Clinical Decision Support System for Diabetic Patients by Predicting Type 2 Diabetes Using Machine Learning Algorithms.

Diabetes is one of the most serious chronic diseases that result in high blood sugar levels. Early prediction can significantly diminish the potential jeopardy and severity of diabetes. In this study, different machine learning (ML) algorithms were applied to predict whether an unknown sample had diabetes or not. However, the main significance of this research was to provide a clinical decision support system (CDSS) by predicting type 2 diabetes using different ML algorithms. For the research purpose, the publicly available Pima Indian Diabetes (PID) dataset was used. Data preprocessing, K-fold cross-validation, hyperparameter tuning, and various ML classifiers such as K-nearest neighbor (KNN), decision tree (DT), random forest (RF), Naïve Bayes (NB), support vector machine (SVM), and histogram-based gradient boosting (HBGB) were used. Several scaling methods were also used to improve the accuracy of the result. For further research, a rule-based approach was used to escalate the effectiveness of the system. After that, the accuracy of DT and HBGB was above 90%. Based on this result, the CDSS was implemented where users can give the required input parameters through a web-based user interface to get decision support with some analytical results for the individual patient. The CDSS, which was implemented, will be beneficial for physicians and patients to make decisions about diabetes diagnosis and offer real-time analysis-based suggestions to improve medical quality. For future work, if daily data of a diabetic patient can be put together, then a better clinical support system can be implemented for daily decision support for patients worldwide.

Achieving Targeted Delivery of Chemotherapeutic Particles to Small Airway Tumors via Pulmonary Route Using Endotracheal Catheters: A CFPD Study.

Tracheobronchial tumors, while uncommon, are often malignant in adults. Surgical removal is the primary therapy for non-metastatic lung malignancies, but it is only possible in a small percentage of non-small-cell lung cancer patients and is limited by the number and location of tumors, as well as the patient's overall health. This study proposes an alternative treatment: administering aerosolized chemotherapeutic particles via the pulmonary route using endotracheal catheters to target lung tumors. To improve delivery efficiency to the lesion, it is essential to understand local drug deposition and particle transport dynamics. This study uses an experimentally validated computational fluid particle dynamics (CFPD) model to simulate the transport and deposition of inhaled chemotherapeutic particles in a 3-dimensional tracheobronchial tree with 10 generations (G). Based on the particle release maps, targeted drug delivery strategies are proposed to enhance particle deposition at two lung tumor sites in G10. Results indicate that controlled drug release can improve particle delivery efficiencies at both targeted regions. The use of endotracheal catheters significantly affects particle delivery efficiencies in targeted tumors. The parametric analysis shows that using smaller catheters can deliver more than 74% of particles to targeted tumor sites, depending on the location of the tumor and the catheter diameter used, compared to less than 1% using conventional particle administration methods. Furthermore, the results indicate that particle release time has a significant impact on particle deposition under the same inhalation profile. This study serves as a first step in understanding the impact of catheter diameter on localized endotracheal injection for targeting tumors in small lung airways.

Exercise-induced CITED4 expression is necessary for regional remodeling of cardiac microstructural tissue helicity.

Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transcriptional co-regulator necessary for cardioprotection, is regionally heterogenous in the heart with preferential significant increases in the lateral wall compared with sedentary mice. Concordantly in this same region, the heart's local microstructural tissue helicity is also selectively increased in exercised mice. Quantification of CITED4 expression and microstructural tissue helicity reveals a significant correlation across both sedentary and exercise mouse cohorts. Furthermore, genetic deletion of CITED4 in the heart prohibits regional exercise-induced microstructural helicity remodeling. Taken together, CITED4 expression is necessary for exercise-induced regional remodeling of the heart's microstructural helicity revealing how a key molecular regulator of cardiac remodeling manifests into downstream local tissue-level changes.

Perspectives on signaling for biological- and processed food-related advanced glycation end-products and its role in cancer progression.

Receptor for advanced glycation end-products (RAGE) is a multifunctional receptor binds a broad spectrum of ligands and mediates responses to cell damage and stress conditions. It also activates programs leading to acute and chronic inflammation and implicated in several pathological diseases, including cancer. In this review, we presented the non-enzymatic reaction of reducing sugar with the amino groups of proteins, lipids, and nucleic acids. This reaction initiates a complex series of rearrangements and dehydrations, and then produces a class of irreversibly cross-linked heterogeneous fluorescent moieties, termed advanced glycation end products (AGEs). There is a growing body of evidence that interaction of processes food-related AGEs with a cell surface receptor RAGE brings out the generation of oxidative stress and subsequently evokes proliferative, angiogenic and inflammatory reactions, thereby being involved in the development and progression of various types of cancers. This review is an insightful assessment of molecular mechanisms through which RAGE signaling contributes to the enhancement and survival of the tumorigenic cell. Here we summarize the procurement of individual ligands of RAGE like amphoterin, calcium-binding proteins, and resultant mediation of RAGE signaling pathway, which partially can elucidate the elevated risk of several cancers. Besides, we summarize many factors or conditions including APE1 (apurinic/apyrimidinic endonuclease 1), retinol mutations, retinoblastoma (Rb), proteinase 3 (PR3) hypoxia and so on through which RAGE signaling presents an establishment of cancerous environment. Additionally, we also reviewed some recent findings that give shreds of evidence for presenting the role of RAGE and its ligands in the advanced stage of cancers.

Modified middle cerebral artery occlusion model provides detailed intraoperative cerebral blood flow registration and improves neurobehavioral evaluation.

BACKGROUND: Middle cerebral artery occlusion (MCAO) with 1 -h ischemia followed by reperfusion is a widely used stroke model in rodents that has significant limitations such as high mortality and severe neurological deficit hampering comprehensive neurobehavioral evaluation. The goal of this study was to establish a mouse model of 30-minute MCAO followed by 48 h of reperfusion and compare it with 1 -h MCAO followed by 24 h of reperfusion. NEW METHOD: Here we propose a modified MCAO model that is favorable for both neurobehavioral and infarct volume evaluation. The model includes shorter ischemic time (30 min) of MCAO followed by 48 h of reperfusion and use of standardized intraoperative partial and total reperfusion, which allows for the detailed evaluation of initial and total reperfusion by means of the monitoring of CBF by LDF. RESULTS AND COMPARISON WITH EXISTING METHOD: Intraoperative CBF parameters and infarct volume (1-h MCAO at 24 h: 69 ±â€¯9; 30-minute MCAO at 48 h: 65 ±â€¯14 mm3) did not significantly differ between groups. Neurological deficit was less severe in 30-minute MCAO group where mice also had significantly longer ambulatory distance and time, lower resting time, and higher vertical count on the OPF. The latency to fall in the rotarod test was significantly higher in 30-minute MCAO group. The mortality was higher after 1 -h MCAO. CONCLUSIONS: 30-minute MCAO followed by 48 h of reperfusion causes intraoperative ischemia, reperfusion and infarct volume comparable with 1 -h MCAO followed by 24 h of reperfusion but results in lower mortality with milder neurological deficit allowing for more extensive neurobehavioral evaluation.

Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion.

Clinical evidence suggests that patients with subcortical ischemic vascular dementia (SIVD) perform better at cognitive tests after exercise. However, the underlying mechanism for this effect is largely unknown. Here, we examined how treadmill exercise changes the cognitive function and white matter cellular pathology in a mouse model of SIVD. Prolonged cerebral hypoperfusion was induced in 2-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into a group that received 6-week treadmill exercise and a sedentary group for observation. In multiple behavioral tests (Y-maze, novel object recognition, and Morris water maze tests), the treadmill exercise training was shown to ameliorate cognitive decline in the hypoperfused SIVD mice. In addition, immunohistological analyses confirmed that there was a larger population of oligodendrocyte precursor cells in the subventricular zone of exercised versus sedentary mice. Although further investigations are needed to confirm a causal link between these findings, our study establishes a model and cellular foundation for investigating the mechanisms through which exercise preserves cognitive function in SIVD.

Neuroprotective potential of exercise preconditioning in stroke.

Stroke is one of leading causes of mortality and morbidity in the world with limited availability of therapeutic intervention. Exercise has been shown to improve stroke functional outcome in different preclinical and clinical setup. Exercise preconditioning induced neuroprotection in preclinical stroke models is believed to be mediated through its ability to restore brain vasculature and blood brain barrier integrity, promote neurogenesis, and help fight against neuroinflammation and excitotoxicity. In this short review, we will summarize the molecular mechanisms of exercise preconditioning described in preclinical stroke studies. We will also discuss the neuroprotective effects of pre-ischemic exercise.

Enkephalin-Fentanyl Multifunctional Opioids as Potential Neuroprotectants for Ischemic Stroke Treatment.

BACKGROUND: Ischemic stroke is one of the leading causes of mortality and morbidity in the world and effective neuroprotectants are yet to be developed. Recent studies have demonstrated excellent neuroprotective effects of a bivalent enkephalin opioid agonist, biphalin in multiple stroke models. METHODS: The purpose of this study is to evaluate novel multifunctional enkephalin-fentanyl opioid agonists, LYS436, LYS739 and LYS416 for their neuroprotective potential using in vitro and in vivo ischemic stroke models and to compare the effect to that of biphalin. RESULTS: In general, all non-selective opioid agonists significantly decreased neuronal cell death and levels of reactive oxygen species in primary neurons subjescted to hypoxia-aglycemia/re-oxygenation or NMDA neurotoxicity. Fluorinated enkephalin-fentanyl conjugate, LYS739 showed enhanced neuroprotection in both in vitro models compared to biphalin. Based on further in vitro screening and comparative studies to biphalin, LYS739 was selected as a lead for in vivo experimentation. A mouse middle cerebral artery occlusion (MCAO) stroke model was utilized to study biphalin and the lead analog, LYS739. Both agonists significantly decreased brain infarct and edema ratios compared to saline treated group. Neurological impairment after stroke was statistically significantly improved in terms of neurological score and locomotor activities with LYS739 and biphalin treatment. Importantly, LYS739 and biphalin demonstrated better neuroprotection compared to fentanyl, and this effect was reversed by non-selective opioid antagonist naltrexone. CONCLUSION: In summary, the results of this study suggest that the multifunctional fluorinated enkephalin analog, LYS739 can be considered as a potential lead for ischemic stroke research and may provide advantages given the multimeric peptide-opiate structure.

Antihyperglycemic and antinociceptive activity evaluation of 'khoyer' prepared from boiling the wood of Acacia catechu in water.

'Khoyer' is prepared by boiling the wood of Acacia catechu in water and then evaporating the resultant brew. The resultant hard material is powdered and chewed with betel leaves and lime with or without tobacco by a large number of the people of Bangladesh as an addictive psycho-stimulating and euphoria-inducing formulation. There are folk medicinal claims that khoyer helps in the relief of pain and is also useful to diabetic patients to maintain normal sugar levels. Thus far no scientific studies have evaluated the antihyperglycemic and antinociceptive effects of khoyer. The present study was carried out to evaluate the possible glucose tolerance efficacy of methanolic extracts of khoyer using glucose-induced hyperglycemic mice, and antinociceptive effects with acetic acid-induced gastric pain models in mice. In antihyperglycemic activity tests, the extract at different doses was administered one hour prior to glucose administration and blood glucose level was measured after two hours of glucose administration (p.o.) using glucose oxidase method. The statistical data indicated the significant oral hypoglycemic activity on glucose-loaded mice at all doses of the extracts tested. Maximum anti-hyperglycemic activity was shown at 400 mg extract per kg body weight, which was less than that of a standard drug, glibenclamide (10 mg/kg body weight). In antinociceptive activity tests, the extract also demonstrated a dose-dependent significant reduction in the number of writhing induced in mice through intraperitoneal administration of acetic acid. Maximum antinociceptive activity was observed at a dose of 400 mg extract per kg body weight, which was greater than that of a standard antinociceptive drug, aspirin, when administered at a dose of 400 mg per kg body weight. The results validate the folk medicinal use of the plant for reduction of blood sugar in diabetic patients, as well as the folk medicinal use for alleviation of pain.

Ethnobotanical, phytochemical and toxicological studies of Xanthium strumarium L.

The present study describes the ethnobotanical, phytochemical, and toxicological evaluations of Xanthium strumarium L. growing in Bangladesh. In toxicity evaluation on rats, the methanol extract of seedlings showed mortality, while both seedling and mature plant extracts raised the serum alanine transaminase and aspartate transaminase values and produced significant abnormalities in the histopathology of liver and kidney of rats. On the other hand, the aqueous soluble fraction of methanol extract of mature plant (LC50 = 0.352 microg/mL) and methanol crude extract of seedlings (LC50 = 0.656 microg/mL) demonstrated significant toxicity in the brine shrimp lethality bioassay. A total of four compounds were purified and characterized as stigmasterol (1), 11-hydroxy-11-carboxy-4-oxo-1(5),2(Z)-xanthadien-12,8-olide (2), daucosterol (3) and lasidiol-10-anisate (4). The present study suggests that X. strumarium is toxic to animal.