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Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis.
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Linaje de la Célula/genética , Células Clonales/metabolismo , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/genética , Mutación , ADN Mitocondrial/genética , Embrión de Mamíferos/embriología , Femenino , Humanos , Masculino , Tasa de MutaciónRESUMEN
Punishment such as electric shock or physical discipline employs a mixture of physical pain and emotional distress to induce behavior modification. However, a neural circuit that produces behavior modification by selectively focusing the emotional component, while bypassing the pain typically induced by peripheral nociceptor activation, is not well studied. Here, we show that genetically silencing the activity of neurons expressing calcitonin gene-related peptide (CGRP) in the parabrachial nucleus blocks the suppression of addictive-like behavior induced by footshock. Furthermore, activating CGRP neurons suppresses not only addictive behavior induced by self-stimulating dopamine neurons but also behavior resulting from self-administering cocaine, without eliciting nocifensive reactions. Moreover, among multiple downstream targets of CGRP neurons, terminal activation of CGRP in the central amygdala is effective, mimicking the results of cell body stimulation. Our results indicate that unlike conventional electric footshock, stimulation of CGRP neurons does not activate peripheral nociceptors but effectively curb addictive behavior.
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Conducta Adictiva , Péptido Relacionado con Gen de Calcitonina , Neuronas , Núcleos Parabraquiales , Animales , Núcleos Parabraquiales/metabolismo , Núcleos Parabraquiales/fisiología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Ratones , Neuronas/metabolismo , Neuronas/fisiología , Conducta Adictiva/metabolismo , Masculino , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/fisiología , Cocaína/farmacología , Conducta Animal/fisiologíaRESUMEN
Understanding somatic mutations and structural variations in domestic pigs (Sus scrofa domestica) is critical due to their increasing importance as model organisms in biomedical research. In this study, we conducted a comprehensive analysis through whole-genome sequencing of skin, organs, and blood samples. By examining two pig pedigrees, we investigated the inheritance and sharedness of structural variants among fathers, mothers, and offsprings. Utilizing single-cell clonal expansion techniques, we observed significant variations in the number of somatic mutations across different tissues. An in-house developed pipeline enabled precise filtering and analysis of these mutations, resulting in the construction of individual phylogenetic trees for two pigs. These trees explored the developmental relationships between different tissues, revealing insights into clonal expansions from various anatomical locations. This study enhances the understanding of pig genomes, affirming their increasing value in clinical and genomic research, and provides a foundation for future studies in other animals, paralleling previous studies in mice and humans. This approach not only deepens our understanding of mammalian genomic variations but also strengthens the role of pigs as a crucial model in human health and disease research.
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Ventriculoperitoneal shunt surgery was developed to manage excessive cerebrospinal fluid (CSF) in the brain's ventricles and is considered a mainstream treatment. Despite the development of the shunt device system, various complications still occur. In this study, we reported 307 cases and a long-term follow-up of at least five years of adult patients who underwent VP shunt surgery and analyzed various factors that may affect revision surgery. A retrospective study was conducted at Asan Medical Center, Korea, a tertiary medical center. We reviewed 307 cases from January 2012 to December 2018. The patients' neurological status, predisposing medical conditions, laboratory findings, and other operation-related factors were reviewed using electrical medical records. The normal function group comprised 272 cases (88.6%), and the overall incidence of revision group comprised 35 cases (11.4%). Of the 35 revision surgery cases, 30 (85.71%) were due to shunt malfunctions, such as obstruction, overdrainage, and valve-related errors while 5 (14.29%) were due to shunt infection. Patient demographics, mental status, and operation time did not influence revision as risk factors. Serum laboratory findings showed no statistical difference between the two groups. The white blood cell (WBC) count in the CSF profile differed significantly between the two groups. The Hakim Programmable valve (Codman, USA) is mainly used in our center. In addition, various shunt systems were used, including Strata Regulatory valve (Medtronic, USA), proGAV (Aesculap, USA), and Accu-Flo (Codman, USA). This study analyzed the factors affecting long-term outcomes. Based on these findings, efforts are needed to achieve more favorable outcomes in the future.
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Hidrocefalia , Derivación Ventriculoperitoneal , Humanos , Derivación Ventriculoperitoneal/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Adulto , Estudios Retrospectivos , Incidencia , Anciano , Estudios de Seguimiento , Hidrocefalia/cirugía , Reoperación , Complicaciones Posoperatorias/epidemiología , Falla de Equipo , Adulto JovenRESUMEN
PURPOSE: Vestibular schwannoma is a benign tumor originating from Schwann cells surrounding the eighth cranial nerve and can cause hearing loss, tinnitus, balance problems, and facial nerve disorders. Because of the slow growth of the tumor, predicting the hearing function of patients with vestibular schwannoma's is important to obtain information that would be useful for deciding the treatment modality. This study aimed to analyze the association between magnetic resonance imaging features and hearing status using a new radiomics technique. METHODS: We retrospectively analyzed 115 magnetic resonance images and hearing results from 73 patients with vestibular schwannoma. A total of 70 radiomics features from each tumor volume were calculated using T1-weighted magnetic resonance imaging. Radiomics features were classified as histogram-based, shape-based, texture-based, and filter-based. The least absolute shrinkage and selection operator method was used to select the radiomics features among the 70 features that best predicted the hearing test. To ensure the stability of the selected features, the least absolute shrinkage and selection operator method was repeated 10 times. Finally, features set five or more times were selected as radiomics signatures. RESULTS: The radiomics signatures selected using the least absolute shrinkage and selection operator method were: minimum, variance, maximum 3D diameter, size zone variance, log skewness, skewness slope, and kurtosis slope. In random forest, the mean performance was 0.66 (0.63-0.77), and the most important feature was Log skewness. CONCLUSIONS: Newly developed radiomics features are associated with hearing status in patients with vestibular schwannoma and could provide information when deciding the treatment modality.
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Imagen por Resonancia Magnética , Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/complicaciones , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Pérdida Auditiva/etiología , Pérdida Auditiva/diagnóstico por imagen , Adulto Joven , Pruebas Auditivas , Audición/fisiología , RadiómicaRESUMEN
Our study investigated the embryo-ototoxic effects of deodorant2 (DA2) on zebrafish embryos, which serve as valuable model organisms due to genetic and physiological similarities to humans. We focused on understanding DA2's impact on zebrafish hair cells, which are vital for sensory perception and balance regulation. DA2, provided by the Ministry of Environment, Republic of Korea, was used at 460 µg/mL in dimethyl sulfoxide (DMSO), with a 0.43% DMSO solvent control group. Three experiments, each using 10 zebrafish specimens from each group, showed an initial 13% hair cell count reduction in the DA2-exposed group. Subsequent experiments demonstrated reductions of 37% and 22%, each with one mortality case. Statistical analysis revealed a significant 24% hair cell count reduction in the DA2-exposed group. We also assessed DA2's impact on zebrafish behavior. Although not statistically significant, differences in distances traveled (0.33-0.39, 95% confidence interval: -0.46-1.1, p = 0.2033) and latencies (-0.016-0.018, 95% confidence interval: -0.052-0.021, p = 0.1917) hinted at negative effects. These results highlight DA2's ototoxic properties affecting zebrafish auditory systems and behavior. Further investigation into DA2's effects on aquatic organisms and potential mitigation strategies are essential. These findings contribute to understanding DA2's safety profile, benefiting aquatic ecosystems and human health assessments.
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Desodorantes , Ototoxicidad , Perciformes , Humanos , Animales , Dimetilsulfóxido , Ecosistema , Pez Cebra , Embrión de MamíferosRESUMEN
OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.
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Radioisótopos de Yodo , Neoplasias de la Tiroides , Humanos , Radioisótopos de Yodo/uso terapéutico , Estudios Prospectivos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Tiroidectomía/métodos , Progresión de la Enfermedad , Resultado del Tratamiento , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: This study aimed to investigate the time trends of surgical outcomes in patients who underwent bilateral axillo-breast approach robotic thyroidectomy (BABA RT) over the last 14 years. METHODS: From February 2008 to September 2021, we conducted a retrospective medical chart review of 5,011 consecutive patients who underwent BABA RT at three Seoul National University-affiliated hospitals. The patients were divided into three groups based on the main model of the da Vinci robotic surgical system to evaluate trends in surgical treatment strategies and outcomes after BABA RT. RESULTS: Of the 5,011 patients (4,706 malignant and 305 benign), the most common histological subtype was papillary thyroid carcinoma (n = 4,584; 97.4%). The mean tumor size significantly increased from 0.8 cm to 1.2 cm (p < 0.05). The mean numbers of metastatic and harvested lymph nodes from the central neck dissection and the lateral neck dissection showed a significant difference and tendency to increase (from 0.9 to 1.6, 4.7 to 6.2, p < 0.05, and from 0.6 to 3.9, 5.3 to 17.9, p < 0.05), respectively, throughout the study period. Permanent hypoparathyroidism decreased from 3.4 to 2.9%. The rate of transient and permanent vocal cord palsy decreased from 15.2 to 2.7% and from 0.7 to 0.2%, respectively. CONCLUSION: With advancements in robotic surgical systems and improvements in the BABA RT technique, surgical indications have expanded to include more advanced thyroid diseases, and surgical outcomes have improved over the last 14 years.
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Carcinoma Papilar , Procedimientos Quirúrgicos Robotizados , Neoplasias de la Tiroides , Humanos , Tiroidectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias de la Tiroides/patología , Estudios Retrospectivos , Carcinoma Papilar/cirugía , Carcinoma Papilar/etiología , Mama/patología , Disección del Cuello/métodos , Axila/patología , Tempo OperativoRESUMEN
BACKGROUND: Skin metastasis from papillary thyroid cancer (PTC) is a rare entity that can occur up to decades after treatment of the primary tumor. Here, we present a patient who developed skin metastasis 10 years after treatment of her primary tumor and describe the molecular findings of the metastatic lesion. CASE PRESENTATION: A 44-year-old female with a history of PTC who underwent a total thyroidectomy and radioactive iodine (RAI) treatment 10 years ago presented with a 1.3-cm skin lesion along the prior thyroidectomy scar. A biopsy revealed metastatic PTC, and the patient underwent surgical excision of the lesion. ThyroSeq molecular testing showed the copresence of BRAFV600E mutation and TERT promoter C228T mutation. The patient subsequently received one round of adjuvant RAI therapy. CONCLUSIONS: A high index of suspicion is warranted in patients with a history of PTC who develop a skin lesion, even several years after remission of the primary disease. In patients with high-risk mutations, such as BRAFV600E and TERT promoter C228T mutations, long-term surveillance of disease recurrence is particularly important.
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Neoplasias Cutáneas , Telomerasa , Neoplasias de la Tiroides , Humanos , Femenino , Adulto , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Proteínas Proto-Oncogénicas B-raf/genética , Radioisótopos de Yodo , Regiones Promotoras Genéticas/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Cutáneas/genética , Mutación , Telomerasa/genéticaRESUMEN
OBJECTIVES: Sometimes performing PORP adequately is challenging when the stapes is tilted or the suprastructure is partially damaged owing to inflammation or infection. In such cases, the implementation of a TORP bypassing the stapes can be a useful alternative. This study aimed to investigate whether bypassing the stapes suprastructure during total ossicular replacement prosthesis (TORP) affects postoperative complications or audiological outcomes. MATERIAL AND METHODS: Among 104 patients who underwent open cavity mastoidectomy and ossiculoplasty using a titanium prosthesis at Korea University Ansan Hospital between January 2012 and December 2019, we compared the preoperative and postoperative audiological results and surgical complications of 52, 21, and 31 patients who underwent partial ossicular replacement prosthesis (PORP), TORP bypassing the remaining stapes suprastructure, and TORP on the stapes footplate or oval window, respectively. RESULTS: The air-bone gap before surgery was significantly different in the TORP on the stapes footplate group (34.2 ± 12.0 dB) than that in the PORP (22.9 ± 13.8 dB) and TORP bypassing the stapes groups (20.7 ± 11.5 dB, p < 0.001). After surgery, there were no significant differences among the groups (p = 0.818). The air-bone gap difference before surgery was associated with the presence of stapes before surgery (p < 0.001). There was no difference in the proportion of postoperative tympanic perforation, whether it was a revision surgery, malleus status, or the size of perforation of the tympanic membrane among the three groups. CONCLUSION: When performing ossiculoplasty using TORP, bypassing the stapes did not affect surgical and audiologic outcomes.
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Prótesis Osicular , Reemplazo Osicular , Humanos , Estribo , Reemplazo Osicular/métodos , Mastoidectomía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
OBJECTIVES: Pediatric idiopathic sudden hearing loss (PISSNHL) is a rare disease with no established factor affecting its prognosis. In this study, we investigate the risk factors affecting the prognosis of PISSNHL. MATERIAL AND METHODS: Among the patients who visited our hospital from January 2010 to December 2021, the characteristics associated prognosis of 54 patients with unilateral PISSNHL were retrospectively confirmed. RESULTS: Patients' recovery was determined by applying Siegel's criteria (SC) and AAO-HNS criteria (AC). Twenty-seven (50 %) and 29 patients (54.3 %) recovered for SC and AC, respectively. Age, sex, side, duration between onset and treatment, administration of intra-tympanic steroid injection, accompanying symptoms (tinnitus and dizziness), BMI, serum creatinine level, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte count (PLR), lymphocyte count, and platelet count were not significantly different between the recovery group and the poor recovery group (P > 0.05). The patients were divided into five groups according to the initial hearing of the affected ear and again according to their audiogram type. The initial hearing levels, hearing level severity, and the audiogram type were significantly different between the deaf group (>100 dB HL) and the non-deaf group (P < 0.05). CONCLUSION: The prognosis of PISSNHL is closely related to the initial hearing at the onset. If the initial hearing level is <100 dB, the recovery rate is approximately 50 %, therefore requiring active treatment and emotional support. It may also be related to the type of audiometric curve.
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Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Humanos , Niño , Pérdida Auditiva Súbita/diagnóstico , Pérdida Auditiva Súbita/tratamiento farmacológico , Pérdida Auditiva Súbita/etiología , Estudios Retrospectivos , Pronóstico , Audición , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/terapia , Factores de RiesgoRESUMEN
OBJECTIVE: Primary aldosteronism (PA) shows histological heterogeneity and clinical variability, including the coexistence of hypercortisolemia. Immunohistochemical analyses of steroidogenic enzymes in adrenal tissues have provided new insights into the pathogenesis of PA. However, a comprehensive analysis of the association between enzyme expression and clinical characteristics of PA has rarely been conducted. We aimed to investigate the correlation between clinical characteristics and steroidogenic enzyme expression in PA. DESIGN: A retrospective case-control study. PATIENTS: Consecutive patients who underwent unilateral adrenalectomy for PA (n = 180). Patients with adrenal Cushing's syndrome (CS) (n = 29) and nonfunctioning adenoma (n = 6) as comparator groups. MEASUREMENTS: A tissue microarray of adrenal adenomas was constructed and immunostained for CYP11B1, CYP11B2 and CYP17A1. The expression of the three enzymes was compared between PA and other adrenal diseases and between PA with and without mild autonomous cortisol excess (MACE). RESULTS: Adrenal adenomas in PA showed lower CYP11B1, higher CYP11B2 and lower CYP17A1 expression than those in adrenal CS (p < .001). Nonfunctioning adenomas showed low expression of the three enzymes. PA with MACE showed higher CYP11B1 expression than PA without MACE. CYP11B1 expression was positively correlated with the severity of hypercortisolemia, and CYP11B2 was positively correlated with that of hyperaldosteronism. The expression of CYP11B1 and CYP11B2 had a negative correlation. Patients with absent clinical improvement after adrenalectomy had lower CYP11B2 expression than those with complete success. CONCLUSIONS: Variable expression of steroidogenic enzymes in adrenal adenoma underlies the clinical heterogeneity of PA and is associated with treatment outcomes.
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Adenoma , Hiperaldosteronismo , Aldosterona , Estudios de Casos y Controles , Citocromo P-450 CYP11B2/genética , Humanos , Estudios Retrospectivos , Esteroide 11-beta-Hidroxilasa/genéticaRESUMEN
OBJECTIVE: Mutations in the telomerase reverse transcriptase (TERT) promoter have been reported as a convincing prognostic factor in papillary thyroid carcinomas (PTCs). We aimed to investigate the frequency of TERT promoter mutations in patients with thyroid cancer and identify the clinicopathological factors associated with them in PTCs. DESIGN: A total of 1086 consecutive cases of thyroid cancer composed of mostly PTCs were included in this study. TERT promoter and BRAF mutations were detected by pyrosequencing and their associations with clinicopathological features of tumour were analyzed. RESULTS: TERT promoter mutations were observed in 1.9% of PTCs, 6.7% of follicular thyroid carcinomas, 8.3% of Hurthle cell carcinomas and 25.0% of poorly differentiated thyroid carcinomas and in a single case of anaplastic thyroid carcinoma. In PTCs, aggressive clinicopathological features, higher stage and BRAF V600E mutation were all found to be associated with TERT promoter mutations. Distant metastasis and disease recurrence were more frequent in TERT promoter-mutated PTCs. In multivariate analysis, age ≥55 years, tall cell variant, mitoses ≥3/10 high-power fields, tumour necrosis, and gross extrathyroidal extension (ETE) were identified as independent factors associated with TERT promoter mutations in PTCs. CONCLUSIONS: This study revealed a relatively low frequency of TERT promoter mutations in Korean patients with PTC. Certain clinicopathological features including old age, tall cell variant, increased mitoses, tumour necrosis and gross ETE were found to be indicative of TERT promoter mutations in PTCs, suggesting that mutational analysis in a particular group of PTCs can be effective in regions with low mutation rates.
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Carcinoma Papilar , Telomerasa , Neoplasias de la Tiroides , Carcinoma Papilar/genética , Humanos , Persona de Mediana Edad , Mutación , Necrosis , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas B-raf/genética , Telomerasa/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patologíaRESUMEN
Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2-/-) normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA â BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.
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Núcleo Amigdalino Central/metabolismo , Conducta Impulsiva , Vías Nerviosas/metabolismo , ARN Mensajero/genética , Receptores de Dopamina D2/genética , Núcleos Septales/metabolismo , Animales , Núcleo Amigdalino Central/fisiopatología , Conducta de Elección , Dopamina/metabolismo , Regulación de la Expresión Génica , Masculino , Ratones , Ratones Noqueados , Vías Nerviosas/fisiopatología , Neuronas/metabolismo , Neuronas/patología , Pruebas Neuropsicológicas , Optogenética , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Tiempo de Reacción , Receptores de Dopamina D2/deficiencia , Núcleos Septales/fisiopatología , Transducción de SeñalRESUMEN
Early life stress (ELS) is strongly associated with psychiatric disorders such as anxiety, depression, and schizophrenia in adulthood. To date, biological, behavioral, and structural aspects of ELS have been studied extensively, but their functional effects remain unclear. Here, we examined NeuroPET studies of dopaminergic, glutamatergic, and serotonergic systems in ELS animal models. Maternal separation and restraint stress were used to generate single or complex developmental trauma. Body weights of animals exposed to single trauma were similar to those of control animals; however, animals exposed to complex trauma exhibited loss of body weight when compared to controls. In behavioral tests, the complex developmental trauma group exhibited a decrease in time spent in the open arm of the elevated plus-maze and an increase in immobility time in the forced swim test when compared to control animals. In NeuroPET studies, the complex trauma group displayed a reduction in brain uptake values when compared to single trauma and control groups. Of neurotransmitter systems analyzed, the rate of decrease in brain uptake was the highest in the serotonergic group. Collectively, our results indicate that developmental trauma events induce behavioral deficits, including anxiety- and depressive-like phenotypes and dysfunction in neurotransmitter systems.
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Encéfalo/metabolismo , Encéfalo/fisiología , Neurotransmisores/metabolismo , Heridas y Lesiones/metabolismo , Heridas y Lesiones/fisiopatología , Animales , Animales Recién Nacidos/metabolismo , Animales Recién Nacidos/fisiología , Ansiedad/metabolismo , Ansiedad/fisiopatología , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/fisiopatología , Conducta Animal/fisiología , Depresión/metabolismo , Depresión/fisiopatología , Modelos Animales de Enfermedad , Conducta Exploratoria/fisiología , Femenino , Masculino , Privación Materna , Aprendizaje por Laberinto/fisiología , Imagen Molecular/métodos , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Natación/fisiologíaRESUMEN
Background and Objectives: Robotic thyroidectomy via the bilateral axillo-breast approach (BABA), first introduced in Korea in 2008, has become a standard method of thyroid removal worldwide. The introduction of robotic surgical systems has enabled more patients to benefit from BABA robotic thyroidectomy, with good postoperative and excellent cosmetic results. To date, no studies have compared the benefits of the four currently available da Vinci robotic systems (S, Si, X, and Xi) for BABA robotic thyroidectomy. To determine the da Vinci model most suitable for BABA robotic thyroidectomy, the present study compared the perioperative outcomes in patients who underwent BABA robotic thyroidectomy using the four da Vinci models. Materials and Methods: This retrospective study evaluated outcomes in patients (n = 750) who underwent BABA robotic thyroidectomy using the four da Vinci systems from 2013 to 2019. The clinicopathologic data, including operation time, were compared. Substudy A compared the da Vinci models S and Si from 2013 to 2017, and substudy B compared models Si, X, and Xi from 2018 to 2019. Results: Substudy A, comparing the da Vinci S and Si systems, found no statistically significant differences between the two groups, whereas substudy B found that operation time was shorter in patients who underwent BABA robotic thyroidectomy with the da Vinci Xi system than with the Si and X systems. Conclusions: The da Vinci model Xi system can benefit patients undergoing BABA robotic thyroidectomy by shortening the operation time.
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Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Estudios Retrospectivos , Tiroidectomía , Resultado del TratamientoRESUMEN
Background and Objectives: Preserving the recurrent laryngeal nerve (RLN) is important in thyroid surgery. However, no standardized surgical method for locating the RLN has been established. We defined a new anatomical definition termed "lower central triangle" (LCT) for consistent identification of RLN and used intraoperative nerve monitoring (IONM) to aid in identification and dissection of RLN. Materials and Methods: Patients undergone thyroidectomy were reviewed retrospectively in Seoul National University Bundang Hospital from January to September 2017. Patients with papillary thyroid carcinoma, follicular neoplasm, and Graves' Disease were included while right side non-RLN in arteriosus lusoria, cancer invasion, pre-existing vocal cord palsy, or under the age of 18 were excluded. RLNs were tested with IONM within LCT consisting of the lower pole as the apex and the common carotid artery as the opposite side. The samples were divided into two groups, IONM and non-IONM. Results: Forty lobes in total were included, 22 in IONM group and 18 in non-IONM group. Groups were not significantly different in age, cancer proportion, and accompanying thyroiditis while sex and nodule size differed. RLN detection time was 10.43 s shorter (p < 0.001), and confirmation time was 10.67 s shorter (p = 0.09) in IONM group than in non-IONM group. Both right and left RLNs were located predominately in the middle of LCT. No transient or permanent vocal cord palsy occurred. Conclusions: While IONM is an appropriate aid for thyroidectomy, our approach using LCT to locate the RLN is a novel definition of anatomy that provides prompt identification of the RLN in thyroid surgery.
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Traumatismos del Nervio Laríngeo Recurrente , Neoplasias de la Tiroides , Humanos , Monitoreo Intraoperatorio , Nervio Laríngeo Recurrente , Estudios Retrospectivos , Neoplasias de la Tiroides/cirugíaRESUMEN
BACKGROUND: Cancers of the thyroid isthmus are less frequent compared with the lobar cancers yet have their own unique clinicopathological characteristics. Herein, we sought to examine the isthmic papillary thyroid carcinomas (PTCs) for the pattern of and risk factors for nodal metastasis and the significance of extrathyroidal extension (ETE). METHODS: The medical records of 3138 patients diagnosed with solitary PTC who had undergone surgery were retrospectively reviewed. Of these, 122 isthmic PTCs were matched to common lobar PTCs at a ratio of 1:3 for age, sex, and nodule size. Patient demographics, surgical findings, and pathology reports were analyzed. RESULTS: Isthmic PTCs comprised 4.6% of all PTCs and had more lymphatic invasion (22.1% vs. 13.4%, p = 0.021), ETE (73.0% vs. 57.1%, p = 0.002), and perithyroidal and prelaryngeal node metastasis (18.0% vs. 9.0%, p = 0.006) compared with lobar PTCs. However, there were no significant differences in the rate of central and lateral node metastasis between the two groups. ETE was identified not to be a risk factor for isthmic PTCs for central and lateral node metastasis, in contrast to lobar PTCs in which ETE was a significant risk factor (odds ratio 3.18, 95% confidence interval [CI] 1.89-5.34; and 4.72, 95% CI 1.04-21.41). CONCLUSION: The rates of central and lateral node metastasis of isthmic PTCs are comparable with that of lobar PTCs despite a higher rate of ETE in the isthmic counterpart. Although the extent of surgery for isthmic PTCs remains to be investigated, careful dissection of perithyroidal and prelaryngeal nodes may be necessary for isthmic PTCs.
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Carcinoma Papilar/patología , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Cáncer Papilar Tiroideo/patología , Glándula Tiroides/patología , Adulto , Anciano , Carcinoma Papilar/cirugía , Femenino , Humanos , Modelos Logísticos , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Cuello , Disección del Cuello , República de Corea , Estudios Retrospectivos , Factores de Riesgo , Cáncer Papilar Tiroideo/cirugía , Glándula Tiroides/cirugía , TiroidectomíaRESUMEN
OBJECTIVES: Vertigo in sudden sensorineural hearing loss (SSNHL) is hypothesized as an extension of the disease caused by the anatomical proximity of the cochlea and vestibule. The present study aimed to demonstrate the association of vestibular function test (VFT) results with SSNHL disease severity and prognosis. MATERIALS AND METHODS: This study assessed clinical records of 263 SSNHL patients admitted to our hospital, between January 2010 and October 2017. Steroid treatment comprised high-dose intravenous dexamethasone (16 mg/d) or oral methylprednisolone (64 mg/d) for 4 days and tapered oral methylprednisolone for 8 days after discharge. Caloric tests were performed in all patients, and cervical vestibular-evoked myogenic potential (c-VEMP) and ocular VEMP (o-VEMP) tests were performed in 209 and 144 patients, respectively. RESULTS: Ninety six patients had vertigo, and caloric abnormalities were observed in 119 patients. Initial PTA in patients with vertigo were worse than in those without vertigo (63.0 dB vs 72.7 dB, P = .002). Initial PTA in patients with abnormal o-VEMP was worse than in those with normal o-VEMP (61.4 dB vs 73.0 dB, P = .004). PTA improvement after steroid treatment in patients with vertigo was lower than in those without vertigo (25.0 dB vs 20.9 dB, P = .028). PTA improvement after treatment in patients with abnormal caloric results was lower than in those with normal caloric results (26.0 dB vs 18.4 dB, P = .013). CONCLUSION: The functions of vestibular organs, particularly the utricle and lateral semicircular canal, are associated with disease severity and hearing outcome in SSNHL patients.
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Pérdida Auditiva Sensorineural/etiología , Vértigo/etiología , Vestíbulo del Laberinto/fisiopatología , Administración Oftálmica , Adolescente , Adulto , Anciano , Pruebas Calóricas , Dexametasona/administración & dosificación , Potenciales Evocados , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Infusiones Intravenosas , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Vértigo/diagnóstico , Vértigo/tratamiento farmacológico , Vértigo/fisiopatología , Adulto JovenRESUMEN
Background and objectives: Currently, few studies have been conducted on postoperative chylothorax, specifically in total thyroidectomy with modified radical neck dissection (MRND) in papillary thyroid carcinoma patients. This study provides the actual incidence, etiology, and clinical features of postoperative chylothorax and reports the clinical outcomes after treatment, which were dependent upon the severity of the complications. Materials and Methods: The medical charts of 111 papillary thyroid cancer (PTC) patients who underwent total thyroidectomy with modified radical neck dissection from January 2016 to December 2018 were reviewed retrospectively. The results were compared in three groups: the no chylothorax group, the subclinical (asymptomatic) group, and the clinical (symptomatic) group. Results: Chylothorax occurred in 23 patients (20.7%, 23/111). Nineteen (82.6%, 19/23) were subclinical chylothorax cases, which implies a small amount of chyle leakage with no respiratory symptoms. Four (17.4%, 4/23) were clinical, meaning they had either respiratory symptoms, such as dyspnea, desaturation, or a large amount of chylothorax in the images. The incidence was significantly higher in patients who underwent left modified radical neck dissection, and this corresponds to the side in which chylothorax occurred. There were also statistical differences in the drainage color, peak amount, or drain removal time. Conclusions: Postoperative chylothorax is a rare complication following neck dissection. However, it can be fatal if the condition progresses. Therefore, patients who undergo total thyroidectomy with modified radical neck dissection, especially on the left side, should be monitored for respiratory symptoms, and serial chest x-ray images obtained.