High-Entropy Pyrochlore A2B2O7 with Both Heavy and Light Rare-Earth Elements at the A Site

A novel class of high-entropy pyrochlore ceramics (HEPCs) with multiple heavy and light rare-earth elements at the A site were successfully synthesized via solid-state reaction. Both the XRD patterns and Raman spectroscopy demonstrated the single pyrochlore structure feature of seven kinds of HEPCs. Electron microscopic images revealed the typical morphology and the homogeneous distribution of all rare-earth elements. It can be concluded that the significance of configuration entropy in the HEPC system has promoted the tervalent lanthanide nuclides to form a single pyrochlore structure. This work is expected to provide guidance for the further design of high-entropy pyrochlore/fluorite ceramics.

A Potential New Role for Zinc in Age-Related Macular Degeneration through Regulation of Endothelial Fenestration

Age-related macular degeneration (AMD) is a common blinding disease in the western world that is linked to the loss of fenestration in the choriocapillaris that sustains the retinal pigment epithelium and photoreceptors in the back of the eye. Changes in ocular and systemic zinc concentrations have been associated with AMD; therefore, we hypothesized that these changes might be directly involved in fenestrae formation. To test this hypothesis, an endothelial cell (bEND.5) model for fenestrae formation was treated with different concentrations of zinc sulfate (ZnSO4) solution for up to 20 h. Fenestrae were visualized by staining for Plasmalemmal Vesicle Associated Protein-1 (PV-1), the protein that forms the diaphragms of the fenestrated endothelium. Size and distribution were monitored by transmission electron microscopy (TEM). We found that zinc induced the redistribution of PV-1 into areas called sieve plates containing ~70-nm uniform size and typical morphology fenestrae. As AMD is associated with reduced zinc concentrations in the serum and in ocular tissues, and dietary zinc supplementation is recommended to slow disease progression, we propose here that the elevation of zinc concentration may restore choriocapillaris fenestration resulting in improved nutrient flow and clearance of waste material in the retina.

Informational Masking Effects of Speech Versus Nonspeech Noise on Cortical Auditory Evoked Potentials

Purpose Background noise has been categorized as energetic masking due to spectrotemporal overlap of the target and masker on the auditory periphery or informational masking due to cognitive-level interference from relevant content such as speech. The effects of masking on cortical and sensory auditory processing can be objectively studied with the cortical auditory evoked potential (CAEP). However, whether effects on neural response morphology are due to energetic spectrotemporal differences or informational content is not fully understood. The current multi-experiment series was designed to assess the effects of speech versus nonspeech maskers on the neural encoding of speech information in the central auditory system, specifically in terms of the effects of speech babble noise maskers varying by talker number. Method CAEPs were recorded from normal-hearing young adults in response to speech syllables in the presence of energetic maskers (white or speech-shaped noise) and varying amounts of informational maskers (speech babble maskers). The primary manipulation of informational masking was the number of talkers in speech babble, and results on CAEPs were compared to those of nonspeech maskers with different temporal and spectral characteristics. Results Even when nonspeech noise maskers were spectrally shaped and temporally modulated to speech babble maskers, notable changes in the typical morphology of the CAEP in response to speech stimuli were identified in the presence of primarily energetic maskers and speech babble maskers with varying numbers of talkers. Conclusions While differences in CAEP outcomes did not reach significance by number of talkers, neural components were significantly affected by speech babble maskers compared to nonspeech maskers. These results suggest an informational masking influence on neural encoding of speech information at the sensory cortical level of auditory processing, even without active participation on the part of the listener.

Case Report: Minimal Neurological Deficit of Two Adult Patients With Weston–Hurst Syndrome Due to Early Craniectomy: Case Series and Review of Literature on Craniectomy

Objectives: We describe two new cases of acute hemorrhagic leucoencephalitis (AHLE), who survived with minimal sequelae due to early measures against increased intracranial pressure, particularly craniotomy. The recently published literature review on treatment and outcome of AHLE was further examined for the effect of craniotomy.Methods: We present two cases from our institution. The outcome of 44 cases from the literature was defined either as good (no deficit, minimal deficit/no daily help) or poor outcome (severe deficit/disabled, death). Patients with purely infratentorial lesions (n = 9) were excluded. Fisher's exact test was applied.Results: Two cases are presented: A 43-year-old woman with rapidly progressive aphasia and right hemiparesis due to a huge left frontal white matter lesion with rim contrast enhancement. Pathology was consistent with AHLE. The second case was a 56-year-old woman with rapidly progressive aphasia and right hemiparesis. Cranial MRI showed a huge left temporo-occipital white matter lesion with typical morphology for AHLE. Both patients received craniotomy within the first 24 h and consequent immunosuppressive-immunomodulatory treatment and survived with minimal deficits. Out of 35 supratentorial reported AHLE cases, seven patients received decompressive craniotomy. Comparing all supratentorial cases, patients who received craniotomy were more likely to have a good outcome (71 vs. 29%).Conclusion: Due to early control of the intracranial pressure, particularly due to early craniotomy; diagnosis per biopsy; and immediate start of immunosuppressive-immunomodulatory therapies (cortisone pulse, plasma exchanges), both patients survived with minimal sequelae. Craniotomy plays an important role and should be considered early on in patients with probable AHLE.

PEDOT:PSS-Coated Polybenzimidazole Electroconductive Nanofibers for Biomedical Applications

Bioelectricity drives several processes in the human body. The development of new materials that can deliver electrical stimuli is gaining increasing attention in the field of tissue engineering. In this work, novel, highly electrically conductive nanofibers made of poly [2,2′-m-(phenylene)-5,5′-bibenzimidazole] (PBI) have been manufactured by electrospinning and then coated with cross-linked poly (3,4-ethylenedioxythiophene) doped with poly (styrene sulfonic acid) (PEDOT:PSS) by spin coating or dip coating. These scaffolds have been characterized by scanning electron microscopy (SEM) imaging and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. The electrical conductivity was measured by the four-probe method at values of 28.3 S·m−1 for spin coated fibers and 147 S·m−1 for dip coated samples, which correspond, respectively, to an increase of about 105 and 106 times in relation to the electrical conductivity of PBI fibers. Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) cultured on the produced scaffolds for one week showed high viability, typical morphology and proliferative capacity, as demonstrated by calcein fluorescence staining, 4′,6-diamidino-2-phenylindole (DAPI)/Phalloidin staining and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] assay. Therefore, all fiber samples demonstrated biocompatibility. Overall, our findings highlight the great potential of PEDOT:PSS-coated PBI electrospun scaffolds for a wide variety of biomedical applications, including their use as reliable in vitro models to study pathologies and the development of strategies for the regeneration of electroactive tissues or in the design of new electrodes for in vivo electrical stimulation protocols.

Eosinophilic Solid and Cystic Renal Cell Carcinoma With Melanin Pigment—Expanding the Morphological Spectrum

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is an emerging entity in renal neoplasia with distinctive histopathological findings and a generally favorable prognosis. The presence of melanin pigment in a renal tumor typically prompts the observer to consider the microphthalmia-associated transcription family translocation renal cell carcinomas. We present a renal tumor occurring in a 19-year-old male patient which had the typical morphology of ESC-RCC but showed the additional finding of focal melanin pigment. This tumor showed strong and diffuse positive immunolabeling with paired box gene 8 and cytokeratin 20, and was negative with epithelial membrane antigen, carbonic anhydrase 9, CD117, cytokeratin 7, and transcription factor E3. Human melanoma black-45 showed focal positivity, but Melan-A was negative. Next-generation sequencing revealed a mutation in the TSC2 gene (c.4490C > G, p.[Pro1497Arg] and c.1257 + 1del) and break apart fluorescence in-situ hybridization with TFE3 and TFEB probes was negative. In this case report, we present the novel finding of melanin pigment occurring in a genetically proven and otherwise typical ESC-RCC, and briefly discuss the differential diagnostic considerations.

The Wide Morphological Spectrum of Deep (Aggressive) Angiomyxoma of the Vulvo-Vaginal Region: A Clinicopathologic Study of 36 Cases, Including Recurrent Tumors

Background: Deep angiomyxoma (DAM) is currently included in the category of “specific stromal tumors of the lower female genital tract”, along with angiomyofibroblastoma, cellular angiofibroma and myofibroblastoma. Given the high rate of local recurrences, it is crucial to recognize DAM from other tumors that possess indolent behaviour. In the present paper, we analyzed the morphological and immunohistochemical features of 42 surgically-resected vulvo-vaginal DAMs (36 primary and 6 recurrent lesions) in order to widen the morphological spectrum of this uncommon tumor. Methods: A series of 36 cases of surgically-resected primary vulvo-vaginal DAMs were retrospectively collected. Locally recurrent tumors were also available for six of these cases. Results: Out of the primary tumors, 25 out of 36 exhibited the classic-type morphology of DAM. In the remaining cases (11/36 cases), the following uncommon features, which sometimes coexist with one another, were observed: (i) alternating myxoid and collagenized/fibrous areas; (ii) hypercellular areas; (iii) neurofibroma-like appearance; (iv) perivascular hyalinization; (v) microcystic/reticular stromal changes; (vi) “microvascular growth pattern”; (vii) perivascular cuffing; (viii) nodular leiomyomatous differentiation; (ix) hypocellular and fibro-sclerotic stroma. Among the six locally recurrent tumors the following features were observed: (i) classic-type morphology; (ii) hypocellular fibro-sclerotic stroma; (iii) extensive perivascular hyalinization, lumen obliteration and formation of confluent nodular sclerotic masses; (iv) hypercellularity. Immunohistochemically, the neoplastic cells of classic-type DAM in both primary and recurrent tumors were diffusely stained with desmin, suggesting a myofibroblastic nature; in contrast, the neoplastic cells showing elongated fibroblastic-like morphology and set in collagenized/fibrosclerotic stroma in both primary and recurrent tumors were negative or only focally stained with desmin, which is consistent with a fibroblastic profile. Conclusion: Although diagnosis of DAM is usually straightforward if typical morphology is encountered, diagnostic problems may arise when a pathologist is dealing with unusual morphological features, especially hypercellularity, extensive collagenous/fibrosclerotic stroma or neurofibroma-like appearance.

Triple Culture of Primary Human Osteoblasts, Osteoclasts and Osteocytes as an In Vitro Bone Model

In vitro evaluation of bone graft materials is generally performed by analyzing the interaction with osteoblasts or osteoblast precursors. In vitro bone models comprising different cell species can give specific first information on the performance of those materials. In the present study, a 3D co-culture model was established comprising primary human osteoblasts, osteoclasts and osteocytes. Osteocytes were differentiated from osteoblasts embedded in collagen gels and were cultivated with osteoblast and osteoclasts seeded in patterns on a porous membrane. This experimental setup allowed paracrine signaling as well as separation of the different cell types for final analysis. After 7 days of co-culture, the three cell species showed their typical morphology and gene expression of typical markers like ALPL, BSPII, BLGAP, E11, PHEX, MEPE, RANKL, ACP5, CAII and CTSK. Furthermore, relevant enzyme activities for osteoblasts (ALP) and osteoclasts (TRAP, CTSK, CAII) were detected. Osteoclasts in triple culture showed downregulated TRAP (ACP5) and CAII expression and decreased TRAP activity. ALP and BSPII expression of osteoblasts in triple culture were upregulated. The expression of the osteocyte marker E11 (PDPN) was unchanged; however, osteocalcin (BGLAP) expression was considerably downregulated both in osteoblasts and osteocytes in triple cultures compared to the respective single cultures.

EBV-Positive Plasmacytomas Involving a Nasopharyngeal Angiofibroma in an Adolescent

We report comprehensive characterization of an unusual collision tumor comprising extramedullary plasmacytomas and nasopharyngeal angiofibroma in a pediatric patient, which has yet to be reported. Histologically, the nasopharyngeal angiofibroma showed typical morphology with a diffuse, dense plasmacytic infiltrate in the stroma. The neoplastic plasma cells showed a spectrum of well-differentiated, plasmablastic, and anaplastic morphology, Epstein-Barr virus encoded RNA (EBER) positivity, and aberrant immunophenotype. Fluorescence in situ hybridization using a plasma cell myeloma targeted panel detected gains of 1q21.3 ( CKS1B, x3), 3q27 ( BCL6, x4), and 11q22.3 ( ATM, x3), but no rearrangement of ALK and MYC. A 50-gene next generation sequencing lymphoma panel failed to detect any pathogenic mutation. Plasmacytoma with EBER positivity and plasmablastic morphology must be distinguished from plasmablastic lymphoma due to different clinical management and prognosis. This case highlights the importance of a thorough pathological evaluation of a mass lesion with synchronous neoplastic processes.