ABSTRACT
BACKGROUND: China is the hotspot of global freshwater crab diversity, but their wild populations are facing severe pressures associated with anthropogenic factors, necessitating the need to map their taxonomic and genetic diversity and design conservation policies. RESULTS: Herein, we sequenced the mitochondrial genome of a Chinese freshwater crab species Bottapotamon fukienense, and found that it is fragmented into two chromosomes. We confirmed that fragmentation was not limited to a single specimen or population. Chromosome 1 comprised 15,111 base pairs (bp) and there were 26 genes and one pseudogene (pseudo-nad1) encoded on it. Chromosome 2 comprised 8,173 bp and there were 12 genes and two pseudogenes (pseudo-trnL2 and pseudo-rrnL) encoded on it. Combined, they comprise the largest mitogenome (23,284 bp) among the Potamidae. Bottapotamon was the only genus in the Potamidae dataset exhibiting rearrangements of protein-coding genes. Bottapotamon fukienense exhibited average rates of sequence evolution in the dataset and did not differ in selection pressures from the remaining Potamidae. CONCLUSIONS: This is the first experimentally confirmed fragmentation of a mitogenome in crustaceans. While the mitogenome of B. fukienense exhibited multiple signs of elevated mitogenomic architecture evolution rates, including the exceptionally large size, duplicated genes, pseudogenisation, rearrangements of protein-coding genes, and fragmentation, there is no evidence that this is matched by elevated sequence evolutionary rates or changes in selection pressures.
Subject(s)
Genome, Mitochondrial , Animals , Chromosomes/genetics , Phylogeny , Evolution, Molecular , Brachyura/genetics , Brachyura/classification , PseudogenesABSTRACT
Although nanocatalytic medicine has demonstrated its advantages in tumor therapy, the outcomes heavily relie on substrate concentration and the metabolic pathways are still indistinct. We discover that violet phosphorus quantum dots (VPQDs) can catalyze the production of reactive oxygen species (ROS) without requiring external stimuli and the catalytic substrates are confirmed to be oxygen (O2) and hydrogen peroxide (H2O2) through the computational simulation and experiments. Considering the short of O2 and H2O2 at the tumor site, we utilize calcium peroxide (CaO2) to supply catalytic substrates for VPQDs and construct nanoparticles together with them, named VPCaNPs. VPCaNPs can induce oxidative stress in tumor cells, particularly characterized by a significant increase in hydroxyl radicals and superoxide radicals, which cause substantial damage to the structure and function of cells, ultimately leading to cell apoptosis. Intriguingly, O2 provided by CaO2 can degrade VPQDs slowly, and the degradation product, phosphate, as well as CaO2-generated calcium ions, can promote tumor calcification. Antitumor immune activation and less metastasis are also observed in VPCaNPs administrated animals. In conclusion, our study unveils the anti-tumor activity of VPQDs as catalysts for generating cytotoxic ROS and the degradation products can promote tumor calcification, providing a promising strategy for treating tumors.
Subject(s)
Apoptosis , Hydrogen Peroxide , Oxidative Stress , Phosphorus , Quantum Dots , Reactive Oxygen Species , Phosphorus/metabolism , Phosphorus/chemistry , Animals , Humans , Quantum Dots/chemistry , Catalysis , Reactive Oxygen Species/metabolism , Mice , Cell Line, Tumor , Apoptosis/drug effects , Hydrogen Peroxide/metabolism , Oxidative Stress/drug effects , Peroxides/metabolism , Peroxides/chemistry , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Nanoparticles/chemistry , Oxygen/metabolism , Oxygen/chemistry , Calcium Compounds/chemistry , Calcium Compounds/metabolism , Female , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistryABSTRACT
OBJECTIVE: To analyze the isolation rate, prevalence trends, species distribution, and drug sensitivity of non-tuberculous mycobacteria (NTM) in Anhui Province, providing a reference for diagnosis and treatment strategies. METHODS: Specimens from suspected mycobacterial infection patients at Anhui Chest Hospital (including outpatients and inpatients) from January 2021 to December 2023 were cultured. Identified NTM strains were analyzed for species distribution and drug sensitivity. RESULTS: Of 10,519 mycobacteria strains cultured, 1,589 were NTM (15.11%). The top four species were Mycobacterium intracellulare (75.36%), Mycobacterium abscessus (11.78%), Mycobacterium kansasii (7.09%), and Mycobacterium avium (2.85%). NTM strains showed high sensitivity to amikacin and clarithromycin (≥90%) and significant sensitivity to rifabutin, moxifloxacin, and rifampicin (89.03%-79.61%). They exhibited high resistance to imipenem/cilastatin, sulfamethoxazole, minocycline, and doxycycline (≥95%). CONCLUSION: NTM isolation rates in Anhui have remained stable, with the predominant species being M. intracellulare, M. kansasii, M. abscessus, and M. avium. NTM strains are highly sensitive to amikacin, clarithromycin, rifabutin, moxifloxacin, and rifampicin. These findings can guide diagnosis, treatment strategies, and drug selection for NTM disease in Anhui Province.
ABSTRACT
Despite advances in therapies, glioblastoma (GBM) recurrence is almost inevitable due to the aggressive growth behavior of GBM cells and drug resistance. Temozolomide (TMZ) is the preferred drug for GBM chemotherapy, however, development of TMZ resistance is over 50% cases in GBM patients. To investigate the mechanism of TMZ resistance and invasive characteristics of GBM, analysis of combined RNA-seq and ChIP-seq was performed in GBM cells in response to TMZ treatment. We found that the PERK/eIF2α/ATF4 signaling was significantly upregulated in the GBM cells with TMZ treatment, while blockage of ATF4 effectively inhibited cell migration and invasion. SPHK1 expression was transcriptionally upregulated by ATF4 in GBM cells in response to TMZ treatment. Blockage of ATF4-SPHK1 signaling attenuated the cellular and molecular events in terms of invasive characteristics and TMZ resistance. In conclusion, GBM cells acquired chemoresistance in response to TMZ treatment via constant ER stress. ATF4 transcriptionally upregulated SPHK1 expression to promote GBM cell aggression and TMZ resistance. The ATF4-SPHK1 signaling in the regulation of the transcription factors of EMT-related genes could be the underlying mechanism contributing to the invasion ability of GBM cells and TMZ resistance. ATF4-SPHK1-targeted therapy could be a potential strategy against TMZ resistance in GBM patients.
Subject(s)
Cell Movement , Drug Resistance, Neoplasm , Endoplasmic Reticulum Stress , Glioblastoma , Neoplasm Invasiveness , Signal Transduction , Temozolomide , Animals , Humans , Activating Transcription Factor 4/metabolism , Activating Transcription Factor 4/genetics , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/drug therapy , Cell Line, Tumor , Cell Movement/drug effects , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Endoplasmic Reticulum Stress/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/pathology , Glioblastoma/genetics , Glioblastoma/metabolism , Glioblastoma/drug therapy , Mice, Nude , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Phosphotransferases (Alcohol Group Acceptor)/genetics , Signal Transduction/drug effects , Temozolomide/pharmacology , Temozolomide/therapeutic useABSTRACT
Only microstructures are used to improve the sensitivity of iontronic pressure sensors. By modulating the compressive modulus, a breakthrough in the sensitivity of the iontronic pressure sensor is achieved. Furthermore, it allows for programmatic tailoring of sensor performance according to the requirements of different applications. Such a new strategy pushes the sensitivity up to a record-high of 25 548.24 kPa-1 and expands the linear pressure range from 15 to 127 kPa. Additionally, the sensor demonstrates excellent mechanical stability over 10 000 compression-release cycles. Based on this, a well-controlled robotic hand that precisely tracks the pressure behavior inside a balloon to autonomously regulate the gripping angle is developed. This paves the way for the application of iontronic pressure sensors in precise sensing scenarios.
ABSTRACT
INTRODUCTION: Arthroscopic procedures for osteoarthritis (OA), in particular arthroscopic meniscectomy, have poorer long-term clinical outcomes compared to those managed non-operatively. In addition, previous arthroscopy is associated with worse outcomes following subsequent total knee arthroplasty (TKA), however there is limited data on the impact on subsequent unicompartmental knee arthroplasty (UKA) outcomes. The aim of the study is to investigate whether patients who had arthroscopy prior to UKA have differences in survivorship or functional outcomes compared to those with no prior arthroscopy. METHODS: All patients who received either a primary medial or lateral UKA at four large tertiary hospitals were included (n = 2,272). Patient data (age, sex, ethnicity, body mass index (BMI), American Society of Anesthesiologists (ASA) status and surgical data) was recorded following systematic review of all clinical notes and radiographs. Differences between survival curves were analysed using log-rank curves. Differences between categorical data was compared using Fisher's exact or Chi-squared tests, and differences between continuous variables were compared using t-tests. RESULTS: There was no difference between the survival curves for UKA patients with previous arthroscopy compared to those with no previous arthroscopy (10 years: 91% UKA with previous arthroscopy vs. 92% no previous arthroscopy; 15 years: 78% previous arthroscopy vs. 86% no previous arthroscopy; p = 0.50). Oxford Knee Score (OKS) was comparable between patients who had previous arthroscopy and those who had no previous arthroscopy at 6 months (38.8 vs. 39.3, p = 0.45), 5 years (42.0 vs. 40.4, p = 0.11) and 10 years (40.8 vs. 40.2, p = 0.71). DISCUSSION: In this large patient cohort with comprehensive review of clinical data and outcomes, we found that prior arthroscopy did not affect survivorship or functional outcomes of UKA patients.
ABSTRACT
BACKGROUND: Colorectal cancer is the second leading cause of cancer-related deaths among digestive tract malignancies, following gastric cancer. Sleep is of great significance for maintaining human health. The incidence of sleep disorders in patients with cancer is approximately twice that observed in the general population. Lack of sleep can prolong hospital stays, increase the likelihood of infection, and increase mortality rates. Therefore, studying the factors related to sleep quality is significant for improving the quality of life of patients with malignant tumors of the digestive tract. AIM: To investigate the relationships among sleep quality, disease uncertainty, and psychological resilience in patients undergoing chemotherapy for digestive tract malignancies. METHODS: A total of 131 patients with malignant digestive tract tumors who were treated at Hefei BOE Hospital between April 2021 and September 2022 were selected as research participants. Based on their Pittsburgh Sleep Quality Index (PSQI) scores, participants were divided into either the sleep disorder group (PSQI score > 7) or the normal sleep group (PSQI score ≤ 7). The clinical data-together with the Mishel Uncertainty in Illness Scale for Adults (MUIS-A) and Connor-Davidson Resilience Scale (CD-RISC) scores-were compared. RESULTS: In this study, 78 (59.54%) patients with digestive tract malignancies developed sleep disorders after chemotherapy. Sleep disorder incidence was higher in patients with colorectal cancer than in those with gastric and esophageal cancers (P < 0.05). The total MUIS-A score and those for each item in the sleep disorder group were higher than those in the normal sleep group. The total CD-RISC score and those for each item in the sleep disorder group were lower than those in the normal sleep group (P < 0.05). The PSQI scores of patients with malignant digestive tract tumors were positively correlated with the scores for lack of disease information, disease uncertainty, and unpredictability in the MUIS-A and negatively correlated with the scores for tenacity, self-improvement, and optimism in the CD-RISC (P < 0.05). CONCLUSION: Patients undergoing chemotherapy for digestive tract malignancies are prone to sleep problems related to disease uncertainty and psychological resilience. Therefore, interventions can be implemented to improve their sleep quality.
ABSTRACT
Protein binding to bile salts (BSs) reduces cholesterol levels, but the exact mechanism is unclear. In this study, we performed simulated gastrointestinal digestion of egg white protein hydrolysate (EWPHs) and included an unenzyme digestion group (CK) to investigate the changes in BSs binding capacity before and after digestion, as well as the relationship between egg white protein (EWP) structure and BSs binding capacity. In addition, peptidomics and molecular docking were used to clarify EWP's binding mechanism. We found that the BSs binding ability of EWPHs was slightly decreased after digestion, but significantly higher than that of the CK group and the digested CK group (D-CK). Particle size analysis and electrophoresis demonstrated that smaller particles and lower molecular weights exhibited enhanced binding capacity to BSs. Fourier Transform infrared spectroscopy (FTIR) results revealed that a disordered structure favored BS binding ability enhancement. Peptides FVLPM and GGGVW displayed hypocholesterolemic efficacy.
ABSTRACT
Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan-cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan-Meier survival analyses to analyze overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.
Subject(s)
Biomarkers, Tumor , Osteopontin , Osteosarcoma , Humans , Osteosarcoma/immunology , Osteosarcoma/mortality , Osteosarcoma/genetics , Osteosarcoma/metabolism , Osteosarcoma/pathology , Osteopontin/genetics , Osteopontin/metabolism , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Prognosis , Bone Neoplasms/immunology , Bone Neoplasms/metabolism , Bone Neoplasms/mortality , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Cell Line, TumorABSTRACT
Host-less lithium metal anode generally suffers from large volume changes and serious dendrite growth during cycling, which poses challenges for its practical application. Interpenetrating phase composites with continuous architectures offer a solution to enhance mechanical properties of materials. Herein, a robust composite Li anode (LBN) material is fabricated through the metallurgical reaction between Li and hexagonal boron nitride (h-BN) with the formation of interpenetrating LiB/Li3BN2 phases. As LiB fibers are anchored by Li3BN2 granules, the collapse and slippage of LiB fibers are suppressed whilst the mechanical strength and structural stability of LBN are reinforced. By rolling, ultrathin (15 µm), freestanding, and electrochemically stable LBN foil can be obtained. The LBN anode exhibits a high average Coulombic efficiency of 99.69% (1 mA cm-2, 3 mAh cm-2) and a long lifespan of 2500 h (1 mA cm-2, 1 mAh cm-2). Notably, the LiCoO2 (with double-sided load 40 mg cm-2)|LBN pouch cell can operate over 450 cycles with a capacity retention of 90.1%. The exceptional cycling stability of LBN can be ascribed to the interpenetrating reinforcement architectures and synergistic electronic/ionic conductivity of the LiB/Li3BN2 dual-lithiophilic-phases. This work provides a new methodology for thin Li strip processing and reinforced-architecture design, with implications beyond battery applications.
ABSTRACT
The perfect integration of microbubbles for efficient ultrasound imaging and nanocarriers for intelligent tumor-targeting delivery remains a challenge in precise tumor theranostics. Herein, we exquisitely fabricated laser-activated and targeted polymersomes (abbreviated as FIP-NPs) for simultaneously encapsulating the photosensitizer indocyanine green (ICG) and the phase change agent perfluorohexane (PFH). The formulated FIP-NPs were nanosize and effectively accumulated into tumors as observed by ICG fluorescence imaging. When the temperature rose above 56 °C, the encapsulated PFH transformed from liquid to gas and the FIP-NPs underwent balloon-like enlargement without structure destruction. Impressively, the enlarged FIP-NPs fused with adjacent polymersomes to form even larger microparticles. This temperature-responsive "nano-to-micro" transformation and fusion process was clearly demonstrated, and FIP-NPs showed greatly improved ultrasound signals. More importantly, FIP-NPs achieved dramatic antitumor efficacy through ICG-mediated phototherapy. Taken together, the novel polymersomes achieved excellent ultrasound/fluorescence dual imaging-guided tumor phototherapy, providing an optimistic candidate for the application of tumor theranostics.
Subject(s)
Indocyanine Green , Optical Imaging , Phototherapy , Polymers , Indocyanine Green/chemistry , Indocyanine Green/therapeutic use , Animals , Mice , Phototherapy/methods , Humans , Optical Imaging/methods , Polymers/chemistry , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Fluorocarbons/chemistry , Neoplasms/diagnostic imaging , Neoplasms/therapy , Temperature , Ultrasonography/methods , Cell Line, Tumor , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use , Theranostic Nanomedicine/methods , Microbubbles/therapeutic useABSTRACT
BACKGROUND AND AIMS: Young people accessing alcohol and other drug (AOD) treatment experience high rates of treatment disengagement, contributing to poorer outcomes. To improve outcomes, it is important to identify factors associated with treatment retention. This study measured the relationships between client characteristics, treatment characteristics, clinical severity measures and completion of treatment among young people. DESIGN, SETTING AND PARTICIPANTS: This study was a retrospective analysis of routinely collected data set in residential- and community-based AOD services in New South Wales, Australia. Routinely collected data from the Network of Alcohol and Other Drug Agencies' (NADA) database were used. Included individuals were aged 10-24 years and accessed treatment between 2012 and 2023 (n = 17 474). MEASUREMENTS: Variables included client-related characteristics, service characteristics and baseline measures of clinical severity [Kessler-10 (K10), EUROHIS-QoL, severity of dependence scale (SDS)]. Multivariable binary logistic regression models assessed the relationships between these characteristics and treatment completion. FINDINGS: Rates of treatment completion were highest among adolescents in community-based treatment (57%) and lowest among young adults in residential treatment (35%). Polysubstance use was negatively associated with treatment completion among adolescents [adjusted odds ratio (adjOR) = 0.71, P < 0.001] and adults (adjOR = 0.70, P < 0.001) in community-based treatment, and adolescents in residential treatment (adjOR = 0.62, P = 0.006), as was housing insecurity (adolescents in community treatment, adjOR = 0.61, P = 0.001; adults in community treatment, adjOR = 0.77, P = 0.002; adolescents in residential treatment, adjOR = 0.42, P = 0.005). Attending youth-specific services was associated with higher treatment completion rates among adults in community-based (adjOR = 1.81, P < 0.001) and residential treatment (adjOR = 1.72, P < 0.001). Varying correlates of treatment completion were identified throughout treatment groups, reflecting the differences in population and/or needs across contexts. CONCLUSIONS: In New South Wales, Australia, fewer than half of young people accessing alcohol and other drug treatment between 2012 and 2023 completed treatment, and completion rates were lower among those facing barriers such as polysubstance use and housing insecurity.
ABSTRACT
Sarcoma is a complex and heterogeneous cancer that has been difficult to study in vitro. While two-dimensional (2D) cell cultures and mouse models have been the dominant research tools, three-dimensional (3D) culture systems such as organoids have emerged as promising alternatives. In this review, we discuss recent developments in sarcoma organoid culture, with a focus on their potential as tools for drug screening and biobanking. We also highlight the ways in which sarcoma organoids have been used to investigate the mechanisms of gene regulation, drug resistance, metastasis, and immune interactions. Sarcoma organoids have shown to retain characteristics of in vivo biology within an in vitro system, making them a more representative model for sarcoma research. Our review suggests that sarcoma organoids offer a potential path forward for translational research in this field and may provide a platform for developing personalized therapies for sarcoma patients.
ABSTRACT
The arene cyclopropanation between diazo compounds and benzene is well known to produce a tautomeric mixture of norcaradiene and cycloheptatriene in favour of the latter species. Nevertheless, previous studies have suggested that the initially formed norcaradiene can be stabilized by a C-7 cyano group with prevention of its 6π-electrocyclic ring opening. According to this feature, a synthetic route to functionalized cyclohexadienes has been designed using α-cyanodiazoacetates and α-diazo-ß-ketonitriles as the starting materials, respectively. The Rh2(esp)2-catalyzed arene cyclopropanation of α-cyanodiazoacetates in benzene afforded the expected 7-alkoxycarbonyl-7-cyanonorcaradienes as isolable compounds, which then served as templates for the second cyclopropanation with ethyl diazoacetate or α-cyanodiazocarbonyls to enable the formation of bis(cyclopropanated) adducts. Their subsequent treatment with SmI2 triggered a double ring-opening process, allowing for the generation of 1,4- and/or 1,3-cyclohexadienes as either regio- or diastereomeric mixtures. On the other hand, the norcaradienes generated from phenyl- or methyl-substituted α-diazo-ß-ketonitriles were found to undergo an in situ rearrangement to yield dihydrobenzofurans that could be converted to benzofuran derivatives by DDQ oxidation.
ABSTRACT
Background: Paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disease, is associated with high maternal and fetal mortality rates. Only 1 medication approved for PNH, the complement component 5 inhibitor eculizumab, has published evidence of use during pregnancy. Key Clinical Question: What were the circumstances and outcomes of the first use of pegcetacoplan, a complement component 3 inhibitor, by a pregnant woman with PNH? Clinical Approach: The patient, with a history of 2 miscarriages and a suboptimal response to eculizumab, had hematologic improvement after switching to pegcetacoplan. She continued pegcetacoplan throughout her pregnancy. At gestational week 30, she developed abruptio placentae and breakthrough hemolysis. She delivered a normal-appearing male infant via emergency cesarean section. The breakthrough hemolysis resolved quickly with short-term intensive pegcetacoplan dosing and add-on eculizumab. To date, her laboratory values remain normal, and she has had no thromboembolic events; her son has not demonstrated growth defects. Conclusion: This is the first report of pegcetacoplan treatment for PNH throughout pregnancy. The mother recovered promptly from breakthrough hemolysis that prompted an emergency delivery. Her son, who was born prematurely but healthy, has developed normally.
ABSTRACT
Oncolytic adenoviruses have emerged as a promising therapeutic approach for cancer therapy. However, systemic delivery of the viruses to metastatic tumors remains a major challenge. Mesenchymal stem cells (MSCs) possess tumor tropism property and can be used as cellular vehicles for delivering oncolytic adenoviruses to tumor sites. Since telomerase activity is found in ~90% of human carcinomas, but undetected in normal adult cells, the human telomerase reverse transcriptase gene (TERT) promoter can be exploited for regulating the replication of oncolytic adenoviruses. Here, we evaluated the antitumor effects of syngeneic murine MSCs loaded with the luciferase-expressing, telomerase-dependent oncolytic adenovirus Ad.GS2 (MSC-Ad.GS2) and Ad.GS2 alone on metastatic MBT-2 bladder tumors. MSCs supported a low degree of Ad.GS2 replication, which could be augmented by coculture with MBT-2 cells or tumor-conditioned medium (TCM), suggesting that viral replication is increased when MSC-Ad.GS2 migrates to tumor sites. MBT-2 cells and TCM enhanced viral replication in Ad.GS2-infected MSCs. SDF-1 is a stem cell homing factor. Our results suggest that the SDF-1/STAT3/TERT signaling axis in MSCs in response to the tumor microenvironment may contribute to the enhanced replication of Ad.GS2 carried by MSCs. Notably, we demonstrate the potent therapeutic efficacy of systemically delivered MSC-Ad.GS2 in pleural disseminated tumor and experimental metastasis models using intrapleural and tail vein injection of MBT-2 cells, respectively. Treatment with MSC-Ad.GS2 significantly reduced tumor growth and prolonged the survival of mice bearing metastatic bladder tumors. Since telomerase is expressed in a broad spectrum of cancers, this therapeutic strategy may be broadly applicable.
ABSTRACT
BACKGROUND: The caretaking process for older adults with depression and physical multimorbidity is complex. Older patients with both psychiatric and physical illnesses require an integrated and comprehensive approach to effectively manage their care. This approach should address common risk factors, acknowledge the bidirectional relationship between somatic and mental health conditions, and integrate treatment strategies for both aspects. Furthermore, active engagement of healthcare providers in shaping new care processes is imperative for achieving sustainable change. OBJECTIVE: To explore and understand the needs and expectations of healthcare providers (HCPs) concerning the care for older patients with depression and physical multimorbidity. METHODS: Seventeen HCPs who work with the target group in primary and residential care participated in three focus group interviews. A constructivist Grounded Theory approach was applied. The results were analyzed using the QUAGOL guide. RESULTS: Participants highlighted the importance of patient-centeredness, interprofessional collaboration, and shared decision-making in current healthcare practices. There is also a need to further emphasize the advantages and risks of technology in delivering care. Additionally, HCPs working with this target population should possess expertise in both psychiatric and somatic care to provide comprehensive care. Care should be organized proactively, anticipating needs rather than reacting to them. Healthcare providers, including a dedicated care manager, might consider collaborating, integrating their expertise instead of operating in isolation. Lastly, effective communication among HCPs, patients, and their families is crucial to ensure high-quality care delivery. CONCLUSION: The findings stress the importance of a comprehensive approach to caring for older adults dealing with depression and physical comorbidity. These insights will fuel the development of an integrated care model that caters to the needs of this population.
Subject(s)
Attitude of Health Personnel , Depression , Focus Groups , Health Personnel , Multimorbidity , Humans , Female , Male , Aged , Depression/therapy , Depression/epidemiology , Depression/psychology , Health Personnel/psychology , Middle Aged , Patient-Centered Care , Adult , Grounded Theory , Qualitative Research , Decision Making, SharedABSTRACT
PURPOSE: To determine if postanesthesia forced-air warming as a nonpharmacologic intervention for emergence delirium (ED)/emergence agitation (EA) decreased the incidence and severity of ED in children aged 18 months to 6 years old. DESIGN: Prospective nonrandomized controlled trial. METHODS: Participants included children aged 18 months to 6 years old receiving general anesthesia within a radiation oncology setting. Status of ED/EA was based on the participants' Pediatric Anesthesia Emergence Delirium (PAED) scale score (two consecutive scores greater than 10 out of 20) or inconsolable agitation behaviors post computed tomography simulation (day 0). Interrater reliability was conducted among the center's perianesthesia care nurses. Participants who scored positive for ED/EA received a forced-air warming blanket for the remainder of treatment with data collection 1 to 14 days postanesthesia. Non-ED/EA participants were followed for 14 days and provided forced-air warming if ED/EA occurred. Data consisted of daily PAED scores and self- or parent-report on the anxiety scale. If the participants received forced-air warming, nurses' clinical observations and parent satisfaction surveys were collected 3 times during the 14-day study period. FINDINGS: A total of 59 participants completed the study (mean age 3.43 years; 60% male; 63% non-Hispanic White); 16 were identified with ED or EA (mean age 3.56 years; 50% male; 69% non-Hispanic White) with an incidence rate of 28%. For the 16 participants with ED/EA, the primary diagnosis consisted of solid tumors and an American Society of Anesthesia Classification III to IV. Prior to the forced-air warming intervention, all 16 participants exhibited inconsolable ED/EA behaviors, including 8 who had PAED scores greater than 10. ED/EA behaviors expressed included inconsolability, confusion, thrashing, and combativeness. Within the 14-day period, 3 participants received forced-air warming on day 1, while the other 13 received an average of 4.23 days of treatment (range 1 to 11 days; mode 1 day; median 4 days). Comparison of PAED scores pre (mean 4.4) and post (mean 1.8) indicated that the use of forced-air warming was statistically significant (P = .001). ED/EA behaviors and PAED scores after the forced-air warming period decreased in all but one participant. Some agitation behaviors were not captured within the PAED score. CONCLUSIONS: Forced-air warming impacted PAED scores and agitation behaviors for studied participants, offering a safe, nonpharmacological nursing intervention that may be an effective tool for helping to manage this baffling condition.
ABSTRACT
OBJECTIVES: To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical features for differentiating between pleomorphic adenoma (PA) and atypical parotid adenocarcinoma (PCA) pre-operation. METHODS: From January 2010 to October 2023, a total of 187 cases of parotid tumors were recruited, and divided into training cohort (102 PAs and 51 PCAs) and testing cohort (24 PAs and 10 atypical PCAs). Clinical and CT image features of tumor were assessed. Both enhanced CT-derived ECV and AEF were calculated. Univariate analysis identified variables with statistically significant differences between the two subgroups in the training cohort. Multivariate logistic regression analysis with the forward variable selection method was used to build four models (clinical model, clinical model+ECV, clinical model+AEF, and combined model). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Delong's test compared model differences, and calibration curve and decision curve analysis (DCA) assessed calibration and clinical application. RESULTS: Age and boundary were chosen to build clinical model, and to construct its ROC curve. Amalgamating the clinical model, ECV, and AEF to establish a combined model demonstrated superior diagnostic effectiveness compared to the clinical model in both the training and test cohorts (AUC = 0.888, 0.867). There was a significant statistical difference between the combined model and the clinical model in the training cohort (p = 0.0145). CONCLUSIONS: ECV and AEF are helpful in differentiating PA and atypical PCA, and integrating clinical and CT image features can further improve the diagnostic performance.
Subject(s)
Adenoma, Pleomorphic , Contrast Media , Parotid Neoplasms , Tomography, X-Ray Computed , Humans , Male , Female , Adenoma, Pleomorphic/diagnostic imaging , Adenoma, Pleomorphic/pathology , Middle Aged , Parotid Neoplasms/diagnostic imaging , Parotid Neoplasms/pathology , Tomography, X-Ray Computed/methods , Diagnosis, Differential , Aged , Adult , ROC Curve , Retrospective Studies , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathologyABSTRACT
This study marks the first utilization of reverse vaccinology to develop recombinant subunit vaccines against Pseudomonas koreensis infection in Empurau (Tor tambroides). The proteome (5538 proteins) was screened against various filters to prioritize proteins based on features that are associated with virulence, subcellular localization, transmembrane helical structure, antigenicity, essentiality, non-homology with the host proteome, molecular weight, and stability, which led to the identification of eight potential vaccine candidates. These potential vaccine candidates were cloned and expressed, with six achieving successful expression and purification. The antigens were formulated into two distinct vaccine mixtures, Vac A and Vac B, and their protective efficacy was assessed through in vivo challenge experiments. Vac A and Vac B demonstrated high protective efficacies of 100 % and 81.2 %, respectively. Histological analyses revealed reduced tissue damage in vaccinated fish after experimental infection, with Vac A showing no adverse effects, whereas Vac B exhibited mild degenerative changes. Quantitative real-time PCR results showed a significant upregulation of TNF-α and downregulation of IL-1ß in the kidneys, spleen, gills, and intestine in both Vac A- and Vac B-immunized fish after challenged with P. koreensis. Additionally, IL-8 exhibits tissue-specific differential expression, with significant upregulation in the kidney, gills, and intestine, and downregulation in the spleen, particularly notable in Vac A-immunized fish. The research underscores the effectiveness of the reverse vaccinology approach in fish and demonstrates the promising potential of Vac A and Vac B as recombinant subunit vaccines.