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BACKGROUND: Hybrid thoracoscopic-laparotomy esophagectomy (hTE) and complete thoracoscopic-laparoscopic esophagectomy (cTLE) are the two most frequently used minimally invasive esophagectomy (MIE) procedures and are broadly utilized for esophageal cancer. We evaluated differences in short- and long-term outcomes between hTE and cTLE in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Patients who underwent MIE for ESCC between September 2009 and February 2016 were included in this retrospective study. Propensity score matching (PSM) was utilized to contrast the postoperative results of hTE and cTLE according to the obtained and analyzed pertinent patient features and postoperative variables. Univariate and multivariate Cox proportional hazard regression analysis was used on possible predictors of survival. RESULTS: Eighty-six well-balanced pairs of patients were available for outcome comparison after PSM. Compared to Group 1 (hTE), the patients in Group 2 (cTLE) had significantly shorter operative times and less intraoperative blood loss, but a higher number of retrieved nodes (p = 0.000, p = 0.003, and p = 0.000, respectively). The incidence of postoperative complications was 40.7% (70/172) and did not significantly differ between the two groups. The patients in Group 2 exhibited higher disease-free survival and disease-specific survival (DSS) than those in Group 1 (p = 0.048 and p = 0.041, respectively). Univariate and multivariate Cox proportional hazard regression analyses showed that pT stage, pN stage, differentiation grade, and the surgical procedure had significant HRs, which suggested that cTLE is associated with better DSS. CONCLUSIONS: cTLE possibly shows better postoperative and oncologic outcomes than hTE.
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Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Laparoscopia/métodos , Laparotomia/métodos , Idoso , Perda Sanguínea Cirúrgica , Esofagectomia/efeitos adversos , Feminino , Humanos , Incidência , Laparoscopia/efeitos adversos , Laparotomia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: The aim of this study is to summarize the causes and implications of intraoperative conversion from minimally invasive esophagectomy (MIE) to open thoracotomy, and to evaluate the effect on long-term survival. METHODS: There were 293 thoracoscopic esophagectomies for esophageal squamous cell carcinoma (ESCC) of the thoracic esophagus performed by the authors from September 2009 to August 2015. Totally, 257 patients were enrolled in this study. These patients were divided into two groups (those underwent complete MIE and those converted to open thoracotomy) and then compared. A standardized preoperative evaluation, as well as a postoperative method of following at a regular frequency were adopted for all of these patients. The clinicopathologic characteristics and the perioperative variables were retrospectively analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. And the Kaplan-Meier method was used to compare survival differences. RESULTS: There were 231 patients (89.9%) underwent successful thoracoscopic esophagectomy (Group 1), and 26 cases (10.1%) required conversion to open procedure (Group 2). The majority of conversion (73.1%, 19/26) occurred in the initial 100 cases. No significant difference in background or clinicopathologic factors between the two groups was observed, but patients in Group 2 had significantly longer operative time and more operative blood loss. Among the 26 patients of Group 2, there were nine cases that need emergent conversion for various reasons. And the most common cause for emergent conversion was intraoperative bleeding. Univariate and multivariate analyses all demonstrated that intraoperative conversion did not significantly influence the overall or recurrence-free survival of these patients. CONCLUSIONS: Univariate analysis and multivariate Cox proportional hazard regression analysis indicated that intraoperative conversion did not significantly influence the OS and RFS rate of these patients. Our results demonstrated that the intraoperative conversion did not affect the long-term survival of patients underwent MIE for ESCC.
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Conversão para Cirurgia Aberta/métodos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Cirurgia Torácica Vídeoassistida/métodos , Toracotomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Feminino , Humanos , Incidência , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Minimally invasive esophagectomy (MIE) has been shown to be a feasible technique for the treatment of esophageal cancer; however, its postoperative morbidity remains high. This retrospective study aimed to evaluate the effect of postoperative complications on long-term outcomes in patients who have undergone MIE for esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study enrolled patients who had undergone MIE for ESCC between September 2009 and November 2014; all procedures were performed by a single surgical team. Relevant patient characteristics and postoperative variables were collected and evaluated. The disease-free survival (DFS) and disease-specific survival (DSS) were determined by the Kaplan-Meier method, and compared by log-rank tests. Possible predictors of survival were subjected to univariate analysis and multivariate Cox proportional hazard regression analysis. RESULTS: In all, data on 214 patients with ESCC were analyzed, including 170 men and 44 women. All study subjects had undergone thoracoscopic or thoracoscopic-laparoscopic esophagectomy and cervical esophagogastric anastomosis. One hundred and thirty patients (60.7%) had postoperative complications (Grades 1-4). The overall DFS and DSS rates were 80.0 and 88.9% at 1 year, 48.6 and 54.2% at 3 years, and 43.2 and 43.5% at 5 years, respectively. Univariate analysis and multivariate Cox proportional hazard regression analysis showed that T stage, N stage, and tumor grade were independent prognostic factors for long-term survival; however, postoperative complications had no significant effect on the DFS or DSS of this patient cohort (log-rank test, p = 0.354 and 0.160, respectively). CONCLUSIONS: Postoperative complications have no significant effect on long-term survival in patients who have undergone MIE for ESCC.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Laparoscopia , Complicações Pós-Operatórias/mortalidade , Toracoscopia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Anastomotic leak (AL) remains a challenging and bothersome complication of minimally invasive esophagectomy (MIE). In this retrospective study, we measured the perioperative albumin (ALB) and prealbumin (PA) of patients who underwent MIE, and investigated the relationship between the occurrence of AL and the altering levels of ALB/PA. PATIENTS AND METHODS: Sixty patients underwent video-assisted thoracoscopic-laparoscopic esophagectomy between September 2013 and August 2014. The preoperative and postoperative levels of ALB and PA were detected, and the baseline of altering levels for ALB and PA were established. According to the decreasing values of postoperative ALB, patients were divided into Group A1 (decreased value of ALB over the average level) and Group A2 (decreased value of ALB not reach the average level). Similarly, patients were also divided into Group P1 and Group P2 according to the average decreasing values of postoperative PA. The incidence of AL and non-anastomotic-relative complications between different groups were calculated and analyzed. RESULTS: One postoperative death occurred (1/60, 1.7 %). Eighteen complications were observed (18/60, 30 %), including seven cases of cervical AL (7/60, 11.7 %). There was no significant difference in background or clinicopathologic factors between different groups. The levels of ALB and PA descended significantly after MIE (p = 0.0000, p = 0.0000, respectively). No correlation between deficient levels of ALB and PA was observed (p = 0.1874, r = 0.0298). There was a significant higher AL incidence in Group P1 than in Group P2 (p = 0.0322). However, the incidence of AL did not exhibit significant difference between Group A1 and Group A2 (p = 0.9252). CONCLUSIONS: MIE appears to be a procedure of obvious influence on the nutrient metabolism of patients. The results demonstrated that patients with severely deficient level of PA had higher risk of AL after MIE.
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Fístula Anastomótica/etiologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Pré-Albumina/análise , Albumina Sérica , Adulto , Idoso , Esofagectomia/efeitos adversos , Feminino , Humanos , Incidência , Laparoscopia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Cirurgia VídeoassistidaRESUMO
Fundamental to neuroscience is the understanding of how the language of neurons relates to behavior. In the lateral geniculate nucleus (LGN), cells show distinct properties such as selectivity for particular wavelengths, increments or decrements in contrast, or preference for fine detail versus rapid motion. No studies, however, have measured how LGN cells respond when an animal is challenged to make a perceptual decision using information within the receptive fields of those LGN cells. In this study we measured neural activity in the macaque LGN during a two-alternative, forced-choice (2AFC) contrast detection task or during a passive fixation task and found that a small proportion (13.5%) of single LGN parvocellular (P) and magnocellular (M) neurons matched the psychophysical performance of the monkey. The majority of LGN neurons measured in both tasks were not as sensitive as the monkey. The covariation between neural response and behavior (quantified as choice probability) was significantly above chance during active detection, even when there was no external stimulus. Interneuronal correlations and task-related gain modulations were negligible under the same condition. A bottom-up pooling model that used sensory neural responses to compute perceptual choices in the absence of interneuronal correlations could fully explain these results at the level of the LGN, supporting the hypothesis that the perceptual decision pool consists of multiple sensory neurons and that response fluctuations in these neurons can influence perception.
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Tomada de Decisões/fisiologia , Corpos Geniculados/fisiologia , Neurônios/fisiologia , Animais , Medições dos Movimentos Oculares , Fixação Ocular/fisiologia , Macaca mulatta , Macaca radiata , Masculino , Modelos Neurológicos , Testes Neuropsicológicos , Estimulação Luminosa , Psicometria , Psicofísica , Percepção Visual/fisiologiaRESUMO
To fully understand the relationship between perception and single neural responses, one should take into consideration the early stages of sensory processing. Few studies, however, have directly examined the neural underpinning of visual perception in the lateral geniculate nucleus (LGN), only one synapse away from the retina. In this study we recorded from LGN parvocellular (P) ON-center and OFF-center neurons while monkeys either passively viewed or actively detected a full range of contrasts. We found that OFF neurons were more sensitive in detecting negative contrasts than ON neurons were in detecting positive contrasts. Also, OFF neurons had higher spontaneous activities, higher peak response amplitudes, and were more sustained than ON neurons in their contrast responses. Puzzlingly, OFF neurons failed to show any significant correlations with the monkeys' perceptual choices, despite their greater contrast sensitivities. If, however, choice probabilities were calculated from interspike intervals instead of spike counts (thus taking into account the higher firing rates of OFF neurons), OFF neurons but not ON neurons were significantly correlated with behavioral choices. Taken together, these results demonstrate in awake, behaving animals that: 1) the ON and OFF pathways do not simply mirror each other in their functionality but instead carry qualitatively different types of information, and 2) the responses of ON and OFF neurons can be correlated with perceptual choices even in the absence of physical stimuli and interneuronal correlations.
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Potenciais de Ação , Comportamento de Escolha/fisiologia , Sensibilidades de Contraste/fisiologia , Corpos Geniculados/fisiologia , Neurônios/fisiologia , Animais , Macaca mulatta , Macaca radiata , Masculino , Estimulação LuminosaRESUMO
BACKGROUND: In patients with esophageal squamous cell carcinoma (ESCC), pathologic examination allows T2 tumors to be further subclassified according to whether the circular or longitudinal muscle layers are invaded. Therefore, we aimed to investigate whether subclassifying the T2 stages can aid in determining the prognosis for patients with ESCC. METHODS: The clinical and pathologic characteristics of 85 ESCC patients with T2 tumors who underwent thoracoscopic esophagectomy between 2008 and 2013 were retrospectively analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. The Kaplan-Meier method was used to compare survival differences with respect to each prognostic factor. RESULTS: Thirty-nine patients had tumors invading the circular muscle layer and were designated as having T2a disease. The remaining 46 patients had T2b disease, with tumors invading the longitudinal muscle layer. The overall 1-, 3-, and 5-year survival rates were 96.1, 53.8, and 36.4 %, respectively, with a median survival of 39.0 months. Univariate analysis indicated that sex, smoking history, grade, location, and tumor length did not significantly influence on survival. Only T stage (P = 0.017) and N stage (P = 0.003) were associated with survival. The results of multivariate Cox proportional hazard regression analysis showed that T stage (P = 0.045) and N stage (P = 0.003) were independent prognostic factors. CONCLUSIONS: N stage and subclassified T stage are independent prognostic factors in patients with T2 tumors. Therefore, we concluded that T2 tumors can be subclassified further into T2a and T2b stages, and patients with different T2 stages may have different prognoses.
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Carcinoma de Células Escamosas/classificação , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/classificação , Neoplasias Esofágicas/patologia , Esofagectomia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Previous studies proposed that CYP1A2 rs762551 polymorphism might be associated with risk of lung cancer by influencing the function of CYP1A2. However, previous studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer reported inconsistent findings. We performed a meta-analysis of the published case-control studies to assess the association between CYP1A2 rs762551 polymorphism and risk of lung cancer. PubMed and Embase were searched to identify relevant studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer, and seven studies with a total of 3,320 subjects were finally included into the meta-analysis. The pooled odds ratio (OR) and 95 % confidence interval (95%CI) was calculated to evaluate the association. Meta-analysis of total studies showed that CYP1A2 rs762551 polymorphism contributed to risk of lung cancer under all four genetic models (C versus A: OR = 1.26, 95%CI 1.13 to 1.40, P < 0.001; CC versus AA: OR = 1.61, 95%CI 1.28 to 2.04, P < 0.001; CC versus AA/AC: OR = 1.52, 95%CI 1.11 to 2.09, P = 0.009; CC/AC versus AA: OR = 1.28, 95%CI 1.10 to 1.48, P = 0.001). Subgroup analysis based on ethnicity further suggested that CYP1A2 rs762551 polymorphism was associated with risk of lung cancer in Caucasians. These results from the meta-analysis suggest that CYP1A2 rs762551 polymorphism contributes to risk of lung cancer.
Assuntos
Citocromo P-450 CYP1A2/genética , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Humanos , Razão de Chances , Fatores de Risco , População Branca/genéticaRESUMO
How people vote often defies rational explanation. Physical traits sometimes sway voters more than policies do-but why? Here we show that rhesus macaques, who have no knowledge about political candidates or their policies, implicitly predict the outcomes of U.S. gubernatorial and senatorial elections based solely on visual features. Given a pair of candidate photos, monkeys spent more time looking at the loser than the winner, and this gaze bias predicted not only binary election outcomes but also the candidates' vote share. Analysis of facial features revealed candidates with more masculine faces were more likely to win an election, and vote share was a linear function of jaw prominence. Our findings endorse the idea that voters spontaneously respond to evolutionarily conserved visual cues to physical prowess and that voting behavior is shaped, in part, by ancestral adaptations shared with nonhuman primates.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy lacking valid prognostic biomarkers. As a member of the High Mobility Group domain-containing DNA-binding proteins, Sox3 has been reported to induce oncogenic transformation of chicken embryo fibroblasts. However, the expression and prognostic value of Sox3 in ESCC remain unclear. METHODS: A total of 30 pairs of ESCC with a corresponding non-neoplastic esophageal epithelium (NE) specimen were investigated for Sox3 expression using RT-PCR and western blot analysis. Tissue microarrays containing 118 ESCC and 30 NE samples were detected for Sox3 expression using immunohistochemical staining. The relationship of Sox3 staining with various clinicopathological characteristics and survival of patients was statistically analyzed. RESULTS: Sox3 expression in ESCC was 3.1- and 2.7-fold higher than in NE at mRNA (P < 0.001) and protein level (P < 0.001), respectively. Positive staining of Sox3 was observed in 77.1 % of the ESCC and 16.7 % of the NE samples (P < 0.001). High expression of Sox3 was significantly correlated with the regional lymph nodes metastasis (RLNM) (P = 0.022) and advanced TNM stage (P = 0.011). Moreover, high expression of Sox3 was significantly associated with poor overall survival (P < 0.001) and recurrence-free survival (P < 0.001) in ESCC patients. Both Sox3 expression (P < 0.001) and RLNM (P = 0.002) were independent prognostic factors for patients with ESCC. CONCLUSIONS: Sox3 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for ESCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Biomarcadores Tumorais/genética , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOXB1/genética , Taxa de Sobrevida , Análise Serial de TecidosRESUMO
BACKGROUND: Thoracoscopic esophagectomy is a feasible technique that has been shown to be safe for the treatment of esophageal cancer. There continues to be controversy about the optimal position during thoracoscopic esophagectomy. In this study, we compared the intraoperative hemodynamic parameters, clinical pathological characteristics, as well as postoperative complications in patients who underwent thoracoscopic esophagectomy in the prone position (PP) or left-lateral decubitus position (LDP). METHODS: Between January 2011 and June 2011, 23 patients underwent thoracoscopic esophagectomies for cancer of the esophagus in LDP (group A). Since February 2011, we have performed thoracoscopic esophagectomies for cancer of the esophagus in PP for 21 patients (group B). The demographics and clinicopathologic factors, as well as the intraoperative hemodynamic parameters, of the two groups were analyzed. RESULTS: No postoperative death occurred in these 44 patients. Overall morbidity was similar in the two groups. No significant difference in the length of operation or number of retrieved mediastinal nodes between the two groups was observed, but the intraoperative blood loss in group A was significantly higher than in group B (P = 0.0228). There was no significant difference of the intraoperative mean arterial pressure, central venous pressure, heart rate, and stroke volume variation between the two groups and various positions. In group A, the cardiac output (CO), cardiac index (CI), as well as stroke volume index (SVI) did not exhibit significant difference after altering patients' position from LDP to SP. However, patients who underwent thorascopic esophagectomy in PP had lower CO, CI, and SVI than in LDP during the thoracoscopic stage. CONCLUSIONS: Compared with the PP, the LDP could provide more excellent hemodynamic parameters during thoracoscopic esophagectomy. However, the various hemodynamic statuses did not exert significant influence on the occurrence of postoperative complications.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Hemodinâmica , Posicionamento do Paciente/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Fístula Anastomótica/etiologia , Arritmias Cardíacas/etiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/fisiopatologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/fisiopatologia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Paralisia das Pregas Vocais/etiologiaRESUMO
BACKGROUND: Minimally invasive esophagectomy is a feasible technique shown to be safe and oncologically adequate for the treatment of esophageal cancer. This study aimed to describe one surgeon's learning curve for video-assisted thoracoscopic esophagectomy with the patient in lateral position. METHODS: From May 2010 to June 2012, 89 thoracoscopic esophagectomies for esophageal cancer were performed by one surgeon. The patients were divided into three groups. Group A included the first 30 cases. Group B comprised cases 31 to 60, and group C included the final 29 cases. The demographic characteristics and the intra- and postoperative variables were collected retrospectively and analyzed. RESULTS: One postoperative death occurred. Eight patients required conversion. No significant difference in background or clinicopathologic factors among the three groups was observed. Compared with group A, a significant decrease in intrathoracic operative time (107.7 ± 16.2 min; P = 0.0000), total operative time (326.3 ± 40.7 min; P = 0.0002), and blood loss (290.8 ± 114.3 ml; P = 0.0129) was observed in group B, whereas more retrieved nodes were harvested (20.1 ± 9.5; P = 0.0002). The last 29 patients (group C) involved significantly less intrathoracic operative time (82.8 ± 18.4 min; P = 0.0386), total operative time (294.7 ± 37.4 min; P = 0.0009), and blood loss (234.7 ± 87.8 ml; P = 0.0125) as well as a shorter postoperative hospital stay (12.4 ± 3.7 days; P = 0.0125) compared with group B. A significant decline in the overall morbidity from group A to group C (P = 0.0005) also was observed. CONCLUSIONS: The results of this study suggest that at least 30 cases were needed to reach the plateau of thoracoscopic esophagectomy. After more than 60 cases of thoracoscopic esophagectomies had been managed, lower morbidity could be obtained.
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Competência Clínica , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Curva de Aprendizado , Posicionamento do Paciente/métodos , Cirurgia Torácica Vídeoassistida/educação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Competitive social interactions, as in chess or poker, often involve multiple moves and countermoves deployed tactically within a broader strategic plan. Such maneuvers are supported by mentalizing or theory-of-mind-reasoning about the beliefs, plans, and goals of an opponent. The neuronal mechanisms underlying strategic competition remain largely unknown. To address this gap, we studied humans and monkeys playing a virtual soccer game featuring continuous competitive interactions. Humans and monkeys deployed similar tactics within broadly identical strategies, which featured unpredictable trajectories and precise timing for kickers, and responsiveness to opponents for goalies. We used Gaussian Process (GP) classification to decompose continuous gameplay into a series of discrete decisions predicated on the evolving states of self and opponent. We extracted relevant model parameters as regressors for neuronal activity in macaque mid-superior temporal sulcus (mSTS), the putative homolog of human temporo-parietal junction (TPJ), an area selectively engaged during strategic social interactions. We discovered two spatially-segregated populations of mSTS neurons that signaled actions of self and opponent, sensitivities to state changes, and previous and current trial outcomes. Inactivating mSTS reduced kicker unpredictability and impaired goalie responsiveness. These findings demonstrate mSTS neurons multiplex information about the current states of self and opponent as well as history of previous interactions to support ongoing strategic competition, consistent with hemodynamic activity found in human TPJ.
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Context: Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective: To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity. Methods: This randomized, double-blind, placebo-controlled, crossover pilot trial (NCT02849743), conducted at an outpatient academic medical center, included patients aged 10 to 35 years with hypothalamic obesity from hypothalamic/pituitary tumors. Participants received intranasal OXT (Syntocinon, 40 USP units/mL, 4â IU/spray) vs excipient-matched placebo, 16 to 24â IU 3 times daily at mealtimes. Weight loss attributable to OXT vs placebo and safety (adverse events) were assessed. Results: Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3 years, IQR 13.3-20.6), 10 completed the entire study. We observed a nonsignificant within-subject weight change of -0.6â kg (95% CI: -2.7, 1.5) attributable to OXT vs placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed. Conclusion: In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was well-tolerated, so future larger studies could examine different dosing, combination therapies, and potential psychosocial benefits.
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Aberrant expression and/or activity of the non-receptor protein tyrosine kinase SFK (Src family kinase) members are commonly observed in progressive stages of human tumours. The aim of the present study was to investigate whether Src is a potential drug target for treating oesophageal squamous cell carcinoma. Compared with the human immortalized oesophageal epithelial cell line SHEE, oesophageal squamous cell carcinoma cells have increased tyrosine phosphorylation activities. We have explored the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases, for the treatment of oesophageal squamous cell carcinoma. We examined that the effects of dasatinib on proliferation, invasion, apoptosis, spindle checkpoint, cell-cycle arrest and kinase activity in vitro using three human oesophageal carcinoma cell lines KYSE30, KYSE180 and EC109. In nude mouse models, dasatinib treatment effectively inhibited the expression of activated Src, resulting in the inhibition of tumour growth. Multiple drug effect isobologram analysis was used to study interactions with the chemotherapeutic drug docetaxel. As expected, the three oesophageal carcinoma cell lines were highly sensitive to dasatinib, but SHEE cells were not sensitive to this drug. Concentration-dependent anti-proliferative effects of dasatinib were observed in the three oesophageal carcinoma cell lines. Dasatinib significantly inhibited oesophageal carcinoma cell invasion and up-regulation of MAD2 (mitotic arrest-deficient 2), as well as inducing cell apoptosis and cell-cycle arrest. Additive and synergistic interactions were observed for the combination of dasatinib and docetaxel. Therefore it was concluded that dasatinib blocks the G1/S transition and inhibits cell growth. These results provided a clear biological rationale to test dasatinib as a single agent or in combination with chemotherapy in oesophageal squamous cell carcinoma. Moreover, we have shown in vitro and in vivo that dasatinib might have therapeutic benefit for patients with oesophageal squamous cell carcinoma who are not eligible for surgery.
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Carcinoma de Células Escamosas/tratamento farmacológico , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Pirimidinas/farmacologia , Tiazóis/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Dasatinibe , Docetaxel , Sinergismo Farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Humanos , Proteínas Mad2 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Repressoras/metabolismo , Taxoides/farmacologia , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismoRESUMO
BACKGROUND: Minimally invasive esophagectomy (MIE) is a feasible technique that has been shown to be safe for the treatment of esophageal cancer. Chylothorax remains a challenging and potentially life-threatening postoperative complication of MIE. In this retrospective series, we evaluated the results of preventive intraoperative thoracic duct ligation in patients who underwent video-assisted thoracoscopic esophagectomy for cancer. METHODS: From May 2009 to June 2010, 70 video-assisted thoracoscopic esophagectomies for cancer of the esophagus (group A) were performed without prophylactic thoracic duct ligation. Since June 2010, 65 patients (group B) with esophageal cancer underwent video-assisted thoracoscopic esophagectomy with routine ligation of the thoracic duct during the operation. RESULTS: No intraoperative or postoperative complications directly related to thoracic duct ligation were recorded. Postoperative chylothorax occurred in seven patients in group A and in one patient in group B (P = 0.0375). CONCLUSIONS: The results of this study suggest that thoracic duct ligation during video-assisted thoracoscopic esophagectomy for cancer is an effective and safe method for prevention of postoperative chylothorax.
Assuntos
Quilotórax/prevenção & controle , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Idoso , Fístula Anastomótica/etiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Ducto TorácicoRESUMO
Social stimuli, like faces, and sexual stimuli, like genitalia, spontaneously attract visual attention in both human and non-human primates. Social orienting behaviour is thought to be modulated by neuropeptides as well as sex hormones. Using a free viewing task in which paired images of monkey faces and anogenital regions were presented simultaneously, we found that male rhesus macaques overwhelmingly preferred to view images of anogenital regions over faces. They were more likely to make an initial gaze shift towards, and spent more time viewing, anogenital regions compared with faces, and this preference was accompanied by relatively constricted pupils. On face images, monkeys mostly fixated on the forehead and eyes. These viewing preferences were found for images of both males and females. Both oxytocin (OT), a neuropeptide linked to social bonding and affiliation, and testosterone (TE), a sex hormone implicated in mating and aggression, amplified the pre-existing orienting bias for female genitalia over female faces; neither treatment altered the viewing preference for male anogenital regions over male faces. Testosterone but not OT increased the probability of monkeys making the first gaze shift towards female anogenital rather than face pictures, with the strongest effects on anogenital images of young and unfamiliar females. Finally, both OT and TE promoted viewing of the forehead region of both female and male faces, which display sexual skins, but decreased the relative salience of the eyes of older males. Together, these results invite the hypothesis that both OT and TE regulate reproductive behaviours by acting as a gain control on the visual orienting network to increase attention to mating-relevant signals in the environment. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.
Assuntos
Ocitocina , Testosterona , Animais , Olho , Feminino , Macaca mulatta/fisiologia , Masculino , Ocitocina/farmacologia , Comportamento SocialRESUMO
Zinc deficiency was implicated in the etiologies of human esophageal squamous cell carcinoma (ESCC). Wild-type p53-induced gene 1 (WIG-1), a kind of zinc finger protein, was cloned from the human 3q26.3 region and encoded a putative polypeptide of 289 amino acids. Our previous studies have demonstrated that the expression of WIG-1 was downregulated in ESCC tissues. Herein, we investigated the effect of zinc on cell proliferation, apoptosis, as well as expression of WIG-1 in EC109 cells. Meanwhile, an RNAi vector of WIG-1 was transfected into EC109 cells and the effect of zinc on WIG-1 expression was investigated. We found that zinc could suppress cell proliferation and induce G0/G1 cell cycle arrest and apoptosis of EC109, and this efficacy might result from the expression altering of several apoptosis-related genes, such as Bax, p21 ( WAF ), and cyclin D1. In particular, upregulation of WIG-1 was observed after zinc supplementation, indicating that WIG-1 might be involved in the zinc-induced cell cycle arrest and apoptosis of EC109 cells by regulating the expression of Bax, p21 ( WAF ), and cyclin D1.
Assuntos
Apoptose/fisiologia , Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte/biossíntese , Ciclo Celular/fisiologia , Neoplasias Esofágicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/biossíntese , Zinco/metabolismo , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proteínas de Transporte/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/biossíntese , Ciclina D1/genética , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Proteínas Nucleares/genética , Proteínas de Ligação a RNA , Transfecção , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética , Regulação para Cima , Zinco/farmacologia , Proteína X Associada a bcl-2/biossínteseRESUMO
OBJECTIVE: Decoy receptor 3 (DcR3) is a soluble receptor, which can bind to and inactivate the apoptosis-inducing ligands. We studied a possible association between DcR3 expression and clinicopathologic features in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The mRNA expression of DcR3 was examined by RT-PCR in 109 primary ESCC patients. For the 52 pairs of DcR3 positive tissues, the protein expression was determined by immunohistochemistry. RESULTS: There was a strong correlation among DcR3 mRNA expression and tumor invasion (P=0.01) and lymph node metastasis (P=0.036). We also found that there was a correlation between DcR3 overexpression with lymph node metastasis (P=0.014) in 52 pairs of DCR3 mRNA positive tissues. CONCLUSIONS: Our finding suggested that the overexpression of DcR3 is significantly related with ESCC clinical staging. DcR3 might be a candidate as a tumor specific biomarker for ESCC.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Adulto , Idoso , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Imuno-Histoquímica , Estudos Longitudinais , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/análise , Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SolubilidadeRESUMO
OBJECTIVE: The systemic review and meta-analysis of the studies published during the past 10 years was designed to optimize the surgical procedures of video-assisted thoracoscopic sympathectomy (VTS) to treat palmar hyperhidrosis (PH). METHODS: Citations from 2000 to 2010 were included regarding the following aspects: selection of ganglia level for VTS, comparison of different techniques for VTS, evaluating clinical efficacy of intraoperative intrapleural analgesia, and postoperative intrapleural drainage. Major clinical outcomes are defined as: cases with postoperative resolution of symptoms, total cases with postoperative compensatory hyperhidrosis (CH), cases with severe or moderate CH, satisfied cases, evaluation of postoperative pain, and postoperative pneumothorax. RESULTS: Systemic review indicates that T3 and T3-4 sympathectomy had the "best" clinical efficacy. Meta-analysis suggests that efficacious rates of PH are nearly similar compared with multiple and single ganglia sympathectomy (100 vs. 95.6%). However, single-ganglia sympathectomy can render a lower risk of total CH compared with multiple-ganglia block. Risk of moderate/severe CH has a similar trend. Additionally, single-ganglia sympathectomy is more potent to satisfy patients postoperatively. One randomized, controlled trial (RCT) that compared different techniques for VTS indicated that the overall success rate of the operation was 95% and the differences were not statistically significant. Two RCTs indicated that there were significant differences between trial group (intraoperative intercostal nerve blocks using bupivacaine) and control group regarding the attenuation of postoperative pain. One RCT suggested that there was no significant difference with or without pleural drainage regarding the incidence of postoperative residual pneumothorax. CONCLUSIONS: T3 sympathectomy is supposed to be recommended for the treatment of PH regardless of using various techniques. Intraoperative intrapleural analgesia using bupivacaine or bupivacaine plus epinephrine is effective to prevent postoperative pain. Pleural drainage after VTS should be abandoned.