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1.
BMC Psychiatry ; 24(1): 244, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566055

ABSTRACT

BACKGROUND: Patients with schizophrenia (SZ) or bipolar disorder (BD) may have increased risk of complications from prescribed opioids, including opioid-induced respiratory depression. We compared prescription opioid pain medication dispensing for patients with SZ or BD versus controls over 5 years to assess dispensing trends. METHODS: This retrospective, observational study analysed US claims data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases for individuals aged 18-64 years with prevalent SZ or BD for years 2015-2019 compared with age- and sex-matched controls. Baseline characteristics, comorbidities, and medication use were assessed. Proportions of individuals dispensed prescription opioids chronically (ie, ≥70 days over a 90-day period or ≥ 6 prescriptions annually) or nonchronically (≥1 prescription, chronic definition not met) were assessed. RESULTS: In 2019, the Commercial and Medicaid databases contained records for 4773 and 30,179 patients with SZ and 52,780 and 63,455 patients with BD, respectively. Patients with SZ or BD had a higher prevalence of comorbidities, including pain, versus controls in each analysis year. From 2015 to 2019, among commercially insured patients with SZ, chronic opioid-dispensing proportions decreased from 6.1% (controls: 2.7%) to 2.3% (controls: 1.2%) and, for patients with BD, from 11.4% (controls: 2.7%) to 6.4% (controls: 1.6%). Chronic opioid dispensing declined in Medicaid-covered patients with SZ from 15.0% (controls: 14.7%) to 6.7% (controls: 6.0%) and, for patients with BD, from 27.4% (controls: 12.0%) to 12.4% (controls: 4.7%). Among commercially insured patients with SZ, nonchronic opioid dispensing decreased from 15.5% (controls: 16.4%) to 10.7% (controls: 11.0%) and, for patients with BD, from 26.1% (controls: 17.5%) to 20.0% (controls: 12.2%). In Medicaid-covered patients with SZ, nonchronic opioid dispensing declined from 22.5% (controls: 24.4%) to 15.1% (controls: 12.7%) and, for patients with BD, from 32.3% (controls: 25.9%) to 24.6% (controls: 13.6%). CONCLUSIONS: The proportions of individuals dispensed chronic or nonchronic opioid medications each year were similar between commercially and Medicaid-insured patients with SZ versus controls and were higher for patients with BD versus controls. From 2015 to 2019, the proportions of individuals who were dispensed prescription opioids chronically or nonchronically decreased for patients with SZ or BD and controls.


Subject(s)
Bipolar Disorder , Schizophrenia , Humans , Analgesics, Opioid/therapeutic use , Bipolar Disorder/drug therapy , Pain , Practice Patterns, Physicians' , Prescriptions , Retrospective Studies , Schizophrenia/drug therapy , United States , Male , Female , Adolescent , Young Adult , Adult , Middle Aged
2.
J Appl Toxicol ; 44(3): 344-354, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37718569

ABSTRACT

Narcissin is a natural flavonoid from some edible and traditional medicinal plants. It has been proven to have multiple biological functions and exhibits potential therapeutic effects on hypertension, cancer, and Alzheimer's disease. However, the toxicity of narcissin is largely unknown. Here, we revealed that narcissin treatment led to reduced hatchability, increased malformation rate, shorter body length, and slowed blood flow in zebrafish. Furthermore, bradycardia, pericardial edema, increased SV-BA distance, diminished stroke volume, ejection fraction, and ventricular short-axis shortening rate were also found. A large accumulation of ROS, increased apoptotic cells, and histopathological changes were detected in the heart region. Moreover, the gene expression profiles and molecular docking analysis indicated that Nrf2/HO-1 and calcium signaling pathways were involved in narcissin-induced toxicity. In conclusion, here we provide the first evidence that demonstrates narcissin-induced developmental toxicity and cardiotoxicity in zebrafish via Nrf2/HO-1 and calcium signaling pathways for the first time.


Subject(s)
Flavonols , NF-E2-Related Factor 2 , Zebrafish , Animals , Zebrafish/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Cardiotoxicity , Calcium Signaling , Molecular Docking Simulation , Embryo, Nonmammalian , Oxidative Stress
3.
Sci Rep ; 13(1): 16817, 2023 10 05.
Article in English | MEDLINE | ID: mdl-37798399

ABSTRACT

Crop divider toes are an essential device of sugarcane harvester. Moving forward against the ground is a critical way to improve the harvesting rate of lodged sugarcane. Height detection is the basis for precise control of crop divider toes moving forward against the ground. Due to the current problem of operating difficulties in manually adjusting the height of crop divider, a height detection system based on a millimeter wave radar sensor was designed to detect the height of crop divider toes from the ground. This paper proposed a height detection method of crop divider toes for sugarcane harvester based on Kalman adaptive adjustment. The data measured by the sensor was pretreated to determine whether the height had changed. Reset the Kalman filter and adjust the parameters when changes occur to improve the filter response speed and ranging accuracy. To adapt to the scenario of quickly adjusting the height of crop divider during the traveling process of sugarcane harvester. A one-way ANOVA test and a two-way ANOVA test were conducted on a simulated test platform. The results of the one-way ANOVA test showed that both forward speed and vegetation cover thickness had a significant effect on height detection accuracy. The results of the two-way ANOVA test showed that the interaction of forward speed and vegetation cover thickness did not have a significant effect on ranging accuracy. It was verified through experiments that both the ranging accuracy and the response speed of height change were significantly improved after the processing of the method in this paper. The mean square error after processing was lower than 2.5 cm. The feasibility of the height detection system was verified by field trials. The results of this study will provide a reference for the design of automatic elevation of crop divider.


Subject(s)
Saccharum , Edible Grain , Radar , Toes
4.
Front Plant Sci ; 14: 1230517, 2023.
Article in English | MEDLINE | ID: mdl-37680364

ABSTRACT

Introduction: Sugarcane stem node detection is one of the key functions of a small intelligent sugarcane harvesting robot, but the accuracy of sugarcane stem node detection is severely degraded in complex field environments when the sugarcane is in the shadow of confusing backgrounds and other objects. Methods: To address the problem of low accuracy of sugarcane arise node detection in complex environments, this paper proposes an improved sugarcane stem node detection model based on YOLOv7. First, the SimAM (A Simple Parameter-Free Attention Module for Convolutional Neural Networks) attention mechanism is added to solve the problem of feature loss due to the loss of image global context information in the convolution process, which improves the detection accuracy of the model in the case of image blurring; Second, the Deformable convolution Network is used to replace some of the traditional convolution layers in the original YOLOv7. Finally, a new bounding box regression loss function WIoU Loss is introduced to solve the problem of unbalanced sample quality, improve the model robustness and generalization ability, and accelerate the convergence speed of the network. Results: The experimental results show that the mAP of the improved algorithm model is 94.53% and the F1 value is 92.41, which are 3.43% and 2.21 respectively compared with the YOLOv7 model, and compared with the mAP of the SOTA method which is 94.1%, an improvement of 0.43% is achieved, which effectively improves the detection performance of the target detection model. Discussion: This study provides a theoretical basis and technical support for the development of a small intelligent sugarcane harvesting robot, and may also provide a reference for the detection of other types of crops in similar environments.

5.
Front Bioeng Biotechnol ; 11: 1249875, 2023.
Article in English | MEDLINE | ID: mdl-37576984

ABSTRACT

The incidence and mortality of cancer are gradually increasing. The highly invasive and metastasis of tumor cells increase the difficulty of diagnosis and treatment, so people pay more and more attention to the diagnosis and treatment of cancer. Conventional treatment methods, including surgery, radiotherapy and chemotherapy, are difficult to eliminate tumor cells completely. And the emergence of nanotechnology has boosted the efficiency of tumor diagnosis and therapy. Herein, the research progress of nanotechnology used for tumor diagnosis and treatment is reviewed, and the emerging detection technology and the application of nanodrugs in clinic are summarized and prospected. The first part refers to the application of different nanomaterials for imaging in vivo and detection in vitro, which includes magnetic resonance imaging, fluorescence imaging, photoacoustic imaging and biomarker detection. The distinctive physical and chemical advantages of nanomaterials can improve the detection sensitivity and accuracy to achieve tumor detection in early stage. The second part is about the nanodrug used in clinic for tumor treatment. Nanomaterials have been widely used as drug carriers, including the albumin paclitaxel, liposome drugs, mRNA-LNP, protein nanocages, micelles, membrane nanocomplexes, microspheres et al., which could improve the drug accumulate in tumor tissue through enhanced permeability and retention effect to kill tumor cells with high efficiency. But there are still some challenges to revolutionize traditional tumor diagnosis and anti-drug resistance based on nanotechnology.

6.
Pak J Med Sci ; 39(3): 752-756, 2023.
Article in English | MEDLINE | ID: mdl-37250537

ABSTRACT

Objectives: To investigate the difference of application of core needle biopsy histology and fine needle aspiration cytology in cervical lymphadenopathy. Methods: A retrospective analysis was made on 80 patients with cervical lymphadenopathy admitted to Baoding No.1 Central Hospital from to October 2018 to February 2020, and they were randomly divided into two groups: core needle group and fine needle group. Patients in the core needle group were given core needle biopsy histology, while those in the fine needle group were given fine needle aspiration cytology, and the puncture results and surgical complications were compared between the two groups. Results: The accuracy rates of the core needle group and the fine needle group in the diagnosis of malignant cervical lymph nodes were 95.83% and 72.22% respectively, with a statistically significant difference (χ²=4.683, p=0.030). The sensitivity, specificity, positive predictive value and negative predictive value of the core needle group were 100.00%, 93.75%, 95.83% and 100.00% respectively, while those of the fine needle group were 86.67%, 90.00%, 86.67% and 90.00% respectively, with no statistically significant differences between the two groups (p>0.05). The complication rate in the core needle group was 22.50%, which was higher than the 5.00% in the fine needle group (χ²=5.165, p=0.023). Conclusions: No significant difference was observed between core needle biopsy histology and fine needle aspiration cytology in diagnosing cervical lymphadenopathy, but the former has a high complication rate.

7.
Biomed Pharmacother ; 160: 114315, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36716661

ABSTRACT

Gastric ulcer (GU) is one of the most prevalent digestive system diseases in humans, and it has been linked to inflammation. Previous studies have demonstrated the anti-inflammatory potential of isoalantolactone (IAL), a sesquiterpene lactone isolated from Radix Inulae. However, the pharmacological effects of IAL on GU and its mechanism of action are still unclear. Hence, the present study is aimed to investigate the anti-inflammatory potential of IAL on GU. Firstly, we assessed the effect of IAL on ethanol-induced injury of human gastric epithelial cells and the levels of inflammatory cytokines in cell culture supernatants. Then, the anti-inflammatory effects of IAL were confirmed in vivo using zebrafish inflammation models. Furthermore, the mechanism of IAL against GU was preliminarily discussed through network pharmacology and molecular docking studies. Quantitative real-time PCR assays were also used to confirm the mechanism of IAL action. ALB, EGFR, SRC, HSP90AA1, and CASP3 were found for the first time as the key targets of the IAL anti-GU. PI3K-Akt signaling pathway and Th17 cell differentiation were identified to play a crucial role in the anti-GU effects of IAL. In conclusion, we found that IAL has anti-inflammatory effects both in vitro and in vivo, and showed potential protective effects against ethanol-induced GU.


Subject(s)
Sesquiterpenes , Stomach Ulcer , Animals , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/prevention & control , Ethanol/pharmacology , Molecular Docking Simulation , Zebrafish/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/prevention & control , Signal Transduction , Sesquiterpenes/pharmacology , Sesquiterpenes/therapeutic use , Anti-Inflammatory Agents/therapeutic use
8.
Psychiatr Serv ; 74(6): 659-662, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36415993

ABSTRACT

Certified peer specialists (CPSs) may be uniquely situated to help address inequities within the behavioral health system. However, CPSs and other mental health care providers often do not have opportunities to discuss their experiences with racism in the workplace. The Southeast Mental Health Technology Transfer Center and Georgia Mental Health Consumer Network offered the six-part Racism and Recovery event series as a space for such discussions (N=356 participants). Participant responses on the Government Performance and Results Act survey (N=239) and supplemental Qualtrics survey (N=213) identified potential actions at the individual and organizational levels for disrupting racism. The responses indicated that the series was a feasible and well-received model for engaging diverse participants.


Subject(s)
Mental Health Services , Racism , Humans , Racism/psychology , Mental Health , Surveys and Questionnaires , Hearing
9.
Pak J Med Sci ; 38(6): 1477-1482, 2022.
Article in English | MEDLINE | ID: mdl-35991229

ABSTRACT

Objectives: To compare the diagnostic efficacy of fine needle aspiration (FNA) and core needle biopsy (CNB) for metastatic lymph nodes guided by contrast-enhanced ultrasound (CEUS), and to provide reference for clinical selection of puncture methods. Methods: A total of 168 patients who were admitted to Baoding No.1 Central Hospital from June 2020 to January 2021 and required puncture of the diseased lymph nodes were included. Seventy six patients were guided by conventional ultrasound, of which 37 received FNA and 39 received CNB. 92 patients were guided by CEUS, of which 41 received FNA and 51 received CNB. The diagnostic accuracy of FNA and CNB guided by conventional ultrasound and CEUS was compared, and the sensitivity, specificity, positive predictive value, and negative predictive value of FNA and CNB in the diagnosis of metastatic lymph nodes guided by CEUS were further compared. Results: The diagnostic accuracy of FNA and CNB guided by CEUS were higher than that guided by conventional ultrasound, with a statistically significant difference (P<0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of FNA and CNB in the diagnosis of metastatic lymph nodes were 95.0%, 95.2%, 95.0%, 95.2%, 100%, 100%, 100%, 100%, respectively, with statistically significant differences (P>0.05). Conclusion: CEUS can guide puncture and improve diagnosis accuracy. No statistical difference can be seen in the diagnostic efficacy of CNB and FNA for metastatic lymph nodes, CNB can provide more diagnostic information, while FNA can replace CNB for metastatic lymph nodes adjacent to blood vessels and difficult to operate.

10.
J Phys Chem B ; 126(28): 5320-5325, 2022 Jul 21.
Article in English | MEDLINE | ID: mdl-35730616

ABSTRACT

The structural relaxation processes in a Ge3As52S45 molecular chalcogenide glass sample were directly studied by X-ray photon correlation spectroscopy (XPCS). XPCS was conducted at the first sharp diffraction peak at q = 1.16 Å-1 at temperatures ranging from 123 K to above the glass transition at 328 K, and the results showed two different dynamical regimes. At a low temperature, the observed glass dynamics are slow and dominated by X-ray-photon-induced effects, which are temperature independent. At a higher temperature, we observed a dramatic decrease in the fluctuation timescales, indicating that the dynamics were mainly due to the intermolecular correlation of the As4S3 molecule in the glass. The timescales in this high-temperature range agree well with those determined from measurements of the Newtonian viscosity. Our XPCS studies suggest an extended length scale of the relaxation process in glassy Ge3As52S45 from the single molecule to the intermolecular range across the glass transition, providing a unique direct probe of the dynamics beyond the length scales of the individual molecule.

11.
Front Sports Act Living ; 3: 757815, 2021.
Article in English | MEDLINE | ID: mdl-34870194

ABSTRACT

Aims: One third of the U.S. adult population is estimated to have obesity-associated prediabetes. Hispanics have a 50% higher type 2 diabetes death rate compared to non-Hispanic whites, yet low participation in lifestyle change programs, making this subgroup an important target for prevention. Our objective was to determine the feasibility and the effects of an intervention implementing the Center for Disease Control and Prevention National Diabetes Prevention Program (NDPP) plus recreational soccer (RS) in Hispanic men. Methods: Overweight and obese Hispanic men, aged 30-57 years with prediabetes at screening were recruited (n = 41). Trained soccer coaches led 30-min facilitated discussion of the NDPP modules after each RS session, with two sessions per week for 12 weeks and once per week for the following 12 weeks. The 1-h RS sessions followed the Football Fitness curriculum. Assessments included body mass index, waist circumference, bioelectrical impedance analysis (InBody 270), blood pressure, glycated hemoglobin (HbA1c), and validated physical fitness tests. Multilevel mixed models assessed the outcomes as a function of time and cohort and incorporated an unstructured covariance structure to examine the changes from baseline to 24 weeks. All analyses were conducted as intent-to-treat using SAS v 9.4. Results: Hispanic males (n = 41; mean age 41.7 [0.1] years) were obese at baseline (mean BMI 32.7, standard error of mean [0.7], mean weight 93.9 [2.2] kg). Attendance rate was 65% overall at 12 weeks but differed between cohorts. Five mild injuries occurred over the trial. After 24 weeks of the NDPP+RS intervention, there were significant decreases in systolic and diastolic blood pressure (%change -4.7[SE 2.4]; 95% CI [-11.5, -1.7] and -6.1 [1.7] mmHg; [-9.6, -2.6], respectively), HbA1c (-0.2 [0.1]; [-0.3, -0.1]), Despite significant reductions in weight (-3.8 [0.7]; [-5.2, -2.5]), waist circumference (-6.6 [0.7] cm; [-8.0, -5.1]), body fat % (-1.9 [0.5]; [-2.8, -1.0]), lean body mass was preserved (-0.9 [0.3]; [-1.6, -0.2]). Conclusion: A 24-week soccer-based adaptation of the Diabetes Prevention Program is safe and feasible among middle-aged Latino men.

12.
Kidney Med ; 3(6): 951-961.e1, 2021.
Article in English | MEDLINE | ID: mdl-34939004

ABSTRACT

RATIONALE & OBJECTIVE: We aimed to test interventions to improve physical activity in persons with advanced chronic kidney disease not yet receiving dialysis. STUDY DESIGN: Randomized controlled trial with parallel-group design. SETTING & PARTICIPANTS: We embedded a pragmatic referral to exercise programming in high-volume kidney clinics servicing diverse populations in San Jose, CA, and Atlanta, GA. We recruited 56 participants with estimated glomerular filtration rates < 45 mL/min/1.73 m2. INTERVENTIONS: We randomly assigned participants to a mobile health (mHealth) group-wearable activity trackers and fitness professional counseling, or an Exercise is Medicine intervention framework (EIM) group-mHealth components plus twice-weekly small-group directed exercise sessions customized to persons with kidney disease. We performed assessments at baseline, 8 weeks at the end of active intervention, and 16 weeks after passive follow-up and used multilevel mixed models to assess between-group differences. OUTCOMES: Activity tracker total daily step count. RESULTS: Of 56 participants, 86% belonged to a racial/ethnic minority group; randomly assigned groups were well balanced on baseline step count. In intention-to-treat analyses, the EIM and mHealth groups both experienced declines in daily step counts, but there was an attenuated reduction in light intensity physical activity (standard error 0.2 [5.8] vs -8.5 [5.4] min/d; P = 0.08) in the EIM compared with the mHealth group at 8 weeks. In as-treated analyses, total daily step count, distance covered, and light and moderate-vigorous activity minutes per day improved in the EIM group and declined in the mHealth group at 8 weeks (standard error +335 [506] vs -884 [340] steps per day; P = 0.05; P < 0.05 for secondary measures), but group differences faded at 16 weeks. There were no differences in quality-of-life and mental health measures during the study. LIMITATIONS: Small sample size, limited duration of study, assessment of intermediate outcomes (steps per day). CONCLUSIONS: A clinic-integrated referral to small-group exercise sessions is feasible, safe, and moderately effective in improving physical activity in an underserved population with high comorbid conditions. FUNDING: Normon S Coplon Applied Pragmatic Clinical Research program. TRIAL REGISTRATION: NCT03311763.

13.
Front Pharmacol ; 12: 642480, 2021.
Article in English | MEDLINE | ID: mdl-33967776

ABSTRACT

Aconitine (AC), one of the bioactive diterpenoid alkaloids extracted from Aconitum plants, is widely used in traditional herbal medicine to treat various diseases. Emerging evidence indicates that AC has attracted great interest for its wide cardiotoxicity and neurotoxicity. However, the toxic effects of AC on embryonic development and its underlying mechanisms remain unclear. Here, a developmental toxicity assay of AC was performed on zebrafish embryos from 4 to 96 h post fertilization (hpf), and its underlying mechanisms were discussed. AC exposure impaired the cardiac, liver, and neurodevelopment. Especially, a high dose of AC (7.27 and 8.23 µM) exposure resulted in malformations at 72 and 96 hpf, including reduced body length, curved body shape, pericardial edema, yolk retention, swim bladder and brain developmental deficiency, and degeneration of dopaminergic neurons. High-concentration AC exposure caused a deficient cardiovascular system with cardiac dysfunctions, increased heart rates at 72 and 96 hpf, and reduced locomotor behavior at 120 hpf. AC treatment significantly increased the ROS level and triggered cell apoptosis in the heart and brain regions of embryos at 96 hpf in 7.27 and 8.23 µM AC treatment zebrafish. Oxidative stress was confirmed by reduced levels of T-SOD activity associated with accumulation of lipid peroxidation in larvae. The expression levels of oxidative stress-related genes (Nrf2, HO-1, Cat, and Sod-1) Erk1/2 and Bcl-2 were significantly downregulated at 96 hpf. The expression pattern of JNK and mitochondrial apoptosis-related genes (Bad, Bax, Cyto C, Casp-9, and Casp-3) was significantly upregulated. Taken together, all these parameters collectively provide the first evidence of AC-induced developmental toxicity in zebrafish embryo/larvae through ROS-medicated mitochondrial apoptosis involving Nrf2/HO-1 and JNK/Erk pathways.

14.
J Org Chem ; 86(9): 6698-6710, 2021 05 07.
Article in English | MEDLINE | ID: mdl-33881860

ABSTRACT

A copper-catalyzed, ligand-free intramolecular C-N coupling of (E)-2-(2-bromophenyl)-3-arylacrylamides has been developed. This protocol provides an efficient and practical synthetic route for the biologically important (E)-3-arylideneindolin-2-ones from o-bromophenylacetic acids and aromatic or conjugated alkenyl aldehydes. Readily available starting materials, mild and noble metal-free conditions, high efficiency, and good tolerability for phenolic hydroxyl groups make this approach attractive and applicable.


Subject(s)
Aldehydes , Copper , Catalysis , Ligands
15.
Gen Hosp Psychiatry ; 70: 44-50, 2021.
Article in English | MEDLINE | ID: mdl-33714795

ABSTRACT

OBJECTIVE: Suicide is a serious public health concern, but little is known about the relationship between access to mental health care and suicide deaths, and whether suicide rates differ by mental health provider Health Professional Shortage Areas (HPSAs). This study investigated the associations between mental health HPSAs and suicide rates. METHOD: We used generalized linear mixed models to test the associations between HPSAs and suicide rates from 2010 to 2018. For each county during a 3-year period, the total number of suicides was obtained from Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (WONDER). RESULTS: Mental health HPSAs had higher suicide rates (adjusted incidence rate ratio (IRR), 1.06 [95% CI, 1.03-1.09]). The interaction terms of mental health HPSAs and time (adjusted IRR, 1.01 [95% CI, 1.00-1.01]) showed that the association between mental health shortage areas and suicide rates has increased over time. CONCLUSIONS: Suicide rates are more common in mental health provider shortage areas, and this association has been growing over time. The study's findings suggest that many communities in the US are likely facing simultaneous challenges of limited access to mental health care, social and economic disadvantage, and high burden of suicide.


Subject(s)
Mental Health , Suicide , Adult , Humans , United States/epidemiology
16.
Eur J Med Chem ; 212: 113019, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33429247

ABSTRACT

Lung cancer is the leading cause of cancer deaths. It has been demonstrated that epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are efficacious in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this work, a new series of 2,4-diaryl pyrimidine derivatives containing cyclopropyl moiety were designed, synthesized and evaluated as novel selective EGFRL858R/T790M inhibitors. The most promising compound, 8l demonstrated excellent kinase inhibitory activity against EGFR double mutation with IC50 value of 0.26 nM. Moreover, 8l provided strong activity against H1975 cells with IC50 value of 0.008 µM and exhibited little toxicity toward four non-tumorigenic cell lines. Furthermore, 8l showed potent anti-tumor efficacy in a murine EGFRL858R/T790M-driven H1975 xenograft model. These results indicated that 8l may be a promising drug candidate for further study.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/metabolism , Humans , Male , Mice , Mice, Nude , Models, Molecular , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship
17.
J Synchrotron Radiat ; 28(Pt 1): 207-213, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33399570

ABSTRACT

Hard X-ray nanodiffraction provides a unique nondestructive technique to quantify local strain and structural inhomogeneities at nanometer length scales. However, sample mosaicity and phase separation can result in a complex diffraction pattern that can make it challenging to quantify nanoscale structural distortions. In this work, a k-means clustering algorithm was utilized to identify local maxima of intensity by partitioning diffraction data in a three-dimensional feature space of detector coordinates and intensity. This technique has been applied to X-ray nanodiffraction measurements of a patterned ferroelectric PbZr0.2Ti0.8O3 sample. The analysis reveals the presence of two phases in the sample with different lattice parameters. A highly heterogeneous distribution of lattice parameters with a variation of 0.02 Šwas also observed within one ferroelectric domain. This approach provides a nanoscale survey of subtle structural distortions as well as phase separation in ferroelectric domains in a patterned sample.

18.
Prog Cardiovasc Dis ; 63(6): 775-785, 2020.
Article in English | MEDLINE | ID: mdl-32603753

ABSTRACT

PURPOSE: One third of the U.S. adult population is estimated to have prediabetes. Hispanics have a 50% higher type 2 diabetes (T2DM) death rate compared to non-Hispanic whites, yet low participation in lifestyle change programs, making this subgroup an important target for prevention efforts. The purpose of this study was to determine the effects of an exercise intervention implementing the Center for Disease Control and Prevention National Diabetes Prevention Program (NDPP) plus recreational soccer (RS) in Hispanic men. METHODS: Overweight and obese Hispanic men, aged 30-57 years with prediabetes at screening were recruited from the community. Trained soccer coaches led 30-min facilitated discussion of the NDPP modules after each RS session, with two weekly sessions delivered over 12 wks, then once a wk until 24 wks. The 1-h RS sessions followed the Football Fitness curriculum structure. Standardized study assessments included objectively measured physical activity via fitness tracker, physical fitness via validated field tests, global positional system soccer specific metrics and behavior change questionnaires. Mixed models assessed the outcomes as a function of time and cohort and incorporated an unstructured covariance structure to examine the difference between baseline, 12 and 24 wks. All analyses were conducted as intent-to-treat and generated using SAS v 9.4. RESULTS: Hispanic males (n = 41; mean age 41.9 [6.2 SD] years) were obese at baseline (mean BMI 32.7, standard error [0.7]). After 24 wks of the NDPP+RS intervention, there were significant beneficial changes in vertical jump (2.8 [1.3] cm; p = 0.048), agility and lower extremity muscular power (figure 8-run) at 12 wks (-4.7% change; p = 0.001) and 24 wks (-7.2% change; p < 0.0001), predicted VO2 max (12 wks: 1.9%; p = 0.007; 24 wks 1.0%; p = 0.036), modified push-ups increased 22% (p < 0.0001) at 12 wks and 31% (p < 0.0001) at 24 wks, dynamic sit-ups increased 10% (p = 0.005) at 12 wks and 15% (p < 0.0001) at 24 wks. CONCLUSION: Among middle-aged Latino men, broad-ranging significant improvements in physical fitness were observed after 24 wks participating in lifestyle education plus RS in a single arm feasibility trial.


Subject(s)
Diabetes Mellitus, Type 2/prevention & control , Healthy Lifestyle , Hispanic or Latino , Obesity/therapy , Physical Fitness , Prediabetic State/therapy , Primary Prevention , Risk Reduction Behavior , Soccer , Adult , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/physiopathology , Feasibility Studies , Georgia , Humans , Male , Middle Aged , Obesity/ethnology , Obesity/physiopathology , Pilot Projects , Prediabetic State/ethnology , Prediabetic State/physiopathology , Sex Factors , Time Factors , Treatment Outcome
19.
Psychiatr Serv ; 71(8): 803-809, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32362226

ABSTRACT

OBJECTIVE: Behavioral health homes, which provide onsite primary medical care in mental health clinics, face challenges in integrating information across multiple health records. This study tested whether a mobile personal health record application improved quality of medical care for individuals treated in these settings. METHODS: This randomized study enrolled 311 participants with a serious mental illness and one or more cardiometabolic risk factors across two behavioral health homes to receive a mobile personal health record application (N=156) or usual care (N=155). A secure mobile personal health record (mPHR) app provided participants in the intervention group with key information about diagnoses, medications, and laboratory test values and allowed them to track health goals. The primary study outcome was a chart-derived composite measure of quality of cardiometabolic and preventive services. RESULTS: At 12-month follow-up, participants in the mPHR group maintained high quality of care (70% of indicated services at baseline and at 12-month follow-up), in contrast to a decline in quality for the usual-care group (71% at baseline and 67% at follow-up), resulting in a statistically significant but clinically modest differential impact between the groups. No differences between the study groups were found in secondary self-reported outcomes, including delivery of chronic illness care, patient activation, and quality of life related to mental or general medical health. CONCLUSIONS: Use of a mPHR app was associated with a statistically significant but clinically modest differential benefit for quality of medical care among individuals with serious mental illness and comorbid cardiometabolic conditions.


Subject(s)
Health Records, Personal , Mental Disorders/therapy , Mental Health Services , Mobile Applications , Female , Humans , Male , Middle Aged , Primary Health Care , Quality of Life , United States
20.
Sci Rep ; 10(1): 5881, 2020 Apr 03.
Article in English | MEDLINE | ID: mdl-32246019

ABSTRACT

Direct quantitative measurements of nanoscale dynamical processes associated with structural relaxation and crystallization near the glass transition are a major experimental challenge. These type of processes have been primarily treated as macroscopic phenomena within the framework of phenomenological models and bulk experiments. Here, we report x-ray photon correlation spectroscopy measurements of dynamics at the crystal-melt interface during the radiation induced formation of Se nano-crystallites in pure Se and in binary AsSe4 glass-forming liquids near their glass transition temperature. We observe a heterogeneous dynamical behaviour where the intensity correlation functions g2(q, t) exhibits either a compressed or a stretched exponential decay, depending on the size of the Se nano-crystallites. The corresponding relaxation timescale for the AsSe4 liquid increases as the temperature is raised, which can be attributed to changes in the chemical composition of the melt at the crystal-melt interface with the growth of the Se nano-crystallites.

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