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1.
Ocul Immunol Inflamm ; : 1-4, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985812

RESUMO

PURPOSE: To demonstrate that the presence of active retinochoroiditis in eyes with previous hyperpigmented old retinochoroidal lesions is not exclusive of ocular toxoplasmosis. METHODS: A case series was constructed by reviewing medical records. RESULTS: Four Brazilian patients presenting active posterior uveitis in eyes with previous hyperpigmented old retinochoroidal lesions were identified. Ocular toxoplasmosis was ruled out in all cases. One case had viral etiology confirmed through vitreous PCR (HSV-2 was positive), and the other 3 cases had a presumed diagnosis of herpetic posterior uveitis. CONCLUSION: Focus active retinitis adjacent to an old cicatricial lesion should not be considered pathognomonic of toxoplasmosis and viral etiology must be considered.

2.
JMIR Med Inform ; 12: e59680, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954456

RESUMO

BACKGROUND: Named entity recognition (NER) is a fundamental task in natural language processing. However, it is typically preceded by named entity annotation, which poses several challenges, especially in the clinical domain. For instance, determining entity boundaries is one of the most common sources of disagreements between annotators due to questions such as whether modifiers or peripheral words should be annotated. If unresolved, these can induce inconsistency in the produced corpora, yet, on the other hand, strict guidelines or adjudication sessions can further prolong an already slow and convoluted process. OBJECTIVE: The aim of this study is to address these challenges by evaluating 2 novel annotation methodologies, lenient span and point annotation, aiming to mitigate the difficulty of precisely determining entity boundaries. METHODS: We evaluate their effects through an annotation case study on a Japanese medical case report data set. We compare annotation time, annotator agreement, and the quality of the produced labeling and assess the impact on the performance of an NER system trained on the annotated corpus. RESULTS: We saw significant improvements in the labeling process efficiency, with up to a 25% reduction in overall annotation time and even a 10% improvement in annotator agreement compared to the traditional boundary-strict approach. However, even the best-achieved NER model presented some drop in performance compared to the traditional annotation methodology. CONCLUSIONS: Our findings demonstrate a balance between annotation speed and model performance. Although disregarding boundary information affects model performance to some extent, this is counterbalanced by significant reductions in the annotator's workload and notable improvements in the speed of the annotation process. These benefits may prove valuable in various applications, offering an attractive compromise for developers and researchers.

3.
SAGE Open Nurs ; 10: 23779608241261622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881678

RESUMO

Introduction: Seasonal influenza remains a challenge in the United Arab Emirates, and vaccination is an important preventive measure. However, fear of needles may be an obstacle in vaccination efforts. Objective: The purpose of this study was to determine, in a non-clinical sample obtained from the UAE, how much of an impact fear of needles has on the decision to receive the seasonal influenza vaccine. Methods: In the period September-December 2022, 372 participants were surveyed on their willingness to be vaccinated, their level of vaccine knowledge, and their level of fear of needles. Logistic regression models were used to assess the impact of fear of needles and vaccine knowledge on the decision to accept the seasonal influenza vaccine. Results: Fear of needles and vaccine knowledge are significant predictors in the decision to receive the vaccine. There were no gender or ethnic differences in fear of needles, but there were differences in the decision to receive the vaccines, with women and non-Arabs being more hesitant. Conclusion: Fear of needles may be an important variable to account for in public policies designed to improve vaccination rates in the UAE. For public health policy in the UAE, this implies that authorities must dedicate efforts to manage fear of needles in the general population. Efforts to address fear of vaccines in the general population must be made with proper training of nurses. Alternatively, authorities may need to seek oral alternatives for the administration of the seasonal influenza vaccine.

4.
Int J Infect Dis ; 146: 107071, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710273

RESUMO

OBJECTIVE: We describe the clinical presentation and ocular viral dynamics in patients with Monkeypox virus-related ophthalmic disease (MPXROD). METHODS: In this case series, we investigated five consecutive patients with confirmed mpox, diagnosed through a positive Monkeypox virus (MPXV) Polymerase Chain Reaction (PCR) test and presenting with ocular symptoms. They were referred from the Reference Center for Sexually Transmitted Infections in São Paulo (CRT) to the Uveitis Sector at the Federal University of São Paulo, between August and December 2022. We performed PCR testing on ocular samples and culture supernatants for MPXV in all patients. Viral sequencing was conducted in one of the cases. RESULTS: Replicating MPXV was identified in at least one ocular sample of all patients, between day 31 and day 145 after the onset of skin lesions. All patients presented with keratitis, 3 with uveitis (60%) and two exhibited hypopyon (40%). The onset of ocular symptoms occurred at a mean of 21.2 days after the appearance of the first skin lesion and persisted, on average, for 61,.6 days, with a worsening trend observed until the initiation of tecovirimat treatment. Tecovirimat treatment was administered to all patients, with initiation occurring between 31 and 145 days after the onset of skin lesions. MPXV genome sequencing of an isolate from one patient classified it as belonging to lineage B1 in clade IIb. CONCLUSION: This study reveals a late onset and persistence of sight threatening ocular disease, along with potential viral infectivity even after systemic resolution in mpox cases. These findings highlight the risk of ongoing transmission from individuals with prolonged ocular manifestations, particularly through ocular discharge.

5.
Pharmaceuticals (Basel) ; 17(5)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38794175

RESUMO

Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κß inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia.

6.
J Med Philos ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805705

RESUMO

While some countries are moving toward legalization, euthanasia is still criticized on various fronts. Most importantly, it is considered a violation of the medical ethics principle of non-maleficence, because it actively seeks a patient's death. But, medical ethicists should consider an ethical alternative to euthanasia. In this article, we defend cryocide as one such alternative. Under this procedure, with the consent of terminally-ill patients, their clinical death is induced, in order to prevent the further advance of their brain's deterioration. Their body is then cryogenically preserved, in the hope that in the future, there will be a technology to reanimate it. This prospect is ethically distinct from euthanasia if a different criterion of death is assumed. In the information-theoretic criterion of death, a person is not considered dead when brain and cardiopulmonary functions cease, but rather, when information constituting psychology and memory is lost.

7.
Int J Mol Sci ; 25(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38791315

RESUMO

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.


Assuntos
Doenças Cardiovasculares , Receptores Depuradores Classe E , Humanos , Receptores Depuradores Classe E/metabolismo , Receptores Depuradores Classe E/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/etiologia , Animais , Lipoproteínas LDL/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia
8.
Nucleic Acids Res ; 52(9): 5152-5165, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647067

RESUMO

Structured noncoding RNAs (ncRNAs) contribute to many important cellular processes involving chemical catalysis, molecular recognition and gene regulation. Few ncRNA classes are broadly distributed among organisms from all three domains of life, but the list of rarer classes that exhibit surprisingly diverse functions is growing. We previously developed a computational pipeline that enables the near-comprehensive identification of structured ncRNAs expressed from individual bacterial genomes. The regions between protein coding genes are first sorted based on length and the fraction of guanosine and cytidine nucleotides. Long, GC-rich intergenic regions are then examined for sequence and structural similarity to other bacterial genomes. Herein, we describe the implementation of this pipeline on 50 bacterial genomes from varied phyla. More than 4700 candidate intergenic regions with the desired characteristics were identified, which yielded 44 novel riboswitch candidates and numerous other putative ncRNA motifs. Although experimental validation studies have yet to be conducted, this rate of riboswitch candidate discovery is consistent with predictions that many hundreds of novel riboswitch classes remain to be discovered among the bacterial species whose genomes have already been sequenced. Thus, many thousands of additional novel ncRNA classes likely remain to be discovered in the bacterial domain of life.


Assuntos
Genoma Bacteriano , RNA Bacteriano , RNA não Traduzido , DNA Intergênico/genética , Genoma Bacteriano/genética , Genômica/métodos , Riboswitch/genética , RNA Bacteriano/genética , RNA Bacteriano/química , RNA não Traduzido/genética , RNA não Traduzido/classificação , RNA não Traduzido/química
9.
Infect Prev Pract ; 6(2): 100361, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38646024

RESUMO

Aims: Hand hygiene (HH) is an essential practice to evade the transmission of germs and minimize community-acquired infections. This study assesses the knowledge, attitude and practice (KAP) of HH and other health and safety measures before, during, and after the COVID-19 pandemic. in university students in the United Arab Emirates (UAE). Methods: A cross-sectional questionnaire study was conducted between December 2022 and March 2023, targeting university students from all disciplines and study levels. A 44-item questionnaire was used which included student demographics, knowledge, attitude, and practice of HH, as well as the anticipated risk of COVID-19 morbidity and mortality. Participants consented before commencing the questionnaire, and the collected data were analysed using the student's t-test and ANOVA test, as required. Results: A total of 378 responses were received nationwide, with a valid response rate of 98%. The HH knowledge revealed an average score of 62%, which was significantly higher in students with moderate family income. Additionally, the average attitude score was 74.7%, as measured on the Likert scale, and the score lacked any correlation with the other variables. HH practice showed an average score of 86.8%, which was correlated with the students' gender and field of study. Conclusions: This study showed a moderate level of knowledge, a good attitude, and good practice around HH and other safety measures among the UAE's university students. Socioeconomic status, gender, and field of study influenced the study outcomes. This study highlights the need for effective awareness campaigns to reinforce students' health and safety, especially for male and non-health science students, in order to protect against communicable diseases.

10.
Acta Psychol (Amst) ; 246: 104245, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636404

RESUMO

This study was conducted at AU to estimate the prevalence of stress and burnout among medical students during the COVID-19 pandemic. This study aimed to provide insights into the levels of stress and burnout experienced by medical students at AU and identify potential risk factors. The research methodology involved a cross-sectional survey using a self-administered questionnaire among 215 College of Medicine AU students. The findings indicated that many participants experienced moderate stress levels, as revealed by data collected on a Likert scale. No significant differences in stress scores were found based on sex, but variations were observed among years of study and living status. An analysis of burnout using the Copenhagen Burnout Inventory showed that over half of the participants experienced moderate levels of burnout. No significant differences in burnout were found based on gender, marital status, residence, GPA, motivation for enrolment, or nationality; however, variations were observed among different age groups and years of study. These findings highlight the need for targeted interventions and support systems to address stress and burnout among AU students by focusing on the identified risk factors. By implementing evidence-based strategies, AU can promote the well-being and resilience of medical students, thereby contributing to their overall success and the future of the healthcare workforce.


Assuntos
Esgotamento Profissional , COVID-19 , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Masculino , Feminino , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Estudos Transversais , Adulto , Adulto Jovem , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Estresse Psicológico , Inquéritos e Questionários , Fatores de Risco , Esgotamento Psicológico/epidemiologia , Universidades , Prevalência
11.
BMC Med Educ ; 24(1): 212, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429676

RESUMO

BACKGROUND: Britain attracts doctors from all over the world to work in the National Health Service. Elucidating the educational backgrounds of award-winning doctors working in the country is potentially an important medical education issue and a merit award audit. Using the British clinical merit award schemes as outcome measures, we identify medical school origins of award-winning doctors who have been identified as having achieved national or international prominence. METHODS: The Clinical Excellence Awards/Distinction Awards schemes select doctors in Britain who are classified as high achievers, with categories for national prominence and above. We used this outcome measure in a quantitative observational analysis of the 2019-20 dataset of all 901 award-winning doctors. Pearson's Chi-Square test was used where appropriate. RESULTS: Five university medical schools (London university medical schools, Glasgow, Edinburgh, Aberdeen and Cambridge) accounted for 59.1% of the psychiatrist award-winning doctors in the 2019 round, despite the dataset representing 85 medical schools. 84.1% of the psychiatrist award-winners were from European medical schools, compared to 92.1% of the non-psychiatrist award-winners. International medical graduates accounted for 22.7% of the award-winning psychiatrists. Psychiatrists with the lower grade national awards came from a more diverse educational background of 17 medical schools. IMGs represented diverse medical schools from five continents and were most represented in the lowest grade of national merit awards at 24.2%. CONCLUSIONS: The majority of the award-winning psychiatrists originated from only five medical schools. A greater diversity of medical school origin existed for the lowest grade national psychiatrist award-winners. International medical graduates contributed substantially to these award-winners; psychiatrist award-winners were more likely to be international medical graduates (22.7%) than non-psychiatrist award-winners (10.8%). This study not only indicates educational centres associated with the production of award-winners but also provides students with a roadmap for rational decision making when selecting medical schools.


Assuntos
Distinções e Prêmios , Estudantes de Medicina , Humanos , Faculdades de Medicina , Psiquiatras , Medicina Estatal
12.
BMC Med Educ ; 24(1): 268, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459549

RESUMO

BACKGROUND: Educators and medical students share the same objective of achieving success in medical practice. Both groups consider doctors' successes to include optimum patient care outcomes and positive career progressions. Accordingly, identifying common educational features of such high-achieving doctors facilitates the generation of excellence amongst future medical trainees. In this study we use data from the British clinical merit award schemes as outcome measures in order to identify medical school origins of doctors who have achieved national or international prominence. METHODS: Britain has Clinical Excellence Awards/Distinction Awards schemes that financially reward all National Health Service doctors in England, Scotland and Wales who are classified as high achievers. We used these outcome measures in a quantitative observational analysis of the 2019-20 dataset of all 901 national award-winning doctors. Where appropriate, Pearson's Chi-Square test was applied. RESULTS: The top five medical schools (London university medical schools, Glasgow, Edinburgh, Oxford and Cambridge) were responsible for 51.2% of the physician merit award-winners in the 2019-20 round, despite the dataset representing 85 medical schools. 91.4% of the physician merit award-winners were from European medical schools. The lowest national award-winners (tier 3) originated from 61 medical schools representing six continents. International medical graduates comprised 11.4% of all award-winners. CONCLUSIONS: The majority of physicians who were national merit award-winners originated from only five, apparently overrepresented, UK university medical schools. In contrast, there was a greater diversity in medical school origin among the lower grade national merit awards; the largest number of international medical graduates were in these tier 3 awards (13.3%). As well as ranking educationally successful university medical schools, this study assists UK and international students, by providing a roadmap for rational decision making when selecting physician and non-physician medical education pathways that are more likely to fulfil their career ambitions.


Assuntos
Distinções e Prêmios , Médicos , Humanos , Faculdades de Medicina , Medicina Estatal , Inglaterra
13.
BMC Med Ethics ; 25(1): 19, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373945

RESUMO

Xenotransplantation has great potential as an alternative to alleviate the shortage of organs for donation. However, given that the animal most suited for xenotransplantation is the pig, there are concerns that people in Muslim countries may be more hesitant to morally approve of these procedures. In this study, the moral approval of xenotransplantation was assessed in a group of 895 participants in Egypt. The results showed that religiosity itself does not predict moral approval of xenotransplantation, but religious identity does, as Muslims are less likely to approve of xenotransplantation than Christians. However, the strongest predictor of moral approval of xenotransplantation was gender, with women displaying less approval. A partial mediating factor in this association was concern for animal welfare. Based on these results, some implications for public policy are discussed.


Assuntos
Princípios Morais , Religião , Humanos , Feminino , Animais , Suínos , Transplante Heterólogo , Egito , Demografia
14.
Animals (Basel) ; 14(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338024

RESUMO

The indiscriminate use of antimicrobials in animal husbandry can result in various types of environmental contamination. Part of the dose of these products is excreted, still active, in the animals' feces and urine. These excreta are widely used as organic fertilizers, which results in contamination with antimicrobial molecules. The impacts can occur in several compartments, such as soil, groundwater, and surface watercourses. Also, contamination by antimicrobials fed or administrated to pigs, chickens, and cattle can reach the meat, milk, and other animal products, which calls into question the sustainability of using these products as part of eco-friendly practices. Therefore, a search for alternative natural products is required to replace the conventional antimicrobials currently used in animal husbandry, aiming to mitigate environmental contamination. We thus carried out a review addressing this issue, highlighting wood vinegar (WV), also known as pyroligneous acid, as an alternative antimicrobial with good potential to replace conventional products. In this regard, many studies have demonstrated that WV is a promising product. WV is a nontoxic additive widely employed in the food industry to impart a smoked flavor to foods. Studies have shown that, depending on the WV concentration, good results can be achieved using it as an antimicrobial against pathogenic bacteria and fungi and a valuable growth promoter for poultry and pigs.

15.
J Sleep Res ; : e14148, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233953

RESUMO

Perceived ethnic discrimination is known to be associated with anxiety and depression, and in turn, anxiety and depression are known to be associated with nightmare frequency and distress. This elicits a question: is perceived ethnic discrimination associated with nightmare frequency and distress? In this study, 179 female university students from the United Arab Emirates were assessed to answer that question. Results showed that while anxiety and depression were related to nightmare experiences, perceived ethnic discrimination was a stronger predictor of nightmare experiences. We posit two explanations for this finding: one based on psychoanalytical insights, and the other based on the Disposition-Stress model with neurobiological correlates. No significant differences were found across ethnicity when it comes to nightmare experiences or perceived ethnic discrimination. This is an encouraging sign of optimal societal integration in the United Arab Emirates.

16.
Camb Q Healthc Ethics ; : 1-8, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38221736

RESUMO

Despite progress, discrimination in public health remains a problem. A significant aspect of this problem relates to how medical resources are allocated. The paradigm of quality-adjusted-life-year (QALY) dictates that medical resources should be allocated on the basis of units measured as length of life and quality of life that are expected after the implementation of a treatment. In this article, I discuss some of the ethical shortcomings of QALY, by focusing on some of its flawed moral aspects, as well as the way it relates to discrimination on the basis of age, race, and disability status. I argue that while this approach seeks to maximize efficiency, it does not place sufficient value on the preservation of life itself. Even more concerning is the fact that the use of QALY disproportionately harms minorities. While QALY is a well-intentioned approach to the allocation of scarce healthcare resources, new alternatives must be sought.

17.
Pediatr Nephrol ; 39(2): 569-577, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37552466

RESUMO

BACKGROUND: In patients requiring mechanical circulatory support (MCS), the incidence of acute kidney injury (AKI) is between 37 and 63%. In this study, we performed an exploratory analysis evaluating the relationship of multiple urine biomarkers with AKI development in pediatric MCS patients. METHODS: This is a single center retrospective study in a pediatric cohort receiving MCS from August 2014 to November 2020. We measured 14 urine biomarkers of kidney injury on day 1 following MCS initiation and analyzed their association with development of AKI in the first 7 days of MCS initiation. RESULTS: Sixty patients met inclusion criteria. Patients with AKI were more likely to be supported by venoarterial extracorporeal membrane oxygenation (65% vs. 8.3%, p < 0.001), compared to the no AKI group and less likely to have ventricular assist devices (10% vs. 50%, p < 0.001). There was a significant increase in the median urine albumin and urine osteoactivin in the AKI group, compared to the no AKI group (p = 0.020 and p = 0.018, respectively). When normalized to urine creatinine (UCr), an increased log osteoactivin/UCr was associated with higher odds of AKI development (OR: 2.05; 95% CI: 1.07, 4.44; p = 0.028), and higher log epidermal growth factor (EGF)/UCr (OR: 0.41; 95% CI: 0.15, 0.96) was associated with decreased odds of AKI. CONCLUSIONS: Early increase in urine osteoactivin is associated with AKI development within 7 days of MCS initiation in pediatric patients. Contrary, an increased urine EGF is associated with kidney protection. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Injúria Renal Aguda , Fator de Crescimento Epidérmico , Humanos , Criança , Estudos Retrospectivos , Biomarcadores/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Creatinina/urina , Fatores de Transcrição
18.
Mol Metab ; 79: 101849, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056691

RESUMO

OBJECTIVE: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. METHODS: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. RESULTS: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. CONCLUSIONS: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.


Assuntos
Injúria Renal Aguda , Rabdomiólise , Camundongos , Animais , Transportadores de Ácidos Monocarboxílicos/metabolismo , Injúria Renal Aguda/metabolismo , Oxirredução , Rabdomiólise/induzido quimicamente , Rabdomiólise/metabolismo , Oxidantes/efeitos adversos
19.
Eur J Nucl Med Mol Imaging ; 51(5): 1395-1408, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38095674

RESUMO

PURPOSE: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as an additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLT nephrotoxicity. METHODS: A bifunctional cyclic peptide, melanocortin 1 ligand (MC1L), labeled with [203Pb]Pb-MC1L, was used for [212Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [212Pb]Pb-MC1L in a dose-escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. RESULTS: Biodistribution analysis identified [212Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [212Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [212Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. CONCLUSION: Urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.


Assuntos
Chumbo , Insuficiência Renal Crônica , Camundongos , Animais , Lipocalina-2/urina , Distribuição Tecidual , Detecção Precoce de Câncer , Biomarcadores , Creatinina
20.
Rev. bras. oftalmol ; 83: e0016, 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1559589

RESUMO

ABSTRACT A 41 year-old man presented with unilateral vision loss for a week and constitutional symptoms for 3 months. Ophthalmic evaluation revealed cotton wool spots on the right eye and widespread retinal necrosis and hemorrhage on the left eye, suggestive of cytomegalovirus uveitis and HIV infection and retinopathy, and confirmed by serology. The patient was treated with ganciclovir and highly active antiretroviral therapy and preserved contralateral vision. Clinicians should be aware of uveitis and retinopathies to prevent irreversible vision loss and systemic conditions.


RESUMO Paciente do sexo masculino, 41 anos, com queixa de perda de acuidade visual unilateral por 1 semana e sintomas constitucionais por 3 meses. Ao exame oftalmológico, apresentava exsudatos algodonosos, em olho direito, e áreas de necrose e hemorragias retinianas, em olho esquerdo, com suspeita de uveíte por citomegalovírus e retinopatia por HIV, confirmadas por sorologias. O paciente foi tratado com ganciclovir e terapia antirretroviral e preservou a visão contralateral. Os oftalmologistas devem estar atentos para casos de uveítes e retinopatias, para prevenirem perda visual irreversível e condições sistêmicas.

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