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PURPOSE: Neither the United States nor the European oncology guidelines include details for appropriate management of hyperglycemia in cancer patients. The aim was to identify fasting and random blood glucose thresholds, and hemoglobin A1c (HbA1c) targets used by oncologists in clinical practice when managing hyperglycemia in patients with cancer undergoing chemotherapy. METHODS: This national, cross sectional study utilized a questionnaire to collect oncologists' perceptions about optimal blood glucose thresholds and HbA1c targets in patients with cancer undergoing chemotherapy. Descriptive statistics were calculated to summarize glucose thresholds, HbA1c targets, and sample characteristics. Responses to an open-ended question about oncologists' approach to hyperglycemia management were analyzed via thematic analysis using an inductive approach. RESULTS: Respondents (n = 229) were on average 52.1 years of age, 67.7% men, and 91.3% White. For patients without diabetes but experiencing hyperglycemia, oncologists targeted lower and upper fasting blood glucose levels between 75-121 mg/dL and 105-135 mg/dL, respectively. For patients with diabetes, the targets for lower and upper fasting blood glucose levels ranged between 100-130 mg/dL and 128-150 mg/dL, respectively. Fasting blood glucose (95.6%) and HbA1c (78.6%) were the most commonly used clinical indicators to consider chemotherapy dose reduction, delay, or discontinuation due to hyperglycemia in patients receiving chemotherapy with curative intent. Among those receiving palliative intent chemotherapy, the preferred clinical parameters were random blood glucose (90.0%), patient-reported blood glucose readings (70.7%), continuous glucose monitoring readings (65.1%), and patient-reported symptoms of hyperglycemia (65.1%). Three main themes emerged about oncologists' approach to hyperglycemia management: 1) identification of high-risk patients; 2) need for early identification, screening, and diagnosis of hyperglycemia; and 3) multiple hyperglycemia management strategies. CONCLUSION: Oncologists reported a wide variation of target blood glucose ranges considered appropriate in patients undergoing chemotherapy. Lack of clear guidance for hyperglycemia management during chemotherapy in the United States may be contributing to a lack of consistency in clinical practice.
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Antineoplásicos , Glucemia , Hemoglobina Glucada , Hiperglucemia , Neoplasias , Oncólogos , Pautas de la Práctica en Medicina , Humanos , Estudios Transversales , Hiperglucemia/inducido químicamente , Masculino , Femenino , Persona de Mediana Edad , Glucemia/análisis , Glucemia/efectos de los fármacos , Hemoglobina Glucada/análisis , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/normas , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Adulto , Anciano , Estados UnidosRESUMEN
Elevated levels of circulating C16:0 glucosylceramides (GluCer) and increased mRNA expression of UDP-glucose ceramide glycosyltransferase (UGCG), the enzyme responsible for converting ceramides (Cer) to GluCer, represent unfavorable prognostic markers in chronic lymphocytic leukemia (CLL) patients. To evaluate the therapeutic potential of inhibiting GluCer synthesis, we genetically repressed the UGCG pathway using in vitro models of leukemic B cells, in addition to UGCG pharmacological inhibition with approved drugs such as eliglustat and ibiglustat, both individually and in combination with ibrutinib, assessed in cell models and primary CLL patient cells. Cell viability, apoptosis, and proliferation were evaluated in vitro, and survival and apoptosis were examined ex vivo. UGCG inhibition efficacy was confirmed by quantifying intracellular sphingolipid levels through targeted lipidomics using mass spectrometry. Other inhibitors of sphingolipid biosynthesis pathways were similarly assessed. Blocking UGCG significantly decreased cell viability and proliferation, highlighting the oncogenic role of UGCG in CLL. The efficient inhibition of UGCG was confirmed by a significant reduction in GluCer intracellular levels. The combination of UGCG inhibitors with ibrutinib demonstrated synergistic effect. Inhibitors that target alternative pathways within sphingolipid metabolism, like sphingosine kinases inhibitor SKI-II, also demonstrated promising therapeutic effects both alone and when used in combination with ibrutinib, reinforcing the oncogenic impact of sphingolipids in CLL cells. Targeting sphingolipid metabolism, especially the UGCG pathway, represents a promising therapeutic strategy and as a combination therapy for potential treatment of CLL patients, warranting further investigation.
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Supervivencia Celular , Leucemia Linfocítica Crónica de Células B , Esfingolípidos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Humanos , Esfingolípidos/metabolismo , Supervivencia Celular/efectos de los fármacos , Glucosiltransferasas/antagonistas & inhibidores , Glucosiltransferasas/metabolismo , Glucosiltransferasas/genética , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Piperidinas/farmacología , Adenina/análogos & derivados , Adenina/farmacología , Antineoplásicos/farmacología , Línea Celular Tumoral , Glucosilceramidas/metabolismo , Pirazoles/farmacología , Pirimidinas/farmacologíaRESUMEN
Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.
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Aim: Our aim is to determine the applicability of other analyses and develop a new formula appropriate for the Vietnamese population. Materials and Methods: A cross-sectional descriptive analysis was conducted on a total of 120 dental arch samples (18-25 years old, 60 males, and 60 females) with <5 mm of tooth crowding, complete teeth on the dental arch, no missing teeth, and no fillings on the mesial or distal sides. Each study sample will be imprinted and measured using conventional as well as digital methods. Result: There was a significant discrepancy between the overall mesiodistal width from canine to second premolar in the maxilla and mandibular measured with electronic calipers on the cast model and the values calculated by the Moyer, Tanaka - Johnston, Gross - Hasund formulae in the mandibular, and measured by digital scanning and results calculated by the Gross-Hasund formula for maxilla and mandibular and the Moyers, Tanaka-Johnston formula for mandibular. The values obtained were compared with those calculated using the Moyers, Tanaka-Johnston, and Gross-Hasund formulae for the mandibular. Additionally, measurements were taken by digital scanning, and the results were calculated using the Gross-Hasund formula for both the maxilla and mandibular, and the Moyers and Tanaka-Johnston formulae for the mandibular. When used to estimate space analysis in the Vietnamese population, the estimation formula for each gender had greater accuracy and reliability than other widely used methods. Conclusions: As the central incisor and first molar are the first permanent teeth to erupt, the mesiodistal width may be readily measured. This new formula may be used to predict the width in the early stages of the mixed dentition.
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Background: Iliac artery stenosis or occlusion is a critical condition that can severely impact a patient's quality of life. The effectiveness of balloon angioplasty and intraluminal stenting for the treatment of iliac artery lesions classified as TASC II A and B was evaluated in this single-center prospective study. Methods: Conducted between October 2016 and September 2020 at Cho Ray Hospital's Vascular Surgery Department, this prospective study involved PAD patients categorized by TASC II A and B classifications who underwent endovascular intervention. Intervention outcomes were assessed peri-procedure and during short-term and mid-term follow-ups. Results: Of the total of 133 patients, 34.6% underwent balloon angioplasty, while 65.4% received stenting. The immediate technical success rate was 97.7%, while the clinical success rate was 62.4%. Complications were minimal, with major limb amputation reported in 1.5% of the cases. There was a significant improvement in Rutherford classification and ABI at short-term follow-up, with a patency rate of 90.2%. The mid-term post-intervention follow-up yielded similar results with an 86.1% patency rate. The mortality rates associated with arterial occlusion were 2.3% during short-term follow-up and 1.7% during mid-term follow-up. Conclusion: Balloon angioplasty and stent placement are effective and safe interventions for TASC II A and B iliac artery occlusions with favorable short and mid-term outcomes. Further, multi-center studies with larger sample sizes are recommended for more comprehensive conclusions, including long-term follow-up assessment.
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This report examines a case of systemic hypersensitivity to tirzepatide in a patient with type 2 diabetes. Tirzepatide (Mounjaro®), a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor, has recently gained FDA approval. Additionally, a literature review was conducted to summarize recent research on tirzepatide's effectiveness and safety. A 67-year-old woman, previously treated with basal insulin, metformin, and semaglutide (a GLP-1 agonist), experienced severe disseminated pruritus and a generalized urticarial rash after her first dose of tirzepatide. This reaction, which subsided with antihistamines, raises questions about possible immunoglobulin E-mediated hypersensitivity. The report highlights the need for increased vigilance regarding allergic reactions to new diabetes medications, particularly in the context of GIP/GLP-1 receptor agonists.
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Root architecture and function are critical for plants to secure water and nutrient supply from the soil, but environmental stresses alter root development. The phytohormone jasmonic acid (JA) regulates plant growth and responses to wounding and other stresses, but its role in root development for adaptation to environmental challenges had not been well investigated. We discovered a novel JA Upregulated Protein 1 gene (JAUP1) that has recently evolved in rice and is specific to modern rice accessions. JAUP1 regulates a self-perpetuating feed-forward loop to activate the expression of genes involved in JA biosynthesis and signalling that confers tolerance to abiotic stresses and regulates auxin-dependent root development. Ectopic expression of JAUP1 alleviates abscisic acid- and salt-mediated suppression of lateral root (LR) growth. JAUP1 is primarily expressed in the root cap and epidermal cells (EPCs) that protect the meristematic stem cells and emerging LRs. Wound-activated JA/JAUP1 signalling promotes crosstalk between the root cap of LR and parental root EPCs, as well as induces cell wall remodelling in EPCs overlaying the emerging LR, thereby facilitating LR emergence even under ABA-suppressive conditions. Elevated expression of JAUP1 in transgenic rice or natural rice accessions enhances abiotic stress tolerance and reduces grain yield loss under a limited water supply. We reveal a hitherto unappreciated role for wound-induced JA in LR development under abiotic stress and suggest that JAUP1 can be used in biotechnology and as a molecular marker for breeding rice adapted to extreme environmental challenges and for the conservation of water resources.
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Ciclopentanos , Oryza , Oxilipinas , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fitomejoramiento , Reguladores del Crecimiento de las Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas/genéticaRESUMEN
The rapid global economic growth driven by industrialization and population expansion has resulted in significant issues, including reliance on fossil fuels, energy scarcity, water crises, and environmental emissions. To address these issues, bioelectrochemical systems (BES) have emerged as a dual-purpose solution, harnessing electrochemical processes and the capabilities of electrochemically active microorganisms (EAM) to simultaneously recover energy and treat wastewater. This review examines critical performance factors in BES, including inoculum selection, pretreatment methods, electrodes, and operational conditions. Further, authors explore innovative approaches to suppress methanogens and simultaneously enhance the EAM in mixed cultures. Additionally, advanced techniques for detecting EAM are discussed. The rapid detection of EAM facilitates the selection of suitable inoculum sources and optimization of enrichment strategies in BESs. This optimization is essential for facilitating the successful scaling up of BES applications, contributing substantially to the realization of clean energy and sustainable wastewater treatment. This analysis introduces a novel viewpoint by amalgamating contemporary research on the selective enrichment of EAM in mixed cultures. It encompasses identification and detection techniques, along with methodologies tailored for the selective enrichment of EAM, geared explicitly toward upscaling applications in BES.
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Ácidos Alcanesulfónicos , Fuentes de Energía Bioeléctrica , Transporte de Electrón , ElectrodosRESUMEN
BACKGROUND: Metabolic dependencies of chronic lymphocytic leukaemia (CLL) cells may represent new personalized treatment approaches in patients harbouring unfavourable features. METHODS: Here, we used untargeted metabolomics and lipidomics analyses to isolate metabolomic features associated with aggressive CLL and poor survival outcomes. We initially focused on profiles associated with overexpression of the adverse metabolic marker glycosyltransferase (UGT2B17) associated with poor survival and drug resistance. RESULTS: Leukaemic B-cell metabolomes indicated a significant perturbation in lipids, predominantly bio-active sphingolipids. Expression of numerous enzyme-encoding genes of sphingolipid biosynthesis pathways was significantly associated with shorter patient survival. Targeted metabolomics further exposed higher circulating levels of glucosylceramides (C16:0 GluCer) in CLL patients relative to healthy donors and an aggressive cancer biology. In multivariate analyses, C16:0 GluCer and sphinganine were independent prognostic markers and were inversely linked to treatment-free survival. These two sphingolipid species function as antagonistic mediators, with sphinganine being pro-apoptotic and GluCer being pro-proliferative, tested in leukemic B-CLL cell models. Blocking GluCer synthesis using ceramide glucosyltransferase inhibitors induced cell death and reduced the proliferative phenotype, which further sensitized a leukaemic B-cell model to the anti-leukaemics fludarabine and ibrutinib in vitro. CONCLUSIONS: Specific sphingolipids may serve as prognostic markers in CLL, and inhibiting enzymatic pathways involved in their biosynthesis has potential as a therapaeutic approach.
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Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Esfingolípidos/genética , Esfingolípidos/metabolismo , Esfingolípidos/uso terapéutico , Metabolómica , Linfocitos B/metabolismoRESUMEN
We report an in situ vaccination, adaptable to nearly any type of cancer, that combines radiotherapy targeting one tumor and intratumoral injection of this site with tumor-specific antibody and interleukin-2 (IL-2; 3xTx). In a phase I clinical trial, administration of 3xTx (with an immunocytokine fusion of tumor-specific antibody and IL-2, hu14.18-IL2) to subjects with metastatic melanoma increases peripheral CD8+ T cell effector polyfunctionality. This suggests the potential for 3xTx to promote antitumor immunity against metastatic tumors. In poorly immunogenic syngeneic murine melanoma or head and neck carcinoma models, 3xTx stimulates CD8+ T cell-mediated antitumor responses at targeted and non-targeted tumors. During 3xTx treatment, natural killer (NK) cells promote CTLA4+ regulatory T cell (Treg) apoptosis in non-targeted tumors. This is dependent on NK cell expression of CD86, which is upregulated downstream of KLRK1. NK cell depletion increases Treg infiltration, diminishing CD8+ T cell-dependent antitumor response. These findings demonstrate that NK cells sustain and propagate CD8+ T cell immunity following 3xTx.
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Interleucina-2 , Melanoma , Ratones , Humanos , Animales , Interleucina-2/metabolismo , Melanoma/metabolismo , Células Asesinas Naturales , Linfocitos T CD8-positivos , VacunaciónRESUMEN
Sera of immune mice that were previously cured of their melanoma through a combined radiation and immunocytokine immunotherapy regimen consisting of 12 Gy of external beam radiation and the intratumoral administration of an immunocytokine (anti-GD2 mAb coupled to IL-2) with long-term immunological memory showed strong antibody-binding against melanoma tumor cell lines via flow cytometric analysis. Using a high-density whole-proteome peptide array (of 6.090.593 unique peptides), we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by these 6 mice and exhibited strong antibody binding only by immune (after successful cure and rechallenge), not naïve (before tumor implantation) sera and developed a robust method to detect these differentially targeted peptides. Confirmatory studies were done to validate these results using 2 separate systems, a peptide ELISA and a smaller scale peptide array utilizing a slightly different technology. To the best of our knowledge, this is the first study of the full set of germline encoded linear peptide-based proteome epitopes that are recognized by immune sera from mice cured of cancer via radio-immunotherapy. We furthermore found that although the generation of B-cell repertoire in immune development is vastly variable, and numerous epitopes are identified uniquely by immune serum from each of these 6 immune mice evaluated, there are still several epitopes and proteins that are commonly recognized by at least half of the mice studied. This suggests that every mouse has a unique set of antibodies produced in response to the curative therapy, creating an individual "fingerprint." Additionally, certain epitopes and proteins stand out as more immunogenic, as they are recognized by multiple mice in the immune group.
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Melanoma , Animales , Ratones , Proteoma , Ratones Endogámicos C57BL , Inmunoterapia , Péptidos , Epítopos , Sueros InmunesRESUMEN
Aims: The objective of this study is to assess the effectiveness of the combined middle and inferior meatal antrostomy (MIMA) in management of patients with maxillary fungal sinusitis. Material and Methods: Design: retrospective cross sectional study. Setting and subjects: From September 2018 to March 2021, fifty-five patients with non-invasive maxillary fungal sinusitis, who underwent transnasal endoscopic combined MIMA. Methods: The study compared patients' pre- and post-operative subjective symptoms, including nasal obstruction, discharge, facial pain or pressure, halitosis, anosmia, and other non-specific symptoms. Endoscopic characteristics of recurrent fungal maxillary sinusitis and postoperative complications were also observed. Closure of the IMA site was evaluated at three and six months post-surgery and patients were categorized into three groups based on closure degree. Results: All clinical symptoms, including nasal discharge, nasal obstruction, nasal pruritus, anosmia, halitosis, sneezing, facial pain, ophthalmic and otologic symptoms, were resolved over six months after combined MIMA in majority of cases (94 - 100%). After three and six months, the postoperative endoscopic evaluation revealed recurrent fungal maxillary sinusitis in 1.8% and 5.4% of cases, respectively. Partial stenosis of the inferior antrostomy was observed in 7.2% and 16% of cases, while complete stenosis was noted in 3.6% and 7.2% of cases after three months and six months. Conclusions: The combined MIMA is effective and has better outcomes than the medial meatal antrostomy approach alone without additional operative time. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03863-6.
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We present a portable multiplexed biosensor platform based on the extended gate field-effect transistor and demonstrate its amplified response thanks to gold nanoparticle-based bioconjugates introduced as a part of the immunoassay. The platform comprises a disposable chip hosting an array of 32 extended gate electrodes, a readout module based on a single transistor operating in constant charge mode, and a multiplexer to scan sensing electrodes one-by-one. Although employing only off-the-shelf electronic components, our platform achieves sensitivities comparable to fully customized nanofabricated potentiometric sensors. In particular, it reaches a detection limit of 0.2 fM for the pure molecular assay when sensing horseradish peroxidase-linked secondary antibody (â¼0.4 nM reached by standard microplate methods). Furthermore, with the gold nanoparticle bioconjugation format, we demonstrate ca. 5-fold amplification of the potentiometric response compared to a pure molecular assay, at the detection limit of 13.3 fM. Finally, we elaborate on the mechanism of this amplification and propose that nanoparticle-mediated disruption of the diffusion barrier layer is the main contributor to the potentiometric signal enhancement. These results show the great potential of our portable, sensitive, and cost-efficient biosensor for multidimensional diagnostics in the clinical and laboratory settings, including e.g., serological tests or pathogen screening.
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Técnicas Biosensibles , Nanopartículas del Metal , Oro , Técnicas Biosensibles/métodos , Potenciometría , Inmunoensayo , ElectrodosRESUMEN
Traditional pork value chains dominate the production and distribution of pork in Vietnam; however, the high level of microbiological contamination in pork may increase the risk of food-borne disease for consumers. There is limited evidence about how to feasibly and scalably reduce microbial contamination in pork sold in traditional markets. This study aimed to assess the effectiveness of light-touch interventions for changing worker behaviour in small-scale slaughterhouses and vendors at traditional pork shops, as well as to identify risk factors for pork contamination. The intervention packages consisted of providing hygiene tools and delivering a food safety training which had been designed in a participatory way and covered 10 small-scale slaughterhouses and 29 pork shops. Pig carcasses, retailed pork, contact surfaces, and hands were sampled to measure the total bacterial count (TBC) and Salmonella contamination before, three and six weeks after the intervention, and trainee practices were observed at the same time. Linear and generalized linear mixed effects models were constructed to identify risk factors for TBC and Salmonella contamination at the slaughterhouses and pork shops. The interventions at slaughterhouses and pork shops both showed a slight reduction of TBC contamination in pig carcasses and Salmonella prevalence in retailed pork, while the TBC in retailed pork decreased only marginally. For slaughterhouses, the regression model indicated that smoking or eating during slaughtering (indicating poor hygienic practices) was associated with TBC increasing, while cleaning floors and wearing boots reduced TBC contamination. For pork shops, using rough materials (cardboard or wood) to display pork was the only factor increasing TBC contamination in pork, whereas cleaning knives was associated with lower TBC. Besides, the presence of supporters and wearing aprons reduced the probability of Salmonella contamination in pork. The findings highlight the effectiveness of light-touch interventions in reducing microbial contamination in pig carcasses at small-scale slaughterhouses and pork at traditional shops over the study period.
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Carne de Cerdo , Carne Roja , Porcinos , Animales , Carne Roja/microbiología , Carne/microbiología , Mataderos , Vietnam , Tacto , Salmonella , Factores de Riesgo , Contaminación de Alimentos/prevención & control , Contaminación de Alimentos/análisisRESUMEN
The development of a reference atlas of the healthy human body requires automated image segmentation of major anatomical structures across multiple organs based on spatial bioimages generated from various sources with differences in sample preparation. We present the setup and results of the Hacking the Human Body machine learning algorithm development competition hosted by the Human Biomolecular Atlas (HuBMAP) and the Human Protein Atlas (HPA) teams on the Kaggle platform. We create a dataset containing 880 histology images with 12,901 segmented structures, engaging 1175 teams from 78 countries in community-driven, open-science development of machine learning models. Tissue variations in the dataset pose a major challenge to the teams which they overcome by using color normalization techniques and combining vision transformers with convolutional models. The best model will be productized in the HuBMAP portal to process tissue image datasets at scale in support of Human Reference Atlas construction.
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Algoritmos , Aprendizaje Automático , Humanos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Background: Vietnam was one of the countries pursuing the goal of "Zero-COVID" and had effectively achieved it in the first three waves of the pandemic. However, the spread of the Delta variant was outbreak first in Vietnam in late April 2021, in which Ho Chi Minh City was the worst affected. This study surveyed the public's knowledge, attitude, perception, and practice (KAPP) toward COVID-19 during the rapid rise course of the outbreak in Ho Chi Minh City. Methods: This cross-sectional survey was conducted from 30th September to 16th November 2021, involving 963 residents across the city. We asked residents a series of 21 questions. The response rate was 76.6%. We set a priori level of significance at α = 0.05 for all statistical tests. Results: The residents' KAPP scores were 68.67% ± 17.16, 77.33% ± 18.71, 74.7% ± 26.25, and 72.31% ± 31, respectively. KAPP scores of the medical staff were higher than the non-medical group. Our study showed positive, medium-strong Pearson correlations between knowledge and practice (r = 0.337), attitude and practice (r = 0.405), and perception and practice (r = 0.671; p < 0.05). We found 16 rules to estimate the conditional probabilities among KAPP scores via the association rule mining method. Mainly, 94% confident probability of participants had {Knowledge=Good, Attitude=Good, Perception=Good}, as well as {Practice=Good} (in rule 9 with support of 17.6%). In opposition to around 86% to 90% of the times, participants had levels of {Perception=Fair, Practice=Poor} given with either {Attitude=Fair} or {Knowledge=Fair} (according to rules 1, 2, and rules 15, 16 with a support of 7-8%). Conclusion: In addition to the government's directives and policies, citizens' knowledge, attitude, perception, and practice are considered one of the critical preventive measures during the COVID-19 pandemic. The results affirmed the good internal relationship among K, A, P, and P scores creating a hierarchy of healthcare educational goals and health behavior among residents.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Transversales , SARS-CoV-2 , Vietnam , Pandemias , Conocimientos, Actitudes y Práctica en Salud , PercepciónRESUMEN
PURPOSE: To assess oncologists' responsibility, comfort, and knowledge managing hyperglycemia in patients undergoing chemotherapy. METHODS: In this cross-sectional study, a questionnaire collected oncologists' perceptions about professionals responsible for managing hyperglycemia during chemotherapy; comfort (score range 12-120); and knowledge (score range 0-16). Descriptive statistics were calculated including Student t-tests and one-way ANOVA for mean score differences. Multivariable linear regression identified predictors of comfort and knowledge scores. RESULTS: Respondents (N = 229) were 67.7% men, 91.3% White and mean age 52.1 years. Oncologists perceived endocrinologists/diabetologists and primary care physicians as those responsible for managing hyperglycemia during chemotherapy, and most frequently referred to these clinicians. Reasons for referral included lack of time to manage hyperglycemia (62.4%), belief that patients would benefit from referral to an alternative provider clinician (54.1%), and not perceiving hyperglycemia management in their scope of practice (52.4%). The top-3 barriers to patient referral were long wait times for primary care (69.9%) and endocrinology (68.1%) visits, and patient's provider outside of the oncologist's institution (52.8%). The top-3 barriers to treating hyperglycemia were lack of knowledge about when to start insulin, how to adjust insulin, and what insulin type works best. Women (ß = 1.67, 95% CI: 0.16, 3.18) and oncologists in suburban areas (ß = 6.98, 95% CI: 2.53, 11.44) had higher comfort scores than their respective counterparts; oncologists working in practices with > 10 oncologists had lower comfort scores (ß = -2.75, 95% CI: -4.96, -0.53) than those in practices with ≤ 10. No significant predictors were identified for knowledge. CONCLUSION: Oncologists expected endocrinology or primary care clinicians to manage hyperglycemia during chemotherapy, but long wait times were among the top barriers cited when referring patients. New models that provide prompt and coordinated care are needed.
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Hiperglucemia , Insulinas , Neoplasias , Oncólogos , Masculino , Humanos , Femenino , Persona de Mediana Edad , Estudios Transversales , Oncología Médica , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios , Hiperglucemia/inducido químicamente , Hiperglucemia/prevención & control , Actitud del Personal de Salud , Pautas de la Práctica en MedicinaRESUMEN
In chronic lymphocytic leukemia (CLL), an elevated glycosyltransferase UGT2B17 expression (UGT2B17HI) identifies a subgroup of patients with shorter survival and poor drug response. We uncovered a mechanism, possibly independent of its enzymatic function, characterized by an enhanced expression and signaling of the proximal effectors of the pro-survival B cell receptor (BCR) pathway and elevated Bruton tyrosine kinase (BTK) phosphorylation in B-CLL cells from UGT2B17HI patients. A prominent feature of B-CLL cells is the strong correlation of UGT2B17 expression with the adverse marker ZAP70 encoding a tyrosine kinase that promotes B-CLL cell survival. Their combined high expression levels in the treatment of naïve patients further defined a prognostic group with the highest risk of poor survival. In leukemic cells, UGT2B17 knockout and repression of ZAP70 reduced proliferation, suggesting that the function of UGT2B17 might involve ZAP70. Mechanistically, UGT2B17 interacted with several kinases of the BCR pathway, including ZAP70, SYK, and BTK, revealing a potential therapeutic vulnerability. The dual SYK and JAK/STAT6 inhibitor cerdulatinib most effectively compromised the proliferative advantage conferred by UGT2B17 compared to the selective BTK inhibitor ibrutinib. Findings point to an oncogenic role for UGT2B17 as a novel constituent of BCR signalosome also connected with microenvironmental signaling.
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Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Transducción de Señal , Fosforilación , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Antígenos de Histocompatibilidad Menor/metabolismoRESUMEN
Reducing high electron and ion heat fluxes is one of the critical issues for shielding satellites and spacecraft. One of the ideas for shielding high particle and heat fluxes is to apply an external magnetic field generated by injecting current filaments. In this work, we model a flow of plasma, which includes electrons and ions in a small region, by using two spatial dimensions and three coordinates for velocities (2D3V) Particle-In-Cell (PIC) code to study the effects of the injected current filaments on particle and heat fluxes to the wall. The plasma enters the simulation domain from the source region at the left boundary and is fully absorbed in the conductor wall at the right boundary. Current filaments are injected to change the magnetic field structure of the system. We compare particle density, particle flux, and heat flux with and without injecting the current filaments into the domain in two dimensions. Based on the simulation results, we found that injecting current filaments can reduce the peak fluxes to the wall and transfer some of those fluxes along the wall. Therefore, injecting the current filaments is a good candidate for shielding satellites and spacecraft from high-energy ion and electron fluxes.
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While evaluations play a critical role in accounting for and learning from context, it is unclear how evaluations can take account of climate change. Our objective was to explore how climate change and its interaction with other contextual factors influenced One Health food safety programs. To do so, we integrated questions about climate change into a qualitative evaluation study of an ongoing, multi-sectoral program aiming to improve pork safety in Vietnam called SafePORK. We conducted remote interviews with program researchers (n = 7) and program participants (n = 23). Based on our analysis, researchers believed climate change had potential impacts on the program but noted evidence was lacking, while program participants (slaughterhouse workers and retailers) shared how they were experiencing and adapting to the impacts of climate change. Climate change also interacted with other contextual factors to introduce additional complexities. Our study underscored the importance of assessing climate factors in evaluation and building adaptive capacity in programming.