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A series of acylhydrazone-based N,N-chelate half-sandwich iridium complexes have been synthesized through a facile route in good yields. The dehydrogenation of a series of aromatic and aliphatic primary alcohols to corresponding carboxylic acids has been accomplished catalyzed by the prepared air stable iridium complexes under mild reaction conditions. Carboxylic acids were obtained in high yields under open flask condition with broad substrates and good tolerance to sensitive functional groups. Such a half-sandwich iridium catalyst system exhibited high catalytic activity and stability, and a high TOF of 316.7 h-1 could be achieved with a catalyst loading as low as 0.05 mol %. Furthermore, the sustainable catalyst could be reused at least five times without obviously losing its activity, highlighting its potential application in industry. Molecular structure of iridium complex 1 was confirmed by single-crystal X-ray analysis.
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Films of piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymer P(VDF-TrFE) have been studied intensively for their potential application in piezoelectric sensing devices. The present work focuses on tuning the piezoelectric properties of P(VDF-TrFE) films via incorporating Ag and polydopamine co-decorated PZT (Ag@PDA@PZT) particles. Ag@PDA@PZT particles can effectively improve the ß-phase content and piezoelectric properties of P(VDF-TrFE) films. The highest open-circuit voltage and short-circuit current of P(VDF-TrFE)-based flexible pressure sensors incorporating Ag@PDA@PZT particles are ~30 V and ~2.4 µA, respectively. The flexible sensors exhibit a response to different body movements, providing a practical and potentially useful basis for human-machine interface applications.
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Few nursing informatics studies focus on selecting nursing diagnoses for critical patients. The absence of data about nursing clinical judgment in the care of patients with cerebral hemorrhage greatly hinders research progress in evidence-based care. A stratified, retrospective study analyzed 115 electronic "intelligent" nursing information system nurse assessments and nursing diagnoses. Data were documented from April 2019 to November 2020 for critically ill patients admitted with cerebral hemorrhage in a 10-bed medical ICU at a 1500-bed tertiary facility, Henan Honliv Hospital, in Henan Province, China. In the selection of nursing diagnoses among nurses of stratified competencies (novice to expert), novice and experienced nurses were found to have significant variances in selecting nursing diagnoses for critically ill patients with cerebral hemorrhage. Novice nurses more frequently selected the Activity Intolerance Risk diagnosis as an initial diagnosis ( P = .025). Experienced nurses selected the Fluid Volume Excess Risk diagnosis more frequently ( P = .003). Consequently, nursing information systems are important in evaluating professional practice. The access to structured, standardized nursing data for the complete nursing process enables nurse managers to comprehensively analyze the nursing care given to patients, the distribution of patient nursing diagnoses, and the status of patient care risks.
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The gut microbiota of insects plays a vital role in digestion, nutrient acquisition, metabolism of dietary toxins, pathogen immunity and maintenance of gut homeostasis. Bacillus thuringinensis (Bt) poisons target insects through its toxins that are activated in the insect gut. The effects of Bt toxins on gut microbiota of insects and their underlying mechanisms are not well understood. In this study, we found that Cry1Ab/2Ab toxins significantly changed the gut bacterial community's structure and reduced the total load of gut bacteria in the Locusta migratoria. In addition, Cry toxins significantly increased the level of reactive oxygen species (ROS) in the gut of locusts. Our results also showed that Cry1Ab/2Ab toxins induced the host gut's immune response by up-regulating of key genes in the Immune deficiency (IMD) and Toll pathway. RNA interference showed that knocking down Relish could narrow the difference in the load, diversity, and composition in gut bacteria caused by Cry toxins. Our findings suggest that Bt potentially influences the gut bacterial community of L. migratoria through host immune response.
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Bacillus thuringiensis , Bacillus , Microbioma Gastrointestinal , Locusta migratoria , Animais , Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/toxicidade , Endotoxinas/toxicidade , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/toxicidade , Imunidade , Insetos , NeópterosRESUMO
OBJECTIVES: To study the effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks. METHODS: The medical data were retrospectively collected from 865 preterm infants with a gestational age of <35 weeks who were admitted to the Neonatal Intensive Care Unit of Xiangya Hospital of Central South University from January 1, 2014 to December 31, 2016. The improved antibiotic use strategy was implemented since January 1, 2015. According to the time of implementation, the infants were divided into three groups: pre-adjustment (January 1, 2014 to December 31, 2014; n=303), post-adjustment â (January 1, 2015 to December 31, 2015; n=293), and post-adjustment â ¡ (January 1, 2016 to December 31, 2016; n=269). The medical data of the three groups were compared. RESULTS: There were no significant differences among the three groups in gestational age, proportion of small-for-gestational-age infants, sex, and method of birth (P>0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment â ¡ groups had a significant reduction in the rate of use of antibiotics and the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days or 4-7 days and a significant reduction in the proportion of infants with a duration of antibiotic use of >7 days in the early postnatal period (P<0.05). Compared with the post-adjustment â group, the post-adjustment â ¡ group had a significant reduction in the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days and a significant reduction in the proportion of infants with a duration of antibiotic use of 4-7 days or >7 days (P<0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment â ¡ groups had significantly shorter duration of parenteral nutrition and length of hospital stay (P<0.05). There were gradual reductions in the incidence rates of grade ≥â ¢ intraventricular hemorrhage (IVH) and late-onset sepsis (LOS) after the adjustment of antibiotic use strategy. The multivariate logistic regression analysis showed that the adjustment of antibiotic use strategy had no effect on short-term adverse clinical outcomes, and antibiotic use for >7 days significantly increased the risk of adverse clinical outcomes (P<0.05). CONCLUSIONS: It is feasible to reduce unnecessary antibiotic use by the improvement in antibiotic use strategy in preterm infants with a gestational age of <35 weeks, which can also shorten the duration of parenteral nutrition and the length of hospital stay and reduce the incidence rates of grade ≥â ¢ IVH and LOS.
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Doenças do Recém-Nascido , Sepse , Antibacterianos/uso terapêutico , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Estudos Retrospectivos , Sepse/epidemiologiaRESUMO
BACKGROUND: Although the structure and physicochemical properties of large ring cyclodextrins (LR-CDs) exhibit unique characteristics, and also possess very strong water solubility and high safety, little is known about the embedding performance of macrocyclodextrin. Encapsulation refers to a complex of tea tree oil (TTO) with the wall material, protecting the core material or changing its properties from adverse external factors, controlling its release rate against the evaporation and degradation of essential oils. In the present study, LR-CDs complexed with TTO were prepared by co-precipitation methods. RESULTS: The mass ratio of LR-CDs-TTO was six and the maximum complexation efficiency was 86.23%. Fourier-transform infrared spectroscopy analysis presented the loss of characteristic peaks related to TTO in the complex and no other additional peaks were observed. X-ray diffraction examination demonstrated several sharp peaks and intensity peaks at the diffraction angle of the TTO-LR-CDs complex. 1 H-NMR indicated a chemical shift as a result of the interaction between the molecules in the inclusion complex. Moreover, the thermal stability and aqueous solubility of TTO were enhanced after synergy with LR-CDs; particularly, the solubility of the complex was increased by 329-fold. The volatile characteristics of the encapsulated and original TTO were identical. CONCLUSION: The results of the present study show that TTO was efficaciously complexed with LR-CDs and exhibited enhanced solubility and thermal stability. © 2020 Society of Chemical Industry.
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Ciclodextrinas/química , Composição de Medicamentos/métodos , Óleos Voláteis/química , Óleo de Melaleuca/química , Composição de Medicamentos/instrumentação , Estabilidade de Medicamentos , Temperatura Alta , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Volatilização , Difração de Raios XRESUMO
A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the HSD17B4 gene. This article reports a case of D-bifunctional protein deficiency caused by HSD17B4 gene mutation and summarizes the epidemiological and clinical features, diagnosis, and treatment of this disease, with a focus on the differential diagnosis of this disease from Ohtahara syndrome.
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Hipotonia Muscular , Deficiência de Proteína , Testes Genéticos , Humanos , Recém-Nascido , Masculino , Mutação , Proteína Multifuncional do Peroxissomo-2/genética , Deficiência de Proteína/genéticaRESUMO
[This corrects the article DOI: 10.1371/journal.ppat.1005387.].
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Hosts encounter an ever-changing array of pathogens, so there is continual selection for novel ways to resist infection. A powerful way to understand how hosts evolve resistance is to identify the genes that cause variation in susceptibility to infection. Using high-resolution genetic mapping we have identified a naturally occurring polymorphism in a gene called Ge-1 that makes Drosophila melanogaster highly resistant to its natural pathogen Drosophila melanogaster sigma virus (DMelSV). By modifying the sequence of the gene in transgenic flies, we identified a 26 amino acid deletion in the serine-rich linker region of Ge-1 that is causing the resistance. Knocking down the expression of the susceptible allele leads to a decrease in viral titre in infected flies, indicating that Ge-1 is an existing restriction factor whose antiviral effects have been increased by the deletion. Ge-1 plays a central role in RNA degradation and the formation of processing bodies (P bodies). A key effector in antiviral immunity, the RNAi induced silencing complex (RISC), localises to P bodies, but we found that Ge-1-based resistance is not dependent on the small interfering RNA (siRNA) pathway. However, we found that Decapping protein 1 (DCP1) protects flies against sigma virus. This protein interacts with Ge-1 and commits mRNA for degradation by removing the 5' cap, suggesting that resistance may rely on this RNA degradation pathway. The serine-rich linker domain of Ge-1 has experienced strong selection during the evolution of Drosophila, suggesting that this gene may be under long-term selection by viruses. These findings demonstrate that studying naturally occurring polymorphisms that increase resistance to infections enables us to identify novel forms of antiviral defence, and support a pattern of major effect polymorphisms controlling resistance to viruses in Drosophila.
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Proteínas de Transporte/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Polimorfismo Genético , Rhabdoviridae , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Drosophila melanogaster/virologia , Genótipo , Dados de Sequência Molecular , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
A hypertrophic scar (HS) is caused by abnormal proliferation of dermal fibroblasts. Thus, promoting hypertrophic scar fibroblast (HSFB) apoptosis is an effective strategy for HS therapy. Ursolic acid (UA) has been widely used as an inducer of apoptosis in diverse cancers. However, whether UA plays an inhibitory role in HS formation is still unknown. In our study, UA was used to treat HSFBs and the cell viability, apoptosis, and collagen synthesis were determined by a Cell Counting Kit 8 assay, flow cytometry, and an H3 -proline incorporation assay, respectively. Autophagy activity was detected by LC3 immunoblotting and electron microscopy, and siRNAs targeting Beclin-1 were used to inhibit autophagy. Western blotting was performed to investigate the molecular changes in HSFBs after various treatments. We found that UA inhibited collagen synthesis and induced cell apoptosis in HSFBs, evidenced by the deregulated expression of Bim, Bcl-2 and Cyto C. Furthermore, we demonstrated that UA induced autophagy and inactivation of autophagy promoted UA-induced apoptosis and collagen synthesis inhibition in HSFBs. Molecular investigation indicated that UA-induced autophagy through upregulation of Beclin-1 and knockdown of Beclin-1 prevent UA-induced autophagy. Overexpression of Bcl-2 prevents UA-induced autophagy, Beclin-1 upregulation, apoptosis and collagen synthesis inhibition in HSFBs. Collectively, our study demonstrated that UA is a novel agent for inhibiting HS formation by promoting apoptosis, especially in combination with an autophagy inhibitor. Our results provide strong evidence of the application of UA in clinical HS treatment.
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Apoptose , Autofagia , Proteína Beclina-1/metabolismo , Cicatriz Hipertrófica/metabolismo , Fibroblastos/citologia , Triterpenos/química , Proliferação de Células , Colágeno/metabolismo , Fibroblastos/metabolismo , Citometria de Fluxo , Humanos , Immunoblotting , Microscopia Eletrônica , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Ácido UrsólicoRESUMO
Emerging infectious diseases are often the result of a host shift, where the pathogen originates from a different host species. Virulence--the harm a pathogen does to its host-can be extremely high following a host shift (for example Ebola, HIV, and SARs), while other host shifts may go undetected as they cause few symptoms in the new host. Here we examine how virulence varies across host species by carrying out a large cross infection experiment using 48 species of Drosophilidae and an RNA virus. Host shifts resulted in dramatic variation in virulence, with benign infections in some species and rapid death in others. The change in virulence was highly predictable from the host phylogeny, with hosts clustering together in distinct clades displaying high or low virulence. High levels of virulence are associated with high viral loads, and this may determine the transmission rate of the virus.
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Drosophila/genética , Drosophila/virologia , Especificidade de Hospedeiro/genética , Vírus de RNA/patogenicidade , Virulência/genética , Animais , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carga ViralRESUMO
BACKGROUND: Hypertrophic scarring (HS) is a severe disease, and results from unusual wound healing. Col1A1 could promote the hypertrophic scar formation, and the expression of Col1A1 in HS tissue was markedly higher than that in the normal. In present study, we aimed to identify miRNAs as post-transcriptional regulators of Col1A1 in HS. METHODS: MicroRNA-98 was selected as the key miRNA comprised in HS. The mRNA levels of miR-98 in HS tissues and the matched normal skin tissues were determined by qRT-PCR. MTT and flow cytometry were used to determine the influence of miR-98 on cell proliferation and apoptosis of HSFBs, respectively. Col1A1 was found to be the target gene of miR-98 using luciferase reporter assay. Luciferase assay was performed to determine the relative luciferase activity in mimic NC, miR-98 mimic, inhibitor NC and miR-98 inhibitor with Col1A13'-UTR wt or Col1A13'-UTR mt reporter plasmids. The protein expression of Col1A1 in HSFBs after transfection with mimic NC, miR-98 mimic, inhibitor NC and miR-98 inhibitor were determined by western blotting. RESULTS: The mRNA level of miR-98 in HS tissues was much higher than that in the control. Transfection of HSFBs with a miR-98 mimic reduced the cell viability of HSFBs and increased the apoptosis portion of HSFBs, while inhibition of miR-98 increased cell viability and decreased apoptosis portion of HSFBs. miR-98 inhibitor increased the relative luciferase activity significantly when cotransfected with the Col1A1-UTR reporter plasmid, while the mutant reporter plasmid abolished the miR-98 inhibitor-mediated increase in luciferase activity. Western blotting revealed that overexpression of miR-98 decreased the expression of Col1A1. CONCLUSIONS: Overexpression of miR-98 repressed the proliferation of HSFBs by targeting Col1A1.
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Apoptose/genética , Colágeno Tipo I/metabolismo , Fibroblastos/metabolismo , MicroRNAs/genética , Processamento Pós-Transcricional do RNA/genética , Estudos de Casos e Controles , Proliferação de Células , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/metabolismo , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Regulação para Baixo , Humanos , MicroRNAs/metabolismoRESUMO
Heritable symbionts that protect their hosts from pathogens have been described in a wide range of insect species. By reducing the incidence or severity of infection, these symbionts have the potential to reduce the strength of selection on genes in the insect genome that increase resistance. Therefore, the presence of such symbionts may slow down the evolution of resistance. Here we investigated this idea by exposing Drosophila melanogaster populations to infection with the pathogenic Drosophila C virus (DCV) in the presence or absence of Wolbachia, a heritable symbiont of arthropods that confers protection against viruses. After nine generations of selection, we found that resistance to DCV had increased in all populations. However, in the presence of Wolbachia the resistant allele of pastrel-a gene that has a major effect on resistance to DCV-was at a lower frequency than in the symbiont-free populations. This finding suggests that defensive symbionts have the potential to hamper the evolution of insect resistance genes, potentially leading to a state of evolutionary addiction where the genetically susceptible insect host mostly relies on its symbiont to fight pathogens.
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Resistência à Doença/genética , Drosophila melanogaster/microbiologia , Drosophila melanogaster/virologia , Genes de Insetos , Seleção Genética , Simbiose , Alelos , Animais , Evolução Molecular , Vírus de Insetos , WolbachiaRESUMO
ClC-3, a member of the ClC chloride (Cl(-)) channel family, has recently been proposed as the primary Cl(-) channel involved in cell volume regulation. Changes in cell volume influence excitability, contraction, migration, pathogen-host interactions, cell proliferation, and cell death processes. In this study, expression and function of ClC-3 channels were investigated during epidermal stem cell (ESC) migration. We observed differential expression of CLC-3 regulates migration of ESCs. Further, whole-cell patch-clamp recordings and image analysis demonstrated ClC-3 expression affected volume-activated Cl(-) current (I Cl,Vol) within ESCs. Live cell imaging systems, designed to observe cellular responses to overexpression and suppression of ClC-3 in real time, indicated ClC-3 may regulate ESC migratory dynamics. We employed IMARIS software to analyze the velocity and distance of ESC migration in vitro to demonstrate the function of ClC-3 channel in ESCs. As our data suggest volume-activated Cl(-) channels play a vital role in migration of ESCs, which contribute to skin repair by migrating from neighboring unwounded epidermis infundibulum, hair follicle or sebaceous glands, ClC-3 may represent a new and valuable target for stem cell therapies.
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Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Cloretos/metabolismo , Células Epidérmicas , Epiderme/metabolismo , Expressão Gênica , Células-Tronco/metabolismo , Animais , Linhagem Celular , Movimento Celular/genética , Vetores Genéticos/genética , Humanos , Lentivirus/genética , Masculino , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Transdução GenéticaRESUMO
Variation in susceptibility to infection has a substantial genetic component in natural populations, and it has been argued that selection by pathogens may result in it having a simpler genetic architecture than many other quantitative traits. This is important as models of host-pathogen co-evolution typically assume resistance is controlled by a small number of genes. Using the Drosophila melanogaster multiparent advanced intercross, we investigated the genetic architecture of resistance to two naturally occurring viruses, the sigma virus and DCV (Drosophila C virus). We found extensive genetic variation in resistance to both viruses. For DCV resistance, this variation is largely caused by two major-effect loci. Sigma virus resistance involves more genes - we mapped five loci, and together these explained less than half the genetic variance. Nonetheless, several of these had a large effect on resistance. Models of co-evolution typically assume strong epistatic interactions between polymorphisms controlling resistance, but we were only able to detect one locus that altered the effect of the main effect loci we had mapped. Most of the loci we mapped were probably at an intermediate frequency in natural populations. Overall, our results are consistent with major-effect genes commonly affecting susceptibility to infectious diseases, with DCV resistance being a near-Mendelian trait.
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Resistência à Doença/genética , Drosophila melanogaster/genética , Drosophila melanogaster/virologia , Variação Genética , Infecções por Rhabdoviridae/genética , Rhabdoviridae , Animais , Mapeamento Cromossômico , Epistasia Genética , Locos de Características QuantitativasRESUMO
OBJECTIVE: To assess the prevalence of body dysmorphic disorder (BDD) in an aesthetic surgery setting in the region of Southwest China, and to ascertain the differences in terms of body images between patients in the aesthetic setting and general Chinese population. This study tracked patient satisfaction with their body image changes while undergoing aesthetic medical procedures to identify whether the condition of patients who were presenting with BDD symptoms or their psychological symptoms could be improved by enhancing their appearance. Additionally, this study explored whether there was improvement in quality of life (QoL) and self-esteem after aesthetic medical procedures. METHODS: A total of 106 female patients who were undergoing aesthetic medical procedures for the first time (plastic surgery, n = 26; minimally invasive aesthetic treatment, n = 42; and aesthetic dermatological treatment, n = 38) were classified as having body dysmorphic disorder symptoms or not having body dysmorphic disorder symptoms, based on the body dysmorphic disorder examination (BDDE), which was administered preoperatively. These patients were followed up for 1 month after the aesthetic procedures. The multidimensional body self-relations questionnaire-appearance scales (MBSRQ-AS) and rosenberg self-esteem scale (RSE-S) were used to assess patients' preoccupation with appearance and self-esteem pre-procedure and 1 month post-procedure. Additionally, 100 female healthy control participants were recruited as a comparative group into this study and they were also assessed using BDDE, MBSRQ-AS, and RSE-S. RESULTS: A total of 14.2 % of 106 aesthetic patients and 1 % of 100 healthy controls were diagnosed with BDD to varying extents. BDDE scores were 72.83 (SD ± 30.7) and 68.18 (SD ± 31.82), respectively, before and after the procedure for the aesthetic patient group and 43.44 (SD ± 15.65) for the healthy control group (F = 34.28; p < 0.001). There was a significant difference between the groups in subscales of MBSRQ-AS, i.e. appearance evaluation (F = 31.31; p < 0.001), appearance orientation (F = 31.65; p < 0.001), body areas satisfaction (F = 27.40; p < 0.001), and RSE-S scores (F = 20.81; p < 0.001). There was no significant difference, however, in subscales of MBSRQ-AS, i.e. overweight preoccupation (F = 1.685; p = 0.187), self-classified weight (F = 0.908; p = 0.404) between groups. All the subscales of MBSRQ-AS showed significant differences between the aesthetic patients (pre-procedure) and female adult norms from Dr. Cash's result given in Table 4 (p < 0.001). The study also showed that there were no significant differences in the scores of BDDE, MBSRQ-AS, and RSE-S of those fifteen aesthetic patients diagnosed with BDD after aesthetic procedures lasting one month. CONCLUSION: There was a high prevalence rate (14.2 %) of body dysmorphic disorder in aesthetic procedure seekers, and it seemed that those patients suffering from BDD were more likely to be dissatisfied with the results of the aesthetic medical procedures. However, general aesthetic patients showed improvement in most assessments which indicated that aesthetic medical procedures could not only enhance patient appearance, but also patient low self-esteem and QoL. Self-satisfaction could also be promoted. A screening procedure for BDD including suitable screening questionnaires might be considered for routine use in aesthetic clinical settings to minimize dissatisfaction and complaints. LEVEL OF EVIDENCE IV: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .
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Transtornos Dismórficos Corporais/psicologia , Transtornos Dismórficos Corporais/cirurgia , Imagem Corporal/psicologia , Qualidade de Vida , Cirurgia Plástica/métodos , Inquéritos e Questionários , Adulto , Transtornos Dismórficos Corporais/diagnóstico , China , Estudos Transversais , Procedimentos Cirúrgicos Dermatológicos/métodos , Procedimentos Cirúrgicos Dermatológicos/psicologia , Estética , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/psicologia , Satisfação do Paciente/estatística & dados numéricos , Prognóstico , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/psicologia , Cirurgia Plástica/psicologia , Resultado do Tratamento , Adulto JovemRESUMO
Variation in susceptibility to infectious disease often has a substantial genetic component in animal and plant populations. We have used genome-wide association studies (GWAS) in Drosophila melanogaster to identify the genetic basis of variation in susceptibility to viral infection. We found that there is substantially more genetic variation in susceptibility to two viruses that naturally infect D. melanogaster (DCV and DMelSV) than to two viruses isolated from other insects (FHV and DAffSV). Furthermore, this increased variation is caused by a small number of common polymorphisms that have a major effect on resistance and can individually explain up to 47% of the heritability in disease susceptibility. For two of these polymorphisms, it has previously been shown that they have been driven to a high frequency by natural selection. An advantage of GWAS in Drosophila is that the results can be confirmed experimentally. We verified that a gene called pastrel--which was previously not known to have an antiviral function--is associated with DCV-resistance by knocking down its expression by RNAi. Our data suggest that selection for resistance to infectious disease can increase genetic variation by increasing the frequency of major-effect alleles, and this has resulted in a simple genetic basis to variation in virus resistance.
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Evolução Biológica , Resistência à Doença/genética , Drosophila melanogaster , Estudo de Associação Genômica Ampla , Alelos , Animais , Mapeamento Cromossômico , Dicistroviridae/genética , Dicistroviridae/patogenicidade , Drosophila melanogaster/genética , Drosophila melanogaster/virologia , Genótipo , Rhabdoviridae/genética , Rhabdoviridae/patogenicidade , Seleção GenéticaRESUMO
To understand the molecular basis of how hosts evolve resistance to their parasites, we have investigated the genes that cause variation in the susceptibility of Drosophila melanogaster to viral infection. Using a host-specific pathogen of D. melanogaster called the sigma virus (Rhabdoviridae), we mapped a major-effect polymorphism to a region containing two paralogous genes called CHKov1 and CHKov2. In a panel of inbred fly lines, we found that a transposable element insertion in the protein coding sequence of CHKov1 is associated with increased resistance to infection. Previous research has shown that this insertion results in a truncated messenger RNA that encodes a far shorter protein than the susceptible allele. This resistant allele has rapidly increased in frequency under directional selection and is now the commonest form of the gene in natural populations. Using genetic mapping and site-specific recombination, we identified a third genotype with considerably greater resistance that is currently rare in the wild. In these flies there have been two duplications, resulting in three copies of both the truncated allele of CHKov1 and CHKov2 (one of which is also truncated). Remarkably, the truncated allele of CHKov1 has previously been found to confer resistance to organophosphate insecticides. As estimates of the age of this allele predate the use of insecticides, it is likely that this allele initially functioned as a defence against viruses and fortuitously "pre-adapted" flies to insecticides. These results demonstrate that strong selection by parasites for increased host resistance can result in major genetic changes and rapid shifts in allele frequencies; and, contrary to the prevailing view that resistance to pathogens can be a costly trait to evolve, the pleiotropic effects of these changes can have unexpected benefits.
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Elementos de DNA Transponíveis/genética , Resistência à Doença/genética , Drosophila melanogaster/genética , Drosophila melanogaster/virologia , Rhabdoviridae , Duplicações Segmentares Genômicas/genética , Alelos , Animais , Evolução Biológica , Mapeamento Cromossômico , Frequência do Gene , Variação Genética , Mutagênese Insercional/genética , RNA Mensageiro/genética , Seleção GenéticaRESUMO
Through a combination of steps including centrifugation, ammonium sulfate gradient precipitation, sephadex G-25 gel chromatography, diethylaminoethyl cellulose 52 ion-exchange chromatography and hydroxyapatite affinity chromatography, carboxylesterase (CarE, EC3.1.1.1) from sixth instar larch caterpillar moth, Dendrolimus superans (Lepidoptera: Lasiocampidae) larvae was purified and its biochemical properties were compared between crude homogenate and purified CarE. The final purified CarE after hydroxyapatite chromatography had a specific activity of 52.019 µmol/(min·mg protein), 138.348-fold of crude homogenate, and the yield of 2.782%. The molecular weight of the purified CarE was approximately 84.78 kDa by SDS-PAGE. Three pesticides (dichlorvos, lambda-cyhalothrin, and avermectins) showed different inhibition to crude CarE and purified CarE, respectively. In vitro median inhibitory concentration indicated that the sensitivity of CarE (both crude homogenate and final purified CarE) to pesticides was in decreasing order of dichlorvos > avermectins > lambda-cyhalothrin. By the kinetic analysis, the substrates alpha-naphthyl acetate (α-NA) and beta-naphthyl acetate (ß-NA) showed lesser affinity to crude extract than purified CarE. The results also indicated that both crude homogenate and purified CarE had more affinity to α-NA than to ß-NA, and the Kcat and Vmax values of crude extract were lower than purified CarE using α-NA or ß-NA as substrate.