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Diamondback moth (DBM, Plutella xylostella) is the most significant pest of cruciferous vegetables as they rapidly develop high-level resistance to many insecticides. Monitoring DBM susceptibility and target-site mutation frequency is essential for pest control. In this study, 10 insecticides were tested on 11 field populations. Frequencies of target-site mutations (including para, ace1, Rdl1, RyR1, and nAChRα6 genes) were estimated by pyrosequencing. Insecticides registered after 2007 for DBM control in Taiwan, i.e., spinetoram, chlorantraniliprole, chlorfenapyr, metaflumizone, and flubendiamide, showed >80% mortality toward several populations; Bacillus thurigiensis, emamectin benzoate, and chlorfluazuron showed medium to low efficacy in all populations; and tolfenpyrad and mevinphos were highly ineffective. Susceptibility to insecticides varied substantially among populations: eight out of nine populations were highly susceptible to spinetoram, but only one was susceptible to flubendiamide. Target-site mutations related to organophosphates, pyrethroids, fipronil, and diamides were detected in all populations, but there were few spinosad and spinetoram mutations. Our three-year field study demonstrated rapid efficacy loss for all insecticides tested, particularly for more toxic insecticides. Skipped-generation selection of a field DBM strain to emamectin benzoate, metaflumizone, chlorantraniliprole, and flubendiamide revealed that mortality rates dropped from 60 to 80% to <10% after 6 generations. Next-generation sequencing was performed to identify possible target gene mutations. A resistance management program that considers the instability of resistance to some chemicals and pertinent data on resistance mechanisms should be established. Identifying compounds to overcome high-frequency field DBM point mutations could be beneficial for pest control.
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Resistência a Inseticidas , Inseticidas , Mariposas , Mutação , Animais , Resistência a Inseticidas/genética , Mariposas/efeitos dos fármacos , Mariposas/genética , Inseticidas/farmacologia , Taiwan , Piretrinas/farmacologia , Benzamidas/farmacologia , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Pirazóis , ortoaminobenzoatos , Proteínas de Insetos/genética , Macrolídeos/farmacologia , Fluorocarbonos , Ftalimidas , Semicarbazonas , SulfonasRESUMO
Objectives: To explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy. Methods: A retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints. Results: Of distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman's ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints. Conclusions: Strong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity.
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Blastocisto , Desenvolvimento Embrionário , Mitocôndrias , Resultado da Gravidez , Humanos , Feminino , Gravidez , Blastocisto/citologia , Blastocisto/fisiologia , Blastocisto/metabolismo , Estudos Retrospectivos , Mitocôndrias/metabolismo , Desenvolvimento Embrionário/fisiologia , Adulto , Técnicas de Cultura Embrionária , Transferência Embrionária/métodos , Diagnóstico Pré-Implantação/métodos , Fertilização in vitro/métodosRESUMO
The antibiotic heliomycin (resistomycin), which is generated from Streptomyces resistomycificus, has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives of heliomycin were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, but the drug targets remained unknown. In this study, we conducted cellular thermal shift assays (CETSA) and molecular docking simulations to identify and validate that heliomycin and its water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged and targeted with sirtuin-1 (SIRT1) in p53-functional SAS and p53-mutated HSC-3 oral cancer cells. We further addressed the cellular outcome of SIRT1 inhibition by these compounds and found that, in addition to SIRT1, the water-soluble 4-dmH preferentially targeted a tumor-associated NADH oxidase (tNOX, ENOX2). The direct binding of 4-dmH to tNOX decreased the oxidation of NADH to NAD+ which diminished NAD+-dependent SIRT1 deacetylase activity, ultimately inducing apoptosis and significant cytotoxicity in both cell types, as opposed to the parental heliomycin-induced autophagy. We also observed that tNOX and SIRT1 were both upregulated in tumor tissues of oral cancer patients compared to adjacent normal tissues, suggesting their clinical relevance. Finally, the better therapeutic efficacy of 4-dmH was confirmed in tumor-bearing mice, which showed greater tNOX and SIRT1 downregulation and tumor volume reduction when treated with 4-dmH compared to heliomycin. Taken together, our in vitro and in vivo findings suggest that the multifaceted properties of water-soluble 4-dmH enable it to offer superior antitumor value compared to parental heliomycin, and indicated that it functions through targeting the tNOX-NAD+-SIRT1 axis to induce apoptosis in oral cancer cells.
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Neoplasias Bucais , Compostos Policíclicos , Sirtuína 1 , Humanos , Animais , Camundongos , Sirtuína 1/metabolismo , Linhagem Celular Tumoral , NAD/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Simulação de Acoplamento Molecular , Apoptose , Neoplasias Bucais/tratamento farmacológicoRESUMO
Scramblase Xk-related protein 8 (Xkr8) regulates the externalization of phosphatidylserine (PS) during apoptosis and holds a pivotal role in fostering tumor immunosuppression. Targeting Xkr8 in conjunction with chemotherapy demonstrated a novel avenue for amplifying antitumor immune response and overcoming chemo-immune resistance. Here we further evaluated this strategy by using a clinically relevant orthotopic model and elucidated the mechanism through in-depth single-cell RNA sequencing (scRNA-seq). We found that Xkr8 knockdown exhibited the potential to lead to immunogenic cell death (ICD) by impeding the normal clearance of apoptotic cells. Co-delivery of Xkr8 small interference RNA (siRNA) and a prodrug conjugate of 5-fluorouracil (5-Fu) and oxoplatin (FuOXP) showed remarkable therapeutic efficacy in an orthotopic pancreatic tumor model with increased infiltration of proliferative NK cells and activated macrophages in the tumor microenvironment (TME). Single-cell trajectory analysis further unveiled that tumor infiltrating CD8+ T cells are differentiated favorably to cytotoxic over exhausted phenotype after combination treatment. Our study sheds new light on the impact of Xkr8 knockdown on TME and solidifies the rationale of combining Xkr8 knockdown with chemotherapy to treat various types of cancers.
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Fluoruracila , Neoplasias Pancreáticas , RNA Interferente Pequeno , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Linhagem Celular Tumoral , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Humanos , RNA Interferente Pequeno/administração & dosagem , Apoptose/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Camundongos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Feminino , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologiaRESUMO
Human leukocyte antigen (HLA) genes play pivotal roles in numerous immunological applications. Given the immense number of polymorphisms, achieving accurate high-throughput HLA typing remains challenging. This study aimed to harness the human pan-genome reference consortium (HPRC) resources as a potential benchmark for HLA reference materials. We meticulously annotated specific four field-resolution alleles for 11 HLA genes (HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, -DRB3, -DRB4 and -DRB5) from 44 high-quality HPRC personal genome assemblies. For sequencing, we crafted HLA-specific probes and conducted capture-based targeted sequencing of the genomic DNA of the HPRC cohort, ensuring focused and comprehensive coverage of the HLA region of interest. We used publicly available short-read whole-genome sequencing (WGS) data from identical samples to offer a comparative perspective. To decipher the vast amount of sequencing data, we employed seven distinct software tools: OptiType, HLA-VBseq, HISAT genotype, SpecHLA, T1K, QzType, and DRAGEN. Each tool offers unique capabilities and algorithms for HLA genotyping, allowing comprehensive analysis and validation of the results. We then compared these results with benchmarks derived from personal genome assemblies. Our findings present a comprehensive four-field-resolution HLA allele annotation for 44 HPRC samples. Significantly, our innovative targeted next-generation sequencing (NGS) approach for HLA genes showed superior accuracy compared with conventional short-read WGS. An integrated analysis involving QzType, T1K, and DRAGEN was developed, achieving 100% accuracy for all 11 HLA genes. In conclusion, our study highlighted the combination of targeted short-read sequencing and astute computational analysis as a robust approach for HLA genotyping. Furthermore, the HPRC cohort has emerged as a valuable assembly-based reference in this realm.
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Scramblase Xkr8 regulates the externalization of phosphatidylserine (PS) during apoptosis and holds a pivotal role in fostering tumor immunosuppression. Targeting Xkr8 in conjunction with chemotherapy demonstrated a novel avenue for amplifying antitumor immune response and overcoming chemo-immune resistance. Here we further evaluated this strategy by using a clinically relevant orthotopic model and elucidated the mechanism through in-depth single-cell RNA sequencing (scRNA-seq). We found that Xkr8 knockdown exhibited the potential to lead to immunogenic cell death (ICD) by impeding the normal clearance of apoptotic cells. Co-delivery of Xkr8 small interference RNA (siRNA) and chemo prodrug FuOXP showed remarkable therapeutic efficacy in an orthotopic pancreatic tumor model with an increase of proliferative NK cells and activated macrophages infiltration in the tumor microenvironment (TME). Single-cell trajectory analysis further unveiled that tumor infiltrating CD8+ T cells are differentiated favorably to cytotoxic over exhausted phenotype after combination treatment. Our study sheds new light on the impact of Xkr8 knockdown on TME and solidifies the rationale of combining Xkr8 knockdown with chemotherapy to treat various types of cancers.
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OBJECTIVE: The purpose of this qualitative study was to examine responses related to entrustment and feedback comments from an assessment tool. DESIGN: Qualitative analyses using semi-structured interviews and analysis of narrative comments. SETTING: Main hospital OR suite at a large academic medical center. PARTICIPANTS: faculty, and residents who work in the OR suite. RESULTS: Seven of the 14 theoretical domains from the Theoretical Domains Framework were identified as influencing faculty decision on entrustment: knowledge, skills, intention, memory/attention/decision processes, environmental context, and resources, beliefs of capabilities, and reinforcement. The majority (651/1116 (58.4%)) of faculty comments were critical/modest praise and relevant, consistent across all 6 EPAs. The written in feedback comments for all 1,116 Web App EPA assessments yielded a total of 1,599 sub-competency specific responses. These responses were mapped to core competencies, and at least once to 13 of the 23 ACGME subcompetencies. CONCLUSIONS: Domains identified as influencing faculty decision on entrustment were knowledge, skills, intention, memory/attention/decision processes, environmental context, and resources, beliefs of capabilities, and reinforcement. Most narrative feedback comments were critical/modest praise and relevant, consistent across each of the EPAs.
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Anestesiologia , Competência Clínica , Docentes de Medicina , Internato e Residência , Humanos , Anestesiologia/educação , Pesquisa Qualitativa , Feminino , Masculino , Educação de Pós-Graduação em Medicina/métodos , Educação Baseada em Competências/métodos , Tomada de Decisões , RetroalimentaçãoRESUMO
BACKGROUND: To implement the ACGME Anesthesiology Milestone Project in a non-North American context, a process of indigenization is essential. In this study, we aim to explore the differences in perspective toward the anesthesiology competencies among residents and junior and senior visiting staff members and co-produce a preliminary framework for the following nation-wide survey in Taiwan. METHODS: The expert committee translation and Delphi technique were adopted to co-construct an indigenized draft of milestones. Descriptive analysis, chi-square testing, Pearson correlation testing, and repeated-measures analysis of variance in the general linear model were employed to calculate the F values and mean differences (MDs). RESULTS: The translation committee included three experts and the consensus panel recruited 37 participants from four hospitals in Taiwan: 9 residents, 13 junior visiting staff members (JVSs), and 15 senior visiting staff members (SVSs). The consensus on the content of the 285 milestones was achieved after 271 minor and 6 major modifications in 3 rounds of the Delphi survey. Moreover, JVSs were more concerned regarding patient care than were both residents (MD = - 0.095, P < 0.001) and SVSs (MD = 0.075, P < 0.001). Residents were more concerned regarding practice-based learning improvement than were JVSs (MD = 0.081; P < 0.01); they also acknowledged professionalism more than JVSs (MD = 0.072; P < 0.05) and SVSs (MD = 0.12; P < 0.01). Finally, SVSs graded interpersonal and communication skills lower than both residents (MD = 0.068; P < 0.05) and JVSs (MD = 0.065; P < 0.05) did. CONCLUSIONS: Most ACGME anesthesiology milestones are applicable and feasible in Taiwan. Incorporating residents' perspectives may bring insight and facilitate shared understanding to a new educational implementation. This study helped Taiwan generate a well-informed and indigenized draft of a competency-based framework for the following nation-wide Delphi survey.
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Anestesiologia , Internato e Residência , Humanos , Anestesiologia/educação , Taiwan , Técnica Delphi , Competência Clínica , Educação de Pós-Graduação em MedicinaRESUMO
An open-cage bis[60]fulleroid (OC) was applied as an electron transport material (ETM) in tin (Sn) halide perovskite solar cells (PSCs). Due to the reduced offset between the energy levels of Sn-based perovskites and ETMs, the power conversion efficiency (PCE) of Sn-based PSCs with OC reached 9.6% with an open-circuit voltage (VOC) of 0.72 V. Additionally, OC exhibited superior thermal stability and provided 75% of the material without decomposition after vacuum deposition. The PSC using vacuum-deposited OC as the ETM could afford a PCE of 7.6%, which is a big leap forward compared with previous results using vacuum-deposited fullerene derivatives as ETMs.
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IMP-3 expression is a poor prognostic factor of melanomas and it promotes melanoma cell migration and invasion by a pathway modulating HMGA2 mRNA expression. We tried to identify other putative targets of IMP-3. We identified putative IMP-3-binding RNAs, including AKT1, MAPK3, RB1 and RELA, by RNA immunoprecipitation coupled with next-generation sequencing. IMP-3 overexpression increased AKT and RELA levels in MeWo cells. siRNAs against AKT1 and RELA inhibited MeWo/Full-length IMP-3 cell migration. IMP-3 knockdown of A2058 cells decreased AKT1 and RELA expression and lowered migration ability. Co-transfection of A2058 cells with AKT1- or RELA-expressing plasmids with IMP-3 siRNA restored the inhibitory effects of IMP-3 knockdown on migration. HMGA2 did not influence AKT1 and RELA expression in melanoma cells. Human melanoma samples with high IMP-3 levels also showed high HMGA2, AKT1 and RELA expression. Our results show that IMP-3 enhances melanoma cell migration through the regulation of the AKT1 and RELA axis.
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Melanoma , Proteínas Proto-Oncogênicas c-akt , Proteínas de Ligação a RNA , Fator de Transcrição RelA , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Melanoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
The multifaceted chemo-immune resistance is the principal barrier to achieving cure in cancer patients. Identifying a target that is critically involved in chemo-immune-resistance represents an attractive strategy to improve cancer treatment. iRhom1 plays a role in cancer cell proliferation and its expression is negatively correlated with immune cell infiltration. Here we show that iRhom1 decreases chemotherapy sensitivity by regulating the MAPK14-HSP27 axis. In addition, iRhom1 inhibits the cytotoxic T-cell response by reducing the stability of ERAP1 protein and the ERAP1-mediated antigen processing and presentation. To facilitate the therapeutic translation of these findings, we develop a biodegradable nanocarrier that is effective in codelivery of iRhom pre-siRNA (pre-siiRhom) and chemotherapeutic drugs. This nanocarrier is effective in tumor targeting and penetration through both enhanced permeability and retention effect and CD44-mediated transcytosis in tumor endothelial cells as well as tumor cells. Inhibition of iRhom1 further facilitates tumor targeting and uptake through inhibition of CD44 cleavage. Co-delivery of pre-siiRhom and a chemotherapy agent leads to enhanced antitumor efficacy and activated tumor immune microenvironment in multiple cancer models in female mice. Targeting iRhom1 together with chemotherapy could represent a strategy to overcome chemo-immune resistance in cancer treatment.
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Células Endoteliais , Neoplasias , Humanos , Feminino , Animais , Camundongos , Linhagem Celular Tumoral , Portadores de Fármacos , Proliferação de Células , Neoplasias/tratamento farmacológico , Receptores de Hialuronatos , Aminopeptidases , Antígenos de Histocompatibilidade Menor , Proteínas de MembranaRESUMO
Polygenic risk score (PRS) predictions often show bias toward the population of available genome-wide association studies (GWASs), which is typically of European ancestry. This study aimed to assess the performance differences of ancestry-specific PRS and test the implementation of multi-ancestry PRS to enhance the generalizability of low-density lipoprotein (LDL) cholesterol predictions in the East Asian (EAS) population. In this study, we computed ancestry-specific and multi-ancestry PRSs for LDL using data obtained from the Global Lipid Genetics Consortium, while accounting for population-specific linkage disequilibrium patterns using the PRS-CSx method in the United Kingdom Biobank dataset (UKB, n = 423,596) and Taiwan Biobank dataset (TWB, n = 68,978). Population-specific PRSs were able to predict LDL levels better within the target population, whereas multi-ancestry PRSs were more generalizable. In the TWB dataset, covariate-adjusted R 2 values were 9.3% for ancestry-specific PRS, 6.7% for multi-ancestry PRS, and 4.5% for European-specific PRS. Similar trends (8.6%, 7.8%, and 6.2%) were observed in the smaller EAS population of the UKB (n = 1,480). Consistent with R 2 values, PRS stratification in EAS regions (TWB) effectively captured a heterogenous variability in LDL blood cholesterol levels across PRS strata. The mean difference in LDL levels between the lowest and highest EAS-specific PRS (EAS_PRS) deciles was 0.82, compared to 0.59 for European-specific PRS (EUR_PRS) and 0.76 for multi-ancestry PRS. Notably, the mean LDL values in the top decile of multi-ancestry PRS were comparable to those of EAS_PRS (3.543 vs. 3.541, p = 0.86). Our analysis of the PRS prediction model for LDL cholesterol further supports the issue of PRS generalizability across populations. Our targeted analysis of the EAS population revealed that integrating non-European genotyping data with a powerful European-based GWAS can enhance the generalizability of LDL PRS.
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INTRODUCTION: The population of Taiwan has a long history of ethno-cultural evolution. The Taiwanese population was isolated from other large populations such as the European, Han Chinese, and Japanese population. The Taiwan Biobank (TWB) project has built a nationwide database, particularly for personal whole-genome sequence (WGS) to facilitate basic and clinical collaboration nationally and internationally, making it one of the most valuable public datasets of the East Asian population. OBJECTIVES: This study provides comprehensive medical genomic findings from TWB WGS data, for better characterization of disease susceptibility and the choice of ideal treatment regimens in Taiwanese population. METHODS: We reanalyzed 1496 WGS using a PrecisionFDA Truth challenge winner method Sentieon DNAscope. Single nucleotide variants (SNV) and small insertions/deletions (INDEL) were benchmarked. We also analyzed pharmacogenomic (PGx) drug-associated alleles, and copy number variants (CNV). Multiple practicing clinicians reviewed and curated the clinically significant variants. Variant annotations can be browsed at TaiwanGenomes (https://genomes.tw). RESULTS: We found that each participant had an average of 6,870.7 globally novel variants and 75.3% (831/1103) of the participants harbored at least one PharmGKB-selected high evidence level human leukocyte antigen (HLA) risk allele. 54 PharmGKB-reported high-level instances of evidence of Cytochrome P450 variant-drug pairs, with a population frequency of over 13.2%. We also identified 23 variants in the ACMG secondary finding V3 gene list from 25 participants, suggesting that 1.67% (25/1496) of the population is harboring at least one medical actionable variant. Our carrier status analyses suggest that one in 25 couples (3.94%) would risk having offspring with at least one pathogenic variant, which is in line with rates found in Japan and Singapore. For pathogenic CNV, we detected 6.88% and 2.02% carrier rates for alpha thalassemia and spinal muscular atrophy, respectively. CONCLUSION: Our study highlights the overall medical insights of a complete Taiwanese genomic profile.
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STUDY OBJECTIVE: The prevention of perioperative hypothermia after anesthesia induction is a critical concern in patients undergoing abdominal surgery. The effectiveness of various warming systems for preventing hypothermia and shivering when applied to specific areas of the body remains undetermined. DESIGN: Systematic review and network meta-analysis. SETTING: Operating room. INTERVENTION: Five electronic databases were searched, including only randomized control trials (RCTs) reporting the effects of warming systems applied to specific body sites on the intraoperative core temperature and postoperative risk of shivering in adults undergoing abdominal surgery. A multivariate random-effects network meta-analysis with a frequentist framework was implemented for data analysis. MEASUREMENTS: The primary outcome was the core body temperature 60 and 120 min after anesthesia induction for abdominal surgery. The secondary outcome was the incidence of postoperative shivering. RESULTS: This review comprised a total of 24 RCTs including 1119 patients. At 60 and 120 min after anesthesia induction, a forced-air warming system applied to the upper body (0.3 °C and 95% confidence intervals = [0.3 to 0.4], 1.0 °C [0.7 to 1.3]), lower body (0.4 °C [0.3 to 0.5], 0.9 °C [0.5 to 1.2]), and underbody (0.5 °C [0.5 to 0.6], 1.2 °C [0.9 to 1.6]) was superior to passive insulation in terms of core body temperature regulation. Compared with passive insulation, the forced-air warming system applied to the lower body (odds ratio = 0.06) or underbody (0.44) and the electric heating blanket to the lower body (0.02) or the whole body (0.07) significantly reduced the risk of shivering. CONCLUSIONS: The results of this NMA revealed that forced-air warming with an underbody blanket effectively elevates core body temperatures in 60 and 120 min after induction of anesthesia and prevents shivering in patients recovering from abdominal surgery.
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Hipotermia , Adulto , Humanos , Hipotermia/etiologia , Hipotermia/prevenção & controle , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Regulação da Temperatura Corporal , Estremecimento , Anestesia Geral/efeitos adversos , Temperatura CorporalRESUMO
Compared to other techniques, RNA sequencing (RNA-Seq) has the advantage of having details of the expression abundance of all transcripts in a single run. In this study, we used RNA-Seq to monitor the maturity and dynamic characteristics of in vitro hepatocyte cultures. Hepatocytes, including mature hepatocytes and small hepatocytes, were analyzed in vitro using RNA-Seq and quantitative polymerase chain reaction (qPCR). The results demonstrated that the gene expression profiles measured by RNA-Seq showed a similar trend to the expression profiles measured by qPCR, and can be used to infer the success of in vitro hepatocyte cultures. The results of the differential analysis, which compared mature hepatocytes against small hepatocytes, revealed 836 downregulated and 137 upregulated genes. In addition, the success of the hepatocyte cultures could be explained by the gene list screened from the adopted gene enrichment test. In summary, we demonstrated that RNA-Seq could become an effective method for monitoring the whole transcriptome of hepatocyte cultures and provide a more comprehensive list of factors related to the differentiation of small hepatocytes into mature hepatocytes. This monitoring system not only shows high potential in medical applications but may also be a novel method for the clinical diagnosis of liver-related diseases.
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Hepatócitos , Transcriptoma , Ratos , Animais , RNA-Seq , Hepatócitos/metabolismo , Análise de Sequência de RNA , Células Cultivadas , FígadoRESUMO
BACKGROUND: The incidence of chronic kidney disease is increasing, but most cases are not diagnosed until the accidental finding of abnormal laboratory data or the presentation of severe symptoms. Patients with chronic kidney disease are reported to have an increased risk of postoperative mortality and morbidities, but previous studies mainly targeted populations undergoing cardiovascular surgery. The authors aimed to evaluate the risk of postoperative mortality and complications in a surgical population with preoperative renal insufficiency (RI). MATERIALS AND METHODS: This retrospective cohort study used data from the National Surgical Quality Improvement Program database between 2013 and 2018 to evaluate the risk of postoperative morbidity and mortality in the surgical population. Patients with estimated glomerular filtration rate less than 60 ml/min/1.73 m 2 were defined as the RI group. Propensity score matching methods and multivariate logistic regression were used to calculate the risk of postoperative morbidity and mortality. RESULTS: After propensity score matching, 502 281 patients were included in the RI and non-RI groups. The RI group had a higher risk of 30-day in-hospital mortality (odds ratio: 1.54, 95% CI: 1.49-1.58) than the non-RI group. The RI group was associated with a higher risk of postoperative complications, including myocardial infarction, stroke, pneumonia, septic shock, and postoperative bleeding. The RI group was also associated with an increased risk of prolonged ventilator use for over 48 h, readmission, and reoperation. CONCLUSION: Patients with preoperative RI have an increased risk of postoperative 30-day mortality and complications. RI group patients with current dialysis, estimated glomerular filtration rate less than or equal to 30 ml/min/1.73 m 2 or concomitant anemia had an elevated risk of postoperative mortality.
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Insuficiência Renal Crônica , Insuficiência Renal , Humanos , Estudos Retrospectivos , Estudos de Coortes , Fatores de Risco , Insuficiência Renal/epidemiologia , Insuficiência Renal/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
The aim of systematic review and meta-analysis was to investigate whether APOE4 was associated with postoperative neurologic dysfunction occurrence in short- or medium-term among surgical patients and to study the potential genetic association among these two entities. We searched electronic databases for reserch studies to evaluate the association of APOE4 with postoperative delirium (POD) or short- and medium term postoperative cognitive dysfunction (POCD). Twenty-two trials (16 prospective and six retrospective) with 6734 patients were included. APOE4 alleles was shown significantly associated with POCD within 1 week (odds ratio, OR, 1.89, 95% confidence interval, CI, 1.36 to 2.6278, p < 0.01) in the random-effects model. A significant association was also noted between APOE4 and POCD in medium-term, 1-3 months, after surgery (OR: 1.67, 95% CI: 1.003-2.839, p = 0.049). However, APOE4 was not significantly associated with POCD 1 year after surgery (OR: 0.98, 95% CI: 0.57-1.70, p = 0.9449) and POD (OR: 1.28, 95% CI: 0.85-1.91, p = 0.23). In conclusion, APOE4 alleles was genetically associated with short- and medium-term postoperative neurological dysfunction and future screening or preventive strategies derived is highly potential to improve outcomes.
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Disfunção Cognitiva , Delírio , Complicações Cognitivas Pós-Operatórias , Humanos , Complicações Cognitivas Pós-Operatórias/diagnóstico , Apolipoproteína E4/genética , Delírio/diagnóstico , Estudos Retrospectivos , Alelos , Estudos Prospectivos , Disfunção Cognitiva/genética , Complicações Pós-Operatórias/prevenção & controleRESUMO
OBJECTIVES: During the COVID-19 outbreak, medical educators' main concern has been how to prepare new physicians and medical students to meet their obligations as healthcare providers under novel circumstances. This study aims at exploring how trainees perceive their commitments as physicians under the threat of a pandemic. DESIGN: A qualitative method was employed. Researchers interviewed medical students under clerkship training (fifth and sixth-year medical students) and new physicians undergoing postgraduate year (PGY) and specialty training. SETTING: A university hospital in Taipei, Taiwan. PARTICIPANTS: The team conducted three focus groups for participants in three separate training stages: clerks, PGY students (PGYs), and residents. Researchers collected data from 31 March to 2 April 2020 and analysed the thematic analysis results. RESULTS: Seventeen medical students and new physicians took part in the focus groups, five of whom (31.25%) were female. Participants consisted of four residents, six PGYs, and seven medical students. Through their responses, the authors determined four major dimensions with corresponding subdimensions that significantly affected their sense of medical professionalism, including medical knowledge and clinical skills, sense of duty towards public health, teamwork and protection of patient rights. CONCLUSIONS: We therefore concluded that participants grew to accept their roles after acquiring the knowledge and skills needed to care for patients with COVID-19. Alternative teaching arrangements and their impact on trainees' clinical performance require further discussion.
Assuntos
COVID-19 , Médicos , Estudantes de Medicina , Humanos , Feminino , Masculino , Profissionalismo , Taiwan/epidemiologia , HospitaisRESUMO
BACKGROUND: Hepatitis C virus (HCV) is a global public health problem, with ~ 11 million people in Africa infected. There is incomplete information on HCV in Sudan, particularly in haemodialysis patients, who have a higher prevalence compared to the general population. Thus, our objectives were to genotype and molecularly characterize HCV isolated from end-stage renal disease haemodialysis patients. METHODS: A total of 541 patients were recruited from eight haemodialysis centres in Khartoum and screened for anti-HCV. Viral loads were determined using in-house real-time PCR in seropositive patients. HCV was genotyped and subtyped using sequencing of amplicons of 5' untranslated (UTR) and non-structural protein 5B (NS5B) regions, followed by phylogenetic analysis of corresponding sequences. RESULTS: The HCV seroprevalence in the study was 17% (93/541), with HCV RNA-positive viremic rate of 7% (40/541). A low HCV load, with a mean of 2.85 × 104 IU/ml and a range of 2.95 × 103 to 4.78 × 106 IU/ml, was detected. Phylogenetic analyses showed the presence of genotypes 1, 3, 4, and 5 with subtypes 1a, 1b, 1 g, 3a, 4a, 4 l, 4 m, 4 s, and 4t. Sequences of HCV from the same haemodialysis units, clustered in similar genotypes and subtypes intimating nosocomial infection. CONCLUSION: HCV infection is highly prevalent in haemodialysis patients from Sudan, with phylogenetic analysis intimating nosocomial infection. HCV genotyping is useful to locate potential transmission chains and to enable individualized treatment using highly effective direct-acting antivirals (DAAs).
Assuntos
Infecção Hospitalar , Hepatite C Crônica , Hepatite C , Falência Renal Crônica , Humanos , Hepacivirus/genética , Genótipo , Antivirais , Estudos Soroepidemiológicos , Filogenia , Diálise Renal , Falência Renal Crônica/terapia , Infecção Hospitalar/epidemiologia , Sudão/epidemiologiaRESUMO
In this study, a miniaturized full-color holographic reconstruction system that uses a single spatial light modulator to achieve full-color image reconstruction was developed. The reconstruction system uses a single light guide for light combination and is therefore less voluminous than conventional reconstruction systems. The experimental results demonstrated that the system had a full-color display, corrected light combination, and eliminated zero-order light. The vibrations of the light guide disrupted the temporal coherence of the laser beam, thus ensuring that the speckle in the reconstructed image was almost imperceptible to the human eye.