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BACKGROUND: The identification of idiopathic inflammatory myopathies (IIMs) requires a comprehensive analysis involving clinical manifestations and histological findings. This study aims to provide insights into the histopathological and immunohistochemical aspects of IIMs. METHODS: This retrospective case series involved 56 patients diagnosed with IIMs at the Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, from 2019 to 2023. The histology and immunohistochemical expression of HLA-ABC, HLA-DR, C5b-9, Mx1/2/3, and p62 were detected. RESULTS: We examined six categories of inflammatory myopathy, including immunemediated necrotizing myopathy (58.9%), dermatomyositis (DM; 23.2%), overlap myositis (8.9%), antisynthetase syndrome (5.4%), inclusion body myositis (IBM; 1.8%), and polymyositis (1.8%). The average age of the patients was 49.7 ± 16.1 years, with a female-to-male ratio of 3:1. Inflammatory cell infiltration in the endomysium was present in 62.5% of cases, perifascicular atrophy was found in 17.8%, and fiber necrosis was observed in 42 cases (75.0%). Rimmed vacuoles were present in 100% of cases in the IBM group. Immunohistochemistry showed the following positivity rates: HLA-ABC (89.2%), HLA-DR (19.6%), C5b-9 (57.1%), and Mx1/2/3 (10.7%). Mx1/2/3 expression was high in DM cases. p62 vacuole deposits were noted in the IBM case. The combination of membrane attack complex and major histocompatibility complex I helped detect IIMs in 96% of cases. CONCLUSIONS: The diagnosis of IIMs and their subtypes should be based on clinical features and histopathological characteristics. Immunohistochemistry plays a crucial role in the diagnosis and differentiation of these subgroups.
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BACKGROUND: Medication errors significantly compromise patient safety in emergency departments. Although previous studies have investigated the prevalence of these errors in this setting, results have varied widely. AIM: The aim was to report pooled data on the prevalence and severity of medication errors in emergency departments, as well as the proportion of patients affected by these errors. METHOD: Systematic searches were conducted in Embase, PubMed, and the Cochrane Library from database inception until June 2023. Studies provided numerical data on medication errors within emergency departments were eligible for inclusion. Random-effects meta-analysis was employed to pool the prevalence of medication errors, the proportion of patients experiencing these errors, and the error severity levels. Heterogeneity among studies was assessed using the I2 statistic and Cochran's Q test. RESULTS: Twenty-four studies met the inclusion criteria. The meta-analysis gave a pooled prevalence of medication errors in emergency departments of 22.6% (95% Confidence Interval [CI] 19.2-25.9%, I2 = 99.9%, p < 0.001). The estimated proportion of patients experiencing medication errors was 36.3% (95% CI 28.3-44.3%, I2 = 99.8%, p < 0.001). Of these errors, 42.6% (95% CI 5.0-80.1%) were potentially harmful but not life-threatening, while no-harm errors accounted for 57.3% (95% CI 14.1-100.0%). CONCLUSION: The prevalence of medication errors, particularly those potentially harmful, underscores potential safety issues in emergency departments. It is imperative to develop and implement effective interventions aimed at reducing medication errors and enhancing patient safety in this setting.
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Flexible bronchoscopy has revolutionized respiratory disease diagnosis. It offers direct visualization and detection of airway abnormalities, including lung cancer lesions. Accurate identification of airway lesions during flexible bronchoscopy plays an important role in the lung cancer diagnosis. The application of artificial intelligence (AI) aims to support physicians in recognizing anatomical landmarks and lung cancer lesions within bronchoscopic imagery. This work described the development of BM-BronchoLC, a rich bronchoscopy dataset encompassing 106 lung cancer and 102 non-lung cancer patients. The dataset incorporates detailed localization and categorical annotations for both anatomical landmarks and lesions, meticulously conducted by senior doctors at Bach Mai Hospital, Vietnam. To assess the dataset's quality, we evaluate two prevalent AI backbone models, namely UNet++ and ESFPNet, on the image segmentation and classification tasks with single-task and multi-task learning paradigms. We present BM-BronchoLC as a reference dataset in developing AI models to assist diagnostic accuracy for anatomical landmarks and lung cancer lesions in bronchoscopy data.
Subject(s)
Bronchoscopy , Lung Neoplasms , Humans , Artificial Intelligence , Lung Neoplasms/diagnostic imaging , Thorax/diagnostic imaging , Anatomic Landmarks/diagnostic imagingABSTRACT
BACKGROUND: Anaplastic lymphoma kinase (ALK) mutations have been identified as a prominent cause of some familial and sporadic neuroblastoma (NB). ALK expression in NB and its relationship with clinical and histopathological features remains controversial. This study investigated ALK expression and its potential relations with these features in NB. METHODS: Ninety cases of NB at the Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam from 01/01/2018 to 12/31/2021, were immunohistochemically stained with ALK (D5F3) antibody. The ALK expression and its relations with some clinical and histopathological features were investigated. RESULTS: The rate of ALK expression in NB was 91.1%. High ALK expression (over 50% of tumor cells were positive with moderate-strong intensity) accounted for 65.6%, and low ALK expression accounted for 34.4%. All the MYCN-amplified NB patients had ALK immunohistochemistry positivity, most cases had high ALK protein expression. The undifferentiated subtype of NB had a lower ALK-positive rate than the poorly differentiated and differentiated subtype. The percentages of ALK positivity were significantly higher in more differentiated histological types of NB (p = .024). There was no relation between ALK expression and: age group, sex, primary tumor location, tumor stage, MYCN status, clinical risk, Mitotic-Karyorrhectic Index, prognostic group, necrosis, and calcification. CONCLUSIONS: ALK was highly expressed in NB. ALK expression was not related to several clinical and histopathological features. More studies are needed to elucidate the association between ALK expression and ALK gene status and to investigate disease progression, especially the oncogenesis of ALK-positive NB.
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Influenza A virus (IAV) is a negative-sense RNA virus that causes seasonal infections and periodic pandemics, inflicting huge economic and human costs on society. The current production of influenza virus for vaccines is initiated by generating a seed virus through the transfection of multiple plasmids in HEK293 cells followed by the infection of seed viruses into embryonated chicken eggs or cultured mammalian cells. We took a system design and synthetic biology approach to engineer cell lines that can be induced to produce all viral components except hemagglutinin (HA) and neuraminidase (NA), which are the antigens that specify the variants of IAV. Upon the transfection of HA and NA, the cell line can produce infectious IAV particles. RNA-Seq transcriptome analysis revealed inefficient synthesis of viral RNA and upregulated expression of genes involved in host response to viral infection as potential limiting factors and offered possible targets for enhancing the productivity of the synthetic cell line. Overall, we showed for the first time that it was possible to create packaging cell lines for the production of a cytopathic negative-sense RNA virus. The approach allows for the exploitation of altered kinetics of the synthesis of viral components and offers a new method for manufacturing viral vaccines.
Subject(s)
Artificial Cells , Influenza A virus , Influenza Vaccines , Animals , Humans , Influenza A virus/genetics , Influenza Vaccines/genetics , HEK293 Cells , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Hemagglutinins , Mammals/metabolismABSTRACT
Through collaboration with international experts, our institution established a highly active and successful hematopoietic stem cell transplant program, providing access to this potentially curative treatment modality for patients with a variety of benign and malignant hematological diseases. The initial development of an autologous stem cell transplant program provided our institution with the infrastructure, equipment, and expertise needed for the subsequent development of an allogeneic stem cell transplant program. Key transplant staff received training from international transplant experts at the NHLBI/NIH, the Mayo Clinic, the Johns Hopkins Hospital, and Nagoya Japan, providing them with the expertise to conduct a variety of different transplant approaches, including PBSC transplants from HLA-matched relatives, unrelated cord blood transplants, haploidentical transplants, and CD34 selected stem cell transplants. Patient characteristics were varied among all groups. The number of allogeneic and autologous transplants performed at the NIHBT has increased steadily every year since the initiation of our transplant program. By 2022, 547 transplant procedures had been performed, including 268 autologous and 279 allogeneic transplants. Allogeneic transplants were performed for both malignant and nonmalignant hematological diseases, with acute leukemia (AL) being the most common indication for allogeneic HCT. The majority of recipients undergoing allogeneic transplantation received G-CSF mobilized PBSC allografts from either HLA identical or haplo-identical relatives, with a smaller percentage of patients receiving a UCB transplant or a PBSC allograft that had been CD34+ selected. Amongst the 279 recipients of an allogeneic transplant, mortality rates within day 100 and beyond day 100 were 12.6% and 26.2% respectively. Overall survival (OS) and event-free survival at 5 years in benign and malignant subgroups were 81% and 73% vs 52% and 48% respectively. Through collaboration with international transplant experts, the National Institute of Hematology and Blood Transfusion in Hanoi has stood up the most active transplant center in the northern region of Vietnam. Patients coming from low-income financial backgrounds are now able to receive a variety of different state-of-the-art transplant approaches that are affordable and have been associated with excellent long-term outcomes.
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Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Hematopoietic Stem Cell Transplantation/methods , Vietnam , Graft vs Host Disease/etiology , Transplantation, Homologous , Leukemia, Myeloid, Acute/therapyABSTRACT
INTRODUCTION: It is increasingly recognised by UK researchers and population health advocates that an important impetus to effective policy action to address health inequalities is activation of public dialogue about the social determinants of health and how inequalities might be addressed. The limited body of existing scholarship reaches varying conclusions on public preferences for responding to health inequalities but with consensus around the importance of tackling poverty. Young people's perspectives remain underexplored despite their increasingly visible role in activism across a range of policy issues and the potential impact of widening inequalities on their generation's health and wellbeing. METHODS: Six groups of young people (39 in total) from two UK cities (Glasgow and Leeds) were engaged in online workshops to explore views on health inequalities and potential solutions. Inspired by calls to employ notions of utopia, artist-facilitators and researchers supported participants to explore the evidence, debating solutions and imagining a more desirable society, using visual and performance art. Drawing together data from discussions and creative outputs, we analysed participants' perspectives on addressing health inequalities across four domains: governance, environment, society/culture and economy. FINDINGS: Proposals ranged from radical, whole-systems change to support for policies currently being considered by governments across the United Kingdom. The consensus was built around embracing more participatory, collaborative governance; prioritising sustainability and access to greenspace; promoting inclusivity and eliminating discrimination and improving the circumstances of those on the lowest incomes. Levels of acceptable income inequality, and how best to address income inequality were more contested. Individual-level interventions were rarely presented as viable options for addressing the social inequalities from which health differences emanate. CONCLUSION: Young people contributed wide-ranging and visionary solutions to debates around addressing the enduring existence of health inequalities in the United Kingdom. Their reflections signal support for 'upstream' systemic change to achieve reductions in social inequalities and the health differences that flow from these. PUBLIC CONTRIBUTION: An advisory group of young people informed the development of project plans. Participants shaped the direction of the project in terms of substantive focus and were responsible for the generation of creative project outputs aimed at influencing policymakers.
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Income , Poverty , Humans , Adolescent , Socioeconomic Factors , United Kingdom , Health Status DisparitiesABSTRACT
Population's biological parameters, including length at first capture, mortalities, exploitation rates, growth coefficient, longevity, and recruitment times, are essential in assessing fishing status, but there is no data on Mystus mysticetus. Therefore, the study was conducted to provide these parameters to assess the fishing status of this species at Cai Rang, Can Tho (CRCT) and Long Phu, Soc Trang (LPST). A collection of 741 individual fish was used for analysis and showed that most fish size groups ranged from 9.0 cm to 12.0 cm, and the asymptotic length was 16.8 cm for both CRCT and LPST populations. The fish population von Bertalanffy curve was L t = 16.80(1 - e-0.51(t + 0.38)) at CRCT and L t = 16.80(1 - e-0.48(t + 0.40)) at LPST. The fish growth coefficient at CRCT (2.16) was higher than at LPST (2.13), whereas the reverse case was true for longevity ranging from 5.88 years (at CRCT) to 6.25 years (at LPST). At CRCT, fishing mortality, natural mortality, total mortality, and exploitation rate were 0.69/year, 1.40/year, 2.09/year, and 0.33, respectively; at LPST, these values were 0.75/year, 1.33/year, 2.08/year, and 0.36, respectively. Although the population parameter of this fish species exhibited a spatial variation, both CRCT and LPST fish resources have not been subjected to overexploit because E (0.33 at CRCT and 0.36 at LPST) is lower than E 0.1 (0.707 at CRCT and 0.616 at LPST).
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COPD patients with asthma features usually benefit from inhaled corticosteroids (ICS)-containing regimens, but their burden and diagnostic criteria remain to be established. The aims of this study were to estimate the proportion of patients with asthma features among patients with physician-diagnosed COPD and to investigate differences in clinical characteristics and current medications between COPD patients with asthma features and patients with COPD alone. A cross-sectional study was conducted at two respiratory out-patient clinics at the University Medical Center in Ho Chi Minh City and Bach Mai Hospital in Ha Noi, Vietnam. COPD patients with asthma features were identified by attending physicians following the approach recommended by the GINA/GOLD joint committee. Of the 332 patients screened, 300 were enrolled in the study. The proportion of COPD patients with asthma features was 27.3% (95% confidence interval (95% CI) 22.6-32.6%). COPD patients with asthma features were younger, with higher FEV1 values, a greater proportion of positive bronchodilator reversibility tests, higher blood eosinophil count, and were more often treated with ICS/LABA (ICS/long-acting bronchodilator beta-2 agonist) than patients with COPD alone. The prevalence of COPD patients with asthma features is particularly high in Vietnam thus requiring appropriate action plans in clinical practice.
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INTRODUCTION: The pro-inflammatory cytokine interferon-gamma (IFN-γ) is reported to be an agent that boosts the immune modulation of mesenchymal stem cells (MSCs). However, the effects of IFN-γ on the chondrogenic potential of treated MSCs have not been evaluated in depth. This study aimed to evaluate the effects of IFN-γ on the immune modulation and chondrogenic potential of human umbilical cord-derived MSCs (hUC-MSCs). METHODS: UC-MSCs were isolated and expanded following published protocols. They were characterized as MSCs before their use in further experiments. The UC-MSCs were treated with IFN-γ at 10 ng/mL for 48 h. Changes in phenotype were investigated based on changes in MSC markers, immunomodulatory genes (TGF-ß, IL-4, and IDO) for immune modulation, and cartilage-related genes during the induction of differentiation (Col1a2, Col2a1, Sox9, Runx2, and Acan) for chondrogenic potential. RESULTS: IFN-γ-treated UC-MSCs maintained MSC markers and exhibited decreased expression of transcriptional regulatory factors in chondrogenesis (Sox9 and Runx2) and the extracellular matrix-specific genes Col1a2 and Acan but not Col2a1 compared to non-treated cells (p < 0.05). Furthermore, the immunomodulatory capability of IFN-γ-treated UC-MSCs was clearly revealed through their increased expression of IDO and IL-4 and decreased expression of TGF-ß compared to non-treated cells (p < 0.05). CONCLUSION: This study demonstrated that UC-MSCs treated with IFN-γ at 10 ng/mL had reduced expression of chondrocyte-specific genes; however, they maintained multi-lineage differentiation and exhibited immunomodulatory properties.
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INTRODUCTION: Pigmented epithelioid angiomyolipoma is a variant of epithelioid angiomyolipoma (EAML) that has not previously been described in children with tuberous sclerosis. CASE PRESENTATION: A 15-year-old boy with tuberous sclerosis had a rapidly enlarging renal mass associated with a left lung nodule. Microscopically it was a pigmented EAML, confirmed by immunohistochemistry. DISCUSSION/CONCLUSION: The pigmented variant of EAML can arise and metastasize from the kidney of a teenager with tuberous sclerosis.
Subject(s)
Angiomyolipoma , Kidney Neoplasms , Tuberous Sclerosis , Male , Adolescent , Humans , Child , Tuberous Sclerosis/complications , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/pathology , Angiomyolipoma/complications , Angiomyolipoma/diagnosis , Angiomyolipoma/pathology , Kidney Neoplasms/complications , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Epithelioid Cells/pathology , Kidney/pathologyABSTRACT
Introduction: Pediatric DLBCL is considered a homogenous group and has superior outcomes compared to adults. This study investigated the clinical pathology and immunohistochemical distinction between adult and pediatric large B-cell lymphoma. Methods: A cross-sectional study of 314 NHLs with the morphology of diffuse pattern, large B-cell, and CD20 expression was investigated. Results: Of 314 cases, there were 6 cases of pleomorphic MCL (all in adults), 19 cases of Burkitt lymphoma (all in children), and 289 cases of DLBCL. Pediatric DLBCL had many striking differences: More frequency in extra-nodal sites; a higher proportion of centroblastic morphology; a predominance of GCB-type; a high proliferation rate; an infrequency of Bcl2 protein expression, and a lack of double-expresser lymphoma. Conclusions: Our study demonstrated the significant biological differences between adult and pediatric DLBCL.
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Lymphoma, Large B-Cell, Diffuse , Humans , Adult , Child , Cross-Sectional Studies , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , PrognosisABSTRACT
An XYZ compliant micropositioner has been widely mentioned in precision engineering, but the displacements in the X, Y, and Z directions are often not the same. In this study, a design and optimization for a new XYZ micropositioner are developed to obtain three same displacements in three axes. The proposed micropositioner is a planar mechanism whose advantage is a generation of three motions with only two actuators. In the design strategy, the proposed micropositioner is designed by a combination of a symmetrical four-lever displacement amplifier, a symmetrical parallel guiding mechanism, and a symmetrical parallel redirection mechanism. The Z-shaped hinges are used to gain motion in the Z-axis displacement. Four flexure right-circular hinges are combined with two rigid joints and two flexure leaf hinges to permit two large X-and-Y displacements. The symmetrical four-lever displacement amplifier is designed to increase the micropositioner's travel. The displacement sensor is built by embedding the strain gauges on the hinges of the micropositioner, which is developed to measure the travel of the micropositioner. The behaviors and performances of the micropositioner are modeled by using the Taguchi-based response surface methodology. Additionally, the geometrical factors of the XYZ micropositioner are optimized by teaching-learning-based optimization. The optimized design parameters are defined with an A of 0.9 mm, a B of 0.8 mm, a C of 0.57 mm, and a D of 0.7 mm. The safety factor gains 1.85, while the displacement achieves 515.7278 µm. The developed micropositioner is a potential option for biomedical sample testing in a nanoindentation system.
Subject(s)
Biocompatible Materials , MotionABSTRACT
Influenza A virus (IAV) infection causes acute respiratory disease with potential severe and deadly complications. Viral pathogenesis is not only due to the direct cytopathic effect of viral infections but also to the exacerbated host inflammatory responses. Influenza viral infection can activate various host signaling pathways that function to activate or inhibit viral replication. Our previous studies have shown that a receptor tyrosine kinase TrkA plays an important role in the replication of influenza viruses in vitro, but its biological roles and functional mechanisms in influenza viral infection have not been characterized. Here we show that IAV infection strongly activates TrkA in vitro and in vivo. Using a chemical-genetic approach to specifically control TrkA kinase activity through a small molecule compound 1NMPP1 in a TrkA knock-in (TrkA KI) mouse model, we show that 1NMPP1-mediated TrkA inhibition completely protected mice from a lethal IAV infection by significantly reducing viral loads and lung inflammation. Using primary lung cells isolated from the TrkA KI mice, we show that specific TrkA inhibition reduced IAV viral RNA synthesis in airway epithelial cells (AECs) but not in alveolar macrophages (AMs). Transcriptomic analysis confirmed the cell-type-specific role of TrkA in viral RNA synthesis, and identified distinct gene expression patterns under the TrkA regulation in IAV-infected AECs and AMs. Among the TrkA-activated targets are various proinflammatory cytokines and chemokines such as IL6, IL-1ß, IFNs, CCL-5, and CXCL9, supporting the role of TrkA in mediating lung inflammation. Indeed, while TrkA inhibitor 1NMPP1 administered after the peak of IAV replication had no effect on viral load, it was able to decrease lung inflammation and provided partial protection in mice. Taken together, our results have demonstrated for the first time an important biological role of TrkA signaling in IAV infection, identified its cell-type-specific contribution to viral replication, and revealed its functional mechanism in virus-induced lung inflammation. This study suggests TrkA as a novel host target for therapeutic development against influenza viral disease.
Subject(s)
Influenza A virus , Influenza, Human , Orthomyxoviridae Infections , Pneumonia , Animals , Cytokines/metabolism , Humans , Influenza A virus/genetics , Interleukin-6/metabolism , Lung/pathology , Mice , Protein-Tyrosine Kinases/metabolism , RNA, Viral/metabolism , Receptor, trkA/metabolism , Tropomyosin/metabolism , Tropomyosin/pharmacology , Virus Replication/physiologyABSTRACT
Background: Risk communication is necessary to improve the booster vaccination rate, but Vietnam does not have a system to collect and disclose such information. Therefore, the purpose of this study was to clarify adverse reactions and their frequency in the early period after booster vaccination, and to obtain primary data for improving the booster vaccination rate. Methods: A cross-sectional survey was conducted among adults aged ≥18 years. Clinical data were collected 14 days after booster vaccination by using a standard questionnaire. Results: A total of 1322 participants were included with median age = 23 and sex ratio (Male/Female) = 0.53. AstraZeneca was the most commonly used vaccine for the first and second doses, while Pfizer was the most commonly used vaccine for booster shots. Injection site pain, fatigue, and myalgia were the most common side effect reported (71.9%, 28.1%, and 21.8%, respectively). Compared to previous COVID-19 vaccine injections, 81.9% of participants reported that their symptoms were similar or milder after receiving the booster dose. They were more likely to present injection site pain (OR = 1.43, p < 0.0001) and lymphadenopathy (OR = 4.76, p < 0.0001) after receiving the booster shot. Fever (OR = 0.33, p < 0.0001) and fatigue (OR = 0.77, p = 0.002) were less often reported after booster shots compared to the first and second injections. The severity of symptoms occurring after booster dose versus first and second doses increased significantly with each additional year of age and among participants receiving the Pfizer and Moderna vaccines. Conclusion: Adverse reactions to booster vaccination are minor and their incidence is the same as for the first or the second vaccination. Multicenter studies with larger sample sizes on the side effects and safety of COVID-19 vaccine booster shots need to be conducted to make the population less worried, in order to increase the vaccination rate, to protect individuals' and communities' health.
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BACKGROUND: As a method to acknowledge the devastating health and economic impacts of tobacco usage worldwide, telephone-based tobacco cessation counseling services have emerged as a potential tool to aid people in their quitting process. This study explores the satisfaction of smokers who use the QUITLINE service and factors associated with their quit attempts and cessation. METHODS: A cross-sectional survey of 110 participants was conducted from June to July 2016 at the Respiratory Center at Bach Mai Hospital, Hanoi, Vietnam. Multivariate logistic regression was used, and it was found that the percentage of people quitting smoking increased after using the service. RESULTS: In total, 65.5% of participants were completely satisfied with the counseling service. The mean score of staff/s capacity/responsiveness, motivation, and service convenience were 4.37 ± 0.78, 4.30 ± 0.81, and 4.27 ± 0.66, respectively. The smoking relapse rate was relatively high at 58.3%, which mainly resulted from cravings and busy work (26.2% and 14.3%, respectively). A higher satisfaction score in "Staffs' capacity and responsiveness" was negatively associated with "ever tried to quit smoking in consecutive 24 h" and actually quit smoking after receiving counseling. Meanwhile, a higher score in the "Motivation" domain was positively associated with both quit attempt indicators as well as actually quitting smoking after receiving counseling (OR = 9.48; 95%CI = 2.27; 39.57). CONCLUSIONS: These results suggest that it is crucial for decision makers to place more focus on countermeasures for smoking relapse and to strengthen the capacity of staff, especially in motivating clients. Interventions should also be maintained throughout a long period of time to prevent relapse.
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The Madin-Darby Canine Kidney (MDCK) cell line is among the most commonly used cell lines for the production of influenza virus vaccines. As cell culture-based manufacturing is poised to replace egg-based processes, increasing virus production is of paramount importance. To shed light on factors affecting virus productivity, we isolated a subline, H1, which had twice the influenza virus A (IAV) productivity of the parent (P) through cell cloning, and characterized H1 and P in detail on both physical and molecular levels. Transcriptome analysis revealed that within a few hours after IAV infection, viral mRNAs constituted over one fifth of total mRNA, with several viral genes more highly expressed in H1 than P. Functional analysis of the transcriptome dynamics showed that H1 and P responded similarly to IAV infection, and were both subjected to host shutoff and inflammatory responses. Importantly, H1 was more active in translation and RNA processing intrinsically and after infection. Furthermore, H1 had more subdued inflammatory and antiviral responses. Taken together, we postulate that the high productivity of IAV hinges on the balance between suppression of host functions to divert cellular resources and the sustaining of sufficient activities for virus replication. Mechanistic insights into virus productivity can facilitate the process optimization and cell line engineering for advancing influenza vaccine manufacturing.
Subject(s)
Madin Darby Canine Kidney Cells , Orthomyxoviridae/genetics , Orthomyxoviridae/physiology , Transcriptome , Virus Replication/physiology , Animals , Apoptosis , Cell Line , Dogs , Hemagglutination , Humans , Influenza A virus/physiology , Influenza Vaccines/immunology , Influenza, HumanABSTRACT
Leaky gut is a condition of increased paracellular permeability of the intestine due to compromised tight junction barriers. In recent years, this affliction has drawn the attention of scientists from different fields, as a myriad of studies prosecuted it to be the silent culprit of various immune diseases. Due to various controversies surrounding its culpability in the clinic, approaches to leaky gut are restricted in maintaining a healthy lifestyle, avoiding irritating factors, and practicing alternative medicine, including the consumption of supplements. In the current study, we investigate the tight junction-modulating effects of processed Aloe vera gel (PAG), comprising 5-400-kD polysaccharides as the main components. Our results show that oral treatment of 143 mg/kg PAG daily for 10 days improves the age-related leaky gut condition in old mice, by reducing their individual urinal lactulose/mannitol (L/M) ratio. In concordance with in vivo experiments, PAG treatment at dose 400 µg/mL accelerated the polarization process of Caco-2 monolayers. The underlying mechanism was attributed to enhancement in the expression of intestinal tight junction-associated scaffold protein zonula occludens (ZO)-1 at the translation level. This was induced by activation of the MAPK/ERK signaling pathway, which inhibits the translation repressor 4E-BP1. In conclusion, we propose that consuming PAG as a complementary food has the potential to benefit high-risk patients.