Emergency surgery in a severe penetrating skull base injury by a screwdriver: case report and literature review

BACKGROUND: Very few cases of severe penetrating injuries to the skull base with a seemingly innocuous object have been described in the literature. Of the cases reported, only ten involve a penetrating screwdriver. However, the choice of therapeutic management, whether it be emergency surgical or non-surgical removal of the penetrating object as well as the selected surgical approach remain quite controversial. CASE PRESENTATION: The authors describe the case of a severe penetrating skull base injury caused by a screwdriver, following an accidental fall from a ladder. The patient was admitted in Glasgow Coma Scale (GCS) 11 with a cerebrospinal fluid (CSF) leak in the right maxillary area. The tri-dimensional computerized tomography (3-D CT) scan revealed an oblique trajectory of the screwdriver shank through the skull base. The authors opted for an emergency surgical extraction of the object. A contra-lateral pterional approach was successfully performed and a two-year follow-up showed no neurological deficits. CONCLUSION: The reported case supports the choice of emergency surgical removal of the object in penetrating skull base injuries involving the anterior skull base with neurovascular lesions. Surgical aspects of the pterional approach, and in particular the left pterional approach as well as other cranio-facial approaches in severe penetrating skull base injuries are discussed

GATK hard filtering: tunable parameters to improve variant calling for next generation sequencing targeted gene panel data

BACKGROUND: NGS technology represents a powerful alternative to the standard Sanger sequencing in the context of clinical setting. The proprietary software that are generally used for variant calling often depend on preset parameters that may not fit in a satisfactory manner for different genes. GATK, which is widely used in the academic world, is rich in parameters for variant calling. However the self-adjusting parameter calibration of GATK requires data from a large number of exomes. When these are not available, which is the standard condition of a diagnostic laboratory, the parameters must be set by the operator (hard filtering). The aim of the present paper was to set up a procedure to assess the best parameters to be used in the hard filtering of GATK. This was pursued by using classification trees on true and false variants from simulated sequences of a real dataset data. RESULTS: We simulated two datasets, with different coverages, including all the sequence alterations identified in a real dataset according to their observed frequencies. Simulated sequences were aligned with standard protocols and then regression trees were built up to identify the most reliable parameters and cutoff values to discriminate true and false variant calls. Moreover, we analyzed flanking sequences of region presenting a high rate of false positive calls observing that such sequences present a low complexity make up. CONCLUSIONS: Our results showed that GATK hard filtering parameter values can be tailored through a simulation study based-on the DNA region of interest to ameliorate the accuracy of the variant calling

Role of MRI Features as a Prognostic Index in Cervical Spondilogenetic Myelopathy

Introduction The importance of a correct preoperative radiological diagnosis in patients with cervical myelopathy has been widely demonstrated. Indeed, few studies still exist about the correlation between postoperative radiographic and clinical modifications. Materials and Methods The authors present a prospective study of 54 patients with cervical spondilogenetic myelopathy, who underwent surgery for corpectomy and anterior fusion with mesh in a period between January 2005 and August 2013. Images of cervical RMN were studied pre-and postoperatively and attention has been focused on alterations of intramedullary signal on T1- and T2-weighted sequences. Pre-and postoperative changes were correlated with clinical data (obtained by means of a Nurick scales and JOA classification—modified by Benzel). In relation to cervical RM-based studies, patients were divided into 3 groups: (A) no intramedullary signal alteration; (B) alterations in T2-weighted sequences; (C) alterations of the signal in both T1- and T2-weighted sequences. Results In all patients, decompression of the cervical spinal cord has been demonstrated by extension of the anteroposterior diameter of the spinal canal and by increase in the thickness of the subarachnoid space. In group A patients, no intramedullary signal changes were highlighted postoperatively. Patients in group B showed improvement on the base of hyperintensity disappearance on T2-weighted MRI, correlating with an improvement in the clinical quadro. Patients of group C have not been showing changes in the intramedullary MRI signal despite spinal cord decompression. Conclusions Signal alterations in T1 are an unfavorable prognostic index and proved to be irreversible. They correlate with a lack of clinical improvement of the patient. Patients in group B are those with the greatest clinical benefit after surgery and in whom clinical improvement correlates clearly with the radiological outcome

Instantaneous limit equilibrium back analyses of major rockslides triggered during the 2016–2017 central Italy seismic sequence

Among the almost 1400 landslides triggered by the shocks of the 2016–2017 central Italy seismic sequence, only a limited number, all classifiable as rockslides, involved volumes larger than 1000 m3 . Four of these failures, including the three largest among the documented landslides, were described in terms of structural and geomechanical investigations in a previous paper. In this study, the estimated acceleration time histories at the rockslide sites were evaluated through a 2D simplified numerical model accounting for the attenuation phenomena and for the topographic effect of the rock cliffs from which the slide detached. Instantaneous stability analyses were carried out to obtain insights into the variability of the instantaneous margin of safety along the motion, over the entire spectrum of mechanisms that could be activated. Finally, some general suggestions on the pseudostatic verification method for 3D cases are proposed, which represent useful indications to hazard evaluation at local and regional scales

Bioactive Limonoids from the Leaves of Azaridachta indica (Neem)

Eight new limonoids (1−8) and one new phenol glycoside (9), along with six known compounds, were isolated from the leaves of Azaridachta indica. The structures of 1−9 were elucidated on the basis of spectroscopic data analysis. Compounds isolated were assayed for their cytotoxicity against different cancer cell lines. Moreover, their ability to interact with the molecular chaperone Hsp90, affecting its biological activity, was tested

Natural iminosugar (+)-lentiginosine inhibits ATPase and chaperone activity of Hsp90

Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and cell viability. The relevance of Hsp90 as a therapeutic target for numerous diseases states has prompted the identification and optimization of novel Hsp90 inhibitors as an emerging therapeutic strategy. We performed a screening aimed to identify novel Hsp90 inhibitors among several natural compounds and we focused on the iminosugar (+)-lentiginosine, a natural amyloglucosidases inhibitor, for its peculiar bioactivity profile. Characterization of Hsp90 inhibition was performed using a panel of chemical and biological approaches, including limited proteolysis, biochemical and cellular assays. Our result suggested that the middle domain of Hsp90, as opposed to its ATP-binding pocket, is a promising binding site for new classes of Hsp90 inhibitors with multitarget anti-cancer potentia

A Novel Quinazoline Inhibits Hsp90 Protein, EGFR and Induces Apoptosis in Leukemia Cells

The objective of the first part of this study was to investigate the Hsp90 protein possible activ ity of a novel quinazoline Her2/ EGFR inhibitor (Co mpound No. 1: 4-(2-(4-Oxo-2-thio xo-1,4-d ihydroquinazolin-3(2H)yl)ethyl)benzenesulfonamide) p reviously synthesized by a collaborating group. Heat shock protein 90 (Hsp90) has a central ro le in regulation of several client proteins involved in cancers [1,2]. Several Hsp90 inhibitors of the natural or synthetic origin d isplayed potent anticancer activity [3,4]. Accordingly, Hsp90 emerged as an attractive target in the design of anticancer agents. To evaluate the binding mode of compound No. 1 into the ATPase site of Hsp90, a co mparative mo lecular docking study was performed using AutoDock 4.2. The results of this studywas compared with that of the co-crystallized ligand (ATI-13387X, Onalespib). The energy minimization process of the chemical structures of No. 1 was done following our previous report [5]. The results of the docking study revealed that No. 1 fit n icely into the ATPase site, and it displayed a binding free energy (Gb) of-7.21 kcal/ mo l and inhibition constant (Ki) of 5.19 µM to Hsp90, co mpared to Gb of-7.90 kcal/ mol and Ki of 1.62 µM for ATI-13387X. Furthermore, to confirm this result, the surface plasmon resonance (SPR) was devised to test the Hsp90 inhibition activity of No.1, wh ich was 51 nM co mpared to Rad icico l and 17AA G (1.8 nM, and 360 nM; respectively). Overall, co mpound No. 1 exh ibited pro mising Hsp90 inhib iting activity. The second part of the study focused on the effect of No. 1, Dinaciclib and their co mbinationsin HL-60 leukemia cells. The comb ination showed synergistic EGFR inhib ition effect in HL-60 cells. Moreover, No. 1, Dinaciclib and their combination caused a significant increase in the Sub-G1 co mpared to control and doxorubicin (24h), at the expense of S and G2/M cell cycle phases. Cyclin D3, was consequently inhibited by each of the two drugs, and synergistically by their comb ination in HL-60 cells. Furthermore, each of the two drugs downregulated Survivin, wh ich was synergistically inhib ited by the co mbination. In conclusion, co mpound No.1, Dinaciclib and their comb inations showed synergestic EGFR inhibit ion; and pro-apoptoticeffect in HL-60 cells.This project was funded by the deanship of scientific research, Umm Alqura University, KSA (DSR: 15-M ED-3-1-0060). Keywords: Novel quinazoline EGFR inhi bi tor, Hs p90 protein, Leukemi a cells

PAPILOMA ESCAMOSO BUCAL - RELATO DE DOIS CASOS

O papiloma escamoso bucal (PEB) é uma lesão proliferativa benigna do epitélio escamoso estratificado. Clinicamente, esta lesão se apresenta sob a forma de um nódulo exofítico mole, indolor, pedunculado ou séssil e com inúmeras projeções superficiais. A etiologia do PEB está associada ao HPV subtipos 6 e 11. Sua ocorrência em boca é relativamente incomum. O objetivo deste trabalho será relatar dois casos de PEB. No caso 1, paciente do sexo feminino apresentava uma lesão indolor, ligeiramente esbranquiçada, séssil e de aspecto verrucoso no soalho bucal. No caso 2, paciente do sexo feminino exibia duas lesões esbranquiçadas similares na região do pilar amigdaliano, indolores, sésseis e com aproximadamente dois anos de evolução. Nos dois casos, as lesões foram totalmente removidas por meio de biopsia excisional e encaminhadas para exame histopatológico. O diagnóstico do PEB foi confirmado pela histopatologia que revelou fragmento de lesão exibindo proliferação epitelial de aspecto digitiforme com áreas centrais de tecido conjuntivo. No tecido epitelial havia áreas de hiperceratose e a presença de coilocitose. O PEB é uma lesão com características próprias, mas que pode ser confundido com outras lesões bucais esbranquiçadas. Neste contexto, o estudo das características histopatológicas continua sendo o recurso mais recomendado para diagnóstico