An alternative diagnostic method of eruptive vellus hair cysts: Report of a familial case with pruritus

Eruptive vellus hair cysts (EVHC) represent a developmental abnormality of vellus hair follicles. Up till now more than 150 cases of EVHC have been published in the literature, but it appears to be more common than recognized. The diagnostic hallmark is the presence of vellus hair shafts within the cystic space. Firstly to evaluate the potential benefit of new diagnostic method of EVHC using a dermatoscope and secondly to report a familial case of EVHC where females were only affected. Five women from the same family with a clinical diagnosis of EVHC were included in the study. The diagnosis of EVHC was confirmed by skin biopsy with histologic examination in four patients. New diagnostic approach of the cyst contents examination with using a handheld dermatoscope was performed in all patients. Numerous vellus hair shafts were detected on the images of the cysts content taken with dermatoscope and applying the above‐mentioned method in all patients. We suggest that it seems possible to differentiate EVHC by using the dermatoscope, which appears to be simple, quick, and less time consuming.     

Theranostic system for ratiometric fluorescence monitoring of peptide-guided targeted drug delivery

Conjugation of an anticancer drug with a cancer-specific carrier and a fluorescent dye to form a theranostic system enables real time monitoring of targeted drug delivery (TDD). However, the fluorescence signal from the dye is affected by the light absorption and scattering in the body, photobleaching, and instrumental parameters. Ratiometric measurements utilizing two fluorescence signals of different wavelengths are known to improve sensitivity, reliability and quantitation of fluorescence measurements in biological media. Herein, a novel theranostic system comprising the anticancer drug chlorambucil (CLB), cancer-specific peptide octreotide amide (OctA), and a long-wavelength dual fluorescent cyanine dye IRD enabling ratiometric monitoring of drug delivery was developed and evaluated on the cancer cell line PANC-1.

Novel theranostic system that first combines a cancer-targeting peptide with a long-wavelength dual fluorescent dye IRD in order to provide ratiometric monitoring of anticancer drug delivery is developed and evaluated in pancreatic cancer cell line.     

First-Phase Ejection Fraction Is a Powerful Predictor of Adverse Events in Asymptomatic Patients With Aortic Stenosis and Preserved Total Ejection Fraction

Objectives

This study investigated the prognostic value of first-phase ejection fraction (EF1) in patients with aortic stenosis (AS), a condition in which left ventricular dysfunction as measured by conventional indices is an indication for valve replacement.

Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway

Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.Chronic stress can have devastating psychological consequences that include depression and cognitive impairment (1–3). Decades of research suggest that the hippocampus, a structure important for learning and memory and implicated in depression, is particularly sensitive to the effects of chronic stress. In animal models, for example, chronic stress impairs hippocampus-dependent forms of learning and memory (2). This sensitivity is partially conferred by a dense concentration of glucocorticoid receptor (GR) in the hippocampus (4), as well as through hippocampal connectivity to important stress response coordinators, such as the amygdala, from which the hippocampus receives abundant glutamatergic inputs (5–7). Following chronic stress, the hippocampus shows marked reductions in dendritic arborization and neurogenesis, along with impaired plasticity (2). Many of these effects have been attributed to connections between the hippocampus and a specific amygdalar subregion, the basolateral amygdala (BLA) (8–10).Abundant evidence suggests that these BLA inputs have a major impact on hippocampus function; for example, the hippocampus and BLA synchronize their activity during fear memory retrieval and fear extinction (11, 12), whereas electrical stimulation of the BLA disrupts the induction of long-term potentiation (LTP), a measure of synaptic plasticity, in the hippocampal CA1 subregion (13). Lesions of the BLA have been shown to block the detrimental effects of repeated stress, a model of chronic stress in rodents, on LTP and spatial memory (8, 10), as well as the deleterious effect of hippocampal GR activation on hippocampus-dependent memory (9). Although the BLA sends abundant projections to the hippocampus (5–7), this region also projects diffusely throughout the brain and thereby regulates a myriad of behaviors, including valence or social interaction (14), as well as hormonal cascades (15). Because of this complexity, whether BLA activity affects hippocampus-dependent learning and memory directly or indirectly through distinct relay brain regions or other downstream mediators, such as stress hormones, remains unclear.Cdk5 (cyclin-dependent kinase 5) plays a pleiotropic role in the nervous system (16). This enzyme is essential for proper brain development and regulates synaptic plasticity and cognitive function. Activation of Cdk5 requires association with a regulatory subunit known as p35. p35 is subjected to calpain-mediated cleavage into p25 in a process dependent on the activation of glutamate receptors, specifically NR2B-containing NMDA receptors, following neurotoxic stimulation, such as exposure to β-amyloid peptides, oxidative stress, or excitotoxicity, as well as in response to physiological neuronal activity (16).A number of studies have implicated p25 production in Alzheimer’s disease (AD)-like phenotypes, including learning and memory impairments (16), and long-term overexpression of p25 in the forebrain is known to lead to cognitive deficits (16). Furthermore, stress and the heightened sensitivity to stress are known risk factors for the development of AD (1). The role of p25 production after repeated stress remains undetermined, however.One pathway through which p25/Cdk5 might be implicated in stress-induced cognitive dysfunction is stress hormone receptor-mediated epigenetic signaling in the hippocampus. Indeed, it was previously shown that GR is activated by p25/Cdk5-dependent phosphorylation on Ser211 (17, 18), and that increased GR phosphorylation leads to increased expression of histone deacetylase 2 (HDAC2) in a mouse model of AD (18). HDAC2 in turn suppresses the expression of genes important for learning and memory (18, 19), suggesting a mechanism by which elevated p25 generation leads to cognitive impairment. Although GR activation has been shown to be required for stress-induced hippocampal dysfunction and is dependent upon its phosphorylation (20–22), and HDAC2 has been shown to be up-regulated in the ventral striatum of mice following chronic stress (23), the possible up-regulation of HDAC2 in the hippocampus after repeated stress, and the role of p25/Cdk5 signaling in this process, are unknown. We tested the hypothesis that p25 is generated in the hippocampus after repeated stress in an amygdala-dependent manner and contributes to stress-associated learning and memory deficits. Blockade of p25 generation would then protect the hippocampus from the detrimental effects of repeated stress.Here we identify that the activity of a specific BLA to dorsal hippocampus neural circuit mediates the detrimental effects of repeated stress on hippocampal learning and memory via a molecular pathway dependent on p25 generation.     

Prenatal Diagnosis of Left Pulmonary Artery-to-Pulmonary Vein Fistula and Its Successful Surgical Repair in a Neonate

Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair.     

The “European zygomatic fracture” research project: The epidemiological results from a multicenter European collaboration

Purpose

Fractures of the zygomaticomaxillary complex (ZMC) are common injuries that may lead to loss of an aesthetically pleasing appearance and functional impairment. The aim of this study was to analyze the demographics, causes, characteristics, and outcomes of zygomatic fractures managed at several European departments of oral and maxillofacial surgery.

The architecture of fibroblast monolayers of different origin differentially influences tumor cell growth

Normal human and murine fibroblasts can inhibit proliferation of tumor cells when co-cultured in vitro. The inhibitory capacity varies depending on the donor and the site of origin of the fibroblast. It requires direct cell-to-cell contact and is not transferable with supernatant. Here, we show that effective inhibition also requires the formation of a morphologically intact fibroblast monolayer before the seeding of the tumor cells. Interference with the formation of the monolayer impairs the inhibition. Subclones of TERT-immortalized fibroblasts were selected on the basis of differences in the growth pattern and related inhibitory activity. Whereas the well-organized "whirly" (WH) growth pattern was associated with strong inhibition, the disorganized "crossy" (CR) growth pattern was linked to reduced inhibition. Time lapse imaging of tumor-fibroblast co-cultures using extended field live cell microscopy revealed that fibroblast monolayers with growth inhibitory capacity also reduced the motility of the tumor cells whereas noninhibitory monolayers had no effect on tumor cell motility. Gene expression pattern of two isogenic pairs of fibroblasts, WH and CR subclones of the TERT immortalized line (inhibitory, and less inhibitory subsequently) and freshly explanted skin (inhibitory) and hernia (noninhibitory) fibroblasts derived from the same patient, identified a set of genes that co-segregated with the inhibitory phenotype. This suggests that our model system may reveal molecular mechanisms involved in contact-mediated microenvironmental surveillance that may protect the organism from the outgrowth of disseminated tumor cells.