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BACKGROUND: Cancer cells have developed molecular strategies to cope with evolutionary stressors in the dynamic tumor microenvironment. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) is a metabolic rheostat that regulates diverse cellular adaptive behaviors, including growth and survival. However, the mechanistic role of PGC1α in regulating cancer cell viability under metabolic and genotoxic stress remains elusive. METHODS: We investigated the PGC1α-mediated survival mechanisms in metabolic stress (i.e., glucose deprivation-induced metabolic stress condition)-resistant cancer cells. We established glucose deprivation-induced metabolic stress-resistant cells (selected cells) from parental tumor cells and silenced or overexpressed PGC1α in selected and parental tumor cells. RESULTS: Several in vitro and in vivo mouse experiments were conducted to elucidate the contribution of PGC1α to cell viability in metabolic stress conditions. Interestingly, in the mouse xenograft model of patient-derived drug-resistant cancer cells, each group treated with an anti-cancer drug alone showed no drastic effects, whereas a group that was co-administered an anti-cancer drug and a specific PMCA inhibitor (caloxin or candidate 13) showed marked tumor shrinkage. CONCLUSIONS: Our results suggest that PGC1α is a key regulator of anti-apoptosis in metabolic and genotoxic stress-resistant cells, inducing PMCA expression and allowing survival in glucose-deprived conditions. We have discovered a novel therapeutic target candidate that could be employed for the treatment of patients with refractory cancers.
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Neoplasias , Ratones , Humanos , Animales , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Neoplasias/tratamiento farmacológico , Estrés Fisiológico , Resistencia a Medicamentos , Microambiente TumoralRESUMEN
The fall armyworm (FAW) Spodoptera frugiperda is an important invasive pest in Africa and Asia. It is a polyphagous pest with at least 353 recorded host plant species, including corn. Chemical control of this pest is unsuccessful because of a developed resistance and harmful effects on the environment. Entomopathogenic fungi are potential biological control agents for FAW. In this study, the native strain of Metarhizium rileyi (KNU-Ye-1), collected from a cornfield at Yeongcheon, Korea, was identified by morphological and molecular characterization. The susceptibility of the fourth-instar larvae of FAW to the native strain M. rileyi was examined in the laboratory. The results showed that the Korean strain of M. rileyi (KNU-Ye-1) was highly virulent to FAW larvae, causing 89% mortality 7 days posttreatment. Therefore, M. rileyi (KNU-Ye-1) identified in this study is highly valuable for the biological control of FAW in the field.
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Metarhizium , Animales , Spodoptera/microbiología , Virulencia , LarvaRESUMEN
Ticagrelor (TCG) has been used as an antiplatelet agent for acute coronary syndrome patients. The aim of this research was to establish a population pharmacokinetic/pharmacodynamic (PK/PD) model of TCG and to apply the model for predicting the PD response of the TCG-loaded self-microemulsifying drug delivery system (TCG-SME) in rats. Pure TCG and TCG-SME (2, 5, and 10 mg/kg of TCG) were orally administered to male Sprague-Dawley rats. Plasma samples were collected at scheduled time-points and then analyzed for TCG plasma concentrations and antiplatelet effects. The inhibition of platelet aggregation of TCG was measured as a PD response. The PK profiles of pure TCG and TCG-SME could be well-explained with a two-compartment PK model. The accuracy of the PK model was assessed with a goodness-of-fit plot and conditional weight residual error (CWRES). Also, the visual predictive check was investigated based on the predictions. A population PK/PD model for pure TCG was established as an indirect response Emax model linked to the two-compartment PK model of pure TCG. The PK/PD model proposed a suitable fitting to link the plasma concentration of TCG simultaneously with platelet aggregation. Based on the PK data of TCG-SME, as well as the established PK/PD model of pure TCG, the PD profiles of TCG-SME were simulated. TCG-SME was more effective in inducing the antiplatelet effect than pure TCG at equivalent doses of TCG. The accuracy of the simulation was verified by comparing the simulated PD profile with the profile observed in rats. The observations were close to the model simulations. In addition, the values of CWRES were almost within ±2. In conclusion, the PK/PD modeling approach can provide a way for predicting mathematically the PD responses from PK profiles of other TCG formulations and a conceptual prediction for future clinical assessment.
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Plaquetas/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/farmacocinética , Ticagrelor/farmacología , Ticagrelor/farmacocinética , Animales , Sistemas de Liberación de Medicamentos/métodos , Masculino , Modelos Biológicos , Agregación Plaquetaria/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The aim of this study was to compare the perioperative outcomes when using a micropuncture access set (MS) to those when using a conventional puncture set (CS) for implantation of totally implantable venous access device (TAVID). METHODS: A total of 314 patients undergoing chemotherapy for colorectal cancer were included between June 2015 and July 2018. Of these, 123 (39.2%) received TAVID implantation using MS and 191 patients (60.8%) received TAVID using CS. Perioperative outcomes and complications were compared between both groups. RESULTS: Baseline characteristics, including body mass index, American Society of Anesthesiologists score, cardiovascular disease, diabetes mellitus, and hyperlipidemia, were not significantly different between the groups. Postoperative complications occurred in 25 patients (8.0%), and the rate and incidence of venous thrombosis were significantly higher in the CS group. There were no significant differences between the groups in other complications such as the rate of port site infection, deep vein thrombosis, obstruction, catheter dislocation, and skin complications (exposure). No incidence of catheter infection, port rotation, intraoperative bleeding, or pneumothorax was observed in this cohort. CONCLUSIONS: MS is a safe and feasible procedure and results in less thrombosis. MS may play an important role in improving outcomes for the implantation of TAVID.
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Antineoplásicos/administración & dosificación , Catéteres de Permanencia/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Infusiones Intravenosas/instrumentación , Punciones , Trombosis de la Vena/prevención & control , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Extremidad Superior/irrigación sanguínea , Trombosis de la Vena/epidemiologíaRESUMEN
PURPOSE: In early rectal cancer cases, the use of local excision is increasing. The general indication for local excision is based on the preoperative stage, but there is often a discrepancy between pre and postoperative stages. We sought to determine the indications for local excision in T1 rectal adenocarcinoma patients by comparing the preoperative clinical and postoperative pathological stages. A second aim was to compare the oncologic outcomes between local excision and radical resection. METHODS: Between 2004 and 2014, 152 T1 rectal adenocarcinoma patients were enrolled. We divided the subjects into two groups, local excision and radical resection, depending on the modality of treatment the patients initially received. The group of patients who underwent radical resection was subsequently subdivided into "excisable" and "non-excisable" groups based on the postoperative pathology. RESULTS: Of 152 patients, 28 patients (18.4%) underwent local excision, while 124 patients (81.6%) underwent radical resection. Of 124 patients, in clinically suspected T2 or less and N0 (93) cases, 50 patients (53.8%) needed treatment beyond local excision, and local excision was sufficient for 43 patients (46.2%). The 3-year overall survival (p = 0.393) and 3-year disease-free survival (p = 0.076) between the local excision and radical resection groups showed no significant difference. CONCLUSIONS: The clinical T stage was overestimated in more than half of the cases. Therefore, if cT1/2 tumors with cN0 are suspected preoperatively, local excision is initially recommended and will allow for determination of underlying pathology. The clinician can then decide whether to monitor or intervene with radical resection.
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Neoplasias del Recto/cirugía , Demografía , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Pronóstico , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Intracortical brain-machine interfaces (BMIs) harness movement information by sensing neuronal activities using chronic microelectrode implants to restore lost functions to patients with paralysis. However, neuronal signals often vary over time, even within a day, forcing one to rebuild a BMI every time they operate it. The term "rebuild" means overall procedures for operating a BMI, such as decoder selection, decoder training, and decoder testing. It gives rise to a practical issue of what decoder should be built for a given neuronal ensemble. This study aims to address it by exploring how decoders' performance varies with the neuronal properties. To extensively explore a range of neuronal properties, we conduct a simulation study. METHODS: Focusing on movement direction, we examine several basic neuronal properties, including the signal-to-noise ratio of neurons, the proportion of well-tuned neurons, the uniformity of their preferred directions (PDs), and the non-stationarity of PDs. We investigate the performance of three popular BMI decoders: Kalman filter, optimal linear estimator, and population vector algorithm. RESULTS: Our simulation results showed that decoding performance of all the decoders was affected more by the proportion of well-tuned neurons that their uniformity. CONCLUSIONS: Our study suggests a simulated scenario of how to choose a decoder for intracortical BMIs in various neuronal conditions.
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Algoritmos , Interfaces Cerebro-Computador , Neuronas/citología , Movimiento , Relación Señal-RuidoRESUMEN
BACKGROUND: Single-port laparoscopic surgery (SPLS) was recently introduced as an innovative minimally invasive surgery method. Retrospective studies have revealed the safety and feasibility of SPLS for colon cancer treatment. However, no prospective randomized trials have been performed. The multicenter, randomized SIMPLE (single-port versus multiport laparoscopic surgery) trial aimed to investigate short-term perioperative outcomes of SPLS for colon cancer treatment, compared with multiport laparoscopic surgery (MPLS). METHODS: Between August 2011 and April 2014, a total of 194 patients with colon cancer were recruited from seven hospitals in Korea. Patients were randomly allocated into the SPLS group (n = 99) or MPLS group (n = 95). The primary endpoint was postoperative complications. Operative, postoperative, and pathologic outcomes were analyzed after 50% of the patient study population had been recruited. RESULTS: The patients' demographic characteristics, operative times, estimated blood volume losses, numbers of harvested lymph nodes, and lengths of both resection margins were not significantly different between groups. In the SPLS group, the rates of conversion to MPLS and open surgery were 12.9 and 2.2%, respectively. Postoperative complications occurred in 10.8% of the SPLS, and 12.5% of the MPLS patients (p = 0.714). Times to functional recovery, pain scores, and amounts of analgesia were similar between groups. CONCLUSION: The results of this interim analysis suggested that SPLS is technically safe and appropriate when used for radical resection of colon cancer. (ClinicalTrials.gov Identifier: NCT01480128).
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Neoplasias del Colon/cirugía , Laparoscopía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Estudios de Equivalencia como Asunto , Femenino , Humanos , Escisión del Ganglio Linfático , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias , Estudios Prospectivos , República de CoreaRESUMEN
BACKGROUND: Shoulder osteoarthritis is a gradual wearing of the articular cartilage concomitant with degenerative rotator cuff tears (RCTs). This pathologic disorder is related to inflammation, oxidative stress, and angiogenesis. Degenerative alterations may prompt production of cytokines and angiogenesis-related proteins, evoking rotator cuff diseases. This study tested the hypothesis that oxidative stress-responsive mediators can influence joint inflammation of patients with RCT. METHODS: Twelve healthy RCT patients not suffering shoulder osteoarthritis were categorized as the control group, and 24 patients were allocated to 2 RCT groups (RCTP1 and RCTP2), according to severity of RCT and glenohumeral arthritis. Cytokines, growth factors, and angiogenic biomarkers in synovial fluids, blood, platelet-rich plasma (PRP), and tendon tissues were analyzed with enzyme-linked immunosorbent assay, immunoblotting, and collagen zymography. RESULTS: Induction of interleukin 8, tumor necrosis factor α, and interleukin 1ß was considerably elevated in synovial fluids of RCTP groups (P = .0398, P = .0428, P = .0828, respectively). The joint inflammation highly enhanced insulin-like growth factor 1 and transforming growth factor ß1 (TGF-ß1) in the synovial fluids and serum. Angiogenesis-related angiopoietin (Ang) 1 and 2, Tie-2, and hypoxia-inducible factor 1α were upregulated in reactive oxygen species-exposed RCTP synovium (P < .05). The production of matrix metalloproteinase 1 markedly increased in synovial fluids of the RCTP group (P = .043), whereas tissue collagen type I expression diminished with reduction of connective tissue growth factor expression (P = .032). Although the secretion of platelet-derived growth factor AB and vascular endothelial growth factor was marginal in the circulation (P = .714, P = .335), platelet-derived growth factor AB, TGF-ß1, Ang-1, and matrix metalloproteinase 1 were enriched in PRP of the RCTP group (P < .001, P = .002, P = .0389, respectively). CONCLUSIONS: Synovial matrix degradation and oxidative stress-triggered angiogenesis may be involved in inducing RCT with joint inflammation. TGF-ß1, Ang-1, and Ang-2 are the major components to repair RCT and to alleviate joint inflammation in PRP therapy.
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Neovascularización Patológica/etiología , Osteoartritis/etiología , Estrés Oxidativo/fisiología , Lesiones del Manguito de los Rotadores/complicaciones , Lesiones del Manguito de los Rotadores/patología , Membrana Sinovial/patología , Proteínas Angiogénicas/metabolismo , Cartílago Articular/metabolismo , Cartílago Articular/patología , Estudios de Casos y Controles , Citocinas/metabolismo , Femenino , Humanos , Masculino , Metaloproteinasa 1 de la Matriz/metabolismo , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Osteoartritis/metabolismo , Osteoartritis/patología , Lesiones del Manguito de los Rotadores/metabolismo , Articulación del HombroRESUMEN
PURPOSE: Total hip arthroplasty with a dual mobility cup (DMC) is a proposed alternative to the widely performed bipolar hemiarthroplasty (BHA) for treating displaced intracapsular femoral neck fractures (DFNF) in the elderly. However, the comparison between the two modalities has not been extensively conducted thus far. METHODS: A retrospective cohort study was conducted with DFNF patients aged over 65 years who were treated either by BHA or DMC. After propensity matching each group comprised 84 patients (168 patients in total) and was analyzed using peri-operative and post-operative parameters. RESULTS: Mean follow-up durations were 22.1 and 21.7 months in the BHA and DMC groups, respectively. The BHA group demonstrated significantly less intra-operative blood loss (p = 0.001) and a shorter length of operation (p < 0.001). However, there was no difference in one-year mortality (p = 0.773). The Harris hip score (HHS) was significantly higher (p = 0.018) in the DMC group. The dislocation rate was not different between the two groups (p = 1.000). CONCLUSION: In DFNF patients aged over 65 years, short-term observation showed DMC to be the preferred treatment over BHA with better clinical outcome, without disadvantages in mortality or dislocation rate. Further long-term investigations are recommended to strengthen these results.
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Artroplastia de Reemplazo de Cadera/métodos , Fracturas del Cuello Femoral/cirugía , Fractura-Luxación/cirugía , Hemiartroplastia/métodos , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Estudios de Cohortes , Femenino , Fracturas del Cuello Femoral/complicaciones , Estudios de Seguimiento , Hemiartroplastia/efectos adversos , Humanos , Masculino , Tempo Operativo , Puntaje de Propensión , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The purpose of the study was to evaluate the effect of a solid mixture of sodium hyaluronate and carboxymethylcellulose (S-HA/CMC) for the prevention of adhesions after iatrogenic mucosal injury in murine nasal cavities. We introduced iatrogenic adhesions into the bilateral nasal cavities of 20 male Sprague-Dawley rats. S-HA/CMC was applied to the left nasal cavity, while no packing was placed in the right nasal cavity as a control. At 1, 2, and 4 weeks post-procedure, we examined the number of adhesions, the ratio of the longest cross-sectional length of adhesion to septal cartilage length (RAC), and the degree of fibrosis. S-HA/CMC significantly reduced the number of adhesions when compared to the control group in total (p = 0.031), but not at each individual time point. The S-HA/CMC group showed significantly shorter RAC than the control group in total (p = 0.044), but not at each individual time point. The total fibrosis score was less severe in the S-HA/CMC group than in the control group (p < 0.001), with a significant difference between the two groups at the second week (p = 0.001). Therefore, in an animal model, S-HA/CMC can prevent post-injury mucosal adhesions suggesting a potential for clinical applications in endoscopic sinus surgery. Further clinical trials are needed to determine the safety and efficacy of S-HA/CMC as nasal packing after endoscopic sinus surgery.
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Carboximetilcelulosa de Sodio/farmacología , Ácido Hialurónico/farmacología , Cavidad Nasal/cirugía , Adherencias Tisulares/prevención & control , Viscosuplementos/farmacología , Animales , Endoscopía , Fibrosis/prevención & control , Modelos Animales , Mucosa Nasal/lesiones , Mucosa Nasal/patología , Mucosa Nasal/cirugía , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Despite many high-quality programs in basic surgical-skill education, the surgical skill of junior doctors varies widely. This, together with the waning interest in surgery as a career among medical students, is a serious issue confronted by hospitals and healthcare systems worldwide. We, therefore, developed and implemented an intensive one-day surgical-skill training course for two purposes; it would improve surgical skills and increase interest in surgery among medical students. METHODS: The surgical-skill training program is named Surgical Skill Weekend (SSW) and it includes hands-on training sessions for surgical-suturing techniques and advanced surgical procedures (i.e. laparoscopic and robot-assisted surgery), hybrid simulation sessions, and an operating-room session where aforementioned sessions are all put together. By the end of the program, students' improvements in surgical-suturing skills were assessed by experts in a form of checklist, and changes in the interest in a surgical career, if there were any, were answered by the students who participated in the program. RESULTS: A total of ninety-one (91) medical students participated in the 2015 and 2016 SSW courses. Their overall satisfaction level with the course was very high (Very satisfied: 78%, Quite satisfied: 22%). All of the participant's surgical-suturing skills significantly improved (median score range: 14-20, P < 0.05) and their interest in a surgical career increased significantly (from 56% to 81%, P < 0.05) by completing the program. CONCLUSIONS: An intensive and comprehensive surgical-skill training program for medical students can not only improve surgical-suturing skills but also increase interest in surgery as a career.
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Selección de Profesión , Cirugía General , Estudiantes de Medicina , Técnicas de Sutura/educación , Competencia Clínica , Curriculum , HumanosRESUMEN
Although a schwannoma can originate from any central or peripheral nerves, schwannomas originating from the nasal tip are extremely rare and only 4 cases have been reported so far in English literature. These 4 cases appeared solely without any other accompanying schwannomas. However, the authors recently treated a patient with a nasal tip schwannoma coexisting with vestibular schwannoma. The nasal tip schwannoma was successfully removed without cosmetic deformity by using an open rhinoplasty approach.
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Neoplasias Primarias Múltiples/diagnóstico , Neuroma Acústico/diagnóstico , Neoplasias Nasales/diagnóstico , Femenino , Humanos , Masculino , Neoplasias Primarias Múltiples/cirugía , Neurilemoma/diagnóstico , Neoplasias Nasales/cirugía , RinoplastiaRESUMEN
Brain-computer interfaces (BCIs) have a potential to revolutionize human-computer interaction by enabling direct links between the brain and computer systems. Recent studies are increasingly focusing on practical applications of BCIs-e.g., home appliance control just by thoughts. One of the non-invasive BCIs using electroencephalography (EEG) capitalizes on event-related potentials (ERPs) in response to target stimuli and have shown promise in controlling home appliance. In this paper, we present a comprehensive dataset of online ERP-based BCIs for controlling various home appliances in diverse stimulus presentation environments. We collected online BCI data from a total of 84 subjects among whom 60 subjects controlled three types of appliances (TV: 30, door lock: 15, and electric light: 15) with 4 functions per appliance, 14 subjects controlled a Bluetooth speaker with 6 functions via an LCD monitor, and 10 subjects controlled air conditioner with 4 functions via augmented reality (AR). Using the dataset, we aimed to address the issue of inter-subject variability in ERPs by employing the transfer learning in two different approaches. The first approach, "within-paradigm transfer learning," aimed to generalize the model within the same paradigm of stimulus presentation. The second approach, "cross-paradigm transfer learning," involved extending the model from a 4-class LCD environment to different paradigms. The results demonstrated that transfer learning can effectively enhance the generalizability of BCIs based on ERP across different subjects and environments.
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In intestinal helminth infections, Th2 immune respones are generally associated with mucin secretion for worm expulsion from the host intestine. In particular, IL-4 and IL-13 are the important cytokines related with intestinal mucus production via STAT6 signalling in nematode infections. However, this perspective has never been studied in Gymnophalloides seoi infection. The present study aimed to observe the STAT6 signalling and cytokine responses in C57BL/6 mice, a mouse strain resistant to infection with this trematode. The results showed that worm expulsion occurred actively during days 1-2 post-infection (PI), when goblet cells began to proliferate in the small intestine. The STAT6 gene expression in the mouse spleen became remarkable from day 2 PI. Moreover, G. seoi infection induced a significant increase of IL-13 from day 4 PI in the spleen of infected mice. Our results suggested that goblet cell hyperplasia and worm expulsion in G. seoi-infected mice should be induced by STAT6 signalling, in which IL-13 may be involved as a dominant triggering cytokine.
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Células Caliciformes/patología , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Factor de Transcripción STAT6/metabolismo , Trematodos/inmunología , Triquinelosis/inmunología , Animales , Crassostrea , Femenino , Hiperplasia/patología , Intestino Delgado/inmunología , Metacercarias , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Organismos Libres de Patógenos Específicos , Bazo/inmunología , Triquinelosis/parasitologíaRESUMEN
Purpose: The number of elderly patients, especially aged ≥80 years, undergoing emergency surgery is gradually increasing. The aim of this study was to find out the trends and results of emergency general surgery for elderly patients over 9 years in an emergency medical center in South Korea, where the population is aging most rapidly. Methods: The clinical characteristics, outcomes, and medical expenses of emergency general surgery for the elderly (aged 65-79 years) and highly elderly (aged ≥80 years) patients who visited to a regional emergency medical center from 2012 to 2020 were analyzed. Results: The number of highly elderly patients increased with each 3-year interval, whereas the proportion of patients aged 19-79 years was similar, and that of pediatric patients was decreasing. The higher the age group, the higher the mortality (young adult vs. elderly vs. highly elderly: odds ratio [OR], 1 vs. 3.689 vs. 11.293; P < 0.001) and complication rates (OR, 1 vs. 2.840 vs. 4.633; P < 0.001), and longer length of hospital stay (ß = 0.949, P = 0.001) even after adjusting for the type of surgery and the American Society of Anesthesiologists physical status classification. Non-covered medical expenses were significantly related to the age groups (ß = 151,608.802, P < 0.001). Conclusion: The higher age group was associated with increased number of unfavorable outcomes after emergency general surgery, along with increased medical cost. Efforts to prevent emergency surgery for elderly patients and a specialized treatment system are needed.
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The influence of temperature on the development and embryonation of Ascaris suum eggs was studied using coarse sand medium in an environmental chamber with 50% humidity. The time required for development and embryonation of eggs was examined under 3 different temperature conditions, 5°C, 25°C, and 35°C. A. suum eggs did not develop over 1 month at the temperature of 5°C. However, other temperature conditions, 25°C and 35°C, induced egg development to the 8-cell-stage at days 5-6 after incubation. All eggs examined developed to the 8-cell stage at day 6 after incubation in the sand medium at 25°C. The higher temperature, 35°C, slightly accelerated the A. suum egg development compared to 25°C, and the development to the 8-cell stage occurred within day 5 after incubation. The formation of larvae in A. suum eggs at temperatures of 35° and 25°C appeared at days 17 and 19 after incubation, respectively. These findings show that 35° condition shortens the time for the development of A. suum eggs to the 8-cell-stage in comparison to 25°C, and suggest the possibility of accelerated transmission of this parasite, resulting from global warming and ecosystem changes.
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Ascaris suum/embriología , Ascaris suum/efectos de la radiación , Animales , Ascaris suum/crecimiento & desarrollo , Medios de Cultivo , Huevos/efectos de la radiación , Humedad , Larva/crecimiento & desarrollo , Larva/efectos de la radiación , Dióxido de Silicio , TemperaturaRESUMEN
Knowledge of the prevalence of human Toxoplasma gondii infection is required in the Republic of Korea. In this study, we surveyed the seroprevalence of T. gondii infection and analyzed the risk factors associated with seropositivity among residents in 2 administrative districts; Seoul and the island of Jeju-do, which have contrasting epidemiologic characteristics. Sera and blood collected from 2,150 residents (1,114 in Seoul and 1,036 in Jeju-do) were checked for IgG antibody titers using ELISA and for the T. gondii B1 gene using PCR. In addition, participants completed a questionnaire that solicited information on gender, age, occupation, eating habits, history of contact with animals, and travel abroad. The T. gondii B1 gene was not detected in all residents examined. However, ELISA showed 8.0% (89 of 1,114 sera) positive for IgG antibodies against T. gondii in Seoul and 11.3% (117 of 1,036 sera) in Jeju-do. In both districts, the positive rates were higher in males than in females, and those 40-79 years of age showed higher rates than other ages. In Seoul, residents older than 70 years of age showed the highest positive rate, 14.9%, whereas in Jeju-do the highest prevalence, 15.6%, was in those in their sixties. The higher seropositive rate in Jeju-do than in Seoul may be related to eating habits and occupations. The present results and a review of related literature are indicative of an increased seroprevalence of T. gondii in Korea in recent years.
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Anticuerpos Antiprotozoarios/sangre , Inmunoglobulina G/sangre , Toxoplasma/inmunología , Toxoplasmosis/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Animales , Niño , ADN Protozoario/sangre , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , República de Corea/epidemiología , Factores de Riesgo , Estudios Seroepidemiológicos , Factores Sexuales , Toxoplasma/genética , Toxoplasmosis/parasitología , Adulto JovenRESUMEN
BACKGROUND: This study assessed the population pharmacokinetics and metabolic conversion of a novel histone deacetylase (HDAC) inhibitor, SD-2007, into its active metabolite, apicidin, in rats. METHODS: SD-2007 was given to rats by intravenous injection (4 mg/kg) and oral administration (40 mg/kg). Serum concentrations of SD-2007 and apicidin were determined by LC-MS/MS. All concentrations were analyzed using a population pharmacokinetic model with 9 compartments in S-ADAPT. RESULTS: The area under the curve for apicidin was 96 ± 16 mg·h/ml after 4 mg/kg administered intravenously and 2,455 ± 1,211 mg·h/ml after 40 mg/kg given orally. The population pharmacokinetic model described all profiles well. After oral administration of SD-2007, the median absolute bioavailability of SD-2007 was 6.67% (range 3.83-9.89) and the median apparent bioavailability was 22.3% (range 15.7-35.8) for apicidin, whereas only a median of 8.85% (range 7.57-9.34) of an intravenous SD-2007 dose was converted to apicidin. CONCLUSIONS: Oral SD-2007 displayed a substantial presystemic metabolism to active apicidin. The high serum concentrations of apicidin after oral administration of SD-2007 may cause significant HDAC inhibition.
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Inhibidores de Histona Desacetilasas/farmacocinética , Péptidos Cíclicos/farmacocinética , Administración Oral , Animales , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Inhibidores de Histona Desacetilasas/administración & dosificación , Inhibidores de Histona Desacetilasas/sangre , Inyecciones Intravenosas , Masculino , Espectrometría de Masas , Péptidos Cíclicos/administración & dosificación , Péptidos Cíclicos/sangre , Ratas , Ratas Sprague-DawleyRESUMEN
While intracortical brain-machine interfaces (BMIs) demonstrate feasibility to restore mobility to people with paralysis, it is still challenging to maintain high-performance decoding in clinical BMIs. One of the main obstacles for high-performance BMI is the noise-prone nature of traditional decoding methods that connect neural response explicitly with physical quantity, such as velocity. In contrast, the recent development of latent neural state model enables a robust readout of large-scale neuronal population activity contents. However, these latent neural states do not necessarily contain kinematic information useful for decoding. Therefore, this study proposes a new approach to finding kinematics-dependent latent factors by extracting latent factors' kinematics-dependent components using linear regression. We estimated these components from the population activity through nonlinear mapping. The proposed kinematics-dependent latent factors generate neural trajectories that discriminate latent neural states before and after the motion onset. We compared the decoding performance of the proposed analysis model with the results from other popular models. They are factor analysis (FA), Gaussian process factor analysis (GPFA), latent factor analysis via dynamical systems (LFADS), preferential subspace identification (PSID), and neuronal population firing rates. The proposed analysis model results in higher decoding accuracy than do the others ( % improvement on average). Our approach may pave a new way to extract latent neural states specific to kinematic information from motor cortices, potentially improving decoding performance for online intracortical BMIs.