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Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL cotreatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal-inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. A 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pretreatment HMO mixture in vitro; thus, this ratio was selected and used for low-, middle-, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as BW loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short-chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggest that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.
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Lipopolisacáridos , Oligosacáridos , Ratones , Animales , Oligosacáridos/farmacología , Inflamación/tratamiento farmacológico , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Trisacáridos/farmacología , Lactosa/análogos & derivadosRESUMEN
BACKGROUND: Identification of clinically useful biomarkers for Nasal Polyposis in chronic rhinosinusitis (CRSwNP) has proven dif-ficult. We analyzed gene expression profiling data to find explanations for this. METHODS: We analyzed mRNA expression profiling data, GSE36830, of six uncinate tissues from healthy controls and six NP from CRSwNP patients. We performed Ingenuity Pathway Analysis (IPA) of differentially expressed genes to identify pathways and predicted upstream regulators. RESULTS: We identified 1,608 differentially expressed genes and 177 significant pathways, of which Th1 and Th2 activation pathway and leukocyte extravasation signaling were most significant. We identified 75 upstream regulators whose activity was predicted to be upregulated. These included regulators of known pathogenic and therapeutic relevance, like IL-4. However, only seven of the 75 regulators were actually differentially expressed in NP, namely CSF1, TYROBP, CCL2, CCL11, SELP, ADORA3, ICAM1. Interes-tingly, these did not include IL-4, and four of the seven were receptors. This suggested a potential explanation for the discrepancy between the predicted and observed expression levels of the regulators, namely that the receptors, and not their ligands, were upregulated. Indeed, we found that 10 receptors of key predicted upstream regulators were upregulated, including IL4R. CONCLUSION: Our findings indicate that the difficulties in finding specific biomarkers for CRSwNP depend on the complex underly-ing mechanisms, which include multiple pathways and regulators, each of which may be subdivided into multiple components such as ligands, soluble and membrane-bound receptors. This suggests that combinations of biomarkers may be needed for CRSwNP diagnostics.
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Pólipos Nasales , Rinitis , Sinusitis , Biomarcadores , Enfermedad Crónica , Humanos , Pólipos Nasales/genética , Rinitis/genética , Transducción de Señal , Sinusitis/genética , TranscriptomaRESUMEN
Two sentences in the Discussion section were incorrect.
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HIV-infected men under the age of 50 years had a lower bone mass compared to that of HIV-uninfected men. Lower CD4 T cell counts, independent of whether antiretroviral therapy (ART) was used, were associated with lower BMD. HIV-infected patients with low CD4 T cell counts may need follow-up and intervention regarding bone health, including younger patients. INTRODUCTION: HIV-infected patients have a low bone mineral density (BMD) owing to multifactorial interaction between common osteoporosis risk factors and HIV-related factors, including chronic inflammation and ART. Although HIV infection and ART might affect bone metabolism, little data is available for patients aged under 50 years. We aimed to investigate the association of HIV infection-induced low CD4 T cell counts and ART with BMD in men aged under 50 years. METHODS: We performed an age- and body mass index-matched case-control study. BMD values of HIV-infected and HIV-uninfected men (< 50 years) were compared, and HIV-infected men were stratified by CD4 T cell counts and ART use. RESULTS: After adjusting confounders, HIV-infected men with CD4 T cell counts ≥ 500 cells/µL (n = 28) and < 500 cells/µL (n = 139) had lower BMD at the femoral neck (FN, p < 0.001) and total hip (TH, p < 0.001) than HIV-uninfected men (n = 167). HIV-infected men with CD4 T cell counts < 500/µL had lower BMD at the lumbar spine (LS, p = 0.034) than those with counts of ≥ 500 cells/µL, but not at FN and TH. The CD4 T cell count (γ = 0.169, p = 0.031) was positively correlated with BMD at LS. There was no significant difference in the BMD (p = 0.499-> 0.999) between the ART-naïve (n = 75) and ART-user group (n = 92). CONCLUSIONS: Despite their relatively younger age, HIV-infected men had a lower BMD than HIV-uninfected men. Lower CD4 T cell counts, irrespective of ART, might result in lower bone mass.
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Densidad Ósea/inmunología , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/fisiopatología , Osteoporosis/inmunología , Absorciometría de Fotón/métodos , Adulto , Factores de Edad , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Densidad Ósea/efectos de los fármacos , Recuento de Linfocito CD4 , Estudios de Casos y Controles , Cuello Femoral/fisiopatología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Articulación de la Cadera/fisiopatología , Humanos , Vértebras Lumbares/fisiopatología , Masculino , Persona de Mediana Edad , Osteoporosis/fisiopatología , Osteoporosis/virologíaRESUMEN
Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.
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BACKGROUND: The standard diagnostic test for allergic contact dermatitis is the patch test, which can also be used to identify irritant contact dermatitis. Doubtful reactions (?+) can be often clinically relevant to individuals and can require additional tests. OBJECTIVES: The purpose of this study was to examine whether autofluorescence (AF) measurements in patients with doubtful reactions are helpful in diagnosing contact dermatitis. METHODS: Patients with a history of contact dermatitis were patch tested on the upper back for 48-hours of occlusion using aqueous solutions of 5% sodium lauryl sulfate. Reaction intensity was scored, and AF was measured on reactive lesions and non-lesions. Three dermatologists classified the results as positive or negative using the fluorescence photographs of patients with a doubtful reaction. RESULTS: Among doubtful reactions, the R/G% values were significantly higher in the AF- based positive group than in the negative group (P = .0086). On the other hand, the heterogeneity values of R, G, and B (HR, HG, HB) were significantly lower in the AF-based positive group (P = .0026, .0046, .0004 respectively). CONCLUSIONS: Measuring AF along with the clinical readings can help confirm doubtful patch test reactions.
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Dermatitis Alérgica por Contacto/diagnóstico , Imagen Óptica/métodos , Pruebas del Parche/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: Primary cilium is required for mechano-biological signal transduction in chondrocytes, and its interaction with extracellular matrix is critical for cartilage homeostasis. However, the role of cilia-associated proteins that affect the function of cilia remains to be elucidated. Here, we show that Dicam has a novel function as a modulator of primary cilia-mediated Indian hedgehog (Ihh) signaling in chondrocytes. METHODS: Cartilage-specific Dicam transgenic mouse was constructed and the phenotype of growth plates at embryonic day 15.5 and 18.5 was analyzed. Primary chondrocytes and tibiae isolated from embryonic day 15.5 mice were used in vitro study. RESULTS: Dicam was mainly expressed in resting and proliferating chondrocytes of the growth plate and was increased by PTHrP and BMP2 in primary chondrocytes. Cartilage-specific Dicam gain-of-function demonstrated increased length of growth plate in long bones. Dicam enhanced both proliferation and maturation of growth plate chondrocytes in vivo and in vitro, and it was accompanied by enhanced Ihh and PTHrP signaling. Dicam was localized to primary cilia of chondrocytes, and increased the number of primary cilia and their assembly molecule, IFT88/Polaris as well. Dicam successfully rescued the knock-down phenotype of IFT88/Polaris and it was accompanied by increased number of cilia in tibia organ culture. CONCLUSION: These findings suggest that Dicam positively regulates primary cilia and Ihh signaling resulting in elongation of long bone.
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Moléculas de Adhesión Celular/metabolismo , Regulación del Desarrollo de la Expresión Génica , Placa de Crecimiento/metabolismo , Proteínas Hedgehog/genética , Transducción de Señal/genética , Animales , Moléculas de Adhesión Celular/genética , Proliferación Celular/genética , Células Cultivadas , Condrocitos/metabolismo , Cilios/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Distribución Aleatoria , Sensibilidad y Especificidad , Regulación hacia ArribaRESUMEN
We study transport mediated by Andreev bound states formed in InSb nanowire quantum dots. Two kinds of superconducting source and drain contacts are used: epitaxial Al/InSb devices exhibit a doubling of tunneling resonances, while, in NbTiN/InSb devices, Andreev spectra of the dot appear to be replicated multiple times at increasing source-drain bias voltages. In both devices, a mirage of a crowded spectrum is created. To describe the observations a model is developed that combines the effects of a soft induced gap and of additional Andreev bound states both in the quantum dot and in the finite regions of the nanowire adjacent to the quantum dot. Understanding of Andreev spectroscopy is important for the correct interpretation of Majorana experiments done on the same structures.
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OBJECTIVES: To compare the efficacy and safety of transoral robotic surgery (TORS) with endoscope-guided coblation tongue base resection. DESIGN: Retrospective case-control study. SETTING: University-based tertiary care medical center. PARTICIPANTS: Patients with obstructive sleep apnoea (OSA) who underwent endoscope-guided tongue base coblation resection or transoral robotic surgery (TORS) in combination with lateral pharyngoplasty at a single institution in South Korea between April 2013 and December 2016 were investigated. Forty-five patients who had moderate-to-severe OSA with tongue base collapse and a minimum follow-up period of 6 months with postoperative polysomnography (PSG) were enrolled in this study. MAIN OUTCOME MEASURES: All patients underwent pre- and postoperative (at least 4 months after surgery) overnight PSG. Available information on results of the PSG, Epworth sleepiness scale and complications of the TORS and coblation groups were compared. RESULTS: Postoperative PSG studies showed improved sleep quality for most patients. The mean postoperative apnoea-hypopnea index (AHI) was reduced significantly from 45.0 to 17.0 events/h (P < .0001) in the TORS group and from 45.6 to 16.2 events/h (P < .0001) in the coblation group. The mean rates of improvement (AHI reduction > 50%) were 75.0% in TORS patients and 62.1% in coblation patients and the difference was not significant. Less frequent postoperative morbidity, including bleeding, taste dysfunction and foreign body sensation, was recorded in TORS patients. CONCLUSIONS: Both the coblation and TORS groups showed similar surgical outcomes, TORS achieved PSG results non-inferior to and complication rates comparable to coblation.
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Ablación por Catéter/métodos , Glosectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Apnea Obstructiva del Sueño/cirugía , Lengua/cirugía , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Complicaciones Posoperatorias/epidemiología , República de Corea/epidemiología , Estudios Retrospectivos , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , Resultado del TratamientoRESUMEN
Uveitis (intraocular inflammation) is a leading cause of loss of vision. Although its aetiology is largely speculative, it is thought to arise from complex genetic-environmental interactions that break immune tolerance to generate eye-specific autoreactive T cells. Experimental autoimmune uveitis (EAU), induced by immunization with the ocular antigen, interphotoreceptor retinoid binding protein (IRBP), in combination with mycobacteria-containing complete Freund's adjuvant (CFA), has many clinical and histopathological features of human posterior uveitis. Studies in EAU have focused on defining pathogenic CD4+ T cell effector responses, such as those of T helper type 17 (Th17) cells, but the innate receptor pathways precipitating development of autoreactive, eye-specific T cells remain poorly defined. In this study, we found that fungal-derived antigens possess autoimmune uveitis-promoting function akin to CFA in conventional EAU. The capacity of commensal fungi such as Candida albicans or Saccharomyces cerevisae to promote IRBP-triggered EAU was mediated by Card9. Because Card9 is an essential signalling molecule of a subgroup of C-type lectin receptors (CLRs) important in host defence, we evaluated further the proximal Card9-activating CLRs. Using single receptor-deficient mice we identified Dectin-2, but not Mincle or Dectin-1, as a predominant mediator of fungal-promoted uveitis. Conversely, Dectin-2 activation by α-mannan reproduced the uveitic phenotype of EAU sufficiently, in a process mediated by the Card9-coupled signalling axis and interleukin (IL)-17 production. Taken together, this report relates the potential of the Dectin-2/Card9-coupled pathway in ocular autoimmunity. Not only does it contribute to understanding of how innate immune receptors orchestrate T cell-mediated autoimmunity, it also reveals a previously unappreciated ability of fungal-derived signals to promote autoimmunity.
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Enfermedades Autoinmunes/inmunología , Proteínas Adaptadoras de Señalización CARD/inmunología , Candida albicans/inmunología , Candidiasis/inmunología , Lectinas Tipo C/inmunología , Saccharomyces cerevisiae/inmunología , Uveítis/inmunología , Animales , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/patología , Proteínas Adaptadoras de Señalización CARD/genética , Candidiasis/inducido químicamente , Candidiasis/patología , Proteínas del Ojo/toxicidad , Lectinas Tipo C/genética , Ratones , Ratones Mutantes , Proteínas de Unión al Retinol/toxicidad , Células Th17/inmunología , Células Th17/patología , Uveítis/inducido químicamente , Uveítis/genética , Uveítis/patologíaRESUMEN
BACKGROUND: Vitiligo is attributable to loss of functional melanocytes and is the most common acquired depigmenting disorder. Oxidative stress and intense ultraviolet irradiation are known to aggravate this condition. The nonhistone high-mobility group box 1 (HMGB1) DNA-binding protein is a physiological activator of immune responses, cellular proliferation and cell death. Although it is implicated in the pathogenesis of autoimmune diseases and cutaneous disorders, the precise role of HMGB1 in melanocytes has yet to be studied. OBJECTIVES: To elucidate the effect of HMGB1 on melanocytic survival and its involvement in the pathogenesis of vitiligo. METHODS: Melanocytes were treated with recombinant HMGB1 (rHMGB1). Thereafter, apoptosis-, autophagy- and melanogenesis-related molecules were detected. Ex vivo skin organ culture was performed after rHMGB1 treatment. Also, levels of HMGB1 were examined in blood and skin specimens from patients with vitiligo. RESULTS: In this study, rHMGB1 increased expression of cleaved caspase 3 and decreased melanin production and expression of melanogenesis-related molecules. rHMGB1-induced caspase 3 activation was confirmed through preincubation with a pan-caspase inhibitor. In ex vivo experiments for the confirmation of HMGB1-induced melanocyte apoptosis, melanocyte disappearance and increased caspase 3 activation were observed in rHMGB1-treated skin tissues. In Western blot analysis and enzyme-linked immunosorbent assay, patients with active vitiligo showed significantly higher blood levels of HMGB1 (vs. healthy controls). Also, greater expression of HMGB1 was observed in vitiliginous skin (vs. uninvolved skin). CONCLUSIONS: External stimuli (e.g. oxidative stress and ultraviolet irradiation) may trigger HMGB1 release by keratinocytes, thereby perpetuating vitiligo through HMGB1-induced melanocytic apoptosis.
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Proteína HMGB1/fisiología , Melanocitos/citología , Vitíligo/etiología , Adulto , Anciano , Autofagia/fisiología , Biomarcadores/metabolismo , Estudios de Casos y Controles , Caspasa 3/metabolismo , Supervivencia Celular , Células Cultivadas , Células Epidérmicas , Epidermis/metabolismo , Femenino , Proteína HMGB1/metabolismo , Humanos , Queratinocitos/metabolismo , Masculino , Melanocitos/metabolismo , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Piel/metabolismo , Rayos Ultravioleta , Vitíligo/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia. METHODS: An Alpha TC1-6 cell line was cultured in control (5 mM) or hyperglycemia (HG, 15 mM) for 72 h. We applied troglitazone with or without PPARγ antagonist (GW9662 10 µM). To investigate the involvement of PI3K/Akt pathway, we applied troglitazone with or without Wortmanin. We measured sodium glucose transporter 2 (SGLT2) and glucagon (GCG) mRNA and protein expression. PPAR gamma, PI3K and Akt protein were also measured. RESULTS: Exposure of alpha TC cells to HG for 72 h increased glucagon mRNA and protein expression. HG decreased SGLT2 mRNA and protein expression. Troglitazone significantly reversed HG-induced reduction of SGLT2 expression and increase of glucagon secretion. PPARγ antagonist (GW9662 10 µM) decreased the expression of SGLT2 and increased glucagon as HG did. Hyperglycemia increased PI3K and pAkt expression in alpha cells. Wortmanin (PI3K inhibitor, 1 µM) reversed HG-induced SGLT2 decrease and glucagon increase. Troglitazone treatment decreased PI3K and pAkt expression in HG. CONCLUSION: In conclusion, PPARγ agonist, troglitazone improved glucose transport SGLT2 dysfunction and subsequent glucagon dysregulation in alpha cell under hyperglycemia. Those effects were through the involvement of PI3K/pAkt signaling pathway. This study may add one more reason for the ideal combination of PPARγ agonist and SGLT2 inhibitor in clinical practice.
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Cromanos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Células Secretoras de Glucagón/metabolismo , Glucagón/metabolismo , Hiperglucemia/fisiopatología , PPAR gamma/agonistas , Transportador 2 de Sodio-Glucosa/metabolismo , Tiazolidinedionas/farmacología , Animales , Células Cultivadas , Células Secretoras de Glucagón/efectos de los fármacos , Células Secretoras de Glucagón/patología , Glucosa/farmacología , Hipoglucemiantes/farmacología , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , TroglitazonaRESUMEN
Paclitaxel (PTX)-loaded gelatin nanoparticles (NPs) were prepared, for the first time, by novel O/W/O emulsion with a single-step emulsion process accompanying solvent diffusion, in contrast to the conventional double-step emulsion processes. Linoleic acid was chosen among the natural fatty acids as the exterior medium for the single-step emulsion process accompanying solvent diffusion. The size mean and zeta potential of the PTX-loaded gelatin NPs in their suspension were 164.95 nm (±6.43 nm) distributed with a polydispersity of 0.074 (±0.046) and -23.85 mV (±12.66 mV), respectively. The size of the PTX-loaded gelatin NPs prepared in this study was the smallest among the reported sizes of PTX-loaded gelatin NPs, which would contribute to the enhanced permeability and retention (EPR). In addition, TEM showed that the loaded PTX was located mostly inside the gelatin NPs unlike previous investigations. Accordingly, the conceptual model of the designed PTX-loaded gelatin nanoparticle was introduced. Sustaining a slow PTX release on a day-time scale without an initial burst release into a release medium was observed along with a delay of more than 2 days (i.e., 50 h) before a bursting PTX release from 50 to 70 h despite the addition of a protein degrading enzyme. The observed PTX-loading efficiency was 54.5%. This loading efficiency was greater than that of previous study using gelatin of bloom 75-100 of Lu et al. to prepare PTX-loaded gelatin NPs using a desolvation method.
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Gelatina/química , Nanopartículas/química , Agua/química , Emulsiones , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Solubilidad , Solventes/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
AIM: The study was designed to assess the correlation between lymph node (LN) size and LN metastasis in patients with rectal neuroendocrine tumours (NETs). METHOD: Forty patients who underwent curative resection with lymphadenectomy for a rectal NET between January 2007 and December 2012 were included. The short and long diameters of entire nodes were microscopically measured using a slide gauge. RESULTS: In all, 1052 LNs were collected from the 40 patients, with 49 (4.7%) showing evidence of metastasis. Metastasis-positive LNs had significantly greater long and short diameters (P < 0.001) than metastasis-negative LNs. Of the 49 metastatic LNs, 29 (59.2%) were ≤ 5 mm in largest diameter. In five patients, the largest metastatic LN was only 2-3 mm in diameter. In clinically node-negative (cN0) patients, 18 (51.4%) patients had metastatic LNs (pN1). CONCLUSION: The size of LNs containing metastasis varied widely, with some being very small. LN size alone is therefore not a sufficient predictor of tumour metastasis in rectal NETs. Radical surgery with lymphadenectomy should be considered for patients with rectal NETs with high risk factors for LN metastasis, even those without LN enlargement.
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Ganglios Linfáticos/patología , Metástasis Linfática , Tumores Neuroendocrinos/patología , Neoplasias del Recto/patología , Adulto , Anciano , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/cirugía , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
AIM: To describe characteristic magnetic resonance imaging (MRI) abnormalities in hyperglycaemia-induced seizures, and evaluate the diagnostic value of contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging. Possible underlying mechanisms of this condition are also discussed. MATERIALS AND METHODS: Eleven patients with hyperglycaemia-induced seizures and MRI abnormalities were retrospectively studied. Clinical manifestations, laboratory findings, MRI findings, and clinical outcomes were analysed. RESULTS: All patients, except one, presented with focal seizures, simple or complex partial seizures, or negative motor seizures. All patients had long-standing uncontrolled diabetes mellitus. The MRI abnormalities observed acutely were focal subcortical hypointensities on T2-weighted imaging and FLAIR imaging in all patients with overlying cortical gyral T2 hyperintensities in five. Focal overlying cortical or leptomeningeal enhancement on contrast-enhanced T1-weighted imaging or contrast-enhanced FLAIR imaging was observed in all patients. Contrast-enhanced FLAIR imaging was superior to contrast-enhanced T1-weighted imaging for detecting characteristic cortical or leptomeningeal enhancement. Diffusion-weighted imaging showed mildly restricted diffusion in four of five patients with cortical gyral T2 hyperintensity. In nine patients, the lesions were localised in the parietal or parieto-occipital lobes. The other two patients showed localised precentral gyral lesions. After treatment, the neurological symptoms, including the seizures, improved in all patients. On clinical recovery, the subcortical T2 hypointensity, gyral or leptomeningeal enhancement, and overlying cortical T2 hyperintensities resolved. CONCLUSION: Recognition of these radiological abnormalities in patients with hyperglycaemia-induced seizures is important in restricting unwarranted investigations and initiating early therapy. These patients generally have a good prognosis.
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Encéfalo/diagnóstico por imagen , Medios de Contraste , Hiperglucemia/complicaciones , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Convulsiones/etiología , Anciano , Encéfalo/patología , Femenino , Humanos , Hiperglucemia/patología , Masculino , Persona de Mediana Edad , Compuestos Organometálicos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Convulsiones/patologíaRESUMEN
BACKGROUND: Sensitive skin is a universal term in the field of cosmetology. In addition, the development and demand for sensitive skin cosmetics is increasing. However, there is no appropriate method for detecting sensitive skin. METHODS: We analyzed the relationship between the frequency of response at each sensation (stinging, burning, and itching) during a lactic acid sting test and the current perception threshold (CPT) value of each frequency. To reconfirm this relationship, we analyzed differences of the CPT value (5 Hz) between the itch responder and non-itch responder groups. RESULTS: There is a significant correlation between itch sensation and CPT values of 5 Hz. The itch responder group showed significantly lower sensory perception value of 5 Hz than the non-itch responder group. CONCLUSION: The CPT value (5 Hz) can be used for scanning for itching sensations when a cosmetic or its ingredients possibly cause the sensation.
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Umbral Diferencial , Estimulación Eléctrica/métodos , Hiperalgesia/fisiopatología , Percepción del Dolor , Prurito/fisiopatología , Piel/fisiopatología , Adulto , Electrodiagnóstico/métodos , Femenino , Humanos , Ácido Láctico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Piel/efectos de los fármacosRESUMEN
Recent advances in computational epigenetics have provided new opportunities to evaluate n-gram probabilistic language models. In this paper, we describe a systematic genome-wide approach for predicting functional roles in inactive chromatin regions by using a sequence-based Markovian chromatin map of the human genome. We demonstrate that Markov chains of sequences can be used as a precursor to predict functional roles in heterochromatin regions and provide an example comparing two publicly available chromatin annotations of large-scale epigenomics projects: ENCODE project consortium and Roadmap Epigenomics consortium.
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Cromatina/genética , Secuencia de Bases , Línea Celular , Mapeo Cromosómico , Biología Computacional , Epigénesis Genética , Genoma Humano , Humanos , Modelos Genéticos , Modelos Estadísticos , Anotación de Secuencia Molecular , Análisis de Secuencia de ADN , Programas InformáticosRESUMEN
Pigs are an attractive animal model to study the progression of cancer because of their anatomical and physiological similarities to human. However, the use of pig models for cancer research has been limited by availability of genetically engineered pigs which can recapitulate human cancer progression. Utilizing genome editing technologies such as CRISPR/Cas9 system allows us to generate genetically engineered pigs at a higher efficiency. In this study, specific CRISPR/Cas9 systems were used to target RUNX3, a known tumour suppressor gene, to generate a pig model that can induce gastric cancer in human. First, RUNX3 knockout cell lines carrying genetic modification (monoallelic or biallelic) of RUNX3 were generated by introducing engineered CRISPR/Cas9 system specific to RUNX3 into foetal fibroblast cells. Then, the genetically modified foetal fibroblast cells were used as donor cells for somatic cell nuclear transfer, followed by embryo transfer. We successfully obtained four live RUNX3 knockout piglets from two surrogates. The piglets showed the lack of RUNX3 protein in their internal organ system. Our results demonstrate that the CRISPR/Cas9 system is effective in inducing mutations on a specific locus of genome and the RUNX3 knockout pigs can be useful resources for human cancer research and to develop novel cancer therapies.
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Sistemas CRISPR-Cas , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Eliminación de Gen , Ingeniería Genética/veterinaria , Porcinos/genética , Secuencia de Aminoácidos , Animales , Biología Computacional , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Técnicas de Cultivo de Embriones , Técnicas de Transferencia NuclearRESUMEN
Primary lymphangioma arising from the ovary is a rare tumor, with only 24 cases reported to date. As it is often accompanied by ascites or recurrence, similar to a malignant tumor, an aggressive treatment approach is used for disease control. In this report, we describe a 75-year-old woman with a left ovarian lymphangioma that increased in size during the menopause period. Microscopic examination of the tumor showed thin-walled multilocular cystic spaces and immunoreactivity for D2-40, a specific marker for lymphatic endothelium, lining the cystic spaces. The patient has been doing well for 5 years postoperatively. Ovarian cystic lymphangioma should be included in the differential diagnosis of an ovarian cyst and long-term follow-up is recommended to exclude malignant behavior. We also summarize a total of 25 cases, including the case presented here.