Induction of heat shock protein expression in SP2/0 transgenic cells and its effect on the production of monoclonal antibodies.

The objective of the current investigation was to evaluate the induction of heat shock proteins (HSPs) in SP2/0 transgenic cells and the effect of these proteins on the production of monoclonal antibodies (mAbs). The SP2/0 cell line expressing the PSG-026 antibody, a biosimilar candidate of golimumab, the culture parameters, and the target protein expression were not justified for industrial production and were used for the experiments. Paracetamol and heat shock were used as chemical and physical inducers of HSPs, respectively. The results showed that paracetamol and heat shock increased the expression of HSP70 and HSP27 at the mRNA and protein levels. The expression of HSPs was greater in paracetamol-treated cells than in heat shock-treated cells. Paracetamol treatment at concentrations above 0.5 mM significantly reduced cell viability and mAb expression. However, treatment with 0.25 mM paracetamol results in delayed cell death and increased mAb production. Heat shock treatment at 45°C for 30 minutes after enhanced mAb expression was applied after pre-treatment with paracetamol. In bioreactor cultures, pretreatment of cells with paracetamol improved cell viability and shortened the lag phase, resulting in increased cell density. The production of mAbs in paracetamol-treated cultures was markedly greater than that in the control. Analysis of protein quality and charge variants revealed no significant differences between paracetamol-treated and control cultures, indicating that the induction of HSPs did not affect protein aggregation or charge variants. These findings suggest that inducing and manipulating HSP expression can be a valuable strategy for improving recombinant protein production in biopharmaceutical processes.

Predictors of Recurrent Urolithiasis in Iran: Findings from a Nationwide Study.

BACKGROUND: Prevention of urinary stone recurrence is the ultimate goal in urolithiasis patients. In this study, we aimed to investigate the national prevalence rate and possible determinants of increased urolithiasis recurrence risk in a nationwide study in Iran. METHODS: All data regarding stone occurrence and recurrence episodes were extracted from the cross-sectional Iran National Stone Survey (INSS) study, and the possible determinants of recurrence were evaluated in the subset of 2913 patients who had a positive history of at least one episode of urolithiasis. RESULTS: The national prevalence rate of recurrent urolithiasis was 2.6% (95% CI: 2.5, 2.8) in Iran. Moreover, the relative ratio of recurrent stone formers to all stone formers was 39.8% (95% CI: 38.0, 41.6). Our univariable truncated negative binomial regressions suggested that a positive history of urolithiasis in the patient's father (prevalence ratio [PR] [95% CI]=1.83 [1.39, 2.41], P<0.001), mother (PR [95% CI]=1.92 [1.39, 2.66], P<0.001) or brother (PR [95% CI]=1.32 [1.03, 1.69], P=0.026); and residence in urban areas (PR [95% CI]=1.27 [1.04, 1.55], P=0.016) were significant predictors of repetitive recurrence episodes. However, when incorporated into a multivariable truncated negative binomial regression model, the only significant predictors of more frequent recurrence episodes were a positive history in father (PR [95% CI]=1.66 [1.24, 2.22], P<0.001) and mother (PR [95% CI]=1.68 [1.20, 2.36], P=0.002); and urban residence (PR [95% CI]=1.24 [1.01, 1.51], P=0.031). CONCLUSION: Our results indicate that a positive family history of urolithiasis in mother and father and residence in urban areas are the significant predictors of recurrence risk in urolithiasis patients in Iran.

Efficacy of intra-ovarian injection of autologous platelet-rich plasma in women with poor responders: a systematic review and meta-analysis.

CONTEXT: The effect of platelet-rich plasma (PRP) on ovarian reserve markers in poor ovarian response (POR) is challenging. AIM: This systematic review and meta-analysis was, therefore, designed to evaluate the effectiveness of intra-ovarian injection of autologous PRP on improving ovarian reserve markers and assisted reproductive technology (ART) outcomes in infertile women with POR. METHODS: A systematic search was conducted for the efficacy of intra-ovarian injection of autologous PRP on the improvement of ovarian reserve markers and ART outcomes in infertile women with POR. The methodological quality of the included studies was checked and eligible studies were included in the meta-analysis to find pooled results. Keywords were primary ovarian insufficiency, premature menopause, poor responder, poor ovarian response, diminished/decreased ovarian reserve, platelet-rich plasma, and intra-ovarian or a combination of them. The effect of PRP on fertility indices was evaluated using the standardized mean difference (SMD). The analysis was performed through STATA version 13. KEY RESULTS: 13 studies containing 1289 patients were included. Mean age, body mass index (BMI) and duration of infertility was 37.63 ± 2.66 years, 24 ± 1.23 kg/m2 and 4.79 ± 1.64 years, respectively. Most of the studies measured the outcomes 2-3/3 months after intra-ovarian injection of autologous PRP. The antral follicular count (AFC) after treatment by PRP is higher with an SMD of 0.95 compared to before treatment. The day 3 follicle-stimulating hormone (FSH) after treatment by PRP is lower with an SMD of - 0.25 compared to before treatment. The day 3 estradiol (E2) after treatment by PRP is higher with an SMD of 0.17 compared to before treatment. The anti-Mullerian hormone (AMH) after treatment by PRP is higher with an SMD of 0.44 compared to before treatment. The total oocytes number after treatment by PRP is higher with an SMD of 0.73 compared to before treatment. The number of MII oocytes after treatment by PRP is higher with an SMD of 0.63 compared to before treatment. The number of cleavage-stage embryos after treatment by PRP is higher with an SMD of 1.31 compared to before treatment. The number of day 5 embryo after treatment by PRP is higher with an SMD of 1.28 compared to before treatment. Pooled estimation of a meta-analysis of prevalence studies reported a prevalence of 22% for clinical pregnancy, 5% for spontaneous pregnancy and 21% for ongoing pregnancy following PRP therapy. CONCLUSION: Intra-ovarian injection of PRP improved ovarian reserve markers with increasing AFC, serum level of AMH and day 3 E2 and decreasing serum level of day 3 FSH. In addition, this treatment improved ART outcomes through the increasing of number total oocytes, number of MII oocytes, number of cleavage-stage embryos and number of day 5 embryos in POR women. IMPLICATIONS: Although treatment of POR women remains challenging, the use of intra-ovarian injection of autologous PRP in POR patients prior to IVF/ICSI cycles is a sign of new hope for increasing the success of IVF/ICSI. However, further well-organized, randomized controlled trials should be conducted to substantiate this result and recommend intra-ovarian injection of PRP as part of routine treatment in women with POR.

The preventive effect of heat-killed Lactobacillus plantarum on male reproductive toxicity induced by cholestasis in rats.

This study investigated the preventive effect of heat-killed Lactobacillus plantarum (L. plantarum) on cholestasis-induced male reproductive toxicity in rats. Rats were divided into control normal, sham control, bile duct ligation (BDL) control, and BDL with heat-killed L. plantarum supplementation groups. The effects on sexual hormones, testicular and epididymal histology, sperm parameters, oxidative stress markers, and inflammatory gene expression were evaluated. Compared to the BDL control group, the BDL + heat-killed L. plantarum group showed higher levels of normal sperm, luteinizing hormone, testosterone, total antioxidant capacity, and catalase activity, indicating improved reproductive function. Conversely, markers of oxidative stress, such as total oxidative status, oxidative stress index, and carbonyl protein, were lower in the BDL + heat-killed L. plantarum group. The expression levels of inflammatory genes tumor necrosis factor-alpha and interleukin-6 were reduced, while interleukin-10 gene expression was increased in the BDL + heat-killed L. plantarum group. Histological evaluation confirmed the positive effects of heat-killed L. plantarum intervention on testicular parameters. In conclusion, heat-killed L. plantarum supplementation protects against cholestasis-induced male reproductive dysfunction in rats, as evidenced by improvements in hormonal balance, sperm quality, oxidative stress, and inflammation.

Longitudinal trend of urolithiasis incidence rates among world countries during past decades.

INTRODUCTION: This study explores the trend of urolithiasis in various countries and categorizes the countries in terms of how their urolithiasis incidence rate has changed over time. METHODS: The incidence rate of urolithiasis in 204 countries from 1990 to 2019, extracted from the Global Burden of Disease study, has been analyzed. RESULTS: According to the results, all regions had experienced an increasing trend in urolithiasis rate, except for Eastern Europe, Central Europe, and Southeast Asia regions (decreasing rates of -71.4, -56.2, and -9.2 per 100000, respectively). Moreover, the Caribbean region had the highest increasing trend of urolithiasis rates, and Central Asia was in the next rank (increasing rate of 48.3 and 34.3 per 100,000, respectively, p-value < .05). Also, African regions revealed significant increasing trends over time (p-value < 0.05). The outstanding findings in cluster analysis showed that Afghanistan, Andorra, and Comoros had the most decreasing trend in urolithiasis rates over time (decreasing rate of -128.2 per 100000, p-value < .001). Cuba, Cyprus, Czechia, the Democratic People's Republic of Korea, Denmark, and Djibouti were in the next rank in terms of decreasing rate (decreasing rate of -92.3 per 100000, p-value < .001). In addition, urolithiasis rates in Congo, Eswatini, Gabon, and Grenada have the most increasing trend (increasing rate of 116.1 per 100000, p-value < .001). CONCLUSION: The trend of urolithiasis rates was significantly increased in most countries, and Congo, Eswatini, Gabon, and Grenada had the highest trend among others. Also, Afghanistan, Andorra, and Comoros revealed the most decreasing rates, and the trend has dropped remarkably in several other countries.

The Effect of Bariatric Surgery on Patients with Heart Failure: a Systematic Review and Meta-analysis.

The current study aims to evaluate the effect of bariatric metabolic surgery (BMS) on the New York Heart Association (NYHA) class and left ventricular ejection fraction (LVEF) in patients with diagnosed heart failure (HF). Fourteen related articles with 217 patients were included in the final analysis. LVEF significantly improved after BMS in patients with HF with a mean difference of 7.78% (CI 95%: 3.72, 11.84, I2 = 83.75, p-value < 0.001). Also, the NYHA class significantly decreased after BMS with a mean difference of - 0.40 (CI 95%: - 0.62, - 0.19, I2: 47.03, p-value < 0.001). A total of 27 patients with obesity and HF were listed for cardiac transplantation after BMS. Of those, 20 patients successfully underwent heart transplantation after BMS.

The effect of L-carnitine on oocyte mitochondrial health and biomarkers on cyclophosphamide chemotherapy drug in mice.

Improving oocyte competence during chemotherapy is widely known as a contributing factor to increasing the probability of fertility. Additionally, the role of cumulus cells in oocyte quality is of utmost importance. Therefore, this study was designed to simultaneously probe into the relative gene expression of oocytes and cumulus cells as biomarkers of oocyte quality with cyclophosphamide and L-carnitine treatment. A total of 60 adult NMRI mice were divided into four groups: control, L-carnitine (LC), cyclophosphamide (CP), and cyclophosphamide+L-carnitine (CP+LC). The relative mRNA expression levels of oocyte quality genes including growth differentiation factor 9 (Gdf9), hyaluronan synthase 2 (Has2), and mitochondrial sirtuin 3 (Sirt3) in oocytes, and genes involved in bilateral communication between cumulus cells and between the oocyte and its neighboring cumulus cells including connexin 37 (Cx37) and connexin 43 (Cx43) were detected by Real-time-PCR. DCFH-DA staining analyzed the level of intracellular ROS in oocytes. Under the influence of L-carnitine, Gdf9, Has2, Cx43, and Cx37 were significantly up-regulated (p ≤ 0.05). However, cyclophosphamide considerably reduced the expression of all these genes (p ≤ 0.05). The expression of the Sirt3 gene in the CP group increased significantly compared to the other groups (p ≤ 0.05). Analysis of fluorescent images revealed that the level of intracellular ROS in the cyclophosphamide group was significantly increased compared to the other groups (p ≤ 0.05), while it plummeted in the L-carnitine group (p ≤ 0.05). L-carnitine as an antioxidant can reduce the destructive effects of cyclophosphamide and enhance bilateral communications between oocytes and cumulus cells, and it may ultimately lead to an increase in the fertility rate.

Fertility-enhancing effects of inositol & vitamin C on cisplatin induced ovarian and uterine toxicity in rats via suppressing oxidative stress and apoptosis.

Cisplatin can lead to infertility due to its negative impact on the uterus and ovaries. This study aimed to explore the effects of Inositol and vitamin C on cisplatin-induced infertility. Forty-eight adult female Wistar rats were divided into eight groups (N = 6) and orally treated for 21 days. The treatments were as follows: negative control (saline), positive control (saline and cisplatin injected into the abdomen on day 15), T1-T3: rats given vitamin C (150 mg/kg), Inositol (420 mg/kg), and vitamin C + Inositol, respectively, along with cisplatin injected into the abdomen on day 15, T4-T6: rats given only vitamin C, Inositol, and vitamin C + Inositol, respectively. Vitamin C and Inositol enhanced cisplatin-induced histopathological improvements in the uterus and ovaries, raising progesterone and estradiol serum levels. Furthermore, the supplements enhanced ESR1 gene expression in the uterus and ovary, reducing uterine and ovarian apoptosis caused by cisplatin through modulation of caspase 3, 8, and Bcl-2 gene levels. These substances decreased ovarian and uterine malondialdehyde levels, boosted total antioxidant capacity and superoxide dismutase, and alleviated oxidative stress. The findings reveal that vitamin C and Inositol shield against cisplatin-related infertility by reducing oxidative stress and apoptosis in the uterus and ovaries.

Neuroprotective Effect of Thiazolidine-2,4-dione Derivatives on Memory Deficits and Neuropathological Symptoms of Dementia on a Scopolamine-Induced Alzheimer's Model in Adult Male Wistar Rats.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with a decline in memory deficits and neuropathological diagnosis with loss of cholinergic neurons in the brains of older adults. Based on these facts and an increasing number of involved people worldwide, this investigation aimed to study the improvement of memory and cognitive impairments via an anticholinergic approach of thiazolidine-2,4-diones (TZDs) in the scopolamine-induced model of Alzheimer type in adult male Wistar rats (n = 40). The results indicated data analysis obtained from in vivo and in vitro tests for (E)-5-(3-hydroxybenzylidene)-3-(2-oxo-2-phenylethyl)thiazolidine-2,4-dione (TZ3O) (2 and 4 mg/kg) with the meta-hydroxy group and (E)-5-(4-methoxybenzylidene)-3-(2-oxo-2-phenylethyl)thiazolidine-2,4-dione (TZ4M) (2 and 3 mg/kg) with the para-methoxy group showed a neuroprotective effect. TZ3O and TZ4M alleviated the scopolamine-induced cognitive decline of the Alzheimer model in adult male Wistar rats. These initial and noteworthy results could be assumed as a starting point for the evolution of new anti-Alzheimer agents.

Lifestyle and occupational risks assessment of bladder cancer using machine learning-based prediction models.

BACKGROUND: Bladder cancer, one of the most prevalent cancers globally, can be regarded as considerable morbidity and mortality for patients. The bladder is an organ that comes in constant exposure to the environment and other risk factors such as inflammation. AIMS: In the current study, we used machine learning (ML) methods and developed risk prediction models for bladder cancer. METHODS: This population-based case-control study is focused on 692 cases of bladder cancer and 692 healthy people. The ML, including Neural Network (NN), Random Forest (RF), Decision Tree (DT), Naive Bayes (NB), Gradient Boosting (GB), and Logistic Regression (LR), were applied, and the model performance was evaluated. RESULTS: The RF (AUC = .86, precision = 79%) had the best performance, and the RT (AUC = .78, precision = 73%) was in the next rank. Based on variable importance analysis in RF, recurrent infection, bladder stone history, neurogenic bladder, smoking and opium use, chronic renal failure, spinal cord paralysis, analgesic, family history of bladder cancer, diabetic mellitus, low dietary intake of fruit and vegetable, high dietary intake of ham, sausage, can and pickles were respectively the most important factors, which effect on the probability of bladder cancer. CONCLUSION: Machine learning approaches can predict the probability of bladder cancer according to medical history, occupational risk factors, and dietary and demographical characteristics.

Effect of two vitamin D repletion protocols on 24-h urine calcium in patients with recurrent calcium kidney stones and vitamin D deficiency: a randomized clinical trial.

OBJECTIVES: To evaluate the effects of two vitamin D repletion therapies (cholecalciferol) on serum levels of 25-hydroxyvitamin D (25(OH)D) and 24-h urine calcium in patients with recurrent calcium kidney stones and vitamin D deficiency (VDD). DESIGN, SETTING, PARTICIPANTS: A parallel-group randomized controlled clinical trial on patients who referred to Labbafinejad kidney stone prevention clinic, Tehran, Iran. From 88 recurrent calcium stone formers, 62 patients completed the study. The age of participants was 18-70 years who had serum 25(OH)D levels of 10-20 ng/ml. INTERVENTION: Participants received oral cholecalciferol 2000 IU daily for 12 weeks or 50,000 IU weekly for 8 weeks. MAIN OUTCOME MEASURES: Study variables including 24-h urine calcium, supersaturations of calcium oxalate and calcium phosphate, serum 25(OH)D and parathyroid hormone were measured at the beginning of the study and after 12 weeks. RESULTS: The 24-h urine calcium significantly increased in both groups (ß = 69.70, p < 0.001), with no significant difference between treatments. Both groups showed no significant change in the supersaturation levels of calcium oxalate and calcium phosphate. Serum levels of 25(OH)D increased significantly (ß = 12.53, p < 0.001), with more increase in the 50,000 IU group (ß = 3.46, p = 0.003). Serum parathyroid hormone decreased in both groups (p < 0.001). CONCLUSIONS: Although both treatment protocols increased 24-h urine calcium, they did not increase the supersaturation state of calcium oxalate or calcium phosphate. Trial registration IRCT20160206026406N4, 13/08/2019.

A Brief Narrative Review of the Underlying Mechanisms Whereby Omega-3 Fatty Acids May Influence Skeletal Muscle: From Cell Culture to Human Interventions.

Skeletal muscle is essential for human locomotion as well as maintaining metabolic homeostasis. Age-related reduction in skeletal muscle mass, strength, and function (i.e., sarcopenia) is a result of pathophysiological processes that include inflammation, alteration of molecular signaling for muscle protein synthesis and degradation, changes in insulin sensitivity, as well as altered skeletal muscle satellite cell activity. Finding strategies to mitigate skeletal muscle loss with age is deemed paramount as the percentage of the population continues to shift towards having more older adults with sarcopenia. Recent research indicates omega-3 fatty acid supplementation can influence anabolic or catabolic pathways in skeletal muscle. Our brief review will provide a synopsis of some underlying mechanisms that may be attributed to omega-3 fatty acid supplementation's effects on skeletal muscle. We will approach this review by focusing on cell culture, animal (pre-clinical models), and human studies evaluating omega-3 fatty acid supplementation, with suggestions for future research. In older adults, omega-3 fatty acids may possess some potential to modify pathophysiological pathways associated with sarcopenia; however, it is highly likely that omega-3 fatty acids need to be combined with other anabolic interventions to effectively ameliorate sarcopenia.

Multiple sclerosis and lower urinary tract symptoms: A survey of prevalence, characteristic and urological evaluations.

Objective: Most multiple sclerosis patients have urological complications such as lower urinary tract symptoms. This study was conducted to evaluate the prevalence of these symptoms and whether they result in a urological evaluation. Methods: A cross-sectional study of 517 multiple sclerosis patients at Tehran's referral multiple sclerosis center and neurology clinics between 2018 and 2022 was performed. Data were collected through interviews after patients completed informed consent forms. Urological examinations, including urine analysis and ultrasonography, were evaluated as final assessments. The data were analyzed using descriptive and inferential statistical tests in Statistical Package for Social Science. Results: Among all participants, the prevalence of lower urinary tract symptoms was 73% (n = 384), with urgency (44.8% n = 232) being the most common symptom. The prevalence of intermittency was significantly higher among women (p = 0.004). There was no gender-significant difference in terms of the prevalence of other symptoms (p > 0.050). Lower urinary tract symptoms were significantly correlated with age, clinical course, disease duration, and disability (p < 0.001). Additionally, 37.3% and 18.7% of patients with lower urinary tract symptoms, as well as 17.9% and 37.5% of patients with multiple sclerosis attacks, respectively, had undergone urine analysis and ultrasonography. Conclusion: Multiple sclerosis patients rarely undergo urological evaluations during the course of their disease. Proper assessment is essential as these symptoms are among the most detrimental manifestations of this disease.

Efficiency of Hesperidin against Liver Fibrosis Induced by Bile Duct Ligation in Rats.

Introduction: Bile duct ligation (BDL) and subsequent cholestasis are associated with oxidative stress and liver injury and fibrosis. Hesperidin (3,5,7-trihydroxyflavanone 7-rhamnoglucoside) is a flavanone glycoside abundant in citrus fruits. It has positive effects on diabetic retinopathy, reduced platelet aggregation, and blood flow alterations and has the potential to reduce liver injury in oxidative stress. The aim of this study was to evaluate the hepatoprotective effects of hesperidin on BDL-induced liver injury in rats. Methods: A total of 48 adult male Wistar rats were equally allocated to six eight-rat groups, namely, a healthy group, a sham group, a BDL+Vehicle group (BDL plus treatment with distilled water), a BDL+VitC group (BDL plus treatment with vitamin C 4.25 µg/kg), a BDL+Hesp100 group (BDL plus treatment with hesperidin 100 mg/kg/day), and a BDL+Hesp200 group (BDL plus treatment with hesperidin 200 mg/kg/day). Treatments were orally provided for 21 consecutive days. Finally, rats were sacrificed through heart blood sampling. Blood samples were centrifuged, and liver function, oxidative stress, and antioxidant parameters were assessed. Liver tissue was also assessed for oxidative stress, antioxidant, and histological parameters. The expression of inflammatory genes, namely, TGFß1, iNOS, Caspase-3, and α-SMA, was measured through polymerase chain reaction. Findings. Hesperidin supplementation was associated with significant decrease in the levels of liver enzymes, bilirubin, nitric oxide, malondialdehyde, protein carbonyl, and inflammatory gene expression; significant increase in the levels of total antioxidant capacity, glutathione, and superoxide dismutase and catalase enzyme activity; and significant improvement in the histological morphology and structure of the liver parenchyma. Conclusion: Hesperidin has significant positive effects on liver morphology and structure, inflammation, fibrosis, and oxidative stress in rats with BDL-induced cholestatic liver injury.

Preparation and characterization of doped hollow carbon spherical nanostructures with nickel and cobalt metals and their catalysis for the green synthesis of pyridopyrimidines.

Fused heterocyclic systems containing the pyrimidine ring structure perform a significant role in numerous biological and pharmaceutical processes. Their properties include antibacterial, antifungal, anti-fever, anti-tumor, and antihistamine. As pyridopyrimidines are important in the essential fields of pharmaceutical chemistry, efficient methods for preparing these heterocycles are presented. In this study, a method for producing improved hollow carbon sphere nanostructures with cobalt and nickel (Co-Ni@HCSs) is presented. The nanocatalyst was prepared and identified by applying Fourier-transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), Brunauer-Emmett-Teller (BET), and elemental mapping techniques. The Co-Ni@HCSs nanocatalyst was proved to be highly efficient in synthesizing pyranopyrimidine derivatives. The sizeable active site, economic catalyst loading, easy workup, reusability, green reaction conditions, and excellent yields of all derivatives are some of the significant features of this process. Also, applying response surface methodology (RSM) and the Box-Behnken design (BBD) techniques allowed us to determine the influential factors of the laboratory variables and identify the optimum conditions for superior catalytic activity. Finally, synthesized organic compounds were identified by utilizing melting point, FT-IR, and hydrogen-1 nuclear magnetic resonance (1H NMR) analyses.

A Comparison of Boron Supplement and Tamsulosin as Medical Expulsive Therapy for Urinary Stones After Extracorporeal Shock Wave Lithotripsy: a Randomized Controlled Clinical Trial.

Treatment with alpha-blockers has been used in many studies to facilitate stone clearance after extra-corporeal shock wave lithotripsy (ESWL), based on mediating ureteral wall relaxation. Ureteral wall edema is another barrier against the stone passage. We aimed to compare the effectiveness of boron supplement (due to its anti-inflammatory effect) and tamsulosin in the passage of stone fragments after ESWL. Eligible patients after ESWL were randomly assigned to two groups and were treated with boron supplement (10 mg/BD) or tamsulosin (0.4 mg per night) for 2 weeks. The primary outcome was the stone expulsion rate according to the remained fragmented stone burden. The secondary outcomes were the time of stone clearance, pain intensity, drug side effects, and the need for auxiliary procedures. In this randomized control trial, 200 eligible patients were treated with boron supplement or tamsulosin. Finally, 89 and 81 patients in the two groups completed the study, respectively. The expulsion rate was 46.6% in the boron and 38.7% in the tamsulosin group, which there was no statistically significant difference between the two groups (p = 0.003), as well as the time of stone clearance (7.47 ± 22.4 vs 6.52 ± 18.45, days, p = 0.648, respectively), after 2-week follow-up. Moreover, pain intensity was the same in both groups. No Significant side effects were reported in the two groups. Boron supplement could be effective as adjuvant medical expulsive therapy after ESWL with no significant side effects in short-term follow-up. Iranian Clinical Trial Registration number and date of registration: IRCT20191026045244N3, 07/29/2020.

A path analysis to investigate the interaction between serum, urinary and demographic factors influencing urine calcium in kidney stone formers.

BACKGROUND: Hypercalciuria is one of the most important urinary risk factors in kidney stone formers. This study aimed to delineate the interaction of some demographic, serum, and urinary risk factors influencing 24-h urinary (24-U) calcium excretion. METHODS: This study was secondary data analysis, using data from 593 kidney stone patients referred to the Labbafinejad kidney stone prevention clinic from March 2015 to May 2019. The study considered serum, urinary and demographic factors that interact to influence 24-U calcium using path analysis. In addition to the direct impact of predictors on the 24-U calcium, this analysis considered the effects of the predictors on the 24-U calcium transmitted by a mediating variable named indirect effects. RESULTS: The results showed that age indirectly affected on 24-U calcium through 25-hydroxy vitamin D (25(OH)D), serum and 24-U creatinine. As well, weight had an indirect effect through 24-urine metabolites (creatinine, citrate, urea, and sodium). Among serum variables, PTH and creatinine significantly directly affected on 24-U calcium. In comparison, 25(OH)D and phosphorus appeared to influence 24-U calcium indirectly through serum parathormone. Regarding 24-U metabolites, sodium, urea, and citrate had a significant direct effect on 24-U calcium. Moreover, 24-U creatinine has a significant direct and indirect effect on 24-U calcium through citrate and urea as mediator variables. CONCLUSION: Serum 25(OH)D and phosphorus, along with age and weight, indirectly affected urinary calcium through a third variable. Other variables (PTH, serum creatinine, and 24-U sodium, urea, and citrate) showed a direct effect on 24-U calcium excretion.

Medical Expulsive Therapy for Pediatric Ureteral Stones: A Meta-Analysis of Randomized Clinical Trials.

To evaluate the efficacy and safety of medical expulsive therapy (MET) for ureteral stones in pediatric patients, Cochrane, PubMed, Web of Science, Scopus, and the reference list of retrieved studies were searched up to September 2022 to identify RCTs on the efficacy of MET. The protocol was prospectively registered at PROSPERO (CRD42022339093). Articles were reviewed, data were extracted by two reviewers, and the differences were resolved by the third reviewer. The risk of bias was assessed using the RoB2. The outcomes, including the stone expulsion rate (SER), stone expulsion time (SET), episode of pain, analgesic consumption, and adverse effects, were evaluated. Six RCTs enrolling 415 patients were included in the meta-analysis. The duration of MET ranged from 19 to 28 days. The investigated medications included tamsulosin, silodosin, and doxazosin. The stone-free rate after 4 weeks in the MET group was 1.42 times that of the control group (RR: 1.42; 95% CI: 1.26-1.61, p < 0.001). The stone expulsion time also decreased by an average of 5.18 days (95% CI: -8.46/-1.89, p = 0.002). Adverse effects were more commonly observed in the MET group (RR: 2.18; 95% CI: 1.28-3.69, p = 0.004). The subgroup analysis evaluating the influence of the type of medication, the stone size, and the age of patients failed to reveal any impact of the aforementioned factors on the stone expulsion rate or stone expulsion time. Alpha-blockers as medical expulsive therapy among pediatric patients are efficient and safe. They increase the stone expulsion rate and decrease the stone expulsion time; however, this included a higher rate of adverse effects, which include headache, dizziness, or nasal congestion.

Transplantation of Exercise-Induced Extracellular Vesicles as a Promising Therapeutic Approach in Ischemic Stroke.

Clinical evidence affirms physical exercise is effective in preventive and rehabilitation approaches for ischemic stroke. This sustainable efficacy is independent of cardiovascular risk factors and associates substantial reprogramming in circulating extracellular vesicles (EVs). The intricate journey of pluripotent exercise-induced EVs from parental cells to the whole-body and infiltration to cerebrovascular entity offers several mechanisms to reduce stroke incidence and injury or accelerate the subsequent recovery. This review delineates the potential roles of EVs as prospective effectors of exercise. The candidate miRNA and peptide cargo of exercise-induced EVs with both atheroprotective and neuroprotective characteristics are discussed, along with their presumed targets and pathway interactions. The existing literature provides solid ground to hypothesize that the rich vesicles link exercise to stroke prevention and rehabilitation. However, there are several open questions about the exercise stressors which may optimally regulate EVs kinetic and boost brain mitochondrial adaptations. This review represents a novel perspective on achieving brain fitness against stroke through transplantation of multi-potential EVs generated by multi-parental cells, which is exceptionally reachable in an exercising body.

Global prevalence of Neisseria gonorrhoeae infection in pregnant women: a systematic review and meta-analysis.

BACKGROUND: Neisseria gonorrhoeae infection (gonorrhoea) is associated with several pregnancy complications, including preterm labour, spontaneous abortion, stillbirth, miscarriage, growth retardation, and intrauterine death. OBJECTIVES: We performed a systematic review and meta-analysis to estimate the global and regional prevalence of gonorrhoea in pregnant women as a scientific basis for further studies. DATA SOURCES: We systematically searched PubMed/MEDLINE, Web of Science, Embase, Scopus, and SciELO databases from inception to 10 July 2022. STUDY ELIGIBILITY CRITERIA: We included cross-sectional, cohort, and case-control studies that reported the prevalence of gonorrhoea in pregnant women. In addition, we included baseline data for randomized controlled trials. PARTICIPANTS: Pregnant women who were tested for gonorrhoea. METHODS: Pooled prevalence estimates at 95% CIs were calculated using a random-effects meta-analysis model. We stratified countries according to WHO-defined regions and socio-economic factors. Moreover, sub-group-, meta-regression, and sensitivity analyses were conducted to investigate the effects of pre-determined factors on prevalence estimates and heterogeneity. RESULTS: We identified 235 studies (249 datasets) on 19 104 175 pregnant women from 71 countries. The worldwide pooled prevalence of gonorrhoea in pregnant women was estimated at 1.85% (95% CI 1.73-1.97%), with the highest rate in the African region (3.53%) (2.84-4.29%) and the lowest rate in the European region (0.52%) (0.27-0.84%). Overall, the prevalence estimates were high among low-income countries (3.03%), pregnant women with HIV (2.81%), and pregnant women <20 years old (8.06%). A significant decreasing trend in prevalence was observed over time (ß = -0.0008, 95% CI -0.0012 to -0.0004, p 0.001). DISCUSSION: Our findings indicate that a substantial number of pregnant women have been infected with gonorrhoea globally, which calls for immediate public health measures to reduce the potential risk of infection. The study highlights the inadequacy or lack of data for many countries, emphasizing the need to expand systematic data collection efforts at national and regional levels.