Machine-learning to Stratify Diabetic Patients Using Novel Cardiac Biomarkers and Integrative Genomics

Background: Diabetes mellitus is a chronic disease that impacts an increasing percentage of people each year. Among its comorbidities, diabetics are two to four times more likely to develop cardiovascular diseases. While HbA1c remains the primary diagnostic for diabetics, its ability to predict long-term, health outcomes across diverse demographics, ethnic groups, and at a personalized level are limited. The purpose of this study was to provide a model for precision medicine through the implementation of machine-learning algorithms using multiple cardiac biomarkers as a means for predicting diabetes mellitus development. Methods: Right atrial appendages from 50 patients, 30 non-diabetic and 20 type 2 diabetic, were procured from the WVU Ruby Memorial Hospital. Machine-learning was applied to physiological, biochemical, and sequencing data for each patient. Supervised learning implementing SHapley Additive exPlanations (SHAP) allowed binary (no diabetes or type 2 diabetes) and multiple classifcation (no diabetes, prediabetes, and type 2 diabetes) of the patient cohort with and without the inclusion of HbA1c levels. Findings were validated through Logistic Regression (LR), Linear Discriminant Analysis (LDA), Gaussian Naïve Bayes (NB), Support Vector Machine (SVM), and Classifcation and Regression Tree (CART) models with tenfold cross validation. Results: Total nuclear methylation and hydroxymethylation were highly correlated to diabetic status, with nuclear methylation and mitochondrial electron transport chain (ETC) activities achieving superior testing accuracies in the predictive model (~84% testing, binary). Mitochondrial DNA SNPs found in the D-Loop region (SNP-73G, -16126C, and -16362C) were highly associated with diabetes mellitus. The CpG island of transcription factor A, mitochondrial (TFAM) revealed CpG24 (chr10:58385262, P=0.003) and CpG29 (chr10:58385324, P=0.001) as markers correlating with diabetic progression. When combining the most predictive factors from each set, total nuclear methylation and CpG24 methylation were the best diagnostic measures in both binary and multiple classifcation sets. Conclusions: Using machine-learning, we were able to identify novel as well as the most relevant biomarkers associated with type 2 diabetes mellitus by integrating physiological, biochemical, and sequencing datasets. Ultimately, this approach may be used as a guideline for future investigations into disease pathogenesis and novel biomarker discover

Recent advances in the application of ionomics in metabolic diseases

Trace elements and minerals play a significant role in human health and diseases. In recent years, ionomics has been rapidly and widely applied to explore the distribution, regulation, and crosstalk of different elements in various physiological and pathological processes. On the basis of multi-elemental analytical techniques and bioinformatics methods, it is possible to elucidate the relationship between the metabolism and homeostasis of diverse elements and common diseases. The current review aims to provide an overview of recent advances in the application of ionomics in metabolic disease research. We mainly focuses on the studies about ionomic or multi-elemental profiling of different biological samples for several major types of metabolic diseases, such as diabetes mellitus, obesity, and metabolic syndrome, which reveal distinct and dynamic patterns of ion contents and their potential benefits in the detection and prognosis of these illnesses. Accumulation of copper, selenium, and environmental toxic metals as well as deficiency of zinc and magnesium appear to be the most significant risk factors for the majority of metabolic diseases, suggesting that imbalance of these elements may be involved in the pathogenesis of these diseases. Moreover, each type of metabolic diseases has shown a relatively unique distribution of ions in biofluids and hair/nails from patients, which might serve as potential indicators for the respective disease. Overall, ionomics not only improves our understanding of the association between elemental dyshomeostasis and the development of metabolic disease but also assists in the identification of new potential diagnostic and prognostic markers in translational medicine

Case series of breast fillers and how things may go wrong: radiology point of view

INTRODUCTION: Breast augmentation is a procedure opted by women to overcome sagging breast due to breastfeeding or aging as well as small breast size. Recent years have shown the emergence of a variety of injectable materials on market as breast fillers. These injectable breast fillers have swiftly gained popularity among women, considering the minimal invasiveness of the procedure, nullifying the need for terrifying surgery. Little do they know that the procedure may pose detrimental complications, while visualization of breast parenchyma infiltrated by these fillers is also deemed substandard; posing diagnostic challenges. We present a case series of three patients with prior history of hyaluronic acid and collagen breast injections. REPORT: The first patient is a 37-year-old lady who presented to casualty with worsening shortness of breath, non-productive cough, central chest pain; associated with fever and chills for 2-weeks duration. The second patient is a 34-year-old lady who complained of cough, fever and haemoptysis; associated with shortness of breath for 1-week duration. CT in these cases revealed non thrombotic wedge-shaped peripheral air-space densities. The third patient is a 37‐year‐old female with right breast pain, swelling and redness for 2- weeks duration. Previous collagen breast injection performed 1 year ago had impeded sonographic visualization of the breast parenchyma. MRI breasts showed multiple non- enhancing round and oval shaped lesions exhibiting fat intensity. CONCLUSION: Radiologists should be familiar with the potential risks and hazards as well as limitations of imaging posed by breast fillers such that MRI is required as problem-solving tool

Characterization of alar ligament on 3.0T MRI: a cross-sectional study in IIUM Medical Centre, Kuantan

INTRODUCTION: The main purpose of the study is to compare the normal anatomy of alar ligament on MRI between male and female. The specific objectives are to assess the prevalence of alar ligament visualized on MRI, to describe its characteristics in term of its course, shape and signal homogeneity and to find differences in alar ligament signal intensity between male and female. This study also aims to determine the association between the heights of respondents with alar ligament signal intensity and dimensions. MATERIALS & METHODS: 50 healthy volunteers were studied on 3.0T MR scanner Siemens Magnetom Spectra using 2-mm proton density, T2 and fat-suppression sequences. Alar ligament is depicted in 3 planes and the visualization and variability of the ligament courses, shapes and signal intensity characteristics were determined. The alar ligament dimensions were also measured. RESULTS: Alar ligament was best depicted in coronal plane, followed by sagittal and axial planes. The orientations were laterally ascending in most of the subjects (60%), predominantly oval in shaped (54%) and 67% showed inhomogenous signal. No significant difference of alar ligament signal intensity between male and female respondents. No significant association was found between the heights of the respondents with alar ligament signal intensity and dimensions. CONCLUSION: Employing a 3.0T MR scanner, the alar ligament is best portrayed on coronal plane, followed by sagittal and axial planes. However, tremendous variability of alar ligament as depicted in our data shows that caution needs to be exercised when evaluating alar ligament, especially during circumstances of injury

National Amyotrophic Lateral Sclerosis (ALS) Registry Annual Meeting, August 7-8, 2018 : summary report

The Agency for Toxic Substances and Disease Registry (ATSDR) established the National ALS Registry to determine how many people in the US are living with ALS, to describe the demographics of ALS patients, and most importantly to examine the risk factors for ALS. Although the Registry\u2019s primary purpose is to capture cases of ALS, the Registry does a lot more than just count cases. The Registry is also:\uf0b7 Funding ALS research,\uf0b7 Collecting specimens from Registry enrollees through the National ALS Biorepository,\uf0b7 Connecting patients with researchers recruiting for ALS clinical trials or epidemiological studies,\uf0b7 Obtaining and analyzing potential etiologic data from Registry enrollees through 17 different online risk factor modules such as occupational history, military history, residential history, history of traumatic brain injury and (TBI), and\uf0b7 Providing data and biospecimens to scientists to further ALS research.ATSDR held the National ALS Registry Annual Meeting in Atlanta on August 7-8, 2018. There were 51 attendees, including persons living with ALS, neurologists, researchers, representatives of national ALS organizations, representatives of pharmaceutical companies, Registry staff, and other ALS experts.Publication date from document properties.2018-ALS-Annual-Meeting-Summary-Report.pdf201

Análise elementar de carnes: desenvolvimento de métodos analíticos e estratégias para o uso de técnicas com fonte de plasma.

A carne é amplamente consumida em todo mundo. Adicionalmente, esse alimento possui uma grande influência na economia brasileira. Em termos nutricionais, a carne é considerada como fonte de elementos essenciais, como cobre, ferro, fósforo, manganês e molibdênio, e, que desempenham importantes funções no organismo humano. Nesse contexto, o objetivo dessa tese é o desenvolvimento de métodos analíticos e investigação de estratégias para a determinação de elementos essenciais e tóxicos em carne por espectrometria de emissão óptica com plasma induzido por micro-ondas (MIP OES) e espectrometria de massa com plasma acoplado indutivamente e configuração tandem (ICP-MS/MS). O uso do MIP OES foi investigado para a determinação do fósforo a partir dos fosfolipídios em carne, Devido a introdução de solvente orgânico no plasma, foram adotadas algumas estratégias como o uso do módulo de controle de gás externo (EGCM) e a correção do sinal do P por padronização interna (Te) e espécie molecular (OH). Para estimar a exatidão do método, os resultados foram comparados a valores obtidos por cromatografia iônica. As recuperações foram 95% para a padronização interna e 94% para a espécie molecular. Os resultados demostraram que o uso dessas correções de sinais foram efetivas e representaram incremento na exatidão. A microextração dispersiva líquidolíquido (DLLME) foi empregada para aumentar a sensibilidade de procedimento para a determinação de molibdênio em carne por MIP OES. A escolha do solvente dispersor e extrator foi baseada nos planejamentos de misturas. Adicionalmente, os parâmetros da DLLME foram otimizados empregando um planejamento Box-Behnken. O material de referência de fígado bovino (NIST, 1577c) foi empregado para avaliar a exatidão, sendo obtida recuperação de 92%. O fator de pré-concentração foi 4,5 e 0,20 ?g g-1 o limite de detecção. Em outro estudo, foi realizada uma avaliação crítica dos nebulizadores no plasma de nitrogênio. Neste tópico os efeitos de quatro nebulizadores (Concêntrico, MiraMist e OneNeb series 1 e 2) foram investigados quanto aos parâmetros fundamentais do plasma, como temperatura e densidade eletrônica. Adicionalmente foi avaliada a reprodutibilidade em diferentes matrizes. A exatidão foi investigada pela xiii aplicação de quatro materiais de referência e pela adição e recuperação em amostra de cachaça, devido a seu teor alcoólico. Os resultados demostraram que os parâmetros fundamentais do plasma foram significativamente afetados pelos nebulizadores. Ademais, o nebulizador OneNeb serie 2 apresentou um melhor desempenho em relação a sensibilidade, eficiência de transporte e precisão. Em outro estudo, a determinação de nove elementos essenciais e tóxicos (As, Cd, Co, Cr, Mn, Mo, Pb, Sr e V) em amostras de carne foi realizada por ICP-MS/MS. Inicialmente, foi avaliado o uso dos gases (O2, H2 e He) no sistema octopolar de reação (ORS) para a redução das possíveis interferências espectrais. A escolha do melhor modo de operação foi baseada na exatidão obtida durante a análise do material de referência de fígado ovino (NIST, 1577b). Para o Cd, Co, Mo, Pb e V não foi necessário o uso de gases. Por outro lado, para Cr e As, o uso do He foi mais adequado, enquanto o emprego do H2 apresentou melhor recuperação para o Sr. Os limites de detecção para esse método variaram entre 0,08 ?g kg-1 (Cd) e 16 ?g kg-1 (Mo). Posteriormente, amostras de carne bovina foram digeridas e analisadas no ICP-MS/MS nos melhores modos de operação. Por meio de um gráfico de correlação observou-se correlação positiva entre o Cd e Pb e Sr e Pb.Orientadora: Dra. Ana Rita de Araujo Nogueira - Embrapa Pecuária Sudeste

Antioxidant effect of Linalool on testicular-injury induced by carbon tetrachloride in male rats

Background: The oxidative stress and generation of free radicals plays an important role in testicular impairment. The aim of this study was to investigate the protective effect of linalool on carbon tetrachloride (CCl4)-induced male reproductive system damage. Methods: In this study, 24 male rats were divided into four groups. Two of the groups were normal control group andCCl4 damage control group which received a daily dose of distilled water for 14 days. Two of the other groups were pretreatment groups; the rats in one of them received a daily dose of 25 mg/kg linalool and those in the other were administered with a daily dose of 100 mg/kg silymarin for 14 days. On the 14th day, the damage control group as well as the pretreatment groups was intraperitoneally injected with 1 ml/kg of the mixture of CCl4and olive oil (1:1). The rats in the normal control group were only administered with olive oil. 48 hours after the injection of CCl4, a part of the testis tissue was separated for conducting antioxidant and malondialdehyde (MDA) tests. Results: The injection of CCl4 into the rats caused a significant increase in the concentration of MDA and insignificant decrease in the level of antioxidants in the testicular lysate as compared to the normal control group (P<0.01). Treatment with linalool improved the level of MDA and enhanced antioxidant as compared to the damage control group (P<0.01). Conclusion: The results of this study indicated that linalool has antioxidant properties and can have a therapeutic effect against CCl4-induced testicular injuries