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1.
J Control Release ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34619227

RESUMO

Fungal infections affect millions of people globally and are often unreceptive to conventional topical or oral preparations because of low drug bioavailability at the infection site, lack of sustained therapeutic effect, and the development of drug resistance. Amphotericin B (AmB) is one of the most potent antifungal agents. It is increasingly important since fungal co-infections associated with COVID-19 are frequently reported. AmB is only administered via injections (IV) and restricted to life-threatening infections due to its nephrotoxicity and administration-related side effects. In this work, we introduce, for the first time, dissolving microneedle patches (DMP) loaded with micronised particles of AmB to achieve localised and long-acting intradermal delivery of AmB for treatment of cutaneous fungal infections. AmB was pulverised with poly (vinyl alcohol) and poly (vinyl pyrrolidone) to form micronised particles-loaded gels, which were then cast into DMP moulds to form the tips. The mean particle size of AmB in AmB DMP tips after pulverisation was 1.67 ±â€¯0.01 µm. This is an easy way to fabricate and load microparticles into DMP, as few steps are required, and no organic solvents are needed. AmB had no covalent chemical interaction with the excipients, but the crystallinity of AmB was reduced in the tips. AmB was completely released from the tips within 4 days in vitro. AmB DMP presented inhibition of Candida albicans (CA) and the killing rate of AmB DMP against CA biofilm inside porcine skin reached 100% within 24 h. AmB DMP were able to pierce excised neonatal porcine skin at an insertion depth of 301.34 ±â€¯46.86 µm. Ex vivo dermatokinetic and drug deposition studies showed that AmB was mainly deposited in the dermis. An in vivo dermatokinetic study revealed that the area under curve (AUC0-inf) values of AmB DMP and IV (Fungizone® bolus injection 1 mg/kg) groups were 8823.0 d∙µg/g and 33.4 d∙µg/g, respectively (264-fold higher). AmB remained at high levels (219.07 ±â€¯102.81 µg/g or more) in the skin until 7 days after the application of AmB DMP. Pharmacokinetic and biodistribution studies showed that AmB concentration in plasma, kidney, liver, and spleen in the AmB DMP group was significantly lower than that in the IV group. Accordingly, this system addressed the systemic side effects of intravenous injection of AmB and localised the drug inside the skin for a week. This work establishes a novel, easy and effective method for long-acting and localised intradermal drug delivery.

2.
Anesthesiology ; 135(5): 877-892, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610092

RESUMO

BACKGROUND: Patients undergoing surgical procedures are vulnerable to repetitive evoked or ongoing nociceptive barrage. Using functional near infrared spectroscopy, the authors aimed to evaluate the cortical hemodynamic signal power changes during ongoing nociception in healthy awake volunteers and in surgical patients under general anesthesia. The authors hypothesized that ongoing nociception to heat or surgical trauma would induce reductions in the power of cortical low-frequency hemodynamic oscillations in a similar manner as previously reported using functional magnetic resonance imaging for ongoing pain. METHODS: Cortical hemodynamic signals during noxious stimuli from the fontopolar cortex were evaluated in two groups: group 1, a healthy/conscious group (n = 15, all males) where ongoing noxious and innocuous heat stimulus was induced by a contact thermode to the dorsum of left hand; and group 2, a patient/unconscious group (n = 13, 3 males) receiving general anesthesia undergoing knee surgery. The fractional power of low-frequency hemodynamic signals was compared across stimulation conditions in the healthy awake group, and between patients who received standard anesthesia and those who received standard anesthesia with additional regional nerve block. RESULTS: A reduction of the total fractional power in both groups-specifically, a decrease in the slow-5 frequency band (0.01 to 0.027 Hz) of oxygenated hemoglobin concentration changes over the frontopolar cortex-was observed during ongoing noxious stimuli in the healthy awake group (paired t test, P = 0.017; effect size, 0.70), and during invasive procedures in the surgery group (paired t test, P = 0.003; effect size, 2.16). The reduction was partially reversed in patients who received a regional nerve block that likely diminished afferent nociceptive activity (two-sample t test, P = 0.002; effect size, 2.34). CONCLUSIONS: These results suggest common power changes in slow-wave cortical hemodynamic oscillations during ongoing nociceptive processing in conscious and unconscious states. The observed signal may potentially promote future development of a surrogate signal to assess ongoing nociception under general anesthesia.

3.
Acta Biomater ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34637933

RESUMO

The development of biocompatible materials with desired functions is essential for tissue engineering and biomedical applications. Hydrogels prepared from these materials represent an important class of soft matter for mimicking extracellular environments. In particular, dynamic hydrogels with responsiveness to environments are quite appealing because they can match the dynamics of biological processes. Among the external stimuli that can trigger responsive hydrogels, light is considered as a clean stimulus with high spatiotemporal resolution, complete bioorthogonality, and fine tunability regarding its wavelength and intensity. Therefore, photoresponsiveness has been broadly encoded in hydrogels for biological applications. Moreover, light can be used to initiate gelation during the fabrication of biocompatible hydrogels. Here, we present a critical review of light manipulation tools for the fabrication of hydrogels and for the regulation of physicochemical properties and functions of photoresponsive hydrogels. The materials, photo-initiated chemical reactions, and new prospects for light-induced gelation are introduced in the former part, while mechanisms to render hydrogels photoresponsive and their biological applications are discussed in the latter part. Subsequently, the challenges and potential research directions in this area are discussed, followed by a brief conclusion. STATEMENT OF SIGNIFICANCE: Hydrogels play a vital role in the field of biomaterials owing to their water retention ability and biocompatibility. However, static hydrogels cannot meet the dynamic requirements of the biomedical field. As a stimulus with high spatiotemporal resolution, light is an ideal tool for both the fabrication and operation of hydrogels. In this review, light-induced hydrogelation and photoresponsive hydrogels are discussed in detail, and new prospects and emerging biological applications are described. To inspire more research studies in this promising area, the challenges and possible solutions are also presented.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34524637

RESUMO

The anaerobic digestion efficiency and methane production of straw was limited by its complex composition and structure. In this study, rice straw (RS), cellulose, and hemicellulose were used as raw materials to study biogas production performance and changes in the volatile fatty acids (VFAs). Further, microbial communities and genetic functions were analyzed separately for each material. The biogas production potential of RS, cellulose, and hemicellulose was different, with cumulative biogas production of 283.75, 412.50, and 620.64 mL/(g·VS), respectively. The methane content of the biogas produced from cellulose and hemicellulose was approximately 10% higher than that produced from RS after the methane content stabilized. The accumulation of VFAs occurred in the early stage of anaerobic digestion in all materials, and the cumulative amount of VFAs in both cellulose and hemicellulose was relatively higher than that in RS, and the accumulation time was 12 and 14 days longer, respectively. When anaerobic digestion progressed to a stable stage, Clostridium was the dominant bacterial genus in all three anaerobic digestion systems, and the abundance of Ruminofilibacter was higher during anaerobic digestion of RS. Genetically, anaerobic digestion of all raw materials proceeded mainly via aceticlastic methanogenesis, with similar functional components. The different performance of anaerobic digestion of RS, cellulose, and hemicellulose mainly comes from the difference of composition of raw materials. Increasing the accessibility of cellulose and hemicellulose in RS feedstock by pretreatment is an effective way to improve the efficiency of anaerobic digestion. Since the similar microbial community structure will be acclimated during anaerobic digestion, there is no need to adjust the initial inoculum when the accessibility of cellulose and hemicellulose changes.

5.
Signal Transduct Target Ther ; 6(1): 346, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561414

RESUMO

Antibody-dependent cellular cytotoxicity (ADCC) responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered ADCC responses contributes to COVID-19 disease development is currently not well understood. To understand the potential correlation between ADCC responses and COVID-19 disease development, we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease. ADCC was elicited by 10 days post-infection, peaked by 11-20 days, and remained detectable until 400 days post-infection. In general, patients with severe disease had higher ADCC activities. Notably, patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased. Importantly, ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern (VOCs) (B.1.1.7, B.1.351, and P.1) as that against the D614G mutant in human patients and vaccinated mice. Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions, which can be applied to estimate the extra-neutralization level against COVID-19, especially lethal COVID-19.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Citotoxicidade Celular Dependente de Anticorpos , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade
6.
J Clin Anesth ; 75: 110498, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34488061

RESUMO

STUDY OBJECTIVE: To determine the effect of dexmedetomidine on acute kidney injury (AKI) following endovascular aortic repair (EVAR) for Stanford type B aortic dissection (TBAD). DESIGN: Randomized, double-blind, placebo-controlled, pilot study. SETTING: University Hospital. PATIENTS: 102 TBAD patients undergoing EVAR procedures were enrolled. Patients with dissection involving aortic arch or renal artery were excluded. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to a dexmedetomidine group (intravenous dexmedetomidine 0.4 µg/kg/h immediately after anesthesia induction and 0.1 µg/kg/h after extubation, which was maintained until 24 h) or a normal saline control group. MEASUREMENTS: The primary outcome was the incidence of AKI within the first two days after surgery, based on the Acute Kidney Injury Network (AKIN) criteria. The secondary outcomes included serum cystatin C and estimated glomerular filtration rate on postoperative days 1, 2, and 7, and in-hospital need for renal replacement therapy (RRT). Long-term outcomes included RRT and all-cause mortality. MAIN RESULTS: Ninety-eight patients completed the study (dexmedetomidine, n = 48; control, n = 50). AKIN stage 1 AKI occurred in 3/48 (6.3%) patients receiving dexmedetomidine, compared with 11/50 (22%) patients receiving normal saline (odds ratio = 0.24, 95% CI: 0.07 to 0.89, P = 0.041). This difference remained significant after adjusting for baseline covariates (adjusted odds ratio = 0.21, 95% CI: 0.05 to 0.84; P = 0.028). Dexmedetomidine led to a lower serum cystatin C on postoperative day 1 (median [IQR] mg/L: 1.31 [1.02-1.72] vs. 1.58 [1.28-1.96]). There were no between-group differences in other secondary or long-term outcomes. During the follow-up (median = 28.4 months), 1 patient in the dexmedetomidine group and 3 patients in the control group required RRT. CONCLUSIONS: Dexmedetomidine reduced the incidence of AKI in TBAD patients after EVAR procedures. The long-term benefits of dexmedetomidine in this patient population warrant further investigation. TRIAL REGISTRATION: ChiCTR-IPR-15006372.

7.
Drug Des Devel Ther ; 15: 3379-3390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34376972

RESUMO

Purpose: Surgical stress promotes tumor metastasis. Interleukin (IL)-17 plays a pivotal role in cancer progression, and high IL-17 expression predicts poor prognosis of non-small-cell lung cancer (NSCLC). Lidocaine may exert tumor-inhibiting effects. We hypothesize that intravenous lidocaine attenuates surgical stress and reduces serum IL-17 levels during video-assisted thoracic surgery (VATS) for NSCLC. Methods: This randomized, double-blind, placebo-controlled trial included 60 early-stage NSCLC patients undergoing VATS, into a lidocaine group (n = 30; intravenous lidocaine bolus 1.0 mg/kg, and 1.0 mg/kg/h until the end of surgery) or a normal saline control group (n = 30). The primary outcome was serum IL-17 level at 24 hours postoperatively. The secondary outcomes included serum IL-17 level at the time of post-anesthesia care unit (PACU) discharge, serum cortisol level at PACU discharge and postoperative 24 hours, pain scores (0-10) from PACU discharge to 48 hours postoperatively, incidences of postoperative nausea and vomiting, dizziness, and arrhythmia during 0-48 hours postoperatively, and 30-day mortality. Long-term outcomes included chemotherapy, cancer recurrence, and mortality. Results: The lidocaine group had lower serum IL-17 at 24 hours postoperatively compared with the control group (23.0 ± 5.8 pg/mL vs 27.3 ± 8.2 pg/mL, difference [95% CI] = -4.3 [-8.4 to -0.2] pg/mL; P = 0.038). The lidocaine group also had reduced serum IL-17 (difference [95% CI] = -4.6 [-8.7 to -0.5] pg/mL), serum cortisol (difference [95% CI] = -37 [-73 to -2] ng/mL), and pain scores (difference [95% CI] = -0.7 [-1.3 to -0.1] points) at PACU discharge. During a median follow-up of 10 (IQR, 9-13) months, 2 patients in the lidocaine group and 6 patients in the control group received chemotherapy, one patient in the control group had cancer recurrence, and no death event occurred. Conclusion: Intravenous lidocaine was associated with reduced serum IL-17 and cortisol following VATS procedures in early-stage NSCLC patients. Trial Registration: ChiCTR2000030629.

8.
Neuroinformatics ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34378155

RESUMO

In this work, we introduce a deep learning architecture for evaluation on multimodal electroencephalographic (EEG) and functional near-infrared spectroscopy (fNIRS) recordings from 40 epileptic patients. Long short-term memory units and convolutional neural networks are integrated within a multimodal sequence-to-sequence autoencoder. The trained neural network predicts fNIRS signals from EEG, sans a priori, by hierarchically extracting deep features from EEG full spectra and specific EEG frequency bands. Results show that higher frequency EEG ranges are predictive of fNIRS signals with the gamma band inputs dominating fNIRS prediction as compared to other frequency envelopes. Seed based functional connectivity validates similar patterns between experimental fNIRS and our model's fNIRS reconstructions. This is the first study that shows it is possible to predict brain hemodynamics (fNIRS) from encoded neural data (EEG) in the resting human epileptic brain based on power spectrum amplitude modulation of frequency oscillations in the context of specific hypotheses about how EEG frequency bands decode fNIRS signals.

10.
Neurobiol Aging ; 106: 103-118, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34274697

RESUMO

Aging is accompanied by global brain atrophy occurring unequally across the brain. Cortical thinning is seen with aging with a larger loss in the frontal and temporal subregions. We explored the link between regional cortical thickness and regional cerebral pulsatility. Sixty healthy individuals were divided into two age groups, young (aged 19-31) and older (aged 65-75) adults. Each participant underwent a near-infrared spectroscopy (NIRS) scan to index regional brain pulsatility from cerebral pulse-transit-time-to-the peak-of-the-pulse (PTTp), an anatomical magnetic resonance imaging (MRI) and a phase-contrast MRI (PC-MRI) scan to measure arterial and cerebrospinal fluid (CSF) pulsatility. In older adults, the greatest association between cerebral pulsatility and cortical thickness was found in superior and middle temporal and superior, middle and inferior frontal areas, which are the regions perfused first by the internal carotid arteries. This association dropped in the postcentral and superior parietal regions. These findings suggest higher brain pulsatility as a potential risk factor contributing to cortical thinning for some brain regions more than others.

11.
Phys Chem Chem Phys ; 23(31): 16855-16867, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34328162

RESUMO

Gelled non-toxic microemulsions have great potential in transdermal drug delivery: the microemulsion provides an optimum solubilizing capacity for drugs and promotes drug permeation through the skin barrier, while the gel network provides mechanical stability. We have formulated such a gelled non-toxic microemulsion consisting of H2O - isopropyl myristate (IPM) - Plantacare 1200 UP (technical-grade alkyl polyglucoside with an average composition of C12G1.4) - 1,2-octanediol in the presence of the low molecular weight gelator (LMWG) 1,3:2,4-dibenzylidene-d-sorbitol (DBS) at an oil-to-water ratio of φ = 0.50. The study at hand aimed to develop gelled non-toxic microemulsions that can contain both oil- and water-soluble drugs and are either water- or oil-based, depending on the application. To accomplish this, we varied the oil-to-water ratio from being water-rich to oil-rich, i.e. 0.2 ≤ φ ≤ 0.8. Phase studies were carried out along the middle phase trajectory, and a suitable LMWG was identified for all φ-ratios. Electrical conductivity measurements showed that the structure can be tuned from water- to oil-continuous by adjusting the amount of 1,2-octanediol and φ-ratios. The existence of the gel network was visualized by freeze-fracture electron microscopy (FFEM) at three different φ-ratios. We found that all systems from φ = 0.35 to φ = 0.80 form strong gels with nearly the same rheological behavior, while the system with φ = 0.20 is a much weaker gel. We attribute this behavior on the one hand to the microemulsion microstructure and on the other hand to the solvent-dependent gelation properties of DBS, which can be described by the Hansen solubility parameters (HSPs).

12.
Ecotoxicol Environ Saf ; 222: 112517, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34303044

RESUMO

BACKGROUND: The health effects of air pollution on heart failure (HF) patients have not been adequately studied. OBJECTIVES: We assessed the associations between long-term air pollution exposure and prognosis in HF patients. METHODS: HF patients were prospectively recruited from 52 hospitals throughout China between August 2016 and May 2018. The participants were followed up for 12 months after discharge from index hospitalization. Long-term air pollution was calculated as annual average level of air pollution before the date of the index hospitalization. Outcomes were defined as HF readmission, cardiovascular death, and composite events. Cox proportional hazards model was applied to quantify the associations between air pollution exposure and clinical outcomes. RESULTS: Of 4866 patients included in the analysis, mean age was 65.2 ± 13.5 years, and 62.5% were male. During 1-year follow-up, 1577 (32.4%) participants were readmitted for HF and 550 (11.3%) died from cardiovascular disease. Though no associations between long-term air pollution and HF readmission in the overall participants, geographic and age heterogeneity in the long-term effects of air pollutants on HF readmission was observed. Air pollutants included PM2.5 [HR (hazard ratio) = 1.146, 95% CI (confidence interval): 1.044, 1.259], PM10 (HR = 1.120, 95% CI: 1.043, 1.203), SO2 (HR = 1.808, 95% CI: 1.190, 2.747), and CO (HR = 3.596, 95% CI: 1.792, 7.218) were associated with higher risk of HF readmission in South China, but not in North China, where people spend less time outdoors and have limited indoor-outdoor ventilation. PM2.5, PM10, O3, and CO among patients ≥ 65 years were found to be associated with higher risk of HF readmission. The effects on composite outcomes were broadly consistent with that of HF readmission. Cardiovascular death was not significantly associated with air pollution in the overall or subgroups. DISCUSSION: Among HF patients who were older, living in South China, more HF readmissions occurred with higher long-term air pollution exposure. The findings suggest that the elderly patients and those living in South China should particularly enhance their personal protection against air pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Insuficiência Cardíaca , Idoso , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Material Particulado/efeitos adversos , Material Particulado/análise , Estudos Prospectivos
13.
Artigo em Inglês | MEDLINE | ID: mdl-34206732

RESUMO

To assess the effectiveness of the containment strategies proposed in Japan, an SEIAQR (susceptible-exposed-infected-asymptomatic-quarantined-recovered) model was established to simulate the transmission of COVID-19. We divided the spread of COVID-19 in Japan into different stages based on policies. The effective reproduction number Re and the transmission parameters were determined to evaluate the measures conducted by the Japanese Government during these periods. On 7 April 2020, the Japanese authority declared a state of emergency to control the rapid development of the pandemic. Based on the simulation results, the spread of COVID-19 in Japan can be inhibited by containment actions during the state of emergency. The effective reproduction number Re reduced from 1.99 (before the state of emergency) to 0.92 (after the state of emergency). The transmission parameters were fitted and characterized with quantifiable variables including the ratio of untracked cases, the PCR test index and the proportion of COCOA app users (official contact confirming application). The impact of these variables on the control of COVID-19 was investigated in the modelling analysis. On 8 January 2021, the Japanese Government declared another state of emergency. The simulated results demonstrated that the spread could be controlled in May by keeping the same strategies. A higher intensity of PCR testing was suggested, and a larger proportion of COCOA app users should reduce the final number of infections and the time needed to control the spread of COVID-19.


Assuntos
COVID-19 , Humanos , Japão , Pandemias , Quarentena , SARS-CoV-2
14.
World J Pediatr ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34254272

RESUMO

BACKGROUND: The aim of this study was to compare nasogastric (NG) feeding with nasojejunal (NJ) feeding when treating pediatric patients with acute pancreatitis (AP). METHODS: We performed a single-center, prospective, randomized, active-controlled trial involving 77 pediatric patients with AP from April 2014 to December 2017. The patients were randomized into two groups: the NG tube feeding group (34 patients) and the NJ tube feeding group (33 patients). The primary outcome measures included the enteral nutrition intolerance, the length of tube feeding time, the recurrent pain of pancreatitis and complications. RESULTS: A total of 62 patients with AP (31 patients for each group) came into the final analysis. No differences were found in baseline characteristics, pediatric AP score and computed tomography severity score between the two groups. Three (9.7%) patients in the NG group and one (3.2%) patient in the NJ group developed intolerance (relative risk = 3.00, 95% confidence interval 0.33-27.29, P = 0.612). The tube feeding time and length of hospital stay of the NG group were significantly shorter than those of the NJ group (P = 0.016 and 0.027, respectively). No patient died in the trial. No significant differences were found in recurrent pain, complications, nutrition delivery efficacy, and side effects between the two groups. CONCLUSIONS: NG tube feeding appears to be effective and safe for acute pediatric pancreatitis compared with NJ tube feeding. In addition, high qualified, large sample sized, randomized controlled trials in pediatric population are needed.

15.
Mater Sci Eng C Mater Biol Appl ; 127: 112226, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225871

RESUMO

In this work, we introduce, for the first time, novel hybrid microneedle patches with implantable poly(lactic-co-glycolic acid) (PLGA) tips aligned with hydrogel-forming microneedle bases (HFMB) using a dissolvable material. A model dye, Nile red, and an antifungal drug, amphotericin B, were loaded into the PLGA tips in a controlled manner by multiple castings. Three different types of pre-formed microneedle bases including conventional dissolving baseplates (MN0), HFMB with needle heights of 600 µm (MN6) and HFMB with needle heights of 800 µm (MN8) were investigated. Compared to the conventional dissolving baseplate (MN0)-based PLGA tipped implantable microneedle design, the addition of the pre-formed HFMB (MN8) improved in vitro and ex vivo insertion capacities of the patches, increased ex vivo drug delivery efficiency up to 80% of the loaded drug and speeded up the implantation process to within 1 min. An adhesion test indicated that the hydrogel baseplate used in this study was easier to peel off from the skin than the dissolving baseplate. In vitro release studies demonstrated that the release of amphotericin B from the drug loading PLGA tips lasts for a week. Antifungal tests of the inserted amphotericin B loaded PLGA tips revealed their antifungal effects against Candida albicans. The MN8 did not dissolve, leaving no viscous residue but absorbed water and disintegrated after immersion into water. The hybrid PLGA-tipped microneedle system will be ideal for rapid implantation and sustained release of amphotericin B for dermal fungal infections. This hybrid patch design is a novel promising technology for delivering drug-eluting microimplants into the skin while ensuring easy and complete removal of the HFMB. It could have many potential applications in implantable intradermal drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Administração Cutânea , Preparações de Ação Retardada , Agulhas , Pele
16.
J Virol ; 95(17): e0074721, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34133897

RESUMO

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is bringing an unprecedented health crisis to the world. To date, our understanding of the interaction between SARS-CoV-2 and host innate immunity is still limited. Previous studies reported that SARS-CoV-2 nonstructural protein 12 (NSP12) was able to suppress interferon-ß (IFN-ß) activation in IFN-ß promoter luciferase reporter assays, which provided insights into the pathogenesis of COVID-19. In this study, we demonstrated that IFN-ß promoter-mediated luciferase activity was reduced during coexpression of NSP12. However, we could show NSP12 did not affect IRF3 or NF-κB activation. Moreover, IFN-ß production induced by Sendai virus (SeV) infection or other stimulus was not affected by NSP12 at mRNA or protein level. Additionally, the type I IFN signaling pathway was not affected by NSP12, as demonstrated by the expression of interferon-stimulated genes (ISGs). Further experiments revealed that different experiment systems, including protein tags and plasmid backbones, could affect the readouts of IFN-ß promoter luciferase assays. In conclusion, unlike as previously reported, our study showed SARS-CoV-2 NSP12 protein is not an IFN-ß antagonist. It also rings the alarm on the general usage of luciferase reporter assays in studying SARS-CoV-2. IMPORTANCE Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-ß activation. However, most of these results were generated from IFN-ß promoter luciferase reporter assay and have not been validated functionally. In our study, we found that, although NSP12 could suppress IFN-ß promoter luciferase activity, it showed no inhibitory effect on IFN-ß production or its downstream signaling. Further study revealed that contradictory results could be generated from different experiment systems. On one hand, we demonstrated that SARS-CoV-2 NSP12 could not suppress IFN-ß signaling. On the other hand, our study suggests that caution needs to be taken with the interpretation of SARS-CoV-2-related luciferase assays.


Assuntos
RNA-Polimerase RNA-Dependente de Coronavírus , Interferon beta , Regiões Promotoras Genéticas , SARS-CoV-2 , RNA-Polimerase RNA-Dependente de Coronavírus/genética , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Células HEK293 , Humanos , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/antagonistas & inibidores , Interferon beta/biossíntese , Interferon beta/genética , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
17.
Br J Anaesth ; 127(2): 215-223, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34082896

RESUMO

BACKGROUND: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery. METHODS: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 µg kg-1 min-1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models. RESULTS: The median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P<0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010). CONCLUSION: Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Estudos de Coortes , Ponte de Artéria Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
FEBS J ; 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34089572

RESUMO

Viruses are obligate intracellular pathogens that rely on cellular machinery for successful replication and dissemination. The host cells encode a number of different strategies to sense and restrict the invading viral pathogens. Caspase-mediated programmed cell death pathways that are triggered by virus infection, such as apoptosis and pyroptosis, provide a means for the infected cells to limit viral proliferation, leading to suicidal cell death (apoptosis) or lytic cell death and alerting uninfected cells to mount anti-viral responses (pyroptosis). However, some viruses can employ activated caspases to dampen the anti-viral responses and facilitate viral replication through cleavage of critical molecules of the innate immune pathways. The regulation of innate immune responses by caspase activation during virus infection has recently become an important topic. In this review, we briefly introduce the characteristics of different classes of caspases and the cell death pathways regulated by these caspases. We then describe how viruses trigger or dampen caspase activation during infection and how these activated caspases regulate three major innate immune response pathways of viral infections: the retinoic acid-inducible gene I-like receptor, toll-like receptor and cyclic GMP-AMP synthase-stimulator of interferon genes pathways.

19.
Signal Transduct Target Ther ; 6(1): 181, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972497

RESUMO

Over 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming "herd-immunity" through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.


Assuntos
Anticorpos Antivirais/imunologia , Infecções Assintomáticas/epidemiologia , COVID-19/imunologia , Imunidade/imunologia , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/genética , COVID-19/sangue , COVID-19/fisiopatologia , COVID-19/virologia , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade
20.
BMC Psychiatry ; 21(1): 270, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034695

RESUMO

BACKGROUND: To examine the relationship between the main caregiver during the "doing-the-month" (a traditional Chinese practice which a mother is confined at home for 1 month after giving birth) and the risk of postpartum depression (PPD) in postnatal women. METHODS: Participants were postnatal women stayed in hospital and women who attended the hospital for postpartum examination, at 14-60 days after delivery from November 1, 2013 to December 30, 2013. Postpartum depression status was assessed using the Edinburgh Postnatal Depression Scale. Univariate and multivariable logistic regressions were used to identify the associations between the main caregiver during "doing-the-month" and the risk of PPD in postnatal women. RESULTS: One thousand three hundred twenty-five postnatal women with a mean (SD) age of 28 (4.58) years were included in the analyses. The median score (IQR) of PPD was 6.0 (2, 10) and the prevalence of PPD was 27%. Of these postnatal women, 44.5% were cared by their mother-in-law in the first month after delivery, 36.3% cared by own mother, 11.1% by "yuesao" or "maternity matron" and 8.1% by other relatives. No association was found between the main caregivers and the risk of PPD after multiple adjustments. CONCLUSIONS: Although no association between the main caregivers and the risk of PPD during doing-the-month was identified, considering the increasing prevalence of PPD in Chinese women, and the contradictions between traditional culture and latest scientific evidence for some of the doing-the-month practices, public health interventions aim to increase the awareness of PPD among caregivers and family members are warranted.


Assuntos
Depressão Pós-Parto , Adulto , Cuidadores , Depressão Pós-Parto/epidemiologia , Feminino , Humanos , Mães , Período Pós-Parto , Gravidez , Fatores de Risco
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