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Introduction: Precise prediction of hospital stay duration is essential for maximizing resource utilization during surgery. Existing lumbar spinal stenosis (LSS) surgery prediction models lack accuracy and generalizability. Machine learning can improve accuracy by considering preoperative factors. This study aimed to develop and validate a machine learning-based model for estimating hospital stay duration following decompression surgery for LSS. Methods: Data from 848 patients who underwent decompression surgery for LSS at three hospitals were examined. Twelve prediction models, using 79 preoperative variables, were developed for postoperative hospital stay estimation. The top five models were chosen. Fourteen models predicted prolonged hospital stay (≥14 days), and the most accurate model was chosen. Models were validated using a randomly divided training sample (70%) and testing cohort (30%). Results: The top five models showed moderate linear correlations (0.576-0.624) between predicted and measured values in the testing sample. The ensemble of these models had moderate prediction accuracy for final length of stay (linear correlation 0.626, absolute mean error 2.26 days, standard deviation 3.45 days). The c5.0 decision tree model was the top predictor for prolonged hospital stay, with accuracies of 89.63% (training) and 87.2% (testing). Key predictors for longer stay included JOABPEQ social life domain, facility, history of vertebral fracture, diagnosis, and Visual Analogue Scale (VAS) of low back pain. Conclusions: A machine learning-based model was developed to predict postoperative hospital stay after LSS decompression surgery, using data from multiple hospital settings. Numerical prediction of length of stay was not very accurate, although favorable prediction of prolonged stay was accomplished using preoperative factors. The JOABPEQ social life domain score was the most important predictor.
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In clinical practice, urethral diseases are not as frequent as conditions affecting other components of the urinary system. Radiological imaging tests, such as retrograde urethrography, CT, MRI, and PET/CT, along with patient history, are crucial for accurately assessing relatively rare urethral lesions. This article aimed to provide a comprehensive overview of urethral lesions, from traumatic changes to neoplasms, and discuss the multimodal imaging findings of various urethral lesions that radiologists should know. To this end, the normal imaging anatomy of the urethra and a step-by-step approach that can be used in clinical practice have been presented to help in the systematic understanding of urethral lesions.
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Invertebrates lack hypothalamic-pituitary-gonadal axis, and have acquired species-specific regulatory systems for ovarian follicle development. Ascidians are marine invertebrates that are the phylogenetically closest living relatives to vertebrates, and we have thus far substantiated the molecular mechanisms underlying neuropeptidergic follicle development of the cosmopolitan species, Ciona intestinalis Type A. However, no ovarian factor has so far been identified in Ciona. In the present study, we identified a novel Ciona-specific peptide, termed PEP51, in the ovary. Immunohistochemical analysis demonstrated the specific expression of PEP51 in oocyte-associated accessory cells, test cells, of post-vitellogenic (stage III) follicles. Immunoelectron microscopy revealed that PEP51 was localized in the cytosol of test cells in early stage III follicles, which lack secretory granules. These results indicate that PEP51 acts as an intracellular factor within test cells rather than as a secretory peptide. Confocal laser microscopy verified that activation of caspase-3/7, the canonical apoptosis marker, was detected in most PEP51-positive test cells of early stage III. This colocalization of PEP51 and the apoptosis marker was consistent with immunoelectron microscopy observations demonstrating that a few normal (PEP51-negative) test cells reside in the aggregates of PEP51-positive apoptotic test cells of early stage III follicles. Furthermore, transfection of the PEP51 gene into COS-7 cells and HEK293MSR cells resulted in activation of caspase-3/7, providing evidence that PEP51 induces apoptotic signaling. Collectively, these results showed the existence of species-specific ovarian peptide-driven cell metabolism in Ciona follicle development. Consistent with the phylogenetic position of Ciona as the closest sister group of vertebrates, the present study sheds new light on the molecular and functional diversity of the regulatory systems of follicle development in the Chordata.
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Ciona intestinalis , Animais , Feminino , Ciona intestinalis/genética , Filogenia , Caspase 3/genética , Aminoácidos/metabolismo , Peptídeos/metabolismo , Folículo Ovariano , VertebradosRESUMO
DNA mismatch repair endonuclease MutL binds two zinc ions. However, the endonuclease activity of MutL is drastically enhanced by other divalent metals such as manganese, implying that MutL binds another catalytic metal at some site other than the zinc-binding sites. Here, we solved the crystal structure of the endonuclease domain of Aquifex aeolicus MutL in the manganese- or cadmium-bound form, revealing that these metals compete with zinc at the same sites. Mass spectrometry revealed that the MutL yielded 5'-phosphate and 3'-OH products, which is characteristic of the two-metal-ion mechanism. Crystallographic analyses also showed that the position and flexibility of a highly conserved Arg of A. aeolicus MutL altered depending on the presence of zinc/manganese or the specific inhibitor cadmium. Site-directed mutagenesis revealed that the Arg was critical for the catalysis. We propose that zinc ion and its binding sites are physiologically of catalytic importance and that the two-metal-ion mechanism works in the reaction, where the Arg plays a catalytic role. Our results also provide a mechanistic insight into the inhibitory effect of a mutagen/carcinogen, cadmium, on MutL.
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Cádmio , Zinco , Manganês , Endonucleases , CatáliseRESUMO
STUDY DESIGN: Retrospective case series. OBJECTIVE: The purpose of this study was to investigate the outcome of multilevel posterior decompression surgery for degenerative lumbar spinal stenosis compared with single-level surgery. SUMMARY OF BACKGROUND DATA: The clinical outcomes of multilevel decompression surgery are still controversial because previous studies have not been designed to randomize or adjust the patient background. MATERIALS AND METHODS: A retrospective review of prospectively collected data from 659 surgically treated lumbar spinal stenosis patients with a minimum 2-year follow-up was performed. Among them, we compared baseline and 2-year postoperative patient-reported outcomes (PROs) including the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire scores of 122 patients who underwent three or more levels of surgery (M group) and 304 patients who underwent single-level surgery (S group). Further analyses were performed of 116 paired patients from both groups who were propensity score matched by age and baseline PROs. RESULTS: The number of perioperative complications including extradural hematoma, surgical site infection, and spinal fluid leakage [M vs. S: 10 (8%) vs. 19 (6%), P =0.47], and frequency of revision surgery [5 (4%) vs. 23 (8%), P =0.10] were similar between the two groups. In the analysis of propensity score-matched patients, there were comparable improvements in the Visual Analog Scale score for lower back pain (2.6 vs. 2.4, P =0.55), buttock-leg pain (3.1 vs. 3.4, P =0.48), and buttock-leg numbness (2.9 vs. 2.9, P =0.77) in both groups. There were also similar improvements in the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire scores including lower back pain, lumbar function, walking ability, and mental health domains, except for the social life function domain (20.7±26.5 vs. 28.0±27.5, P =0.04). CONCLUSIONS: Despite the longer surgical time and a larger volume of estimated blood loss, multilevel decompression surgery showed similar improvement to that of single-level surgery in terms of recovery of PROs and frequency of revision surgery. Multilevel decompression surgery provides good clinical outcomes with acceptable complication and revision rates when selecting appropriate patient and spinal levels.
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Dor Lombar , Estenose Espinal , Humanos , Descompressão Cirúrgica/efeitos adversos , Estudos Retrospectivos , Dor Lombar/etiologia , Constrição Patológica/cirurgia , Vértebras Lombares/cirurgia , Resultado do Tratamento , Dor nas Costas/cirurgia , Canal Medular/cirurgiaRESUMO
BACKGROUND CONTEXT: Although the results of decompression surgery for lumbar spinal canal stenosis (LSS) are favorable, it is still difficult to predict the postoperative health-related quality of life of patients before surgery. PURPOSE: The purpose of this study was to develop and validate a machine learning model to predict the postoperative outcome of decompression surgery for patients with LSS. STUDY DESIGN/SETTING: A multicentered retrospective study. PATIENT SAMPLE: A total of 848 patients who underwent decompression surgery for LSS at an academic hospital, tertiary center, and private hospital were included (age 71±9 years, 68% male, 91% LSS, level treated 1.8±0.8, operation time 69±37 minutes, blood loss 48±113 mL, and length of hospital stay 12±5 days). OUTCOME MEASURES: Baseline and 2 years postoperative health-related quality of life. METHODS: The subjects were randomly assigned in a 7:3 ratio to a model building cohort and a testing cohort to test the models' accuracy. Twelve predictive algorithms using 68 preoperative factors were used to predict each domain of the Japanese Orthopedic Association Back Pain Evaluation Questionnaire and visual analog scale scores at 2 years postoperatively. The final predictive values were generated using an ensemble of the top five algorithms in prediction accuracy. RESULTS: The correlation coefficients of the top algorithms for each domain established using the preoperative factors were excellent (correlation coefficient: 0.95-0.97 [relative error: 0.06-0.14]). The performance evaluation of each Japanese Orthopedic Association Back Pain Evaluation Questionnaire domain and visual analog scale score by the ensemble of the top five algorithms in the testing cohort was favorable (mean absolute error [MAE] 8.9-17.4, median difference [MD] 8.1-15.6/100 points), with the highest accuracy for mental status (MAE 8.9, MD 8.1) and the lowest for buttock and leg numbness (MAE 1.7, MD 1.6/10 points). A strong linear correlation was observed between the predicted and measured values (linear correlation 0.82-0.89), while 4% to 6% of the subjects had predicted values of greater than±3 standard deviations of the MAE. CONCLUSIONS: We successfully developed a machine learning model to predict the postoperative outcomes of decompression surgery for patients with LSS using patient data from three different institutions in three different settings. Thorough analyses for the subjects with deviations from the actual measured values may further improve the predictive probability of this model.
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Descompressão Cirúrgica , Estenose Espinal , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Estudos Retrospectivos , Qualidade de Vida , Constrição Patológica/cirurgia , Vértebras Lombares/cirurgia , Resultado do Tratamento , Estenose Espinal/cirurgia , Dor nas Costas/cirurgia , Aprendizado de Máquina , Canal MedularRESUMO
Omics studies contribute to the elucidation of genomes and profiles of gene expression. In the ascidian Ciona intestinalis Type A (Ciona robusta), mass spectrometry (MS)-based peptidomic studies have detected numerous Ciona-specific (nonhomologous) neuropeptides as well as Ciona homologs of typical vertebrate neuropeptides and hypothalamic peptide hormones. Candidates for cognate G protein-coupled receptors (GPCRs) for these peptides have been found in the Ciona transcriptome by two ways. First, Ciona homologous GPCRs of vertebrate counterparts have been detected by sequence homology searches of cognate transcriptomes. Second, the transcriptome-derived GPCR candidates have been used for machine learning-based systematic prediction of interactions not only between Ciona homologous peptides and GPCRs but also between novel Ciona peptides and GPCRs. These data have ultimately led to experimental evidence for various Ciona peptide-GPCR interactions. Comparative transcriptomics between the wildtype and Ciona vasopressin (CiVP) gene-edited Ciona provide clues to the biological functions of CiVP in ovarian follicular development and whole body growth. Furthermore, the transcriptomes of follicles treated with peptides, such as Ciona tachykinin and cionin (a Ciona cholecystokinin homolog), have revealed key regulatory genes for Ciona follicle growth, maturation, and ovulation, eventually leading to the verification of essential and novel molecular mechanisms underlying these biological events. These findings indicate that omics studies, combined with artificial intelligence and single-cell technologies, pave the way for investigating in greater details the nervous, neuroendocrine, and endocrine systems of ascidians and the molecular and functional evolution and diversity of peptidergic regulatory networks throughout chordates.
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Ciona intestinalis , Neuropeptídeos , Hormônios Peptídicos , Animais , Inteligência Artificial , Ciona intestinalis/genética , Ciona intestinalis/metabolismo , Feminino , Neuropeptídeos/metabolismo , Hormônios Peptídicos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Vertebrados/metabolismoRESUMO
Myoclonus and ataxia, with or without opsoclonus, have recently been recognized as a central nervous system syndrome associated with coronavirus disease-2019 (COVID-19). A 52-year-old Japanese man developed myoclonus and ataxia 16 days after the onset of COVID-19. Brain single-photon emission computed tomography (SPECT) revealed hyperperfusion in the cerebellum and hypoperfusion in the cerebral cortices with frontal predominance during the acute stage, which improved over two months. This study indicates that brain perfusion SPECT can be effective in detecting functional alterations in COVID-19-related myoclonus and ataxia.
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COVID-19 , Mioclonia , Síndrome de Opsoclonia-Mioclonia , Encéfalo/diagnóstico por imagem , COVID-19/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Dissinergia Cerebelar Mioclônica , Mioclonia/complicações , PerfusãoRESUMO
Tracheobronchial schwannomas are rare diseases. Common signs and symptoms of this tumor include cough, wheezing, and dyspnea. In contrast, pneumothorax is an exceptional presentation. This study reports the first case of bronchial schwannoma presenting with pneumothorax. A 79-year-old woman was diagnosed with pneumothorax by chest radiography. Chest computed tomography unexpectedly revealed a tumor occluding the right main bronchus. Following the pathological diagnosis of bronchial schwannoma, the patient underwent thoracoscopic tumor enucleation. The airway lumens are consequently secured postoperatively. We reviewed the literature and discussed the mechanisms and treatment options for bronchial benign tumor-associated pneumothorax. Pneumothorax should be aware of a rare presentation of non-malignant tracheobronchial tumors.
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OBJECTIVE: To clarify the diagnostic performance of the three-dimensional reconstructed virtual image (3D-RVI) in evaluating RENAL nephrometry score (RENAL-NS). METHODS: This study included 130 patients who underwent preoperative contrast-enhanced computed tomography followed by partial nephrectomy for renal tumors suggestive of renal cell carcinoma. RENAL-NS was calculated prior to the surgery, and tumor resection was performed referring to the score. We retrospectively reviewed preoperative contrast-enhanced computed tomography images. We calculated the inter-observer variability of RENAL-NS using 3D-RVI vs two-dimensional (2D) imaging and compared the ability of RENAL-NS using 3D-RVI vs 2D imaging to predict the risk of opening of the urinary collecting system. We also compared the two modalities for the time required to evaluate RENAL-NS. RESULTS: RENAL-NS evaluated using 3D-RVI showed a higher inter-observer agreement compared to 2D-imaging (rs = 0.85 vs rs = 0.65). The "nearness to sinus" score was more strongly associated with the opening of the urinary collecting system when evaluated using 3D-RVI than 2D-imaging (AUC = 0.71 vs AUC = 0.57, P = .016). RENAL-NS using 2D-imaging required a significantly longer time compared to 3D-RVI (P = .036). CONCLUSION: Using 3D-RVI improves the accuracy, reliability and efficiency of RENAL-NS evaluation in preoperative assessment and can play an important role in preoperative assessment and intraoperative navigation.
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Neoplasias Renais , Nefrectomia , Humanos , Imageamento Tridimensional/métodos , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Extraneural recurrence of a medulloblastoma is rare with dismal prognosis. A 9-year-old girl with medulloblastoma was treated with gross total resection followed by a combination of chemotherapy and radiotherapy. Fourteen months after treatment completion, she developed multifocal bone metastases. Despite chemotherapy combined with irradiation, she died 18 months after recurrence due to progressive disease. Fluorescence in situ hybridization on formalin-fixed paraffin-embedded tissue sections revealed MYCN amplification and TP53 loss, consistent with the genetic alterations of a rapidly progressive subgroup of recurrent medulloblastomas. In clinical practice, dismal biologic features can be determined using fluorescence in situ hybridization in defective materials.
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Neoplasias Encefálicas , Neoplasias Cerebelares , Meduloblastoma , Neoplasias Encefálicas/patologia , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/terapia , Criança , Feminino , Humanos , Hibridização in Situ Fluorescente , Meduloblastoma/genética , Meduloblastoma/patologia , Meduloblastoma/terapia , Proteína Proto-Oncogênica N-Myc/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Patients with diffuse idiopathic skeletal hyperostosis (DISH) are susceptible to spinal column injuries with neurological deterioration. Previous studies indicated that the prevalence of diabetes mellitus (DM) in patients with DISH was higher than that in patients without DISH. This study investigates the impact of DM on surgical outcomes for spinal fractures in patients with DISH. METHODS: We retrospectively evaluated 177 spinal fractures in patients with DISH (132 men and 45 women; mean age, 75 ± 10 years) who underwent surgery from a multicenter database. The subjects were classified into two groups according to the presence of DM. Perioperative complications, neurological status by Frankel grade, mortality rate, and status of surgical site infection (SSI) were compared between the two groups. RESULTS: DM was present in 28.2% (50/177) of the patients. The proportion of men was significantly higher in the DM group (DM group: 86.0% vs. non-DM group: 70.1%) (p = 0.03). The overall complication rate was 22.0% in the DM group and 19.7% in the non-DM group (p = 0.60). Poisson regression model revealed that SSI was significantly associated with DM (DM group: 10.0% vs. non-DM group: 2.4%, Relative risk: 4.5) (p = 0.048). Change in neurological status, mortality rate, instrumentation failure, and nonunion were similar between both groups. HbA1c and fasting blood glucose level (SSI group: 7.2% ± 1.2%, 201 ± 67 mg/dL vs. non-SSI group: 6.6% ± 1.1%, 167 ± 47 mg/dL) tended to be higher in patients with SSI; however, there was no significant difference. CONCLUSIONS: In spinal fracture in patients with DISH, although DM was an associated factor for SSI with a relative risk of 4.5, DM did not negatively impact neurological recovery. Perioperative glycemic control may be useful for preventing SSI because fasting blood glucose level was high in patients with SSI.
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Diabetes Mellitus , Hiperostose Esquelética Difusa Idiopática , Fraturas da Coluna Vertebral , Idoso , Idoso de 80 Anos ou mais , Glicemia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperostose Esquelética Difusa Idiopática/complicações , Hiperostose Esquelética Difusa Idiopática/diagnóstico por imagem , Hiperostose Esquelética Difusa Idiopática/cirurgia , Masculino , Estudos Retrospectivos , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in various cancer cells and contributes to tumor progression. We have previously shown that PGRMC1 forms a unique heme-stacking functional dimer to enhance EGF receptor (EGFR) activity required for cancer proliferation and chemoresistance, and the dimer dissociates by carbon monoxide to attenuate its biological actions. Here, we determined that glycyrrhizin (GL), which is conventionally used to ameliorate inflammation, specifically binds to heme-dimerized PGRMC1. Binding analyses using isothermal titration calorimetry revealed that some GL derivatives, including its glucoside-derivative (GlucoGL), bind to PGRMC1 potently, whereas its aglycone, glycyrrhetinic acid (GA), does not bind. GL and GlucoGL inhibit the interaction between PGRMC1 and EGFR, thereby suppressing EGFR-mediated signaling required for cancer progression. GL and GlucoGL significantly enhanced EGFR inhibitor erlotinib- or cisplatin (CDDP)-induced cell death in human colon cancer HCT116 cells. In addition, GL derivatives suppressed the intracellular uptake of low-density lipoprotein (LDL) by inhibiting the interaction between PGRMC1 and the LDL receptor (LDLR). Effects on other pathways cannot be excluded. Treatment with GlucoGL and CDDP significantly suppressed tumor growth following xenograft transplantation in mice. Collectively, this study indicates that GL derivatives are novel inhibitors of PGRMC1 that suppress cancer progression, and our findings provide new insights for cancer treatment.
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BACKGROUND. Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, partly because of challenges in early diagnosis. However, the prognosis for earlier stages (carcinoma in situ or category T1a invasive carcinoma) is relatively favorable. OBJECTIVE. The purpose of this study was to investigate findings of an earlier diagnosis of PDAC on CT examinations performed at least 1 year before the diagnosis of clinical stage I PDAC. METHODS. This retrospective study included 103 patients with clinical stage I PDAC and a CT examination performed at least 1 year before the CT examination that detected PDAC, as well as 103 control patients without PDAC on CT examinations separated by at least 10 years. The frequency and temporal characteristics of focal pancreatic abnormalities (pancreatic mass, main pancreatic duct [MPD] change, parenchymal atrophy, faint parenchymal enhancement, cyst, and parenchymal calcification) seen on CT examinations conducted before diagnosis (prediagnostic CT) were determined. RESULTS. A focal pancreatic abnormality was present on the most recent prediagnostic CT examination in 55/103 (53.4%) patients with PDAC versus 21/103 (20.4%) control patients (p < .001). In patients with PDAC, the most common focal abnormalities on prediagnostic CT were atrophy (39/103, 37.9%), faint enhancement (17/65, 26.2%), and MPD change (14/103, 13.6%), which were all more frequent in patients with PDAC than in control patients (p < .05). In 54/55 (98.2%) patients with PDAC, the PDAC corresponded to the site of a focal abnormality (exact location or the abnormality's upstream or downstream edge) on prediagnostic CT. Frequency of focal abnormalities decreased with increasing time before CT that detected PDAC (> 1 to ≤ 2 years before diagnosis, 64.9%; > 2 to ≤ 3 years, 49.2%; > 3 to ≤ 5 years, 41.8%; > 5 to ≤ 7 years, 29.7%; > 7 to ≤ 10 years, 18.5%; more than 10 years, 0%). Mean duration from the finding's initial appearance to diagnosis of PDAC was 4.6 years for atrophy, 3.3 years for faint enhancement, and 1.1 years for MPD change. CONCLUSION. Most patients with clinical stage I PDAC showed focal pancreatic abnormalities on CT performed at least 1 year before diagnosis. Focal MPD change exhibited the shortest duration from its development to subsequent diagnosis, whereas atrophy and faint enhancement exhibited a relatively prolonged course. CLINICAL IMPACT. These findings could facilitate earlier PDAC diagnosis and thus improve prognosis.
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Adenocarcinoma/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologia , Estudos RetrospectivosRESUMO
Importance: Repeat expansion of CGG in LRP12 has been identified as the causative variation of oculopharyngodistal myopathy (OPDM). However, to our knowledge, the clinicopathologic features of OPDM with CGG repeat expansion in LRP12 (hereafter referred to as OPDM_LRP12) remain unknown. Objective: To identify and characterize the clinicopathologic features of patients with OPDM_LRP12. Design, Setting, and Participants: This case series included 208 patients with a clinical or clinicopathologic diagnosis of oculopharyngeal muscular dystrophy (OPDM) from January 1, 1978, to December 31, 2020. Patients with GCN repeat expansions in PABPN1 were excluded from the study. Repeat expansions of CGG in LRP12 were screened by repeat primed polymerase chain reaction and/or Southern blot. Main Outcomes and Measures: Clinical information, muscle imaging data obtained by either computed tomography or magnetic resonance imaging, and muscle pathologic characteristics. Results: Sixty-five Japanese patients with OPDM (40 men [62%]; mean [SD] age at onset, 41.0 [10.1] years) from 59 families with CGG repeat expansions in LRP12 were identified. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM. The expansions ranged from 85 to 289 repeats. A negative correlation was observed between the repeat size and the age at onset (r2 = 0.188, P = .001). The most common initial symptoms were ptosis and muscle weakness, present in 24 patients (37%). Limb muscle weakness was predominantly distal in 53 of 64 patients (83%), but 2 of 64 patients (3%) had predominantly proximal muscle weakness. Ptosis was observed in 62 of 64 patients (97%), and dysphagia or dysarthria was observed in 63 of 64 patients (98%). A total of 21 of 64 patients (33%) had asymmetric muscle weakness. Aspiration pneumonia was seen in 11 of 64 patients (17%), and 5 of 64 patients (8%) required mechanical ventilation. Seven of 64 patients (11%) developed cardiac abnormalities, and 5 of 64 patients (8%) developed neurologic abnormalities. Asymmetric muscle involvement was detected on computed tomography scans in 6 of 27 patients (22%) and on magnetic resonance imaging scans in 4 of 15 patients (27%), with the soleus and the medial head of the gastrocnemius being the worst affected. All 42 muscle biopsy samples showed rimmed vacuoles. Intranuclear tubulofilamentous inclusions were observed in only 1 of 5 patients. Conclusions and Relevance: This study suggests that OPDM_LRP12 is the most frequent OPDM subtype in Japan and is characterized by oculopharyngeal weakness, distal myopathy that especially affects the soleus and gastrocnemius muscles, and rimmed vacuoles in muscle biopsy.
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Expansão das Repetições de DNA , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Distrofias Musculares/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Debilidade Muscular , Músculo Esquelético/patologia , Linhagem , Adulto JovemRESUMO
Background: Indications for subthalamic nucleus deep brain stimulation (STN-DBS) surgery are determined basically by preoperative motor function; however, postoperative quality of life (QOL) is not necessarily associated with improvements in motor symptoms, suggesting that neuropsychiatric symptoms might be related to QOL after surgery in patients with Parkinson's disease. Objectives: We aimed to examine temporal changes in neuropsychiatric symptoms and their associations with QOL after STN-DBS. Materials and Methods: We prospectively enrolled a total of 61 patients with Parkinson's disease (mean age = 65.3 ± 0.9 years, mean disease duration = 11.9 ± 0.4 years). Motor function, cognitive function, and neuropsychiatric symptoms were evaluated before and after DBS surgery. Postoperative evaluation was performed at 3 months, 1 year, and 3 years after surgery. Results: Of the 61 participants, 54 completed postoperative clinical evaluation after 3 months, 47 after 1 year, and 23 after 3 years. Frontal lobe functions, depression, and verbal fluency significantly worsened 3 years after STN-DBS. Non-motor symptoms such as impulsivity and the Unified PD Rating Scale (UPDRS) part I score were associated with QOL after STN-DBS. Conclusions: Frontal lobe functions, depression, and verbal fluency significantly worsened 3 years after STN-DBS. The UPDRS part I score and higher impulsivity might be associated with QOL after STN-DBS.
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In vertebrates, gonadotropin-releasing hormone (GnRH) peptide is the central mediator of reproduction. Homologous peptides have previously also been identified in molluscan species. However, emerging evidence suggests that these molecules might serve diverse regulatory functions and proposes to consider them as corazonin (CRZ). We previously isolated the full-length cDNA of the invGnRH/CRZ peptide (termed ly-GnRH/CRZ) in the well-established invertebrate model species, the great pond snail Lymnaea stagnalis; however, its predicted functions remain to be verified. In this study, we first confirmed the presence of the deduced active peptide from the central nervous system of L. stagnalis. Further, we performed in vivo and in vitro studies to explore the functions of ly-GnRH/CRZ. Injection of sexually mature specimens with synthetic active peptide had an inhibitory effect on locomotion and an acceleratory effect on egg-laying, but had no effect on feeding. The previously predicted modulatory effect of ly-GnRH/CRZ was supported by its identified co-localization with serotonin on the surface of the heart atria. Lastly, we demonstrated not only the presence of ly-GnRH/CRZ in the penial complex but also that ly-GnRH/CRZ-containing neurons project to the efferent penis nerve, suggesting ly-GnRH/CRZ may directly modulate the motor output of this peripheral tissue. Overall, our findings strongly support that ly-GnRH/CRZ is a multifunctional neuropeptide. These results contribute to the understanding of the GnRH superfamily and, more broadly, disciplines such as comparative endocrinology and neurobiology.
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Lymnaea/fisiologia , Neuropeptídeos/fisiologia , Animais , Evolução Biológica , Sistema Nervoso Central/metabolismo , Comportamento Alimentar , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/fisiologia , Locomoção , Lymnaea/química , Neuropeptídeos/química , OviparidadeRESUMO
STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to compare the utility and cost-effectiveness of multilevel lateral interbody fusion (LIF) combined with posterior spinal fusion (PSF) (L group) and conventional PSF (with transforaminal lumbar interbody fusion) (P group) in adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: The clinical and radiographic outcomes of multilevel LIF for ASD have been reported favorable; however, the cost benefit of LIF in conjunction with PSF is still controversial. METHODS: Retrospective comparisons of 88 surgically treated ASD patients with minimum 2-year follow-up from a multicenter database (L group [nâ=â39] and P group [nâ=â49]) were performed. Demographic and radiographic data, health-related quality of life (HRQoL), and the direct hospitalization cost for the initial surgery and 2-year total hospitalization cost were analyzed. RESULTS: Analyses of sagittal spinal alignment showed no significant difference between the two groups at baseline and 2 years post-operation. Surgical time was longer in the L group (L vs. P: 354 vs. 268âminutes, Pâ<â0.01), whereas the amount of blood loss was greater in the P group (494 vs. 678âmL, Pâ=â0.03). The HRQoL was improved similarly at 2 years post-operation (L vs. P: SRS-22 total score, 3.86 vs. 3.80, Pâ=â0.54), with comparable revision rates (L vs. P: 18% vs. 10%, Pâ=â0.29). The total direct cost of index surgery was significantly higher in the L group (65,937 vs. 49,849 USD, Pâ<â0.01), which was mainly due to the operating room cost, including implant cost (54,466 vs. 41,328 USD, Pâ<â0.01). In addition, the 2-year total hospitalization cost, including revision surgery, was also significantly higher in the L group (70,847 vs. 52,560 USD, Pâ<â0.01). CONCLUSION: LIF with PSF is a similarly effective surgery for ASD when compared with conventional PSF. However, due to the significantly higher cost, additional studies on the cost-effectiveness of LIF in different ASD patient cohorts are warranted. LEVEL OF EVIDENCE: 3.
Assuntos
Análise Custo-Benefício , Procedimentos Neurocirúrgicos/economia , Fusão Vertebral/economia , Coluna Vertebral/cirurgia , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Reoperação , Estudos Retrospectivos , Fusão Vertebral/efeitos adversosRESUMO
PURPOSE: We aimed to investigate atypical papillary renal cell carcinoma (PRCC) presenting with early contrast enhancement and late washout and to investigate the correlation between the CT attenuation value of the corticomedullary phase (CMP) of contrast-enhanced CT in PRCCs and the endothelial cell counts of these tumors. METHODS: Twenty-two patients with pathologically confirmed PRCC were enrolled in this study. PRCCs were categorized into 18 typical PRCCs and 4 atypical PRCCs. The CT attenuation value of the lesion in the CMP was measured in the maximal section of the tumor using the region of interest. Microvessel density (MVD) was evaluated as a histopathologic parameter using tissue specimens immunohistochemically stained with an anti-ERG antibody. The CT attenuation value and MVD were compared between atypical and typical PRCCs using the Mann-Whitney U test, where p < 0.05 was considered significant. The correlations between CT attenuation value and MVD were evaluated in all PRCCs using single linear regression analysis. RESULTS: The mean CT attenuation value and the MVD were significantly higher in atypical than in typical PRCCs. Correlation analyses revealed a weak positive correlation between the CT attenuation value and MVD. CONCLUSIONS: We confirmed several cases of atypical PRCC that present with early contrast enhancement, such as clear cell renal cell carcinoma. In addition, a positive correlation was found between the CT attenuation value in the CMP of PRCCs and the vascular endothelial cell count.