Comparative Effect of Photobiomodulation on Human Semen Samples Pre and Post Cryopreservation

Abstract

The primary objective of this study is to evaluate and to compare the effects of photobiomodulation (PBM) on sperm parameters both before and after cryopreservation. In this regard, 24 freshly ejaculated semen samples from normozoospermic men were included in this study. Each semen sample was randomly divided into three groups (1 ml aliquot for each group): the control group (group one) underwent conventional sperm cryopreservation (n = 24), group two underwent pre-freezing PBM exposure (810 nm, diode laser, and 0.6 J/cm2) (n = 24), and group three underwent post freezing and thawing PBM exposure (n = 24). Indicators of sperm quality, including total sperm motility (TSM), progressive sperm motility (PSM), DNA fragmentation, lipid peroxidation levels, apoptosis-like changes, and gene expression levels of protamine (PRM) 1, PRM2, and adducin 1 alpha (ADD1), were investigated in a blinded style. Due to the beneficial effect of pre-freezing PBM therapy, group 2 exhibited the highest TSM and PSM levels compared to groups 1 and 3. At the same time, DNA fragmentation and lipid peroxidation were significantly reduced in the group 2 compared to the group 1 (p = 0.024 p = 0.016, respectively). Evaluation of apoptotic/necrotic changes revealed that parameters including early apoptosis, dead, and necrotic cells decreased in the group 2 compared to the either groups 1 (p = 0. 008, p = 0. 032, p = 0. 02, respectively) or group 3 (p = 0.037, p = 0.108, p = 0.083). There were no significant differences in the expression levels of PRM1, PRM2, and ADD1 among the study groups. Based on our results, PBM therapy prior to cryopreservation, even in the normal semen samples, plays a significant protective role against cryo-damage by preserving the functional parameters of spermatozoa.

Keywords: Apoptosis; Cryo damage; Cryopreservation; Oxidative stress; Photobiomodulation; Semen analysis.

DOI: 10.1007/s43032-021-00805-x

Comparison of outcomes and complications in conventional versus ultrasound-accelerated catheter directed thrombolysis for treatment of pulmonary embolism: A systematic review and meta-analysis

Abstract

 Background: Acute submassive a massive pulmonary embolism are known as leading causes of cardiovascular morbidity and mortality in emergency departments. Choosing the optimal type of catheter directed thrombolysis (CDT) for treatment of pulmonary embolism presents a quandary to the practitioners. To the best of our knowledge, there is no meta-analysis comparing superiority of conventional CDT and ultrasound-accelerated catheter directed thrombolysis (USACDT). Therefore, in this meta-analysis, we aimed to compare conventional CDT with USACDT regarding clinical outcomes and safety profile.

Methods: A systematic literature search of previous published studies comparing conventional CDT with USACDT regarding clinical outcomes and safety profile was carried out in the electronic databases including MEDLINE, Scopus, EBSCO, Google Scholar, Web of Science, and Cochrane from inception to December 2021. Data were analyzed by comprehensive meta-analysis software (CMA, version 3).

Results: The meta-analysis included nine studies with a total of 705 patients. Our meta-analysis showed that there is no significant difference between two groups with respect to pulmonary arterial systolic pressure (SMD: -0.084; 95% CI: -0.287 to 0.12; p: 0.41), RV/LV (SMD: -0.003; 95% CI: -0.277 to 0.270; p: 0.98), and Miller score (SMD: -0.345; 95% CI: -1.376 to 0.686; p: 0.51). Similarly, we found no statistically significant differences between two groups regarding major and minor bleeding (p > .05).

Conclusion: Our meta-analysis showed that when compared with USACDT, conventional CDT provides similar clinical and hemodynamic outcomes or safety for treatment of pulmonary embolism without the need for very expensive technologies. However, randomized clinical trials are required to further investigate cost-effectiveness of USACDT in comparison with conventional CDT.

Keywords: Pulmonary embolism; bleeding; catheter-directed thrombolysis; meta-analysis; ultrasound-accelerated thrombolysis.

DOI: 10.1177/02676591221108811

Expression analysis of mTOR-associated lncRNAs in multiple sclerosis

Abstract

mTOR has been shown to be involved in the regulation of immune responses and differentiation of immune cells. This protein is a candidate molecule for unraveling the molecular mechanisms of autoimmune disorders such as multiple sclerosis (MS). We designed the current study to assess expression of MTOR, and four associated long non-coding RNAs (lncRNAs), namely SNHG1, SNHG3, SHNG5 and DANCR in the peripheral blood of patients with MS compared with healthy controls. Analysis of real-time PCR results has shown down-regulation of SNHG5 and DANCR in MS patients compared with controls. Sex of study participants had no significant effect on expression of either genes and the interaction of sex and disease on expression levels of all studied genes were insignificant. There was a significant negative correlation between expression levels of MTOR gene and disease duration. No other significant correlations were detected between genes expressions and clinical/demographic data. SNHG5 and DANCR transcript levels had AUC values of 0.88 and 0.68 in separation of patients with MS from healthy controls, respectively. Taken together, our study suggests participation of two mTOR-related lncRNAs, i.e. SNHG5 and DANCR in the pathophysiology of MS.

Keywords: DANCR; Multiple sclerosis; SHNG5; SNHG1; SNHG3; lncRNA; mTOR

DOI: 10.1007/s11011-022-01010-8

Factors Affecting Resiliency Among Volunteers in Disasters: A Systematic Literature Review

Abstract

Objective: Volunteers need considerable resiliency to cope with formidable challenges during their operations in disaster scenes. The present study was conducted to identify factors affecting the different aspects of resiliency among volunteers in disasters.

Material and methods: The databases of Web of Science, Scopus, PubMed, ProQuest, Google Scholar, World Health Organization Library, International Committee of the Red Cross (ICRC) Library, PsycArticles, and SafetyLit were searched until September 29, 2018. The main search terms were resiliency, disaster, humanitarian aid worker, and volunteer.

Results: A total of 548 documents were obtained and screened based on the inclusion and exclusion criteria. A number of 8 documents was selected for the final analysis. The main factors contributing to the resilience of volunteers at the 3 stages of pre-, during, and post-disasters were classified into 3 groups of individual, environmental, and organizational. Important factors affecting resilience of volunteers in disasters included previous disaster response experience and disaster-related training.

Conclusion: Resiliency should be deemed integral to relief operations. Considering the main factors affecting volunteers resiliency, it is highly suggested that organizations active in humanitarian endeavors explore the factors impacting on resilience among their volunteers via various research methods and seek to select those with higher degrees of resilience in order to avert untoward consequences in their missions.

Keywords: disasters; resilience; systematic literature review; volunteers

DOI: 10.1017/dmp.2020.283

A Review on the Role of miR-1246 in the Pathoetiology of Different Cancers

Abstract

miR-1246 is a microRNA firstly recognized through application of a high throughput sequencing technique in human embryonic stem cells. Subsequent studies have shown the role of this microRNA in the carcinogenesis. miR-1246 has been found to exert oncogenic roles in colorectal, breast, renal, oral, laryngeal, pancreatic and ovarian cancers as well as melanoma and glioma. In lung, cervical and liver cancers, studies have reported contradictory results regarding the role of miR-1246. miR-1246 has been reported to regulate activity of RAF/MEK/ERK, GSK3β, Wnt/β-catenin, JAK/STAT, PI3K/AKT, THBS2/MMP and NOTCH2 pathways. In addition to affecting cell cycle progression and proliferation, miR-1246 can influence stemness and resistance of cancer cells to therapeutics. In the current review, we describe the summary of in vitro and in vivo studies about the influence of miR-1246 in carcinogenesis in addition to studies that measured expression levels of miR-1246 in clinical samples.

Keywords: MiR-1246; biomarker; cancer; diagnosis; expression; in vitro; in vivo; miRNA

DOI: 10.3389/fmolb.2021.771835

Identification of expression of CCND1-related lncRNAs in breast cancer

Abstract

Cyclin D1 has been shown to participate in the pathogenesis of breast cancer. This cell cycle-related protein has direct or indirect interactions with long non-coding RNAs (lncRNAs). In the present two-step study, we first identified CCND1-related lncRNAs through an in silico approach. Then, we measured expression of CCND1 mRNA and five lncRNAs in paired breast cancer samples and their matched non-cancerous samples obtained from adjacent tissues. HOTTIP expression was significantly higher in breast cancer tissues compared with adjacent tissues (expression ratio (95% CI)= 4.63 (1.56-13.76), P value= 0.0070). Similarly, CBR3-AS1 was up-regulated in cancerous tissues compared with control tissues (expression ration (95% CI)= 3.26 (1.35-7.86), P value= 0.0122). Expression of HOTTIP was higher in estrogen receptor (ER) negative samples compared with ER positive ones (-4.35 ± 1.33 versus -4.63 ± 0.62, P value=0.002). CBR3-AS1 could differentiate between these two sets of samples with AUC±SD, sensitivity, specificity and P values of 0.7 ± 0.05, 0.9, 0.49 and 0.003, respectively. These values were 0.68 ± 0.04, 0.87, 0.34 and 0.04 for HOTTIP. Although we could not find difference in expression of CCND1 between these two sets of samples, we reported up-regulation of two CCND1-related lncRNAs in breast cancer samples. These lncRNAs are putative markers for breast cancer.

Keywords: Breast cancer; CCND1; LncRNA

DOI: 10.1016/j.prp.2022.154009

Association analysis of MALAT1 polymorphisms and risk of psoriasis among Iranian patients

Abstract

MALAT1 is a long non-coding transcript that affects immune reactions, thus being involved in the pathoaetiology of immune-related conditions. We investigated the associations between two genetic variants in MALAT1 and susceptibility to psoriasis in the Iranian population. The G allele of rs619586 has been shown to be less common among cases versus controls (odds ratios (OR; 95% confidence intervals (CI)) = 0.57 (0.36-0.9)), adjusted p = .02). This single nucleotide polymorphism has been associated with the risk of psoriasis in a dominant model (AG + GG vs. AA: OR (95% CI) = 0.56 (0.35-0.92), adjusted p = .04) as well as log-additive model (OR (95% CI) = 0.59 (0.38-0.92), adjusted p = .04). The rs3200401 was not associated with psoriasis in any of the supposed inheritance models. This study potentiates rs619586 as a risk locus for psoriasis in the Iranian population.

Keywords: MALAT1; lncRNA; psoriasis; rs3200401; rs619586

DOI: 10.1111/iji.12562

Elderberry Diet Restores Spermatogenesis in the Transient Scrotal Hyperthermia-Induced Mice

Abstract

Over the past years, several studies have also reported the adverse effects of hyperthermia on normal testicular tissues in several species including mice, rats, and humans. These deleterious impacts include temporarily drop in relative weight of testis along with a temporary partial or complete infertility. Sambucus nigra, also known as elderberry or sweet elder, is a source of bioactive compounds that has drawn growing attention for its potential beneficial effects in preventing and treating several diseases. This experimental research divided 30 mice into the following three groups: (1) control, (2) hyperthermia, and (3) hyperthermia receiving elderberry diet for 35 days. Scrotal hyperthermia was induced by water bath with 43 °C for 30 min. Then, the mice were euthanized, and their sperm samples were collected for sperm parameters analysis. Then, we took the testis samples for histopathological experimentations, immunohistochemistry against TNF-α and caspase-3 and serum testosterone, FSH and LH levels. Our outputs indicated that elderberry diet could largely improve the sperms parameters and stereological parameters, like spermatogonia, primary spermatocyte, round spermatid, and Leydig cells together with an increasing level of the serum testosterone compared to the scrotal hyperthermia induced mice. In addition, it was found that the expression of TNF-α and caspase-3 significantly decreased in the treatment groups by elderberry diet compared to the scrotal hyperthermia-induced mice. In conclusion, it could be concluded that elderberry diet may be regarded as an alternative treatment for improving the spermatogenesis process in the scrotal hyperthermia induced mice.

LINK: https://link.springer.com/article/10.1007/s43032-022-00865-7

Accuracy of SelectMDx compared to mpMRI in the diagnosis of prostate cancer: a systematic review and diagnostic meta-analysis

Abstract

Background: The SelectMDx test is a promising biomarker that is developed based on detecting urinary messenger RNA in combination with clinical prostate cancer (PCa) risk factors. We aimed to compare SelectMDx and mpMRI as a diagnostic test in detecting PCa and high grade(HG)-PCa in men suspected to have PCa.

Methods: According to PRISMA, a systematic search was performed using major web databases for studies published before September 30, 2021. Studies that compared sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SelectMDx and/or mpMRI were included. The bivariate random model that plotted sensitivity, specificity, PPV, NPV, and likelihood ratio (LR) for PCa and HG-PCa detection was applied to compare SelectMDx, mpMRI, and combination strategies (both positive and one or both positive).

Results: Seven studies comprising 1328 patients who had undergone SelectMDx and mpMRI to detect PCa were included. Regarding PCa detection, SelectMDx had a pooled sensitivity of 81%, specificity of 69.8%, PPV of 64.7%, NPV of 85%, and LRs of +2.68 to -0.27, while mpMRI had a pooled sensitivity of 80.8%, specificity of 73.4%, PPV of 72.4%, NPV of 83.5%, and LRs of +3.03 to -0.26. The one or both positive strategy had the highest sensitivity (96.3%), NPV (95.7%), and the lowest -LR (0.06). While the both positive strategy had the highest specificity (80.9%), the PPV (76.5%) and +LR (3.68). In the scenario of PI-RADS 3 lesions not being biopsied in case of a negative SelectMDx (n = 44), unnecessary biopsies would be reduced by 42% (44/105) while the risk of missing HG-PCa would be 9% (4/44).

Conclusion: The performance of SelectMDx is comparable to that of mpMRI with regards to PCa and HG-PCa detection. In addition, this biomarker could help refine the clinical decision-making regarding the necessity of a biopsy in patients suspected to has been PCa.

DOI: 10.1038/s41391-022-00538-1

Comparison of Clinicopathologic and Oncological Outcomes Between Transurethral En Bloc Resection and Conventional Transurethral Resection of Bladder Tumor: A Systematic Review, Meta-Analysis, and Network Meta-Analysis with Focus on Different Energy Sources

Abstract

Introduction: It has been hypothesized that transurethral en bloc (TUEB) of bladder tumor offers benefits over conventional transurethral resection of bladder tumor (cTURBT). This study aimed to compare disease outcomes of TUEB and cTURBT with focus on the different energy sources. Methods: A systematic search was performed using PubMed and Web of Science databases in June 2021. Studies that compared the pathological (detrusor muscle presence), oncological (recurrence rates) efficacy, and safety (serious adverse events [SAEs]) of TUEB and cTURBT were included. Random- and fixed-effects meta-analytic models and Bayesian approach in the network meta-analysis was used. Results: Seven randomized clinical trials (RCTs) and seven non-RCTs (NRCT), with a total of 2092 patients. The pooled 3- and 12-month recurrence risk ratios (RR) of five and four NRCTs were 0.46 (95% CI 0.29-0.73) and 0.56 (95% CI 0.33-0.96), respectively. The pooled 3- and 12-month recurrence RRs of four and seven RCTs were 0.57 (95% CI 0.25-1.27) and 0.89 (95% CI 0.69-1.15), respectively. The pooled RR for SAEs such as prolonged hematuria and bladder perforation of seven RCTs was 0.16 (95% CI 0.06-0.41) in benefit of TUEB. Seven RCTs (n = 1077) met our eligibility criteria for network meta-analysis. There was no difference in 12-month recurrence rates between hybridknife, laser, and bipolar TUEB compared with cTURBT. Contrary, laser TUEB was significantly associated with lower SAEs compared with cTURBT. Surface under the cumulative ranking curve ranking analyses showed with high certainty that laser TUEB was the best treatment option to access all endpoints. Conclusion: While NRCTs suggested a recurrence-free benefit to TUEB compared with cTURBT, RCTs failed to confirm this. Conversely, SAEs were consistently and clinically significantly better for TUEB. Network meta-analyses suggested laser TUEB has the best performance compared with other energy sources. These early findings need to be confirmed and expanded upon.

Keywords: TUEB; TURBT; bladder cancer; en bloc; transurethral en bloc; transurethral resection

DOI: 10.1089/end.2021.0688

Contrast-enhanced voiding urosonography, a possible candidate for the diagnosis of vesicoureteral reflux in children and adolescents; a systematic review and meta-analysis

Abstract

Introduction: The diagnostic value of contrast-enhanced voiding urosonography (ceVUS) in the diagnosis of vesicoureteral reflux (VUR) is still a subject of dispute. Objective: Assessing the diagnostic value of ceVUS in VUR, performing a systematic review and meta-analysis. Methods: An extensive search on Medline, Embase, Scopus and Web of Science databases was conducted by the end of 2020. The inclusion criteria were studies on the diagnostic value of ceVUS for VUR. Two independent researchers summarized the included articles and the findings were reported as area under the curve (AUC), sensitivity and specificity with a 95% confidence interval (95% CI). Results: Finally, the data of 36 articles were included in the present meta-analysis (2768 children). The VUS assessment showed that 1297 of the cases were true positives, 3661 were true negatives, 398 were false positives and 169 were false negatives. The AUC, sensitivity and specificity of ceVUS with the first-generation contrast agent in the diagnosis of VUR in children and adolescents were obtained as 0.97 (95% CI: 0.95, 0.98), 0.92 (95% CI: 0.86, 0.96) and 0.94 (95% CI: 0.95, 0.98), respectively. Moreover, AUC, sensitivity and specificity of ceVUS with the second-generation contrast agent were 0.97 (95% CI: 0.95, 0.98), 0.93 (95% CI: 0.86, 0.97) and 0.91 (95% CI: 0.86, 0.95). Conclusion: The findings of the present study showed that diagnostic value of ceVUS with both first-generation and second-generation contrast agents for VUR, is in an excellent range. Although it seems that ceVUS may be applied as a radiation-free alternative to imaging techniques such as VCUG, the presence of 3% of false negatives in this test is a limitation. Since the lack of punctual management of VUR is associated with serious renal complications in children, future studies are recommended to be focused on the evaluation of the Benefit-risk evaluation of ceVUS.

DOI: https://doi.org/10.1016/j.jpurol.2021.10.023

En Bloc Resection for Bladder Tumors: An Updated Systematic Review and Meta-Analysis of Its Differential Effect on Safety, Recurrence and Histopathology

Abstract

Purpose: En bloc resection for bladder tumors has been developed to overcome shortcomings of conventional transurethral resection of bladder tumors with regard to safety, pathological evaluation and oncologic outcomes. However, the potential benefits and utility compared to conventional transurethral resection of bladder tumors have not been conclusively demonstrated. We aimed to update the current evidence with focus on the pathological benefits of en bloc resection for nonmuscle-invasive bladder cancer. Materials and methods: The PubMed®, Web of Science™ and Scopus® databases were searched in August 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they compared safety, and pathological and clinical outcomes in patients who underwent en bloc resection with conventional transurethral resection of bladder tumors. Results: Overall, 29 studies comprising 4,484 patients were eligible for this meta-analysis. Among 13 randomized controlled trials, the pooled 12- and 24-month recurrence risk ratios were not statistically different between the 2 surgical techniques (0.96, 95% CI 0.74-1.23 and 0.83, 95% CI 0.55-1.23, respectively). The pooled risk ratio for bladder perforation was 0.13 (95% CI 0.05-0.34) in favor of en bloc resection. In randomized controlled trials, the differential rates of detrusor muscle presence (pooled RR 1.31, 95% CI 1.19-1.43) and of detectable muscularis mucosae (pooled RR 2.69, 95% CI 1.81-3.97) were more likely in patients receiving en bloc resection. Patients who underwent en bloc resection had a lower rate of residual tumor at repeat transurethral resection than those treated with conventional transurethral resection of bladder tumors in 1 randomized controlled trial and 3 observational studies (pooled RR 0.47, 95% CI 0.31-0.71). Conclusions: En bloc resection for bladder tumors seems to be safer, and to yield superior histopathological information and performance compared to conventional transurethral resection of bladder tumors. Despite the failure to improve the recurrence rate, the more accurate histopathological analysis is likely to improve clinical decision making and care delivery in nonmuscle-invasive bladder cancer.

Keywords: pathology; recurrence; urinary bladder neoplasms.

DOI: 10.1097/JU.0000000000002444

Sitagliptin/metformin improves the fertilization rate and embryo quality in polycystic ovary syndrome patients through increasing the expression of GDF9 and BMP15: A new alternative to metformin (a randomized trial)

Abstract

The aim of this study was to investigate the effects of sitagliptin/metformin (sitaformin), metformin and sitagliptin in PCOS patients. PCOS is a hormonal disorder and therefore the use of treatments that modulate hormone levels Like AMH, testosterone, insulin, leptin and especially FAI and HOMA-IR can reclaim the symptoms of PCOS. PCOS also increases oxidative stress and lipid peroxidation. Therefore, in clinical and research trials, the level of these factors is usually examined to reduce patients symptoms. Participants were randomly assigned to receive metformin, sitagliptin, sitaformin or placebo Treatment was carried out 2 months before the start of the ovulation cycle and continued until the day of ovum pick up. The serum levels of HOMA-IR and FAI decreased significantly in the treated groups compared to the placebo. The serum and the FF levels of leptin also decreased significantly in the sitaformin group when compared to the metformin and sitagliptin groups. Moreover, the serum and FF levels of AMH and MDA had a significant decrease in the sitaformin and sitagliptin group compared to the placebo. The mRNA expression and protein levels of GDF9 and BMP15 in the cumulus cells increased significantly in the sitaformin compared to metformin and sitagliptin groups. The expression level of GDF9 and BMP15 mRNA were positively correlated with the fertilization rate and grade I embryos. Sitaformin improves levels of GDF9 and BMP15 in PCOS compared to metformin and sitagliptin, which can increase the rate of fertilization and grade I embryos.

DOI: https://doi.org/10.1016/j.jri.2022.103499

Impact of the preoperative modified Glasgow Prognostic Score on disease outcome after radical cystectomy for urothelial carcinoma of the bladder

Abstract

Background: To investigate the predictive and prognostic value of the preoperative modified Glasgow Prognostic Score (mGPS) in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Methods: We conducted a retrospective analysis of an established multicenter database consisting of 4335 patients who were treated with RC±adjuvant chemotherapy for UCB between 1979 and 2012. The mGPS of each patient was calculated on the basis of preoperative serum C-reactive protein and albumin. Uni- and multivariable logistic and Cox regression analyses were performed. The discriminatory ability of the models was assessed by calculating the area under receiver operating characteristics curves (AUC) and concordance-indices (C-Index). The additional clinical net-benefit was assessed using the decision curve analysis (DCA). Results: A mGPS of 0, 1, and 2 was observed in 3,158 (72.8%), 1,020 (23.5%), and 157 (3.6%) patients, respectively. On multivariable logistic regression analyses, mGPS of 1 or 2 were associated with an increased risk of pT3/4 disease at RC (OR 1.25, P=0.004 and OR 2.58, SP<0.001, respectively) and/or lymph node metastasis (OR 1.7, P<0.001 and OR 3.9, P<0.001, respectively). Addition of the mGPS to a predictive model based on preoperatively available variables improved its accuracy for prediction of lymph node metastasis (change of AUC +3.7%, P<0.001). On multivariable Cox regression analyses, mGPS of 1 or 2 remained associated with worse recurrence-free survival (HR 1.14, P=0.03 and HR 1.89 P<0.001, respectively), cancer-specific survival (HR 1.16, P=0.032 and HR 2.1, P<0.001, respectively) and overall survival (HR 1.5, P=0.007 and HR 1.92 P<0.001, respectively) compared to mGPS of 0. The additional discriminatory ability of the mGPS for prognosis of survival outcomes in separate models that included either established pre- or postoperative variables did not improve the C-Index by a prognostically relevant degree (change of C-Index <2% for all models). On DCA, the inclusion of the mGPS did not meaningfully improve the net-benefit for clinical decision-making regarding survival outcomes. Conclusions: We confirmed that an elevated mGPS is an independent risk factor for non-organ confined disease and poor survival outcomes in patients with UCB undergoing RC. However, the mGPS showed little value in improving the discriminatory ability of predictive and prognostic models that relied on either pre- or postoperative clinicopathological variables. The discriminatory ability of this biomarker in the age of immunotherapy warrants further evaluation.

DOI: 10.23736/S2724-6051.21.04216-6

miR-106b-5p Intensifies the Proliferative Potential of Spermatogonial Stem Cells as a Prerequisite for Male Infertility Treatment

Abstract

Background: Although numerous studies have investigated the molecular basis of male infertility, various aspects of this area have remained uncovered. Over the past years, researchers have reported the significant potential of miRNAs in posttranscriptional regulatory roles. By targeting mRNAs, these notable molecules can modulate the processes related to male infertility. On the other side, the outstanding potential of male germline stem cells, SSCs, includes their application in infertility treatment. SSCs retain normal spermatogenesis and fertility by adjusting both SSC self-renewal and differentiation. Therefore, for the characterization and manipulation of SSCs, effective and efficient in vitro culture methods are essential in supporting their maintenance and development. In this regard, the present investigation was undertaken to evaluate the impact of one of the recently conspicuous miRNAs, miR-106b, in SSCs enrichment. As a result, we first found that the SSCs induced with miR-106b-5p highly express TGF-β1, which is known as a regulator of epigenetic modifiers and downstream genes. We next sought to show that self-renewal markers, including c-Myc, Oct-4, and Sox2, are increased in the induced SSC group. The intended miRNA also induced the inhibitor of differentiation 4 (ID4) and aided to remain unmethylated in SSCs. Additionally, for the tumorigenicity possibility of the manipulation, we indicated that PTEN, a tumor-suppressor gene, expressed remarkably in the induced SSCs. In conclusion, our findings showed that miR-106b-5p enhances the proliferative potential of SSCs, making it a substantial factor for therapeutic strategies of male infertility.

DOI:10.1007/s43032-022-00884-4

Relationship between long-term use of Ritalin and semen parameters in patients referred to psychiatric centres

Abstract

Some studies have shown that Ritalin can interfere with the growth and development of the reproductive system and can also have a serious and harmful effect on sperm parameters, so we decided to conduct studies in this field on the human sample. In a case-control study, 100 adult men aged 21-31 years with hyperactivity were divided into two groups of 50 past users and 50 current users and, 50 patients who had not used Ritalin before were included as the control group. Data were analysed using SPSS software, version 20. Analysis of variance, Pearson correlation coefficient, and regression analysis was used to assess the correlation between variables. The results also showed that there was a statistically significant difference between the current users and the control group in terms of sperm count, abnormality, and motility (p < .47). Comparison of the user group in the past and the control group showed that there was no statistically significant difference in terms of sperm count (p < .59), but there was a significant difference in terms of sperm motility and abnormality between the two groups (p < .001). The present study showed that long-term use of Ritalin can have negative effects on sperm parameters in humans.

Keywords: ADHD; Ritalin; psychiatric; semen parameters.

DOI: 10.1111/and.14594

Chemotherapy is superior to checkpoint inhibitors after radical surgery for urothelial carcinoma: a systematic review and network meta-analysis of oncologic and toxicity outcomes

Abstract

Objective To determine the oncologic and toxicity outcomes of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) compared to adjuvant chemotherapy in patients treated with radical surgery for urothelial carcinoma (UC). Methods We used the Bayesian approach in the network meta-analysis of different therapy regimens compared to observation or placebo. Results Nine studies comprised of 2,444 patients met the eligibility criteria. In bladder UC, chemotherapy, atezolizumab, and nivolumab did not improve disease progression compared to observation/placebo. In upper tract UC (UTUC), chemotherapy was significantly associated with a lower likelihood of disease progression compared to observation/placebo, while atezolizumab and nivolumab were not. Based on the analysis of the treatment ranking, adjuvant chemotherapy appeared as the best treatment approach in both bladder UC and UTUC. The risk of adverse events with ICIs was comparable to that of observation/placebo. Conclusion Our analysis suggests a superior oncologic benefit to adjuvant chemotherapy over ICIs in patients treated with radical surgery for both bladder UC and UTUC.

Keywords: urothelial carcinomaadjuvant therapyICIPD-L1PD-1chemotherapy

Emerging role of non-coding RNAs in the course of HIV infection