In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also has an interesting aspect as a mesenchymal stem cell reservoir. The splenic mesenchymal stem cells contribute to tissue repair in damaged tissue, and thus, the infusion can be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

The switch from intermittently scanned continuous glucose monitoring (isCGM) to real-time (rt) CGM could improve glycemic management in suboptimal controlled type 1 diabetes patients, but long-term study is lacking. We evaluated retrospectively the ambulatory glucose profile (AGP) in such patients after switching from Free Style libre 1 (FSL1) to Dexcom G4 (DG4) over 1 year. Patients (n=21, 43±15 years, BMI 25±5, HbA1c 8.1±1.0%) had severe hypoglycemia and/or HbA1c≥8%. AGP metrics (time-in-range (TIR) 70-180 mg/dL, time-below-range (TBR)<70 mg/dL or <54 mg/dL, glucose coefficient of variation (%CV), time-above-range (TAR) >180 mg/dL or >250 mg/dL, glucose management indicator (GMI), average glucose) were collected the last 3 months of FSL1 use (M0) and of DG4 for 3, 6 (M6) and 12 (M12) months of use. Values were means ± standard deviation or medians [Q1;Q3]. At M12 versus M0, the higher TIR (50±17 vs. 45±16, P=0.036), and lower TBR<70 mg/dL (2.5 [1.6;5.5] vs. 7.0 [4.5;12.5], P=0.0007), TBR<54 mg/dL (0.7 [0.4;0.8] vs. 2.3 [0.8;7.0], P=0.007) and %CV (39±5 vs. 45±8, P=0.0009), evidenced a long-term effectiveness of the switch. Compared to M6, TBR<70mg/dL decreased, %CV remained stable, while the improvement on hyperglycemia exposure decreased (higher GMI, TAR and average glucose). This switch was a relevant therapeutic option, though a loss of benefit on hyperglycemia stressed the need for optimized management of threshold alarms. Nevertheless, few patients attained the recommended values for AGP metrics, and the reasons why some patients are “responders” vs “non-responders” warrant to be investigated.

Racial and ethnic disparities exist in diabetes prevalence, health services utilization, and out-comes including disabling and life-threatening complications. Home health care may especially benefit older adults with diabetes through individualized education, advocacy, care coordina-tion, and psychosocial support for patients and their caregivers. This study examined factors as-sociated with hospital discharge to home health care and subsequent utilization of home health care among a cohort of Medicare beneficiaries with diabetes, age 50 and older, living in the United States. The cohort (n=786,758) was followed for 14 days after a diabetes-related index hospitalization, using linked Medicare administrative, claims, and assessment data (2014-2016). Multivariate logistic regression models included patient demographics, comorbidities, hospital length of stay, geographic region, neighborhood area deprivation, and rural/urban setting. In ful-ly adjusted models, hospital discharge to home health care was significantly less likely among Hispanic (OR 0.8, 95% CI 0.8-0.8) and American Indian (OR 0.8, CI 0.8-0.8) compared to white patients. Among those discharged to home health care, all racial/ethnic minority patients were less likely to receive services within 14-days. Further work should focus on eliminating systemic racism in home health care referral and systemic barriers to receiving home health care services.

Immunomodulation as means of immunotherapy has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulator used in immunotherapy approaches. Similarly, nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) has extensively been shown to play a role as an immuno-modulator during inflammation. Given their mutual roles in downregulating the immune response, current study examined the influence of PPARγ ligands i.e thiazolidinedione (TZD) class of drugs on Foxp3 expression and possible crosstalk between PPARγ and nTreg cells of NOD and NOR mice. Results showed that TZD drug, ciglitazone and natural ligand of PPARγ 15d-prostaglandin downregulated Foxp3 expression in activated nTreg cells from both NOD and NOR mice. Interestingly, addition of the PPARγ inhibitor, GW9662 further downregulated Foxp3 expression in these cells from both mice. We also found that PPARγ ligands negatively regulate Foxp3 expression in activated nTreg cells via PPARγ-independant mechanism(s). These results demonstrate that both natural and synthetic PPARγ ligands capable of suppressing Foxp3 expression in activated nTreg cells of NOD and NOR mice. This may suggest that the effect of PPARγ ligands in modulating Foxp3 expression in activated nTreg cells is different from their reported effects on effector T cells. Given the capability to suppress foxp3 gene, it is possible to be tested as immunomodulators in cancer-related studies.

The Seven Country study showed that traditional Japanese diet and Mediterranean diets are protective against cardiovascular diseases (CVDs). Japanese diet is considered the healthiest because it provides highest longevity and health to Japanese. DASH diet and Mediterranean style diets are also considered the healthy diets, although, it is possible that Indo-Mediterranean style diet may provide better protective effects among patients with CVDs, compared to other diets. The concept of Indo-Mediterranean type of diets was developed, after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France; The Lyon Heart Study. These workers found that eating alpha-linolenic acid rich Mediterranean style diet can cause significant decline in CVDs and all-cause mortality. Later on in 2018, PREDIMED Study from Spain also reported that a modified Mediterranean style diet can cause significant decline in CVDs, type 2 diabetes mellitus (T2DM) and cancer. The Indo-Mediterranean diet may be superior to DASH diet and Mediterranean diet because it contains millets, porridge, beans and spices; turmeric, cumin, fenugreek and coriander which may have better anti-inflammatory and cardio-protective effects. These foods are rich sources of nutrients; flavonoids, calcium and iron as well as proteins which are useful in the prevention of under as well as over-nutrition and related diseases. It is known that DASH diet and Mediterranean style diets have similar influence on CVDs. However, Indo-Mediterranean style diet, may be as good as Japanese diet, due to improved food diversity and high content of antioxidants in the diets.

We aimed to assess the caffeine intake before and during pregnancy, compliance with caffeine recommendations during pregnancy (200 mg/day) and factors associated with higher intakes before and in first trimester of pregnancy. Caffeine consumption was collected in a Spanish cohort of pregnant women through a validated food questionnaire, before and in each trimester of gestation (T1, T2 and T3). 463 pregnant women were recruited and follow-up through pregnancy. Compliance with caffeine intake recommendations during pregnancy and quintiles of mg/day of caffeine before and in T1 of pregnancy were calculated. A multivariate logistic regression, comparing extreme quintiles of consumption (Q1 vs Q5) was used. Mean caffeine intake before pregnancy was 120.05 mg/day (SD 117.85), 42.76 mg/day (SD 63.90) at 12th GW, 42.00 mg/day (SD 59.76) at 24th GW and 39.34 mg/day (SD 50.9) at 32nd GW (p&lt;0.001). 86% of women complied with caffeine recommendations during pregnancy. At pregnancy (T1), being an active smoker was associated with Q5 &gt; 100.1 mg/day, aOR = 22.69; 95% CI 4.67- 110.26. igh diet quality, aOR = 0.30; 95% CI, 0.13- 0.68, and moderate physical activity level, aOR= 0.44; 95% CI, 0.19-1.00, were inversely associated with Q5 &gt; 100.1 mg/day. Pregnant women are mostly adhering to current caffeine intake guidelines. Higher caffeine intake at pregnancy is associated with other unhealthy habits during pregnancy.

The novel coronavirus (COVID-19) was first reported in the U.S. on December 29, 2019 and has spread rapidly throughout the country, affecting individuals with varying severity due to their risk status. According to the Centers for Disease Control and Prevention, it is estimated that 45.4% of US adults are at higher risk for complications from coronavirus disease because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. In this study, we developed a mathematical model to assess the impact of a COVID-19 vaccine among low and high risk groups. Numerical simulations shows vaccinating both low and high risk groups simultaneously, rather than prioritizing the vaccine on high risk group only, further reduces the daily mortality. The result supports the need for an aggressive vaccination program, regardless of whether individuals are within the low or high risk population.

BackgroundGood management behavior in patients with diabetes mellitus can reduce disease complications and improve quality of life. This philosophical problem is very important for nurses who are able to provide management care for diabetic patients. The purpose of this literature review is to describe the concept, model or theory that can be used in improving the management of diabetes mellitus patients.MethodsThe method used is by searching several studies published through the Scopus database, PubMed, CINAHL, SpingerLink, and web of science (WOS). The search strategy uses a combination of the terms MeSH Terms. The research questions were designed using the principles of the PICOS framework. Selected studies were published from 2017-2022.ResultsA total of 15 studies were included, with 12 using quantitative methodology and 3 were qualitative. The studies were conducted across various countries. The majority of articles used the concept of self-management intervention based on digital-based development and e-health (n=6), Dorothea Orem's self-care deficit nursing theory n=2) and the transtheoretical model (n=2). These concepts, models and theories are able to improve good self-management through lifestyle changes, psychosocial, cultural acculturation and increase in spiritual values (n=6).ConclusionTransitional change focuses on changing the modifiable factors found in the concepts, models and theories of the articles obtained. Future research can be developed to assess the existence of elaborations and modifications based on the philosophy that people with diabetes are responsible for their own health.

Much epidemiological research confirms a correlation between a high consumption of sugar sweetened beverages and obesity, diabetes and cardiovascular diseases. In many of these studies, soft drinks, fruit drinks with added sugars and 100% fruit juices without added sugars were considered as one separate category and the total consumption was calculated cumulatively. Being able to make statements about the effects of individual types of drinks, as present in these clusters, is therefore impossible. However, recent data from well-controlled studies and meta-analyses on consumption of 100% fruit juice show that there is no effect on diabetes risks. Adults and children who choose to drink 100% juice appear to have a healthier lifestyle, consume better quality food and usually have a more favorable body weight. Although 100% fruit juice in relation to soft drinks contains a range of nutrients that are considered to be beneficial for health, the associated positive effects can be nullified by high sugar intake, in case of excessive consumption. That is why a golden rule can be applied: "100% fruit juice, as part of a healthy diet, is a healthy choice provided that you do not consume more juice than present in max. 1-3 fruits at a time. In the case of orange juice, this corresponds to a champagne glass full of juice (100-150ml). In this respect 100% fruit juice should be perceived as a nutritional drink that can be consumed with a meal and not as a thirst quencher.

Modern day civilization is dependent on energy generation by fossil fuels. But the major drawback of using fossil fuels is environmental pollution. Microalgae are potential candidate for production of various products of interest, such as proteins, mini food, pigments and triglycerides that can be converted into biofuels. Lignocellulosic feedstocks are the most abundantly available raw material of plants that can serve as a promising feedstock for cultivating bacteria, fungi, yeasts and microalgae to produce biofuels and other value-added products. Owing to the abundant availability of these low/no cost substrates, can be utilized as feedstocks for cultivating microalgae to generate biogas/biodiesel. Likewise, there is much room to exploit defatted algal biomass to be used as animal/fish feed and oil producing/accumulating genes knowledge in future to produce high and good quality biodiesel and biogas.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

Recent advancements of computer and electronic systems have motivated the extensive use of intelligent systems for automation of agricultural industries. In this study, the temperature variation of the mushroom growing room is modeled through using a multi-layered perceptron (MLP) and radial basis function networks. Modeling has been done based on the independent parameters including ambient temperature, water temperature, fresh air and circulation air dampers, and water tap. According to the obtained results from the networks, the best network for MLP is found to be the second repetition with 12 neurons in the hidden layer and 20 neurons in the hidden layer for radial basis function networks. The obtained results from comparative parameters for two networks showed the highest correlation coefficient (0.966), the lowest root mean square error (RMSE) (0.787) and the lowest mean absolute error (MAE) (0.02746) for radial basis function. Therefore, the neural networks with radial basis function was selected as the optimal predictor for the behavior of the system.

Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising from diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include the prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function, and calcium regulation. The present review summarizes the recent findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

The aim of this study was to assess if the ovine articular cartilage serine proteinase inhibitors (SPIs) were related to the Kunitz inter-α-trypsin inhibitor (ITI) family. Ovine articular cartilage was finely diced and extracted in 6M urea and SPIs isolated by sequential anion exchange, HA affinity and Sephadex G100 gel permeation chromatography. Selected samples were also subjected to chymotrypsin and concanavalin-A affinity chromatography. Eluant fractions from these isolation steps were monitored for protein and trypsin inhibitory activity and pooled fractions assessed by affinity blotting using biotinylated trypsin to detect active SPIs and by Western blotting using antibodies to α1-microglobulin, bikunin, TSG-6 and 2-B-6 (+) CS stub epitope generated by chondroitinase-ABC digestion. This identified 2-B-6 (+) positive 220-250,120, 58 and 36 kDa SPIs. The 58 kDa SPI contained α1-microglobulin, bikunin and chondroitin-4-sulphate stub epitope consistent with its identity as the α1-microglobulin-bikunin (AMBP) precursor and was also isolated by concanavalin-A lectin affinity chromatography indicating it had N-glycosylation. Kunitz protease inhibitor (KPI) species of 36, 26, 12 and 6 kDa could be autolytically generated by prolonged storage of the aforementioned 120 and 58 kDa SPIs; chymotrypsin affinity chromatography also generated the 6kDa SPI. KPI domain 1 and 2 SPIs were separated by concanavalin lectin affinity chromatography, domain 1 displayed affinity for this lectin indicating it had N-glycosylation. KPI 1 and 2 both displayed potent inhibitory activity towards trypsin, chymotrypsin, kallikrein, leucocyte elastase and cathepsin G. Localisation of versican, lubricin and HA in the surface regions of articular cartilage represented probable binding sites for the ITI SPs with likely importance in the preservation of joint function.

Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.

Pre-diabetes is a serious health condition where blood sugar levels are higher than normal, but not high enough yet to be diagnosed as type 2 diabetes. Pre-diabetes puts one at an increased risk of developing type 2 diabetes and heart disease Methodology: A cross-sectional study was carried out on 384 patients aged 20-70 years old, attending the dental clinics to assess the risk for diabetes, using the FINDRISC questionnaire, HbA1c blood test and a periodontal examination. Results: The mean age of participants was 38.90±10.74. 32.3% were categorized as no risk, 46.6% low risk, while 19% and 2.1% moderate and high risk of developing diabetes respectively. Tests for serum HbA1c Level showed 46.1 % had normal HbA1c followed by 18.0% and 3.6 % were pre-diabetic and diabetic respectively. 19.3% of participants had periodontal pockets measuring more than 4mm and 15.9% measuring more than 6mm. Conclusion: The study has proven to be useful in identifying patients at high-risk of developing diabetes. Controlling and managing periodontal disease could be a new aspect to include in the standards for diabetes care. Dental settings could be a successful platform to carry out the screening and risk stratification of pre-diabetic patients.

The issue of sustainability has long been the subject of interest of the architecture engineering and construction sector. All three aspects of sustainability - economic, environmental and social - can be affected through appropriate construction waste management. Construction and demolition waste (CDW) is one of the largest worldwide waste streams, therefore it is given great attention by all stakeholders (investors, contractors, authorities, etc.). Researches have shown that one of the main barriers to insufficiency CDW recovery is inadequate policies and legal frameworks to manage CDW. It is also one of the EU's environmental priorities. Aim of the article is to confirm the economic potential of construction and demolition waste audit processing through case study. A pre-demolition waste audit has been processed for unused building of shopping center in the town Snina in Slovakia. Subsequently, a comparison of economic parameters (waste disposal costs and transport costs) of recommended CDW management was performed. This comparison confirmed the economic benefits of environmentally friendly construction waste management methods according to the waste audit results, which will also increase the sustainability of construction projects. In addition, the cost parameters of selected waste disposal methods could be another dimension of building information modelling.

Artificial intelligence, a key technological tool in the era of the 4th Industrial Revolution, is being actively applied to education beyond industry, economy, and culture. In the future society, understanding and using artificial intelligence technology will be considered an essential skill for everyone, and the professionalism of AI education for pre-service teachers nurturing future talents is also important. This study verifies the effectiveness of pre-service teachers after undergoing a 15-week extension program consisting of AI Literacy Education (10 weeks), AI-Linked Subjet Education (3 weeks), and Micro-teaching (2 weeks) which was designed to enhance the AI ​​education professionalism of pre-service teachers. The AI Literacy Education section consisted of understanding AI, AI ethics, and basic programming, and the education was conducted through both experience and practice. After that, the pre-service teachers analyzed the curriculum of the 5th and 6th grades of an elementary school, and developed a subject-related education program using AI tools in three stages. Using the developed program, micro-teaching classes were conducted twice. The study results are as follows. First, there was a change in the positive perception of AI (p<.05). Second, the understanding of AI educational technology tools was improved and the recognition of the usefulness of developing a curriculum-related program was expanded. Third, the importance of teacher competency development was learned through the micro-teaching, and the students' understanding of the learning process was expanded.

Abstract: In network science and big data, the concept of finding meaningful infrastructures in networks has emerged as a method of finding groups of entities with similar properties within very complex systems. The whole concept is generally based on finding subnetworks which have more properties (links) amongst nodes belonging to the same cluster than nodes in other groups (A concept presented by Girvan and Newman, 2002). Today meaningful infrastructure identification is applied in all types of networks from computer networks, to social networks to biological networks. In this article we will look at how meaningful infrastructure identification is applied in biological networks. This concept is important in biological networks as it helps scientist discover patterns in proteins or drugs which helps in solving many medical mysteries. This article will encompass the different algorithms that are used for meaningful infrastructure identification in biological networks. These include Genetic Algorithm, Differential Evolution, Water Cycle Algorithm (WCA), Walktrap Algorithm, Connect Intensity Iteration Algorithm (CIIA), Firefly algorithms and Overlapping Multiple Label Propagation Algorithm. These al-gorithms are compared with using performance measurement parameters such as the Mod-ularity, Normalized Mutual Information, Functional Enrichment, Recall and Precision, Re-dundancy, Purity and Surprise, which we will also discuss here.

Type 2 Diabetes Mellitus is being increasingly associated with dysfunction of cognition. Dementia, including vascular dementia and Alzheimer’s disease, is being recognized as comorbidities of this metabolic disorder. The progressive hallmarks of this cognitive dysfunction include mild impairment of cognition and cognitive decline. Dementia and mild impairment of cognition appear in older patients primarily. Studies on risk factors, neuropathology, and brain imaging have provided important suggestions for mechanisms that lie behind the development of dementia. It is a significant challenge to understand the disease processes related to diabetes which affect the brain and lead to dementia development. The connection between Diabetes Mellitus and dysfunction of cognition has been observed in many human and animal studies that have noted mechanisms related to Diabetes Mellitus are possibly responsible for aggravating cognitive dysfunction. This article attempts to narrate the possible association between type 2 diabetes and Dementia, reviewing studies that have noted this association in vascular dementia and Alzheimer’s disease and helping to explain the potential mechanisms behind the disease process. The Google search for ‘Diabetes Mellitus and Dementia’ was carried out. Also, the search was done using ‘Diabetes Mellitus,’ ‘Vascular Dementia,’ ‘Alzheimer’s Disease.’ The literature search was done from Google Scholar, Pubmed, Embase, ScienceDirect, and MEDLINE. Keeping in mind the increasing rate of Diabetes Mellitus, it is important to establish the type 2 diabetes effect on the brain and diseases of neurodegeneration. This narrative review aims to build awareness regarding different types of dementia and their relationship with diabetes.

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

In the present work a novel, portable and innovative eNose composed of a surface acoustic wave (SAW) sensor array based ZIF-8, and ZIF-67 nanocrystals (pure and combined with gold nanoparticles) as sensitive layers has been tested as a non-invasive system to detect and differentiate disease markers, such as acetone, ethanol and ammonia, related with early diagnosis of diabetes mellitus through exhaled breath. The sensors have been prepared by spin coating, achieving continuous and homogenous sensitive layers. Low concentrations (5 ppm, 10 ppm and 25ppm) of the marker analytes were measured, obtaining high sensitivities, good reproducibility, short time response and fast signal recovery.

Forest fires are part of a set of natural disasters that have always affected regions of the world typically characterized by a tropical climate with long periods of drought. However, due to climate change in recent years, other regions of our planet have also been affected by this phenomenon, never seen before. One of them is certainly the Italian peninsula, and especially the regions of southern Italy. For this reason, the scientific community, as well as remote sensing one, is highly concerned in developing reliable techniques to provide useful support to the competent authorities. In particular, three specific tasks have been carried out in this work: (i) fire risk prevention, (ii) active fire detection, and (iii) post-fire area assessment. To accomplish these analyses, the capability of a set of spectral indices, derived from spaceborne remote sensing (RS) data, is assessed to monitor the forest fires. The spectral indices are obtained from Sentinel-2 multispectral images of the European Space Agency (ESA), which are free of charge and openly accessible. Moreover, the twin Sentinel-2 sensors allow to overcome some restrictions on time delivery and observation repeat time. The performance of the proposed analyses were assessed experimentally to monitor the forest fires occurred in two specific study areas during the summer of 2017: the volcano Vesuvius, near Naples, and the Lattari mountains, near Sorrento (both in Campania, Italy).

During the past few decades, hybrid nanoparticles (HNPs) based on a magnetic material and gold have attracted interest for applications in catalysis, diagnostics and nanomedicine. In this paper, magnetic CoFe2O4/Au HNPs with an average particle size of 10–20 nm decorated with 2-nm gold clusters were prepared using methionine as a reducer and an anchor between CoFe2O4 and gold. The obtained nanoparticles were studied by X-Ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectroscopy and X-Ray photoelectron spectroscopy (XPS) and UV-Vis spectroscopy techniques. The TEM images of the HNPs obtained after one, six and ten gold deposition cycles showed that the surface of cobalt ferrite was covered with gold nanoclusters, which slightly increased with an increase in the number of gold deposition cycles (from 2.12 ± 0.15 nm after one cycle to 2.46 ± 0.13 nm after ten cycles) without any change in surface density. The magnetic measurements showed that the obtained HNPs possessed typical ferrimagnetic behaviour, which corresponds to that of CoFe2O4 nanoparticles. The toxicity evaluation of the synthesised HNPs on Chlorella vulgaris indicated that they can be applied to biomedical applications such as magnetic hyperthermia, photothermal therapy, drug delivery, bioimaging and biosensing.

Obesity is an issue of public health concern as it contributes to chronic non-communicable diseases despite the fact that it is preventable. Dietary practices and environment have been associated with increased risk of cardiovascular diseases, hypertension, overweight and obesity among young people. This study aimed to assess the dietary patterns associated with obesity among Babcock University students. A descriptive cross-sectional study was used to obtain data from 391 participants. Results reveal respondent’s knowledge was 12.06 ± 2.3 translating to an 80% prevalence performance, level of perception was 37.23 ± 9.23 with prevalence of 59.0%, dietary practices was 19.6 ± 5.23 with 59% prevalence. Factors influencing dietary practices revealed mean score of 15.2 ± 4.5 with 72.3% prevalence performance. The factors identified in this study has a great influence on dietary practices of the study participants. In conclusion Babcock University students have an excellent knowledge of dietary practices related to obesity. They also had good dietary practices. The identified factors had a great influence on the study participants.

In the case of type 2 diabetes, inhibitors of glycogen phosphorylase (GP) might prevent unwanted glycogenolysis under high glucose conditions and thus aim at the reduction of excessive glucose production by the liver. Anomeric spironucleosides, such as hydantocidin, present a rich synthetic chemistry and important biological function, e.g., inhibition of GP. Herein, the Suárez radical methodology is successfully applied to synthesize the first example of a 1,6-dioxa-4-azaspiro[4.5]decane system, not been previously constructed via a radical pathway, starting from 6-hydroxymethyl-b-D-glucopyranosyluracil. It is shown that in the rigid pyranosyl conformation the required [1,5]-radical translocation is a minor process. The stereochemistry of the spirocycles obtained was unequivocally determined based on the chemical shifts of key sugar protons in the ¹H NMR spectra. The two spirocycles were found to be modest inhibitors of RMGPb.

Surimi-based products occupy an important position in the aquatic product processing industry. To enhance the quality and flavor of surimi-based products, the effects of pre-emulsified safflower seed oil on the texture, water-holding capacity (WHC), microstructure, and flavor of Nemipterus virgatus surimi gel was evaluated. The texture and whiteness of gel were improved, and the WHC increased (P &lt; 0.05) as the content of safflower seed oil increased up to 2 mL per 100 g surimi. Furthermore, the drops of pre-emulsified safflower seed oils with an average diameter of less than 0.10 μm were evenly distributed in gel matrix. Microstructure and infrared spectroscopy analyses indicated that low-content pre-emulsified safflower seed oil acted as filler particles to occupy void spaces, resulting in gel exhibiting a dense network structure. Volatile analysis showed the gel containing pre-emulsified oil enriched volatile compounds, mainly resulting from oxidation and decomposition of oils by the activation of lipoxygenase, which synergistically contributes to unique flavors of gel. Consequently, low-content pre-emulsified safflower seed oil can used to enhance the quality and flavor of N. virgatus surimi-based products. These findings are especially relevant to the current growing interest in low-fat and high-protein diets.

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants (cat, sod, gpx, and gst) and the components of the insulin signaling pathway (insulin Rβ, irs-1, pi3k, akt, mtor) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes’ gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nfκb. Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components.

Metformin use in pregnancy is increasing worldwide as randomised controlled trial (RCT) evidence is emerging demonstrating its safety and efficacy. The Metformin in Gestational Diabetes (MiG) RCT changed practice in many countries demonstrating that metformin had similar pregnancy outcomes to insulin therapy with less maternal weight gain and a high degree of patient acceptability. A multicentre RCT is currently assessing the addition of metformin to insulin in pregnant women with type 2 diabetes. RCT evidence is also available for the use of metformin for women with Polycystic Ovarian Syndrome and for non-diabetic women with obesity. No evidence of an increase in congenital malformations or miscarriages has been observed even when metformin is started before pregnancy and continued to term. Body composition and metabolic outcomes at two, seven and nine years have now been reported for the offspring of mothers treated in the MiG study. In this review, we will briefly discuss the action of metformin and then consider the evidence from the key clinical trials.

Studies comparing provider and patient views and experiences of self-management within primary healthcare are particularly scarce in disadvantaged settings. In this qualitative study, patient and provider perceptions of self-management were investigated in five socio-economically disadvantaged communities in Stockholm. Twelve individual interviews and three group interviews were conducted. Semi-structured interview guides included questions on perceptions of diabetes diagnosis, diabetes care services available at primary health care centers, patient and provider interactions, and self-management support. Data was analysed using thematic analysis. Two overarching themes were identified. These were characterized by inherent dilemmas representing confusions and conflicts that patients and providers experienced in their daily life or practice respectively: adopting and maintaining new routines through practical and appropriate lifestyle choices (patients); and balancing expectations and pre-conceptions of self-management (providers). Patients found it difficult to tailor information and lifestyle advice to fit their daily life. Healthcare providers recognized that patients were in need of support to change behavior, but saw themselves as inadequately equipped to deal with the different cultural and social aspects of self-management. This study highlights patient and provider dilemmas that influence the interaction and collaboration between patients and providers with respect to communication and uptake of self-management advice.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease, and typical pathologic findings include abnormally hyperphosphorylated tau aggregation and neurofibrillary tangles. Insulin resistance and hyperglycemia have been assessed as risk factors for AD development. As the maintenance of optimal blood glucose levels is an important indicator of diabetes mellitus (DM) treatment, diet control is essential. AMPK is a crucial sensor of cellular bioenergetics for controlling anabolic and catabolic metabolism. Diet restriction to achieve euglycemia can increase AMPK activity in the liver and heart. Since AMPK is a direct regulator of tau phosphorylation, we hypothesized that strict diet control to achieve euglycemia affects tau protein phosphorylation through increased AMPK activity in the hippocampus of DM rats. To confirm this hypothesis, we generated insulin-deficient DM rats by subtotal pancreatectomy. Animals were categorized into the restriction (R) group, control (C) group and ad libitum (AL) group according to the diet. We found that tau phosphorylation was significantly increased in the R group compared with the C or AL group. AMPK activity in the R group significantly increased compared to that of the C group or AL group, as expected. Furthermore, the R group showed more critical tau pathology in the hippocampus than the other groups. These results suggest that diet control to achieve euglycemia in insulin-deficient DM conditions is harmful because of the increased possibility of AD development through increased tau phosphorylation by AMPK activation in the hippocampus. We propose that not only hyperglycemia but also euglycemia, which is beneficial in DM patients, must be considered a potential risk factor for AD development, especially when euglycemia is achieved by diet control during insulin deficiency.

The objective of this study was to identify circulating miRNAs affected by disease duration in newly diagnosed children with type 1 diabetes. Forty children and adolescents from The Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12 and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR and quantified for 179 human plasma miRNAs. The effect of disease duration was analyzed by mixed models for repeated measurements, adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p and hsa-miR-497-5p) were found to significantly change expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies ICA, IA-2A, GADA65 and 4 cytokines IL-4, IL-10, IL-21, IL-22 were associated with the miRNAs at different time points. Pathway analysis revealed association with various immune-mediated signaling pathways. Eight miRNAs, involved in immunological pathways changed expression levels during the first five years after diagnosis in children with type 1 diabetes, and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease.

As the incidence and prevalence of diabetes increases, intervention through dietary education is becoming more important for diabetes control. This systematic review aimed to confirm the ef-fect of dietary intervention education on diabetes control. The study subjects were type 2 diabet-ic patients, and the main outcome variable was glycosylated hemoglobin level (HbA1c). The target studies were randomized controlled trials. Thirty-six studies were included in the analysis, of which 33 were included in the meta-analysis. The effect size between the dietary education and general intervention, was -0.42 (n=5,639, MD=-0.42; 95% CI -0.53 to -0.31) and was signifi-cantly different (Z=7.73, P<.001). When subgroup analyses were performed following the appli-cation periods, intervention methods, and intervention contents, the mean differences in 4–6-month application, individual education, diet-exercise-psychosocial intervention were -0.51, (n=2,742, 95% CI -0.71 to -0.32), -0.63 (n=627, 95% CI -1.00 to -0.26), and -0.51 (n=3.244, 95% CI -0.71 to -0.32), respectively. Dietary education interventions provided for at least 3 months were highly effective in controlling blood sugar levels. Regarding the education method, individual-ized education was more effective, and for this, contact or non-contact education may be applied. Combining diet, exercise, and psychosocial intervention is more effective than diet education alone.

Background: Fetal overgrowth is related to many perinatal complications including stillbirth, cesarean section, maternal and neonatal injuries, and shoulder dystocia. It is related to maternal diabetes, obesity, and gestational weight gain, but also happens in low-risk pregnancies. There is ongoing discussion regarding definitions, methods of detection, and classification. The method used for detection is of crucial importance as it draws a line between those at risk and low-risk populations. Methods: In this a narrative review of relevant evidence identified through PubMed search with one of the general terms (macrosomia, large-for-gestational-age) combined with the outcome of interest. Results: This revive summarizes evidence on the relation of fetal overgrowth with stillbirth, cesarean sections, shoulder dystocia, anal sphincter injury, and hemorrhage. Customized growth charts help to detect mothers and fetuses at risk of those complications. Relations between fetal overgrowth and diabetes, maternal weight, and gestational weight gain. Conclusions: a substantial proportion of complications are an effect of the fetus growing above its potential and should be recognized as a new dangerous condition of Fetal Growth Acceleration

Background: The course of obesity and type 2 diabetes (T2D) development is highly dependent on adipose tissue (AT) angiogenesis. Moreover, angiogenic microRNAs (miRNAs) play pivotal role in AT functionality. The aim of this study was to analyze the relationship of the human AT miR-221-3p/222-3p cluster and their regulatory network with obesity and T2D. Methods: miR-221-3p/222-3p and their target genes (TG) expression levels were measured in visceral and subcutaneous ATs from patients classified according to their BMI and to their glycemic status with a high degree of insulin resistance (IR) and T2D. In silico analyses of miR-221-3p/222-3p and their TGs were performed to identify relevant signaling pathways. Results: A multivariate analysis, including the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, showed significant differences considering the variables; tissue depot, obesity, IR and T2D altogether as independent variables. In addition, miRNAs and their TGs were differentially expressed according to obesity degree, glycemic status, and AT depot type. Our in silico analysis showed that miR-221-3p/222-3p cluster TGs are mostly involved in angiogenesis, WNT signaling pathway and apoptosis. Conclusion: These findings suggest that the miR-221-3p/222-3p cluster and their related regulatory networks could represent tangible targets for the management of obesity and associated metabolic disorders

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19) that has resulted in a global pandemic. The clinical symptoms of the disease vary from mild illness to acute respiratory issues. Older age, diabetes, cardiac diseases predict poor prognosis in COVID-19 patients. Various reports mention the incidence of liver injury with transient elevations in the levels of aminotransferases (liver function enzymes). The clinical characteristics, etiology and underlying pathophysiological mechanisms associated with liver damage in SARS-CoV2 infected patients need to be explored. This review highlights the severity of the hepatic injury in COVID-19.

Kersting’s groundnut is an important source of protein and essential nutrients that contribute to food security in West Africa. However, the crop is still underexploited by the populations and under-researched by the scientific community. This study aimed to investigate the genetic diversity and population structure of 217 Kersting’s groundnut accessions from five origins using 886 DArTseq markers. Gene diversity was low and ranged from 0.049 to 0.064. The number of private alleles greatly varied among populations (42–192) and morphotypes (40–339). Moderate to very high levels of selfing and inbreeding were observed among populations (s=56–85%, F_IS=0.389–0.736) and morphotypes (s=57–82%, F_IS=0.400–0.691). Moreover, little to very high genetic differentiations were observed among populations (0.006≤F_IS≤0.371) and morphotypes (0.029≤F_IS≤0.307). Analysis of molecular variance partitioned 38.5% of the genetic variation among and 48.7% within populations (P<0.001). Significant isolations by distance were detected between populations (R²=0.612, P=0.011) and accessions (R²=0.499, P<0.001). Discriminant analysis of principal components and neighbour joining consistently distinguished eight distinct clusters. These data provide a global picture of the existing genetic diversity for Kersting’s groundnut and will guide the choice of breeding strategies to increase production.

Type-2 diabetes mellitus (T2DM) have been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and used for serum lipid analysis, HbA1c, plasma glucose estimation and DNA extraction. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs 4.06 increased odds for T2DM in patients <60 years vs ≥60 years. Both rs7903146 and rs12255372 are significantly associated with increased odds of T2DM in women, overweight/obese; T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p<0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup- women and those with T2DM-NFH, yet have cardiometabolic risk.

The functioning of the parents’ emotional sphere is very important to a child’s mental and physical health. This study focused on investigating the association between mothers’ emotional intelligence (EI) and paediatric type I diabetes (T1DM) disease management in their children. We hypothesized that mothers’ EI is associated with T1DM outcomes. Mothers of children with T1DM aged 6-12 years were surveyed. One hundred and thirty-four mothers, the main caregivers of their diabetic children, provided measures of EI and completed a demographic questionnaire. The primary indicator of diabetes management was haemoglobin A1c (HbA1c; the main form of glycosylated haemoglobin). EI scales and subscales were associated with glycaemic management indices. Logistic regression analysis was applied for the assessment of the association between parents’ EI and their paediatric with T1DM disease management. The analysis demonstrated a statistically significant correlation between T1DM management and mothers’ ability to understand and control own emotions, to transform their own negative emotions into positive and to control own negative emotions. Mothers’ EI scales and subscales of understanding and regulating their own emotions, subscales of transforming their own negative emotions into positive ones and controlling their own negative emotions were statistically reliable predictors of glycaemic control in children with T1DM.

A good management of diabetes requires at the same time self-regulation behaviour and a balanced involvement of family components. This study’s aims were: understanding fear of injections and perceptions of family conflicts in preadolescents and adolescents with type 1 diabetes mellitus and their mothers, comparing their perceptions, and identifying the risk factors impacting patients’ quality of life. Participants were one hundred and two patients (Mean age = 14.63, SD = 2.43; age range = 10-19 years; Females = 52) and their mothers (Mean age = 46.94, SD = 6.2, age range = 27-63 years), who filled in self and proxy-report questionnaires. Twenty % of patients and 14.7% of their mothers reported clinical score for fear of self-injection and blood testing. Mothers reported higher fear of injecting and family conflicts compared with the patients. Age, fear of injecting and family conflicts impacted significantly on patients’ quality of life perceptions. Clinical consideration and recommendations are given basing on the empirical results.

Type 2 diabetes (T2D) is associated with increased cardiovascular morbidity, mortality, and hospital admissions. There is variability in clinical practice. The objectives are to analyze the variability in the control of Blood Pressure (BP), HbA1c, and LDL-C in T2D patients and its influence on admissions due to cardiovascular events (CVE) Methods: We analyzed the electronic records in Primary Care Health centers in Navarra (Spain) and hospital admission for CVE. We follow 480637 people from 2012 to 2016. We calculated indicators of control of patients with T2D for each year, percentage with: HbA1c &lt; 7%; HbA1c &gt;= 9%; BP &lt;140/90 mmHg; LDL-C &lt;100 mg/dl. We used logistic and Cox regression. Results: Patients in the best control GP practices cluster are 2.5 times more likely to have HbA1c &lt;7% [OR: 2.46 (95% CI: 2.29-3.64)]. Poor HbA1c control ≥ 9% is more likely in the worst control cluster [OR: 1.73 (95% CI:1.63-1.83)]. The probability of admission for CVE increases with age, being male, low income, obesity, history of CVE, having HbA1c ≥ 9%, and belonging to a GP practice in the cluster of HbA1C ≥ 9% worst control. In contrast, it decreases in patients with HbA1c &lt;7%, BP&lt;140/90 mmHg and LDL &lt;100 mg/dl.

Artificial groundwater recharge is commonly used for drinking water supply. The resulting water quality is highly dependent on the raw water quality. In many cases, pre-treatment is required. Pre-treatment improves the drinking water quality, although how and to what extent it affects the subsequent pond water quality and infiltration process, is still unknown. We evaluated two treatment systems by applying different pre-treatment methods for raw water from a eutrophic and temperate lake. An artificial recharge pond was divided into two parts, where one received raw water, only filtered through a micro-screen with 500 µm pores (control treatment), while the other part received pre-treated lake water using chemical flocculation with polyaluminium chloride (PACl) combined with sand filtration, i.e. continuous contact filtration (contact filter treatment). Water quality such as cyanobacterial biomass, microcystin-LR as well as organic matter and nutrients were measured in both treatment processes. We found cyanobacterial biomass and microcystin-LR level after the contact filter treatment was significantly different from the control treatment and also significantly different in the pond water. In addition, with contact filter treatment, total phosphorus (TP) and organic matter removal were significantly improved in the end water, TP was reduced by 96 % (< 20 µg/L) and the total organic carbon (TOC) was reduced by 66 % instead of 55 % (TOC content around 2.1 mg/L instead of 3.0 mg/L). This full-scale onsite experiment demonstrated effective pre-treatment would benefit a more stable water quality system, with less variance and lower cyanotoxin risk. In a broader drinking water management perspective, the presented method is promising to reduce cyanotoxin risk, as well as TP and TOC, which are all predicted to increase with global warming and extreme weather.

Disease-related data and information collected by physicians, patients, and researchers seem insignificant at first glance. Still, the same unorganized data contain valuable information that is often hidden. The task of data mining techniques is to extract patterns to classify the data accurately. One of the various Data mining and its methods have been used often to diagnose various diseases. In this study, a machine learning (ML) technique based on distributed computing in the Apache Spark computing space is used to diagnose diabetics or hidden pattern of the illness to detect the disease using a large dataset in real-time. Implementation results of three ML techniques of Decision Tree (DT) technique or Random Forest (RF) or Support Vector Machine (SVM) in the Apache Spark computing environment using the Scala programming language and WEKA show that RF is more efficient and faster to diagnose diabetes in big data.

Abstract—Low-frequency Fahræus–Lindqvist-driven (not blood pressure-driven) oscillations in the small vessels are crucial because oscillations in small vessels support nutrient supply. Understanding of this is critical in type 2 diabetes mellitus (T2DM) to develop therapeutic measures to prevent Alzheimer's Disease Related Dementias: vascular factors contribute to cerebrovascular disease as well as mild cognitive impairment and dementia, which are predicted to affect 152 million people by 2050 (Alzheimer's Disease International London, UK, 2019). In this clinical study, we performed functional near-infrared spectroscopy (fNIRS) of the forehead to investigate the effect of the Mini-Cog with three-item recall test on the prefrontal cortex (PFC) activation and the relative oscillatory power in the 0.01–0.02-Hz (Fahræus–Lindqvist effect) and 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency bands in elderly (60 years and older) T2DM and age-matched controls. We found a significant (p<0.01) difference in the PFC activation between elderly subjects with T2DM and age-matched elderly controls. Moreover, power spectral density (PSD) analysis revealed a significantly lower relative power in 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency band in elderly subjects with T2DM during the Mini-Cog three-item recall test. Furthermore, a drop in the oscillatory power in the 0.01–0.02-Hz frequency band during Mini-Cog three-item recall test was found more pronounced in the elderly subjects with T2DM. Therefore, our study highlighted portable brain imaging to capture cerebrovascular reactivity to cognitive load that may provide a biomarker of cerebrovascular dysfunction in T2DM.Clinical Relevance— Our study establishes forehead portable brain imaging for monitoring cerebrovascular function in T2DM under cognitive load.

In this review, we discuss the insulin resistance (IR) and its development in the insulin target tissues that leads to diabetes. Also, we highlight the use of induced pluripotent stem cells (iPSCs) to understand the mechanisms underlying the development of IR. IR is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Although there are currently several mouse models for both IR and T2D that had provided a lot of information about the disease, these models cannot recapitulate all the aspects of this complex disease as seen in each individual. Patient-specific iPSCs can overcome the hurdles faced with the classical mouse models for studying IR. iPSC technology can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of the genome editing and iPSCs may provide important information about the inherited factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes.

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into 4 different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting the novel interventional strategies for metabolic disorders/complications.

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. MicroRNA-375 (miR-375) ranks among top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 hour before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to identification of 8 microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients, by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis in insulin-secreting beta-cells is essential. Several pathophysiological conditions and pharmacological agents disrupt the ER homeostasis, thereby causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways whenever the ER stress persists. ER stress has been linked to several diseases, such as cancers, obesity, and diabetes. Thus, the regulation of ER stress may provide possible therapeutic targets for many diseases. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, resulting in irreversible UPR activation and cells death. Despite much progress in understanding the pathophysiology of UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provided up-to-date information regarding the current status of UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

Emerging evidence suggests that sustained diabetes-associated factors such as inflammation, hyperinsulinemia, and hyperglycemia are major contributors to aberrant cell proliferation and subsequent neoplastic transformation. Epidemiological studies have also highlighted that diabetes promoting a sedentary lifestyle, with or without the direct involvement of insulin, is frequently linked to cancer. However, our knowledge regarding the molecular mechanisms that correlate hyperglycemia to oncogenic transformations remains limited. In this regard, a recent study has proved that hyperglycemia inactivates AMPK, which results in the destabilization of the TET2 and its tumour-suppressive role ultimately predisposing diabetes mellitus patients to cancer. To the management of hyperglycemia associated with oncogenesis, we need to explore a reverse pharmacology-based ethnopharmacological approach. Botanical-derived natural products are structurally and functionally more diverse with fewer or no side effects on humans. The present review discusses the molecular link between hyperglycemia and cancer progression with the effect of natural products as therapeutic agents on the hyperglycemia-cancer associated signalling pathway.

OpenAI has managed to turn 100 million heads in two months towards their new Language model tool (LM) ChatGPT. The third generation Generative Pretrained Transformer (GPT-3) has the capacity to tackle simple to complex and sophisticated problems, while providing reasoning behind its generated answers. ChatGPT can be used to increase productivity and improve efficiency and face challenging problems. Programming mobile applications is a challenging task that requires professional software engineers, skills and abilities to be developed. The following paper takes a case study approach to assess how novice app developers can use ChatGPT to generate Java scripts that will be used in Android studio to create a functional application. The results after, many iterations and ongoing conversations with ChatGPT managed to create an application for the anticipated function. Important insights have been drawn from the case study that could set the ground for any novice user seeking to create applications using Java scripting and Android Studio.

Older adults with diabetes are at elevated risk of complications following hospitalization. Home health care services mitigate the risk of adverse events and facilitate a safe transition home. In the United States, when home health care services are prescribed, federal guidelines require they begin within two days of hospital discharge. This study examined the association between timing of home health care initiation and 30-day rehospitalization outcomes in a cohort of 786,734 Medicare beneficiaries following a diabetes-related index hospitalization. Of these patients, 26.6% were discharged to home health care. To evaluate the association between timing of home health care initiation and 30-day rehospitalizations, multivariate logistic regression models including patient demographics, clinical, geographic variables, and neighborhood socio-economic variables were used. Inverse probability-weighted propensity scores were incorporated into the analysis to account for potential confounding between the timing of home health care initiation and the outcome in the cohort. Compared to patients who received home health care within the recommended first two days, patients who received delayed services (3-7 days after discharge) had higher odds of rehospitalization (OR 1.28, 95% CI 1.25-1.32). Among patients who received late services (8-14 days after discharge), the odds of rehospitalization were four times greater than for patients receiving services within 2 days (OR 4.12, 95% CI 3.97-4.28). Timely initiation of home health care following diabetes-related hospitalizations is one strategy to improve outcomes.

Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The present standard-of-care for type 1 diabetes is exogenic insulin substitutional therapy. The most advanced stretegies in this area is the development of hybrid-closed loop system and the producing of long-acting insulins. Progresses in stem cell therapies have started to revolutionize the care of patients with type 1 diabetes; however, significant challenges remain including the limited islets availability, difficulties in maintaining the viability, the heterogeneity within a complex pathology and in patients’ responses to treatment. On the way, a considerable amount of efforts in maximizing the islet transplantation effectiveness by controlling the advantageous of different stem cell approaches. With the availability and the use of big data, the concept of precision medicine is gaining wide attention worldwide and could bring the dream of “presonlaized” therapies as a reality in the near future. Here we review the current range of treatments available as well as recent pre-clinical breakthroughs in the field of personlaized medicine for type 1 diabetes.

The intricate nature of congenital heart disease requires understanding of complex, patient-specific three-dimensional dynamic anatomy of the heart, from imaging data such as three-dimensional echocardiography for successful outcomes from surgical and interventional procedures. Conventional clinical systems use flat screens and therefore display remains two-dimensional, which undermines the full understanding of the three-dimensional dynamic data. Additionally, control of three-dimensional visualisation with two-dimensional tools is often difficult, so used only by imaging specialists. In this paper we describe a virtual reality system for immersive surgery planning using dynamic three-dimensional echocardiography, which enables fast prototyping for visualisation such as volume rendering, multi-planar reformatting, flow visualisation, and advanced interaction such as three-dimensional cropping, windowing, measurement, haptic feedback, automatic image orientation, and multi-user interactions. The available features were evaluated by imaging and non-imaging clinicians, showing that the virtual reality system can help improve understanding and communication of the three-dimensional echocardiography imaging and potentially benefit congenital heart disease treatment.

Accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated its effect on the number of macrophages and endothelial cells (ECs) within the CM. Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and Transglutaminase II, respectively. Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and 4-fold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p<0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals.

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, an-tagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including inter-section points to the new generation of antidiabetic drugs. We provide insight into the effective-ness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

This study presents a pre-processing approach adopted for the radar reflectivity data assimilation and results of simulations with the Harmonie numerical weather prediction model. The method shows an improvement of precipitation prediction within the radar location area in both the rain rates and spatial pattern presentation. With the assimilation of radar data, the model simulates larger water content in the middle troposphere within the layer from 1 to 6 km, with major variations at 2.5–3 km; it also reproduces better the mesoscale belt and cell patterns of precipitation fields.

Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease characterized not only by hyperglycemia but also various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarizes our current knowledge on epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contribution of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

Motor functions are deteriorated by aging. Some conditions may magnify this deterioration. To examine whether hemodialysis (HD) process would negatively impact gait and balance beyond diabetes condition among mid-age adults (48-64 years) and older adults (65+ years). One hundred and ninety-six subjects (age=66.2±9.1 years, body-mass-index=30.1±6.4 kg/m², female=56%) in 5 groups were recruited: mid-age adults with diabetes undergoing HD (Mid-age HD+, n=38) and without HD (Mid-age HD-, n=40); older adults with diabetes undergoing HD (Older HD+, n=36) and without HD (Older HD-, n=37); and non-diabetic older adults (Older DM-, n=45). Gait parameters (stride velocity, stride length, gait cycle time, and double support) and balance parameters (ankle, hip, and center of mass sways) were quantified using validated wearable platforms. Groups with diabetes had overall poorer gait and balance compared to the non-diabetic group (p<0.050). Among people with diabetes, the HD+ had significantly worsened gait and balance when comparing to the HD- (Cohen’s effect size d=0.63-2.32, p<0.050). Between-group difference was more pronounced among older adults with the largest effect size observed for stride length (d=2.32, p<0.001). Results suggested that deterioration in gait speed among the HD+ was correlated with age (r=-0.440, p<0.001), while this correlation was diminished among the HD-. Interestingly, results also suggested that poor gait in the Older HD- related to poor balance, while no correlation was observed between poor balance and poor gait among the Older HD+. Using objective assessments, results confirmed that the presence of diabetes can deteriorate gait and balance, and this deterioration can be magnified by HD process. Among non-HD people with diabetes, poor static balance described poor gait. However, among people with diabetes undergoing HD, age was a dominate factor describing poor gait irrespective of static balance. Results also suggested feasibility of using wearable platforms to quantify motor performance during routine dialysis clinic visits. These objective assessments may assist in identifying early deterioration in motor function, which in turn may promote timely intervention.

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

Background:Peripheral neuropathy (PN) can result in either partial or complete loss of distal sensation resulting in an increased fall risk. Walkasins^® uses a shoe insert to detect the magnitude and direction of sway and sends signals to a leg unit that provides sensory balance cues. The objective of this case report is to describe the long-term influence of the Walkasins^® lower limb sensory neuroprosthesis on balance and gait for an individual with diabetic PN.Case Description:A fifty-one-year-old male with a 3-year history of PN and a 10-year history of type II diabetes mellitus was fitted with Walkasins^® and utilized the shoe inserts 8-10 hours/day for more than 1 year. Although, vibration and tactile thresholds were severely impaired at his 1^st metatarsophalangeal joint and the lateral malleolus bilaterally he could perceive tactile stimuli from the Walkasins^® above the ankles.Outcomes:Following Walkasins^® use, his Activities-specific Balance Confidence Scale (ABC) scores improved from 33% to 80%. His mean Vestibular Activities of Daily Living (VADL) scores decreased from 3.54 to 1. His Functional Gait Assessment (FGA) scores increased from 13/30 to 28/30 and his miniBESTest scores improved from 15/28 to 26/28. Gait speed increased from 0.23 m/sec to 1.5 m/sec. The patient described a decrease in pain and cramping throughout his lower extremities and an increase in function.Discussion:Gait and balance improved with the use of the Walkasins^® and participation in the Neuro Wellness Program. This improvement suggests that the use of sensory substitution devices, such as the Walkasins^®, may replace sensory deficits related to gait and balance dysfunction experienced by patients with PN. Further research is needed to determine if other patients will have a similar response and what the necessary threshold of sensory function is to benefit from use of the Walkasins^®.

Abstract Diabetes mellitus (DM) is an independent risk-factor for cardiovascular diseases. Plant-based dietary-patterns have been shown to positively impact the effects this cardiovascular risk-factor. The purpose of this study is to investigate the association of adherence to moringa, plantains, moringa-plantain combined, and other plant based dietary-patterns with glycemic-control among persons with type-2-diabetes Mellitus (T2DM). Facility-based cross-sectional-study was conducted among 530 T2DM patients in Ghana. Structured-questionnaires were used to collect demographic, anthropometric, and clinical variables. Adherence to plant-based dietary-patterns were assessed with 24-hour dietary-recall questionnaire. SPSS version-22 was used in data analysis. BMI, HbA1c%, HDL-cholesterol and LDL-cholesterol were significantly correlated with adherence to plant-based dietary-patterns (p-value < 0.05). After adjusting for confounders, adherence to: Plantain diets, standardized regression coefficient β (95%CI): -0.098 (-0.321, -0.022), Yam, β (95%CI): 0.148 (0.066, 0.496), Moringa diets β (95%CI): -0.095 (-0.325,-0.011) and Bean-diets β (95%CI): -0.112 (-0.577-.007) were significantly associated with glycemic control. Also adherence to: Plantain-moriga combined diets β (95%CI): -0.406 (-0.413, -0.049) and Plantain-beans combined diets β (95%CI): -0.128 (-0.188, -0.038) were significantly associated with glycemic control. Adherence to Plantain, Yam, Beans, Plantain-moriga combined diets, and Plantain-beans combined diets could be associated with glycemic control. Keywords: Diabetes mellitus, Adherence, Moringa, Plantain, Glycemic control, Ghana.

Background: The world-wide rate of obesity is increasing continuously, representing a serious medical threat since it is associated with a variety of diseases including type 2 diabetes, cardiovascular disease, and numerous cancers. Sophora japonica is used as a traditional herb for medicinal purposes in eastern Asia. However, the anti-obesity effects of S. japonica fruit have not been explored. Objective: The aim of this study is to investigate the inhibition of adipocyte differentiation and adipogenesis by an ethanol extract of S. japonica fruit (EESF) in 3T3-L1 pre-adipocytes. Methods: MTT assay, Oil Red O staining, and Triglyceride contents were used to investigate lipid accumulation in 3T3-L1 cells to clarify adipocyte differentiation. The expression levels of various molecular signals associated with adipogenesis and lipogenesis were examined by western blot analysis. Results: Our results demonstrate that EESF suppressed the terminal differentiation of 3T3-L1 pre-adipocytes in a dose-dependent manner, as confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining. EESF significantly reduced the accumulation of cellular triglyceride, which was associated with a significant inhibition of the levels of pro-adipogenic transcription factors, downregulated the expression levels of adipocyte-specific proteins. Furthermore, EESF treatment effectively increased the phosphorylation of AMPK and ACC. Conclusions: These results together indicate that EESF has significant effects on the inhibition of adipogenesis and acts by stimulating the AMPK signaling pathway. Further studies will be needed to identify the active compounds in S. japonica.

Background: Level of perceived competence as a basic psychological need could trigger achievement of diabetes self-management goals. Due to lack of a specific data collection tool to measure level of self-competence among Persian speaking patients with diabetes this study was conducted for cross-cultural adaptation and psychometric assessment of the Persian version of Perceived Competence Scale for Diabetes (PCSD-P). Methods: Standard translation/back-translation procedure was carried out to prepare a preliminary draft of the PCSD-P. Content and face validity of the early draft were checked by an expert panel including 15 scholars in the field of health education and promotion as well as nursing education with experience of working and research on diabetes. The final drafted questionnaire was completed by 177 randomly selected patients with type 2 diabetes. Based on the collected data structural validity of the contrived version was appraised using exploratory and confirmatory factor analysis (EFA, CFA). Cronbach's alpha and Intraclass Correlation coefficients (ICC) were used to check the scale’s reliability and internal consistency. ; (3) Results: The estimated measures of Content Validity Index (CVI= 0.95) and Content Validity Ratio (CVR= 0.8) were in the range of acceptable recommended limits. The EFA analysis results demonstrated a single factor solution according to the items’ loadings for the component. The model fit indices i.e. RMSEA= 0.000, CFI=1, TLI=1, GFI= 0.998, NFI= 0.999 RFI= 0.995 confirmed consistency of the hypothesized one-factor solution. Values of the internal consistency and reliability coefficients were also in the vicinity of acceptable range (α= 0.892, ICC=0. 886, P= 0.001). Conclusions: The study findings revealed good internal validity and applicability of the PCSD-P to measure degree of self-competence among Persian speaking type 2 diabetes patients to manage the chronic disease. Due to unrepresentativeness of the study sample future cross-cultural test of PCSD-P on diverse and broader Persian speaking populations is recommended.

Radio Frequency Interference (RFI) detection and characterization play a critical role to in ensuring the security of all wireless communication networks. Advances in Machine Learning (ML) have led to the deployment of many robust techniques dealing with various types of RFI. To sidestep an unavoidable complicated feature extraction step in ML, this paper proposes an efficient end-to-end method using the latest advances in deep learning to extract the appropriate features of the RFI signal. Moreover, this study utilizes the benefits of transfer learning to determine both the type of received RFI signals and their modulation types. To this end, the scalogram of the received signals is used as the input of the pre-trained convolutional neural networks (CNN), followed by a fully-connected classifier. This study considers a digital video stream as the signal of interest (SoI), transmitted in a real-time satellite-to-ground communication using DVB-S2 standards. To create the RFI dataset, the SoI is combined with three well-known jammers namely, continuous-wave interference (CWI), multi- continuous-wave interference (MCWI), and chirp interference (CI). This study investigated four well-known pre-trained CNN architectures, namely, AlexNet, VGG-16, GoogleNet, and ResNet-18, for the feature extraction to recognize the visual RFI patterns directly from pixel images with minimal preprocessing. Moreover, the robustness of the proposed classifiers is evaluated by the data generated at different signal to noise ratios (SNR).

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. We aimed to assess whether a time trend in AAM with associated disease risk is also present in Mexico. For this, we used data of 30,826 women from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, whereas Welch-ANOVA was used to test for a time trend. AAM decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years). AAM (in years) was negatively associated with weight (β = -1.01 kg; 95 % CI -1.006, -1,004) and BMI (β = -1.01 kg/m2; -1.007, -1.006), and positively with height (β = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.

BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.

Background: The dietary factors and nutrients contributing to the prevention of microalbuminuria in type 2 diabetic nephropathy is unclear, so we investigated dietary factors affecting urinary albumin excretion in patients with type 2 diabetes. Methods: 42 patients with type 2 diabetes were participated, the subjects were divided to a normal albuminuria group (urinary albumin / creatinine ratio of less than 30 mg / g Cr) and a microalbuminuria group of 30 mg / g to 299 mg / g Cr. We performed casual blood sampling and conducted a food frequency questionnaire survey. Results: There were no significant differences in age, BMI and other physiological and biochemical data, the average daily intake of energy and many of nutrients, while β-cryptoxanthin was significantly lower in the microalbuminuria group than in the normal group (506.4 ± 793.9 μg/day vs. 715.3 ± 500.3 μg/day, p <0.05). The intake of 17 food groups per day showed that the intakes of fruits were significantly lower in the microalbuminuria group than in the normal group (76.9 ± 134.1 g vs. 111.9 ± 84.5 g, p <0.05). Conclusion: These results suggest that fruits and foods rich in β-cryptoxanthin would make it possible to prevent diabetic nephropathy progression.

Rising child obesity rate creates a need for tools quantifying metabolic changes in obese children and adolescents for purposes of comorbidities early detection or prevention. A candidate for such role seem to be miRNAs – in vivo serving as the suppressing factors of the gene expression. The aim of this study was to review the recent discoveries in this field and to conclude directions of research or application of studied molecules. Repeated browsing of databases, followed by screening for eligibility of results, led to final approval of 9 articles. Filtered studies examined the differences in miRNA (miR) expression levels of obese subjects and children suffering from obesity comorbidities. Studies concerning the endothelial dysfunction (ED) identified miR-630 as a possible treatment option. Search for the alternative markers in diagnosis of non-alcoholic fatty liver disease (NAFLD) suggested value of miR-199a-5p and miR-122. MiR-486, miR-146b and miR-15b may serve as a panel of markers grading the development of type 2 diabetes mellitus (T2DM) in children, although further research raised doubts in that matter. Another panel of miRNA molecules was indicated as useful in early detection of alterations leading to metabolic syndrome (MetS). No valid link between studied miRNAs and atherosclerosis (AS) was found. MiRNAs seem to be promising prognostic markers for the diagnosis of NAFLD, T2DM and MetS in children. Further studies are required to support these findings.

This study explores the impact of the ‘pre-intervention effects’ of a community-based interventions. This refers to participatory research processes and parallel publicity in the media on changes in alcohol use and relevant mechanisms (rules and norms about alcohol, accessibility of alcohol in a formal setting) among adolescents before any intervention is implemented. In a quasi-experimental study, adolescent data were collected twice by means of self-report among adolescents living in two municipalities (control and experimental condition). Regression analysis showed pre-intervention main effects on adolescents’ perceived accessibility of alcohol in a formal setting. Moreover, among adolescents aged 15 years and older, the normative decline in strictness of rules and norms was less steep in the experimental condition compared to the control condition. Also, adolescents aged 14 years and younger in the experimental condition reported more weekly drinking compared to their peers in the control condition. No differential effects across gender were found. To conclude, applying a co-creational approach in the development of an intervention, not only contributes to more effective interventions in the end, but involvement of and discussions in the community at the start of intervention planning are contributing to changes in targeted factors. This implies that public discussions about the development of intervention strategies should be considered as an essential feature of co-creation in community-based interventions.

A divergent selection experiment on environmental sensitivity was performed in rabbits. The aim of this study was to estimate the correlated response in kits’ weight and its survival, and weight distance from birth to weaning. Weight distance was calculated as the absolute values of the differences between the individual value and the mean value of its litter. Also, relationship between probability of survival at 4 d of age and weight at birth was studied. Environmental sensitivity was measured as litter size variability. A total of 2484 kits from 127 does of the low line (selected for reducing litter size variability) and 1916 kits of 114 does of the high line (selected for increasing litter size variability) of the 12th generation were weighed. Bayesian methodology was used to estimate the correlated response to selection, and LOGISTIC procedure of SAS was used to estimate the relationship between weight and probability of survival. Both lines showed similar individual weight at birth and at weaning, and similar survival at birth and at 4 d of age. Survival at weaning was higher in the low line than in the high line (0.67 and 0.62; P= 0.93). Weight distance was higher at birth but lower at weaning in the low line (47.8 g and 54.1 g; P=0.98). Kit’s weight at birth affected its survival. In conclusion, selection for environmental sensitivity showed correlated response in kits survival and in homogeneity of litter weight at weaning.

We transformed the existing learning program Language Shower, which is used in some Norwegian day-care centers in the Grorud district of Oslo municipality, into a digital solution using an app for smartphone or tablet with the option for further enhancement of presentation by a NAO robot. The solution was tested in several iterations and multiple day-care centers over several weeks. Measurements of the children’s progress across learning sessions indicate a positive impact of the program using a robot as compared to the program without robot. In-situ observations and interviews with day care center staff confirmed the solution’s many advantages, but also revealed some important areas for improvement. In particular, the speech recognition needs to be more flexible and robust, and special measures have to be in place to handle children speaking simultaneously.

Type two diabetes mellitus (T2DM) represents a chronic condition with increasing prevalence worldwide among the older population. T2DM condition increases the risk of micro and macro-vascular complications as well as the risk of geriatric syndromes as falls, fractures and cognitive impairment. The management of T2DM in the older population represents a challenge for the cli-nician, and a Comprehensive Geriatric Assessment should always be prioritized, in order to tailor the glycate haemoglobin target according to functional and cognitive status comorbidities, life ex-pectancy and type of therapy. According to the most recent guidelines, older adults with T2DM should be cathegorized in three groups: healthy patients with good functional status, patients with complications and reduced functionality and patients at the end of life; for each group the target for the glycemic control is different, also according to the type of treatment drug. The therapeutic ap-proach should always begin with lifestyle changes; after that, several lines of therapies are available, with different mechanism of action and potential effect other than glucose level reduction. Partic-ular interest is growing around sodium-glucose cotransporter-2 inhibitors, due to their effect on the cardiovascular system. In this review we evaluate the therapeutic options available for the treat-ment of older diabetic patients, to ensure a correct treatment approach

Diabetes is a group of diseases characterized by loss of β cell mass and/or -function, resulting in hyperglycemia. Approx. 537 million people worldwide suffer from diabetes – a number which is expected to increase. Diabetes is primarily treated by exogenous insulin, which comes with the challenges of maintaining glycemic control to prevent ketoacidosis and severe complications. The need for a curative treatment has initiated the research in β cell regeneration. Several studies in mice have identified essential genes for β cell fate, which can be manipulated in other cells to induce generation of new β cells. Zebrafish, a regeneration-positive animal model, has shown several different sources of new β cells, including regeneration by self-replication, neogenesis by duct-associated progenitor cells, and transdifferentiation of other endocrine islet cells. The animal models used in this research area are either limited by their low regenerative ability (mice), or their small size and remoteness from humans (zebrafish). There is a need for new animal models of diabetes, in which the molecular pathways of endogenous regeneration can be studied. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells. The axolotl has shown great regenerative capability, as they have proven capable of regenerating amputated limbs, and hearts with myocardial infarction, among other organs. This study aims to establish a diabetic axolotl model, investigate their regenerative ability in the pancreas, and examine the potential systemic effects of the induced disease. In a pilot study, five different protocols using STZ (streptozotocin) were tested, and the most optimal protocol was found. Furthermore, the glucose tolerance test was optimized to characterize the glycemic state of the animals. The effect of the treatment on blood glucose levels was measured to characterize the development and decline of the disease. The histological changes in the pancreas were examined. Moreover, the systemic effects of the STZ treatment were investigated in blood and urine. The study indicated that it is possible to induce diabetes in the axolotl, but variations between the animals should be minimized, or the sample size should be increased to conduct a satisfying experiment, as it was not possible to induce diabetes in all animals. Regeneration was not observed histologically, but a restoration of blood glucose levels was seen over the span of the experiment. Lastly, edema formation was observed in some of the STZ-treated animals, but the cause of edema remains undetermined.

Type 2 diabetes has been linked to the expression of Human Leukocyte Antigens, principally to the major Histocompatibility Complex Class II and only scarce reports to Major Histocompatibility Complex class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC class I related to Type 2 diabetes in the Mexican population using the GWAS SIGMA database. This database contains information of 3,848 Mexican individuals with type 2 diabetes and 4,366 control individuals from the same population without clinical or hereditary history of the disease. The searching criteria considered a P value < 0.005 and odds ratio, OR > 1.0. Ten novel statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01), and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related with the development of Type 2 diabetes complications.

Objective: Diabetes is associated with increased cardiovascular and cerebrovascular disease-related mortality. We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), total and active glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). Methods: This study consisted of four groups in Medicine Hospital between April- October, 2017: Control group (mean ages: 50.3 ± 10.7 years, 20 females and 15 males), diabetic group (DM) (mean ages: 53.9 ± 11.1, 14 females and 23 males), CAD group (mean ages: 62.6 ± 11.8, 17 females and 17 males) and CAD+ DM group: (mean ages: 62.6 ± 11.8 years, 18 females and 18 males). Results: Both CAD and CAD+DM groups have higher CIMT levels than controls. CAD+DM group have also significantly higher CIMT levels than DM group. Left external carotid artery (ECA) was only found different in DM group from controls. When compared with controls, DM, CAD groups have low DPP-4 and GLP-1_total concentration. Control group have significantly lower SFRP-4 levels than DM, CAD and CAD+DM (p<0.001) groups. Serum GLP-1_total levels were found to be significantly low in CAD+DM group when compared to control group. Conclusion: DPP-4 and SFRP-4 levels are predictive marker for atherosclerosis in diabetes, correlates well with HOMA-IR particularly in diabetes. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD. Large cohorts and at-risk populations are needed to confirm the predictive value of these findings.

Chronic unpredictable environmental stress (CUES) may induce predisposition to diabetes mellitus. This study investigates the role of CUES on impaired homeostasis. Stressed group mice (n = 20) were exposed to CUES for 16 weeks. Weekly body weight, feed consumption, feed efficiency ratio, fasting blood glucose were monitored. Plasma HbA1c, plasma cortisol, plasma epinephrine and plasma insulin, serum lipids, antioxidants and carbohydrate metabolizing enzymes activity were assessed along with DNA damage and histopathological examination of liver, kidney, pancreas, spleen and skeletal muscles. Fasting blood glucose levels & HbA1c in the stressed were significantly higher compared to control (p < 0.001). Serum lipids were found insignificantly higher in stressed mice compared to control. Body weights of the stressed mice and feed efficiency ratio were found significant (p < 0.001). Plasma corticosterone, plasma epinephrine, HOMA-IR was found to be significantly higher in the stressed group (p < 0.001). Plasma insulin level was found to be significantly lower in the stressed group (p < 0.001). Significant changes were observed in antioxidants level, carbohydrate metabolizing enzymes activity, peripheral tissues and DNA integrity. CUES initiates pathogenesis of diabetes.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

We propose a notion of $(q,\sigma,\tau)$-differential graded algebra, which generalizes the notions of $(\sigma,\tau)$-differential graded algebra and $q$-differential graded algebra. We construct two examples of $(q,\sigma,\tau)$-differential graded algebra, where the first one is constructed by means of generalized Clifford algebra with two generators (reduced quantum plane), where we use a $(\sigma,\tau)$-twisted graded $q$-commutator. In order to construct the second example, we introduce a notion of $(\sigma,\tau)$-pre-cosimplicial algebra.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we explored whether PAK signaling should be targeted via chemoprevention to reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Systematic literature review provided the effect of anti-diabetic drugs on PAK signaling. Review of clinical studies revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-dependent diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM involves Wnt and G-protein signaling which is altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone is promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Growing evidence suggests that healthcare provider advice may increase tobacco cessation, reduce alcohol use, and improve the adoption of desirable lifestyle behaviors among patients. However, how brief interventions and other provider-patient interactions can shape cumulative adoption of multiple modifiable behaviors is less well studied for diabetes prevention and control. Using weighted internet panel survey data from a large socio-demographically diverse urban population in the United States (n=1,003), the present study describes differences in group characteristics among those who had been “ever diagnosed” with prediabetes/diabetes versus those who had not. It also examines the associations between the cumulative adoption of lifestyle behaviors and each of the following: a) lifetime prediabetes/diabetes diagnosis; b) brief lifestyle intervention exposure (i.e., received provider advice/encouragement); and c) recent provider-patient communication about diabetes. There were several group differences in “ever diagnosed” prediabetes/diabetes status by age, employment status, health status, nutrition knowledge, blood pressure/hypertension diagnosis, and diabetes-related health behaviors (p<0.05). Each of the three provider-patient interactions of interest were positively associated with a higher cumulative sum of adopted modifiable lifestyle behaviors for diabetes prevention and management. Results suggest that provider advice/provider-patient interactions of any type can have a salutary impact on whether individuals with prediabetes or type 2 diabetes will engage in recommended lifestyle behavior modifications.

The aim of this study was to evaluate the relationship between serum levels of advanced glycation end products (AGEs) and abdominal aortic calcification (AAC) in patients with type 2 diabetes mellitus (DM2). This was a prospective cross-sectional study conducted from January 2017 to June 2018. One-hundred and four consecutive patients with DM2 were given lateral lumbar X-rays in order to quantify aortic abdominal calcification AAC. Circulating levels of AGEs and classical cardiovascular risk factors were determined. Clinical history was also registered. Patients with higher AGEs values had higher grades of aortic calcification and higher number of diabetic related complications. Multivariate logistic regression analysis showed that being older, male and having high levels of AGEs and triglycerides were the independent risk factors associated to moderate-severe AAC when compared to no-mild AAC. Our results suggest that AGEs plays a role in the pathogenesis of aortic calcifications. In addition, the measurement of AGEs levels may be useful for assessing the severity of AAC in the setting of diabetic complications.

This work presents updated reconstructions of watershed runoff to San Francisco Estuary from tree-ring data to AD 903, coupled with models relating runoff to freshwater flow to the estuary and salinity intrusion. We characterize pre-development freshwater flow and salinity conditions in the estuary over the past millennium and compare this characterization with contemporary conditions to better understand the magnitude and seasonality of changes over this time. This work shows that the instrumented flow record spans the range of runoff patterns over the past millennium (averaged over five, ten, twenty and one hundred years), and thus serves as a reasonable basis for planning-level evaluations of historical hydrologic conditions in the estuary. Over annual timescales we show that, although median freshwater flow to the estuary has not changed significantly, it has been more variable over the past century compared to pre-development flow conditions. We further show that the contemporary period is generally associated with greater spring salinity intrusion and lesser summer-fall salinity intrusion relative to the pre-development period. Thus, salinity intrusion in summer and fall months was a common occurrence under pre-development conditions and has been moderated in the contemporary period due to the operations of upstream reservoirs, which were designed to hold winter and spring runoff for release in summer and fall. This work also confirms a dramatic decadal-scale hydrologic shift in the watershed from very wet to very dry conditions during the late 19th and early 20th centuries; while not unprecedented, these shifts have been seen only a few times in the past millennium. This shift resulted in an increase in salinity intrusion in the first three decades of the 20th century, as documented through early records. Population growth and extensive watershed modification during this period exacerbated this underlying hydrologic shift. Putting this shift in the context of other anthropogenic drivers is important in understanding the historical response of the estuary and in setting salinity targets for estuarine restoration. By characterizing the long-term behavior of San Francisco Estuary, this work supports decision-making in the State of California related to flow and salinity management for restoration of the estuarine ecosystem.

Bisphenols are widely used in the synthesis of polycarbonate plastics, epoxy resins and thermal paper, which are used in manufacturing items of daily use. Packaged foods and drinks are the main sources of exposure to bisphenols. These chemicals affect humans and animals by disrupting the estrogen, androgen, progesterone, thyroid, and aryl hydrocarbon receptor functions. Bisphenols exert numerous harmful effects because of their interaction with receptors, ROS formation, lipid peroxidation, mitochondrial dysfunction, and cell signal alterations. Both cohort and case-control studies have determined an association between bisphenol exposure and increased risk of cardiovascular diseases, neurological disorders, reproductive abnormalities, obesity, and diabetes. Prenatal exposure to bisphenol results in developmental disorders in animals. These chemicals also affect the immune cells and play a significant role in initiating the inflammatory response. Exposure to bisphenols exhibit age, gender, and dose-dependent effects. Even at low concentrations, bisphenols exert toxicity, and hence deserve a critical assessment for their uses. Since bisphenols have a global influence on human health, the need to discover the underlying pathways involved in all disease conditions is essential. Furthermore, it is important to promote the use of alternatives for bisphenols, thereby restricting their uses.

During the few years, various algorithms have been developed to extract features from high-resolution satellite imagery. For the classification of these extracted features, several complex algorithms have been developed. But these algorithms do not possess critical refining stages of processing the data at the preliminary phase. Various satellite sensors have been launched such as LISS3, IKONOS, QUICKBIRD, and WORLDVIEW etc. Before classification and extraction of semantic data, imagery of the high resolution must be refined. The whole refinement process involves several steps of interaction with the data. These steps are pre-processing algorithms that are presented in this paper. Pre-processing steps involves Geometric correction, radiometric correction, Noise removal, Image enhancement etc. Due to these pre-processing algorithms, the accuracy of the data is increased. Various applications of these pre-processing of the data are in meteorology, hydrology, soil science, forest, physical planning etc. This paper also provides a brief description of the local maximum likelihood method, fuzzy method, stretch method and pre-processing methods, which are used before classifying and extracting features from the image.

Objective: The hypoglycemic, hepatorenalprotective, and antioxidant Activities of Cyperus rotundus rhizomes extract in an alloxan-induced diabetic rat model were investigated in this work.Methods: 25 Male rats were divided into 5 groups: normal control, diabetic control, diabetic of C. rotundus (200 mg/kg b.w), diabetic of C. rotundus (400 mg/kg b.w), diabetic of glibenclamide (0.6mg/kg).Treatments were administered orally for 6 weeks.Results: A single injection of alloxan to rats (150mg/kg b.w) caused pathological alterations in all studied parameters and histological structure of the pancreas. On the other hand, results showed that oral administration of C. rotundus rhizomes extract in dose of 200 and 400 mg/kg caused significant reduction in glucose, HbA1C%, α-amylase level and plasma lactate together with significant elevation in serum insulin, serum pyruvate with an improvement in insulin resistance. In line with amelioration of the diabetic state, C. rotundus rhizomes extract improved of the liver and kidney functions, and oxidative marker levels. Moreover, the extract succeeded to reduce the elevated serum total cholesterol, triglyceride (TG) and low-density lipoprotein- cholesterol (LDL-C) levels and to elevate the reduced high-density lipoprotein- cholesterol (HDL-C) level of diabetic rats.Conclusion: The investigation data concluded that C. rotundus rhizomes extract could be used as alternative treatments as antidiabetic, antioxidant and antihyperlipidemic, and agent as well as in liver and kidney protective in alloxan induced-diabetic rats. This may be related to the presence of saponin glycosides, polyphenols, flavonoids, and terpenoids in the ethanolic extract of C. rotundus rhizomes, which was discovered by phytochemical screening in this study to be present in the plant.

Cardiotonic glycoside toxins, originally isolated from plants or amphibians, have been proposed as mammalian cardiotonic hormones. This paper is a review and update of the discovery of [i] a new class of steroid hormones, [ii] the path for their biosynthesis and [iii] some preliminary data on their function. The compounds are phosphoester conjugates and share a characteristic structural feature, a lactone ring, with [a] one class of synthetic potassium sparing diuretics and with [b] plant and amphibian cardiotonic steroids. Purification was initially monitored by cross reaction with steroid sulfate assays and later with digoxin-specific assays. Six compounds were purified by HPLC to near homogeneity and characterized by Tandem mass spectroscopy (MS-MS) and 31P-NMR. Three were digoxin-like materials (DLM) with 23 carbon atoms. The two extra carbon atoms form a spiral lactone E-ring. Several additional spiral lactones have been identified by MS-MS. In a pilot study, based on MS analysis, we evaluated phosphocholine steroid levels in individual serum samples in patients with pre-eclampsia (n=20). The control group of normotensive pregnant women (n=20) was used to estimate the mean and standard deviation. Twelve of the women with pre-eclampsia had a z-score over 2 for at least one of the four phosphocholine steroids. In contrast, only 1 sample from the normotensive women had a z-score over 2. The observation that there are two patterns, one with elevated phosphocholine steroid levels and one without the elevation, suggests that there may be two different underlying causes of pre-eclampsia. We now need to extend the study to determine which pattern predicts progression to life-threatening hypertension in pregnant women. This pilot study illustrates that it is possible to evaluate individual endogenous cardiotonic hormones without relying on antibodies developed to plant or amphibian toxins.

During type 1 diabetes mellitus (T1DM) development, beta-cells undergo intense endoplasmic reticulum (ER) stress that could result in apoptosis through the failure of adaptation to the unfolded protein response (UPR). Islet transplantation is considered an attractive alternative among beta-cell replacement therapies for T1DM. To avoid the loss of beta-cells that will jeopardize the transplant´s outcome, several strategies are being studied. We have previously shown that prolactin induces protection against pro-inflammatory cytokines and redox imbalance-induced beta-cell death by increasing heat shock protein B1 (HSPB1) levels. Since the role of HSPB1 in beta cells has not been deeply studied, we investigated the mechanisms involved in unbalanced protein homeostasis caused by intense ER stress and overload of the proteasomal protein degradation pathway. We tested whether HSPB1-mediated cytoprotective effects involved UPR modulation and improvement of protein degradation via the ubiquitin-proteasome system. We demonstrated that increased levels of HSPB1: attenuated levels of pro-apoptotic proteins like CHOP and BIM, increased protein ubiquitination and the speed of proteasomal protein degradation. Our data showed that HSPB1 induced resistance to proteotoxic stress and thus enhanced cell survival via an increase in beta-cell proteolytic capacity. These results could contribute to generate strategies aiming at optimization of beta-cell replacement therapies.

Anti-diabetic effects of Glycine soja seed extract (GS) on Type 2 diabetes mellitus mouse model and human hepatocytes induced insulin resistance were investigated. 3 weeks old db/db mice were divided into 5 groups (n = 6) including two control groups and 3 GS treated groups with different doses. Oral administration of GS for 6 weeks to diabetic db/db mice reduced blood glucose level significantly in a dose dependent manner by 44.7% (300 mg/kg/day), 30.9% (150 mg/kg/day) and 21.1% (75 mg/kg/day). GS treatment also lowered significantly plasma level of HbA1c, insulin, IGF-1 and leptin, and increased that of adiponectin. GS treatment activated AMPK, and down-regulated GLUT2 in liver tissues of mice while up-regulated GLUT4 in muscle tissues of mice. In in vitro study with insulin resistance induced human hepatocyte, GS treatment increased glucose uptake and increased the activities of Akt and PPAR-γ in response to insulin. Treatment of GS appears to reduce blood glucose level by regulating energy metabolism positively through various metabolic pathways and reducing insulin resistance in Type 2 diabetes mellitus.

The introduction of tenofovir-derived prodrugs has revolutionised the prevention and management of HIV, which has coincided with 23% reduction in new HIV incidences globally. To date, there are two formulations of tenofovir-derived nucleoside reverse transcriptase inhibitor (NRTI): tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and tenofovir alafenamide fumarate/emtricitabine (TAF/FTC). Although these prodrugs have shown favourable safety profile, their effects on cardiovascular health are differ from one another: TDF/FTC exhibits potential lipid-lowering effect, TAF/FTC demonstrates potential lipid-inducing effect, which is a major risk factor for cardiovascular diseases. However, this issue has not been previously elucidated, especially among the marginalised populations [lesbian, gay, bisexual and transgender (LGBT) and men who have sex with men (MSM)] who are likely be the main users of these prodrugs. This is of clinically significance as the cardiovascular health in these populations is often overlooked, in addition to a lack of appropriate cardiovascular risk prediction algorithm. Therefore, this review aims to (1) highlight the cardiovascular risks of tenofovir-derived prodrugs in the marginalized populations, and also to (2) establish the importance of having a cardiovascular risk prediction model that is specific to this particular populations so that their health management could be more comprehensive.

Pancreatic β-cell-specific clock knock-out mice develop β cell oxidative-stress and failure, as well as glucose-intolerance. How inflammatory stress affects the cellular clock is under-investigated. Real-time recording of Per2:luciferase reporter activity in murine and human pancreatic islets demonstrated that the proinflammatory cytokine Interleukin-1β (IL-1β) lengthened the circadian period. qPCR-profiling of core clock gene expression in insulin-producing cells suggested that the combination of the proinflammatory cytokines IL-1β and Interferon-γ (IFN-γ) caused pronounced but uncoordinated increases in mRNA levels of multiple core clock genes, in particular of Reverse-erythroblastosis virus α (Rev-erbα), in a dose- and time-dependent manner. The REV-ERBα/β agonist SR9009, used to mimic cytokine-mediated Rev-erbα induction, reduced constitutive and cytokine-induced Brain and muscle arnt-like 1 (Bmal1) mRNA levels in INS-1 cells as expected. SR9009 induced reactive oxygen species (ROS), reduced insulin-1/2 (Ins-1/2) mRNA and accumulated- and glucose-stimulated insulin secretion, reduced cell-viability, and increased apoptosis levels, reminiscent of cytokine toxicity. In contrast low (<5,0 μM) concentrations of SR9009 increased Ins-1 mRNA and accumulated insulin-secretion without affecting INS-1 cell viability, mirroring low-concentration IL-1β mediated β-cell stimulation. Inhibiting nitric oxide (NO) synthesis, the lysine deacetylase HDAC3 and the immunoproteasome reduced cytokine-mediated increases in clock gene expression. In conclusion, the cytokine-combination perturbed the intrinsic clocks operative in mouse and human pancreatic islets and induced uncoordinated clock gene expression in INS-1 cells, the latter effect associated with NO, HDAC3 and immunoproteasome activity.

There is a confusion in the original design concept for the tensioning of longitudinally connected reinforcement of CRTSII slab ballastless track. In order to clarify the effect of tension value of longitudinal reinforcement on mechanical characteristics of ballastless track, a three dimensional finite element model considering the nonlinear interaction between the track slab and CA mortar of CRTSII slab ballastless track was established. The mechanical characteristics of the track structure under longitudinal tension load and temperature gradient load of the longitudinal joint were calculated. A method of applying pre-stress to post-pouring concrete was proposed according to the concept of pre-stress loss of pretensioning pre-stressed concrete, reasonable tensile force value was proposed after the crack width and the reinforcement stress of the ballastless track in the operation stage were checked and calculated according to the concrete design principle. When the tension force is greater than 300 kN, it’s harmful to the bonding between the slab and mortar layer, which is prone to interlayer damage. In order to adding pre-stress to concrete of wide joints to ensure the longitudinal stability of ballastless track and the reinforcement stress and crack width to meet the design requirements. It is suggested that the tension force value should be 230 kN, and the temperature difference between reinforcement and concrete should be 30 °C before the initial curdle of wide joint concrete.

This present study was designed to find out whether the acankoreagenin showed the antidiabetic and renoprotective effects in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats. Type I diabetes was induced by a single intraperitoneal injection of STZ (70 mg/kg). At the end of the experiment, rats were euthanized and serum/plasma was separated for the determination of glucose, insulin, glycated hemoglobin A1c (HbA1c), C-peptide, biochemical parameters, and kidney function. One kidney was used for determining glutathione, superoxide dismutas, malondialdehyde, and tumor necrosis factor-alpha levels. The other kidney and pancreas were used for histopathological studies and immunohistochemical measurement of transforming growth factor beta (TGF-β) or NF-κB. Acankoreagenin (2 mg/kg) treatments led to a significant reduction in blood glucose assessed via oral glucose tolerance test (OGTT) in diabetic rats at 2 h. The treatment also resulted in improved body weight, decreased HbA1c, restored lipid profile, and renal oxidative stress. By inhibiting NF-κB, the release of proinflammatory cytokines was suppressed and by inhibiting TGF-β, the renal fibrosis was suppressed in STZ-induced diabetic rat model. Histopathological injury was also observed in pancreatic and renal tissues. These findings support the beneficial effect of acankoreagenin treatment in DN, which could be attributed to its antidiabetic and renoprotective effects.

The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rate of morbidity and mortality around the world, in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristic of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species; namely, Salvia africana-lutea, Leonotis ocymifolia and Plectranthus madagascariensis, for their glucose uptake ability. Methanolic extracts were produced from the arterial part of each plant. Compounds were identified using different spectroscopic techniques. The glucose uptake ability of each compound was then evaluated in mammalian cells using 2-deoxyglucose-6-phosphate. The cytotoxicity of each compound was established via the MTT assay. Chromatographic purification of the three plant species yielded fifteen pure terpenoids. Compounds 1 (p = 0.0031), 8 (p = 0.0053), and 6 (p = 0.0086), showed a marked increase in glucose uptake, with p values of p=0.0031, p=0.0053 and p=0.0086, respectively. Additionally, 1, 4 and 6 exhibited cytotoxicity toward mammalian tissue with a decrease in cell viability of ~70%, ~68% and ~67%, respectively. The results suggested that several compounds demonstrated a marked increase in glucose uptake while two of the compounds exhibited signs of cytotoxicity. It may, therefore, be suggested that these compounds be considered as potential candidates for novel plant-derived alternative therapies in the treatment of type 2 diabetes.

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with the pathogenesis of hypertension, but so far, the mechanism has not been well defined. We hypothesize that exposure to Cd causes a decline in the glomerular filtration rate (GFR), which in turn, causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73m2 (low eGFR). The mean blood Cd and mean urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. Prevalence odds ratio (POR) for hypertension rose twofold in those with a medium Cd burden and blood Cd levels of 0.61-1.69 µg/L. In the hypertensive group, the eGFR was inversely associated with age (β =−0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). Mean eGFR in those with hypertension was 7.5 mL/min/1.73m2 lower than those who were normotensive with the same Cd body burden. In addition, higher systolic blood pressure (SBP) values were associated with older age (β = 0.243), higher BMI (β = 0.113), lower eGFR (β = −0.106) and diabetes (β = 0.216). Mean SBP in those who had low eGFR and medium and heavy Cd body burden was 9.5 mmHg higher than those with the same Cd body burden and a normal eGFR. Thus, chronic environmental exposure to Cd that produces urinary and blood Cd levels of 0.57-0.61 µg/L, increases the risk of hypertension, and this could be mediated by a declining GFR.

Background: The number of people with type 2 diabetes is increasing daily, and therefore effective therapy is needed to successfully regulate glycemia and reduce the risk of associated complications. Recently, an oral formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has become available. Therefore, the aim of our study was to compare the effectiveness of the new oral formulation and the existing injectable formulation of semaglutide in terms of glycemic and body weight control in a real-world setting. Patients and methods: This was a single-center retrospective observational study conducted at the Rijeka Clinical Hospital Centre. A total of 106 patients with inadequately controlled type 2 diabetes (HbA1 ≥ 7%) on different oral or basal insulin supported oral therapy were recruited from the diabetes outpatient clinic, and data from electronic medical records were retrospectively collected and analyzed from May 2021 to November 2022. All subjects were GLP-1 RA naive and consequently prescribed 0.5 or 1.0 mg once weekly injectable semaglutide (IS) or 7 mg or 14 mg once daily oral semaglutide (OS) for at least 6 months. Glycated hemoglo-bin (HbA1c), body weight, and body mass index (BMI) were assessed prior to semaglutide administration and after a 6-month follow-up period. The primary endpoint was the change from baseline in HbA1c, and sec-ondary endpoints were the change in body weight and the proportion of participants with a reduction in body weight of ≥ 5% and ≥ 10%, respectively, 6 months after the initiation of semaglutide treatment. Results: At 6-month follow-up, no significant difference was observed between the two formulations in terms of HbA1c reduction (IS -1.1% vs OS -1.4%, p=0.126) and weight loss (IS -6.50 kg vs OS -5.90 kg, p=0.714). Exactly the same proportion of participants in both groups achieved a weight loss of ≥ 5% (56.7%, n=30). A weight loss ≥ 10% was observed in 20.7% (n=11) of participants administered IS and 15.1% (n=8) of participants adminis-tered OS, respectively (p=0.454). Conclusion: In a real-world setting, oral semaglutide as add-on therapy to ongoing antihyperglycemic treatment in patients with inadequately controlled type 2 diabetes who had not previously received GLP-1 RA demonstrated the same effectiveness as injectable semaglutide in terms of gly-cemic control and weight loss after 6 months of treatment.

Diabetes mellitus leads to cardiovascular complications including impaired cardiac β-adrenoceptor (β-AR) function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) improve outcomes in heart failure patients and animal models thereof. Therefore, we have investigated the effects of EMPA on in vivo cardiac function (pressure-volume loop analysis) and β-AR-mediated contractile responses (papillary strips) in streptozotocin (STZ; 40 mg/kg, i.p.)-induced diabes in male Sprague Dawley rats (control, EMPA-treated control, diabetic, EMPA-treated diabetic) in a design reflecting late-onset treatment. 13-16 weeks after STZ injection treatment with a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contration and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some but not all parameters. Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes is manifest. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.

Aim of this study was to evaluate the accuracy and usability of a novel continuous glucose moni-toring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed sensor performance of two GlucoMen® Day CGM systems worn simultaneously in eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed reg-ularly over 14 days at home. Participants underwent two standardized 5-hour meal challenges with frequent plasma glucose (PG) measurements using a laboratory reference instrument at the research center. When comparing CGM to PG the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD of CGM vs SMBG was 13.1 [3.5-18.6]%. In the consensus error grid (CEG) analysis, 98% of both CGM/PG and CGM/SMBG pairs were in the clinically acceptable zones A and B. The analysis confirms that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. The needle-free insertion technology is well toler-ated by users and reduces medical waste compared to conventional CGM systems.

Background: Nutrient supplements are widely used for type 2 diabetes (T2D) yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycemic control, measures of insulin sensitivity and secretion), adverse events, and GRADE assessments. Quality was assessed using AMSTAR-2. Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C and omega-3 polyunsaturated fatty acids (-3 PUFAs) were superior to placebo for the primary outcome of HbA1c (MD -0.54%, -0.54% and ES -0.27 respectively). Probiotics were superior to placebo for HbA1c (WMD -0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD -0.17%). Magnesium, zinc, Vitamin C, probiotics and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.