End-To-End Procedure For IORT in Brain Metastases and Film Dosimetry.

Purpose: The study is intended to perform an end-to-end test of the entire intraoperative process using cadaver heads. A simulation of tumor removal was performed, followed by irradiation of the bed and measurement of absorbed doses with radiochromic films. Materials and Methods: Low-energy X-ray intraoperative radiotherapy (IORT) was used for irradiation. A computed tomography study was performed at each site and the absorbed doses calculated by the treatment planning system, as well as absorbed doses with radiochromic films, were studied. Results: The absorbed doses in the organs at risk (OAR) were evaluated in each case, obtaining maximum doses within the tolerance limits. The absorbed doses in the target were verified and the deviations were <1%. Conclusions: These tests demonstrated that this comprehensive procedure is a reproducible quality assurance tool which allows continuous assessment of the dosimetric and geometric accuracy of clinical brain IORT treatments. Furthermore, the absorbed doses measured in both target and OAR are optimal for these treatments.

An open-source development based on photogrammetry for a real-time IORT treatment planning system.

PURPOSE: This study presents a treatment planning system for intraoperative low-energy photon radiotherapy based on photogrammetry from real images of the surgical site taken in the operating room. MATERIAL AND METHODS: The study population comprised 15 patients with soft-tissue sarcoma. The system obtains the images of the area to be irradiated with a smartphone or tablet, so that the absorbed doses in the tissue can be calculated from the reconstruction without the need for computed tomography. The system was commissioned using 3D printing of the reconstructions of the tumor beds. The absorbed doses at various points were verified using radiochromic films that were suitably calibrated for the corresponding energy and beam quality. RESULTS: The average reconstruction time of the 3D model from the video sequence in the 15 patients was 229,6±7,0 s. The entire procedure, including video capture, reconstruction, planning, and dose calculation was 520,6±39,9 s. Absorbed doses were measured on the 3D printed model with radiochromic film, the differences between these measurements and those calculated by the treatment planning system were 1.4% at the applicator surface, 2.6% at 1 cm, 3.9% at 2 cm and 6.2% at 3 cm. CONCLUSIONS: The study shows a photogrammetry-based low-energy photon IORT planning system, capable of obtaining real-time images inside the operating room, immediately after removal of the tumor and immediately before irradiation. The system was commissioned with radiochromic films measurements in 3D-printed model.

Prevalencia del segundo conducto en dientes anteroinferiores usando Tomografía Computadorizada Cone Beam / Second root canal prevalence in lower anterior teeth using Cone Beam Computed Tomography

Introducción: Es un error común pensar que los dientes anteroinferiores, por lo general, tienen un solo conducto radicular con una sola raíz. Sin embargo, un estudio realizado por Vertucci et. al., (1974), mostraron una alta prevalencia (13%) de dos conductos radiculares en los dientes anteroinferiores, lo que estimuló más investigaciones. Objetivo: El propósito de este estudio fue determinar la prevalencia del segundo conducto radicular en los dientes anteroinferiores en una población nicaragüense, estos fueron detectados por medio de tomografía computadorizada (Cone Beam). Materiales y Métodos: En el estudio se analizaron 293 piezas dentales, de canino a canino de la arcada inferior. Para realizar el análisis se utilizó el software libre Radiant DICOM Viewer 2021.2.2, se realizaron cortes sagitales, axiales y coronales para ver la prevalencia del segundo conducto radicular. Resultados: De las 293 piezas dentarias analizadas se encontró que 259 presentaban un solo conducto que correspondía al 88.4% y 34 dientes presentaban dos conductos que correspondían al 11.6%. De acuerdo con el análisis tomográfico, se encontró que en los cortes axiales y sagitales fue donde se observó la presencia del segundo conducto. Con respecto a la presencia del segundo conducto de acuerdo al tercio del canal radicular se identificó que la mayoría se presentó en el tercio medio (52.94%), seguido por coronal (29.41%) y por último el tercio apical (17.65%). De acuerdo con la clasificación de Vertucci se encontró que se presenta un mayor porcentaje del tipo I con 88.40%, seguido por el tipo III con 4.44%, después el tipo V con 3.41%, y el tipo II con 2.39%. El de menor porcentaje fue el tipo VI con 1.37%, mientras que, en las piezas analizadas, no se encontraron los tipos IV, VII y VIII. Conclusión: Basados en los resultados obtenidos en este estudio, la prevalencia de un segundo conducto en dientes anteroinferiores fue de 11.6%.

Title The prevalence of a second root canal in mandibular anterior teeth using Cone Beam Computed Tomography. Abstract Introduction: It is a common misconception that the mandibular anterior teeth usually have a single root canal with a single root. However, a study by Vertucci et. al., (1974), showed a high prevalence (13%) of two root canals in the lower anterior teeth, which stimulated further investigations. Objective: The purpose of this study was to determine the prevalence of the second root canal in the mandibular anterior teeth in a Nicaraguan population, these were detected by means of computed tomography (Cone Beam). Materials and methods: In the study, 293 teeth were analyzed, from canine to canine of the mandibular teeth. To perform the analysis, the free software Radiant DICOM Viewer 2021.2.2 was used, sagittal, axial and coronal views were made to see the prevalence of the second root canal. Results: Of the 293 teeth analyzed, it was found that 259 had a single root canal corresponding to 88.4%, and 34 teeth had two root canals corresponding to 11.6%. According to the tomographic analysis, it was found that the presence of the second root canal was observed only in the axial and sagittal views. Regarding the presence of the second canal according to the third of the root canal, it was identified that the majority presented in the middle third (52.94%), followed by coronal (29.41%) and finally the apical third (17.65%). According to the Vertucci classification, it was found that there is a higher percentage of type I with 88.40%, followed by type III with 4.44%, then type V with 3.41%, and type II with 2.39%. The one with the lowest percentage was type VI with 1.37%, while in the pieces analyzed, types IV, VII and VIII were not found. Conclusion: Based on the results obtained in this study, the prevalence of a second root canal in lower anterior teeth was 11.6%.

Modular automated microfluidic cell culture platform reduces glycolytic stress in cerebral cortex organoids.

Organ-on-a-chip systems combine microfluidics, cell biology, and tissue engineering to culture 3D organ-specific in vitro models that recapitulate the biology and physiology of their in vivo counterparts. Here, we have developed a multiplex platform that automates the culture of individual organoids in isolated microenvironments at user-defined media flow rates. Programmable workflows allow the use of multiple reagent reservoirs that may be applied to direct differentiation, study temporal variables, and grow cultures long term. Novel techniques in polydimethylsiloxane (PDMS) chip fabrication are described here that enable features on the upper and lower planes of a single PDMS substrate. RNA sequencing (RNA-seq) analysis of automated cerebral cortex organoid cultures shows benefits in reducing glycolytic and endoplasmic reticulum stress compared to conventional in vitro cell cultures.

Feasibility of electronic brachytherapy in cervix cancer-A dosimetric comparison of different brachytherapy techniques.

INTRODUCTION: This study analyzes cases in which electronic brachytherapy (eBT) led to acceptable treatment plans in cervical cancer. Findings were compared with dosimetry values obtained in 192Ir-based treatments according to the high-risk clinical target volume (HR-CTV) and the disease stage. MATERIAL AND METHODS: We retrospectively analyzed 48 patients with cervical cancer from two centers. The patients were treated with 192Ir based on MRI. It was possible to use interstitial needles via an Utrecht-type applicator. Dosimetry was simulated using eBT and the parameters D90 and D98 (HR-CTV) and D2cc, D1cc, and D0.1cc (bladder, rectum, and sigmoid colon) were evaluated. The Mann-Whitney U test was used for comparison. The overall cohort of patients was analyzed, as were the sub-cohorts based on stage (FIGO stages I+IIA, IIB and III-IV). Finally, the dosimetry of the eBT plans was evaluated, and the plans obtained were classified as "good", "acceptable", or "poor". RESULTS: Statistically significant differences were found between the eBT and 192Ir plans for D98 (HR-CTV), D1cc and D0.1cc (bladder), and D1cc and D0.1cc (sigmoid colon). A total of 31 cases (64.6%) were considered good, seven (14.6%) were considered acceptable, and 10 (20.8%) were considered poor. For volumes <30 cc, all the plans were good or acceptable; for volumes >30 cc, 54.3% were good, and 71.4% were good or acceptable. By stage, eBT plans for patients with stage IB-IIA disease were good in 100%, whereas those for patients with stage IIB were good in 70.6% and III-IV disease were good in 50%. CONCLUSIONS: eBT provides appropriate dosimetry for treatment of cervical cancer in selected cases.

Picroscope: low-cost system for simultaneous longitudinal biological imaging.

Simultaneous longitudinal imaging across multiple conditions and replicates has been crucial for scientific studies aiming to understand biological processes and disease. Yet, imaging systems capable of accomplishing these tasks are economically unattainable for most academic and teaching laboratories around the world. Here, we propose the Picroscope, which is the first low-cost system for simultaneous longitudinal biological imaging made primarily using off-the-shelf and 3D-printed materials. The Picroscope is compatible with standard 24-well cell culture plates and captures 3D z-stack image data. The Picroscope can be controlled remotely, allowing for automatic imaging with minimal intervention from the investigator. Here, we use this system in a range of applications. We gathered longitudinal whole organism image data for frogs, zebrafish, and planaria worms. We also gathered image data inside an incubator to observe 2D monolayers and 3D mammalian tissue culture models. Using this tool, we can measure the behavior of entire organisms or individual cells over long-time periods.

Treatment of cervical cancer with electronic brachytherapy.

PURPOSE: We report the first cervical cancer cases treated with interstitial electronic brachytherapy (eBT) at our hospital and compare them with plans made with high-dose-rate interstitial brachytherapy based on Ir192 (HDR-BT). MATERIALS AND METHODS: Eight patients with cervical cancer were treated with the Axxent eBT device (Xoft, Inc.). Planning was with magnetic resonance imaging and computed tomography following the recommendations of the EMBRACE protocol. The dosimetry parameters of organs at risk (OAR) were evaluated for the bladder, rectum, and sigmoid colon (D2cc, D1cc, and D0.1cc). In addition, the V150 and V200 of irradiated tissue were compared for both eBT and HDR-BT. All patients received intensity-modulated external beam radiation therapy with a regimen of 23 sessions of 2 Gy followed by four sessions of 7 Gy of eBT performed over 2 weeks (two sessions followed by another two sessions a week later) following the EMBRACE recommendations. Each of the eight patients was followed to assess acute toxicity associated with treatment. RESULTS: The doses reaching OAR for eBT plans were lower than for HDR-BT plans. As for acute toxicity associated with eBT, very few cases of mucositis were detected. No cases of rectal toxicity and one case with grade 1 urinary toxicity were detected. The results at 1 month are equally good, and no relapses have occurred to date. CONCLUSIONS: The first results of treatment with the Axxent eBT device are promising, as no recurrences have been observed and toxicity is very low. eBT is a good alternative for treating cervical cancer in centers without access to conventional HDR.

Revealing cancer subtypes with higher-order correlations applied to imaging and omics data.

BACKGROUND: Patient stratification to identify subtypes with different disease manifestations, severity, and expected survival time is a critical task in cancer diagnosis and treatment. While stratification approaches using various biomarkers (including high-throughput gene expression measurements) for patient-to-patient comparisons have been successful in elucidating previously unseen subtypes, there remains an untapped potential of incorporating various genotypic and phenotypic data to discover novel or improved groupings. METHODS: Here, we present HOCUS, a unified analytical framework for patient stratification that uses a community detection technique to extract subtypes out of sparse patient measurements. HOCUS constructs a patient-to-patient network from similarities in the data and iteratively groups and reconstructs the network into higher order clusters. We investigate the merits of using higher-order correlations to cluster samples of cancer patients in terms of their associations with survival outcomes. RESULTS: In an initial test of the method, the approach identifies cancer subtypes in mutation data of glioblastoma, ovarian, breast, prostate, and bladder cancers. In several cases, HOCUS provides an improvement over using the molecular features directly to compare samples. Application of HOCUS to glioblastoma images reveals a size and location classification of tumors that improves over human expert-based stratification. CONCLUSIONS: Subtypes based on higher order features can reveal comparable or distinct groupings. The distinct solutions can provide biologically- and treatment-relevant solutions that are just as significant as solutions based on the original data.

Volumetric electromagnetic phase-shift spectroscopy of brain edema and hematoma.

Motivated by the need of poor and rural Mexico, where the population has limited access to advanced medical technology and services, we have developed a new paradigm for medical diagnostic based on the technology of "Volumetric Electromagnetic Phase Shift Spectroscopy" (VEPS), as an inexpensive partial substitute to medical imaging. VEPS, can detect changes in tissue properties inside the body through non-contact, multi-frequency electromagnetic measurements from the exterior of the body, and thereby provide rapid and inexpensive diagnostics in a way that is amenable for use in economically disadvantaged parts of the world. We describe the technology and report results from a limited pilot study with 46 healthy volunteers and eight patients with CT radiology confirmed brain edema and brain hematoma. Data analysis with a non-parametric statistical Mann-Whitney U test, shows that in the frequency range of from 26 MHz to 39 MHz, VEPS can distinguish non-invasively and without contact, with a statistical significance of p<0.05, between healthy subjects and those with a medical conditions in the brain. In the frequency range of between 153 MHz to 166 MHz it can distinguish with a statistical significance of p<0.05 between subjects with brain edema and those with a hematoma in the brain. A classifier build from measurements in these two frequency ranges can provide instantaneous diagnostic of the medical condition of the brain of a patient, from a single set of measurements. While this is a small-scale pilot study, it illustrates the potential of VEPS to change the paradigm of medical diagnostic of brain injury through a VEPS classifier-based technology. Obviously substantially larger-scale studies are needed to verify and expand on the findings in this small pilot study.

Phased whole-genome genetic risk in a family quartet using a major allele reference sequence.

Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (< 1,000 base pairs). We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.

Incidencia de falla orgánica múltiple en tres instituciones de salud / Incidence of multiple organic failure in three healt institutions

La falla orgánica múltiple es un síndrome que se presenta como complicación en la evolución de los pacientes en estado crítico que ingresan a las unidades de cuidados intensivos. Se piensa que es consecuencia de un estado de hipermetabolismo secundario a la extensión de la respuesta inflamatoria que se traduce en alteraciones circulatorias e intervención de mediadores de daño tisular, lo cual lleva progresivamente al deterioro fisiológico y a la muerte. Con base en los criterios modificados por Ruokonen se realizó un estudio prospectivo, longitudinal, descriptivo y observacional para establecer la incidencia de falla orgánica múltiple en tres unidades de cuidados intensivos. Las fallas orgánicas más frecuentes fueron cardiovascular, respiratoria, neurológica y renal, observándose que las dos primeras están asociadas a una mayor mortalidad. Las sepsis se encontró asociada a la falla orgánica múltiple en el 67.5 por ciento de los pacientes. La edad, el puntaje APACHE II, la cantidad y duración de las fallas orgánicas aumentan de manera directa la mortalidad en estos pacientes. La incidencia fue de 11.4 por ciento, 20.3 por ciento y 3.6 por ciento para los Hospitales General de México, PEMEX Picacho y Gabriel Mancera, respectivamente. Se hace énfasis en la importancia de la detección y del abordaje terapéutico temprano de este síndrome a fin de disminuir la alta mortalidad que causa entre los pacientes en estado crítico