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* Context.--Despite several studies focusing on the validation of whole slide imaging (WSI) across organ systems or subspecialties, the use of WSI for specific primary diagnosis tasks has been underexamined. Objective.--To assess pathologist performance for the histologic subtyping of individual sections of ovarian carcinomas using a light microscope and WSI. Design.--A panel of 3 experienced gynecologic pathologists provided reference subtype diagnoses for 212 histologic sections from 109 ovarian carcinomas based on optical microscopy review. Two additional attending pathologists provided diagnoses and also identified the presence of a set of 8 histologic features important for ovarian tumor subtyping. Two experienced gynecologic pathologists and 2 fellows reviewed the corresponding WSI images for subtype classification and feature identification. Results.--Across pathologists specialized in gynecologic pathology, concordance with the reference diagnosis for the 5 major ovarian carcinoma subtypes was significantly higher for a pathologist reading on a microscope than each of 2 pathologists reading on WSI. Differences were primarily due to more frequent classification of mucinous carcinomas as endometrioid with WSI. Pathologists had generally low agreement in identifying histologic features important to ovarian tumor subtype classification with either an optical microscopy or WSI. This result suggests the need for refined histologic criteria for identifying such features. Interobserver agreement was particularly low for identifying intracytoplasmic mucin with WSI. Inconsistencies in evaluating nuclear atypia and mitoses with WSI were also observed. Conclusions.--Further research is needed to specify the reasons for these diagnostic challenges and to inform users and manufacturers of WSI technology., More than 90% of ovarian malignancies consist of epithelial cancers, (1) which are further classified into 5 major subtypes, namely high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), clear cell [...]

Context.--The increases in overall life expectancy and in lens surgeries performed on younger patients have resulted in a significant increase in the anticipated duration of artificial intraocular lenses (IOLs) in the eye. Thus, the physicochemical properties of the IOL become a critical issue, and several types of postoperative IOL opacifications have been reported. Objective.--To describe the microscopic characteristics of opacified IOLs. Glistenings and subsurface nanoglistenings are fluid-related phenomena developing mainly in hydrophobic acrylic IOLs and are associated with aqueous influx into the IOL matrix. Calcification presents in hydrophilic acrylic or silicone IOLs as deposits of hydroxyapatite or other phases of calcium. Snowflake degeneration is less common, and it manifests in older polymethyl methacrylate IOLs. Data Sources.--PubMed and ScienceDirect databases were searched for the following keywords: intraocular lens, IOL, cataract surgery, phacoemulsification, opacification, glistening, subsurface nanoglistenings, calcifica tion, snowflake degeneration. English-language articles published up to October 15, 2019 were included in the study. The manuscript contains mainly a literature review; however, it was supplemented with original investigations from the David J. Apple International Laboratory for Ocular Pathology. Conclusions.--Glistenings and subsurface nanoglistenings should be evaluated in a hydrated state and at room temperature; they manifest as microvacuoles sized from 1.0 to greater than 25.0 [micro]m and less than 200 nm, respectively. Calcification deposits are situated on or underneath the surface of the IOL and can be stained with a 1% alizarin red solution or with the von Kossa method. Snowflake degeneration manifests as 'particles' or 'crystals,' causing whitish IOL discoloration. Scanning electron microscopy or energy dispersive X-ray spectroscopy may improve the diagnostic accuracy. (Arch Pathol Lab Med. 2021;145:759-767; doi: 10.5858/arpa.2019-0626-RA, Phacoemulsification cataract surgery is the most common surgical procedure performed in medicine. In 2016, more than 20 million surgeries were carried out worldwide, of which 4.5 million were in the [...]

This new periodic column will help clinicians evaluate their proficiency and gain new knowledge in the general principles of dermoscopy. To assess your diagnostic skills, please assess cases 1 through [...]

ABSTRACT Lentigo maligna (LM) is an in situ variant of cutaneous melanoma, which usually occurs in sun-damaged skin. Surgical treatment of LM is often difficult and not well accepted by [...]

This periodic column will help clinicians evaluate their own proficiency and gain new knowledge in the general principles of dermoscopy. To assess diagnostic skills, review questions 1 to 4- Answers [...]

Objective To evaluate the relative cost-effectiveness in different sub-Saharan African settings of presumptive treatment, field-standard microscopy and rapid diagnostic tests (RDTs) to diagnose malaria. Methods We used a decision tree model and probabilistic sensitivity analysis applied to outpatients presenting at rural health facilities with suspected malaria. Costs and effects encompassed those for both patients positive on RDT (assuming artemisinin-based combination therapy) and febrile patients negative on RDT (assuming antibiotic treatment). Interventions were defined as cost-effective if they were less costly and more effective or had an incremental cost per disability-adjusted life year averted of less than US$ 150. Data were drawn from published and unpublished sources, supplemented with expert opinion. Findings RDTs were cost-effective compared with presumptive treatment up to high prevalences of Plasmodium falciparum parasitaemia. Decision-makers can be at least 50% confident of this result below 81% malaria prevalence, and 95% confident below 62% prevalence, a level seldom exceeded in practice. RDTs were more than 50% likely to be cost-saving below 58% prevalence. Relative to microscopy, RDTs were more than 85% likely to be cost-effective across all prevalence levels, reflecting their expected better accuracy under real-life conditions. Results were robust to extensive sensitivity analysis. The cost-effectiveness of RDTs mainly reflected improved treatment and health outcomes for non-malarial febrile illness, plus savings in antimalarial drug costs. Results were dependent on the assumption that prescribers used test results to guide treatment decisions. Conclusion RDTs have the potential to be cost-effective in most parts of sub-Saharan Africa. Appropriate management of malaria and non-malarial febrile illnesses is required to reap the full benefits of these tests. Bulletin of the World Health Organization 2008;86:101-110. Objectif Evaluer le rapport cout-efficacite dans differents pays d'Afrique subsaharienne du traitement presomptif, de la microscopie classique sur le terrain et des tests diagnostiques rapides (TDR) dans le diagnostic du paludisme. Methodes Nous avons fait appel a un module d'arbre de decisions et a une analyse probabiliste de sensibilite, qui ont ete appliques aux patients se presentant en ambulatoire dans des 6tablissements de soins ruraux avec une presomption de paludisme. Nous avons evalue les couts et les effets du traitement la fois pour les patients positifs aux TDR (en les supposant sous traitement par une polytherapie a base d'artemisinine) et les patients febriles negatifs a ces tests (en les supposant sous traitement antibiotique). Nous avons consider que les interventions etalent efficientes sous rangle economique si elles etaient moins couteuses et plus efficaces ou si elles fournissaient un coot marginal par annee de vie corrigee de I'incapacite evite inferieur US $150. Les donnees ont ete extraites de sources publiees et non publiees, completees par des avis d'experts. Resultats Les TDR se sont reveles efficaces sur le plan economique par comparaison avec le traitement presomptif jusqu'a des valeurs elevees de la parasitemie due a Plasmodium falciparum. Les d6cideurs peuvent accorder a ce resultat un niveau de confiance de 50 % lorsque la prevalence du paludisme est inferieure a 81% et de 95 % lorsque cette prevalence est infeieure a 62 %, niveau rarement depasse dans la pratique. Au-dessous de 58 % de prevalence, la probabilite que les TDR permettent des economies etait superieure a 50 %. Par rapport la microscopie, les tests avaient une probabilite de plus de 85 % d'avoir un bon ratio cout-efficacite sur I'ensemble des niveaux de prevalence, en accord avec la meilleure precision qu'on s'attend a leur voir fournir en conditions reelles. Ces resultats ont resiste a une analyse de sensibilite approfondie. Le rapport cout-efficacite des TDR refletait principalement I'amelioration des traitements et des issues des maladies febriles non palustres, ainsi que les economies realisees sur les coots des antipaludiques. Ces resultats supposaient que les prescripteurs aient utilise les reponses des tests pour guider les decisions therapeutiques. Conclusion Les TDR sont en mesure d'avoir un bon rapport coutefficacite dans la plupart des regions de l'Afrique subsaharienne. Une prise en charge appropriee du paludisme et des maladies febriles non palustres est necessaire pour tirer un benefice maximal de ces tests. Objetivo Evaluar en diferentes entornos subsaharianos la costoeficacia relativa del tratamiento de sospecha, la microscopia estandar de campo y las pruebas de diagnostico rapido (PDR) de la malaria. Metodos Se aplico un modelo de arbol decisional y un analisis de sensibilidad probabilistico a pacientes ambulatorios que acudieron a establecimientos de salud rurales con presunta malaria. Se consideraron los costos y los efectos tanto para los pacientes positivos en la PDR (suponiendo que se administraron tratamiento combinado con artemisinina) como para los pacientes febriles negativos en la PDR (suponiendo que se administraron antibioticos). Se definieron como costoeficaces las intervenciones que fueron menos costosas y mas eficaces o que habfan tenido un costo marginal por AVAD (ano de vida ajustado en funcion de la discapacidad) ganado de menos de US$150. Los datos empleados se extrajeron de trabajos publicados o ineditos y se complementaron con la opinion de expertos. Resultados Las PDR fueron costoeficaces en comparacion con el tratamiento de sospecha hasta valores altos de la prevalencia de parasitemia por Plasmodium falciparum. Las instancias decisorias pueden confiar con una probabilidad de al menos un 50% en ese resultado por debajo de una prevalencia de malaria del 81%, y del 95% por debajo de una prevalencia del 62%, nivel rara vez superado en la practica. Las PDR tenian una probabilidad mayor del 50% de ser costoeficaces por debajo de una prevalencia del 58%. En lo que respecta a la microscopia, las PDR tenian mas de un 85% de probabilidades de ser costoeficaces en todos los niveles de prevalencia, lo que refleja la mayor exactitud previsible en condiciones reales. Un extenso analisis de sensibilidad revelo que los resultados eran robustos. La costoeficacia de las PDR se debio principalmente al mejor tratamiento y resultados sanitarios conseguidos con las dolencias febriles no malaricas, mas lo ahorrado en concepto de medicamentos antimalaricos. Los resultados dependen del supuesto de que los prescriptores tomaron sus decisiones terapeuticas en funcion de los resultados de las pruebas. Conclusion Las PDR pueden ser costoeficaces en la mayoria del Africa subsahariana, pero para poder sacar el maximo provecho de esas pruebas hay que tratar adecuadamente la malaria y las enfermedades febriles no malaricas., Introduction The introduction of high-cost antimalarial drugs such as artemisinin-based combination therapy (ACT) is encouraging malaria-endemic countries in sub-Saharan Africa to reassess diagnostic practices. Traditional practice for outpatients has been [...]

A scanning phosphorescence quenching microscopy technique, designed to prevent accumulated [O.sub.2] consumption by the method, was applied to P[O.sub.2] measurements in mesenteric tissue. In an attempt to further increase the accuracy of the measurements, albumin-bound probe was topically applied to the tissue and an objective-mounted pressurized bag was used to reduce the oxygen transport bypass through the thin layer of fluid over the mesentery. P[O.sub.2] was measured at multiple sites perpendicular to the blood/wall interface in the vicinity of 84 mesenteric arterioles (7-39 [micro]m in diameter) at distances of 5, 15, 30, 60, 120, and 180 [micro]m in seven anesthetized Sprague-Dawley rats, thereby creating P[O.sub.2] profiles. Interstitial P[O.sub.2] above and immediately beside arterioles was found to agree with known intravascular values. No significant difference in P[O.sub.2] profiles was found between small and large arterioles, indicating a small longitudinal P[O.sub.2] gradient in the precapillary mesenteric microvasculature. In addition, the P[O.sub.2] profiles were used to calculate oxygen consumption in the mesenteric tissue (56-65 nl [O.sub.2]x[cm.sup.-3]x[s.sup.-1]). Correction of these values for contamination with ambient oxygen yielded an oxygen consumption rate of 60-68 nl [O.sub.2]x[cm.sup.-3]x[s.sup.-1], the maximal limit for consumption in the mesentery. The results were compared with measurements made by other workers in regard to the employed techniques. microcirculation; oxygen tension gradients; phosphorescence quenching microscopy

Familial hypertrophic cardiomyopathy is a disease characterized by left ventricular and/or septal hypertrophy and myofibrillar disarray. It is caused by mutations in sarcomeric proteins, including the ventricular isoform of myosin regulatory light chain (RLC). The E22K mutation is located in the RLC [Ca.sup.2+]-binding site. We have studied transgenic (Tg) mouse cardiac myofibrils during single-turnover contraction to examine the influence of E22K mutation on 1) dissociation time ([[tau].sub.1]) of myosin heads from thin filaments, 2) rebinding time ([[tau].sub.2]) of the cross bridges to actin, and 3) dissociation time ([[tau].sub.3]) of ADP from the active site of myosin. [[tau].sub.1] was determined from the increase in the rate of rotation of actin monomer to which a cross bridge was bound. [[tau].sub.2] was determined from the rate of anisotropy change of the recombinant essential light chain of myosin labeled with rhodamine exchanged for native light chain (LC1) in the cardiac myofibrils. [[tau].sub.3] was determined from anisotropy of muscle preloaded with a stoichiometric amount of fluorescent ADP. Cross bridges were induced to undergo a single detachment-attachment cycle by a precise delivery of stoichiometric ATP from a caged precursor. The times were measured in Tg-mutated (Tg-m) heart myofibrils overexpressing the E22K mutation of human cardiac RLC. Tg wild-type (Tg-wt) and non-Tg muscles acted as controls, [[tau].sub.1] was statistically greater in Tg-m than in controls. [[tau].sub.2] was shorter in Tg-m than in non-Tg, but the same as in Tg-wt. [[tua].sub.3] was the same in Tg-m and controls. To determine whether the difference in [[tau].sub.1] was due to intrinsic difference in myosin, we estimated binding of Tg-m and Tg-wt myosin to fluorescently labeled actin by measuring fluorescent lifetime and time-resolved anisotropy. No difference in binding was observed. These results suggest that the E22K mutation has no effect on mechanical properties of cross bridges. The slight increase in [[tau].sub.1] was probably caused by myofibrillar disarray. The decrease in [[tau].sub.2] of Tg hearts was probably caused by replacement of the mouse RLC for the human isoform in the Tg mice. confocal microscopy; anisotropy

Hyperspectual interferometric microscopy uses a unique combination of optics and algorithm design to extract information. Local brain activity rapidly changes local blood flow and red blood cell concentration (absorption) and oxygenation (color). We demonstrate that brain activity evoked during whisker stimulation can be detected with hyperspectral interferometric micriscopy to identify the active whisker--spectral band. Algorithms can be flexibly optimized to discover, detect, quantify, and visualize a wide range of significant biological events, including changes relevant to the diagnosis and treatment of disease. OCIS codes: 100.0100, 100.2000, 100.2960, 170.4580.

We report the application of confocal imaging and fluorescence correlation spectroscopy (FCS) to characterize chemically well-defined lipid bilayer models for biomembranes. Giant unilamellar vesicles of dilauroyl phosphatidylcholine/dipalmitoyl phosphatidylcholine (DLPC/DPPC)/cholesterol were imaged by confocal fluorescence microscopy with two fluorescent probes, 1,1[prime]-dieicosanyl-3,3,3[prime],3[prime]-tetramethylindocarbocyanine perchlorate (DiI-[C.sub.20]) and 2- (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-l-hexadecanoyl-sn-glycero-3-phosphocholine (Bodipy-PC). Phase separation was visualized by differential probe partition into the coexisting phases. Three-dimensional image reconstructions of confocal z-scans through giant unilamellar vesicles reveal the anisotropic morphology of coexisting phase domains on the surface of these vesicles with full two-dimensional resolution. This method demonstrates by direct visualization the exact superposition of like phase domains in apposing monolayers, thus answering a long-standing open question. Cholesterol was found to induce a marked change in the phase boundary shapes of the coexisting phase domains. To further characterize the phases, the translational diffusion coefficient, [D.sub.T], of the DiI-[C.sub.20] was measured by FCS. [D.sub.T] values at [approximately]25 [degrees] C ranged from [approximately]3 x [10.sup.-8] [cm.sup.2]/s in the fluid phase, to [approximately]2 x [10.sup.-9] [cm.sup.2]/s in high-cholesterol-content phases, to [approximately]2 x [10.sup.-10] [cm.sup.2]/s in the spatially ordered phases that coexist with fluid phases. In favorable cases, FCS could distinguish two different values of [D.sub.T] in a region of two-phase coexistence on a single vesicle.

A method to measure osmotic water permeabilty (Pf) of plasma membranes in cell layers was developed, and applied to cells and epithelia expressing molecular water channels. The integrated intensity f monochromatic light in phase contrast or dark field microscope was found to depend on relative cell voluem. The results confirm light microscopy with spatial filtering as a technically simple and quantitative way of measuring water permeability in cell layers.

The effect of polyethylene glycol with pendant amino groups on the higher order structure of isolated long DNA chains was investigated. Its efficiency in the compaction of the the DNA was compared with that induced by neutral polyethylene glycol. Considering the salt efffect, results reveal that polyethylene glycol with pendant amino groups exhibit similar properties to that induced by neutral polyethylene glycol.

It is possible to use laser confocal fluorescence microscopy to demonstrate intercellular adhesion molecule (ICAM-1) expression in rat microvessels in vivo. This can make a valuable contribution to the study of constitutive expression of the ICAM-1 among capillaries, arterioles and venules in the mesentery and liver. It appears that postcapillary venules act as an active gateway, being prepared to assist in the adhesion of circulating leukocytes exposed to proinflammatory stimuli in acute inflammation.

A novel fluorescence video microscope was used to examine interconnections between alterations in intracellular calcium concentration (Ca2+)i and intracellular pH in Madin-Darby canine kidney cells and kidney glomerular epithelial cells subjected to different stimulus. Considerable differences in (Ca2+)i and pHi in glomerular epithelial cells and Madin-Darby canine kidney cells in their resting condition and during response to NH4Cl loading, was observed. A need for synchronized and sustained rectification of calcium determinations with existing pH received from correlating regions of the cellular pH map was observed.

Details about an experimental technique designed to help distinguish and document whether a patient has been sexually assaulted have been presented. The technology involves linking two magnifying tools to a video camera, computer, and printer. One magnifying tool called a colposcope is used to examine trauma to the vaginal tissues and a light staining microscope is used to visualize the presence of sperm. This technology has been used in 15 investigations of sexual assault.