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Background: Transarterial chemo(embolization) is preferred for treating unresectable hepatocellular carcinoma (uHCC); however, because of emerging immune-targeted therapies, its efficacy is at stake. This systematic review pioneers to evaluate the clinical efficacy and safety of transarterial chemo(embolization) combined with immune-targeted therapy for uHCC patients. Methods: PubMed, Embase, and Cochrane Library were searched for studies comparing immune-targeted therapy with or without transarterial chemo(embolization) until 31 May 2024. The complete response (CR) rate, objective response rate (ORR), and disease control rate (DCR) were considered to be the primary outcomes calculated for the clinical outcomes of transarterial chemo(embolization) combined with immune-targeted therapy, along with progression-free survival (PFS) and overall survival (OS). The incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. Results: Sixteen studies, encompassing 1,789 patients receiving transarterial chemo(embolization) plus immune-targeted therapy and 1,215 patients receiving immune-targeted therapy alone, were considered eligible. The combination of transarterial chemo(embolization) and immune-targeted therapy demonstrated enhanced outcomes in CR (OR = 2.12, 95% CI = 1.35-3.31), ORR (OR = 2.78, 95% CI = 2.15-3.61), DCR (OR = 2.46, 95% CI = 1.72-3.52), PFS (HR = 0.59, 95% CI = 0.50-0.70), and OS (HR = 0.51, 95% CI = 0.44-0.59), albeit accompanied by a surge in ALT (OR = 2.17, 95% CI = 1.28-3.68) and AST (OR = 2.28, 95% CI = 1.42-3.65). The advantages of additional transarterial chemo(embolization) to immune-targeted therapy were also verified in subgroups of first-line treatment, intervention techniques, with or without extrahepatic metastasis, Child-Pugh grade A or B, and with or without tumor thrombus. Conclusion: The combination of transarterial chemo(embolization) and immune-targeted therapy seems to bolster local control and long-term efficacy in uHCC, albeit at the expense of hepatic complications. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier 474669.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/efectos adversos , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Terapia Combinada , Resultado del Tratamiento , Terapia Molecular DirigidaRESUMEN
Immobilized microbial technology has recently emerged as a prominent research focus for the remediation of heavy metal pollution because of its superior treatment efficiency, ease of operation, environmental friendliness, and cost-effectiveness. This study investigated the adsorption characteristics and mechanisms of Cd2+ solutions by Lactobacillus plantarum adsorbed immobilized on distiller's grains biochar (XIM) and Lactobacillus plantarum-encapsulated immobilized on distiller's grains biochar (BIM). The findings reveal that the maximum adsorption capacity and efficiency were achieved at a pH solution of 6.0. Specifically, at an adsorption equilibrium concentration of cadmium at 60 mg/L, XIM and BIM had adsorption capacities of 8.40 ± 0.30 mg/g and 12.23 ± 0.05 mg/g, respectively. BIM demonstrated noticeably greater adsorption capacities than XIM at various cadmium solution concentrations. A combination of isothermal adsorption modeling, kinetic modeling, scanning electron microscopy-energy dispersive X-ray spectroscopy, X-ray diffractometer (XRD), and Fourier-transform infrared spectroscopy (FTIR) analyses showed that cadmium adsorption by XIM primarily involved physical adsorption and pore retention. In contrast, the adsorption mechanism of BIM was mainly attributed to the formation of Cd(CN)2 crystals.
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BACKGROUND: Multidisciplinary collaborative care has been widely recommended as an effective strategy for managing diabetes; however, the cardiovascular risk factors of patients with diabetes are often inadequately managed in primary care settings. This study aimed to assess the effect of multidisciplinary collaboration on cardiovascular risk factors among patients with diabetes in primary care settings. METHODS: Five databases (i.e., Medline, Embase, CINAHL, SCOPUS and CENTRAL) were systematically searched to retrieve randomised controlled trials. Studies were eligible for inclusion if the interventions included a multidisciplinary team with professionals from at least three health disciplines and focused on patients with diabetes in primary care settings. A random-effects model was used to calculate the pooled effects. RESULTS: In total, 19 studies comprising 6538 patients were included in the meta-analysis. The results showed that compared with usual care, multidisciplinary collaborative care significantly reduced cardiovascular risk factors, including mean systolic blood pressure (-3.27â¯mm Hg, 95â¯% confidence interval [CI]: -4.72 to -1.82, p < 0.01), diastolic blood pressure (-1.4â¯mm Hg, 95â¯% CI: -2.32 to -0.47, p < 0.01), glycated haemoglobin (-0.42â¯%, 95â¯% CI: -0.59 to -0.25, p < 0.01), low-density lipoprotein (-0.16â¯mmol/L, 95â¯% CI: -0.26 to -0.06, p < 0.01) and high-density lipoprotein (0.06â¯mmol/L, 95â¯% CI: 0.00-0.12, p < 0.05). The subgroup analysis showed multidisciplinary collaboration was more effective in reducing cardiovascular risk factors when it comprised team members from a number of different disciplines, combined pharmacological and non-pharmacological components, included both face-to-face and remote interactions and was implemented in high-income countries. CONCLUSION: Multidisciplinary collaborative care is associated with reduced cardiovascular risk factors among patients with diabetes in primary care. Further studies need to be conducted to determine the optimal team composition.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Factores de Riesgo de Enfermedad Cardiaca , Grupo de Atención al Paciente , Atención Primaria de Salud , Humanos , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Diabetes Mellitus/terapia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Resultado del Tratamiento , Anciano , Prestación Integrada de Atención de Salud , Medición de Riesgo , Adulto , Conducta Cooperativa , Comunicación Interdisciplinaria , Factores de RiesgoRESUMEN
BACKGROUND: This study evaluates primary care practices' engagement with various features of a quality improvement (QI) intervention for patients with coronary heart disease (CHD) in four Australian states. METHODS: Twenty-seven practices participated in the QI intervention from November 2019 -November 2020. A combination of surveys, semi-structured interviews and other materials within the QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease (QUEL) study were used in the process evaluation. Data were summarised using descriptive statistical and thematic analyses for 26 practices. RESULTS: Sixty-four practice team members and Primary Health Networks staff provided feedback, and nine of the 63 participants participated in the interviews. Seventy-eight percent (40/54) were either general practitioners or practice managers. Although 69% of the practices self-reported improvement in their management of heart disease, engagement with the intervention varied. Forty-two percent (11/26) of the practices attended five or more learning workshops, 69% (18/26) used Plan-Do-Study-Act cycles, and the median (Interquartile intervals) visits per practice to the online SharePoint site were 170 (146-252) visits. Qualitative data identified learning workshops and monthly feedback reports as the key features of the intervention. CONCLUSION: Practice engagement in a multi-featured data-driven QI intervention was common, with learning workshops and monthly feedback reports identified as the most useful features. A better understanding of these features will help influence future implementation of similar interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134.
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Enfermedad Coronaria , Atención Primaria de Salud , Mejoramiento de la Calidad , Femenino , Humanos , Masculino , Australia , Enfermedad Coronaria/terapia , Manejo de la EnfermedadRESUMEN
Microbial nitrogen fixation presents a viable alternative to chemical fertilizers, yet the limited colonization and specificity of naturally occurring nitrogen-fixing microorganisms present significant challenges to their widespread application. In this study, we identified a nitrogen fixation gene cluster (VNnif) in Vibrio natriegens (VN) and tested its nitrogenase activity through the acetylene reduction assay. We investigated the potential utilization of nitrogenase by incorporating the nitrogenase gene cluster from VN into plant growth-promoting rhizosphere bacteria Pseudomonas protegens CHA0 and enhancing its activity to 48.16 nmol C2H2/mg/h through promoter replacement and cluster rearrangement. The engineered strain CHA0-PVNnif was found to positively impact the growth of Arabidopsis thaliana col-0 and Triticum aestivum L. (wheat). This study expanded the role of plant growth-promoting rhizobacteria (PGPR) and provided a research foundation for enhancing nitrogenase activity.
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Proteínas Bacterianas , Fijación del Nitrógeno , Nitrogenasa , Vibrio , Arabidopsis/genética , Arabidopsis/microbiología , Arabidopsis/enzimología , Arabidopsis/crecimiento & desarrollo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Familia de Multigenes , Nitrogenasa/metabolismo , Nitrogenasa/genética , Rizosfera , Triticum/microbiología , Triticum/genética , Triticum/crecimiento & desarrollo , Triticum/metabolismo , Vibrio/genética , Vibrio/crecimiento & desarrollo , Vibrio/enzimologíaRESUMEN
Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.
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Passive acoustic monitors analyze sound signals emitted by seafloor gas bubbles to measure leakage rates. In scenarios with low-flux gas leaks, individual bubble sounds are typically non-overlapping. Measurement methods for these bubble streams aim to estimate the frequency peak of each bubble sound, which correlates with the bubble's size. However, the presence of ocean ambient noise poses challenges to accurately estimating these frequency peaks, thereby affecting the measurement of gas leakage rates in shallow sea environments using passive acoustic monitors. To address this issue, we propose a robust measurement method that includes a noise-robust sparse time-frequency representation algorithm and an adaptive thresholding approach for detecting bubble frequencies. We demonstrate the effectiveness of our proposed method using experimental data augmented with ocean ambient noise and ship-transit noise recorded from a bay area.
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Messenger RNA (mRNA) vaccines represent a landmark in vaccinology, especially with their success in COVID-19 vaccines, which have shown great promise for future vaccine development and disease prevention. As a platform technology, synthetic mRNA can be produced with high fidelity using in vitro transcription (IVT). Magnesium plays a vital role in the IVT process, facilitating the phosphodiester bond formation between adjacent nucleotides and ensuring accurate transcription to produce high-quality mRNA. The development of the IVT process has prompted key inquiries about in-process characterization of magnesium ion (Mg++) consumption, relating to the RNA polymerase (RNAP) activation, fed-batch mode production yield, and mRNA quality. Hence, it becomes crucial to monitor the free Mg++ concentration throughout the IVT process. However, no free Mg++ analysis method has been reported for complex IVT reactions. Here we report a robust capillary zone electrophoresis (CZE) method with indirect UV detection. The assay allows accurate quantitation of free Mg++ for the complex IVT reaction where it is essential to preserve IVT samples in their native-like state during analysis to avoid dissociation of bound Mg complexes. By applying this CZE method, the relationships between free Mg++ concentration, the mRNA yield, and dsRNA impurity level were investigated. Such mechanistic understanding facilitates informed decisions regarding the quantity and timing of feeding starting materials to increase the yield. Furthermore, this approach can serve as a platform method for analyzing the free Mg++ in complex sample matrices where preserving the native-like state of Mg++ binding is key for accurate quantitation.
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Electroforesis Capilar , Magnesio , ARN Mensajero , Transcripción Genética , Electroforesis Capilar/métodos , Magnesio/análisis , ARN Mensajero/genética , ARN Mensajero/análisis , SARS-CoV-2/genética , HumanosRESUMEN
Chronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.
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Microbioma Gastrointestinal , Melatonina , Probióticos , Enfermedad Pulmonar Obstructiva Crónica , Animales , Ratones , Antioxidantes , Pediococcus pentosaceus , Melatonina/farmacología , TriptófanoRESUMEN
BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for almost 18 million deaths annually. People with CVDs have a five times greater chance of suffering a recurrent cardiovascular event than people without known CVDs. Although drug interventions have been shown to be cost-effective in reducing the risk of recurrent cardiovascular events, adherence to medication remains suboptimal. As a scalable and cost-effective approach, mobile phone text messaging presents an opportunity to convey health information, deliver electronic reminders, and encourage behaviour change. However, it is uncertain whether text messaging can improve medication adherence and clinical outcomes. This is an update of a Cochrane review published in 2017. OBJECTIVES: To evaluate the benefits and harms of mobile phone text messaging for improving medication adherence in people with CVDs compared to usual care. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registers. We also checked the reference lists of all primary included studies and relevant systematic reviews and meta-analyses. The date of the latest search was 30 August 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim of improving adherence to medication for the secondary prevention of cardiovascular events. The comparator was usual care. We excluded cluster-RCTs and quasi-RCTs. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were medication adherence, fatal cardiovascular events, non-fatal cardiovascular events, and combined CVD event. Secondary outcomes were low-density lipoprotein cholesterol for the effect of statins, blood pressure for antihypertensive drugs, heart rate for the effect of beta-blockers, urinary 11-dehydrothromboxane B2 for the antiplatelet effects of aspirin, adverse effects, and patient-reported experience. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 18 RCTs involving a total of 8136 participants with CVDs. We identified 11 new studies in the review update and seven studies in the previous version of the review. Participants had various CVDs including acute coronary syndrome, coronary heart disease, stroke, myocardial infarction, and angina. All studies were conducted in middle- and high-income countries, with no studies conducted in low-income countries. The mean age of participants was 53 to 64 years. Participants were recruited from hospitals or cardiac rehabilitation facilities. Follow-up ranged from one to 12 months. There was variation in the characteristics of text messages amongst studies (e.g. delivery method, frequency, theoretical grounding, content used, personalisation, and directionality). The content of text messages varied across studies, but generally included medication reminders and healthy lifestyle information such as diet, physical activity, and weight loss. Text messages offered advice, motivation, social support, and health education to promote behaviour changes and regular medication-taking. We assessed risk of bias for all studies as high, as all studies had at least one domain at unclear or high risk of bias. Medication adherence Due to different evaluation score systems and inconsistent definitions applied for the measurement of medication adherence, we did not conduct meta-analysis for medication adherence. Ten out of 18 studies showed a beneficial effect of mobile phone text messaging for medication adherence compared to usual care, whereas the other eight studies showed either a reduction or no difference in medication adherence with text messaging compared to usual care. Overall, the evidence is very uncertain about the effects of mobile phone text messaging for medication adherence when compared to usual care. Fatal cardiovascular events Text messaging may have little to no effect on fatal cardiovascular events compared to usual care (odds ratio 0.83, 95% confidence interval (CI) 0.47 to 1.45; 4 studies, 1654 participants; low-certainty evidence). Non-fatal cardiovascular events We found very low-certainty evidence that text messaging may have little to no effect on non-fatal cardiovascular events. Two studies reported non-fatal cardiovascular events, neither of which found evidence of a difference between groups. Combined CVD events We found very low-certainty evidence that text messaging may have little to no effect on combined CVD events. Only one study reported combined CVD events, and did not find evidence of a difference between groups. Low-density lipoprotein cholesterol Text messaging may have little to no effect on low-density lipoprotein cholesterol compared to usual care (mean difference (MD) -1.79 mg/dL, 95% CI -4.71 to 1.12; 8 studies, 4983 participants; very low-certainty evidence). Blood pressure Text messaging may have little to no effect on systolic blood pressure (MD -0.93 mmHg, 95% CI -3.55 to 1.69; 8 studies, 5173 participants; very low-certainty evidence) and diastolic blood pressure (MD -1.00 mmHg, 95% CI -2.49 to 0.50; 5 studies, 3137 participants; very low-certainty evidence) when compared to usual care. Heart rate Text messaging may have little to no effect on heart rate compared to usual care (MD -0.46 beats per minute, 95% CI -1.74 to 0.82; 4 studies, 2946 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Due to limited evidence, we are uncertain if text messaging reduces medication adherence, fatal and non-fatal cardiovascular events, and combined cardiovascular events in people with cardiovascular diseases when compared to usual care. Furthermore, text messaging may result in little or no effect on low-density lipoprotein cholesterol, blood pressure, and heart rate compared to usual care. The included studies were of low methodological quality, and no studies assessed the effects of text messaging in low-income countries or beyond the 12-month follow-up. Long-term and high-quality randomised trials are needed, particularly in low-income countries.
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Enfermedades Cardiovasculares , Teléfono Celular , Cumplimiento de la Medicación , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención Secundaria , Envío de Mensajes de Texto , Humanos , Prevención Secundaria/métodos , Enfermedades Cardiovasculares/prevención & control , Sistemas Recordatorios , Sesgo , Persona de Mediana Edad , Accidente Cerebrovascular/prevención & control , Infarto del Miocardio/prevención & controlRESUMEN
OBJECTIVE: Minimally invasive atlantoaxial surgery offers the benefits of reduced trauma and quicker recovery. Previous studies have focused on feasibility and technical aspects, but the lack of comprehensive safety information has limited its availability and widespread use. This study proposes to define the feasibility and range of surgical safety using the intersection of the greater occipital nerve and the inferior border of the inferior cephalic oblique as a reference point. METHODS: Dissection was performed on 10 fresh cadavers to define the anatomical reference point as the intersection of the greater occipital nerve and the inferior border of the inferior cephalic oblique muscle. The study aimed to analyze the safety range of minimally invasive atlantoaxial fusion surgery by measuring the distance between the anatomical reference point and the transverse foramen of the axis, the distance between the anatomical reference point and the superior border of the posterior arch of the atlas, and the distance between the anatomical reference point and the spinal canal. Measurements were compared using Student's t test. RESULTS: The point where the occipital greater nerve intersects with the inferior border of the inferior cephalic oblique muscle was defined as the anatomical marker for minimally invasive posterior atlantoaxial surgery. The distance between this anatomical marker and the transverse foramen of the axis was measured to be 9.32 ± 2.04 mm. Additionally, the distance to the superior border of the posterior arch of the atlas was found to be 21.29 ± 1.93 mm, and the distance to the spinal canal was measured to be 11.53 ± 2.18 mm. These measurement results can aid surgeons in protecting the vertebral artery and dura mater during minimally invasive posterior atlantoaxial surgery. CONCLUSIONS: The intersection of the greater occipital nerve with the inferior border of the inferior cephalic oblique muscle is a safe and reliable anatomical landmark in minimally invasive posterior atlantoaxial surgery.
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Vértebras Cervicales , Procedimientos Quirúrgicos Mínimamente Invasivos , Humanos , Vértebras Cervicales/cirugía , Arteria Vertebral , CadáverRESUMEN
Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.
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Hiperuricemia , Lacticaseibacillus rhamnosus , Humanos , Hiperuricemia/terapia , Nucleósidos , Lactobacillus , Prolina , PurinasRESUMEN
BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Mental health is considered an important risk factor affecting the treatment of cardiovascular disease. However, little is known about the use of secondary prevention strategies for CVD in patients with both cancer and CVD. This study aimed to compare the utilisation of primary care chronic disease management plans, mental health care and guideline-indicated cardioprotective medications among CVD patients with and without cancer. METHODS: Retrospective cross-sectional study utilising clinical data of patients with CVD from 50 Australian primary care practices. Outcomes included the use of chronic disease management plans, mental health care, guideline-indicated cardioprotective medications and influenza vaccination. Logistic regression, accounting for demographic and clinical covariates and clustering effects by practices, was used to compare the two groups. RESULTS: Of the 15,040 patients with CVD, 1,486 patients (9.9%) concurrently had cancer. Patients with cancer, compared to those without, were older (77.6 vs 71.8 years, p<0.001), more likely to drink alcohol (62.6% vs 55.7%, p<0.001), have lower systolic (130.3±17.8 vs 132.5±21.1 mmHg, p<0.001) and diastolic (72.2±11 vs 75.3±34 mmHg, p<0.001) blood pressure. Although suboptimal for both groups, patients with cancer were significantly more likely to have general practice management plans (GPMPs) (51.4% vs 43.2%, p<0.001), coordination of team care arrangements (TCAs) (46.2% vs 37.0%, p<0.001), have a review of either GPMP or TCA (42.8% vs 34.7%, p<0.001), have a mental health treatment consultation (15.4% vs 10.5%, p=0.004) and be prescribed blood pressure-lowering medications (70.1% vs 66.0%, p=0.002). However, there were no statistical differences in the prescription of lipid-lowering or antiplatelet medications. After adjustments for covariates and multiple testing, patients with cancer did not show a difference in GPMPs, TCAs, and a review of either, but were more likely to receive mental health treatment consultations than those without cancer (odds ratio 1.76; 95% confidence interval 1.42-2.19). CONCLUSIONS: Less than half of patients with CVD had a GPMP, TCA or review of either. Although those patients with cancer were more likely to receive these interventions, still around half the patients did not. Medicare-funded GPMPs, TCAs and a review of either GPMP or TCA were underutilised, and future studies should seek to identify ways of improving access to these services.
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Enfermedades Cardiovasculares , Neoplasias , Atención Primaria de Salud , Humanos , Estudios Transversales , Masculino , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Femenino , Estudios Retrospectivos , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Anciano , Enfermedad Crónica , Australia/epidemiología , Servicios de Salud Mental/estadística & datos numéricos , Cardiotónicos/uso terapéutico , Persona de Mediana Edad , Manejo de la EnfermedadRESUMEN
Human cerebellum encompasses numerous neurons, exhibiting a distinct developmental paradigm from cerebrum. Here we conducted scRNA-seq, scATAC-seq and spatial transcriptomic analyses of fetal samples from gestational week (GW) 13 to 18 to explore the emergence of cellular diversity and developmental programs in the developing human cerebellum. We identified transitory granule cell progenitors that are conserved across species. Special patterns in both granule cells and Purkinje cells were dissected multidimensionally. Species-specific gene expression patterns of cerebellar lobes were characterized and we found that PARM1 exhibited inconsistent distribution in human and mouse granule cells. A novel cluster of potential neuroepithelium at the rhombic lip was identified. We also resolved various subtypes of Purkinje cells and unipolar brush cells and revealed gene regulatory networks controlling their diversification. Therefore, our study offers a valuable multi-omics landscape of human fetal cerebellum and advances our understanding of development and spatial organization of human cerebellum.
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BACKGROUND: To analyze and compare the biomechanical characteristics of the new combined cervical fusion device (NCCFD) and the traditional cage-plate construct (CPC) to ascertain its effectiveness in anterior cervical discectomy and fusion (ACDF) using finite element analysis. METHODS: A finite element model of the cervical spine, inclusive of the occipital bone was created and validated. In the ACDF model, either CPC or NCCFD was implanted at the C2-C3 segment of the model. A pure moment of 1.0 Nm combined with a follower load of 50 N was directed onto the superior surfaces of the occipital bone to determine flexion, extension, lateral bending (left and right), and axial rotation (left and right). The range of motion (ROM), stress distribution at the bone-implant interface, and facet joint forces were investigated and compared between CPC and NCCFD systems. RESULT: The results showed that the ROMs of the fused levels in both models were nearly zero, and the motions of the unfused segments were similar. In addition, the maximum displacement exhibited nearly identical values for both models. The maximum stress of NCCFD screws in lateral bending and rotational conditions is significantly higher than that of the CPC, while the NCCFD model's maximum stress remains within an acceptable range. Comparing the maximum fusion stress, it was found that the CPC experiences much lower fusion stress in anterior flexion and extension than the NCCFD, with no significant difference between the two in lateral bending and rotational states. Stress on the cage was mainly concentrated on both sides of the wings. Comparing the maximum IDP in the CPC and NCCFD, it was observed that maximum stresses rise in extension and lateral bending for both models. Lastly, stress distributions of the facet joints were generally similar across the two devices. CONCLUSION: NCCFD not only provides the same level of biomechanical stability as CPC but also avoids postoperative complications associated with uneven force damage to the implant. The device offers a novel surgical alternative for ACDF in C2-C3 level.
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Discectomía , Fusión Vertebral , Análisis de Elementos Finitos , Fenómenos Biomecánicos , Discectomía/métodos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Placas Óseas , Fusión Vertebral/métodos , Rango del Movimiento ArticularRESUMEN
AIM: Increased cardiovascular events are common in cancer survivors and contribute to an emerging cardio-oncology patient group requiring secondary prevention strategies including cardiac rehabilitation (CR). This study aimed to compare characteristics and outcomes for patients participating in CR with and without an existing cancer diagnosis. METHOD: Observational cohort study including consecutive patients enrolled in a single-centre outpatient CR program in Western Sydney between 2018-2022. Clinical history, demographics and CR outcome data were collected as part of standard care at program enrolment and completion. Patients with and without a cancer diagnosis were compared at enrolment and outcomes were analysed in both groups. RESULTS: A total of 1,792 patients enrolled in CR, 191 (11%) had a documented history of cancer; prostate (18%), skin (12%), colon (9%) and breast (8%) malignancies were most prevalent. The most common treatments were surgical resection (80%) and chemotherapy or radiotherapy (37%). Cardio-oncology patients were older (68.8±10.6 vs 59.8±13.7yrs, p<0.001), more likely female (33% vs 21%, p<0.001), born in Australia (46% vs 35%, p=0.004), non-partnered (34% vs 25%, p=0.002) and had a prior history of hypertension (65% vs 56%, p=0.010) or stroke (8% vs 5%, p=0.045). After adjusting for age and sex, the overall cohort improved their mean peak exercise capacity and waist circumference after CR, however there were no differences between groups. There were also no between-group differences for adherence and completion of CR program or any other cardiovascular risk factors. Sub-analyses revealed a clinically meaningful improvement in waist circumference for cancer patients with a history of radiation therapy and a blunted peak exercise capacity adaptation for those with a history of chemotherapy treatment. CONCLUSIONS: Despite differences in demographic and clinical characteristics of CR patients with and without cancer, all patients showed significant and clinically relevant improvements in peak exercise capacity and waist circumference after CR. Results also highlighted potential associations between specific cancer treatments and changes in fitness outcomes, which warrants further evaluation.
Asunto(s)
Rehabilitación Cardiaca , Neoplasias , Humanos , Masculino , Femenino , Rehabilitación Cardiaca/métodos , Neoplasias/rehabilitación , Neoplasias/epidemiología , Neoplasias/complicaciones , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Supervivientes de Cáncer/estadística & datos numéricos , Estudios Retrospectivos , Enfermedades Cardiovasculares/epidemiología , Australia/epidemiología , Nueva Gales del Sur/epidemiologíaRESUMEN
BACKGROUND: Nursing professional identity (NPI) is essential for nurses to develop their nursing profession. It reflects the competencies consistent with the professional practices of nurses and contributes to them providing better healthcare and public health. The formation process of NPI started with undergraduate nursing education and continued throughout the nursing career. OBJECTIVE: To explore nursing students' perceptions of facilitators and barriers to the formation of NPI during their study. METHODS: A 4-year longitudinal, qualitative research design with yearly semi-structured interviews undertaken from 2019 to 2022. The reflexive thematic analysis methodology was applied for the data analysis. RESULTS: Ninety-three nursing students were recruited, joining a group or individual interview. The four-year nursing baccalaureate program revealed a dynamic formation process of NPI: "Outsider of nursing", "Entering the nursing courses", "Building nursing competence", and "Thinking and acting like a nurse". A total of 12 themes were identified to present the barriers and facilitators to the NPI formation at different stages. Specifically, the six barriers include conflict between their ideals and reality, sociocultural stereotypes about nursing, the negative impact of COVID-19, the pre-internship concerns, struggling to meet expectations, and potential danger and discrimination in the healthcare settings. The enablers were: self-motivation and inner belief towards the nursing profession, the power of role models, the improvement of nursing capacity, well integration into the healthcare professional teams, understanding of the clinical environment, and recognition and encouragement from others. CONCLUSIONS: The formation of nursing students' NPI is an ever-changing process, with various intrinsic and extrinsic influences during their four-year study. Nursing educators are suggested to prepare and develop students' professional comportment in their theoretical and clinical practice to develop their professional identity as a nurse.
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Bachillerato en Enfermería , Estudiantes de Enfermería , Humanos , Bachillerato en Enfermería/métodos , Investigación Cualitativa , Atención a la Salud , Identificación SocialRESUMEN
Aim: To investigate the relationship between potential abnormal epigenetic modification and immune cell infiltration in patients with cervical carcinoma. Materials & methods: RNA expression profiles from The Cancer Genome Atlas database were used to explore the relationship between key biomarkers and tumor-infiltrating immune cells and for clinical specimen validation. Results: Two nomogram models were developed, one with specific ceRNA and the other based on biological markers of related tumor-infiltrating immune cells. Moreover, a key biomarker (RIPOR2), which was significantly relevant to CD8 T cells. Conclusion: RIPOR2 and CD8 T cells play a crucial role in the development and progression of cervical carcinoma, suggesting their potential as markers for guiding future therapeutic strategies.
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Carcinoma , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , Pronóstico , ARN Endógeno Competitivo , NomogramasRESUMEN
BACKGROUND: The Plan-Do-Study-Act (PDSA) cycle is an iterative framework that has been gaining traction in primary care for quality improvement. However, its implementation remains understudied. This study evaluated the completion, achievement of goal, content quality, and enablers and barriers associated with completion of high-quality PDSA cycles in cardiovascular disease management in general practices. METHODS: This study analysed data from intervention practices of the QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living people with coronary heart disease (QUEL) study. Content quality of cycles was assessed using a scoring system created based on established criteria of ideal PDSA cycles in the healthcare context. Practice-level factors associated with completion and cycles achieving the planned goal were explored through logistic regression models, and with content quality score through linear regression model. Enablers and barriers were assessed using thematic analysis of practices' responses to the PDSA sections. RESULTS: Ninety-seven cycles were reported by 18/26 (69%) practices. Seventy-seven percent of the cycles were completed and 68% achieved the planned goal. Content quality was low, with a median score of 56% (interquartile interval: 44%, 67%). Odds of cycles that were completed and achieved what was planned increased by 3.6- and 9.6-fold, respectively, with more general practitioners (GPs) within practices. Content quality was higher by 15% with more GPs. Lack of interprofessional engagement was a barrier to implementation. CONCLUSIONS: Cycles were well completed, but poor in content quality, with high variability between practices. Human or capital resources and organisational support may be critical for the completion and cycles achieving the planned goals.
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Médicos Generales , Mejoramiento de la Calidad , Humanos , Calidad de la Atención de Salud , Atención a la Salud , Atención Primaria de SaludRESUMEN
Cardiovascular disease due to atherosclerosis is one of the leading causes of death worldwide; however, the underlying mechanism has yet to be defined. The sodium-dependent glucose transporter 2 inhibitor (SGLT2i) empagliflozin is a new type of hypoglycemic drug. Recent studies have shown that empagliflozin not only reduces high glucose levels but also exerts cardiovascular-protective effects and slows the process of atherosclerosis. The purpose of this study was to elucidate the mechanism by which empagliflozin ameliorates atherosclerosis. Male apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat Western diet to establish an atherosclerosis model. The area and size of atherosclerotic lesions in ApoE-/- mice were then assessed by performing hematoxylin-eosin (HE) staining after empagliflozin treatment. Concurrently, oxidized low-density lipoprotein (oxLDL) was used to mimic atherosclerosis in three different types of cells. Then, following empagliflozin treatment of macrophage cells (RAW264.7), human aortic smooth muscle cells (HASMCs), and human umbilical vein endothelial cells (HUVECs), western blotting was applied to measure the levels of autophagy-related proteins and proinflammatory cytokines, and green fluorescent protein (GFP)-light chain 3 (LC3) puncta were detected using confocal microscopy to confirm autophagosome formation. Oil Red O staining was performed to detect the foaming of macrophages and HASMCs, and flow cytometry was used for the cell cycle analysis. 5-ethynyl-2'-deoxyuridine (EdU), cell counting kit-8 (CCK-8), and scratch assays were also performed to examine the proliferation and migration of HASMCs. Empagliflozin suppressed the progression of atherosclerotic lesions in ApoE-/- mice. Empagliflozin also induced autophagy in RAW246.7 cells, HASMCs, and HUVECs via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, and it significantly increased the levels of the Beclin1 protein, the LC3B-II/I ratio, and p-AMPK protein. In addition, empagliflozin decreased the expression of P62 and the protein levels of inflammatory cytokines, and it inhibited the foaming of RAW246.7 cells and HASMCs, as well as the expression of inflammatory factors by inducing autophagy. Empagliflozin activated autophagy through the AMPK signaling pathway to delay the progression of atherosclerosis. Furthermore, the results of flow cytometry, EdU assays, CCK-8 cell viability assays, and scratch assays indicated that empagliflozin blocked HASMCs proliferation and migration. Empagliflozin activates autophagy through the AMPK signaling pathway to delay the evolution of atherosclerosis, indicating that it may represent a new and effective drug for the clinical treatment of atherosclerosis.