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Kien Xuan Nguyen,1,&ast; Tien Viet Tran,2 Thuan Duc Nghiem,3 Tuan Ngoc Tran,1 Thang Ba Ta,4 Ba Van Nguyen,5 Tuan Dinh Le,6,&ast; Son Tien Nguyen,6 Kien Trung Nguyen,7 Hoa Trung Dinh,8 Dinh Cong Pho,9 Toan Nguyen Duy,10,&ast; Pham Quoc Toan11 1Department of Military Medical Command and Organization, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 2Department of Infectious Diseases, Military Hospital 103, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 3Department of Otolaryngology, Military Hospital 103, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 4Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 5Department of Oncology, Military Hospital 103, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 6Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 7Center of Hematology and Blood Transfusion, Military Hospital 103, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 8Department of Requested Treatment, National Hospital of Endocrinology, Hanoi, Vietnam; 9Department of Military Science, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 10Cardiovascular Center, Military Hospital 103, Vietnam Medical Military University, Hanoi, 10000, Vietnam; 11Department of Nephrology, Military Hospital 103, Vietnam Military Medical University, Hanoi, 10000, Vietnam&ast;These authors contributed equally to this workCorrespondence: Pham Quoc Toan, Department of Nephrology, Military Hospital 103, Vietnam Military Medical University, 160 Phung Hung Street, Phuc La Ward, Ha Dong District, Hanoi, Vietnam, Email toannephro@gmail.comIntroduction: Metacognition plays an essential role in competency-based medical education. Metacognitive skills consist of knowledge and regulation metacognition. This study was conducted to investigate the metacognition of undergraduate students and its correlation with students’ academic performance.Methods: The metacognitive skills inventory comprised 52 binary-scale items administered to 202 Vietnam Military Medical University medical students. The entire semester and clinical results were used to measure their academic performance.Results: Medical students’ total metacognitive awareness score was high (median 0.8). The median metacognitive knowledge score was significantly lower than the metacognitive regulation score (0.7 vs 0.8, respectively). The participants with a total metacognition score ≥ 0.8 had significantly higher academic results (full semester exam results of 7.4 and clinical exam of 7.5). The group of participants in the military, having sports habits and usually searching academic documents in English, had a higher proportion of total metacognitive awareness score ≥ 0.8 than the group without these above characteristics (with the percentages of 53.3%, 59%, and 64.3%, respectively; p < 0.05). The number of books read by participants with a total metacognitive awareness score ≥ 0.8 was significantly higher than those with a total metacognitive awareness score < 0.8 (3.5 compared to 2.4 books).Conclusion: Metacognitive awareness of Vietnam Military Medical University medical students was likely to be high. A high score of metacognitive awareness could predict high academic performance. Being a military student, playing sports, reading books, and searching English documents were predictors of better metacognitive awareness.Keywords: metacognition, medical student, metacognitive awareness, academic performance

Duck hepatitis A virus (DHAV) causes an acute and highly contagious disease in young ducklings worldwide. Despite the widespread use of the DHAV vaccine, many outbreaks still occur in Vietnam. In this study, we determined the full-length genome sequence of two DHAV isolates (NC and NT) obtained from infected ducks in 2009 and 2013, and compared them with the attenuated DHAV-1 vaccine strain (namely, VXXT) currently used in Vietnam. The NC and NT strains belong to the virulent DHAV-3 genotype, and their genomes consist of 7791 and 7790 nucleotides (nt), respectively. Both genomes contain one large open reading frame (ORF) of 6756 nt, encoding a polyprotein of 2251 amino acids and possess a typical picornavirus genome organization. The majority of predicted C-terminal cleavage sites in the polyprotein were Q/S or Q/G. Phylogenetic analysis of the nucleotide sequence of the full ORF revealed that all virulent Vietnamese strains are closely related to Chinese DHAV-3 strains. Noticeably, the virulent Vietnamese DHAV-3 strains had relatively low nucleotide identity with the DHAV-1 vaccine strain (73.5%). The study showed that an antigenicity-matched DHAV-3 vaccine is urgently required for use in Vietnam.

Objective: Type 2 diabetes is characterized by diminished pancreatic β-cell mass and function. Insulin signaling within the β-cells has been shown to play a critical role in maintaining the essential function of the β-cells. Under basal conditions, enhanced insulin-PI3K signaling via deletion of phosphatase with tensin homology (PTEN), a negative regulator of this pathway, leads to increased β-cell mass and function. In this study, we investigated the effects of prolonged β-cell-specific PTEN deletion in models of type 2 diabetes.Research Design and Methods: Two models of type 2 diabetes were employed: a high-fat diet (HFD) model and a db/db model that harbors a global leptin-signaling defect. A Cre-loxP system driven by the rat insulin promoter (RIP) was employed to obtain mice with β-cell-specific PTEN deletion (RIPcre(+) Pten(fl/fl)).Results: PTEN expression in islets was upregulated in both models of type 2 diabetes. RIPcre(+) Pten(fl/fl) mice were completely protected against diabetes in both models of type 2 diabetes. The islets of RIPcre(+) Pten(fl/fl) mice already exhibited increased β-cell mass under basal conditions, and there was no further increase under diabetic conditions. Their β-cell function and islet PI3K signaling remained intact, in contrast to HFD-fed wild-type and db/db islets that exhibited diminished β-cell function and attenuated PI3K signaling. These protective effects in β-cells occurred in the absence of compromised response to DNA-damaging stimuli.Conclusions: PTEN exerts a critical negative effect on both β-cell mass and function. Thus PTEN inhibition in β-cells can be a novel therapeutic intervention to prevent the decline of β-cell mass and function in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Presents an abstract of 'Acute Stressor Exposure Both Suppresses Acquired Immunity and Potentiates Innate Immunity,' by M. Fleshner, K.T. Nguyen, C.S. Cotter, L.R. Watkins and S.F. Maier, published in the 1998 issue of 'The American Journal of Physiology.'

The emergence of bacteria that are resistant to antibiotics is on track to become a major global health crisis. Therefore, there is an urgent need for new treatment options. Here, we studied the implementation of tissue-nanotransfection (TNT) to treat Staphylococcus aureus-infected wounds by delivering gene cargos that boost the levels of naturally produced antimicrobial peptides. The Cathelicidin Antimicrobial Peptide gene (CAMP), which produces the antimicrobial peptide LL-37, was used as model gene cargo. In vitro evaluation showed successful transfection and an increase in the transcription and translation of CAMP-coding plasmid in mouse primary epithelial cells. Moreover, we found that the extracellular vesicles (EVs) derived from the transfected cells (in vitro and in vivo) carried significantly higher concentrations of CAMP transcripts and LL-37 peptide compared to control EVs, possibly mediating the trafficking of the antimicrobial contents to other neighboring cells. The TNT platform was then used in vivo on an excisional wound model in mice to nanotransfect the CAMP-coding plasmid on the edge of infected wounds. After 4 days of daily treatment, we observed a significant decrease in the bacterial load in the CAMP-treated group compared to the sham group. Moreover, histological analysis and bacterial load quantification also revealed that TNT of CAMP on S. aureus-infected wounds was effective in treating biofilm progression by reducing the bacterial load. Lastly, we observed a significant increase in macrophage recruitment to the infected tissue, a robust increase in vascularization, as well as and an increased expression of IL10 and Fli1. Our results demonstrate that TNT-based delivery of gene cargos coding for antimicrobial compounds to the wound is a promising approach for combating biofilm infections in wounds., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

The entire transcribed sequences (from the 5' terminus of 18S to the 3' terminus of 28S rRNA genes) of the ribosomal transcription units (rTU*) of five Asian Paragonimus species were obtained and characterized. The rTU* length was 7661 bp for P. heterotremus (LC strain, Vietnam), 7422 bp for P. iloktsuenensis (Amami strain, Japan), 6932 bp for P. skrjabini miyazakii (OkuST1 strain, Japan), 7422 bp for P. ohirai (Kino strain, Japan), and three strains of P. westermani: 8616 bp (Megha strain, India), 7292 bp (Bogil strain, South Korea), and 7052 bp (QT2 strain, Vietnam) without intergenic spacer region (IGS). All seven Asian Paragonimus strains' genetic characteristics were described, including the length of individual genes/regions, repeat polymorphism, base composition, and skewness. To investigate the superfamilial relationships in the Xiphidiata, with a focus on the Troglotrematoidea and its associated superfamilies, we used the PhyML software package to create three comprehensive maximum-likelihood phylogenies. The datasets used were 83 concatenated 28S + 18S, 83 single complete 18S, and 157 single, partial 28S rDNA sequences, respectively, from entire rTUs and/or accessible ribosomal sequences of the same species from the suborders Xiphidiata, Echinostomata, and Haplosplanchnata, with a Schistosoma sequence as an outgroup. Three phylogenetic trees revealed that Echinostomata and Haplosplanchnata are monophyletic, while Xiphidiata is polyphyletic and contains the monophyletic Troglotrematoidea. The concatenated 18S + 28S and single 18S phylogenies revealed well-bootstrap supported seven superfamilies (Troglotrematoidea, Haploporoidea, Gorgoderoidea, Brachycladioidea, Microphalloidea, Plagiorchioidea, and Opecoeloidea) that are monophyletic in the Xiphidiata. The Haploporoidea was a basal superfamily nested close to the Gorgoderoidea and Troglotrematoidea and was not supported as a distinct suborder Haploporata. Six of seven xiphidiatan superfamilies were monophyletic in the partial 28S phylogeny, with the exception of Opecoeloidea, which was separated into two different subclades: Opecoelidae and Stenakridae/Zdzitowieckitrematidae. The monophyletic Haploporoidea/Haploporata was separated from the Gorgoderoidea associates and placed in a marginal group in Xiphidiata. There were two notable clusters in the Paragonimidae: mixed-Paragonimus, which included a fairly compact group of P. heterotremus strains, and P. westermani/siamensis, which was divided into geographical/country strain groups. In conclusion, combined ribosomal rDNA sequences were more effective than single rDNA markers in resolving interfamilial and familial relationships. The ribosomal datasets presented here will be useful for taxonomic reassessment, as well as evolutionary and population genetics research in the Troglotrematoidea and other superfamilies in the Xiphidiata and the class Trematoda., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Idiopathic pulmonary fibrosis (IPF) is a lethal disorder characterized by relentless progression of lung fibrosis that causes respiratory failure and early death. Currently, no curative treatments are available, and existing therapies include a limited selection of antifibrotic agents that only slow disease progression. The development of novel therapeutics has been hindered by a limited understanding of the disease's etiology and pathogenesis. A significant challenge in developing new treatments and understanding IPF is the lack of in vitro models that accurately replicate crucial microenvironments. In response, three-dimensional (3D) in vitro models have emerged as powerful tools for replicating organ-level microenvironments seen in vivo. This review summarizes the state of the art in advanced 3D lung models that mimic many physiological and pathological processes observed in IPF. We begin with a brief overview of conventional models, such as 2D cell cultures and animal models, and then explore more advanced 3D models, focusing on lung-on-a-chip systems. We discuss the current challenges and future research opportunities in this field, aiming to advance the understanding of the disease and the development of novel devices to assess the effectiveness of new IPF treatments.

Background: The continuous increase in drug-resistant strains, the lack of novel antibiotics, and the fewer options available to combat antibiotic-resistant infections in pediatrics pose significant challenges to the eradication of Helicobacter pylori (H. pylori) in children. This study evaluated the efficacy of first-line therapy with bismuth quadruple therapy in H. pylori-positive pediatric patients with peptic ulcers., Materials and Methods: 136 patients (aged between 8 and 17 years) diagnosed with active peptic ulcers with H. pylori infection were enrolled in this study. Patients with H. pylori strain sensitive to tetracycline and metronidazole were assigned to bismuth quadruple therapy, including a proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole. Antibiotic resistance of H. pylori was analyzed by the Epsilometer test. Treatment efficacy was evaluated at 12 weeks based on H. pylori eradication and peptic ulcer healing rates. H. pylori infection status was evaluated by a 13 C-urea breath test., Results: Most isolates showed extremely high rates of resistance to commonly prescribed antibiotics used for children, including clarithromycin (97.0%) and amoxicillin (84.6%), while the low rate of resistance to levofloxacin (16.2%). The overall success rate of eradication therapy in the intention-to-treat and the per-protocol group were 86.0% and 89.3%, respectively. Peptic ulcer healing rates for total patients at 6 weeks and 12 weeks were 75.0% and 97.7%, respectively. There were no entail unpleasant adverse events, and peptic ulcer symptoms decreased steadily over time in all cases., Conclusions: The bismuth quadruple therapy with a 2-week PPI pretreatment and followed by prolonged PPI was highly successful in eradicating H. pylori infection and healing ulcers in pediatric patients with active peptic ulcer. This might be preferable as a first-line empiric treatment regimen for H. pylori-positive pediatric patients with peptic ulcers, especially in populations with high rates of resistance to amoxicillin and clarithromycin., (© 2024 John Wiley & Sons Ltd.)

Astrocytes play many essential roles in the central nervous system (CNS) and are altered significantly in disease. These reactive astrocytes contribute to neuroinflammation and disease progression in many pathologies, including glioblastoma (GB), an aggressive form of brain cancer. Current in vitro platforms do not allow for accurate modeling of reactive astrocytes. In this study, we sought to engineer a simple bioengineered hydrogel platform that would support the growth of primary human astrocytes and allow for accurate analysis of various reactive states. After validating this platform using morphological analysis and qPCR, we then used the platform to begin investigating how astrocytes respond to GB derived extracellular vesicles (EVs) and soluble factors (SF). These studies reveal that EVs and SFs induce distinct astrocytic states. In future studies, this platform can be used to study how astrocytes transform the tumor microenvironment in GB and other diseases of the CNS. STATEMENT OF SIGNIFICANCE: Recent work has shown that astrocytes help maintain brain homeostasis and may contribute to disease progression in diseases such as glioblastoma (GB), a deadly primary brain cancer. In vitro models allow researchers to study basic mechanisms of astrocyte biology in healthy and diseased conditions, however current in vitro systems do not accurately mimic the native brain microenvironment. In this study, we show that our hydrogel system supports primary human astrocyte culture with an accurate phenotype and allows us to study how astrocytes change in response to a variety of inflammatory signals in GB. This platform could be used further investigate astrocyte behavior and possible therapeutics that target reactive astrocytes in GB and other brain diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Individuals with malocclusion require an orthodontic diagnosis and treatment plan based on the severity of their condition. Assessing and monitoring changes in periodontal structures before, during, and after orthodontic procedures is crucial, and intraoral ultrasound (US) imaging has been shown a promising diagnostic tool in imaging periodontium. However, accurately delineating and analyzing periodontal structures in US videos is a challenging task for clinicians, as it is time-consuming and subject to interpretation errors. This paper introduces DetSegDiff, an edge-enhanced diffusion-based network developed to simultaneously detect the cementoenamel junction (CEJ) and segment alveolar bone structure in intraoral US videos. An edge feature encoder is designed to enhance edge and texture information for precise delineation of periodontal structures. Additionally, we employed the spatial squeeze-attention module (SSAM) to extract more representative features to perform both detection and segmentation tasks at global and local levels. This study used 169 videos from 17 orthodontic patients for training purposes and was subsequently tested on 41 videos from 4 additional patients. The proposed method achieved a mean distance difference of 0.17 ± 0.19 mm for the CEJ and an average Dice score of 90.1% for alveolar bone structure. As there is a lack of multi-task benchmark networks, thorough experiments were undertaken to assess and benchmark the proposed method against state-of-the-art (SOTA) detection and segmentation individual networks. The experimental results demonstrated that DetSegDiff outperformed SOTA approaches, confirming the feasibility of using automated diagnostic systems for orthodontists., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

TP53 is the most commonly mutated gene in cancer, but it remains recalcitrant to clinically meaningful therapeutic reactivation. We present here the discovery and characterization of a small molecule chemical inducer of proximity that activates mutant p53. We named this compound TR anscriptional A ctivator of p 53 ( TRAP-1 ) due to its ability to engage mutant p53 and BRD4 in a ternary complex, which potently activates mutant p53 and triggers robust p53 target gene transcription. Treatment of p53 Y220C expressing pancreatic cell lines with TRAP-1 results in rapid upregulation of p21 and other p53 target genes and inhibits the growth of p53 Y220C -expressing cell lines. Negative control compounds that are unable to form a ternary complex do not have these effects, demonstrating the necessity of chemically induced proximity for the observed pharmacology. This approach to activating mutant p53 highlights how chemically induced proximity can be used to restore the functions of tumor suppressor proteins that have been inactivated by mutation in cancer.

The silver nanoparticles-sodium alginate-chitosan (AgNPs-Alg-Chi) nanocomposite film is a compelling material with demonstrated antibacterial efficacy against various pure bacterial strains. However, its potential cytotoxicity at elevated Ag doses warrants investigation. There is a notable dearth of studies assessing its antibacterial effectiveness against clinically relevant bacterial strains, notably Cutibacterium acnes . This study aims to assess the antibacterial efficacy of the low-dose AgNPs-Alg-Chi nanocomposite films on both pure bacterial strains and strains isolated from clinical samples obtained from 65 acne patients. The films were synthesized using green methods, incorporating kumquat ( Citrus japonica ) extract as a silver ion-reducing agent. The material characterization methods include UV-Vis and FTIR spectroscopies, SEM-EDS, XPS, cell culture, and MTT assay. We successfully fabricated the AgNPs-Alg-Chi nanocomposite films with a low-loading dose of Ag NPs (≤11 μg mL -1 , and 37.8 ± 11.5 nm in size). The AgNPs-Alg-Chi nanocomposite film demonstrated comparable antibacterial efficacy to the AgNPs-Chi solution, with MIC values ranging from 3.67 to 5.50 μg mL -1 ( p > 0.05) across all strains. Importantly, the AgNPs-Alg-Chi films demonstrated excellent biocompatibility with human keratinocytes (HaCaT cells), maintaining cell viability above 70%. The present AgNPs-Alg-Chi nanocomposite films synthesized by a green approach demonstrated potent antibacterial activity, making them promising for further development into suitable products for human use., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cancer-associated fibroblasts (CAFs) are abundant stromal cells residing in a tumor microenvironment (TME) which are associated with the progression of tumor. Herein, we developed novel CAFs-targeting polymeric nanoparticles encapsulating a synthetic 8- O -methylfusarubin (OMF) compound (OMF@NPs-anti-FAP). Anti-FAP/fibroblast activation protein antibody was employed as a CAFs-targeting ligand. The physicochemical properties of the synthesized nanomaterials were firstly investigated with various techniques. The cytocompatibility of polymeric nanoparticles (NPs) was elicited through cell viability of CAFs and human breast epithelial cells, MCF-10A. Additionally, the anti-FAP-conjugated NPs displayed different degrees of cellular internalization regarding the FAP expression level on the CAFs' surface. However, CAFs exposed to NPs containing OMF demonstrated significant cell death which were associated with the apoptotic pathway as confirmed by caspase-3/7 activity. Upon OMF@NPs-anti-FAP treatment, an enhanced toxicity was clearly observed in 3D spheroid models. High FAP-expressed PC-B-132CAFs demonstrated a high percentage of cell death compared to other cells with a low level of FAP expression analyzed by flow cytometry (e.g. MCF-10A, HDFa, and PC-B-142CAFs). This result emphasized the importance of anti-FAP antibody as a targeting ligand. These findings suggest that the fabricated nanosystem of OMF-loaded polymeric NPs with CAFs' high specificity holds a potential NP-based platform for improvement in breast cancer treatment., Competing Interests: All the authors read the manuscript before submission and declared that they have no conflict of interest., (© 2024 The Authors.)

Rheumatic heart disease leads to significant cardiovascular morbidity and mortality globally. This case presentation emphasizes the importance of considering patients' unique socioeconomic factors, such as crowded living conditions and multigenerational housing, to implement culturally sensitive approaches to prevention, diagnosis, secondary antibiotic prophylaxis, and management., Competing Interests: Dr Jonathan Soverow has received institutional research support from Eli Lilly and Novartis. All other authors have reported that they have no relationships relevant to the contents of this article to disclose.

Background: Hospital medicine patient distribution models (PDM) assign patients to inpatient services on hospital admission. Models balance tradeoffs including patient handoffs, physician wellness, subspecialty care, and other factors to ensure optimal outcomes; however, equity is rarely considered. Handoffs during inpatient care can result in medical error and worse patient outcomes. This study evaluates the impact of a PDM that prioritizes use of specialty care services and an overflow service (OS) during high census on racial inequities in handoff frequency., Methods: A single-center retrospective cohort study of inpatient encounters on hospital medicine services from July 2017 to December 2019 was conducted. The primary exposures included being discharged by a general medicine service (GMS) or cared for by an OS. The primary outcome was handoffs per day of stay, analyzed by multivariable regression adjusted for age, gender, race, ethnicity, insurance, discharge from GMS, and care from OS., Results: A total of 4165 inpatient hospitalizations with the majority of their stay on a hospital medicine service were reviewed. Patients discharged by GMS (78.2% vs. 58.1%, p < .001) and cared for by OS (78.7% vs. 67.0%, p < .001) were more likely to identify as Black. Multivariable analysis showed a handoff risk ratio of 1.53 (p < .001) for OS patients and 1.06 (p = .01) if discharged from GMS, but race alone did not significantly affect risk of handoffs., Conclusion: The PDM prioritization drove increased handoffs disproportionately for Black patients. Multivariable analysis showed that race alone did not contribute to increased handoffs suggesting the creation of a systemic bias in patient care., (© 2024. W. Montague Cobb-NMA Health Institute.)

Mineralization of scaffolds is essential for alveolar ridge preservation and bone tissue engineering, enhancing the mechanical strength and bioactivity of scaffolds, and promoting better integration with natural bone tissue. While the in situ mineralization method using concentrated SBF solutions is promising, there is limited comprehensive research on its effects. In this study, it is demonstrate that soaking gelatin/alginate scaffolds (GAS) in fivefold concentrated SBF significantly reduces the mineralization time to 3-7 days but also leads to considerable degradation and loss of the scaffold's original microstructure. The ratio of gelatin to alginate is optimized to improve the properties of GAS. The optimized GAS sample, when soaked in concentrated SBF to form GAS/HAp, exhibited hydroxyapatite (HAp) crystal formation starting from day 3, with mature hexagonal crystals forming by day 7. However, this process also caused significant decomposition and deformation of the scaffold's pore structure. Additionally, the biocompatibility of GAS and GAS/HAp is evaluated through in vitro, in ovo, haemolysis, and anti-ROS assays. The findings highlight the impact of SBF 5× on the mineralization of GAS, laying the groundwork for further research in alveolar ridge preservation and bone tissue engineering., (© 2024 Wiley‐VCH GmbH.)

Stimuli-responsive peptides, particularly pH-responsive variants, hold significant promise in biomedical and technological applications by leveraging the broad pH spectrum inherent to biological environments. However, the limited number of natural pH-responsive amino acids within biologically relevant pH ranges presents challenges for designing rational pH-responsive peptide assemblies. In our study, we introduce a novel approach by incorporating a library of non-natural amino acids featuring chemically diverse tertiary amine side chains. Hydrophobic and ionic properties of these non-natural amino acids facilitate their incorporation into the assembly domain when uncharged, and electrostatic repulsion promotes disassembly under lower pH conditions. Furthermore, we observed a direct relationship between the number of substitutions and the hydrophobicity of these amino acids, influencing their pH-responsive properties and enabling rational design based on desired transitional pH ranges. The structure-activity relationship of these pH-responsive peptides was evaluated by assessing their antimicrobial properties, as their antimicrobial activity is triggered by the disassembly of peptides to release active monomers. This approach not only enhances the specificity and controllability of pH responsiveness but also broadens the scope of peptide materials in biomedical and technological applications., (© 2024 Wiley-VCH GmbH.)

Background: Afatinib, a second-generation epidermal growth factor receptor(EGFR) tyrosine kinase, has proven effective for non-small-cell lung cancer (NSCLC) patients with EGFR mutations through randomized controlled trials and real-world studies. Elderly patients exhibit unique characteristics in terms of physical condition and comorbidities, leading to differences in clinical practice for selecting the initial dosage and making dose adjustments compared to younger patients. This study aims to evaluate the effectiveness and adverse effects of first-line Afatinib treatment in elderly patients with NSCLC harboring EGFR mutations in Vietnam in a real-world context., Methods: We conducted a retrospective analysis of 135 patients, aged 65 years and older, across nine cancer centers in Vietnam. These patients, who harbored drug-sensitive EGFR mutations (excluding de novo T790M), received first-line Afatinib treatment between April 2018 and June 2022. The primary endpoints, time to treatment failure (TTF), and overall survival (OS) were assessed using the Kaplan-Meier method, and comparisons were conducted using the log-rank test. Secondary endpoints included the overall response rate (ORR) according to RECIST 1.1 and adverse effects as classified by CTCAE 4.0., Results: The median age was 71.2 years (SD ± 5.3). Comorbidities included cardiovascular disease (20.7%), diabetes (5.2%), chronic obstructive pulmonary disease (2.2%), and hepatitis B (0.7%). Common mutations constituted 71.9% of cases, with uncommon mutations representing 28.1%. Brain metastases were observed in 24.4% of patients. Initial treatment doses were 40 mg for 35.6% of patients and 30 mg for 62.2%. With a median follow-up of 34.3 months, the median TTF was 16.3 months (95% CI: 15.4-19.5), and the median OS was 32.9 months (95% CI: 28.9-37.5). Factors associated with decreased OS included poor performance status, current smoking, and the presence of uncommon mutations. The ORR was 77.8%, with a complete response of 11.1% and a disease control rate of 94.1%. The most common toxicities were dermatologic and mucosal, including diarrhea (55.6%), rash (48.9%), and stomatitis (40.7%), predominantly in grades 1 and 2. Initiating treatment at doses below 40 mg significantly reduced most toxicities compared to the 40 mg dose. The presence of brain metastases did not significantly affect ORR, TTF, or OS. Starting treatment at doses below 40 mg significantly lowered the response rate but did not impact TTF or OS., Conclusion: First-line treatment with Afatinib in elderly patients with NSCLC and EGFR mutations demonstrates significant efficacy and manageable toxicity in a Vietnamese multicenter real-life setting. The effectiveness of Afatinib was confirmed, with known and well-controlled adverse effects, supporting its use in this patient population.

A common problem in confocal microscopy is the decrease in intensity of excitation light and emission signal from fluorophores as they travel through 3D specimens, resulting in decreased signal detected as a function of depth. Here, we report a visualization program compatible with widely used fluorophores in cell biology to facilitate image interpretation of differential protein disposition in 3D specimens. Glioblastoma cell clusters were fluorescently labeled for mitochondrial complex I (COXI), P2X7 receptor (P2X7R), β-Actin, Ki-67, and DAPI. Each cell cluster was imaged using a laser scanning confocal microscope. We observed up to ∼70% loss in fluorescence signal across the depth in Z-stacks. This progressive underrepresentation of fluorescence intensity as the focal plane deepens hinders an accurate representation of signal location within a 3D structure. To address these challenges, we developed ProDiVis: a program that adjusts apparent fluorescent signals by normalizing one fluorescent signal to a reference signal at each focal plane. ProDiVis serves as a free and accessible, unbiased visualization tool to use in conjunction with fluorescence microscopy images and imaging software., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nguyen, Sathler, Estevez, Logan and Franco.)

We present a protocol to generate highly multiplexed spatial data at cellular and subcellular resolutions using iterative indirect immunofluorescence imaging (4i). We describe streamlined steps for using 4i across fixed cultured cells, formalin-fixed paraffin-embedded (FFPE) tissue sections, and metaphase chromosome spreads. We detail procedures for sample preparation, antibody and DNA staining, immunofluorescence imaging, antibody elution, and image processing. This protocol is adapted for high-throughput analysis of fixed cultured cells and addresses sample-specific challenges such as intrinsic tissue autofluorescence and chromosome fragility. For complete details on the use and execution of this protocol for fixed cultured cells, please refer to Comandante-Lou et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Carpaine, a major alkaloid in papaya leaves, has considerable cardiovascular benefits alongside its notable effects on muscle relaxation when utilized in medicine. In this study, the coupling of acid-base extraction and flotation was developed to completely remove the use of toxic solvents. This method entails the extraction of carpaine from Carica papaya L. leaves using hot water extraction alongside ultrasound-assisted extraction followed by the condensation of the species using surfactant-assisted flotation. The acid-base extraction was applied to alter the solubility of carpaine as desired at different stages of the process. The results showed that the carpaine extraction yield using all the treatments in conjunction was significantly higher compared to the control samples in which the acid-base extraction or flotation was not applied. The TLC and GC-FID results suggested that the bubbles introduced during the flotation were highly specific toward their interactions with carpaine in its hydrophobic complex form. The quantity of carpaine extracted using our method, in comparison to the amount of carpaine obtained using a different method from a previous study that utilized ethanolic extraction, exhibited a 2.32-fold greater extraction yield. This work demonstrates the importance of flexible utilization of both surface and bulk chemistry in achieving an improved solution for a technical problem., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Three species of the Rutaceae family, including Acronychia pedunculata, Euodia lepta, and Severinia monophylla have been used in traditional medicine. However, the comparison of the chemical composition, anti-cancer, and anti-inflammatory effects of the leaf essential oils of these species have not been investigated yet. A total of 38 compounds were identified via gas chromatography-mass spectrometry, comprising 96.5-99.8 % of the total composition. Both A. pedunculata and E. lepta essential oils exhibited strong inhibitory effects against cancer cells (IC 50 : 59.04-97.52 μg/mL) while that of S. monophylla showed a lower anti-cancer effect (IC 50 >100 μg/mL). Among three essential oils, only the E. lepta leaf oil demonstrated a high anti-inflammatory effect on LPS-stimulated macrophages (IC 50 =6.47±0.65 μg/mL), while the others showed a moderate anti-inflammatory effect (IC 50 >50 μg/mL). Molecular docking studies also suggested the binding potential of the key compounds from three essential oils against inducible nitric oxide synthase and cyclooxygenase-2, two proteins associated with inflammatory response, with the negative energies ranging from -41.0 to -71.9 kcal/mol. The present findings suggest the leaf essential oils from these species as potential medicines for treatment of cancer or inflammation associated diseases, especially the ones from A. pedunculata and E. lepta oils., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Tumors develop in an oxidative environment characterized by peroxynitrite production and downstream protein tyrosine (Y) nitration. We showed that tyrosine nitration supports schwannoma cell proliferation and regulates cell metabolism in the inheritable tumor disorder NF2-related Schwannomatosis (NF2-SWN). Here, we identified the chaperone Heat shock protein 90 (Hsp90) as the first nitrated protein that acts as a metabolic switch to promote schwannoma cell proliferation. Doubling the endogenous levels of nitrated Hsp90 in schwannoma cells or supplementing nitrated Hsp90 into normal Schwann cells increased their proliferation. Metabolically, nitration on either Y33 or Y56 conferred Hsp90 distinct functions; nitration at Y33 (Hsp90 NY33 ) down-regulated mitochondrial oxidative phosphorylation, while nitration at Y56 (Hsp90 NY56 ) increased glycolysis by activating the purinergic receptor P2X7 in both schwannoma and normal Schwann cells. Hsp90 NY33 and Hsp90 NY56 showed differential subcellular and spatial distribution corresponding with their metabolic and proliferative functions in schwannoma three-dimensional cell culture models. Collectively, these results underscore the role of tyrosine nitration as a post-translational modification regulating critical cellular processes. Nitrated proteins, particularly nitrated Hsp90, emerge as a novel category of tumor-directed therapeutic targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The colorectal cancer (CRC) screening uptake rate is substantially lower in ethnic minority populations than in the general population. Racial and ethnic minority individuals experience more barriers in obtaining a screening test for CRC when compared with the non-Hispanic White population., Objective: To examine the effectiveness of community health worker-led interventions in improving the CRC screening uptake rate in racial and ethnic minority populations., Methods: Five databases, EMBASE, CINAHL, MEDLINE, Scopus, and PubMed, were systematically searched, and reference lists of the identified articles were manually searched for relevant articles in May 2022. Only randomized controlled trials were included., Results: A total of 10 randomized controlled trials conducted in the United States were included in this review. The findings of the meta-analysis showed that CRC screening uptake was enhanced in participants receiving community health worker-led interventions compared with those receiving no intervention (odds ratio, 2.25; 95% confidence interval, 1.48-3.44; P < .001). The subgroup analysis by diverse racial and ethnic groups and number of components (single vs multiple) of the community health worker-led interventions showed that multicomponent interventions were more effective in increasing the CRC uptake rate among all racial and ethnic groups regardless of their background., Conclusions: Multicomponent community health worker-led interventions can improve CRC screening uptake in racial and ethnic minority populations., Implications for Practice: The findings of the present review show that multicomponent community health worker-led interventions are shown to be effective to improve the CRC screening uptake targeting other racial and ethnic minority groups in other countries., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The prevalence of chronic pain of service members (SMs) in the U.S. is estimated to be higher (roughly 31-44%) compared to that of civilian population (26%). This higher prevalence is likely due to the high physical demands related combat and training injuries that are not immediately resolved and worsen over time. Mental Health America reports that chronic pain can lead to other mental health conditions such as severe anxiety, depression, bipolar disorder, and post-traumatic stress disorder. Such mental health conditions can negatively affect job performance, reduce readiness for military duties, and often lead to patterns of misuse of opioid after SMs entering civilian life. The primary objective of this narrative review is to present a summarized guideline for the treatment of two types of pain that likely affect SMs, namely nociceptive somatic pain and neuropathic pain. This review focused on a stepwise approach starting with nonopioid interventions prior to opioid therapy. The secondary objective of this review is to elucidate the primary mechanisms of action and pathways associated with these two types of pain., Methods: We followed the Scale for Assessment of Narrative Review Articles when transcribing this narrative review article to enhance the quality and brevity of this review. This Scale has 0.77% an intra-class coefficient of correlation, 95% confidence interval and 0.88 inter-rater reliability. We searched PubMed, Google Scholar, WorldCAT, and the Cochrane Library for the primary and secondary articles that targeted mechanisms of action, pathways, and pharmacological modalities for nociceptive somatic and neuropathic pain that were published from 2011 to 2022. We excluded articles related to pediatric, some specific pain conditions such as cancer-related pain, palliative care, end-of-life care, and articles that were not written in English language. For pharmacologic selection, we adopted the guidelines from the Policy for Implementation of a Comprehensive Policy on Pain Management by the Military Health Care system for the Fiscal Year 2021; the Clinical Practice Guidance for Opioid Therapy for Chronic Pain by the Department of Defense/Veterans Health Administration (2022); the (2021) Implementation of a Comprehensive Policy on Pain Management by the Military Health Care System; and the (2022) Guideline for Prescribing Opioids for Chronic Painby the Centers for Disease Control., Discussion: From the knowledge of the mechanisms of action and pathways, we can be more likely to identify the causative origins of pain. As a result, we can correctly diagnose the type of pain, properly develop an efficient and personalized treatment plan, minimize adverse effects, and optimize clinical outcomes. The guideline, however, does not serve as a substitute for clinical judgment in patient-centered decision-making. Medication choices should be individualized judiciously based on the patient's comorbid conditions, available social and economic resources, and the patient's preferences to balance the benefits and risks associated with various pain medications and to achieve optimal pain relief and improve the patient's quality of life., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)