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Genome-wide association studies have identified ICOSLG, which encodes the inducible costimulator ligand (ICOSLG or ICOSL) as a susceptibility locus for inflammatory bowel disease. ICOSL has been implicated in the enhancement of pattern recognition receptor signaling in dendritic cells, induction of IL-10 production by CD4 T cells, and the generation of high-affinity antibodies to specific antigens-all of which can potentially explain its involvement in gastrointestinal inflammation. Here, we show that murine ICOSL deficiency results in significant enrichment of IL-10-producing CD4 T cells particularly in the proximal large intestine. Transient depletion of IL-10-producing cells from adult ICOSL-deficient mice induced severe colonic inflammation that was prevented when mice were first treated with metronidazole. ICOSL-deficient mice displayed reduced IgA and IgG antibodies in the colon mucus and impaired serum antibody recognition of microbial antigens, including flagellins derived from mucus-associated bacteria of the Lachnospiraceae family. Confirming the synergy between ICOSL and IL-10, ICOSL deficiency coupled with CD4-specific deletion of the Il10 gene resulted in juvenile onset colitis that was impeded when pups were fostered by ICOSL-sufficient dams. In this setting, we found that both maternally acquired and host-derived antibodies contribute to the life anti-commensal antibody repertoire that mediates this protection in early life. Collectively, our findings reveal a partnership between ICOSL-dependent anti-commensal antibodies and IL-10 in adaptive immune regulation of the microbiota in the large intestine. Furthermore, we identify ICOSL deficiency as an effective platform for exploring the functions of anti-commensal antibodies in host-microbiota mutualism.
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Linfócitos T CD4-Positivos/imunologia , Microbioma Gastrointestinal/imunologia , Ligante Coestimulador de Linfócitos T Induzíveis/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Interleucina-10/metabolismo , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Linfócitos T CD4-Positivos/metabolismo , Colo/imunologia , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Ligante Coestimulador de Linfócitos T Induzíveis/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Interleucina-10/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Knockout , Transdução de Sinais/imunologia , Simbiose/imunologiaRESUMO
BACKGROUND: While hepatitis A and B are well-known causes of acute liver failure (ALF), few well-documented cases of hepatitis C virus (HCV) infection (absent preexisting liver disease or other liver insults) have been described that result in ALF. We reviewed the Acute Liver Failure Study Group registry for evidence of HCV as a primary or contributing cause to ALF. METHODS: From January 1998 to January 2017, 2,332 patients with ALF (INR ≥ 1.5, any degree of hepatic encephalopathy) and 667 with acute liver injury (ALI; INR ≥ 2.0, no hepatic encephalopathy) were enrolled. Anti-HCV testing was done routinely, with confirmatory RT-PCR testing for HCV RNA where necessary. RESULTS: A total of 136 patients were anti-HCV-antibody positive, as follows: 56 HCV RNA negative, 65 HCV RNA positive, and 8 with no result nor sera available for testing. Only three subjects with ALI/ALF were determined to represent acute HCV infection. Case 1: 47-year-old female with morbid obesity (BMI 52.4) developed ALF and recovered, experiencing anti-HCV seroconversion. Case 2: 37-year-old female using cocaine presented with ALI and fully recovered. Case 3: 54-year-old female developed ALF requiring transplantation and was anti-HCV negative but viremic prior to transplant experiencing anti-HCV seroconversion thereafter. Among 1636 APAP overdose patients, the 52 with concomitant chronic HCV had higher 3-week mortality than the 1584 without HCV (31% vs 17%, p = 0.01). CONCLUSIONS: ALI/ALF solely related to acute hepatitis C infection is very rare. Chronic HCV infection, found in at least 65 (2.2%) of ALI/ALF patients studied, contributed to more severe outcomes in APAP ALI/ALF; ClinicalTrials.gov number, NCT000518440. Trial Registration ClinicalTrials.gov number NCT000518440.
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Encefalopatia Hepática , Hepatite C , Falência Hepática Aguda , Feminino , Humanos , Pessoa de Meia-Idade , Adulto , Hepatite C/complicações , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/etiologia , América do Norte , Encefalopatia Hepática/etiologia , Hepacivirus/genética , RNARESUMO
BACKGROUND: Although patients with non-traumatic spinal cord injury (NTSCI) have distinct epidemiological characteristics compared to those with traumatic spinal cord injury, no previous study has reported the incidence of NTSCI on a national scale in Korea. In this study, we examined the trend in incidence of NTSCI in Korea and described the epidemiological characteristics of patients with NTSCI using nationwide insurance data. METHODS: National Health Insurance Service data were reviewed for the period from 2007 to 2020. The International Classification of Diseases, 10th revision, was used to identify patients with NTSCI. Inpatients with newly diagnosed NTSCI on their first admission during the study period were included. Crude incidence was calculated using the annual number of NTSCI cases divided by the mid-year population estimates. Age-specific incidence was calculated by dividing the number of cases in 10-year age groups by the total number of individuals in that age group. Age-adjusted incidence was calculated using direct standardization. Annual percentage changes were calculated using Joinpoint regression analysis. The Cochrane-Armitage trend test was conducted to examine the trends of NTSCI incidence according to the types or etiologies of NTSCI. RESULTS: The age-adjusted incidence of NTSCI increased continuously from 24.11 per million in 2007 to 39.83 per million in 2020, with a significant annual percentage change (4.93%, P < 0.05). The age-specific incidence for those in their 70s and 80s or older was the highest and rapidly increased from 2007 to 2020. According to the types of paralysis in NTSCI, the proportion of tetraplegia decreased, whereas those of paraplegia and cauda equina increased significantly from 2007 to 2020. The proportion of degenerative diseases was the largest among all etiologies and increased significantly during the study period. CONCLUSION: The annual incidence of NTSCI in Korea is increasing significantly, particularly among older adults. As Korea is one of the countries with most rapidly aging population in the world, these results have significant implications, indicating that preventive strategies and sufficient rehabilitation medical services are warranted for the population of older adults.
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Medicina , Traumatismos da Medula Espinal , Humanos , Idoso , Incidência , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/etiologia , Causalidade , República da Coreia/epidemiologiaRESUMO
Given the gut microbiome's rise as a potential frontier in cancer pathogenesis and therapy, leveraging microbial analyses in the study of breast tumor progression and treatment could unveil novel interactions between commensal bacteria and disease outcomes. In breast cancer, the Hedgehog (Hh) signaling pathway is a potential target for treatment due to its aberrant activation leading to poorer prognoses and drug resistance. There are limited studies that have investigated the influences of orally administered cancer therapeutics, such as Vismodegib (a pharmacological, clinically used Hh inhibitor) on the gut microbiota. Using a 4T1 mammary carcinoma mouse model and 16 S rRNA sequencing, we longitudinally mapped alterations in immunomodulating gut microbes during mammary tumor development. Next, we identified changes in the abundance of commensal microbiota in response to Vismodegib treatment of 4T1 mammary tumor-bearing mice. In addition to remodeling gut microbiota, Vismodegib treatment elicited an increase in proliferative CD8+ T cells in the colonic immune network, without any remarkable gastrointestinal-associated side effects. To our knowledge, this is the first study to assess longitudinal changes in the gut microbiome during mammary tumor development and progression. Our study also pioneers an investigation of the dynamic effects of an orally delivered Hh inhibitor on the gut microbiome and the gut-associated immune-regulatory adaptive effector CD8+ T cells. These findings inform future comprehensive studies on the consortium of altered microbes that can impact potential systemic immunomodulatory roles of Vismodegib.
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Carcinoma , Microbioma Gastrointestinal , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Proteínas Hedgehog , Linfócitos T CD8-Positivos , Modelos Animais de DoençasRESUMO
The novel wound-healing biologic EPICERTIN, a recombinant analog of cholera toxin B subunit, is in early development for the management of ulcerative colitis. This study established for the first time the pharmacokinetics (PK), bioavailability (BA), and acute safety of EPICERTIN in healthy and dextran sodium sulfate-induced colitic mice and healthy rats. For PK and BA assessments, single administrations of various concentrations of EPICERTIN were given intravenously or intrarectally to healthy and colitic C57BL/6 mice and to healthy Sprague-Dawley rats. After intravenous administration to healthy animals, the drug's plasma half-life (t 1/2) for males and females was 0.26 and 0.3 hours in mice and 19.4 and 14.5 hours in rats, respectively. After intrarectal administration, drug was detected at very low levels in only four samples of mouse plasma, with no correlation to colon epithelial integrity. No drug was detected in rat plasma. A single intrarectal dose of 0.1 µM (0.6 µg/mouse) EPICERTIN significantly facilitated the healing of damaged colonic epithelium as determined by disease activity index and histopathological scoring, whereas 10-fold higher or lower concentrations showed no effect. For acute toxicity evaluation, healthy rats were given a single intrarectal administration of various doses of EPICERTIN with sacrifice on Day 8, recording body weight, morbidity, mortality, clinical pathology, and gross necropsy observations. There were no drug-related effects of toxicological significance. The no observed adverse effect level (intrarectal) in rats was determined to be 5 µM (307 µg/animal, or 5.2 µg drug/cm2 of colorectal surface area), which is 14 times the anticipated intrarectally delivered clinical dose. SIGNIFICANCE STATEMENT: EPICERTIN is a candidate wound-healing biologic for the management of ulcerative colitis. This study determined for the first time the intravenous and intrarectal pharmacokinetics and bioavailability of the drug in healthy and colitic mice and healthy rats, and its acute safety in a dose-escalation study in rats. An initial therapeutic dose in colitic mice was also established. EPICERTIN delivered intrarectally was minimally absorbed systemically, was well tolerated, and induced epithelial wound healing topically at a low dose.
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Produtos Biológicos , Colite Ulcerativa , Cicatrização , Administração Tópica , Animais , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Produtos Biológicos/farmacocinética , Colite Ulcerativa/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Roedores , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: MicroRNA (miR)-214-3p is emerging as an important tumor suppressor in esophageal cancer. In this study, we examined the interaction between miR-214-3p and RAB14, a membrane trafficking protein shown to exert oncogenic functions in other malignancies, in esophageal cancer cells. METHODS: Studies were performed in a human esophageal epithelial cell line and a panel of esophageal cancer cell lines, as well in human specimens. MiR-214-3p expression was measured by digital PCR. Biotinylated RNA pull-down and luciferase reporter assays assessed binding. The xCELLigence RTCA system measured cell migration and invasion in real time. A lentiviral expression vector was used to create an esophageal cancer cell line stably expressing miR-214-3p. RESULTS: MiR-214-3p expression was decreased in esophageal cancer cell lines and human specimens compared to non-malignant controls. RAB14 mRNA stability and protein expression were decreased following miR-214-3p overexpression. Binding between miR-214-3p and RAB14 mRNA was observed. Either forced expression of miR-214-3p or RAB14 silencing led to a marked decrease in cellular migration and invasion. Esophageal cancer cells stably expressing miR-214-3p demonstrated decreased growth in a subcutaneous murine model. CONCLUSIONS: These results further support the tumor-suppressive role of miR-214-3p in esophageal cancer cells by demonstrating its ability to regulate RAB14 expression.
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Neoplasias Esofágicas , MicroRNAs , Proteínas rab de Ligação ao GTP , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
In recent years, as all actions of Internet users become information, the importance of personal information is emphasized, but in reality, the management of personal information is still insufficient. With the advent of the concept of sharing systems such as the sharing economy, the numbers of IoT application services (for example, a healthcare service using sharing IoT devices, or a vehicle sharing system with IoT devices) using users' personal information are increasing, but the risk of using personal information is not managed. To solve this issue, the European GDPR stipulates the content of personal information protection. In this paper, we present a method to securely manage personal information in IoT devices in IoT application environments in accordance with the GDPR. We first describe the lifecycle stages of personal information occurring in IoT application services and propose a method to securely manage personal information at each stage of the lifecycle according to the flow of personal information in IoT devices. We also evaluated the usefulness and applicability of the proposed scheme through two service scenarios. Since the proposed method satisfies the requirements for personal information management in IoT application environments, it is expected to contribute to the development of the IoT business field that handles personal information.
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OBJECTIVE: To evaluate the ultrasonographic findings obtained following various degrees of elbow flexion in patients with cubital tunnel syndrome (CuTS). DESIGN: Retrospective, cross-sectional study. SETTING: General teaching hospital, rehabilitation unit. SUBJECTS: Electrophysiological and ultrasonographic assessments were performed on 11 elbows of healthy controls and 21 elbows of 17 patients with CuTS. METHODS: Dynamic movement of the ulnar nerve during elbow motion was measured. To measure ulnar nerve dynamic movement during elbow motion, the distance from the medial epicondyle (ME) to the nearest surface of the ulnar nerve toward the ME was measured at the cubital tunnel inlet at elbow extension (0°), elbow flexion to 60°, and elbow flexion to 90°. RESULTS: The distance between the ME and ulnar nerve was lower in CuTS patients than in healthy patients at all elbow flexion angles. This difference was statistically significant at 0° and 60° elbow flexion (P < 0.05). When calculating the cutoff value, the distance between the ME and ulnar nerve at full elbow extension for CuTS diagnosis was 0.53 cm (sensitivity = 71.4%, specificity = 90.7%). The distance ratio between the ME and ulnar nerve for diagnosis of ulnar neuropathy at the elbow was 24.4% (sensitivity = 76.2%, specificity = 100%). CONCLUSION: Measurement of the distance between the ME and ulnar nerve in full elbow extension may facilitate the diagnosis of patients with CuTS. These findings may be important for CuTS diagnosis, as they were also observed in patients with mild-stage CuTS.
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Síndrome do Túnel Ulnar , Estudos Transversais , Síndrome do Túnel Ulnar/diagnóstico por imagem , Cotovelo/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Nervo Ulnar/diagnóstico por imagem , UltrassonografiaRESUMO
Network coding is a reasonable way to increase network efficiency in response to an increase of sensed data in the Internet of Things (IoT). In network coding, intermediate nodes combine packets received from neighboring nodes, transform, and transmit encoded packets that can be decoded at the destination. This scheme is based on trust among nodes. If any malicious node joins the network, it can act as an intermediate node that could fabricate encoded packets. It might be more difficult to identify the authenticity of such encoded packets since packets that are received at the destination might not originate from a single source, but be combined with several other packets originating from multiple sources. In this paper, we propose a scheme on how to detect attacked packets among the received packets at a destination and how to recover the original message from the packets including the attacked "look-like-valid" packets. This scheme shows that a destination could recover the valid message with just the received packets including some attacked packets and will result in a quite efficient performance in network coding.
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TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/ß-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial effects on intestinal epithelial cell (IEC) responses to injury. In CD patients, intestinal stem cell and progenitor cell Wnt/ß-catenin signaling correlates with inflammation status. TNF-deficient (Tnf-/-) mice exhibited increased apoptosis, less IEC proliferation, and less Wnt signaling when stimulated with anti-CD3 mAb. Bone marrow (BM) chimera mice revealed that mucosal repair depended on TNF production by BM-derived cells and TNFR expression by radioresistant IECs. Wild-typeâTnfr1/2-/- BM chimera mice with chronic dextran sodium sulfate colitis exhibited delayed ulcer healing, more mucosal inflammation, and impaired Wnt/ß-catenin signaling, consistent with the hypothesis that epithelial TNFR signaling participates in mucosal healing. The direct effect of TNF on stem cells was demonstrated by studies of TNF-induced Wnt/ß-catenin target gene expression in murine enteroids and colonoid cultures and TNF-induced ß-catenin activation in nontransformed human NCM460 cells (TOPFlash) and mice (TOP-GAL). Together, these data support the hypothesis that TNF plays a beneficial role in enhancing Wnt/ß-catenin signaling during ulcer healing in IBD. These novel findings will inform clinicians and therapeutic chemists alike as they strive to develop novel therapies for IBD patients.
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Células-Tronco Adultas/fisiologia , Anticorpos Monoclonais/uso terapêutico , Colite/imunologia , Células Epiteliais/fisiologia , Doenças Inflamatórias Intestinais/imunologia , Mucosa Intestinal/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Linhagem Celular , Sulfato de Dextrana , Humanos , Doenças Inflamatórias Intestinais/terapia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Proteínas Wnt/metabolismo , Cicatrização , beta Catenina/metabolismoRESUMO
Quaternary ammoniums are cations having widespread use in organic electrolytes for high performance electrochemical double layer capacitors (EDLCs) due to their various advantages such as high electrochemical stability and inexpensive production cost. However, the decomposition of quaternary ammoniums via Hofmann elimination hinders their applications for EDLCs operating at elevated temperatures. This study systematically investigates the reactivity of four different quaternary ammoniums (tetraethyl-, triethylmethyl-, diethyldimethyl-, and trimethylethyl-ammonium) in EDLC by utilizing density functional theory calculations and Brownian dynamics simulations complemented with molecular dynamics simulations. It is found that ammonium stability reduces upon increasing the number of ethyl branches that have a stronger positive charge than the methyl groups. However, the contribution of the entropy change to the reaction free energy makes trimethylethylammonium less stable than diethyldimethylammonium at room temperature although the former has less ethyl branches than the latter. Trimethylethylammonium becomes the most stable at a high temperature of 488 K above which the activation free energy becomes effectively negligible and thus the number of reactive sites determines the overall stability. The fundamental understanding of the ammonium decompositions through Hofmann elimination demonstrated in this study is expected to contribute to developing new long-life organic electrolyte systems for high-temperature applications.
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The oro-esophageal tube (OE tube) is widely used in dysphagia patients although its success rate for transition to oral feeding is reported only in stroke patients. The aim of this study was to evaluate the feasibility and outcome of OE tube feeding for patients with dysphagia resulting from various etiologies. The authors reviewed the medical records of 1995 dysphagic patients that had undergone videofluoroscopic swallowing study (VFSS) in a tertiary hospital from April 2002 through December 2009. Of these, 97 patients were recommended to use OE tube feeding based on the VFSS findings. Follow-up VFSS were performed on 54 patients. The mean duration of tube use at the time of follow-up VFSS was 274 days. We evaluated clinical information including age, sex, diet, etiology of dysphagia, location of lesions, duration of intervention, and complications of OE tube feeding. Initially, all 54 patients were fed using the OE tube. After their last follow-up evaluation, 19 patients (35.2 %) resumed full oral feeding without the OE tube, 12 patients (22.2 %) used partial OE tube feeding, and 23 patients (42.6 %) continued OE tube feeding only. Full oral feeding was achieved again most often in brain tumor, stroke, and head and neck cancer patients (54.5, 27.3, and 20.0 %, respectively). Mild adverse events, such as blood-tinged sputum, nausea, dyspepsia, and regurgitation of food, were reported in 4 patients. OE tube feeding is a feasible feeding method also in conditions other than stroke such as brain tumors, and head and neck cancers.
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Transtornos de Deglutição/terapia , Deglutição/fisiologia , Nutrição Enteral/instrumentação , Esôfago/fisiopatologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Desenho de Equipamento , Esôfago/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Fluoroscopia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Gravação em VídeoRESUMO
The purpose of the study was to investigate the influence of the chin-tuck maneuver on the movements of swallowing-related structures in healthy subjects and formulate standard instructions for the maneuver. A total of 40 healthy volunteers (20 men and 20 women) swallowed 10 mL of diluted barium solution in a "normal and comfortable" position (NEUT), a comfortable chin-down position (DOWN), and a strict chin-tuck position (TUCK). Resting state anatomy and kinematic changes were analyzed and compared between postures. Although angles of anterior cervical flexion were comparable between DOWN (46.65 ± 9.69 degrees) and TUCK (43.27 ± 12.20), the chin-to-spine distance was significantly shorter in TUCK than in other positions. Only TUCK showed a significantly shorter anteroposterior diameter of the laryngeal inlet (TUCK vs. NEUT, 14.0 ± 4.3 vs. 16.3 ± 5.0 mm) and the oropharynx (18.8 ± 3.1 vs. 20.5 ± 2.8 mm) at rest. The maximal horizontal displacement of the hyoid bone was significantly less in TUCK (9.6 ± 3.0 mm) than in NEUT (12.6 ± 2.6 mm; p < 0.01) or DOWN (12.1 ± 3.0 mm; p < 0.01). TUCK facilitated movement of the epiglottic base upward (TUCK vs. NEUT, 15.8 ± 4.7 vs. 13.3 ± 4.5 mm; p < 0.01). In contrast, DOWN increased the horizontal excursion of the epiglottic base and reduced movement of the vocal cords. These results quantitatively elucidated the biomechanical influences of the chin-tuck maneuver including reduced horizontal movement of the hyoid bone, facilitation of vertical movement of the epiglottic base, and narrowing of the airway entrance. Comparing DOWN and TUCK, only TUCK induced significant changes in the airway entrance, hyoid movement, and epiglottic base retraction.
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Queixo , Deglutição , Adulto , Idoso , Fenômenos Biomecânicos , Queixo/anatomia & histologia , Feminino , Voluntários Saudáveis , Humanos , Osso Hioide , Laringe/anatomia & histologia , Laringe/fisiologia , Masculino , Pessoa de Meia-IdadeAssuntos
Dispareunia/etiologia , Histerectomia/efeitos adversos , Neuroma/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Neoplasias Vaginais/diagnóstico , Adulto , Feminino , Humanos , Neuroma/complicações , Neuroma/patologia , Neuroma/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/cirurgia , Vagina , Neoplasias Vaginais/complicações , Neoplasias Vaginais/patologia , Neoplasias Vaginais/cirurgiaRESUMO
The videofluoroscopic dysphagia scale (VDS) was developed as an objective predictor of the prognosis of dysphagia after stroke. We evaluated the clinical validity of the VDS for various diseases. We reviewed the medical records of 1,995 dysphagic patients (1,222 men and 773 women) who underwent videofluoroscopic studies in Seoul National University Hospital from April 2002 through December 2009. Their American SpeechLanguageHearing Association's National Outcome Measurement System (ASHA NOMS) swallowing scale, clinical dysphagia scale (CDS), and VDS scores were evaluated on the basis of the clinical and/or videofluoroscopic findings by the consensus of two physiatrists. The correlations between the VDS and the other scales were calculated. The VDS displayed significant correlations with the ASHA NOMS swallowing scale and the CDS in every disease group (p < 0.001 in all groups, including central and peripheral nervous system disorders), and these correlations were more apparent for spinal cord injury, peripheral nerve system disorders, and neurodegenerative diseases (correlation coefficients between the VDS and the ASHA NOMS swallowing scale: −0.603, −0.602, and −0.567, respectively). This study demonstrated that the VDS is applicable to dysphagic patients with numerous etiologies that cause dysphagia
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Transtornos de Deglutição/diagnóstico , Deglutição/fisiologia , Fluoroscopia/métodos , Traumatismos da Medula Espinal/complicações , Acidente Vascular Cerebral/complicações , Gravação em Vídeo/métodos , Adulto , Idoso , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To establish reference values for the computerized cognitive test and evaluate cognitive function improvements across different age groups, we introduce the computerized Cognitive Function Test program (eCFT), specifically designed for children. We aimed to establish eCFT reference values and assess cognitive function improvements across different age groups. METHODS: We included children aged 3-6 years with confirmed normal cognition based on the Korean Developmental Screening Test for Infants and Children and Kaufman Assessment Battery for Children-II. The eCFT consists of 8 subtests for visual perception, attention, memory, and executive function. RESULTS: A total of 66 participants (36 males and 30 females) with an average age of 4.4 years participated. The age 6 group consistently outperformed both age group 3 and 4 in terms of correct responses. With regard to the completed stage, the "selective auditory stimulus" test findings were 2.0 and 3.9 for the age 3 and age 6 groups, respectively (p<0.05). The "trail-making" test findings were 1.7, 2.1, 2.6, and 2.8, respectively (between ages 3 and 6, p<0.01; between ages 4 and 6, p<0.05); moreover, the age 5 group surpassed the age 3 group (2.6 and 1.7, respectively, p<0.05). CONCLUSION: The eCFT is an easily accessible tool to evaluate cognitive function in young children. We introduce reference values with a cutoff range for preschool-aged children, enabling early intervention for those with cognitive impairment. Given its accessibility and relatively short evaluation time, the eCFT has potential for clinical use.
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The significance of discontinuous growth (DG) of the tumor to include tumor deposits and intramural metastasis in esophageal adenocarcinoma (EAC) is unclear. Esophagectomy specimens from 151 treatment-naïve and 121 treated patients with EAC were reviewed. DG was defined as discrete (≥2 mm away) tumor foci identified at the periphery of the main tumor in the submucosa, muscularis propria, and/or periadventitial tissue. Patients' demographics, clinicopathologic parameters, and oncologic outcomes were compared between tumors with DG versus without DG. DGs were identified in 16% of treatment-naïve and 29% of treated cases ( P =0.01). Age, gender, and tumor location were comparable in DG+ and DG- groups. For the treatment-naïve group, DG+ tumors were larger with higher tumor grade and stage and more frequent extranodal extension, lymphovascular/perineural invasion, and positive margin. Patients with treated tumors presented at higher disease stages with higher rates of recurrence and metastasis compared with treatment-naïve patients. In this group, DG was also associated with TNM stage and more frequent lymphovascular/perineural spread and positive margin, but not with tumor size, grade, or extranodal extension. In multivariate analysis, in all patients adjusted for tumor size, lymphovascular involvement, margin, T and N stage, metastasis, neoadjuvant therapy status, treatment year, and DG, DG was found to be an independent adverse predictor of survival outcomes in EAC. DG in EAC is associated with adverse clinicopathologic features and worse patient outcomes. DG should be considered throughout the entire clinicopathologic evaluation of treatment-naïve and treated tumors as well as in future staging systems.
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Adenocarcinoma , Neoplasias Esofágicas , Humanos , Prognóstico , Relevância Clínica , Extensão Extranodal/patologia , Neoplasias Esofágicas/cirurgia , Adenocarcinoma/patologia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
Levetiracetam is a commonly prescribed antiepileptic agent and has rarely been linked to hepatotoxicity. This case describes a patient with drug-induced autoimmune hepatitis secondary to levetiracetam.
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BACKGROUND: The prognostic value of mucinous adenocarcinomas (MCAs, exhibiting >50% extracellular mucin) of the colorectum, in relation to their anatomic location is not well studied. MATERIALS AND METHODS: We compared MCAs (n = 175) with non-MCAs (NMCAs, n = 1015) and the cancer-specific survival rates were evaluated, based on their anatomic site, by univariate Kaplan-Meier and multivariate Cox methods. Subsets of these tumors were immunostained for MUC1, MUC2, Bcl-2, and p53. RESULTS: MCAs were more commonly found in the right colon, were of high-grade, and were more prevalent in younger patients (<40 years). They exhibited strong expression of MUC2 and Bcl-2 and showed less p53 nuclear staining. In contrast, most NMCAs were low-grade with high expression of MUC1. MCAs of the rectum were associated with poorer outcomes relative to NMCAs (HR 1.85, CI 95% 1.15-2.97), even though the distributions of advanced-stage tumors were similar. CONCLUSION: Late-stage disease and age were poor independent prognostic indicators of cancer-specific deaths across all tumor locations. In summary, rectal MCAs have a poor prognosis.