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* The traditional surgical pathology assessment requires tissue to be removed from the patient, then processed, sectioned, stained, and interpreted by a pathologist using a light microscope. Today, an array of alternate optical imaging technologies allow tissue to be viewed at high resolution, in real time, without the need for processing, fixation, freezing, or staining. Optical imaging can be done in living patients without tissue removal, termed in vivo microscopy, or also in freshly excised tissue, termed ex vivo microscopy. Both in vivo and ex vivo microscopy have tremendous potential for clinical impact in a wide variety of applications. However, in order for these technologies to enter mainstream clinical care, an expert will be required to assess and interpret the imaging data. The optical images generated from these imaging techniques are often similar to the light microscopic images that pathologists already have expertise in interpreting. Other clinical specialists do not have this same expertise in microscopy, therefore, pathologists are a logical choice to step into the developing role of microscopic imaging expert. Here, we review the emerging technologies of in vivo and ex vivo microscopy in terms of the technical aspects and potential clinical applications. We also discuss why pathologists are essential to the successful clinical adoption of such technologies and the educational resources available to help them step into this emerging role. doi: 10.5858/arpa.2018-0298-RA), Optical imaging technologies have emerged as viable modalities for clinical diagnosis and patient management. A confluence of events has facilitated this progress: (1) the advancement and validation of technologies that [...]

Micrograph analysis and characterization is a key function of many materials laboratories supporting manufacturing, quality control, and R&D. While classic methods are subjective and resource intensive, advancements in capture technology [...]

Penrose's pentagonal P2 quasi-crystal.sup.1-4 is a beautiful, hierarchically organized multiscale structure in which kite- and dart-shaped tiles are arranged into local motifs, such as pentagonal stars, which are in turn arranged into various close-packed superstructural patterns that become increasingly complex at larger length scales. Although certain types of quasi-periodic structure have been observed in hard and soft matter, such structures are difficult to engineer, especially over large areas, because generating the necessary, highly specific interactions between constituent building blocks is challenging. Previously reported soft-matter quasi-crystals of dendrimers.sup.5, triblock copolymers.sup.6, nanoparticles.sup.7 and polymeric micelles.sup.8 have been limited to 12- or 18-fold symmetries. Because routes for self-assembling complex colloidal building blocks.sup.9-11 into low-defect dynamic superstructures remain limited.sup.12, alternative methods, such as using optical and directed assembly, are being explored.sup.13,14. Holographic laser tweezers.sup.15 and optical standing waves.sup.16 have been used to hold microspheres in local quasi-crystalline arrangements, and magnetic microspheres of two different sizes have been assembled into local five-fold-symmetric quasi-crystalline arrangements in two dimensions.sup.17. But a Penrose quasi-crystal of mobile colloidal tiles has hitherto not been fabricated over large areas. Here we report such a quasi-crystal in two dimensions, created using a highly parallelizable method of lithographic printing and subsequent release of pre-assembled kite- and dart-shaped tiles into a solution-dispersion containing a depletion agent. After release, the positions and orientations of the tiles within the quasi-crystal can fluctuate, and these tiles undergo random, Brownian motion in the monolayer owing to frequent collisions between neighbouring tiles, even after the system reaches equilibrium. Using optical microscopy, we study both the equilibrium fluctuations of the system at high tile densities and also the 'melting' of the pattern as the tile density is lowered. At high tile densities we find signatures of a five-fold pentatic liquid quasi-crystalline phase, analogous to a six-fold hexatic liquid crystal. Our fabrication approach is applicable to tiles of different sizes and shapes, and with different initial positions and orientations, enabling the creation of two-dimensional quasi-crystalline systems (and other systems that possess multiscale complexity at high tile densities) beyond those of current self- or directed-assembly methods.sup.18-20. We anticipate that our approach for generating lithographically pre-assembled monolayers could be extended to create three-dimensional Brownian systems of fluctuating particles with custom-designed shapes through holographic lithography.sup.21,22 or stereolithography.sup.23.A lithographic patterning and release method is used to create a dense, fluctuating, Brownian system of mobile colloidal kite- and dart-shaped Penrose tiles over large areas that retains quasi-crystalline order., Author(s): Po-Yuan Wang [sup.1] [sup.2] , Thomas G. Mason [sup.1] [sup.3] Author Affiliations:(1) Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, USA(2) Department of Materials Science and [...]

Fibrolamellar carcinoma is a rare primary hepatocellular malignancy arising in noncirrhotic livers of young individuals. Patients commonly present with a large solitary liver mass and nonspecific symptoms. Characteristic histologic features include large polygonal cells with oncocytic cytoplasm and prominent nucleoli separated into trabeculae and cords by dense parallel bands of collagen. Important differential diagnoses include classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma, which may be distinguished by a judicious panel of immunohistochemical studies, including cytokeratin 7, CD68, and hepatocyte paraffin 1 (HepPar-1). In addition, fibrolamellar carcinomas are characterized by activation of protein kinase A. Prognosis of fibrolamellar carcinoma is similar to classical hepatocellular carcinoma occurring in the absence of liver cirrhosis and is strongly correlated with tumor resectability. Other treatment options include liver transplant, chemotherapy, and hepatic artery embolization. In this article, we review the clinical features, gross and microscopic pathology, molecular genetics, differential diagnosis, treatment, and prognosis of this rare and interesting tumor. doi: 10.5858/arpa.2017-0083-RS, Fibrolamellar carcinoma (FLC) is a unique primary hepatocellular malignancy, encompassing patient demographics, risk factors, and tumor markers distinct from those of classical hepatocellular carcinoma (HCC). While the histologic features of [...]

* Context.--Spindle cell neoplasms arising in the skin comprise a heterogeneous group of tumors with divergent lineages. Cutaneous spindle cell neoplasms are relatively common and present surgical pathologists with diagnostic challenges. Recognition of their histopathologies is important for correct diagnosis and management. The current review presents a pattern-based diagnostic approach to common cutaneous spindle cell neoplasms that often cause diagnostic difficulties. Objective.--To provide a useful guide for diagnosis of cutaneous spindle cell neoplasms. Data Sources.--PubMed (US National Library of Medicine) reports and the authors' personal experiences are reviewed. Conclusions.--The authors briefly summarize the histologic features and differential diagnoses of common cutaneous spindle cell neoplasms. doi: 10.5858/arpa.2018-0112-RA, Cutaneous neoplasms entirely or predominantly composed of spindle cells constitute a heterogeneous group of mesenchymal and nonmesenchymal tumors. Cutaneous spindle cell neoplasms are often diagnostically challenging because of considerable morphologic [...]

Background Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Methods Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40 weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. Results During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32 weeks and was completed by 36 weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32 weeks, and the last sample with S-shaped bodies was from a fetus aged 36 weeks. Conclusions The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life., Author(s): Marija Dakovic Bjelakovic [sup.1] , Slobodan Vlajkovic [sup.1] , Aleksandar Petrovic [sup.2] , Marko Bjelakovic [sup.3] , Milorad Antic [sup.1] Author Affiliations: (Aff1) 0000 0001 0942 1176, grid.11374.30, Institute [...]

* Context.--Distinguishing chromophobe renal cell carcinoma (chRCC), especially in the presence of eosinophilic cytoplasm, from oncocytoma on hematoxylin-eosin can be difficult and often requires time-consuming ancillary procedures that ultimately may not be informative.Objective.--To explore the potential of multiphoton microscopy (MPM) as an alternative and rapid diagnostic tool in differentiating oncocytoma from chRCC at subcellular resolution without tissue processing.Design.--Unstained, deparaffinized tissue sections from 27 tumors (oncocytoma [n = 12], chRCC [n = 12], eosinophilic variant of chRCC [n = 1], and atypical oncocytic renal neoplasm [n = 2]) were imaged with MPM. Morphologic evaluation and automated quantitative morphometric analysis were conducted to distinguish between chRCC and oncocytoma.Results.--The typical cases of oncocytomas (12 of 12) and chRCC (12 of 12) could be readily differentiated on MPM based on the morphologic features similar to hematoxylin-eosin. The most striking MPM signature of both of the tumors was the presence of autofluorescent intracytoplasmic granules, which are not seen on hematoxylin-eosin-stained slides. Although we saw these granules in both types of tumors, they appeared distinct, based on their size, shape, cytoplasmic distribution, and autofluorescence wavelengths, and were valuable in arriving at a definitive diagnosis. For oncocytomas and chRCC, high diagnostic accuracies of 100% and 83.3% were achieved on blinded MPM and morphometric analysis, respectively.Conclusions.--To the best of our knowledge, this is the first demonstration of MPM to distinguish chRCC from oncocytoma in fixed tissues. Our study was limited by small sample size and only a few variants of oncocytic tumors. Prospective studies are warranted to assess the utility of MPM as a diagnostic aid in oncocytic renal tumors.(Arch Pathol Lab Med. 2018;142:383-390; doi: 10.5858/arpa.2017-0056-OA), Kidney tumors are a heterogeneous group of benign and malignant neoplasms with varied histomorphologic features and clinical outcomes. (1,2) Most of these tumors are readily identified and differentiated from each [...]

Objective To investigate changes in malaria prevalence in Papua New Guinea after the distribution of long-lasting Insecticide-treated nets, starting in 2004, and the introduction of artemisinin-based combination therapy in 2011. Methods Two malaria surveys were conducted in 2010-2011 and 2013-2014. They included 77 and 92 randomly selected villages, respectively. In each village, all members of 30 randomly selected households gave blood samples and were assessed for malaria infection by light microscopy. In addition, data were obtained from a malaria survey performed in 2008-2009. Results The prevalence of malaria below 1600 m in altitude decreased from 11.1% (95% confidence interval, CI: 8.5-14.3) in 2008-2009 to 5.1% (95% CI 3.6-7.4) in 2010-2011 and 0.9% (95% CI 0.6-1.5) in 2013-2014. Prevalence decreased with altitude. Plasmodium falciparum was more common than P. vivax overall, but not everywhere, and initially the prevalence of P. vivax infection decreased more slowly than P. falciparum infection. Malaria infections were clustered in households. In contrast to findings in 2008-2009, no significant association between net use and prevalence was found in the later two surveys. The prevalence of both fever and splenomegaly also decreased but their association with malaria infection became stronger. Conclusion Large-scale insecticide-treated net distribution was associated with an unprecedented decline in malaria prevalence throughout Papua New Guinea, including epidemic-prone highland areas.The decline was accompanied by broader health benefits, such as decreased morbidity. Better clinical management of nonmalarial fever and research into residual malaria transmission are required. Objectif Etudier les changements observes a legard de la prevalence du paludisme en Papouasie-Nouvelle-Gulnee suite a la distribution, depuis 2004, de moustiquaires impregnees d'Insecticides de longue duree et a l'introduction, depuis 2011, d'une combinaison therapeutique a base d'artemisinine. Methodes Deux enquetes portant sur le paludisme ont ete menees en 2010-2011 et 2013-2014. Elles incluaient respectivement 77 et 92 villages, selectionnes d'une maniere aleatoire. Dans chacun de ces villages, tous les membres de 30 foyers selectionnes aleatoirement ont donne des echantillons sanguins et ete soumis a un test de depistage de l'infection palustre par microscopie optique. Des donnees ont par ailleurs ete tirees d'une enquete sur le paludisme realisee en 2008-2009. Resultats La prevalencedu paludisme a moins de 1600 m d'altitude est passee de 11,1 % (intervalle de confiance, IC, a 95%: 8,5-14,3) en 2008-2009 a 5,1 % (IC a 95%: 3,6-7,4) en 2010-2011 et 0,9% (IC a 95%: 0,6-1,5) en 2013-2014. La prevalence diminuait avec l'altitude. Plasmodium falciparum n'etait pas systematiquement plus courant que R vivax, mais l'etait dans l'ensemble et, dans un premier temps, la prevalence de l'infection a R vivax a diminue plus lentement que la prevalence de l'Infection a P. falciparum. Les infections palustres ont ete regroupees par foyers. Contrairement a ce qu'indiquaient les resultats obtenus en 2008-2009, aucune correlation significative entre l'utilisation d'une moustiquaire et la prevalence n'a ete constatee dans le cadre des deux dernieres enquetes. Les prevalences de la fievre et de la splenomegalle ont egalement diminue, mais leur correlation avec l'infection palustre est devenue plus forte. Conclusion La distribution a grande echelle de moustiquaires impregnees d'insecticides a ete associee a un declin sans precedent de la prevalence du paludisme dans l'ensemble de la Papouasie-Nouvelle-Guinee, et notamment dans les reglons montagneuses sujettes aux epidemies. Ce declin s'est accompagne d'autres bienfaits sur la sante, et notamment d'une diminution de la morbidite. Il est necessaire d'ameliorer la prise en charge clinique de la fievre non palustre ainsi que les recherches sur la transmission residuelle du paludisme. Objetivo Investigar los cambios en la prevalencia de la malaria en Papua Nueva Guinea tras la distribucion de mosquiteros tratados con insecticida de larga duracion, a partir de 2004, y la introduccion de terapias combinadas basadas en la artemisinina en 2011. Metodos Se llevaron a cabo dos encuestas sobre la malaria en 2010-2011 y 2013-2014. Incluian 77y 92 aldeas seleccionadas al azar, respectivamente. En cada aldea, todos los miembros de 30 hogares seleccionados al azar dieron muestras de sangre y se evaluaron de infeccion de malaria con microscopio optico. Ademas, se obtuvieron datos de la encuesta sobre la malaria realizada en 2008-2009. Resultados La prevalencia de la malaria por debajo de 1600 m de altitud descendio del 11.1% (intervalo de confidencia (IC) del 95%: 8.5-14.3) en 2008-2009 al 5.1% (95% IC 3.6-7.4) en 2010-2011 y 0.9% (95% IC 0.6-1.5) en 2013-2014. La prevalencia descendia con la altitud. Plasmodium falciparum fue mas comun que P. vivax en general, pero no en todas partes e inicialmente la prevalencia de la infeccion P. vivax descendio mas lentamente que la infeccion P. falciparum. Las infecciones de malaria se agruparon en los hogares. Al contrario que los hallazgos en 2008-2009, no se encontro ninguna asociacion significativa entre el uso del mosquitero y la prevalencia en las dos ultimas encuestas. La prevalencia tanto de la fiebre como de la esplenomegalia tambien descendio, pero su asociacion con la infeccion de malaria se hizo mas fuerte. Conclusion La distribucion de mosquiteros tratados con insecticida a gran escala se asocio con un descenso sin precedentes en la prevalencia de la malaria en toda Papua Nueva Guinea, incluidas las areas altas con propension a causar epidemias. El descenso estuvo acompanado de beneficios saludables mas amplios, como el descenso de la morbilidad. Se requieren una mejor gestion clinica de la fiebre no relacionada con la malaria y la Investigacion de la transmision residual de la malaria., Introduction Historically, malaria has been endemic throughout Papua New Guinea, except in highland areas over 1600 m, where temperatures are low and there is no stable local transmission, though imported [...]

The impulse acoustic microscopy method was applied to observe the bulk microstructure and to measure sonic velocities and elastic moduli in the carbon nanocomposite specimens prepared by a traditional method and with the use of a vacuum mixer. It is shown that carbon nanoparticles tend to cluster and form micron-sized aggregates. The impulse acoustic microscopy technique makes it possible to visualize a nonuniform distribution of carbon nanofillers over the specimen bulk. Both nanotube and nanoplatelets conglomerates are visible most likely due to the air containing. Results of the elastic measurements demonstrate homogeneity of elastic properties over the material bulk and a weak dependence of sonic velocities and elastic moduli on the filler content. Reduction of the air content and enhancement of elastic properties are observed when increasing the nanofiller content and employing the vacuum mixing technology in nanocomposite fabrication., INTRODUCTION Essential changes in material properties of nanocomposites result from formation of extensive networks of contacting nanoparticles with high values of the aspect ratio--nanotubes, nanoplatelets, nanoflakes, and so forth. A [...]

Non-destructive inspection of carbon fiber-reinforced (CFR) composites applied to aerospace industry attracts wide attention. In this article, high frequency (50-100 MHz) focused ultrasound has been applied to study defects and destruction processes in the bulk microstructure of the CFR material and constructions under the mechanical loading. It has been shown that the impulse acoustic microscopy provides detecting areas of structural failures and adhesion losses at the millimeter and micron level. Behavior of the CFR laminate structure fabricated by prepreg or infusion technology has been investigated under the tensile and impact loading., INTRODUCTION Application of fiber-reinforced polymers (FRP) is extensive in aviation industry due to their excellent strength-to-weight ratio. The sufficient strength is achieved by reinforcement of polymer matrix by regular packaging [...]

Author(s): Ekaterini Siomou [sup.1] , Maria Baziou [sup.1] , Evagelos Premetis [sup.2] , Cristina Vercellati [sup.3] , Nikolaos Chaliasos [sup.1] , Alexandros Makis [sup.1] Author Affiliations: (1) Department of Pediatrics, [...]

Retention of long-term repopulating hematopoietic stem cells (LT-HSCs) in the bone marrow is essential for hematopoiesis and for protection from myelotoxic injury. We report that signaling cascades that are traditionally viewed as coagulation related also control retention of endothelial protein C receptor-positive (EPCR[sup.+]) LT-HSCs in the bone marrow and their recruitment to the blood via two pathways mediated by protease activated receptor 1 (PAR1). Thrombin-PAR1 signaling induces nitric oxide (NO) production, leading to EPCR shedding mediated by tumor necrosis factor-[alpha]-converting enzyme (TACE), enhanced CXCL12-CXCR4-induced motility and rapid stem and progenitor cell mobilization. Conversely, bone marrow blood vessels provide a microenvironment enriched with activated protein C (aPC) that retains EPCR[sup.+] LT-HSCs by limiting NO generation, reducing Cdc42 activity and enhancing integrin VLA4 affinity and adhesion. Inhibition of NO production by aPC-EPCR-PAR1 signaling reduces progenitor cell egress from the bone marrow, increases retention of bone marrow NO[sup.low] EPCR[sup.+] LT-HSCs and protects mice from chemotherapy-induced hematological failure and death. Our study reveals new roles for PAR1 and EPCR in controlling NO production to balance maintenance and recruitment of bone marrow EPCR[sup.+] LT-HSCs, with potential clinical relevance for stem cell transplantation., Author(s): Shiri Gur-Cohen [1]; Tomer Itkin [1]; Sagarika Chakrabarty [2]; Claudine Graf [3]; Orit Kollet [1]; Aya Ludin [1]; Karin Golan [1]; Alexander Kalinkovich [1]; Guy Ledergor [1, 4]; Eitan [...]

Byline: Sameer. Vyas, Vikas. Bhatia, Gargi. Dass, Naveen. Sankhyan Hemispheric status epilepticus showing both macroscopic (MR angiography) and microscopic (arterial spin labelling) perfusion abnormalities with crossed cerebellar diachisis is an [...]

Byline: Benedict. Samuel, Joy. Michael, J. Chandrasingh, Santosh. Kumar, Antony. Devasia, Nitin. Kekre Introduction: The aim was to study the accuracy of Xpert® (Cepheid Inc., Sunnyvale, CA, USA) Mycobacterium tuberculosis/rifampicin [...]

During the last few decades, there have been major advancements in optical imaging techniques in both technology development and validation studies for use in clinical applications. These optical imaging techniques [...]

Byline: P. Jahagirdar, A. Kale, S. Hallikerimath Introduction: Odontogenic lesions represent a range of conditions, the features of which probably depend on the stage of induction towards tooth formation reached [...]

Byline: Nikita. Lodha, Shital. Poojary Background: The mycological study of pityriasis versicolor is usually done by potassium hydroxide (KOH) mount and culture. However, KOH mount lacks a color contrast and [...]