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Antecedentes: Los abordajes quirúrgicos de la región selar han sido un reto para los neurocirujanos. Con la introducción de la técnica endoscópica se ha minimizado el trauma quirúrgico, pero esta técnica no se encuentra exenta de complicaciones., Objetivo: Describir nuestra experiencia institucional en pacientes sometidos a resección de macroadenomas hipofisarios por vía microquirúrgica endonasal transesfenoidal asistida por endoscopia con énfasis en las complicaciones resultantes., Método: Revisamos los expedientes electrónicos de 17 pacientes sometidos a dicho procedimiento de manera consecutiva entre 2017 y 2018, y recabamos variables como edad, sexo, clasificación imagenológica, tiempo de diagnóstico al momento de la cirugía, complicaciones posoperatorias y recurrencia., Resultados: La edad promedio de los pacientes fue de 45.23 años y el 70.59% eran mujeres. Radiológicamente predominó el grado 2 Knosp (47.05%). La complicación principal fue diabetes insípida transitoria (23.52%), seguida por la fístula de líquido cefalorraquídeo (11.76%)., Conclusiones: El manejo microquirúrgico asistido por endoscopia ha demostrado ser un recurso valioso para tratar macroadenomas hipofisarios, pero presenta grados variables de complicaciones, por lo cual se requiere la adquisición de habilidades para el uso del endoscopio, la planeación preoperatoria adecuada y el manejo conjunto multidisciplinario con el fin de evitarlas., Background: Surgical approaches to the sellar region have been a challenge for the neurosurgeon. With the introduction of the endoscopic technique, surgical trauma has been minimized, however it is not free of complications., Objective: To describe our institutional experience in patients undergoing resection of pituitary macroadenomas by endoscopic-assisted microsurgical approach, with emphasis on the resulting complications., Method: We reviewed the electronic files of 17 patients who underwent this procedure consecutively between 2017 and 2018, collecting variables such as age, sex, imaging classification, time of diagnosis at the time of surgery, postoperative complications and recurrence., Results: The average age of the patients was 45.23 years, with 70.59% women. Radiologically, grade 2 Knosp predominated (47.05%). The main complication was transient diabetes insipidus (23.52%) followed by cerebrospinal fluid fistula (11.76%)., Conclusions: The endoscopic-assisted microsurgical approach has proven to be a valuable resource for treating pituitary macroadenomas, however it presents variable degrees of complications, which requires the acquisition of skills for the use of the endoscope, adequate preoperative planning, and multidisciplinary joint management in order to avoid them., (Copyright: © 2021 Permanyer.)

Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11 th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.

The postconcussion syndrome following mild traumatic brain injuries (mTBI) has been regarded as a mostly benign syndrome that typically resolves in the immediate months following injury. However, in some individuals, symptoms become chronic and persistent. This has been a striking feature of the mostly blast-related mTBIs that have been seen in veterans returning from the recent conflicts in Iraq and Afghanistan. In these veterans a chronic syndrome with features of both the postconcussion syndrome and post-traumatic stress disorder has been prominent. Animal modeling of blast-related TBI has developed rapidly over the last decade leading to advances in the understanding of blast pathophysiology. However, most studies have focused on acute to subacute effects of blast on the nervous system and have typically studied higher intensity blast exposures with energies more comparable to that involved in human moderate to severe TBI. Fewer animal studies have addressed the chronic effects of lower level blast exposures that are more comparable to those involved in human mTBI or subclinical blast. Here we describe a rat model of repetitive low-level blast exposure that induces a variety of anxiety and PTSD-related behavioral traits including exaggerated fear responses that were present when animals were tested between 28 and 35 weeks after the last blast exposure. These animals provide a model to study the chronic and persistent behavioral effects of blast including the relationship of PTSD to mTBI in dual diagnosis veterans., (Published by Elsevier B.V.)

One of the most striking features of the mammalian epididymis is the secretion of lysosomal enzymes (LE). These LE may play a role in sperm maturation. In the present study we investigated the activity and distribution of four LE (?-galactosidase (?-Gal), N-acetyl-?-D-glucosaminidase (?-NAG), ?-mannosidase (?-Man) and ?-glucuronidase (?-Glu)) in bull epididymis at two different ages (6 months and 4 years) to determine whether these enzymes vary with sexual maturity. In young, sexually immature (SI) bulls we found high LE activity in the epididymal tissue that accounts for a developed and active lysosomal apparatus. In contrast, low LE activity was measured in sexually mature (SM) bulls, and ?-NAG and ?-Gal were mostly secreted into the lumen. We also attempted to correlate LE distribution with the expression and functionality of mannose-6-phosphate receptors (MPRs), which are thought to be involved in proper delivery of LE to lysosomes. The cation-dependent MPR was highly expressed in SI bulls, with expression decreasing during adulthood, whereas the expression of the cation-independent MPR was higher in SM than SI bulls. In addition, the four enzymes recovered from the epididymal lumen interact with both MPRs at each age. We conclude that the activity and distribution of LE in bull epididymis varies with sexual maturity and that the distribution is regulated differently by the two types of MPR. These findings could provide some molecular basis for male infertility.

Closed tibiae plateau fractures are common injuries in the emergency room. The optimal treatment is not well defined or established. For this reason, there are several surgical management options: open reduction and internal fixation, closed reduction and percutaneous synthesis, external fixation, and even conservative treatment for this kind of fracture. The mechanism of production of this fracture is through large varus or valgus deformation to which is added a factor of axial load. The trauma may be direct or indirect. The degree of displacement, fragmentation and involvement of soft tissues like ligaments, menisci, vascular and nerve structures are determined by the magnitude of the force exerted. Any intra-articular fracture treatment can lead to an erroneous instability, deformity and limitation of motion with subsequent arthritic changes, leading to joint incongruity, limiting activity and significantly altering the quality of life. Open reduction and internal fixation with anatomic restitution is the method used in this type of fracture. However, the results of numerous publications can be questioned due to the inclusion in the same study of fractures treated with very different methods.

Transgenic systems are widely used to study the cellular and molecular basis of human neurodegenerative diseases. A wide variety of model organisms have been utilized, including bacteria (Escherichia coli), plants (Arabidopsis thaliana), nematodes (Caenorhabditis elegans), arthropods (Drosophila melanogaster), fish (zebrafish, Danio rerio), rodents (mouse, Mus musculus and rat, Rattus norvegicus) as well as non-human primates (rhesus monkey, Macaca mulatta). These transgenic systems have enormous value for understanding the pathophysiological basis of these disorders and have, in some cases, been instrumental in the development of therapeutic approaches to treat these conditions. In this review, we discuss the most commonly used model organisms and the methodologies available for the preparation of transgenic organisms. Moreover, we provide selected examples of the use of these technologies for the preparation of transgenic animal models of neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) and discuss the application of these technologies to AD as an example of how transgenic modeling has affected the study of human neurodegenerative diseases.

Myelin abnormalities exist in schizophrenia leading to the hypothesis that oligodendrocyte dysfunction plays a role in the pathophysiology of the disease. The expression of the mRNA for the peripheral myelin protein-22 (PMP-22) is decreased in schizophrenia and recent genetic evidence suggests a link between PMP-22 and schizophrenia. While PMP-22 mRNA is found in both rodent and human brain it has been generally thought that no protein expression occurs. Here we show that PMP-22 protein is present in myelin isolated from adult mouse and human brain. These results suggest that PMP-22 protein likely plays a role in the maintenance and function of central nervous system (CNS) myelin and provide an explanation for why altered PMP-22 expression may be pathophysiologically relevant in a CNS disorder such as schizophrenia.

Transgenic animals are extensively used to study in vivo gene function as well as to model human diseases. The technology for producing transgenic animals exists for a variety of vertebrate and invertebrate species. The mouse is the most utilized organism for research in neurodegenerative diseases. The most commonly used techniques for producing transgenic mice involves either the pronuclear injection of transgenes into fertilized oocytes or embryonic stem cell-mediated gene targeting. Embryonic stem cell technology has been most often used to produce null mutants (gene knockouts) but may also be used to introduce subtle genetic modifications down to the level of making single nucleotide changes in endogenous mouse genes. Methods are also available for inducing conditional gene knockouts as well as inducible control of transgene expression. Here, we review the main strategies for introducing genetic modifications into the mouse, as well as in other vertebrate and invertebrate species. We also review a number of recent methodologies for the production of transgenic animals including retrovirus-mediated gene transfer, RNAi-mediated gene knockdown and somatic cell mutagenesis combined with nuclear transfer, methods that may be more broadly applicable to species where both pronuclear injection and ES cell technology have proven less practical.

Mutations in presenilin-1 (PS1) and presenilin-2 (PS2) cause familial Alzheimer's disease (FAD). Presenilins influence multiple molecular pathways and are best known for their role in the gamma-secretase cleavage of type I transmembrane proteins including the amyloid precursor protein (APP). PS1 and PS2 FAD mutant transgenic mice have been generated using a variety of promoters. PS1-associated FAD mutations have also been knocked into the endogenous mouse gene. PS FAD mutant mice consistently show elevations of Abeta42 with little if any effect on Abeta40. When crossed with plaque forming APP FAD mutant lines, the PS1 FAD mutants cause earlier and more extensive plaque deposition. Although single transgenic PS1 or PS2 mice do not form plaques, they exhibit a number of pathological features including age-related neuronal and synaptic loss as well as vascular pathology. They also exhibit increased susceptibility to excitotoxic injury most likely on the basis of exaggerated calcium release from the endoplasmic reticulum. Electrophysiologically long-term potentiation in the hippocampus is increased in young PS1 FAD mutant mice but this effect appears to be lost with aging. In most studies neurogenesis in the adult hippocampus is also impaired by PS1 FAD mutants. Mice in which PS1 has been conditionally knocked out in adult forebrain on a PS2 null background (PS1/2 cDKO) develop a striking neurodegeneration that mimics AD neuropathology in being associated with neuronal and synaptic loss, astrogliosis and hyperphosphorylation of tau, although it is not accompanied by plaque deposits. The relevance of PS transgenic mice as models of AD is discussed.

Alzheimer's disease is the most common cause of senile dementia in the United States and Europe. At present, there is no effective treatment. Given the disease's prevalence and poor prognosis, the development of animal models has been a high research priority. Transgenic modeling has been pursued on the basis of the amyloid hypothesis and has taken advantage of mutations in the amyloid precursor protein and the presenilins that cause familial forms of Alzheimer's disease. Modeling has been most aggressively pursued in mice, for which the techniques of genetic modification are well developed. Transgenic mouse models now exist that mimic a range of Alzheimer's disease-related pathologies. Although none of the models fully replicates the human disease, the models have contributed significant insights into the pathophysiology of beta-amyloid toxicity, particularly with respect to the effects of different beta-amyloid species and the possible pathogenic role of beta-amyloid oligomers. They have also been widely used in the preclinical testing of potential therapeutic modalities and have played a pivotal role in the development of immunotherapies for Alzheimer's disease that are currently in clinical trials. These models will, without a doubt, continue to play central roles in preclinical testing and be used as tools for developing insights into the biological basis of Alzheimer's disease., ((c) 2010 Mount Sinai School of Medicine.)

Neurobiology of speech and language has previously been studied in the KE family, in which half of the members have severe impairment in both speech and language. The gene responsible for the phenotype was mapped to chromosome 7q31 and identified as the FOXP2 gene, coding for a transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain. Because of linkage studies implicating 7q31 in autism, where language impairment is a component of the disorder, and in specific language impairment, FOXP2 has also been considered as a potential susceptibility locus for the language deficits in autism and/or specific language impairment. In this study, we characterized mice with a disruption in the murine Foxp2 gene. Disruption of both copies of the Foxp2 gene caused severe motor impairment, premature death, and an absence of ultrasonic vocalizations that are elicited when pups are removed from their mothers. Disruption of a single copy of the gene led to modest developmental delay but a significant alteration in ultrasonic vocalization in response to such separation. Learning and memory appear normal in the heterozygous animals. Cerebellar abnormalities were observed in mice with disruptions in Foxp2, with Purkinje cells particularly affected. Our findings support a role for Foxp2 in cerebellar development and in a developmental process that subsumes social communication functions in diverse organisms.

Phosphatidylinositol 3-kinase (PI3K) promotes cell survival and communication by activating its downstream effector Akt kinase. Here we show that PS1, a protein involved in familial Alzheimer's disease (FAD), promotes cell survival by activating the PI3K/Akt cell survival signaling. This function of PS1 is unaffected by gamma-secretase inhibitors. Pharmacological and genetic evidence indicates that PS1 acts upstream of Akt, at or before PI3K kinase. PS1 forms complexes with the p85 subunit of PI3K and promotes cadherin/PI3K association. Furthermore, conditions that inhibit this association prevent the PS1-induced PI3K/Akt activation, indicating that PS1 stimulates PI3K/Akt signaling by promoting cadherin/PI3K association. By activating PI3K/Akt signaling, PS1 promotes phosphorylation/inactivation of glycogen synthase kinase-3 (GSK-3), suppresses GSK-3-dependent phosphorylation of tau at residues overphosphorylated in AD and prevents apoptosis of confluent cells. PS1 FAD mutations inhibit the PS1-dependent PI3K/Akt activation, thus promoting GSK-3 activity and tau overphosphorylation at AD-related residues. Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway.

Adrenaline is able to increase the oxidative damage caused by some xenobiotic agents in the liver. Ethanol produces oxidative changes in hepatic tissue, while an acute intoxication with alcohol increases adrenaline blood levels. The aim of this study was to determine whether adrenaline increases ethanol-induced hydroxyl free radical production in isolated hepatocytes. Adrenaline augmented hydroxyl radicals in a concentration-dependent manner and was blocked by chloroethylclonidine, an alpha(1B)-adrenoceptor antagonist, while adrenaline plus ethanol added their individual effects. It is suggested that adrenaline increases hydroxyl radicals by an alpha(1B)-adrenoceptor-mediated mechanism, while ethanol does so by a receptor-independent mechanism.