Topographic Patterns of Intracranial Meningioma Recurrences-Systematic Review with Clinical Implication.

BACKGROUND: While several risk factors for recurrences have been defined, the topographic pattern of meningioma recurrences after surgical resection has been scarcely investigated. The possibility of theoretically predicting the site of recurrence not only allows us to better understand the pathogenetic bases of the disease and consequently to drive the development of new targeted therapies, but also guides the decision-making process for treatment strategies and tailored follow-ups to decrease/prevent recurrence. METHODS: The authors performed a comprehensive and detailed systematic literature review of the EMBASE and MEDLINE electronic online databases regarding the topographic pattern of recurrence after surgical treatment for intracranial meningiomas. Demographics and histopathological, neuroradiological and treatment data, pertinent to the topography of recurrences, as well as time to recurrences, were extracted and analyzed. RESULTS: Four studies, including 164 cases of recurrences according to the inclusion criteria, were identified. All studies consider the possibility of recurrence at the previous dural site; three out of four, which are the most recent, consider 1 cm outside the previous dural margin to be the main limit to distinguish recurrences closer to the previous site from those more distant. Recurrences mainly occur within or close to the surgical bed; higher values of proliferation index are associated with recurrences close to the original site rather than within it. CONCLUSIONS: Further studies, including genomic characterization of different patterns of recurrence, will better clarify the main features affecting the topography of recurrences. A comparison between topographic classifications of intracranial meningioma recurrences after surgery and after radiation treatment could provide further interesting information.

Gender gap in deep brain stimulation for Parkinson's disease: preliminary results of a retrospective study.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment of PD for both women and men. However, discussions have been reported about the impact of STN-DBS surgery in PD. The aim of our study is to identify differences between men and women in terms of pre- and post-DBS symptoms and try to explain the possible causes. In the current study, we evaluated the gender impact on STN-DBS in PD at the Department of Neurosurgery of University of Naples "Federico II" from 2013 to 2021. Motor and non-motor symptoms were evaluated. To compare the data before and after surgery and between the genders, Wilcoxon-Mann-Whitney tests were performed. A total of 43 patients with PD were included; of them, 17 (39%) were female. Baseline evaluation revealed no gender differences in the age of onset (p = 0.87). Not significant differences were noted in the Unified Parkinson's Disease Rating Scale (UPDRS) pre-surgery score, but if we consider UPDRS subscores of motor examination, significant clinical improvement was reported in both male and female in terms of UPDRS pre- and post-surgery (p < 0.001). STN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in motor domains. Improving our knowledge in this field can allow us to implement strategies to identify new directions in the development of an adequate treatment of PD in terms of surgical intervention and in consideration of the gender.

Effect of process conditions on the growth of three-dimensional dermal-equivalent tissue obtained by microtissue precursor assembly.

Bottom-up approach is an appealing strategy to build complex three-dimensional (3D) viable tissues in vitro starting from microtissue precursors (µTP). In this work we biofabricated a thick dermal-like tissue by sequentially combining two steps: a µTPs production and assembly followed by tissue maturation in a purpose-built bioreactor. The µTPs were produced by first seeding bovine primary fibroblasts on gelatine microparticles and then cultivating them in stirring conditions until a thick layer of ~80 µm of de novo synthesized extracellular matrix uniformly covered the microparticle surface. The µTPs were then loaded into a cylindrical chamber (2 mm in depth and 35 mm in diameter) and let to maturate and assemble into a 3D viable biohybrid tissue under specific fluid flow conditions. Several combinations of perfusion and/or tangential fluid flow were applied and their effect on the tissue formation and maturation was assessed. Results show that structural composition and mechanical features of the final 3D bioengineered tissue are strongly affected by the hydrodynamic environment and demonstrate that by optimizing culture conditions a 3D viable tissue with properties similar to that of native derma could be produced.

Engineered dermal equivalent tissue in vitro by assembly of microtissue precursors.

Tissue-engineered constructs can be fabricated by the assembly of smaller building blocks in order to mimic much of the native biology that is often made from repeating functional units. Our aim was to realize a three-dimensional (3-D) tissue-like construct in vitro by inducing the assembly of functional micrometric tissue precursors (microTPs). MicroTPs were obtained by dynamic cell seeding of bovine fibroblasts on porous gelatine microcarriers using a spinner flask bioreactor. During the dynamic seeding, cells adhered, proliferated and synthesized a thin layer of extracellular matrix (ECM) in and around the macroporous beads, generating the microTPs. The analysis showed that the ECM produced was rich in type I collagen. The cells and ECM layer around the microTPs allowed their biological sintering via cell-cell and cell-matrix interaction after only a few days of dynamic seeding. The assembling ability of microTPs was exploited by placing them in a maturation chamber. After 1 week of culture disc-shaped constructs (1cm in diameter, 1mm in thickness) of completely assembled microTPs were collected. The biohybrid obtained presented both a homogeneous and compact aspect. Moreover, histological and immunohistochemical analyses revealed an abundant ECM, rich in type I collagen, interconnecting the microTPs. The results obtained in this survey pave the way to realizing a 3-D dermal tissue equivalent by means of a bottom-up tissue engineering approach.

Testicular activity of Mos in the frog, Rana esculenta: a new role in spermatogonial proliferation.

Mos is a MAPK kinase kinase with an expression that is highly restricted to the gonads. Its function is mainly associated to the meiotic metaphase II arrest occurring during female gametogenesis, whereas to our knowledge, its role during spermatogenesis has not yet clarified. In the present paper, we report the isolation of c-mos cDNA and the identification of a 60-kDa Mos protein from the testis of the anuran amphibian, Rana esculenta. Both the transcript and the protein are always present at low levels in the testis during the frog annual sexual cycle, with single significant peaks of expression in March and May, respectively. Mos is mainly localized in the cytoplasm of primary and secondary spermatogonia (SPG). Therefore, we have used treatments with ethane-dimethane sulphonate (EDS), which blocks spermatogonial mitosis in frogs. Four days after a single EDS injection, Mos expression in SPG highly increases concomitantly with the temporary arrest of mitosis. From 8 to 28 days after the injection, the normal proliferative activity of SPG is restored, and Mos expression gradually decreases to control levels. These results strongly indicate that the c-mos proto-oncogene exerts a new role associated to the regulation of spermatogonial proliferation.

Ethane 1,2-dimethane sulphonate is a useful tool for studying cell-to-cell interactions in the testis of the frog, Rana esculenta.

Ethane 1,2-dimethane sulphonate (EDS), a toxin which specifically destroys Leydig cells (LC), has been used to study cellular interactions in the testis of the frog Rana esculenta. Animals received three consecutive EDS injections and were sacrificed on day 4, 8, and 28 from the first injection. No significant morphological differences were observed between present observation and that obtained, in a previous experiment, after four consecutive EDS injections. In fact, on day 4, in the germinal tubules adjacent to apparently normal LC, Sertoli cells surrounding primary spermatogonia (I SPG) show heterochromatic nuclei and loss of cellular adhesion. Interestingly, I SPG surrounded by the heterochromatic Sertoli cells present grossly swollen mitochondria with ballooned cristae. On day 8, sometimes in the interstitium many LC appear strongly damaged and the germinal tubules appear disorganized; the only cell type still distinguishable is the I SPG. On day 28 from the first EDS injection a new population of LC reappear in the interstitium and spermatogenesis normalizes. These data confirm the close relationship between the interstitial and the geminal compartments. Immunocytochemical data obtained using a polyclonal antibody anticonnexin-43 (Cx-43, the most abundant Cx found in mammalian testis) demonstrate the presence of Cx-43 in the frog testis. In particular, Cx-43 is present between LC in the interstitium, between Sertoli and germ cells in the cysts and between Sertoli cells and I SPG. Cx-43 immunopositivity sharply decreases on day 4 from the first EDS injection simultaneously with the loss of cellular adhesion between Sertoli and germ cells. On day 8 and 28 from the first EDS injection Cx-43, immunopositivity is restored and, this data is also supported by Western blot analysis. Our data provide, for the first time, evidence that Cx-43 protein is present in the frog testis and confirm that EDS is a useful tool for studying cellular communication at the paracrine pathway or through direct contact depending on the gap junctional pathway in R. esculenta testis

Cytoplasmic versus nuclear localization of Fos-related proteins in the frog, Rana esculenta, testis: in vivo and direct in vitro effect of a gonadotropin-releasing hormone agonist.

Evidence has been accumulated indicating that GnRH-like peptides are present in a variety of extrabrain areas of mammalian and nonmammalian vertebrates. A pioneer study carried out in the frog, Rana esculenta, demonstrated that testicular GnRH induced spermatogonial proliferation. Recently, we have shown that in proliferating spermatogonia (SPG) of frogs, a change of localization of the oncoprotein Fos, from the cytoplasm to the nucleus, occurs. This leads to the hypothesis that one or more testicular GnRH peptides may regulate SPG proliferation through Fos family proteins. Therefore, in vivo experiments in intact R. esculenta and in vitro incubations of testis fragments have been carried out using GnRH agonist (GnRHa; buserelin) and GnRH antagonist (D-pGlu(1),D-Phe(2),D-Trp(3,6)-GnRH). Cytoplasmic and nuclear Fos-like protein localization has been found by Western blot analysis in testicular extracts. Immunocytochemistry confirmed that cytoplasmic immunostaining was restricted to SPG; change of localization into the nuclear compartment was observed after GnRHa treatment. Northern blot analysis showed that treatments of testis fragments with GnRHa did not modify testicular c-fos mRNA expression. On the contrary, a Fos-like protein of 52 kDa, while not affected in vivo, disappeared from testicular cytosolic extracts after in vitro treatment with GnRHa. Contemporaneously, a 55-kDa Fos-related signal appeared in nuclear extracts. The GnRH antagonist counteracted the effects of GnRHa. Furthermore, in vivo treatments showed that GnRHa acted negatively on a 43-kDa nuclear Fos-related signal and that gonadotropins caused the decrease of 52-kDa cytoplasmic signal. In conclusion, we show, to our knowledge for the first time, that Fos is regulated by GnRHa directly (not through the pituitary) at the testicular level. The main effect appears to be related to Fos translocation from cytoplasmic to nuclear compartments of SPG.

Temporal and spatial localization of prothymosin alpha transcript in the Harderian gland of the frog, Rana esculenta.

The Harderian gland (hg) is the only orbital gland of the frog Rana esculenta, and it has the essential function of lubricating the eyes. The hg secretory activity is seasonal, showing the highest value in summer. There is, at present, no data on gene expression of the frog hg. This study reports, for the first time, on the temporal and spatial expression of a cDNA clone encoding for the prothymosin alpha (Prot-alpha), a highly acidic nuclear protein present in virtually all mammalian cells. Northern blot analysis revealed a single 1.7 kb transcript detected in the frog hg throughout the year, with a lowest expression in September in concomitance with the minimum secretory activity. In situ hybridization indicated that hg secretory cells express Prot-alpha transcript, and the hybridization signal was less intense in the September gland. The constant expression of the frog Prot-alpha mRNA during the whole year suggests a constitutive role for this molecule in the hg. In addition, taking into account that, in mammals, many immunomodulatory functions have been attributed to this protein, it is suggested that frog Prot-alpha might contribute to the hg immunity processes, probably acting as a protective agent against infections of the eyeball. Interestingly, although the presence of Prot-alpha gene in animals other than mammals has been considered to be highly unlikely, the present paper confirms the presence of Prot-alpha transcript in a nonmammalian vertebrate, the frog R. esculenta.

First evidence of prothymosin alpha in a non-mammalian vertebrate and its involvement in the spermatogenesis of the frog Rana esculenta.

A cDNA clone encoding for a Prothymosin alpha (Prot-alpha) has been isolated and characterized from the testis of the frog Rana esculenta. Frog Prothymosin alpha (fProt-alpha) predicted a 109 amino acid protein with a high homology to the mammalian Prot-alpha. fProt-alpha contains 28 aspartic and 25 glutamic acid residues and presents the typical basic KKQK amino acid sequence in the close carboxyl terminal region. Northern blot analysis revealed that fProt-alpha is highly expressed in the testis. A different expression of fProt-alpha transcript was found during the frog reproductive cycle with a peak in September/October in concomitance with germ cell maturation, strongly suggesting a role for this protein in the testicular activity. In situ hybridization evidenced that the only germ cells expressing fProt-alpha are the primary and secondary spermatocytes; in addition, the hybridization signal was stronger in the October testis. Taken together, our findings indicate that fProt-alpha might contribute to the efficiency of frog spermatogenesis with a role during the meiosis. This study is the first report on the isolation and characterization of a Prot-alpha in a non-mammalian vertebrate. In addition, our results indicate that the testis of the frog R. esculenta may be a useful model to increase the knowledge concerning the physiological role of Prot-alpha in vertebrates.