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1.
Cell ; 183(4): 935-953.e19, 2020 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-33186530

RESUMEN

Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific laminar positions within visual cortex, and, for most types, the cells mapping to a t-type exhibit consistent electrophysiological and morphological properties. These properties display both discrete and continuous variation among t-types. Through multimodal integrated analysis, we define 28 met-types that have congruent morphological, electrophysiological, and transcriptomic properties and robust mutual predictability. We identify layer-specific axon innervation pattern as a defining feature distinguishing different met-types. These met-types represent a unified definition of cortical GABAergic interneuron types, providing a systematic framework to capture existing knowledge and bridge future analyses across different modalities.


Asunto(s)
Corteza Cerebral/citología , Fenómenos Electrofisiológicos , Neuronas GABAérgicas/citología , Neuronas GABAérgicas/metabolismo , Transcriptoma/genética , Animales , Femenino , Perfilación de la Expresión Génica , Hipocampo/fisiología , Canales Iónicos/metabolismo , Masculino , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo
2.
Cell ; 179(3): 713-728.e17, 2019 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-31626771

RESUMEN

The ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) contains ∼4,000 neurons that project to multiple targets and control innate social behaviors including aggression and mounting. However, the number of cell types in VMHvl and their relationship to connectivity and behavioral function are unknown. We performed single-cell RNA sequencing using two independent platforms-SMART-seq (∼4,500 neurons) and 10x (∼78,000 neurons)-and investigated correspondence between transcriptomic identity and axonal projections or behavioral activation, respectively. Canonical correlation analysis (CCA) identified 17 transcriptomic types (T-types), including several sexually dimorphic clusters, the majority of which were validated by seqFISH. Immediate early gene analysis identified T-types exhibiting preferential responses to intruder males versus females but only rare examples of behavior-specific activation. Unexpectedly, many VMHvl T-types comprise a mixed population of neurons with different projection target preferences. Overall our analysis revealed that, surprisingly, few VMHvl T-types exhibit a clear correspondence with behavior-specific activation and connectivity.


Asunto(s)
Hipotálamo/citología , Neuronas/clasificación , Conducta Social , Animales , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Hipotálamo/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neuronas/fisiología , Conducta Sexual Animal , Análisis de la Célula Individual , Transcriptoma
3.
Cell ; 162(5): 948-59, 2015 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-26317464

RESUMEN

With the explosion of genome-wide studies of regulated transcription, it has become clear that traditional definitions of enhancers and promoters need to be revisited. These control elements can now be characterized in terms of their local and regional architecture, their regulatory components, including histone modifications and associated binding factors, and their functional contribution to transcription. This Review discusses unifying themes between promoters and enhancers in transcriptional regulatory mechanisms.


Asunto(s)
Elementos de Facilitación Genéticos , Regulación de la Expresión Génica , Regiones Promotoras Genéticas , Transcripción Genética , Animales , ARN Polimerasas Dirigidas por ADN/metabolismo , Humanos , ARN Largo no Codificante/metabolismo , Factores de Transcripción/metabolismo
4.
Proc Natl Acad Sci U S A ; 121(24): e2322009121, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38843187

RESUMEN

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.


Asunto(s)
Diferenciación Celular , Lupus Eritematoso Sistémico , Osteopontina , Factores de Transcripción , Animales , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/patología , Osteopontina/metabolismo , Osteopontina/genética , Ratones , Humanos , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Células T Auxiliares Foliculares/inmunología , Células T Auxiliares Foliculares/metabolismo , Femenino , Modelos Animales de Enfermedad , Ratones Noqueados
5.
Cell ; 140(5): 704-16, 2010 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-20211139

RESUMEN

Angelman Syndrome is a debilitating neurological disorder caused by mutation of the E3 ubiquitin ligase Ube3A, a gene whose mutation has also recently been associated with autism spectrum disorders (ASDs). The function of Ube3A during nervous system development and how Ube3A mutations give rise to cognitive impairment in individuals with Angleman Syndrome and ASDs are not clear. We report here that experience-driven neuronal activity induces Ube3A transcription and that Ube3A then regulates excitatory synapse development by controlling the degradation of Arc, a synaptic protein that promotes the internalization of the AMPA subtype of glutamate receptors. We find that disruption of Ube3A function in neurons leads to an increase in Arc expression and a concomitant decrease in the number of AMPA receptors at excitatory synapses. We propose that this deregulation of AMPA receptor expression at synapses may contribute to the cognitive dysfunction that occurs in Angelman Syndrome and possibly other ASDs.


Asunto(s)
Síndrome de Angelman/fisiopatología , Proteínas del Citoesqueleto/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Células Cultivadas , Cognición , Humanos , Ratones , Ratones Noqueados , Receptores AMPA/metabolismo , Sinapsis/metabolismo , Ubiquitinación
6.
Nano Lett ; 24(15): 4633-4640, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38568864

RESUMEN

The glycerol oxidation reaction (GOR) run with photoelectrochemical cells (PECs) is one of the most promising ways to upgrade biomass because it is thermodynamically favorable, while irreversible overoxidation leads to unsatisfactory product selectivities. Herein, a tunable one-dimensional nanoconfined environment was introduced into the GOR process, which accelerated mass transfer of glycerol via the microscale fluid effect and changed the main oxidation product from formic acid (FA) to glyceraldehyde (GLD), which led to retention of the heavier multicarbon products. The rate of glycerol diffusion in the nanochannels increased by a factor of 4.92 with decreasing inner diameters. The main product from the PEC-selective oxidation of glycerol changed from the C1 product FA to the C3 product GLD with a great selectivity of 60.7%. This work provides a favorable approach for inhibiting further oxidation of multicarbon products and illustrates the importance of microenvironmental regulation in biomass oxidation.

7.
Breast Cancer Res Treat ; 203(1): 95-102, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37796365

RESUMEN

PURPOSE: Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in node positive (cN1) breast cancer patients who had clinical complete response in the axilla (cN0) following neoadjuvant chemotherapy (NAC), due to the presumed high false negative rate associated with SLNB in such scenario. This study aimed to determine whether there is a significant difference in the axillary recurrence rate (ARR) and long-term survival in this group of patients, receiving SLNB alone versus axillary lymph node dissection (ALND). METHODS: A retrospective cohort of cN1 patients who were rendered cN0 by NAC from January 2014 to December 2018 were identified from the Asan Medical Center database. Patients' characteristics and outcomes were collected and analyzed. RESULTS: 902 cN1 patients treated with NAC and turned cN0 were identified. 477 (52.9%) patients achieved complete pathological response in the axilla (ypN0). At a median follow up of 65 months, ARR was 3.2% in the SLNB only group and 1.8% in the ALND group (p = 0.398). DFS and OS were significantly worse in patients with ALND as compared to patients with SLNB only (p = 0.011 and 0.047, respectively). We noted more patients in the ALND group had T3-4 tumor. In the subgroup analysis, we showed that in the T1-2 subgroup (n = 377), there was no statistically significant difference in DFS and OS (p = 0.242 and 0.671, respectively) between SLNB only and ALND group. CONCLUSION: Our findings suggest that cN1 patients who were converted to ypN0 following NAC may be safely treated with SLNB only.


Asunto(s)
Neoplasias de la Mama , Ganglio Linfático Centinela , Humanos , Femenino , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Escisión del Ganglio Linfático , Axila/patología , Ganglios Linfáticos/patología , Ganglio Linfático Centinela/patología
8.
Breast Cancer Res Treat ; 206(3): 495-507, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38658448

RESUMEN

PURPOSE: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). METHODS: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. RESULTS: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011). CONCLUSION: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary.


Asunto(s)
Axila , Neoplasias de la Mama , Ganglios Linfáticos , Metástasis Linfática , Biopsia del Ganglio Linfático Centinela , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Persona de Mediana Edad , Metástasis Linfática/patología , Estudios Retrospectivos , Factores de Riesgo , Adulto , Anciano , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Escisión del Ganglio Linfático , Invasividad Neoplásica , Mastectomía , Anciano de 80 o más Años
9.
Breast Cancer Res Treat ; 205(1): 117-125, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38332198

RESUMEN

PURPOSE: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). METHODS: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). RESULTS: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. CONCLUSION: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR.


Asunto(s)
Neoplasias de la Mama , Mastectomía Segmentaria , Recurrencia Local de Neoplasia , Pezones , Puntaje de Propensión , Humanos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Femenino , Persona de Mediana Edad , Pezones/cirugía , Mastectomía Segmentaria/métodos , Estudios Retrospectivos , Adulto , Anciano , Resultado del Tratamiento , Tratamientos Conservadores del Órgano/métodos , Estudios de Seguimiento
10.
Small ; : e2404958, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136205

RESUMEN

Organic-inorganic hybrid perovskites have attracted significant attention for optoelectronic applications due to their efficient photoconversion properties. However, grain boundaries and irregular crystal orientations in polycrystalline films remain issues. This study presents a method for producing crystalline-orientation-controlled perovskite single-crystal films using retarded solvent evaporation. It is shown that single-crystal films, grown via inverse temperature crystallization within a confined space, exhibit enhanced optoelectronic property. Using interfacial polymer layer, this method produces high-quality perovskite single-crystalline films with varying crystal orientations. Density functional theory calculations confirm favorable adsorption energies for (110) surfaces with methylammonium iodide and PbI2 terminations on poly(3-hexylthiophene), and stronger adsorption for (224) surfaces with I and methylammonium terminations on polystyrene, influenced by repulsive forces between the thiophene group and the perovskite surface. The correlation between charge transport characteristics and perovskite single-crystalline properties highlights potential advancements in perovskite optoelectronics, improving device performance and reliability.

11.
Arterioscler Thromb Vasc Biol ; 43(3): 482-491, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36727522

RESUMEN

BACKGROUND: In cross-sectional and retrospective cohort studies, we examined comparative associations between nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) and risk of having or developing coronary artery calcification (CAC). METHODS: Participants who had health examinations between 2010 and 2019 were analyzed. Liver ultrasonography and coronary artery computed tomography were used to diagnose fatty liver and CAC. Participants were divided into a MAFLD and no-MAFLD group and then NAFLD and no-NAFLD groups. Participants were further divided into no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD groups. Logistic regression modeling was performed. Cox proportional hazard model was used to examine the risk of incident CAC in participants without CAC at baseline and who had at least two CAC measurements. RESULTS: In cross-sectional analyses, 162 180 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of prevalent CAC (NAFLD: adjusted odds ratio [OR], 1.34 [95% CI, 1.29-1.39]; MAFLD: adjusted OR, 1.44 [95% CI, 1.39-1.48]). Among the 4 groups, the MAFLD-only group had the strongest association with risk of prevalent CAC (adjusted OR, 1.60 [95% CI, 1.52-1.69]). Conversely, the NAFLD-only group was associated with a lower risk of prevalent CAC (adjusted OR, 0.76 [95% CI, 0.66-0.87]). In longitudinal analyses, 34 233 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of incident CAC (NAFLD: adjusted hazard ratio, 1.68 [95% CI, 1.43-1.99]; MAFLD: adjusted hazard ratio, 1.82 [95% CI, 1.56-2.13]). Among these 4 groups, the MAFLD-only group had the strongest associations with risk of incident CAC (adjusted hazard ratio, 2.03,[95% CI, 1.62-2.55]). The NAFLD-only group was not independently associated with risk of incident CAC (adjusted hazard ratio, 0.88 [95% CI, 0.44-1.78]) Conclusions: Both NAFLD and MAFLD are significantly associated with an increased prevalence and incidence of CAC. These associations tended to be stronger for MAFLD.


Asunto(s)
Enfermedad de la Arteria Coronaria , Enfermedad del Hígado Graso no Alcohólico , Humanos , Estudios Transversales , Estudios Longitudinales , Estudios Retrospectivos , Enfermedad de la Arteria Coronaria/diagnóstico
12.
Nature ; 563(7729): 72-78, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30382198

RESUMEN

The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex.


Asunto(s)
Perfilación de la Expresión Génica , Neocórtex/citología , Neocórtex/metabolismo , Animales , Biomarcadores/análisis , Femenino , Neuronas GABAérgicas/metabolismo , Ácido Glutámico/metabolismo , Masculino , Ratones , Corteza Motora/anatomía & histología , Corteza Motora/citología , Corteza Motora/metabolismo , Neocórtex/anatomía & histología , Especificidad de Órganos , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Corteza Visual/anatomía & histología , Corteza Visual/citología , Corteza Visual/metabolismo
13.
Surg Endosc ; 38(3): 1512-1522, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38253696

RESUMEN

BACKGROUND: The extent of postoperative pain following transoral thyroidectomy is not well-understood and remains a subject of debate. This study aims to analyze and compare postoperative pain levels between patients undergoing transoral and conventional transcervical thyroidectomy. METHODS: A prospective evaluation on postoperative pain was conducted in 310 patients undergoing conventional thyroidectomy and 194 undergoing transoral thyroidectomy. Pain levels were evaluated using the numerical rating scale (NRS, ranging from 0 to 10) through preoperative and postoperative questionnaires at specified time points: 1, 3, and 6 days, and 1 and 3 months following surgery. Propensity score-matched analysis was carried out based on six covariates: sex, age, body mass index, extent of thyroidectomy, tumor size, and central neck dissection. RESULTS: After propensity score matching based on the six covariates, 121 patient pairs were identified from each group. Within this matched cohort, postoperative pain scores significantly worsened 1 day after surgery but showed progressive recovery up to 3 months post-surgery in both groups. The transoral group exhibited higher postoperative pain scores than the conventional group from day 1 (4.43 ± 2.6 vs. 3.11 ± 2.5, p < 0.001) to day 6 (1.76 ± 1.9 vs. 1.13 ± 1.6, p = 0.016) post-surgery, with no significant difference noted at 1 month. Among transoral procedures, pain scores were significantly higher for the endoscopic approach compared to the robotic approach on days 1 (5.52 ± 2.3 vs. 4.29 ± 2.3, p = 0.028) and 3 (3.52 ± 2.5 vs. 2.64 ± 2.0, p = 0.047) post-surgery. CONCLUSIONS: Postoperative pain was significantly higher in transoral thyroidectomy compared to conventional thyroidectomy up to 6 days post-surgery. Within the transoral group, the robotic procedure resulted in lower pain levels than the endoscopic approach during the early postoperative period.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias de la Tiroides , Humanos , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Puntaje de Propensión , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Dolor Postoperatorio/cirugía , Disección del Cuello/efectos adversos , Disección del Cuello/métodos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos
14.
Nutr Metab Cardiovasc Dis ; 34(7): 1769-1778, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38644081

RESUMEN

BACKGROUND AND AIMS: This cohort study investigated associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with risk of increase in arterial stiffness (AS), measured as brachial-ankle pulse wave velocity (baPWV). METHODS AND RESULTS: Participants who had health examinations between 2006 and 2019 were analyzed for fatty liver and increased baPWV using liver ultrasonography and automatic volume plethysmography device. Participants were classified based on presence of MAFLD or NAFLD and further divided into subgroups: no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD. Subgroups were additionally stratified by sex. Cox proportional hazard model was utilized to analyze the risk of developing baPWV ≥1400 cm/s in participants without baseline elevation of the baPWV. The NAFLD and MAFLD groups exhibited higher risks of increased baPWV (NAFLD: adjusted hazard ratio (aHR), 1.35 [95% CI, 1.29-1.42]; MAFLD: aHR, 1.37 [95% CI, 1.31-1.43]) compared to group without the conditions. Incidence of NAFLD or MAFLD were higher in men than in women but aHR of developing the increase in AS was higher in women. In subgroup analysis, the MAFLD-only group presented the strongest associations with increase in AS (aHR, 1.53 [95% CI, 1.43-1.64]), with the trend more pronounced in women than in men (Women, aHR, 1.63 [95% CI, 1.08-2.46]; Men, aHR 1.45 [95% CI, 1.35-1.56]). CONCLUSIONS: Both NAFLD and MAFLD are significantly associated with elevated AS. These associations tended to be stronger in MAFLD than in NAFLD, in women than in men.


Asunto(s)
Índice Tobillo Braquial , Enfermedad del Hígado Graso no Alcohólico , Análisis de la Onda del Pulso , Rigidez Vascular , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Estudios Longitudinales , Factores de Riesgo , Medición de Riesgo , Adulto , Incidencia , Factores de Tiempo , Factores Sexuales , Pronóstico , Anciano
15.
Langenbecks Arch Surg ; 409(1): 117, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38598044

RESUMEN

BACKGROUND: The oncologic safety and surgical completeness of remote-access thyroidectomies are not yet clearly established. This study evaluates the oncologic outcomes and surgical completeness of three prevalent remote-access thyroidectomies: the gasless transaxillary approach (GTAA), bilateral axillo-breast approach (BABA), and transoral approach (TOA), in comparison with conventional transcervical thyroidectomy (CTT). METHODS: Literature searches were conducted in PubMed, EMBASE, and the Cochrane Library databases, covering the period from 2000 to 2023. Network meta-analyses were performed on selected studies, focusing on recurrence and surgical completeness. Surgical completeness was assessed using stimulated serum thyroglobulin levels and the count of retrieved lymph nodes. RESULTS: The review included 48 studies, encompassing a total of 16,356 patients. The number of retrieved lymph nodes was comparable among BABA, TOA, and CTT, while GTAA might be less effective. Stimulated serum thyroglobulin levels showed no significant differences across the four groups. However, the proportion of patients with stimulated thyroglobulin levels below 1.0 ng/mL was significantly lower in GTAA compared to the other groups. The overall recurrence rates were 1.31% for CTT, 0.89% for GTAA, 0.62% for BABA, and 0% for TOA, with no significant differences in recurrence rates when adjusted for follow-up duration. CONCLUSIONS: This study demonstrated that the oncologic outcomes of GTAA, BABA, and TOA are comparable to those of CTT, based on recurrence rates. In terms of surgical completeness, BABA and TOA showed equivalence to CTT, whereas GTAA might be inferior to the other techniques.


Asunto(s)
Tiroglobulina , Tiroidectomía , Humanos , Mama , Metaanálisis en Red
16.
Eur Arch Otorhinolaryngol ; 281(3): 1505-1513, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38127099

RESUMEN

PURPOSE: The Self-Assessment Questionnaire for Cosmetic Outcomes (SAQCO) was developed by us to evaluate the cosmetic outcome of patients after thyroidectomy. This study aimed to examine the reliability and validity of SAQCO. METHODS: We analyzed the cosmetic outcomes of 368 patients who underwent thyroidectomy and completed the SAQCO 1 year after surgery. The one-dimensionality, reliability, and validity of SAQCO were assessed using factor analysis models, Cronbach's alpha, and test-retest statistics. The differences in cosmesis indices between patient characteristics and surgical parameters were analyzed through comparative and regression analyses. RESULTS: The unidimensional convergence of SAQCO was examined. A Cronbach's alpha of 0.91, strong item-total correlation values (from 0.77 to 0.89), and a test-retest correlation value of 0.86 indicated the internal consistency and reliability of the SAQCO. The cosmesis index was significantly highest in the transoral (92.3 points) and transaxillary groups (90.9 points), followed by the postauricular (84.8 points) and transcervical groups (76.4 points). CONCLUSION: This study examined the reliability and validity of the SAQCO and showed that it is a suitable questionnaire for assessing cosmetic satisfaction of patients after thyroidectomy. The transoral and transaxillary approaches yield significantly superior cosmetic results compared to the conventional transcervical and postauricular approaches.


Asunto(s)
Autoevaluación (Psicología) , Tiroidectomía , Humanos , Tiroidectomía/métodos , Estudios Transversales , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Psicometría
17.
Sensors (Basel) ; 24(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38610526

RESUMEN

Gold nanoparticles (AuNPs) are good candidates for donor material in energy transfer systems and can easily be functionalized with various ligands on the surface with Au-S bonding. Cyclodextrin (CD) forms inclusion complexes with fluorophores due to its unique structure for host-guest interaction. In this study, we fabricated ßCD-functionalized AuNPs using different lengths of thiol ligands and recognized cholesterol to confirm the energy-transfer-based turn-on fluorescence mechanism. AuNP-ßCD conjugated with various thiol ligands and quenched the fluorescein (Fl) dye, forming ßCD-Fl inclusion complexes. As the distance between AuNPs and ßCD decreased, the quenching efficiency became higher. The quenched fluorescence was recovered when the cholesterol replaced the Fl because of the stronger binding affinity of the cholesterol with ßCD. The efficiency of cholesterol recognition was also affected by the energy transfer effect because the shorter ßCD ligand had a higher fluorescence recovery. Furthermore, we fabricated a liposome with cholesterol embedded in the lipid bilayer membrane to mimic the cholesterol coexisting with lipids in human serum. These cellular cholesterols accelerated the replacement of the Fl molecules, resulting in a fluorescence recovery higher than that of pure lipid. These discoveries are expected to give guidance towards cholesterol sensors or energy-transfer-based biosensors using AuNPs.


Asunto(s)
Oro , Nanopartículas del Metal , Humanos , Colesterol , Transferencia de Energía , Fluoresceína , Compuestos de Sulfhidrilo
18.
Int J Mol Sci ; 25(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39273687

RESUMEN

The global obesity epidemic, exacerbated by the sedentary lifestyle fostered by the COVID-19 pandemic, presents a growing socioeconomic burden due to decreased physical activity and increased morbidity. Current obesity treatments show promise, but they often come with expensive medications, frequent injections, and potential side effects, with limited success in improving obesity through increased energy expenditure. This study explores the potential of a refined sulfated polysaccharide (SPSL), derived from the brown seaweed Scytosiphon lomentaria (SL), as a safe and effective anti-obesity treatment by promoting energy expenditure. Chemical characterization revealed that SPSL, rich in sulfate and L-fucose content, comprises nine distinct sulfated glycan structures. In vitro analysis demonstrated potent anti-lipogenic properties in adipocytes, mediated by the downregulation of key adipogenic modulators, including 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Inhibiting AMPK attenuated the anti-adipogenic effects of SPSL, confirming its involvement in the mechanism of action. Furthermore, in vivo studies using zebrafish models showed that SPSL increased energy expenditure and reduced lipid accumulation. These findings collectively highlight the therapeutic potential of SPSL as a functional food ingredient for mitigating obesity-related metabolic dysregulation by promoting energy expenditure. Further mechanistic and preclinical investigations are warranted to fully elucidate its mode of action and evaluate its efficacy in obesity management, potentially offering a novel, natural therapeutic avenue for this global health concern.


Asunto(s)
Adipogénesis , Metabolismo Energético , Fucosa , Alimentos Funcionales , Obesidad , Polisacáridos , Algas Marinas , Pez Cebra , Animales , Metabolismo Energético/efectos de los fármacos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Polisacáridos/química , Polisacáridos/farmacología , Algas Marinas/química , Fucosa/metabolismo , Adipogénesis/efectos de los fármacos , Ratones , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Humanos , Sulfatos/química , Sulfatos/metabolismo , PPAR gamma/metabolismo , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/química , Fármacos Antiobesidad/uso terapéutico , Células 3T3-L1 , Proteínas Quinasas Activadas por AMP/metabolismo
19.
J Sci Food Agric ; 104(9): 5010-5020, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38314949

RESUMEN

BACKGROUND: Cruciferous vegetable sprout has been highlighted as a promising functional material rich in bioactive compounds called isothiocyanates (ITCs) and it can be grown in very short periods in controlled indoor farms. However, because ITCs content depends on multiple factors such as cultivar, germination time and myrosinase activity, those variables need to be controlled during germination or extraction to produce functional materials enriched in ITCs. Sulforaphene (SFEN), an ITC found primarily in radishes (Raphanus sativus L.), exerts beneficial effects on obesity. However, the optimal germination and extraction conditions for radish sprout (RSP) to increase SFEN content remain unascertained, and the extract's anti-obesity effect has yet to be evaluated. RESULTS: The present study found that the SFEN content was highest in purple radish sprout (PRSP) among the six cultivars investigated. Optimal SFEN content occurred after 2 days of PRSP germination (2 days PRSP). To maximize the dry matter yield, total ITCs and SFEN contents in RSP extract, we found the optimal conditions for extracting PRSP [27.5 °C, 60 min, 1:75.52 solute/solvent (w/v), no ascorbic acid] using response surface methodology. Consistent with high SFEN content, 2 days PRSP extract significantly outperformed 3 days or 4 days PRSP extract in inhibiting lipid accumulation in 3T3-L1 cells. Moreover, 2 days PRSP extract suppressed adipogenesis and lipogenesis-related protein expression. CONCLUSION: Regarding the cultivar, germination time and extraction conditions, optimally produced PRSP extract contains high SFEN content and exerts anti-obesity effects. Thus, we suggest PRSP extract as a potent functional material for obesity prevention. © 2024 Society of Chemical Industry.


Asunto(s)
Germinación , Isotiocianatos , Extractos Vegetales , Raphanus , Raphanus/química , Raphanus/crecimiento & desarrollo , Raphanus/metabolismo , Germinación/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Isotiocianatos/farmacología , Isotiocianatos/aislamiento & purificación , Isotiocianatos/química , Isotiocianatos/análisis , Ratones , Animales , Células 3T3-L1 , Sulfóxidos
20.
BMC Oral Health ; 24(1): 750, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943102

RESUMEN

BACKGROUND: Iatrogenic mandibular nerve damage resulting from oral surgeries and dental procedures is painful and a formidable challenge for patients and oral surgeons alike, mainly because the absence of objective and quantitative methods for diagnosing nerve damage renders treatment and compensation ambiguous while often leading to medico-legal disputes. The aim of this study was to examine discriminating factors of traumatic mandibular nerve within a specific magnetic resonance imaging (MRI) protocol and to suggest tangible diagnostic criteria for peripheral trigeminal nerve injury. METHODS: Twenty-six patients with ipsilateral mandibular nerve trauma underwent T2 Flex water, 3D short tau inversion recovery (STIR), and diffusion-weighted imaging (DWI) acquired by periodically rotating overlapping parallel lines with enhanced reconstruction (PROPELLER) pulse sequences; 26 injured nerves were thus compared with contra-lateral healthy nerves at anatomically corresponding sites. T2 Flex apparent signal to noise ratio (FSNR), T2 Flex apparent nerve-muscle contrast to noise ratio (FNMCNR) 3D STIR apparent signal to noise ratio (SSNR), 3D STIR apparent nerve-muscle contrast to noise ratio (SNMCNR), apparent diffusion coefficient (ADC) and area of cross-sectional nerve (Area) were evaluated. RESULTS: Mixed model analysis revealed FSNR and FNMCNR to be the dual discriminators for traumatized mandibular nerve (p < 0.05). Diagnostic performance of both parameters was also determined with area under the receiver operating characteristic curve (AUC for FSNR = 0.712; 95% confidence interval [CI]: 0.5660, 0.8571 / AUC for FNMCNR = 0.7056; 95% confidence interval [CI]: 1.011, 1.112). CONCLUSIONS: An increase in FSNR and FNMCNR within our MRI sequence seems to be accurate indicators of the presence of traumatic nerve. This prospective study may serve as a foundation for sophisticated model diagnosing trigeminal nerve trauma within large patient cohorts.


Asunto(s)
Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Lesiones del Nervio Mandibular/diagnóstico por imagen , Imagenología Tridimensional/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Nervio Mandibular/diagnóstico por imagen , Anciano , Adulto Joven , Traumatismos del Nervio Trigémino/diagnóstico por imagen , Relación Señal-Ruido
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