Efficacy and safety of Hyadex for treatment of vesicoureteral reflux: a multicenter experience.

OBJECTIVE: This study was performed to evaluate the efficacy and safety of dextranomer/cross-linked hyaluronic acid (Hyadex) in patients with a clinical diagnosis of vesicoureteral reflux (VUR). METHODS: In this cross-sectional multicenter observational study, Hyadex was used in four different centers for the endoscopic treatment of VUR from 2020 to 2022. The study involved 74 patients (93 renal units) who were diagnosed with VUR according to voiding cystourethrography (VCUG) findings and were considered suitable for subureteric endoscopic treatment. The follow-up time (control VCUG time) was 3 months. RESULTS: In the VCUG evaluation, grade I VUR was found in 13 renal units, grade II in 23 renal units, grade III in 42 renal units, and grade IV in 12 renal units. The success rates of Hyadex treatment according to the degree of VUR were as follows: 84.6% for grade I, 82.6% for grade II, 71.4% for grade III, and 66.0% for grade IV. No major complications were observed. CONCLUSION: Endoscopic subureteric Hyadex injection had high success rates in appropriately selected patients with VUR and may be used as the first-line treatment for children with VUR.

A Retrospective Analysis of 83 Patients with Testicular Mass Who Underwent Testis-Sparing Surgery: The Eurasian Uro-oncology Association Multicenter Study.

INTRODUCTION: Herein, we analyzed the histopathological, oncological and functional outcomes of testis-sparing surgery (TSS) in patients with distinct risk for testicular cancer. METHODS: This is a multicenter retrospective study on consecutive patients who underwent TSS. Patients were categorized in high- or low-risk testicular germ cell tumor (TGCT) according to the presence/absence of features compatible with testicular dysgenesis syndrome. Histology was categorized per size and risk groups. RESULTS: TSS was performed in 83 patients (86 tumors) of them, 27 in the high-risk group. Fifty-nine patients had a non-tumoral contralateral testis present. Sixty masses and 26 masses were benign and TGCTs, respectively. No statistical differences were observed in mean age (30.9 ± 10.32 years), pathological tumor size (14.67 ± 6.7 mm) between risk groups or between benign and malignant tumors (p = 0.608). When categorized per risk groups, 22 (73.3%) and 4 (7.1%) of the TSS specimens were malignant in the high- and low-risk patient groups, respectively. Univariate analysis showed that the only independent variable significantly related to malignant outcome was previous history of TGCT. During a mean follow-up of 25.5 ± 22.7 months, no patient developed systemic disease. Local recurrence was detected in 5 patients and received radical orchiectomy. Postoperative testosterone levels remained normal in 88% of those patients with normal preoperative level. No erectile dysfunction was reported in patients with benign lesions. CONCLUSION: TSS is a safe and feasible approach with adequate cancer control, and preservation of sexual function is possible in 2/3 of patients harboring malignancy. Incidence of TGCT varies extremely between patients at high and low risk for TGCT requiring a careful consideration and counseling.

What is the impact of inflammasome mechanisms on male infertility?

BACKGROUND: Mechanisms to explain inflammation in male infertility of unknown cause are still being investigated. The inflammasome is a key regulator of innate immunity in the inflammatory response to infections. Our study aims to investigate the effects of varicocele on infertility, its relationship with antioxidant and inflammasome mechanisms, and how it could be guided in azoospermic or nonazoospermic patients. METHODS: A cross-sectional cohort study was conducted at the department of urology in our university hospital. Eightyeight randomly selected men aged 20-45 admitted to our hospital because of infertility between September 2019 and July 2020 were included in the study. Patients were divided into four equal groups according to their clinical status, those with/without azoospermia and with/without varicocele. Blood and semen samples were taken from the patients. NOD-like receptor pyrin domain-containing 3 (NLRP3) and interleukin-1 beta (IL1ß) and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were measured in serum and semen, and the groups were compared statistically. RESULTS: Serum and semen NLRP3, IL1ß, TAS, TOS, and OSI values of the patients with varicocele or azoospermia were significantlyhigher than those without either varicocele or azoospermia (p < 0.05). The oxidative stress markers TAS, TOS, and OSI values were significantly higher in the other groups than those without azoospermia and varicocele (p < 0.05). DISCUSSION: Inflammasome mechanisms, such as NLRP3 and IL1-ß molecules, may provide additional benefit in evaluating the need and benefit of surgical or medical treatment in infertility with and without vascular pathology and with and without azoospermia.

Comparison of two different minimally invasive techniques used in bladder stone surgery for preschool-aged children.

BACKGROUND: This study was designed to compare the outcomes of mini-percutaneous cystolithotomy (mPCL) and transurethral cystolithotripsy (TUCL) in treating bladder stones in preschool-aged children (≤6 years old). METHODS: Twenty-four patients treated with mPCL and 28 patients treated with TUCL for bladder stones were compared retrospectively. The operative and postoperative outcomes of both groups were analyzed. RESULTS: The mean age and gender distribution were similar between the groups. The mean stone size was 16.5 ± 0.5 mm for the mPCL group and 14.9 ± 5.7 mm for the TUCL group (p = 0.318). The mean operative time was 41.1 ± 9.9 min for the mPCL group and 39.0 ± 12.3 min for the TUCL group (p = 0.182). Catheterization times and hospitalization times were statistically significantly longer in the mPCL group (p = 0.000). The rate of urinary retention after urethral catheter removal was significantly higher in the TUCL group (p < 0.05). Reintervention was performed for one patient in Group 1 due to urinary leakage and for five patients in Group 2 due to urinary retention. The stone-free rate (SFR) after a single procedure was 100% in the mPCL group and 89.3% in the TUCL group (p = 0.099). After auxiliary procedures performed for three patients, the overall SFR also reached 100% for the TUCL group. DISCUSSION: Both mPCL and TUCL are effective methods in the treatment of bladder stones of <30 mm in the preschool age group. Although TUCL has some advantages over mPCL, such as shorter hospital stays and catheterization times, there is a risk of urinary retention with increased stone sizes. It may be more advantageous to apply mPCL for the reduction of complications and reintervention rates, especially in small children with bladder stones of >20 mm.

Do inflammatory markers such as NLRP3 and IL1-ß have an effect on the prediction of testicular sperm extraction success in infertile men?

Infertility is defined as the inability of couples to have a baby without contraception after at least 1 year of regular sexual intercourse. Mechanisms to explain inflammation in male infertility of unknown causes are still being investigated. The inflammasome is a key regulator of innate immunity, which is involved in the inflammatory response to infections and various diseases through the activation of caspase-1 and the use of inflammatory cytokines. Although many factors are believed to affect the success of mTESE in infertile patients with non-obstructive azoospermia (NOA), the inflammation mechanisms in the environment have not been clearly explained in the aetiology of infertility. In this study, we aimed to investigate the effect of NLRP3 and similar inflammasome mechanisms on antioxidant mechanisms on the success of mTESE. A total of 24 NOA patients with micro-testicular sperm extraction (mTESE +) and no sperm found (mTESE -) participated in the study between January 2020 and January 2021. NLRP3, IL1-ß, TAS, TOS and OSI amounts in serum and seminal plasma parameters were compared statistically, and their effects on mTESE success were investigated. FSH, LH, estradiol and testosterone values did not differ significantly (p > 0.05) in the group with mTESE (-) and mTESE (+). Serum IL-1 Beta, NLRP3, TOS, TAS, and OSI values did not differ significantly (p > 0.05) in the group with mTESE (-) and mTESE (+). Seminal plasma TOS and OSI values were significantly lower in the group with mTESE (+) than the group with mTESE (-). Although inflammasomes such as NLRP3 and IL1-ß do not have a significant predictive value in the success of mTESE, we think the high seminal plasma values of infertile patients may be understandable with further studies. This study was conducted to determine how inflammasomes are involved in IL-1ß, pathway NLRP3, and sperm retrieval in micro testicular sperm extraction (mTESE) in infertile men.

Intersubunit Coupling Enables Fast CO2-Fixation by Reductive Carboxylases.

Enoyl-CoA carboxylases/reductases (ECRs) are some of the most efficient CO2-fixing enzymes described to date. However, the molecular mechanisms underlying the extraordinary catalytic activity of ECRs on the level of the protein assembly remain elusive. Here we used a combination of ambient-temperature X-ray free electron laser (XFEL) and cryogenic synchrotron experiments to study the structural organization of the ECR from Kitasatospora setae. The K. setae ECR is a homotetramer that differentiates into a pair of dimers of open- and closed-form subunits in the catalytically active state. Using molecular dynamics simulations and structure-based mutagenesis, we show that catalysis is synchronized in the K. setae ECR across the pair of dimers. This conformational coupling of catalytic domains is conferred by individual amino acids to achieve high CO2-fixation rates. Our results provide unprecedented insights into the dynamic organization and synchronized inter- and intrasubunit communications of this remarkably efficient CO2-fixing enzyme during catalysis.

Relationship between erectile dysfunction and Helicobacter pylori: A prospective controlled pilot study.

This study sought to investigate the correlation between Helicobacter pylori (Hp) and arteriogenic erectile dysfunction (ED). This study included 30 patients diagnosed with ED due to penile arterial insufficiency, in accordance with the International Index of Erectile Function scores and penile Doppler ultrasonography results, and 30 healthy individuals without ED in the control group. The levels of fasting blood glucose, serum lipid and C-reactive protein (CRP) were recorded. Enzyme-linked immunosorbent assay revealed that the levels of Hp-specific Immunoglobulin G (IgG) antibodies in the patient and control groups were 39.7 ± 23.2 and 21.0 ± 19.8 arbU/ml, respectively (p = .001); the mean CRP levels were 0.3 ± 0.2 and 0.1 ± 0.1 mg/dl, respectively (p = .01). A positive correlation was detected between ED and the levels of Hp-specific IgG and CRP. Further comprehensive studies supporting these preliminary results may facilitate the use of Hp seropositivity as an auxiliary marker in the diagnosis of ED. These findings may also guide future research on the clinical benefits of Hp eradication strategies for the prevention and treatment of ED.

Discovery of Azaindolin-2-One as a Dual Inhibitor of GSK3ß and Tau Aggregation with Potential Neuroprotective Activity.

The inhibition of glycogen synthase kinase 3ß (GSK3ß) activity through pharmacological intervention represents a promising approach for treating challenging neurodegenerative disorders like Alzheimer's disease. Similarly, abnormal tau aggregate accumulation in neurons is a hallmark of various neurodegenerative diseases. We introduced new dual GSK3ß/tau aggregation inhibitors due to the excellent clinical outcome of multitarget drugs. Compound (E)-2f stands out among the synthesized inhibitors as a promising GSK3ß inhibitor (IC50 1.7 µM) with a pronounced tau anti-aggregation effect in a cell-based model of tauopathy. Concurrently, (E)-2f was demonstrated to be non-toxic to normal cells, making it a promising neuroprotective lead compound that needs further investigation.

Are there factors in the disease of peroneal necrotizing fasciitis which should be used when choosing the anesthetic technique?: Descriptive analysis of a cohort from two centers.

BACKGROUND: This study aims to examine the factors affecting the selection of anaesthesia method in Fournier's gangrene. METHODS: A retrospective evaluation was made of 113 patients operated on because of Fournier's gangrene between January-May 2019. The operations were performed under spinal anaesthesia in 78 cases (Group S) and under general anaesthesia in 35 cases (Group G). The patients were evaluated regarding age, gender, the anaesthesia method used (spinal, general) anaesthetic agent applied, presence of sepsis, and biochemical, hematological and inflammatory parameters. RESULTS: When the patients were evaluated regarding the Fournier Gangrene Severity Index (FGSI), patients in Group S had lower scores (p=0.001). Examination of the tomography images revealed that in 13 (37.1%) patients, air values were seen in the right or left gluteal area, or both, extending to the subcutaneous tissue. In the evaluation of the factors affecting the selection of general anaesthesia, a positive correlation was determined between an increase in FGSI (r=0.482, p=0.001) and the presence of sepsis (r=0.485, p=0.001) and gluteal region involvement (r=0.628, p<0.001). CONCLUSION: The selection of anaesthesia method in Fournier gangrene patients is a complex process affected by factors, such as the patients' general condition, sepsis, and whether or not there is bleeding diathesis. The risk -benefit balance in the selection of anaesthesia method should be evaluated individually for patients.

Is there a relationship between renal scarring and neutrophil-to-lymphocyte ratio in patients with vesicoureteral reflux?

OBJECTIVES: Vesicoureteral reflux (VUR) exacerbates the risk of renal scarring by establishing a ground for pyelonephritis. It is known that the inflammatory process is more influential than the direct damage caused by bacterial infection in the development of renal scars after pyelonephritis. Therefore, the present study aims to investigate the relationship between renal scarring and systemic inflammatory markers in patients with VUR. MATERIAL AND METHODS: Hundred and ninety-two patients (116 females, 76 males) diagnosed with VUR were divided into two groups based on the presence or absence of renal scarring and into three groups according to the grade of VUR (low, moderate and high). Neutrophil count, lymphocyte count, mean platelet volume (MPV) and neutrophil-to-lymphocyte ratio (NLR) were compared among the groups. RESULTS: Of the 192 patients, 102 had renal scarring. The age and gender distribution did not differ significantly between the groups with and without renal scarring (p > 0.05). However, the grade of reflux and lymphocyte count were significantly higher in the group with renal scarring (p < 0.05), and the NLR was significantly lower in the group with renal scarring (p < 0.05). The lymphocyte count was significantly higher (p < 0.05) and NLR was significantly lower in the high-grade VUR group (p < 0.05). However, MPV values did not differ significantly (p > 0.05) between the groups. CONCLUSIONS: NLR can be used to predict renal scarring in patients with VUR, especially in the period of 3-6 months after the first attack of infection, and may even serve as a candidate marker for treatment selection. However, larger series and prospective studies are needed.

Do we have a limit for retrograde intrarenal surgery for solitary kidney stone?

OBJECTIVE: The management of urolithiasis in patients with a solitary kidney is challenging for urologists. This study aimed to evaluate the safety of retrograde intrarenal surgery (RIRS) in the treatment of stones in patients with solitary kidney and to reply to the question if there is any limit for this surgery. METHODS: Between January 2016 and December 2019, we enrolled 52 patients who had a solitary kidney and underwent RIRS. We collected data on preoperative patient characteristics, stone dimensions, and postoperative outcomes. Stone size, duration of operation, duration of fluoroscopy, type of anesthesia, and degree of surgical complication were evaluated retrospectively. Surgeries performed in less and more than 60 minutes and with and without complications were compared. RESULTS: A total of 52 patients with a kidney stone and a solitary kidney were evaluated. The mean stone size was 14 ± 0.4 cm and surgical success rate was 87.3%. In our study, 13 patients (24.5%) had grade 1 minor complications, and none required a blood transfusion. The mean operation time was 51.9 ± 17.3 minutes. The postoperative creatinine value increased in 6 patients. The duration of operation in the group with complications was significantly higher than that in the group without complications. In patients who underwent an operation lasting ≥ 60 minutes, stone size, fluoroscopy time, and complication rate were significantly higher than in patients who underwent an operation lasting ≤ 60 minutes. CONCLUSION: Our opinion is to be careful in patients with a solitary kidney with a big stone and we recommend assigning these procedure to experienced hands for not exceeding 60 minutes in one session.

EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy.

Glioma, particularly its most malignant form, glioblastoma multiforme (GBM), is the most common and aggressive malignant central nervous system tumor. The drawbacks of the current chemotherapy for GBM have aroused curiosity in the search for targeted therapies. Aberrantly overexpressed epidermal growth factor receptor (EGFR) in GBM results in poor prognosis, low survival rates, poor responses to therapy and recurrence, and therefore EGFR-targeted therapy stands out as a promising approach for the treatment of gliomas. In this context, a series of pentacyclic triterpene analogues were subjected to in vitro and in silico assays, which were conducted to assess their potency as EGFR-targeted anti-glioma agents. In particular, compound 10 was the most potent anti-glioma agent with an IC50 value of 5.82 µM towards U251 human glioblastoma cells. Taking into account its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), compound 10 exerts selective antitumor action towards Jurkat human leukemic T-cells. This compound also induced apoptosis and inhibited EGFR with an IC50 value of 9.43 µM compared to erlotinib (IC50 = 0.06 µM). Based on in vitro and in silico data, compound 10 stands out as a potential orally bioavailable EGFR-targeted anti-glioma agent endowed with the ability to cross the blood-brain barrier (BBB).

Comparison of Conservative and Surgical Treatments in Symptomatic Pregnancy Hydronephrosis.

OBJECTIVES: This study aimed to evaluate the factors affecting the treatment choice in pregnant women with symptomatic hydronephrosis. METHODS: Hospital records of pregnant women who visited our clinic due to symptomatic hydronephrosis between December 2010 and December 2020 were analysed retrospectively. Patients were divided into 2 groups: conservative and surgical (JJ stent) treatment groups. Age, gestational week, primipara, trimester, visual analogue scale (VAS), and preterm birth rates as well as clinical, laboratory, and ultrasonography findings were compared between the groups. RESULTS: The study included 227 pregnant women (conservative treatment group, 133; JJ stent group, 94). Age, gestational week, primipara, trimester, hydronephrosis side, fever, pyelonephritis, pyuria, preterm labour and abortion, as well as blood urea nitrogen, creatinine, C-reactive protein, and white blood cell levels did not differ significantly between the groups (p > 0.05). In the JJ stent group, VAS, creatinine value, culture positivity rate, degree of hydronephrosis, and renal pelvis anterior-posterior (AP) diameter were significantly higher than those in the conservative treatment group (p < 0.05). The cut-off value for renal pelvis AP diameter was 16.5 mm in the first 2 trimesters and 27.5 mm in the third trimester. CONCLUSIONS: Surgical treatment should not be delayed in pregnant women who do not respond to conservative treatment and have impaired renal function and grade 3-4 hydronephrosis. Early surgical intervention is necessary in patients with a renal pelvis AP diameter of >16.5 mm in the first 2 trimesters and >27.5 in the third trimester.

Design, synthesis and investigation of the mechanism of action underlying anti-leukemic effects of the quinolinequinones as LY83583 analogs.

Literature conclusively shows that one of the quinolinequinone analogs (6-anilino-5,8-quinolinequinone), referred to as LY83583 hereafter, an inhibitor of guanylyl cyclase, was used as the inhibitor of the cell proliferation in cancer cells. In the present work, a series of analogs of the LY83583 containing alkoxy group(s) in aminophenyl ring (AQQ1-15) were designed and synthesized via a two-step route and evaluated for their in vitro cytotoxic activity against four different cancer cell lines (K562, Jurkat, MT-2, and HeLa) and human peripheral blood mononuclear cells (PBMCs) by MTT assay. The analog (AQQ13) was identified to possess the most potent cytotoxic activity against K562 human chronic myelogenous (CML) cell line (IC50 = 0.59 ± 0.07 µM) with significant selectivity (SI = 4.51) compared to imatinib (IC50 = 5.46 ± 0.85 µM; SI = 4.60). Based on its superior cytotoxic activity, the analog AQQ13 was selected for further mechanistic studies including determination of its apoptotic effects on K562 cell line via annexin V/ethidium homodimer III staining potency, ABL1 kinase inhibitory activity, and DNA cleaving capacity. Results ascertained that the analog AQQ13 induced apoptosis in K562 cell line with notable DNA-cleaving activity. However, AQQ13 demonstrated weak ABL1 inhibition indicating the correlation between anti-K562 and anti-ABL1 activities. In continuance, respectively conducted in silico molecular docking and Absorption, Distribution, Metabolism, and Excretion (ADME) studies drew attention to enhanced binding interactions of AQQ13 towards DNA and its high compatibility with the potential limits of specified pharmacokinetic parameters making it as a potential anti-leukemic drug candidate. Our findings may provide a new insight for further development of novel quinolinequinone-based anticancer analogs against CML.

Structure based design, synthesis, and evaluation of anti-CML activity of the quinolinequinones as LY83583 analogs.

Quinone-based small molecules are the promising structures for antiproliferative drug design and can induce apoptosis in cancer cells. Among them, one of the quinolinequinones, named as 6-anilino-5,8-quinolinequinone, LY83583 has the ability to inhibit the growth of cancer cells as an inhibitor of cyclase. The biological potential of all synthesized compounds as the analogs of the identified lead molecule LY83583 that possessed the antiproliferative efficiency was determined. The two series of the LY83583 analogs containing electron-withdrawing or electron-donating group(s) were synthesized and subsequently in vitro evaluated for their cytotoxic activity against K562, Jurkat, MT-2, and HeLa cell lines using MTT assay. All the LY83583 analogs showed antiproliferative activity with good IC50 values (less than positive control imatinib). Four analogs from each series were also selected for the determination of selectivity against human peripheral blood mononuclear cells (PBMCs). The analog AQQ15 showed high potency towards all cancer cell lines with almost similar selectivity of imatinib. In order to get a better insight into cytotoxic effects of the analog AQQ15 in K562 cells, further apoptotic effects due to annexin V/ethidium homodimer III staining, ABL1 kinase inhibition, and DNA cleaving ability were examined. The analog AQQ15 induced apoptotic cell death in K562 cells with 34.6% compared to imatinib (6.5%). This analog showed no considerable ABL1 kinase inhibitory activity but significant DNA cleavage activity indicating DNA fragmentation-induced apoptosis. Besides, molecular docking studies revealed that the analog AQQ15 established proper interactions with the deoxyribose sugar attached with the nucleobases adenine and guanidine respectively, in the minor groove of the double helix of DNA. In silico predicted pharmacokinetic parameters of this analog were found to comply with the standard range making it an efficient anticancer drug candidate for further research.

Urolithiasis and Its Treatment in Pregnant Women: 10-Year Clinical Experience From a Single Centre.

INTRODUCTION: Urolithiasis during pregnancy is an important health concern that can affect maternal and foetal health. If left untreated, it can cause obstetric complications, such as spontaneous abortion and preterm delivery. In this study, we aimed to evaluate urolithiasis and its treatment in pregnant women. METHODS: We analysed data of 57 patients diagnosed with urolithiasis during pregnancy between January 2010 and December 2020. Patients' age, gestational age, urolithiasis history, physical examination findings, laboratory findings, location and size of the stone and applied treatment methods were examined. The effectiveness and complications of the applied treatment methods were evaluated. RESULTS: The mean age of 57 patients included in our study was 27 (27.8 ± 5.6) years and their mean gestational age was 20 (20.3 ± 9.2) weeks. The mean stone size was 9 mm (9.09 ± 4.37). The most common symptom at the time of presentation to the hospital was flank pain (93%). Kidney stones were detected in 34 patients and ureteral stones in 23 patients. Although conservative treatment was sufficient in 26 (45.6%) patients, 31 (54.4%) patients required surgical intervention. Major obstetric complications, such as preterm delivery and abortion, did not occur in any of the patients. CONCLUSION: The diagnosis and treatment of pregnant women with urolithiasis should be managed in a multidisciplinary manner. While determining the treatment options, foetal and maternal health should be considered.

A different look at genetic factors in individuals with non-obstructive azoospermia or oligospermia in our research study: To whom, which threshold, when, in what way? / Diferente perspectiva de los factores genéticos en individuos con azoospermia no obstructiva u oligospermia en nuestro estudio: ¿a quién realizarlo?; ¿con qué umbral?; ¿en qué momento?; ¿de qué modo?

INTRODUCTION: In our study, we sought answers to many questions about male infertility from a different perspective. The first step in male infertility is anamnesis, physical examination and sperm count. The European Academy of Andrology recommends examination of genetic causes in individuals with fewer than 5million/ml semen counts. The American Urological Association and American Society for Reproductive Medicine have guidelines recommending performing karyotype and AZF subgroup deletion testing in azoospermia and fewer than 5 million sperm total count. Klinefelter syndrome and Y chromosome microdeletions are still very important in male infertility. Based on patients with Klinefelter syndrome or Y microdeletion, we sought answers to many questions in male infertility. MATERIALS AND METHODS: In the presented study 327 male patients with having fewer than 15millionsperm/ml detected in at least two consecutive sperm analysis were examined. Patients were divided into sub-groups according to the presence of semen count, chromosomal anomaly and Y microdeletion. In addition, FSH, LH and testosterone levels were analyzed. RESULTS: Numerical chromosomal anomalies were observed in 34 (10.4%) of 327 patients, and all of these anomalies were found as 47, XXY. Individuals with no AZF microdeletion constituted 95.1% (n=311) of the study group. The overall frequency of AZF microdeletions was 4.9% (16/327). No AZF microdeletions were detected for the patients who have sperm counts above 2million/ml. FSH, LH and testosterone levels were found significantly different between the groups. DISCUSSION: The results of our study provide another layer of evidence to demonstrate the controversial threshold value of the EAA. In light of our data and current literature, we recommend to set the threshold value at 2million/ml for semen analysis. Further studies conducted in different ethnic groups and larger patient groups would contribute to clarify what exact value should be used to apply genetic tests

INTRODUCCIÓN: En nuestro estudio, buscamos respuestas a muchas preguntas relativas a la infertilidad masculina, desde una perspectiva diferente. El primer paso en la infertilidad masculina es la anamnesis, el examen físico y el recuento seminal. La Academia Europea de Andrología recomienda el examen de las causas genéticas en individuos con menos de 5millones/ml de recuento seminal. La Asociación Americana de Urología y la Sociedad Americana de Medicina Reproductiva cuentan con directrices que recomiendan la realización de pruebas de cariotipos y deleción del subgrupo AZF en los casos de azoospermia y un recuento seminal total inferior a 5millones/ml. El síndrome de Klinefelter y las micro-deleciones del cromosoma Y siguen siendo muy importantes en la infertilidad masculina. Basándonos en los pacientes con síndrome de Klinefelter o micro-deleción del cromosoma Y, buscamos respuestas a muchas cuestiones de la infertilidad masculina. MATERIALES Y MÉTODOS: En el presente estudio examinamos 327 varones con valores inferiores a 15 millones de esperma/ml detectados en al menos 2 análisis seminales consecutivos. Dividimos a los pacientes en subgrupos con arreglo a la presencia de recuento seminal, anomalía cromosómica y micro-deleción del cromosoma Y. Además, analizamos los niveles de FSH, LH y testosterona. RESULTADOS: Se observaron anomalías cromosómicas numéricas en 34 (10,4%) de los 327 pacientes, encontrándose dichas anomalías como 47, XXY. Los individuos sin micro-deleción AZF constituyeron el 95,1% (n=311) del grupo de estudio. La frecuencia general de las micro-deleciones AZF fue del 4,9% (16/327). No se detectaron micro-deleciones AZF para los pacientes con recuentos seminales superiores a 2millones/ml. Los niveles de FSH, LH y testosterona fueron significativamente diferentes entre los grupos. DISCUSIÓN: Los resultados de nuestro estudio aportan otra evidencia para demostrar el controvertido valor umbral de EAA. A la luz de nuestros datos y de la literatura actual, recomendamos establecer el valor umbral en 2millones/ml para el análisis seminal. Los futuros estudios a realizar en diferentes grupos étnicos y muestras de mayor tamaño de pacientes contribuirían a clarificar qué valor exacto debería utilizarse para solicitar pruebas genéticas

Usability of shear wave elastography to predict the success of extracorporeal shock-wave lithotripsy: prospective pilot study.

The present study is intended to investigate the usability of shear wave elastography (SWE) in predicting the success of extracorporeal shock-wave lithotripsy (ESWL) used in kidney stone treatment. ESWL was performed on a total number of 52 patients diagnosed with kidney stones between May 2019 and July 2020. The presence of a residual stone greater than 4 mm was accepted as failure. The patients were divided into two groups as ESWL success and ESWL failure. SWE and Hounsfield unit (HU) measurements of stones were performed in all patients before ESWL. The two groups were compared in terms of age, gender, stone localisation, stone size, body mass index (BMI), skin-to-stone distance, HU, and SWE values of the stones. ESWL was successful in 30 of the 52 patients included in the study, while it failed in 22 of them. While the mean SWE value was 7.3 (7.9 ± 2.2) kPa in patients with success in ESWL, it was 14.6 (17.9 ± 10.2) kPa in those with failed ESWL. The mean HU was 883.5 (841.4 ± 191.1) in patients with success in ESWL and 1078 (1115.5 ± 183) in those with failed ESWL. Both SWE and HU values of the stones were found to be statistically significantly lower in the successful group (p < 0.05). It was seen that SWE and HU values were correlated to each other. The groups of successful and failed ESWL did not differ significantly in terms of age, gender distribution, stone size, BMI, and skin-to-stone distance (p > 0.05). With SWE, the hardness of the stone can be measured and its suitability for ESWL can be evaluated. It can be used as an alternative parameter to HU before ESWL treatment, since it has a lower cost compared to computed tomography (CT) and does not contain radiation.

A different look at genetic factors in individuals with non-obstructive azoospermia or oligospermia in our research study: To whom, which threshold, when, in what way?

INTRODUCTION: In our study, we sought answers to many questions about male infertility from a different perspective. The first step in male infertility is anamnesis, physical examination and sperm count. The European Academy of Andrology recommends examination of genetic causes in individuals with fewer than 5million/ml semen counts. The American Urological Association and American Society for Reproductive Medicine have guidelines recommending performing karyotype and AZF subgroup deletion testing in azoospermia and fewer than 5 million sperm total count. Klinefelter syndrome and Y chromosome microdeletions are still very important in male infertility. Based on patients with Klinefelter syndrome or Y microdeletion, we sought answers to many questions in male infertility. MATERIALS AND METHODS: In the presented study 327 male patients with having fewer than 15millionsperm/ml detected in at least two consecutive sperm analysis were examined. Patients were divided into sub-groups according to the presence of semen count, chromosomal anomaly and Y microdeletion. In addition, FSH, LH and testosterone levels were analyzed. RESULTS: Numerical chromosomal anomalies were observed in 34 (10.4%) of 327 patients, and all of these anomalies were found as 47, XXY. Individuals with no AZF microdeletion constituted 95.1% (n=311) of the study group. The overall frequency of AZF microdeletions was 4.9% (16/327). No AZF microdeletions were detected for the patients who have sperm counts above 2million/ml. FSH, LH and testosterone levels were found significantly different between the groups. DISCUSSION: The results of our study provide another layer of evidence to demonstrate the controversial threshold value of the EAA. In light of our data and current literature, we recommend to set the threshold value at 2million/ml for semen analysis. Further studies conducted in different ethnic groups and larger patient groups would contribute to clarify what exact value should be used to apply genetic tests.

A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors.

BACKGROUND: After the approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are at various stages of clinical evaluation. OBJECTIVES: Due to the importance of the thiazole scaffold in targeted anticancer drug discovery, the goal of this work is to identify new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of Chronic Myeloid Leukemia (CML). METHODS: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on the K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on Mitogen-Activated Peripheral Blood Mononuclear Cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different Tyrosine Kinases (TKs), including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), a molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger's Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p. RESULTS: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase, forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three. CONCLUSION: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.