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PURPOSE: Displaced supracondylar humerus fractures are treated with open or closed reduction and percutaneous pinning. In 2012, our management of patients with a displaced fracture changed from closed reduction in the emergency department (ED) to in situ splinting prior to closed reduction and pinning in the operating room (OR). The purpose of this study was to investigate if outcomes or complications differ between these two management methods. METHODS: Patients less than ten years old with a Gartland type II or III supracondylar humerus fracture between 2008 and 2016 were included. Cases of polytrauma were excluded. Radiographic outcomes were assessed at follow-up. The Fisher's exact test was used for categorical variables and the Wilcoxon rank sums tests for continuous variables. RESULTS: In all, 157 patients were included, 89 with reduction in the ED and 68 without. There was no significant difference between the groups related to demographic factors or fracture characteristics. Patients managed without reduction in the ED had a lower average delay from ED to OR compared with those treated with reduction (16 hours versus 22 hours, p < 0.005) and a shorter hospital length of stay (34 hours versus 40 hours, p < 0.005). CONCLUSION: No difference in complications or outcomes was found between patients with Type II or III supracondylar fractures treated initially with or without closed reduction in the ED. Patients treated without ED reduction were taken to the OR sooner and remained in the hospital for a shorter period of time. Splinting in situ reduces anaesthesia exposure without increasing postoperative complications or suboptimal outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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PURPOSE: To evaluate sensitivity, specificity and accuracy of a radiographic slipped capital femoral epiphysis (SCFE)-diagnosis among medical specialists. METHODS: Three paediatricians, three paediatric radiologists and three paediatric orthopaedic surgeons completed two rounds of a survey of anteroposterior and frog-leg lateral radiographs of patients with a diagnosis of SCFE (25), femoroacetabular impingement (four), Legg-Calvé-Perthes (11) or no hip pathology (ten). Intra- and interobserver agreement among specialties regarding the diagnosis of a SCFE were assessed using Cohen's kappa coefficient (κ). Diagnostic accuracy of SCFE relative to the benchmark, a combination of the radiographic diagnosis based on Klein's line, clinical symptoms and surgical treatment, was assessed computing sensitivity, specificity and accuracy. RESULTS: Intraobserver agreement between the surveys was moderate among paediatricians (κ-range, 0.44 to 0.52), moderate to almost perfect among orthopaedic surgeons (κ-range, 0.79 to 0.88) and almost perfect among paediatric radiologists (κ-range, 0.83 to 1.00). Interobserver agreement for survey 1 and 2 was slight among paediatricians (mean κ, 0.19), substantial among orthopaedic surgeons (mean κ, 0.77) and almost perfect among paediatric radiologists (mean κ, 0.86). Sensitivity of SCFE-diagnosis was high among radiologists and orthopaedic surgeons (88% to 100% for both specialties), but lower for paediatricians (24% to 76%). Specificity was high among radiologists and orthopaedic surgeons (72% to 84%), however, variable among paediatricians (56% to 80%). Accuracy of a SCFE-diagnosis was highest in radiologists (84% to 92%), followed by orthopaedic surgeons (80% to 88%) and paediatricians (48% to 78%). CONCLUSION: SCFE can be detected on radiographs by different medical specialties. Intra- and interobserver agreement, specificity, sensitivity and accuracy for radiographic SCFE-diagnosis amongst paediatric radiologists and orthopaedic surgeons are better than that of general paediatricians. LEVEL OF EVIDENCE: II.
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The human DEAD-box Y (DBY) RNA helicase (aka DDX3Y) gene is thought to be the major azoospermia factor a (AZFa) gene in proximal Yq11. Men with its deletion display no somatic pathologies, but suffer from complete absence of germ cells. Accordingly, DDX3Y protein is expressed only in the germline in spermatogonia, although the transcripts were found in many tissues. Here, we show the complex transcriptional control of a testis-specific DDX3Y transcript class with initiation at different sites upstream of the gene's open reading frame (5'Untranslated Region; UTR) and with polyadenylation in their proximal 3'UTR. The most distal transcriptional start site (TSS; â¼1 kb upstream) was mapped in MSY2, a Y-specific minisatellite. As this testis-specific 5'UTR was subsequently processed by three alternative splicing events, it has been tentatively designated 'exon-T'(estis). The MSY2 sequence unit was also found upstream of the mouse Ddx3y gene. However, only after its tandem amplification on the Y chromosome of Platyrrhini (new world monkeys) and Catarrhini (old world monkeys) did MSY2 become part of a novel distal promoter for DDX3Y expression in testis tissue and provides a second transcriptional start site (T-TSS-II) in Catarrhini. We therefore suggest that the development of a novel distal DDX3Y promoter in primates, which is activated only in testis tissue, is probably part of the gene's germline translation control.
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Cromosomas Humanos Y/genética , ARN Helicasas DEAD-box/genética , Regulación de la Expresión Génica , Proteínas de Plasma Seminal/genética , Testículo/metabolismo , Regiones no Traducidas 3' , Regiones no Traducidas 5' , Empalme Alternativo , Animales , Azoospermia/genética , Azoospermia/metabolismo , Azoospermia/patología , Secuencia de Bases , Catarrinos/genética , Deleción Cromosómica , Sitios Genéticos , Células Germinativas/patología , Humanos , Masculino , Ratones , Antígenos de Histocompatibilidad Menor , Platirrinos/genética , Poliadenilación , Regiones Promotoras Genéticas , Proteínas de Unión al ARN/genética , Secuencias Repetidas en Tándem , Testículo/patología , Sitio de Iniciación de la TranscripciónRESUMEN
Corticotropin releasing hormone (CRH) is the central modulator of the mammalian hypothalamic-pituitary-adrenal (HPA) axis. In addition, CRH affects other processes in the brain including learning, memory, and synaptic plasticity. Moreover, CRH has been shown to play a role in nerve cell survival under apoptotic conditions and to serve as an endogenous neuroprotectant in vitro. Employing mice overexpressing murine CRH in the CNS, we observed a differential response of CRH-overexpressing mice (CRH-COEhom-Nes) to acute excitotoxic stress induced by kainate compared with controls (CRH-COEcon-Nes). Interestingly, CRH-overexpression reduced the duration of epileptic seizures and prevented kainate-induced neurodegeneration and neuroinflammation in the hippocampus. Our findings highlight a neuroprotective action of CRH in vivo. This neuroprotective effect was accompanied by increased levels of brain-derived neurotrophic factor (BDNF) in CRH-COEhom-Nes mice, suggesting a potential role for BDNF in mediating CRH-induced neuroprotective actions against acute excitotoxicity in vivo.
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Hormona Liberadora de Corticotropina/metabolismo , Degeneración Nerviosa/etiología , Degeneración Nerviosa/prevención & control , Síndromes de Neurotoxicidad/complicaciones , Análisis de Varianza , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Muerte Celular/efectos de los fármacos , Hormona Liberadora de Corticotropina/genética , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Indoles , Proteínas de Filamentos Intermediarios/genética , Proteínas de Filamentos Intermediarios/metabolismo , Ácido Kaínico/toxicidad , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Nestina , Proteínas de Neurofilamentos , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/patología , Lectinas de Plantas/metabolismo , Proteínas/genética , ARN no Traducido , Tiempo de Reacción/fisiología , Convulsiones/inducido químicamenteRESUMEN
The azoospermia factor (AZF) locus in Yq11 is now functionally subdivided in three distinct spermatogenesis loci: AZFa, AZFb and AZFc. After knowledge of the complete genomic Y sequence in Yq11, 14 Y genes encoding putatively functional proteins and expressed in human testis are found to be located in one of the three AZF intervals. Therefore, a major question for each infertility clinic performing molecular screening for AZF deletions has now raised concerning the functional contribution of the encoded AZF proteins to human spermatogenesis. Additionally, it has been shown that distinct chromatin regions in Yq11 overlapping with the genomic AZFb and AZFc intervals are probably involved in the pre-meiotic X and Y chromosome pairing process. An old hypothesis on the germ line function of AZF becomes therefore revitalized. It proposed a specific chromatin folding code in Yq11, which controls the condensation cycle of the Y chromosome in the male germ line. Thus, with the exception of AZF proteins functionally expressed during the pre-meiotic differentiation and proliferation of spermatogonia, the need for AZF proteins functionally expressed at meiosis or during the post-meiotic spermatid maturation process is difficult to assess before the identification of specific mutations in the corresponding AZF gene causing male infertility.
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Proteínas de Plasma Seminal/genética , Secuencia de Aminoácidos , Mapeo Cromosómico , Sitios Genéticos , Humanos , Infertilidad Masculina/genética , Masculino , Datos de Secuencia Molecular , Proteínas de Plasma Seminal/química , Homología de Secuencia de Aminoácido , Espermatogénesis/genéticaRESUMEN
A disintegrin and metalloprotease (ADAM) 10 is the main candidate enzyme for the alpha-secretase processing of the amyloid precursor protein (APP). Neuron-specific ADAM10 overexpression proved beneficial in the APP[V717I] mutant Alzheimer mouse model [Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113:1456-1464]. Since Alzheimer patients have a high prevalence for epileptic seizures, we investigated the effects of ADAM10 modulation under conditions of experimentally induced epileptic seizures. In this context we also examined whether ADAM10 effects were influenced by APP levels. Therefore we compared severity of kainate-induced seizures, neurodegeneration and inflammation in double transgenic mice overexpressing functional ADAM10 or a dominant negative ADAM10 mutant in the APP[V717I] background with single transgenic ADAM10 modulated mice. Double transgenic dominant negative ADAM10dn/APP[V717I] mice suffered from stronger epileptic seizures, had a longer recovery period and showed more neurodegeneration and glial activation in the hippocampal region than double transgenic mice moderately overexpressing functional ADAM10 (ADAM10mo/APP[V717I]) and APP[V717I] mice with endogenous ADAM10 levels. This suggests that ADAM10 activity is necessary to provide neuroprotection against excitotoxicity in the APP[V717I] mouse model. Interestingly, increased expression of functional ADAM10 above the endogenous level did not correlate with a better protection against seizures and neurodegeneration. Furthermore, ADAM10 dominant negative mice without transgenic APP overexpression (ADAM10dn) were seizing for a shorter time and showed less neuronal cell death and neuroinflammation after kainate injection than wild-type mice, which shows beneficial effects of ADAM10 inhibition in context with neurodegeneration. In contrast, mice with a high ADAM10 overexpression showed more seizures and stronger neuronal damage and inflammation than wild-type mice and mice with moderate ADAM10 overexpression. Hence, additional cleavage products of ADAM10 may counterbalance the neuroprotective effect of alpha-secretase-cleaved APP in the defense against excitotoxicity. Our findings highlight the need of a careful modulation of ADAM10 activity for neuroprotection depending on substrate availability and on neurotoxic stress conditions.