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   Table of Contents - Current issue
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January-February 2020
Volume 22 | Issue 1
Page Nos. 1-122

Online since Friday, January 3, 2020

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INVITED EDITORIAL  

Prosthetic urology: past, present, and future p. 1
Peter N Tsambarlis, Wayne J G Hellstrom
DOI:10.4103/aja.aja_102_19  PMID:31571641
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INVITED REVIEW Top

Epidemiology regarding penile prosthetic surgery p. 2
Jose A Saavedra-Belaunde, Jonathan Clavell-Hernandez, Run Wang
DOI:10.4103/aja.aja_124_19  PMID:31793443
With the onset of a metabolic syndrome epidemic and the increasing life expectancy, erectile dysfunction (ED) has become a more common condition. As incidence and prevalence increase, the medical field is focused on providing more appropriate therapies. It is common knowledge that ED is a chronic condition that is also associated with a myriad of other disorders. Conditions such as aging, diabetes mellitus, hypertension, obesity, prostatic hypertrophy, and prostate cancer, among others, have a direct implication on the onset and progression of ED. Characterization and recognition of risk factors may help clinicians recognize and properly treat patients suffering from ED. One of the most reliable treatments for ED is penile prosthetic surgery. Since the introduction of the penile prosthesis (PP) in the early seventies, this surgical procedure has improved the lives of thousands of men, with reliable and satisfactory results. The aim of this review article is to characterize the epidemiology of men undergoing penile prosthetic surgery, with a discussion about the most common conditions involved in the development of ED, and that ultimately drive patients into electing to undergo PP placement.
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Risk profiling in patients undergoing penile prosthesis implantation p. 8
Linda M Huynh, Mohamad M Osman, Faysal A Yafi
DOI:10.4103/aja.aja_92_19  PMID:31489849
Penile prosthesis implantation is the gold standard of surgical therapy for patients with medication-refractory erectile dysfunction. However, this umbrella definition includes significant heterogeneity and associated risk profiles that should be candidly discussed and addressed perioperatively. Factors associated with operative success and patient satisfaction are often surgery specific; however, risk profiling via patient selection, preoperative optimization, proper device selection, and intraoperative consideration are highly correlated. Some examples of common risk profiles include comorbidity(ies) such as cardiovascular disease, diabetes mellitus, prior abdominal surgery, Peyronie's disease, and psychological risk factors. Similarly, integration of surgeon- and patient-amenable characteristics is key to decreasing risk of infection, complication, and need for revision. Finally, patient risk profiling provides a unique context for proper device selection and evidence-based intraoperative considerations.
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Biomedical engineering and erectile restoration: design considerations for urologic prosthetics p. 15
Jonathan J Lund
DOI:10.4103/aja.aja_115_19  PMID:31719264
For patients with moderate-to-severe erectile dysfunction, implantable penile prostheses continue to be a viable treatment. Medical device developers apply design controls during the development cycle to ensure that a product performs as intended in the final use environment. This process relies heavily on the principles of systems engineering and documents every facet of performance, unmet need, and risk. To better understand design philosophy, it is important to frame benchmarked performance outcomes in the context of the ideal state. Careful consideration of erectile anatomy and physiology, including flaccid state, transitional phases, and full tumescence, informs penile prosthesis design philosophy and provides the foundation for product advancement.
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Fundamentals of prosthetic urology p. 20
Kole P Akula, Omer A Raheem
DOI:10.4103/aja.aja_108_19  PMID:31696834
The field of prosthetic urology demonstrates the striking impact that simple devices can have on quality of life. Penile prosthesis and artificial urinary sphincter implantation are the cornerstone procedures on which this specialty focuses. Modern research largely concentrates on decreasing the rates of complication and infection, as the current devices offer superior rates of satisfaction when revision is not necessary. These techniques are also able to salvage sexual function and continence in more difficult patient populations including female-to-male transgender individuals, those with ischemic priapism, and those with erectile dysfunction and incontinence secondary to prostatectomy. This review summarizes modern techniques, outcomes, and complications in the field of prosthetic urology.
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Updates in penile prosthesis infections p. 28
Amanda R Swanton, Ricardo M Munarriz, Martin S Gross
DOI:10.4103/aja.aja_84_19  PMID:31489848
Inflatable penile prostheses are an important tool in the treatment of medically refractory erectile dysfunction. One of the major complications associated with these prostheses is infections, which ultimately require device explanation and placement of a new device. Over the past several decades, significant work has been done to reduce infection rates and optimize treatment strategies to reduce patient morbidity. This article reviews the current state of knowledge surrounding penile prosthesis infections, with attention to the evidence for methods to prevent infection and best practices for device reimplantation.
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Pain management strategies in penile implantation p. 34
Jeffrey L Ellis, Andrew M Higgins, Jay Simhan
DOI:10.4103/aja.aja_91_19  PMID:31464206
The opioid epidemic continues to be a serious public health concern. Many have pointed to prescription drug misuse as a nidus for patients to become addicted to opioids and as such, urologists and other surgical subspecialists must critically define optimal pain management for the various procedures performed within their respective disciplines. Controlling pain following penile prosthesis implantation remains a unique challenge for urologists, given the increased pain patients commonly experience in the postoperative setting. Although most of the existing urological literature focuses on interventions performed in the operating room, there are many studies that examine the role of preoperative adjunctive pain medicine in diminishing postoperative narcotic requirements. There are relatively few studies looking at postoperative strategies for managing pain in prosthetic surgery with follow-up past the immediate hospitalization. This review assess the various strategies employed for managing pain following penile implantation through the lens of the current state of the opioid crisis, thus examining how urologists can responsibly treat pain without contributing to the growing threat of opioid addiction.
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Penile prosthesis implant in the special populations: diabetics, neurogenic conditions, fibrotic cases, concurrent urinary continence surgery, and salvage implants p. 39
Eric Chung
DOI:10.4103/aja.aja_127_19  PMID:31793445
Penile prosthesis implant (PPI) remains an effective and safe treatment option for men with erectile dysfunction (ED). However, PPI surgery can be associated with a higher risk of complications in certain populations. This article provides a critical review of relevant publications pertaining to PPI in men with diabetes, significant corporal fibrosis, spinal cord injury, concurrent continence surgery, and complex salvage cases. The discussion of each category of special populations includes a brief review of the surgical challenges and a practical action-based set of recommendations. While specific patient populations posed considerable challenges in PPI surgery, strict pre- and postoperative management coupled with safe surgical practice is a prerequisite to achieving excellent clinical outcomes and high patient satisfaction rate.
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Artificial urinary sphincter surgery in the special populations: neurological, revision, concurrent penile prosthesis and female stress urinary incontinence groups p. 45
Eric Chung
DOI:10.4103/aja.aja_128_19  PMID:31793444
The artificial urinary sphincter (AUS) remains the standard of care in men with severe stress urinary incontinence (SUI) following prostate surgery and radiation. While the current AUS provides an effective, safe, and durable treatment option, it is not without its limitations and complications, especially with regard to its utility in some “high-risk” populations. This article provides a critical review of relevant publications pertaining to AUS surgery in specific high-risk groups such as men with spinal cord injury, revision cases, concurrent penile prosthesis implant, and female SUI. The discussion of each category includes a brief review of surgical challenge and a practical action-based set of recommendations. Our increased understandings of the pathophysiology of various SUI cases coupled with effective therapeutic strategies to enhance AUS surgery continue to improve clinical outcomes of many patients with SUI.
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Modern treatment strategies for penile prosthetics in Peyronie's disease: a contemporary clinical review p. 51
Matthew J Ziegelmann, M Ryan Farrell, Laurence A Levine
DOI:10.4103/aja.aja_81_19  PMID:31424027
Peyronie's disease is a common condition resulting in penile deformity, psychological bother, and sexual dysfunction. Erectile dysfunction is one common comorbid condition seen in men with Peyronie's disease, and its presence significantly impacts treatment considerations. In a man with Peyronie's disease and significant erectile dysfunction who desires the most reliable treatment, penile prosthesis placement should be strongly considered. In some instances, such as those patients with relatively mild curvature, prosthesis placement alone may result in adequate straightening. However, many patients will require additional straightening maneuvers such as manual modeling, penile plication, and tunica albuginea incision with or without grafting. For patients with severe penile shortening, penile length restoration techniques may also be considered. Herein, we provide a comprehensive clinical review of penile prosthesis placement in men with Peyronie's disease. Specifically, we discuss preoperative indications, intraoperative considerations, adjunctive straightening maneuvers, and postoperative outcomes.
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Management of urethral atrophy after implantation of artificial urinary sphincter: what are the weaknesses? p. 60
Nathaniel H Heah, Ronny B W Tan
DOI:10.4103/aja.aja_110_19  PMID:31736473
The use of artificial urinary sphincter (AUS) for the treatment of stress urinary incontinence has become more prevalent, especially in the “prostate-specific antigen (PSA)-era”, when more patients are treated for localized prostate cancer. The first widely accepted device was the AMS 800, but since then, other devices have also entered the market. While efficacy has increased with improvements in technology and technique, and patient satisfaction is high, AUS implantation still has inherent risks and complications of any implant surgery, in addition to the unique challenges of urethral complications that may be associated with the cuff. Furthermore, the unique nature of the AUS, with a control pump, reservoir, balloon cuff, and connecting tubing, means that mechanical complications can also arise from these individual parts. This article aims to present and summarize the current literature on the management of complications of AUS, especially urethral atrophy. We conducted a literature search on PubMed from January 1990 to December 2018 on AUS complications and their management. We review the various potential complications and their management. AUS complications are either mechanical or nonmechanical complications. Mechanical complications usually involve malfunction of the AUS. Nonmechanical complications include infection, urethral atrophy, cuff erosion, and stricture. Challenges exist especially in the management of urethral atrophy, with both tandem implants, transcorporal cuffs, and cuff downsizing all postulated as potential remedies. Although complications from AUS implants are not common, knowledge of the management of these issues are crucial to ensure care for patients with these implants. Further studies are needed to further evaluate these techniques.
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The modern testicular prosthesis: patient selection and counseling, surgical technique, and outcomes p. 64
Solomon Hayon, Jamie Michael, R Matthew Coward
DOI:10.4103/aja.aja_93_19  PMID:31744995
The testicular prosthesis can be an afterthought for providers when performing an orchiectomy for testicular cancer, torsion, atrophic testis, or trauma. However, data suggest that patients find the offer of a testicular prosthesis and counseling regarding placement to be extremely important from both a pragmatic and a psychosocial perspective. Only two-thirds of men undergoing orchiectomy are offered an implant at the time of orchiectomy and of those offered about one-third move forward with prosthesis placement. The relatively low acceptance rate is in stark contrast with high patient satisfaction and low complication rates for those who undergo the procedure. The most common postoperative patient concerns are minor and involve implant positioning, size, and weight. Herein, we provide an up-to-date review of modern preoperative evaluation, patient selection, expectation management, surgical technique, and expected outcomes for testicular prostheses.
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Future considerations in prosthetic urology p. 70
Landon Trost
DOI:10.4103/aja.aja_103_19  PMID:31571642
Since their popularization, genitourinary prosthetics have remained a gold-standard therapy for the treatment of erectile dysfunction and stress urinary incontinence and in cases of testicular loss or dysfunction. They have also represented an area of significant innovation, which has contributed to excellent long-term outcomes. Given this history, the objective of the current review was to provide a 5–10-year outlook on anticipated trends and developments in the field of genitourinary prosthetics. To accomplish this objective, a PubMed and patent search was performed of topics relating to penile and testicular prostheses and urinary sphincters. In regard to penile prostheses, findings demonstrated several new concepts including temperature-sensitive alloys, automated pumps, devices designed specifically for neophalluses, and improved malleable designs. With artificial urinary sphincters, new concepts include the ability to add or remove fluid from an existing system, two-piece systems, and new mechanisms to occlude the urethra. For testicular prosthetics, future implementations may not only better replicate the feel of a biological testicle but also add endocrinological functions. Beyond device innovation, the future of prosthetics is also one of expanding geographic boundaries, which necessitates variable cost modeling and regulatory considerations. Surgical trends are also changing, with a greater emphasis on nonnarcotic, postoperative pain control, outpatient surgeries, and adjunctive techniques to lengthen the penis and address concomitant stress incontinence, among others. Concomitant with device and surgical changes, future considerations also include a greater need for education and training, particularly given the rapid expansion of sexual medicine into developing nations.
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INVITED RESEARCH HIGHLIGHT Top

Darolutamide: a novel androgen-signaling agent in nonmetastatic castration-resistant prostate cancer p. 76
Jeanny B Aragon-Ching
DOI:10.4103/aja.aja_52_19  PMID:31249268
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ORIGINAL ARTICLES Top

The role of tyrosine phosphatase Shp2 in spermatogonial differentiation and spermatocyte meiosis p. 79
Yang Li, Wen-Sheng Liu, Jia Yi, Shuang-Bo Kong, Jian-Cheng Ding, Yi-Nan Zhao, Ying-Pu Tian, Gen-Sheng Feng, Chao-Jun Li, Wen Liu, Hai-Bin Wang, Zhong-Xian Lu
DOI:10.4103/aja.aja_49_19  PMID:31210146
The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11–13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.
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Reduced semen quality in patients with testicular cancer seminoma is associated with alterations in the expression of sperm proteins p. 88
Tânia R Dias, Ashok Agarwal, Peter N Pushparaj, Gulfam Ahmad, Rakesh Sharma
DOI:10.4103/aja.aja_17_19  PMID:31006710
Testicular cancer seminoma is one of the most common types of cancer among men of reproductive age. Patients with this condition usually present reduced semen quality, even before initiating cancer therapy. However, the underlying mechanisms by which testicular cancer seminoma affects male fertility are largely unknown. The aim of this study was to investigate alterations in the sperm proteome of men with seminoma undergoing sperm banking before starting cancer therapy, in comparison to healthy proven fertile men (control group). A routine semen analysis was conducted before cryopreservation of the samples (n = 15 per group). Men with seminoma showed a decrease in sperm motility (P = 0.019), total motile count (P = 0.001), concentration (P = 0.003), and total sperm count (P = 0.001). Quantitative proteomic analysis identified 393 differentially expressed proteins between the study groups. Ten proteins involved in spermatogenesis, sperm function, binding of sperm to the oocyte, and fertilization were selected for validation by western blot. We confirmed the underexpression of heat shock-related 70 kDa protein 2 (P = 0.041), ubiquinol-cytochrome C reductase core protein 2 (P = 0.026), and testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (P = 0.016), as well as the overexpression of angiotensin I converting enzyme (P = 0.005) in the seminoma group. The altered expression levels of these proteins are associated with spermatogenesis dysfunction, reduced sperm kinematics and motility, failure in capacitation and fertilization. The findings of this study may explain the decrease in the fertilizing ability of men with seminoma before starting cancer therapy.
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Consecutive nightly measurements are needed for accurate evaluation of nocturnal erectile capacity when the first-night laboratory recording is abnormal p. 94
Zi-Jun Zou, Shi-Tao Chen, Gong-Chao Ma, Yu-Fen Lai, Xiao-Jian Yang, Jia-Rong Feng, Zhi-Jun Zang, Tao Qi, Bo Wang, Lei Ye, Yan Zhang
DOI:10.4103/aja.aja_40_19  PMID:31134919
Multiple measurements of nocturnal penile tumescence and rigidity (NPTR) are widely accepted as a method to differentiate psychogenic erectile dysfunction (ED) from organic ED. However, direct evidence remains limited regarding the first-night effect on NPTR measurement using the RigiScan. Here, we evaluated the first-night effect on the results of NPTR measurement to validate the necessity of NPTR measurement for two consecutive nights, particularly when abnormal first-night measurements are recorded in a laboratory setting. We retrospectively reviewed 105 patients with a complaint of ED, who underwent NPTR measurement using the RigiScan in the Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China), for two consecutive nights, during the period from November 2015 to May 2016. NPTR parameters were collected and analyzed. We found that more effective nocturnal erections were detected during the second night than during the first night (P <0.001). Twenty percent of all patients had no effective erection during the first night, but exhibited at least one effective erection during the second night. The negative predictive value of NPTR measurement during the first night was 43.2%; this was significantly lower than that on the second night (84.2%; P = 0.003). Most NPTR parameters were better on the second night than on the first night. The first-night effect might be greater among patients younger than 40 years of age. In conclusion, two consecutive nightly measurements of NPTR can avoid a false-abnormal result caused by the first-night effect; moreover, these measurements more accurately reflect erectile capacity, especially when the first-night record is abnormal in a laboratory setting.
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Altered microRNA profiles of testicular biopsies from patients with nonobstructive azoospermia p. 100
Hai-Tao Zhang, Zhe Zhang, Kai Hong, Wen-Hao Tang, De-Feng Liu, Jia-Ming Mao, Yu-Zhuo Yang, Hao-Cheng Lin, Hui Jiang
DOI:10.4103/aja.aja_35_19  PMID:31134916
Many studies have shown that microRNAs (miRNAs) play vital roles during the spermatogenesis. However, little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia (NOA). Using microarray technology, the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined. Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs. The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which were then validated with a larger sample size. Correlations between the miRNA expression levels and clinical characteristics were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia. Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups. Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis, cell cycle, and mitotic prometaphase. In the subsequent qRT-PCR assays, the selected miRNA expression levels were consistent with the microarray results, and similar validated results were obtained with a larger sample size. Some clinical characteristics were significantly associated with the expression of certain miRNAs. In particular, we identified a combination of two miRNAs (miR-10b-3p and miR-34b-5p) that could serve as a predictive biomarker of azoospermia. This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis. These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.
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The association of stromal antigen 3 (STAG3) sequence variations with spermatogenic impairment in the male Korean population p. 106
Yeojung Nam, Kyung Min Kang, Se Ra Sung, Ji Eun Park, Yun-Jeong Shin, Seung Hun Song, Ju Tae Seo, Tae Ki Yoon, Sung Han Shim
DOI:10.4103/aja.aja_28_19  PMID:31115363
The stromal antigen 3 (STAG3) gene, encoding a meiosis-specific cohesin component, is a strong candidate for causing male infertility, but little is known about this gene so far. We identified STAG3 in patients with nonobstructive azoospermia (NOA) and normozoospermia in the Korean population. The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis. A total of 30 sequence variations were identified in this study. Of the total, seven were exonic variants, 18 were intronic variants, one was in the 5'-UTR, and four were in the 3'-UTR. Pathogenic variations that directly caused NOA were not identified. However, two variants, c.3669+35C>G (rs1727130) and +198A>T (rs1052482), showed significant differences in the frequency between the patient and control groups (P = 0.021, odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.098–2.918) and were tightly linked in the linkage disequilibrium (LD) block. When pmir-rs1052482A was cotransfected with miR-3162-5p, there was a substantial decrease in luciferase activity, compared with pmir-rs1052482T. This result suggests that rs1052482 was located within a binding site of miR-3162-5p in the STAG3 3'-UTR, and the minor allele, the rs1052482T polymorphism, might offset inhibition by miR-3162-5p. We are the first to identify a total of 30 single-nucleotide variations (SNVs) of STAG3 gene in the Korean population. We found that two SNVs (rs1727130 and rs1052482) located in the 3'-UTR region may be associated with the NOA phenotype. Our findings contribute to understanding male infertility with spermatogenic impairment.
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Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord p. 112
Diego Moreno, Cristian M Sobarzo, Livia Lustig, Marcelo G Rodríguez Peña, Vanesa Anabella Guazzone
DOI:10.4103/aja.aja_30_19  PMID:31115365
The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.
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LETTERS TO THE EDITOR Top

Updating semen analysis: a subpopulation approach p. 118
Almudena Garcia-Molina, Anthony Valverde, Daznia Bompart, Carina Caldeira, Alberto Vendrell, Carles Soler
DOI:10.4103/aja.aja_33_19  PMID:31169137
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Subinguinal microsurgical varicocelectomy is safe and effective in a solitary testicle p. 120
Piotr Dobronski, Karolina Dobronska, Lukasz Kupis, Piotr Radziszewski
DOI:10.4103/aja.aja_37_19  PMID:31210150
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INVITED COMMENTARY Top

Teasing apart the multiple roles of Shp2 (Ptpn11) in spermatogenesis p. 122
Geoffrey J Maher, Anne Goriely
DOI:10.4103/aja.aja_79_19  PMID:31361219
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