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1.
Nature ; 580(7801): 52-55, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32238942

RESUMO

Conservation laws are deeply related to any symmetry present in a physical system1,2. Analogously to electrons in atoms exhibiting spin symmetries3, it is possible to consider neutrons and protons in the atomic nucleus as projections of a single fermion with an isobaric spin (isospin) of t = 1/2 (ref. 4). Every nuclear state is thus characterized by a total isobaric spin T and a projection Tz-two quantities that are largely conserved in nuclear reactions and decays5,6. A mirror symmetry emerges from this isobaric-spin formalism: nuclei with exchanged numbers of neutrons and protons, known as mirror nuclei, should have an identical set of states7, including their ground state, labelled by their total angular momentum J and parity π. Here we report evidence of mirror-symmetry violation in bound nuclear ground states within the mirror partners strontium-73 and bromine-73. We find that a J π = 5/2- spin assignment is needed to explain the proton-emission pattern observed from the T = 3/2 isobaric-analogue state in rubidium-73, which is identical to the ground state of strontium-73. Therefore the ground state of strontium-73 must differ from its J π = 1/2- mirror bromine-73. This observation offers insights into charge-symmetry-breaking forces acting in atomic nuclei.

2.
Plant Mol Biol ; 114(3): 53, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714550

RESUMO

Plants have a variety of regulatory mechanisms to perceive, transduce, and respond to biotic and abiotic stress. One such mechanism is the calcium-sensing CBL-CIPK system responsible for the sensing of specific stressors, such as drought or pathogens. CBLs perceive and bind Calcium (Ca2+) in response to stress and then interact with CIPKs to form an activated complex. This leads to the phosphorylation of downstream targets, including transporters and ion channels, and modulates transcription factor levels and the consequent levels of stress-associated genes. This review describes the mechanisms underlying the response of the CBL-CIPK pathway to biotic and abiotic stresses, including regulating ion transport channels, coordinating plant hormone signal transduction, and pathways related to ROS signaling. Investigation of the function of the CBL-CIPK pathway is important for understanding plant stress tolerance and provides a promising avenue for molecular breeding.


Assuntos
Proteínas de Plantas , Transdução de Sinais , Estresse Fisiológico , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas/genética , Plantas/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Cálcio/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
3.
Gastroenterology ; 165(4): 874-890.e10, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37263309

RESUMO

BACKGROUND & AIMS: Transforming growth factor-b (TGFb) plays pleiotropic roles in pancreatic cancer, including promoting metastasis, attenuating CD8 T-cell activation, and enhancing myofibroblast differentiation and deposition of extracellular matrix. However, single-agent TGFb inhibition has shown limited efficacy against pancreatic cancer in mice or humans. METHODS: We evaluated the TGFß-blocking antibody NIS793 in combination with gemcitabine/nanoparticle (albumin-bound)-paclitaxel or FOLFIRINOX (folinic acid [FOL], 5-fluorouracil [F], irinotecan [IRI] and oxaliplatin [OX]) in orthotopic pancreatic cancer models. Single-cell RNA sequencing and immunofluorescence were used to evaluate changes in tumor cell state and the tumor microenvironment. RESULTS: Blockade of TGFß with chemotherapy reduced tumor burden in poorly immunogenic pancreatic cancer, without affecting the metastatic rate of cancer cells. Efficacy of combination therapy was not dependent on CD8 T cells, because response to TGFß blockade was preserved in CD8-depleted or recombination activating gene 2 (RAG2-/-) mice. TGFß blockade decreased total α-smooth muscle actin-positive fibroblasts but had minimal effect on fibroblast heterogeneity. Bulk RNA sequencing on tumor cells sorted ex vivo revealed that tumor cells treated with TGFß blockade adopted a classical lineage consistent with enhanced chemosensitivity, and immunofluorescence for cleaved caspase 3 confirmed that TGFß blockade increased chemotherapy-induced cell death in vivo. CONCLUSIONS: TGFß regulates pancreatic cancer cell plasticity between classical and basal cell states. TGFß blockade in orthotropic models of pancreatic cancer enhances sensitivity to chemotherapy by promoting a classical malignant cell state. This study provides scientific rationale for evaluation of NIS793 with FOLFIRINOX or gemcitabine/nanoparticle (albumin-bound) paclitaxel chemotherapy backbone in the clinical setting and supports the concept of manipulating cancer cell plasticity to increase the efficacy of combination therapy regimens.


Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator de Crescimento Transformador beta/metabolismo , Antineoplásicos/uso terapêutico , Gencitabina , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Albuminas , Fatores de Crescimento Transformadores/uso terapêutico , Microambiente Tumoral , Neoplasias Pancreáticas
4.
Opt Express ; 32(9): 16132-16139, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859249

RESUMO

The nonlinear Schrödinger equation (NLSE) under nonlocal nonlinear media (NNM) is described and the approximate analytical solutions of the vector multipole solitons and vortex optical soliton clusters are obtained via the variational method. The results show that the structure of the optical solitons is determined by modulation depth and topological charge. In the propagation process, the spatial soliton has an observable rotation property. Under certain conditions, the rotating space modulated vortex optical solitons degenerate into circular symmetric vortex optical solitons. The results can be extended to other physical systems.

5.
Opt Express ; 32(1): 551-575, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175082

RESUMO

Silicon photonic ring resonator thermometers have been shown to provide temperature measurements with a 10 mK accuracy. In this work we identify and quantify the intrinsic on-chip impairments that may limit further improvement in temperature measurement accuracy. The impairments arise from optically induced changes in the waveguide effective index, and from back-reflections and scattering at defects and interfaces inside the ring cavity and along the path between light source and detector. These impairments are characterized for 220 × 500 nm Si waveguide rings by experimental measurement in a calibrated temperature bath and by phenomenological models of ring response. At different optical power levels both positive and negative light induced resonance shifts are observed. For a ring with L = 100 µm cavity length, the self-heating induced resonance red shift can alter the temperature reading by 200 mK at 1 mW incident power, while a small blue shift is observed below 100 µW. The effect of self-heating is shown to be effectively suppressed by choosing longer ring cavities. Scattering and back-reflections often produce split and distorted resonance line shapes. Although these distortions can vary with resonance order, they are almost completely invariant with temperature for a given resonance and do not lead to measurement errors in themselves. The effect of line shape distortions can largely be mitigated by tracking only selected resonance orders with negligible shape distortion, and by measuring the resonance minimum wavelength directly, rather than attempting to fit the entire resonance line shape. The results demonstrate the temperature error due to these impairments can be limited to below the 3 mK level through appropriate design choices and measurement procedures.

6.
Osteoporos Int ; 35(6): 951-969, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38300316

RESUMO

Fracture liaison services (FLS) have been proven clinically effective and cost-effective in preventing subsequent fractures among patients with an existing fragility fracture. Little is known about their monetary benefits such as their return on investment (ROI). This systematic review aimed to investigate the ROI of FLS and identify the FLS characteristics with better ROI. Studies on the cost-effectiveness of FLS published between January 2000 and December 2022 were searched from MEDLINE, EMBASE, PubMed, and Cochrane Central. Two independent reviewers conducted study selection and data extraction. ROI was calculated based on the difference between monetary benefits and FLS costs divided by the FLS costs. Subgroup analysis of ROI was performed across FLS types and FLS design details. A total of 23 FLS were included in this review. The majority of them were targeting patients aged over 50 years having fractures without identified sites. The mean ROI of these FLS was 10.49 (with a median ROI of 7.57), and 86.96% of FLS had positive ROI. FLS making treatment recommendations yielded the highest ROI (with a mean ROI of 18.39 and a median of 13.60). Incorporating primary care providers (with a mean ROI of 16.04 and a median of 13.20) or having them as program leaders (with a mean ROI of 12.07 and a median of 12.07) has demonstrated a high ROI. FLS for specific fracture sites had great monetary return. Intensive FLS such as type A and B FLS programs had higher ROI than non-intensive type C and D FLS. This review revealed a 10.49-fold monetary return of FLS. Identified characteristics contributing to greater economic return informed value-for-money FLS designs. Findings highlight the importance of FLS and the feasibility of expanding their contribution in mitigating the economic burden of osteoporotic fracture and are conducive to the promotion of FLS internationally.


Assuntos
Análise Custo-Benefício , Fraturas por Osteoporose , Humanos , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Prevenção Secundária/organização & administração , Prevenção Secundária/economia
7.
Phys Rev Lett ; 132(9): 092501, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489643

RESUMO

Three ΔI=1 bands with the πg_{9/2}⊗νg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.

8.
Phys Rev Lett ; 132(7): 072502, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38427897

RESUMO

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

9.
BMC Neurol ; 24(1): 145, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684956

RESUMO

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.


Assuntos
Cerebelo , Paralisia Cerebral , Estimulação Encefálica Profunda , Transtornos dos Movimentos , Humanos , Paralisia Cerebral/terapia , Paralisia Cerebral/fisiopatologia , Estimulação Encefálica Profunda/métodos , Criança , Adolescente , Adulto Jovem , Transtornos dos Movimentos/terapia , Cerebelo/diagnóstico por imagem , Masculino , Feminino , Adulto
10.
Ultrasound Obstet Gynecol ; 63(4): 481-488, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37820067

RESUMO

OBJECTIVE: Placental vascular reactivity (PlVR) indicates the ability of the placental vasculature to match blood supply to fetal demand. Many pregnancy disorders alter the characteristics of PlVR, resulting in suboptimal oxygen delivery, although current understanding is limited by the lack of non-invasive, repeatable methods to measure PlVR in utero. Our objective was to quantify PlVR by measuring the placental response to transient changes in maternal carbon dioxide (CO2) using blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI). We hypothesized that PlVR will increase with gestational age to meet the changing demands of a growing fetus, and that PlVR will be driven by a maternal response to changes in CO2 concentration. METHODS: This was a cross-sectional study of 35 women with a healthy singleton pregnancy, of whom 31 were included in the analysis. The median gestational age was 32.6 (range, 22.6-38.4) weeks. Pregnant women were instructed to follow audiovisual breathing cues during a MRI scan. Maternal end-tidal CO2 (EtCO2) was measured concurrently with resting placental BOLD MRI for a total of 7-8 min. Preprocessing of magnetic resonance images consisted of manual delineation of placental anatomy and motion correction. In each placental voxel, vascular reactivity was computed using a coherence-weighted general linear model between MRI signal and EtCO2 stimulus. Global PlVR was computed as the mean of voxel-wise PlVR values across the placenta. RESULTS: PlVR, quantified by the placental response to induced, transient changes in maternal CO2, was consistently measured in utero using BOLD MRI. PlVR increased non-linearly with advancing gestational age (P < 0.001) and was higher on the fetal side of the placenta. PlVR was associated positively with fetal brain volume after accounting for gestational age. PlVR did not show any significant associations with maternal characteristics. CONCLUSIONS: We present, for the first time, a non-invasive paradigm to quantify PlVR in ongoing human pregnancies without the use of exogenous gases or contrast agents. Our findings suggest that PlVR is driven by a fetal response to changes in maternal CO2. Ease of translation to the clinical setting makes PlVR a promising biomarker for the identification and management of high-risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Placenta , Complicações na Gravidez , Gravidez , Feminino , Humanos , Lactente , Placenta/irrigação sanguínea , Estudos Transversais , Dióxido de Carbono , Imageamento por Ressonância Magnética/métodos , Oxigênio
11.
J Phys Chem A ; 128(11): 2191-2199, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38456900

RESUMO

Barrierless bond dissociation reactions play an important role in fuel combustion. In this work, the pressure-dependent dissociation rate constants of ethylamine (EA) are accurately determined using variable-reaction-coordinate variational transition-state theory combined with the system-specific quantum Rice-Ramsperger-Kassel method. Before the kinetics calculations, the performances of four density functional theory methods in describing the bond dissociation of EA are evaluated against the benchmark method, FIC-MRCISD(T)+Q/cc-pVTZ, and the MN15-L/cc-pVTZ method is the best choice. By comparison of the Gibbs free energies and the rate constants for the bond dissociation reactions of EA, ethanol, and propane, the influence of functional groups on the reaction kinetics is discussed. The kinetics calculations show that the dissociation rate constants of EA are sensitive to pressure at low pressures and high temperatures, and the dominant channel is the reaction that yields C2H5 and NH2 radicals. A literature combustion model of EA is updated with our calculations, and the satisfactory agreement between the model predictions and reported ignition delay times of EA suggests the reliability of our calculations.

12.
Clin Radiol ; 79(6): e842-e853, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582632

RESUMO

AIM: We design a feasibility study to obtain a set of metabolic-hemodynamic habitats for tackling tumor spatial metabolic patterns with hemodynamic information. MATERIALS AND METHODS: Preoperative data from 69 high-grade gliomas (HGG) patients with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to March 2020) after concurrent chemoradiotherapy (CCRT). Four vascular habitats were automatically segmented by multiparametric magnetic resonance imaging (MRI). The metabolic information, either at enhancing or edema tumor regions, was obtained by two neuroradiologists. The relative habitat volumes were used for weight estimation procedures for computing the coefficients of a linear regression model using weighted least squares (WLS) for metabolite semiquantifications (i.e. the Cho/NAA ratio and the Cho/Cr ratio) at vascular habitats. Multivariate Cox proportional hazard regression analyses are used to obtain the odds ratio (OR) and develop a nomogram using weighted estimators corresponding to each covariate derived from Cox regression coefficients. RESULTS: There was a strongly correlation between perfusion indexes and the Cho/Cr ratio (rCBV, r=0.71) or Cho/NAA ratio (rCBV, r=0.66) at high-angiogenic enhancing tumor habitats (HAT) habitat. Compared isocitrate dehydrogenase (IDH) mutation to their wild type, the IDH wild type had significantly decreased Cho/Cr ratio (IDH mutation: Cho/Cr ratio = 2.44 ± 0.33, IDH wildtype: Cho/Cr ratio = 2.66 ± 0.36, p=0.02) and Cho/NAA ratio (IDH mutation: Cho/Cr ratio = 4.59 ± 0.61, IDH wildtype: Cho/Cr ratio = 4.99 ± 0.66, p=0.022) at the HAT. The C-index for the median progression-free survival (PFS) prediction was 0.769 for the Cho/NAA nomogram and 0.747 for the Cho/Cr nomogram through 1000 bootstrapping validation. CONCLUSIONS: Our findings suggest that spatial metabolism combined with hemodynamic heterogeneity is associated with individual PFS to HGG patients post-CCRT.


Assuntos
Neoplasias Encefálicas , Estudos de Viabilidade , Glioma , Hemodinâmica , Intervalo Livre de Progressão , Humanos , Glioma/diagnóstico por imagem , Glioma/patologia , Glioma/terapia , Feminino , Masculino , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Pessoa de Meia-Idade , Hemodinâmica/fisiologia , Adulto , Estudos Prospectivos , Idoso , Imageamento por Ressonância Magnética Multiparamétrica/métodos
13.
Clin Radiol ; 79(1): e112-e118, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872027

RESUMO

AIM: To investigate the prognostic value of the composite posterior circulation Acute Stroke Prognosis Early Computed tomography (CT) Score (ASPECTS)-Collaterals (pcASCO) score, which combines diffusion-weighted imaging (DWI) posterior circulation ASPECTS (pcASPECTS) and the magnetic resonance angiography (MRA)-collateral circulation score at baseline among patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy. MATERIALS AND METHODS: Patients with acute posterior circulation ischaemic stroke who underwent mechanical thrombectomy were analysed retrospectively. The DWI-pcASPECTS and MRA-collateral circulation score before treatment and the modified Rankin Scale (mRS) at 90 days after treatment were used as the endpoints. An mRS ≤2 was defined as a good prognosis, and an mRS ≥3 was defined as a poor prognosis. Multivariate logistic regression was used to analyse independent predictors of functional outcome 90 days after mechanical thrombectomy. RESULTS: Mechanical thrombectomy was performed in 57 patients; 38 patients had a good prognosis, 19 patients had a poor prognosis, and 33 patients were successfully recanalised. Univariate logistic regression found that National Institute of Health Stroke Scale (NIHSS) score (OR: 1.18, p<0.001), pcASPECTS (OR: 1.91, p=0.028) and pcASCO score (OR: 0.51, p=0.001) were factors of good functional outcome. Receiver operating characteristic curve (ROC curve) analysis showed that the diagnostic efficiency of the NIHSS and pcASCO was better (AUC = 0.88, 0.83, p<0.05) than that of the pcASPECTS (AUC = 0.65). The prediction model was established by age, NIHSS, and pcASCO, and the diagnostic efficiency of the prediction model was better (AUC = 0.94). CONCLUSIONS: The composite MR-pcASCO score can be used as an important predictor of the prognosis of patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Prognóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , Trombectomia/métodos , Espectroscopia de Ressonância Magnética
14.
J Endocrinol Invest ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662129

RESUMO

PURPOSE: The study aimed to establish a mouse model of Graves' disease (GD) with Graves' orbitopathy (GO; GD + GO) that can represent the clinical disease characteristics. METHODS: A eukaryotic expression plasmid of insulin-like growth factor 1 receptor (IGF-1R) α subunit (pcDNA3.1/IGF-1Rα) and a thyrotropin receptor (TSHR) A subunit plasmid (pcDNA3.1/TSHR-289) were injected in female BALB/c mice followed by immediate electroporation to induce a GD + GO model. Grouping was performed according to the frequency of injection (2- to 4-week intervals) and type of injected plasmids: T: pcDNA3.1/TSHR-289( +), I: pcDNA3.1/IGF-1Rα( +), or co-injection T + I: pcDNA3.1/TSHR-289( +) and pcDNA3.1/IGF-1Rα( +). Serum TSH, T4, TSAb, TSBAb, body weight, and blood glucose levels were evaluated. Thyroid 99mTcO4- imaging and retrobulbar magnetic resonance imaging (MRI) were performed, and bilateral eye muscle volumes were measured. Immunohistochemistry and hematoxylin-eosin staining were performed on the relevant tissues, and semi-quantitative analysis was performed. RESULTS: A total of 60% of mice (3/5, one mouse died) in the T group developed GD + GO. In the T + I group, 83.3% of mice (5/6) developed GD + GO. Mice in the I group did not develop GD. Compared with the control group, serum T4, TSAb, and TSBAb of the mice in the GD + GO model groups were increased to varying degrees (P < 0.05), and serum TSH and body weight were significantly lower compared to the control group (P < 0.05). The thyroid uptake capacity of 99mTcO4- and the volume of eye muscle of mice in the GD + GO group were significantly higher compared to the control group (P < 0.05). The thyroid and retrobulbar muscles of these mice showed varying inflammatory infiltration and interstitial muscle edema. The severity of GD + GO in the co-injection group was not related to injection frequency; however, GD and ocular signs in co-injection mice were more severe compared to the T group. CONCLUSIONS: We successfully induced a GD + GO mouse model by a repeated co-injection of pcDNA3.1/IGF-1Rα and pcDNA3.1/TSHR-289 plasmids. Injection of pcDNA3.1/IGF-1Rα alone failed to induce GD. Co-injection of two plasmids induced more severe GD + GO than pcDNA3.1/TSHR-289( +) alone.

15.
Ann Vasc Surg ; 103: 1-8, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38301849

RESUMO

BACKGROUND: The extent of practice setting's influence on transcarotid artery revascularization (TCAR) outcomes is not yet established. This study seeks to assess and compare TCAR outcomes in academic and community-based healthcare settings. METHODS: Retrospective review of prospectively maintained, systemwide TCAR databases from 2 institutions was performed between 2015 and 2022. Patients were stratified based on the setting of surgical intervention (i.e., academic or community-based hospitals). Relevant demographics, medical conditions, anatomic characteristics, intraoperative and postoperative courses, and adverse events were captured for multivariate analysis. RESULTS: We identified 973 patients who underwent TCAR, 570 (58.6%) were performed at academic and 403 (41.4%) at community-based hospitals. An academic facility was defined as a designated teaching hospital with 24/7 service-line coverage by a trainee-led surgical team. Baseline comorbidity between cohorts were similar but cases performed at academic institutions were associated with increased complexity, defined by high cervical stenosis (P < 0.001), prior dissection (P < 0.01), and prior neck radiation (P < 0.001). Intraoperatively, academic hospitals were associated with longer operative time (67 min vs. 58 min, P < 0.001), higher blood loss (55 mLs vs. 37 mLs, P < 0.001), and longer flow reversal time (9.5 min vs. 8.4 min, P < 0.05). Technical success rate was not statistically different. In the 30-day perioperative period, we observed no significant difference with respect to reintervention (1.5% vs. 1.5%, P ≥ 0.9) or ipsilateral stroke (2.7% vs. 2.0%, P = 0.51). Additionally, no difference in postoperative myocardial infarction (academic 0.7% vs. community 0.2%, P < 0.32), death (academic 1.9% vs. community 1.4%, P < 0.57), or length of stay (1 day vs. 1 day, P < 0.62) was seen between the cohorts. CONCLUSIONS: Cases performed at academic centers were characterized by more challenging anatomy, more frequent cardiovascular risk factors, and less efficient intraoperative variables, potentially attributable to case complexity and trainee involvement. However, there were no differences in perioperative outcomes and adverse events between the cohorts, suggesting TCAR can be safely performed regardless of practice setting.


Assuntos
Centros Médicos Acadêmicos , Bases de Dados Factuais , Hospitais Comunitários , Complicações Pós-Operatórias , Humanos , Feminino , Masculino , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Fatores de Tempo , Fatores de Risco , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Medição de Risco , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Hospitais de Ensino , Doenças das Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade
16.
Public Health ; 227: 154-162, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38232563

RESUMO

OBJECTIVES: To determine the prevalence of cardiometabolic diseases (CMDs) among adults with abdominal obesity and to evaluate the necessity of differentiating severity of abdominal obesity. STUDY DESIGN: Cross-sectional study and prospective cohort study. METHODS: National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2020 were included for cross-sectional analyses. Class I, II and III abdominal obesity were created by dividing waist circumference within sex-specific abdominal obesity range into tertiles. Age-standardized prevalence of CMDs was estimated and differences by severity of abdominal obesity were compared using Poisson regressions. Prospective analyses were performed using NHANES data between 1988 and 2018 with linked mortality data. Cox proportional hazards models were used to assess the association between severity of abdominal obesity and mortality. RESULTS: Among 23,168 adults included (mean age: 47.8 years, 49.3% men), 13,307 (57.4%) had abdominal obesity. Among adults with abdominal obesity, the estimated prevalence of diabetes was 17.3% (95% confidence interval: 16.3%, 18.2%), hypertension 39.3% (38.2%, 40.3%), dyslipidemia 59.5% (58.0%, 61.1%), cardiovascular disease 9.0% (8.3%, 9.8%), chronic kidney disease 16.8% (15.9%, 17.7%) and non-alcoholic fatty liver disease 39.9% (38.4%, 41.4%). The estimated prevalence was 55.5% (53.8%, 57.2%) for having ≥2 CMDs. Compared with class I abdominal obesity, class III abdominal obesity was related to a 43%-184% higher prevalence of CMDs and a 44% higher risk of all-cause mortality. CONCLUSIONS: The prevalence of CMDs was high and multimorbidity of CMDs was common among US adults with abdominal obesity. The prevalence of CMDs and risk of mortality differed significantly by severity of abdominal obesity.


Assuntos
Doenças Cardiovasculares , Obesidade Abdominal , Adulto , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade Abdominal/epidemiologia , Estudos Prospectivos , Estudos Transversais , Inquéritos Nutricionais , Obesidade/epidemiologia , Doenças Cardiovasculares/epidemiologia , Prevalência , Fatores de Risco
17.
J Environ Manage ; 361: 121272, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38820790

RESUMO

Air pollution has been one of the biggest environmental challenges for cities in their pursuit of sustainability. The removal of air pollutants usually entails a cost that can negatively impact economic activities. Assessing urban environmental performance can offer valuable insights for cities to balance their economic production and environmental protection. This paper develops a novel approach to measuring environmental performance by using the Euclidean distance function. An appealing feature of this approach is its ability in endogenously allocating the optimization pathway to each emitter, thereby avoiding arbitrary estimation results and distorted managerial implications. We apply this approach to study the environmental performance of Chinese key environmental protection cities. We find the heterogeneity in performance estimates and endogenous optimization pathways. Prioritizing the reduction of a specific type of emissions while simultaneously increasing industrial output value seems to be the most appropriate objective for the majority of cities. Our study can serve as a basis for urban governments to pinpoint the underlying factors contributing to low urban environmental performance and establish diverse objectives for enhancing environmental performance.


Assuntos
Poluição do Ar , Cidades , China , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise , Conservação dos Recursos Naturais
18.
Br Poult Sci ; 65(2): 137-143, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265055

RESUMO

1. Two experiments were conducted to explore the effects of an exogenous sfericase protease on the apparent ileal nutrient digestibility of soybean meal (SBM) and rapeseed meal (RSM) in broiler chickens.2. In each experiment, a total of 256 sixteen-day-old male Cobb 500 broilers were fed one of four semi-purified experimental diets, comprising two different batches (A and B) of samples for either SBM (Exp. 1) or RSM (Exp. 2) without or with an exogenous sfericase (0 or 30,000 NFP/kg). Each experimental diet was fed to eight replicate pens of broiler chickens from 16 to 21 d of age (eight birds per cage), and ileal digesta were collected for measuring the digestibility coefficients.3. In Exp. 1, the amino acid digestibility was greater (P < 0.05) in SBM B compared with SBM A for Arg and Val, and a similar trend (P < 0.1) was observed for Tyr, Leu and Thr. Exogenous sfericase increased (P < 0.10) digestibility of most of amino acids except Gly, His and Trp. There was an interaction between SBM source and sfericase, whereby digestibility of P, N and Asp was increased by sfericase for SBM B but not for SBM A. In Exp. 2, there was no interaction (P > 0.05) between RSM source and sfericase for ileal nutrient digestibility. Digestibility was greater in RSM A compared to RSM B for all non-essential AA and most essential AA (except for Trp), while the reverse was noted for Ca and P (P < 0.05). Exogenous sfericase increased (P < 0.1) digestibility for all amino acids except Cys and Met.4. In conclusion, the current studies showed that both SBM and RSM batches influenced amino acid digestibility. Sfericase protease supplementation increased amino acid digestibility for both SBM and RSM. The digestibility effects were greater in the SBM batch with low digestibility for N and Asp which was in line with an increase in P digestibility.


Assuntos
Brassica napus , Brassica rapa , Serina Endopeptidases , Animais , Masculino , Aminoácidos/metabolismo , Brassica napus/metabolismo , Galinhas/metabolismo , Peptídeo Hidrolases/metabolismo , Farinha , Digestão , Dieta/veterinária , Brassica rapa/metabolismo , Íleo/metabolismo , Glycine max , Ração Animal/análise , Nutrientes , Fenômenos Fisiológicos da Nutrição Animal
19.
Br Poult Sci ; : 1-14, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916443

RESUMO

1. This study investigates the molecular mechanisms affecting brooding in Zhedong white geese by examining differences in reproductive endocrine levels, ovarian histology and transcriptomics.2. Twenty 18-month-old Zhedong white geese were selected to examine their ovaries using histological, biochemical, molecular biological, and high-throughput sequencing techniques during the laying and brooding periods.3. The results showed that the number of atretic follicles and apoptotic cells in the ovaries increased significantly (p < 0.05), the levels of follicle-stimulating hormone, luteinising hormone, gonadotropin-releasing hormone and oestradiol decreased significantly (p < 0.05), and the level of prolactin increased significantly (p < 0.01) during the brooding stage.4. In broody geese, the expression of CASP3, CASP9, P53, BAX, and Cyt-c were considerably higher (p < 0.05), but BCL2 expression was significantly lower (p < 0.05).5. In ovarian tissues, 260 differentially expressed lncRNAs, 13 differentially expressed miRNA and 60 differentially expressed mRNA were all discovered using transcriptome sequencing analysis. Functional enrichment analysis revealed that the differentially expressed mRNA and non-coding RNA target genes were primarily involved in ECM-receptor interaction, cell adhesion, cardiac muscle contraction, mTOR signalling, and the calcium signalling pathway.6. In conclusion, follicular atrophy and apoptosis occurred in the ovaries and serum reproductive hormone levels were significantly changed during the brooding period of Zhedong white geese. COL3A1, COL1A2, GRIA1, RNF152, miR-192, and miR-194 may be important candidates for the regulation of brooding behaviour, with the mTOR signalling pathway playing a key role.

20.
Br Poult Sci ; 65(3): 307-314, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38393940

RESUMO

1. Feathers are an important product from poultry, and the state of feather growth and development plays an important role in their economic value.2. In total, 120 eggs were selected for immunoblotting and immunolocalisation experiments of ERK and ß-catenin proteins in different developmental stages of goose embryos. The ERK protein was highly expressed in the early stage of goose embryo development, while ß-catenin protein was highly expressed in the middle stage of embryo development.3. The 120 eggs were divided into four treatment groups, including an uninjected group (BLANK), a group injected with 100 µl of cosolvent (CK), a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 5 mg/kg AZD6244 containing cosolvent (AZD5) and a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 15 mg/kg AZD6244 containing cosolvent (AZD15). The eggs were injected on the ninth day of embryonic development (E9). Samples were collected at E21.5 to observe feather width, feather follicle diameter, ERK and Wnt/ß-catenin pathway protein expression.4. The AZD5 and AZD15 doses were within the embryonic safety range compared to the BLANK and CK groups and had no significant effect on the survival rate and weight at the inflection point, but significantly reduced the feather width and feather follicle diameter (p < 0.05). The AZD6244 treatment inhibited ERK protein phosphorylation levels and blocked the Wnt/ß-catenin pathway, which in turn significantly down-regulated the expression levels of FZD4, ß-catenin, TCF4 and LEF1 (p < 0.05), with an inhibitory effect in the AZD15 group being more significant. The immunohistochemical results of ß-catenin and p-ERK were consistent with Western blot results.5. The small molecule inhibitor AZD6244 regulated the growth and development of feather follicles in goose embryos by the ERK and Wnt/ß-catenin pathways.


Assuntos
Plumas , Gansos , Via de Sinalização Wnt , Animais , Via de Sinalização Wnt/efeitos dos fármacos , Plumas/efeitos dos fármacos , Plumas/química , beta Catenina/metabolismo , beta Catenina/genética , Desenvolvimento Embrionário/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Proteínas Aviárias/metabolismo , Proteínas Aviárias/genética , Benzamidas , Fluorocarbonos
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