Modulation of Angiotensin II-Induced Cellular Hypertrophy by Cannflavin-C: Unveiling the Impact on Cytochrome P450 1B1 and Arachidonic Acid Metabolites.

This research aimed to clarify the impacts of cannflavin-C on angiotensin II (Ang II)-induced cardiac hypertrophy and their potential role in modulating cytochrome P450 1B1 (CYP1B1) and arachidonic acid (AA) metabolites. Currently there is no evidence to suggest that cannflavin-C; a prenylated flavonoid, has any significant effects on the heart or cardiac hypertrophy. The metabolism of arachidonic acid (AA) into midchain hydroxyeicosatetraenoic acids (HETEs), facilitated by CYP1B1 enzyme, plays a role in the development of cardiac hypertrophy which is marked by enlarged cardiac cells. Adult human ventricular cardiomyocytes cell line (AC16) were cultured and exposed to cannflavin-C in the presence and absence of Ang II. The assessment of mRNA expression pertaining to cardiac hypertrophic markers and CYPs was conducted via real-time polymerase chain reaction (PCR) while the quantification of CYPs protein levels was carried out through western blot analysis. Ang II induced hypertrophic markers myosin heavy chain (ß/α-MHC), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) and increased cell surface area, while cannflavin-C mitigated these effects. Gene and protein expression analysis revealed that cannflavin-C downregulated CYP1B1 gene expression, protein level as well as the enzyme activity assessed by 7-methoxyresorufin O-deethylase (MROD). Arachidonic acid metabolites analysis, using LC-MS/MS, demonstrated that Ang II increased midchain (R/S)-HETEs concentrations, which were attenuated by cannflavin-C. This study provides novel insights into the potential of cannflavin-C in modulating arachidonic acid metabolites and attenuating Ang II-induced cardiac hypertrophy, highlighting the importance of this compound as potential therapeutic agents for cardiac hypertrophy. Significance Statement This study demonstrates that cannflavin-C offers protection against cellular hypertrophy induced by Ang II. The significance of this research lies in its novel discovery, which elucidates a mechanistic pathway involving the inhibition of CYP 1B1 by cannflavin-C. This discovery opens up new avenues for leveraging this compound in the treatment of heart failure.

The utility of Hibiscus sabdariffa L. to prepare metal oxides NPs for clinical application on osteoporosis supported by theoretical study.

Green synthesis of metal oxides as a treatment for bone diseases is still exploring. Herein, MgO and Fe2O3 NPs were prepared from the extract of Hibiscus sabdariffa L. to study their effect on vit D3, Ca+2, and alkaline phosphatase enzyme ALP associated with osteoporosis. Computational chemistry was utilized to gain insight into the possible interactions. These oxides were characterized by X-ray diffraction, SEM, FTIR, and AFM. Results revealed that green synthesis of MgO and Fe2O3 NPs was successful with abundant. MgO NPs were in vitro applied on osteoporosis patients (n = 35) and showed a significant elevation of vit D3 and Ca+2 (0.0001 > p < 0.001) levels, compared to healthy volunteers (n = 25). Thus, Hibiscus sabdariffa L. is a good candidate to prepare MgO NPs, with a promising enhancing effect on vit D3 and Ca+2 in osteoporosis. In addition, interactions of Fe2O3 and MgO NPs with ALP were determined by molecular docking study.

Exploring the Mediating Role of Sleep Deficit-Related Functional Status in Subacute Stroke Survivors.

Background: Understanding post-stroke fatigue (PSF) and its associated factors is crucial for effective therapy and rehabilitation. This study aimed to assess the mediating role of the excessive daytime sleepiness-related functional status (SFS) on the relationship between sleep and the severity of fatigue in subacute stroke survivors. Methods: Subacute stroke survivors (n = 50; male = 38; female = 12), completed a cross-sectional study involving the Pittsburgh sleep quality index (PSQI), the Epworth sleepiness scale (ESS), the insomnia severity index (ISI), the functional outcome of the sleep questionnaire (FOSQ), and the fatigue severity scale (FSS). Results: The SFS mediated the association between the severity of fatigue and sleep problems. The PSQI and FOSQ (b = -0.37, p < 0.001), and the FOSQ and FSS were correlated (b = -0.18, p < 0.05), with a significant indirect effect of the PSQI on the FSS. The ISI correlated with the FOSQ (b = -0.20, p < 0.001), with significant direct (b = 0.15, p < 0.001), as well as indirect, effects of the ISI on the FSS. The ESS correlated with the FOSQ (b = -0.23, p < 0.001), with a significant indirect effect of the ESS on the FSS. Conclusions: In subacute stroke survivors, fatigue and sleep are linked. Increased understanding of sleep-PSF may help in exploring new targets for supplement therapy.

Utilization of Laparoscopic Choledochoscopy During Bile Duct Exploration and Evaluation of the Wiper Blade Maneuver for Transcystic Intrahepatic Access.

OBJECTIVE: This study aims to examine the indications, techniques, and outcomes of choledochoscopy during laparoscopic bile duct exploration and evaluate the results of the wiper blade maneuver (WBM) for transcystic intrahepatic choledochoscopy. SUMMARY OF BACKGROUND DATA: Choledochoscopy has traditionally been integral to bile duct explorations. However, laparoscopic era studies have reported wide variations in choledochoscopy availability and use, particularly with the increasing role of transcystic exploration. METHODS: The indications, techniques, and operative and postoperative data on choledochoscopy collected prospectively during transcystic and choledo- chotomy explorations were analyzed. The success rates of the WBM were evaluated for the 3 mm and 5 mm choledochoscopes. RESULTS: Of 935 choledochoscopies, 4 were performed during laparoscopic cholecystectomies and 931 during 1320 bile duct explorations (70.5%); 486 transcystic choledochoscopies (52%) and 445 through choledochotomies (48%). Transcystic choledochoscopy was utilized more often than blind exploration (55.7%% vs 44.3%) in patients with emergency admissions, jaundice, dilated bile ducts on preoperative imaging, wide cystic ducts, and large, numerous or impacted bile duct stones. Intrahepatic choledochoscopy was successful in 70% using the 3 mm scope and 81% with the 5 mm scope. Choledochoscopy was necessary in all 124 explorations for impacted stones. Twenty retained stones (2.1%) were encountered but no choledochoscopy related complications. CONCLUSIONS: Choledochoscopy should always be performed during a chol- edochotomy, particularly with multiple and intrahepatic stones, reducing the incidence of retained stones. Transcystic choledochoscopy was utilized in over 50% of explorations, increasing their rate of success. When attempted, the transcystic WBM achieves intrahepatic access in 70%-80%. It should be part of the training curriculum.

6-Formylindolo[3,2-b]carbazole Protects Against Angiotensin II-Induced Cellular Hypertrophy through the Induction of Cytochrome P450 1A1 and Its Associated 19(S)-HETE Metabolite In Vitro.

Aryl hydrocarbon receptor (AhR) is a multifunctional receptor that regulates cytochrome P450 1A1 (CYP1A1), an arachidonic acid (AA) metabolizing enzyme producing 19-hydroxyeicosatetraenoic acid (HETE). 6-formylindolo[3,2-b]carbazole (FICZ) demonstrates great affinity toward the AhR. Recently, we have shown that 19(S)-HETE is preferentially cardioprotective. This study investigates the role of FICZ on AhR and cytochrome P450 (CYP) 1A1-mediated AA metabolism and whether it attenuates angiotensin (Ang) II-induced cardiac hypertrophy. Adult human ventricular cardiomyocytes cell line treated with FICZ in the presence and absence of Ang II 10 µM. Protein levels of AhR and CYPs were determined by Western blot analysis and the mRNA expression of cardiac hypertrophic markers and CYPs were determined by real-time polymerase chain reaction. CYP1A1 enzyme activity and proteasomal degradation were determined by 7-ethoxyresorufin O-deethylase and proteasome 20S activity assays, respectively. Liquid chromatography tandem mass spectrometry was used to measure AA metabolites. Our results show that Ang II-induced cardiac hypertrophy modulates AA metabolites in an enantioselective manner, and that FICZ activates AhR in a time-dependent manner, inhibits AhR proteasomal degradation, induces CYP1A1, increases the concentration of 19(S)-HETE, and attenuates Ang II-induced cardiac hypertrophy by inhibiting the hypertrophic markers and decreasing cell surface area through midchain-HETE-dependent mechanism. In conclusion, the results demonstrate the ability of FICZ to protect against Ang II-induced cardiac hypertrophy by increasing the concentration of 19(S)-HETE through AhR regulated enzyme induction and inhibition of midchain-HETEs metabolites. SIGNIFICANCE STATEMENT: This study shows that 6-formylindolo[3,2-b]carbazole attenuate angiotensin II-induced cellular hypertrophy. The novel findings of our investigation are in characterizing the aryl hydrocarbon receptor involvement and the enantioselective differences in arachidonic acid metabolism in cardiac hypertrophy, which opens a new pathway to tackle and eventually treat heart failure.

17-(R/S)-hydroxyeicosatetraenoic acid (HETE) induces cardiac hypertrophy through the CYP1B1 in enantioselective manners.

Cardiac cellular hypertrophy is the increase in the size of individual cardiac cells. Cytochrome P450 1B1 (CYP1B1) is an extrahepatic inducible enzyme that is associated with toxicity, including cardiotoxicity. We previously reported that 19-hydroxyeicosatetraenoic acid (19-HETE) inhibited CYP1B1 and prevented cardiac hypertrophy in enantioselective manner. Therefore, our aim is to investigate the effect of 17-HETE enantiomers on cardiac hypertrophy and CYP1B1. Human adult cardiomyocyte (AC16) cells were treated with 17-HETE enantiomers (20 µM); cellular hypertrophy was evaluated by cell surface area and cardiac hypertrophy markers. In addition, CYP1B1 gene, protein and activity were assessed. Human recombinant CYP1B1 and heart microsomes of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats were incubated with 17-HETE enantiomers (10-80 nM). Our results demonstrated that 17-HETE induced cellular hypertrophy, which is manifested by increase in cell surface area and cardiac hypertrophy markers. 17-HETE enantiomers allosterically activated CYP1B1 and selectively upregulated CYP1B1 gene and protein expression in AC16 cells at uM range. In addition, CYP1B1 was allosterically activated by 17-HETE enantiomers at nM range in recombinant CYP1B1 and heart microsomes. In conclusion, 17-HETE acts as an autocrine mediator, leading to the cardiac hypertrophy through induction of CYP1B1 activity in the heart.

The enantioselective separation and quantitation of the hydroxy-metabolites of arachidonic acid by liquid chromatography - tandem mass spectrometry.

Arachidonic acid (AA) is a polyunsaturated fatty acid with a structure of 20:4(ω-6). Cytochrome P450s (CYPs) metabolize AA to several regioisomers and enantiomers of hydroxyeicosatetraenoic acids (HETEs). The hydroxy-metabolites (HETEs) exist as enantiomers in the biological system. The chiral assays developed for HETEs are so far limited to a few assays reported for midchain HETEs. The developed method is capable of quantitative analysis for midchain, subterminal HETE enantiomers, and terminal HETEs in microsomes. The peak area or height ratios were linear over concentrations ranging (0.01 -0.6 µg/ml) with r2 > 0.99. The intra-run percent error and coefficient of variation (CV) were ≤ ± 12 %. The inter-run percent error and coefficient of variation (CV)were ≤ ± 13 %, and ≤ 15 %, respectively. The matrix effect for the assay was also within the acceptable limit (≤ ± 15 %). The recovery of HETE metabolites ranged from 70 % to 115 %. The method showed a reliable and robust performance for chiral analysis of cytochrome P450-mediated HETE metabolites.

Predicting cholangiocarcinoma in primary sclerosing cholangitis: using artificial intelligence, clinical and laboratory data.

BACKGROUND: Primary sclerosing cholangitis (PSC) patients have a risk of developing cholangiocarcinoma (CCA). Establishing predictive models for CCA in PSC is important. METHODS: In a large cohort of 1,459 PSC patients seen at Mayo Clinic (1993-2020), we quantified the impact of clinical/laboratory variables on CCA development using univariate and multivariate Cox models and predicted CCA using statistical and artificial intelligence (AI) approaches. We explored plasma bile acid (BA) levels' predictive power of CCA (subset of 300 patients, BA cohort). RESULTS: Eight significant risk factors (false discovery rate: 20%) were identified with univariate analysis; prolonged inflammatory bowel disease (IBD) was the most important one. IBD duration, PSC duration, and total bilirubin remained significant (p < 0.05) with multivariate analysis. Clinical/laboratory variables predicted CCA with cross-validated C-indexes of 0.68-0.71 at different time points of disease, significantly better compared to commonly used PSC risk scores. Lower chenodeoxycholic acid, higher conjugated fraction of lithocholic acid and hyodeoxycholic acid, and higher ratio of cholic acid to chenodeoxycholic acid were predictive of CCA. BAs predicted CCA with a cross-validated C-index of 0.66 (std: 0.11, BA cohort), similar to clinical/laboratory variables (C-index = 0.64, std: 0.11, BA cohort). Combining BAs with clinical/laboratory variables leads to the best average C-index of 0.67 (std: 0.13, BA cohort). CONCLUSIONS: In a large PSC cohort, we identified clinical and laboratory risk factors for CCA development and demonstrated the first AI based predictive models that performed significantly better than commonly used PSC risk scores. More predictive data modalities are needed for clinical adoption of these models.

A proposed difficulty grading system for laparoscopic bile duct exploration: benefits to clinical practice, training and research.

BACKGROUND: A gap remains between the mounting evidence for single session management of bile duct stones and the adoption of this approach. Laparoscopic bile duct exploration (LBDE) is limited by the scarcity of training opportunities and adequate equipment and by the perception that the technique requires a high skill-set. The aim of this study was to create a new classification of difficulty based on operative characteristics and to stratify postoperative outcomes of easy vs. difficult LBDE irrespective of the surgeon's experience. METHODS: A cohort of 1335 LBDEs was classified according to the location, number and size of ductal stones, the retrieval technique, utilisation of choledochoscopy and specific biliary pathologies encountered. A combination of features indicated easy (Grades I and II A & B) or difficult (Grades III A and B, IV and V) transcystic or transcholedochal explorations. RESULTS: 78.3% of patients with acute cholecystitis or pancreatitis, 37% with jaundice and 46% with cholangitis had easy explorations. Difficult explorations were more likely to present as emergencies, with obstructive jaundice, previous sphincterotomy and dilated bile ducts on ultrasound scans. 77.7% of easy explorations were transcystic and 62.3% of difficult explorations transductal. Choledochoscopy was utilised in 23.4% of easy vs. 98% of difficult explorations. The use of biliary drains, open conversions, median operative time, biliary-related complications, hospital stay, readmissions, and retained stones increased with the difficulty grade. Grades I and II patients had 2 or more hospital episodes in 26.5% vs. 41.2% for grades III to V. There were 2 deaths in difficulty Grade V and one in Grade IIB. CONCLUSION: Difficulty grading of LBDE is useful in predicting outcomes and facilitating comparison between studies. It ensures fair structuring and assessment of training and progress of the learning curve. LBDEs were easy in 72% with 77% completed transcystically. This may encourage more units to adopt this approach.

Genome-Wide Association Mapping of Bacterial Leaf Streak Resistance in Two Elite Barley Breeding Panels.

Bacterial leaf streak (BLS), caused chiefly by the pathogen Xanthomonas translucens pv. translucens, is becoming an increasingly important foliar disease of barley in the Upper Midwest. The deployment of resistant cultivars is the most economical and practical method of control. To identify sources of BLS resistance, we evaluated two panels of breeding lines from the University of Minnesota (UMN) and Anheuser-Busch InBev (ABI) barley improvement programs for reaction to strain CIX95 in the field at St. Paul and Crookston, MN, in 2020 and 2021. The percentage of resistant lines in the UMN and ABI panels with mid-season maturity was 1.8% (6 of 333 lines) and 5.2% (13 of 251 lines), respectively. Both panels were genotyped with the barley 50K iSelect SNP array, and then a genome-wide association study was performed. A single, highly significant association was identified for BLS resistance on chromosome 6H in the UMN panel. This association was also identified in the ABI panel. Seven other significant associations were detected in the ABI panel: two each on chromosomes 1H, 2H, and 3H and one on chromosome 5H. Of the eight associations identified in the panels, five were novel. The discovery of resistance in elite breeding lines will hasten the time needed to develop and release a BLS-resistant cultivar.

Sex- and enantiospecific differences in the formation rate of hydroxyeicosatetraenoic acids in rat organs.

Hydroxyeicosatetraenoic acids (HETEs) are hydroxylated arachidonic acid (AA) metabolites that are classified into midchain, subterminal, and terminal HETEs. Hydroxylation results in the formation of R and S enantiomers for each HETE, except for 20-HETE. HETEs have multiple physiological and pathological effects. Several studies have demonstrated sex-specific differences in AA metabolism in different organs. In this study, microsomes from the heart, liver, kidney, lung, intestine, and brain of adult male and female Sprague-Dawley rats were isolated and incubated with AA. Thereafter, the enantiomers of all HETEs were analyzed by liquid chromatography-tandem mass spectrometry. We found significant sex- and enantiospecific differences in the formation levels of different HETEs in all organs. The majority of HETEs, especially midchain HETEs and 20-HETE, showed significantly higher formation rates in male organs. In the liver, the R enantiomer of several HETEs showed a higher formation rate than the corresponding S enantiomer (e.g., 8-, 9-, and 16-HETE). On the other hand, the brain and small intestine demonstrated a higher abundance of the S enantiomer. 19(S)-HETE was more abundant than 19(R)-HETE in all organs except the kidney. Elucidating sex-specific differences in HETE levels provides interesting insights into their physiological and pathophysiological roles and their possible implications for different diseases.

MicroRNAs as potential biopredictors for premenopausal osteoporosis: a biochemical and molecular study.

BACKGROUND: Circulating micro-RNAs have been proposed as a new type of biomarker in several diseases, particularly those related to bone health. They have shown great potential due to their feasibility and simplicity of measurement in all body fluids, especially urine, plasma, and serum. AIM: This study aimed to evaluate the expression of a set of mRNAs, namely miR-21, miR-24, mir-100, miR-24a, miR-103-3p, and miR-142-3p. Their proposed roles in the progression of osteoporosis were identified using a real-time polymerase chain reaction (RT-PCR) analysis in premenopausal women. In addition, their correlations with osteocalcin (OC), bone-specific alkaline phosphatase (BAP), and deoxypyridinoline (DPD) bone markers were explored. METHODS: A total of 85 healthy premenopausal women aged 25-50 years old were included in this study. Based on a DXA scan (Z-score) analysis and calcaneus broadband ultrasound attenuation scores (c-BUAs), measured via quantitative ultrasound (QUS), the subjects were classified into three groups: normal group (n = 25), osteopenia (n = 30), and osteoporosis (n = 30). Real-time-PCR and immunoassay analyses were performed to determine miRNA expression levels and serum OC, s-BAP, and DPD, respectively, as biomarkers of bone health. RESULTS: Among the identified miRNAs, only miR-21, miR-24, and mir-100 were significantly upregulated and increased in the serum of patients with osteopenia and osteoporosis, and miR-24a, miR-103-3p, and miR-142-3p were downregulated and significantly decreased in osteoporosis. Both upregulated and downregulated miRNAs were significantly correlated with BMD, c-BUA, OC, s-BAP, and DPD. CONCLUSION: A group of circulating miRNAs was shown to be closely correlated with the parameters BMD, c-BUA, OC, s-BAP, and DPD, which are traditionally used for bone-health measurements. They could be identified as non-invasive biomarkers in premenopausal patients with osteoporosis. More studies with large sample sizes are recommended to estimate the mechanistic role of miRNAs in osteoporosis pathogenesis and to provide evidence for the use of these miRNAs as a non-invasive method of diagnosing clinical osteoporosis, especially in premenopausal patients.

Laparoscopic bile duct exploration during pregnancy: a multi-center case series and literature review.

BACKGROUND: The physiological changes of pregnancy increase the risk of gallstone formation and choledocholithiasis. Traditionally, endoscopic retrograde cholangiopancreatography (ERCP) has been the main approach for managing choledocholithiasis during pregnancy, but recent progress in laparoscopic bile duct exploration (LBDE) has demonstrated this technique as a safe and effective alternative option. METHODS: A retrospective multicenter study of all patients who underwent LBDE during pregnancy from five centers with proven experience in LBDE between January 2010 and June 2020 was performed. The primary endpoint was to analyze the role of LBDE during pregnancy and to further characterize its position as a safe and effective alternative for the management of choledocholithiasis. A systematic review of the published literature relating to LBDE during pregnancy until February 2022 was also performed. RESULTS: Five institutions reported performing LBDE during pregnancy in 8 patients. Median surgical time was 75 min (range: 60-140 min). The bile duct was cleared successfully in all patients, and the median hospital stay was 2 days (range: 1-3 days). The literature review identified a total of 7 patients with a successful CBD clearance rate of 86%. There were no major maternal, fetal, or pregnancy-related complications in any of the total 15 patients included. The symptomatic common bile duct lithiasis with deranged liver function tests was the most frequent indication (n=7). CONCLUSION: LBDE during pregnancy appears to be safe and effective. More evidence reporting outcomes of LBDE during pregnancy is needed before any strong recommendations can be made.

Stigma Toward Mental Illness Among Saudi Medical Students: Pre and Post Psychiatry Course Comparison.

ABSTRACT: This cross-sectional study aims to compare pre- versus post-psychiatry course stigma levels toward mental illnesses among King Saud University medical students and identify which factors could affect stigma degree. The sample included 384 randomly chosen students. The overall scores of the used scale, the 15-item Opening Minds Scale for Healthcare Providers (OMS-HC-15), indicated no statistically significant difference between the before- and the after-psychiatry-course groups. The univariate analysis for differences in OMS-HC-15 score according to the sociodemographic characteristics of the pre psychiatry course group indicated that the factors associated with the total OMS-HC-15 score were sex ( p < 0.001), being diagnosed with mental illness ( p < 0.001), and having a relative diagnosed with mental illness ( p = 0.005). Among the post psychiatry course group, the univariate analysis indicated that the same factors, namely, sex ( p = 0.001), being diagnosed with mental illness ( p = 0.006), and having a relative diagnosed with mental illness ( p = 0.007), were associated with the total OMS-HC-15 score. Further studies at a larger scale to confirm generalizability of the results are warranted.

Hand grip strength, vitamin D status, and diets as predictors of bone health in 6-12 years old school children.

BACKGROUND: Vitamin D and calcium-rich foods, exposure to sunlight, and physical activities (PA) play a pivotal role in promoting the production of sufficient vitamin D and improving grip strength needed for better bone health among school children. PURPOSE: This study aimed to determine the effects of hand grip muscle strength (HGS), vitamin D in addition to diets, and PA on bone health status among 6-12 years old schoolchildren. METHODS: This study was based on a cross-sectional observational design, which was descriptive in nature. A diverse sample of 560 elementary school children aged 6-12 years old were invited to participate in this descriptive cross-sectional study. The Dual-Energy X-Ray Absorptiometry (DXA), QUS technique, and ACTi graph GT1M accelerometer were used respectively as a valid tools to identify BMD, BMC, and other parameters of bone health like c-BUA values and bone stiffness (SI), and physical activity (PA) of all individuals participated in this study. In addition, a hydraulic dynamometer was used to measure hand grip strength among the participants. Moreover, an immunoassay technique was used to measure the serum levels of vitamin 25(OH)D level, and bone metabolism markers; NTX, DPD, Ca, and sBAP in all participants. Bone loss (osteoporosis) was cross-sectionally predicted in 19.64% of the total population, most of whom were girls (14.3% vs. 5.4% for boys; P = 0.01). Compared to boys, the incidence of osteoporosis was higher and significantly correlated in girls with lower HGS, deficient vitamin D, inadequate vitamin D and Ca intake, greater adiposity, poor PA, and lower sun exposure. Also, in girls, lower vitamin 25(OH)D levels, and poor HGS were shown to be significantly associated with lower values of BMD, BMC, SI, and higher values of bone resorption markers; NTX, DPD, and sBAP and lower serum Ca than do in boys. The findings suggested that deficient vitamin D, lower HGS, adiposity, PA, and sun exposure as related risk factors to the pravelence of bone loss among school children, particularly in girls. In addition, these parameters might be considered diagnostic non-invasive predictors of bone health for clinical use in epidemiological contexts; however, more studies are required.

Effect of a Home-Based Mobile Health App Intervention on Physical Activity Levels in Patients With Heart Failure: A Randomized Controlled Trial.

BACKGROUND: The use of mobile health applications (apps) is an effective strategy in supporting patients' self-management of heart failure (HF) in home settings, but it remains unclear whether they can be used to reduce sedentary behaviors and increase overall physical activity levels. AIM: The aims of this study were to determine the effect of an 8-week home-based mobile health app intervention on physical activity levels and to assess its effects on symptom burden and health-related quality of life. METHOD: In this study, we collected repeated-measures data from 132 participants with HF (60.8 ± 10.47 years) randomized into a usual care group (n = 67) or an 8-week home-based mobile health app intervention group (n = 65). The intervention was tailored to decrease the time spent in sedentary behavior and to increase the time spent in physical activities performed at light or greater intensity levels. Physical activity levels were monitored for 2 weeks before the intervention and during the 8-week intervention using the Samsung mobile health app. Heart failure symptom burden and health-related quality of life were assessed at baseline, 2 weeks from baseline assessment, and immediately post intervention. RESULTS: At week 8, all participants in the intervention group demonstrated an increase in the average daily step counts above the preintervention counts (range of increase: 2351-7925 steps/d). Only 29 participants (45%) achieved an average daily step count of 10 000 or higher by week 6 and maintained their achievement to week 8 of the intervention. Repeated-measures analysis of variance showed a significant group-by-time interaction, indicating that the intervention group had a greater improvement in physical activity levels, symptom burden, and health-related quality of life than the usual care group. CONCLUSION: Home-based mobile health app-based interventions can increase physical activity levels and can play an important role in promoting better HF outcomes.

The Ameliorative Effect of Pioglitazone against Neuroinflammation Caused by Doxorubicin in Rats.

Doxorubicin (DOX) is a chemotherapeutic agent that is linked with complications such as cardiotoxicity and cognitive dysfunction, known as chemobrain. Chemobrain affects up to 75% of cancer survivors, and there are no known therapeutic options for its treatment. This study aimed to determine the protective effect of pioglitazone (PIO) against DOX-induced cognitive impairment. Forty Wistar female rats were equally divided into four groups: control, DOX-treated, PIO-treated, and DOX + PIO-treated. DOX was administered at a dose of 5 mg/kg, i.p., twice a week for two weeks (cumulative dose, 20 mg/kg). PIO was dissolved in drinking water at a concentration of 2 mg/kg in the PIO and DOX-PIO groups. The survival rates, change in body weight, and behavioral assessment were performed using Y-maze, novel object recognition (NOR), and elevated plus maze (EPM), followed by estimation of neuroinflammatory cytokines IL-6, IL-1ß, and TNF-α in brain homogenate and RT-PCR of a brain sample. Our results showed a survival rate of 40% and 65% in the DOX and DOX + PIO groups, respectively, compared with a 100% survival rate in the control and PIO treatment groups at the end of day 14. There was an insignificant increase in body weight in the PIO group and a significant reduction in the DOX and DOX + PIO groups as compared with the control groups. DOX-treated animals exhibited impairment of cognitive function, and the combination PIO showed reversal of DOX-induced cognitive impairment. This was evidenced by changes in IL-1ß, TNF-α, and IL-6 levels and also by mRNA expression of TNF- α, and IL-6. In conclusion, PIO treatment produced a reversal of DOX-induced memory impairment by alleviating neuronal inflammation by modulating the expression of inflammatory cytokines.

Cytotoxicity against A549 Human Lung Cancer Cell Line via the Mitochondrial Membrane Potential and Nuclear Condensation Effects of Nepeta paulsenii Briq., a Perennial Herb.

The genus Nepeta belongs to the largest Lamiaceae family, with 300 species, which are distributed throughout the various regions of Africa, Asia, India, and America. Along with other plant families distinguished by their medicinal and therapeutic values, the Nepeta genus of Lameaceae remains relatively valuable. Hence, the phytochemicals of N. paulsenii Briq. were extracted using different plant parts, i.e., leaves, stem, roots, flowers, and the whole plant by using various solvents (ethanol, water, and ethyl acetate), obtaining 15 fractions. Each extract of dried plant material was analyzed by FT-IR and GC-MS to identify the chemical constituents. The cytotoxicity of each fraction was analyzed by MTT assay and mitochondrial membrane potential and nuclear condensation assays against lung cancer cells. Among the ethyl acetate and ethanolic extracts, the flowers showed the best results, with IC50 values of 51.57 µg/mL and 50.58 µg/mL, respectively. In contrast, among the water extracts of the various plant segments, the stem showed the best results, with an IC50 value of 123.80 µg/mL. 5-flourouracil was used as the standard drug, providing an IC50 value of 83.62 µg/mL. The Hoechst 33342 stain results indicated apoptotic features, i.e., chromatin dissolution and broken down, fragmented, and crescent-shaped nuclei. The ethanolic extracts of the flowers showed more pronounced apoptotic effects on the cells. The mitochondrial membrane potential indicated that rhodamine 123 fluorescence signals suppressed mitochondrial potential due to the treatment with the extracts. Again, the apoptotic index of the ethanolic extract of the flowers remained the highest. Hence it can be concluded that the flower part of N. paulsenii Briq. was found to be the most active against the A459 human lung cancer cell line.

Nursing students perspectives of psychosocial care: cross-sectional study.

BACKGROUND: Psychosocial care is an integral component of holistic nursing practices. This study aimed to examine how fourth-year nursing students at Mutah University perceive various care characteristics, specifically psychosocial care. METHODS: A quantitative cross-sectional study was conducted using the Caring Dimension Inventory (CDI). Data were obtained from 105 nursing students before graduating from a Jordanian public educational institution. Data analyzed using the scoring of CDI and descriptive statistics. RESULTS: The mean scores in the professional and technical domain of care were statistically higher for fourth-year nursing students (4.69 ± 0.25). This exceeded their scores in the psychosocial domain of care (3.37 ± 1.20). This suggests that fourth-year nursing students prioritize professional and technical care over psychosocial care. CONCLUSIONS: Fourth-year nursing students tended to perceive the technical aspects of care as more significant than the psychosocial aspects. This highlights the need for nursing schools and healthcare providers to reconsider their focus and prioritize the importance of psychosocial care.

Influences of habitat and seasonal changes on gonadal maturation of Echinometra mathaei (Echinodermata: Echinoidea) and Tridacna squamosa (Mollusca: Bivalvia) in the Red Sea, Egypt.

The present work is aimed at investigating the effects of seasonal changes and habitat conditions on reproductive state and gonadal development of two macrobenthic fauna. Echinometra mathaei and Tridacna squamosa were collected seasonally (summer and winter) in July 2019 and January 2020 from three sites along the Red Sea coast, Egypt: Hamraween, Sedy Malek, and Porto Ghalb. Sexual differences and gonadal maturation in the two species were determined by performing biopsies of their gonads followed by morphologic analyses. Hematoxylin and eosin-stained gonadal sections were examined and analyzed. In E. mathaei, reproductive behavior was more active in the summer than in the winter; in T. squamosa, reproductive behavior was active almost all the year, especially during the winter. The reproductive activity and gonadal maturation of both species were affected by environmental factors. The results indicated that temperature is a vital factor affecting the reproductive activity of both species. This study concluded that temperature fluctuations may pose significant challenges to coastal marine ecosystems.