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1.
Comput Biol Med ; 180: 108957, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39098236

RESUMO

The tremors of Parkinson's disease (PD) and essential tremor (ET) are known to have overlapping characteristics that make it complicated for clinicians to distinguish them. While deep learning is robust in detecting features unnoticeable to humans, an opaque trained model is impractical in clinical scenarios as coincidental correlations in the training data may be used by the model to make classifications, which may result in misdiagnosis. This work aims to overcome the aforementioned challenge of deep learning models by introducing a multilayer BiLSTM network with explainable AI (XAI) that can better explain tremulous characteristics and quantify the respective discovered important regions in tremor differentiation. The proposed network classifies PD, ET, and normal tremors during drinking actions and derives the contribution from tremor characteristics, (i.e., time, frequency, amplitude, and actions) utilized in the classification task. The analysis shows that the XAI-BiLSTM marks the regions with high tremor amplitude as important in classification, which is verified by a high correlation between relevance distribution and tremor displacement amplitude. The XAI-BiLSTM discovered that the transition phases from arm resting to lifting (during the drinking cycle) is the most important action to classify tremors. Additionally, the XAI-BiLSTM reveals frequency ranges that only contribute to the classification of one tremor class, which may be the potential distinctive feature to overcome the overlapping frequencies problem. By revealing critical timing and frequency patterns unique to PD and ET tremors, this proposed XAI-BiLSTM model enables clinicians to make more informed classifications, potentially reducing misclassification rates and improving treatment outcomes.

2.
Int J Biol Macromol ; 277(Pt 1): 133938, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39029815

RESUMO

Arrowroot starch (AS)-based films potential is influenced by its low-cost processing and high transparency packaging material but low tensile strength; hence, AS was blended with kappa-carrageenan (KC) to improve mechanical properties of AS-based films and enhance its potential use in food packaging or coating applications. AS-KC-based films were characterized based on structural, physicomechanical, thermal, pasting properties, and coating application in sweet cherry. The films demonstrated high tensile strength from 3.2 to 29.4 MPa and low elongation properties from 160.3 % to 1.9 %. Moreover, AS/KC films exhibited peak viscosities of 18.7 to 34.8 RVU, and thermal analysis depicted lower weight losses (59-45 %) compared to AS-based films (62 %). In addition, sweet cherry samples coated with AS/KC films and stored at 20 °C for 15 days depicted lower weight losses (26.6 %) compared to non-coated samples (>41 %), which indicated the potential use of the film's coating application in extending the shelf life and quality of fresh fruits.

3.
Technol Cancer Res Treat ; 23: 15330338241260331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860337

RESUMO

OBJECTIVE: To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP (P < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUCmin > 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). CONCLUSION: Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.


Assuntos
Carcinoma Hepatocelular , Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Meglumina , Compostos Organometálicos , Curva ROC , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Meglumina/análogos & derivados , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Aumento da Imagem/métodos , Idoso de 80 Anos ou mais
4.
Sci Adv ; 10(23): eadm9589, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38838142

RESUMO

DNA replication stress (RS) is a widespread phenomenon in carcinogenesis, causing genomic instability and extensive chromatin alterations. DNA damage leads to activation of innate immune signaling, but little is known about transcriptional regulators mediating such signaling upon RS. Using a chemical screen, we identified protein arginine methyltransferase 5 (PRMT5) as a key mediator of RS-dependent induction of interferon-stimulated genes (ISGs). This response is also associated with reactivation of endogenous retroviruses (ERVs). Using quantitative mass spectrometry, we identify proteins with PRMT5-dependent symmetric dimethylarginine (SDMA) modification induced upon RS. Among these, we show that PRMT5 targets and modulates the activity of ZNF326, a zinc finger protein essential for ISG response. Our data demonstrate a role for PRMT5-mediated SDMA in the context of RS-induced transcriptional induction, affecting physiological homeostasis and cancer therapy.


Assuntos
Replicação do DNA , Imunidade Inata , Proteína-Arginina N-Metiltransferases , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Humanos , Transdução de Sinais , Arginina/metabolismo , Arginina/análogos & derivados , Estresse Fisiológico , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Dano ao DNA , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
5.
Clin Infect Dis ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916975

RESUMO

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically-relevant sub-phenotypes can be reproducibly identified amongst patients with SAB. METHODS: We studied three cohorts of hospitalised adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n=458), the UK ARREST randomised trial (n=758), and the Spanish SAFO randomised trial (n=214). Latent class analysis was used to identify sub-phenotypes using routinely-collected clinical data, without considering outcomes. Mortality and microbiologic outcomes were then compared between sub-phenotypes. RESULTS: Included patients had predominantly methicillin-susceptible SAB (1366/1430,95.5%). We identified five distinct, reproducible clinical sub-phenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the sub-phenotypes. 84-day mortality was highest in sub-phenotype A, and lowest in B and E. Microbiologic outcomes were worse in sub-phenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased 84-day mortality in sub-phenotype B and improved microbiologic outcomes in sub-phenotype C. CONCLUSIONS: We have identified reproducible and clinically-relevant sub-phenotypes within SAB, and provide proof-of-principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these sub-phenotypes could contribute to a personalised medicine approach to SAB.

6.
Abdom Radiol (NY) ; 49(7): 2242-2249, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38824474

RESUMO

OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.


Assuntos
Carcinoma Hepatocelular , Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Meglumina , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Idoso , Meglumina/análogos & derivados , Compostos Organometálicos , Adulto , Microvasos/diagnóstico por imagem , Microvasos/patologia , Aumento da Imagem/métodos
7.
Clin Infect Dis ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767234

RESUMO

BACKGROUND: We aimed to test the hypothesis that development of metastatic infection represents a distinct clinical endpoint from death due to SAB. METHODS: We conducted a retrospective observational study of adults with SAB between 20/12/2019 and 23/08/2022 (n=464). Simple logistic regression, odds ratios, and z-scores were used to compare host, clinical and microbiologic features. RESULTS: Co-occurrence of attributable mortality and metastatic infection was infrequent. Charlson Comorbidity Index and age were strongly associated with attributable mortality, but not metastatic infection. We compared patients with fatal SAB (without clinically-apparent metastatic complications, 14·4% of cohort), metastatic SAB (without attributable mortality, 22·2%), neither complication (56·7%), and overlapping fatal/metastatic SAB (6·7%). Compared to SAB without complications, fatal SAB was specifically associated with older age and multi-morbidity. Metastatic SAB was specifically associated with community acquisition, persistent fever, persistent bacteraemia, and recurrence. Endocarditis was over-represented in the fatal/metastatic SAB overlap group, which shared patient characteristics with fatal SAB. In contrast to other (predominantly musculoskeletal) metastatic complications, endocarditis was associated with increased mortality, with death occurring in older multi-morbid patients later after SAB onset. CONCLUSIONS: Patients with SAB experience distinct clinical endpoints: (i) early death, associated with multi-morbidity and age; (ii) metastatic (predominantly musculoskeletal) SAB; (iii) endocarditis, associated with late death occurring in older people with multi-morbidity, and (iv) bacteraemia without complications. These distinctions could be important for selecting appropriate outcomes in clinical trials: different interventions might be required to reduce mortality vs. improve clinical response in patients with metastatic SAB.

8.
Nat Commun ; 15(1): 2113, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459052

RESUMO

Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL. We reveal transcriptomic differences between macrophages within RLTs (light zone /dark zone, germinal center/ interfollicular), and between disease states (RLTs/ DLBCL), which we then use to generate six spatially-derived macrophage signatures (MacroSigs). We proceed to interrogate these MacroSigs in macrophage and DLBCL single-cell RNA-sequencing datasets, and in gene-expression data from multiple DLBCL cohorts. We show that specific MacroSigs are associated with cell-of-origin subtypes and overall survival in DLBCL. This study provides a spatially-resolved whole-transcriptome atlas of macrophages in reactive and malignant lymphoid tissues, showing biological and clinical significance.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Linfoma Difuso de Grandes Células B/patologia , Perfilação da Expressão Gênica , Transcriptoma , Centro Germinativo/patologia , Microambiente Tumoral/genética
9.
Sci Rep ; 13(1): 18622, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37903843

RESUMO

The distinction between Parkinson's disease (PD) and essential tremor (ET) tremors is subtle, posing challenges in differentiation. To accurately classify the PD and ET, BiLSTM-based recurrent neural networks are employed to classify between normal patients (N), PD patients, and ET patients using accelerometry data on their lower arm (L), hand (H), and upper arm (U) as inputs. The trained recurrent neural network (RNN) has reached 80% accuracy. The neural network is analyzed using layer-wise relevance propagation (LRP) to understand the internal workings of the neural network. A novel explainable AI method, called LRP-based approximate linear weights (ALW), is introduced to identify the similarities in relevance when assigning the class scores in the neural network. The ALW functions as a 2D kernel that linearly transforms the input data directly into the class scores, which significantly reduces the complexity of analyzing the neural network. This new classification method reconstructs the neural network's original function, achieving a 73% PD and ET tremor classification accuracy. By analyzing the ALWs, the correlation between each input and the class can also be determined. Then, the differentiating features can be subsequently identified. Since the input is preprocessed using short-time Fourier transform (STFT), the differences between the magnitude of tremor frequencies ranging from 3 to 30 Hz in the mean N, PD, and ET subjects are successfully identified. Aside from matching the current medical knowledge on frequency content in the tremors, the differentiating features also provide insights about frequency contents in the tremors in other frequency bands and body parts.


Assuntos
Tremor Essencial , Doença de Parkinson , Humanos , Tremor , Inteligência Artificial , Redes Neurais de Computação , Peso ao Nascer
10.
Br J Surg ; 110(11): 1451-1457, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37682691

RESUMO

BACKGROUND: The conventional approach to treatment for Paget's disease of the breast has been mastectomy, but there is an increasing trend to consider breast-conserving surgery (BCS) followed by radiotherapy (RT) in these patients. This study aimed to provide an updated systematic review and meta-analysis comparing outcomes after BCS with RT versus mastectomy in the treatment of Paget's disease of the breast. METHODS: Studies before May 2021 were included. Primary outcomes were overall survival and local recurrence. Separate analyses of Paget's disease associated with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were undertaken. Meta-regression was used to adjust for imbalance in the proportion of IDC among patients selected to undergo BCS versus mastectomy. RESULTS: Overall survival in patients with Paget's disease who underwent BCS with RT was higher than for those who underwent mastectomy with pooled mortality hazard ratio (HR) of 0.68, (95% per cent c.i. 0.45 to 1.01). Patients with Paget's disease with DCIS had higher overall survival after BCS with or without RT versus mastectomy, with adjusted HR of 0.14 (0.10 to 0.20) and 0.28 (0.22 to 0.36), respectively. For patients with Paget's disease and IDC, overall survival was lower for BCS with or without RT versus mastectomy, with adjusted HR of 0.84 (0.57 to 1.25) and 1.64 (1.04 to 2.58), respectively. In Paget's disease and IDC, local recurrence risk was much higher for BCS with RT, RR 26.8 (1.60 to 456) versus without RT, RR 51.8 (6.80 to 391). In patients with Paget's disease and DCIS, risk of local recurrence versus mastectomy was lower for BCS with RT 0.72 (0.11 to 4.50) but slightly higher for BCS alone 1.38 (0.09 to 21.20). CONCLUSION: BCS with RT may be a comparable treatment alternative to mastectomy for patients with Paget's disease with DCIS, and for selected patients with Paget's disease and IDC.

11.
Pathogens ; 12(4)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37111448

RESUMO

The ongoing global emergence of arthropod-borne (arbo) viruses has accelerated research into the interactions of these viruses with the immune systems of their vectors. Only limited information exists on how bunyaviruses, such as Rift Valley fever virus (RVFV), are sensed by mosquito immunity or escape detection. RVFV is a zoonotic phlebovirus (Bunyavirales; Phenuiviridae) of veterinary and human public health and economic importance. We have shown that the infection of mosquitoes with RVFV triggers the activation of RNA interference pathways, which moderately restrict viral replication. Here, we aimed to better understand the interactions between RVFV and other vector immune signaling pathways that might influence RVFV replication and transmission. For this, we used the immunocompetent Aedes aegypti Aag2 cell line as a model. We found that bacteria-induced immune responses restricted RVFV replication. However, virus infection alone did not alter the gene expression levels of immune effectors. Instead, it resulted in the marked enhancement of immune responses to subsequent bacterial stimulation. The gene expression levels of several mosquito immune pattern recognition receptors were altered by RVFV infection, which may contribute to this immune priming. Our findings imply that there is a complex interplay between RVFV and mosquito immunity that could be targeted in disease prevention strategies.

12.
J Alzheimers Dis ; 94(s1): S45-S66, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776068

RESUMO

BACKGROUND: Neurodegenerative diseases (NDs) impose significant financial and healthcare burden on populations all over the world. The prevalence and incidence of NDs have been observed to increase dramatically with age. Hence, the number of reported cases is projected to increase in the future, as life spans continues to rise. Despite this, there is limited effective treatment against most NDs. Interferons (IFNs), a family of cytokines, have been suggested as a promising therapeutic target for NDs, particularly IFN-α, which governs various pathological pathways in different NDs. OBJECTIVE: This systematic review aimed to critically appraise the currently available literature on the pathological role of IFN-α in neurodegeneration/NDs. METHODS: Three databases, Scopus, PubMed, and Ovid Medline, were utilized for the literature search. RESULTS: A total of 77 journal articles were selected for critical evaluation, based on the inclusion and exclusion criteria. The studies selected and elucidated in this current systematic review have showed that IFN-α may play a deleterious role in neurodegenerative diseases through its strong association with the inflammatory processes resulting in mainly neurocognitive impairments. IFN-α may be displaying its neurotoxic function via various mechanisms such as abnormal calcium mineralization, activation of STAT1-dependent mechanisms, and increased quinolinic acid production. CONCLUSION: The exact role IFN-α in these neurodegenerative diseases have yet to be determine due to a lack in more recent evidence, thereby creating a variability in the role of IFN-α. Future investigations should thus be conducted, so that the role played by IFN-α in neurodegenerative diseases could be delineated.


Assuntos
Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/patologia , Interferon-alfa/uso terapêutico , Citocinas , Bases de Dados Factuais
14.
CVIR Endovasc ; 5(1): 32, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35792985

RESUMO

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is widely used as a first-line revascularisation option in patients with chronic limb threatening ischemia (CLTI). This study aimed to evaluate the short-term endovascular revascularisation treatment outcomes of a cohort of Rutherford 6 (R6) CLTI patients, from a multi-ethnic Asian population in Singapore. Patients with R6 CLTI who underwent endovascular revascularisation from June 2019 to February 2020 at Singapore General Hospital, a tertiary vascular centre in Singapore, were included and followed up for one year. Primary outcome measures included number and type of reinterventions required, 3-, 6- and 12-month mortality, 6- and 12-month amputation free survival (AFS), wound healing success and changes in Rutherford staging after 3, 6 and 12 months. RESULTS: Two hundred fifty-five procedures were performed on 86 patients, of whom 78 (90.7%) were diabetics, 54 (62.8%) had coronary artery disease (CAD) and 54 (62.8%) had chronic kidney disease (CKD). 42 patients (48.8%) required reintervention within 6 months. Multivariate analysis revealed that the presence of CAD was a significant independent predictor for reintervention. Mortality was 15.1%, 20.9% and 33.7% at 3, 6 and 12 months respectively. AFS was 64.0% and 49.4% at 6 and 12 months. Inability to ambulate, congestive heart failure (CHF), dysrhythmia and CKD were significant independent predictors of lower 12-month AFS. CONCLUSIONS: PTA for R6 CLTI patients was associated with relatively high mortality and reintervention rates at one year. CAD was an independent predictor of reintervention. More research is required to help risk stratify which CLTI patients would benefit from an endovascular-first approach versus conservative treatment or an immediate major lower extremity amputation policy.

15.
J Educ Health Promot ; 11: 110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573625

RESUMO

BACKGROUND: Behavioral addiction to smartphones is a common phenomenon in the present digital age, wherein indulgence in these devices is compulsive and impacts physical, social, and psychological health of the population. The smartphones effect on a dental student's life is detrimental to their academics, health, and efficiency in providing clinical patient care. To assess use and addiction of smartphones among dental students under six major domains and to compare this based on their gender, ethnicity, and year of study. MATERIALS AND METHODS: A cross-sectional study using a validated questionnaire, Smartphone addiction scale was conducted among 349 undergraduate students (N = 349) at a private dental school in Malaysia. RESULTS: Overall results are presented as mean scores under six domains with total score as 142.40 (33.65). The total scores compared between two genders did not show statistical difference, however on comparing individual domains, females (25.25) had higher mean score for daily life disturbance (P = 0.013) and males (30.17) for cyberspace-oriented relationship (P = 0.001). Chinese students had higher scores with respect to withdrawal (32.45) and cyberspace-oriented relationship (29.48) as compared to other ethnicities. Year 4 students show higher scores than other years in daily life disturbance (27.44), tolerance (16.81), and overuse (16.51). CONCLUSION: Our research presents the extent and pattern of smartphone of usage and addiction among the undergraduate students at a dental school in Malaysia. The indicators of addiction highlighted in the study are pivotal in spreading awareness regarding this overuse and addiction as well as planning further research in this area.

16.
Int J Radiat Biol ; 98(10): 1519-1531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311621

RESUMO

PURPOSE: With technological advancements in radiation therapy for tumors of the central nervous system (CNS), high doses of ionizing radiation can be delivered to the tumors with improved accuracy. Despite the reduction of ionizing radiation-induced toxicity to surrounding tissues of the CNS, a wide array of side effects still occurs, particularly late-delayed changes. These alterations, such as white matter damages and neurocognitive impairments, are often debilitative and untreatable, significantly affecting the quality of life of these patients, especially children. Oligodendrocytes, a major class of glial cells, have been identified to be one of the targets of radiation toxicity and are recognized be involved in late-delayed radiation-induced neuropathological changes. These cells are responsible for forming the myelin sheaths that surround and insulate axons within the CNS. Here, the effects of ionizing radiation on the oligodendrocyte lineage as well as the common clinical manifestations resulting from radiation-induced damage to oligodendrocytes will be discussed. Potential prophylactic and therapeutic strategies against radiation-induced oligodendrocyte damage will also be considered. CONCLUSION: Oligodendrocytes and oligodendrocyte progenitor cells (OPCs) are radiosensitive cells of the CNS. Here, general responses of these cells to radiation exposure have been outlined. However, several findings have not been consistent across various studies. For instance, cognitive decline in irradiated animals was observed to be accompanied by obvious demyelination or white matter changes in several studies but not in others. Hence, further studies have to be conducted to elucidate the level of contribution of the oligodendrocyte lineage to the development of late-delayed effects of radiation exposure, as well as to classify the dose and brain region-specific responses of the oligodendrocyte lineage to radiation. Several potential therapeutic approaches against late-delayed changes have been discussed, such as the transplantation of OPCs into irradiated regions and implementation of exercise. Many of these approaches show promising results. Further elucidation of the mechanisms involved in radiation-induced death of oligodendrocytes and OPCs would certainly aid in the development of novel protective and therapeutic strategies against the late-delayed effects of radiation.


Assuntos
Oligodendroglia , Qualidade de Vida , Animais , Diferenciação Celular , Linhagem da Célula , Sistema Nervoso Central , Bainha de Mielina , Oligodendroglia/patologia , Oligodendroglia/fisiologia
17.
J Thromb Thrombolysis ; 53(3): 646-662, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34581945

RESUMO

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 µg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.


Assuntos
COVID-19 , Hemostáticos , Trombofilia , Trombose , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , COVID-19/complicações , Fator VIII , Fibrinogênio/análise , Humanos , Estudos Prospectivos , Tromboelastografia , Trombofilia/diagnóstico , Trombofilia/etiologia , Trombose/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Fator de von Willebrand
18.
Cells ; 10(12)2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34944078

RESUMO

Population aging is occurring rapidly worldwide, challenging the global economy and healthcare services. Brain aging is a significant contributor to various age-related neurological and neuropsychological disorders, including Alzheimer's disease and Parkinson's disease. Several extrinsic factors, such as exposure to ionizing radiation, can accelerate senescence. Multiple human and animal studies have reported that exposure to ionizing radiation can have varied effects on organ aging and lead to the prolongation or shortening of life span depending on the radiation dose or dose rate. This paper reviews the effects of radiation on the aging of different types of brain cells, including neurons, microglia, astrocytes, and cerebral endothelial cells. Further, the relevant molecular mechanisms are discussed. Overall, this review highlights how radiation-induced senescence in different cell types may lead to brain aging, which could result in the development of various neurological and neuropsychological disorders. Therefore, treatment targeting radiation-induced oxidative stress and neuroinflammation may prevent radiation-induced brain aging and the neurological and neuropsychological disorders it may cause.


Assuntos
Encéfalo/patologia , Senescência Celular/efeitos da radiação , Radiação Ionizante , Animais , Autofagia/efeitos da radiação , Humanos , Mitocôndrias/patologia , Mitocôndrias/efeitos da radiação , Estresse Oxidativo/efeitos da radiação
19.
Nutr Diet ; 78(2): 121-127, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31701642

RESUMO

AIM: Restrictive diets are commonly prescribed to cardiac patients for therapeutic and preventative reasons. However, these are often contraindicated for malnourished, older patients. The present study aimed to explore dietary behaviours of malnourished older cardiac inpatients and identify sources of nutritional information. METHODS: A cross-sectional study was conducted over 4 months in a cardiology ward. Data on inpatients' habitual dietary behaviour, duration and reasons for dietary practices, and sources of nutrition advice were obtained during a dietetic assessment. From the reported reasons for dietary practices, diets were categorised by the treating dietitian into 'clinically indicated' (CI) or 'not clinically indicated' (NCI) diets. RESULTS: Sixty-seven malnourished patients were included, with mean age 76.6 ± 8.3 years and BMI 19.5 ± 6.2 kg/m2 . Twenty-six (38.8%) reported at least one dietary restriction, 14 (20.9%) were on a high energy-high protein diet prior to hospitalisation and 27 (40.3%) were on nonrestrictive diets. Five (19.2%) restrictive diets were assessed as CI at the time of admission, while 21 (80.8%) were NCI diets. CI diets were mostly recommended by dietitians (n = 15, 78.9%). Recommendations for NCI restrictive diets came mainly from 'Other' sources (n = 10, 55.6%) including the internet, friends and family. CONCLUSIONS: Restrictive diets are common among malnourished cardiac inpatients with the majority no longer clinically indicated. It is important for dietitians to explore current dietary practices of malnourished older inpatients on admission. Inpatients following NCI diets may require additional time for education around nutritional priorities.


Assuntos
Pacientes Internados , Desnutrição , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dieta , Humanos , Estado Nutricional
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