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Leishmaniasis is considered one of the most critical health concerns in the world. Unfortunately, no protective vaccines exist and conventional treatments are relatively ineffective. Therefore, new strategies are necessary against leishmaniasis. In recent years, exosomes have shown promising therapeutic outcomes in various diseases, including infectious diseases. In this regard, we aimed to explore the effect of the exosome, pyrimethamine and their combination on the anti-parasitic function of RAW264.7 cells against Leishmania major. Exosomes were isolated from the C57BL/6 peritoneal macrophages. L. major infected and non-infected RAW264.7 cells treated with exosomes, pyrimethamine (PM), and exosomes along with PM. The effect of the treatments was analysed on phagocytosis, efferocytosis, the intracellular parasite count, arginase activity, nitric oxide (NO) and reactive oxygen species (ROS) production. Exosomes could significantly elevate the phagocytosis, efferocytosis, NO and ROS in both infected and non-infected groups (Pv < 0.05). The exosomes reduced the arginase activity in both groups (Pv < 0.05). The intracellular parasite count was significantly lower after treatment with exosomes (Pv < 0.05). These results demonstrate that MQ-derived exosomes can enhance in vitro anti-parasitic responses against L. major. This provides a potential pathway for more effective treatments and underscores the importance of further research in this area., (© 2024 John Wiley & Sons Ltd.)

Purpose: Percutaneous nephrolithotomy (PCNL) has undergone extensive modification to reduce complications. One of the recent advances in minimally invasive procedures is the advent of ultra-mini PCNL (UM-PCNL), which provides miniaturized access to the kidney. However, the specific instruments applied in UM-PCNL may not be found in centers with limited resources. This study evaluated the safety, feasibility, results, and short-term complication rates of performing UM-PCNL using a semi-rigid ureteroscope in preschool children., Materials and Methods: Between September 2013 and September 2021, a total of 68 patients, including 42 boys and 26 girls with a mean age of 3.2 ± 2.4 years, underwent UM-PCNL with a 4.5French tip ureteroscope instead of an ultra-mini nephroscope in children aged less than 7 years old. The procedure was done under general anesthesia in the prone position. The nephrostomy tract was dilated to 12F. Stones were fragmented using a pneumatic lithotripter. Irrigation was done with normal saline., Results: The early stone-free rate (SFR) was 91%, and the short-term total SFR was 97%. No statistically significant difference was found in pre-operative and post-operative Hb, BUN, Cr, Na+, and K+. Fever (11 patients) and ileus (5 patients) constituted the majority of complications, and only one patient required a blood transfusion. None of the cases undergoing UM-PCNL with this method required a re-do PCNL., Conclusion: Our experience shows that with sufficient experience in handling semi-rigid ureteroscopes, urologists practicing in centers with limited resources could perform UM-PCNL with relatively favorable outcomes.

Background: The biomechanical analysis of spine and postural misalignments is important for surgical and non-surgical treatment of spinal pain. We investigated the examiner reliability of sagittal cervical alignment variables compared to the reliability and concurrent validity of computer vision algorithms used in the PostureRay ® software 2024. Methods: A retrospective database of 254 lateral cervical radiographs of patients between the ages of 11 and 86 is studied. The radiographs include clearly visualized C1-C7 vertebrae that were evaluated by a human using the software. To evaluate examiner reliability and the concurrent validity of the trained CNN performance, two blinded trials of radiographic digitization were performed by an extensively trained expert user (US) clinician with a two-week interval between trials. Then, the same clinician used the trained CNN twice to reproduce the same measures within a 2-week interval on the same 254 radiographs. Measured variables included segmental angles as relative rotation angles (RRA) C1-C7, Cobb angles C2-C7, relative segmental translations (RT) C1-C7, anterior translation C2-C7, and absolute rotation angle (ARA) C2-C7. Data were remotely extracted from the examiner's PostureRay ® system for data collection and sorted based on gender and stratification of degenerative changes. Reliability was assessed via intra-class correlations (ICC), root mean squared error (RMSE), and R 2 values. Results: In comparing repeated measures of the CNN network to itself, perfect reliability was found for the ICC (1.0), RMSE (0), and R 2 (1). The reliability of the trained expert US was in the excellent range for all variables, where 12/18 variables had ICCs ≥ 0.9 and 6/18 variables were 0.84 ≤ ICCs ≤ 0.89. Similarly, for the expert US, all R 2 values were in the excellent range (R 2 ≥ 0.7), and all RMSEs were small, being 0.42 ≤ RMSEs ≤ 3.27. Construct validity between the expert US and the CNN network was found to be in the excellent range with 18/18 ICCs in the excellent range (ICCs ≥ 0.8), 16/18 R 2 values in the strong to excellent range (R 2 ≥ 0.7), and 2/18 in the good to moderate range (R 2 RT C6/C7 = 0.57 and R 2 Cobb C6/C7 = 0.64. The RMSEs for expert US vs. the CNN network were small, being 0.37 ≤ RMSEs ≤ 2.89. Conclusions: A comparison of repeated measures within the computer vision CNN network and expert human found exceptional reliability and excellent construct validity when comparing the computer vision to the human observer.

Aging is a significant risk factor for Alzheimer's disease (AD), although the precise mechanism and molecular basis of AD are not yet fully understood. Epigenetic mechanisms, such as DNA methylation and hydroxymethylation, mitochondrial DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), play a role in regulating gene expression related to neuron plasticity and integrity, which are closely associated with learning and memory development. This review describes the impact of dynamic and reversible epigenetic modifications and factors on memory and plasticity throughout life, emphasizing their potential as target for therapeutic intervention in AD. Additionally, we present insight from postmortem and animal studies on abnormal epigenetics regulation in AD, as well as current strategies aiming at targeting these factors in the context of AD therapy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: 10%-15% of the world's population suffers from kidney stones. Nearly 50% increase was observed in diagnosing and treating nephrolithiasis in the last decades. Effective medical treatment for the disease is not yet well established. Moreover, there is an increasing global demand to manage diseases using complementary and alternative medicine. This study aimed to formulate and assess the safety and efficacy of a multi-ingredient formulation from traditional Persian medicine (TPM) known as Mofatet powder in patients suffering from calcium kidney stones., Materials and Methods: The aqueous extract of Mofatet powder was prepared, freeze-dried, and formulated as capsules. 26 patients in the drug group and 25 patients in the placebo group used 500 mg capsules of the drug/placebo twice daily for 5 weeks. Ultrasonography/kidney, ureter and bladder imaging, urine analysis, and biochemical parameters were evaluated before and after the intervention., Results: The imaging results showed a 60.73% decrease ( P < 0.001) in stone size in the drug group. Moreover, the urinary calcium decreased ( P = 0.02) and the urinary magnesium increased ( P < 0.001) in the drug group. No remarkable changes were observed in the placebo group in these parameters. No significant effect was observed in aspartate transaminase, alanine transaminase, serum creatinine, and blood urea nitrogen levels in none of the groups., Conclusion: This study suggests that Mofatet powder was effective in reducing calcium kidney stones size with no potential nephro/hepatotoxicity. After confirming these results in larger clinical trials with longer duration, this formulation can be considered a treatment for nephrolithiasis., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Research in Medical Sciences.)

Background and Aim: Metabolic syndrome (MetS) increases the risk of atherosclerosis and diabetes, but there are no approved predictive markers. This study assessed the role of specific genetic variations in MetS susceptibility and their impact on clinical manifestations., Method: In this study, a genotype-phenotype assessment was performed for IKZF3 (rs907091), microRNA-let-7a-2 (rs1143770), and lncRNA-CDKN2B-AS1 (rs1333045)., Results: Analyses indicate that while rs907091 and rs1143770 may have potential associations with MetS susceptibility and an increased risk of atherosclerosis and diabetes, there is an observed trend suggesting that the rs1333045 CC genotype may be associated with a decreased risk of MetS. The genotypes and allele frequencies of rs1333045 were significantly different between studied groups (OR = 0.56, 95% CI 0.38-0.81, p = 0.002, and OR = 0.71, 95% CI 0.55-0.92, p = 0.008), with the CC genotype displaying increased levels of HDL. Furthermore, the rs907091 TT genotype was associated with increased triglyceride, cholesterol, and HOMA index in MetS patients. Subjects with the CC genotype for rs1143770 had higher HbA1c and BMI. In silico analyses illustrated that rs907091 C remarkably influences the secondary structure and the target site of a broad spectrum of microRNAs, especially hsa-miR-4497. Moreover, rs1333045 creates a binding site for seven different microRNAs., Conclusion: Further studies on other populations may help confirm these SNPs as useful predictive markers in assessing the MetS risk., (© 2024 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Transition to novel environments, such as groundwater colonization by surface organisms, provides an excellent research ground to study phenotypic evolution. However, interspecific comparative studies on evolution to groundwater life are few because of the challenge in assembling large ecological and molecular resources for species-rich taxa comprised of surface and subterranean species. Here, we make available to the scientific community an operational set of working tools and resources for the Asellidae, a family of freshwater isopods containing hundreds of surface and subterranean species. First, we release the World Asellidae database (WAD) and its web application, a sustainable and FAIR solution to producing and sharing data and biological material. WAD provides access to thousands of species occurrences, specimens, DNA extracts and DNA sequences with rich metadata ensuring full scientific traceability. Second, we perform a large-scale dated phylogenetic reconstruction of Asellidae to support phylogenetic comparative analyses. Of 424 terminal branches, we identify 34 pairs of surface and subterranean species representing independent replicates of the transition from surface water to groundwater. Third, we exemplify the usefulness of WAD for documenting phenotypic shifts associated with colonization of subterranean habitats. We provide the first phylogenetically controlled evidence that body size of males decreases relative to that of females upon groundwater colonization, suggesting competition for rare receptive females selects for smaller, more agile males in groundwater. By making these tools and resources widely accessible, we open up new opportunities for exploring how phenotypic traits evolve in response to changes in selective pressures and trade-offs during groundwater colonization., (© 2023 John Wiley & Sons Ltd.)

The aberrant regulation of the Notch signaling pathway, which is a fundamental developmental pathway, has been implicated in a wide range of human cancers. The Notch pathway can be activated by both canonical and noncanonical Notch ligands, and its role can switch between acting as an oncogene or a tumor suppressor depending on the context. Epigenetic modifications have the potential to modulate Notch and its ligands, thereby influencing Notch signal transduction. Consequently, the utilization of epigenetic regulatory mechanisms may present novel therapeutic opportunities for both single and combined therapeutics targeted at the Notch signaling pathway. This review offers insights into the mechanisms governing the regulation of Notch signaling and explores their therapeutic potential.

Objectives: To investigate the predictive factors of delayed post-percutaneous nephrolithotomy (PCNL) haemorrhage because of arteriovenous fistula (AVF) or pseudoaneurysm (PA) and compare the factors between AVF and PA., Patients and Methods: This is a case-control study with a case-to-control ratio of 1:3. Out of 5077 patients who underwent PCNL from April 2015 to April 2018 in three different teaching hospitals, 113 had post-PCNL haemorrhages because of AVF and/or PA. Seventy-two patients met the inclusion criteria and entered the study as cases, while 216 patients without any postoperative complications were selected as controls., Results: Of all 72 studied patients with complications after PCNL, 35 (48.6%) had AVF, and the rest had PA. The regression model revealed that a history of diabetes (odds ratio [OR]: 2.799, 95% confidence interval [CI]: 1.392-5.630, p -value = 0.004) and renal anomalies (OR: 2.929, 95% CI: 1.108-7.744, p -value = 0.03) were associated with developing delayed post-PCNL haemorrhage. However, no differences were seen between AVF and PA regarding selected variables ( p -value > 0.05)., Conclusion: History of diabetes and renal anomalies were predictive factors for delayed post-PCNL haemorrhage, but no predictive factors were found to differentiate PA and AVF from one another., Competing Interests: Not applicable., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Objectives: Stuttering is a common problem at all ages that is required to be treated since childhood. Atomoxetine is currently used for the treatment of attention deficit hyperactivity disorder (ADHD). It can be effective for the treatment of stuttering due to its selective inhibition of norepinephrine reuptake and dopaminergic properties. Therefore, this randomized controlled trial aimed to evaluate the effect of atomoxetine on children's stuttering., Materials & Methods: The children aged 4-12 years and diagnosed with stuttering, referred to Pediatric Neurology and Psychology clinics , were randomly divided into experimental (n=50) and control (n=50) groups. One group received atomoxetine plus speech therapy, and the other group received only speech therapy. Both groups completed the Stuttering Severity Instrument-Fourth Edition at the baseline (on the first visit) and 3 months after the intervention. The results were compared between the two groups using SPSS software (version 21)., Results: Most of the children (67%) were male. Moreover, 24%, 46%, and 30% of the subjects were within the age ranges of < 60, 60-95, and > 95 months, respectively. Nearly half of the patients (52%) had a positive family history of stuttering. Stuttering severity was the highest within the age range of 60-95 months, in left-handed children, in those who used formula, and in those who felt insecure in the family; however, there was no difference in stuttering severity based on child's gender, concomitant ADHD, multilingualism, facial or movement tics, sleeping hours, and using teats. The mean stuttering severity reduced in both groups (P<0.001), with a greater decrease in the experimental group, compared to that of the control group (P=0.011)., Conclusion: Atomoxetine plus speech therapy is effective for the treatment of children's stuttering and can be used as a complementary treatment strategy in such patients., Competing Interests: The present study wasnt financially supported by anyone, (© 2022 The Authors.)

Nowadays, the entry of organic compounds into water resources is one of the leading global concerns due to the lack of water resources and rapid population growth. In this research, anodic oxidation (AO) method was used to remove 5-fluorouracil (5-FU) from aqueous solutions via Ni/RuO 2 and Ti/IrO 2 -TiO 2 -RuO 2 electrodes as cathode and anode, respectively. For this purpose, the characterization analysis of the electrodes, including X-ray diffraction, scanning electron microscopy, energy dispersive X-ray, and atomic force microscopy were performed. The electrochemical performance of the anode was investigated via cyclic voltammetry analysis. Then, the effect of operational variables, including applied current (mA), initial pH of the solution, initial 5-FU concentration (mg/L), and process time (min) on the 5-FU removal efficiency under the AO process was evaluated via artificial neural network (ANN) modeling. The results revealed that the maximum 5-FU removal efficiency was 96.96%. The applied current intensity, pH, initial 5-FU concentration, and process time were 300 mA, 5, 20 mg/L, and 140 min, respectively. Moreover, the investigation of 5-FU removal by-products and mineralization efficiency of the AO process was carried out via gas chromatography-mass spectrometry and total organic carbon analysis, respectively. The total organic carbon mineralization efficiency was 84.80% after 6 h of reaction time. The reusability and stability of the Ti/IrO 2 -TiO 2 -RuO 2 anode on 5-FU removal efficiency were measured and showed an approximately 5% decay in 5-FU removal efficiency after eight consecutive runs. The overall results and analysis confirmed this method is capable of removing 5-FU through Ti/IrO 2 -TiO 2 -RuO 2 anode and Ni/RuO 2 cathode from aqueous medium., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The objective of the study was to assess the outcome and feasibility of ultrasonography (US)-guided minimally invasive percutaneous nephrolithotomy (mini-PCNL) in children., Materials and Methods: Twenty-five children with upper urinary tract stones who had undergone US-guided mini-PCNL from June 2017 to June 2020 were enrolled in this study. Patients' demographic information and post-treatment results were retrospectively gathered and analysed. Pyelocaliceal system was punctured in prone position using US guidance, and the tract was dilated using single-shot dilation technique. All steps of renal access were done using only US. Mini-PCNL in all cases was done by using 15 Fr rigid nephroscope. Stones were fragmented with a pneumatic lithotripter and evacuated., Results: The patients' mean age was 6.30 ± 3.25 years (range: 1.5-15). The mean stone size was 16.04 ± 3.93 mm (range: 10-30). The mean access time to the stone was 1.50 ± 0.62 min (range: 1-4). The mean operation time was 94.66 ± 3.05 min (range: 90-100 min). The final stone-free rate was 96%. Post-operation fever occurred in 4 (16%) patients who were treated successfully with an antibiotic. No major complications occurred., Conclusions: We recommend US-guided mini-PCNL as a harmless alternative treatment option, in children with renal calculi due to its excellent outcomes and little complications., Competing Interests: None

Background: The relationship between dietary variety, adequacy, moderation, and balanced diet as diet quality indices and cardiovascular risk factors has not been yet evaluated amongst patients with Mmyocardial Iinfarction (MI)., Method: This cross-sectional study was conducted on 225 males and 93 females with MI who were admitted in two heart hospitals, Shiraz, Iran from November 2019 to April 2020. Dietary intake was assessed using a validated food frequency questionnaire and the Diet Quality Index-International (DQI-I). DQI-I included four subscales, namely variety (20 scores), adequacy (40 scores), moderation (30 scores), and balanced diet (10 scores)., Results: The mean age of the participants was 54 ± 8 years. The mean scores of total DQI-I and variety, adequacy, moderation, and balanced diet subscales were 58 ± 12.2, 12.7 ± 3.8, 28.5 ± 7.0, 9.88 ± 5.6, and 7.8 ± 1.1, respectively. The results showed that waist circumference (WC) was influenced by adequacy (-0.26 ± 0.04) and moderation (-0.28 ± 0.03) subscales, while body mass index (BMI)was only related to the moderation subscale (0.15 ± 0.07). Additionally, low density lipoprotein (LDL) cholesterol was influenced by variety (-0.18 ± 0.01), adequacy (-0.14 ± 0.02), moderation (-0.2 ± 0.02), and balanced diet (-0.2 ± 0.003) subscales, while total cholesterol was associated with the adequacy subscale (-0.18 ± 0.01). In addition, high density lipoprotein (HDL) cholesterol was related to variety (0.16 ± 0.03), moderation (0.14 ± 0.04), and balanced diet (0.13 ± 0.01) subscales,while triglyceride was only influenced by the variety subscale (-0.15 ± 0.004)., Conclusion: Dietary advice based on variety, adequacy, moderation, and balanced diet could be useful in practice to provide personalized messages to improve the risk factors amongst patients with MI., (© 2022. The Author(s).)

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.