactive lipids that activate cannabinoid receptor, CB1, to regulate synaptic transmission and mediate cognitive functions and many behaviors, including sleep. We used targeted mass spectrometry to measure changes in forebrain synaptic eCBs during the sleep/wake cycle in juvenile and adolescent mice of both sexes. We find that eCBs lack a daily rhythm in juvenile mice, while in adolescents AEA and related oleoyl ethanolamide are increased during the sleep phase in a circadian manner. Next, we manipulated the eCB system using selective pharmacology and measured the effects on sleep behavior in developing and adult mice of both sexes using a noninvasive piezoelectric home-cage recording apparatus. Enhancement of eCB signaling through inhibition of 2-AG or AEA degradation, increased dark-phase sleep amount and bout length in developing and adult males, but not in females. Inhibition of CB1 by injection of the antagonist AM251 reduced sleep time and caused sleep fragmentation in developing and adult males and females. Our data suggest that males are more sensitive to the sleep-promoting effects of enhanced eCBs but that tonic eCB signaling supports sleep behavior through multiple stages of development in both sexes. This work informs the further development of cannabinoid-based therapeutics for sleep disruption.The purpose of this study was to characterize today's radiation and cancer biology educators of radiation oncology residents, and the biology courses they teach. An e-mail list of 133 presumptive resident biology educators was compiled, and they were invited to participate in a 46-item survey. Survey questions were designed to collect information about the educational and academic backgrounds of the educators, how they self-identify, characteristics of the courses they teach, the value that they assign to their teaching activities, their level of satisfaction with their courses and how they see these courses being taught in the future. Findings of this survey were compared and contrasted with prior surveys of biology educators (conducted 12 and 20 years ago, respectively), and with more recent surveys of radiation oncology residents and radiation oncology residency program directors conducted in 2018 and 2019. A total of 67 survey responses were received. Biology educators range in age, academic rank and yearurses have remained quite variable in length and content over long periods point to the need for a consensus core curriculum for resident education in radiation and cancer biology. Both current educators and program directors also support making online teaching resources available, diversifying course instructors and consolidating biology teaching across multiple training programs.
Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non-small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors.

STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients ≥1 dose of entrectinib; response-evaluable patients measurable/evaluable baseline disease and ≥1 dose at RP2D.

At data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2-18.4).

Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions.
Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions.
Elder abuse, or mistreatment affects at least 1 in 10 older adults. Financial abuse, or exploitation, of older adults is among the most commonly reported forms of abuse. Few validated measures exist to measure this construct. We aim to present a new psychometrically validated measure of financial abuse of older adults.

Classical test theory and item response theory (IRT) methodologies were used to examine a five-item measure of financial abuse of older adults, administered as part of the New York State Elder Mistreatment Survey.

Factor analysis revealed a single factor best fits the data, which we labeled as financial abuse. Moreover, IRT analyses revealed that these items discriminated well between abused and non-abuse persons and provided information at high levels of the latent trait θ, as is expected in cases of abuse.

The Five-Item Victimization of Exploitation (FIVE) Scale has acceptable psychometric properties and has been used successfully in large scale survey research. We recommend this measure as an indicator of financial abuse in elder abuse, or mistreatment prevalence research studies.
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