Reestablishment of spermatogenesis after more than 20 years of cryopreservation of rat spermatogonial stem cells reveals an important impact in differentiation capacity.

Treatment of cancer in children is increasingly successful but leaves many prepubertal boys suffering from infertility or subfertility later in life. A current strategy to preserve fertility in these boys is to cryopreserve a testicular biopsy prior to treatment with the expectation of future technologies allowing for the reintroduction of stem cells and restoration of spermatogenesis. Spermatogonial stem cells (SSCs) form the basis of male reproduction, differentiating into all germ cell types, including mature spermatozoa and can regenerate spermatogenesis following transplantation into an infertile testis.

Comparison of Diffusion Signal Models for Fiber Tractography in Eloquent Glioma Surgery-Determination of Accuracy Under Awake Craniotomy Conditions.

Objective: Fiber tractography (FT) has become an important noninvasive tool to ensure maximal safe tumor resection in eloquent glioma surgery. Intraoperatively applied FT is still predominantly based on diffusion tensor imaging (DTI). However, reconstruction schemes of high angular resolution diffusion imaging data for high-resolution FT (HRFT) are gaining increasing attention.

Roles of Stra8 and Tcerg1l in retinoic acid induced spermatogonial differentiation in mouse†.

Retinoic acid (RA) induces spermatogonial differentiation, but the mechanism by which it operates remains largely unknown. We developed a germ cell culture assay system to study genes involved in spermatogonial differentiation triggered by RA. Stimulated by RA 8 (Stra8), a RA-inducible gene, is indispensable for meiosis initiation, and its deletion results in a complete block of spermatogenesis at the pre-leptotene/zygotene stage.

Is antibiotic prophylaxis expendable in parotid gland surgery? A retrospective analysis of surgical site infection rates.

Objectives: To evaluate the rate of surgical site infection (SSI) and associated risk factors after parotid gland surgery including the impact of antibiotic prophylaxis.

Design: Retrospective single-centre clinical study.

Setting: Tertiary referral centre for head and neck surgery.

Mental Health Specialist Video Consultations Versus Treatment-as-Usual for Patients With Depression or Anxiety Disorders in Primary Care: Randomized Controlled Feasibility Trial.

Background: Most people affected by depression or anxiety disorders are treated solely by their primary care physician. Access to specialized mental health care is impeded by patients' comorbidity and immobility in aging societies and long waiting times at the providers' end. Video-based integrated care models may leverage limited resources more efficiently and provide timely specialized care in primary care settings.

Robotic-Assisted Versus Conventional Open Partial Nephrectomy (Robocop): A Propensity Score-Matched Analysis of 249 Patients.

Objectives: The objective of this study was to compare open partial nephrectomy (OPN) and robotic-assisted PN (RAPN) based on a propensity score-matched sample and to test the Comprehensive Complication Index (CCI) as an end point for complications.

Methods: Patients undergoing PN from 2010 to 2018 at a university care center were included. OPN and RAPN cases were matched in a 2:1 ratio using propensity score-matching with age, gender, BMI, RENAL score, and tumor size as confounders.

FGF9 promotes mouse spermatogonial stem cell proliferation mediated by p38 MAPK signalling.

Objectives: Fibroblast growth factor 9 (FGF9) is expressed by somatic cells in the seminiferous tubules, yet little information exists about its role in regulating spermatogonial stem cells (SSCs).

Materials And Methods: Fgf9 overexpression lentivirus was injected into mouse testes, and PLZF immunostaining was performed to investigate the effect of FGF9 on spermatogonia in vivo. Effect of FGF9 on SSCs was detected by transplanting cultured germ cells into tubules of testes.

Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data.

Background And Aims: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation.

Approach And Results: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study.

Cluster-randomised trial evaluating a complex intervention to improve mental health and well-being of employees working in hospital - a protocol for the SEEGEN trial.

Background: Health care employees in Germany and worldwide are exposed to a variety of stressors. However, most of the hospitals in Germany lack a systematic workplace health management. Thus, this study aims at the evaluation of the effects of a behavioural as well as organisational (´complex´) intervention on the mental health and well-being of hospital staff.

Going Beyond Diffusion Tensor Imaging Tractography in Eloquent Glioma Surgery-High-Resolution Fiber Tractography: Q-Ball or Constrained Spherical Deconvolution?

Objective: As a result of the resolution of intravoxel fiber crossing, high-resolution fiber tractography (HRFT) provides advantages over conventional diffusion tensor imaging (DTI) for fiber tractography (FT). Nevertheless, neurosurgically applied FT is still predominantly based on DTI. Although the application of HRFT is evolving, there is still a lack of data about which method should be preferred.

Validating the Xerostomia Inventory in a radiation-induced xerostomia population in German language.

Objectives: Though xerostomia is a frequent oral symptom, there is no validated disease-specific questionnaire in German. The purpose of this study was to translate and validate versions of the Xerostomia Inventory and the Summated Xerostomia Inventory in a German-speaking population.

Participants And Methods: Thirty-nine patients including 18 patients suffering from radiation-induced xerostomia enrolled in this study.

Isolation, Cryopreservation, and Transplantation of Spermatogonial Stem Cells.

Spermatogonial stem cell (SSC) culture and transplantation pave the way for clinical restoration of fertility in male prepubertal cancer survivors. In this chapter we detail the steps for isolating and freezing testicular tissue along with protocols for the subsequent recovery from cryopreservation and transplantation of cells into a recipient testis. Transplantation of cultured or thawed SSCs provides not only a functional assay for identification of stem cells, a critical tool for the study of the germline stem cell niche in model organisms, but also a framework for reconstitution of spermatogenesis in humans.

Optimal selection of genetic variants for adjustment of population stratification in European association studies.

Population stratification is usually corrected relying on principal component analysis (PCA) of genome-wide genotype data, even in populations considered genetically homogeneous, such as Europeans. The need to genotype only a small number of genetic variants that show large differences in allele frequency among subpopulations-so-called ancestry-informative markers (AIMs)-instead of the whole genome for stratification adjustment could represent an advantage for replication studies and candidate gene/pathway studies. Here we compare the correction performance of classical and robust principal components (PCs) with the use of AIMs selected according to four different methods: the informativeness for assignment measure ($IN$-AIMs), the combination of PCA and F-statistics, PCA-correlated measurement and the PCA weighted loadings for each genetic variant.

Methods and results from the genome-wide association group at GAW20.

Background: This paper summarizes the contributions from the Genome-wide Association Study group (GWAS group) of the GAW20. The GWAS group contributions focused on topics such as association tests, phenotype imputation, and application of empirical kinships. The goals of the GWAS group contributions were varied.

Spermatogonial stem cells.

Spermatogonial stem cells (SSCs) are the most primitive spermatogonia in the testis and have an essential role to maintain highly productive spermatogenesis by self-renewal and continuous generation of daughter spermatogonia that differentiate into spermatozoa, transmitting genetic information to the next generation. Since the 1950s, many experimental methods, including histology, immunostaining, whole-mount analyses, and pulse-chase labeling, had been used in attempts to identify SSCs, but without success. In 1994, a spermatogonial transplantation method was reported that established a quantitative functional assay to identify SSCs by evaluating their ability to both self-renew and differentiate to spermatozoa.

Control procedures and estimators of the false discovery rate and their application in low-dimensional settings: an empirical investigation.

Background: When many (up to millions) of statistical tests are conducted in discovery set analyses such as genome-wide association studies (GWAS), approaches controlling family-wise error rate (FWER) or false discovery rate (FDR) are required to reduce the number of false positive decisions. Some methods were specifically developed in the context of high-dimensional settings and partially rely on the estimation of the proportion of true null hypotheses. However, these approaches are also applied in low-dimensional settings such as replication set analyses that might be restricted to a small number of specific hypotheses.

Spermatogonial Stem Cell Transplantation to the Testis.

Spermatogonial stem cells (SSCs) are located in the basal region of the seminiferous tubules and provide a self-renewing reservoir from which progenitor spermatogonia arise and transiently amplify in number before transition to a differentiating state. SSC transplantation involves grafting mouse testicular cells into the seminiferous tubules of an aspermic recipient testis that is generated either by chemical (e.g.

Culture and Expansion of Primary Undifferentiated Spermatogonial Stem Cells.

This protocol describes a culture method for supporting the maintenance and expansion of a primary mouse undifferentiated spermatogonial population containing spermatogonial stem cells (SSCs). The doubling time for SSCs in culture is relatively slow. Once established, SSC lines are split 1:2 to 1:4 every 7 d.

Isolation of the Spermatogonial Stem Cell-Containing Fraction from Testes.

A testis cell fraction enriched for spermatogonial stem cells (SSCs) compared with the unfractionated total testis cell population can be isolated from testes after birth and adult stages. This protocol involves dissociating the seminiferous tubules into a single-cell suspension, using enzymes and mechanical disruption. This is followed by the selection of the Thy1 cell fraction that contains nearly the entire SSC population and is enriched for these cells compared with the total testis cell population.

Chemokine (C-X-C) Ligand 12 Facilitates Trafficking of Donor Spermatogonial Stem Cells.

The chemokine (C-X-C) receptor type 4 (CXCR4) is an early marker of primordial germ cells (PGCs) essential for their migration and colonization of the gonads. In spermatogonial stem cells (SSCs), the expression of CXCR4 is promoted by the self-renewal factor, glial cell line-derived neurotrophic factor (GDNF). Here, we demonstrate an important role of CXCR4 during donor mouse SSCs reoccupation of the endogenous niche in recipient testis.

Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer.

Purpose: Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach.

Materials And Methods: We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011.

Testicular tissue cryopreservation in prepubertal male children: an analysis of parental decision-making.

Background: Infertility is an unfortunate treatment-related consequence for some pediatric malignancies as well as some non-malignant conditions treated with stem cell transplant. Unlike pubertal males, prepubertal males cannot produce semen for cryopreservation. This manuscript reports on the acceptability and safety of a multi-institutional protocol for offering testicular tissue cryopreservation to families of prepubertal male children at highest risk for infertility.

The germline stem cell niche unit in mammalian testes.

This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations.

Fertile offspring derived from mouse spermatogonial stem cells cryopreserved for more than 14 years.

Background: Approximately 80% of childhood cancers can now be cured but a side effect of treatment results in about one-third of the surviving boys being infertile or severely subfertile when they reach reproductive age. Currently, more than 1 in 5000 men of reproductive age who are childhood cancer survivors suffer from this serious quality of life problem. It is possible to obtain a testicular biopsy before treatment to preserve the spermatogonial stem cells (SSCs) of the male by cryopreservation, but the results of long-term storage of SSCs on their subsequent functional ability to generate normal offspring has not been examined in any mammalian species.

Spermatogonial stem cell self-renewal requires ETV5-mediated downstream activation of Brachyury in mice.

Insight regarding mechanisms controlling gene expression in the spermatogonial stem cell (SSC) will improve our understanding of the processes regulating spermatogenesis and aid in treating problems associated with male infertility. In the present study, we explored the global gene expression profiles of the glial cell line-derived neurotrophic factor (GDNF)-regulated transcription factors Ets (E-twenty-six) variant gene 5 (Etv5); B-cell chronic lymphocytic leukemia (CLL)/lymphoma 6, member B (Bcl6b); and POU domain, class-3 transcription factor 1 (Pou3f1). We reasoned that these three factors may function as a core set of transcription factors, regulating genes responsible for maintaining the SSC population.