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1.
Medicine (Baltimore) ; 100(41): e27457, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731120

RESUMO

ABSTRACT: Human papillomavirus (HPV) vaccination in young women is low. Women aged 21 to 65 years in the United States (U.S.) have not reached the Healthy People 2020 objective of 93% for cervical cancer screening. The main aim of this study was to investigate the association between HPV vaccination status and cervical cancer screening among privately insured women aged 21 to 26 years in the U.S.This was a retrospective cohort study using the IBM MarketScan database (2006-2016). The study population included 190,982 HPV-vaccinated women and 763,928 matched unvaccinated women. Adjusted incidence rate ratio (IRR) and the 95% confidence intervals (CIs) were obtained using the generalized estimating equations models with a Poisson distribution.Among a total of 954,910 women included in the analysis, age (mean [SD]) was 23.3 [1.6] years. During 967,317 person-years of follow-up, a total of 475,702 incidents of cervical cancer screening were identified. The incidence density rates of cervical cancer screening were 461 per 1000 person-years (PY) for unvaccinated women and 787 per 1000 PY for those who received 3 doses of the HPV vaccine. After adjusting for other covariates, the IRR of cervical cancer screening was 34% higher among HPV-vaccinated women with at least one vaccine dose than unvaccinated women (adjusted IRR = 1.34, 95% CI: 1.33-1.35; P < .0001). The IRR of cervical cancer screening varied by the dose of HPV vaccination. There was evidence of a linear dose-response relationship between the number of HPV vaccine doses and cervical cancer screening (P-trend < .0001). Compared with unvaccinated women, the IRR of cervical cancer screening were 14%, 39%, and 60% higher among those who received 1, 2, and 3 doses of the HPV vaccine, respectively.In this large retrospective cohort study of privately insured women, HPV-vaccinated women were more likely to be screened for cervical cancer compared with unvaccinated women.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Neoplasias do Colo do Útero/prevenção & controle , Cobertura Vacinal/estatística & dados numéricos , Adulto , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Seguro Saúde/estatística & dados numéricos , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
2.
Front Pharmacol ; 12: 747450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658883

RESUMO

Remdesivir, a nucleotide analog prodrug, has displayed pharmacological activity against SARS-CoV-2. Recently, eicosanoids are widely involved in regulating immunity and inflammation for COVID-19 patients. Rats were intravenously administered remdesivir at a dose of 5 mg/kg, and series of blood samples were collected before and after treatment. Targeted metabolomics regarding the eicosanoid profile were investigated and quantitated simultaneously using the previously reported reliable HPLC-MS/MS method. Additionally, interplay relationship between metabolomics and pharmacokinetic parameters was performed using the Pearson correlation analysis and PLS model. For the longitudinal metabolomics of remdesivir, metabolic profiles of the same rat were comparatively substantial at discrete sampling points. The metabolic fingerprints generated by individual discrepancy of rats were larger than metabolic disturbance caused by remdesivir. As for the transversal metabolomics, the prominent metabolic profile variation was observed between the baseline and treatment status. Except for TXB2, the inflammatory- and immunology-related eicosanoids of resolvin D2, 5-HEPE, 5-HETE, and DHA were significantly disturbed and reduced after single administration of remdesivir (p < 0.05, p < 0.001). Moreover, the metabolite of PGE2 correlated with GS-441524 (active metabolite of remdesivir) concentration and pharmacokinetic parameters of Cmax, AUC0-t, AUC0-infinity, and CL significantly. Eicosanoid metabolic profiles of remdesivir at both longitudinal and transversal levels were first revealed using the robust HPLC-MS/MS method. This initial observational eicosanoid metabolomics may lighten the therapy for fighting COVID-19 and further provide mechanistic insights of SARS-CoV-2 virus infection.

3.
AIDS Care ; : 1-8, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581640

RESUMO

Hepatitis C virus (HCV) infection is common among people living with HIV. HIV and HCV coinfected patients have higher overall mortality rates compared with HIV mono-infected patients. With its high cure rate of HCV infection, direct-acting antiviral (DAA) treatment provides an opportunity to improve the survival of the HIV/HCV coinfected population. The objective of this study is to investigate the association between DAA treatment and all-cause mortality among HIV/HCV coinfected people. The study included 7103 Medicare beneficiaries in the United States who were infected with both HIV and HCV between 2014 and 2017. Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) of death for patients with and without DAA treatment while controlling for patient characteristics. During the study period, 1675 patients initiated DAA treatment (23.6%). The adjusted hazard ratio (aHR) of all-cause mortality between patients with and without DAA treatment was 0.37 (95% CI, 0.29-0.48), regardless of cirrhosis status. DAA treatment was associated with a smaller reduction in all-cause mortality for females (aHR, 0.50 [95% CI, 0.30-0.85]) compared with males (aHR, 0.34 [95% CI, 0.25-0.46]). DAA treatment was associated with improved survival among all HIV/HCV coinfected patients regardless of sex or HCV disease progression.

4.
Expert Rev Hematol ; 14(sup1): 1-18, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34369834

RESUMO

Hemophilia A and von Willebrand disease (VWD) are inherited rare bleeding disorders affecting normal hemostasis. Patients with VWD, especially those with severe disease types, share some similarities to patients with hemophilia A in their burden of disease: they suffer from an increased risk of potentially severe and life-threatening bleeds and associated long-term consequences, such as impaired joint health and overall lower quality of life. However, the two bleeding disorders differ in their primary cause and affected patient population, and comprise a range of different bleeding phenotypes with varying unmet needs. Generating scientific evidence to advance health care for patients with rare bleeding disorders is challenging due to the low prevalence and heterogeneity of affected populations, including patient demographics and symptom severities. Innovative study designs are needed to adequately answer relevant scientific questions and address patients' unmet needs. In support of advancing clinical outcomes and treatment options for these patients, at the recent EAHAD 2021 annual congress, novel approaches and data from clinical and real-world observational studies, as well as systematic literature analyses, were presented. Herein, extracts from seven selected posters reporting research in hemophilia A and VWD funded by Takeda are discussed.

5.
Vaccines (Basel) ; 9(8)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34452016

RESUMO

The need for a cold chain system during storage and transport substantially increases the cost of vaccines. Virus-like particles (VLPs) are among the best countermeasures against foot and mouth disease virus (FMDV). However, VLPs are composed of pure proteins, and thus, are susceptible to heat. To address this problem, four simple biomimetic mineralization methods with the use of calcium phosphate were developed to improve heat tolerance via biomineralization. The results showed that biomineralization can significantly improve the heat resistance of VLPs. The biomineralized VLPs can be stored at low as 25 °C for eight days, and 37 °C for four days. Animal experiments showed that biomineralization had no effect on the immunogenicity of VLPs or the expression of specific antibodies (Abs) and neutralizing Abs. Even after heat treatment at 37 °C for four days, the biomineralized VLPs remained immunogenic and produced highly specific and neutralizing Abs with a high rate of protection. These results suggest that these biomineralization approaches can promote the thermal stability of VLPs against and significantly reduce dependence on cold storage and delivery systems.

6.
J Steroid Biochem Mol Biol ; 214: 105986, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34454009

RESUMO

Bile acids (BAs) are steroidal compounds that play important roles in the occurrence and development of liver injury. However, comprehensive characterization of BAs was rarely reported due to the limitations of both standards access and detection sensitivity. In this study, a parallel derivatization strategy was established for the sensitive and comprehensive profiling of unconjugated and glycine-conjugated BAs by using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Two structural analogues 2-hydrazinyl-4,6-dimethylpyrimidine (DMP) and 2-hydrazinylpyrimidine (DP) were used as the parallel derivatization reagents for BAs labeling, facilitating the improvements of both detection sensitivities and chromatographic performances. The derivatization reactions can be completed in 20 min at room temperature, with derivatization efficacy higher than 99 %. Through derivatization, the sensitivity of BAs increased dozens or hundreds of times compared to their non-derivatized forms. Due to the structural similarities of derivatized BAs, general MS parameters can be forged for the analysis of DMP and DP labeled BAs. In addition, the DP labeled BAs were incorporated into the DMP derivatized biological samples for both the discovery and comprehensive characterization of BAs. Retention time shift (RTS) and peak area ratio (PAR) induced by the parallel DMP and DP labeled BAs were used for the rapid identification of BAs from complex biological samples. More than 200 BAs were profiled in rat serum using this parallel derivatization strategy. Further, the new strategy was successfully implemented in BAs profiling of serum samples from tripterysium glycosides-induced liver injury rat model. The disturbance of the BA metabolism network was further interpreted.

7.
Oncol Rep ; 46(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34278502

RESUMO

Gastric cancer (GC) is the third leading cause of cancer­related mortality and the fifth most common type of cancer worldwide. GC stem cells (GCSCs) have been reported to be responsible for the malignant behavior of GC. However, the key molecular mechanism controlling GCSC function remains unclear. The present study aimed to investigate the function of retinoic acid­related orphan receptor ß (RORß) in GC. The expression levels of RORß in GC cells and clinical GC tissues were analyzed using western blotting, reverse transcription­quantitative PCR (RT­qPCR) and immunohistochemistry. The association between RORß expression levels and GCSC markers was analyzed using Gene Set Enrichment Analysis, and GeneChip was performed to identify differentially expressed genes between control and RORß­overexpressing GC cells. CCK­8 and flow cytometric assays were used to evaluate the effect of RORß on cell viability and apoptosis, respectively. The effect of RORß on the self­renewal capacity of GCSCs was measured using a sphere formation assay, the expression levels of induced pluripotent stem (iPS) factors and epithelial­mesenchymal transition (EMT)­related factors were measured by RT­qPCR and western blotting, and the tumorigenic capacity was measured by an in vivo mouse model. Finally, the impact of RORß on the Wnt signaling pathway was determined using western blotting and a TOP/FOP flash assay. The results revealed that the expression levels of RORß were downregulated in GC tissues compared with para­carcinoma tissues, and were inversely associated with the expression levels of GCSC markers. The overexpression of RORß upregulated the expression levels of the pro­apoptotic gene, Bcl­2 like protein 11, which subsequently inhibited the viability and promoted the apoptosis of GC cells. In addition, RORß decreased the sphere forming ability, and downregulated the expression levels of iPS cell­ and EMT­related factors. In vivo, RORß suppressed the tumorigenic capacity and stemness of GC cells. Mechanistically, RORß was revealed to decrease the activity of the Wnt/ß­catenin signaling pathway in GCSCs. In conclusion, the findings of the present study identified RORß as a novel suppressor of GCSCs and highlighted the prospect of RORß as a novel candidate target for stem cell­based GC therapy.

8.
Anal Bioanal Chem ; 413(23): 5811-5820, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34302183

RESUMO

Remdesivir is a nucleotide analog prodrug that has received much attention since the outbreak of the COVID-19 pandemic in December 2019. GS-441524 (Nuc) is the active metabolite of remdesivir and plays a pivotal role in the clinical treatment of COVID-19. Here, a robust HPLC-MS/MS method was developed to determine Nuc concentrations in rat plasma samples after a one-step protein precipitation process. Chromatographic separation was accomplished on Waters XBrige C18 column (50 × 2.1 mm, 3.5 µm) under gradient elution conditions. Multiple reaction monitoring transitions in electrospray positive ion mode were m/z 292.2 → 163.2 for Nuc and 237.1 → 194.1 for the internal standard (carbamazepine). The quantitative analysis method was fully validated in line with the United States Food and Drug Administration guidelines. The linearity, accuracy and precision, matrix effect, recovery, and stability results met the requirements of the guidelines. Uncertainty of measurement and incurred sample reanalysis were analyzed to further ensure the robustness and reproducibility of the method. This optimized method was successfully applied in a rat pharmacokinetics study of remdesivir (intravenously administration, 5 mg kg-1). The method can act as a basis for further pharmacokinetic and clinical efficacy investigations in patients with COVID-19. Graphical abstract.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Adenosina/sangue , Adenosina/farmacocinética , Adenosina/normas , Monofosfato de Adenosina/sangue , Monofosfato de Adenosina/farmacocinética , Monofosfato de Adenosina/normas , Alanina/sangue , Alanina/farmacocinética , Alanina/normas , Animais , Antivirais/farmacocinética , Antivirais/normas , Limite de Detecção , Masculino , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes
9.
ACS Omega ; 6(23): 15236-15245, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34151102

RESUMO

Influenza A virus (IAV) poses a significant threat to human health, which calls for the development of efficient detection methods. The present study constructed a fluorescence resonance energy transfer (FRET) system based on novel fluorescent probes and graphene oxide (GO) for detecting H5N1 IAV hemagglutinin (HA). Here, we synthesized small (sub-20 nm) sandwich-structured upconversion nanoparticles (UCNPs) (SWUCNPs for short) with a high energy transfer efficiency, which allows for controlling the emitter in a thin shell. The π-π stacking interaction between the aptamer and GO shortens the distance between the fluorescent probe and the receptor, thereby realizing fluorescence resonance energy transfer (FRET). When HA is present, the aptamer enables changes in their conformations and move away from GO surface. Fluorescence signals display a linear relationship between HA quantitation in the range of 0.1-15 ng mL-1 and a limit of detection (LOD) of 60.9 pg mL-1. The aptasensor was also applicable in human serum samples with a linear range from 0.2 to 12 ng mL-1 and a limit of detection of 114.7 pg mL-1. This strategy suggested the promising prospect of the aptasensor in clinical applications because of the excellent sensing performance and sensitivity. This strategy may be promising for vitro diagnostics and provides new insights into the functioning of the SWUCNPs system.

10.
Telemed Rep ; 2(1): 143-147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34041510

RESUMO

Background: Rural patients with chronic hepatitis C virus (HCV) infection may be less likely to access HCV care than those in urban areas. A telementoring, task-shifting model has been implemented to address the unmet needs of HCV care. Evidence is needed on whether this intervention improves HCV care in rural HCV patients. Methods: We compared three key HCV care indicators among Medicare patients with chronic hepatitis C in 2014-2016 by urban-rural status between New Mexico with a telementoring program and Pennsylvania without such a program. We classified each patient's urban-rural status based on his or her ZIP code of residence. We used multivariable log-binomial regressions to examine the relative probability of receiving HCV care by urban and rural status in two states. Results: In New Mexico, 41.3% of HCV patients resided in rural areas (N = 1155). In Pennsylvania, rural patients accounted for 13.2% (N = 1775). The unadjusted overall rates of receiving HCV RNA or genotype testing within 12 months before HCV treatment were 76.1% in "rural-New Mexico" versus 73.3% in "rural-Pennsylvania," 66.2% in "urban-New Mexico," and 70.2% in "urban-Pennsylvania." Post-treatment HCV RNA testing rate was also high in "rural-New Mexico" (83.0%). After adjusting for demographic and clinical characteristics, "rural-New Mexico" HCV patients who received HCV treatment still had the highest probability of taking HCV RNA or genotype testing before HCV treatment, compared with other groups (relative risk [95% confidence interval]: 0.91 [0.84-1.00] in "rural-Pennsylvania," 0.85 [0.78-0.93] in "urban-New Mexico," and 0.93 [0.87-1.00] in "urban-Pennsylvania"). Conclusions: The telementoring program may help improve HCV care in rural patients.

11.
J Virol ; 95(16): e0017721, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34011545

RESUMO

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals that causes a significant economic burden globally. Vaccination is the most effective FMD control strategy. However, FMD virus (FMDV) particles are prone to dissociate when appropriate physical or chemical conditions are unavailable, such as an incomplete cold chain. Such degraded vaccines result in compromised herd vaccination. Therefore, thermostable FMD particles are needed for use in vaccines. This study generated thermostable FMDV mutants (M3 and M10) by serial passages at high temperature, subsequent amplification, and purification. Both mutants contained an alanine-to-threonine mutation at position 13 in VP1 (A1013T), although M3 contained 3 additional mutations. The selected mutants showed improved stability and immunogenicity in neutralizing antibody titers, compared with the wild-type (wt) virus. The sequencing analysis and cryo-electron microscopy showed that the mutation of alanine to threonine at the 13th amino acid in the VP1 protein (A1013T) is critical for the capsid stability of FMDV. Virus-like particles containing A1013T (VLPA1013T) also showed significantly improved stability to heat treatment. This study demonstrated that Thr at the 13th amino acid of VP1 could stabilize the capsid of FMDV. Our findings will facilitate the development of a stable vaccine against FMDV serotype O. IMPORTANCE Foot-and-mouth disease (FMD) serotype O is one of the global epidemic serotypes and causes significant economic loss. Vaccination plays a key role in the prevention and control of FMD. However, the success of vaccination mainly depends on the quality of the vaccine. Here, the thermostable FMD virus (FMDV) mutants (M3 and M10) were selected through thermal screening at high temperatures with improved stability and immunogenicity compared with the wild-type virus. The results of multisequence alignment and cryo-electron microscopy (cryo-EM) analysis showed that the Thr substitution at the 13th amino acid in the VP1 protein is critical for the capsid stability of FMDV. For thermolabile type O FMDV, this major discovery will aid the development of its thermostable vaccine.


Assuntos
Proteínas do Capsídeo/imunologia , Capsídeo/imunologia , Vírus da Febre Aftosa/imunologia , Vacinas Virais/imunologia , Substituição de Aminoácidos , Animais , Capsídeo/química , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Microscopia Crioeletrônica , Febre Aftosa/prevenção & controle , Vírus da Febre Aftosa/genética , Vírus da Febre Aftosa/metabolismo , Cobaias , Temperatura Alta , Imunogenicidade da Vacina , Mutação , Estabilidade Proteica , Sorogrupo , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Virologia
12.
Plant J ; 107(2): 467-479, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33942410

RESUMO

Association of RNA polymerase V (Pol V) with chromatin is a critical step for RNA- directed DNA methylation (RdDM) in plants. Although the methylated DNA-binding proteins SUVH2 and SUVH9 and the chromatin remodeler-containing complex DRD1-DMS3-RDM1 are known to be required for the association of Pol V with chromatin, the molecular mechanisms underlying the association of Pol V with different chromatin environments remain largely unknown. Here we found that SUVH9 interacts with FVE, a homolog of the mammalian retinoblastoma-associated protein, which has been previously identified as a shared subunit of the histone deacetylase complex and the polycomb-type histone H3K27 trimethyltransferase complex. We demonstrated that FVE facilitates the association of Pol V with chromatin and thus contributes to DNA methylation at a substantial subset of RdDM target loci. Compared with FVE-independent RdDM target loci, FVE-dependent RdDM target loci are more abundant in gene-rich chromosome arms than in pericentromeric heterochromatin regions. This study contributes to our understanding of how the association of Pol V with chromatin is regulated in different chromatin environments.

13.
Arch Virol ; 166(8): 2131-2140, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34003358

RESUMO

Inactivated foot-and-mouth disease virus (FMDV) vaccines have been used widely to control foot-and-mouth disease (FMD). However, the virions (146S) of this virus are easily dissociated into pentamer subunits (12S), which limits the immune protective efficacy of inactivated vaccines when the temperature is higher than 30 °C. A cold-chain system can maintain the quality of the vaccines, but such systems are usually not reliable in limited-resource settings. Thus, it is imperative to improve the thermostability of vaccine strains to guarantee the quality of the vaccines. In this study, four recombinant FMDV strains containing single or multiple amino acid substitutions in the structural proteins were rescued using a previously constructed FMDV type O full-length infectious clone (pO/DY-VP1). We found that single or multiple amino acid substitutions in the structural proteins affected viral replication to different degrees. Furthermore, the heat and acid stability of the recombinant viruses was significantly increased when compared with the parental virus. Three thermally stable recombinant viruses (rHN/DY-VP1Y2098F, rHN/DY-VP1V2090A-S2093H, and rHN/DY-VP1V2090A-S2093H-Y2098F) were prepared as inactivated vaccines to immunize pigs. Blood samples were collected every week to prepare sera, and a virus neutralization test showed that the substitutions S2093H and Y2098F, separately or in combination, did not affect the immunogenicity of the virus, but the Y2098F mutation increased the thermostability significantly (p < 0.05). Therefore, the rHN/DY-VP1Y2098F mutant should be considered for use in future vaccines.


Assuntos
Substituição de Aminoácidos , Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Proteínas Estruturais Virais/genética , Vacinas Virais/administração & dosagem , Animais , Linhagem Celular , Cricetinae , Armazenamento de Medicamentos , Vírus da Febre Aftosa/genética , Cobaias , Imunização , Testes de Neutralização , Pobreza , Sorogrupo , Suínos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/genética , Vacinas de Produtos Inativados/imunologia , Proteínas Estruturais Virais/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologia , Replicação Viral/efeitos dos fármacos
14.
MycoKeys ; 80: 1-17, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007241

RESUMO

Two new wood-rotting fungi in the family Hymenochaetaceae, Fulvifomes dracaenicola sp. nov. and Hymenochaete dracaenicola sp. nov., are described and illustrated from tropical China based on morphological characteristics and molecular data. It is worth to mention that both of them grow on Dracaena cambodiana which is a kind of angiosperm tree distributed in tropical regions. F. dracaenicola is characterised by perennial, pileate, triquetrous basidioma with yellowish brown fresh pores which becoming honey yellow with silk sheening upon drying, a dimitic hyphal system in trama and monomitic in context, and subglobose basidiospores measuring 4.8-5 × 4-4.1 µm. H. dracaenicola is characterised by annual, resupinate basidioma with a clay buff hymenophore, a dimitic hyphal system, absence of tomentum and cortex, presence of subulate setae, absence of cystidia, presence of cystidioles and simple hyphidia, and oblong ellipsoid basidiospores measuring 5.2-5.8 × 2.5-2.8 µm. The phylogenetic analyses based on ITS + nLSU rDNA sequences confirm the placement of two new species respectively in Fulvifomes and Hymenochaete. Phylogenetically closely related species to the two new species are discussed.

15.
ACS Appl Mater Interfaces ; 13(16): 18563-18580, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33861071

RESUMO

Hybrid surfaces with tunable topography, chemistry, and stiffness have potential to rebuild native extracellular matrix (ECM) and manipulate cell behavior in vitro. However, the fabrication of controllable hybrid surfaces is still challenging. In this study, colloidal self-assembly technology was used to program particles into highly ordered structures with hybrid chemistry and stiffness at biointerfaces. These colloidal self-assembled patterns (cSAPs), including unary, binary, and ternary cSAPs, composed of silicon (Si), polystyrene (PS), and/or poly(N-isopropylacrylamide) (pNIPAM) nanogels (PNGs), were fabricated using either coassembly or layer-by-layer (LBL) methods. The selected binary cSAPs (i.e., PS/PNG and PNG/PS) have a tunable surface topography and wettability between 25 and 37 °C; thus, they can be used as dynamic cell culture substrates. Human adipose-derived mesenchymal stem cells (hASCs), bone marrow-derived mesenchymal stem cells (hBMSCs), and macrophages (THP-1) were investigated on these hybrid cSAPs under a static or dynamic system. The results showed that hybrid cSAPs significantly influenced the focal adhesions, cell morphology, cell migration, and gene expressions of stem cells. In general, stem cells had more vinculin puncta, smaller spreading size, and faster migration speed than the TCPS control. Hybrid cSAPs up-regulated gene expressions of focal adhesion kinase (FAK) and chondrocytes (AGG and SOX9) under static culture, while they also up-regulated osteocytes (COL1 and RUNX2) under dynamic culture. THP-1 macrophages were at M0 state on all cSAPs under static culture. However, cells became sensitive under dynamic culture. For example, some M1 genes (i.e., IL6, CD68, and TNFα) and M2 genes (i.e., IL10 and CD206) were down-regulated, while other M1 genes (i.e., IL1ß) and M2 genes (i.e., TGF-ß and IL1ra) were up-regulated, depending on the particle combinations. In conclusion, new hybrid cSAPs with thermoresponsive surface properties are versatile materials for stem cells and macrophages manipulation.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Temperatura , Tecido Adiposo/citologia , Linhagem Celular , Coloides , Humanos , Regulação para Cima/efeitos dos fármacos , Molhabilidade
16.
ACS Appl Mater Interfaces ; 13(18): 20982-20994, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33913681

RESUMO

The generation of complex physicochemical signals on the surface of biomedical materials is still challenging despite the fact that a broad range of surface modification methods have been developed over the last few decades. Colloidal self-assembled patterns (cSAPs) are combinations of unique colloids differing in size and surface chemistry acting as building blocks that can be programmed to generate surface patterns with exquisite control of complexity. This study reports on producing a variety of pre-modified colloids for the fabrication of cSAPs as well as post-assembly modifications to yield complex surfaces. The surface of cSAPs presents hierarchical micro- and nanostructures, localized hydrophilic/hydrophobic characteristics, and tunable surface functionality imparted by the individual colloids. The selected cSAPs can control bacterial adhesion (S. aureus, P. aeruginosa, and E. coli) and affect the cell cycle of human bone marrow stem cells (hBMSCs). Moreover, in a mouse subcutaneous model, cSAPs with selective [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium (SBMA) modification can reduce the inflammatory response after being challenged with bacteria. This study reveals that functionalized cSAPs are versatile tools for controlling cellular responses at biointerfaces, which is instructive for biomaterials or biodevices.


Assuntos
Materiais Biocompatíveis , Coloides/química , Escherichia coli/fisiologia , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/fisiologia , Células-Tronco/citologia , Animais , Aderência Bacteriana , Células da Medula Óssea/citologia , Ciclo Celular , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Propriedades de Superfície
17.
Gen Psychiatr ; 34(2): e100247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912798

RESUMO

Background: People living with HIV/AIDS (PLWHA) must contend with a significant burden of disease. However, current studies of this demographic have yielded wide variations in the incidence of suicidality (defined as suicidal ideation, suicide attempt and suicide deaths). Aims: This systematic review and meta-analysis aimed to assess the lifetime incidence and prevalence of suicidality in PLWHA. Methods: Publications were identified from PubMed (MEDLINE), SCOPUS, OVID (MEDLINE), Joanna Briggs Institute EBP and Cochrane Library databases (from inception to before 1 February 2020). The search strategy included a combination of Medical Subject Headings associated with suicide and HIV. Researchers independently screened records, extracted outcome measures and assessed study quality. Data were pooled using a random-effects model. Subgroup and meta-regression analyses were conducted to explore the associated risk factors and to identify the sources of heterogeneity. Main outcomes were lifetime incidence of suicide completion and lifetime incidence and prevalence of suicidal ideation and suicide attempt. Results: A total of 185 199 PLWHA were identified from 40 studies (12 cohorts, 27 cross-sectional and 1 nested case-control). The overall incidence of suicide completion in PLWHA was 10.2/1000 persons (95%CI: 4.5 to 23.1), translating to 100-fold higher suicide deaths than the global general population rate of 0.11/1000 persons. The lifetime prevalence of suicide attempts was 158.3/1000 persons (95%CI: 106.9 to 228.2) and of suicidal ideation was 228.3/1000 persons (95%CI: 150.8 to 330.1). Meta-regression revealed that for every 10-percentage point increase in the proportion of people living with HIV with advanced disease (AIDS), the risk of suicide completion increased by 34 per 1000 persons. The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations for the suicide deaths was graded as 'moderate' quality. Conclusions: The risk of suicide death is 100-fold higher in people living with HIV than in the general population. Lifetime incidence of suicidal ideation and attempts are substantially high. Suicide risk assessments should be a priority in PLWHA, especially for those with more advanced disease.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33926104

RESUMO

The contamination of soil by lead (Pb) is a serious and widespread problem in China, especially in mining areas. This paper summarized the available data regarding Pb-contaminated soils around various metal mines in China. Based on these data, the Pb concentration in the soil and its temporal and spatial changes were analyzed. Potential ecological hazards and adult lead models were also used to estimate ecological and health risks. The results indicated that the concentration of Pb was closely related with the type of mine. Compared with other types of mine, soil around lead-zinc (Pb-Zn) and tin (Sn) mines with high Pb contents in the metallic ores and high pollutant emission coefficient were more strongly polluted by Pb. The characteristic spatial and temporal variations of Pb pollution status in China were clarified, and the results showed that the concentration was high in the southern, southwestern, and central regions of China where many mining areas were located, and the mean value passed a turning point in 2012. Ecological risk assessments indicated that some areas around mines were at considerable to high risk, and the risk was relatively severe in Pb-Zn mining areas. According to the adult lead model, Pb-Zn mines had a greater impact on blood Pb concentration than the other types of mine.


Assuntos
Metais Pesados , Poluentes do Solo , Adulto , China , Monitoramento Ambiental , Humanos , Chumbo , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
19.
PLoS One ; 16(3): e0247051, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33657163

RESUMO

An in-depth study on the characteristics of coke in the hearths of blast furnaces is of great significance for explaining the mechanism of coke deterioration in blast furnaces. In the present work, the changes in macromorphology, degree of graphitization, and microstructure of the coke taken from different hearth locations of a 5,800 m3 superlarge blast furnace during its intermediate repair period were systematically studied. Significant differences were found between cokes obtained from the edge ("edge coke") and from the center ("center coke") of the hearth in terms of properties and degradation mechanisms. Edge coke was severely eroded by liquid metal, and only a small amount of slag was detected in the coke porosity, whereas center coke was basically free from erosion by liquid metal, and a large amount of slag was detected in the coke porosity. The degree of graphitization of edge coke was higher than that of center coke. The carburizing effect of liquid metal was the main cause of the degradation of edge coke and made it smaller or even disappear. Center coke was degraded due to the combination of two factors: slag inserted into micropores on the surface of center coke loosened the surface structure; and graphite-like flakes that appeared on the center coke surface lowered the strength and caused cracks in the surface.


Assuntos
Coque/análise , Grafite/análise , China , Metalurgia , Microscopia Eletrônica de Varredura , Microscopia de Polarização , Tamanho da Partícula , Difração de Raios X
20.
Ann Epidemiol ; 56: 26-33.e1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33775279

RESUMO

PURPOSE: Contact tracing has proven successful at controlling coronavirus 2019 (COVID-19) globally, and the Center for Health Security has recommended that the United States add 100,000 contact tracers to the current workforce. METHODS: To address gaps in local contact tracing, health professional students partnered with their academic institution to conduct contact tracing for all COVID-19 cases diagnosed onsite, which included identifying and reaching their contacts, educating participants, and providing social resources to support effective quarantine and isolation. RESULTS: From March 24 to May 28, 536 laboratory-confirmed COVID-19 cases were contacted and reported an average of 2.6 contacts. Contacts were informed of their exposure, asked to quarantine, and monitored for the onset of symptoms. Callers reached 94% of cases and 84% of contacts. Seventy-four percent of cases reported at least one contact. Household members had higher rates of reporting symptoms (odds ratio, 1.65; 95% confidence interval, 1.19-2.28). The average test turnaround time decreased from 21.8 days for the first patients of this program to 2.3 days on the eleventh week. CONCLUSIONS: This provides evidence for the untapped potential of community contact tracing to respond to regional needs, confront barriers to effective quarantine, and mitigate the spread of COVID-19.


Assuntos
COVID-19/diagnóstico , Busca de Comunicante/métodos , Pandemias , Estudantes , Centros Médicos Acadêmicos , COVID-19/prevenção & controle , Humanos , Quarentena , Estados Unidos
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