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1.
Cell Mol Life Sci ; 81(1): 286, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970652

RESUMO

Paralog factors are considered to ensure the robustness of biological processes by providing redundant activity in cells where they are co-expressed. However, the specific contribution of each factor is frequently underestimated. In the developing spinal cord, multiple families of transcription factors successively contribute to differentiate an initially homogenous population of neural progenitors into a myriad of neuronal subsets with distinct molecular, morphological, and functional characteristics. The LIM-homeodomain transcription factors Lhx3, Lhx4, Isl1 and Isl2 promote the segregation and differentiation of spinal motor neurons and V2 interneurons. Based on their high sequence identity and their similar distribution, the Lhx3 and Lhx4 paralogs are considered to contribute similarly to these processes. However, the specific contribution of Lhx4 has never been studied. Here, we provide evidence that Lhx3 and Lhx4 are present in the same cell populations during spinal cord development. Similarly to Lhx3, Lhx4 can form multiproteic complexes with Isl1 or Isl2 and the nuclear LIM interactor NLI. Lhx4 can stimulate a V2-specific enhancer more efficiently than Lhx3 and surpasses Lhx3 in promoting the differentiation of V2a interneurons in chicken embryo electroporation experiments. Finally, Lhx4 inactivation in mice results in alterations of differentiation of the V2a subpopulation, but not of motor neuron production, suggesting that Lhx4 plays unique roles in V2a differentiation that are not compensated by the presence of Lhx3. Thus, Lhx4 could be the major LIM-HD factor involved in V2a interneuron differentiation during spinal cord development and should be considered for in vitro differentiation of spinal neuronal populations.


Assuntos
Diferenciação Celular , Interneurônios , Proteínas com Homeodomínio LIM , Medula Espinal , Fatores de Transcrição , Animais , Proteínas com Homeodomínio LIM/metabolismo , Proteínas com Homeodomínio LIM/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Interneurônios/metabolismo , Interneurônios/citologia , Medula Espinal/citologia , Medula Espinal/metabolismo , Medula Espinal/embriologia , Embrião de Galinha , Camundongos , Neurônios Motores/metabolismo , Neurônios Motores/citologia , Humanos , Regulação da Expressão Gênica no Desenvolvimento
2.
Int J Mol Sci ; 25(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38673975

RESUMO

Previously, we reported that epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR1/ADGRE1) is abnormally expressed in colon cancer (CC) and is a risk factor for lymph node metastasis (LNM) and poor recurrence-free survival in patients with abundant tumor-associated macrophages (TAMs). However, the signaling pathways associated with EMR1 expression in CC progression remain unclear. In this study, we aimed to explore the role of EMR1 and its signaling interactions with macrophages in CC progression. Spatial transcriptomics of pT3 microsatellite unstable CC tissues revealed heightened Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in EMR1-HL CC with LNM compared to EMR1-N CC without LNM. Through in vitro coculture of CC cells with macrophages, EMR1 expression by CC cells was found to be induced by TAMs, ultimately interacting with upregulated JAK/STAT signaling, increasing cell proliferation, migration, and motility, and reducing apoptosis. JAK2/STAT3 inhibition decreased the levels of EMR1, JAK2, STAT1, and STAT3, significantly impeded the proliferation, migration, and mobility of cells, and increased the apoptosis of EMR1+ CC cells compared to their EMR1KO counterparts. Overall, TAMs-induced EMR1 upregulation in CC cells may promote LNM and CC progression via JAK2/STAT1,3 signaling upregulation. This study provides further insights into the molecular mechanisms involving macrophages and intracellular EMR1 expression in CC progression, suggesting its clinical significance and offering potential interventions to enhance patient outcomes.


Assuntos
Neoplasias do Colo , Janus Quinase 2 , Transdução de Sinais , Macrófagos Associados a Tumor , Humanos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Progressão da Doença , Regulação para Cima , Proliferação de Células , Linhagem Celular Tumoral , Movimento Celular/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Apoptose/genética
3.
J Med Internet Res ; 25: e45975, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37467013

RESUMO

BACKGROUND: Effective health interventions for North Korean refugees vulnerable to metabolic disorders are currently unelucidated. OBJECTIVE: This study aimed to evaluate the effects of digital health interventions in North Korean refugees using a wearable activity tracker (Fitbit device). METHODS: We conducted a prospective, randomized, open-label study on North Korean refugees aged 19-59 years between June 2020 and October 2021 with a 12-week follow-up period. The participants were randomly assigned to either an intervention group or a control group in a 1:1 ratio. The intervention group received individualized health counseling based on Fitbit data every 4 weeks, whereas the control group wore the Fitbit device but did not receive individualized counseling. The primary and secondary outcomes were the change in the mean daily step count and changes in the metabolic parameters, respectively. RESULTS: The trial was completed by 52 North Korean refugees, of whom 27 and 25 were in the intervention and control groups, respectively. The mean age was 43 (SD 10) years, and 41 (78.8%) participants were women. Most participants (44/52, 95.7%) had a low socioeconomic status. After the intervention, the daily step count in the intervention group increased, whereas that in the control group decreased. However, there were no significant differences between the 2 groups (+83 and -521 steps in the intervention and control groups, respectively; P=.500). The effects of the intervention were more prominent in the participants with a lower-than-average daily step count at baseline (<11,667 steps/day). After the 12-week study period, 85.7% (12/14) and 46.7% (7/15) of the participants in the intervention and control groups, respectively, had an increased daily step count (P=.05). The intervention prevented the worsening of the metabolic parameters, including BMI, waist circumference, fasting blood glucose level, and glycated hemoglobin level, during the study period. CONCLUSIONS: The wearable device-based physical activity intervention did not significantly increase the average daily step count in the North Korean refugees in this study. However, the intervention was effective among the North Korean refugees with a lower-than-average daily step count; therefore, a large-scale, long-term study of this intervention type in an underserved population is warranted. TRIAL REGISTRATION: Clinical Research Information Service KCT0007999; https://cris.nih.go.kr/cris/search/detailSearch.do/23622.


Assuntos
Refugiados , Dispositivos Eletrônicos Vestíveis , Humanos , Feminino , Adulto , Masculino , Projetos Piloto , Estudos Prospectivos , República Democrática Popular da Coreia , Exercício Físico/psicologia
4.
Medicina (Kaunas) ; 59(2)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36837484

RESUMO

Background and Objectives: Difficult intubation, which may be encountered unexpectedly during anesthesia, can increase patients' morbidity and mortality. The McGRATH video laryngoscope is known to provide improved laryngeal visibility in patients with difficult or normal airways. The purpose of this study was to evaluate the efficacy of the McGRATH video laryngoscope for orotracheal intubation compared with that of conventional Macintosh laryngoscopes in simulated difficult airway scenarios. Materials and Methods: In this randomized controlled trial, patients who were scheduled for surgery under general anesthesia requiring orotracheal intubation were assigned to the Macintosh laryngoscope (n = 50) or McGRATH video laryngoscope (n = 45) groups. In this study, to create a simulated difficult airway condition, the subjects performed manual in-line stabilization and applied a soft cervical collar. The primary outcome was the rate of successful intubation within 30 s. The time required for an intubation, glottis grade, intubation difficulty scale (IDS score), the subjective ease of intubation, and optimal external laryngeal manipulation (OLEM) were evaluated. In addition, complications caused by each blade were investigated. Results: The intubation success rate within 30 s was not significantly different between the two groups (44 (88.0%) vs. 36 (80.0%), p = 0.286). The glottic grade was better in the McGRATH group than in the Macintosh group (p = 0.029), but neither the intubation time (26.3 ± 8.2 s vs. 24.2 ± 5.0 s, p = 0.134) nor the rates of oral bleeding (2 (4.0%) vs. 0 (0.0%)) and tooth injury (0 (0.0%) vs. 1 (2.2%)) were significantly different between the two groups. Conclusions: The use of the McGRATH video laryngoscope did not improve the intubation success rate or shorten the intubation time. However, the McGRATH video laryngoscope provided a better glottis view than the conventional Macintosh laryngoscope in patients with a simulated difficult airway.


Assuntos
Laringoscópios , Humanos , Laringoscopia , Intubação Intratraqueal , Anestesia Geral
5.
Dermatol Ther ; 35(6): e15498, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388594

RESUMO

Current therapeutic agents for onychomycosis have limited efficacy or cause side effects. Recently, successful treatment using fractional CO2 lasers has been reported; however, the results are inconsistent. We analyzed the real-world effectiveness of a Fractional CO2 laser for the treatment of Onychomycosis A single-center retrospective chart review was conducted during January 2015-December 2018. Patients, diagnosed with onychomycosis through fungal culture and/or potassium hydroxide staining, underwent three or more fractional CO2 laser treatments and used topical antifungal agents. Treatment effects were assessed by using clinical images at 6, 12 months, and the last visit. Ninety-six patients were included; they underwent an average of 7.7 laser treatment sessions. Finally, 15 patients (15.6%) showed complete response (100% clearing of all nails), 24 patients (25%) showed partial response, and 57 patients (59.4%) showed no response (no 100% clearing of nails among all treated toenails per patient including mild improvement or temporary cosmetic improvement). Multivariable logistic regression analysis revealed longer disease duration (p = 0.006, OR = 1.16 [95% CI: 1.05-1.31]), patients with diabetes (p = 0.021, OR = 9.82 [95% CI: 1.75-94.01]) and fewer number of laser treatment sessions (p = 0.001, OR = 0.76 [95% CI: 0.64-0.89]) were significantly associated with non-response group. In conclusion, fractional CO2 laser with topical antifungal could be a safe alternative treatment in patients with onychomycosis, who are difficult to take oral antifungals.


Assuntos
Lasers de Gás , Onicomicose , Antifúngicos , Dióxido de Carbono/uso terapêutico , Terapia Combinada , Humanos , Lasers de Gás/efeitos adversos , Onicomicose/tratamento farmacológico , Onicomicose/terapia , Estudos Retrospectivos , Resultado do Tratamento
6.
Bioelectromagnetics ; 43(4): 268-277, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35476222

RESUMO

This study aimed to evaluate the effectiveness of using low-level, low-frequency pulsed electromagnetic field (LLLF_PEMF) stimulation to improve atopic dermatitis induced by 2,4-dinitrochlorobenzene (DNCB). Twenty 6-week-old hairless mice were randomly divided into Normal (n = 5), PEMF 15 Hz (n = 5), PEMF 75 Hz (n = 5), and Sham (n = 5) groups. Following the onset of atopic dermatitis symptoms, PEMF groups (15 and 75 Hz) were stimulated with LLLF_PEMF (15 mT) for 8 h per day for 1 week. Sensory evaluation analysis revealed a significant difference between the PEMF 15 Hz group and Sham group (P < 0.05), but these differences were not visually obvious. While both the PEMF and Sham groups had atopic dermatitis lesions, lesion size was significantly smaller in the two PEMF groups than in the Sham group (P < 0.001). Additionally, changes in epithelial thickness because of skin inflammation significantly decreased for both PEMF groups, compared with the Sham group (P < 0.001). In conclusion, these results suggest that PEMF stimulation in vivo triggers electro-chemical reactions that affect immune response. © 2022 Bioelectromagnetics Society.


Assuntos
Dermatite Atópica , Campos Eletromagnéticos , Animais , Camundongos , Dermatite Atópica/terapia , Campos Eletromagnéticos/efeitos adversos
7.
Am J Dermatopathol ; 44(2): 121-125, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34816803

RESUMO

ABSTRACT: Lennert lymphoma is a lymphoepithelioid variant of peripheral T-cell lymphoma (not otherwise specified) with characteristics that do not fit into other peripheral T-cell lymphoma categories. Lennert lymphoma is primarily a nodal disease, and skin involvement may be exhibited. Cutaneous manifestations in Lennert lymphoma are nonspecific and include erythematous papules, nodules, and small plaques. Histological examination of cutaneous involvement characteristically presents epithelioid histiocytes and atypical small lymphocytes around vessels or appendages. A lymph node (LN) biopsy is essential for Lennert lymphoma diagnosis. In Lennert lymphoma, immunohistochemistry of both LNs and the involved skin reveals T-cell marker positivity. Although most Lennert lymphoma cases present with a single-positive CD4/CD8 immunophenotype, few cases present with a double-positive CD4/CD8 immunophenotype. We report a case of a 54-year-old woman presenting with fever, chills, general weakness, and a skin rash of erythematous patches on the trunk, extremities, and buttocks. A skin biopsy of the buttocks revealed atypical lymphocytes around the dermal vessels. In immunohistochemistry, these atypical lymphocytes stained positive for CD3, CD4, CD8, and CD68 but negative for CD20, CD30, and granzyme B. Similarly, a biopsy of the axillary LN revealed numerous epithelioid cells with atypical lymphocytes, exhibiting positivity for CD3, CD4, CD8, and CD68 but negativity for CD20, CD30, and S-100. Ki-67 was overexpressed in both the skin and LN. The final diagnosis of the patient was Lennert lymphoma with cutaneous involvement and a rare double-positive CD4/CD8 immunophenotype. The patient was transferred to another hospital for chemotherapy as per her request.


Assuntos
Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Exantema/etiologia , Feminino , Humanos , Pessoa de Meia-Idade
8.
Int J Med Sci ; 18(10): 2117-2127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859518

RESUMO

Background: Assessment the depth of dexmedetomidine sedation using electroencephalographic (EEG) features can improve the quality of procedural sedation. Previous volunteer studies of dexmedetomidine-induced EEG changes need to be validated, and changes in bicoherence spectra during dexmedetomidine sedation has not been revealed yet. We aimed to investigate the dexmedetomidine-induced EEG change using power spectral and bicoherence analyses in the clinical setting. Patients and Methods: Thirty-six patients undergoing orthopedic surgery under spinal anesthesia were enrolled in this study. Dexmedetomidine sedation was conducted by the stepwise increase in target effect site concentration (Ce) while assessing sedation levels. Bispectral index (BIS) and frontal electroencephalography were recorded continuously, and the performance of BIS and changes in power and bicoherence spectra were analyzed with the data from the F3 electrode. Results: The prediction probability values for detecting different sedation levels were 0.847, 0.841, and 0.844 in BIS, 95% spectral edge frequency, and dexmedetomidine Ce, respectively. As the depth of sedation increased, δ power increased, but high ß and γ power decreased significantly (P <0.001). α and spindle power increased significantly under light and moderate sedation (P <0.001 in light vs baseline and deep sedation; P = 0.002 and P <0.001 in moderate sedation vs baseline and deep sedation, respectively). The bicoherence peaks of the δ and α-spindle regions along the diagonal line of the bicoherence matrix emerged during moderate and deep sedation. Peak bicoherence in the δ area showed sedation-dependent increases (29.93%±7.38%, 36.72%±9.70%, 44.88%±12.90%; light, moderate, and deep sedation; P = 0.008 and P <0.001 in light sedation vs moderate and deep sedation, respectively; P = 0.007 in moderate sedation vs deep sedation), whereas peak bicoherence in the α-spindle area did not change (22.92%±4.90%, 24.72%±4.96%, and 26.96%±8.42%, respectively; P=0.053). Conclusions: The increase of δ power and the decrease of high-frequency power were associated with the gradual deepening of dexmedetomidine sedation. The δ bicoherence peak increased with increasing sedation level and can serve as an indicator reflecting dexmedetomidine sedation levels.


Assuntos
Raquianestesia/métodos , Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Monitorização Neurofisiológica/métodos , Dor Processual/prevenção & controle , Adulto , Idoso , Estado de Consciência/efeitos dos fármacos , Monitores de Consciência , Sedação Profunda/métodos , Relação Dose-Resposta a Droga , Eletroencefalografia , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Monitorização Neurofisiológica/instrumentação , Procedimentos Ortopédicos/efeitos adversos , Dor Processual/etiologia , Adulto Jovem
9.
Cell Mol Life Sci ; 77(20): 4117-4131, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31822965

RESUMO

Paralog factors are usually described as consolidating biological systems by displaying redundant functionality in the same cells. Here, we report that paralogs can also cooperate in distinct cell populations at successive stages of differentiation. In mouse embryonic spinal cord, motor neurons and V2 interneurons differentiate from adjacent progenitor domains that share identical developmental determinants. Therefore, additional strategies secure respective cell fate. In particular, Hb9 promotes motor neuron identity while inhibiting V2 differentiation, whereas Chx10 stimulates V2a differentiation while repressing motor neuron fate. However, Chx10 is not present at the onset of V2 differentiation and in other V2 populations. In the present study, we show that Vsx1, the single paralog of Chx10, which is produced earlier than Chx10 in V2 precursors, can inhibit motor neuron differentiation and promote V2 interneuron production. However, the single absence of Vsx1 does not impact on V2 fate consolidation, suggesting that lack of Vsx1 may be compensated by other factors. Nevertheless, Vsx1 cooperates with Chx10 to prevent motor neuron differentiation in early V2 precursors although these two paralog factors are not produced in the same cells. Hence, this study uncovers an original situation, namely labor division, wherein paralog genes cooperate at successive steps of neuronal development.


Assuntos
Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Interneurônios/fisiologia , Neurônios Motores/fisiologia , Medula Espinal/fisiologia , Fatores de Transcrição/genética , Animais , Diferenciação Celular/genética , Linhagem Celular , Regulação da Expressão Gênica no Desenvolvimento/genética , Células HEK293 , Humanos , Camundongos
10.
Am J Dermatopathol ; 43(4): 298-299, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33156024

RESUMO

ABSTRACT: Patients with eosinophilic pustular folliculitis (EPF), a sterile eosinophilic infiltration of hair follicles, often present with papulopustules that tend to form annular plaques. Histopathologic examination revealed eosinophilic infiltration around the pilosebaceous units and eosinophilic microabscess formation. Although the pathogenesis of EPF is unknown, T-helper type 2 immune responses were suggested to be important based on their stimulating effect on the sebaceous glands. Here, we report the first case of EPF associated with herpes zoster, indicating that herpes zoster and EPF are correlated with T-helper type 2 immune responses.


Assuntos
Eosinofilia/patologia , Foliculite/patologia , Herpes Zoster/patologia , Herpesvirus Humano 3/patogenicidade , Dermatopatias Vesiculobolhosas/patologia , Pele/patologia , Eosinofilia/tratamento farmacológico , Eosinofilia/imunologia , Eosinofilia/virologia , Feminino , Foliculite/tratamento farmacológico , Foliculite/imunologia , Foliculite/virologia , Herpes Zoster/imunologia , Herpes Zoster/virologia , Herpesvirus Humano 3/imunologia , Antagonistas dos Receptores Histamínicos/uso terapêutico , Interações Hospedeiro-Patógeno , Humanos , Pele/efeitos dos fármacos , Pele/imunologia , Pele/virologia , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Dermatopatias Vesiculobolhosas/imunologia , Dermatopatias Vesiculobolhosas/virologia , Esteroides/uso terapêutico , Células Th2/imunologia , Resultado do Tratamento , Adulto Jovem
11.
Hepatology ; 69(3): 1122-1134, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30230575

RESUMO

Regulation of the protein stability of epigenetic regulators remains ill-defined despite its potential applicability in epigenetic therapies. The histone H3-lysine 4-methyltransferase MLL4 is an epigenetic transcriptional coactivator that directs overnutrition-induced obesity and fatty liver formation, and Mll4+/- mice are resistant to both. Here we show that the E3 ubiquitin ligase UBE3A targets MLL4 for degradation, thereby suppressing high-fat diet (HFD)-induced expression of the hepatic steatosis target genes of MLL4. In contrast to Mll4+/- mice, Ube3a+/- mice are hypersensitive to HFD-induced obesity and fatty liver development. Ube3a+/-;Mll4+/- mice lose this hypersensitivity, supporting roles of increased MLL4 levels in both phenotypes of Ube3a+/- mice. Correspondingly, our comparative studies with wild-type, Ube3a+/- and Ube3a-/- and UBE3A-overexpressing transgenic mouse livers demonstrate an inverse correlation of UBE3A protein levels with MLL4 protein levels, expression of the steatosis target genes of MLL4, and their decoration by H3-lysine 4-monomethylation, a surrogate marker for the epigenetic action of MLL4. Conclusion: UBE3A indirectly exerts an epigenetic regulation of obesity and steatosis by degrading MLL4. This UBE3A-MLL4 regulatory axis provides a potential therapeutic venue for treating various MLL4-directed pathogeneses, including obesity and hepatic steatosis.


Assuntos
Fígado Gorduroso/genética , Regulação da Expressão Gênica/fisiologia , Histona-Lisina N-Metiltransferase/metabolismo , Hipernutrição/genética , Ubiquitina-Proteína Ligases/fisiologia , Animais , Feminino , Masculino , Camundongos
12.
Int J Med Sci ; 17(17): 2728-2734, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162800

RESUMO

Background: Pressure-controlled ventilation volume-guaranteed (PCV-VG) is being increasingly used for ventilation during general anesthesia. Carbon dioxide (CO2) pneumoperitoneum in the Trendelenburg position is routinely used during robot-assisted laparoscopic gynecologic surgery. Here, we hypothesized that PCV-VG would reduce peak inspiratory pressure (Ppeak), compared to volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV). Methods: In total, 60 patients were enrolled in this study and randomly assigned to receive VCV, PCV, or PCV-VG. Hemodynamic variables, respiratory variables, and arterial blood gases were measured in the supine position 15 minutes after the induction of anesthesia (T0), 30 and 60 minutes after CO2 pneumoperitoneum and Trendelenburg positioning (T1 and T2, respectively), and 15 minutes after placement in the supine position at the end of anesthesia (T3). Results: The Ppeak was higher in the VCV group than in the PCV and PCV-VG groups (p=0.011). Mean inspiratory pressure (Pmean) was higher in the PCV and PCV-VG groups than in the VCV group (p<0.001). Dynamic lung compliance (Cdyn) was lower in the VCV group than in the PCV and PCV-VG groups (p=0.001). Conclusion: Compared to VCV, PCV and PCV-VG provided lower Ppeak, higher Pmean, and improved Cdyn, without significant differences in hemodynamic variables or arterial blood gas results during robot-assisted laparoscopic gynecologic surgery with Trendelenburg position.


Assuntos
Acidose Respiratória/diagnóstico , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Laparoscopia/efeitos adversos , Respiração Artificial/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Acidose Respiratória/etiologia , Acidose Respiratória/fisiopatologia , Acidose Respiratória/prevenção & controle , Adulto , Pressão Atrial , Gasometria , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Humanos , Capacidade Inspiratória , Laparoscopia/métodos , Masculino , Pressões Respiratórias Máximas , Pessoa de Meia-Idade , Pneumoperitônio Artificial/efeitos adversos , Pneumoperitônio Artificial/métodos , Mecânica Respiratória/fisiologia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Adulto Jovem
13.
Development ; 143(20): 3763-3773, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27578785

RESUMO

Neurons in the hypothalamic arcuate nucleus relay and translate important cues from the periphery into the central nervous system. However, the gene regulatory program directing their development remains poorly understood. Here, we report that the LIM-homeodomain transcription factor Isl1 is expressed in several subpopulations of developing arcuate neurons and plays crucial roles in their fate specification. Mice with conditional deletion of the Isl1 gene in developing hypothalamus display severe deficits in both feeding and linear growth. Consistent with these results, their arcuate nucleus fails to express key fate markers of Isl1-expressing neurons that regulate feeding and growth. These include the orexigenic neuropeptides AgRP and NPY for specifying AgRP-neurons, the anorexigenic neuropeptide αMSH for POMC-neurons, and two growth-stimulatory peptides, growth hormone-releasing hormone (GHRH) for GHRH-neurons and somatostatin (Sst) for Sst-neurons. Finally, we show that Isl1 directly enhances the expression of AgRP by cooperating with the key orexigenic transcription factors glucocorticoid receptor and brain-specific homeobox factor. Our results identify Isl1 as a crucial transcription factor that plays essential roles in the gene regulatory program directing development of multiple arcuate neuronal subpopulations.


Assuntos
Núcleo Arqueado do Hipotálamo/embriologia , Núcleo Arqueado do Hipotálamo/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Fatores de Transcrição/metabolismo , Proteína Relacionada com Agouti/genética , Proteína Relacionada com Agouti/metabolismo , Animais , Imunoprecipitação da Cromatina , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Células HEK293 , Humanos , Imuno-Histoquímica , Imunoprecipitação , Proteínas com Homeodomínio LIM/genética , Camundongos , Gravidez , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética
14.
Development ; 143(10): 1721-31, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26965372

RESUMO

LIM homeodomain factors regulate the development of many cell types. However, transcriptional coactivators that mediate their developmental function remain poorly defined. To address these, we examined how two related NLI-dependent LIM complexes, which govern the development of spinal motor neurons and V2a interneurons, activate the transcription in the embryonic spinal cord. We found that single-stranded DNA-binding proteins are recruited to these LIM complexes via NLI, and enhance their transcriptional activation potential. Ssdp1 and Ssdp2 (Ssdp1/2) are highly expressed in the neural tube and promote motor neuron differentiation in the embryonic spinal cord and P19 stem cells. Inhibition of Ssdp1/2 activity in mouse and chick embryos suppresses the generation of motor neurons and V2a interneurons. Furthermore, Ssdp1/2 recruit histone-modifying enzymes to the motor neuron-specifying LIM complex and trigger acetylation and lysine 4 trimethylation of histone H3, which are well-established chromatin marks for active transcription. Our results suggest that Ssdp1/2 function as crucial transcriptional coactivators for LIM complexes to specify spinal neuronal identities during development.


Assuntos
Cromatina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Neurônios/metabolismo , Medula Espinal/citologia , Ativação Transcricional/genética , Sequência de Aminoácidos , Animais , Padronização Corporal , Embrião de Galinha , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Embrião de Mamíferos/metabolismo , Humanos , Interneurônios/metabolismo , Camundongos , Neurônios Motores/citologia , Neurônios Motores/metabolismo , Mutação/genética , Neurônios/citologia , Ligação Proteica/genética , Ratos , Medula Espinal/embriologia , Medula Espinal/metabolismo , Transativadores/metabolismo
15.
J Cutan Pathol ; 46(3): 221-225, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30499160

RESUMO

Multinucleate cell angiohistiocytoma (MCAH) is a rare cutaneous disease entity characterized by multiple red-to-brown or violaceous papules usually located on the acral regions, such as the face and the distal arms and legs. It affects elderly women more than men and rarely occurs at a young age. The exact pathogenic mechanism of MCAH is not yet clearly understood. We report an exceptionally rare case of a 14-year-old boy who presented with multiple asymptomatic erythematous papules and a single flat brownish plaque on the left chest. The brownish plaque lesion histologically showed proliferation of dilated small vessels in the upper-mid dermis and numerous oddly shaped multinucleate cells intermingled with lymphocytes and macrophages. The erythematous papules also showed dilated small vessels in the upper-mid dermis and multiple interstitial histiocytic infiltrations, but no multinucleate cells were detected. In immunohistochemistry studies, CD68 and vimentin staining were positive for both specimens. Based on the clinicopathological findings and immunohistochemistry studies, MCAH was diagnosed. To the best of our knowledge, this is the first case report of MCAH occurring in young age and showing two different clinical and histological phases at the same time.


Assuntos
Histiocitoma Fibroso Benigno/patologia , Neoplasias Cutâneas/patologia , Adolescente , Humanos , Masculino
17.
BMC Anesthesiol ; 19(1): 133, 2019 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351445

RESUMO

BACKGROUND: During lumbar spine surgery, patients are placed in the prone position for surgical access. The prone position has various effects on cardiac and pulmonary function, including a decreased cardiac index (CI), decreased dynamic lung compliance (Cdyn), and increased peak inspiratory pressure (Ppeak). In this study, we compared the volume-controlled ventilation mode (VCV) and pressure-controlled ventilation with volume guaranteed mode (PCV-VG) based on hemodynamic and pulmonary variables in the prone position during lumbar spine surgery. METHODS: Thirty-six patients scheduled for lumbar spine surgery in the prone position were enrolled in this prospective, randomized clinical trial. The patients were randomly assigned to receive VCV or PCV-VG. Hemodynamic variables, respiratory variables, and arterial blood gases were measured in the supine position 15 min after the induction of anesthesia, 15 min after placement in the prone position, 30 min after placement in the prone position, and 15 min after placement in the supine position at the end of anesthesia. RESULTS: The hemodynamic variables and arterial blood gas results did not differ significantly between the two groups. Lower Ppeak values were observed in the PCV-VG group than in the VCV group (p = 0.045). The Cdyn values in the VCV group were lower than those in the PCV-VG group (p = 0.040). CONCLUSION: PCV-VG led to lower Ppeak and improved Cdyn values compared with VCV, showing that it may be a favorable alternative mode of mechanical ventilation for patients in the prone position during lumbar spine surgery. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (NCT03571854). The initial registration date was 6/18/2018.


Assuntos
Vértebras Lombares/cirurgia , Decúbito Ventral , Respiração Artificial/métodos , Adulto , Gasometria , Débito Cardíaco , Feminino , Frequência Cardíaca , Humanos , Capacidade Inspiratória , Complacência Pulmonar , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
J Korean Med Sci ; 34(20): e151, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31124327

RESUMO

BACKGROUND: Most depth of anesthesia (DOA) monitors rely on the temporal characteristics of a single-channel electroencephalogram (EEG) and cannot provide spatial or connectivity information. Phase lag entropy (PLE) reflects DOA by calculating diverse connectivity from temporal patterns of phase relationships. The aim of this study was to compare the performance of PLE and bispectral index (BIS) monitors for assessing DOA during anesthesia induction, nerve integrity monitoring (NIM), and anesthesia emergence. METHODS: Thirty-five patients undergoing elective thyroid surgery with recurrent laryngeal nerve NIM received propofol and remifentanil via target-controlled infusion. After applying PLE and BIS monitors, propofol infusion was initiated at a calculated effect site concentration (Ce) of 2 µg/mL and then increased in 1-µg/mL Ce increments. After propofol Ce reached 5 µ/mL, a remifentanil infusion was begun, and anesthesia induction was considered complete. During NIM, PLE and BIS values were compared at a specific time points from platysma muscle exposure to subcutaneous tissue closure. PLE and BIS values were recorded continuously from preanesthetic state to full recovery of orientation; bias and limits of agreement between monitors were calculated. RESULTS: PLE and BIS values decreased progressively with increasing propofol Ce during anesthetic induction and increased by stages during emergence. The prediction probabilities of PLE and BIS for detecting propofol Ce changes were 0.750 and 0.756, respectively, during induction and 0.749 and 0.746, respectively, during emergence. No aberrant PLE or BIS values occurred during NIM. Correlation coefficients for BIS and PLE were 0.98 and 0.92 during induction and emergence, respectively. PLE values were significantly higher than BIS values at full recovery of orientation. Estimated bias between monitors was -4.16 ± 8.7, and 95% limits of agreement were -21.21 to 12.89. CONCLUSION: PLE is a reasonable alternative to BIS for evaluating consciousness and DOA during general anesthesia and during NIM. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003490.


Assuntos
Anestésicos Intravenosos/administração & dosagem , Monitores de Consciência , Propofol/administração & dosagem , Glândula Tireoide/cirurgia , Adulto , Anestesia Geral , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Nanosci Nanotechnol ; 18(3): 2117-2120, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29448725

RESUMO

We present a light trapping structure consisting of gold and silver (AuAg) bimetallic non-alloyed nanoparticles (BNNPs) on a silicon dioxide (SiO2) spacer layer over crystalline silicon (c-Si) film, designed to improve the absorption of thin-film c-Si solar cells. Prior to fabrication of the AuAg BNNPs on the SiO2 spacer layer, numerical investigations were carried out using electromagnetic field simulation following the finite-difference time-domain method. The hemispherical Au8Ag8 BNNPs were fabricated and deposited on a 15 nm-thick SiO2 spacer layer, which enhanced light trapping in the c-Si film over a broad wavelength range (450-1100 nm). Specifically, more than 85% of the incident light was absorbed in the c-Si film at 620 nm wavelengths due to the strong scattering of the Au8Ag8 BNNPs. To the best of our knowledge this is the first case presenting such a theoretical calculation and experimental study of the efficient light trapping by AuAg BNNPs on space layer for increasing the absorption in thin-film c-Si solar cells.

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