Tonic-clonic seizures as a possible complication for cerebrospinal fluid leakage after intradural spinal surgery, a case report

Abstract Background Cerebrospinal fluid leakage is a well-known spinal surgery complication, especially in adults population. Pseudomeningocele is its most common manifestation and it can bring to some conditions, such as intracranial hypotension, infections and wound healing complication. Epilepsy is not classically associated to CSF leakage. We described a case of a female patient who developed tonic-clonic seizures associated with a pseudomeningocele after a detethering surgery. Case description A 16 year old female was admitted to our department for surgical treatment of a tethered cord for a sacral lipoma. Her medical history was remarkable mental retardation with psychiatric disturbs and hypothyroidism. She underwent a surgical intervention for the detethering of conus and dura was closed by a suture and fibrin glue. During third postoperative day she started to suffer a severe occipital headache, followed by tonic-clonic seizures. During suture removal, a collection suspected for a pseudomeningocele was found and chemical and radiological exams confirmed the dubious. Despite a continuous bed rest, collection continued to form. So, we decided to perform a surgical revision and to close dural defect. After intervention, patient did not suffer postural headache anymore and after 3 and 6 months she was found in good health. Conclusion We described the importance of significant morbidity, i.e. that of tonic clonic seizures as a sign of an occult CSF leakage after spinal surgery. Here, hydrocephalus as a condition was present, the change in pressure of CSF can determine seizures as well as promote this complication. A pseudomeningocele is not a trivial complication

Molecular and in vivo studies of a glutamate-class prolyl-endopeptidase for coeliac disease therapy

The digestion of gluten generates toxic peptides, among which a highly immunogenic proline-rich 33-mer from wheat α-gliadin, that trigger coeliac disease. Neprosin from the pitcher plant is a reported prolyl endopeptidase. Here, we produce recombinant neprosin and its mutants, and find that full-length neprosin is a zymogen, which is self-activated at gastric pH by the release of an all-β pro-domain via a pH-switch mechanism featuring a lysine plug. The catalytic domain is an atypical 7+8-stranded β-sandwich with an extended active-site cleft containing an unprecedented pair of catalytic glutamates. Neprosin efficiently degrades both gliadin and the 33-mer in vitro under gastric conditions and is reversibly inactivated at pH > 5. Moreover, co-administration of gliadin and the neprosin zymogen at the ratio 500:1 reduces the abundance of the 33-mer in the small intestine of mice by up to 90%. Neprosin therefore founds a family of eukaryotic glutamate endopeptidases that fulfils requisites for a therapeutic glutenase.This study was supported in part by grants from Spanish and Catalan public and private bodies (grant/fellowship references PID2019-107725RG-I00 to F.X.G.-R., A.R.B., U.E. and T.G.; BES-2016-076877 to S.R.M., BES-2015-074583 to L.A.M., Beatriu de Pinós 2018BP00163 to U.E., 2017SGR3 and Fundació La Marató de TV3 201815 to F.X.G.-R., U.E., A.R.B. and T.G.)

Quantum Griffiths effects and smeared phase transitions in metals: theory and experiment

In this paper, we review theoretical and experimental research on rare region effects at quantum phase transitions in disordered itinerant electron systems. After summarizing a few basic concepts about phase transitions in the presence of quenched randomness, we introduce the idea of rare regions and discuss their importance. We then analyze in detail the different phenomena that can arise at magnetic quantum phase transitions in disordered metals, including quantum Griffiths singularities, smeared phase transitions, and cluster-glass formation. For each scenario, we discuss the resulting phase diagram and summarize the behavior of various observables. We then review several recent experiments that provide examples of these rare region phenomena. We conclude by discussing limitations of current approaches and open questions.Comment: 31 pages, 7 eps figures included, v2: discussion of the dissipative Ising chain fixed, references added, v3: final version as publishe

A Randomly-Controlled Study on the Cardiac Function at the Early Stage of Return to the Plains after Short-Term Exposure to High Altitude

High altitude acclimatization and adaptation mechanisms have been well clarified, however, high altitude de-adaptation mechanism remains unclear. In this study, we conducted a controlled study on cardiac functions in 96 healthy young male who rapidly entered the high altitude (3700 m) and returned to the plains (1500 m) after 50 days. Ninety eight healthy male who remained at low altitude were recruited as control group. The mean pulmonary arterial pressure (mPAP), left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), cardiac function index (Tei index) were tested. Levels of serum creatine kinase isoform MB (CK-MB), lactate dehydrogenase isoenzyme-1 (LDH-1), endothelin-1 (ET-1), nitrogen oxide (NO), serum hypoxia-inducible factor-1α (HIF-1α), 8-iso-prostaglandin F2α (8-iso PGF2α), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at an altitude of 3700 m and 1500 m respectively. The results showed that after short-term exposure to high altitude mPAP and Tei index increased significantly, while LVEF and LVFS decreased significantly. These changes were positively correlated with altitude. On the 15th day after the subjects returned to low altitude, mPAP, LVEF and LVFS levels returned to the same level as those of the control subjects, but the Tei index in the returned subjects was still significantly higher than that in the control subjects (P<0.01). We also found that changes in Tei index was positively correlated with mPAP, ET-1, HIF-1α and 8-iso PGF2α levels, and negatively correlated with the level of NO, LVEF, LVFS, CK-MB and LDH-1. These findings suggest that cardiac function de-adapts when returning to the plains after short-term exposure to high altitude and the function recovery takes a relatively long time

La calidad del aceite de oliva virgen: Posibles nuevos criterios para su evaluación

The present study consists in the evaluation of twenty five parameters for determining the influence of continuous system of pastes centrifugation, discontinuous press system and partial extraction system on obtaining of virgin olive oil, and their possible utilization as new quality parameters. Also, those indexes more related to quality than to spoilt degree (acid value, peroxide value and K270) were determined. The tested oils have been obtained in three oil-mills, from three different olive varieties, in two ripening states.El presente estudio consiste en la evaluación de veinticinco variables, para determinar la influencia que los sistemas de obtención del aceite de oliva virgen (sistema continuo de centrifugación de pastas, sistema discontinuo de prensas y sistema de extracción parcial) pueden tener sobre las mismas, así como su posible utilización como nuevos parámetros de calidad para estos aceites. Parámetros que estén más relacionados con los atributos de calidad que con el grado de deterioro (índice de acidez, índice de peróxidos y K270) de estos aceites. Los aceites ensayados se han obtenido en tres almazaras industriales a partir de tres variedades diferentes de aceitunas y en dos grados de madurez

Ezrin Ubiquitylation by the E3 Ubiquitin Ligase, WWP1, and Consequent Regulation of Hepatocyte Growth Factor Receptor Activity

The membrane cytoskeleton linker ezrin participates in several functions downstream of the receptor Met in response to Hepatocyte Growth Factor (HGF) stimulation. Here we report a novel interaction of ezrin with a HECT E3 ubiquitin ligase, WWP1/Aip5/Tiul1, a potential oncogene that undergoes genomic amplification and overexpression in human breast and prostate cancers. We show that ezrin binds to the WW domains of WWP1 via the consensus motif PPVY477 present in ezrin’s C-terminus. This association results in the ubiquitylation of ezrin, a process that requires an intact PPVY477 motif. Interestingly ezrin ubiquitylation does not target the protein for degradation by the proteasome. We find that ezrin ubiquitylation by WWP1 in epithelial cells leads to the upregulation of Met level in absence of HGF stimulation and increases the response of Met to HGF stimulation as measured by the ability of the cells to heal a wound. Interestingly this effect requires ubiquitylated ezrin since it can be rescued, after depletion of endogenous ezrin, by wild type ezrin but not by a mutant of ezrin that cannot be ubiquitylated. Taken together our data reveal a new role for ezrin in Met receptor stability and activity through its association with the E3 ubiquitin ligase WWP1. Given the role of Met in cell proliferation and tumorigenesis, our results may provide a mechanistic basis for understanding the role of ezrin in tumor progression

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

BACKGROUND: p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. METHODS: p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. RESULTS: p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. CONCLUSION: Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man

Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis

<p>Abstract</p> <p>Background</p> <p>The inter-alpha-trypsin inhibitors (ITI) are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by <it>AMBP </it>– and five homologous heavy chains (encoded by <it>ITIH1</it>, <it>ITIH2</it>, <it>ITIH3</it>, <it>ITIH4</it>, and <it>ITIH5</it>), contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis.</p> <p>Methods</p> <p>We systematically investigated differential gene expression of the <it>ITIH </it>gene family, as well as <it>AMBP </it>and the interacting partner <it>TNFAIP6 </it>in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas) using cDNA dot blot analysis (Cancer Profiling Array, CPA), semiquantitative RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>We found that <it>ITIH </it>genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, <it>ITIH </it>genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose <it>ITIH2 </it>expression in human breast cancer. Loss of <it>ITIH2 </it>expression in 70% of cases (n = 50, CPA) could be confirmed by real-time PCR in an additional set of breast cancers (n = 36). Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p < 0.001) between ITIH2 expression and estrogen receptor (ER) expression indicating that ER may be involved in the regulation of this ECM molecule.</p> <p>Conclusion</p> <p>Altogether, this is the first systematic analysis on the differential expression of <it>ITIH </it>genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.</p

Breast MRI: guidelines from the European Society of Breast Imaging

The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity—as in all breast imaging modalities—depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yield MR-only visible questionable lesions that require an MR-guided intervention for clarification, MRI should only be offered by institutions that can also offer a MRI-guided breast biopsy or that are in close contact with a site that can perform this type of biopsy for them. Radiologists involved in breast imaging should ensure that they have a thorough knowledge of the MRI techniques that are necessary for breast imaging, that they know how to evaluate a breast MRI using the ACR BI-RADS MRI lexicon, and most important, when to perform breast MRI. This manuscript provides guidelines on the current best practice for the use of breast MRI, and the methods to be used, from the European Society of Breast Imaging (EUSOBI)