In-sample stability and postsampling analysis of 21 illicit drugs, their metabolites and cotinine in wastewater.

A thorough understanding of the degradation of chemical biomarkers in wastewater after the sampling is critical in the surveillance of illicit drug use based on the back-calculation technique. Herein, three temperatures, eight groups of matrices, and acidification were applied to simulate the preservation condition of 21 illicit drugs, their metabolites, and cotinine for a 240-day stability study. It was proved that the temperature, matrices, and acidification play vital roles in their stability in wastewater. Most of them demonstrated high stability (transformation rates < 20%) during room temperature for 45 days, and the transformation rates decreased while the storage temperature reduced. The stability of the target compounds such as cocaine (COC), 6-monoacetylmorphine (6-MAM), and amphetamine (AM) is influenced by matrices. Acidification prevented the majority of analytes from transforming, making it a feasible solution for preservation after sampling. A model that combined the effects of temperature and matrix was developed to back-calculate the concentration of target compounds during the postsampling process. The feasibility of this model was validated by correcting the loss of COC and 6-MAM from 24.2% and 16.2% to 2.98% and 2.77%. This study simulated a typical large-scale sampling and storage scenario. The effect of the temperature, pH, and matrix on in-sample stability and the postsampling analysis of selected target compounds was investigated for the first time in this study.

Assessing cognitive impairment in an ethnically diverse cohort of oldest-old: the life after 90 study.

BACKGROUND: Though dementia rates vary by racial or ethnic groups, it is unknown if these disparities remain among those aged 90 or older. AIMS: To test this hypothesis, we used baseline clinical evaluation of 541 ethnically and racially diverse individuals participating in the LifeAfter90 Study to assess how associations between core demographic characteristics and measures of physical and cognitive performance differ across the racial/ethnic groups. METHODS: Participants in this study were long-term non-demented members of Kaiser Permanente Northern California. They were clinically evaluated and diagnosed with normal or impaired cognition (mild cognitive impairment and dementia) through an in-person comprehensive clinical assessment consisting of a detailed medical history, physical and neurological examination, functional, and cognitive tests. RESULTS: The average age at enrollment was 93.0 ± 2.6 years, 62.4% female and 34.2% non-Hispanic White. At initial evaluation 301 participants had normal cognition and 165 had mild cognitive impairment (MCI) and despite screening, 69 participants were determined to have dementia. Age, education, 3MS, FAQ and CDR scores were significantly associated with cognitive impairment (normal versus MCI and dementia), but not gender. There was a significant univariate association between race/ethnicity and cognitive impairment (p < 0.02) being highest among Black (57.4%) and lowest among Asian (32.7%) individuals. After adjustment for age, gender, and education, however, prevalence of cognitive impairment was not influenced by race or ethnicity. CONCLUSION: Our results confirm the ability to reliably assess clinical diagnosis in a diverse sample of very old individuals.

Using Automatic Assessment of Speech Production to Predict Current and Future Cognitive Function in Older Adults.

Neurodegenerative conditions like Alzheimer disease affect millions and have no known cure, making early detection important. In addition to memory impairments, dementia causes substantial changes in speech production, particularly lexical-semantic characteristics. Existing clinical tools for detecting change often require considerable expertise or time, and efficient methods for identifying persons at risk are needed. This study examined whether early stages of cognitive decline can be identified using an automated calculation of lexical-semantic features of participants' spontaneous speech. Unimpaired or mildly impaired older adults (N = 39, mean 81 years old) produced several monologues (picture descriptions and expository descriptions) and completed a neuropsychological battery, including the Modified Mini-Mental State Exam. Most participants (N = 30) returned one year later for follow-up. Lexical-semantic features of participants' speech (particularly lexical frequency) were significantly correlated with cognitive status at the same visit and also with cognitive status one year in the future. Thus, automated analysis of speech production is closely associated with current and future cognitive test performance and could provide a novel, scalable method for longitudinal tracking of cognitive health.

Factor structure of the Modified Mini Mental State (3MS) exam among participants in inpatient neurorehabilitation.

OBJECTIVE: To evaluate the factor structure of the Modified Mini Mental State (3MS) Exam and its suitability as a cognitive screening tool among individuals admitted to an inpatient rehabilitation unit for new-onset neurological injury/illness. METHOD: A retrospective chart review was conducted. Of the 187 individuals meeting the inclusion criteria, 116 had a diffuse pattern of neurological injury/illness; 71 had a focal injury/illness. Confirmatory and exploratory factor analyses (CFA; EFA) were conducted for the whole sample and separately by group. RESULTS: The CFA suggested poor fit indices. The EFA of the total sample suggested a three-factor solution (Orientation/Awareness; Learning/Recall and Executive Functioning; Psychomotor Ability). The EFA of the diffuse subsample suggested a three-factor solution (Attention and Learning/Recall; Psychomotor Ability; Expressive Language). The Orientation/Awareness, Learning/Recall, Executive Functioning, Psychomotor Ability, and Expressive Language four-factor solution observed among the focal subsample was considered invalid. CONCLUSION: The 3MS provides information about the pattern of cognitive performance among individuals in neurorehabilitation; clinicians are advised to interpret total scores with caution. Among individuals with focal injuries/illnesses, clinicians might use the 3MS to compare the pattern of cognitive ability to expectations for performance and to support strengths-based approaches to participation in rehabilitation therapies.

Adaptation of the Modified Mini-Mental State Examination (3MS) and Determination of Its Normative Values in Turkey.

BACKGROUND/AIMS: This study aimed to adapt the Modified Mini-Mental State Examination (3MS) and determine its normative values in Turkey. METHODS: After translation and cultural adaptation processes, a population-based study was conducted between February and June 2016 in Ankara with individuals over the age of 55 years. Subjects with a previous diagnosis of dementia along with neuropsychiatric disorders that might affect cognition were excluded. Data analyses were performed to assess the association of sociodemographic variables with 3MS scores. RESULTS: Two versions of the Turkish 3MS (for educated and minimally educated individuals) were developed. A total of 2,235 participants were included in the field study. After exclusion, the data on the final sample of 1,909 individuals were analyzed, where age, gender, and education accounted for variance in 3MS scores. Younger age and higher educational attainment were associated with better 3MS performance. CONCLUSIONS: A widely applicable dementia screening test was adapted to Turkish and its normative values were determined. The test will make it possible to evaluate the cognitive performance of both educated and minimally educated elderly individuals based on their age, gender, and educational level.

Structure optimization of a new class of PPARγ antagonists.

Peroxisome proliferator-activated receptor gamma (PPARγ) modulators have found wide application for the treatment of cancers, metabolic disorders and inflammatory diseases. Contrary to PPARγ agonists, PPARγ antagonists have been much less studied and although they have shown immunomodulatory effects, there is still no therapeutically useful PPARγ antagonist on the market. In contrast to non-competitive, irreversible inhibition caused by 2-chloro-5-nitrobenzanilide (GW9662), the recently described (E)-2-(5-((4-methoxy-2-(trifluoromethyl)quinolin-6-yl)methoxy)-2-((4-(trifluoromethyl)benzyl)oxy)-benzylidene)-hexanoic acid (MTTB, T-10017) is a promising prototype for a new class of PPARγ antagonists. It exhibits competitive antagonism against rosiglitazone mediated activation of PPARγ ligand binding domain (PPARγLBD) in a transactivation assay in HEK293T cells with an IC50 of 4.3 µM against 1 µM rosiglitazone. The aim of this study was to investigate the structure-activity relationships (SAR) of the MTTB scaffold focusing on improving its physicochemical properties. Through this optimization, 34 new derivatives were prepared and characterized. Two new potent compounds (T-10075 and T-10106) with much improved drug-like properties and promising pharmacokinetic profile were identified.

A prospective evaluation of the depression-nutrient intake reverse causality hypothesis in a cohort of community-dwelling older Canadians.

Studies have investigated the potential protective effects that diet may have on late-life depression incidence. This disorder can, however, affect the person's food intake, widely known as the reverse causality hypothesis of depression. To test this hypothesis, we compared mean nutrient intakes from three 24-h recalls during the year depression was detected (Geriatric Depression Scale ≥11 or antidepressant medication) with intakes from 1 year earlier among community-dwelling older adults (67-83 years) followed up annually in the 4-year Québec Longitudinal Study on Nutrition and Aging, who were free of depression and cognitive impairment at baseline. Participants (n 158, 64·4 % female) who became depressed and had data available for all follow-up years were matched by age group and sex with non-depressed participants. General linear mixed models were adjusted for percentage changes in physical activity, functional autonomy and stressful life events reported at the time of positive screening. A significant group effect for the dietary intake of all three B-vitamins was observed, as depression cases had consistently lower dietary intakes than controls (P<0·01). Over time, intakes of dietary vitamin B12 declined within depressed participants in bivariate analysis, but there was no time×group effect for any nutrient tested in the multivariate analyses. Intakes of energy, protein, saturated fat and total dietary fibre did not change in cases v. CONTROLS: Among community-dwelling older adults, declines in dietary vitamins B6, B12 and folate may precede depression incidence. To help preventative efforts by programmes and practitioners, longitudinal cohorts of longer duration should investigate the extent of the decline in dietary intakes relative to the time of depression.

Cognitive Impairment and Progression of CKD.

BACKGROUND: Cognitive impairment is common among patients with chronic kidney disease (CKD); however, its prognostic significance is unclear. We assessed the independent association between cognitive impairment and CKD progression in adults with mild to moderate CKD. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: Adults with CKD participating in the CRIC (Chronic Renal Insufficiency Cohort) Study. Mean age of the sample was 57.7±11.0 years and mean estimated glomerular filtration rate (eGFR) was 45.0±16.9mL/min/1.73m(2). PREDICTOR: Cognitive function was assessed with the Modified Mini-Mental State Examination at study entry. A subset of participants 55 years and older underwent 5 additional cognitive tests assessing different domains. Cognitive impairment was defined as a score > 1 SD below the mean score on each test. Covariates included demographics, kidney function, comorbid conditions, and medications. OUTCOMES: Incident end-stage renal disease (ESRD) and incident ESRD or 50% decline in baseline eGFR. RESULTS: In 3,883 CRIC participants, 524 (13.5%) had cognitive impairment at baseline. During a median 6.1 years of follow-up, 813 developed ESRD and 1,062 developed ESRD or a ≥50% reduction in eGFR. There was no significant association between cognitive impairment and risk for ESRD (HR, 1.07; 95% CI, 0.87-1.30) or the composite of ESRD or 50% reduction in eGFR (HR, 1.06; 95% CI, 0.89-1.27). Similarly, there was no association between cognitive impairment and the joint outcome of death, ESRD, or 50% reduction in eGFR (HR, 1.06; 95% CI, 0.91-1.23). Among CRIC participants who underwent additional cognitive testing, we found no consistent association between impairment in specific cognitive domains and risk for CKD progression in adjusted analyses. LIMITATIONS: Unmeasured potential confounders, single measure of cognition for younger participants. CONCLUSIONS: Among adults with CKD, cognitive impairment is not associated with excess risk for CKD progression after accounting for traditional risk factors.

Quantitative determination of potential genotoxic impurities in metformin hydrochloride and empagliflozin tablets through ultra-performance liquid chromatographymass spectrometry.

An increasing number of drug research institutions consider genotoxic impurity research a core task in drug research and development. Peroxides in drugs may directly or indirectly attack and damage cell DNA, posing a potential carcinogenic risk to the human body. Currently, the literature only studies hydroperoxide impurities, and benzyl peroxide has not been studied yet. In this study, an effective method for ultra-performance liquid chromatographymass spectrometry (UPLCMS/MS) was established and verified to detect and quantify the potential genotoxic impurity (PGI), empagliflozin benzyl peroxide, in metformin-empagliflozin combination formulations, which has not been reported thus far. A Waters ACQUITY UPLC HSS T3 (3.0 ×100 mm, 1.8 µm) column was used to achieve chromatographic separation with gradient elution. The mass spectrometry conditions were optimized using electrospray ionization in the negative mode. Following the International Conference of Harmonization (ICH) guidelines, this methodology can quantify PGIs at 1.35 ng/mL (5.4 ppm) in samples. This validated method exhibited good linearity over a concentration range of 5.4 to 36 ppm, and the accuracy of this method was in the range of 83.2-95.0% for empagliflozin benzyl peroxide. This approach fills the gap in the detection method for benzyl peroxide impurities in metformin hydrochloride and empagliflozin tablets, providing technical support for the quality control of the drug.

The Drug Burden Index Is Associated With Measures of Cognitive Function Among Older Adults in the Health, Aging, and Body Composition Study.

BACKGROUND: Anticholinergic and sedative medications affect cognition among older adults. The Drug Burden Index (DBI) is a validated measure of exposure to these medications, with higher DBI scores indicating higher drug burden. This ancillary analysis investigated the association between DBI and cognition assessed by the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSST). METHODS: The Health, Aging, and Body Composition Study was a prospective study of community-dwelling adults aged 70-79 years at enrollment. Using data from years 1, 5, and 10, DBI was calculated using medication data per participant. Linear mixed modeling was used to assess cross-sectional and longitudinal effects of DBI on 3MS and DSST. Adjusted models included biological sex, race, education level, APOE status, and death. Sensitivity analyses included testing the strength of the associations for each year and testing attrition due to death as a possible confounding factor via Cox-Proportional Hazard models. RESULTS: After adjustment, DBI was inversely associated with 3MS and DSST scores. These associations became stronger in each subsequent year. Neither DBI at year 1 nor within-person change in DBI were predictive of longitudinal declines in either cognitive measure. Sensitivity analyses indicated that DBI, 3MS, and DSST were associated with a greater risk of attrition due to death. CONCLUSIONS: Results suggest that in years when older adults had a higher DBI scores, they had significantly lower global cognition and slower processing speed. These findings further substantiate the DBI as a useful pharmacological tool for assessing the effect of medication exposure.

Regulation of selective PPARγ modulators in the differentiation of osteoclasts.

Diabetes is the most common chronic disease in the world and causes complications with many diseases, such as heart disease and osteoporosis. Osteoporosis is a systemic bone disease characterized by imbalance in bone resorption and bone formation. Osteoclast is type of bone cell that functions in bone resorption and plays a critical role in bone remodeling. Rosiglitazone and pioglitazone, which belong to Thiazolidinediones(TZDs), are commonly used antidiabetic drugs. As PPARγ full agonists, they can activate PPARγ in a ligand-dependent way. Recent studies indicate that these PPARγ full agonists have some side effects, such as weight gain and bone loss, which may increase the risk of osteoporosis. In contrast, selective PPARγ Modulators (SPPARγMs) are novel PPARγ ligands that can activate PPARγ in different ways and lead to distinct downstream genes. Mice bone marrow cells were stimulated with recombinant mouse RANKL and M-CSF to generate osteoclasts. To determine the effect on osteoclasts formation, PPARγ ligands (Rosiglitazone, Fmoc-L-Leu, and Telmisartan) were added at the beginning of the culture. Rosiglitazone significantly increased the differentiation of multinucleated osteoclasts, while osteoclasts formation triggered by SPPARγMs was much less than that displayed by rosiglitazone. We found that the enhancement of PPARγ ligands may be associated with TRAF6 and downstream ERK signal pathway. We also demonstrated osteoclasts show characteristic M2 phenotype and can be further promoted by PPARγ ligands, especially rosiglitazone. In conclusion, reduced osteoclasts differentiation characteristic of SPPARγMs highlights SPPARγMs potential as therapeutic targets in diabetes, versus traditional antidiabetic drugs.

Is International HIV Dementia Scale good enough to diagnose HIV-associated neurocognitive disorders?

Introduction: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise impairment of multiple cognitive domains and cause significant morbidity. International HIV Dementia Scale (IHDS) is a quite sensitive and specific method for screening for HAND, and Modified Mini-Mental State Examination (3MS), though nonspecific, contains more parameters for screening for neurocognition. Hence, we compared 3MS and IHDS as screening tools for HAND with an aim to find out which was a better screening tool for HAND. Methods: Using 3MS and IHDS, we assessed the cognitive status of 200 HIV-positive patients (65% males) and 84 controls, presenting to the Department of Medicine, King George's Medical University, Lucknow, India from September 2015 to September 2019. Results: According to 3MS, 42 (21%) HIV-positive patients were neurocognitively impaired (mean 76.24 ± 1.51), and 158 (79%) patients were not (mean 87.02 ± 4.16). As per IHDS, 185 (92.5%) HIV patients were neurocognitively impaired (mean 8.45 ± 0.88), and 15 (7.5%) patients were not (mean 11.13 ± 0.35). The mean 3MS score of controls was 87.56 ± 4.26, and the IHDS score was 9.73 ± 1.00. According to Patient Health Questionnaire-9 (PHQ-9), moderate depression occurred in only 3.5% of the patients, and the rest had only minimal or mild depression. In IHDS, psychomotor speed was the most affected parameter, whereas in 3MS, similarities were the most affected. Conclusion: IHDS may be over diagnosing neurocognitive impairment in HIV patients due to difficulty in understanding the test, especially psychomotor speed testing. 3MS may be more accurate for detecting neurocognitive impairment in HIV patients, and scale combining both these methods may be a still better choice.

Plant leaf veins coupling feature representation and measurement method based on DeepLabV3.

The plant leaf veins coupling feature representation and measurement method based on DeepLabV3+ is proposed to solve problems of slow segmentation, partial occlusion of leaf veins, and low measurement accuracy of leaf veins parameters. Firstly, to solve the problem of slow segmentation, the lightweight MobileNetV2 is selected as the extraction network for DeepLabV3+. On this basis, the Convex Hull-Scan method is applied to repair leaf veins. Subsequently, a refinement algorithm, Floodfill MorphologyEx Medianblur Morphological Skeleton (F-3MS), is proposed, reducing the burr phenomenon of leaf veins' skeleton lines. Finally, leaf veins' related parameters are measured. In this study, mean intersection over union (MIoU) and mean pixel accuracy (mPA) reach 81.50% and 92.89%, respectively, and the average segmentation speed reaches 9.81 frames per second. Furthermore, the network model parameters are compressed by 89.375%, down to 5.813M. Meanwhile, leaf veins' length and width are measured, yielding an accuracy of 96.3642% and 96.1358%, respectively.

Revealing heterogeneity in correlation times of EGFP encapsulated in complex coacervate core micelles by analysis of fluorescence anisotropies.

Encapsulation of enhanced green fluorescent protein (EGFP) in complex coacervate core micelles (C3Ms) can be established by mixing EGFP with diblock polymers at equal charge ratio. It has previously been shown that this encapsulation system is highly dynamic, implying existence of different populations; GFP free in solution or complexed with polymers (small complexes) and EGFP encapsulated in C3Ms. We performed time resolved fluorescence anisotropy experiments to determine the relative populations of EGFP encapsulated in C3Ms using three different fluorescence anisotropy decay analysis methods. First, Maximum Entropy Method (MEM) data analysis was employed for five different EGFP concentrations in C3Ms that were mixed with dark fluorescent proteins (10, 20, 30, 40 and 50% EGFP, respectively). In all cases, correlation-time distributions between 0.1 and 100 ns (on a logarithmic timescale) are clearly visible showing bimodal distribution. The distribution between 0.1 and 2.0 ns is due to homo-FRET between EGFP molecules packed in micelles and the distribution between 8 and 30 ns coincides with the correlation-time distribution of free EGFP in solution. The fraction of homo-FRET distribution linearly increases with increase of relative micellar EGFP concentrations. These MEM results were corroborated by two different analysis methods: global population analysis of all five fluorescence anisotropy decays arising from EGFP in micelles together with the one of free EGFP (direct analysis of anisotropies) and global associative population analysis of anisotropies by fitting parallel and perpendicular fluorescence decay components. In contrast to global analyses approaches, the MEM method directly reveals distributions of correlation times without any prior information about the sample. However, global associative analysis of anisotropies by fitting parallel and perpendicular fluorescence decay components is the only method that allows to estimate accurately fractions of free fluorophores in solution and encapsulated fluorophores.

Electric cyclist injury of the collision between right turn of truck and electric bicycle.

In order to focus on the injury mechanism of electric cyclists in the collision accident between right turn of truck and electric bicycle, Pc-Crash is used to value the injury of the electric cyclist in this paper. Through repeated tests in Pc-Crash, it was found that two dynamic response process were existed. The electric bicycle and cyclist collided with truck, and the electric bicycle and cyclist were thrown to the ground due to the impact force. Finally, they were crushed under certain conditions. The multi-rigid-body truck model is built on the theories of multi-rigid-body modeling and multi-rigid-body collision to get the value of the crushed part which the single rigid model can't calculate. After that, we analyze HIC, continuous 3 ms resultant acceleration of chest, the shear force of femur and leg, based on the electric bicycle speed, the mass of electric bicycle and cyclist, the height of cyclist's seat. We found that when the electric cyclist is not crushed by the truck, the value of each damage index is below the threshold. But when the cyclist is crushed by the truck, the damage index of the part where the cyclist is crushed exceeds the threshold, and causes fatal injury to the cyclist. So, reducing the possibility of crushing can improve the safety level of electric cyclists.

Identification of S1PR3 gene signature involved in survival of sepsis patients.

BACKGROUND: Sepsis is a life-threatening complication of infection that rapidly triggers tissue damage in multiple organ systems and leads to multi-organ deterioration. Up to date, prognostic biomarkers still have limitations in predicting the survival of patients with sepsis. We need to discover more prognostic biomarkers to improve the sensitivity and specificity of the prognosis of sepsis patients. Sphingosine-1-phosphate (S1P) receptor 3 (S1PR3), as one of the S1P receptors, is a prospective prognostic biomarker regulating sepsis-relevant events, including compromised vascular integrity, antigen presentation, and cytokine secretion. Until now, no S1PR3-related prognostic gene signatures for sepsis patients have been found. METHODS: This study intends to obtain an S1PR3-associated gene signature from whole blood samples to be utilized as a probable prognostic tool for patients with sepsis. RESULTS: We obtained an 18-gene S1PR3-related molecular signature (S3MS) from the intersection of S1PR3-associated genes and survival-associated genes. Numerous important immunity pathways that regulate the progression of sepsis are enriched among our 18 genes. Significantly, S3MS functions greatly in both the discovery and validation cohort. Furthermore, we demonstrated that S3MS obtains significantly better classification performance than random 18-gene signatures. CONCLUSIONS: Our results confirm the key role of S1PR3-associated genes in the development of sepsis, which will be a potential prognostic biomarker for patients with sepsis. Our results also focus on the classification performance of our S3MS as biomarkers for sepsis, which could also provide an early warning system for patients with sepsis.

Lower Levels of Education Are Associated with Cognitive Impairment in the Old Order Amish.

BACKGROUND: Lower education has been reported to be associated with dementia. However, many studies have been done in settings where 12 years of formal education is the standard. Formal schooling in the Old Order Amish communities (OOA) ends at 8th grade which, along with their genetic homogeneity, makes it an interesting population to study the effect of education on cognitive impairment. OBJECTIVE: The objective of this study was to examine the association of education with cognitive function in individuals from the OOA. We hypothesized that small differences in educational attainment at lower levels of formal education were associated with risk for cognitive impairment. METHODS: Data of 2,426 individuals from the OOA aged 54-99 were analyzed. The Modified Mini-Mental State Examination (3MS-R) was used to classify participants as CI or normal. Individuals were classified into three education categories: <8, 8, and >8 years of education. To measure the association of education with cognitive status, a logistic regression model was performed adding age and sex as covariates. RESULTS: Our results showed that individuals who attained lowest levels of education (<8 and 8) had a higher probability of becoming cognitvely impaired compared with people attending >8 years (OR = 2.96 and 1.85). CONCLUSION: Even within a setting of low levels of formal education, small differences in educational attainment can still be associated with the risk of cognitive impairment. Given the homogeneity of the OOA, these results are less likely to be biased by differences in socioeconomic backgrounds.

Acidic Exopolysaccharide Produced from Marine Bacillus amyloliquefaciens 3MS 2017 for the Protection and Treatment of Breast Cancer.

PURPOSE: This study was planned to investigate the anti-breast-cancer property of acidic exopolysaccharide produced from marine Bacillus amyloliquefaciens 3MS 2017 (BAEPS) in an animal model, which previously showed in-vitro anti-breast-cancer activity, by studying its potential participation in various targeted mechanisms. METHODS: Mammary carcinoma in female Sprague-Dawley rats, both in prophylactic and in curative designs, was chemically induced using 7,12-dimethylebenz-(a)-anthracene (DMBA). B. amyloliquefaciens 3MS 2017 anti-breast-cancer property was evaluated by studying its effects on cancer-growth-rate-limiting enzymes (aromatase and Na+/K+ ATPase), sexual hormones (estrogen and progesterone), antioxidant and inflammatory biomarkers (cyclooxygenase-1; COX-1 and cyclooxygenase-2; COX-2). The incidence of breast cancer by DMBA was dependent on the level of carcinoembryonic antigen (CEA) and aromatase. RESULTS: 7,12-Dimethylebenz-(a)-anthracene female rats were characterized by a significant increase in cancer-related biomarkers with an increase of oxidative stress biomarkers, in comparison with the negative control. Potent BAEPS anticancer activity on DMBA rats was exhibited either as a prophylactic or as a curative agent, which appeared via restoring the aromatase and Na+/K+ ATPase subunits levels and CEA close to the normal level. Besides, BAEPS modulated a sexual hormone, in comparison with the cancer control group (P ⩽ .05). B. amyloliquefaciens 3MS 2017 selectively inhibited COX-2 in parallel with promising antioxidant properties. The curative characters of BAEPS were more promising than the prophylactic. CONCLUSION: The anti-breast-cancer characters accompanied with a good safety margin may be attributed to its inhibitory effect on cancer-growth-rate-limiting enzymes, estrogen production, COX-2 level and lipid peroxidation, concurrent with enhancing COX-1 level, progesterone production, and antioxidant status.

γ-Mangostin isolated from Garcinia mangostana L. suppresses inflammation and alleviates symptoms of osteoarthritis via modulating miR-124-3p/IL-6/NF-κB signaling.

Osteoarthritis (OA) a disease associated with joints and become severe with age, due to softening, inflammation and degradation of cartilage in joints. The agents that can target OA is needed, specifically without any side effects. Garcinia mangostana L. (Mangosteen) a tropical fruit used to treat many skin and stomach associated ailments. γ- Mangostin (γ-MS) a key bioactive substance present in mangosteen. Here, we aimed to explore γ-MS potential in targeting the pro-inflammatory cytokine, factors and miRs in OA progression. Significantly, γ-MS suppresses the inflammatory cytokines (IL-6, TNF-α, and INF- γ) and factors (NF-κB, STAT3, and COX-2) which regulates/participate in the catabolic process of cartilage destruction. Result of Hematoxylin-eosin (H&E) staining of tissue sections of OA joints of γ-MS treated and non-treated mice confirm γ-MS improves the signs of injuries, and maintains the structural integrity of the articular cartilage (epiphyseal disk joints and bone marrow) and reduces inflammation. Mechanistically, γ-MS targets miR-98-5p and miR-124-3p which are found to suppress the expression IL-6 and NF-κB, respectively. But in OA these miRs are inhibited, especially miR-124-3p which regulates not only NF-κB but also TNF-α, IL-6 and MMP7. With a further investigation underway, γ-MS represents an important source for treating and managing OA.

Normative performance of healthy older individuals on the Modified Mini-Mental State (3MS) examination according to ethno-racial group, gender, age, and education level.

OBJECTIVE: To present normative performance data on the Modified Mini-Mental State (3MS) examination for healthy community-dwelling older individuals according to gender, age, education level, and ethno-racial group. METHOD: More than 19,000 generally healthy older men and women without a diagnosis of dementia were recruited from the general population in Australia and the U.S. for the ASPirin in Reducing Events in the Elderly (ASPREE) study. The 3MS exam was administered as part of the baseline screening and individuals scoring above 77 were eligible to participate. RESULTS: The sample comprised 16,360 Australian whites, 1080 U.S. whites, 895 African-Americans and 316 Hispanic/Latinos. The median age of participants was 74 years (range 65-98), with an average of 12 years of education and 56% were female. Increasing age and fewer years of completed education were associated with lower scores on the 3MS. Women scored higher than men in most age and education categories. Differences across ethno-racial groups were found. With factor analysis, four factors were identified which accounted for 35% of the between-person variance in 3MS scores for white Australians. CONCLUSIONS: This large cohort of older individuals provides some of the most comprehensive 3MS normative data to be generated for whites (Australian and U.S.), Hispanic/Latinos and African-Americans, by age, gender, and educational attainment. These findings will serve as important reference standards for monitoring cognitive function in generally healthy older individuals, becoming increasingly important as this fraction of the population increases.