Search

Background: The prevalence of secondary causes of hypertension in young adults is unknown, and therefore, there is no consensus about the indication of screening of secondary hypertension (2HTN) in this population. The objective was to report the prevalence and the causes of 2HTN in young subjects., Methods: In this cross-sectional study, 2090 patients with confirmed hypertension aged 18 to 40 years with full workup for 2HTN screening were included. We assessed the prevalence of 2HTN and analyzed the factors associated., Results: Among 2090 patients, 619 (29.6%) had a 2HTN. The most frequent diagnoses of 2HTN in descending order were primary aldosteronism (n=339; 54.8%), renovascular hypertension (n=114; 18.4%), primary kidney disease (n=80; 12.9%), pheochromocytoma/functional paraganglioma (n=37; 5.9%), hypertension caused by drugs or substances (n=32; 6.0%), and other diagnoses (n=17; 2.7%). Patients with blood pressure <160/100 mm Hg did not have a lower prevalence of 2HTN regardless of the number of treatments. The prevalence of 2HTN was higher in the decade between 30 and 40 years of age than between 18 and 30 years of age ( P =0.024). Female sex, hypokalemia, treatment with at least 2 medications, no familial history of hypertension, body mass index <25 kg/m², and diabetes were associated with a higher prevalence of 2HTN., Conclusions: The prevalence of 2HTN is high among young patients with hypertension (29.6% in our cohort), regardless of age and blood pressure level. All patients with hypertension under 40 years of age should be screened for secondary causes., Competing Interests: None.

Among carotenoids, ꞵ-carotene has the highest biological activity and is found as an all-trans isomer in many biological systems. Blakeslea trispora is a microorganism that is of interest to industries for the commercial production of ꞵ-carotene. This study investigated the effect of different bacteria on carotenogenesis in B. trispora. The B. trispora bisexual mold was cultured in a production medium, and different bacterial cells were added to it after 24 h. Then, the culture conditions and the culture medium were optimized in the presence of the selected bacteria using the experimental design. The percentage of carotenoids obtained from the mixed culture was determined using high-performance liquid chromatography (HPLC). Results showed that Kocuria rhizophila had the greatest effect on increasing the production of carotenoids in B. trispora. The highest content of carotenoids obtained during optimization was 770 ± 7.5 mg/L, a 6.8-fold increase compared to the control. HPLC analysis of carotenoids indicated the presence of two main peaks, ꞵ-carotene and γ -carotene, in which the primary carotenoid was ꞵ-carotene followed by γ -carotene with a lower content. Therefore, due to the importance of ꞵ-carotene in industry, the use of biostimulants is one of the appropriate strategies to increase the production of this pigment in industry., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Background: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension., Methods: We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data., Results: Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P <0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P <0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P <0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P =0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication ( P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P =0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P =0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P =0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P =0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups ( P for interaction, 0.84). There was significant heterogeneity between trials., Conclusions: RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medication.

Introduction: Breast cancer (BC) is the most common type of cancer and the second cause of cancer-related death among women. Psychological treatments such as cognitive behavioral therapy (CBT) have been used as an effective method in the treatment of depression and anxiety in BC patients, and their effectiveness has been approved in various studies., Objective: The present study aimed to systematically investigate the effectiveness of CBT on depression and anxiety symptoms in BC patients and survivors., Methods: Electronic databases such as PubMed, Scopus, Web of Science [WOS], ScienceDirect, Cochrane Library, and Google Scholar were systematically searched from "October 2023" to "February 2024." The quality of the included studies was evaluated using the Critical Appraisal Skills Programme (CASP). In this study, the randomized controlled trials and quasi-experimental studies that assessed the effectiveness of CBT, cognitive behavioral group therapy (CBGT), and the combination of CBT with other psychological studies on depression and anxiety of BC patients and survivors were reviewed., Results: Out of the 16 included studies, six used CBT, and six used CBGT. In the other four studies, a combination of CBT with other psychological interventions was implemented as an interventional program. Among 16 included studies, 14 studies showed that CBT, CBGT, and a combination of CBT with other psychological interventions significantly decreased the anxiety and depression scores among BC patients and survivors (p < 0.05), and only in two studies, no significant effect was observed., Conclusion: As most included studies showed the effectiveness of CBT in decreasing the depression and anxiety scores among BC patients and survivors, this study strongly suggests CBT as an effective non-pharmacological method for the treatment of psychiatric disorders of BC patients during cancer treatments and also for BC survivors., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Several high-quality, randomized, sham-controlled trials have provided evidence supporting the efficacy and safety of radiofrequency, ultrasound and alcohol catheter-based renal denervation (RDN) for reducing blood pressure (BP). A French clinical consensus document has therefore been developed to propose guidance for the appropriate use of RDN in the management of hypertension along with a dedicated care pathway and management strategy. The French experts group concluded that RDN can serve as an adjunct therapy for patients with confirmed uncontrolled, resistant essential hypertension despite treatment with≥3 antihypertensive drugs, including a long-acting calcium channel blocker, a renin-angiotensin system blocker and a thiazide/thiazide-like diuretic at maximally tolerated doses. Patients should have (1) an estimated glomerular filtration rate of≥40mL/min/1.73m 2 ; (2) an eligible renal artery anatomy on pre-RDN scans and (3) exclusion of secondary forms of hypertension. Additional indications might be considered for patients with difficult-to-control hypertension. Any indication of RDN should be validated by multidisciplinary hypertension teams consisting of both hypertension specialists and endovascular interventionalists in European Society of Hypertension (ESH) Excellence Centres or ESH-BP clinics. Patients should be informed about the benefit/risk ratio of RDN. Expertise in renal artery interventions and training in RDN techniques are needed for endovascular interventionalists conducting RDN procedures while centres offering RDN should have the necessary resources to manage potential complications effectively. Lastly, all patients undergoing RDN should have their data collected in a nationwide French registry to facilitate monitoring and evaluation of RDN outcomes, contributing to ongoing research and quality improvement efforts., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Hypertension is a major public health issue due to its association with cardiovascular disease risk. Despite the availability of effective antihypertensive drugs, rates of blood pressure (BP) control remain suboptimal. Renal denervation (RDN) has emerged as an effective non-pharmacological, device-based treatment option for patients with hypertension. The multicenter, single-arm, observational Global Paradise™ System (GPS) registry has been designed to examine the long-term safety and effectiveness of ultrasound RDN (uRDN) with the Paradise System in a large population of patients with hypertension., Methods: The study aims to enroll up to 3000 patients undergoing uRDN in routine clinical practice. Patients will be recruited over a 4-year period and followed for 5 years (at 3, 6, and 12 months after the uRDN procedure and annually thereafter). Standardized home BP measurements will be taken every 3 months with automatic upload to the cloud. Office and ambulatory BP and adverse events will be collected as per routine clinical practice. Quality-of-Life questionnaires will be used to capture patient-reported outcomes., Conclusions: This observational registry will provide real-world information on the safety and effectiveness of uRDN in a large population of patients treated during routine clinical practice, and also allow for a better understanding of responses in prespecified subgroups. The focus on home BP in this registry is expected to improve completeness of long-term follow-up and provide unique insights into BP over time., (© 2023. The Author(s).)

Endovascular ultrasound renal denervation (uRDN) reduced blood pressure (BP) compared to sham at 2 months in patients with resistant hypertension in the multicenter, blinded, randomized, sham-controlled RADIANCE-HTN TRIO trial. This analysis evaluates longer-term outcomes of patients randomized to uRDN. Patients with resistant hypertension to a 3-drug combination pill were randomized to uRDN (n = 69) or sham (n = 67). From 2-5 months, patients followed a standardized anti-hypertensive medication (AHM) titration protocol. At 6 months, patients were unblinded and received AHM per standard of care. In the uRDN group, 71% (49/69) completed 36-month follow-up. Screening office BP was 159/103 on 3.9 AHM. Baseline office BP on the single-pill combination was 153/99 mmHg. At 36 months, office BP changed by -14.5 ± 26.1/-9.0 ± 14.8 mmHg from screening (p < 0.001 for both) and -8.0 ± 24.5/-5.0 ± 14.6 mmHg from baseline (p = 0.007; p = 0.022) on 3.7 AHM. The efficacy of uRDN was durable to 36 months in patients with resistant hypertension with no safety concerns., (© 2024. The Author(s).)

Background: The prognostic significance of immune checkpoint expression in the tumor microenvironment has been widely investigated in colorectal cancers. However, the results of these studies are inconsistent and limited to some immune checkpoints., Objective: The study aimed to investigate the correlation between different immune checkpoint expression and clinicopathological features and prognostic parameters., Methods: We conducted a systematic review and meta-analysis of the published literature in PubMed, Web of Science-Core Collection, Scopus, Embase, and Cochrane databases to summarize the association between various immune checkpoints expression on both tumor cells and immune cells with clinicopathological features and prognostic parameters in patients with colorectal cancer., Results: One hundred four studies incorporating 22,939 patients were included in our meta-analysis. Our results showed that among the B7 family, the high expression of B7H3, B7H4, PD-1, and PD-L1 on tumor cells and tumor tissue was significantly associated with higher T stage, advanced tumor, node, metastasis (TNM) stage, presence of vascular invasion, and lymphatic invasion. In addition, patients with high expression of B7H3, B7H4, PD-1, PD-L1, and PD-L2 were associated with shorter overall survival. High expression of PD-1 and PD-L1 in immune cells correlated with the absence of lymph node metastasis, lower TNM stage, early T stage, poor overall survival, and disease-free survival, respectively. Moreover, we found significant positive correlations between CD70 and Galectin-3 expression with advanced T stage. HLA-II overexpression was correlated with the absence of lymph node metastasis (odds ratio = 0.21, 95% CI = 0.11-0.38, P  < 0.001) and early TNM stage (odds ratio = 0.35, 95% CI = 0.26-0.47, P  < 0.001)., Conclusions: Overexpression of B7H3, B7H4, PD-1, PD-L1, PD-L2, CD70, and Galectin-3 on tumors is significantly associated with unfavorable clinicopathological characteristics and poor prognostic factors. Hence, these immune checkpoints can serve as predictive biomarkers for prognosis and the clinicopathological features of colorectal cancer because this is essential to identify patients suitable for anticancer therapy with immune checkpoint inhibitors., Competing Interests: The authors have no competing interests to declare., (© 2024 Published by Elsevier Inc.)

Objective: The purpose of this study was to investigate the effects of 8 weeks of high-intensity interval training (HIIT) and vitamin D3 supplementation on Chemokine (C-C motif) Ligand 5 (CCL-5) and C-C motif chemokine receptor 5 (CCR5) in the white adipose tissue (WAT) of male rats with type 2 diabetes (T2DM)., Materials and Methods: The experimental study involved 40 male Wistar rats divided into 5 groups (n=8). These groups were healthy control (HC), diabetic control (DC), diabetic+HIIT (DHIIT), diabetic+vitamin D3 (DD3), and diabetic+HIIT+vitamin D3 (DHIITD3). The rats completed 8 weeks of HIIT, consisting of 12 sessions lasting 1 minute each at an intensity of 90-95% of their maximum running speed. Additionally, the rats were administered a weekly dose of 10,000 IU/kg of vitamin D3 for 8 weeks., Results: The levels of CCL-5 (P<0.001) and CCR5 (P=0.003) were found to be higher in the DC group as compared to the HC group. However, when HIIT training and vitamin D3 were administered together, there was a decrease in CCL-5 (P=0.001) and CCR5 (P<0.001) in the DHIITD3 group (P=0.001). Similarly, vitamin D3 alone reduced CCR5 levels in the DD3 group (P< 0.001). Also, the decrease of CCR5 in the DD3 group was higher than in the DHIIT group (P=0.022), and the DHIITD3 group was higher than in the DHIIT group (P<0.001), but there was no difference between the DD3 and DHIITD3 groups (P≥0.05)., Conclusion: The results indicate that combining HIIT training with vitamin D3 has a greater effect on reducing the expression of CCL-5 and CCR5 in the white adipose tissue of rats with type 2 diabetes induced by streptozotocin (STZ) and a high-fat diet (HFD), compared to the effects of each one alone. It is recommended that the study be conducted by measuring the variables involved in the mechanisms and the changes in CCL-5 and CCR5.

Objective: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear., Methods: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality., Results: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P  = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P  = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P  = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries., Conclusions: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We aimed to determine the influence of coronavirus disease 2019 (COVID-19) pandemic on blood pressure (BP) control assessed by ambulatory blood pressure monitoring (ABPM)., Methods: Office BP and ABPM data from two visits conducted within a 9-15 months interval were collected from patients treated for hypertension. In the prepandemic group, both visits took place before, while in the pandemic group, Visit-1 was done before and Visit-2 during the pandemic period., Results: Of 1811 collected patients 191 were excluded because they did not meet the required ABPM time frames. Thus, the study comprised 704 patients from the pandemic and 916 from the prepandemic group. Groups did not differ in sex, age, duration of hypertension, frequency of first line antihypertensive drug use and mean 24 h BP on Visit-1. The prevalence of sustained uncontrolled hypertension was similar in both groups. On Visit-2 mean 24 h BP, daytime and nighttime systolic BP and diastolic BP were higher in the pandemic compared to the prepandemic group ( P  < 0.034). The prevalence of sustained uncontrolled hypertension on Visit-2 was higher in the pandemic than in the prepandemic group [0.29 (95% confidence interval (95% CI): 0.26-0.33) vs. 0.25 (95% CI: 0.22-0.28), P  < 0.037]. In multivariable adjusted analyses a significant difference in BP visit-to-visit change was observed, with a more profound decline in BP between visits in the prepandemic group., Conclusions: This study using ABPM indicates a negative impact of the COVID-19 pandemic on BP control. It emphasizes the need of developing strategies to maintain BP control during a pandemic such as the one induced by COVID-19., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

Objective: The safety of assisted reproductive technology can be assessed by examining birth weight as an outcome measure. The objective of this study was to evaluate the effect of endometrial thickness during embryo transfer on newborn birth weight and preterm labor., Methods: We conducted a retrospective cohort study at the infertility department of a teaching hospital affiliated with a university of medical sciences. Eligible women were ≥18 years old and conceived a singleton pregnancy with embryo transfer and an endometrial thickness of ≥7 mm. None of the patients had diabetes, blood hypertension, and polycystic ovarian syndrome. We assessed maternal and newborn characteristics and perinatal pregnancy outcomes., Results: In total, 100 eligible patients with a mean (SD) age of 32.8 (6.2) years were included. The mean endometrial thickness during embryo transfer was 9.1 (1.2) mm, and the mean birth weight was 3040.7 (565.3)g. There were no statistically significant associations between endometrial thickness and preterm labor (p=0.215) and between endometrial thickness and stillbirth or intra-uterine fetal death (p=0.880). However, after adjusting for confounding factors, the association of endometrial thickness with birth weight was statistically significant [b=124.6 (51.6), p=0.018]., Conclusions: Within the range of ≥7mm, endometrial thickness during embryo transfer is a predictor of newborn weight; however, it is not related to the risk of preterm labor, stillbirth, or intra-uterine fetal death.

In this study, rapid expansion of a supercritical solution into a Liquid Solvent (RESOLV) was used for the first time to produce pharmaceutical nanoparticles of Prazosin hydrochloride (PRH). The Taguchi method (robust design) was utilized to design the experiments and ensure obtaining the optimal process conditions. The pressure (15-25 MPa), temperature (308-328 K) and nozzle diameter (300-700 μm) effects on the morphology and size distribution of the resulting particles were also examined. The size of the particles decreased from about 40 μm to the range of (252-418 nm). FTIR, DLS, FESEM, XRD, DSC were used to characterize the primary and processed PRH particles. According to DSC investigations, RESOLV-produced PRH showed lower crystallinity than original PRH., (© 2024. The Author(s).)

Cancer stem cells (CSCs) are one of the cell types that account for cancer heterogeneity. The cancer cells arrest in G0 and generate non-CSC progeny through self-renewal and pluripotency, resulting in tumor recurrence, metastasis, and resistance to chemotherapy. They can stimulate tumor relapse and re-grow a metastatic tumor. So, CSCs is a promising target for eradicating tumors, and developing an anti-CSCs therapy has been considered. In recent years competing endogenous RNA (ceRNA) has emerged as a significant class of post-transcriptional regulators that affect gene expression via competition for microRNA (miRNA) binding. Furthermore, aberrant ceRNA expression is associated with tumor progression. Recent findings show that ceRNA network can cause tumor progression through the effect on CSCs. To overcome therapeutic resistance due to CSCs, we need to improve our current understanding of the mechanisms by which ceRNAs are implicated in CSC-related relapse. Thus, this review was designed to discuss the role of ceRNAs in CSCs' function. Targeting ceRNAs may open the path for new cancer therapeutic targets and can be used in clinical research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: During epidemics, the number of individuals whose mental health is affected is greater than those affected by the infection itself. This is because psychological factors have a direct relationship with the primary causes of the disease and mortality worldwide. Therefore, an increasing investment in research and strategic actions for mental health is essential globally, given the prevalence of infectious diseases. The aim of this study was to elucidate and describe the strategies for mental health preparedness and response during epidemics, with a focus on the COVID-19 pandemic in Iran., Methods: A qualitative study was conducted in Iran from 2022 to 2023. Purposeful Sampling was employed, continuing until data saturation was achieved. Data collection involved semi-structured interviews and observational notes with 20 managers and experts possessing expertise, experience, and knowledge in mental health. Ultimately, the participants' opinions, based on their experiences, were analyzed using the qualitative content analysis method with a conventional approach, resulting in the categorization of data into codes, subcategories, and categories., Results: The study revealed participants' opinions and experiences, categorized into two overarching categories: Preparedness, Policy-Making, and Planning Strategies (with four subcategories), and Response Strategies (comprising thirteen subcategories)., Conclusion: The opinions and experiences of managers and experts in this study revealed that an appropriate mental health response during pandemics requires preparedness before the occurrence of such crises and the implementation of suitable response strategies after the occurrence. Managers, policymakers, and decision-makers in this field should pay attention to the solutions derived from the experiences of such crises to respond more preparedly in the future., (© 2024. The Author(s).)

Fusobacterium nucleatum, (F. nucleatum) as a known factor in inducing oncogenic, invasive, and inflammatory responses, can lead to an increase in the incidence and progression of colorectal cancer (CRC). Cancer-associated fibroblasts (CAF) are also one of the key components of the tumor microenvironment (TME), which lead to resistance to treatment, metastasis, and disease recurrence with their markers, secretions, and functions. This study aimed to investigate the effect of F. nucleatum on the invasive phenotype and function of fibroblast cells isolated from normal and cancerous colorectal tissue. F. nucleatum bacteria were isolated from deep periodontal pockets and confirmed by various tests. CAF cells from tumor tissue and normal fibroblasts (NF) from a distance of 10 cm of tumor tissue were isolated from 5 patients by the explant method and were exposed to secretions and ghosts of F. nucleatum. The expression level of two markers, fibroblast activation protein (FAP), and α-smooth muscle actin (α-SMA), and the amount of production of two cytokines TGF-β and IL-6 from fibroblast cells were measured by flow cytometry and ELISA test, respectively before and after exposure to different bacterial components. The expression of the FAP marker was significantly higher in CAF cells compared to NF cells (P < 0.05). Also, the expression of IL-6 in CAF cells was higher than that of NF cells. In investigating the effect of bacterial components on the function of fibroblastic cells, after comparing the amount of IL-6 produced between the normal tissue of each patient and his tumoral tissue under 4 treated conditions, it was found that the amount of IL-6 production from the CAF cells of patients in the control group, treated with heat-killed ghosts and treated with paraformaldehyde-fixed ghosts had a significant increase compared to NF cells (P < 0.05). Due to the significant increase in FAP marker expression in fibroblast cells of tumor tissue compared to normal tissue, it seems that FAP can be used as a very good therapeutic marker, especially in patients with high levels of CAF cells. Various components of F. nucleatum could affect fibroblast cells differentially and at least part of the effect of this bacterium in the TME is mediated by CAF cells., (© 2024. The Author(s).)

Acetaminophen (paracetamol) is one of the most popular analgesics for the management of fever and pain but few reports have investigated its antidepressant-like effect. Moreover, the role of the opioidergic pathway has been indicated in depression pathophysiology. This study aimed to examine the involvement of the opioid receptors in the antidepressant-like effect of acetaminophen after acute and sub-chronic administration using mice forced swimming test (FST). Our finding showed that administration of acetaminophen (50 and 100 mg/kg, i.p.) 30 min before the FST produced an antidepressant effect which was reduced by naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). Moreover, we observed that acetaminophen in higher doses (200 and 400 mg/kg) was ineffective. Also, the response of the non-effective dose of acetaminophen (25 mg/kg) was potentiated by the non-effective dose of morphine (0.1 mg/kg) in the FST that was antagonized by naloxone. Also, in contrast to morphine (10 mg/kg), acetaminophen (100 mg/kg, i.p.) induced neither tolerance to the anti-immobility behavior nor withdrawal syndrome after repeated administration. In addition, RT-PCR showed that hippocampal mu- and kappa-opioid receptor mRNA expression increased in mice after repeated administration of acetaminophen; however, morphine therapy for 6 days did not affect kappa-opioid receptor expression. Our findings demonstrated that acetaminophen in lower doses but not high doses revealed an antidepressant-like activity without inducing tolerance and withdrawal syndromes. Moreover, the observed effect of acetaminophen may be via altering the opioid system, particularly hippocampal mu- and kappa-receptors., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90 mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system., Methods: Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP ('control' patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs)., Results: A mean reduction in office SBP of 8.5 mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463-£5739 [€6341-€6661]); modelling demonstrated > 99% probability that the ICER is below the £20,000-£30,000 (€23,214-€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks., Conclusions: Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication., (© 2024. The Author(s).)

The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10 mg/kg during the 1st week, followed by a weekly dose escalation of 1 mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6 weeks of moderate-intensity treadmill aerobic training, lasting 60 min per day, 5 days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25 g/kg daily for 6 weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1β), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1β, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1β, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes., Aim: To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension., Methods: We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data., Results: Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials., Conclusions: RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication., Clinical Perspective: What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.

In the present study, we present a pyranopyrazole-TiO 2 which is encapsulated with a niosome as nanocarrier for delivery of curcumin into breast cancer cells. Nanocarrier porous TiO 2 is biocompatible and with a high specific surface area and a large pore volume and was used to carry pyranopyrazole, which has been reported as an anti-cancer. Niosome in the outer layer, helpful for loading curcumin into the niosomal layer, demonstrates a pH-dependent release and can be effective for cancer treatment. Entrapment efficiency of curcumin was found at 81.02% in carriers. The results of MTT and flow cytometry revealed that apoptosis is notably enhanced by loading curcumin on pyranopyrazole-TiO 2 @niosome. Also, there was high biocompatibility with MCF-10A, while exhibiting significant anti-cancer and anti-metastatic effects on MCF-7, whose cell viability was 38.79% in the loaded curcumin on carrier and was more than other samples even, than free curcumin (42.82%). Furthermore, the regulation of gene expression in cancer cells decreased the regulation of MMP-2 and MMP-9 genes and increased the expression of caspase-3 and caspase-9 genes. Finally, fluorescence activity in MCF-7 significantly increased after treatment with samples., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Synovial sarcoma, a rare soft tissue malignancy typically arising from synovial tissue, primarily manifests in the extremities but it may uncommonly present in other locations such as kidneys. Primary renal synovial sarcoma is an uncommon sarcoma with high mortality and recurrence rates. Here, we present a teenage boy with primary renal synovial sarcoma who was referred to our institution., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Background: During the pandemic, patients with dementia were identified as a vulnerable population. X (formerly Twitter) became an important source of information for people seeking updates on COVID-19, and, therefore, identifying posts (formerly tweets) relevant to dementia can be an important support for patients with dementia and their caregivers. However, mining and coding relevant posts can be daunting due to the sheer volume and high percentage of irrelevant posts., Objective: The objective of this study was to automate the identification of posts relevant to dementia and COVID-19 using natural language processing and machine learning (ML) algorithms., Methods: We used a combination of natural language processing and ML algorithms with manually annotated posts to identify posts relevant to dementia and COVID-19. We used 3 data sets containing more than 100,000 posts and assessed the capability of various algorithms in correctly identifying relevant posts., Results: Our results showed that (pretrained) transfer learning algorithms outperformed traditional ML algorithms in identifying posts relevant to dementia and COVID-19. Among the algorithms tested, the transfer learning algorithm A Lite Bidirectional Encoder Representations from Transformers (ALBERT) achieved an accuracy of 82.92% and an area under the curve of 83.53%. ALBERT substantially outperformed the other algorithms tested, further emphasizing the superior performance of transfer learning algorithms in the classification of posts., Conclusions: Transfer learning algorithms such as ALBERT are highly effective in identifying topic-specific posts, even when trained with limited or adjacent data, highlighting their superiority over other ML algorithms and applicability to other studies involving analysis of social media posts. Such an automated approach reduces the workload of manual coding of posts and facilitates their analysis for researchers and policy makers to support patients with dementia and their caregivers and other vulnerable populations., (©Mehrnoosh Azizi, Ali Akbar Jamali, Raymond J Spiteri. Originally published in JMIR Formative Research (https://formative.jmir.org), 04.06.2024.)

Background: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment., Methods: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated., Results: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents ( P =0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P =0.022) and adrenalectomy (72% versus 54%; P =0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels., Conclusions: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220., Competing Interests: Disclosures None.

Antibiotic resistance is increasingly seen as a future concern, but antibiotics are still commonly used in animals, leading to their accumulation in humans through the food chain and posing health risks. The development of nanomaterials has opened up possibilities for creating new sensing strategies to detect antibiotic residues, resulting in the emergence of innovative nanobiosensors with different benefits like rapidity, simplicity, accuracy, sensitivity, specificity, and precision. Therefore, this comprehensive review provides pertinent and current insights into nanomaterials-based electrochemical/optical sensors for the detection of antibitic residues (ANBr) across milk and dairy products. Here, we first discuss the commonly used ANBs in real products, the significance of ANBr, and also their binding/biological properties. Then, we provide an overview of the role of using different nanomaterials on the development of advanced nanobiosensors like fluorescence-based, colorimetric, surface-enhanced Raman scattering, surface plasmon resonance, and several important electrochemical nanobiosensors relying on different kinds of electrodes. The enhancement of ANB electrochemical behavior for detection is also outlined, along with a concise overview of the utilization of (bio)recognition units. Ultimately, this paper offers a perspective on the future concepts of this research field and commercialized nanomaterial-based sensors to help upgrade the sensing techniques for ANBr in dairy products., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The MYC gene is a regulatory and proto-oncogenic gene that is overexpressed in the majority of prostate cancers (PCa). Numerous studies have indicated that aberrant expression of microRNAs is involved in the initiation and progression of prostate cancer. In this investigation, we assessed the impact of miR-377 on MYC through luciferase assay. Real-time PCR was employed to determine whether miR-377 could reduce the levels of MYC mRNA in transfected PCa cell lines (PC-3 and DU145) and change in the mRNA levels of BCL-2/Bax, PTEN, and CDK4 as a consequence of MYC downregulation. Moreover, we analyzed the effects of miR-377 on apoptosis, proliferation, cell cycle, and wound healing. Our findings demonstrate that miR-377 effectively targets MYC mRNA, as confirmed by luciferase assay and Real-time PCR. We observed a significant reduction in BCL-2 and CDK4 expression, along with an increase in Bax and PTEN, in prostate cancer cell lines upon MYC suppression. Additionally, elevated levels of miR-377 in PCa cell lines induced apoptosis, inhibited proliferation and migration, and arrested the cell cycle. Taken together, these results unveil the inhibitory role of miR-377 in MYC function within PCa, thereby suggesting its potential as a therapeutic target for the treatment of this malignancy., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.

Purpose: Abdominal aorta calcium (AAC) burden and dilatation are associated with an increased risk of mortality. The purpose of this study was to investigate determinants of AAC and abdominal aorta size in patients with essential hypertension., Materials and Methods: Patients with uncomplicated essential hypertension who had undergone non-enhanced abdominal CT to rule out secondary hypertension in addition to biological test were recruited between 2010 and 2018. A semi-automatic system was designed to estimate the aortic size (diameter, length, volume) and quantify the AAC from mesenteric artery to bifurcation using the Agatston score. Determinants of aortic size and those related to AAC were searched for using uni- and multivariables analyses., Results: Among 293 randomly selected patients with hypertension (age 52 ± 11 [SD] years) included, 23% had resistant hypertension. Mean abdominal aorta diameter was 20.1 ± 2.1 (SD) mm. Eight (3%) patients had abdominal aorta aneurysm ≥ 30 mm and 58 (20%) had dilated abdominal aorta ≥ 27 mm. Median AAC score was 38 and calcifications were detected in the infra- and supra-renal abdominal aortic portions in 59% and 26% of the patients, respectively. After adjustment for age, male sex and body surface area, abdominal aorta diameter was positively associated with diastolic blood pressure (P = 0.0019). Smoking was the single variable associated with calcified abdominal aorta (P < 0.001) after adjustment for cofactors. In patients with calcifications of abdominal aorta, the score increased with smoking history (P < 0.001), statins treatment (P < 0.01), greater number of anti-hypertensive drugs (P < 0.01), larger abdominal aorta (P < 0.05) and greater systolic blood pressure (P < 0.05). Patients with resistant hypertension had more AAC in the supra-renal abdominal aorta portion than those without resistant hypertension (P < 0.01)., Conclusion: In patients with essential hypertension, abdominal aorta dilation is related with diastolic blood pressure while AAC is associated with smoking history and resistant hypertension when located to the supra-renal abdominal aorta portion., Competing Interests: Declaration of Competing Interest The authors have no disclosures related to the content of this study., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: Tuberculosis (TB) continues to pose a threat to communities worldwide and remains a significant public health issue in several countries. We assessed the role of heteroresistance and efflux pumps in bedaquiline (BDQ)-resistant Mycobacterium tuberculosis isolates., Methods: Nineteen clinical isolates were included in the study, of which fifteen isolates were classified as MDR or XDR, while four isolates were fully susceptible. To evaluate BDQ heteroresistance, the Microplate Alamar Blue Assay (MABA) method was employed. For screening mixed infections, MIRU-VNTR was performed on clinical isolates. Mutations in the atpE and Rv0678 genes were determined based on next-generation sequencing data. Additionally, real-time PCR was applied to assess the expression of efflux pump genes in the absence and presence of verapamil (VP)., Results: All 15 drug-resistant isolates displayed resistance to BDQ. Among the 19 total isolates, 21.05% (4/19) exhibited a heteroresistance pattern to BDQ. None of the isolates carried a mutation of the atpE and Rv0678 genes associated with BDQ resistance. Regarding the MIRU-VNTR analysis, most isolates (94.73%) showed the Beijing genotype. Fifteen (78.9%) isolates showed a significant reduction in BDQ MIC after VP treatment. The efflux pump genes of Rv0676c, Rv1258c, Rv1410c, Rv1634, Rv1819, Rv2459, Rv2846, and Rv3065 were overexpressed in the presence of BDQ., Conclusions: Our results clearly demonstrated the crucial role of heteroresistance and efflux pumps in BDQ resistance. Additionally, we established a direct link between the Rv0676c gene and BDQ resistance. The inclusion of VP significantly reduced the MIC of BDQ in both drug-susceptible and drug-resistant clinical isolates., (© 2024. The Author(s).)

Background: Disasters have affected the physical and mental health of people around the world. Since nurses are frontlines in disasters, it seems necessary to prepare for this responsibility. This study investigates the effect of psychological first-aid virtual education on the communication skills of nurses in disasters such as COVID pandemic., Methods: In a randomized controlled trial, 55 nurses were selected by purposive sampling method from two hospitals in Isfahan and Tehran, Iran in December-November 2022 and randomly replaced in the intervention group who participated in psychological first aid virtual training and control group. The data were collected through the personal information form and Communication Skills -Test-Revised (CSTR)., Results: Two groups were homogeneous in terms of communication skills (p = 0.177), the total score of communication skills was significant between the two groups after the intervention (p < 0.0001). Regarding communication skills, in the pre-intervention phase, the subscale of "the ability to receive and send messages" and "insight into the communication process" the difference before the intervention was not significant between the two groups (p > 0.05). However, it was significant between the two groups after the intervention (p < 0.05), and regarding "emotional control", "listening skills", and "communication along with assertiveness" the difference before and after the intervention was not significant between the two groups (p > 0.05)., Conclusion: Pre-disaster training and virtual education can increase nurses' communication skills in their ability to handle a disaster such as COVID pandemic. Virtual education of post-disaster psychological interventions is suggested., Trial Registration: IRCT20220923056023N1; date: 2023-01-31., (© 2024. The Author(s).)

Background: Enterobacter cloacae ( E. cloacae ) is one of the most common Enterobacteriaceae causing nosocomial infections. Plasmid-mediated quinolone resistance (PMQR) determinants have been considered recently. This study evaluated the abundance of PMQR genes in strains of E. cloacae obtained from clinical samples in Kermanshah, Iran., Methods: In this descriptive cross-sectional study, after collecting 113 isolates of E. cloacae , their identity was confirmed using specific biochemical tests. After determining their drug resistance patterns using disc diffusion, the phenotypic frequency of extended-spectrum beta-lactamase (ESBL)-producing isolates was measured by the double-disk synergy test (DDST) method. The isolates were examined for the presence of qnrA , qnrB , qnrS , and aac(6')-Ib-cr genes by the polymerase chain reaction (PCR) assay., Results: The antibiotic resistance rate of E. cloacae isolates varied from 9.7% to 60.2%; among them, 78% were multidrug-resistant (MDR). The highest quinolone resistance was observed in ESBL-producing strains of E. cloacae . The frequency of positive isolates for PMQR and ESBL was 79.6% and 57.5%, respectively. The genes aac(6')-ib-cr (70.8%) and qnrB (38.1%) had the highest frequency among other genes. The number of isolates simultaneously carrying 2 and 3 genes was 64 and 5 isolates, respectively., Conclusion: The obtained results indicate a high degree of quinolone resistance among ESBL-producing E. cloacae strains. Nevertheless, there was a significant relationship between the PMQR gene and ESBL-positive isolates. Therefore, special attention should be paid to molecular epidemiological studies on antibiotic resistance to quinolones and beta-lactamases in these strains., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Mandana Afsharian et al.)

Background and Purpose: Cholestasis is caused by a malfunction of the biliary liver system. Oxidative stress plays an essential role in the progression of cholestasis. This study aimed to investigate the antioxidant and hepatoprotective effects of ethanolic extract of Juniperus excelsa M. Bieb (JE) fruits on hepatic impairment induced by bile duct ligation (BDL) in rats., Experimental Approach: Forty male Wistar rats were randomly divided into 4 groups; sham control + vehicle (SC), BDL + vehicle (BDL), BDL + JE extract (BDL + JE), and SC + extract (SC + JE). One day after surgery, the animals were treated with vehicle or ethanolic extract of JE (500 mg/kg/day) for 7 days. Finally, the blood was taken for biochemical and oxidative stress analysis. Furthermore, the liver tissue of rats was removed for histological examination., Findings/results: Treatment with the extract of JE decreased the ALP level, whereas it enhanced total protein content compared to the BDL group. Also, JE increased the activity of SOD and GPx, as well as FRAP content compared to the BDL group; while it did not significantly affect the levels of MDA and inflammation markers. However, JE could not improve BDL-induced histopathological alterations in hepatic tissue., Conclusion and Implication: This study demonstrated that JE may be useful as an adjuvant therapy by attenuating ALP activity, increasing serum total protein and FRAP content, as well as improving the antioxidant enzymes activity of SOD and GPx. However, further research is warranted to explore the other underlying mechanisms of action., Competing Interests: The authors declared no conflict of interest in this study., (Copyright: © 2024 Research in Pharmaceutical Sciences.)

The development of biodegradable active packaging films with hydrophobic characteristics is vital for extending the shelf life of food and reducing the reliance on petroleum-based plastics. In this study, novel hydrophobic cerium-based metal-organic framework (Ce-MOF) nanoparticles were successfully synthesized. The Ce-MOF nanoparticles were then incorporated into the cassava starch matrix at varying concentrations (0.5 %, 1.5 %, 3 %, and 4 % w/w of total solid) to fabricate cassava-based active packaging films via the solution casting technique. The influence of Ce-MOF on the morphology, thermal attributes, and physicochemical properties of the cassava film was subsequently determined through further analyses. Biomedical analysis including antioxidant activity and the cellular morphology evaluation in the presence of the films was also conducted. The results demonstrated that the consistent dispersion of Ce-MOF nanofillers within the cassava matrix led to a significant enhancement in the film's crystallinity, thermal stability, antioxidant activity, biocompatibility, and hydrophobicity. The introduction of Ce-MOF also contributed to the film's reduced water solubility. Considering these outcomes, the developed cassava/Ce-MOF films undoubtedly have significant potential for active food packaging applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Serratiopeptidase is a bacterial metalloprotease used in a variety of medical applications. The multidimensional properties of serratiopeptidase make it noticeable as a miraculous enzyme. Anti-coagulant, anti-inflammatory and anti-biofilm activity of serratiopeptidase making it useful in reducing pain and swelling associated with various conditions including arthritis, diabetes, cancer, swelling, pain and also thrombolytic disorders. It breaks down fibrin, thins the fluids formed during inflammation and due to its anti-biofilm activity, can be used in the combination of antibiotics to reduce development of antibiotic resistance. However, some drawbacks like sensitivity to environmental conditions and low penetration into cells due to its large size have limited its usage as a potent pharmaceutical agent. To overcome such limitations, improved versions of the enzyme were introduced using protein engineering in our previous studies. Novel functional serratiopeptidases with shorter length and higher stability have seemingly created a hope for using this enzyme as a more effective therapeutic enzyme. This review explains the structural properties and functional aspects of serratiopeptidase, its main characteristics and properties, pre-clinical and clinical applications of the enzyme, improved qualities of the modified forms, different formulations of the enzyme, and the potential future developments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Globally, breast cancer is the second most common cause of cancer-related deaths among women. In breast cancer, microRNAs (miRNAs) are essential for both the initiation and development of tumors. It has been suggested that the tumor suppressor microRNA-561-3p (miR-561-3p) is crucial in arresting the growth of cancer cells. Further research is necessary to fully understand the role and molecular mechanism of miR-561 in human BC. The aim of this study was to investigate the inhibitory effect of miR-561-3p on ZEB1, HIF1A, and MYC expression as oncogenes that have the most impact on PD-L1 overexpression and cellular processes such as proliferation, apoptosis, and cell cycle in breast cancer (BC) cell lines. The expression of ZEB1, HIF1A, and MYC genes and miR-561-3p were measured in BC clinical samples and cell lines via qRT-PCR. The luciferase assay, MTT, Annexin-PI staining, and cell cycle experiments were used to assess the effect of miR-561-3p on candidate gene expression, proliferation, apoptosis, and cell cycle progression. Flow cytometry was used to investigate the effects of miR-561 on PD-L1 suppression in the BC cell line. The luciferase assay showed that miRNA-561-3p targets the 3'-UTRs of ZEB1, HIF1A and MYC genes significantly. In BC tissues, the qRT-PCR results demonstrated that miR-561-3p expression was downregulated and the expression of ZEB1, HIF1A and MYC genes was up-regulated. It was shown that overexpression of miR-561-3p decreased PD-L1 expression and BC cell proliferation, and induced apoptosis and cell cycle arrest through downregulation of candidate oncogenes. Furthermore, inhibition of candidate genes by miR-561-3p reduced PD-L1 at both mRNA and protein levels. Our research investigated the impact of miR-561-3p on the expression of ZEB1, HIF1A and MYC in breast cancer cells for the first time. Our findings may help clarify the role of miR-561-3p in PD-L1 regulation and point to this miR as a potential biomarker and novel therapeutic target for cancer immunotherapy., (© 2024. The Author(s).)

Background: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials., Methods: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used., Results: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT ( P =0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients ( P =0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P =0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P <0.001) and -5.2 mm Hg (-7.1, -3.3; P <0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups., Conclusions: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260., Competing Interests: Disclosures Dr Azizi reports receiving grants from the European Horizon 2020 program; grants and nonfinancial support from Recor Medical, Idorsia, and Novartis; and personal fees from Alnylam Pharmaceuticals, Cincor, Medtronic, AstraZeneca, and Novartis. Dr Sharp has received personal fees from Recor Medical, Medtronic, Boston Scientific, Penumbra, and Philips. Dr Fisher has received grant support and personal fees from Recor Medical and personal fees from Medtronic. Dr Lobo has received personal fees from Recor Medical, Medtronic, Ablative Solutions, and Vascular Dynamics; and has received grants from Medtronic. Dr Daemen received institutional grant or research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Microport, Pie Medical, and Recor Medical, and consultancy or speaker fees from Abbott Vascular, Abiomed, ACIST Medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, Recor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care, and Medtronic. Dr Lurz has received institutional grant support from Recor Medical, Edwards Lifesciences, and Abbott. Dr Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, project ID 322900939), and Deutsche Herzstiftung; and has received scientific support from Ablative Solutions, Medtronic, and Recor Medical, and speaker honoraria or consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, Recor Medical, Servier, and Terumo. Dr Schmieder has received grant support and personal fees from Recor Medical, Medtronic, and Ablative Solutions. Dr Basile has received grant support from Recor Medical and Ablative Solutions. Dr Bloch has received personal fees from Recor Medical and Medtronic. Dr Weber has received personal fees from Recor Medical, Medtronic, and Ablative Solutions. Dr Saxena has received grant support from Recor Medical, Ablative Solutions, Applied Therapeutics, Vascular Dynamics, and MSD; and has received consulting fees from Recor Medical, Esperion Inc., Daiichi Sankyo Inc., Novartis, and Vifor Pharma. Dr Wang reports no relationships relevant to the contents of this article to disclose. Dr Sanghvi has received grant support and personal fees from Recor Medical and Medtronic and has received grant support from CSI. Dr Jenkins reports institutional funding to Ochsner Medical Center from Medtronic, Abbott, Abiomed, and Recor Medical; and in addition to research grants, he has received honoraria for speaking engagements or proctoring consulting from Abbott, Recor Medical, and Medtronic. Dr Devireddy has received personal fees from Recor Medical, Medtronic, Edwards Lifesciences, and Shockwave Medical. Dr Rader has received personal fees from Recor Medical, Medtronic, and Bristol Myers Squibb. Dr Gosse has received research grant support from Recor Medical. L. Claude and Dr Dimitri Augustin are employees of Recor Medical. Dr McClure is an employee of NAMSA, a contractor for Recor Medical. Dr Kirtane reports institutional funding to Columbia University or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and Recor Medical; in addition to research grants, institutional funding includes fees paid to Columbia University or Cardiovascular Research Foundation for speaking engagements or consulting; personal fees for consulting from Neurotronic; and travel expenses or meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, Recor Medical, Chiesi, OpSens, Zoll, and Regeneron.

Background: The interaction between commensal bacteria and the host is essential for health and the gut microbiota-brain axis plays a vital role in this regard. Obesity as a medical problem not only affect the health of the individuals, but also the economic and social aspects of communities. The presence of any dysbiosis in the composition of the gut microbiota disrupts in the gut microbiota-brain axis, which in turn leads to an increase in appetite and then obesity. Because common treatments for obesity have several drawbacks, the use of microbiota-based therapy in addition to treatment and prevention of obesity can have other numerous benefits for the individual. In this review, we intend to investigate the relationship between obesity and the gut microbiota-brain axis as well as novel treatment strategies based on this axis with an emphasis on gut microbiota., Competing Interests: This study does not include any conflict of interest for the authors., (© The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Background: Consecutive droughts and quantitative and qualitative reduction of surface and underground water resources have caused an increase in greenhouse and hydroponic cultivation for most garden crops, including strawberries, in Iran. On the other hand, most of the inputs of greenhouse crops in Iran are imported. To possibility of replacing vermicompost with peat moss under hydroponic cultivation, an experiment was done in a split plot based on randomized complete blocks design in three replications in Isfahan (Iran) Agricultural and Natural Resources Research Center in 2019. The main treatment was substrate at four levels included different levels of vermicompost (30 and 50%) and peat moss (30 and 50%) in combination with perlite and sub-treatment were Selva and Camarosa cultivars., Results: The results showed that Camarosa cultivar and Selva cultivar in (perlite/ peat moss 50:50) and Selva cultivar in (perlite / vermicompost 70:30) had maximum yield. Leaf number and chlorophyll index were maximum in Camarosa cultivar in peat moss substrates. Strawberry cultivars had the highest root fresh weight, the content of vitamin C and total soluble solids (TSS) in substrates containing vermicompost. Camarosa cultivar in (perlite / peat moss50:50) and Selva cultivar in (perlite /vermicompost 50:50) had maximum root dry weight. Also, the highest number of inflorescences was related to substrates containing peat moss and (perlite /vermicompost 70:30). Maximum amount of fresh and dry weight of shoots were observed in (perlite/ peat moss70:30). Selva cultivar had more inflorescences (16.5%) than Camarosa cultivar and Camarosa cultivar produced more fresh and dry weight of shoots (16.5%, 23.01%) than Selva cultivar., Conclusion: Expriment results highlighted the importance of considering both main and sub-treatments in agricultural research, as they interacted to influence various growth and yield parameters. 50% vermicompost treatment combined with perlite had a positive impact on plant growth and in quality index such as vitamin C content and TSS was highest. while the choice of cultivar affected different aspects of plant development. Selva cultivar was known to be more tolerant to salinity caused by vermicompost. Vermicompost is local and more economical, also salt resistant cultivars are recommended in a controlled (30%) amount of vermicompost., (© 2024. The Author(s).)

Background: The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic., Methods: A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes., Results: There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98-1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07-5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI, .09-.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI, .96-1.24)., Conclusions: In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes., Clinical Trials Registration: NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90)., Competing Interests: Potential conflicts of interests . T. B. reports grants or contracts from Novo Nordisk, Simonsen, Lundbeck, Kai, Erik and Susanna Olesen's Charitable Found, GSK, Pfizer, Boehringer Ingelheim, Gilead Sciences, MSD, Pentabase, Roche, Novartis, Kancera AB, Janssen, and Astra Zeneca; consulting fees from GSK and Pfizer; honoraria for lectures from GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, Abbvie, and Astra Zeneca; and donation of trial medication from Eli Lilly. P. E. K. reports participation on Data Safety Monitoring Board or Advisory Board on trials “Specific and non-specific effects of measles and BCG vaccines for mother and child (MATVAC)”, “Evaluating the effectiveness of different BCG strains in Guinea-Bissau: A randomized trial of the impact on neonatal hospital admissions”, and “BCG vaccine to reduce unplanned absenteeism due to COVID-19 illness of health care workers in Guinea-Bissau and Mozambique. A multi-center single-blinded randomized controlled trial (BCG-COVID-RCT)”, and “A randomized trial of providing BCG vaccination immediately to neonates admitted to the intensive care unit in Guinea-Bissau: Effect on mortality”. C. W. reports honoraria for a lecture from Novartis; and participation on the Advisory Board on COVID-19 Treatments, Danish government. I. S. J. reports honoraria from Pfizer for being chairman for the European Congress of Clinical Microbiology and Infectious Diseases 2023 COVID-19 symposium. M. G. N. reports to be scientific founder and have stock in TTxD and Lemba. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The emergence of carbapenem-resistant and extensively drug-resistant (XDR) Acinetobacter baumannii as well as inadequate effective antibiotics calls for an urgent effort to find new antibacterial agents. The therapeutic efficacy of two human scFvs, EB211 and EB279, showing growth inhibitory activity against A. baumannii in vitro, was investigated in immunocompromised mice with A. baumannii pneumonia., Results: The data revealed that infected mice treated with EB211, EB279, and a combination of the two scFvs showed better survival, reduced bacterial load in the lungs, and no marked pathological abnormalities in the kidneys, liver, and lungs when compared to the control groups receiving normal saline or an irrelevant scFv., Conclusions: The results from this study suggest that the scFvs with direct growth inhibitory activity could offer promising results in the treatment of pneumonia caused by XDR A. baumannii., (© 2024. The Author(s).)

Background and Objectives: During the rollout of coronavirus 2019 (COVID-19) vaccines, older adults in high-income countries were often prioritized for inoculation in efforts to reduce COVID-19-related mortality. However, this prioritization may have contributed to intergenerational tensions and ageism, particularly with the limited supply of COVID-19 vaccines. This study examines Twitter discourse to understand vaccine-related ageism during the COVID-19 pandemic to inform future vaccination policies and practices to reduce ageism., Research Design and Methods: We collected 1,369 relevant tweets on Twitter using the Twint application in Python from December 8, 2020, to December 31, 2021. Tweets were analyzed using thematic analysis, and steps were taken to ensure rigor., Results: Our research identified four main themes including (a) blame and hostility: "It's all their fault"; (b) incompetence and misinformation: "clueless boomer"; (c) ageist political slander; and (d) combatting ageism: advocacy and accessibility., Discussion and Implications: Our findings exposed issues of victim-blaming, hate speech, pejorative content, and ageist political slander that is deepening the divide of intergenerational conflict. Although a subset of tweets countered negative outcomes and demonstrated intergenerational solidarity, our findings suggest that ageism may have contributed to COVID-19 vaccine hesitancy among older adults. Consequently, urgent action is needed to counter vaccine misinformation, prohibit aggressive messaging, and promote intergenerational unity during the COVID-19 pandemic and beyond., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Unlike MCF-7 cells, MDA-MB-231 cells are unresponsive to hormone therapy and often show resistance to chemotherapy and radiotherapy. Here, the antiproliferative effect of biocompatible montmorillonite (Mt) nanosheets on MDA-MB-231 and MCF-7 human breast cancer cells was evaluated by MTT assay, flow cytometry, and qRT-PCR. The results showed that the Mt IC 50 for MDA-MB-231 and MCF-7 cells in a fetal bovine serum (FBS)-free medium was ~50 and ~200 µg/mL, and in 10% FBS medium ~400 and ~2000 µg/mL, respectively. Mt caused apoptosis in both cells by regulating related genes including Cas-3 , P53 , and P62 in MDA-MB-231 cells and Bcl-2 , Cas-8 , Cas-9 , P53 , and P62 in MCF-7 cells. Also, Mt arrested MCF-7 cells in the G0/G1 phase by altering Cyclin-D1 and P21 expression, and caused sub-G1 arrest and necrosis in both cells, possibly through damaging the mitochondria. However, fewer gene expression changes and more sub-G1 arrest and necrosis were observed in MDA-MB-231 cells, confirming the higher vulnerability of MDA-MB-231 cells to Mt. Furthermore, MDA-MB-231 cells appeared to be much more vulnerable to Mt compared to other cell types, including normal lung fibroblast (MRC-5), colon cancer (HT-29), and liver cancer (HepG2) cells. The higher vulnerability of MDA-MB-231 cells to Mt was inferred to be due to their higher proliferation rate. Notably, Mt cytotoxicity was highly dependent on both the Mt concentration and serum level, which favors Mt for the local treatment of MDA-MB-231 cells. Based on these results, Mt can be considered as an antiproliferative nanoagent against MDA-MB-231 cells and may be useful in the development of local nanoparticle-based therapies.

In recent years, the widespread use of the Internet has led to increasing concerns about problematic behaviors related to excessive Internet use and their potential consequences. This study aimed to investigate the relationship between Internet addiction (IA), body mass index (BMI), and emotion dysregulation (ED). Specifically, the study aimed to determine if IA significantly predicts obesity and if both Internet addiction and obesity can be significantly predicted by ED. 367 school-attending adolescents (M age  = 13.35; SD  = 0.82; 49% girls) in Tekab participated in the study. Participants completed the Difficulties in Emotion Regulation Scale (DERS) and the Internet Addiction Test (IAT), while BMI was calculated using self-reported data to assess their obesity levels. The results indicated that ED significantly predicted both IA and increased BMI levels ( p  < 0.001). Furthermore, IA also significantly predicted elevated BMI levels ( p  < 0.001). Our findings showed that ED significantly predicted both higher IA and BMI values, while IA also significantly predicted elevated BMI levels These results have important implications for treatment. To address excessive Internet use or overeating behavior in individuals with either condition, it may be necessary to target the underlying emotional dysregulation that contributes to the problem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Azizi, Abbasi and Aghaei.)

The aim of this study was to investigate the effect of whey coating containing dill ( Anethum graveolens L .) essential oil nanoliposome on the physicochemical, microbiological and sensory characteristics of rainbow trout ( Oncorhynchus mykiss ). Treatments comprise: sample without coating (control), coating containing whey, coating containing whey with essential oil (whey-EO) and coating containing whey with nano EO (whey-NEO). The particle size, zeta potential, polydispersity index and the encapsulation efficiency were ranged from 142 to 159 nm, -16.3 to -11.7 mV, 0.79 to 0.88 Mw/Mn and 45.85-70.01 %, respectively. Microbial analysis, after 21 days, the maximum and minimum of TVC (total viable counts), TPC (total psychrophilic counts) and LAB (lactic acid bacteria) counts were related to control (8.16 for TVC, 8.46 for TPC and 7.7 log CFU/g for LAB) and whey + NEO (7 for TVC, 7.3 for TPC and 6.16 log CFU/g for LAB), respectively. Also, results of pH, peroxide value (PV), thiobarbituric acid reactive substances (TBARS) and total volatile base-nitrogen (TVB-N) after 21 days were ranged from 6.3 (whey-NEO) to 7.5 (control), from 11.5(whey-NEO) to 20.9 mEq/Kg (control), from 5.23(whey-NEO) to 8.34 mg MDA/kg (control) and from 22.5 (whey-NEO) to 37 mg N/100 g (control), respectively. Finally, in all sensory evaluation items (texture, off-odor, discoloration and red color), the best result after 21 days was related to whey-NEO (score = 1). Consequently, the edible coating comprising whey and nanoliposome of EO could be effective to the maintenance of fish's microbiological, physicochemical, and sensory properties., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)