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PURPOSE: Robotic-assisted total knee arthroplasty (r-TKA) facilitates precise bone resection and lower limb alignment, yet accuracy and functional recovery for severe varus/valgus deformity is not well-documented. The aim of study was to investigate whether r-TKA improves implant alignment in the coronal and sagittal view and early functional recovery compared to conventional TKA(c-TKA). METHODS: This comparative study included 86 patients with symptomatic knee arthritis who underwent primary TKA at our institution between 1st May and 31th November 2021. Radiological parameters evaluated included hip-knee-ankle angle (HKAA), femoral varus-valgus angle (FVVA), tibial varus-valgus angle (TVVA), posterior tibial slope angle (PTSA), femoral sagittal angle (FSA), posterior condylar offset ratio, and Insall-Salvati index. Operative time, stay length, and complications were reviewed from patient records. The hospital for special surgery (HSS), Visual Analogue Scale (VAS) and knee joint motion range were evaluated at the six-month follow-up. RESULTS: The c-TKA and r-TKA groups had no significant differences in HKAA (179.73 ± 3.76°, range: 172.10-188.90° vs. 180.53 ± 2.91°, range: 173.30-188.32°, p = 0.277), FVVA (96.13 ± 2.61°, range: 90.27-101.52° vs. 96.38 ± 2.23°, range: 90.98-100.95°, p = 0.636), and TVVA (88.74 ± 2.03°, range: 83.75-92.74° vs. 89.43 ± 1.83°, range: 85.32-94.15°, p = 1.000). Outlier of mechanical alignment incidence (> 3°) was significantly lower in r-TKA compared with c-TKA, 17.50% (7/40) vs. 41.30% (19/46), (p = 0.017). PTSA of r-TKA remained significantly lower than c-TKA (p = 0.009) in mild-deformity patients. For severe varus/valgus deformity, r-TKA had a significantly lesser HKAA-outlier incidence (p = 0.025), PTSA-outlier incidence (p = 0.019), and lower PTSA (p < 0.001) compared with c-TKA. The r-TKA functional outcome was better than c-TKA regarding HSS (93.12 ± 1.97, range: 90-95, 95%CI:92.11-94.13 vs. 91.33 ± 2.50, range: 85-95, 95%CI:90.20-92.69, p = 0.036), and VAS (0.24 ± 0.44, range:0-1 vs. 0.72 ± 0.75, range:0-2, p = 0.026), knee joint flexion (118.53° ± 8.06, range: 105-130°, 95%CI:114.39-122.67° vs. 112.22 ± 8.09°, range: 100-130°, 95%CI:108.20-116.24° ,p = 0.027) for severe varus/valgus deformity. CONCLUSION: r-TKA improved lower-limb coronal alignment, sagittal implant position, and early functional recovery for patients with severe varus/valgus deformity of the knee. r-TKA did not confer substantial advantages over c-TKA in both radiological and clinical outcomes for the mild varus/valgus deformity.
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Artroplastia do Joelho , Pirenos , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Extremidade InferiorRESUMO
AIMS: To investigate the level of spiritual health in older patients with chronic obstructive pulmonary disease (COPD) from the core dimensions and to explore its associated factors. DESIGN: A cross-sectional study. METHODS: Participants were recruited from four hospitals between September 2020 and June 2021, using a convenience sampling. Older patients with COPD (n = 162) completed the demographic and disease-related information questionnaires, Function Assessment of Chronic Illness Therapy Spiritual Scale, 10-item Connor-Davidson Resilience Scale, General Self-efficacy Scale, Social Support Rating Scale, COPD Assessment Test, 15-item Geriatric Depression Scale and modified Medical Research Council Dyspnea Scale. Descriptive statistics, Pearson and Spearman correlation analyses, t-tests, one-way ANOVA and multiple linear regression models were used. RESULTS: Older patients with COPD have a moderate level of spiritual health. The multiple linear regression analysis showed that psychological resilience, general self-efficacy, social support, symptom burden and monthly income were associated with the core dimensions of spiritual health. CONCLUSION: Chinese older patients with COPD have a moderate level of spiritual health. Psychological resilience, general self-efficacy, social support, monthly income and symptom burden were associated with the core dimensions of spiritual health. IMPACT: This study is the first to investigate the level of spiritual health in older patients with COPD from the core dimensions and to explore its associated factors, providing a basis for developing spiritual intervention programs. Our findings can help us realize that intervention strategies of psychological resilience, general self-efficacy and social support can all be used to enhance spiritual health. Nurses should focus on the spiritual health of older COPD patients with high symptom burden and low monthly income. PATIENT OR PUBLIC CONTRIBUTION: Although we did not directly involve patients and the public because of the COVID-19 pandemic, the results of the study will be disseminated to patients and the public through WeChat and seminars.
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Doença Pulmonar Obstrutiva Crônica , Resiliência Psicológica , Humanos , Idoso , Estudos Transversais , Pandemias , Inquéritos e Questionários , Qualidade de Vida/psicologiaRESUMO
This umbrella review aim to explore the effect of topical antibiotics in infection prevention after primary joint arthroplasty, and provide a specific theoretical basis for clinical treatment. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, EMBASE, Medline, and the Cochrane Library on infection prevention by topical antibiotics from inception to 10 April 2023. The two researchers individually and strictly screened the literature according to the inclusion and exclusion criteria, performed the literature quality evaluation and data extraction, and used Stata 17 for data analysis. This study included six studies with one systematic review and five meta-analyses. The pooled analysis showed that topical antibiotic administration effectively reduced the incidence of overall infection and periprosthetic joint infection. However, it does not reduce the risk of superficial infection. Besides, the topic of antibiotics significantly increases the incidence of other sterile complications of the incision. According to the current evidence, topical application of antibiotics can reduce the incidence of overall infection and periprosthetic joint infection after primary joint arthroplasty. Although it increases the incidence of complications such as delayed healing of incisions, the pros and cons should be weighed in clinical decision making. However, they should not be discarded due to side effects.
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Infecções Relacionadas à Prótese , Ferida Cirúrgica , Humanos , Antibacterianos/uso terapêutico , Artroplastia/efeitos adversos , Infecções Relacionadas à Prótese/prevenção & controle , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
BACKGROUND: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. RESULTS: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). CONCLUSIONS: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.
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Bacillus subtilis , Células Matadoras Naturais , Animais , Camundongos , Células Matadoras Naturais/metabolismo , Linfócitos T/metabolismo , Interferon gama , FagocitoseRESUMO
INTRODUCTION: The objective of this study was to investigate the ankle alignment alterations after the correction of knee varus deformity in MAKO robot-assisted total knee arthroplasty (MA-TKA). METHODS: A retrospective analysis was conducted for 108 patients with TKA from February 2021 to February 2022. Patients were divided into two groups based on MAKO robot involvement during the procedure: the MA-TKA group (n = 36) and the conventional manual total knee arthroplasty (CM-TKA) group (n = 72). The patients were divided into four subgroups according to the degree of surgical correction of the knee varus deformity. Seven radiological measurements were evaluated pre and post-surgery: mechanical tibiofemoral angle (mTFA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), tibial plafond inclination angle (TPIA), talar inclination angle (TIA), and tibiotalar tilt angle (TTTA). TTTA is a quantitative representation of the extent of ankle incongruence. RESULTS: The number of mTFA, mLDFA, and MPTA outliers in the MA-TKA group was significantly lower compared to the CM-TKA group (P<0.05). Knee varus deformity was properly corrected and the mechanical axis was restored in all patients, regardless of the treatment group. Only for varus corrections ≥ 10° did TTTA change significantly (p < 0.01) and ankle varus incongruence aggravate post-operation. The ΔTTTA correlated negatively with ΔTFA (r=-0.310,P = 0.001) and correlated positively with ΔTPIA (r = 0.490,P = 0.000). When the varus correction was ≥ 7.55°, the probability of ankle varus incongruence exacerbation increased 4.86-fold. CONCLUSION: Compared with CM-TKA, MA-TKA osteotomy showed more precision but was unable to reduce post-operation ankle varus incongruence. When the varus correction ≥ 10°, ankle varus incongruence aggravated, while when the varus correction ≥ 7.55°, the probability of ankle varus incongruence increased 4.86-fold. This may occasion the pathogenesis of ankle pain following TKA.
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Artroplastia do Joelho , Genu Varum , Osteoartrite do Joelho , Robótica , Humanos , Artroplastia do Joelho/efeitos adversos , Tornozelo/cirurgia , Genu Varum/cirurgia , Estudos Retrospectivos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Osteoartrite do Joelho/cirurgiaRESUMO
BACKGROUND: Telehealth and online health information provide patients with increased access to healthcare services and health information in chronic disease management of older patients with chronic diseases, addressing the challenge of inadequate health resources and promoting active and informed participation of older patients in chronic disease management. There are few qualitative studies on the application of telehealth and online health information to chronic disease management in older patients. Chronic obstructive pulmonary disease is one of the most common chronic diseases in older adults. Telehealth is widely used in the management of chronic obstructive pulmonary disease. The purpose of this study was to explore the perceptions and experiences of older patients and healthcare providers in the application of telehealth and online health information to chronic disease management of chronic obstructive pulmonary disease. METHODS: A qualitative descriptive study with data generated from 52 individual semi-structured interviews with 29 patients [Law of the People's Republic of China on the protection of the rights and interests of older people (2018 Revised Version) = >60 years old] with chronic obstructive pulmonary disease and 23 healthcare providers. The inductive thematic analysis method was used for data analysis. RESULTS: Four themes and 16 sub-themes were identified in this study. Four themes included: faced with a vast amount of online health information, essential competencies and personality traits ensuring older patients' participation and sustained use, user experience with the use of technology, being in a complex social context. CONCLUSION: The ability of patients to understand health information should be fully considered while facilitating access to online health information for older patients. The role of health responsibility and user experience in older patients' participation and sustained use of telehealth and online health information needs to be emphasised. In addition, the complex social context is a determining factor to be considered, particularly the complex impact of a reliance on offspring and social prejudice on the behaviour of older adults using telehealth and online health information.
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Doença Pulmonar Obstrutiva Crônica , Telemedicina , Idoso , Gerenciamento Clínico , Pessoal de Saúde , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Pesquisa QualitativaRESUMO
In the present study, antagonistic activity of bacterial strain BS-Z15, was evaluated against Verticillium dahlia. The fermented broth of BS-Z15 inhibited the growth of Verticillium dahliae. The genome of strain BS-Z15 had a total size of 4,068,702 base pairs and contained 4318 genes, of which 4196 are coding sequences and 122 are non-coding RNA. Among these genes, nine genomic islands, 86 tRNAs, 13 sRNAs, and one prophage was determined. With the help of annotation databases, most unigene functions were identified. At the same time, genomic comparison between BS-Z15 and 12 Bacillus members showed that the genes of BS-Z15 were closely related to the Bacillus group, and were conserved between the two groups, including most of the genes associated with fungal antagonism. BS-Z15 contains genes involved in a variety of antagonistic mechanisms, including genes encoding or synthesizing mycosubtilin, chitinases (but not CHIA and CHIB), glycoside hydrolases, iron nutrients, and antibiosis. However, it only contained the complete mycosubtilin- and bacilibactin-related operators in the reported main antifungal gene cluster of B. subtilis. Mycosubtilin and bacilibactin may be the main active antifungal substance. Besides, some genes could encode products related to biofilm production, which may be related to the colonization ability of the strain in plant rhizospheres. The complete genome of B. subtilis BS-Z15 provided new insights into the potential metabolites it produces related to its biocontrol activity.
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Antibiose , Ascomicetos , Bacillus , Genoma Bacteriano , Microbiologia do Solo , Bacillus/genética , Genoma Bacteriano/genética , Gossypium/microbiologia , RizosferaRESUMO
BACKGROUND: Comprehensive geriatric assessment (CGA) interventions can improve functional ability and reduce mortality in older adults, but the effectiveness of CGA intervention on the quality of life, caregiver burden, and length of hospital stay remains unclear. The study aimed to determine the effectiveness of CGA intervention on the quality of life, length of hospital stay, and caregiver burden in older adults by conducting meta-analyses of randomised controlled trials (RCTs). METHODS: A literature search in PubMed, Embase, and Cochrane Library was conducted for papers published before February 29, 2020, based on inclusion criteria. Standardised mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CIs) was calculated using the random-effects model. Subgroup analyses, sensitivity analyses, and publication bias analyses were also conducted. RESULTS: A total of 28 RCTs were included. Overall, the intervention components common in different CGA intervention models were interdisciplinary assessments and team meetings. Meta-analyses showed that CGA interventions improved the quality of life of older people (SMD = 0.12; 95% CI = 0.03 to 0.21; P = 0.009) compared to usual care, and subgroup analyses showed that CGA interventions improved the quality of life only in participants' age > 80 years and at follow-up ≤3 months. The change value of quality of life in the CGA intervention group was better than that in the usual care group on six dimensions of the 36-Item Short-Form Health Survey questionnaire (SF-36). Also, compared to usual care, the CGA intervention reduced the caregiver burden (SMD = - 0.56; 95% CI = - 0.97 to - 0.15, P = 0.007), but had no significant effect on the length of hospital stay. CONCLUSIONS: CGA intervention was effective in improving the quality of life and reducing caregiver burden, but did not affect the length of hospital stay. It is recommended that future studies apply the SF-36 to evaluate the impact of CGA interventions on the quality of life and provide supportive strategies for caregivers as an essential part of the CGA intervention, to find additional benefits of CGA interventions.
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Avaliação Geriátrica , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Sobrecarga do Cuidador , Cuidadores , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To understand the perceptions and experiences of older patients with chronic obstructive pulmonary disease (COPD) and healthcare professionals (HCPs) regarding shared decision-making in pulmonary rehabilitation (PR). DESIGN: A qualitative study using single, semi-structured interviews, and thematic analysis. SETTING: Face-to-face interviews were conducted in the Jiangnan University, in hospital and in patients' homes. PARTICIPANTS: Twenty-two older patients with COPD and 29 HCPs. METHODS: An initial codebook and semi-structured interview guide were developed based on the shared decision-making 3-circle conceptual model. Thematic analysis was used to analyze data. RESULTS: The study identified 10 themes that describe the perceptions and experiences of patients and HCPs involved in PR decision-making: (1) patients' confidence, (2) patients' perceptions of the cost-benefit of decisions, (3) patients' perceived stress about the consequences of decision-making, (4) HCPs' perceived stress on shared decision-making, (5) cognitive biases of patients toward illness and rehabilitation, (6) shared decision-making as a knowledge gap, (7) the knowledge gap between patients and HCPs, (8) authority effect, (9) family support, (10) human resources. These themes were then divided into three groups according to their characteristics: (1) the feelings of the participants, (2) knowledge barriers, and (3) support from the social system. CONCLUSION: Patients and HCPs described their negative perceptions and experiences of participating in decision-making in PR. The implementation of shared decision-making in PR is currently limited; therefore, health education for patients and families should be strengthened and a training system for HCPs in shared decision-making should be established.
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Pessoal de Saúde , Doença Pulmonar Obstrutiva Crônica , Atenção à Saúde , Humanos , Percepção , Pesquisa QualitativaRESUMO
PURPOSE: Cerebrospinal fluid leakage (CSFL) is a common complication during spinal surgery. This study aimed to compare dural closure with different suture types, sizes, and techniques, and adhesives to reduce the occurrence of CSFL. MATERIALS AND METHODS: Using a pig spine model, the PDS II 4-0, 5-0, 6-0, Vicryl 4-0, 5-0, 6-0, and Prolene 4-0, 5-0, 6-0 sutures were compared by calculating the permeability after suturing. Spraying bioprotein glue was also tried. Next, 120 patients who underwent surgery for intraspinal subdural tumors were enrolled and received 5-0 PDSII, Vicryl, or Prolene for dura repair. RESULTS: In the animal model study, Vicryl 5-0 showed a reduced leakage flow rate compared with 5-0 Prolene and 5-0 PDS II. In the clinical study, postoperative drainage in the Vicryl group was smaller than that in the other groups during the first 3 days after surgery (p < 0.05). Drainage volume of patients with postoperative cerebrospinal fluid leakage in the Vicryl group was smaller than that in the other groups during the first 3 days after surgery (p < 0.05).There were 12 patients (23.1%, 12/52) in the Vicryl group, 20 patients (55.6%, 20/36) in the PDS group, and 16 patients (50.0%, 16/32) in the Prolene group who had CSFL.The incidence of CSFL was significantly reduced in Vicryl group compared with the other groups(P < 0.05). CONCLUSIONS: 5-0 Vicryl sutures significantly reduced the dural leakage flow rate in an animal spine model. Fibrin glue can reinforce dural repair after surgery. 5-0 Vicryl was associated with a lower occurrence of CSFL in patients.
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PURPOSE: In this study, a simulator for training lateral ventricular puncture (LVP) was developed using three-dimensional (3D) printing technology, and its function of improving the skills of LVP in young interns was evaluated. METHODS: A virtual 3D craniocerebral simulator of a 51-year-old female patient with hydrocephalus was reconstructed with 3D printing technology. The anatomical and practical validity were assessed by all interns on a 13-item Likert scale. The usefulness of this simulator was evaluated once a week by two neurosurgeons, based on the performance of the interns, using the objective structured assessment of technical skills (OSATS) scale. RESULTS: The Likert scale showed that all participants agreed with the overall appearance of the simulator. Also, the authenticity of the skull was the best, followed by the lateral ventricles, analog generation system of intraventricular pressure, cerebrum, and the scalp. This simulator could help the participants' learning about the anatomy of the lateral ventricle, effective training, and repeating the steps of LVP. During training, the interns' ratio of success in LVP elevated gradually. At each evaluation stage, all mean performance scores for each measure based on the OSATS scale were higher than the previous. CONCLUSIONS: The 3D printed simulator for LVP training provided both anatomical and practical validity, and enabled young doctors to master the LVP procedures and skills.
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Ventrículos Laterais , Crânio , Competência Clínica , Feminino , Humanos , Ventrículos Laterais/cirurgia , Pessoa de Meia-Idade , Neurocirurgiões , Impressão Tridimensional , PunçõesRESUMO
BACKGROUND: The application of telemedicine in home pulmonary rehabilitation interventions for the management of patients with chronic obstructive pulmonary disease (COPD) has achieved promising results. OBJECTIVE: This study aimed to develop a WeChat official account (Pulmonary Internet Explorer Rehabilitation [PeR]) based on social media. It further evaluated the effect of PeR on the quality of life, symptoms, and exercise self-efficacy of patients with COPD. METHODS: The functional modules of PeR were developed by a multidisciplinary team according to the electronic health-enhanced chronic care model (eCCM) components. A total of 106 patients were randomly selected (53 in the PeR group and 53 in the outpatient face-to-face group [FtF]). Pulmonary rehabilitation intervention was conducted for 3 months, and the outcome was observed for 3 months. The primary outcome was patient quality of life measured with the COPD assessment test (CAT). The secondary outcomes were evaluated using the modified Medical Research Council scale (mMRC), exercise self-regulatory efficacy scale (Ex-SRES), and St George's Respiratory Questionnaire (SGRQ). RESULTS: The intention-to-treat analysis was used in the study. A total of 94 participants completed the 6-month pulmonary rehabilitation program. No statistically significant differences were observed in CAT (F1,3=7.78, P=.001), Ex-SRES (F1,3=21.91, P<.001), and mMRC scores (F1,3=29.64, P<.001) between the two groups with the variation in time tendency. The Ex-SRES score had a significant effect on the CAT score (P=.03). The partial regression coefficient of Ex-SRES to CAT was 0.81, and Exp (B) was 2.24. CONCLUSIONS: The telemedicine technology was effective using the eCCM combined with a behavioral intervention strategy centering on self-efficacy. Pulmonary rehabilitation at home through PeR and FtF could improve the sense of self-efficacy and quality of life and alleviate symptoms in patients with COPD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022770; https://tinyurl.com/tmmvpq3.
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Doença Pulmonar Obstrutiva Crônica/reabilitação , Qualidade de Vida/psicologia , Telemedicina/métodos , Idoso , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Adverse alterations in the composition of the gut microbiota have been implicated in the development of obesity and a variety of chronic diseases. Re-engineering the gut microbiota to produce beneficial metabolites is a potential strategy for treating these chronic diseases. N-acyl-phosphatidylethanolamines (NAPEs) are a family of bioactive lipids with known anti-obesity properties. Previous studies showed that administration of Escherichia coli Nissle 1917 (EcN) engineered with Arabidopsis thaliana NAPE synthase to produce NAPEs imparted resistance to obesity induced by a high-fat diet that persisted after ending their administration. In prior studies, mice were pre-treated with ampicillin prior to administering engineered EcN for 8 weeks in drinking water. If use of antibiotics and long-term administration are required for beneficial effects, implementation of this strategy in humans might be problematic. Studies were therefore undertaken to determine if less onerous protocols could still impart persistent resistance and sustained NAPE biosynthesis. Administration of engineered EcN for only 2 weeks without pre-treatment with antibiotics sufficed to establish persistent resistance. Sustained NAPE biosynthesis by EcN was required as antibiotic treatment after administration of the engineered EcN markedly attenuated its effects. Finally, heterologous expression of human phospholipase A/acyltransferase-2 (PLAAT2) in EcN provided similar resistance to obesity as heterologous expression of A. thaliana NAPE synthase, confirming that NAPEs are the bioactive mediator of this resistance.
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Fármacos Antiobesidade/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Engenharia Metabólica , Obesidade/prevenção & controle , Fosfatidiletanolaminas/metabolismo , Probióticos/administração & dosagem , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Antibacterianos/administração & dosagem , Arabidopsis/enzimologia , Dieta Hiperlipídica/métodos , Modelos Animais de Doenças , Escherichia coli/genética , Humanos , Camundongos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Resultado do TratamentoRESUMO
Food intake induces synthesis of N-acylphosphatidylethanolamines (NAPEs) in the intestinal tract. While NAPEs exert leptin-like (leptogenic) effects, including reduced weight gain and food intake, the mechanisms by which NAPEs induce these leptogenic effects remain unclear. One key question is whether intestinal NAPEs act directly on cognate receptors or first require conversion to N-acylethanolamides (NAEs) by NAPE-hydrolyzing phospholipase D (NAPE-PLD). Previous studies using Nape-pld-/- mice were equivocal because intraperitoneal injection of NAPEs led to nonspecific aversive effects. To avoid the aversive effects of injection, we delivered NAPEs and NAEs intestinally using gut bacteria synthesizing these compounds. Unlike in wild-type mice, increasing intestinal levels of NAPE using NAPE-synthesizing bacteria in Nape-pld-/- mice failed to reduce food intake and weight gain or alter gene expression. In contrast, increasing intestinal NAE levels in Nape-pld-/- mice using NAE-synthesizing bacteria induced all of these effects. These NAE-synthesizing bacteria also markedly increased NAE levels and decreased inflammatory gene expression in omental adipose tissue. These results demonstrate that intestinal NAPEs require conversion to NAEs by the action of NAPE-PLD to exert their various leptogenic effects, so that the reduced intestinal NAPE-PLD activity found in obese subjects may directly contribute to excess food intake and obesity.
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Leptina/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfolipase D/metabolismo , Animais , Arabidopsis/enzimologia , Hidrólise , CamundongosRESUMO
Background Coronary computed tomography angiography (CTA) allows the evaluation of coronary plaque volume and low attenuation (lipid-rich) component, for plaque vulnerability assessment. Purpose To determine the effect of iterative reconstruction (IR) on coronary plaque volume and composition. Material and Methods Consecutive patients without coronary artery disease were prospectively enrolled for 256-slice CT. Images were reconstructed with both filtered back projection (FBP) and a hybrid IR algorithm (iDose4, Philips) levels 1, 3, 5, and 7. Coronary plaques were assessed according to predefined Hounsfield unit (HU) attenuation intervals, for total plaque and HU-interval volumes. Results Fifty-three patients (mean age, 53.6 years) were included. Noise was significantly decreased and signal-to-noise ratio (SNR) / contrast-to-noise (CNR) were both significantly improved at all IR levels in comparison to FBP. Plaque characterization was performed in 41 patients for a total of 125 plaques. Total plaque volume ranged from 104.4 ± 120.7 to 107.4 ± 128.9 mm3 and low attenuation plaque component from 40.5 ± 54.7 to 43.5 ± 58.9 mm3, with no statistically significant differences between all IR levels and FBP ( P = 0.786 and P ≥ 0.078, respectively). Conclusion IR improved image quality. Total and low attenuation plaque volumes were similar using either IR or FBP.
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Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Algoritmos , Doença da Artéria Coronariana/patologia , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/patologiaRESUMO
Robust, sensitive, and rapid molecular detection tools are essential prerequisites for disease diagnosis and epidemiological control. However, the current mainstream tests necessitate expensive equipment and specialized operators, impeding the advancement of molecular diagnostics. The CRISPR-Cas system is an integral component of the bacterial adaptive immune system, wherein Cas proteins recognize PAM sequences by binding to CRISPR RNA, subsequently triggering DNA or RNA cleavage. The discovery of the CRISPR-Cas system has invigorated molecular diagnostics. With further in-depth research on this system, its application in molecular diagnosis is flourishing. In this review, we provide a comprehensive overview of recent research progress on the CRISPR-Cas system, specifically focusing on its application in molecular diagnosis.
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Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Humanos , Patologia Molecular/métodos , Técnicas de Diagnóstico MolecularRESUMO
In the original publication [...].
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The significance of USP11 as a critical regulator in cancer has garnered substantial attention, primarily due to its catalytic activity as a deubiquitinating enzyme. Nonetheless, a thorough evaluation of USP11 across various cancer types in pan-cancer studies remains absent. Our analysis integrates data from a variety of sources, including five immunotherapy cohorts, thirty-three cohorts from The Cancer Genome Atlas (TCGA), and sixteen cohorts from the Gene Expression Omnibus (GEO), two of which involve single-cell transcriptomic data. Our findings indicate that aberrant USP11 expression is predictive of survival outcomes across various cancer types. The highest frequency of genomic alterations was observed in uterine corpus endometrial carcinoma (UCEC), with single-cell transcriptome analysis revealing significantly higher USP11 expression in plasmacytoid dendritic cells and mast cells. Notably, USP11 expression was associated with the infiltration levels of CD8+ T cells and natural killer (NK) activated cells. Additionally, in the skin cutaneous melanoma (SKCM) phs000452 cohort, patients with higher USP11 mRNA levels during immunotherapy experienced a significantly shorter median progression-free survival. USP11 emerges as a promising molecular biomarker with significant potential for predicting patient prognosis and immunoreactivity across various cancer types.
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Lipid aldehydes including isolevuglandins (IsoLGs) and 4-hydroxynonenal modify phosphatidylethanolamine (PE) to form proinflammatory and cytotoxic adducts. Therefore, cells may have evolved mechanisms to degrade and prevent accumulation of these potentially harmful compounds. To test if cells could degrade isolevuglandin-modified phosphatidylethanolamine (IsoLG-PE), we generated IsoLG-PE in human embryonic kidney 293 (HEK293) cells and human umbilical cord endothelial cells and measured its stability over time. We found that IsoLG-PE levels decreased more than 75% after 6 h, suggesting that IsoLG-PE was indeed degraded. Because N-acyl phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) has been described as a key enzyme in the hydrolysis of N-acyl phosphatidylethanoamine (NAPE) and both NAPE and IsoLG-PE have large aliphatic headgroups, we considered the possibility that this enzyme might also hydrolyze IsoLG-PE. We found that knockdown of NAPE-PLD expression using small interfering RNA (siRNA) significantly increased the persistence of IsoLG-PE in HEK293 cells. IsoLG-PE competed with NAPE for hydrolysis by recombinant mouse NAPE-PLD, with the catalytic efficiency (V(max)/K(m)) for hydrolysis of IsoLG-PE being 30% of that for hydrolysis of NAPE. LC-MS/MS analysis confirmed that recombinant NAPE-PLD hydrolyzed IsoLG-PE to IsoLG-ethanolamine. These results demonstrate that NAPE-PLD contributes to the degradation of IsoLG-PE and suggest that a major physiological role of NAPE-PLD may be to degrade aldehyde-modified PE, thereby preventing the accumulation of these harmful compounds.