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1.
Emerg Infect Dis ; 29(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732066

RESUMO

We conducted a genomic analysis of monkeypox virus sequences collected early in the 2022 outbreak, during July-August , in Washington, USA. Using 109 viral genomes, we found low overall genetic diversity, multiple introductions into the state, ongoing community transmission, and potential for co-infections by multiple strains.

2.
Eur J Med Res ; 28(1): 11, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611198

RESUMO

BACKGROUND: We used microarrays to analyse the changes in long non-coding RNAs (lncRNAs) and mRNAs in aorta tissue in model rats with lipopolysaccharide-induced sepsis and determined the lncRNA-mRNA and lncRNA-miRNA-mRNA functional networks. METHODS: Wistar rats were intraperitoneally injected with lipopolysaccharide, and the lncRNA and mRNA expression profiles in the aorta were evaluated using microarrays. The functions of the differentially expressed mRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. We then constructed coding/non-coding co-expression and competing endogenous RNA networks to study the mechanisms related to sepsis in rats. RESULTS: We identified 503 differentially expressed lncRNAs and 2479 differentially expressed mRNAs in the model rats with lipopolysaccharide-induced sepsis. Mitochondrial fission process 1 (MTFP1) was the most significantly down-regulated mRNA. Bioinformatics analysis showed that the significantly down-regulated mRNAs in the sepsis models were in pathways related to mitochondrial structure, function, and energy metabolism. Coding/non-coding co-expression and competing endogenous RNA analyses were conducted using 12 validated lncRNAs in combination with all mRNAs. The coding/non-coding co-expression analysis showed that the 12 validated lncRNAs were mainly regulatory factors for abnormal energy metabolism, including mitochondrial structure damage and aberrant mitochondrial dynamics. The competing endogenous RNA analysis revealed that the potential functions of these 12 lncRNAs might be related to the inflammatory response. CONCLUSION: We determined the differentially expressed lncRNAs and mRNAs in the aorta of septic rats using microarrays. Further studies on these lncRNAs will help elucidate the mechanism of sepsis at the genetic level and may identify potential therapeutic targets.


Assuntos
MicroRNAs , RNA Longo não Codificante , Sepse , Ratos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Lipopolissacarídeos , Ratos Wistar , Sepse/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Redes Reguladoras de Genes , Perfilação da Expressão Gênica
3.
Foods ; 12(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36613434

RESUMO

Quality deterioration is a major problem restricting the fresh-cut potato industry. The present study investigated the effect of sodium nitroprusside (SNP) treatment on the quality of fresh-cut potatoes during short-term storage. The treatment was carried out immediately either before or after cutting, using an SNP concentration of 200 µmol/L. The results showed that SNP treatment inhibited the accumulation of malondialdehyde (MDA) and total soluble solids (TSSs). SNP treatment also decreased the firmness, chewing properties, and ascorbic acid (AsA) content in potatoes, maintaining high levels of total phenols (TPs), total flavonoids (TFs), nitric oxide (NO), and superoxide dismutase (SOD). Furthermore, SNP treatment restrained the rise of phenylalanine ammonia-lyase (PAL), peroxidase (POD), and polyphenol oxidase (PPO), as well as the electrolyte leakage (EL) rate. After SNP treatment, the nitrite content in the potatoes was within security scope. Comparing potatoes treated before and after cutting, the best result was noted in the potatoes soaked in SNP before cutting, which displayed the smallest losses in firmness (11.24%), chewing properties (34.30%), and AsA (40.35%), and maximum increases in TPs (32.84%), TFs (2.83-time), NO (76.11%), and SOD activity (93.15%). Moreover, this group presented the minimum MDA content, EL rate, and TSS values and the lowest PAL, POD, and PPO activities. These results indicated that 200 µmol/L SNP applied for 20 min, particularly before cutting, is an efficient alternative technology that can be used in the fresh-cut potato industry.

4.
J Thromb Haemost ; 21(1): 117-132, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695375

RESUMO

BACKGROUND: Trimethylamine N-oxide (TMAO), a gut microbe-generated metabolite, elicits thrombotic events by enhancing platelet reactivity; however, no studies have reported the effects of TMAO on the metabolism of and response to clopidogrel. OBJECTIVES: To determine whether choline and TMAO could significantly impair metabolic activation of and platelet response to clopidogrel in choline- or TMAO-fed mice and the mechanisms involved. METHODS: Male mice were fed with vehicle control (Ctrl), TMAO, choline alone or in combination with 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 for 14 days and then treated with Ctrl or a single oral dose of clopidogrel. Plasma TMAO, protein levels of clopidogrel-metabolizing enzymes in the liver, plasma concentrations of clopidogrel and its metabolites, and adenosine diphosphate-induced platelet aggregation and activation were measured. In addition, HepG2 cells were treated with Ctrl or TMAO alone or in combination with N-acetyl-L-cysteine, ML385, or apocynin, and CES1, reactive oxygen species (ROS), and Nrf2 protein levels were measured, respectively. RESULTS: TMAO significantly increased Ces1 protein expression and activity and clopidogrel hydrolysis in the liver as well as intracellular ROS and CES1 levels and Nrf2 nucleus translocation in HepG2 cells but decreased the formation of clopidogrel active metabolite and impaired platelet response to clopidogrel. Furthermore, concomitant use of 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 effectively reversed choline- or TMAO-induced impairment of inhibition of platelet aggregation by clopidogrel in mice, respectively. CONCLUSIONS: Choline and TMAO impair the metabolic activation of and platelet response to clopidogrel through the activation of the NOX-dependent ROS/Nrf2/CES1 pathway, suggesting novel strategies for overcoming clopidogrel resistance from bench to bedside.


Assuntos
Colina , Fator 2 Relacionado a NF-E2 , Masculino , Animais , Camundongos , Colina/metabolismo , Clopidogrel , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio , Ativação Metabólica , Acetilcisteína/farmacologia , Acetilcisteína/metabolismo
5.
BJPsych Open ; 9(1): e27, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700253

RESUMO

BACKGROUND: Trauma exposure can cause post-traumatic stress symptoms (PTSS), and persistently experiencing PTSS may lead to the development of post-traumatic stress disorder (PTSD). Research has shown that PTSS that emerged within days of trauma was a robust predictor of PTSD development. AIMS: To investigate patterns of early stress responses to trauma and their associations with development of PTSD. METHOD: We recruited 247 civilian trauma survivors from a local hospital emergency department. The PTSD Checklist for DSM-5 (PCL-5) and Acute Stress Disorder Scale (ASDS) were completed within 2 weeks after the traumatic event. Additionally, 3 months post-trauma 146 of these participants completed a PTSD diagnostic interview using the Clinician Administered PTSD Scale for DSM-5. RESULTS: We first used latent profile analysis on four symptom clusters of the PCL-5 and the dissociation symptom cluster of the ASDS and determined that a four-profile model ('severe symptoms', 'moderate symptoms', 'mild symptoms', 'minimal symptoms') was optimal based on multiple fit indices. Gender was found to be predictive of profile membership. We then found a significant association between subgroup membership and PTSD diagnosis (χ2(3) = 11.85, P < 0.01, Cramer's V = 0.263). Post hoc analysis revealed that this association was driven by participants in the 'severe symptoms' profile, who had a greater likelihood of developing PTSD. CONCLUSIONS: These findings fill the knowledge gap of identifying possible subgroups of individuals based on their PTSS severity during the early post-trauma period and investigating the relationship between subgroup membership and PTSD development, which have important implications for clinical practice.

6.
J Biopharm Stat ; : 1-10, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36715485

RESUMO

Phase 1 oncology studies focus on safety of novel treatments and identifying a dose associated with acceptable toxicity level. Various model-based designs have been proposed for guiding dose escalation and estimating maximum tolerated dose in dose-finding studies. However, these methods are either excessively conservative or imprudent by allowing overly toxic doses. Transparent and easy to implement model-assisted designs have also received increasing attention but require pre-set rules including perceived dose levels. Therefore, we propose a hybrid model-based design that has a high probability to select MTD with a good balance of overdose control by disentangling in two separate models, which is flexible and easy to implement. Extensive simulations show the model to have real promise.

7.
Physiol Genomics ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645668

RESUMO

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) exert pivotal roles in suppressing immune rejection in organ transplantation. However, the function of BMSCs on immune rejection in renal transplantation remains unclear. This study aimed to evaluate the effect and underlying mechanism of BMSCs on immune rejection in renal transplantation. METHODS: Following the establishment of the renal allograft mouse model, the isolated primary BMSCs were injected intravenously into the recipient mice. Enzyme-linked immunosorbent assay, flow cytometry, hematoxylin-eosin staining, and Western blot assays were conducted to investigate BMSCs' function in vivo and in vitro. Mechanistically, the underlying mechanism of BMSCs on immune rejection in renal transplantation was investigated in in vivo and in vitro models. RESULTS: Functionally, BMSCs alleviated the immune rejection in renal transplantation mice and facilitated B cell activation and the production of IL-10+ Regulatory B cells (Bregs). Furthermore, the results of mechanism studies revealed that BMSCs induced the production of IL-10+ Bregs by facilitating a proliferation-inducing ligand (APRIL) phosphorylation to enhance immunosuppression and repressed renal transplant rejection by promoting APRIL phosphorylation to induce IL-10+ Bregs. CONCLUSION: BMSCs prevent renal transplant rejection by facilitating APRIL phosphorylation to induce IL-10+ Bregs.

8.
Biochem Biophys Res Commun ; 638: 155-162, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36459879

RESUMO

Moderate acute stress responses are beneficial for adaptation and maintenance of homeostasis. Exposure of male rat to stress induces effects in the bed nucleus of the stria terminalis (BNST), for it can be activated by the same stimuli that induce activation of the hypothalamic-pituitary-adrenal axis. However, the underlying mechanism of the BNST on male stress reactivity remains unclear. In this study, we explored whether systematic administration of dexmedetomidine (DEXM) altered the acute stress reactivity through its effect on the BNST. Male Sprague-Dawley rats in the stress (STRE) group, DEXM group, and the DEXM + GSK-650394 (GSK, an antagonist of serum- and glucocorticoid-inducible kinase 1 (SGK1)) group, except those in the vehicle (VEH) group, underwent 1-h restraint plus water-immersion (RPWI) exposure. All the rats proceeded the open field test (OFT) 24 h before RPWI and 1 h after RPWI. After the second OFT, the rats received VEH, DEXM (75 µg/kg i.p.), or were pretreated with GSK (2 µM i.p.) 0.5 h ahead of DEXM respectively. The third OFT was conducted 6 h after drug administration and then the rats were sacrificed. The rats that experienced RPWI showed dramatically elevated serum corticosterone (CORT), multiplied neuronal nitric oxide synthase (nNOS) and SGK1 in the BNST, and terrible OFT behavior. We discovered when the nNOS and SGK1 were decreased in the rat BNST through DEXM treatment, the serum CORT was reduced and the OFT manifestation was ameliorated, whereas these were restrained by GSK application. Our results reveal that modest interventions to SGK1 and nNOS in the BNST improve the male rat reactivity to acute stress, and DEXM was one modulator of these effects.

9.
Pestic Biochem Physiol ; 188: 105263, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464368

RESUMO

The leafminer Liriomyza trifolii is an important insect pest of ornamental and vegetable crops worldwide. Cyromazine is an effective, commonly-used insecticide that functions as a growth regulator, but its effect on L. trifolii has not been previously reported. In this study, transcriptome analysis was undertaken in L. trifolii exposed to cyromazine. Clusters of orthologous groups analysis indicated that a large number of differentially expressed genes responding to cyromazine were categorized as "lipid transport and metabolism", "post-translational modification, protein turnover, chaperones", and "cell wall/membrane/envelope biogenesis". Gene ontology analysis indicated that pathways associated with insect hormones, growth and development, and cuticle synthesis were significantly enriched. In general, the transcriptome results showed that the genes related to insect hormones were significantly expressed after treatment with cyromazine. Furthermore, the combined exposure of L. trifolii to cyromazine and the hormone analogues 20-hydroxyecdysone (20E) or juvenile hormone (JH) indicated that hormone analogues can change the expression pattern of hormone-related genes (20EP and JHEH) and pupal length. The combined application of cyromazine with 20E improved the survival rate of L. trifolii, whereas the combination of JH and cyromazine reduced survival. The results of this study help elucidate the mechanistic basis for cyromazine toxicity and provide a foundation for understanding cyromazine resistance.


Assuntos
Dípteros , Hormônios de Inseto , Inseticidas , Animais , Dípteros/genética , Inseticidas/toxicidade , Triazinas/toxicidade , Hormônios Juvenis/farmacologia
10.
Front Plant Sci ; 13: 1085497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36570962

RESUMO

Introduction: Alfalfa (Medicago sativa) is a kind of high quality leguminous forage species, which was widely cultivated in the world. Leaf senescence is an essential process in plant development and life cycle. Here, we reported the isolation and functional analysis of an alfalfa SENESCENCE-ASSOCIATED GENE113 (MsSAG113), which belongs to the PP2C family and mainly plays a role in promoting plant senescence. Methods: In the study, Agrobacterium-mediated, gene expression analysis, next generation sequencing, DNA pull-down, yeast single hybridization and transient expression were used to identify the function of MsSAG113 gene. Results: The MsSAG113 gene was isolated from alfalfa, and the transgenic plants were obtained by Agrobacterium-mediated method. Compared with the wildtype, transgenic plants showed premature senescence in leaves, especially when cultivated under dark conditions. Meanwhile, application of exogenous hormones ABA, SA, MeJA, obviously acclerated leaf senescence of transgenic plants. Furthermore, the detached leaves from transgenic plants turned yellow earlier with lower chlorophyll content. Transcriptome analysis identified a total of 1,392 differentially expressed genes (DEGs), involving 13 transcription factor families. Of which, 234 genes were related to phytohormone synthesis, metabolism and transduction. Pull-down assay and yeast one-hybrid assay confirmed that alfalfa zinc finger CCCH domain-containing protein 39 (MsC3H-39) could directly bind the upstream of MsSAG113 gene. In conclusion, the MsSAG113 gene plays a crucial role in promoting leaf senescence in alfalfa via participating in the hormone regulatory network. Discussion: This provides an essential basis for further analysis on the regulatory network involving senescence-associated genes in alfalfa.

11.
medRxiv ; 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36561171

RESUMO

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape. One Sentence Summary: Analysis of SARS-CoV-2 genomes in King County, Washington show that diverse areas in the same metropolitan region can have different epidemic dynamics.

12.
Am J Transl Res ; 14(11): 7898-7906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505339

RESUMO

OBJECTIVE: To determine the median effective concentration (EC50) of remifentanil to inhibit pupillary reflex dilation (PRD) induced by endotracheal intubation using a modified sequential test method. METHODS: In this prospective study, 34 patients undergoing elective surgery under general anesthesia were selected. The induction of anesthesia was started using propofol with an effect-site concentration (Ce(pro)) of 4.0 µg/mL. The effect-site concentration of remifentanil (Ce(Remi)) was set according to the modified sequential test method, with 0.42 ng/mL as the initial concentration for the first patient. The gradient ratio was 1.1. The Ce(Remi) of each patient was determined by whether the PRD of the previous patient disappeared during endotracheal intubation. If the PRD disappeared, a lower concentration was applied. Otherwise, a higher concentration was applied. The experiment ended after 9 crosses of PRD disappearance-presence and PRD presence-disappearance. The EC50 of remifentanil and 95% confidence interval (CI) were calculated using the Dixon and Massey's method. The Probit regression procedure was used to derive the EC50, 95% effective concentration (EC95) of remifentanil and their 95% CIs. RESULTS: The EC50 of remifentanil to inhibit PRD induced by endotracheal intubation was 4.41 ng/mL (95% CI, 4.32 to 4.49 ng/mL) and the EC95 was 5.24 ng/mL (95% CI, 4.78 to 7.68 ng/mL). In 34 patients, the time to reach the maximum change in heart rate, systolic blood pressure, mean arterial pressure and Bispectral index was 75.00 (60.00-98.00) s, 95.00 (75.00-133.00) s, 95.00 (75.00-135.00) s, and 100.00 (78.00-113.00) s, respectively, which was significantly longer than the time (42.00 (25.00-47.00) s) needed for pupillary diameter (P<0.05). CONCLUSION: The EC50 of remifentanil to inhibit PRD induced by endotracheal intubation was 4.41 ng/mL and the EC95 was 5.24 ng/mL. The time to reach the maximum pupillary diameter change was shorter than the time needed for heart rate, blood pressure, and Bispectral index. This prospective study was registered in the China Clinical Trials Registration Center (ChiCTR2100043771, https://www.chictr.org.cn).

13.
Biopharm Drug Dispos ; 43(6): 247-254, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36519186

RESUMO

As an analog of clopidogrel and prasugrel, vicagrel is completely hydrolyzed to intermediate thiolactone metabolite 2-oxo-clopidogrel (also the precursor of active thiol metabolite H4) in human intestine, predominantly by AADAC and CES2; however, other unknown vicagrel hydrolases remain to be identified. In this study, recombinant human Raf kinase inhibitor protein (rhRKIP) and pooled human intestinal S9 (HIS9) fractions and microsome (HIM) preparations were used as the different enzyme sources; prasugrel as a probe drug for RKIP (a positive control), vicagrel as a substrate drug of interest, and the rate of the formation of thiolactone metabolites 2-oxo-clopidogrel and R95913 as metrics of hydrolase activity examined, respectively. In addition, an IC50 value of inhibition of rhRKIP-catalyzed vicagrel hydrolysis by locostatin was measured, and five classical esterase inhibitors with distinct esterase selectivity were used to dissect the involvement of multiple hydrolases in vicagrel hydrolysis. The results showed that rhRKIP hydrolyzed vicagrel in vitro, with the values of Km , Vmax , and CLint measured as 20.04 ± 1.99 µM, 434.60 ± 12.46 nM/min/mg protein, and 21.69 ± 0.28 ml/min/mg protein, respectively, and that an IC50 value of locostatin was estimated as 1.24 ± 0.04 mM for rhRKIP. In addition to locostatin, eserine and vinblastine strongly suppressed vicagrel hydrolysis in HIM. It is concluded that RKIP can catalyze the hydrolysis of vicagrel in the human intestine, and that vicagrel can be hydrolyzed by multiple hydrolases, such as RKIP, AADAC, and CES2, concomitantly.


Assuntos
Hidrolases , Proteína de Ligação a Fosfatidiletanolamina , Humanos , Cloridrato de Prasugrel/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Clopidogrel , Hidrolases/metabolismo , Esterases/metabolismo , Intestinos
14.
BMC Pregnancy Childbirth ; 22(1): 861, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411456

RESUMO

BACKGROUND: Fetal growth restriction (FGR) occurs in up to 10% of pregnancies and is a leading cause of perinatal mortality and neonatal morbidity. Three-dimensional ultrasonography of intracranial structure volume revealed significant differences between fetuses with FGR and appropriate for gestational age (AGA) fetuses. We aimed to compare the frontal lobe development between fetuses with FGR and appropriately grown fetuses and evaluate the impact of fetal circulatory redistribution (FCR) on frontal lobe development in fetuses with FGR. METHODS: We performed a case-control study at our institution from August 2020 to April 2021. The frontal antero-posterior diameter (FAPD) and occipito-frontal diameter (OFD) were measured on the trans-ventricle view and we calculated the Z-scores for FAPD and OFD standardized for gestational age (GA) and transverse cerebellar diameter (TCD) by performing a standard regression analysis followed by weighted regression of absolute residual values in appropriately grown fetuses. We calculated the FAPD/OFD ratio as 100 × FAPD/OFD and FAPD/HC (head circumference) as 100 × FAPD/HC. To compare intracranial parameters, we randomly selected a control group of appropriately grown fetuses matched with the FGR group at the time of ultrasonography. We performed between-group comparisons of the FAPD Z-score, OFD Z-score, FAPD/OFD ratio and FAPD/HC. Similarly, we compared intracranial parameters between fetuses with FGR with and without FCR. RESULTS: FAPD/OFD ratio was curvilinear related to all the independent variables (GA, BPD, FL, and TCD). Compared with appropriately grown fetuses, fetuses with FGR showed a significantly lower FAPD/OFD ratio, FAPD Z-score, and FAPD/HC. There was no significant difference in the FAPD Z-score, FAPD/OFD ratio, and FAPD/HC between FGR fetuses with and without FCR. CONCLUSIONS: The FAPD/OFD ratio varied during pregnancy, with a mild reduction before and a mild increase after about 33 gestational weeks. Fetuses with FGR showed reduced frontal lobe growth; moreover, fetal frontal lobe development disorders were not significantly different in fetuses with FCR. TRIAL REGISTRATION: Date: 09-27-2017; Number: [2017]239.


Assuntos
Doenças do Recém-Nascido , Ultrassonografia Pré-Natal , Gravidez , Recém-Nascido , Feminino , Humanos , Estudos de Casos e Controles , Ultrassonografia Pré-Natal/métodos , Feto , Ultrassonografia , Retardo do Crescimento Fetal/diagnóstico por imagem , Lobo Frontal
15.
Viruses ; 14(11)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36366490

RESUMO

Monkeypox virus, the causative agent of the 2022 monkeypox outbreak, is a double-stranded DNA virus in the Orthopoxvirus genus of the Poxviridae family. Genes in terminal regions of Orthopoxvirus genomes mostly code for host-pathogen interaction proteins and are prone to selective pressure and modification events. Using viral whole genome sequencing, we identified twenty-five total clinical samples with ORF-disrupting mutations, including twenty samples encoding nonsense mutations in MPXVgp001/191 (OPG001), MPXVgp004/188 (OPG015), MPXVgp010 (OPG023), MPXVgp030 (OPG042), MPXVgp159 (OPG0178), or MPXVgp161 (OPG181). Additional mutations include a frameshift leading to an alternative C-terminus in MPXVgp010 (OPG023) and an insertion in an adenine homopolymer at the beginning of the annotated ORF for MPXVgp153 (OPG151), encoding a subunit of the RNA polymerase, suggesting the virus may instead use the start codon that encodes Met9 as annotated. Finally, we detected three samples with large (>900 bp) deletions. These included a 913 bp deletion that truncates the C-terminus of MPXVgp010 (OPG023); a 4205 bp deletion that eliminates MPXVgp012 (OPG025), MPXVgp013 (OPG027), and MPXVgp014 (OPG029) and truncates MPXVgp011 (OPG024; D8L) and MPXVgp015 (OPG030); and a 6881 bp deletion that truncates MPXVgp182 (OPG210) and eliminates putative ORFs MPXVgp184, MPXVgp185 (OPG005), and MPXVgp186, as well as MPXVgp187 (OPG016), and MPXVgp188 (OPG015) from the 3' ITR only. MPXVgp182 encodes the monkeypox-specific, highly immunogenic surface glycoprotein B21R which has been proposed as a serological target. Overall, we find greater than one-tenth of our sequenced MPXV isolates have at least one gene inactivating mutation and these genes together comprised greater than one-tenth of annotated MPXV genes. Our findings highlight non-essential genes in monkeypox virus that may be evolving as a result of selective pressure in humans, as well as the limitations of targeting them for therapeutics and diagnostic testing.


Assuntos
Vírus da Varíola dos Macacos , Varíola dos Macacos , Humanos , Varíola dos Macacos/diagnóstico , Vírus da Varíola dos Macacos/genética , Mutação , Ohio , Washington , Fases de Leitura Aberta
16.
World J Clin Cases ; 10(29): 10787-10793, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36312507

RESUMO

BACKGROUND: Sperm granuloma is a rare disease in clinical andrology and its incidence is still unclear worldwide. According to the existing literature, sperm granuloma often occurs unilaterally. Clinical and ultrasound features are similar to epididymal tuberculosis, chronic epididymitis and other diseases. Sperm granuloma is usually diagnosed based on postoperative histopathological and immunohistochemical examination. CASE SUMMARY: A 46-year-old man was admitted to the hospital due to the presence of a left scrotal mass for 3 mo and aggravation of pain for 1 wk. The lesions at both sites were surgically resected. Postoperative pathological examination showed that the left spermatic cord mass and the right epididymal mass were consistent with sperm granuloma. The sperm granulomas then recurred 3 mo after surgery. There is little change in the local mass so far. CONCLUSION: The case report is helpful for our understanding of this disease. In clinical diagnosis, it should be distinguished from epididymal tuberculosis, chronic epididymitis and other diseases. Color Doppler ultrasound can be used as a preferred examination method but postoperative pathological examination is still needed for diagnosis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36212957

RESUMO

Background: Disruption of the vascular immunological inflammatory microenvironment is linked to metabolic memory impairment. Even though it has been proven that the Shen-Qi compound (SQC) can efficiently halt metabolic memory and preserve vascular endothelial cells, extensive studies need to be done to investigate if it can also change the vascular immune-inflammatory microenvironment by regulating the immune system. This will help figure out the role of stopping metabolic memory. Methods: After 4 weeks on a high-fat diet (HFD), GK rats were used to create a model for diabetic thoracic aortic problems. The effect and mechanisms of SQC on diabetic thoracic aortic complications were assessed by hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), biochemical analysis, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), reverse transcription, real-time polymerase chain reaction (RT-qPCR), immunofluorescence (IF), western blot, and luciferase reporter assays. Results: SQC treatment ameliorates the HFD-induced pathological symptoms as well as the HFD-induced increased concentrations of fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) and decreased concentrations of high-density lipoprotein cholesterol (HDL-C). Besides, SQC counteracted the HFD-induced average fluorescence intensity of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), as well as the concentrations of endothelin-1 (ET-1) and monocyte chemoattractant protein-1 (MCP-1), while rescuing the HFD-induced concentrations of nitric oxide (NO) and nitric oxide synthetase (NOS). Also, SQC decreases apoptosis and oxidative stress in rats with diabetic thoracic aortic complications. In addition, SQC facilitated the polarization of macrophages, stimulated the activation of dendritic cells, and regulated the inflammatory milieu in rats with diabetic thoracic aortic complications. Furthermore, SQC also modulated the miR-223-3p/RBP-J/IRF8 axis in the macrophages of rats with diabetic thoracic aortic complications. Conclusion: SQC ameliorated diabetic thoracic aortic complications through the regulation of apoptosis, oxidative stress, and inflammatory microenvironment mediating by the miR-223-3p/RBP-J/IRF8 axis.

19.
Front Rehabil Sci ; 3: 855502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189056

RESUMO

Background: The common standards of disability assessment for long-term care (LTC) insurance are currently absent. The International Classification of Functioning, Disability and Health (ICF) was designed for a better description of health and functioning, which could fill the demand gap for the standards of disability assessment and be a promising tool for the development of LTC insurance system. Objectives: To validate a disability assessment scale for disabled elderly individuals based on the ICF for LTC in the Chinese context. Methods: The present study is a cross-sectional study. A disability assessment tool based on the ICF was developed by referring to other assessment tools and an expert consensus meeting in the initial phase of the study. The developed tool was used to evaluate 1,610 elderly individuals in the LTC institutions. The Cronbach's α coefficient and split-half reliability were applied to test the internal consistency of the tool, while the Interclass correlation coefficients (ICCs) were used to evaluate the interrater reliability (IRR). Factor analysis was performed to verify the construct validity of the tool. The scores from the Medical Outcomes Short Form-12 (SF-12) were correlated with that from the disability assessment tool, to assess the criterion-related validity. Results: The Cronbach's α coefficient and split-half reliability of the disability assessment tool were 0.969 and 0.877, respectively. The ICCs of the sum scale was 0.85, and the ICCs of each of the 20 items in the scale ranged from 0.78 to 0.94. The items were divided into three factors through analysis, which is consistent with the structure expectation. The scores of each item and the sum score of the disability assessment scale were negatively correlated with the scores of the physical and psychological fields in SF-12 (p < 0.001). Overall, the data indicated that the tool was characterized by good internal consistency, IRR, construct validity, and criterion-related validity. Conclusions: The disability assessment tool based on the ICF is a reliable and valid tool for the collection of information on functioning across various LTC settings. The information of disability provided evidence for the distribution of LTC service and guided the development of LTC insurance standards.

20.
Am J Obstet Gynecol MFM ; 5(1): 100759, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36191891

RESUMO

BACKGROUND: Double aortic arch is the most common form of complete vascular ring. The trachea and/or esophagus could be compressed by the complete vascular ring, which may lead to early respiratory and/or esophageal symptoms in children with double aortic arch. Accurate prenatal assessment of tracheal compression could provide relevant information for perinatal clinical management of double aortic arch and emergency treatment of infants with double aortic arch. The fetal trachea is filled with amniotic fluid and can be clearly visualized with prenatal ultrasound. Previous studies reported the use of prenatal ultrasound to measure the tracheal internal diameters in normal fetuses and showed a linear correlation between the fetal tracheal internal diameters and gestational age. However, to the best of our knowledge, few studies have quantitatively evaluated tracheal compression in fetuses with double aortic arch using ultrasound. OBJECTIVE: This study aimed to evaluate the tracheal compression caused by the vascular ring in fetuses with double aortic arch using prenatal ultrasound and to analyze the relationship between tracheal compression and postnatal clinical symptoms. STUDY DESIGN: The data of fetuses with double aortic arch diagnosed with prenatal ultrasound at 2 institutions from January 2011 to April 2021 were retrospectively analyzed. Singleton pregnancies with normal fetuses as the control group were prospectively recruited. The tracheal compression-evaluated by comparing the tracheal internal diameter z scores against the gestational age-was assessed in fetuses with double aortic arch and in normal fetuses. The live-born infants with double aortic arch were divided into symptomatic and asymptomatic groups for the comparison of z scores. The receiver operating characteristic curve for the tracheal internal diameter z score cutoffs and prediction of symptomatic infants with double aortic arch was plotted. Intraobserver and interobserver agreements were investigated. RESULTS: A total of 26 fetuses with double aortic arch were diagnosed, and 14 fetuses (53.8%) with double aortic arch were delivered alive. Among the 14 live-born infants, 7 (50.0%) were symptomatic, whereas 7 (50.0%) were asymptomatic. The tracheal internal diameter z scores were significantly lower in the double aortic arch group than in the normal groups (-0.62±1.36 vs 0.00±0.78; P<.001). The tracheal internal diameter z scores were significantly lower in the symptomatic group than in the asymptomatic group (-1.42±0.92 vs -0.49±0.96; P=.018). The area under the curve was 0.878 (95% confidence interval, 0.689-1.000). Using a tracheal internal diameter z scores cutoff of -1.21, the sensitivity was 71%, and the specificity was close to 100%. The intraclass correlation coefficients of interobserver and intraobserver agreements were 0.987 (95% confidence interval, 0.980-0.992) and 0.975 (95% confidence interval, 0.955-0.987), respectively. CONCLUSION: The clinical symptoms in infants with double aortic arch were associated with prenatal tracheal compression, which can be prenatally evaluated using ultrasound. If fetuses are diagnosed with double aortic arch, prenatal surveillance of the tracheal internal diameters and comparison with z score reference ranges could provide pertinent information that would aid perinatal clinical management.

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