The Effect of Presleep Focal Attention Load on Subsequent Sleep Patterns

The hypothesis that a load on focal attention prior to sleep results in subsequent changes in sleep patterns was investigated. Eight females and 2 males slept in the laboratory for 4 nights: 2 adaptation nights, 1 experimental night preceded by a focal attention load, and 1 control night preceded by relaxed activity. On the experimental night, time in bed, total sleep time, and stage REM sleep were significantly longer than on the control night. The results support the hypothesis and suggest that attention during REM sleep has a unique character.     

Hemorrhage associated with “bone crisis” in Gaucher's disease identified by magnetic resonance imaging

Children suffering from Gaucher's disease were examined by magnetic resonance imaging (MRI) during a characteristic episode of bone crisis. An unexpectedly high intramedullary as well as subperiosteal signal was observed on both the T1 and T2-weighted sequences in 5 patients, suggesting a subacute hemorrhage or hematoma. It is conceivable that such a painful hemorrhage is an important component of the bone crisis phenomenon. Furthermore, in these cases this is a specific sign which may enable differentiation of bone crises from other types of bone pain associated with Gaucher's disease.     

Imaging in glaucoma

Structural assessment using the imaging technologies discussed herein provides reproducible quantitative measurements of posterior segment ocular structures. These measurements have been found to provide useful data for glaucoma detection in various regions of the posterior segment. Further studies are needed to evaluate the utility of these technologies for pre-perimetric glaucoma detection and for monitoring glaucoma progression over an extended period.     

Functional magnetic resonance imaging monitoring of pathological changes in rodent livers during hyperoxia and hypercapnia

Liver diseases and regeneration are associated with hemodynamic changes denoting pathological alterations. Determining and monitoring physiological and pathological liver changes is essential for diagnostic and therapeutic objectives. Our aim was to determine the feasibility of functional magnetic resonance imaging (fMRI) during hypercapnia and hyperoxia for monitoring liver pathology. Liver fMRI images were acquired in rodents following acute bleeding, partial hepatectomy, and fibrosis. Results were quantitated and confirmed by histology. Changes induced by hyperoxia and hypercapnia following hemorrhage significantly correlated with the percentage of blood loss, reflecting lower liver perfusion and diminished vessel responsiveness to gas saturation. Hepatectomy resulted in an early decline in signal intensity changes due to hyperoxia, suggesting a decrease in liver perfusion and blood content. Following hepatectomy, signal intensity changes due to hypercapnia increased, signifying a change in liver perfusion from a mainly portal to a more arterial source. Two weeks after induction of fibrosis, signal intensity changes due to hypercapnia became much lower and those due to hyperoxia were much higher than those in normal livers, reflecting the increased perfusion due to the inflammatory process as confirmed by histologic analysis. With fibrosis progression, signal intensity changes induced by hypercapnia and hyperoxia were gradually attenuated, indicating structural and functional alterations of the liver vasculature during fibrosis. CONCLUSION: In various liver pathologies, fMRI response to hypercapnia and hyperoxia is sensitive to changes in liver hemodynamic status involved in hepatic damage or recovery; thus, this technique may offer an additional noninvasive diagnostic tool for evaluation and follow-up of liver diseases by means of examining perfusion-related alterations.     

Antibody Drug Conjugates: Preclinical Considerations

The development path for antibody drug conjugates (ADCs) is more complex and challenging than for unmodified antibodies. While many of the preclinical considerations for both unmodified and antibody drug conjugates are shared, special considerations must be taken into account when developing an ADC. Unlike unmodified antibodies, an ADC must preferentially bind to tumor cells, internalize, and traffic to the appropriate intracellular compartment to release the payload. Parameters that can impact the pharmacological properties of this class of therapeutics include the selection of the payload, the type of linker, and the methodology for payload drug conjugation. Despite a plethora of in vitro assays and in vivo models to screen and evaluate ADCs, the challenge remains to develop improved preclinical tools that will be more predictive of clinical outcome. This review will focus on preclinical considerations for clinically validated small molecule ADCs. In addition, the lessons learned from Mylotarg®, the first in class FDA-approved ADC, are highlighted.     

Cytocompatibility of novel extracellular matrix protein analogs of biodegradable polyester polymers derived from α-hydroxy amino acids

One of the challenges in regenerative medicine is the development of novel biodegradable materials to build scaffolds that will support multiple cell types for tissue engineering. Here we describe the preparation, characterization, and cytocompatibility of homo- and hetero-polyesters of α-hydroxy amino acid derivatives with or without lactic acid conjugation. The polymers were prepared by a direct condensation method and characterized using gel permeation chromatography, ¹H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, optical activity, and solubility. The surface charge of the polymers was evaluated using zeta potential measurements. The polymers were coated onto glass cover slips followed by characterization using nano-surface profiler, thin film reflectometry, and atomic force microscopy (AFM). Their interaction with endothelial and neuronal cells was assessed using adhesion, proliferation, and differentiation assays. Of the characterized polymers, Poly-HOVal-LA, but not Poly-(D)HOPhe, significantly augmented nerve growth factor (NGF)-induced neuronal differentiation of the PC12 pheochromcytoma cells. In contrast, Poly-HOLeu increased by 20% the adhesion of endothelial cells, but did not affect PC12 cell differentiation. NGF-induced Erk1/2 phosphorylation in PC12 cells grown on the different polymers was similar to the effect observed for cells cultured on collagen type I. While no significant association could be established between charge and the differentiative/proliferative properties of the polymers, AFM analysis indicated augmentation of NGF-induced neuronal differentiation on smooth polymer surfaces. We conclude that overall selective cytocompatibility and bioactivity might render α-hydroxy amino acid polymers useful as extracellular matrix-mimicking materials for tissue engineering.     

Intolerance of Uncertainty Moderates the Association Between Potentially Morally Injurious Events and Suicide Ideation and Behavior Among Combat Veterans

Exposure to potentially morally injurious events (PMIEs) among combat veterans has been acknowledged as significant stressful combat events that may lead to mental health problems, including self‐injurious thoughts and behavior (SITB). However, few studies have examined the risk and protective factors that can explain the conditions in which PMIEs may contribute to the development and maintenance of SITB. In the current study, we aimed to examine the association between PMIEs and SITB among combat veterans and explore the moderating roles of intolerance of uncertainty (IU) in this association. A volunteer sample of 191 Israeli combat veterans was recruited during 2017. Participants completed validated self‐report questionnaires in a cross‐sectional study. Results indicated that two separate measures of PMIEs, the Perceived Perpetration by Oneself and Others subscale of the Moral Injury Events Scale (MIES) and the Causes subscale of the Moral Injury Questionnaire (MIQ–Causes), were positively associated with higher levels of SITB. Moreover, beyond the contributions of reserve duty, posttraumatic stress symptoms, and depressive symptoms, MIQ–Causes scores significantly predicted current SITB. Importantly, under low and average levels of inhibitory IU, significant positive effects were revealed for the MIQ–Causes on current SITB, R² = .34. Although veterans exposed to PMIEs are more prone to SITB, even years after their release from military service, their IU may temper the link between experiences of PMIEs and SITB.