Auscultación cervical: alternativa no invasiva en el diagnóstico de disfagia en niños con problemas de neurodesarrollo

Los niños y las niñas con disfunciones neurológicas tienen frecuentemente disfagia, condición que les ocasiona infecciones respiratorias a repetición, desnutrición, mala calidad de vida; su oportuno diagnóstico permite decidir sobre la mejor intervención. La videofluoroscopia y de videoendoscopia son técnicas diagnósticas invasivas, costosas y por lo tanto difíciles de hacerlas, lo que ocasiona retardo en el diagnóstico e intervención. Hoy en día existen nuevas tecnologías médicas no invasivas que pueden ser muy eficaces, una de ellas es la auscultación cervical que escucha los sonidos de la deglución mediante un estetoscopio u otro dispositivo de medición como la colocación de un micrófono o un acelerómetro en la superficie del cuello. Este método tiene como principio que los sonidos y/o movimientos biológicos normales de la deglución son diferentes de los anormales. En este artículo se presenta una revisión de la pertinencia social del diagnóstico de la disfagia, de las aplicaciones clínicas de la auscultación cervical y los dispositivos usados para realizarla, como una base para establecer su potencial de uso para la detección de disfagia en niños con problemas de neurodesarrollo. Estas orientaciones teóricas permiten al médico tener actuaciones más acertadas en el diagnóstico integral de niños y niñas con disfunción neurológica

Ultrassons em Endodontia

Introdução: O presente trabalho aborda as diferentes utilizações da tecnologia de Ultrassons na área da Endodontia. Atualmente, a utilização de ultrassons nesta área, ocupa um lugar de destaque, tendo-se tornado num equipamento indispensável nas varias áreas de abordagem, no âmbito do tratamento endodôntico. As aplicações clínicas, em que a utilização da tecnologia ultrassónica assume um papel de destaque, são: o refinamento de cavidades de acesso, localização de canais radiculares, preparação de istmos, remoção de espigões e instrumentos fraturados, ativação de soluções de irrigação, desobturação de canais radiculares, condensação de MTA e preparação apical para retrobturação em cirurgia apical. Objetivos: Esta dissertação tem como objetivo principal explorar, através de uma revisão de literatura, a importância e papel do Ultrassons em Endodontia. Procedeu-se a uma revisão bibliográfica, analisando a literatura que versa o tema, de modo a investigar o Ultrassom em Endodontia, nas suas diferentes dimensões: a evolução da técnica, o protocolo em toda a sua extensão, a sua utilidade e aplicabilidade na prática clínica. Material e Métodos: Pesquisa bibliográfica através de motores de pesquisa on-line como: b-On, Pubmed, Scielo, Science Direct, ResearchGate e Google Académico. De seguida, foram selecionados os artigos definidos com limites temporais e critérios de inclusão entre 2000 e 2016. Na aplicando dos critérios de exclusão foram rejeitados artigos dos quais o teor não teria relevância para a concretização do trabalho, artigos com idiomas estrageiros (com exceção de Inglês, Espanhol e Italiano), artigos fora dos limites temporais e estudos em animais. A pesquisa resultou total de 356 artigos dos quais foram utilizados 113. Conclusões: A introdução do ultrassom levou a cirurgia Endodôntica a um outro nível de precisão, esta tecnologia desempenha cada vez mais um papel essencial tanto na Medicina Dentária como na Endodontia, sendo estes capazes de apresentar melhoria e desenvolvimentos significativos na manutenção e tratamento dentário. O uso de Ultrassons em Endodontia é um meio auxiliar de tratamento útil, no o refinamento de cavidades de acesso, localização de canais radiculares, preparação de istmos, remoção de espigões e instrumentos fraturados, ativação de soluções de irrigação, desobturação de canais radiculares, condensação de MTA e preparação apical para retrobturação em cirurgia apical.

Curva de aprendizaje para ecografía cardiaca en residentes de primer y segundo año de medicina crítica de la universidad del rosario en el año 2016

La ecografía básica cardiaca (ECB) es una herramienta útil en la Unidad de Cuidados intensivos al facilitar la realización de ciertas intervenciones. No se ha definido el número de repeticiones necesarias para obtener un nivel de competencia adecuado. La evidencia encontrada indica un número mínimo de cincuenta repeticiones, para alcanzar cierto grado de habilidad.

New methodologies in CT perfusion and MRI analysis to develop cancer imaging biomarkers

Quantitative imaging in oncology aims at developing imaging biomarkers for diagnosis and prediction of cancer aggressiveness and therapy response before any morphological change become visible. This Thesis exploits Computed Tomography perfusion (CTp) and multiparametric Magnetic Resonance Imaging (mpMRI) for investigating diverse cancer features on different organs. I developed a voxel-based image analysis methodology in CTp and extended its use to mpMRI, for performing precise and accurate analyses at single-voxel level. This is expected to improve reproducibility of measurements and cancer mechanisms’ comprehension and clinical interpretability. CTp has not entered the clinical routine yet, although its usefulness in the monitoring of cancer angiogenesis, due to different perfusion computing methods yielding unreproducible results. Instead, machine learning applications in mpMRI, useful to detect imaging features representative of cancer heterogeneity, are mostly limited to clinical research, because of results’ variability and difficult interpretability, which make clinicians not confident in clinical applications. In hepatic CTp, I investigated whether, and under what conditions, two widely adopted perfusion methods, Maximum Slope (MS) and Deconvolution (DV), could yield reproducible parameters. To this end, I developed signal processing methods to model the first pass kinetics and remove any numerical cause hampering the reproducibility. In mpMRI, I proposed a new approach to extract local first-order features, aiming at preserving spatial reference and making their interpretation easier. In CTp, I found out the cause of MS and DV non-reproducibility: MS and DV represent two different states of the system. Transport delays invalidate MS assumptions and, by correcting MS formulation, I have obtained the voxel-based equivalence of the two methods. In mpMRI, the developed predictive models allowed (i) detecting rectal cancers responding to neoadjuvant chemoradiation showing, at pre-therapy, sparse coarse subregions with altered density, and (ii) predicting clinically significant prostate cancers stemming from the disproportion between high- and low- diffusivity gland components.

A single-sided NMR approach to study structural differences of bovine articular tissue

This thesis work has been developed in collaboration between the Department of Physics and Astronomy of the University of Bologna and the IRCCS Rizzoli Orthopedic Institute during an internship period. The study aims to investigate the sensitivity of single-sided NMR in detecting structural differences of the articular cartilage tissue and their correlation with mechanical behavior. Suitable cartilage indicators for osteoarthritis (OA) severity (e.g., water and proteoglycans content, collagen structure) were explored through four NMR parameters: T2, T1, D, and Slp. Structural variations of the cartilage among its three layers (i.e., superficial, middle, and deep) were investigated performing several NMR pulses sequences on bovine knee joint samples using the NMR-MOUSE device. Previously, cartilage degradation studies were carried out, performing tests in three different experimental setups. The monitoring of the parameters and the best experimental setup were determined. An NMR automatized procedure based on the acquisition of these quantitative parameters was implemented, tested, and used for the investigation of the layers of twenty bovine cartilage samples. Statistical and pattern recognition analyses on these parameters have been performed. The results obtained from the analyses are very promising: the discrimination of the three cartilage layers shows very good results in terms of significance, paving the way for extensive use of NMR single-sided devices for biomedical applications. These results will be also integrated with analyses of tissue mechanical properties for a complete evaluation of cartilage changes throughout OA disease. The use of low-priced and mobile devices towards clinical applications could concern the screening of diseases related to cartilage tissue. This could have a positive impact both economically (including for underdeveloped countries) and socially, providing screening possibilities to a large part of the population.

R-loops and G4-structures: from DNA damage to innate immune response gene activation

Non-B DNA structures like R-loops and G-quadruplexes play a pivotal role in several cellular vital processes like DNA transcription regulation. Misregulation of said non-canonical DNA structures can often lead to genome instability, DNA damage, and, eventually, to the activation of an innate immune response. For such reasons they have been studied as adjuvants in anticancer therapies. Here we studied drugs targeting R-loops (Top1 poisons) and G4s (hydrazone derivatives) in order to observe their effects in terms of DNA damage induction and, subsequently, activation of innate immune response. We studied how non-cytotoxic doses of ampthotecin and LMP-776 impact on genome instability, are capable to induce DNA damage and micronuclei, and, eventually lead to an innate immune gene response via the cGAS/STING pathway. G-quadruplexes are another ubiquitous, non-canonical DNA structure, more abundant in telomeric regions, demonstrating a marked relation with the impairment of telomerase and the regulation of DNA replication and transcription. Furthermore, we investigated the properties of new-synthesized molecules belonging to the highly promising class of hydrazone derivatives, in terms of cytotoxicity, ability to stabilize G4-structures, induce DNA damage, and activate interferon-B production. Both Top1 poisons and G4-stabilizers possess several features that can be very useful in clinical applications, in light of their ability to stimulate innate immune response factors and exert a certain cell-killing power, plus they offer a broad and diverse range of treatment options in order to face a variety of patient treatment needs. It is for these very reasons that it is of uttermost importance that further studies are conducted on these compounds, in order to synthesize new and increasingly powerful and flexible ones, with fewer side effects to customize therapies on specific cancers’ and patients’ features.

Integrating structural variant calling, annotation and prioritization into whole genome analysis workflows: a practical application in the molecular diagnosis of neurodevelopmental disorders

Background: WGS is increasingly used as a first-line diagnostic test for patients with rare genetic diseases such as neurodevelopmental disorders (NDD). Clinical applications require a robust infrastructure to support processing, storage and analysis of WGS data. The identification and interpretation of SVs from WGS data also needs to be improved. Finally, there is a need for a prioritization system that enables downstream clinical analysis and facilitates data interpretation. Here, we present the results of a clinical application of WGS in a cohort of patients with NDD. Methods: We developed highly portable workflows for processing WGS data, including alignment, quality control, and variant calling of SNVs and SVs. A benchmark analysis of state-of-the-art SV detection tools was performed to select the most accurate combination for SV calling. A gene-based prioritization system was also implemented to support variant interpretation. Results: Using a benchmark analysis, we selected the most accurate combination of tools to improve SV detection from WGS data and build a dedicated pipeline. Our workflows were used to process WGS data from 77 NDD patient-parent families. The prioritization system supported downstream analysis and enabled molecular diagnosis in 32% of patients, 25% of which were SVs and suggested a potential diagnosis in 20% of patients, requiring further investigation to achieve diagnostic certainty. Conclusion: Our data suggest that the integration of SNVs and SVs is a main factor that increases diagnostic yield by WGS and show that the adoption of a dedicated pipeline improves the process of variant detection and interpretation.

The predictive role of the human gut microbiota in covid-19: implications for disease severity and post-covid syndrome

The COVID-19 pandemic, sparked by the SARS-CoV-2 virus, stirred global comparisons to historical pandemics. Initially presenting a high mortality rate, it later stabilized globally at around 0.5-3%. Patients manifest a spectrum of symptoms, necessitating efficient triaging for appropriate treatment strategies, ranging from symptomatic relief to antivirals or monoclonal antibodies. Beyond traditional approaches, emerging research suggests a potential link between COVID-19 severity and alterations in gut microbiota composition, impacting inflammatory responses. However, most studies focus on severe hospitalized cases without standardized criteria for severity. Addressing this gap, the first study in this thesis spans diverse COVID-19 severity levels, utilizing 16S rRNA amplicon sequencing on fecal samples from 315 subjects. The findings highlight significant microbiota differences correlated with severity. Machine learning classifiers, including a multi-layer convoluted neural network, demonstrated the potential of microbiota compositional data to predict patient severity, achieving an 84.2% mean balanced accuracy starting one week post-symptom onset. These preliminary results underscore the gut microbiota's potential as a biomarker in clinical decision-making for COVID-19. The second study delves into mild COVID-19 cases, exploring their implications for ‘long COVID’ or Post-Acute COVID-19 Syndrome (PACS). Employing longitudinal analysis, the study unveils dynamic shifts in microbial composition during the acute phase, akin to severe cases. Innovative techniques, including network approaches and spline-based longitudinal analysis, were deployed to assess microbiota dynamics and potential associations with PACS. The research suggests that even in mild cases, similar mechanisms to hospitalized patients are established regarding changes in intestinal microbiota during the acute phase of the infection. These findings lay the foundation for potential microbiota-targeted therapies to mitigate inflammation, potentially preventing long COVID symptoms in the broader population. In essence, these studies offer valuable insights into the intricate relationships between COVID-19 severity, gut microbiota, and the potential for innovative clinical applications.

Articular Cartilage in the Knee: Current MR Imaging Techniques and Applications in Clinical Practice and Research

Magnetic resonance (MR) imaging is the most important imaging modality for the evaluation of traumatic or degenerative cartilaginous lesions in the knee. It is a powerful noninvasive tool for detecting such lesions and monitoring the effects of pharmacologic and surgical therapy. The specific MR imaging techniques used for these purposes can be divided into two broad categories according to their usefulness for morphologic or compositional evaluation. To assess the structure of knee cartilage, standard spin-echo (SE) and gradient-recalled echo (GRE) sequences, fast SE sequences, and three-dimensional SE and GRE sequences are available. These techniques allow the detection of morphologic defects in the articular cartilage of the knee and are commonly used in research for semiquantitative and quantitative assessments of cartilage. To evaluate the collagen network and proteoglycan content in the knee cartilage matrix, compositional assessment techniques such as T2 mapping, delayed gadolinium-enhanced MR imaging of cartilage (or dGEMRIC), T1 rho imaging, sodium imaging, and diffusion-weighted imaging are available. These techniques may be used in various combinations and at various magnetic field strengths in clinical and research settings to improve the characterization of changes in cartilage. (C)RSNA, 2011 , radiographics.rsna.org

Location of innervation zones of sternocleidomastoid and scalene muscles - a basis for clinical and research electromyography applications

Objectives: Advances in surface electromyography (sEMG) techniques provide a clear indication that refinement of electrode location relative to innervation zones (IZ) is required in order to optimise the accuracy, relevance and repeatability of the sEMG signals. The aim of this study was to identify the IZ for the sternocleidomastoid and anterior scalene muscles to provide guidelines for electrode positioning for future clinical and research applications. Methods: Eleven volunteer subjects participated in this study. Myoelectric signals were detected from the sternal and clavicular heads of the stemocleidomastoid and the anterior scalene muscles bilaterally using a linear array of 8 electrodes during isometric cervical flexion contractions. The signals were reviewed and the IZ(s) were identified, marked on the subjects' skin and measurements were obtained relative to selected anatomical landmarks. Results: The position of the IZ lay consistently around the mid-point or in the superior portion of the muscles studied. Conclusions: Results suggest that electrodes should be positioned over the lower portion of the muscle and not the mid-point, which has been commonly used in previous studies. Recommendations for sensor placement on these muscles should assist investigators and clinicians to ensure improved validity in future sEMG applications. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Rapid bacterial genome sequencing: methods and applications in clinical microbiology.

The recent advances in sequencing technologies have given all microbiology laboratories access to whole genome sequencing. Providing that tools for the automated analysis of sequence data and databases for associated meta-data are developed, whole genome sequencing will become a routine tool for large clinical microbiology laboratories. Indeed, the continuing reduction in sequencing costs and the shortening of the 'time to result' makes it an attractive strategy in both research and diagnostics. Here, we review how high-throughput sequencing is revolutionizing clinical microbiology and the promise that it still holds. We discuss major applications, which include: (i) identification of target DNA sequences and antigens to rapidly develop diagnostic tools; (ii) precise strain identification for epidemiological typing and pathogen monitoring during outbreaks; and (iii) investigation of strain properties, such as the presence of antibiotic resistance or virulence factors. In addition, recent developments in comparative metagenomics and single-cell sequencing offer the prospect of a better understanding of complex microbial communities at the global and individual levels, providing a new perspective for understanding host-pathogen interactions. Being a high-resolution tool, high-throughput sequencing will increasingly influence diagnostics, epidemiology, risk management, and patient care.

Genus-specific kinetoplast-DNA PCR and parasite culture for the diagnosis of localised cutaneous leishmaniasis: applications for clinical trials under field conditions in Brazil

The positivities of two methods for the diagnosis of localised cutaneous leishmaniasis (CL) were estimated in 280 patients enrolled in a clinical trial. The trial was conducted in an endemic area of Leishmania (Viannia) braziliensis and trial participants were patients with skin ulcers and positive leishmanin skin tests. Patients underwent aspirative skin punctures of the ulcerated lesions and lymph nodes for in vitro cultures, which were processed under field conditions at the local health centre. Skin lesion biopsies were tested at a reference laboratory using kinetoplastid DNA (kDNA)-PCR to detect DNA. The median time required to obtain a positive culture from the skin samples was seven days and the contamination rate of the samples was 1.8%. The positivities of the cultures from skin lesions, kDNA-PCR and the combination of the two methods were 78.2% (95% CI: 73-82.6%), 89.3% (95% CI: 85.1-92.4%) and 97.1% (95% CI: 94.5-98.5%). We conclude that parasite culture is a feasible method for the detection of Leishmania in field conditions and that the combination of culture and PCR has a potential role for the diagnosis of CL in candidates for clinical trials.

Plastinated Ethmoidal Region : I. Preparation and Applications in Clinical Teaching.

Ethmoidal regions weer prepared and dissected to demonstrate regional sinus anatomy and endoscopic surgery approaches from six human heads. After perparation, the specimens were plastinated using the standard S10 technique. A CT-scan of each ethmoidal block was performed before and after preparation of the block to access shrinkage. The plastinated specimens were successfully introduced into clinical teaching of sinus anatomy and surgery. One advantage of using these specimens is their long-lasting preservation without deterioration of the tissue. The specimens were well suited for comparative radiographic and ondoscopic studies, and the CT-scans allowed an exact measurement of tissue shrinkage due to plastination. Increaseed tissue rigidity and shrionkage due to plastination has to be taken into account for subsequent endoscopic observation.