A novel AIE-based mitochondria-targeting fluorescent probe for monitoring of the fluctuation of endogenous hypochlorous acid in ferroptosis models.

Ferroptosis is a way of cell death mainly due to the imbalance between the production and degradation of lipid reactive oxygen species, which is closely associated with various diseases. Endogenous hypochlorous acid (HOCl) mainly produced in mitochondria is regarded as an important signal molecule of ferroptosis. Therefore, monitoring the fluctuation of endogenous HOCl is beneficial to better understand and treat ferroptosis-related diseases. Inspired by the promising aggregation-induced emission (AIE) properties of tetraphenylethene (TPE), herein, we rationally constructed a novel AIE-based fluorescent probe, namely QTrPEP, for HOCl with nice mitochondria-targeting ability and high sensitivity and selectivity. Probe QTrPEP consisted of phenylborate ester and the AIE fluorophore of quinoline-conjugated triphenylethylene (QTrPE). HOCl can brighten the strong fluorescence through a specific HOCl-triggered cleavage of the phenylborate ester bond and release of QTrPE, which has been demonstrated by MS, HPLC, and DLS experiments. In addition, combining QTrPE-doped test strips with a smartphone-based measurement demonstrated the excellent performance of the probe to sense HOCl. The obtained favorable optical properties and negligible cytotoxicity allowed the use of this probe for tracking of HOCl in three different cells. In particular, this work represents the first AIE-based mitochondria-targeting fluorescent probe for monitoring the fluctuation of HOCl in ferroptosis.

A Novel Method for Targeted Identification of Essential Proteins by Integrating Chemical Reaction Optimization and Naive Bayes Model.

Targeted identification of essential proteins is of great significance for species identification, drug manufacturing, and disease treatment. It is a challenge to analyze the binding mechanism between essential proteins and improve the identification speed while ensuring the accuracy of the identification. This paper proposes a novel method called EPCRO for identifying essential proteins, which incorporates the chemical reaction optimization (CRO) algorithm and the naive Bayes model to effectively detect essential proteins. In EPCRO, the naive Bayes model is employed to analyze the homogeneity between proteins. In order to improve the identification rate and speed of essential proteins, the protein homogeneity rate is integrated into the CRO algorithm to balance between local and global searches. EPCRO is experimentally compared with 17 existing methods (including, DC, SC, IC, EC, LAC, NC, PeC, WDC, EPD-RW, RWHN, TEGS, CFMM, BSPM, AFSO-EP, CVIM, RWEP, and EPPSODC) based on biological datasets. The results show that EPCRO is superior to the above methods in identification accuracy and speed.

Mechanical Properties and Hydration Degree of Magnesium Potassium Phosphate Cement Modified by Sintered Silt Ash.

The effective utilization rate of river-dredged silt was extremely low, and common disposal methods such as dumping it into the ocean have already threatened the ecological environment. To demonstrate that dredged silt can be used as a mineral admixture to modify magnesium potassium phosphate cement (MKPC), the mechanical properties and hydration degree of sintered silt ash (SSA)-blended MKPC in the early stage of hydration were studied systematically in this paper, with MKPC as the reference group. The mechanical experiment results showed that in the process of increasing the SSA content to 25%, the compressive strength first increased and then decreased. Among the samples, the compressive strength of cement aged by 1d and 3d with 15% content was the highest, which increased by 11.5% and 17.2%, respectively, compared with the reference group. The setting time experiment found that with the increase in SSA content, the hydration reaction rate of MKPC slowed down significantly. Its effect of delaying hydration was most obvious when the SSA content was 10-15%. The X-ray diffraction pattern showed that there was no large amount of new crystalline substances formed in the hydration product. The results obtained by scanning electron microscopy show that the microstructure tended to be denser and the hydration products tended to be plump when the SSA content was in the range of 0-15%. The non-contact electrical resistivity experiment showed that the addition of SSA delayed the early hydration of MKPC. Combined with the above experiment results, it was found that when the content of SSA was less than 15%, it not only delayed the early hydration of MKPC, but also deepened its hydration degree.

Medical expenditure trajectory and HbA1c progression prior to and after clinical diagnosis of type 2 diabetes in a commercially insured population in the USA.

INTRODUCTION: Medical expenditures of individuals with type 2 diabetes escalate before clinical diagnosis. How increases in medical expenditures are related to glucose levels remains unclear. We examined changes in HbA1c and medical expenditures in years prior to and shortly after type 2 diabetes diagnosis. RESEARCH DESIGN AND METHODS: Using insurance claims and laboratory test results from a commercially insured population in the USA, we built three (2014, 2015, 2016) longitudinal cohorts with type 2 diabetes up to 10 years before and 2 years after the diagnosis (index year). We identified diabetes diagnosis using International Classification of Diseases, Ninth Revision and Tenth Revision codes and antidiabetic medication use. We ran two individual fixed regression models with annual total medical expenditures and average HbA1c values as dependent variables and number of years from diagnosis as the main independent variable and examined the risk-adjusted movement of the outcomes. RESULTS: Our study included 9847 individuals (83 526 person-years). Medical expenditures and HbA1c levels increased before and peaked at the diagnosis year. Medical expenditures were $8644 lower 10 years and $5781 lower 1 year before diagnosis compared with the index year. HbA1c was 12.18 mmol/mol (1.11 percentage points) and 3.49 mmol/mol (0.32 percentage points) lower, respectively. Average annual increases in medical expenditures and HbA1c values over the prediagnosis period were $318 and 0.97 mmol/mol (0.09 percentage points), respectively. CONCLUSIONS: Medical expenditures and HbA1c values followed similar trajectories before and after diabetes diagnosis. Our results can inform economic evaluations of programs and policies aimed at preventing type 2 diabetes.

Influence of Mycorrhiza on C:N:P Stoichiometry in Senesced Leaves.

Senesced leaves play a vital role in nutrient cycles in the terrestrial ecosystem. The carbon (C), nitrogen (N) and phosphorus (P) stoichiometries in senesced leaves have been reported, which are influenced by biotic and abiotic factors, such as climate variables and plant functional groups. It is well known that mycorrhizal types are one of the most important functional characteristics of plants that affect leaf C:N:P stoichiometry. While green leaves' traits have been widely reported based on the different mycorrhiza types, the senesced leaves' C:N:P stoichiometries among mycorrhizal types are rarely investigated. Here, the patterns in senesced leaves' C:N:P stoichiometry among plants associated with arbuscular mycorrhizal (AM), ectomycorrhizal (ECM), or AM + ECM fungi were explored. Overall, the senesced leaves' C, with 446.8 mg/g in AM plants, was significantly lower than that in AM + ECM and ECM species, being 493.1 and 501.4 mg/g, respectively, which was mainly caused by boreal biomes. The 8.9 mg/g senesced leaves' N in ECM plants was significantly lower than in AM (10.4 mg/g) or AM + ECM taxa (10.9 mg/g). Meanwhile, the senesced leaves' P presented no difference in plant associations with AM, AM + ECM and ECM. The senesced leaves' C and N presented contrary trends with the changes in mean annual temperature (MAT) and mean annual precipitation (MAP) in ECM or AM + ECM plants. The differences in senesced leaves' C and N may be more easily influenced by the plant mycorrhizal types, but not P and stoichiometric ratios of C, N and P. Our results suggest that senesced leaves' C:N:P stoichiometries depend on mycorrhizal types, which supports the hypothesis that mycorrhizal type is linked to the evolution of carbon-nutrient cycle interactions in the ecosystem.

A New Type 2 Diabetes Microsimulation Model to Estimate Long-Term Health Outcomes, Costs, and Cost-Effectiveness.

OBJECTIVES: This study aimed to develop a microsimulation model to estimate the health effects, costs, and cost-effectiveness of public health and clinical interventions for preventing/managing type 2 diabetes. METHODS: We combined newly developed equations for complications, mortality, risk factor progression, patient utility, and cost-all based on US studies-in a microsimulation model. We performed internal and external validation of the model. To demonstrate the model's utility, we predicted remaining life-years, quality-adjusted life-years (QALYs), and lifetime medical cost for a representative cohort of 10 000 US adults with type 2 diabetes. We then estimated the cost-effectiveness of reducing hemoglobin A1c from 9% to 7% among adults with type 2 diabetes, using low-cost, generic, oral medications. RESULTS: The model performed well in internal validation; the average absolute difference between simulated and observed incidence for 17 complications was < 8%. In external validation, the model was better at predicting outcomes in clinical trials than in observational studies. The cohort of US adults with type 2 diabetes was projected to have an average of 19.95 remaining life-years (from mean age 61), incur $187 729 in discounted medical costs, and accrue 8.79 discounted QALYs. The intervention to reduce hemoglobin A1c increased medical costs by $1256 and QALYs by 0.39, yielding an incremental cost-effectiveness ratio of $9103 per QALY. CONCLUSIONS: Using equations exclusively derived from US studies, this new microsimulation model achieves good prediction accuracy in US populations. The model can be used to estimate the long-term health impact, costs, and cost-effectiveness of interventions for type 2 diabetes in the United States.

A qualitative synthesis of drawing-based research on the illness-related experiences of children living with physical health problems.

The strengths of drawing-based approaches for encouraging children's participation in health research and facilitating communication with them have been increasingly acknowledged in the medical literature. However, there is a lack of methodological discussion on drawing-based approaches suitable for researching children living with physical health problems. The present study systematically reviewed qualitative research using drawing-based approaches on the experiences of children living with physical health problems and summarised how the approaches were used as well. We identified 54 studies from five databases. The characteristics of qualitative methods and drawing-based approaches were analysed. To obtain an overall understanding of the illness-related experiences of these children, qualitative data generated from the included studies were synthesised using the thematic synthesis approach. This systematic review highlights the appropriateness and accuracy of the use of drawings-based approaches in health research with children on their illness-related experiences, fostering inclusive participation and engagement of young generations.

A New Method on Construction of Brain Effective Connectivity Based on Functional Magnetic Resonance Imaging.

Most of the existing methods about the causal relationship based on functional magnetic resonance imaging (fMRI) data are either the hypothesis-driven methods or based on a linear model, which can result in the deviation for detecting the original brain activity. Therefore, it is necessary to develop a new method for detecting the effective connectivity (EC) of the brain activity by the nonlinear calculation. In this study, we firstly proposed a new technology evaluating effective connectivity of the human brain based on back-propagation neural network with nonlinear model, named EC-BP. Next, we simulated four time series for assessing the feasibility and accuracy of EC-BP compared to Granger causality analysis (GCA). Finally, the proposed EC-BP was applied to the brain fMRI from 60 healthy subjects. The results from the four simulated time series showed that the proposed EC-BP can detect the originally causal relationship, consistent with the actual causality. However, the GCA can not find nonlinear causality. Based on the analysis of the fMRI data from the healthy participants, EC-BP and GCA showed the huge differences in the top 50 connections in descending order of EC. EC-BP showed all ECs related to hippocampus and parahippocampus, whereas GCA showed most ECs related to the paracentral lobule, caudate, putamen, and pallidum, which represents the brain regions with most frequent information passing measured by different methods. The proposed EC-BP method can provide supplementary information to GCA, which will promote more comprehensive detection and evaluation of brain EC.

Estimating costs of diabetes complications in people <65 years in the U.S. using panel data.

AIMS: To estimate the cost of diabetes complications in the United States (U.S.). METHODS: We constructed longitudinal panel data using one of the largest claims databases in the U.S. for privately insured Type 1 (T1DM) and type 2 (T2DM) diabetes patients with a follow-up time of one to ten years. Complication costs were estimated both in years of the first occurrence and in subsequent years, using individual fixed-effects models. All costs were in 2016 dollars. RESULTS: 47,166 people with T1DM and 608,237 with T2DM were included in our study. Aside from organ transplants, which were rare, the estimated average costs for the top three most costly conditions in the first vs. subsequent years were: end stage renal disease ($73,534 vs. $97,431 for T1DM; $94,231 vs. $98,981 for T2DM), congestive heart failure ($41,681 vs. $14,855 for T1DM; $31,202 vs. $7062 for T2DM), and myocardial infarction ($40,899 vs. $9496 for T1DM; $45,251 vs. $8572 for T2DM). For both diabetes types, retinopathy and neuropathy tend to have the lowest cost estimates. CONCLUSIONS: Our study provides the latest and most comprehensive cost estimates for a broad set of diabetes complications needed to evaluate the long-term cost-effectiveness of interventions for preventing and managing diabetes.

Current and projected future economic burden of Parkinson's disease in the U.S.

Parkinson's disease (PD) is one of the world's fastest growing neurological disorders. Much is unknown about PD-associated economic burdens in the United States (U.S.) and other high-income nations. This study provides a comprehensive analysis of the economic burdens of PD in the U.S. (2017) and projections for the next two decades. Multiple data sources were used to estimate the costs of PD, including public and private administrative claims data, Medicare Current Beneficiary Survey, Medical Expenditure Panel Survey, and a primary survey (n = 4,548) designed for this study. We estimated a U.S. prevalence of approximately one million individuals with diagnosed Parkinson's disease in 2017 and a total economic burden of $51.9 billion. The total burden of PD includes direct medical costs of $25.4 billion and $26.5 billion in indirect and non-medical costs, including an indirect cost of $14.2 billion (PWP and caregiver burden combined), non-medical costs of $7.5 billion, and $4.8 billion due to disability income received by PWPs. The Medicare program bears the largest share of excess medical costs, as most PD patients are over age 65. Projected PD prevalence will be more than 1.6 million with projected total economic burden surpassing $79 billion by 2037. The economic burden of PD was previously underestimated. Our findings underscore the substantial burden of PD to society, payers, patients, and caregivers. Interventions to reduce PD incidence, delay disease progression, and alleviate symptom burden may reduce the future economic burden of PD.

Changes of the postcentral cortex in irritable bowel syndrome patients.

The postcentral cortex (poCC) is commonly found to respond to visceral stimulation, but researchers usually pay less attention to this role of the poCC in the patients with functional gastrointestinal disorders, because it is a primary receptor for general bodily feeling of touch, such as temperature and pain. The current study focuses on the changes around the poCC in irritable bowel syndrome (IBS) patients based on the resting-state functional magnetic resonance imaging, aiming to investigate whether the poCC-centric brain metrics may be directly related to visceral perception. In the study, we calculated the regional homogeneity, seed-based correlation (SBC) and nodal centralities of the poCC to explore the changes in the regional activity and information flow around the poCC in IBS patients. Moreover, we examined the performance of the poCC-centric features in classifying the IBS group and healthy group in comparison to those features unrelated to the poCC. The results found that central alterations around the poCC in IBS patients were associated with the level of visceral pain, and exhibited a better discriminative power than those around the whole brain and the insula when classifying the IBS group and healthy group. In conclusion, the preliminary investigation provided fundamental advances in understanding the roles of the poCC in the pathphysiology of the IBS.

Identifying High-Cost Medicare Beneficiaries: Impact of Neighborhood Socioeconomic Disadvantage.

The objective of this observational longitudinal study of Maryland fee-for-service Medicare beneficiaries (2015-2016) was to investigate whether using data on neighborhood socioeconomic disadvantage in addition to individual clinical risk data improves identification of high-cost Medicare beneficiaries. Neighborhood socioeconomic disadvantage is measured using the Area Deprivation Index (ADI), a validated composite measure based on publically-available US census data (2011-2015) for Maryland census block groups. Hierarchical Condition Categories (HCC) score, health care utilization, and spending were obtained from Centers for Medicare & Medicaid Services Chronic Condition Warehouse beneficiary file and Part A and Part B claims data (2015). Total cost of care (TCOC) was calculated for 2016. Descriptive and multivariate analyses were performed to examine the relationship of residency in neighborhoods with high ADI and subsequent year health care spending. Among 615,637 Maryland Medicare fee-for-service beneficiaries, those living in neighborhoods with the greatest disadvantage vs. the least disadvantage incur significantly greater costs in the subsequent year (ADI Quintile 5 $12,439 versus Quintile 1 $8920, P < .001). Clinical risk exacerbates this disparity. Among beneficiaries in the highest HCC score quintile, costs are 27% ($5458, P < .001) higher among beneficiaries in the highest compared with the lowest ADI quintiles without risk adjustment and 24% ($4599, P < .001) higher with risk adjustment. Several sensitivity analyses found the relationship between ADI and TCOC robust. Association between neighborhood socioeconomic disadvantage and health care cost is most pronounced among the most clinically complex Maryland Medicare beneficiaries. Using ADI in combination with HCC score may facilitate more precise targeting of care management resources.

In Vitro and In Vivo Neuroprotective Effects of Stellettin B Through Anti-Apoptosis and the Nrf2/HO-1 Pathway.

Pharmaceutical agents for halting the progression of Parkinson's disease (PD) are lacking. The current available medications only relieve clinical symptoms and may cause severe side effects. Therefore, there is an urgent need for novel drug candidates for PD. In this study, we demonstrated the neuroprotective activity of stellettin B (SB), a compound isolated from marine sponges. We showed that SB could significantly protect SH-SY5Y cells against 6-OHDA-induced cellular damage by inhibiting cell apoptosis and oxidative stress through PI3K/Akt, MAPK, caspase cascade modulation and Nrf2/HO-1 cascade modulation, respectively. In addition, an in vivo study showed that SB reversed 6-OHDA-induced a locomotor deficit in a zebrafish model of PD. The potential for developing SB as a candidate drug for PD treatment is discussed.

The Economic Burden of Elevated Blood Glucose Levels in 2017: Diagnosed and Undiagnosed Diabetes, Gestational Diabetes Mellitus, and Prediabetes.

OBJECTIVE: This study was conducted to update national estimates of the economic burden of undiagnosed diabetes, prediabetes, and gestational diabetes mellitus (GDM) in the United States for year 2017 and provide state-level estimates. Combined with published estimates for diagnosed diabetes, these updated statistics provide a detailed picture of the economic costs associated with elevated blood glucose levels. RESEARCH DESIGN AND METHODS: This study estimated medical expenditures exceeding levels occurring in the absence of diabetes or prediabetes and the indirect economic burden associated with reduced labor force participation and productivity. Data sources analyzed included Optum medical claims for ∼5.8 million commercially insured patients continuously enrolled from 2013 to 2015, Medicare Standard Analytical Files containing medical claims for ∼2.8 million Medicare patients in 2014, and the 2014 Nationwide Inpatient Sample containing ∼7.1 million discharge records. Other data sources were the U.S. Census Bureau, Centers for Disease Control and Prevention, and Centers for Medicare & Medicaid Services. RESULTS: The economic burden associated with diagnosed diabetes (all ages), undiagnosed diabetes and prediabetes (adults), and GDM (mothers and newborns) reached nearly $404 billion in 2017, consisting of $327.2 billion for diagnosed diabetes, $31.7 billion for undiagnosed diabetes, $43.4 billion for prediabetes, and nearly $1.6 billion for GDM. Combined, this amounted to an economic burden of $1,240 for each American in 2017. Annual burden per case averaged $13,240 for diagnosed diabetes, $5,800 for GDM, $4,250 for undiagnosed diabetes, and $500 for prediabetes. CONCLUSIONS: Updated statistics underscore the importance of reducing the burden of prediabetes and diabetes through better detection, prevention, and treatment.

Economic Costs Attributable to Diabetes in Each U.S. State.

OBJECTIVE: To estimate direct medical and indirect costs attributable to diabetes in each U.S. state in total and per person with diabetes. RESEARCH DESIGN AND METHODS: We used an attributable fraction approach to estimate direct medical costs using data from the 2013 State Health Expenditure Accounts, 2013 Behavioral Risk Factor Surveillance System, and the Centers for Medicare & Medicaid Services' 2013-2014 Minimum Data Set. We used a human capital approach to estimate indirect costs measured by lost productivity from morbidity (absenteeism, presenteeism, lost household productivity, and inability to work) and premature mortality, using the 2008-2013 National Health Interview Survey, 2013 daily housework value data, 2013 mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research, and mean wages from the 2014 Bureau of Labor Statistics. Costs were adjusted to 2017 U.S. dollars. RESULTS: The estimated median state economic cost was $5.9 billion, ranging from $694 million to $55.5 billion, in total and $18,248, ranging from $15,418 to $30,915, per person with diabetes. The corresponding estimates for direct medical costs were $2.8 billion (range $0.3-22.9) and $8,544 (range $6,591-12,953) and for indirect costs were $3.0 billion (range $0.4-32.6) and $9,672 (range $7,133-17,962). In general, the estimated state median indirect costs resulting from morbidity were larger than costs from mortality both in total and per person with diabetes. CONCLUSIONS: Economic costs attributable to diabetes were large and varied widely across states. Our comprehensive state-specific estimates provide essential information needed by state policymakers to monitor the economic burden of the disease and to better plan and evaluate interventions for preventing type 2 diabetes and managing diabetes in their states.

Diabetes diagnosis and management among insured adults across metropolitan areas in the U.S.

This study provides diabetes-related metrics for the 50 largest metropolitan areas in the U.S. in 2012-including prevalence of diagnosed and undiagnosed diabetes, insurance status of the population with diabetes, diabetes medication use, and prevalence of poorly controlled diabetes. Diabetes prevalence estimates were calculated using cross-sectional data combining the Behavioral Risk Factor Surveillance System, American Community Survey, National Nursing Home Survey, Census population files, and National Health and Nutrition Examination Survey. Analysis of medical claims files (2012 de-identified Normative Health Information database, 2011 Medicare Standard Analytical Files, and 2008 Medicaid Analytic eXtract) produced information on treatment and poorly controlled diabetes by geographic location, insurance type, sex, and age group. Among insured adults with diagnosed type 2 diabetes in 2012, the proportion receiving diabetes medications ranged from 83% in Oklahoma City, Oklahoma, to 65% in West Palm Beach, Florida. The proportion of treated patients with medical claims indicating poorly controlled diabetes was lowest in Minneapolis, Minnesota (36%) and highest in Texas metropolitan areas of Austin (51%), San Antonio (51%), and Houston (50%). Estimates of diabetes detection and management across metropolitan areas often differ from state and national estimates. Local metrics of diabetes management can be helpful for tracking improvements in communities over time.

Future Health and Economic Impact of Comprehensive Tobacco Control in DoD: A Microsimulation Approach.

Background: Tobacco use is a major concern to the Military Health System of the Department of Defense (DoD). The 2011 DoD Health Related Behavior Survey reported that 24.5% of active duty personnel are current smokers, which is higher than the national estimate of 20.6% for the civilian population. Overall, it is estimated that tobacco use costs the DoD $1.6 billion a year through related medical care, increased hospitalization, and lost days of work, among others. Methods: This study evaluated future health outcomes of Tricare Prime beneficiaries aged 18-64 yr (N = 3.2 million, including active duty and retired military members and their dependents) and the potential economic impact of initiatives that DoD may take to further its effort to transform the military into a tobacco-free environment. Our analysis simulated the future smoking status, risk of developing 25 smoking-related diseases, and associated medical costs for each individual using a Markov Chain Monte Carlo microsimulation model. Data sources included Tricare administrative data, national data such as Centers for Disease Control and Prevention mortality data and National Cancer Institute's cancer registry data, as well as relative risks of diseases obtained from a literature review. Findings: We found that the prevalence of active smoking among the Tricare Prime population will decrease from about 24% in 2015 to 18% in 2020 under a status quo scenario. However, if a comprehensive tobacco control initiative that includes a 5% price increase, a tighter clean air policy, and an intensified media campaign were to be implemented between 2016 and 2020, the prevalence of smoking could further decrease to 16%. The near 2 percentage points reduction in smoking prevalence represents an additional 81,240 quitters and translates to a total lifetime medical cost savings (in 2016 present value) of $968 million, with 39% ($382 million) attributable to Tricare savings. Discussion: A comprehensive tobacco control policy within the DoD could significantly decrease the prevalence and lifetime medical cost of tobacco use. If the smoking prevalence among Prime beneficiaries could reach the Healthy People 2020 goal of 12%, through additional measures, the lifetime savings could mount to $2.08 billion. To achieve future savings, DoD needs to pay close attention to program design and implementation issues of any additional tobacco control initiatives.

The 1-Tosylpentan-3-one Protects against 6-Hydroxydopamine-Induced Neurotoxicity.

Previous studies have demonstrated that the marine compound austrasulfone, isolated from the soft coral Cladiella australis, exerts a neuroprotective effect. The intermediate product in the synthesis of austrasulfone, dihydroaustrasulfone alcohol, attenuates several inflammatory responses. The present study uses in vitro and in vivo methods to investigate the neuroprotective effect of dihydroaustrasulfone alcohol-modified 1-tosylpentan-3-one (1T3O). Results from in vitro experiments show that 1T3O effectively inhibits 6-hydroxydopamine-induced (6-OHDA-induced) activation of both p38 mitogen-activated protein kinase (MAPK) and caspase-3 in SH-SY5Y cells; and enhances nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling. Hoechst staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining results reveal that 1T3O significantly inhibits 6-OHDA-induced apoptosis. In addition, the addition of an Akt or HO-1 inhibitor decreases the protective effect of 1T3O. Thus, we hypothesize that the anti-apoptotic activity of 1T3O in neuronal cells is mediated through the regulation of the Akt and HO-1 signaling pathways. In vivo experiments show that 1T3O can reverse 6-OHDA-induced reduction in locomotor behavior ability in zebrafish larvae, and inhibit 6-OHDA-induced tumor necrosis factor-alpha (TNF-α) increase at the same time. According to our in vitro and in vivo results, we consider that 1T3O exerts its anti-apoptotic activities at SH-SY5Y cells after 6-OHDA challenges, probably via the regulation of anti-oxidative signaling pathways. Therefore, this compound may be a promising therapeutic agent for neurodegenerations.

Structural elucidation and immunostimulatory activity of polysaccharide isolated by subcritical water extraction from Cordyceps militaris.

Water-soluble polysaccharides were obtained from Cordyceps militaris (C. militaris) (CMP) by subcritical water extraction (SWE). Two polysaccharides fractions, CMP-W1 and CMP-S1, were isolated from CMP using DEAE-52 cellulose and Sephadex G-150 column chromatography. The structural characteristics of CMP-W1 and CMP-S1 were investigated. The results showed that the molecular weight of CMP-W1 and CMP-S1 are 3.66×105Da and 4.60×105Da, respectively, and both of them were heteropolysaccharides composed of d-mannose, d-glucose, d-galactose with the molar ratios of 2.84:1:1.29 and 2.05:1:1.09, respectively. FT-IR spectra analysis suggested that CMP-W1 and CMP-S1 belonged to pyranose form sugar and protein free. For immunostimulatory activity assay in vitro, CMP-W1 and CMP-S1 significantly promoted lymphatic spleen cell proliferation of mice. Therefore, the polysaccharides obtained from C. militaris by SWE can be used as potential natural immunostimulant in functional foods or medicine.

Geographic Variation in Antidiabetic Agent Adherence and Glycemic Control Among Patients with Type 2 Diabetes.

BACKGROUND: Medication nonadherence is an imperative public health concern. Among patients with type 2 diabetes mellitus (T2DM), poor adherence to antidiabetic agents is strongly associated with suboptimal glycemic control. Poor adherence and hyperglycemia greatly increase diabetes-related morbidity and mortality. At a national level, diabetes drug adherence using average proportion of days covered (PDC) is estimated to range between 36% and 81%, with an estimated range for diabetes control between 38% and 47%. At a state level no such studies exist. OBJECTIVE: To estimate the level of medication adherence to antidiabetic agents and of diabetes control, and their association among patients with T2DM receiving medication treatment at the state and the Metropolitan Statistical Area (MSA) levels among the populations covered by commercial insurance, Medicare, or Medicaid. METHODS: The study population included adults with T2DM aged ≥18 years who were identified using ICD-9-CM code 250.xx, who received diabetes medication, and who were covered by private insurance, Medicare, or Medicaid in each state, the District of Columbia, and the top 50 MSAs. Medication adherence was measured by average PDC and the percentage of population that had a PDC ≥ 80%. Diabetes control was identified using ICD-9-CM diagnosis codes. Patients who were not diagnosed with uncontrolled diabetes (250.x2 and 250.x3) were identified as being under control. The administrative claims databases used for this study included the 2012 medical and pharmacy claims from a large U.S. health plan, the complete 2011 Medicare Standard Analytical File linked with Part D claims, and the 2008 Mini-Medicaid Analytic eXtract (Mini-Max). Medication adherence and diabetes control were adjusted for age and sex to allow comparison across insurance coverage, states, and MSAs. RESULTS: For an insured patient population with T2DM that received diabetic drug treatment, average PDC was 79%. However, 35% of patients did not achieve an adherence of at least 80% of PDC. In addition, at least 40% of patients did not have their diabetes under control. Across insurance types, we found that patients insured with Medicare had relatively high average PDC and adherence levels (83% and 71%) in comparison with the commercially insured population (77% and 60%) and Medicaid patients (75% and 57%). In contrast, commercially insured patients had relatively better diabetes control (69%) than those insured with Medicare and Medicaid (54% and 53%, respectively). At a state level, we found that commercially insured and Medicare populations have relatively smaller geographic variation in drug adherence than the Medicaid population. CONCLUSIONS: This study identified gaps in T2DM drug adherence and pinpointed geographic areas that lag in terms of diabetes drug adherence or diabetes control and would benefit from implementing strategies to increase drug adherence.