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Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods:Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 coun-tries were analyzed descriptively, with a Delphi process used for expert recommendations. Results:Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoosper-mia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differ-entiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions:Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Verheij syndrome (VRJS) is a rare microdeletion syndrome of chromosome 8q24.3 that is characterized by severe growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, psychomotor retardation, cardiac and renal defects, and dysmorphic facial features. Pathogenic variants of PUF60 (Poly-U Binding Splicing Factor 60 kDa) have been found to cause VRJS. Here we present a Turkish patient with Verheij syndrome who has typical facial dysmorphic features and renal and cardiac abnormalities, scoliosis, tethered cord, and mild intellectual disability. This is a case report of a 11-year-old female child who presented with Verheij syndrome. Blood samples were collected from the patient and the family. We performed whole exome sequencing was used to identify potential genetic mutations. We also used 3-dimensional protein structure analysis to identify the effect of the mutation. A de-novo in-frame variant (c.449_457delCAAAGGGGG; p.Ala150_Phe152del) of the PUF60 gene was identified by whole exome sequencing. According to ACMG guidelines in 2015, the mutation is classified as pathogenic and it has been reported in the clinvar database. Results of in-silico prediction software tools predicted the mutation was pathogenic. Protein structure analysis showed that the three residues affected by the in-frame deletion form could lead to impaired stability and function of the PUF60 protein. To date, 25 patients have been reported with PUF60 mutations in the medical literature. In this article, we report a patient with VRJS who had the unusual findings of tethered cord syndrome and renal abnormalities. As far as we know, this is the first patient from Turkey who has been diagnosed with Verheij syndrome. [ABSTRACT FROM AUTHOR]

Abstract MYC dysregulation is pivotal in the onset and progression of IDH-mutant gliomas, mostly driven by copy-number alterations, regulatory element alterations, or epigenetic changes. Our pilot analysis uncovered instances of relative MYC overexpression without alterations in the proximal MYC network (PMN), prompting a deeper investigation into potential novel oncogenic mechanisms. Analysing comprehensive genomics profiles of 236 “IDH-mutant 1p/19q non-co-deleted” lower-grade gliomas from The Cancer Genome Atlas, we identified somatic genomic alterations within the PMN. In tumours without PMN-alterations but with MYC-overexpression, genes correlated with MYC-overexpression were identified. Our analyses yielded that 86/236 of astrocytomas exhibited no PMN-alterations, a subset of 21/86 displaying relative MYC overexpression. Within this subset, we discovered 42 genes inversely correlated with relative MYC expression, all on 19q. Further analysis pinpointed a minimal common region at 19q13.43, encompassing 15 genes. The inverse correlations of these 15 genes with relative MYC overexpression were re-confirmed using independent scRNAseq data. Further, the micro-deleted astrocytoma subset displayed significantly higher genomic instability compared to WT cases, but lower instability compared to PMN-hit cases. This newly identified 19q micro-deletion represents a potential novel mechanism underlying MYC dysregulation in astrocytomas. Given the prominence of 19q loss in IDH-mutant gliomas, our findings bear significant implications for understanding gliomagenesis.

Hydrogels have been extensively used for tissue engineering applications due to their versatility in structure and physical properties, which can mimic native tissues. Although significant progress has been made toward designing hydrogels for soft tissue repair, engineering hydrogels that resemble load‐bearing tissues is still considered a great challenge due to their specific mechanophysical demands. Herein, microporous, tough, yet highly compressible poly(vinyl alcohol) (PVA)‐based hydrogels are reported for potential applications in repairing or replacing different load‐bearing tissues. The synergy of freeze‐thawing and the Hofmeister effect, which controlled the spatial arrangement and aggregation of polymer chains, facilitated the formation of microstructured frameworks with tunable porosity. While the maximum mechanical strength, toughness, and stretchability of the engineered hydrogel were ≈390 kPa, ≈388 kJ m−3, and ≈170%, respectively, Young's modulus based on compression testing wasfound to be in the range of ≈0.02–0.30 MPa, highlighting the all‐in‐one mechanically enriched nature of the hydrogel. Furthermore, the minimal swelling and degradation rate of the engineered hydrogel met the specific requirements for load‐bearing tissues. Finally, excellent antibacterial resistance as well as in vitro biocompatibility of the hydrogel demonstrates its potential for the replacement of load‐bearing tissues.

“Click” cycloadditions offer effective pathways for the modifications of supramolecular structures, polymers, and nanomaterials. These reactions include bioorthogonal mechanisms that do not interfere with the biological processes, providing a type of chemistry to operate directly in living environments, such as cells and animals. As a result, the “click” cycloadditions represent highly and selective tools for tailoring the properties of nanomedicine scaffolds, expanding the efficacy of multiple therapeutic strategies. We focused this minireview on the bioorthogonal cycloadditions, presenting an insight into the strategies to modify nanostructured biomedical scaffolds inside living systems. We organized the contributions according to the three main mechanisms of “click” cycloadditions: strain-promoted sydnone-alkyne, tetrazine ligation, and strain-promoted [3+2] azido-alkyne.

The visualization of the cervix and subsequent manipulations during transcervical applications in sheep might require a degree of straining reflexes while using the Collin Speculum. Therefore, this study aimed to develop and to evaluate the feasibility of a new alternative speculum design for non-surgical assisted reproductive procedures in small ruminants. Collin speculum (CS) and the new "Onder speculum" (OS) were used to assess cervical entrance in 30 ewes. The OS efficiency for a successful cervical retraction was also evaluated. Data showed that the cervical entrance was visible in 8 out of the 30 females with CS, while it was observed in all the animals when using OS (P

The defense expenditure is an essential part of government expenditures due to political preferences, geopolitical conditions, and level of economic development of a country. If one of them makes war risk for the country, governments tend to increase defense expenditures and the share of it in the budget will rise. In the literature, behavior of government expenditures is tried to explain via Peacock and Wiseman’s “displacement effect” hypothesis. The hypothesis claims that ratio of government expenditures to gross domestic product increases permanently when policy makers increase it once. So, if Peacock and Wiseman’s “displacement effect” hypothesis is valid, that would share of defense expenditures in the central government budget will rise and share of other expenditure items will decrease. Its socio-economic outcomes will be different. In this study, we aim to test behavior of defense expenditures of government in the NATO member countries to better understand how government manage expenditures. We modify “displacement effect” hypothesis by proportioning defense expenditures to gross domestic product. If it is not stationary, displacement effect hypothesis is valid, vice versa. Results imply that in most of the member countries displacement hypothesis for ratio of defense expenditures to GDP is valid, except Hungarian economy.

Electrochemical impedance spectroscopy (EIS) measurement, performed in the presence of a redox agent, is a convenient method to measure molecular interactions of electrochemically inactive compounds taking place on the electrode surface. High sensitivity of the method, being highly advantageous, can be also associated with nonspecific impedance changes that could be easily mistaken for specific interactions. Therefore, it is necessary to be aware of all possible causes and perform parallel control experiments to rule them out. We present the results obtained during the early stages of aptamer-based sensor development, utilizing a model system of human alpha thrombin interacting with a thiolated DNA aptamer, immobilized on gold electrodes. EIS measurements took place in the presence of iron ferrocyanides. In addition to known method limitations, that is, inability to discriminate between specific and nonspecific binding (both causing impedance increase), we have found other factors leading to nonspecific impedance changes, such as: (i) initial electrode contamination; (ii) repetitive measurements; (iii) additional cyclic voltammetry (CV) or differential pulse voltammetry (DPV) measurements; and (iv) additional incubations in the buffer between measurements, which have never been discussed before. We suggest ways to overcome the method limitations.

Abstract Background There is an ongoing search for standardized scales appropriate for each culture to evaluate professionalism, which is one of the basic competencies of a physician. The Professionalism Mini-evaluation Exercise (P-MEX) instrument was originally developed in Canada to meet this need. In this study, it was aimed to adapt the P-MEX to Turkish and to evaluate the validity and reliability of the Turkish version. Methods A total of 58 residents at Bakirkoy Dr. Sadi Konuk Training and Research Hospital were assessed with the Turkish version of P-MEX by 24 raters consisting of faculty members, attending physicians, peer residents, and nurses during patient room visits, outpatient clinic and group practices. For construct validity, the confirmatory factor analysis was performed. For reliability, Cronbach’s alpha scores were calculated. Generalizibility and decision studies were undertaken to predict the reliability of the validated tool under different conditions. After the administration of P-MEX was completed, the participants were asked to provide feedback on the acceptability, feasibility, and educational impact of the instrument. Results A total of 696 forms were obtained from the administration of P-MEX. The content validity of P-MEX was found to be appropriate by the faculty members. In the confirmatory factor analysis of the original structure of the 24-item Turkish scale, the goodness-of-fit parameters were calculated as follows: CFI = 0.675, TLI = 0.604, and RMSEA = 0.089. In the second stage, the factors on which the items loaded were changed without removing any item, and the model was modified. For the modified model, the CFI, TLI, and RMSEA values were calculated as 0.857, 0.834, and 0.057, respectively. The decision study on the results obtained from the use of P-MEX in a Turkish population revealed the necessity to perform this evaluation 18 times to correctly evaluate professionalism with this instrument. Cronbach’s alpha score was 0.844. All the faculty members provided positive feedback on the acceptability, feasibility, and educational impact of the adapted P-MEX. Conclusion The findings of this study showed that the Turkish version of P-MEX had sufficient validity and reliability in assessing professionalism among residents. Similarly, the acceptability and feasibility of the instrument were found to be high, and it had a positive impact on education. Trial registration 2020/249, Bakirkoy Dr. Sadi Konuk Training and Research Hospital.

Abstract Background Transient hypothyroxinemia of prematurity (THOP) is defined as a low level of circulating thyroxine (T4), despite low or normal thyroid-stimulating hormone (TSH) levels. Aims: We aimed to evaluate the incidence of THOP, the clinical and laboratory findings of preterm infants with this condition and the levothyroxine (L-T4) treatment. Methods Preterm infants (n = 181) delivered at 24–34 weeks of gestation were evaluated by their thyroid function tests that were performed between the 10th and 20th days of postnatal life and interpreted according to the gestational age (GA) references. Clinical and laboratory characteristics of the patients with THOP and normal thyroid function tests were compared. Patients with THOP and treated with L-T4 were compared with the ones who were not regarding laboratory, and clinical characteristics. Results Incidence of hypothyroxinemia of prematurity was 45.8% (n = 83). Euthyroidism, primary hypothyroidism, and subclinical hypothyroidism were diagnosed in 47.5% (n = 86), 5% (n = 9) and 1.7% (n = 3) of the patients, respectively. Mean birth weight (BW) and GA were significantly lower in the hypothyroxinemia group than in the euthyroid group (p

The aim of the present study was to evaluate the effects of insulin supplemented extender on bull semen at a post-thaw stage. Semen samples were collected four times from a Zavot bull which is endangered species in Türkiye. Semen samples were diluted with Tris based extender supplemented with 10 IU or 15 IU of insulin and control. Motility and plasma membrane integrity were evaluated by a phase-contrast microscope. Acrosome integrity (Fitc-Peanut Agglutinin), mitochondrial membrane potential (Rhodamine 123), nitric oxide level (4,5-Diaminofluorescein-2/diacetate) were evaluated with dual staining propidium iodide using flow cytometry. Motility and plasma membrane functional integrity were better preserved compared to control group (P0.05), but increased insulin negatively affected acrosome integrity (p0.05). There were not any significant differences among groups in terms of nitric oxide level (P>0.05). In conclusion, it was thought that insulin involved in energy metabolism and improved preservation of bull semen.

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

To investigate the relationship between lesion size determined using multiparametric magnetic resonance imaging (mpMRI) and histopathological findings of specimens obtained after mpMRI fusion biopsy and radical prostatectomy (RP). We retrospectively analysed 290 patients with PCa who underwent an MRI fusion biopsy. We measured the diameter of suspicious tumour lesions on diffusion-weighted mpMRI and stratified the cohort into two groups. Group A included patients with a suspicious tumour lesion 10 mm and Group B included those with a suspicious tumour lesion > 10 mm. In Group B, the PI-RADS score determined in mpMRI was higher than Group A, and there was a statistically significant difference between the two groups in terms of clinical T-stage. The PCa detection rate and the number of positive cores were statistically significantly higher in Group B than in Group A. In addition, there was a statistically significant difference between the two groups in relation to the biopsy, the International Society of Urological Pathology (ISUP) grade values, and the presence of clinically significant PCa. In Group B, pathological T-stage and extraprostatic extension (EPE) and surgical margin (SM) positivity were found to be higher among the patients who underwent RP. In the multivariate analysis, the mpMRI lesion size being > 10 mm was found to be an independent predictive factor for SM and EPE positivity. The clinical results of this study support the modification of the lesion size threshold as 10 mm for use in the differentiation of PI-RADS scores 4 and 5.

Objective: In this study, it was aimed to investigate Legionella spp. and other pathogenic microorganisms in swab samples taken from different units of a tertiary healthcare hospital between July 25, 2019 and November 1, 2019. Materials and Methods: Ninety-two swab samples were taken from the mechanical ventilator, air conditioner filters, water outlets, and sink faucets in the laboratory, operating room and different intensive care units of the hospital. All samples were centrifuged and inoculated directly onto buffered coal yeast extract agar, a medium selective for Legionella and other conventional media. 16S rRNA sequence analysis was performed for identification at the species level by randomly selecting 6 samples that were positive for Legionella by culture and serological tests. Results: Growth compatible with Legionella spp. colonies was observed in 24 (26.08%) cultures. Only three of the 6 serogrouped samples were confirmed by molecular identification. Two of these were identified as Legionella pneumophila subsp. pneumophila and the other as Legionella anisa. Penicillium spp., Aspergillus flavus, Acinetobacter baumannii, Morganella morganii, Moraxella spp., and Pseudomonas aeruginosa were isolated from the filters of mechanical ventilators and Escherichia coli from a tap sample. Conclusion: Potential Legionella spp. exposure in high-risk patients should be eliminated with increased sampling frequency and effective control measures.

The universally conserved protein YidC aids in the insertion and folding of transmembrane polypeptides. Supposedly, a charged arginine faces its hydrophobic lipid core, facilitating polypeptide sliding along YidC’s surface. How the membrane barrier to other molecules may be maintained is unclear. Here, we show that the purified and reconstituted E. coli YidC forms an ion-conducting transmembrane pore upon ribosome or ribosome-nascent chain complex (RNC) binding. In contrast to monomeric YidC structures, an AlphaFold parallel YidC dimer model harbors a pore. Experimental evidence for a dimeric assembly comes from our BN-PAGE analysis of native vesicles, fluorescence correlation spectroscopy studies, single-molecule fluorescence photobleaching observations, and crosslinking experiments. In the dimeric model, the conserved arginine and other residues interacting with nascent chains point into the putative pore. This result suggests the possibility of a YidC-assisted insertion mode alternative to the insertase mechanism.

Low-grade gliomas (LGG) are central nervous system Grade I tumors, and as they progress they are becoming one of the deadliest brain tumors. There is still great need for timely and accurate diagnosis and prognosis of LGG. Herein, we aimed to identify diagnostic and prognostic biomarkers associated with LGG, by employing diverse computational approaches. For this purpose, differential gene expression analysis on high-throughput transcriptomics data of LGG versus corresponding healthy brain tissue, derived from TCGA and GTEx, respectively, was performed. Weighted gene co-expression network analysis of the detected differentially expressed genes was carried out in order to identify modules of co-expressed genes significantly correlated with LGG clinical traits. The genes comprising these modules were further used to construct gene co-expression and protein-protein interaction networks. Based on the network analyses, we derived a consensus of eighteen hub genes, namely, CD74, CD86, CDC25A, CYBB, HLA-DMA, ITGB2, KIF11, KIFC1, LAPTM5, LMNB1, MKI67, NCKAP1L, NUSAP1, SLC7A7, TBXAS1, TOP2A, TYROBP, and WDFY4. All detected hub genes were up-regulated in LGG, and were also associated with unfavorable prognosis in LGG patients. The findings of this study could be applicable in the clinical setting for diagnosing and monitoring LGG.

Byline: A.H. Aydin, Y. Bulut, O. Yavuz Dyestuff production units and dyeing units have always had pressing need techniques that allow economical pre-treatment for colour in the effluent. The effectiveness of adsorption for dye removal from wastewaters has made it an ideal alternative to other expensive treatment options. Removal of acid green 25 and acid red 183 from aqueous solution by different adsorbent such as shells of almond and hazelnut, and poplar and walnut sawdust were investigated. Equilibrium isotherms have been determined and analysed using the Freundlich equations. Parameters of Freundlich isotherm have been determined using adsorption data. Capacities of adsorbent follow as walnut > poplar > almond > hazelnut for AG25 and almond > walnut > poplar > hazelnut for AR183, respectively.

Abstract Background Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants. Results We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes. Conclusions Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS.

Background: Cardiopulmonary bypass (CPB) causes systemic oxidative stress response and endothelial damage in systemic organs. We investigated the effects of positive end-expiratory pressure (PEEP) and mechanical ventilation (MV) applications on oxidative stress in CPB. Methods: Seventy-one patients were recruited and 60 completed the study. Randomized groups: MV off (Group 1); MV on, tidal volume (TV) at 3–4 mL.kg-1 (Group 2); MV on, TV at 3–4 mL.kg-1, PEEP at 5 cmH2O (Group 3), n = 20 in each group. As oxidative stress markers, we used glutathione peroxidase (GPx), total antioxidant status (TAS), total oxidant status (TOS), total and native thiol (TT, NT), malondialdehyde (MDA), and catalase. We also investigated the correlation between oxidative stress and postoperative intubation time. Results: The postoperative GPx levels in Group 2 were higher than Group 3 (p = 0.017). In groups 2 and 3, TAS levels were higher postoperatively than intraoperatively (p = 0.001, p = 0.019, respectively). In Group 2, the TT levels were higher postoperatively than preoperatively and intraoperatively (p = 0.008). In Group 3, the postoperative MDA levels were higher than preoperatively (p = 0.001) and were higher than both postoperative levels of Group 1 and 2 (p = 0.043, p = 0.003). As the preoperative TAS (Group 2) decreased and the postoperative NT (Group 2) and catalase (Group 3) increased, the postoperative intubation time lengthened. Conclusion: MV ( 3–4 mL.kg-1) alone seems to be the most advantageous strategy. Prolonged postoperative intubation time was associated with both increased NT and catalase levels.