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1.
Am J Transplant ; 24(2S1): S534-S556, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38431366

RESUMO

This year's chapter on vascularized composite allograft (VCA) encompasses reviews of data collected from 2014 (when VCA was included in the Final Rule) through 2022. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and has remained consistent from the prior report. The data continue to be limited by sample size, with trends persistently demonstrating a predominance of White males in the young/middle-aged population as both donors and recipients for nonuterus VCA transplants, and White women younger than 35 years as the predominant recipients of uterus transplant. Similar to the 2021 report, there were only eight failed uterus grafts and one failed nonuterus VCA graft reported from 2014 through 2022. Standardization of definitions of success and failure as well as outcome measures for the different VCA types remain unmet needs in VCA transplantation.


Assuntos
Aloenxertos Compostos , Alotransplante de Tecidos Compostos Vascularizados , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Estados Unidos , Aloenxertos Compostos/transplante , Doadores de Tecidos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38741198

RESUMO

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

3.
Purinergic Signal ; 20(2): 115-125, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37246192

RESUMO

During the establishment of neuronal circuits, axons and dendrites grow and branch to establish specific synaptic connections. This complex process is highly regulated by positive and negative extracellular cues guiding the axons and dendrites. Our group was pioneer in describing that one of these signals are the extracellular purines. We found that extracellular ATP, through its selective ionotropic P2X7 receptor (P2X7R), negatively regulates axonal growth and branching. Here, we evaluate if other purinergic compounds, such as the diadenosine pentaphosphate (Ap5A), may module the dynamics of dendritic or axonal growth and branching in cultured hippocampal neurons. Our results show that Ap5A negatively modulates the dendrite's growth and number by inducing transient intracellular calcium increases in the dendrites' growth cone. Interestingly, phenol red, commonly used as a pH indicator in culture media, also blocks the P2X1 receptors, avoided the negative modulation of Ap5A on dendrites. Subsequent pharmacological studies using a battery of selective P2X1R antagonists confirmed the involvement of this subunit. In agreement with pharmacological studies, P2X1R overexpression caused a similar reduction in dendritic length and number as that induced by Ap5A. This effect was reverted when neurons were co-transfected with the vector expressing the interference RNA for P2X1R. Despite small hairpin RNAs reverting the reduction in the number of dendrites caused by Ap5A, it did not avoid the dendritic length decrease induced by the polyphosphate, suggesting, therefore, the involvement of a heteromeric P2X receptor. Our results are indicating that Ap5A exerts a negative influence on dendritic growth.


Assuntos
Trifosfato de Adenosina , Fosfatos de Dinucleosídeos , Receptores Purinérgicos P2 , Trifosfato de Adenosina/farmacologia , Receptores Purinérgicos P2/metabolismo , Neurônios/metabolismo , Dendritos/metabolismo , Hipocampo/metabolismo
4.
Photochem Photobiol Sci ; 23(5): 901-918, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38584224

RESUMO

Pd/ZnO nanocomposites were successfully synthesized by means of one and two pot synthesis and applied in the photodegradation of Rh6G. The nanocomposites were characterized by XRD, SEM, TEM, FTIR and micro-Raman spectroscopies. It was found the presence of PdZn2, PdO and agglomerated particles in the support surface for the Palladium-based nanocomposites fabricated by one-pot route; the two-step method allowed the formation of spherical Pd nanoparticles, with homogeneous distribution in the nanocomposite matrix, with an average size of 2.16 nm. The results show higher photocatalytic efficiency for the samples fabricated under the two-step approach compared to the one-pot synthesis. Based on experimental results, density functional theory (DFT) calculations were carried out to understand the enhancement photocatalytic of Pd/ZnO nanocomposites. To achieve it, the ZnO (001) and (101) surfaces were built and decorated by different Pd coverages. The theoretical results indicated two different photocatalytic mechanisms. In ZnO (001) case, the electrons flowed from surface to Pd, generating the superoxide radical anion (⋅O2-). Furthermore, the density of states of the ZnO (001) surface was modified by impurity Pd-d states at proximity to the conduction states, which may work as electron acceptors states. On the other hand, we found that the electrons flow from Pd to ZnO (101) surface, inducing the formation of ⋅OH and ⋅O2- for the degradation of Rh6G. The density of states of the ZnO (101) revealed a reduction in its bandgap, due to Pd-d states localized above valence states. Hence, our theoretical results suggest that the Pd-d states may facilitate the mobility of electrons and holes in (001) and (101) surfaces, respectively, reducing the rate of charge recombination.

5.
Nature ; 563(7731): 365-368, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30429552

RESUMO

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

6.
Appl Opt ; 63(13): 3600-3608, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856545

RESUMO

The generation of self-focusing beams of extreme ultraviolet (XUV) radiation using the focal cone high harmonic generation (FCHHG) technique is examined for high energy lasers. The FCHHG geometry is created by passing a focusing laser beam through a gas sheet prior to reaching focus and thus creating a converging beam of high harmonic radiation. This leads to a larger interaction area that increases the total area of XUV emission while not exceeding the saturation intensity of the target atoms or increasing the density of the atoms. Such a method allows for scaling of HHG to any incident laser power. An experiment was conducted demonstrating such scaling to incident 400 TW pulses, showing both the expected spectral signature of HHG and the converging cone of XUV radiation. It was found that this technique is very sensitive to spatial non-uniformity in the driving laser, which has become more prevalent in high energy laser systems.

7.
Occup Med (Lond) ; 74(3): 218-224, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38527057

RESUMO

BACKGROUND: Occupational footwear is intended to provide protection against the risks associated with work activities. The choice of footwear is complex due to the welfare, health and safety conditions of workers. AIMS: To identify the injuries and problems caused by occupational footwear through a systematic review of the existing literature. METHODS: A literature search was carried out in the Cumulative Index to Nursing and Allied Health Literature, Dialnet Plus, Pubmed, Scientific Electronic Library Online, Medline, Scopus and Web of Science databases over the period 2000-23, following the PRISMA Declaration guidelines. RESULTS: A total of 27 studies were included in the review. The results indicated that there is a wide variety of injuries caused by occupational footwear: from dermal injuries (e.g. calluses) and injuries to the nail apparatus to inflammatory pathologies such as plantar fasciitis or bursitis. In addition, inappropriate footwear can cause pain in the ankle and foot, knees, hips and lower back. Other results include the discomfort derived from the footwear itself. CONCLUSIONS: Inappropriate footwear can cause injuries to the foot and other related bone structures. Further studies are needed on the detection of foot injuries caused by occupational footwear and the levels of action at this level to improve the worker's health, the adaptability of the footwear to the wearer, and the worker's comfort and adherence to the footwear.


Assuntos
Traumatismos Ocupacionais , Sapatos , Humanos , Bursite/etiologia , Fasciíte Plantar/etiologia , Traumatismos do Pé/etiologia , Doenças Profissionais/etiologia , Traumatismos Ocupacionais/etiologia , Sapatos/efeitos adversos
8.
Rhinology ; 62(1): 2-12, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37814591

RESUMO

BACKGROUND: Dexmedetomidine has been shown to effectively control intraoperative bleeding and improve surgical field visualization. However, its value in endonasal surgeries remains a matter of debate. METHODOLOGY: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for studies comparing dexmedetomidine with placebo in endonasal surgeries. Outcomes included bleeding, operative time (OT), surgeon’s satisfaction, postoperative pain (POP), and nausea/vomiting (PONV). For statistical analysis, we used RevMan 5.4.1, and assessed heterogeneity with I2 statistics. RESULTS: We included a total of 1386 patients from 22 studies. In the placebo group, there was higher bleeding volume, whereas the dexmedetomidine group showed lower scores on the Fromme-Boezaart scale. Additionally, the surgeon satisfaction risk ratio (RR) increased, and OT was reduced in the dexmedetomidine group. The dexmedetomidine group had lower incidences of POP and PONV. CONCLUSIONS: In endonasal surgeries, dexmedetomidine was associated with improvements in surgical field visualization as evidenced by reduced intraoperative bleeding and postoperative morbidities.


Assuntos
Dexmedetomidina , Humanos , Dexmedetomidina/uso terapêutico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Suplementos Nutricionais
9.
Am J Transplant ; 23(2 Suppl 1): S523-S545, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-37132342

RESUMO

Year 2020 marked the first OPTN/SRTR Annual Data Report that included a chapter on vascularized composite allograft (VCA), which encompassed reviews of data collected between 2014 (when VCA was included in the Final Rule) and 2020. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and trended downward in 2021. While data continue to be limited by sample size, trends continue to show a predominance in White, young/middle-aged, male recipients. Similar to the 2020 report, eight uterus and one non-uterus VCA graft failures were reported from 2014 through 2021. Critical to advancement of VCA transplantation will be the standardization of definitions, protocols, and outcome measures for the different VCA types. Like intestinal transplants, it is likely that VCA transplants will be concentrated and performed at referral transplant centers.


Assuntos
Aloenxertos Compostos , Transplantes , Alotransplante de Tecidos Compostos Vascularizados , Pessoa de Meia-Idade , Masculino , Humanos , Estados Unidos , Aloenxertos Compostos/transplante
10.
J Neuroinflammation ; 20(1): 135, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264394

RESUMO

INTRODUCTION: Gut microbiota plays a critical role in the regulation of immune homeostasis. Accordingly, several autoimmune disorders have been associated with dysbiosis in the gut microbiota. Notably, the dysbiosis associated with central nervous system (CNS) autoimmunity involves a substantial reduction of bacteria belonging to Clostridia clusters IV and XIVa, which constitute major producers of short-chain fatty acids (SCFAs). Here we addressed the role of the surface receptor-mediated effects of SCFAs on mucosal T-cells in the development of CNS autoimmunity. METHODS: To induce CNS autoimmunity, we used the mouse model of experimental autoimmune encephalomyelitis (EAE) induced by immunization with the myelin oligodendrocyte glycoprotein (MOG)-derived peptide (MOG35-55 peptide). To address the effects of GPR43 stimulation on colonic TCRαß+ T-cells upon CNS autoimmunity, mucosal lymphocytes were isolated and stimulated with a selective GPR43 agonist ex vivo and then transferred into congenic mice undergoing EAE. Several subsets of lymphocytes infiltrating the CNS or those present in the gut epithelium and gut lamina propria were analysed by flow cytometry. In vitro migration assays were conducted with mucosal T-cells using transwells. RESULTS: Our results show a sharp and selective reduction of intestinal propionate at the peak of EAE development, accompanied by increased IFN-γ and decreased IL-22 in the colonic mucosa. Further analyses indicated that GPR43 was the primary SCFAs receptor expressed on T-cells, which was downregulated on colonic TCRαß+ T-cells upon CNS autoimmunity. The pharmacologic stimulation of GPR43 increased the anti-inflammatory function and reduced the pro-inflammatory features in several TCRαß+ T-cell subsets in the colonic mucosa upon EAE development. Furthermore, GPR43 stimulation induced the arrest of CNS-autoreactive T-cells in the colonic lamina propria, thus avoiding their infiltration into the CNS and dampening the disease development. Mechanistic analyses revealed that GPR43-stimulation on mucosal TCRαß+ T-cells inhibits their CXCR3-mediated migration towards CXCL11, which is released from the CNS upon neuroinflammation. CONCLUSIONS: These findings provide a novel mechanism involved in the gut-brain axis by which bacterial-derived products secreted in the gut mucosa might control the CNS tropism of autoreactive T-cells. Moreover, this study shows GPR43 expressed on T-cells as a promising therapeutic target for CNS autoimmunity.


Assuntos
Encefalomielite Autoimune Experimental , Receptores de Antígenos de Linfócitos T alfa-beta , Camundongos , Animais , Autoimunidade , Disbiose , Sistema Nervoso Central , Glicoproteína Mielina-Oligodendrócito/toxicidade , Peptídeos , Camundongos Endogâmicos C57BL
11.
Opt Express ; 31(18): 29452-29464, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710745

RESUMO

In this work, we develop experimentally a Fabry-Perot fiber optic interferometer applied to the measurement of autocorrelation of complex dynamic pulses generated by a figure-eight fiber laser. The principle is based in the superposition of multiple pulses, which requires two partially reflecting flat surfaces in parallel, resulting in a simple and compact autocorrelator design. The autocorrelation trace obtained exhibits a typical double-scaled structure for noise-like pulses (NLPs), with an ultrashort coherence spur on the order of 100 fs riding upon a broad pedestal of 120 ps. Finally, we show experimentally that the developed Fabry-Perot device is able to measure accurately the autocorrelation of NLPs, as confirmed by comparing the measurement with that of a conventional autocorrelator scheme based on a Michelson interferometer, with the additional advantages of a more compact setup and a much easier alignment procedure compared to the latter.

12.
Phys Rev Lett ; 130(12): 120601, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37027873

RESUMO

Significant progress has been made with multipartite entanglement of discrete qubits, but continuous variable systems may provide a more scalable path toward entanglement of large ensembles. We demonstrate multipartite entanglement in a microwave frequency comb generated by a Josephson parametric amplifier subject to a bichromatic pump. We find 64 correlated modes in the transmission line using a multifrequency digital signal processing platform. Full inseparability is verified in a subset of seven modes. Our method can be expanded to generate even more entangled modes in the near future.

13.
BMC Cardiovasc Disord ; 23(1): 13, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635626

RESUMO

BACKGROUND: Right ventricular (RV) dysfunction in patients with non-ischemic dilated cardiomyopathy (NICM) is associated with cardiovascular events. To analyze the feasibility of assessing RV myocardial deformation by feature tracking (FT)-cardiac magnetic resonance (CMR), and its usefulness as a prognostic marker. METHODS: Retrospective study of NICM patients undergoing CMR. Longitudinal FT-RV free wall (LFT-RVFW) and fractional area change (FAC) were obtained. Correlation with standard RV parameters was studied. An association with combined event (heart failure (HF), ICD implantation or cardiovascular death) was assessed using a logistic regression model. RESULTS: 98 patients (64 ± 13 years) were included. Left ventricular (LV) systolic function (LVEF 29.5 ± 9.6%, 47% with LVEF ≥ 30%) and RV (RVEF 52.2 ± 14.6%, 72% with RVEF ≥ 45%). Follow-up of 38 ± 17 months, 26.5% presented at least one admission for HF. An excellent correlation of LFT-RVFW (r = 0.82) and FAC (r = 0.83) with RVEF was evident. No association of RV-FT parameters with prognosis entire study population was found. However, in patients with LVEF ≥ 30%, admissions for HF were associated with lower LFT-RVFW (-21.6 ± 6.6% vs -31.3 ± 10%; p = 0.006) and FAC (36.6 ± 9.6% vs 50.5 ± 13.4%; p < 0.001) values. Similar differences were observed when only patients with RVEF ≥ 45% were considered. An LFT-RVFW cut-off point of -19.5% and FAC of 36.5% showed good prognostic performance. Decreased LFT-RVFW or FAC represented an independent predictor of combined event in patients with LVEF ≥ 30%. CONCLUSIONS: In NICM patients without severe LV dysfunction, decreased values of LFT-RVFW and/or FAC were associated with HF admissions, independently of RVEF.


Assuntos
Cardiomiopatia Dilatada , Insuficiência Cardíaca , Disfunção Ventricular Direita , Humanos , Estudos Retrospectivos , Imagem Cinética por Ressonância Magnética , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/etiologia , Cardiomiopatia Dilatada/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Função Ventricular Direita , Volume Sistólico
14.
J Opt Soc Am A Opt Image Sci Vis ; 40(11): 1994-2001, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38038064

RESUMO

We show the construction of 3D solids (volumetric 3D models) of SARS-CoV-2 viral particles from the tomographic studies (videos) of SARS-CoV-2-infected tissues. To this aim, we propose a video analysis (tomographic images) by frames (medical images of the virus), which we set as our metadata. We optimize the frames by means of Fourier analysis, which induces a periodicity with simple structure patterns to minimize noise filtering and to obtain an optimal phase of the objects in the image, focusing on the SARS-CoV-2 cells to obtain a medical image under study phase (MIS) (process repeated over all frames). We build a Python algorithm based on Legendre polynomials called "2DLegendre_Fit," which generates (using multilinear interpolation) intermediate images between neighboring MIS phases. We used this code to generate m images of size M×M, resulting in a matrix with size M×M×M (3D solid). Finally, we show the 3D solid of the SARS-CoV-2 viral particle as part of our results in several videos, subsequently rotated and filtered to identify the glicoprotein spike protein, membrane protein, envelope, and the hemagglutinin esterase. We show the algorithms in our proposal along with the main MATLAB functions such as FourierM and Results as well as the data required for the program execution in order to reproduce our results.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Análise de Fourier , Tomografia , Vírion , Algoritmos
15.
Appl Opt ; 62(24): 6534-6541, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37706848

RESUMO

In this work, we study multimodal interference filters with a graphite oxide coating. Use of the multimodal interference filter shows a distinctive peak in the signal spectrum, and when using the exfoliated graphite coated multimodal interference filter, the signal shows different spectral changes, such as the full width at half maximum of the curve, the maximum power, and central wavelength, which indicates that graphite oxide absorbs part of the energy. In addition, microscope observations when a He-Ne laser is passed through the filter confirm that graphite oxide is adhered to the filter.

16.
BMC Public Health ; 23(1): 265, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750794

RESUMO

BACKGROUND: A tax of one-Mexican peso per liter of sugar-sweetened beverage (SSB) came into effect in January 2014 in Mexico as a national health policy to tackle the high overweight and obesity prevalence. Previous studies have shown an overall reduction in SSB purchases after the tax implementation. However, it remains unknown whether and to what extent SSB consumers switched to cheaper taxed beverages, attenuating the potential effect of the policy. Our study's objective was to estimate changes in household purchases of taxed SSBs by tertiles of SSB prices (low, middle, and high) in urban areas after the SSB tax implementation in 2014. METHODS: Based on purchase data for 2012-2015 from households living in 54 Mexican cities with a population > 50,000 inhabitants, we calculated unit-value SSB prices for the full period and sorted them on a monthly basis to create monthly price tertiles. We merged these price tertiles to household purchases and created average monthly ml/capita/day SSB purchases by price tertile at the city level. We assessed SSB purchase switching patterns before and after the tax implementation through price-tertile stratified linear models. The main variable in the models was a dummy indicator that allowed us to identify the pre-tax period (2012-13) and post-tax period (2014-15). We controlled our models for time trends and contextual economic variables. RESULTS: In the regression adjusted models, we found a statistically significant purchase reduction ranging between 10.80 and 13.79 ml/capita/day (p-value < 0.001) across taxed beverages from the middle-price SSB after the tax implementation. We observed no statistically significant reductions in purchases of low-price SSBs and high-price SSBs. CONCLUSIONS: Our findings show purchase reductions in the middle-price SSBs, which represents ≈30% of the overall SSB purchases in urban Mexico. Future studies should be conducted to test if the redesign of the current the tax, by either doubling the tax amount or taxing sugar content, might reduce more effectively purchases across all SSBs.


Assuntos
Bebidas Adoçadas com Açúcar , Humanos , México , Impostos , Comportamento do Consumidor , Bebidas , Comércio
17.
Mol Cell Neurosci ; 118: 103684, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34826608

RESUMO

Glial cell line-derived neurotrophic factor (GDNF) promotes differentiation, proliferation, and survival in different cell types, including dopaminergic neurons. Thus, GDNF has been proposed as a promising neuroprotective therapy in Parkinson's disease. Although findings from cellular and animal models of Parkinson's disease were encouraging, results emerging from clinical trials were not as good as expected, probably due to the inappropriate administration protocols. Despite the growing information on GDNF action mechanisms, many aspects of its pharmacological effects are still unclear and data from different studies are still contradictory. Considering that GDNF action mechanisms are mediated by its receptor tyrosine kinase Ret, which activates PI3K/AKT and MAPK/ERK signaling pathways, we aimed to investigate Ret activation and its effect over both signaling pathways in midbrain cell cultures treated with GDNF at different doses (0.3, 1, and 10 ng/ml) and times (15 min, 24 h, 24 h (7 days), and 7 continuous days). The results showed that short-term or acute (15 min, 24 h, and 24 h (7 days)) GDNF treatment in rat midbrain neurons increases Tyrosine hydroxylase (TH) expression and the phosphorylation levels of Ret (Tyr 1062), AKT (Ser 473), ERK1/2 (Thr202/Tyr204), S6 (Ser 235/236), and GSK3-ß (Ser 9). However, the phosphorylation level of these kinases, TH expression, and dopamine uptake, decreased below basal levels after long-term or prolonged treatment with 1 and 10 ng/ml GDNF (7 continuous days). Our data suggest that long-term GDNF treatment inactivates the receptor by an unknown mechanism, affecting its neuroprotective capacity against degeneration caused by 6-OHDA or rotenone, while short-term exposure to GDNF promoted dopaminergic cell survival. These findings highlight the need to find new and more effective long-acting therapeutic approaches for disorders in which GDNF plays a beneficial role, including Parkinson's disease. In this regard, it is necessary to propose new GDNF treatment guidelines to regulate and control its long-term expression levels and optimize the clinical use of this trophic factor in patients with Parkinson's disease.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial , Doença de Parkinson , Animais , Neurônios Dopaminérgicos/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Mesencéfalo/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-ret/metabolismo , Proteínas Proto-Oncogênicas c-ret/uso terapêutico , Ratos , Tirosina 3-Mono-Oxigenase/metabolismo
18.
Genes Dev ; 29(8): 803-16, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25877919

RESUMO

Embryonic stem cells are maintained in a self-renewing and pluripotent state by multiple regulatory pathways. Pluripotent-specific transcriptional networks are sequentially reactivated as somatic cells reprogram to achieve pluripotency. How epigenetic regulators modulate this process and contribute to somatic cell reprogramming is not clear. Here we performed a functional RNAi screen to identify the earliest epigenetic regulators required for reprogramming. We identified components of the SAGA histone acetyltransferase complex, in particular Gcn5, as critical regulators of reprogramming initiation. Furthermore, we showed in mouse pluripotent stem cells that Gcn5 strongly associates with Myc and that, upon initiation of somatic reprogramming, Gcn5 and Myc form a positive feed-forward loop that activates a distinct alternative splicing network and the early acquisition of pluripotency-associated splicing events. These studies expose a Myc-SAGA pathway that drives expression of an essential alternative splicing regulatory network during somatic cell reprogramming.


Assuntos
Processamento Alternativo , Reprogramação Celular/genética , Epigenômica , Histona Acetiltransferases/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Animais , Diferenciação Celular , Movimento Celular/genética , Células Cultivadas , Células-Tronco Embrionárias , Regulação da Expressão Gênica no Desenvolvimento , Histona Acetiltransferases/genética , Camundongos , Células-Tronco Pluripotentes , Interferência de RNA , Processamento Pós-Transcricional do RNA/genética
19.
Aesthetic Plast Surg ; 47(3): 1155-1161, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36307563

RESUMO

BACKGROUND: Rhinoplasty is one of the most common aesthetic surgical procedures, and yet its postoperative complication profile remains somewhat ill-defined and underreported. The purpose of this study was to examine the quality of complication reporting in the rhinoplasty literature and provide a framework for future complication classification. METHODS: Studies were identified from a previously published 2019 systematic review conducted at Duke University Medical Center. Each included study was again reviewed to determine the reported complications and definitions. Reported complications were analyzed to determine occurrence rate, definition presence/absence, definition location, subjectivity/objectivity, and presence of severity grading system. RESULTS: A total of 30 studies were included. Overall, 63% (n = 19) of studies failed to provide a single definition for any reported complications. The remaining 11 studies (37%) provided at least one definition for their reported complications. Grading/severity scales were included by 8 studies. A specific complication was identified as a "primary outcome" in 15 cases. Definitions were included for 11 (73%) of these 15 complications. Complications denoted as "primary outcomes" were significantly more likely to have an included definition (p <0.01). CONCLUSIONS: Postoperative complications following rhinoplasty are inadequately defined in the available literature, with over sixty percent of studies failing to define a single-reported complication. When complication definitions are included, they are often subjective in nature and rarely include a grading or severity scale. In the absence of standardized rhinoplasty complication definitions, comparing complication rates across studies is exceedingly difficult, and the ability to conduct high-quality meta-analyses is limited. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Rinoplastia , Humanos , Rinoplastia/efeitos adversos , Rinoplastia/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Centros Médicos Acadêmicos , Estética , Estudos Retrospectivos
20.
J Environ Manage ; 344: 118173, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37336017

RESUMO

The quality of life and human survival is dependent on sustainable development and sanitation of water bodies in an environment. The present research focuses on cyclicity data of more than 750,000 records of parameters associated with the water quality from a rural-urban river monitoring stations in real-time from River Atoyac in Central Mexico. The events detected in the instrumental records correlated with 2528 laboratory and instrumental determinations. The 64 polluting compounds were grouped into inorganic compounds (metals and metalloids) and organic compounds (pesticides, herbicides, hydrocarbons). Metal associated compounds were grouped along mechanical, pharmaceutical and textile industries which associates itself with the entry of polluting components. The cyclicity of the events was detected through Discrete Fourier Transformation time series analysis identifying the predominant events in each station. These highlight the events at 23-26 h corresponding to a circadian pattern of the metabolism of the city. Likewise, pollution signals were detected at 3.3, 5.5, and 12-14 h, associated with discharges from economic activities. Multivariate statistical techniques were used to identify the circadian extremes of a regionalized cycle of polluting compounds in each of the stations. The results of this research allow pollution prevention using a mathematical analysis of time series of different quality parameters collected at monitoring stations in real-time as a tool for predicting polluting events. The DFT analysis makes it possible to prevent polluting events in different bodies of water, allowing to support the development of public policies based on the supervision and control of pollution.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água , Humanos , Monitoramento Ambiental/métodos , Rios , Análise de Fourier , México , Qualidade de Vida , Poluentes Químicos da Água/análise
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