Surgical biomicroscopy-guided intra-operative optical coherence tomography (iOCT) image super-resolution.

PURPOSE: Intra-retinal delivery of novel sight-restoring therapies will require the precision of robotic systems accompanied by excellent visualisation of retinal layers. Intra-operative Optical Coherence Tomography (iOCT) provides cross-sectional retinal images in real time but at the cost of image quality that is insufficient for intra-retinal therapy delivery.This paper proposes a super-resolution methodology that improves iOCT image quality leveraging spatiotemporal consistency of incoming iOCT video streams. METHODS: To overcome the absence of ground truth high-resolution (HR) images, we first generate HR iOCT images by fusing spatially aligned iOCT video frames. Then, we automatically assess the quality of the HR images on key retinal layers using a deep semantic segmentation model. Finally, we use image-to-image translation models (Pix2Pix and CycleGAN) to enhance the quality of LR images via quality transfer from the estimated HR domain. RESULTS: Our proposed methodology generates iOCT images of improved quality according to both full-reference and no-reference metrics. A qualitative study with expert clinicians also confirms the improvement in the delineation of pertinent layers and in the reduction of artefacts. Furthermore, our approach outperforms conventional denoising filters and the learning-based state-of-the-art. CONCLUSIONS: The results indicate that the learning-based methods using the estimated, through our pipeline, HR domain can be used to enhance the iOCT image quality. Therefore, the proposed method can computationally augment the capabilities of iOCT imaging helping this modality support the vitreoretinal surgical interventions of the future.

Organotin Schiff bases as halofluorochromic dyes: green synthesis, chemio-photophysical characterization, DFT, and their fluorescent bioimaging in vitro.

Fluorescent bioimaging is an excellent tool in cellular biology, and it will be a powerful technique in modern medicine as a noninvasive imaging technology where tumoral and normal cells must be distinguished. One of the differences between normal and cancer cells is the intracellular pH. Therefore, the design and synthesis of pH-responsive fluorescent materials are required. Organotin Schiff bases showed halofluorochromic behavior in solution. Microwave-assisted synthesis showed better reaction times and chemical yields compared with conventional heating. All compounds were fully characterized by spectroscopic and spectrometric techniques. The halofluorochromism study showed that some molecules in acidic media have the maximum luminescence intensity due to protonation. All the fluorescent tin complexes showed cell staining on hepatocyte and MCF-7 cells by confocal microscopy. The theoretical study has enabled us to rationalize the optical properties and the halofluorochromism for compounds 1 and 2 synthesized in this work. Our results showed that the emission decrease, in the acid and basic media for compounds 1 and 2, respectively, is caused by intramolecular charge transfer (ICT) deactivation.

Deep iterative vessel segmentation in OCT angiography.

This paper addresses retinal vessel segmentation on optical coherence tomography angiography (OCT-A) images of the human retina. Our approach is motivated by the need for high precision image-guided delivery of regenerative therapies in vitreo-retinal surgery. OCT-A visualizes macular vasculature, the main landmark of the surgically targeted area, at a level of detail and spatial extent unattainable by other imaging modalities. Thus, automatic extraction of detailed vessel maps can ultimately inform surgical planning. We address the task of delineation of the Superficial Vascular Plexus in 2D Maximum Intensity Projections (MIP) of OCT-A using convolutional neural networks that iteratively refine the quality of the produced vessel segmentations. We demonstrate that the proposed approach compares favourably to alternative network baselines and graph-based methodologies through extensive experimental analysis, using data collected from 50 subjects, including both individuals that underwent surgery for structural macular abnormalities and healthy subjects. Additionally, we demonstrate generalization to 3D segmentation and narrower field-of-view OCT-A. In the future, the extracted vessel maps will be leveraged for surgical planning and semi-automated intraoperative navigation in vitreo-retinal surgery.

Learned optical flow for intra-operative tracking of the retinal fundus.

PURPOSE: Sustained delivery of regenerative retinal therapies by robotic systems requires intra-operative tracking of the retinal fundus. We propose a supervised deep convolutional neural network to densely predict semantic segmentation and optical flow of the retina as mutually supportive tasks, implicitly inpainting retinal flow information missing due to occlusion by surgical tools. METHODS: As manual annotation of optical flow is infeasible, we propose a flexible algorithm for generation of large synthetic training datasets on the basis of given intra-operative retinal images. We evaluate optical flow estimation by tracking a grid and sparsely annotated ground truth points on a benchmark of challenging real intra-operative clips obtained from an extensive internally acquired dataset encompassing representative vitreoretinal surgical cases. RESULTS: The U-Net-based network trained on the synthetic dataset is shown to generalise well to the benchmark of real surgical videos. When used to track retinal points of interest, our flow estimation outperforms variational baseline methods on clips containing tool motions which occlude the points of interest, as is routinely observed in intra-operatively recorded surgery videos. CONCLUSIONS: The results indicate that complex synthetic training datasets can be used to specifically guide optical flow estimation. Our proposed algorithm therefore lays the foundation for a robust system which can assist with intra-operative tracking of moving surgical targets even when occluded.

Boron Schiff bases derived from α-amino acids as nucleoli/cytoplasm cell-staining fluorescent probes in vitro.

The size, shape, and number of nucleoli in a cell's nucleus might help to distinguish a malignant from a benign tumor. Cellular biology and histopathology often require better visualization to understand nucleoli-related processes, thus organelle-specific fluorescent markers are needed. Here, we report the design, synthesis, and fully chemo-photophysical characterization of fluorescent boron Schiff bases (BOSCHIBAs), derived from α-amino acids (i.e., phenylalanine, tyrosine and tryptophan), with nucleoli- and cytoplasm-specific staining in cells. It is the first time that Boron Schiff bases derived from α-amino acids act as notorious dual (nucleoli and cytoplasm) cell-staining fluorescent probes. The boron derivatives not only showed good photostability and acceptable quantum yields (∼5%) in solution, but also exhibited low cytotoxicity (>90% cell viability at 0.1 and 1 µg mL-1), which make them good candidates to be used in medical diagnosis.

Implementing Systems Medicine: A Medical Informatics Perspective.

Systems medicine is a paradigm for translating in silico methods developed for modelling biological systems into the field of medicine. Such approaches rely on the integration of as many data sources as possible, both in the dimension of disease knowledge and patient data. This is a challenging task that can only be implemented in clinical routine with the help of suitable information technology from the field of Medical Informatics. For the research project "Clinically-applicable, omics-based assessment of survival, side effects, and targets in multiple myeloma" (CLIOMMICS) we developed a prototypical systems medicine application system. It is based on a three-level-architecture covering data representation, decision support, and user interface. The core decision support component is implemented as a case-based reasoning engine. However, the architecture follows a modular design that allows to replace individual components as needed.

Organotin Dyes Bearing Anionic Boron Clusters as Cell-Staining Fluorescent Probes.

Within the cell nucleus, in the nucleoli, ribosomal RNAs are synthesized and participate in several biological processes. To better understand nucleoli-related processes, their visualization is often required, for which specific markers are needed. Herein, we report the design of novel fluorescent organotin compounds derived from 4-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide and their cytoplasm and nucleoli staining of B16F10 cells in vitro. Tin compounds bearing an aliphatic carbon chain (-C12 H25 ) and an electron-donating group (-OH) were prepared, and the latter could be derivatized to bear the boron cluster anions [B12 H12 ]2- and [3,3'-Co(1,2-C2 B9 H11 )2 ]- (COSAN). All of the conjugates have been fully characterized and their luminescence properties have been assessed. In general, they show good quantum yields in solution (24-49 %), those for the COSAN derivatives being lower. Remarkably, the linking of [B12 H12 ]2- and COSAN to the complexes made them more soluble, without being detrimental to their luminescence properties. Living B16F10 cells were treated with all of the compounds to determine their fluorescence staining properties; the compounds bearing the aliphatic chain showed a reduced staining capacity due to the formation of aggregates. Notably, the complexes bearing different boron clusters showed different staining effects; those bearing [B12 H12 ]2- showed extraordinary staining of the nucleoli and cytoplasm, whereas those bearing COSAN were only detected in the cytoplasm. The remarkable fluorescence staining properties shown by these organotin compounds make them excellent candidates for fluorescence bioimaging in vitro.

Union makes strength: a worldwide collaborative genetic and clinical study to provide a comprehensive survey of RD3 mutations and delineate the associated phenotype.

Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration (RD), and the most common cause of incurable blindness diagnosed in children. It is occasionally the presenting symptom of multisystemic ciliopathies which diagnosis will require a specific care of patients. Nineteen LCA genes are currently identified and three of them account for both non-syndromic and syndromic forms of the disease. RD3 (LCA12) was implicated as a LCA gene based on the identification of homozygous truncating mutations in two LCA families despite the screening of large cohorts of patients. Here we provide a comprehensive survey of RD3 mutations and of their clinical expression through the screening of a cohort of 852 patients originating worldwide affected with LCA or early-onset and severe RD. We identified three RD3 mutations in seven unrelated consanguineous LCA families - i.e., a 2 bp deletion and two nonsense mutations - predicted to cause complete loss of function. Five families originating from the Southern Shores of the Mediterranean segregated a similar mutation (c.112C>T, p.R38*) suggesting that this change may have resulted from an ancient founder effect. Considering the low frequency of RD3 carriers, the recurrence risk for LCA in non-consanguineous unions is negligible for both heterozygote and homozygote RD3 individuals. The LCA12 phenotype in our patients is highly similar to those of patients with mutant photoreceptor-specific guanylate cyclase (GUCY2D/LCA1). This observation is consistent with the report of the role of RD3 in trafficking of GUCYs and gives further support to a common mechanism of photoreceptor degeneration in LCA12 and LCA1, i.e., inability to increase cytoplasmic cGMP concentration in outer segments and thus to recover the dark-state. Similar to LCA1, LCA12 patients have no extraocular symptoms despite complete inactivation of both RD3 alleles, supporting the view that extraocular investigations in LCA infants with RD3 mutations should be avoided.

Bruxismo en pacientes pediátricos / Bruxism in pediatric patients

El bruxismo en el paciente pediátrico al igual que en el adulto es un hábito para-funcional que consiste en apretar los dientes de forma involuntaria o voluntaria, fundamentalmente durante el sueño o vigilia en la dentición temporaria y permanente originando fuerzas de tensión sobre los músculos, tejidos y estructuras que forman parte del sistema estomatognático de los cuales proceden trastornos temporomandibulares o disturbios temporomandibulares, dolores de cabeza, de oído, lesiones en piezas dentarias, pulpa dentaria y parodonto. El objetivo de este trabajo es presentar el concepto, la etiología multifactorial, epidemiología, sintomatología más frecuentes del bruxismo hallada en niños y adolescentes, así como el tratamiento adecuado para cada edad y exponer además sobre los hallazgos fisiopatológicos de estudios realizados en países de la región. Finalmente concluye que el bruxismo es un transtorno cuya frecuencia está en aumento en la sociedad moderna, la falta de prevención y atención pueden conducir a graves daños en la cavidad oral y articulación mandibular interfiriendo el desarrollo normal del macizo craneofacial. Por su etiopatogenia multifactorial compuesta por factores psicológicos, emocionales, neurológicos, sistémicos y factores locales. La prevención del tratamiento requiere la participación de un equipo inter-disciplinario compuesto por el odontopediatra, médico pediatra, psicólogo, fisioterapeuta, logopeda, que permitan lograr un equilibrio en las funciones orofaciales, corporales y conductuales del paciente que transcurre etapas de desarrollo y crecimiento.

Thinner abuse alters peak of frequency of EEG spectra analyses / El abuso de tíner altera el pico de frecuencia del análisis espectral del EEG

STUDY OBJECTIVE: The aim of the investigation was to use electroencephalography (EEG) to study whether long-term thinner abuse may result in the slowing, disorganization and asymmetry of the EEG cortical rhythms. METHOD: Twenty-two patients attending with antecedent of thinner abuse only, and twenty two controls without alcohol, smoking, and drug abuse in the same age range and gender were studied. EEG recording were compared by means of the analyses of peak of frequency (POF), frequency of disorganization, and asymmetry of the background activity in patients and controls at rest eyes-closed condition in electrodes P3, P4, O1, and O2. RESULTS: Significant differences in POF among groups was observed in P3 and P4 location showing lower values in thinner abusers, but not in O1 and O2 locations. Frequencies of disorganization and asymmetry showed significantly higher proportions in thinner abusers. Bivariate correlations among POF at the four electrode location and time of thinner abuse showed significant values. However after partial correlation calculation correcting for age, significant values disappeared. CONCLUSION: Thus thinner abuse relates with slowing of POF in the EEG of patients with thinner abuse associated with disorganization, and asymmetry depending on time of abuse.

OBJETIVO: Utilizar el electroencefalograma (EEG) para estudiar si el abuso o intoxicación crónica por tíner produce lentificación, desorganización y asimetría de la actividad eléctrica cortical. MÉTODO: Se estudiaron 22 pacientes con antecedentes de intoxicación crónica por tíner y 22 sujetos sin antecedentes de abuso de tíner, alcohol, cigarro o drogas en el mismo rango de edad y en igual número de acuerdo al género. Se registro el EEG cuantitativo y se compararon: el promedio del pico de frecuencia (PoF), la frecuencia de desorganización de la actividad de fondo y la presencia de asimetría inter-hemisférica en la condición de reposo físico y mental entre las regiones de los electrodos P3, P4, O1 y O2. RESULTADOS: Se encontraron diferencias significativas en el PoF entre los grupo estudiados en P3 y P4 observándose valores menores en el grupo con antecedente de intoxicación crónica con tíner, sin embargo estas diferencias no fueron observadas en O1 y O2. La frecuencia de desorganización y de asimetría fue mayor entre los pacientes con antecedente de intoxicación crónica con tíner. Las correlaciones bivariadas entre el PoF en las cuatro localizaciones y el tiempo de consumo de tíner mostraron valores significativos, sin embargo, cuando fueron corregidas por la edad desaparecieron. CONCLUSION: La intoxicación crónica por tíner se relaciona a una lentificación del PoF del EEG de estos pacientes asociada con desorganización y asimetría que dependen parcialmente del tiempo de consumo.

Thinner abuse alters peak of frequency of EEG spectra analyses.

STUDY OBJECTIVE: The aim of the investigation was to use electroencephalography (EEG) to study whether long-term thinner abuse may result in the slowing, disorganization and asymmetry of the EEG cortical rhythms. METHOD: Twenty-two patients attending with antecedent of thinner abuse only, and twenty two controls without alcohol, smoking, and drug abuse in the same age range and gender were studied. EEG recording were compared by means of the analyses of peak of frequency (POF), frequency of disorganization, and asymmetry of the background activity in patients and controls at rest eyes-closed condition in electrodes P3, P4, O1, and O2. RESULTS: Significant differences in POF among groups was observed in P3 and P4 location showing lower values in thinner abusers, but not in O1 and O2 locations. Frequencies of disorganization and asymmetry showed significantly higher proportions in thinner abusers. Bivariate correlations among POF at the four electrode location and time of thinner abuse showed significant values. However after partial correlation calculation correcting for age, significant values disappeared. CONCLUSION: Thus thinner abuse relates with slowing of POF in the EEG of patients with thinner abuse associated with disorganization, and asymmetry depending on time of abuse.

Biosynthesis of glycoproteins in the pathogenic fungus Candida albicans: activation of dolichol phosphate mannose synthase by cAMP-mediated protein phosphorylation.

Following incubation with ATP and a cAMP-dependent protein kinase under optimal conditions of lipid acceptor, phospholipid and metal ion requirements, the transfer activity of partially purified dolichol phosphate mannose synthase (DPMS) increased about 60% and this activation correlated with a 50% increase in V(max) with no alteration in the apparent K(m) for GDP-Manose. Phosphorylation with [gamma-(32)P]ATP resulted in the labeling of several polypeptides, one of which exhibited the molecular weight of the enzyme (30 kDa) and was also recognized using a specific anti-DPMS monoclonal antibody. This and the fact that the phosphate label could be removed by an alkaline phosphatase indicate that Candida DPMS may be regulated by phosphorylation-dephosphorylation, a mechanism that has been proposed for the enzyme in other organisms.

EEG alpha desynchronization from rest to silent reading in school children

Objetivo: estudiar la asimetría cerebral en el electroencefalograma (EEG) durante la realización de una tarea de lectura silente. Métodos: se estudió un grupo de escolares durante una tarea de lectura silente buscando lateralización cerebral para el procesamiento verbal, hipotetizando que hay una desincronización asimétrica en la banda alfa provocada por la actividad cognoscitiva. Se estudiaron 25 escolares masculinos de 9-10 años con nivel de lectura adecuado a su edad, provenientes de escuelas públicas y privadas de la Ciudad de México. Se les realizó un estudio de EEG de 16 canales, los registros fueron realizados en reposo con los ojos cerrados y posteriormente durante la lectura en silencio de un texto con material acorde a su edad. El EEG fue analizado por medio de la transformada rápida de Fourier. Se calculó la potencia relativa por espectro de frecuencia dividido en las bandas: delta, theta, alfa, beta-1, beta-2, beta-3. Se compararon los datos de reposo y lectura en las bandas alfa y beta. Resultados: se observaron diferencias significativas en la distribución regional de la potencia relativa durante la lectura asociadas a un reducción generalizada de la actividad alfa, principalmente en el hemisferio izquierdo, así como un incremento frontal de los ritmos beta-2 y beta-3 durante la lectura. Conclusiones: la lectura silente puede producir una desincronización lateralizada del EEG con una reducción de la actividad alfa de predominio en el hemisferio izquierdo; así como, un aumento de los ritmos beta frontales, estas zonas son de conocida participación en el procesamiento del lenguaje.