Monitoring Disease Progression Research Articles

A Protocol for Evaluating Digital Technology for Monitoring Sleep and Circadian Rhythms in Older People and People Living with Dementia in the Community.

Sleep and circadian rhythm disturbance are predictors of poor physical and mental health, including dementia. Long-term digital technology-enabled monitoring of sleep and circadian rhythms in the community has great potential for early diagnosis, monitoring of disease progression, and assessing the effectiveness of interventions. Before novel digital technology-based monitoring can be implemented at scale, its performance and acceptability need to be evaluated and compared to gold-standard methodology in relevant populations. Here, we describe our protocol for the evaluation of novel sleep and circadian technology which we have applied in cognitively intact older adults and are currently using in people living with dementia (PLWD). In this protocol, we test a range of technologies simultaneously at home (7-14 days) and subsequently in a clinical research facility in which gold standard methodology for assessing sleep and circadian physiology is implemented. We emphasize the importance of assessing both nocturnal and diurnal sleep (naps), valid markers of circadian physiology, and that evaluation of technology is best achieved in protocols in which sleep is mildly disturbed and in populations that are relevant to the intended use-case. We provide details on the design, implementation, challenges, and advantages of this protocol, along with examples of datasets.

Analysis of white matter tract integrity using diffusion kurtosis imaging reveals the correlation of white matter microstructural abnormalities with cognitive impairment in type 2 diabetes mellitus.

This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements. A total of 73 patients with T2DM and 57 healthy controls (HCs) matched for age, sex, and education level were enrolled and underwent diffusional kurtosis imaging and cognitive assessments. Tract-based spatial statistics (TBSS) and atlas-based region of interest (ROI) analysis were performed to compare group differences in diffusional metrics, including fractional anisotropy (FA), mean diffusivity (MD), axonal water fraction (AWF), intra-axonal diffusivity (Daxon), axial extra-axonal space diffusivity (De,//), and radial extra-axonal space diffusivity (De,⊥) in multiple white matter (WM) regions. Relationships between diffusional metrics and clinical and cognitive functions were characterized. In the TBSS analysis, the T2DM group exhibited decreased FA and AWF and increased MD, De,∥, and De,⊥ in widespread WM regions in comparison with the HC group, which involved 56.28%, 32.07%, 73.77%, 50.47%, and 75.96% of the mean WM skeleton, respectively (P < 0.05, TFCE-corrected). De,⊥ detected most of the WM changes, which were mainly located in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiations, sagittal stratum, cingulum (cingulate gyrus), fornix (stria terminalis), superior longitudinal fasciculus, and uniform fasciculus. Additionally, De,⊥ in the genu of the corpus callosum was significantly correlated with worse performance in TMT-A (β = 0.433, P < 0.001) and a longer disease duration (β = 0.438, P < 0.001). WMTI is more sensitive than diffusion tensor imaging in detecting T2DM-related WM microstructure abnormalities and can provide novel insights into the possible pathological changes underlying WM degeneration in T2DM. De,⊥ could be a potential imaging marker in monitoring disease progression in the brain and early intervention treatment for the cognitive impairment in T2DM.

Evaluating circulating tumour cell enrichment techniques to establish an appropriate method for clinical application in glioblastomas.

Brain tumours reduce life expectancy for an average of 20 years per patient, the highest of any cancer. A third of brain tumour patients visit their GP at least five times before diagnosis and many of those are diagnosed late through emergency departments. A possible solution to this challenge is to utilise a "liquid biopsy" blood test designed for circulating tumour cells (CTCs). Such a test could be applied at a primary healthcare centre, contributing to informed decision making for diagnostic imaging referrals. Furthermore, it could also be applied at secondary health care centres for the ongoing monitoring of disease recurrence. There is increased interest in CTC enrichment methods as a potential approach for faster diagnosis and monitoring of disease progression. The aim of this review to compare four CTC enrichment methods - OncoQuick®, Screen Cell®, pluriBead® and Cell Search® - with the objective of identifying a suitable method for application in the clinical setting for the isolation of CTCs from glioblastomas.

Analysis of congenital Zika syndrome clinicopathologic findings reported in the 8 years since the Brazilian outbreak

Aim: A Zika virus outbreak that began in Brazil, developed into an international public health emergency that extended from February 2015 until November 2016. Zika-infected pregnant women gave birth to a cohort of infants with congenital Zika syndrome (CZS) originally defined by severe microcephaly, retinal scarring, joint deformities, and hypertonia. This study examines the nature, extent, and severity of all CZS clinicopathologic findings described to date, compiled and analyzed by system. It reviews studies monitoring disease progression and proposing classification schemes for CZS stages. The teratogenic cellular and molecular mechanisms implicated in CZS pathogenesis are also discussed. Methods: A systematic review was conducted by literature search through WorldCat.org and ProQuest Central databases to identify studies on case series from the 2015–2016 CZS outbreak. Results: Twenty-six reports were included describing radiologic, ophthalmologic, audiologic, orthopedic, and laboratory test results in CZS cases including stillborns between 2016 and 2023. CZS neuropathology included prenatal and postnatal microcephaly, cerebral calcifications, quadriparesis, epilepsy, ventriculomegaly, reduced cerebral parenchyma, malformation of cortical development, and sleep electroencephalogram disturbances. Visual deficits were due to retinal and optic nerve lesions. Conductive and sensorineural hearing deficits were stable. Hypertonia, hypotonia, and spasticity with foot, hip, knee, and shoulder deformities resulted in arthrogryposis and restricted joint mobility. There was enlargement of immune organs, increased leukocyte counts, and cytokine dysregulation. Oro-craniofacial deformities affected the midface and caused dental eruption delay. Additional studies proposed that these systemic teratogenic effects could be attributable to transplacental Zika virus infection of multiple fetal progenitor cell lineages. Conclusions: The CZS-associated impairments in brain, eye, musculoskeletal, and immunologic functions caused disabilities that varied from moderate to severe, and significantly increased age-specific mortality rates. Further research is warranted to assess progression, classify stages, elucidate the precise molecular mechanisms mediating Zika teratogenicity, develop suitable therapeutic strategies, and design supportive social policies.

Reproducibility of heart rate recovery measures across differing modalities and intensities of submaximal exercise in healthy volunteers: A healthy volunteer study

PurposeSubmaximal exercise tests (SET) are an easier to conduct and less physically demanding alternative to cardiopulmonary exercise testing for assessment of pre-operative fitness. Assessment of heart rate recovery (HRR) following SETs offers an easily obtained marker of vagal reactivation and sympathetic withdrawal and therefore provides an indication of an individual’s fitness. This study sought to assess the reproducibility of HRR across different workloads and modalities of SET.MethodsThirty-four healthy volunteers were recruited to undergo two SETs at 40% and 60% of their predicted maximal workload. A second group of thirty-one healthy volunteers were recruited to undergo three SETs of differing modalities; Cycle ergometry, Step and Shuttle Walk tests. HRR was quantified using the conventional indices HRR1 and HRR2 (calculated as heart rate (HR) on exercise cessation minus HR at 1 and 2 min of rest) and a novel area under the HRR vs. time curve (HRRAUC) method. Reproducibility of results was assessed using intra-class correlation coefficient (ICC) and limits of agreements.ResultsThe results showed that HRR1 and HRR2 were poorly reproducible across differing workloads and exercise modalities (ICC < 0.45 for all comparisons) whereas HRRAUC proved to be at least moderately reproducible (ICC > 0.52 for all comparisons).ConclusionsThese results suggest that HRRAUC may be a superior way of quantifying HRR following SETs, adding objectivity to SET results. Quantifying HRRAUC could prove to have useful clinical applications for pre-operative risk assessment, assessing fitness to undergo treatment and monitoring disease progression.

Liquid Biopsy: A Game Changer for Type 2 Diabetes.

As the burden of type 2 diabetes (T2D) continues to escalate globally, there is a growing need for novel, less-invasive biomarkers capable of early diabetes detection and monitoring of disease progression. Liquid biopsy, recognized for its minimally invasive nature, is increasingly being applied beyond oncology, and nevertheless shows its potential when the collection of the tissue biopsy is not possible. This diagnostic approach involves utilizing liquid biopsy markers such as cell-free nucleic acids, extracellular vesicles, and diverse metabolites for the molecular diagnosis of T2D and its related complications. In this context, we thoroughly examine recent developments in T2D liquid biopsy research. Additionally, we discuss the primary challenges and future prospects of employing liquid biopsy in the management of T2D. Prognosis, diagnosis and monitoring of T2D through liquid biopsy could be a game-changing technique for personalized diabetes management.

Prevalence and Associated Factors of Urinary Tract Infections among Diabetes Mellitus Patients at KIU-TH from January to December 2022

Globally, an estimated 150 million individuals are affected by urinary tract infections (UTIs) every year, with a significant number of those affected being diabetics. The International Diabetes Federation (IDF) reported that in the year 2019, there were about 60 million cases of patients suffering from diabetes who developed UTIs. The study assessed the prevalence and associated factors of urinary tract infections among diabetic mellitus patients in the medical ward at KIUTH. The objectives were to find out the prevalence and the factors associated with urinary tract infections among diabetic patients in the medical ward of KIU-TH. The study was descriptive, and it involved 87 patient files selected by purposive sampling, in which a checklist was the main tool of data collection. The study showed that female gender was significantly associated with the occurrence of urinary tract infection in diabetic patients at OR 0.17 (0.05–4.29) and PV 0.01. The study also shows that having other disease comorbidities was significantly associated with the occurrence of UTI among diabetic patients at OR 0.58 (0.35-8.07) and PV 0.002. The study also shows that having late diabetic disease among diabetic patients was also significantly associated with the occurrence of UTI among diabetic patients at OR 0.69 (0.35-8.19) and PV 0.004. The study concluded that 48 (55.2%) of diabetic patients had had a urinary tract infection, and therefore the study recommends that diabetic patients should be health educated on the causes and control of UTI so as to prevent their occurrences. The study also recommends that the government increase service provisions like treatments to reduce the occurrence of opportunistic conditions in UTIs, and the patients should be encouraged to seek regular medical checkups so that they monitor disease progression. Keywords: Diabetics, UTIs, Patients, Diabetes mellitus.

Retinal OCT biomarkers and their association with cognitive function-clinical and AI approaches.

Retinal optical coherence tomography (OCT) biomarkers have the potential to serve as early, noninvasive, and cost-effective markers for identifying individuals at risk for cognitive impairments and neurodegenerative diseases. They may also aid in monitoring disease progression and evaluating the effectiveness of interventions targeting cognitive decline. The association between retinal OCT biomarkers and cognitive performance has been demonstrated in several studies, and their importance in cognitive assessment is increasingly being recognized. Machine learning (ML) is abranch of artificial intelligence (AI) with an exponential number of applications in the medical field, particularly its deep learning (DL) subset, which is widely used for the analysis of medical images. These techniques efficiently deal with novel biomarkers when their outcome for the applications of interest is unclear, e.g., for diagnosis, prognosis prediction, disease staging, or any other relevance to clinical practice. However, using AI-based tools for medical purposes must be approached with caution, despite the many efforts to address the black-box nature of such approaches, especially due to the general underperformance in datasets other than those used for their development. Retinal OCT biomarkers are promising as potential indicators for decline in cognitive function. The underlying mechanisms are currently being explored to gain deeper insights into this relationship linking retinal health and cognitive function. Insights from neurovascular coupling and retinal microvascular changes play an important role. Further research is needed to establish the validity and utility of retinal OCT biomarkers as early indicators of cognitive decline and neurodegenerative diseases in routine clinical practice. Retinal OCT biomarkers could then provide anew avenue for early detection, monitoring and intervention in cognitive impairment with the potential to improve patient care and outcomes.

Adapting transfer learning models to dataset through pruning and Avg-TopK pooling

This study focuses on efficiently adapting transfer learning models to address the challenges of creating customized deep learning models for specific datasets. Designing a model from scratch can be time-consuming and complex due to factors like model complexity, size, and dataset structure. To overcome these obstacles, a novel approach is proposed using transfer learning models. The proposed method involves identifying relevant layers in transfer learning models and removing unnecessary ones using a layer-based variance pruning technique. This results in the creation of new models with improved computational efficiency and classification performance. By streamlining the models through layer-based variance pruning, the study achieves enhanced accuracy and faster computation. Experiments were conducted using the COVID-19 dataset and well-known transfer learning models, including InceptionV3, ResNet50V2, DenseNet201, VGG16, and Xception to validate the approach. Among these models, the variance-based layer pruning technique was applied to InceptionV3 and DenseNet201, yielding the best results. When these pruned models were combined with the new pooling layer, Avg-TopK, the proposed method achieved an outstanding image classification accuracy of 99.3%. Comparisons with previous models and literature studies indicate that the proposed approach outperforms existing methods, showcasing state-of-the-art performance. This high-performance approach provides great potential for diagnosing COVID-19 and monitoring disease progression, especially on hardware-limited devices. By leveraging transfer learning models, pruning, and efficient pooling techniques, the study presents a promising strategy for tackling challenges in custom model design, leading to exceptional results in such as image classification and segmentation tasks. The proposed methodology holds the potential to yield exceptional outcomes across a spectrum of tasks, encompassing disciplines such as image classification and segmentation.

Advanced detection of cervical cancer biomarkers using engineered filamentous phage nanofibers.

Cervical cancer is a major global health concern, characterized by its high incidence and mortality rates. The detection of tumor markers is crucial for managing cancer, making treatment decisions, and monitoring disease progression. Vascular endothelial growth factor (VEGF) and programmed death-ligand 1 (PDL-1) are key targets in cervical cancer therapy and valuable biomarkers in predicting treatment response and prognosis. In this study, we found that combining the measurement of VEGF and soluble PDL-1 can be used for diagnosing and evaluating the progression of cervical cancer. To explore a more convenient approach for detecting and assessing cervical cancer, we designed and prepared an engineered fd bacteriophage, a human-safe viral nanofiber, equipped with two peptides targeting VEGF and PD-L1. The dual-display phage nanofiber specifically recognizes and binds to both proteins. Utilizing this nanofiber as a novel capture agent, we developed a new enzyme-linked immunosorbent assay (ELISA) method. This method shows significantly enhanced detection sensitivity compared to conventional ELISA methods, which use either anti-VEGF or anti-PD-L1 antibodies as capture agents. Therefore, the phage dual-display nanofiber presents significant potential in detecting cancer markers, evaluating medication efficacy, and advancing immunotherapy drug development. KEY POINTS: • The combined measurement of VEGF and soluble Programmed Death-Ligand 1(sPD-L1) demonstrates an additive effect in the diagnosis of cervical cancer. Fd phage nanofibers have been ingeniously engineered to display peptides that bind to VEGF and PD-L1, enabling the simultaneous detection of both proteins within a single assay • Genetically engineered phage nanofibers, adorned with two distinct peptides, can be utilized for the diagnosis and prognosis of cancer and can be mass-produced cost-effectively through bacterial infections • Employing dual-display fd phage nanofibers as capture probes, the phage ELISA method exhibited significantly enhanced detection sensitivity compared to traditional sandwich ELISA. Furthermore, phage ELISA facilitates the detection of a single protein or the simultaneous detection of multiple proteins, rendering them powerful tools for protein analysis and diagnosis across various fields, including cancer research.

Plasma N-terminal containing tau fragments (NTA-tau): a biomarker of tau deposition in Alzheimer’s Disease

BackgroundNovel phosphorylated-tau (p-tau) blood biomarkers (e.g., p-tau181, p-tau217 or p-tau231), are highly specific for Alzheimer’s disease (AD), and can track amyloid-β (Aβ) and tau pathology. However, because these biomarkers are strongly associated with the emergence of Aβ pathology, it is difficult to determine the contribution of insoluble tau aggregates to the plasma p-tau signal in blood. Therefore, there remains a need for a biomarker capable of specifically tracking insoluble tau accumulation in brain.MethodsNTA is a novel ultrasensitive assay targeting N-terminal containing tau fragments (NTA-tau) in cerebrospinal fluid (CSF) and plasma, which is elevated in AD. Using two well-characterized research cohorts (BioFINDER-2, n = 1,294, and BioFINDER-1, n = 932), we investigated the association between plasma NTA-tau levels and disease progression in AD, including tau accumulation, brain atrophy and cognitive decline.ResultsWe demonstrate that plasma NTA-tau increases across the AD continuum¸ especially during late stages, and displays a moderate-to-strong association with tau-PET (β = 0.54, p < 0.001) in Aβ-positive participants, while weak with Aβ-PET (β = 0.28, p < 0.001). Unlike plasma p-tau181, GFAP, NfL and t-tau, tau pathology determined with tau-PET is the most prominent contributor to NTA-tau variance (52.5% of total R2), while having very low contribution from Aβ pathology measured with CSF Aβ42/40 (4.3%). High baseline NTA-tau levels are predictive of tau-PET accumulation (R2 = 0.27), steeper atrophy (R2 ≥ 0.18) and steeper cognitive decline (R2 ≥ 0.27) in participants within the AD continuum. Plasma NTA-tau levels significantly increase over time in Aβ positive cognitively unimpaired (βstd = 0.16) and impaired (βstd = 0.18) at baseline compared to their Aβ negative counterparts. Finally, longitudinal increases in plasma NTA-tau levels were associated with steeper longitudinal decreases in cortical thickness (R2 = 0.21) and cognition (R2 = 0.20).ConclusionOur results indicate that plasma NTA-tau levels increase across the AD continuum, especially during mid-to-late AD stages, and it is closely associated with in vivo tau tangle deposition in AD and its downstream effects. Moreover, this novel biomarker has potential as a cost-effective and easily accessible tool for monitoring disease progression and cognitive decline in clinical settings, and as an outcome measure in clinical trials which also need to assess the downstream effects of successful Aβ removal.

Bridging the clinical-research gap: Harnessing an electronic data capture, integration, and visualization platform to systematically assess prospective patient-reported outcomes in mitochondrial medicine

PurposeOptimizing individualized clinical care in heterogeneous rare disorders, such as primary mitochondrial disease (PMD), will require gaining more comprehensive and objective understanding of the patient experience by longitudinally tracking quantifiable patient-specific outcomes and integrating subjective data with clinical data to monitor disease progression and targeted therapeutic effects. MethodsElectronic surveys of patient (and caregiver) reported outcome (PRO) measures were administered in REDCap within clinical domains commonly impaired in patients with PMD in the context of their ongoing routine care, including quality of life, fatigue, and functional performance. Descriptive statistics, group comparisons, and inter-measure correlations were used to evaluate system feasibility, utility of PRO results, and consistency across outcome measure domains. Real-time tracking and visualization of longitudinal individual-level and cohort-level data were facilitated by a customized data integration and visualization system, MMFP-Tableau. ResultsAn efficient PRO electronic capture and analysis system was successfully implemented within a clinically and genetically heterogeneous rare disease clinical population spanning all ages. Preliminary data analyses demonstrated the flexibility of this approach for a range of PROs, as well as the value of selected PRO scales to objectively capture qualitative functional impairment in four key clinical domains. High inter-measure reliability and correlation were observed. Between-group analyses revealed that adults with PMD reported significantly worse quality of life and greater fatigue than did affected children, while PMD patients with nuclear gene disorders reported lower functioning relative to those with an mtDNA gene disorder in several clinical domains. ConclusionIncorporation of routine electronic data collection, integration, visualization, and analysis of relevant PROs for rare disease patients seen in the clinical setting was demonstrated to be feasible, providing prospective and quantitative data on key clinical domains relevant to the patient experience. Further work is needed to validate specific PROs in diverse PMD patients and cohorts, and to formally evaluate the clinical impact and utility of harnessing integrated data systems to objectively track and integrate quantifiable PROs in the context of rare disease patient clinical care.

Retinal ganglion cell and microvascular density loss in hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is characterized by progressive degeneration of distal axons in the long corticospinal tracts. Loss of retinal cells and microvascular networks has neither been suspected nor investigated. We concurrently examined the retinal microvasculature and retinal layer morphology in patients with HSP to assess whether retinal features may portray disease and its progression. Fifteen patients with HSP and 30 healthy controls were included in this cross-sectional case-control study. Disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Severity of ataxia was determined by the Scale for the Assessment and Rating of Ataxia (SARA). Retinal microvasculature was measured by means of optical coherence tomography angiography (OCT-A) and morphology of retinal layers using structural OCT. Mixed-effects models were applied for data analysis. HSP patients showed significantly reduced vessel density of the superficial vascular plexus (SVP), reduced ganglion cell layer (GCL) volume, reduced inner plexiform layer (IPL) volume and reduced temporal-inferior peripapillary retinal nerve fiber layer (pRNFL) thickness versus healthy controls. GCL volume reduction correlated significantly with the worsening of visual acuity and higher SARA scores. These findings demonstrate that, in HSP both cells and vascular networks of the retina are compromised. Assessment of the retinal GCL, IPL and SVP may aid in diagnosis and monitoring of disease progression as well as provide novel structural outcome measures for clinical trials.

Exploring the potential of combining transcranial magnetic stimulation and electroencephalography to investigate mild cognitive impairment and Alzheimer's disease: a systematic review.

Transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are non-invasive techniques used for neuromodulation and recording brain electrical activity, respectively. The integration of TMS-EEG has emerged as a valuable tool for investigating the complex mechanisms involved in age-related disorders, such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). By systematically synthesizing TMS-EEG studies, this review aims to shed light on the neurophysiological mechanisms underlying MCI and AD, while also exploring the practical applications of TMS-EEG in clinical settings. PubMed, ScienceDirect, and PsychInfo were selected as the databases for this review. The 22 eligible studies included a total of 592 individuals with MCI or AD as well as 301 cognitively normal adults. TMS-EEG assessments unveiled specific patterns of corticospinal excitability, plasticity, and brain connectivity that distinguished individuals on the AD spectrum from cognitively normal older adults. Moreover, the TMS-induced EEG features were observed to be correlated with cognitive performance and the presence of AD pathological biomarkers. The comprehensive examination of the existing studies demonstrates that the combination of TMS and EEG has yielded valuable insights into the neurophysiology of MCI and AD. This integration shows great potential for early detection, monitoring disease progression, and anticipating response to treatment. Future research is of paramount importance to delve into the potential utilization of TMS-EEG for treatment optimization in individuals with MCI and AD.

Glycosaminoglycans: Participants in Microvascular Coagulation of Sepsis.

Sepsis represents a syndromic response to infection and frequently acts as a common pathway leading to fatality in the context of various infectious diseases globally. The pathology of severe sepsis is marked by an excess of inflammation and activated coagulation. A substantial contributor to mortality in sepsis patients is widespread microvascular thrombosis-induced organ dysfunction. Multiple lines of evidence support the notion that sepsis induces endothelial damage, leading to the release of glycosaminoglycans, potentially causing microvascular dysfunction. This review aims to initially elucidate the relationship among endothelial damage, excessive inflammation, and thrombosis in sepsis. Following this, we present a summary of the involvement of glycosaminoglycans in coagulation, elucidating interactions among glycosaminoglycans, platelets, and inflammatory cells. In this section, we also introduce a reasoned generalization of potential signal pathways wherein glycosaminoglycans play a role in clotting. Finally, we discuss current methods for detecting microvascular conditions in sepsis patients from the perspective of glycosaminoglycans. In conclusion, it is imperative to pay closer attention to the role of glycosaminoglycans in the mechanism of microvascular thrombosis in sepsis. Dynamically assessing glycosaminoglycan levels in patients may aid in predicting microvascular conditions, enabling the monitoring of disease progression, adjustment of clinical treatment schemes, and mitigation of both acute and long-term adverse outcomes associated with sepsis.

Revolutionizing Cancer Care: Liquid Biopsy Redefining Surgical Biopsy Paradigms

Liquid biopsy, a non-invasive method for analyzing circulating biomarkers in bodily fluids, has garnered significant interest as a potential alternative to traditional surgical tissue biopsy in oncology. This review explores the current landscape of liquid biopsy technologies, their clinical applications, and their potential to complement or replace surgical tissue biopsy in cancer diagnosis, treatment monitoring, and prognostication. We examine the various analytes detected in liquid biopsies, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), exosomes, and microRNAs, and discuss their utility in detecting genetic alterations, assessing treatment response, and monitoring disease progression. Furthermore, we compare the advantages and limitations of liquid biopsy with surgical tissue biopsy, highlighting factors such as invasiveness, accessibility, and the ability to capture tumor heterogeneity. We also address ongoing challenges in standardization, sensitivity, and specificity of liquid biopsy assays and discuss future directions aimed at optimizing their clinical utility. Overall, this review provides insights into the evolving role of liquid biopsy as a potential alternative to surgical tissue biopsy in oncology and underscores its potential to improve patient care and outcomes.

INTO THE DARKNESS AND SILENCE: EVISCERATION IN A DEAF-MUTE- BLIND PATIENT WITH NEGLECTED GLAUCOMA

Introduction : Glaucoma can have a potentially devastating effect on patient’s vision and quality of life if not treated properly. We described a neglected glaucoma case in a deaf-mute-blind patient that leads to evisceration.&#x0D; Case Illustration : A 64-year-old deaf-mute female came to our emergency room with chief complaint of bloody discharge from her right eye 12 hours prior to admission with no history of trauma. Patient’s right eye has been blind for the last four years; her left eye has been nonfunctional since she was in her 30s. She went to a primary clinic during this time but did not get any diagnoses. Physical examination revealed uveal prolapse of the right eye with infiltrates around the remaining cornea; and phtisical left eye with IOP of 30 mmHg and opaque cornea. We performed evisceration with dermato-fat graft of the right eye.&#x0D; Discussion : Glaucoma is a challenging disease, especially in developing countries. It is difficult to diagnose due to its nature to be asymptomatic until late in the disease course. The loss of vision is painless and insidious; resulting in late diagnosis unless patients are screened for glaucoma early on. Patient in this report is particularly difficult for the caretaker since she is a deaf-mute patient; resulting in a suspected undiagnosed glaucoma that leads to evisceration and blindness.&#x0D; Conclusion : Glaucoma care generally necessitates routine follow-up for monitoring of disease progression and medication adjustments. Good screening system, family support, and integration of eye care into existing healthcare systems is needed for early detection to reduce blindness from glaucoma.

Unveiling Ocular Manifestations in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder characterized by immune dysregulation and multi-organ involvement. In this concise brief review, we highlight key insights into Ocular Systemic Lupus Erythematosus (SLE), an intricate autoimmune disorder with diverse organ involvement. Emphasizing the formation of autoantibodies and immune complex deposition, we delve into the inflammation and damage affecting ocular structures. Clinical presentations, ranging from mild dry eye syndrome to severe conditions like retinal vasculitis, necessitate a comprehensive diagnostic approach, including clinical exams, serological testing, and imaging studies. Differential diagnosis involves distinguishing SLE-related ocular manifestations from other autoimmune and non-inflammatory ocular conditions. The multidisciplinary management approach, involving rheumatologists, ophthalmologists, and immunologists, tailors treatment based on ocular involvement severity, encompassing corticosteroids, immunosuppressive agents, and biologics. Follow-up is crucial for monitoring disease progression and treatment response. Future perspectives revolve around advancing molecular understanding, refining diagnostic tools, and exploring targeted therapies. Novel research areas include genetic factors, microbiome composition, and biotechnology for tailored and effective SLE ocular treatments.

The effect of human PBMCs immobilization on their Аβ42 aggregates-dependent proinflammatory state on a cellular model of Alzheimer's disease.

The leading pathological mechanisms of Alzheimer's disease are amyloidosis and inflammation. The presented work was aimed to study the effect of human peripheral blood mononuclear cells (hPBMcs) cells-matrix adhesion on their pro-inflammatory state in vitro. Although direct interaction of Аβ42 to PBMC is not a cellular model of Alzheimer's disease, PBMCs may serve as test cells to detect Аβ42-dependent molecular effects in monitoring disease progression. Peripheral blood mononuclear cells (PBMCs) are used to assess changes in cytokines released in response to diseases or Alzheimer's disease-specific cytotoxic molecules such as Aβ42. The effect of recombinant amyloid β-peptide rАβ42 on the concentration of endogenous amyloid β-peptide Aβ40 and pro-inflammatory cytokines TNFα and IL-1β in human peripheral blood mononuclear cells that were cultured in suspension and immobilized in alginate microcarriers for 24 h were investigated. The localization and accumulation of Aβ40 and rAβ42 peptides in cells, as well as quantitative determination of the concentration of Aβ40 peptide, TNFα and IL-1β cytokines, was performed by intravital fluorescence imaging. The results were qualitatively similar for both cell models. It was determined that the content of TNFα and Aβ40 in the absence of rAβ42 in the incubation medium did not change for 24 h after incubation, and the content of IL-1β was lower compared to the cells that were not incubated. Incubation of cells in vitro with exogenous rAβ42 led to an increase in the intracellular content of TNFα and Aβ40, and no accumulation of IL-1β in cells was observed. The accumulation of Aβ40 in the cytoplasm was accompanied by the aggregation of rAβ42 on the outer surface of the cell plasma membrane. It was shown that the basic levels of indicators and the intensity of the response of immobilized cells to an exogenous stimulus were significantly greater than those of cells in suspension. To explore whether non-neuronal cells effects in alginate microcarriers were cell-matrix adhesion mediated, we tested the effect of blocking β1 integrins on proamyloidogenic and proinflammation cellular state. Immobilization within alginate hydrogels after incubation with the β1 integrins blocking antibodies showed a remarkable inhibition of TNFα and Aβ40 accumulation in rAβ42-treated cells. It can be concluded that activation of signal transduction and synthesizing activity of a portion of mononuclear cells of human peripheral blood is possible (can significantly increase) in the presence of cell-matrix adhesion.

Metabolomics unveils the exacerbating role of arachidonic acid metabolism in atherosclerosis.

Atherosclerosis is a complex vascular disorder characterized by the deposition of lipids, inflammatory cascades, and plaque formation in arterial walls. A thorough understanding of its causes and progression is necessary to develop effective diagnostic and therapeutic strategies. Recent breakthroughs in metabolomics have provided valuable insights into the molecular mechanisms and genetic factors involved in atherosclerosis, leading to innovative approaches for preventing and treating the disease. In our study, we analyzed clinical serum samples from both atherosclerosis patients and animal models using laser desorption ionization mass spectrometry. By employing methods such as orthogonal partial least-squares discrimination analysis (OPLS-DA), heatmaps, and volcano plots, we can accurately classify atherosclerosis (AUC = 0.892) and identify key molecules associated with the disease. Specifically, we observed elevated levels of arachidonic acid and its metabolite, leukotriene B4, in atherosclerosis. By inhibiting arachidonic acid and monitoring its downstream metabolites, we discovered the crucial role of this metabolic pathway in regulating atherosclerosis. Metabolomic research provides detailed insights into the metabolic networks involved in atherosclerosis development and reveals the close connection between abnormal metabolism and the disease. These studies offer new possibilities for precise diagnosis, treatment, and monitoring of disease progression, as well as evaluating the effectiveness of therapeutic interventions.