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CRISPR-Cas12c/d proteins share limited homology with Cas12a and Cas9 bacterial CRISPR RNA (crRNA)-guided nucleases used widely for genome editing and DNA detection. However, Cas12c (C2c3)- and Cas12d (CasY)-catalyzed DNA cleavage and genome editing activities have not been directly observed. We show here that a short-complementarity untranslated RNA (scoutRNA), together with crRNA, is required for Cas12d-catalyzed DNA cutting. The scoutRNA differs in secondary structure from previously described tracrRNAs used by CRISPR-Cas9 and some Cas12 enzymes, and in Cas12d-containing systems, scoutRNA includes a conserved five-nucleotide sequence that is essential for activity. In addition to supporting crRNA-directed DNA recognition, biochemical and cell-based experiments establish scoutRNA as an essential cofactor for Cas12c-catalyzed pre-crRNA maturation. These results define scoutRNA as a third type of transcript encoded by a subset of CRISPR-Cas genomic loci and explain how Cas12c/d systems avoid requirements for host factors including ribonuclease III for bacterial RNA-mediated adaptive immunity.
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Bactérias/genética , Proteínas de Bactérias/genética , Sistemas CRISPR-Cas , Endodesoxirribonucleases/genética , Genoma Bacteriano/imunologia , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , Bactérias/classificação , Bactérias/imunologia , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Sequência de Bases , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Endodesoxirribonucleases/metabolismo , Escherichia coli/genética , Escherichia coli/imunologia , Escherichia coli/metabolismo , Conformação de Ácido Nucleico , Filogenia , RNA Bacteriano/química , RNA Bacteriano/metabolismo , RNA Guia de Cinetoplastídeos/genética , RNA Guia de Cinetoplastídeos/metabolismo , Pequeno RNA não Traduzido/química , Pequeno RNA não Traduzido/metabolismo , Alinhamento de Sequência , Homologia de Sequência do Ácido NucleicoRESUMO
The Hsp90 chaperone machinery in eukaryotes comprises a number of distinct accessory factors. Cns1 is one of the few essential co-chaperones in yeast, but its structure and function remained unknown. Here, we report the X-ray structure of the Cns1 fold and NMR studies on the partly disordered, essential segment of the protein. We demonstrate that Cns1 is important for maintaining translation elongation, specifically chaperoning the elongation factor eEF2. In this context, Cns1 interacts with the novel co-factor Hgh1 and forms a quaternary complex together with eEF2 and Hsp90. The in vivo folding and solubility of eEF2 depend on the presence of these proteins. Chaperoning of eEF2 by Cns1 is essential for yeast viability and requires a defined subset of the Hsp90 machinery as well as the identified eEF2 recruiting factor Hgh1.
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Proteínas de Choque Térmico HSP90/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Chaperonas Moleculares/metabolismo , Elongação Traducional da Cadeia Peptídica , Fator 2 de Elongação de Peptídeos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Cristalografia por Raios X , Peptidil-Prolil Isomerase F , Ciclofilinas/genética , Ciclofilinas/metabolismo , Proteínas de Choque Térmico HSP90/química , Proteínas de Choque Térmico HSP90/genética , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Modelos Moleculares , Chaperonas Moleculares/química , Chaperonas Moleculares/genética , Ressonância Magnética Nuclear Biomolecular , Fator 2 de Elongação de Peptídeos/química , Fator 2 de Elongação de Peptídeos/genética , Ligação Proteica , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Relação Estrutura-AtividadeRESUMO
Neoadjuvant treatment of non-small cell lung cancer challenges the traditional processing of pathology specimens. Induction therapy before resection allows evaluation of the efficacy of neoadjuvant agents at the time of surgery. Many clinical trials use pathologic tumor response, measured as major pathologic response (MPR, ≤10% residual viable tumor [RVT]) or complete pathologic response (CPR, 0% RVT) as a surrogate of clinical efficacy. Consequently, accurate pathologic evaluation of RVT is crucial. However, pathologic assessment has not been uniform, which is particularly true for sampling of the primary tumor, which instead of the traditional processing, requires different tissue submission because the focus has shifted from tumor typing alone to RVT scoring. Using a simulation study, we analyzed the accuracy rates of %RVT, MPR, and CPR of 31 pretreated primary lung tumors using traditional grossing compared with the gold standard of submitting the entire residual primary tumor and identified the minimum number of tumor sections to be submitted to ensure the most accurate scoring of %RVT, MPR, and CPR. Accurate %RVT, MPR, and CPR calls were achieved in 52%, 87%, and 81% of cases, respectively, using the traditional grossing method. Accuracy rates of at least 90% for these parameters require either submission of all residual primary tumor or at least 20 tumor sections. Accurate %RVT, MPR, and CPR scores cannot be achieved with traditional tumor grossing. Submission of the entire primary tumor, up to a maximum of 20 sections, is required for the most accurate reads.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Neoadjuvante/métodos , Pulmão/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear. METHODS: A retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy. RESULTS: Higher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR. CONCLUSION: In conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.
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Síndrome do Ovário Policístico , Masculino , Gravidez , Feminino , Recém-Nascido , Humanos , Síndrome do Ovário Policístico/complicações , Androgênios , Sulfato de Desidroepiandrosterona , Estudos Retrospectivos , Sêmen , DesidroepiandrosteronaRESUMO
This study employed a green microwave synthesis technique to produce carbon quantum dots (CQDs) from araucaria heterophylla gum extract. The produced CQDs emit a distinct blue fluorescent light, contributing a remarkable quantum yield of 14.69%. Their average particle size measures at 1.62 ± 0.39 nm. Furthermore, these CQDs demonstrate excellent water solubility and maintain high fluorescence stability despite ionic strength, pH and time variations. Moreover, we present here for the first time that the synthesized CQDs demonstrate a rapid, exceptionally sensitive, and discerning fluorescence quenching phenomenon (IFE) concerning Cefprozil (CPR). The fluorescent probe was sensitive and specific with good linear relationships for CPR in the 0-18 µM range. The limit of detection for relationships for CPR was 2.51 µM. This study provides novel opportunities for producing high-quality luminescent CQDs that meet the requirements for various biological and environmental applications.
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BACKGROUND: High-quality cardiopulmonary resuscitation (CPR) can restore spontaneous circulation (ROSC) and neurological function and save lives. We conducted an umbrella review, including previously published systematic reviews (SRs), that compared mechanical and manual CPR; after that, we performed a new SR of the original studies that were not included after the last published SR to provide a panoramic view of the existing evidence on the effectiveness of CPR methods. METHODS: PubMed, EMBASE, and Medline were searched, including English in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) SRs, and comparing mechanical versus manual CPR. A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) and GRADE were used to assess the quality of included SRs/studies. We included both IHCA and OHCA, which compared mechanical and manual CPR. We analyzed at least one of the outcomes of interest, including ROSC, survival to hospital admission, survival to hospital discharge, 30-day survival, and survival to hospital discharge with good neurological function. Furthermore, subgroup analyses were performed for age, gender, initial rhythm, arrest location, and type of CPR devices. RESULTS: We identified 249 potentially relevant records, of which 238 were excluded. Eleven SRs were analyzed in the Umbrella review (January 2014-March 2022). Furthermore, for a new, additional SR, we identified eight eligible studies (not included in any prior SR) for an in-depth analysis between April 1, 2021, and February 15, 2024. The higher chances of using mechanical CPR for male patients were significantly observed in three studies. Two studies showed that younger patients received more mechanical treatment than older patients. However, studies did not comment on the outcomes based on the patient's gender or age. Most SRs and studies were of low to moderate quality. The pooled findings did not show the superiority of mechanical compared to manual CPR except in a few selected subgroups. CONCLUSIONS: Given the significant heterogeneity and methodological limitations of the included studies and SRs, our findings do not provide definitive evidence to support the superiority of mechanical CPR over manual CPR. However, mechanical CPR can serve better where high-quality manual CPR cannot be performed in selected situations.
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Reanimação Cardiopulmonar , Humanos , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/normas , Parada Cardíaca Extra-Hospitalar/terapia , Revisões Sistemáticas como Assunto/métodosRESUMO
INTRODUCTION: By using a novel survey our study aimed to assess the challenges ECMO and Critical Care (CC) teams face when initiating and managing patient's ECMO support. METHODS: A qualitative survey-based observational study was performed of members of 2 Critical Care Medicine organizations involved in decision-making around the practice of Extracorporeal Membrane Oxygenation (ECMO). The range of exploratory questions covered ethical principles of informed consent, autonomy and goals of care discussions, beneficence, non-maleficence (offering life-sustaining treatments in end-of-life care), and justice (insurance-related limitations of treatment). Questions also covered pragmatic practice and quality improvement areas, such as exploring whether palliative care or ethics teams were involved in such decision-making. RESULTS: 305 members received the survey links, and a total of 61 completed surveys were received, for an overall response rate of 20% among all eligible members. Only 70% of the participants who manage ECMO patients are involved in the ECMO initiation decision process. The majority do not involve Ethics or Palliative care at the initial ECMO initiation decision step. Of the ethical and moral dilemmas reported, the majority revolved around 1. Prognostication of patients receiving VV and VA ECMO support, 2. Lack of knowledge of patient's wishes and goals, 3. Disconnect between expectations of families and outcomes and 4. Staff moral distress around when to stop ECMO in case of futility. CONCLUSION: Our survey highlights areas of distress and dilemma which have been stressed before in the initiation, management, and outcomes of ECMO patients, however with the increasing use of this modality of cardiopulmonary mechanical support being offered, the survey results can offer a guidance using sound ethical principles.
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Cuidados Críticos , Oxigenação por Membrana Extracorpórea , Oxigenação por Membrana Extracorpórea/ética , Humanos , Cuidados Críticos/ética , Cuidados Críticos/métodos , Inquéritos e Questionários , Pesquisa Qualitativa , Cuidados Paliativos/ética , Cuidados Paliativos/métodos , Consentimento Livre e Esclarecido/ética , Masculino , Feminino , Tomada de Decisão Clínica/ética , Tomada de Decisões/ética , Beneficência , Planejamento de Assistência ao Paciente , Assistência Terminal/éticaRESUMO
PURPOSE: According to meta-analytic data, the prognosis of a cancer patient post-cardiopulmonary resuscitation (CPR) is relatively similar to the general population. However, preselection of patients, the details of CPR, patient-specific characteristics, and post-CPR care are poorly described. The aim of this study is to identify prognostic factors in order to recognize cancer patient profiles more likely to benefit from CPR. METHODS: This is a retrospective study on a series of patients with solid or hematological malignancies who received CPR between January 2010 and December 2020 in a cancer institute. RESULTS: Sixty-eight patients were included. The ratio of solid to hematological malignancy was 44/24, of which 32 were metastatic solid tumors. Median age was 61 years. Hypoxemia (29%) was the primary factor for cardiac arrest, followed by septic shock (21%). ICU mortality and hospital mortality were 87% and 88% respectively. Younger age, the presence of hematological malignancy, or a metastatic solid tumor were poor predictors for in-hospital mortality. Similarly, cardiac arrest in the ICU, as the final consequence of a pathological process, and a resuscitation time of more than 10 min have a negative influence on prognosis. CONCLUSIONS: This study shows that CPR is a useful intervention in cancer patients, even in the elderly patient, especially in non-metastatic solid tumors where cardiac arrest is the consequence of an acute event and not a terminal process.
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Reanimação Cardiopulmonar , Mortalidade Hospitalar , Neoplasias , Humanos , Reanimação Cardiopulmonar/métodos , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Neoplasias/complicações , Neoplasias/terapia , Feminino , Idoso , Prognóstico , Parada Cardíaca/terapia , Idoso de 80 Anos ou mais , Adulto , Fatores Etários , Unidades de Terapia Intensiva/estatística & dados numéricosRESUMO
It is unclear if cardiopulmonary resuscitation is an aerosol-generating procedure and whether this poses a risk of airborne disease transmission to healthcare workers and bystanders. Use of airborne transmission precautions during cardiopulmonary resuscitation may confer rescuer protection but risks patient harm due to delays in commencing treatment. To quantify the risk of respiratory aerosol generation during cardiopulmonary resuscitation in humans, we conducted an aerosol monitoring study during out-of-hospital cardiac arrests. Exhaled aerosol was recorded using an optical particle sizer spectrometer connected to the breathing system. Aerosol produced during resuscitation was compared with that produced by control participants under general anaesthesia ventilated with an equivalent respiratory pattern to cardiopulmonary resuscitation. A porcine cardiac arrest model was used to determine the independent contributions of ventilatory breaths, chest compressions and external cardiac defibrillation to aerosol generation. Time-series analysis of participants with cardiac arrest (n = 18) demonstrated a repeating waveform of respiratory aerosol that mapped to specific components of resuscitation. Very high peak aerosol concentrations were generated during ventilation of participants with cardiac arrest with median (IQR [range]) 17,926 (5546-59,209 [1523-242,648]) particles.l-1 , which were 24-fold greater than in control participants under general anaesthesia (744 (309-2106 [23-9099]) particles.l-1 , p < 0.001, n = 16). A substantial rise in aerosol also occurred with cardiac defibrillation and chest compressions. In a complimentary porcine model of cardiac arrest, aerosol recordings showed a strikingly similar profile to the human data. Time-averaged aerosol concentrations during ventilation were approximately 270-fold higher than before cardiac arrest (19,410 (2307-41,017 [104-136,025]) vs. 72 (41-136 [23-268]) particles.l-1 , p = 0.008). The porcine model also confirmed that both defibrillation and chest compressions generate high concentrations of aerosol independent of, but synergistic with, ventilation. In conclusion, multiple components of cardiopulmonary resuscitation generate high concentrations of respiratory aerosol. We recommend that airborne transmission precautions are warranted in the setting of high-risk pathogens, until the airway is secured with an airway device and breathing system with a filter.
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Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Humanos , Animais , Suínos , Reanimação Cardiopulmonar/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Coração , Respiração , ExpiraçãoRESUMO
INTRODUCTION: Considering the few studies evaluating bystander cardiopulmonary resuscitation (CPR) performance, we sought to analyze differences in bystander CPR performance with and without the use of our self-developed animated GIFs based on dispatcher-assisted CPR simulation. METHODS: A total of 80 adults who had not received CPR training over the past two years participated in the study. Among them, 40 people were classified into the auditory group (receiving CPR instructions only over the phone), and the other 40 people were classified into the audiovisual group (receiving CPR instructions over the phone after receiving images on a smartphone). All participants were asked to perform adult and infant CPR for 2 min. CPR performance was recorded using two video cameras (front and side) and analyzed by two emergency physicians, whereas CPR quality was measured using Resusci Anne & Baby QCPR Mk II (Laerdal). RESULTS: In the adult CPR study, the audiovisual group had higher performance scores for adequacy of "knee position," "hand posture," "elbow extension," and "vertical compression," as well as higher Standard Posture Completeness and Instruction Performance scores (p < 0.001). No significant difference in CPR quality was observed between the two groups. In the infant CPR study, audiovisual group had higher performance scores in adequacy of "compression site," "finger posture," and "vertical compression," as well as higher Standard Posture Completeness and Instruction Performance scores (p < 0.001). Regarding CPR quality, the audiovisual group had higher scores for "adequate compression rate ratio" (p = 0.047). CONCLUSION: Audiovisual guidance using animated GIFs more effectively improved CPR Standard Posture Completeness and Instruction Performance than did traditional auditory guidance.
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Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Reanimação Cardiopulmonar/métodos , Telefone , Smartphone , Simulação por Computador , PressãoRESUMO
BACKGROUND: Effective education is considered by the American Heart Association (AHA) as a vital variable in improving outcomes of cardiac arrest. Studies have shown that the level of knowledge and attitude of non-healthcare providers towards resuscitation training varies widely across the globe. While some training methods and barriers to training have been discussed, the literature is still quite vague and unclear regarding resuscitation training, particularly in the Middle East. This study's focus on the efficacy of resuscitation training in this region of the world may help dictate how to better implement education initiatives aimed towards non-healthcare providers in developing countries. METHODOLOGY: A systematic review and meta-analysis were conducted on studies published from inception until March 2023. Observational studies assessing CPR knowledge and skills among non-healthcare workers in Arab countries were included. Data were extracted from PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus. Data analysis was performed using Rstudio with a random effects model. RESULTS: 50 studies were included in this review and meta-analysis, revealing that 55% of participants had prior knowledge of CPR, while only 28% considered their knowledge sufficient. The majority (76%) supported mandatory CPR training, and 86% were willing to attend training if offered. This study found that prior knowledge of cardiopulmonary resuscitation (CPR) varied among populations. This meta-analysis also compiled results regarding CPR technique defined by correct compression to ventilation ratio, compression depth, compression rate, location of chest compression, and correct sequence. The overall results from this meta-analysis showed that, of these factors, compression rate and depth were the two factors that were most often administered incorrectly. In all, the results from this study demonstrated that CPR training in Arab countries was favorably viewed overall, with the majority of participants indicating both support for mandatory CPR training and general willingness to attend training if offered the opportunity. CONCLUSION: Given the overall positive view and willingness to learn CPR skills, healthcare policy makers should adopt a more comprehensive focus on strategies that enhance the accessibility and opportunity for CPR training for non-healthcare populations in Arab countries. Future training programs should implement strategies to highlight the ideal combination of compression rates and depth to learners to ensure correct and efficacious delivery of CPR with increased focus on the practical portion during refresher courses to promote retention.
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Reanimação Cardiopulmonar , Conhecimentos, Atitudes e Prática em Saúde , Reanimação Cardiopulmonar/educação , Humanos , Oriente MédioRESUMO
BACKGROUND: Bystander-initiated cardiopulmonary resuscitation (CPR) can improve survival rates in individuals with out-of-hospital cardiac arrest (OHCA). Two CPR approaches are commonly utilized, standard (S-CPR) with mouth-to-mouth breathing and compression-only (CO-CPR). We conducted a systematic review and meta-analysis to compare clinical outcomes associated with S-CPR versus CO-CPR in OHCA. METHODS: A systematic literature search was conducted using PubMed, EMBASE, and the Cochrane Library. Eligible studies included randomized controlled trials (RCTs) focused on adult OHCA patients receiving CO-CPR or S-CPR. Forest plots were generated for pooled data analysis using Review Manager version 5.4. Random-effect analyses were used, and statistical significance was set at p < .05. RESULTS: Four randomized controlled trials were included in the final analysis, encompassing a total sample size of 4987 patients (2482 in the CO-CPR group and 2505 in the S-CPR group). CO-CPR was associated with significantly improved 1-day survival compared with S-CPR (OR = 1.15; 95% CI: 1.02-1.31; p = .03) and survival to hospital discharge (OR = 1.25; 95% CI: 1.01-1.55; p = .04). No heterogeneity was observed among the studies for either outcome. CONCLUSION: CO-CPR emerges as a promising strategy for improving outcomes in OHCA compared to S-CPR. However, further large-scale RCTs are required to generate more robust evidence.
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OBJECTIVE: Our aim was to investigate the significance of cerebro-placento-uterine ratio CPUR, a new Doppler index, and fetal cardiac parameters (Mod MPI, EFT) in early-onset preeclampsia (EOPE) and to examine whether these parameters are related to perinatal outcome. STUDY DESIGN: Forty participants diagnosed with EOPE (preeclampsia cases diagnosed before 34 weeks of gestation) and 40 healthy pregnant women were included in this study. Demographic data were recorded. Doppler parameters such as middle cerebral artery (MCA), umbilical artery (UA), and uterine artery (Ut-A), and left modified myocardial performance index (Mod-MPI) and epicardial fat thickness (EFT) were measured. Cerebroplacental ratio (CPR) was determined by dividing MCA pulsatility index (PI) by UA PI. CPUR was calculated as the ratio of CPR to mean UtA-PI (CPUR = CPR/UtA-PI). All parameters were compared between the EOPE and control groups. Correlation tests were used to examine the relationship between Doppler parameters and perinatal outcome. p values less than 0.05 were considered statistically significant. RESULTS: The pulsatility index of the middle cerebellar artery, CPUR and CPR values were statistically lower in the EOPE group than in the control group (p = 0.002; p = <0.001; p = <0.001; respectively). No statistical differences were found between groups for isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), ejection time (ET), left mod-MPI, EFT (p = 0.117; p = 0.093; p = 0.398; p = 0.882; p = 0.202, respectively). Umbilical artery Doppler pulsatility index (PI), mean uterine artery Doppler pulsatility index (PI), were higher in the EOPE group than in the control group (p = 0.006; and p = <0.001, respectively). The CPUR value for predicting EOPE was ≤1.3652 with 74. 4% sensitivity and 94.9% specificity. Positive correlations were found between CPUR, CPR, and some neonatal parameters. CONCLUSION: CPUR, a new index combining fetal and uterine Doppler indices, may add contribution to predict adverse perinatal outcome and EOPE.
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Artéria Cerebral Média , Placenta , Pré-Eclâmpsia , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Artérias Umbilicais , Artéria Uterina , Humanos , Feminino , Gravidez , Ultrassonografia Pré-Natal/métodos , Adulto , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/diagnóstico por imagem , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/fisiopatologia , Ultrassonografia Doppler/métodos , Artérias Umbilicais/diagnóstico por imagem , Artérias Umbilicais/fisiopatologia , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Placenta/diagnóstico por imagem , Placenta/irrigação sanguínea , Coração Fetal/diagnóstico por imagem , Coração Fetal/fisiopatologia , Útero/irrigação sanguínea , Útero/diagnóstico por imagem , Fluxo Pulsátil/fisiologiaRESUMO
Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens are synthesized from testosterone and androstenedione by the endoplasmic reticulum membrane-bound P450 aromatase/cytochrome P450 oxidoreductase complex (CYP19/CPR). Here, we report the characterization of novel mammalian CYP19 isoforms encoded by CYP19 gene copies. These CYP19 isoforms are all defined by a combination of mutations in the N-terminal transmembrane helix (E42K, D43N) and in helix C of the catalytic domain (P146T, F147Y). The mutant CYP19 isoforms show increased androgen conversion due to the KN transmembrane helix. In addition, the TY substitutions in helix C result in a substrate preference for androstenedione. Our structural models suggest that CYP19 mutants may interact differently with the membrane (affecting substrate uptake) and with CPR (affecting electron transfer), providing structural clues for the catalytic differences.
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Aromatase , Animais , Feminino , Humanos , Gravidez , Aminoácidos , Androstenodiona , Aromatase/genética , Aromatase/metabolismo , Estrogênios/metabolismo , Mamíferos/metabolismo , Isoformas de Proteínas , Estrutura Terciária de Proteína/genética , Estrutura Secundária de Proteína/genéticaRESUMO
The versatility of cytochrome P450 reductase (CPR) in transferring electrons to P450s from other closely related species has been extensively exploited, e.g., by using An. gambiae CPR (AgCPR), as a homologous surrogate, to validate the role of An. funestus P450s in insecticide resistance. However, genomic variation between the AgCPR and An. funestus CPR (AfCPR) suggests that the full metabolism spectrum of An. funestus P450s might be missed when using AgCPR. To test this hypothesis, we expressed AgCPR and AfCPR side-by-side with CYP6P9a and CYP6P9b and functionally validated their role in the detoxification of insecticides from five different classes. Major variations were observed within the FAD- and NADP-binding domains of AgCPR and AfCPR, e.g., the coordinates of the second FAD stacking residue AfCPR-Y456 differ from that of AgCPR-His456. While no significant differences were observed in the cytochrome c reductase activities, when co-expressed with their endogenous AfCPR, the P450s significantly metabolized higher amounts of permethrin and deltamethrin, with CYP6P9b-AfCPR membrane metabolizing α-cypermethrin as well. Only the CYP6P9a-AfCPR membrane significantly metabolized DDT (producing dicofol), bendiocarb, clothianidin, and chlorfenapyr (bioactivation into tralopyril). This demonstrates the broad substrate specificity of An. funestus CYP6P9a/-b, capturing their role in conferring cross-resistance towards unrelated insecticide classes, which can complicate resistance management.
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Anopheles , Resistência a Inseticidas , Inseticidas , NADPH-Ferri-Hemoproteína Redutase , Piretrinas , Anopheles/genética , Anopheles/efeitos dos fármacos , Anopheles/enzimologia , Anopheles/metabolismo , Animais , Resistência a Inseticidas/genética , NADPH-Ferri-Hemoproteína Redutase/metabolismo , NADPH-Ferri-Hemoproteína Redutase/genética , Inseticidas/farmacologia , Inseticidas/metabolismo , Piretrinas/farmacologia , Piretrinas/metabolismo , Oxirredução , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Especificidade por Substrato , Nitrilas/metabolismo , Nitrilas/farmacologia , Permetrina/farmacologiaRESUMO
PURPOSE: Examine the prone cardiopulmonary resuscitation techniques in patients undergoing surgery. DESIGN: Systematic review. METHODS: Using the preferred reporting items for systematic reviews and meta-analysis guidelines, PubMed, CINAHL, Cochrane Library, Google Scholar, and gray literature databases were searched to obtain eligible studies. The methodological quality of the case studies was assessed using the tool proposed by Murad and colleagues. Case reports involving surgical patients in a prone position were included. FINDINGS: A total of 21 patients undergoing neurologic or spinal surgeries were evaluated. The most common cardiac rhythms observed before arrest were pulseless electrical activity, asystole, ventricular tachycardia, ventricular fibrillation, and sudden bradycardia. The etiologies of the cardiac arrests included venous air embolism, hemorrhagic shock, and hypovolemia. Posterior compressions at T7 to T9 vertebral segment, with or without counterpressure, were immediately instituted. Return of spontaneous circulation was achieved in each instance, with an average time to return of spontaneous circulation of 5.60 minutes. Using a quality assessment tool, we determined that all case reports were of high quality and exhibited a low risk of bias. CONCLUSIONS: Prone resuscitation during neurosurgical or spinal surgeries has demonstrated promising outcomes. Additionally, the findings of this review further emphasize the need to train health care personnel in the techniques of prone cardiopulmonary resuscitation.
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Background: Cardiopulmonary resuscitation (CPR) is a major rescue measure for cardiac arrest (CA) patients, and chest compression is the key to CPR. The Thumper device was designed to facilitate manual compression during CPR. However, current randomized controlled trials (RCTs) provide controversial findings on the efficacy of the Thumper device. Objectives: This meta-analysis aimed to compare the clinical benefits of using the Thumper device with manual chest compressions during the provision of CPR for patients in CA. Methods: Relevant studies were retrieved from various databases, including Ovid, PubMed, Web of Science, EMBASE, Cochrane, and CNKI, and by manually searching the reference lists of research and review articles. All RCTs published in either English or Chinese until June 31, 2020, were included in the meta-analysis. The odds ratios (ORs) and their 95% confidence intervals (95% CIs) for the return of spontaneous circulation (ROSC), survival rate (SR), and the incidence of rib fractures (RFs) were compared between the manual and Thumper chest compressions. Results: A total of 2164 records were identified, of which 16 were RCTs with an overall risk of bias ranging from low to medium classification. Following CPR, the odds ratios for ROSC, SR, and RF were significantly better for the Thumper chest compression with ORs of 2.56 (95% CI 2.11-3.11, I 2 = 0%), 4.06 (95% CI 2.77-5.93, I 2 = 0%), and 0.24 (95% CI 0.14-0.41, I 2 = 0%), respectively. Conclusions: The Thumper compression devices may improve patient outcome, when used at inhospital cardiac arrest. This review suggests a potential role for mechanical chest compression devices for in-hospital cardiac arrest, but there is an urgent need for high-quality research, particularly adequately powered randomised trials, to further examine this role.
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OBJECTIVES: To describe the techniques used for percutaneous veno-arterial extracorporeal membrane oxygenation (VA-ECMO) cannulation and decannulation in children with the pediatric interventional cardiologist (PIC) as the primary operator, and present outcomes of this initial clinical experience. BACKGROUND: Percutaneous VA-ECMO during cardiopulmonary resuscitation (CPR) has been successfully performed in adults, but currently, not much data exists on children. METHODS: This is a single-center study including VA-ECMO cannulations performed by the PIC between 2019 and 2021. Efficacy was defined as the successful initiation of VA-ECMO without surgical cutdown. Safety was defined as the absence of additional procedures related to cannulation. RESULTS: Twenty-three percutaneous VA-ECMO cannulations were performed by PIC on 20 children with 100% success. Fourteen (61%) were performed during ongoing CPR, and nine for cardiogenic shock. The Median age was 15 (0.15-18) years, and the median weight was 65 (3.3-180) kg. All arterial cannulations were via the femoral artery except in one, 8-week-old infant who was cannulated in the carotid artery. A distal perfusion cannula was placed in the ipsilateral limb in 17 (78%). The median time from initiating cannulation to ECMO flow was 35 (13-112) minutes. Two patients required arterial graft placement at the time of decannulation and one needed below-knee amputation. ECMO support was maintained for a median of 4 (0.3-38) days. Thirty-day survival was 74%. CONCLUSION: Percutaneous VA-ECMO cannulations can be effectively performed, even during CPR with the Pediatric Interventional Cardiologist being the primary operator. This is an initial clinical experience. Future outcome studies compared with standard surgical cannulations are necessary to advocate routine percutaneous VA-ECMO in children.
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Cateterismo Periférico , Oxigenação por Membrana Extracorpórea , Adulto , Humanos , Criança , Adolescente , Oxigenação por Membrana Extracorpórea/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/métodos , Resultado do Tratamento , Estudos Retrospectivos , Choque CardiogênicoRESUMO
Measuring the phase synchronization between different brain regions in functional brain networks is a common approach to investigate many psychological disorders such as Attention Deficit Hyperactivity Disorder (ADHD). The emotional processing deficit in ADHD children is one of the main obstacles in their social interactions. In this study, the nonlinear Correlation between Probability of Recurrences (CPR) method is used for the first time to construct functional brain networks of 22 boys with ADHD and 22 healthy ones during watching four visual-emotional stimuli types. Topological features of brain networks, including shortest path length, clustering coefficient, and nodes strengths, are investigated in groups of ADHD and healthy. The results indicate a significantly (P-Values < 0.01) greater average clustering coefficient and lower shortest path length in the brain networks of ADHD individuals than the healthy ones. Accordingly, in the ADHD brain networks, the information exchange in both local and global scales is abnormally more than the healthy ones, leading to a hyper-synchronization in this group. The topological alterations of ADHD brain networks are mainly observed in the brain's frontal and occipital lobes, indicating impaired brain function of this group in emotional and visual processing. This survey demonstrates that the CPR method can be a good candidate for distinguishing the phase interactions of ADHD and healthy brain networks. Therefore, this study can contribute to further insights into the nonlinear dynamics analysis of brain networks in ADHD individuals.
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Transtorno do Deficit de Atenção com Hiperatividade , Masculino , Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Imageamento por Ressonância Magnética , Encéfalo , Emoções , Rede Nervosa , Vias NeuraisRESUMO
BACKGROUND: Little is known about how to effectively increase bystander cardiopulmonary resuscitation (CPR), so we evaluated the 10-year trend of the proportion of bystander CPR in an area with wide dissemination of chest compression-only CPR (CCCPR) training combined with conventional CPR training.MethodsâandâResults: We conducted a descriptive study after a community intervention, using a prospective cohort from September 2010 to December 2019. The intervention consisted of disseminating CCCPR training combined with conventional CPR training in Toyonaka City since 2010. We analyzed all non-traumatic out-of-hospital cardiac arrest (OHCA) patients resuscitated by emergency medical service personnel. The primary outcome was the trend of the proportion of bystander CPR. We conducted multivariate logistic regression models and assessed the adjusted odds ratio (AOR) using a 95% confidence interval (CI) to determine bystander CPR trends. Since 2010, we have trained 168,053 inhabitants (41.9% of the total population of Toyonaka City). A total of 1,508 OHCA patients were included in the analysis. The proportion of bystander CPR did not change from 2010 (43.3%) to 2019 (40.0%; 1-year incremental AOR 1.02 [95% CI: 0.98-1.05]). CONCLUSIONS: The proportion of bystander CPR did not increase even after wider dissemination of CPR training. In addition to continuing wider dissemination of CPR training, other strategies such as the use of technology are necessary to increase bystander CPR.