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Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.
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Cicatriz/metabolismo , Colágeno Tipo V/deficiencia , Colágeno Tipo V/metabolismo , Lesiones Cardíacas/metabolismo , Contracción Miocárdica/genética , Miofibroblastos/metabolismo , Animales , Cicatriz/genética , Cicatriz/fisiopatología , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Colágeno Tipo V/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Femenino , Fibrosis/genética , Fibrosis/metabolismo , Regulación de la Expresión Génica/genética , Integrinas/antagonistas & inhibidores , Integrinas/genética , Integrinas/metabolismo , Isoproterenol/farmacología , Masculino , Mecanotransducción Celular/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía de Fuerza Atómica/instrumentación , Microscopía Electrónica de Transmisión , Contracción Miocárdica/efectos de los fármacos , Miofibroblastos/citología , Miofibroblastos/patología , Miofibroblastos/ultraestructura , Análisis de Componente Principal , Proteómica , RNA-Seq , Análisis de la Célula IndividualRESUMEN
Giant axonal neuropathy (GAN) is caused by mutations in the GAN gene encoding for gigaxonin (GIG), which functions as an adaptor of the CUL3-RBX1-GIG (CRL3GIG) E3 ubiquitin ligase complex. The pathological hallmark of GAN is characterized by the accumulation of densely packed neurofilaments (NFs) in the axons. However, there are fundamental knowledge gaps in our understanding of the molecular mechanisms by which the ubiquitin-proteasome system controls the homeostasis of NF proteins. Recently, the deubiquitylating enzyme USP15 was reported to play a crucial role in regulating ubiquitylation and proteasomal degradation of CRL4CRBN substrate proteins. Here, we report that the CRL3GIG-USP15 pathway governs the destruction of NF proteins NEFL and INA. We identified a specific degron called NEFLL12 degron for CRL3GIG. Notably, mutations in the C-terminal Kelch domain of GIG, represented by L309R, R545C, and C570Y, disrupted the binding of GIG to NEFL and INA, leading to the accumulation of these NF proteins. This accounts for the loss-of-function mutations in GAN patients. In addition to regulating NFs, CRL3GIG also controls actin filaments by directly targeting actin-filament-binding regulatory proteins TPM1, TPM2, TAGLN, and CNN2 for proteasomal degradation. Thus, our findings broadly impact the field by providing fundamental mechanistic insights into regulating extremely long-lived NF proteins NEFL and INA by the CRL3GIG-USP15 pathway and offering previously unexplored therapeutic opportunities to treat GAN patients and other neurodegenerative diseases by explicitly targeting downstream substrates of CRL3GIG.
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Neuropatía Axonal Gigante , Proteínas de Neurofilamentos , Humanos , Proteínas del Citoesqueleto/metabolismo , Ubiquitina , Ligasas , Axones/metabolismo , Neuropatía Axonal Gigante/genética , Neuropatía Axonal Gigante/patología , Neuropatía Axonal Gigante/terapia , Proteasas Ubiquitina-EspecíficasRESUMEN
INTRODUCTION: Intracranial atherosclerotic disease (ICAD) has been identified as a major cause of acute basilar artery occlusion (BAO).This study compared the characteristics and treatment outcomes in acute BAO patients with and without ICAD. METHODS: A prospective cohort study was conducted at 115 People's Hospital, Ho Chi Minh city, Vietnam from August 2021 to June 2023. Patients with acute BAO who underwent endovascular treatment within 24 h from symptom onset were included (thrombectomy alone or bridging with intravenous alteplase). The baseline characteristics and outcomes were analyzed and compared between patients with and without ICAD. Good functional outcome was defined as mRS ≤3 at 90 days. RESULTS: Among the 208 patients enrolled, 112 (53.8%) patients were categorized in the ICAD group, and 96 (46.2%) in the non-ICAD group. Occlusion in the proximal segment of the basilar artery was more common in patients with ICAD (55.4% vs. 21.9%, p < 0.001), whereas the distal segment was the most common location in the non-ICAD group (58.3% vs. 10.7%, p < 0.001). Patients in the ICAD group were more likely to undergo treatment in the late window, with a higher mean onset-to-treatment time compared to the non-ICAD group (11.6 vs. 9.5 h, p = 0.01). In multivariable logistic regression analysis, distal segment BAO was negatively associated with ICAD (aOR 0.13, 95% CI: 0.05-0.32, p < 0.001), while dyslipidemia showed a positive association (aOR 2.44, 95% CI: 1.15-5.17, p = 0.02). There was a higher rate for rescue stenting in the ICAD compared to non-ICAD group (15.2% vs. 0%, p < 0.001). However, no significant differences were found between the two groups in terms of good outcome (45.5% vs. 44.8%, p = 0.91), symptomatic hemorrhage rates (4.5% vs. 8.3%, p = 0.25), and mortality (42% vs. 50%, p = 0.25). CONCLUSION: ICAD was a common etiology in patients with BAO. The location segment of BAO and dyslipidemia were associated with ICAD in patients with BAO. There was no difference in 90-day outcomes between BAO patients with and without ICAD undergoing endovascular therapy.
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The capability to produce suture material using three-dimensional (3D) printing technology may have applications in remote health facilities where rapid restocking of supplies is not an option. This is a feasibility study evaluating the usability of 3D-printed sutures in the repair of a laceration wound when compared with standard suture material. The 3D-printed suture material was manufactured using a fused deposition modelling 3D printer and nylon 3D printing filament. Study participants were tasked with performing laceration repairs on the pigs' feet, first with 3-0 WeGo nylon suture material, followed by the 3D-printed nylon suture material. Twenty-six participants were enrolled in the study. Survey data demonstrated statistical significance with how well the 3D suture material performed with knot tying, 8.9 versus 7.5 (p = 0.0018). Statistical significance was observed in the 3D-printed suture's ultimate tensile strength when compared to the 3-0 Novafil suture (274.8 vs. 199.8 MPa, p = 0.0096). The 3D-printed suture also demonstrated statistical significance in ultimate extension when compared to commercial 3-0 WeGo nylon suture (49% vs. 37%, p = 0.0215). This study was successful in using 3D printing technology to manufacture suture material and provided insight into its usability when compared to standard suture material.
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Estudios de Factibilidad , Impresión Tridimensional , Técnicas de Sutura , Suturas , Resistencia a la Tracción , Animales , Porcinos , Laceraciones/cirugía , Ensayo de Materiales , Nylons , Cicatrización de Heridas , Humanos , Modelos Animales de EnfermedadRESUMEN
Targeted protein degradation by the ubiquitin-proteasome system represents a new strategy to destroy pathogenic proteins in human diseases, including cancer and neurodegenerative diseases. The immunomodulatory drugs (IMiDs) thalidomide, lenalidomide, and pomalidomide have revolutionized the treatment of patients with multiple myeloma (MM) and other hematologic malignancies, but almost all patients eventually develop resistance to IMiDs. CRBN, a substrate receptor of CUL4-RBX1-DDB1-CRBN (CRL4CRBN) E3 ubiquitin ligase, is a direct target for thalidomide teratogenicity and antitumor activity of IMiDs (now known as Cereblon E3 ligase modulators: CELMoDs). Despite recent advances in developing potent CELMoDs and CRBN-based proteolysis-targeting chimeras (PROTACs), many questions apart from clinical efficacy remain unanswered. CRBN is required for the action of IMiDs, but its protein expression levels do not correlate with intrinsic resistance to IMiDs in MM cells, suggesting other factors involved in regulating resistance to IMiDs. Our recent work revealed that the CRL4CRBN-p97 pathway is required for degradation of natural substrate glutamine synthetase (GS) and neosubstrates. Here, I show that USP15 is a key regulator of the CRL4CRBN-p97 pathway to control stability of GS and neosubstrates IKZF1, IKZF3, CK1-α, RNF166, GSPT1, and BRD4, all of which are crucial drug targets in different types of cancer. USP15 antagonizes ubiquitylation of CRL4CRBN target proteins, thereby preventing their degradation. Notably, USP15 is highly expressed in IMiD-resistant cells, and depletion of USP15 sensitizes these cells to lenalidomide. Inhibition of USP15 represents a valuable therapeutic opportunity to potentiate CELMoD and CRBN-based PROTAC therapies for the treatment of cancer.
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Glutamato-Amoníaco Ligasa/metabolismo , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Proteasas Ubiquitina-Específicas/metabolismo , Ubiquitinación/fisiología , Células HEK293 , Humanos , Agentes Inmunomoduladores/metabolismo , Mieloma Múltiple/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
The degree of contamination of retail meat with colistin-resistant bacteria and its potential contribution to dissemination within communities remains to be determined. Thus, we aimed to elucidate the contamination status of colistin-resistance genes, indicative of colistin-resistant bacteria, in retail meats in Vietnam. In total, 46 chicken and 49 pork meats from stores in Vietnam and Japan were examined. Multiplex real-time polymerase chain reaction with TaqMan probes was performed for detecting mcr-1, mcr-3, and Escherichia coli 16S rRNA. Colistin-resistant bacteria in meats were isolated using selective media. The minimum inhibitory concentrations of colistin were determined using the broth microdilution method. The results showed that 70.7% of chicken meats in Vietnam were contaminated with both mcr-1 and mcr-3. Meanwhile, mcr-1 and mcr-3 were detected in 15.9% and 40.9% of pork meat, respectively. Only mcr-3 was detected in 40% of chicken in Japan. In addition, mcr-1-harboring E. coli and mcr-3-harboring Aeromonas were isolated from chicken meats in Vietnam. Some of these isolates showed colistin resistance. These results showed that most retail meats were highly contaminated with colistin-resistance genes. Notably, our results suggest that mcr-3 is more prevalent in the contaminated samples compared with mcr-1.
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Antibacterianos , Pollos , Colistina , Farmacorresistencia Bacteriana , Proteínas de Escherichia coli , Escherichia coli , Microbiología de Alimentos , Carne , Pruebas de Sensibilidad Microbiana , Vietnam , Colistina/farmacología , Animales , Pollos/microbiología , Farmacorresistencia Bacteriana/genética , Antibacterianos/farmacología , Proteínas de Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Escherichia coli/genética , Carne/microbiología , Porcinos , ARN Ribosómico 16S/genética , Japón , Contaminación de Alimentos/análisis , Carne de Cerdo/microbiología , Transferasas (Grupos de Otros Fosfatos Sustitutos)RESUMEN
For the colloidal nanophotonic structures, a transmission electron microscope (TEM) grid has been widely used as a substrate of dark-field microscopy because a nanometer-scale feature can be effectively determined by TEM imaging following dark-field microscopic studies. However, an optically lossy carbon layer has been implemented in conventional TEM grids. A broadband scattering from the edges of the TEM grid further restricted an accessible signal-to-noise ratio. Herein, we demonstrate that the freely suspended, ultrathin, and wide-scale transparent nanomembrane can address such challenges. We developed a 1 mm by 600 µm scale and 20 nm thick poly(vinyl formal) nanomembrane, whose area is around 180 times wider than a conventional TEM grid, so that the possible broadband scattering at the edges of the grid was effectively excluded. Also, such nanomembranes can be formed without the assistance of carbon support; allowing us to achieve the highest signal-to-background ratio of scattering among other substrates.
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INTRODUCTION: In United States, health care workers have been immersed in the COVID-19 pandemic since February 2020. Since availability of COVID-19 vaccines, there is limited literature investigating the incidence of unknown COVID-19 infections in physicians and Advanced Practitioner Providers (APPs) working in emergency departments (EDs). The primary objective is to determine the incidence unknown COVID-19 infection within a cohort of emergency physicians (EPs) and APPs. METHODS: Prospective observational study at a tertiary academic center with emergency medicine residency and 64,000 annual ED visits. EPs/APPs providing care to ED patients over the prior 12 months were eligible. Serum samples were collected between May 1 and June 30, 2022. Analysis utilized Luminex xMAP® SARS-CoV-2 Multi-Antigen IgG Assay for antibodies to Nucleocapsid, Receptor-binding domain, and Spike subunit 1. Mean Fluorescent Intensity (MFI) ≥ 700 was considered positive. Subjects completed 12 question survey assessing demographics and previously confirmed COVID-19 infection. Fisher's exact test evaluated associations of demographics and clinical characteristics with confirmed COVID-19 status. Analyses performed using SAS, Version 9.4. P < 0.05 considered statistically significant. RESULTS: Sixty-nine of 81 eligible subjects (85.2%) participated, 58.0% were male, 97.1% white, with mean age of 37. Eighteen subjects had MFI ≥ 700 strongly suggestive of prior infection, with 17.7% unknown. No statistically significant difference between age, gender, race, children in home, or household member with previously COVID-19 infection. CONCLUSION: Unknown previous COVID-19 infection was less then expected in this cohort of EPs/APPs, and no association with individual characteristics, previously infected household member, or children in the home.
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COVID-19 , Médicos , Niño , Humanos , Masculino , Estados Unidos/epidemiología , Adulto , Femenino , COVID-19/epidemiología , SARS-CoV-2 , Vacunas contra la COVID-19 , Pandemias/prevención & control , Incidencia , Anticuerpos Antivirales , Inmunoglobulina GRESUMEN
PURPOSE: Image-free handheld robotic-assisted total knee arthroplasty (RATKA) has shown to achieve desired limb alignment compared to conventional jig-based instrumented total knee arthroplasty (CTKA). The aim of this prospective randomized controlled trial (RCT) was to evaluate the accuracy of a semi-autonomous imageless handheld RATKA compared to CTKA in order to achieve the perioperative planned target alignment of the knee postoperatively. METHODS: Fifty-two patients with knee osteoarthritis were randomized in 1:1 ratio to undergo unilateral CTKA or an imageless handheld RATKA. A full-length lower limb CT-scan was obtained pre- and 6-week postoperative. The primary outcomes were radiologic measurements of achieved target hip-knee-ankle axis (HKA-axis) and implant component position including varus and external rotation and flexion of the femur component, and posterior tibial slope. The proportion of outliers in above radiographic outcomes, defined as > 3° deviation in postoperative CT measurements as compared to perioperative planned target, were also noted. Knee phenotypes were compared with use of the Coronal Plane Alignment of the Knee (CPAK) classification. RESULTS: Baseline conditions were comparable between both groups. The overall proportion and percentage of outliers (n = 38, 24.4% vs n = 9, 5.8%) was statistically significant (p < 0.001) in favor of RATKA. The achieved varus-valgus of the femoral component (varus 1.3° ± 1.7° vs valgus - 0.1° ± 1.9°, p < 0.05) with statistically significant less outliers (0% vs 88.5%, p < 0.01), the achieved HKA-axis (varus 0.4° ± 2.1° vs valgus - 1.2° ± 2.1°, p < 0.05) and the posterior tibial slope (1.4° ± 1.1° vs 3.2° ± 1.8°, p < 0.05) were more accurate with RATKA. The most common postoperative CPAK categories were type II (50% CTKA vs 61.5% RATKA), type I (3.8% CTKA vs 23.1% RATKA) and type V (26.9% CTKA vs 15.4% RATKA). CPAK classification III was only found in CTKA (19.2%). Type VI, VII, VIII, and IX were rare in both populations. CONCLUSIONS: The present trial demonstrates that an imageless handheld RATKA system can be used to accurately perioperatively plan the desired individual component implant positions with less alignment outliers whilst aiming for a constitutional alignment. LEVEL OF EVIDENCE: I.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Procedimientos Quirúrgicos Robotizados , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Monitoring and estimating the density of microalgae in a closed cultivation system is a critical task in culturing algae since it allows growers to optimally control both nutrients and cultivating conditions. Among the estimation techniques proposed so far, image-based methods, which are less invasive, nondestructive, and more biosecure, are practically preferred. Nevertheless, the premise behind most of those approaches is simply averaging the pixel values of images as inputs of a regression model to predict density values, which may not provide rich information of the microalgae presenting in the images. In this work, we propose to exploit more advanced texture features extracted from captured images, including confidence intervals of means of pixel values, powers of spatial frequencies presenting in images, and entropies accounting for pixel distribution. These diverse features can provide more information of microalgae, which can lead to more accurate estimation results. More importantly, we propose to use the texture features as inputs of a data-driven model based on L1 regularization, called least absolute shrinkage and selection operator (LASSO), where their coefficients are optimized in a manner that prioritizes more informative features. The LASSO model was then employed to efficiently estimate the density of microalgae presenting in a new image. The proposed approach was validated in real-world experiments monitoring the Chlorella vulgaris microalgae strain, where the obtained results demonstrate its outperformance compared with other methods. More specifically, the average error in the estimation obtained by the proposed approach is 1.54, whereas those obtained by the Gaussian process and gray-scale-based methods are 2.16 and 3.68, respectively.
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Chlorella vulgaris , Microalgas , Biomasa , NutrientesRESUMEN
Owing to their high redox potential and availability of numerous diffusion channels in metal-organic frameworks, Prussian blue analogs (PBAs) are attractive for metal ion storage applications. Recently, vanadium ferrocyanides (VFCN) have received a great deal of attention for application in sodium-ion batteries, as they demonstrate a stable capacity with high redox potential of ~3.3 V vs. Na/Na+. Nevertheless, there have been no reports on the application of VFCN in lithium-ion batteries (LIBs). In this work, a facile synthesis of VFCN was performed using a simple solvothermal method under ambient air conditions through the redox reaction of VCl3 with K3[Fe(CN)6]. VFCN exhibited a high redox potential of ~3.7 V vs. Li/Li+ and a reversible capacity of ~50 mAh g-1. The differential capacity plots revealed changes in the electrochemical properties of VFCN after 50 cycles, in which the low spin of Fe ions was partially converted to high spin. Ex situ X-ray diffraction measurements confirmed the unchanged VFCN structure during cycling. This demonstrated the high structural stability of VFCN. The low cost of precursors, simplicity of the process, high stability, and reversibility of VFCN suggest that it can be a candidate for large-scale production of cathode materials for LIBs.
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PURPOSE: Anastomotic leak (AL) following ileocolic anastomosis is a cause of significant morbidity and mortality. Stapled end-to-side (ESA), stapled side-to-side (SSA), and handsewn anastomoses (HSA) are commonly performed techniques. There is however conflicting data on the superiority of one technique over the other. The aim of this study was to compare the outcomes of ESA against SSA and HSA. METHODS: This retrospective cohort study was conducted at a tertiary colorectal unit. All patients who underwent an ileocolic anastomosis from October 2008 to May 2020 were included. Exclusion criteria were missing data on anastomotic technique or clinicopathological variables. Primary outcomes were AL and anastomotic bleeding (AB). Secondary outcomes were length of stay (LoS) and return of gut function. RESULTS: A total of 1390 patients met the inclusion criteria. A total of 976 (70%) ESA, 308 (22%) SSA, and 108 (8%) HSA were performed. AL occurred in 17/1390 (1.2%) patients, and 54/1390 (3.9%) had AB. On adjusted analysis, ESA experienced a lower AL when compared with SSA (OR 4.93, p = 0.005), with a trend towards a lower AL when compared to HSA (OR 2.6, p = 0.27). There was no difference in AB between all techniques: ESA vs. SSA (OR 1.07 p = 0.84), and ESA vs. HSA (OR 0.24 p = 0.76). Both stapled techniques were associated with a shorter return to gut function compared to HSA; 3.3 vs. 4.2 days (p < 0.001). There was no difference in LoS. CONCLUSION: ESA has the lowest leak rate when compared to other anastomotic techniques without any increased risk of anastomotic bleeding.
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Colon , Grapado Quirúrgico , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Colectomía/efectos adversos , Colectomía/métodos , Colon/cirugía , Humanos , Estudios Retrospectivos , Grapado Quirúrgico/efectos adversos , Técnicas de Sutura/efectos adversosRESUMEN
BACKGROUND: The nasopharyngeal swab is the gold standard collection method for COVID-19, but is invasive and painful, subsequently resulting in poor patient acceptance. This investigation explores the process of developing and validating an alternative respiratory pathogen collection device that relies on a nasopharyngeal irrigation mechanic. The primary objective was to determine if sufficient pathological sampling can be achieved by mechanism of nasopharyngeal irrigation that is proportionate to the nasopharyngeal swab method. METHODS: The study device was designed using Shapr3D modeling software and fabricated on a fused deposition modeling printer. Fifteen participants were enrolled with each receiving a saline nasopharyngeal washing using the study device. Specimen adequacy was evaluated by two real-time reverse transcriptase polymerase chain reaction (PCR) testing methods to identify the presence of the human RNase P gene. Results were evaluated quantitatively through interpretation of the PCR cycle threshold (Ct). RESULTS: All 15 specimens tested positive for the presence of RNaseP, demonstrating specimen cellularity, adequate extraction of nucleic acids, and the absence of inhibitors to amplification. The mean Ct value was 29.5 (Applied Biosystems TaqPath RT-qPCR) and 30.7 (NECoV19). All participants felt the study device irrigation procedure was faster than the nasopharyngeal swab, with none experiencing any discomfort from the irrigation mechanism. CONCLUSION: The importance of early diagnostic testing and its role in countermeasures for communicable diseases such as COVID-19 is well established in the literature. Innovation to bolster our testing infrastructure is more important now than ever. This study was successful in developing and validating an alternative nasopharyngeal respiratory pathogen collection device that utilizes fluid debridement as its core mechanic. Data from this pilot study demonstrated the study device was successful in producing high-quality specimens for PCR testing. Feedback from the study participants was also in favor of the study device when compared to the nasopharyngeal swab.
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COVID-19 , Ácidos Nucleicos , Humanos , Pandemias , Proyectos Piloto , COVID-19/diagnóstico , COVID-19/epidemiología , Ribonucleasa P/genética , SARS-CoV-2 , Nasofaringe , Manejo de Especímenes/métodos , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Tuberculosis (TB) still remains the burden in Indonesia. One of the factors that may influence the treatment success of TB is patient's adherence. However, the hepatotoxicity of the TB medicine may decrease the patient's adherence. Our study's aim is to investigate the relationship between the patient's knowledge and the hepatotoxicity with medication adherence of TB patients in Banyumas Regency. This study was conducted at one Community Lung Health Center and two hospitals in Banyumas Regency, Purwokerto, Center of Java, Indonesia. The respondents were 91 TB patients with hepatotoxicity characterized by an increased aspartate transaminase (AST) and alanine aminotransferase (ALT). The level of the patients' knowledge about the hepatotoxicity effect was determined using a questionnaire. The patients' adherence was determined using the Medication Adherence Rating Scale -5 (MARS) questionnaire and pill count methods. Most of the patients were male (53.8%), the age was in the range of 18-29 years old (3.5%), they have no smoking history (59.3%), and their last education majorly was senior high school (46.2%). Most TB patients had poor knowledge (47.3%) and the hepatotoxic effect often appeared in grade 1 (61.5%). The TB patients with a good and moderate level of knowledge were 17.6% and 35.2%, respectively. The TB patients with moderate and severe hepatotoxicity were 39.4% and 1.1%, respectively. The measurement of the level of respondents' adherence using MARS-5 showed that 51.6% of patients had good adherence. We determined the rest of the drug-using pill count method, which resulted in 62.6% of patients adhering to taking antituberculosis drugs. TB patients with a sufficient knowledge and those with mild hepatotoxicity show the higher adherence (p < 0.001). There is a significant relationship between a high level of the patient's knowledge about hepatotoxicity effect, less severity of the hepatotoxic effect, and increased patient adherence in taking the medication.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Tuberculosis , Adolescente , Adulto , Alanina Transaminasa/uso terapéutico , Antituberculosos/efectos adversos , Aspartato Aminotransferasas/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Femenino , Humanos , Indonesia/epidemiología , Masculino , Cumplimiento de la Medicación , Tuberculosis/inducido químicamente , Tuberculosis/tratamiento farmacológico , Adulto JovenRESUMEN
STUDY PURPOSE: Distrust of the healthcare system is longstanding in the black community. This may especially threaten the health of the population when a highly contagious infection strikes. This study aims to compare COVID-19-related perspectives and behaviours between hospitalised black patients who trust versus distrust doctors and healthcare systems. STUDY DESIGN: Cross-sectional study at a tertiary care academic hospital in Baltimore, Maryland. Hospitalised adult black patients without a history of COVID-19 infection were surveyed between November 2020 and March 2021 using an instrument that assessed COVID-19-related matters. Analyses compared those who trusted versus mistrusted doctors and healthcare systems. RESULTS: 37 distrusting hospitalised black patients were compared with 103 black patients who trusted doctors and healthcare systems. Groups had similar sociodemographics (all p>0.05). Distrustful patients were less likely to think that they were at high risk of contracting COVID-19 (54.0% vs 75.7%; p=0.05), less likely to believe that people with underlying medical conditions were at higher risk of dying from the virus (86.4% vs 98.0%; p=0.01) and less likely to be willing to accept COVID-19 vaccination (when available) (51.3% vs 77.6%; p<0.01) compared with those who were trusting. CONCLUSION: Healthcare distrustful hospitalised black patients were doubtful of COVID-19 risk and hesitant about vaccination. Hospitalisations are concentrated exposures to the people and processes within healthcare systems; at these times, seizing the opportunity to establish meaningful relationships with patients may serve to gain their trust.
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Negro o Afroamericano , COVID-19 , Confianza , Adulto , Humanos , COVID-19/epidemiología , Estudios Transversales , Pandemias , Baltimore , Negro o Afroamericano/psicología , Conocimientos, Actitudes y Práctica en SaludRESUMEN
OBJECTIVES: Low-middle income countries, such as Vietnam have a greater burden from stroke than high-income countries. Few health professionals have stroke specialist training, and the quality of care may vary between hospitals. To support improvements to stroke care, we aimed to gain a better understanding of the resources available in hospitals in Vietnam to manage acute stroke. MATERIALS AND METHODS: The survey questions were adapted from the Australian Organisational Survey of Stroke Services (Stroke Foundation). The final 65 questions covered the topics: hospital size and admissions for stroke; use of clinical protocols and assessments conducted; team structure and coordination; communication and team roles. The survey was distributed electronically or via paper form in Vietnamese to clinical leaders of 91 eligible hospitals (November-December 2020). Data were summarised descriptively. RESULTS: Sixty-six (73%) hospitals responded, and doctors predominately completed the survey (98%). Approximately 70% of hospitals had a stroke unit; median 630 acute strokes/year (IQR: 250-1200) and >90% used stroke clinical protocols. The daytime nurse-patient ratio was 1:4. There was a perceived lack of access to allied health staff, including psychologists/neuropsychologists, occupational therapists, and speech pathologists. Only 50% reported having a standardised rehabilitation assessment process. CONCLUSIONS: This is the first large-scale cross-sectional, national overview of stroke services in Vietnam. Future research should include a systematic clinical audit of stroke care to confirm aspects of the data from these hospitals. Repeating the survey in future years will enable the tracking of progress and may influence capacity building for stroke care in Vietnam.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Estudios Transversales , Vietnam/epidemiología , Australia , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Encuestas y CuestionariosRESUMEN
In line with the activities of Task Group 103 under the International Commission on Radiological Protection (ICRP), the present study was conducted to develop a new set of alimentary tract organs consisting of the oral cavity, oesophagus, stomach, small intestine, and colon for the newborn, 1 year-old, 5 year-old, 10 year-old, and 15 year-old males and females for use in the pediatric mesh-type reference computational phantoms (MRCPs). The developed alimentary tract organs of the pediatric MRCPs, while nearly preserving the original topology and shape of those of the pediatric voxel-type reference computational phantoms (VRCPs) of ICRPPublication 143, present considerable anatomical improvement and include all micrometre-scale target and source regions as prescribed in ICRPPublication 100. To investigate the dosimetric impact of the developed alimentary tract organs, organ doses and specific absorbed fractions were computed for certain external exposures to photons and electrons and internal exposures to electrons, respectively, which were then compared with the values computed using the current ICRP models (i.e. pediatric VRCPs and ICRP-100 stylised models). The results showed that for external exposures to penetrating radiations (i.e. photons >0.04 MeV), there was generally good agreement between the compared values, within a 10% difference, except for the oral mucosa. For external exposures to weakly penetrating radiations (i.e. low-energy photons and electrons), there were significant differences, up to a factor of â¼8300, owing to the geometric difference caused by the anatomical enhancement in the MRCPs. For internal exposures of electrons, there were significant differences, the maximum of which reached a factor of â¼73 000. This was attributed not only to the geometric difference but also to the target mass difference caused by the different luminal content mass and organ shape.
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Protección Radiológica , Mallas Quirúrgicas , Niño , Preescolar , Simulación por Computador , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Método de Montecarlo , Fantasmas de Imagen , Fotones , Dosis de Radiación , Protección Radiológica/métodos , Radiometría/métodosRESUMEN
Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like PCBs (DL-PCBs) were examined in chicken egg and soil samples collected from Dong Nai Province, southern Vietnam. PCDD/F and DL-PCB levels in egg samples ranged from 5.74 to 1320 (median 350) and from 120 to 51,200 (median 1470) pg/g lipid weight (lw), respectively. Toxic equivalents to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TEQ) in egg samples ranged from 0.817 to 245 (median 10.8) pg TEQ/g lw. Higher dioxin levels were found in free-range eggs than non-free-range ones. We found significant correlation between TEQ levels in paired egg and soil samples collected from the Bien Hoa Airbase and some communities adjacent to industrial areas (Spearman's ρ = 0.671; p < 0.05), suggesting the co-occurrence of legacy and current dioxin emission sources in these areas.
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Dioxinas , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animales , Pollos , Dibenzofuranos , Dibenzofuranos Policlorados , Dioxinas/análisis , Contaminación de Alimentos/análisis , Bifenilos Policlorados/análisis , Dibenzodioxinas Policloradas/análisis , Suelo , VietnamRESUMEN
How people make initial and collective sense under crises remains unanswered. This paper addresses this question using the control of COVID-19 in Vietnam as a case study. Our results suggest that sensemaking under crises is influenced by an institutional propensity for prevention that has developed gradually over time. Local governments play a vital role in fostering collective sensemaking which enables concerted actions in epidemic control. However, biases are inherent in sensemaking, including a delay in access to vaccine and a violation of privacy. For policy makers, this study suggests that developing specific prevention policies and programs, building large-scale coordination capacity, and promoting local initiatives are necessary for coping with epidemics. For theory development, the study explores how institutions condition sensemaking and specifies several mechanisms in which local authorities could facilitate collective sensemaking in crises.
RESUMEN
The neural transcription factor SOX11 is usually highly expressed in typical mantle cell lymphoma (MCL), but it is absent in the more indolent form of MCL. Despite being an important diagnostic marker for this hard-to-treat malignancy, the mechanisms of aberrant SOX11 expression are largely unknown. Herein, we describe 2 modes of SOX11 regulation by the cell-cycle regulator cyclin D1 (CCND1) and the signal transducer and activator of transcription 3 (STAT3). We found that ectopic expression of CCND1 in multiple human MCL cell lines resulted in increased SOX11 transcription, which correlated with increased acetylated histones H3K9 and H3K14 (H3K9/14Ac). Increased H3K9/14Ac and SOX11 expression was also observed after histone deacetylase 1 (HDAC1) or HDAC2 was depleted by RNA interference or inhibited by the HDAC inhibitor vorinostat. Mechanistically, we showed that CCND1 interacted with and sequestered HDAC1 and HDAC2 from the SOX11 locus, leading to SOX11 upregulation. Interestingly, our data revealed a potential inverse relationship between phosphorylated Y705 STAT3 and SOX11 expression in MCL cell lines, primary tumors, and patient-derived xenografts. Functionally, inactivation of STAT3 by inhibiting the upstream Janus kinase (JAK) 1 or JAK2 or by STAT3 knockdown was found to increase SOX11 expression, whereas interleukin-21 (IL-21)-induced STAT3 activation or overexpression of the constitutively active form of STAT3 decreased SOX11 expression. In addition, targeting SOX11 directly by RNA interference or indirectly by IL-21 treatment induced toxicity in SOX11+ MCL cells. Collectively, we demonstrate the involvement of CCND1 and STAT3 in the regulation of SOX11 expression, providing new insights and therapeutic implications in MCL.