ABSTRACT
Hypereosinophilic syndrome is a rare systemic condition characterized by eosinophil-mediated organ damage. Cardiac involvement is common and typically occurs in sequential stages. We present two cases that demonstrate these different stages and presentations of eosinophilia-mediated myocardial disease, where multimodality imaging was essential for the diagnosis. More importantly, they demonstrate, for the first time, the dissociation between the eosinophil count and patients' clinical evolution, suggesting the need for close follow up even after the eosinophilia has been controlled. Learning objective: Cardiac involvement in hypereosinophilic syndrome typically occurs in three stages - necrotic, thrombotic, and fibrotic. Although cardiac damage is mediated by eosinophils, the blood eosinophil count and patients' clinical evolution are dissociated. Therefore, eosinophil count on its own is not an adequate marker of clinical evolution, and cardiac follow up should be continued even after the eosinophilia has been controlled.
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UNESCO's Intergovernmental Oceanographic Commission launched the United Nations Decade of Ocean Science for Sustainable Development in 2021 to boost global and sustainable Ocean governance. The initiative resulted from historical and political dynamics at the global and lower political scales, with maritime environmental and economic concerns becoming more prominent in 2010. The Ocean Decade's pillars include science and research, sustainability, conservation, and bridging gaps for a global Ocean-Climate-Biodiversity nexus. The Sustainable Development Goals recognized the importance of oceans and marine resources, and the Ocean was officially perceived as a determining factor of Climate Change at CoP 21 in 2015. Portugal has built integrated and far-reaching policies for ocean governance, including significant involvement with an international perspective since the Lisbon World Exhibition in 1998. In addition, the national government established a Ministry of the Sea in 2015 to re-develop relations with its maritime space. This article analyzes and compares the discourse of the United Nations' Sustainable Development Goals reports and the Portuguese government programs (2005-2022) to explore the prominent trends in Portuguese Ocean governance discourse and how global and national perspectives interact. Through this case study, the research aims to develop insights into the multiscalar impacts of promoting global and sustainable Ocean governance and its interaction with national perspectives.
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Prostate cancer (PCa) remains a significant global health concern, being a major cause of cancer morbidity and mortality worldwide. Furthermore, profound understanding of the disease is needed. Prostate inflammation caused by external or genetic factors is a central player in prostate carcinogenesis. However, the mechanisms underlying inflammation-driven PCa remain poorly understood. This review dissects the diagnosis methods for PCa and the pathophysiological mechanisms underlying the disease, clarifying the dynamic interplay between inflammation and leukocytes in promoting tumour development and spread. It provides updates on recent advances in elucidating and treating prostate carcinogenesis, and opens new insights for the use of bioactive compounds in PCa. Polyphenols, with their noteworthy antioxidant and anti-inflammatory properties, along with their synergistic potential when combined with conventional treatments, offer promising prospects for innovative therapeutic strategies. Evidence from the use of polyphenols and polyphenol-based nanoparticles in PCa revealed their positive effects in controlling tumour growth, proliferation, and metastasis. By consolidating the diverse features of PCa research, this review aims to contribute to increased understanding of the disease and stimulate further research into the role of polyphenols and polyphenol-based nanoparticles in its management.
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In this work, we demonstrate the development and first application of nanocapillary sampling followed by analytical flow liquid chromatography-mass spectrometry for single-cell lipidomics. Around 260 lipids were tentatively identified in a single cell, demonstrating remarkable sensitivity. Human pancreatic ductal adenocarcinoma cells (PANC-1) treated with the chemotherapeutic drug gemcitabine can be distinguished from controls solely on the basis of their single-cell lipid profiles. Notably, the relative abundance of LPC(0:0/16:0) was significantly affected in gemcitabine-treated cells, in agreement with previous work in bulk. This work serves as a proof of concept that live cells can be sampled selectively and then characterized using automated and widely available analytical workflows, providing biologically relevant outputs.
Subject(s)
Lipidomics , Pancreatic Neoplasms , Humans , Chromatography, Liquid , Lipidomics/methods , Lipids/analysis , Tandem Mass Spectrometry , Pancreatic Neoplasms/drug therapy , Gemcitabine , Pancreatic NeoplasmsABSTRACT
Noncommunicable diseases (NCDs) present a major public health challenge, prompting their inclusion in the United Nations' 2030 Agenda for Sustainable Development. In response, the World Health Organization (WHO) has implemented various initiatives, including a comprehensive monitoring framework with global targets and indicators. However, the extent to which these initiatives have shaped the scientific discourse remains unclear. This article addresses this knowledge gap through a two-fold approach. Firstly, a bibliometric analysis of 14,187 studies spanning over 60 years is conducted, identifying key contributors and trends. Secondly, the content analysis compares these trends to the goals established by the WHO. The findings indicate that the WHO initiatives have accelerated scientific research, and elevated global targets and indicators as central themes in scholarly discussions, since 2011. This study takes an innovative approach that contributes to the advancement of knowledge in this field, by providing valuable insights into the impact of WHO initiatives on the scientific debate surrounding NCDs, and offering guidance for policymakers, researchers, and stakeholders engaged in combating these diseases.
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Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been shown to enhance fingermark recovery compared to standard processes used by police forces, but there is no data to show how generally applicable the improvement is. Additionally, ToF-SIMS can be run in either positive or negative ion mode (or both), and there is no data on which mode of operation is most effective at revealing fingerprints. This study aims to fill these gaps by using ToF-SIMS to image fingerprints deposited on two common exhibit-type surfaces (polyethylene and stainless steel) using 10 donors and ageing fingerprints in either ambient, rainwater, or underground for 1 and 5 months. In all, 120 fingerprints were imaged using ToF-SIMS, and each was run in positive and negative modes. A fingerprint expert compared the fingerprint ridge detail produced by the standard process to the ToF-SIMS images. In over 50% of the samples, ToF-SIMS was shown to improve fingerprint ridge detail visualised by the respective standard process for all surfaces tested. In over 90% of the samples, the ridge detail produced by ToF-SIMS was equivalent to standard development across all different ageing and exposure conditions. The data shows that there is a benefit to running the ToF-SIMS in both positive and negative modes, even if no ridge detail was seen in one mode.
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This work aims to clarify the psychosocial variables that lead women to undertake and those that prevent them from doing so. Two studies were conducted using a mixed methodology to compensate for the inherent weaknesses of using each approach. The first study was based on the collection of quantitative data using the GloPEW questionnaire with a sample of 296 people. The second study, of a qualitative nature, was carried out through focus groups with a sample of 26 people. The results show that self-efficacy and emotional intelligence are the main factors to develop to promote entrepreneurship among women. Although the data show statistical strength, it seems necessary to expand the sample and incorporate more profiles of female entrepreneurs, for example, with different levels of training, given the complexity and variety of intervening factors.
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The colocation of elemental species with host biomolecules such as lipids and metabolites may shed new light on the dysregulation of metabolic pathways and how these affect disease pathogeneses. Alkali metals have been the subject of extensive research, are implicated in various neurodegenerative and infectious diseases and are known to disrupt lipid metabolism. Desorption electrospray ionisation (DESI) is a widely used approach for molecular imaging, but previous work has shown that DESI delocalises ions such as potassium (K) and chlorine (Cl), precluding the subsequent elemental analysis of the same section of tissue. The solvent typically used for the DESI electrospray is a combination of methanol and water. Here we show that a novel solvent system, (50:50 (%v/v) MeOH:EtOH) does not delocalise elemental species and thus enables elemental mapping to be performed on the same tissue section post-DESI. Benchmarking the MeOH:EtOH electrospray solvent against the widely used MeOH:H2O electrospray solvent revealed that the MeOH:EtOH solvent yielded increased signal-to-noise ratios for selected lipids. The developed multimodal imaging workflow was applied to a lung tissue section containing a tuberculosis granuloma, showcasing its applicability to elementally rich samples displaying defined structural information.
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Metabolic flux is the final output of cellular regulation and has been extensively studied for carbon but much less is known about nitrogen, which is another important building block for living organisms. For the tuberculosis pathogen, this is particularly important in informing the development of effective drugs targeting the pathogen's metabolism. Here we performed 13 C15 N dual isotopic labeling of Mycobacterium bovis BCG steady state cultures, quantified intracellular carbon and nitrogen fluxes and inferred reaction bidirectionalities. This was achieved by model scope extension and refinement, implemented in a multi-atom transition model, within the statistical framework of Bayesian model averaging (BMA). Using BMA-based 13 C15 N-metabolic flux analysis, we jointly resolve carbon and nitrogen fluxes quantitatively. We provide the first nitrogen flux distributions for amino acid and nucleotide biosynthesis in mycobacteria and establish glutamate as the central node for nitrogen metabolism. We improved resolution of the notoriously elusive anaplerotic node in central carbon metabolism and revealed possible operation modes. Our study provides a powerful and statistically rigorous platform to simultaneously infer carbon and nitrogen metabolism in any biological system.
Subject(s)
Carbon , Nitrogen , Carbon/metabolism , Carbon Isotopes/metabolism , Nitrogen/metabolism , Metabolic Flux Analysis , Bayes Theorem , Models, BiologicalABSTRACT
The processes routinely used by police forces to visualise fingermarks in casework may not provide sufficient ridge pattern quality to aid an investigation. Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS) has been proposed as a technique to enhance fingermark recovery. The technique is currently designated a Category C process in the Fingermark Visualisation Manual (FVM) as it shows potential for effective fingermark visualisation but has not yet been fully evaluated. Here the sensitivity of ToF-SIMS on three common exhibit-type surfaces - paper, polyethylene and stainless-steel was compared to standard processes. An adapted Home Office grading scale was used to evaluate the efficacy of fingerprint development by ToF-SIMS and to provide a framework for comparison with standard processes. ToF-SIMS was shown to visualise more fingerprints than the respective standard process, for all surfaces tested. In addition, ToF-SIMS was applied after the standard processes and successfully enhanced the fingerprint detail, even when the standard process failed to visualise ridge detail. This demonstrates the benefit for incorporating it into current operational fingermark development workflows. Multivariate analysis (MVA), using simsMVA, was additionally explored as a method to simplify the data analysis and image generation process.
Subject(s)
Dermatoglyphics , Spectrometry, Mass, Secondary Ion , Humans , Spectrometry, Mass, Secondary Ion/methods , Police , Multivariate AnalysisABSTRACT
Characterizing proton beam damage in biological materials is of interest to enable the integration of proton microprobe elemental mapping techniques with other imaging modalities. It is also of relevance to obtain a deeper understanding of mechanical damage to lipids in tissues during proton beam cancer therapy. We have developed a novel strategy to characterize proton beam damage to lipids in biological tissues based on mass spectrometry imaging. This methodology is applied to characterize changes to lipids in tissues ex vivo, irradiated under different conditions designed to mitigate beam damage. This work shows that performing proton beam irradiation at ambient pressure, as well as including the application of an organic matrix prior to irradiation, can reduce damage to lipids in tissues. We also discovered that, irrespective of proton beam irradiation, placing a sample in a vacuum prior to desorption electrospray ionization imaging can enhance lipid signals, a conclusion that may be of future benefit to the mass spectrometry imaging community.
Subject(s)
Multimodal Imaging , ProtonsABSTRACT
Vibriosis, an often-fatal disease induced by pathogenic members of the Vibrionaceae family, causes severe economic losses in aquacultures. To mitigate/avoid vibriosis outbursts, it is vital to detect and quantify these pathogens as early as possible. However, standard microbiological methods are time-consuming and often underestimate cell counts, which calls for the development of valid alternatives. In this study, real-time polymerase chain reaction (qPCR) was employed to detect the pathogenic species Vibrio alginolyticus, Listonella anguillara, and Vibrio harveyi using a new primer pair targeting the groEL gene. In addition, the DNA extraction efficiency of three methods, two commercial kits and the boiling method, was compared. The most efficient method was the DNeasy Blood and Tissue kit, with a detection limit ranging between 154 and 600 CFU mL-1 in the case of V. alginolyticus and L. anguillara, and 48 CFU mL-1 for V. harveyi. Thus, this study presents the development and evaluation of a method for the early quantification of all three species in saline suspensions. However, the results obtained by spiking a microalgae sample with V. harveyi emphasize the importance of adjusting the DNA control's standard curve to the relevant extraction matrices, as it affects the DNA extraction efficiency and may hamper an accurate quantification with qPCR.
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Positive body image (PBI) has received attention in the recent research literature. Despite this, its role in daily functioning in different cultural contexts, particularly its potential relationship with academic outcomes, is still lacking. This study aimed to offer an international perspective on the association between PBI and body mass index (BMI), perceived academic achievement, and educational aspirations, as well as the mediating role of self-esteem. A cross-national study was conducted in eight European countries with a total of 2653 female university students. Participants completed an online survey measuring PBI (conceptualized as body appreciation), self-esteem, perceived academic achievement and aspirations, and body mass index (BMI). Results revealed differences in PBI between countries (low magnitude). PBI correlated negatively with BMI in all national groups (low-to-moderate magnitude). Mediation analysis showed that self-esteem mediated the association between PBI and academic variables. Findings from this study suggest that building students' self-esteem and PBI can be a suitable way to boost academic success.
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Chemotherapy-associated cardiotoxicity is a common adverse event. Immune checkpoint inhibitors (ICI) - a new class of monoclonal antibodies - have revolutionized the management of various diseases. Their use is expected to increase in the near future and their cardiac side effects have been increasingly recognized. CLINICAL CASE: We describe a case of a 67-year-old female patient with urothelial carcinoma undergoing treatment with pembrolizumab who presented to the emergency department with progressive fatigue, retrosternal pain and palpitations for three days. On admission she was diagnosed with acute heart failure (HF). The electrocardiogram revealed a right bundle branch block and ventricular bigeminy. Blood tests showed elevated troponin I, while transthoracic echocardiography revealed severe left ventricular dysfunction. Coronary angiography excluded coronary artery disease. Cardiac magnetic resonance revealed moderate left ventricular dysfunction and late gadolinium enhancement typical of myocarditis. Endomyocardial biopsy confirmed the diagnosis of lymphocytic myocarditis. In the first 48h of hospitalization, she developed transient complete AV block. Corticoid and HF therapy were initiated, leading to symptom improvement and disappearance of the rhythm disturbances. She was discharged on the 12th day, maintaining moderate LV dysfunction, which improved only mildly at a subsequent outpatient assessment. She died suddenly 35 days after discharge. CONCLUSION: Lymphocytic myocarditis is a serious cardiac side effect of ICI therapy. Pembrolizumab is increasingly used, so it is important to be aware of its effects, in order to perform an early diagnosis and provide adequate treatment. Corticosteroid therapy seems to be crucial in preventing disease progression and enabling ventricular remodeling.
Subject(s)
Antineoplastic Agents , Carcinoma, Transitional Cell , Myocarditis , Urinary Bladder Neoplasms , Ventricular Dysfunction, Left , Female , Humans , Aged , Immune Checkpoint Inhibitors/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Contrast Media , Urinary Bladder Neoplasms/drug therapy , Gadolinium/therapeutic use , Myocarditis/diagnosisSubject(s)
Herpes Simplex , Retinal Necrosis Syndrome, Acute , Humans , Retinal Necrosis Syndrome, Acute/diagnosis , Retinal Necrosis Syndrome, Acute/drug therapy , Retinal Necrosis Syndrome, Acute/etiology , Herpes Simplex/complications , Herpes Simplex/diagnosis , Herpes Simplex/drug therapy , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , DNA, ViralABSTRACT
BACKGROUND: The COVID-19 pandemic is likely to represent an ongoing global health issue given the potential for new variants, vaccine escape and the low likelihood of eliminating all reservoirs of the disease. Whilst diagnostic testing has progressed at a fast pace, the metabolic drivers of outcomes-and whether markers can be found in different biofluids-are not well understood. Recent research has shown that serum metabolomics has potential for prognosis of disease progression. In a hospital setting, collection of saliva samples is more convenient for both staff and patients, and therefore offers an alternative sampling matrix to serum. METHODS: Saliva samples were collected from hospitalised patients with clinical suspicion of COVID-19, alongside clinical metadata. COVID-19 diagnosis was confirmed using RT-PCR testing, and COVID-19 severity was classified using clinical descriptors (respiratory rate, peripheral oxygen saturation score and C-reactive protein levels). Metabolites were extracted and analysed using high resolution liquid chromatography-mass spectrometry, and the resulting peak area matrix was analysed using multivariate techniques. RESULTS: Positive percent agreement of 1.00 between a partial least squares-discriminant analysis metabolomics model employing a panel of 6 features (5 of which were amino acids, one that could be identified by formula only) and the clinical diagnosis of COVID-19 severity was achieved. The negative percent agreement with the clinical severity diagnosis was also 1.00, leading to an area under receiver operating characteristics curve of 1.00 for the panel of features identified. CONCLUSIONS: In this exploratory work, we found that saliva metabolomics and in particular amino acids can be capable of separating high severity COVID-19 patients from low severity COVID-19 patients. This expands the atlas of COVID-19 metabolic dysregulation and could in future offer the basis of a quick and non-invasive means of sampling patients, intended to supplement existing clinical tests, with the goal of offering timely treatment to patients with potentially poor outcomes.
Subject(s)
COVID-19 , Amino Acids/metabolism , Biomarkers/metabolism , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19 Testing , Chromatography, Liquid/methods , Humans , Mass Spectrometry/methods , Metabolomics/methods , Pandemics , Saliva/metabolismABSTRACT
Seaweeds are an important source of nutrients and bioactive compounds and have a high potential as health boosters in aquaculture. This study evaluated the effect of dietary inclusion of Gracilaria gracilis biomass or its extract on the European seabass (Dicentrarchus labrax) gut microbial community. Juvenile fish were fed a commercial-like diet with 2.5% or 5% seaweed biomass or 0.35% seaweed extract for 47 days. The gut microbiome was assessed by 16S rRNA amplicon sequencing, and its diversity was not altered by the seaweed supplementation. However, a reduction in Proteobacteria abundance was observed. Random forest analysis highlighted the genera Photobacterium, Staphylococcus, Acinetobacter, Micrococcus and Sphingomonas, and their abundances were reduced when fish were fed diets with algae. SparCC correlation network analysis suggested several mutualistic and other antagonistic relationships that could be related to the predicted altered functions. These pathways were mainly related to the metabolism and biosynthesis of protective compounds such as ectoine and were upregulated in fish fed diets supplemented with algae. This study shows the beneficial potential of Gracilaria as a functional ingredient through the modulation of the complex microbial network towards fish health improvement.
Subject(s)
Bass , Gastrointestinal Microbiome , Gracilaria , Animal Feed/analysis , Animals , Bass/metabolism , Diet , Plant Extracts/metabolism , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolismABSTRACT
Elemental imaging is widely used for imaging cells and tissues but rarely in combination with organic mass spectrometry, which can be used to profile lipids and measure drug concentrations. Here, we demonstrate how elemental imaging and a new method for spatially resolved lipidomics (DAPNe-LC-MS, based on capillary microsampling and liquid chromatography mass spectrometry) can be used in combination to probe the relationship between metals, drugs, and lipids in discrete areas of tissues. This new method for spatial lipidomics, reported here for the first time, has been applied to rabbit lung tissues containing a lesion (caseous granuloma) caused by tuberculosis infection. We demonstrate how elemental imaging with spatially resolved lipidomics can be used to probe the association between ion accumulation and lipid profiles and verify local drug distribution.