political decisions on the future direction of tasks and finances of Finnish community pharmacies in this framework. Government-funded studies are underway to guide decision making. Ongoing Covid-19 crisis has demonstrated the readiness of Finnish community pharmacies to adapt fast to meet the changing societal needs.

This study examined the effects of a national policy advocating rational drug use (RDU), namely, the 'RDU Service Plan’, starting in fiscal year 2017 and implemented by the Thai Ministry of Public Health (MOPH), on trends in antibiotic prescribing rates for outpatients. The policy was implemented subsequent to a voluntary campaign involving 136 hospitals, namely, the 'RDU Hospital Project’, which was implemented during fiscal years 2014-2016.

Hospital-level antibiotic prescribing rates in fiscal years 2014-2019 for respiratory infections, acute diarrhea, and fresh wounds were aggregated for two hospital groups using equally weighted averages early adopters of RDU activities through the RDU Hospital Project and late adopters under the RDU Service Plan. Pre-/post-policy annual changes in the prescribing levels and trends were compared between the two groups using an interrupted time-series analysis.

In fiscal years 2014-2016, decreases in antibiotic prescribing rates for respiratory infections and acute diarrhea in both groups reflected a trend that existed before the RDU Service Plan was implemented. The immediate effect of the RDU Service Plan policy occurred in fiscal year 2017, when the prescribing level among the late adopters dropped abruptly for all three conditions with a greater magnitude than in the decrease among the early adopters, despite nonsignificant differences. The medium-term effect of the RDU Service Plan was identified through a further decreasing trend during fiscal years 2017-2019 for all conditions in both groups, except for acute diarrhea among the early adopters.

The national policy on rational drug use effectively reduced antibiotic prescribing for common but questionable outpatient conditions.

The national policy on rational drug use effectively reduced antibiotic prescribing for common but questionable outpatient conditions.

To quantify the use of the interprofessional team member (ITM) domain of entrustable professional activities (EPAs) by North Dakota pharmacists across practice sites, roles in practice, and by preceptor status.

Survey methods were used to characterize the self-reported frequency with which pharmacists undertake core EPAs and supporting tasks in the ITM domain. The survey was administered to registered pharmacists practicing in North Dakota (n=990) during the fall of 2018, of which 457 (46.1%) responded. After eliminating responses with incomplete or missing information, 119 responses were available for analysis.

For the overall EPA ITM domain, „Collaborate as a member of an interprofessional team population” pharmacists reported performing these activities an average (mean) of 3.3 times per month (SD=2.3). Within this domain, the highest reported example activity was „Use setting appropriate communication skills when interacting with others” (mean=4.1, SD 1.8), followed by „Communicate a patient’s medication-related problem(s) to another health professional” (mean=3.3, SD 2.0), and „Contribute medication-related expertise to the team’s work” (mean=3.1, SD=2.2). ITM domain and supporting example activities were performed at a greater rate in hospitals, community health centers and long-term-care facilities. For most items, preceptors reported a greater use of activities, than did non-preceptors.

North Dakota pharmacists currently complete tasks outlined in the ITM domain of the EPAs, although their contributions are varied by task, role, and preceptor status.

North Dakota pharmacists currently complete tasks outlined in the ITM domain of the EPAs, although their contributions are varied by task, role, and preceptor status.

The objective of this study was to assess adherence to the Mediterranean diet (MeD) and the risk of stroke in the Lebanese population.

A hospital based case-control study was conducted in Lebanon between January 1

, 2015 and December 31

, 2016. Data were collected prospectively using a standardized questionnaire. Adherence to the MeD was assessed based on the total number of points a patient can have on the MeD scale. Data were analysed using SPSS version 24. The strength of association between the risk of stroke and adherence to MeD was expressed in odds ratio (OR) through 95% confidence interval. P-value <0.05 determined statistical significance.

Around 205 stroke cases and 445 hospitalized stroke-free patients were included in this study. In the total study sample, the MeD had a minimum of 2 and a maximum of 11 points with a median of 7 points. Stroke patients had a lower MeD median compared to controls (6 vs 8 points). Around 29.5% of the total sample had a MeD score within the first quartile (52.3% of them had a stroke) and 24% of all included subjects scored within the last quartile (7% of them hospitalized for stroke) (p<0.001). The higher the adherence to MeD the lower the risk of stroke. High adherence to MeD was associated with a decreased risk of stroke, OR 0.1 (95%CI, 0.04-0.24; p<0.001).

Higher adherence to MeD significantly decreases the risk of stroke in the Lebanese population. Good lifestyle choices are encouraged in order to prevent many vascular diseases including stroke.

Higher adherence to MeD significantly decreases the risk of stroke in the Lebanese population. Good lifestyle choices are encouraged in order to prevent many vascular diseases including stroke.

The Minor Ailment Service (MAS) in Scottish community pharmacy allows eligible people to gain improved access to care by providing free treatment for self-limiting conditions.

To determine the perceptions and experiences of individuals using MAS and to quantify the potential impact on usage of other healthcare services.

A cross-sectional survey was conducted of patients accessing MAS across Scotland during June and July 2018. Questionnaire items included reasons for choosing treatment through MAS, which other services they may have accessed had MAS not been available, experiences of consultation, overall satisfaction, and perceived effectiveness of treatment. Those accessing MAS were given a study pack including an information sheet, pre-piloted questionnaire, and pre-paid return envelope. Participants had the option to consent to an optional one-week follow up questionnaire that focused on perceived effectiveness of treatment after seven days and any further access to healthcare services such as generalthcare services is evidenced through the number of participants who reported these services as a point of access to care should community pharmacy not be available. This national evaluation demonstrates MAS to be a positively experienced service and outlines the factors determining access for treatment of minor ailments.

Positive perceptions and experiences of those using MAS demonstrate a highly regarded service in terms of satisfaction and experience of consultation. The capacity for MAS to impact on the use of higher-cost healthcare services is evidenced through the number of participants who reported these services as a point of access to care should community pharmacy not be available. This national evaluation demonstrates MAS to be a positively experienced service and outlines the factors determining access for treatment of minor ailments.

Community pharmacy teams (CPTs) have an established role in assisting self-medication, contributing to the safe and effective use of non-prescription medicines.

The study aimed to describe CPTs’ performance in self-medication consultation, client-reported outcomes, and satisfaction. A secondary purpose was to develop an explanatory model for better understanding clients’ satisfaction with this service.

Descriptive, cross-sectional exploratory study. Data were collected in a purposive sample of pharmacy clients recruited in six community pharmacies in Portugal. CPTs adopted a structured approach to self-medication consultations, encompassing 11 quality criteria (five for case evaluation and six for counselling). An evaluation score, a counselling score and an overall quality score were estimated. Client-reported outcomes and satisfaction were ascertained via a follow-up telephone interview. Besides descriptive statistics, the association with several independent variables on the clients’ overall satisfacmacists’ clinical role. A larger study is warranted to confirm these findings.Multiple genes have been implicated to have a role in asthma predisposition by association studies. Pediatric patients often manifest a more extensive form of this disease and a particularly severe disease course. It is likely that genetic predisposition could play a more substantial role in this group. This study is aimed at identifying the spectrum of rare and novel variation in known pediatric asthma susceptibility genes using whole exome sequencing analysis in nine individual cases of childhood onset allergic asthma. DNA samples from the nine children with a history of bronchial asthma diagnosis underwent whole exome sequencing on Ion Proton. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. The analysis showed 21 variants in the subjects, 13 had been previously identified, and 8 were novel. Also, among of which, nineteen were nonsynonymous and 2 were nonsense. With regard to the novel variants, the 2 nonsynonymous variants in the PRKG1 gene (PRKG1 p.C519W and PRKG1 p.G520W) were presented in 4 cases, and a nonsynonymous variant in the MAVS gene (MAVS p.A45V) was identified in 3 cases. The variants we found in this study will enrich the variant spectrum and build up the database in the Saudi population. Novel eight variants were identified in the study which provides more evidence in the genetic susceptibility in asthma among Saudi children, providing a genetic screening map for the molecular genetic determinants of allergic disease in Saudi children, with the goal of reducing the impact of chronic diseases on the health and the economy. We believe that the advanced specified statistical filtration/annotation programs used in this study succeeded to release such results in a preliminary study, exploring the genetic map of that disease in Saudi children.

At present, the diagnostic accuracy of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is insufficient. It remains controversial whether prothrombin induced by vitamin K absence II (PIVKA-II) has a better diagnostic value than AFP for HCC patients.

To investigate the diagnostic role of PIVKA-II alone or in combination with AFP in Chinese HCC patients.

Serum AFP and PIVKA-II levels were detected and analyzed in 308 HCC afflicted patients and 120 unafflicted controls. The receiver operator curve (ROC) and area under the curve (AUC) were conducted to evaluate the clinical value of AFP and PIVKA-II for diagnosing HCC and early HCC.

In the whole HCC cohort, the diagnostic values of PIVKA-II were better than that of AFP. The AUC of PIVKA-II and AFP was 0.90 (95% CI 0.87-0.94) and 0.79 (95% CI 0.74-0.84), respectively. „AFP + PIVKA-II” yielded a high sensitivity of 95.1% and a specificity of 83.3%, with the AUC 0.89 (95% CI 0.85-0.93). In the early stage HCC group, the diagnostic accuPVTT and help to optimize the therapeutic strategy.The present study is aimed at examining the serum levels of brain-derived neurotrophic factor (BDNF) and investigating its role in differential diagnosis of colorectal cancer (CRC). Materials and Methods. In a Chinese population, we conducted a case-control study to compare the diagnostic performance of serum levels of BDNF and carcinoembryonic antigen (CEA) for CRC. We enrolled 61 healthy controls, 31 patients with adenomas, and 81 patients with CRC. We explored the correlation between serum levels of BDNF and several pathological features, such as tumor differentiation and TNM staging. Results. The serum levels of BDNF were significantly (p less then 0.0001) higher in patients with CRC (10.64 ± 3.84, n = 81) than in the healthy controls (4.69 ± 1.69 ng/mL, n = 61). Serum BDNF also correlated with tumor size, tumor differentiation, and TNM staging (p less then 0.05). For early diagnosis, the combination of BDNF (AUC 0.719; 95% CI, 0.621-0.816) and CEA (AUC 0.733; 95% CI, 0.632-0.909) slightly improved the diagnostic performance for CRC (AUC 0.823; 95% CI, 0.737-0.909). Conclusions. Combined detection of serum BDNF and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis of CRC.Sarcopenia is the most common feature of hepatic cirrhosis characterized by progressive loss of muscle mass and function and increases permanently the mortality and morbidity rates among those patients. The incidence of sarcopenia in cirrhotic patients ranged 40-70% associating with impaired quality of life and augmented rates of infection. Based on these issues, this review is aimed at determining the prevalence and main causes of sarcopenia among cirrhotic patients and recognizing the recent diagnostic and physical treatment modalities that prevent risk factors for sarcopenia in those patients. No ideal modality is currently demonstrated for diagnosing sarcopenia in hepatic diseases, particularly cirrhosis; however, recent studies reported different diagnostic modalities for muscle function in different individuals including handgrip strength, skeletal muscle index, six-min walk test, liver frailty index, short physical performance battery, and radiological assessments for quadriceps and psoas muscles. Exercise training and therapeutic nutrition are strongly recommended for controlling sarcopenia in cirrhotic patients. The exercise program is designed and carried out on a frequent basis within an extensive scheduled time aimed at improving functional performance, aerobic capacity, and healthy conditions. Finally, a combination of exercise training and therapeutic nutrition is powerfully recommended to control sarcopenia in cirrhosis.Epigenetic gene silencing by aberrant DNA methylation leads to loss of key cellular pathways in tumorigenesis. In order to analyze the effects of DNA methylation on prostate cancer, we established LNCaP-derived human prostate cancer cells that can pharmacologically induce global reactivation of hypermethylated genes by the methyl-CpG targeted transcriptional activation (MeTA) method. The MeTA suppressed the growth of LNCaP-derived cells and induced apoptosis. Microarray analysis indicated that PYCARD (PYD and CARD domain containing) encoding an apoptosis-inducing factor was upregulated by 65-fold or more after treatment with MeTA. We analyzed DNA methylation statuses using 50 microdissected primary prostate cancer tissues and found an extremely high frequency of tumor-specific promoter hypermethylation of PYCARD (90%, 45/50). Moreover, DNA methylation status was significantly associated with Gleason score (P = 0.0063); the frequency of tumor-specific hypermethylation was 96% (44/46) in tumors with Gleason score ≥ 7, whereas that in tumors with Gleason score 6 was 25% (1/4). Immunohistochemical analyses using these 50 cases indicated that only 8% (4/50) of cancerous tissues expressed PYCARD, whereas 80% (40/50) of corresponding normal prostate epithelial and/or basal cells expressed PYCARD. In addition, there was no relationship between PYCARD immunostaining and the Gleason score in cancerous tissue and surrounding normal tissue. Inducible expression of PYCARD inhibited cell proliferation by induction of apoptosis. These results suggest that aberrant methylation of PYCARD is a distinctive feature of prostate cancers with Gleason score ≥ 7 and may play an important role in escaping from apoptosis in prostatic tumorigenesis.The Kessler Foundation Neglect Assessment Process (KF-NAP) is an assessment tool for unilateral spatial neglect (USN), which is the scoring method for the Catherine Bergego Scale (CBS) based on detailed instructions. This study is aimed at determining the reliability and validity of the Japanese version of the KF-NAP (KF-NAP-J), evaluating the improvement of neglect assessment with KF-NAP-J, and comparing it with the original CBS for subacute stroke patients. We assessed subacute stroke patients admitted to our intensive rehabilitation hospital. Two KF-NAP-trained occupational therapists (OTs) assessed 22 patients. Before implementing the KF-NAP at the hospital, two other OTs assessed the other 23 patients using the CBS. We evaluated the interrater reliability of the KF-NAP and CBS using intraclass correlation coefficients (ICC) for the total scores, weighted kappa statistics for each subscale, and internal consistency using Cronbach’s alpha. We assessed the validity of the KF-NAP against the Behavioral Inattention Test (BIT) and Functional Independence Measure (FIM) using Spearman’s correlation coefficient. The reliability of both the KF-NAP and CBS was excellent. The weighted kappa results demonstrated that each subscale was in better agreement with the KF-NAP than with the CBS. In the KF-NAP, all eight subscales in which weighted kappa could be calculated were in significant agreement, and two were almost in perfect agreement. The KF-NAP moderately correlated with the subscales of BIT and FIM representing USN and activities of daily living. The USN detection rates of KF-NAP and BIT in the KF-NAP group were 63.6% and 22.7%, respectively. These results suggest that the KF-NAP, as well as the CBS, is useful to assess USN, which strongly impacts the rehabilitation outcomes in subacute stroke patients.Limited research exists about factors that influence the sustainability of preventive school mental health interventions when research support ends. This study assessed barriers and facilitators to sustaining RAP (Relax, be Aware, do a Personal rating) Club, a trauma-informed universal mental health intervention, in urban schools following efficacy trial implementation. Between 2016-2018, 13 Baltimore City schools implemented RAP Club. We evaluated RAP Club sustainability using semi-structured interviews with administrators (n=10) and school staff trained to deliver the intervention (n=11), as well as review of intervention fidelity logs (n=137) and notes from supervision calls (n=10) with school staff and research team members who implemented the program. Although most school staff described RAP Club as acceptable and beneficial, none of the 13 schools sustained the intervention. Barriers to sustainability included low self-efficacy among school staff trained to deliver the intervention, school staff turnover, logistical challenges with space and time in the regular school calendar to deliver the program, insufficient funding to sustain the program outside of the research context, and limited planning and ongoing communication between school personnel and researchers about sustainability. Recommendations for increasing post-trial program sustainability include developing sustainability plans with schools during the pre-implementation phase, enhancing ongoing support for school staff during the implementation phase, and using academic-community partnerships to facilitate sustainability and intervention scale-up during the post-implementation phase. Increasing sustainability of beneficial school-based mental health programs has the potential to reduce mental health disparities and promote health equity.

Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers. The purpose of this study is to evaluate the value of anti-CarP and anti-PAD4 in a well-characterized population of RA patients and healthy controls (HCs).

A total of 122 RA patients and 30 HCs were enrolled in the study. Serum levels of ACPA, anti-PAD4, anti-CarP and RF were determined by enzyme-linked immunosorbent immunoassays (ELISAs). Synthetic carbamylated peptides were used in the ELISA assay to determine the protein targets of the anti-CarP antibodies.

Rates of ACPA, RF, anti-PAD4 and anti-CarP positivity were 85.2%, 67.2%, 55.7% and 46.7% in RA, and 0%, 0%, 6.7% and 6.7% in HC respectively. In the RA population, 25.4% of patients had all four types of antibodies positive, while 6.6% had no antibodies. There was a significant correlation between anti-PAD4 and ACPAs (

 = 0.39), RF and ACPAs, (

 = 0.3) and RF and anti-CarP, (

 = 0.3). There was no correlation between ACPAs and anti-CarP. Anti-CarP positivity was noted in 49 (47.1%) and 45 (54.9%) of ACPAs and RF positive patients respectively. In addition, five anti-CarP+ patients did not have ACPA nor RF.

Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.

Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.

Peginterferon beta-1a administered every 2 weeks

subcutaneous (SC) injection is approved to treat adult patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing forms of multiple sclerosis (RMS). However, associated injection site reactions (ISRs) can lead to treatment discontinuation. Prior studies with interferon beta-1a reported a lower frequency of ISRs with intramuscular (IM) administration than with SC administration. IM administration of peginterferon beta-1a may therefore represent a useful alternative treatment option.

A phase I, open-label, two-period crossover study randomized healthy volunteers to receive a single dose of peginterferon beta-1a 125 mcg administered IM followed by a single 125 mcg dose administered SC after a 28-day washout or vice versa. Blood samples were collected up to 504 h post dose to determine pharmacokinetic (PK) and pharmacodynamic (PD) profiles. The primary endpoint was assessment of bioequivalence based on maximum serum concentration (C

) and areesults demonstrate bioequivalence between peginterferon beta-1a IM and SC and support the consideration of IM injection of peginterferon beta-1a as a viable treatment option in patients with RRMS and RMS.This paper presents a low-cost, efficient, and portable in vivo method for identifying axes of rotation of the proximal interphalangeal and distal interphalangeal joints in an index finger. The approach is associated with the screw displacement representation of rigid body motion. Using the matrix exponential method, a detailed derivation of general spatial displacement of a rigid body in the form of screw displacement including the Rodrigues’ formulae for rotation is presented. Then, based on a gyroscope sensor, a test framework for determining axes of rotation of finger joints is established, and experiments on finding the directions of joint axes of the PIP and DIP joints are conducted. The results obtained highly agree with those presented in literature through traditional but complex methods.Surface electromyography- (sEMG-) based hand grasp force estimation plays an important role with a promising accuracy in a laboratory environment, yet hardly clinically applicable because of physiological changes and other factors. One of the critical factors is the muscle fatigue concomitant with daily activities which degrades the accuracy and reliability of force estimation from sEMG signals. Conventional qualitative measurements of muscle fatigue contribute to an improved force estimation model with limited progress. This paper proposes an easy-to-implement method to evaluate the muscle fatigue quantitatively and demonstrates that the proposed metrics can have a substantial impact on improving the performance of hand grasp force estimation. Specifically, the reduction in the maximal capacity to generate force is used as the metric of muscle fatigue in combination with a back-propagation neural network (BPNN) is adopted to build a sEMG-hand grasp force estimation model. Experiments are conducted in the three cases (1) pooling training data from all muscle fatigue states with time-domain feature only, (2) employing frequency domain feature for expression of muscle fatigue information based on case 1, and 3) incorporating the quantitative metric of muscle fatigue value as an additional input for estimation model based on case 1. The results show that the degree of muscle fatigue and task intensity can be easily distinguished, and the additional input of muscle fatigue in BPNN greatly improves the performance of hand grasp force estimation, which is reflected by the 6.3797% increase in R2 (coefficient of determination) value.The electroencephalography (EEG) signals have been used widely for studying the brain neural information dynamics and behaviors along with the developing impact of using the machine and deep learning techniques. This work proposes a system based on the fast Fourier transform (FFT) as a feature extraction method for the classification of human brain resting-state electroencephalography (EEG) recorded signals. In the proposed system, the FFT method is applied on the resting-state EEG recordings and the corresponding band powers were calculated. The extracted relative power features are supplied to the classification methods (classifiers) as an input for the classification purpose as a measure of human tiredness through predicting lactate enzyme level, high or low. To validate the suggested method, we used an EEG dataset which has been recorded from a group of elite-level athletes consisting of two classes not tired, the EEG signals were recorded during the resting-state task before performing acute exercise and tired, the EEG signals were recorded in the resting-state after performing an acute exercise. The performance of three different classifiers was evaluated with two performance measures, accuracy and precision values. The accuracy was achieved above 98% by the K-nearest neighbor (KNN) classifier. The findings of this study indicated that the feature extraction scheme has the ability to classify the analyzed EEG signals accurately and predict the level of lactate enzyme high or low. Many studying fields, like the Internet of Things (IoT) and the brain computer interface (BCI), can utilize the findings of the proposed system in many crucial decision-making applications.Rowers with disc degeneration may have motor control dysfunction during rowing. This study is aimed at clarifying the trunk and lower extremity muscle synergy during rowing and at comparing the muscle synergy between elite rowers with and without lumbar intervertebral disc degeneration. Twelve elite collegiate rowers (with disc degeneration, n = 6; without disc degeneration, n = 6) were included in this study. Midline sagittal images obtained by lumbar T2-weighted magnetic resonance imaging were used to evaluate disc degeneration. Participants with one or more degenerated discs were classified into the disc degeneration group. A 2000 m race trial using a rowing ergometer was conducted. Surface electrodes were attached to the right rectus abdominis, external oblique, internal oblique, latissimus dorsi, multifidus, erector spinae, rectus femoris, and biceps femoris. The activity of the muscles was measured during one stroke immediately after 20% and 80% of the rowing trial. Nonnegative matrix factorization was used to extract the muscle synergies from the electromyographic data. To compare the muscle synergies, a scalar product (SP) evaluating synergy coincidence was calculated, and the muscle synergies were considered identical at SP > 75%. Both groups had only one module in the 20% and 80% time points of the trial. At the 20% time point of the 2000 m rowing trial, the SP of the module was 99.8%. At the 80% time point, the SP of the module was 99.9%. The SP results indicate that, at 20% and 80% time points, both groups had the same module. The module showed a high contribution in all muscles. The activation coefficients indicated that the module was always highly activated throughout the rowing stroke in both groups. The trunk and lower extremity muscles are mobilized through the rowing stroke and maintain coordination during rowing. There was no difference in the muscle synergy between the rowers with and without lumbar intervertebral disc degeneration.Urban development has driven extensive modification of the global landscape. This shift in land use and land cover alters ecological functioning, and thereby affects sustainable management agendas. Urbanization fundamentally reshapes the soils that underlay landscapes, and throughout the soil profile, extends impacts of urbanization far below the landscape surface. The impacts of urbanization on deeper soils that are beyond the reach of regular land management are largely unknown, and validation of general theories of convergent ecosystem properties are thwarted by a dearth of both level of measurement effort and the substantial heterogeneity in soils and urban landscapes. Here, we examined two soil properties with strong links to ecological functioning-carbon and mineral-fraction particle size-measured in urban soils, and compared them to their pre-urbanization conditions across a continental gradient encompassing global soil diversity. We hypothesized that urbanization drove convergence of soils properties es.In genetic association analysis, several relevant phenotypes or multivariate traits with different types of components are usually collected to study complex or multifactorial diseases. Over the past few years, jointly testing for association between multivariate traits and multiple genetic variants has become more popular because it can increase statistical power to identify causal genes in pedigree- or population-based studies. However, most of the existing methods mainly focus on testing genetic variants associated with multiple continuous phenotypes. In this investigation, we develop a framework for identifying the pleiotropic effects of genetic variants on multivariate traits by using collapsing and kernel methods with pedigree- or population-structured data. The proposed framework is applicable to the burden test, the kernel test, and the omnibus test for autosomes and the X chromosome. The proposed multivariate trait association methods can accommodate continuous phenotypes or binary phenotypes and further can adjust for covariates. Simulation studies show that the performance of our methods is satisfactory with respect to the empirical type I error rates and power rates in comparison with the existing methods.At present, human health is threatened by many diseases, and lung cancer is one of the most dangerous tumors that threaten human life. In most developing countries, due to the large population and lack of medical resources, it is difficult for doctors to meet patients’ needs for medical treatment only by relying on the manual diagnosis. Based on massive medical information, the intelligent decision-making system has played a great role in assisting doctors in analyzing patients’ conditions, improving the accuracy of clinical diagnosis, and reducing the workload of medical staff. This article is based on the data of 8,920 nonsmall cell lung cancer patients collected by different medical systems in three hospitals in China. Based on the intelligent medical system, on the basis of the intelligent medical system, this paper constructs a nonsmall cell lung cancer staging auxiliary diagnosis model based on convolutional neural network (CNNSAD). CNNSAD converts patient medical records into word sequences, uses convolutional neural networks to extract semantic features from patient medical records, and combines dynamic sampling and transfer learning technology to construct a balanced data set. The experimental results show that the model is superior to other methods in terms of accuracy, recall, and precision. When the number of samples reaches 3000, the accuracy of the system will reach over 80%, which can effectively realize the auxiliary diagnosis of nonsmall cell lung cancer and combine dynamic sampling and migration learning techniques to train nonsmall cell lung cancer staging auxiliary diagnosis models, which can effectively achieve the auxiliary diagnosis of nonsmall cell lung cancer. The simulation results show that the model is better than the other methods in the experiment in terms of accuracy, recall, and precision.Xuefu Zhuyu Decoction (XFZY) is an ancient compound widely used in the treatment of coronary heart disease. However, its efficacy evaluation is not complete and its mechanism of action is not clear enough. In an attempt to address these problems, the efficacy was evaluated by meta-analysis and the mechanism was elucidated by the network pharmacology method. We systematically searched relevant studies in PubMed, Chinese National Knowledge Infrastructure Database (CNKI), Cochrane Library, Wanfang Data, and other databases from 2007 to 2019. The association between XFZY treatment and CHD was estimated by risk ratio (RR) and corresponding 95% confidence intervals (95% CIs). The compounds and the potential protein targets of XFZY were obtained from TCMSP, and active compounds were selected according to their oral bioavailability and drug similarity. The potential genes of coronary heart disease were obtained from TTD, OMIM, and GeneCards. The potential pathways related to genes were determined by GO and KEGG pathwthways.Metabolic syndrome (MetS) is a pathological state of metabolic disorders that primarily occur in human proteins, fats, and carbohydrates. It is a complex cluster of core metabolic disorder syndromes including obesity, hyperglycemia, dyslipidemia, and hypertension, and vascular endothelial injury, occurring over time. The currently available treatment options cannot effectively manage MetS. In our previous research, we revealed ChaiQi decoction (CQD) as an effective prescription for improving MetS; however, the specific mechanism remains unclear. Herein, we assessed the efficacy and mechanism of CQD in ApoE gene knockout (ApoE-) mice. Mice were administered with CQD daily for 12 weeks, and the measurement of their body weight was taken monthly. To evaluate the metabolic levels of mice, we determined the fasting blood glucose (FBG), fasting serum insulin (FINS), insulin resistance index (IRI), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein ch inflammatory response and thus may be utilized as a novel MetS therapy.Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients’ brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

Poststroke aphasia (PSA) is a disabling condition that decreases the quality of life, and the duration of the disease harms the quality of life of PSA patients. Acupuncture has been widely employed for PSA. There is some evidence for the immediate treatment efficacy of acupuncture for PSA; however, long-term results after acupuncture may be poorer.

This is a multicentre, randomized, blinded, nonacupoint (NA) acupuncture controlled, multimodal neuroimaging clinical trial. A total of 48 subjects with subacute PSA will be randomly assigned to an acupoint group or an NA control group. The acupoint group will receive acupuncture with normal needling at DU20, EX-HN1, HT5, GB39, EX-HN12, EX-HN13, and CV23. The NA control group will receive acupuncture in locations not corresponding to acupuncture points as sham acupoints. Both groups will receive identical speech and language therapy thrice a week for four weeks. The primary outcome will be the change in the aphasia quotient (AQ) score measured by the Western Aposis Scale score for ischaemic stroke, etc. Magnetic resonance imaging (MRI) and electroencephalogram (EEG) will also be performed at 4-time intervals as secondary outcomes. All scores and image evaluations will be taken at the same point as the linguistic evaluation. The multilevel evaluation technique will be used to assess the long-term efficacy of acupuncture therapy. MRI scans and EEG will be used to assess acupuncture-related neuroplasticity changes. Discussion. The results from our trial will help to supply evidence for the long-term acupuncture effects for PSA over a long follow-up period. It will provide valuable information for future studies in the field of PSA treatment. The trial was registered at the Chinese Clinical Trial Registry on 16 March 2020 (ChiCTR2000030879).

Currently, obesity and its comorbidities have become a serious threat to human health necessitating urgent development of safe and effective therapy for their management.

In this research, a novel polyherbal formulation (F2) was prepared by mixing specific proportions of royal jelly and lemon juice with ethanol extracts of

,

, and

. The antioxidant activity was assessed using DPPH and ABTS assay methods. The antiobesity potential of the F2 was assessed

using 3T3-L1 fibroblast and

using a high-fat diet (HFD) fed C57BL/6J mice model. F2 was administered in mice at the dose of 23 mg/kg and 46 mg/kg, twice daily by oral gavage. A well-accepted antiobesity agent,

(GC), at 200 mg/kg was used as a positive control.

F2 was observed to exhibit synergistic antiadipogenic activity in 3T3-L1 cells. This inhibition was reinforced by the downregulation of specific adipogenic transcription factors. Furthermore, F2 was also found to reduce mice body weight gain, food efficiency ratio, fasting blood glucose level, fat deposition into the liver, and mass of white adipose tissue. F2 also played a role in the excretion of fat consumed by the mice. For most of the assays performed, the F2 (46 mg/kg) was comparable to the positive control GC (200 mg/kg). In addition, potential and synergistic antioxidant activity was observed on F2.

The results revealed that the formulation F2 exhibited potential antiobesity activity through the inhibition of adipocyte differentiation, dietary fat absorption, and reduction of free fatty acids deposition in tissues.

The results revealed that the formulation F2 exhibited potential antiobesity activity through the inhibition of adipocyte differentiation, dietary fat absorption, and reduction of free fatty acids deposition in tissues.Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the action of this compound in the testicles make it difficult to assess its effects to define a safe dose. Thus, we systematically reviewed the preclinical evidence of the impact of isoflavone on testicular function. We also determined which form (aglycones or glycosylated) was the most used, which allowed us to understand the main biological processes involved in testicular function after isoflavone exposure. This systematic review was carried out according to the PRISMA guidelines using a structured search on the biomedical databases MEDLINE (PubMed), Scopus, and Web of Science, recovering and analyzing 22 original studies. The bias analysis and the quality of the studies were assessed by the criteria described in the risk of bias tool developed by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). The aglycones and glycosylated isoflavones proved to be harmful to the reproductive health, and the glycosylates at doses of 50, 100, 146, 200, 300, 500, and 600 mg/kg, in addition to 190 and 1000 mg/L, appear to be even more harmful. The main testicular pathologies resulting from the use of isoflavones are associated with Leydig cells resulting from changes in molecular functions and cellular components. The most used isoflavone to evaluate testicular changes was the genistein/daidzein conjugate. The consumption of high doses of isoflavones promotes changes in the functioning of Leydig cells, inducing testicular changes and leading to infertility in murine models.Cinobufotalin injection is a water-soluble preparation extracted from the skin secretion of Bufo bufo gargarizans Cantor or B. melanotictus Schneider, which has been widely used as an adjuvant treatment in lung cancer patients. This study aimed to evaluate the clinical efficacy and safety of cinobufotalin (PubChem CID 259776) injection as an adjunctive treatment for lung cancer. We designed a meta-analysis that performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We aim to include randomized controlled trials by systematically searching the PubMed, EMBASE, CNKI, Wanfang database, VIP, CBM, the Cochrane Central Register of Controlled Trials, and Chinese Clinical Trial Registry from inception to Mar 1, 2020, comparing the difference between the use of cinobufotalin injection as an adjunctive treatment and a control group without cinobufotalin injection. The objective response rate (ORR) and quality of life (QOL) will be defined as the primary outcomes, wever, multicenter, large-sample, high-quality clinical research results are still needed to reveal the therapeutic effect of cinobufotalin injection in small-cell lung cancer (PROSPERO registration number CRD42020170052).

To evaluate the therapeutic effect of epigallocatechin gallate (EGCG) on precancerous lesions of gastric carcinoma (PLGC) and to determine whether EGCG protects against PLGC by regulating PI3K/Akt/mTOR pathway.

Twenty-four male Wistar rats were randomly divided into 3 groups normal control group (NC), PLGC model group (MC), and group of PLGC rats treated with EGCG (MC + EGCG). 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) and sodium salicylate were combined and used to establish the PLGC rat animal model. The therapeutic effect of EGCG on PLGC was evaluated by body weight and pathological lesions of gastric mucosa in PLGC rats. Quantitative polymerase chain reaction (qPCR) was applied to measure the mRNA expressions of PI3K, Akt, and mTOR. The protein expressions of cleaved caspase-3, PTEN, PI3K, p-PI3K, Akt, p-Akt, p-mTOR, and mTOR were determined by automated western immunoblotting.

The body weight decreased in PLGC rats while EGCG significantly increased body weight. The gastric mucosa of PLGC rats exhibited the pathological lesions of atrophy, intestinal metaplasia, and atypical hyperplasia while EGCG could ameliorate the pathological lesions. EGCG could upregulate the expressions of cleaved caspase-3 and PTEN and reduce the expressions of PI3K, Akt, and mTOR.

EGCG ameliorated pathological lesions of PLGC and exerted the effect of apoptosis promotion in PLGC rats. The apoptotic pathway triggered by EGCG may be related to inhibition of PI3K/Akt/mTOR pathway. It provided a theoretical basis for the PLGC treatment and gastric cancer prevention.

EGCG ameliorated pathological lesions of PLGC and exerted the effect of apoptosis promotion in PLGC rats. The apoptotic pathway triggered by EGCG may be related to inhibition of PI3K/Akt/mTOR pathway. It provided a theoretical basis for the PLGC treatment and gastric cancer prevention.Intake of a high-fat diet (HFD) is closely related to disorders of the intestinal microbiota, which plays a key role in the pathogenesis of obesity. Duyun compound green tea, an ancient Chinese drink, is widely consumed to reduce weight, although the mechanism is not clear. In this study, 50 mice were randomly divided into 5 groups normal control group (CK), HFD model control group (NK), positive control group with medicine (YK), low-dose compound tea group (DL), and high-dose compound tea group (DH). After 4 weeks of intervention, the feces of mice were taken under sterile conditions and evaluated using Illumina high-throughput sequencing technology. The results showed that the diversity of intestinal microbiota was the highest in the CK group, the lowest in the NK group, and relatively increased in the compound tea treatment group. Second, there were differences in intestinal microbiota in each group, among which the beneficial bacteria in the intestinal tract of the CK group were higher than those in the other groups, while the beneficial bacteria in each compound tea treatment group were more abundant than those in the NK group, in which harmful bacteria in the intestinal tract were found to be the highest. These results suggest that compounds in tea may be able to attenuate imbalances of intestinal microbiota induced by poor diet, acting as a therapeutic agent in obesity or other diseases associated with gut dysbiosis.

Ethiopia has several medicinal plants that have been used for their antidiarrheal activity.

is the most commonly used medicinal plant for the management of diarrhea in Ethiopia. Thus, this study’s aim is to investigate the antidiarrheal effect of solvent fractions of

.

Antidiarrheal activity of extract fractions obtained from different solvents was evaluated by using small intestine transit, enteropooling, and castor oil-induced diarrhea animal models. In all animal models, the solvent fractions treated groups were treated with three different doses (100 mg/kg, 200 mg/kg, and 400 mg/kg) of the solvent fractions, while the negative control group was treated with a vehicle (distilled water), and positive control group was treated with loperamide.

The acute toxicity test revealed that the LD

of

is > 2000 mg/kg. In castor oil-induced, the solvent fractions of

(at 200 mg/kg and 400 mg/kg) significantly (

< 0.05-0.001) prolonged the stool frequency, reduced the weight of feces, and delayeeaves for the treatment of diarrhea.

Machine learning may be a useful tool for predicting metabolic syndrome (MetS), and previous studies also suggest that the risk of MetS differs according to Sasang constitution type. The present study investigated the development of MetS prediction models utilizing machine learning methods and whether the incorporation of Sasang constitution type could improve the performance of those prediction models.

Participants visiting a medical center for a health check-up were recruited in 2005 and 2006. Six kinds of machine learning were utilized (K-nearest neighbor, naive Bayes, random forest, decision tree, multilayer perceptron, and support vector machine), as was conventional logistic regression. Machine learning-derived MetS prediction models with and without the incorporation of Sasang constitution type were compared to investigate whether the former would predict MetS with higher sensitivity. Age, sex, education level, marital status, body mass index, stress, physical activity, alcohol consumption, and smoking were included as potentially predictive factors.

A total of 750/2,871 participants had MetS. Among the six types of machine learning methods investigated, multiplayer perceptron and support vector machine exhibited the same performance as the conventional regression method, based on the areas under the receiver operating characteristic curves. The naive-Bayes method exhibited the highest sensitivity (0.49), which was higher than that of the conventional regression method (0.39). The incorporation of Sasang constitution type improved the sensitivity of all of the machine learning methods investigated except for the K-nearest neighbor method.

Machine learning-derived models may be useful for MetS prediction, and the incorporation of Sasang constitution type may increase the sensitivity of such models.

Machine learning-derived models may be useful for MetS prediction, and the incorporation of Sasang constitution type may increase the sensitivity of such models.

To assess the preventive effects of acupuncture at back-shu and front-mu acupoints on rats with restraint water-immersion stress (RWIS)-induced gastric ulcer.

Thirty-six rats were randomly divided into four groups for 10 days of treatment as follows the normal group received no treatment; the model group received RWIS-induced gastric ulcer; the omeprazole group was administered omeprazole orally every 2 days; and the electroacupuncture group received electroacupuncture at the RN12 and BL21 acupoints every 2 days. After 10 days of treatment, except for the normal group, all rats were induced with gastric ulcer by RWIS for 3 h. The ulcer index (UI), ulcer inhibition rate, and histopathological score were calculated. We determined the levels of tumor necrosis factor (TNF)-

and interleukin (IL)-6 in serum, and the activities of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and glutathione peroxidase (GSH-Px) in serum and gastric tissues. Protein expression of Mpoints played a role in preventing gastric ulcer by inhibiting extracellular signals, stimulating kinases in serum and gastric tissues, and activating the inhibition of the TLR4 signaling pathway.