Citations

SummaryAimsNeurodegenerative disorders are caused by progressive neuronal loss in the brain, and hence, compounds that could promote neuritogenesis may have therapeutic values. In this study, the effects of bis(heptyl)‐cognitin (B7C), a multifunctional dimer, on neurite outgrowth were investigated in both PC12 cells and primary cortical neurons.MethodsImmunocytochemical staining was used to evaluate the proneuritogenesis effects, and Western blot and short hairpin RNA assays were applied to explore the underlying mechanisms.ResultsB7C (0.1–0.5 μM) induced robust neurite outgrowth in PC12 cells, as evidenced by the neurite‐bearing morphology and upregulation of growth‐associated protein‐43 expression. In addition, B7C markedly promoted neurite outgrowth in primary cortical neurons as shown by the increase in the length of β‐III‐tubulin‐positive neurites. Furthermore, B7C rapidly increased ERK phosphorylation. Specific inhibitors of alpha7‐nicotinic acetylcholine receptor (α7‐nAChR) and MEK, but not those of p38 or JNK, blocked the neurite outgrowth as well as ERK phosphorylation induced by B7C. Most importantly, genetic depletion of α7‐nAChR significantly abolished B7C‐induced neurite outgrowth in PC12 cells.ConclusionB7C promoted neurite outgrowth through the activation of α7‐nAChR/ERK pathway, which offers novel insight into the potential application of B7C in the treatment of neurodegenerative disorders.

ABSTRACT Inflammation is a major cause of respiratory impairment during Pneumocystis pneumonia. Studies support a significant role for cell wall β-glucans in stimulating inflammatory responses. Fungal β-glucans are comprised of d -glucose homopolymers containing β-1,3-linked glucose backbones with β-1,6-linked glucose side chains. Prior studies in Pneumocystis carinii have characterized β-1,3 glucan components of the organism. However, recent investigations in other organisms support important roles for β-1,6 glucans, predominantly in mediating host cellular activation. Accordingly, we sought to characterize β-1,6 glucans in the cell wall of Pneumocystis and to establish their activity in lung cell inflammation. Immune staining revealed specific β-1,6 localization in P. carinii cyst walls. Homology-based cloning facilitated characterization of a functional P. carinii kre6 ( Pckre6 ) β-1,6 glucan synthase in Pneumocystis that, when expressed in kre6 -deficient Saccharomyces cerevisiae , restored cell wall stability. Recently synthesized β-1,6 glucan synthase inhibitors decreased the ability of isolated P. carinii preparations to generate β-1,6 carbohydrate. In addition, isolated β-1,6 glucan fractions from Pneumocystis elicited vigorous tumor necrosis factor alpha (TNF-α) responses from macrophages. These inflammatory responses were significantly dampened by inhibition of host cell plasma membrane microdomain function. Together, these studies indicate that β-1,6 glucans are present in the P. carinii cell wall and contribute to lung cell inflammatory activation during infection.

The relation between somatosensory mechanisms and self-injury among children with neurologic impairments associated with developmental delay is not well understood. We evaluated the feasibility of procuring skin biopsies to examine epidermal nerve fiber density and reported self-injury. Following informed parental consent, epidermal skin biopsies were obtained from a distal leg site with no pre-existing skin damage from 11 children with global developmental delay (55% male; mean age = 36.8 months, 17-63 months). Visual microscopic examination and quantitative analyses showed extremely high epidermal nerve fiber density values for some children. Children with reported self-injury (5/11) had significantly ( P < .02) greater density values (138.8, standard deviation = 45.5) than children without self-injury (80.5, standard deviation = 17.5). Results from this novel immunohistologic analysis of skin in very young children with neurodevelopmental delays suggest it may be a useful tool to study peripheral innervation as a possible sensory risk factor for self-injury.

The flipped classroom represents an essential component in curricular reform. Technological advances enabling asynchronous and distributed learning are facilitating the movement to a competency-based paradigm in healthcare education. At its most basic level, flipping the classroom is the practice of assigning students didactic material, traditionally covered in lectures, to be learned before class while using face-to-face time for more engaging and active learning strategies. The development of more complex learning systems is creating new opportunities for learning across the continuum of medical education as well as interprofessional education. As medical educators engage in the process of successfully flipping a lecture, they gain new teaching perspectives, which are foundational to effectively engage in curricular reform. The purpose of this article is to build a pedagogical and technological understanding of the flipped classroom framework and to articulate strategies for implementing it in medical education to build competency.

AbstractBackgroundThe collaborative care model (CCM) has been consistently shown to achieve effectiveness in depression management compared to usual care. In the present study, we aimed to determine the impact of age on cost metrics in patients who were treated with CCM for 6 months after a diagnosis of depression.MethodsThe upper quartile of age was 50 years and older (n = 56), and the comparison group was composed of patients in the three younger quartiles, aged 18–49 years (n = 163).ResultsPatients in the older age group had an elevated median Current Procedure Terminology cost rank of 255.5 compared to 168.0 for the younger patients (P < 0.001). Multiple logistic regression analysis revealed that being in the upper quartile of age (≥50 years) (odds ratio = 2.272, 95% confidence interval: 1.064–4.851; P = 0.034) and having higher numbers of clinical visits 6 months prior to index (odds ratio = 1.209, 95% confidence interval: 1.118–1.307; P < 0.001) were significant predictor variables of being cost rank outliers (>80th percentile) in patients with CCM.ConclusionMedical cost utilization in the 6 months after diagnosis of depression was significantly higher in patients in the upper age quartile (≥50 years) enrolled in CCM than those in the lower quartiles (age <50).