Innovative Educational Design: The Development of Autonomous Schools

Innovative Educational Design: The Development of Autonomous Schools captures an educator’s journey in developing an economically integrated, urban Expeditionary Learning charter school, an autoethnography of an educator embracing an entrepreneurial spirit and traversing the years prior to opening a school and obtaining unanimous approval from the authorizing board of education. Autoethnography provides the researcher with an opportunity to turn scholarly interests inward, bringing personal experiences to center stage revealing the culture of founding school leaders. Similar to an ethnographer describing the culture of a group of people and learning what it is like to be a part of the group from the viewpoint of members of that group, the researcher describes experiences designing an autonomous Expeditionary Learning charter school in an urban environment in the Rocky Mountain region. Autoethnography adheres to the anthropological and social approaches to scientific inquiry, providing opportunities for the autoethnographer to reflect upon, analyze, and interpret story within the broader sociocultural context. Personal memory data, self-reflective data, and external data were utilized to explore the aspects of the researcher’s experiences developing an Expeditionary Learning charter school that would best support future education entrepreneurs in designing autonomous schools. An additional purpose of this autoethnographic study is to illuminate the problems and possibilities for preparing effective school leaders and providing early career support to nurture their professional development. With insights into the researcher’s experiences founding a downtown school, the author identifies important aspects of school design, including school culture, leadership, educational program, teaching, and governance and reveals the hidden competencies school leaders need to possess to succeed in an increasingly changing educational landscape. The author hopes that this autoethnography will reveal the complexities facing autonomous school leaders as they navigate state and district level authorization processes and, in the process, provide an opportunity for new knowledge, insight, and transformation for the author, the reader, and the field of choice and innovation in education

Desmoplastic Trichoepithelioma and Melanocytic Nevus: Dermoscopic and Reflectance Confocal Microscopy Presentation of a Rare Collision Tumor

A 27-year-old woman presented with a 2-year history of an asymptomatic papule located on her right cheek. The physical examination revealed a firm, well-defined with a raised annular border, skin-colored papule, 5 mm in maximum diameter

Verrucous Melanoma Simulating Melanoacanthoma: Dermoscopic, Reflectance Confocal Microscopic and High-Definition Optical Coherence Tomography Presentation of a Rare Melanoma Variant

info:eu-repo/semantics/publishedVersio

Dermoscopic and Reflectance Confocal Microscopic Presentation of Hailey‐Hailey Disease: a Case Series

Background/purpose: Hailey-Hailey disease is a rare inherited acantholytic skin disorder characterized by heterogeneous clinical presentation. Its differential diagnosis might be wide, including other genodermatoses, inflammatory, and infectious skin diseases. Although histopathology remains as diagnostic gold standard, noninvasive techniques such as dermoscopy and reflectance confocal microscopy may assist clinical examination. Herein, we aim to further characterize the dermoscopic and reflectance confocal microscopic presentation of Hailey-Hailey disease with histologic correlation. Methods: Eight patients with Hailey-Hailey disease were consecutively recruited. All patients were examined using dermoscopy and reflectance confocal microscopy. Results: In all cases, dermoscopy enabled the visualization of polymorphous vessels, including glomerular and linear-looped vessels, within a pink-whitish background. Reflectance confocal microscopy revealed wide suprabasilar partial acantholysis and clefting, crusts, dilated papillae with tortuous vessels, and inflammatory cells. Dyskeratosis, uplocated papillae, and adnexal sparing were also observed. Conclusion: Although definite diagnosis was obtained by histopathology in all cases, dermoscopy and reflectance confocal microscopy allowed the identification of common features (even in cases with dissimilar clinical presentation) that may support an early diagnosis of Hailey-Hailey disease, and its differentiation from other more frequent skin disorders.info:eu-repo/semantics/publishedVersio

Cortical circuit alterations precede motor impairments in Huntington's disease mice

Huntington's disease (HD) is a devastating hereditary movement disorder, characterized by degeneration of neurons in the striatum and cortex. Studies in human patients and mouse HD models suggest that disturbances of neuronal function in the neocortex play an important role in disease onset and progression. However, the precise nature and time course of cortical alterations in HD have remained elusive. Here, we use chronic in vivo two-photon calcium imaging to longitudinally monitor the activity of identified single neurons in layer 2/3 of the primary motor cortex in awake, behaving R6/2 transgenic HD mice and wildtype littermates. R6/2 mice show age-dependent changes in cortical network function, with an increase in activity that affects a large fraction of cells and occurs rather abruptly within one week, preceeding the onset of motor defects. Furthermore, quantitative proteomics demonstrate a pronounced downregulation of synaptic proteins in the cortex, and histological analyses in R6/2 mice and human HD autopsy cases reveal a reduction in perisomatic inhibitory synaptic contacts on layer 2/3 pyramidal cells. Taken together, our study provides a time-resolved description of cortical network dysfunction in behaving HD mice and points to disturbed excitation/inhibition balance as an important pathomechanism in HD

Ensemble-Based Virtual Screening Reveals Potential Novel Antiviral Compounds for Avian Influenza Neuraminidase

Avian influenza virus subtype H5N1 is a potential pandemic threat with human-adapted strains resistant to antiviral drugs. Although virtual screening (VS) against a crystal or relaxed receptor structure is an established method to identify potential inhibitors, the more dynamic changes within binding sites are neglected. To accommodate full receptor flexibility, we use AutoDock4 to screen the NCI diversity set against representative receptor ensembles extracted from explicitly solvated molecular dynamics simulations of the neuraminidase system. The top hits are redocked to the entire nonredundant receptor ensemble and rescored using the relaxed complex scheme (RCS). Of the 27 top hits reported, half ranked very poorly if only crystal structures are used. These compounds target the catalytic cavity as well as the newly identified 150- and 430-cavities, which exhibit dynamic properties in electrostatic surface and geometric shape. This ensemble-based VS and RCS approach may offer improvement over existing strategies for structure-based drug discovery

Reflectance Confocal Microscopy for Diagnosis of Mammary Paget's Disease

5Mammary Paget’s disease (MPD) is an uncommon intra-epidermal adenocarcinoma of the nipple-areola complex, occurring in 1–5% of all breast carcinomas (1). MPD is difficult to diagnose clinically as it mimics a variety of both inflammatory and neoplastic skin diseases (2). Pigmented mammary Paget’s disease (PMPD) corresponds to an even less common variant, frequently simulating other pigmented lesions of the nipple, including melanoma (3–5). According to the epidermotropic theory, Paget cells (PCs) originate from cancer cells that migrate via the lactiferous ducts along the basal membrane, to invade the epidermis of the nipple and areola (6, 7). Considering its intra-epidermal spreading, PCs are therefore potentially demonstrable using non-invasive diagnostic techniques with near-cellular resolution, such as reflectance confocal microscopy (RCM) (8). The aim of this study was retrospectively to describe the RCM features of 5 cases of MPD, with dermoscopic and histopathological correlation.opennoneopenOliveira, André; Zalaudek, Iris; Arzberger, Edith; Massone, Cesare; Hofmann-Wellenhof, RainerOliveira, Andrã©; Zalaudek, Iris; Arzberger, Edith; Massone, Cesare; Hofmann-Wellenhof, Raine

Superiority of Formalin-Fixed Paraffin-Embedded Brain Tissue for in vitro Assessment of Progressive Supranuclear Palsy Tau Pathology With [F-18]PI-2620

Objectives: Autoradiography on brain tissue is used to validate binding targets of newly discovered radiotracers. The purpose of this study was to correlate quantification of autoradiography signal using the novel next-generation tau positron emission tomography (PET) radiotracer [18F]PI-2620 with immunohistochemically determined tau-protein load in both formalin-fixed paraffin-embedded (FFPE) and frozen tissue samples of patients with Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP). Methods: We applied [18F]PI-2620 autoradiography to postmortem cortical brain samples of six patients with AD, five patients with PSP and five healthy controls, respectively. Binding intensity was compared between both tissue types and different disease entities. Autoradiography signal quantification (CWMR = cortex to white matter ratio) was correlated with the immunohistochemically assessed tau load (AT8-staining, %-area) for FFPE and frozen tissue samples in the different disease entities. Results: In AD tissue, relative cortical tracer binding was higher in frozen samples when compared to FFPE samples (CWMRfrozen vs. CWMRFFPE: 2.5-fold, p < 0.001), whereas the opposite was observed in PSP tissue (CWMRfrozen vs. CWMRFFPE: 0.8-fold, p = 0.004). In FFPE samples, [18F]PI-2620 autoradiography tracer binding and immunohistochemical tau load correlated significantly for both PSP (R = 0.641, p < 0.001) and AD tissue (R = 0.435, p = 0.016), indicating a high agreement of relative tracer binding with underlying pathology. In frozen tissue, the correlation between autoradiography and immunohistochemistry was only present in AD (R = 0.417, p = 0.014) but not in PSP tissue (R = −0.115, p = n.s.). Conclusion: Our head-to-head comparison indicates that FFPE samples show superiority over frozen samples for autoradiography assessment of PSP tau pathology by [18F]PI-2620. The [18F]PI-2620 autoradiography signal in FFPE samples reflects AT8 positive tau in samples of both PSP and AD patients

Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants.

Introduction: The role of TOMM40-APOE 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Methods: We dissected genetic profiles within the TOMM40-APOE region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls. Results: TOMM40-L/APOE-ε4 alleles were associated with DLB (OR TOMM40 -L = 3.61; P value = 3.23 × 10-9; OR APOE -ε4 = 3.75; P value = 4.90 × 10-10) and earlier age at onset of DLB (HR TOMM40 -L = 1.33, P value = .031; HR APOE -ε4 = 1.46, P value = .004), but not with PDD. The TOMM40-L/APOE-ε4 effect was most pronounced in DLB individuals with concomitant AD pathology (OR TOMM40 -L = 4.40, P value = 1.15 × 10-6; OR APOE -ε4 = 5.65, P value = 2.97 × 10-8) but was not significant in DLB without AD. Meta-analyses combining all APOE-ε4 data in DLB confirmed our findings (ORDLB = 2.93, P value = 3.78 × 10-99; ORDLB+AD = 5.36, P value = 1.56 × 10-47). Discussion: APOE-ε4/TOMM40-L alleles increase susceptibility and risk of earlier DLB onset, an effect explained by concomitant AD-related pathology. These findings have important implications in future drug discovery and development efforts in DLB

Superiority of Formalin-Fixed Paraffin-Embedded Brain Tissue for in vitro Assessment of Progressive Supranuclear Palsy Tau Pathology With [18F]PI-2620

Objectives: Autoradiography on brain tissue is used to validate binding targets of newly discovered radiotracers. The purpose of this study was to correlate quantification of autoradiography signal using the novel next-generation tau positron emission tomography (PET) radiotracer [18F]PI-2620 with immunohistochemically determined tau-protein load in both formalin-fixed paraffin-embedded (FFPE) and frozen tissue samples of patients with Alzheimer’s disease (AD) and Progressive Supranuclear Palsy (PSP). Methods: We applied [18F]PI-2620 autoradiography to postmortem cortical brain samples of six patients with AD, five patients with PSP and five healthy controls, respectively. Binding intensity was compared between both tissue types and different disease entities. Autoradiography signal quantification (CWMR = cortex to white matter ratio) was correlated with the immunohistochemically assessed tau load (AT8-staining, %-area) for FFPE and frozen tissue samples in the different disease entities. Results: In AD tissue, relative cortical tracer binding was higher in frozen samples when compared to FFPE samples (CWMRfrozen vs. CWMRFFPE: 2.5-fold, p < 0.001), whereas the opposite was observed in PSP tissue (CWMRfrozen vs. CWMRFFPE: 0.8-fold, p = 0.004). In FFPE samples, [18F]PI-2620 autoradiography tracer binding and immunohistochemical tau load correlated significantly for both PSP (R = 0.641, p < 0.001) and AD tissue (R = 0.435, p = 0.016), indicating a high agreement of relative tracer binding with underlying pathology. In frozen tissue, the correlation between autoradiography and immunohistochemistry was only present in AD (R = 0.417, p = 0.014) but not in PSP tissue (R = −0.115, p = n.s.). Conclusion: Our head-to-head comparison indicates that FFPE samples show superiority over frozen samples for autoradiography assessment of PSP tau pathology by [18F]PI-2620. The [18F]PI-2620 autoradiography signal in FFPE samples reflects AT8 positive tau in samples of both PSP and AD patients