Testicular piRNA Analysis Identified Dysregulated piRNAs in Non-obstructive Azoospermia.

Male infertility has remained idiopathic in a remarkable proportion of all cases. Gonadal expression of PIWI-interacting RNAs (piRNAs) has been shown to be vital to normal spermatogenesis, as they are expressed in almost all types of testicular germ cells. These molecules and their related Piwi proteins strictly regulate transposable elements' activity and gene expression. We aimed to identify dysregulated piRNAs in idiopathic non-obstructive azoospermic (NOA) testis by global expression analysis. Testis tissue samples from 18 azoospermic patients (ten NOA and eight OA) were studied by small RNA sequencing. To validate high-throughput sequencing data, quantitative real-time polymerase chain reactions for two differentially altered piRNAs were performed. Bioinformatics analyses were undertaken to identify pathways affected by piRNA dysregulation. In the NOA group, 1328 piRNAs were identified to be differentially expressed, of which 1322 were downregulated and 6 were upregulated. Bioinformatics analysis corroborated the involvement of dysregulated piRNA in spermatogenesis. We also identified 64 clusters of differentially expressed piRNAs, of which 42 clusters had a minimum of ten absolute piRNA hits. Our study suggests that piRNAs show significant dysregulation in infertility. Their target genes play a role in their self-biogenesis, probably by regulating their own production through a feedback mechanism. The downregulated piRNAs may find value as biomarkers for the presence of spermatozoa in the testis of azoospermic individuals, while the upregulated piRNAs are great candidates for further investigation of their precise functions in spermatogenesis.

The prognostic value of estimated glomerular filtration rate on admission for death within 30 days among COVID-19 inpatients using fractional polynomial and spline smoothing.

BACKGROUND: The common regression models included estimated glomerular filtration rate (eGFR) in the continuous and categorical form for predicting the mortality in COVID-19 inpatients. However, the relationship may be non-linear, and categorizing implies a loss of information. This study aimed to assess the effect of eGFR on admission on death within 30 days among COVID-19 inpatients using flexible and smooth transformations of eGFR and compare the results against the common models. METHODS: A retrospective study was conducted on hospitalized COVID-19 patients between April 2019 and July 2019 in Hamadan, Western Iran. The effect of eGFR on the death within 30 days was evaluated using different modeling: categorization, linear, unrestricted cubic spline (USC) with 4 knots, and fractional polynomial (FP). The results adjusted for older age and intensive care unit (ICU) admission. Discrimination power and model performance of the best-fitting model was evaluated using the area under the ROC (AUROC) and Brier score. RESULTS: In total, 2945 patients (median age 61 years; interquartile range 48-73 years) were included, of whom the mortality rate was 9.23%. The relationship between the eGFR and death within 30 days is non-linear, so the degree-2 FP with powers (- 2, - 1) is the best-fitting model. Using the FP model, the risk increased exponentially in eGFR < 45 and then increased linearly and slowly. The AUROC of the FP model involving eGFR, older age, and ICU admission was 0.92 (95% CI 0.90-0.93) with a Brier score of 0.09. CONCLUSION: There is a non-linear and asymmetric relationship between eGFR and death within 30 days among COVID-19 inpatients. Kidney function can be measured in COCID-19 patients on admission to know better understanding about prognosis of the patients.

Comparison of Diagnostic Value between 99mTechnetium-Methylene Diphosphate Bone Scan and 99mTechnetium-Prostate-specific Membrane Antigen Scan in Patients with Prostate Cancer with Osseous Metastases.

Background: Prostate cancer (PCa) ranks as the second most prevalent cancer among men globally. The utilization of efficient and cost-effective diagnostic and therapeutic approaches holds paramount importance in the diagnosis and treatment of these patients, significantly impacting treatment outcomes. This study focuses on the investigation and comparison of two commonly employed scans within the treatment process for these patients. Methods: In this prospective study, which spanned over 2 years, 40 patients diagnosed with PCa underwent examination using two scans: 99m Technetium-Prostate-specific Membrane Antigen (99mTC-PSMA) Scan and between Technetium-Methylene Diphosphate (99mTC-MDP) Bone Scan. The findings of these scans were then compared with each other, as well as with the results obtained from magnetic resonance imaging and the prostate-specific antigen level. The analysis of the results was conducted utilizing SPSS 22 software, and descriptive statistical methods were employed to present the findings. Results: In this prospective study, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the 99mTC-MDP Bone Scan were found to be 88.2%, 83.3%, 96.7%, 55.5%, and 87.5%, respectively. Similarly, for the 99mTC-PSMA Scan, the corresponding values were 94.1%, 83.3%, 96.4%, 83.3%, and 92.5%, respectively. Conclusions: Based on the findings of this study, it can be concluded that the diagnostic accuracy of the 99mTC-PSMA Scan is marginally higher compared to the 99mTC-MDP Bone Scan. Therefore, for patients who are limited to only one scan, the 99mTC-PSMA Scan appears to be the preferable choice.

Prostate Specific Antigen Nadir After Radical Cystoprostatectomy in Patients With Benign Prostatic Tissue: A Benchmark To Define Biochemical Recurrence after Radical Prostatectomy.

PURPOSE: Biochemical failure after radical prostatectomy has been defined based on retrospective studies in men who underwent RP for localized prostate cancer. Nevertheless, retrospective strategy and possibility of extra-prostatic extension overshadowed the accurateness of the aforementioned cut-off value. To define a more precise PSA nadir value, we estimated serum PSA after cystoprostatectomy in cases with bladder urothelial cancer and no evidence of prostate cancer. MATERIALS AND METHODS: Study population consists of 52 subsequent patients who underwent radical cystoprostatectomy for muscle-invasive bladder cancer between December 2010 and December 2013. Patients with prostate adenocarcinoma and/or high grade prostate intraepithelial neoplasia were excluded from enrollment. Other exclusion criteria were prostate involvement with urothelial carcinoma, neoadjuvant or adjuvant chemotherapy and radiation therapy. Between all cases, 41 were enrolled for study. Serum PSA level was measured using immunochemiluminescence method among 6 months to 3 years after operation in study participants. RESULTS: Forty-one patients with mean age of 66.4 ± 8.9 were assessed in this study. Average serum PSA level after radical cysto-prostatectomy was .037 ± .031 ng/mL (from .002 to .1). Serum PSA level was not impressed with type of diversion or interval between operation and PSA measurement. Average serum PSA level in this study was meaningfully lesser than .2 ng/mL which is contemplated as PSA nadir value after RP. CONCLUSION: Serum PSA level of 0.2 ng/mL as the definition for biochemical recurrence after RP may delay salvage treatment. Our results showed that cut off value of ?0.1 ng/mL may be more precise in the era of early salvage treatment.

Prophylactic effect of mycophenolate mofetil on early outcomes of living donor kidney transplantation.

INTRODUCTION: Living donor transplantation allows a priori scheduling and the recipient can receive immunosuppressive prophylaxis several days before surgery, which is preoperative induction therapy with oral agents. We evaluated the impact of preoperative mycophenolate mofetil on the outcomes of living donor kidney transplantations. MATERIALS AND METHODS: In a randomized controlled trial was from November 2008 to November 2010, 99 patients receiving their first living donor kidney transplantation were divided into the mycophenolate mofetil (500 mg) and placebo groups, and received 2 tablets per day for 5 days before transplantation. RESULTS: Forty-nine patients received mycophenolate mofetil and 48 received placebo. The mean serum creatinine on discharge day and hospitalization period were significantly less with mycophenolate mofetil compared to placebo (1.62 ± 1.00 mg/dL versus 1.22 ± 0.24 mg/dL, P = 0.03 and 20.8 ± 11.2 days versus 13.5 ± 4.4 days, P < .001, respectively). No delayed graft function was observed. Slow graft function was 2-fold higher in the placebo group (14.6% versus 8.2%, P = .32). Acute rejection was seen in 12.2% of the patients with mycophenolate mofetil and in 29.2% of the controls (P = .04). Serum creatinine levels at discharge were significantly lower in the mycophenolate mofetil group compared with that in the placebo group (P = .03). CONCLUSIONS: Prophylactic administration of mycophenolate mofetil before living donor kidney transplantation reduced hospitalization period, improved early graft function, and decreased the risk of acute rejection in the first month posttransplant.

Does inhibin-B help us to confidently refuse diagnostic testicular biopsy in azoospermia?

BACKGROUND: In the recent years, the use of laboratory blood factors such as FSH and inhibin-B for the assessment of spermatogenesis in different studies has increased; of course, the conflicting results have also been achieved. OBJECTIVE: To investigate if the measurement of inhibin-B can help surgeon to reduce unnecessary diagnostic testicular biopsies in males with azoospermia. MATERIALS AND METHODS: This cross-sectional study was done during July 2006 to September 2007 on 41 patients with azoospermia. FSH and inhibin-B were measured and bilateral open testicular biopsy was performed for all patients. RESULTS: Sperm was seen in 29% of biopsies that in 100% of these samples inhibin-B was more than 100 pg/mL and FSH was less than twice the normal (p=0.001). Inhibin-B had significant correlation inversely with testicular fibrosis and Sertoli cell only syndrome (p=0.043 and p=0.011, respectively) and directly with incomplete spermatocytic maturation arrest and obstructive azoospermia (p=0.027 and p=0.013, respectively). FSH was only correlated with obstructive azoospermia (p=0.001). CONCLUSION: We suggest that if FSH is less than twice the normal, inhibin-B should be measured and if its level is less than 100 pg/mL, we can cancel about the half of unnecessary diagnostic testicular biopsies.

Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility: a comparative study.

PURPOSE: To compare the effects of L-carnitine with clomiphene citrate in idiopathic infertile men. MATERIALS AND METHODS: Fifty-two men with idiopathic infertility were recruited in this randomized controlled trial. They were randomly assigned into 2 treatment groups, group 1 (n = 20) and group 2 (n = 32), who received L-carnitine 25 mg/day and clomiphene citrate 2 gr/day, respectively, for a period of 3 months. RESULTS: Comparing the effect of L-carnitine and clomiphene on sperm parameters before and after the treatment, both medications had influence on sperm count and motility (P = .01). L-carnitine significantly increased the semen volume (P = .001), while clomiphene citrate was significantly associated with the motility percentage and normal morphology (P = .008). CONCLUSION: It seems that the use of clomiphene citrate and L-carnitine, either individually or in combination, as the first step of idiopathic male infertility treatment is reasonable, safe, and effective.