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1.
Acta Pharmacol Sin ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824461

RESUMO

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.

2.
Biochem Biophys Res Commun ; 551: 14-20, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33714754

RESUMO

The blood-brain barrier (BBB) is the most critical obstacle in the treatment of central nervous system disorders, such as glioma, the most typical type of brain tumor. To overcome the BBB and enhance drug-penetration abilities, we used angiopep-2-modified liposomes to deliver arsenic trioxide (ATO) across the BBB, targeting the glioma. Angiopep-2-modified calcium arsenite-loaded liposomes (A2-PEG-LP@CaAs), with uniformly distributed hydrodynamic diameter (96.75 ± 0.57 nm), were prepared using the acetate gradient method with high drug-loading capacity (7.13 ± 0.72%) and entrapment efficiency (54.30 ± 9.81%). In the acid tumor microenvironment, arsenic was responsively released, thereby exerting an anti-glioma effect. The anti-glioma effect of A2-PEG-LP@CaAs was investigated both in vitro and in vivo. As a result, A2-PEG-LP@CaAs exhibited a potent, targeted anti-glioma effect mediated by the lipoprotein receptor-related (LRP) receptor, which is overexpressed in both the BBB and glioma. Therefore, A2-PEG-LP@CaAs could dramatically promote the anti-glioma effect of ATO, as a promising strategy for glioma therapy.

3.
Eur J Pharm Sci ; 159: 105713, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33453389

RESUMO

Rhein (RH) is a candidate for the treatment of kidney diseases. However, clinical application of RH is impeded by low aqueous solubility and oral bioavailability. Deoxycholic acid-conjugated nanoparticles (DNPs) were prepared by ionic interaction for enhancing intestinal absorption by targeting the apical sodium-dependent bile acid transporter in the small intestine. Resultant DNPs showed relatively high entrapment efficiency (90.7 ± 0.73)% and drug-loading efficiency (6.5 ± 0.29)% with a particle size of approximately 190 nm and good overall dispersibility. In vitro release of RH from DNPs exhibited sustained and pH-dependent profiles. Cellular uptake and apparent permeability coefficient (Papp) of the DNPs were 3.25- and 5.05-fold higher than that of RH suspensions, respectively. An in vivo pharmacokinetic study demonstrated significantly enhanced oral bioavailability of RH when encapsulated in DNPs, with 2.40- and 3.33-fold higher Cmax and AUC0-inf compared to RH suspensions, respectively. DNPs are promising delivery platforms for poorly absorbed drugs by oral administration.

4.
Nat Cell Biol ; 23(1): 99-108, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33398178

RESUMO

Detection of endogenous signals and precise control of genetic circuits in the natural context are essential to understand biological processes. However, the tools to process endogenous information are limited. Here we developed a generalizable endogenous transcription-gated switch that releases single-guide RNAs in the presence of an endogenous promoter. When the endogenous transcription-gated switch is coupled with the highly sensitive CRISPR-activator-associated reporter we developed, we can reliably detect the activity of endogenous genes, including genes with very low expression (<0.001 relative to Gapdh; quantitative-PCR analysis). Notably, we could also monitor the transcriptional activity of typically long non-coding RNAs expressed at low levels in living cells using this approach. Together, our method provides a powerful platform to sense the activity of endogenous genetic elements underlying cellular functions.


Assuntos
Células-Tronco Embrionárias Murinas/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Regiões Promotoras Genéticas , RNA Guia/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Animais , Sistemas CRISPR-Cas , Células HEK293 , Humanos , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Neuroblastoma/patologia , RNA Guia/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
5.
Int J Pharm ; : 120162, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33307159

RESUMO

Due to the lack of effective therapeutic targets and the passive delivery of a limited quantity of nanoparticles to the tumors, the photothermal conversion agents used in photothermal therapy (PTT) have not been effective in treating triple-negative breast cancer (TNBC). As a result, there is a need to improve the tumor-targeting ability of these photothermal conversion agents. To address this, a microwave-triggered heat shock protein (HSP)-targeted gold nano-system (cmHSP-AuNC), with a gold nanocage (AuNC) as a photothermal conversion agent and anti-HSP monoclonal antibody (cmHSP) as a targeting ligand, was fabricated. cmHSP-AuNC was characterized based on morphology, particle size, zeta potentials, absorption spectrum, and photothermal conversion ability. The expression of HSP70 in 4T1 cells after microwave irradiation was verified by western blotting, and the optimal treatment conditions to achieve the highest expression were determined. Both in vitro and in vivo results indicated that the induction through microwave irradiation could effectively activate the HSP70 overexpression in TNBC, thereby significantly improving the targeting ability, tumor accumulation and anti-tumor efficacy of cmHSP-AuNC. This study proposes a promising strategy for improving the targeting ability and therapeutic efficacy of PTT.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33162028

RESUMO

Glioma is the most typical malignant brain tumor, and the chemotherapy to glioma is limited by poor permeability for crossing blood-brain-barrier (BBB) and insufficient availability. In this study, angiopep-2 modified lipid-coated mesoporous silica nanoparticle loading paclitaxel (ANG-LP-MSN-PTX) was developed to transport paclitaxel (PTX) across BBB mediated by low-density lipoprotein receptor-related protein 1 (LRP1), which is over-expressed on both BBB and glioma cells. ANG-LP-MSN-PTX was characterized with homogeneous hydrodynamic size, high drug loading capacity (11.08%) and a sustained release. In vitro experiments demonstrated that the targeting efficiency of PTX was enhanced by ANG-LP-MSN-PTX with higher penetration ability (10.74%) and causing more C6 cell apoptosis. ANG-LP-MSN-PTX (20.6%) revealed higher targeting efficiency compared with LP-MSN-PTX (10.6%) via blood and intracerebral microdialysis method in the pharmacokinetic study. The therapy of intracranial C6 glioma bearing rats was increasingly efficient, and ANG-LP-MSN-PTX could prolong the survival time of model rats. Taken together, ANG-LP-MSN-PTX might hold great promise as a targeting delivery system for glioma treatment.

7.
Elife ; 92020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32876563

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) and transmissible gastroenteritis virus (TGEV) are two highly infectious and lethal viruses causing major economic losses to pig production. Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for known receptor proteins CD163 and pAPN and show that DKO pigs are completely resistant to genotype 2 PRRSV and TGEV. We found no differences in meat-production or reproductive-performance traits between wild-type and DKO pigs, but detected increased iron in DKO muscle. Additional infection challenge experiments showed that DKO pigs exhibited decreased susceptibility to porcine deltacoronavirus (PDCoV), thus offering unprecedented in vivo evidence of pAPN as one of PDCoV receptors. Beyond showing that multiple gene edits can be combined in a livestock animal to achieve simultaneous resistance to two major viruses, our study introduces a valuable model for investigating infection mechanisms of porcine pathogenic viruses that exploit pAPN or CD163 for entry.


Assuntos
Antígenos CD13/deficiência , Infecções por Coronavirus/prevenção & controle , Coronavirus/patogenicidade , Gastroenterite Suína Transmissível/prevenção & controle , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Receptores de Superfície Celular/deficiência , Vírus da Gastroenterite Transmissível/patogenicidade , Animais , Animais Geneticamente Modificados , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/imunologia , Composição Corporal , Antígenos CD13/genética , Antígenos CD13/imunologia , Coronavirus/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Suscetibilidade a Doenças , Gastroenterite Suína Transmissível/genética , Gastroenterite Suína Transmissível/imunologia , Gastroenterite Suína Transmissível/virologia , Técnicas de Silenciamento de Genes , Interações entre Hospedeiro e Microrganismos , Indústria de Embalagem de Carne , Fenótipo , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Sus scrofa/genética , Suínos , Vírus da Gastroenterite Transmissível/imunologia , Ganho de Peso
8.
Ann Thorac Surg ; 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32730840

RESUMO

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has shown to reduce hospital stay and pain compared with and open lobectomy to treat non-small cell lung cancer (NSCLC). Due to the low rate of deaths, it is difficult to show differences in survival in individual works. Our objective was to compare short and long-term mortality developing a systematic review and meta-analysis. METHODS: We systematically searched studies that compared VATS versus open lobectomy and provided data on 30-day mortality or long-term survival (>5 years). For long-term outcomes, studies must include patients with the same cancer stage or, if several stages were included, the studies had to control for cancer stage in their PS model. A pooled OR and HR was respectively calculated for short and long-term outcomes. RESULTS: 33 works were identified comprising 61633 patients. VATS led to lower postoperative mortality, OR=0.64 (CI 95% 0.56-0.73) and higher long-term survival, HR=0.88 (CI 95% 0.81-0.96). Disease-free survival was similar: HR=0.94 (CI 95% 0.80-1.10). CONCLUSIONS: For NSCLC treated with lobectomy, VATS is associated with lower postoperative mortality and greater long-term survival. Disease-free survival is similar between both groups.

9.
Mater Sci Eng C Mater Biol Appl ; 113: 110929, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32487376

RESUMO

The synovial tissues are natural sites of drug delivery for the treatment of rheumatoid arthritis. Our previous study showed that mixed monoterpenes edge-activated PEGylated transfersomes (MMPTs) could significantly enhance the percutaneous absorption of sinomenine (SIN), an anti-inflammation drug. The aim of this study was to investigate the potential of MMPTs for delivery of SIN to the synovial tissues in joint cavities. To this end, conventional liposomes (LPSs) were used as a reference. Transmission electron microscope, constant pressure extrusion method, and differential scanning calorimetry (DSC) were used for physicochemical characterization of the formulations. Confocal laser scanning microscopy (CLSM) and double-sited microdialysis coupled with LC-MS/MS were exploited to study the distribution of MMPTs in different skin layers and pharmacokinetics of SIN in the blood and the joint cavities. The results showed that mixed monoterpenes could significantly enhance the elasticity of MMPTs, evidenced by a decrease in the main transition temperature (Tm) and transition enthalpy (△H). CLSM analyses demonstrated that MMPTs were distributed in deep layers of the skin, indicating that MMPTs might transport SIN through the skin. In contrast, LPSs were confined in the stratum corneum, which deterred SIN from penetrating through the skin. The results from double-sited microdialysis pharmacokinetics showed that in the joint cavities the steady state concentration (Css) and AUC0→t of SIN from MMPTs were 2.1-fold and 2.5-fold of those from LPSs, respectively. In contrast, in the blood the Css and AUC0→t of SIN from MMPTs were about 1/3 of those from LPSs. This study suggested that MMPTs could enhance the delivery of SIN to the joint cavities. A combination of CLSM and double-sited microdialysis could give an insight into the mechanism of transdermal and local drug delivery.

10.
Animals (Basel) ; 10(6)2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32481564

RESUMO

The Meishan pig is a traditional Chinese native breed, known for its excellent reproduction performance that is widely used in commercial pig production through two-way or three-way crossbreeding systems. However, the lean meat yield of Meishan crossbred pigs is still very low and cannot meet the market demand. To evaluate the lean meat yield of Meishan crossbred pigs, six wild-type Meishan sows were artificially inseminated by using the MSTN+/- Duroc boar semen in this experiment. Some reproductive performance-related traits of Meishan sows were recorded to ensure that semen from MSTN knockout Duroc boar did not affect offspring production, including total births, live births, sex, and litter weight. In total, 73 piglets were obtained and 63 were alive. Male to female ratio was close to 1: 1. because of factors such as disease, only 43 pigs were utilized, including 28 MSTN mutant pigs (MSTN+/-) and 15 MSTN homozygous pigs (MSTN+/+). We compared the growth performance and carcass performance of these full or half-sib populations and found that there were no differences between MSTN+/- and MSTN+/+ genotypes for live animal measures including average daily gain (ADG), body dimensions, or ultrasonic measurement of fat thickness when pigs were harvested after 120 days of feeding. Conversely, the MSTN+/- pigs had higher dressing percentage and lean meat percentage, lower level of carcass fat, larger longissimus muscle area, less percentage of skin and skeleton, thinner average backfat thickness, and lower intramuscular fat (IMF) content than MSTN+/+ pigs. In conclusion, the production of MSTN+/- mutant progeny from Meishan females resulted in improved carcass composition, providing a feasible solution to improve the lean meat yield of Chinese local fat-type pig breeds.

11.
Respir Med ; 162: 105870, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32056677

RESUMO

OBJECTIVES: To survey the frequency of extra-pulmonary symptoms reported by a sample of patients with severe asthma, their contribution to quality of life and relationship to treatment pathways. METHODS: Consenting patients (N = 100) attending a severe asthma clinic completed questionnaire measures of extra-pulmonary symptoms (the General symptom Questionnaire, GSQ), pulmonary symptoms (Asthma Control Test, ACT), quality of life (the Severe Asthma Questionnaire, SAQ) and health status (EQ-5D-5L). RESULTS: A median of 21 extra-pulmonary symptoms were reported per week. GSQ correlated -0.65 with the ACT and 0.69 with the SAQ. Linear regression showed that both the ACT and GSQ were significant predictors of SAQ mean score, p < 0.001. In patients not receiving biologics, those with high cumulative OCS exposure (≥1120 mg per year) had significantly worse scores (p < 0.05) on all questionnaires except the ACT and GSQ compared to those with low cumulative OCS exposure. DISCUSSION: Extra-pulmonary symptoms were common in this sample of people with severe asthma. Extra-pulmonary and pulmonary symptoms contribute equal variance to the score of HRQoL, showing that they are equally important contributors to patients' experience of severe asthma. Extra-pulmonary symptoms are often overlooked in clinical medicine and in measures of quality of life. Participants receiving biologic treatments had lower extra-pulmonary symptoms possibly indicating that biologics reduce systemic symptoms more effectively than other treatments.


Assuntos
Asma , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Comorbidade , Progressão da Doença , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Omalizumab/uso terapêutico , Prednisolona/uso terapêutico , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
12.
Biol Reprod ; 102(1): 116-132, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31435642

RESUMO

As the follicle develops, the thickening of the granulosa compartment leads to progressively deficient supply of oxygen in granulosa cells (GCs) due to the growing distances from the follicular vessels. These conditions are believed to cause hypoxia in GCs during folliculogenesis. Upon hypoxic conditions, several types of mammalian cells have been reported to undergo cell cycle arrest. However, it remains unclear whether hypoxia exerts any impact on cell cycle progression of GCs. On the other hand, although the GCs may live in a hypoxic environment, their mitotic capability appears to be unaffected in growing follicles. It thus raises the question whether there are certain intraovarian factors that might overcome the inhibitory effects of hypoxia. The present study provides the first evidence suggesting that cobalt chloride (CoCl2)-mimicked hypoxia prevented G1-to-S cell cycle progression in porcine GCs. In addition, we demonstrated that the inhibitory effects of CoCl2 on GCs cell cycle are mediated through hypoxia-inducible factor-1 alpha/FOXO1/Cdkn1b pathway. Moreover, we identified insulin-like growth factor-I (IGF-I) as an intrafollicular factor required for cell cycle recovery by binding to IGF-I receptor in GCs suffering CoCl2 stimulation. Further investigations confirmed a role of IGF-I in preserving G1/S progression of CoCl2-treated GCs via activating the cyclin E/cyclin-dependent kinase2 complex through the phoshatidylinositol-3 kinase/protein kinase B (AKT)/FOXO1/Cdkn1b axis. Although the present findings were based on a hypoxia mimicking model by using CoCl2, our study might shed new light on the regulatory mechanism of GCs cell cycle upon hypoxic stimulation.

13.
Animals (Basel) ; 9(12)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31795468

RESUMO

The aim of this study is to establish an ovarian stress model, and to investigate the effects of stress on follicular development. Our data showed that continuous intraperitoneal injection of CORT successfully created a stressful environment in the ovary. To assess the effects of CORT on ovarian functions, 80 three-week-old ICR (Institute of Cancer Research) female mice were randomly divided into control group and treatment group. All mice were injected intraperitoneally with pregnant horse serum gonadotropin (PMSG). At the same time, the treatment group were injected with CORT (1 mg/mouse) at intervals of 8 h; while the control group was injected with same volume of methyl sulfoxide (DMSO). Blood, ovaries, or ovarian granulosa cell samples were collected at 24 h, 48 h, and 55 h after PMSG injection. The results showed that, compared with the control group, CORT-injected mice revealed a significant decrease in ovulation rates, ovarian weight, ovarian index, the number of secondary follicles and mature follicles, levels of estrogen and progesterone, and mRNA expression of steroid synthase-related genes. Collectively, our findings clearly demonstrated that CORT injection could represent an effective practice to simulate stresses that inhibit ovarian functions by reducing follicular development and ovulation.

14.
Polymers (Basel) ; 11(12)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810159

RESUMO

Isotactic polybutylene-1 (iPB) has lots of advantages and is best used as hot water pipe. However, to transform into stable crystal form I, the iPB needs as long as 7 days. In this process, the irreversible damage brings great difficulties to the use of the iPB. The method which convert it directly into crystal I has shortcomings such as being requiring complex operation and being expensive. In this study, an innovative idea was put forward, not paying attention to the crystal transformation of iPB but only focusing on reducing the time it can be applied. In this study, bamboo powder was modified by the silane coupling agent KH570 (KBP) to prepare iPB/KBP composite. The infiltration test and Fourier transform infrared (FTIR) analysis showed that the hydrophilicity of KBP is greatly reduced, which can greatly improve the compatibility of the iPB and KBP. The tensile strength, tensile modulus, flexural strength, and flexural modulus of the composites storage for 3 days is equal to the pure iPB with storage 7 days with the KBP additions of 3%, 3%, 7%, and 5%, respectively. The heat deformation temperature (HDT) of the composite with 3% KBP after 1-day storage reached the value of pure iPB storage for 7 days. This provides more space and possibilities for the industrialization of the iPB. The crystallization behavior of iPB/KBP composites proves that the addition of KBP accelerates the crystallization rate of iPB, but the crystallinity of the iPB/KBP composites is not changed. The SEM photograph of iPB/KBP composites showed that when the KBP addition was low the compatibility between KBP and iPB was good. When the KBP addition was increased the agglomeration of KBP in the iPB was very obvious, which leads to the poor mechanical properties of the composite.

15.
Cochrane Database Syst Rev ; 11: CD012348, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782528

RESUMO

BACKGROUND: Children who are securely attached to at least one parent are able to be comforted by that parent when they are distressed and explore the world confidently by using that parent as a 'secure base'. Research suggests that a secure attachment enables children to function better across all aspects of their development. Promoting secure attachment, therefore, is a goal of many early interventions. Attachment is mediated through parental sensitivity to signals of distress from the child. One means of improving parental sensitivity is through video feedback, which involves showing a parent brief moments of their interaction with their child, to strengthen their sensitivity and responsiveness to their child's signals. OBJECTIVES: To assess the effects of video feedback on parental sensitivity and attachment security in children aged under five years who are at risk for poor attachment outcomes. SEARCH METHODS: In November 2018 we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, nine other databases and two trials registers. We also handsearched the reference lists of included studies, relevant systematic reviews, and several relevant websites SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that assessed the effects of video feedback versus no treatment, inactive alternative intervention, or treatment as usual for parental sensitivity, parental reflective functioning, attachment security and adverse effects in children aged from birth to four years 11 months. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: This review includes 22 studies from seven countries in Europe and two countries in North America, with a total of 1889 randomised parent-child dyads or family units. Interventions targeted parents of children aged under five years, experiencing a wide range of difficulties (such as deafness or prematurity), or facing challenges that put them at risk of attachment issues (for example, parental depression). Nearly all studies reported some form of external funding, from a charitable organisation (n = 7) or public body, or both (n = 18). We considered most studies as being at low or unclear risk of bias across the majority of domains, with the exception of blinding of participants and personnel, where we assessed all studies as being at high risk of performance bias. For outcomes where self-report measures were used, such as parental stress and anxiety, we rated all studies at high risk of bias for blinding of outcome assessors. Parental sensitivity. A meta-analysis of 20 studies (1757 parent-child dyads) reported evidence of that video feedback improved parental sensitivity compared with a control or no intervention from postintervention to six months' follow-up (standardised mean difference (SMD) 0.34, 95% confidence interval (CI) 0.20 to 0.49, moderate-certainty evidence). The size of the observed impact compares favourably to other, similar interventions. Parental reflective functioning. No studies reported this outcome. Attachment security. A meta-analysis of two studies (166 parent-child dyads) indicated that video feedback increased the odds of being securely attached, measured using the Strange Situation Procedure, at postintervention (odds ratio 3.04, 95% CI 1.39 to 6.67, very low-certainty evidence). A second meta-analysis of two studies (131 parent-child dyads) that assessed attachment security using a different measure (Attachment Q-sort) found no effect of video feedback compared with the comparator groups (SMD 0.02, 95% CI -0.33 to 0.38, very low-certainty evidence). Adverse events. Eight studies (537 parent-child dyads) contributed data at postintervention or short-term follow-up to a meta-analysis of parental stress, and two studies (311 parent-child dyads) contributed short-term follow-up data to a meta-analysis of parental anxiety. There was no difference between intervention and comparator groups for either outcome. For parental stress the SMD between video feedback and control was -0.09 (95% CI -0.26 to 0.09, low-certainty evidence), while for parental anxiety the SMD was -0.28 (95% CI -0.87 to 0.31, very low-certainty evidence). Child behaviour. A meta-analysis of two studies (119 parent-child dyads) at long-term follow-up found no evidence of the effectiveness of video feedback on child behaviour (SMD 0.04, 95% CI -0.33 to 0.42, very low-certainty evidence). A moderator analysis found no evidence of an effect for the three prespecified variables (intervention type, number of feedback sessions and participating carer) when jointly tested. However, parent gender (both parents versus only mothers or only fathers) potentially has a statistically significant negative moderation effect, though only at α (alpha) = 0.1 AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that video feedback may improve sensitivity in parents of children who are at risk for poor attachment outcomes due to a range of difficulties. There is currently only little, very low-certainty evidence regarding the impact of video feedback on attachment security, compared with control: results differed based on the type of measure used, and follow-up was limited in duration. There is no evidence that video feedback has an impact on parental stress or anxiety (low- and very low-certainty evidence, respectively). Further evidence is needed regarding the longer-term impact of video feedback on attachment and more distal outcomes such as children's behaviour (very low-certainty evidence). Further research is needed on the impact of video-feedback on paternal sensitivity and parental reflective functioning, as no study measured these outcomes. This review is limited by the fact that the majority of included parents were mothers.


Assuntos
Desenvolvimento Infantil , Emoções , Apego ao Objeto , Pais/psicologia , Criança , Educação Infantil , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Materials (Basel) ; 12(20)2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31635146

RESUMO

In this study, the evolution of the mechanical properties of Fe-30Mn-9Al-1C steel has been determined in tensile tests at strain rates of 10-4 to 102 s-1. The results show that the strain rate sensitivity becomes a negative value when the strain rate exceeds 100 s-1 and this abnormal evolution is attributed to the occurrence of dynamic strain aging. Due to the presence of intergranular κ-carbides, the fracture modes of steel include ductile fracture and intergranular fracture. The values of dislocation arrangement parameter M were obtained using a modified Williamson-Hall plot. It has been found that once the strain rate sensitivity becomes negative, the interaction of dislocations in the steel is weakened and the free movement of dislocation is enhanced. Adiabatic heating promotes the dynamic recovery of steel at a high strain rate.

17.
Materials (Basel) ; 12(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487877

RESUMO

Titanium alloys are widely used in many fields because of their excellent comprehensive properties. However, its poor friction and wear properties limit its many potential applications. In general, the surface roughness of important parts manufactured by titanium alloy should meet certain requirements. As a low-cost and high-efficiency processing method, barrel finishing has been used for the surface finishing of titanium alloys. The main material removal mechanism of barrel finishing is micro-cutting/grinding, which is similar to the material wear mechanism under some conditions. In addition, titanium alloys are subjected to a low force in common surface finishing processes. Cryogenic treatment is a method that can improve the comprehensive properties of titanium alloys. Therefore, the friction and wear behavior of cryogenically treated Ti-6Al-4V titanium alloy (CT Ti alloy) and non-cryogenically treated Ti-6Al-4V titanium alloy (NT Ti alloy) at a low load and scratch speed was studied comparatively in this paper. The results show that the CT Ti alloy exhibits a lower friction coefficient and wear rate under both dry and wet wear conditions. Under wet conditions, the stabilized friction coefficient is lower than that under dry conditions. The stabilized friction coefficient of CT Ti alloy is 0.18 after reaching a stable wear stage under wet conditions. Under dry wear conditions, the NT Ti alloy mainly showed typical abrasive wear, heavy adhesion wear and oxidation wear characters. The wear mechanisms of CT Ti alloy are mainly abrasive wear, slight adhesion wear and oxidation wear. Under wet wear conditions, the wear mechanism of NT Ti alloy is abrasive wear and slight adhesion wear. After cryogenic treatment, the mechanism for CT Ti alloy is slight abrasive wear.

18.
Immun Inflamm Dis ; 7(4): 239-249, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31441602

RESUMO

BACKGROUND: Asthma is a disease of the lung and a systemic disease. Functional disorders are associated with multiple systemic abnormalities that have been explained by complexity models. The aim was to test the similarity in type and aetiology between the extra-pulmonary symptoms of severe asthma and the symptoms of fibromyalgia. METHODS: One Hundred patients recruited from a specialist severe asthma clinic and 1751 people reporting different functional disorder diagnoses recruited via the internet completed the same 60-item questionnaire. Symptom patterns were compared between groups using a new measure, the symptom pattern similarity index where 0 = no relationship, 1 = identical patterns between groups. RESULTS: Severe asthma patients report numerous extra-pulmonary symptoms. The similarity index between the symptom pattern of the asthma patients with other groups was irritable bowel syndrome = 0.54, chronic fatigue syndrome = 0.69, and fibromyalgia = 0.75. The index between fibromyalgia and asthma patients with the most and least frequent extra-pulmonary symptoms was 0.81 and 0.55 respectively. CONCLUSIONS: Patients with severe asthma have numerous extra-pulmonary symptoms similar in type and pattern to the symptoms of fibromyalgia. The similarity of the symptom pattern between asthma and fibromyalgia increases as the number of extra-pulmonary symptoms increases as predicted by network theory and previously shown to be the case with other functional disorders. These findings support the hypothesis that functional disorders and extra-pulmonary asthma symptoms have a common complexity or network aetiology. Evidence based behavioural interventions for fibromyalgia may be helpful for patients with severe asthma reporting extra-pulmonary symptoms.


Assuntos
Asma , Síndrome de Fadiga Crônica , Fibromialgia , Síndrome do Intestino Irritável , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Asma/complicações , Asma/epidemiologia , Asma/fisiopatologia , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/etiologia , Síndrome de Fadiga Crônica/fisiopatologia , Feminino , Fibromialgia/epidemiologia , Fibromialgia/etiologia , Fibromialgia/fisiopatologia , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/etiologia , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Pessoa de Meia-Idade
19.
BMJ Open ; 9(6): e026092, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31217315

RESUMO

INTRODUCTION: Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes. METHODS AND ANALYSIS: We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty. ETHICS AND DISSEMINATION: The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: PROSPERO International prospective register of systematic reviews (CRD42017068915).


Assuntos
Microcefalia/complicações , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Metanálise como Assunto , Microcefalia/epidemiologia , Microcefalia/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Cuidado Pré-Natal , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Zika virus , Infecção por Zika virus/transmissão
20.
Materials (Basel) ; 12(13)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31247922

RESUMO

The fabricated Mg-Al alloy consists of α-Mg phase and Mg-Mg17Al12 eutectic phase. The corrosion behavior of cast Mg-Al alloy in sulphuric acid (H2SO4) and acetic acid (HAc) aqueous solutions was investigated. The Mg-Al alloy shows general corrosion in H2SO4 solution, and the α-Mg dendrites revealed a slightly faster corrosion rate than that of the eutectics. In HAc solution, the alloy shows an obvious selective corrosion characteristic, with the α-Mg dendrites being corroded preferentially. Grain orientation plays an important role in corrosion behavior of the alloy in the HAc solutions.

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