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As a byproduct of mitochondrial respiration or metabolism, reactive oxygen species (ROS) can act as a signaling molecule to activate NLR family pyrin domain containing 3 (NLRP3) inflammasome, thereby triggering immune response. NLRP3 inflammasome acts as a sensor of various danger signals and is central to the control of pyroptosis occurrence. Macrophage pyroptosis is closely related to atherosclerosis, arthritis, pulmonary fibrosis and other inflammatory diseases. Methylophiopogonanone A (MO-A) is a main homoisoflavonoid in Chinese herb Ophiopogonis Radix, which has antioxidant effect. However, it is not clear whether MO-A can alleviate macrophage pyroptosis by inhibiting oxidative stress. Here we have shown that MO-A increases the activities of superoxide dismutase (SOD) and catalase (CAT), inhibits the production of ROS, reduces the activation of NLRP3 inflammasome and the release of lactate dehydrogenase (LDH), and inhibits pyroptosis in macrophages induced by lipopolysaccharides (LPS) and adenosine triphosphate (ATP). These effects can be reversed by the ROS promoter H2O2. Therefore, MO-A can inhibit macrophage pyroptosis through the ROS/NLRP3 pathway and may be considered as a candidate drug for the treatment of inflammatory diseases.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Trifosfato de Adenosina , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
PURPOSE: Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography (MIBI-SPECT/CT) is a common technology used for primary hyperparathyroidism (PHPT) localization in clinical practice. However, the clinicopathologic factors affecting the accuracy of MIBI-SPECT/CT and the potential limitations remain unclear. METHODS: Retrospectively enrolled PHPT patients (n = 280) were analyzed from August 2017 to December 2019. RESULTS: Of 96 patients with PHPT (mean age, 54 years; 63 females), 17 had discordance between MIBI-SPECT/CT and intraoperative findings. Among the 17 patients with discordance, 58.8% had major discordance, which occurred in most patients with multigland disease (MGD). Compared with concordant patients, discordant patients exhibited increased frequencies of autoimmune thyroid disease (29.4% vs 10.1%, p = 0.035), MDG (41.2% vs 3.8%, p = 0.035), higher PTH (296 pg/mL vs 146 pg/mL; p = 0.012),and lower phosphorus levels (0.77 mmol/L vs 0.90 mmol/L; p = 0.024). MDG (odds ratio [OR], 16.95; 95% CI 2.10-142.86), parathyroid lesion size of 12 mm or less (OR, 6.93; 95% CI 1.41-34.10), and a PTH level higher than 192.5 pg/mL (OR, 12.66; 95% CI 2.17-71.43) were independently associated with discordant MIBI-SPECT/CT results. CONCLUSION: MGD was most strongly associated with discordance between MIBI-SPECT/CT and intraoperative findings followed by a PTH level higher than 192.5 pg/mL and parathyroid lesion size of 12 mm or less. Surgeons should recognize these potential limitations, which may improve the preoperative procedure by encouraging further localization imaging and promptly facilitate intraoperative troubleshooting.
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Hiperparatireoidismo Primário , Glândulas Paratireoides , Paratireoidectomia , Cuidados Pré-Operatórios/métodos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Cálcio/sangue , Correlação de Dados , Precisão da Medição Dimensional , Feminino , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/métodos , Paratireoidectomia/estatística & dados numéricos , Fósforo/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/normasRESUMO
Earthquakes are one of the most unpredictable natural disasters. A series of secondary and derived disaster events may occur afterwards and lead to even more consequences. In such situations, a seismic risk analysis that takes into account secondary and derived disaster events is vital in reducing the risks of such disasters. The absence of a holistic seismic risk analysis model-one that takes into account the derived disaster events-may mean that the serious consequences of the disaster chains set off by earthquakes are neglected. This article proposes a comprehensive seismic risk analysis that enables a better understanding of seismic disaster chains and rescue scenarios. The approach is based on a Bayesian network constructed using scenario-based methods. The final network structure is achieved by learning parameters. To determine the critical secondary disasters and the key emergency-response measures, probability adaptation and updating using the Bayesian model were performed. The practical application of the model is illustrated using the Wenchuan earthquake and the Jiuzhaigou earthquake in China. The two examples show that the model can be used to predict the potential effects of secondary disasters and the final seismic losses. The results of the model can help decisionmakers gain a comprehensive understanding of seismic risk and implement practical emergency-rescue measures to reduce risk and losses.
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Objective: To quantitatively analyze the reticulin fiber intensity density (RFD) in patients with myelodysplastic syndrome (MDS) by using the computer-aided grid point method, and preliminarily explore its correlation with the prognosis of MDS patients. Methods: Bone marrow (BM) slices from 32 primary MDS patients treated in Tongren Hospital Shanghai Jiao Tong University School of Medicine from February 2017 to December 2019 were observed. Images were taken by the optical microscope imaging system after the Gomori staining. The computer grid marking software was developed according to the principle of the mesh micrometer to assess RFD, meanwhile, the artificial semi-quantitative were used to assess the fibrosis of bone marrow. The co-relation between the above two methods was evaluated, and the relationship between RFD and prognosis of MDS patients were further investigated with Cox regression analysis. Results: Of the patients, there were 17 males and 15 females with a median age of 69 years (32-91 years). The RFD quantitatively analyzed by the computer-based method was positively correlated with the myelofibrosis grade by the artificial semi-quantitative analysis (r=0.497, P=0.004). The RFD in patients diagnosed with MDS complicated with excess blasts (MDS-EB) was significantly higher than that in the non-MDS-EB group((9.55%±0.75%) vs (1.71%±0.23%), P<0.001). Cox regression model analysis showed that the RFD of MDS patients had better prognostic value when compared with the artificial semi-quantitative analysis, which was also a poor prognostic factor (RR=1.337, 95%CI: 1.085-1.648, P=0.006). The overall survival (OS) of patients with RFD>5.54% was significantly shorter than that with RFD≤5.54% (P=0.001). The OS of MDS-EB patients with RFD>9.81% was significantly shorter than that in patients with RFD≤9.81% (P=0.003). Conclusion: Abnormal proliferative fibrosis of bone marrow is a potential high-risk factor for poor prognosis of MDS patients.
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Síndromes Mielodisplásicas , Mielofibrose Primária , Idoso , China , Feminino , Humanos , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
This paper describes a theory for mode locking and frequency comb generation by four-wave mixing in a semiconductor quantum-dot active medium. The derivation uses a multimode semiclassical laser theory that accounts for fast carrier collisions within an inhomogeneous distribution of quantum dots. Numerical simulations are presented to illustrate the role of active medium nonlinearities in mode competition, gain saturation, carrier-induced refractive index and creation of combination tones that lead to locking of beat frequencies among lasing modes in the presence of cavity material dispersion.
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AIMS: To assess the effects of 'clinical' and 'intensification inertia' by evaluating the impact of different intensification interventions on the probability of HbA1c goal attainment using real-world data. METHODS: Electronic health records (Cleveland Clinic, 2005-2016) were used to identify 7389 people with Type 2 diabetes mellitus and HbA1c ≥53 mmol/mol (≥7.0%), despite a stable regimen of two oral antihyperglycaemic drugs for ≥6 months. The participants were stratified by index HbA1c and analysed over a 6-month period for pharmacological intensification, and then for 12 additional months for HbA1c goal attainment (<53 mmol/mol). RESULTS: The probability of HbA1c goal attainment (Kaplan-Meier analysis) in the group with index HbA1c 53-63 mmol/mol (7.0-7.9%) was highest with the addition of oral antidiabetic drugs [57.3% (95% CI 52.1, 62.0)] or glucagon-like peptide-1 receptor agonists [56.7% (95% CI 40.4, 68.6)], in the 64-74 mmol/mol (8.0-8.9%) group with the addition of oral antidiabetic drugs [31.9% (95% CI 25.1, 38.1)] or insulin [30.6% (95% CI 18.3, 41.0)], and in the ≥75 mmol/mol (≥9.0%) group with the addition of glucagon-like peptide-1 receptor agonists [53.0% (95% CI 31.8, 67.6)] or insulin [43.5% (95% CI 36.4, 49.8)]. CONCLUSIONS: Numerical, but not statistically significant, differences in HbA1c goal attainment probability by type of intensification were most marked in people with the highest index HbA1c [≥75 mmol/mol (≥9.0%)]; in this group, injectable therapy showed trends toward greater glycaemic control benefits. Additional research into the phenomenon of intensification inertia is warranted.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico/métodos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Resultado do TratamentoRESUMO
Agricultural land use is typically associated with high stream nutrient concentrations and increased nutrient loading to lakes. For lakes, evidence for these associations mostly comes from studies on individual lakes or watersheds that relate concentrations of nitrogen (N) or phosphorus (P) to aggregate measures of agricultural land use, such as the proportion of land used for agriculture in a lake's watershed. However, at macroscales (i.e., in hundreds to thousands of lakes across large spatial extents), there is high variability around such relationships and it is unclear whether considering more granular (or detailed) agricultural data, such as fertilizer application, planting of specific crops, or the extent of near-stream cropping, would improve prediction and inform understanding of lake nutrient drivers. Furthermore, it is unclear whether lake N and P would have different relationships to such measures and whether these relationships would vary by region, since regional variation has been observed in prior studies using aggregate measures of agriculture. To address these knowledge gaps, we examined relationships between granular measures of agricultural activity and lake total phosphorus (TP) and total nitrogen (TN) concentrations in 928 lakes and their watersheds in the Northeastern and Midwest U.S. using a Bayesian hierarchical modeling approach. We found that both lake TN and TP concentrations were related to these measures of agriculture, especially near-stream agriculture. The relationships between measures of agriculture and lake TN concentrations were more regionally variable than those for TP. Conversely, TP concentrations were more strongly related to lake-specific measures like depth and watershed hydrology relative to TN. Our finding that lake TN and TP concentrations have different relationships with granular measures of agricultural activity has implications for the design of effective and efficient policy approaches to maintain and improve water quality.
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Lagos , Fósforo , Agricultura , Teorema de Bayes , China , Monitoramento Ambiental , Nitrogênio/análise , Fósforo/análiseRESUMO
Objective: To explore the feasibility of short-term efficacy prognosis prediction model for HCC patients undergoing transcatheter arterial chemoembolization (TACE) based on MRI-based radiomics technique. Methods: A total of 123 patients with liver cancer who received TACE treatment in Lishui Central Hospital from June 2016 to July 2018 were retrospectively collected, including 90 males and 33 females, with an average age of 24-83 (58±10) years. All the patients were pathologically confirmed as hepatocellular carcinoma and underwent MRI scan before surgery.All patients were followed up 3-4 months after TACE, and further divided into training group (n=85, 42 of which were effective and 43 cases were ineffective) and the validation group (n=38, 19 of which were effective and 19 were ineffective) according to the modified response evaluation criteria in solid tumors (mRECIST). There was no statistical difference in the general information between the two groups of patients, which was comparable. Then, preoperative T(2)WI images were used for radiomics analysis, texture parameters were screened based on R language, and short-term efficacy prediction model of TACE for training group and verification group was constructed. Results: T(2)WI image analysis of each patient received 396 different texture parameters, and further used Lasso dimensionality reduction and 10 times cross-validation screening to obtain 5 characteristic texture parameters, specifically stdDeviation, ClusterProminence_angle135_offset4, Correlation_angle135_offset4, Inertia_angle135_offset4, InverseDifferenceMoment_angle45_offset4. According to the above five texture parameters and their corresponding coefficient values, the corresponding radiomics scores (Radscore) were calculated, and the prediction models of the training group and the verification group were further constructed.It was found that the area under the ROC curve of the training group was 0.812 (95%CI: 0.722-0.901), the sensitivity and specificity were 83.7% and 69.0%, respectively. The area under the ROC curve of the validation group was 0.801 (95%CI:0.654-0.947), and the sensitivity and specificity were 89.5% and 63.2%, respectively. Conclusion: The constructed TACE prediction model in the present study has high prediction accuracy, sensitivity and specificity.The short-term efficacy prognosis prediction model for HCC based on MRI is constructed, stable and reliable.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Feminino , Humanos , Idioma , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Objective: To investigate the clinicopathological features and outcome of gastroenteropancreatic high-grade neuroendocrine tumors. Methods: A total of 60 gastroenteropancreatic high-grade neuroendocrine tumors were collected from January 1st, 2013 to December 31th, 2018 at Fudan University Shanghai Cancer Center, with available pathology databases and clinic follow-up information. At the same time, 157 cases of gastrointestinal pancreatic neuroendocrine neoplasm (NEN) diagnosed at the hospital in 2018 were collected and the incidence of NEN at all grades was compared. Results: There were 32 males and 28 females, aged 13-80 years (mean 54 years). Pancreas primary was the most common (48%, 29/60). Nodal metastatic rate was 9/16 and distant metastatic rate was 41%(18/44). Liver was the most common site of metastasis. Among all the gastroenteropancreatic neuroendocrine neoplasms diagnosed in the hospital in 2018, the incidence of high-grade neuroendocrine tumors was the lowest (7%, 11/157). High-grade neuroendocrine tumors had typical pathologic features of well-differentiated/moderate neuroendocrine tumors, but with significant differences in mitotic rates. By immunohistochemical staining, most of the tumors expressed neuroendocrine markers and somatostatin receptor 2 was positive in 60% (12/20) of the cases. The average Ki-67 index was 30%-40%, and there was significant difference between cases (18%-80%). The overall survival of high-grade neuroendocrine tumors was 43 months, and the disease-free survival was 12 months. Conclusions: High-grade neuroendocrine tumor is a rare group of neuroendocrine tumors, with unique clinicopathological features and good prognosis. Pathological classification and grading of gastroenteropancreatic neuroendocrine neoplasms can help clinicians to select appropriate treatment and accurately evaluate prognosis.
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Tumores Neuroendócrinos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Neoplasias Intestinais , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Pancreáticas , Estudos Retrospectivos , Organização Mundial da Saúde , Adulto JovemRESUMO
The linewidth enhancement factor α is a key parameter determining the spectral and dynamical behavior of semiconductor lasers. Here, we propose and demonstrate a method for determining this parameter based on a direct measurement of variations in the laser gain and emission spectrum when subject to delayed optical feedback. We then use our approach to determine the pump current dependent linewidth enhancement factor of a high-ß quantum dot micropillar laser. The validity of our approach is confirmed comparing it to two conventional methods, one based on the comparison of the linewidths above and below threshold and the other based on injection locking properties. Furthermore, the pump power dependence of α is quantitatively described by simulations based on a quantum-optical model.
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Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433). INTRODUCTION: Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients. METHODS: Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. All analyses were performed with STATA 12.0 and R software (Version 3.4.4). We estimated the risk ratio (RR) and 95% confidence interval (CI) by combining RRs for fracture effects of included trials. RESULTS: There were 54 eligible random control trials (RCTs) with 49,602 participants, including 28,353 patients treated with GLP-1 RAs. Relative to placebo, exenatide (RR, 0.17; 95% CI 0.03-0.67) was associated with lowest risk of fracture among other GLP-1 RAs. Exenatide had the highest probability to be the safest option with regard to the risk of fracture (0.07 ), followed by dulaglutide (1.04%), liraglutide (1.39%), albiglutide (5.61%), lixisenatide (8.07%), and semaglutide (18.72%). A statistically significant inconsistency was observed in some comparisons. CONCLUSION: The Bayesian network meta-analysis suggests that GLP-1 RAs were associated with a decreased bone fracture risk compared to users of placebo or other anti-hyperglycemic drugs in type 2 diabetes mellitus patients, and exenatide is the best option agent with regard to the risk of fracture.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Exenatida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Teorema de Bayes , Diabetes Mellitus Tipo 2/complicações , Humanos , Fraturas por Osteoporose/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We report lasing from nonpolar p-i-n InGaN/GaN multi-quantum well core-shell single-nanowire lasers by optical pumping at room temperature. The nanowire lasers were fabricated using a hybrid approach consisting of a top-down two-step etch process followed by a bottom-up regrowth process, enabling precise geometrical control and high material gain and optical confinement. The modal gain spectra and the gain curves of the core-shell nanowire lasers were measured using micro-photoluminescence and analyzed using the Hakki-Paoli method. Significantly lower lasing thresholds due to high optical gain were measured compared to previously reported semipolar InGaN/GaN core-shell nanowires, despite significantly shorter cavity lengths and reduced active region volume. Mode simulations show that due to the core-shell architecture, annular-shaped modes have higher optical confinement than solid transverse modes. The results show the viability of this p-i-n nonpolar core-shell nanowire architecture, previously investigated for next-generation light-emitting diodes, as low-threshold, coherent UV-visible nanoscale light emitters, and open a route toward monolithic, integrable, electrically injected single-nanowire lasers operating at room temperature.
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Gálio/química , Índio/química , Lasers , Nanofios/química , Nitrogênio/química , Luz , Nanocompostos/química , Nanotecnologia , Tamanho da Partícula , Semicondutores , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
OBJECTIVE: To investigate emergency room (ER) revisits and hospital readmissions following adenotonsillectomy (T&A) in children with sleep-disordered breathing (SDB), and correlations between SDB severity and ER revisits. DESIGN: Retrospective chart review study. SETTING: Tertiary referral centre. PARTICIPANT: 610 consecutive children underwent T&A for treating SDB. MAIN OUTCOME MEASURES: Sleep-disordered breathing severity was defined according to the apnoea-hypopnoea index (AHI) (primary snoring = AHI < 1; mild = AHI 1-5; moderate = AHI 5-10; and severe = AHI > 10). Revisit and readmission patterns within 30 days of the surgery were extracted and analysed. RESULTS: Of these children (mean age = 7.2 years; males = 72%), 49 (8.0%) had first ER revisit, nine (1.5%) had second ER revisits, and one (0.2%) had third ER revisits. Reasons for ER revisits were bleeding related (46%) or non-bleeding related (54%). The timing for revisits was 6.9±1.9 postoperative days for bleeding-related revisits and 9.3±10.0 days for non-bleeding-related revisits. Treatment strategies during these revisits were treat and release in 44 children (74.6%), admission for observation in eight children (13.5%), and admission for surgery in seven children (11.9%). The incidence of ER revisit and hospital readmission was similar among children with all levels of SDB severity. Multivariable logistic regression analysis showed that young children (<3 years) experienced an increased risk of non-bleeding-related revisits (odds ratio [OR] = 4.1). CONCLUSIONS: Children with severe SDB do not experience increased risks of revisit or readmission; however, young children are at increased risk of non-bleeding-related revisits.
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Adenoidectomia/métodos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Síndromes da Apneia do Sono/cirurgia , Tonsilectomia/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Readmissão do Paciente/tendências , Polissonografia , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico , Taiwan/epidemiologiaRESUMO
Inhalation injury from exposure to fire smoke is one of the causes of burn-related death. In this study, a realistic three-dimensional human upper airway model was built from magnetic resonance imaging (MRI) scanned images, including the nasal, oral, pharynx, larynx, trachea and part of the first generation of the tracheobronchial tree, as well as a tissue region from the pharynx to the upper bronchi. The Transition Shear Stress Transport (SST-transition) turbulence model, Pennes bioheat transfer equation, convective boundary conditions and a Lagrangian frame were applied and verified with experimental measurements to simulate the airflow fields, temperature distributions and particle deposition in the human airway model. The effects of flow rate, inhalation temperature and particle diameter were studied. It showed that the oral cavity is more likely to be affected by the inlet air conditions. The mucosa in the oral, pharynx and larynx are more likely to cause the thermal injury. The inspiration flow rate significantly influences the airflow fields, temperature distributions and particle deposition fraction interior of the human upper airway model, especially in the pharynx-larynx region. The rising flow rate, inhalation air temperature and particle diameter all contribute to boosting the total deposition fraction in the model. The heated particles with a higher temperature are more likely to be deposited in the oral cavity and the influence of the inlet temperature has a minor influence in the case of a bigger particle diameter.
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Queimaduras por Inalação/fisiopatologia , Modelos Biológicos , Ventilação Pulmonar , Respiração , Convecção , Temperatura Alta , Humanos , Material Particulado/efeitos adversosRESUMO
UNLABELLED: Increased neuropeptide Y (NPY) expression occurred in the glucocorticoid-induced osteoporotic skeleton. NPY knockout mice exhibited a minor response to the glucocorticoid-mediated exacerbation of bone accretion and fatty marrow pathogenesis. NPY deletion restored SITR1 signaling and enhanced PPARγ ubiquitination of bone tissue, an alternative strategy for ameliorating glucocorticoid-induced skeletal deterioration. INTRODUCTION: Glucocorticoid excess is observed to worsen the pathogenesis of osteoporosis and fatty marrow. This study was undertaken to investigate the contribution of neuropeptide Y (NPY) to glucocorticoid-induced bone loss and marrow adiposity. METHODS: NPY knockout and wild-type mice were administered methylprednisolone for four consecutive weeks. Bone mineral density, microarchitecture, and calcein-labeled mineral acquisition were quantified by µCT, dual energy X-ray absorptiometry, and histomorphometry. Expression of osteogenic and adipogenic markers and acetylation states of PPARγ were detected by RT-quantitative PCR, immunoprecipitation, and immunoblotting. RESULTS: High NPY levels were associated with glucocorticoid-induced trabecular bone deterioration and marrow fat accumulation. Mice lacking NPY had high bone mass concomitant with spacious trabecular and cortical bone microstructure. NPY deletion shielded skeletal tissues from the glucocorticoid-induced impediment of bone mass, trabecular morphometric characteristics, mineral accretion activity, and fatty marrow development. Ex vivo, NPY deficiency sustained osteogenic differentiation capacity and curtailed the glucocorticoid-mediated escalation of adipocyte formation reactions of primary bone-marrow mesenchymal cells. NPY deletion appeared to modulate Y1 and Y2 receptors, sirtuin 1, ERK, and p38 signaling pathways, an effect that facilitated hypoacetylation and ubiquitination of adipogenic transcription factor PPARγ in the skeletal tissues exposed to glucocorticoid stress. CONCLUSIONS: NPY mediates the glucocorticoid-induced disturbance of mineral accretion and marrow adipogenesis through post-translational modification of PPARγ. This study brings a new molecular insight into the disintegration of adipogenic and osteogenic activities within glucocorticoid-mediated osteoporotic skeletons. Control of NPY is an alternative strategy to ameliorate glucocorticoid-induced bone destruction and fatty marrow.
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Adiposidade , Medula Óssea/patologia , Neuropeptídeo Y/fisiologia , Osteogênese , Osteoporose/fisiopatologia , Animais , Glucocorticoides/efeitos adversos , Masculino , Camundongos , Camundongos Knockout , Neuropeptídeo Y/genética , Osteoporose/induzido quimicamenteRESUMO
OBJECTIVES: In contrast to obstructive sleep apnea (OSA), central sleep apnea (CSA) in obese children has received lesser attention. As pediatric CSA is more prevalent than expected and adversely impacts health, this study aims to elucidate the major factors associated with central apnea index (CAI) and compare CSA between obese and non-obese children. METHODS: Retrospective analysis was performed in a tertiary referral medical center. Children with sleep-disordered breathing (SDB) ranging from 2-18 years old were enrolled. All participants completed history taking, otolaryngological examination and overnight polysomnography. CSA was defined as having CAI exceeding 1 h(-1). CAI and the prevalence of CSA were analyzed in children of different age groups, weight statuses and adenotonsillar sizes. RESULTS: A total of 487 cases were included. The prevalence of CSA was 13.3% (65/487). CAI was negatively correlated with age (r=-0.32, P<0.001). Obese children had a significantly lower CAI than that of non-obese ones (0.20 ± 0.36 vs 0.48 ± 0.82 h(-1), P<0.001). Multiple linear regression analysis demonstrated a relationship between CAI, age and obesity as 'CAI=0.883-0.055 × Age -0.22 × (Obesity)'. CONCLUSIONS: In children with SDB, younger ones have a significantly higher CAI than older ones. Additionally, obese children had a lower CAI than non-obese ones.
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Tonsila Faríngea/patologia , Tonsila Palatina/patologia , Obesidade Infantil/fisiopatologia , Síndromes da Apneia do Sono/complicações , Apneia do Sono Tipo Central/fisiopatologia , Adolescente , Análise de Variância , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Obesidade Infantil/complicações , Obesidade Infantil/prevenção & controle , Polissonografia , Prevalência , Estudos Retrospectivos , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/etiologia , TonsilectomiaRESUMO
The changes in excitation dependence of efficiency with temperature are modeled for a wurtzite InGaN light-emitting diode. The model incorporates bandstructure changes with carrier density because of screening of quantum-confined Stark effect. Bandstructure is computed by solving Poisson and k · p equations in the envelope approximation. The information is used in a dynamical model for populations in momentum-resolved electron and hole states. Application of the approach shows the interplay of quantum-well and barrier emissions giving rise to shape changes in efficiency versus current density with changing temperature, as observed in some experiments.
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We investigate the dependence of the amplitude-phase coupling in quantum-dot (QD) lasers on the charge-carrier scattering timescales. The carrier scattering processes influence the relaxation oscillation parameters, as well as the frequency chirp, which are both important parameters when determining the modulation performance of the laser device and its reaction to optical perturbations. We find that the FM/AM response exhibits a strong dependence on the modulation frequency, which leads to a modified optical response of QD lasers when compared to conventional laser devices. Furthermore, the frequency response curve changes with the scattering time scales, which can allow for an optimization of the laser stability towards optical perturbations.
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OBJECTIVE: To investigate the impacts of body weight status on surgical outcomes and shifts of body weight status after adenotonsillectomy(T&A) in children with obstructive sleep apnea (OSA). METHODS: From 2009 to 2011, 161 children (mean age, 7.0 ± 3.4 years; 78% boys) were included. All the children had clinical symptoms and preoperative polysomnographic evaluations diagnosis of OSA. Children were divided into four weight status groups (underweight, normal weight, overweight and obese), based on age and gender corrected body mass index (BMI). RESULTS: Following T&A, the four different weight status groups significantly improved in apnea/hypopnea index (AHI) and minimum oxygen saturation. However, 49.1% of the children (79/161) had residual OSA (AHI ≥ 1). The incidence of residual OSA (AHI ≥ 1) in the obese group was 75%, which was significantly higher than the other three groups (P<0.01). Weight status changes after T&A were documented, and 54% (13/24) of the underweight children shifted to normal weight status within 6 months after surgery. CONCLUSION: Although sleep parameters improved in all weight statuses, obese children had a higher incidence of residual OSA postoperatively. About half of the underweight children shifted to normal weight status after T&A.