Gonocyte transformation to spermatogonial stem cells occurs earlier in patients with undervirilisation syndromes

Aim

Fertility post-orchidopexy is dependent on transformation of neonatal gonocytes (G) into adult dark spermatogonia at about 3 months, the same time as gonadotrophins stimulate androgen secretion. We examined how androgen blockade affects transformation of gonocytes to spermatogonial stem cells (SSC) during this period in patients with undervirilisation syndromes.

Methods

Patients with undervirilisation syndromes (n = 30, 1.5 weeks–16 years) underwent review of medical records, pathology reports, and H&E slides of testes (ethics HREC32164). Fluorescent immunohistochemistry against anti-Mullerian hormone (AMH, Sertoli cells), mouse VASA homologue (MVH, germ cells) and DAPI (nuclei) allowed the number of MVH-positive gonocytes/spermatogonial stem cells per seminiferous tubular cross-section (G/T or SSC/T) to be counted.

Results

Gonocytes (MVH-positive cells in the tubular lumen) were present in 15/16 patients under 2 years old. SSC (MVH-positive cells on the tubule basement membrane) were present in 25/30 patients. With increasing age, the mean number of SSC/T decreased from ~ 4 to 0, and G/T decreased from ~ 1.5 to 0. SSC were present in CAIS and PAIS patients at 1.5 and 3.5 weeks old, respectively.

Conclusions

Gonocytes transform into SSC earlier than expected in patients with undervirilisation syndromes. Lack of androgens may stimulate non-androgenic regulators to trigger transformation. Understanding how gonocytes transform may enable optimization of spermatogonial development to preserve fertility post-orchidopexy.     

Randomised clinical trial on 7-days-a-week postoperative radiotherapy vs. concurrent postoperative radio-chemotherapy in locally advanced cancer of the oral cavity/oropharynx

Objective:To compare the efficacy and tolerance of 7-days-a-week accelerated postoperative radiotherapy (p-CAIR) vs postoperative radio-chemotherapy (p-RTCT)Methods:Between September 2007 and October 2013, 111 patients were enrolled and randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week (n = 57, p-CAIR) or 63 Gy in 1.8 Gy fractions 5-days-a-week with concurrent cisplatin 80–100 mg per square meter of body-surface area on days 1, 22 and 43 of the radiotherapy course (p-RTCT). It represents approximately 40% of the intended trial size, that was closed prematurely due to slowing accrual. Only high-risk patients with squamous cell cancer of the oropharynx/oral cavity, considered fit for concurrent treatment were enrolled.Results:The rate of locoregional control (LRC) did not differ significantly between treatment arms (p = 0.18, HR = 0.56), 5 year LRC tended, however, to favour p-RTCT (81%) vs p-CAIR (62%). There was no difference in overall survival between treatment arms (p = 0.90, HR = 1.03).The incidence and severity of acute mucosal reactions and late reactions did not differ significantly between treatment arms. Haematological toxicity of p-RTCT was, however, considerably increased compared to p-CAIRConclusion:Concurrent postoperative RTCT tended to improve locoregional control rate as compared to p-CAIR. This, however, did not transferred into improved overall survival. Postoperative RTCT was associated with a substantial increase in haematological toxicity that negatively affected treatment compliance in this arm.Advances in knowledge:To our knowledge, this is the first trial that compares accelerated radiotherapy and radio-chemotherapy in postoperative treatment for oralcavity/oropharyngeal cancer     

Obraz kliniczny neurofibromatozy typu 1 na podstawie obserwowanych przypadków

Neurofibromatosis type 1 (NF1) eponymically called von Recklinghausen disease is autosomal dominant disease and remains an example of phakomatose. They are congenital, genetic disorders affecting mainly nervous and integumentary system. The aim of this study is to report six cases of NF1 in which diagnostic management is based on clinical findings in physical examination: observing characteristic dermatological and ophthalmological manifestations such as cafe au lait spots, Crowe sign (axillary and inguinal freckling), neurofibromas or Lish nodules within the eyes. Existence of those characteristic findings frequently precedes important pathologies (neoplasia) in different areas of the body, especially in nervous system. In the paper we emphasize that genetic MLPA test does not always correlate with clinical manifestation, what had been observed in our patients as well.     

The release of metal ions from orthodontic appliances: Animal tests

Objective:To investigate the release of metal ions from an orthodontic appliance in tests on animals (pigs).Materials and Methods:An animal test was conducted on 24 pigs divided equally into an experimental and a control group. In total, 12 sets of experimental orthodontic plates were surgically inserted into pig snouts in the experimental group for 6 months. Noninvasive matrices (hair [0, 3, and 6 months]) and invasive matrices (kidneys, liver, lungs, aorta, and oral mucosa) were collected for multi-elemental analysis (inductively coupled plasma optical emission spectrometry) from the experimental and control groups.Results:The greatest differences in the content of toxic metals were found in the aorta (Ni level was 4.8 times higher in experimental than in the control group), in the cheek (Ni 3.5 times higher), and in the hair sampled after 3 months (Cr 3.4 times higher).Conclusions:The obtained data indicate that the products of corrosion have passed into selected tissues of pigs; however, the doses of toxic metal ions released from the appliance did not reach toxic levels.     

Adhesion of human uroepithelial cells to E-selectin: Possible involvement of sialosyl LewisA-ganglioside

In a previous study we showed that tumorigenic and invasive human uroepithelial cell lines are characterized by the presence of sialosyl Le^a (sLe^a) ganglioside. Our data suggested that expression of this glycolipid correlated with acquisition of the malignant phenotype by human urothelial cells. To evaluate the postulated adhesion function of sLe^a antigen, we studied the adherence of 6 human urothelial cell lines with different expressions of this carbohydrate structure to E-selectin-expressing CHO cells. The only cell line that bound specifically to E-selectin was Hu 1703He, which expressed the highest level of sLe^a antigen. The involvement of carbohydrate-E-selectin interaction in the adhesion of Hu 1703He cells was indicated by the following facts: (i) anti-E-selectin monoclonal antibody (MAb) completely abolished binding to E-selectin-expressing CHO cells; (ii) removal of sialic acid from Hu 1703He cells highly decreased the adhesion. Adhesion correlated with the presence of several sLe^a-carrying glycoproteins, which was shown by immunoblotting of Hu 1703He cell lysate with anti-sLe^a MAb 19-9. The binding of antibody was abolished when cell lysate was treated with O-sialoglycoprotein endopeptidase, suggesting that sLe^a is present on O-linked oligosaccharides. However, incubation of Hu 1703He cells with O-sialoglycoprotease had no effect on adhesion to E-selectin or on binding of 19-9 MAb to the cell surface. Our data suggest that (i) protein-bound sLe^a oligosaccharides represent only a minor portion of whole sLe^a antigen produced by uroepithelial cells; (ii) effective binding to E-selectin occurs when sLe^a oligosaccharide present on cell-surface glycosphingolipids is expressed in high density since the cell lines with moderate expression of sLe^a ganglioside did not bind to E-selectin-transfected CHO cells. © 1996 Wiley-Liss, Inc.     

On the Miscibility of Nematic Liquid Crystals with Ionic Liquids and Joint Reaction for High Helical Twisting Power Product(s)

Mixtures of nematic liquid crystals (LCs) with chiral ionic liquids (CILs) may find application as active materials for electrically driven broadband mirrors. Five nematic liquid crystal hosts were mixed with twenty three ionic liquids, including chiral ones, and studied in terms of their miscibility within the nematic phase. Phase diagrams of the mixtures with CILs which exhibited twisted nematic phase were determined. Miscibility, at levels between 2 and 5 wt%, was found in six mixtures with cyanobiphenyl-based liquid crystal host—E7. On the other hand, the highest changes in the isotropization temperature was found in the mixtures with isothiocyanate-based liquid crystal host—1825. Occurrence of chemical reactions was found. A novel chiral binaphtyl-based organic salt [N₁₁₁₁₆][BNDP] was synthesized and, in reaction to the 1825 host, resulted in high helical twisting power product(s). Selectivity of the reaction with the isothiocyanate-based liquid crystal was found.     

Influence of the Shear Cap Size and Stiffness on the Distribution of Shear Forces in Flat Slabs

The scope of this paper is to investigate analytically and numerically the influence of shear cap size and stiffness on the distribution of shear forces in flat slabs in a slab–column-connections-reinforced concrete structure. The effect of support (shear cap) stiffness on the calculation of the length of the shear control perimeter according to the available methods is presented. Based on the analysis, the authors indicate in what range of support stiffness the corner concentrations become important in the calculation of the punching resistance. For shear caps with high flexibility (α1 ≤ 0.5), the concentration of internal forces in the corners does not occur. The authors compare the numerical results obtained from the calculation methods and indicate the correlations, which can be useful guidance for structural designers. In the case of large shear caps, the simplified MC2010 method gives a significantly lower value of the effective control perimeter length compared to more accurate methods. This paper is intended to provide scientists, civil engineers, and designers with guidelines on which factors influence punching shear load capacity of the slab–column connections with shear caps.     

Motor Unit Fatigability following Chronic Carnosine Supplementation in Aged Rats

Studies suggest that carnosine (beta-alanyl-L-histidine) is effective in treating neuromuscular diseases associated with aging, but there is still a need to clarify its role in motor units (MUs) function during aging. In this study, 40 male Wistar rats aged 15 months were randomly assigned to a control or to two experimental groups in which 0.1% carnosine supplementation was performed for 10 or 34 weeks. After 34 weeks, we examined fast fatigable (FF), fast fatigue-resistant (FR) and slow (S) MUs’ force properties and fatigability, as well as antioxidant potential, advanced glycation end products, activity of enzymes, and histidyl dipeptides content in the medial gastrocnemius muscle. Short- and long-term carnosine supplementation maintained the force of FF MUs at a higher level during its rapid decline seen from the initial 10 to 70 s of the fatigue test. In FF, especially long-term, and in FR MUs, especially short-term, carnosine supplementation resulted in less rapid force decline during the initial 70 s of the second fatigue protocol. Carnosine supplementation did not change muscle antioxidant potential and mortality rate (~35% in all groups), nor muscle mass with aging. Moreover, instead of the expected increase, a decrease in histidyl dipeptides by ~30% in the red portion of medial gastrocnemius muscle after long-term supplementation was found. After chronic carnosine supplementation, the specific changes in fatigue resistance were observed in FF and FR units, but not in S MU types that were not accompanied by an improvement of antioxidant potential and activity of glycolytic or oxidative enzymes in aged rats. These observations indicate that carnosine supplementation during aging may generate different physiological adaptations which should be considered as an important factor when planning treatment strategies.     

Impact of Surfactant and Calcium Sulfate Type on Air-Entraining Effectiveness in Concrete

The paper presents the evaluation of the influence of calcium sulfate on the air void microstructure in concrete and its action mechanism depending on the character of the air-entraining agent. Gypsum dehydration has been previously proven to negatively influence the air void structure of air-entrained concrete. Ettringite, nucleating from tricalcium aluminate and calcium sulfate, influences the adsorption and mode of action of anionic-based polycarboxylate ether admixtures. The authors suspected the admixture’s air-entraining mechanism was also affected by these characteristics. Gypsum dehydration was confirmed to influence the air void structure. In the case of the anionic surfactant, the content of air bubbles smaller than 300 µm was lower compared to cement with gypsum and hemihydrate. On the other hand, the content of air voids with a diameter up to 60 µm, which are the most favorable, was higher. The results obtained led to the conclusion that the mechanism of air entrainment was twofold, and in most cases occurred through the lowering of surface tension and/or through the adsorption of surfactant on cement grains. The adsorptive mechanism was proved to be more effective in terms of the total air content and the structure of the air void system. The results and conclusions of the study provide guidelines to determine the proper surfactant type to reduce the risk of improper air entrainment of concrete, and emphasize the importance of gypsum dehydration of cement in the process of air entrainment.