Multifunctional antimicrobial biometallohydrogels based on amino acid coordinated self-assembly

There is a real need for new antibiotics against self‐evolving bacteria. One option is to use biofriendly broad‐spectrum and mechanically tunable antimicrobial hydrogels that can combat multidrug‐resistant microbes. Whilst appealing, there are currently limited options. Herein, broad‐spectrum antimicrobial biometallohydrogels based on the self‐assembly and local mineralization of Ag+‐coordinated Fmoc‐amino acids are reported. Such biometallohydrogels have the advantages of localized delivery and sustained release, reduced drug dosage and toxicity yet improved bioavailability, prolonged drug effect, and tunable mechanical strength. Furthermore, they can directly interact with the cell walls and membrane, resulting in the detachment of the plasma membrane and leakage of the cytoplasm. This leads to cell death, triggering a significant antibacterial effect against both Gram‐negative (Escherichia coli) and Gram‐positive (Staphylococcus aureus) bacteria in cells and mice. This study paves the way for developing a multifunctional integration platform based on simple biomolecules coordinated self‐assembly toward a broad range of biomedical applications

Dual Immunotherapy in advanced or Metastatic Non-Small Cell Lung Cancer: a Network Meta-Analysis

OBJECTIVES: Recently, there has been extensive research on dual immunotherapy for advanced or metastatic non-small cell lung cancer (NSCLC), yet a comprehensive evaluation is lacking. This study aimed to rank the available treatment options and assess the efficacy and safety of dual immunotherapy regimens through the implementation of a Bayesian network meta-analysis (NMA). MATERIALS AND METHODS: A thorough search was conducted to recognize eligible randomized controlled trials (RCTs) on March 20, 2023. Overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were evaluated to identify the efficacy and safety of dual immunotherapy regimens. The surface under the cumulative ranking curve (SUCRA) and RESULTS: Eleven clinical trials involving six different regimens were included in this study. The combination of anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) antibodies with anti-T-cell immunoglobulin and ITIM domain (TIGIT) antibodies emerged as the most promising regimen for improving OS and PFS, followed by anti-PD-1/PD-L1 + anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) + chemotherapy treatment and anti-PD-1/PD-L1 + anti-CTLA-4 treatment. The forest plots demonstrated that these three regimens were all superior to chemotherapy. The above results were observed in both unselected treatment line and first-line settings. The least likely to be associated with TRAEs and grade ≥3 TRAEs were respectively anti-CTLA-4 treatment and anti-PD-1/PD-L1 + anti-TIGIT treatment, with anti-PD-1/PD-L1 + anti-CTLA-4 + chemotherapy treatment to be the worst. CONCLUSIONS: This NMA validated the promising efficacy and safety of dual immunotherapy in advanced or metastatic NSCLC. Among them, anti-PD-1/PD-L1 + anti-TIGIT regimen emerges as a highly potential therapeutic approach. Ongoing research efforts should focus on improving treatment regimens, identifying biomarkers, and managing TRAEs to optimize the patient benefits of dual immunotherapy

Loss of \u3ci\u3eActa2\u3c/i\u3e in Cardiac Fibroblasts Does Not Prevent the Myofibroblast Differentiation or Affect the Cardiac Repair After Myocardial Infarction

In response to myocardial infarction (MI), quiescent cardiac fibroblasts differentiate into myofibroblasts mediating tissue repair. One of the most widely accepted markers of myofibroblast differentiation is the expression of Acta2 which encodes smooth muscle alpha-actin (SMαA) that is assembled into stress fibers. However, the requirement of Acta2/SMαA in the myofibroblast differentiation of cardiac fibroblasts and its role in post-MI cardiac repair remained unknown. To answer these questions, we generated a tamoxifen-inducible cardiac fibroblast-specific Acta2 knockout mouse line. Surprisingly, mice that lacked Acta2 in cardiac fibroblasts had a normal post-MI survival rate. Moreover, Acta2 deletion did not affect the function or histology of infarcted hearts. No difference was detected in the proliferation, migration, or contractility between WT and Acta2-null cardiac myofibroblasts. Acta2-null cardiac myofibroblasts had a normal total filamentous actin level and total actin level. Acta2 deletion caused a significant compensatory increase in the transcription level of non-Acta2 actin isoforms, especially Actg2 and Acta1. Moreover, in myofibroblasts, the transcription levels of cytoplasmic actin isoforms were significantly higher than those of muscle actin isoforms. In addition, we found that myocardin-related transcription factor-A is critical for myofibroblast differentiation but is not required for the compensatory effects of non-Acta2 isoforms. In conclusion, the Acta2 deletion does not prevent the myofibroblast differentiation of cardiac fibroblasts or affect the post-MI cardiac repair, and the increased expression and stress fiber formation of non-SMαA actin isoforms and the functional redundancy between actin isoforms are able to compensate for the loss of Acta2 in cardiac myofibroblasts

3D acoustic wave sparsely activated localization microscopy with phase change contrast agents

Objective The aim of this study is to demonstrate 3-dimensional (3D) acoustic wave sparsely activated localization microscopy (AWSALM) of microvascular flow in vivo using phase change contrast agents (PCCAs). Materials and Methods Three-dimensional AWSALM using acoustically activable PCCAs was evaluated on a crossed tube microflow phantom, the kidney of New Zealand White rabbits, and the brain of C57BL/6J mice through intact skull. A mixture of C3F8 and C4F10 low-boiling-point fluorocarbon gas was used to generate PCCAs with an appropriate activation pressure. A multiplexed 8-MHz matrix array connected to a 256-channel ultrasound research platform was used for transmitting activation and imaging ultrasound pulses and recording echoes. The in vitro and in vivo echo data were subsequently beamformed and processed using a set of customized algorithms for generating 3D super-resolution ultrasound images through localizing and tracking activated contrast agents. Results With 3D AWSALM, the acoustic activation of PCCAs can be controlled both spatially and temporally, enabling contrast on demand and capable of revealing 3D microvascular connectivity. The spatial resolution of the 3D AWSALM images measured using Fourier shell correlation is 64 μm, presenting a 9-time improvement compared with the point spread function and 1.5 times compared with half the wavelength. Compared with the microbubble-based approach, more signals were localized in the microvasculature at similar concentrations while retaining sparsity and longer tracks in larger vessels. Transcranial imaging was demonstrated as a proof of principle of PCCA activation in the mouse brain with 3D AWSALM. Conclusions Three-dimensional AWSALM generates volumetric ultrasound super-resolution microvascular images in vivo with spatiotemporal selectivity and enhanced microvascular penetration

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

A CONCEPTUAL MODEL OF ADOLESCENT`SATTACHMENT AND RESILIENCE TO DAILY STRESSORS: IMPLICATIONS FOR COVID-19 NORMALIZATION PERIOD AND AFTERWARDS

Resilience is a concept that has captured intensified attention since COVID-19. Over decades, resilience research has been done across diverse domains focused on stress responses to adversity. For adolescents who are undergoing a “storm and stress” phase in transition to adulthood, everyday stresses should be managed timely and properly so that resilience is in place when needed. Within the frameworks of attachment and resilience, the author conducted this narrative review proposing a conceptual model to discuss adolescents’ attachment and resilience to daily stressors during and following the pandemic. Theoretical and empirical evidence showed building relationships and regulating emotions are instrumental in nurturing adolescents’ resilience. This review may have implications for the prevention and intervention of adolescents’ mental health during and after COVID-19, which may aid in the transition to adulthood and later life well-being

An Examination of Chinese Adolescents’ Resilience and Their Perceptions of Parental and Peer Attachment

Resilience is a concept that has captured more scholarly attention under the ongoing COVID-19 pandemic, which challenges the resilience of individuals and countries against unforeseen global catastrophes. More literature documented resilience to various negative situations such as COVID-19 pandemic, earthquakes, maltreatment, and severe illness. Less attention was accorded to resilience to everyday stressors. However, normative daily stresses should be managed timely and properly so that resilience is in place when needed. Within the framework of attachment theory and resilience theory, this study aimed to investigate the impact of adolescents’ perceptions of attachments to parents and peers on their resilience to everyday stressful experiences. Through a cross-sectional quantitative approach, the present study examined a Chinese adolescent sample (N = 2,378; ages 10-19) from elementary, junior high, and high school students in Chinese urban and rural areas. The correlation analysis revealed significant associations between parent attachment and resilience and between peer attachment and resilience. The hierarchical linear regression analysis showed maternal, paternal, and peer attachment were robust predictors of adolescent resilience, with peer attachment presenting the highest predictive strength among the three. The results of independent sample t-tests and MANOVA analyses revealed different levels of gender and age differences between adolescents’ attachment and resilience. Despite some limitations, this study contributes to literature by providing a large sample size (N = 2,378), integrating attachment and resilience theory, and empirically evidencing resilience as an ordinary construct reflected in everyday experiences. Moreover, empirical data were not only reported on the results of three subscales of mother, father and peer, but also provided on three specific dimensions (trust, communication and alienation). The results from this sample have implications for parents and adolescents, schools and teachers, and policy, practice, and research

Multifunctional Plasmonic Grating Based on the Phase Modulation of Excitation Light

Multifunctional optical devices are desirable at all times due to their features of flexibility and high efficiency. Based on the principle that the phase of excitation light can be transferred to the generated surface plasmon polaritons (SPPs), a plasmonic grating with three functions is proposed and numerically demonstrated. The Cherenkov SPPs wake or nondiffracting SPPs Bessel beam or focusing SPPs field can be correspondingly excited for the excitation light, which is modulated by a linear gradient phase or a symmetrical phase or a spherical phase, respectively. Moreover, the features of these functions such as the propagation direction of SPPs wake, the size and direction of the SPPs Bessel beam, and the position of SPPs focus can be dynamically manipulated. In consideration of the fact that no extra fabrication is required to obtain the different SPPs fields, the proposed approach can effectively reduce the cost in practical applications