Early Disease Markers Research Articles

Evaluation of serum levels of Irisin as a marker of endothelial dysfunction in patients with type 2 diabetes mellitus

Insulin resistance and obesity have been associated with irisin, a protein in fat cells. The levels of irisin in patients with type 2 diabetes mellitus (T2DM) were significantly lower than those in non-diabetics. This study aimed to examine the relationship between serum irisin levels and endothelial dysfunction in patients with T2DM. There were 90 participants in this study. We matched 65 patients with T2DM with 25 healthy control participants. A series of tests were performed on the participants, including fasting blood glucose, 2 hours postprandial blood glucose, glycated haemoglobin, triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), TG/HDL-C ratio and albumin/creatinine ratio. In addition to measuring high-sensitivity C-reactive protein (hs-CRP). Enzyme-linked immunosorbent assay (ELISA) technique was used for estimating irisin concentrations. Flow-mediated dilation (FMD) was significantly lower in patients with T2DM; however, there was a non-statistically significant difference between healthy controls and patients with T2DM regarding serum Irisin level. CRP and LDL levels were inversely correlated with circulating irisin levels. In a stepwise regression analysis, only the hs-CRP and LDL were statistically significant in predicting irisin level. In patients with T2DM, serum levels of irisin were inversely correlated with hyperglycaemia, body mass index and per cent body fat; this suggests that detecting irisin levels early can prevent cardiovascular diseases from progressing. According to the study results, serum irisin serves as a predictive marker for early cardiovascular disease, thus preventing the disease from progressing. There is a need for further research in order to understand how irisin contributes to the development of atherosclerosis and the development of diabetic complications.

Challenges and opportunities of diagnostic markers of Alzheimer's disease based on structural magnetic resonance imaging.

This article aimed to carry out a narrative literature review of early diagnostic markers of Alzheimer's disease (AD) based on both micro and macro levels of pathology, indicating the shortcomings of current biomarkers and proposing a novel biomarker of structural integrity that associates the hippocampus and adjacent ventricle together. This could help to reduce the influence of individual variety and improve the accuracy and validity of structural biomarker. This review was based on presenting comprehensive background of early diagnostic markers of AD. We have compiled those markers into micro level and macro level, and discussed the advantages and disadvantages of them. Eventually the ratio of gray matter volume to ventricle volume was put forward. The costly methodologies and related high patient burden of "micro" biomarkers (cerebrospinal fluid biomarkers) hinder the implementation in routine clinical examination. In terms of "macro" biomarkers- hippocampal volume (HV), there is a large variation of it among population, which undermines its validity Considering the gray matter atrophies while the adjacent ventricular volume enlarges, we assume the hippocampal to ventricle ratio (HVR) is a more reliable marker than HV alone the emerging evidence showed hippocampal to ventricle ratio predicts memory functions better than HV alone in elderly sample. The ratio between gray matter structures and adjacent ventricular volumes counts as a promising superior diagnostic marker of early neurodegeneration.

The urinary proteome infers dysregulation of mitochondrial, lysosomal, and protein reabsorption processes in chronic kidney disease of unknown etiology (CKDu).

Chronic kidney disease (CKD) of uncertain etiology (CKDu) is a global health concern affecting tropical farming communities. CKDu is not associated with typical risk factors (e.g., diabetes) and strongly correlates with environmental drivers. To gain potential insights into disease etiology and diagnosis, here we report the first urinary proteome comparing patients with CKDu and non-CKDu controls from Sri Lanka. We found 944 differentially abundant proteins. In silico analyses identified 636 proteins of likely kidney and urogenital origin. As expected, renal tubular injury in patients with CKDu was evinced by increases in albumin, cystatin C, and β2-microglobulin. However, several proteins typically elevated under CKD, including osteopontin and α-N-acetylglucosaminidase, were decreased in patients with CKDu. Furthermore, urinary excretion of aquaporins found higher in CKD was lower in CKDu. Comparisons with previous CKD urinary proteome datasets revealed a unique proteome for CKDu. Notably, the CKDu urinary proteome was relatively similar to that of patients with mitochondrial diseases. Furthermore, we report a decrease in endocytic receptor proteins responsible for protein reabsorption (megalin and cubilin) that correlated with an increase in abundance of 15 of their cognate ligands. Functional pathway analyses identified kidney-specific differentially abundant proteins in patients with CKDu denoted significant changes in the complement cascade and coagulation systems, cell death, lysosomal function, and metabolic pathways. Overall, our findings provide potential early detection markers to diagnose and distinguish CKDu and warrant further analyses on the role of lysosomal, mitochondrial, and protein reabsorption processes and their link to the complement system and lipid metabolism in CKDu onset and progression.NEW & NOTEWORTHY CKDu is a global health concern debilitating a number of tropical rural farming communities. In the absence of typical risk factors like diabetes and hypertension and the lack of molecular markers, it is crucial to identify potential early disease markers. Here, we detail the first urinary proteome profile to distinguish CKDu from CKD. Our data and in silico pathway analyses infer the roles of mitochondrial, lysosomal, and protein reabsorption processes in disease onset and progression.

Beta-Amyloid Peptide in Tears: An Early Diagnostic Marker of Alzheimer's Disease Correlated with Choroidal Thickness.

We aimed to evaluate the diagnostic role of Alzheimer's disease (AD) biomarkers in tears as well as their association with retinal and choroidal microstructures. In a cross-sectional study, 35 subjects (age 71.7 ± 6.9 years) were included: 11 with prodromal AD (MCI), 10 with mild-to-moderate AD, and 14 healthy controls. The diagnosis of AD and MCI was confirmed according to a complete neuropsychological evaluation and PET or MRI imaging. After tear sample collection, β-amyloid peptide Aβ1-42 concentration was analyzed using ELISA, whereas C-terminal fragments of the amyloid precursor protein (APP-CTF) and phosphorylated tau (p-tau) were assessed by Western blot. Retinal layers and choroidal thickness (CT) were acquired by spectral-domain optical coherence tomography (SD-OCT). Aβ1-42 levels in tears were able to detect both MCI and AD patients with a specificity of 93% and a sensitivity of 81% (AUC = 0.91). Tear levels of Aβ1-42 were lower, both in the MCI (p < 0.01) and in the AD group (p < 0.001) when compared to healthy controls. Further, Aβ1-42 was correlated with psychometric scores (p < 0.001) and CT (p < 0.01). CT was thinner in the affected patients (p = 0.035). No differences were observed for APP-CTF and p-tau relative abundance in tears. Testing Aβ1-42 levels in tears seems to be a minimally invasive, cost-saving method for early detection and diagnosis of AD.

MiRNAs as non-invasive biomarkers in the serum of Oral Squamous Cell Carcinoma (OSCC) and Oral Potentially Malignant Disorder (OPMD) patients

ObjectiveCell-free microRNAs have shown differential levels in the serum of individuals under disease conditions suggesting its potential to act as biomarkers. A population specific miRNA signature in oral cancer is reported in different studies. We aim to identify a set of serum specific miRNAs that may differentiate oral cancer, oral pre-malignant conditions from the healthy individuals. DesignWe investigated the levels of 24 miRNAs in the serum of 47 Oral squamous cell carcinoma (OSCC) patients, 20 patients with Oral potentially malignant disorders (OPMD) and 42 healthy controls from Eastern India. Small RNAs were isolated from serum samples followed by cDNA synthesis. Levels of miRNAs were determined using qRT-PCR. The sources of serum specific miRNAs were evaluated using GTEx-RNAseq and TCGA-HNSCC database. ResultsFive miRNAs, miR-483–5p, miR-31–5p, Let-7b-5p, miR-486–5p and miR-30e-5p showed significant elevation in OSCC patients. An Elastic-Net model with 4 miRNAs classified OSCC from healthy controls with 80 % sensitivity, 64.3 % specificity, and 72.4 % accuracy. Mir-483–5p and miR-31–5p was significantly overexpressed in OSCC tissues as well as significantly higher in the serum of Leukoplakia and Verrucous carcinoma patients suggesting their potential as early disease markers. MiR-483–5p showed a consistent elevated level in the serum/plasma of oral cancer patients across different population and was found to be tumour specific while, the rest of the miRNAs showed variable results across different studies. ConclusionsOur study suggested that the serum miRNAs in oral cancer and pre-malignant disorder conditions can be used as a non-invasive marker for screening of these oral conditions.

Peering into tissues

The first method to combine tissue clearing and proteomics allows researchers to peer into tissues to find early markers of disease. By making tissues almost transparent, researchers can reach in and pluck out particular areas to study their proteins. The study authors say the method will be useful for understanding processes such as plaque formation early in Alzheimer’s disease and how atherosclerotic deposits become lesions ( Cell 2022, DOI: 10.1016/j.cell.2022.11.021 ). Many maladies need to be treated earlier, says Ali Ertürk of the Helmholtz Institute of Tissue Engineering and Regenerative Medicine and an author of this study. “Otherwise, the chances [of success] are very low.” To understand how diseases begin in model organisms and improve interventions, scientists must find the small part of a mostly healthy organ that has just begun to go wrong—but this can be difficult. Ertürk and coauthor Matthias Mann of the Max Planck Institute of Biochemistry

Determining the Bulk of the Iceberg of Proteinuric Chronic Kidney Disease in School Children, in South West Nigeria

Introduction: Chronic kidney disease [CKD], as defined by the National Kidney Foundation/Kidney Disease and Outcome Quality Initiative (KDOQI) Group, refers to bilateral kidney injury and/or impaired kidney function of at least 3 months duration. Persistent proteinuria has been recognized as one of the early markers of chronic kidney disease and has been associated with persistent and progressive damage in both children and adult. This study was conducted with the aim of determining the prevalence and severity of persistent proteinuria over three months in primary school children in Ile-Ife. It was a cross-sectional study done over a period of six months. The subjects were 1335 primary school pupils, aged 6 to 14 years selected by multi stage random sampling method from twelve primary schools from a total of 96,301 pupils in the two Local Government Areas (LGA) of Ile-Ife, after meeting the recruitment criteria. The biodata, physical examination, blood pressure measurements and urine testing by dipstick were carried out on all the recruited pupils according to standard protocols while serial monitoring of proteinuria and estimated glomerular filtration rate was done for those with persistent proteinuria over 6 months. Results: Initially 34 (2.6%) of the subjects recruited had significant proteinuria with a M:F ratio of 1:1.6 following first screening and it was persistent in six (0.4%) of them subsequently over three months with a M:F ratio of 1:1.5. The severity of the persistent proteinuria was in the range of 30 mg/dL to 100 mg/dL. Three of them (50%) had worsened level of proteinuria from 30 mg/dL to 100 mg/dl on follow up. Conclusion: Children with undetected persistent proteinuria stand the risk of further glomerular damage over time.

Late-life Onset Psychosis-like Symptoms Assessed in the Mild Behavioral Impairment Framework are Associated Impaired Performance on the Stroop Task

Late-life onset psychosis and milder delusion-like ideation are known risk factors for cognitive decline and dementia. The Mild Behavioural Impairment (MBI) framework was developed to capture specific psychotic-like symptoms relevant to dementia prognosis in older adults. This study aims to investigate the cognitive deficits associated with MBI-psychosis and their implications for understanding the underlying mechanisms and potential treatment targets. The study recruited participants between November 2021 and July 2022 from the PROTECT study registry. Participants completed the Cambridge Gambling Task, Stroop, Trail Making, Paired Associates Learning, Verbal Reasoning, Digit Span and Self-Ordered Search. Psychotic symptom status was assessed using the Mild Behavioural Impairment Checklist (MBI-C), with participants categorized as MBI-psychosis if they or their study partner reported any psychotic symptoms. Out of 2,111 eligible participants invited, 417 consented to participate. There were no significant differences in age, sex, education level, or mental health history between the MBI-psychosis and No Psychosis groups. Participants with MBI-psychosis exhibited significantly worse performance on the Stroop task (p=0.0002, Cohen’s d=0.37) compared to those without psychosis. There was also some evidence of impairment in verbal reasoning, though it did not reach significance after Bonferroni correction. No significant differences were found on other cognitive measures. This cross-sectional study provides insight into the cognitive deficits associated with MBI-psychosis. The finding of impaired Stroop task performance in individuals with MBI-psychosis is noteworthy, as this deficit is commonly observed in earlier-life major psychotic disorders. Further research is needed to explore the neural underpinnings of these deficits and to determine whether they represent early markers of neurodegenerative disease or other factors.

Correlation of Global DNA Methylation with Symptom Severity in Drug-Naïve Bipolar Disorder Patients: A Cross-sectional Study

health problem in India. Global Deoxyribonucleic Acid (DNA) methylation studies could provide a significant clues toward the early identification of high-risk individuals. Aim: To estimate the levels of global DNA methylation in drugnaïve bipolar disorder patients and healthy controls and to correlate the global DNA methylation levels with the severity of the disease. Materials and Methods: A cross-sectional study was conducted in the Department of Psychiatry at SCB Medical College, Cuttack, Odisha, India, from January 2019 to March 2020. A total of 50 bipolar disorder patients and 50 age-matched healthy adult controls were recruited from the Outpatient Departments (OPD) of the hospital, and the severity of bipolar disorder was assessed using Young's Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D). DNA methylation levels were estimated from serum samples of the subjects using a methylated DNA quantification kit. The data was analysed using Statistical Package for Social Sciences (SPSS) version 25.0. The Kruskal-Wallis test was used to compare the DNA methylation scores, and the Pearson’s correlation test was used to correlate DNA methylation levels with disease severity. A p-value &lt;0.05 was considered significant. Results: The mean age of the study participants was 34.44±12.45 years. A total of 100 subjects were included in the study, with 50 being bipolar disorder patients and the remaining 50 in the control group. Bipolar cases, particularly depression, had higher levels of DNA methylation than controls (p=0.0001). On correlation analysis, patients with Bipolar Depression (BD) had a significant correlation with DNA methylation (p-value &lt;0.001) compared to patients with mania and controls. Conclusion: Bipolar patients, especially those with BD, exhibit higher levels of global DNA methylation in genes compared to healthy control groups. Global DNA methylation can serve as an important early disease marker for bipolar patients, aiding in prevention and early detection efforts.

Dilemma of cohort study-A concept of early disease markers for measured risk factors.

Dilemma of cohort study-A concept of early disease markers for measured risk factors.

Cerebrovascular damage in subjective cognitive decline: A systematic review and meta-analysis.

Subjective cognitive decline (SCD) has been postulated as an early marker of Alzheimer's Disease (AD) but it can also be associated to other non-AD pathologies such as Vascular Dementia (VaD). Nevertheless, there is scarce data about SCD as a potential harbinger of cerebrovascular pathology. Thus, we conducted a systematic review and meta-analysis on the association between SCD and cerebrovascular damage measured by neuroimaging markers. This study was performed following the PRISMA guidelines. The search was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin to December 8th, 2021. Primary studies including cognitively unimpaired adults with SCD and neuroimaging markers of cerebrovascular damage (i.e., white matter signal abnormalities, WMSA) were selected. Qualitative synthesis and meta-analysis of studies with a case-control design was performed. Of 241 articles identified, 21 research articles were selected. Eight case-control studies were included for the meta-analysis. A significant overall effect-size was observed for the mean WMSA burden in SCD relative to controls, where the WMSA burden was higher in SCD. Our findings show the potential usefulness of SCD as a harbinger of cerebrovascular disease in cognitively healthy individuals. Further research is needed in order to elucidate the role of SCD as a preclinical marker of vascular cognitive impairment.

Mild behavioral impairment and functional connectivity in dementia‐free elderly

AbstractBackgroundMild Behavioral Impairment (MBI), characterized by de novo emergent and persistent neuropsychiatric symptoms in later life, may be used to improve early detection of neurodegenerative disease. While alterations in resting‐state networks have been demonstrated in early‐stage Alzheimer’s disease (AD), few studies have explored these networks in MBI. Here, we assessed activity in the default mode network (DMN) and the salience network (SN), using resting‐state functional magnetic resonance imaging (fMRI), in association with MBI. We hypothesized that the strength of functional connectivity (FC) within the DMN and SN would be reduced in dementia‐free persons with MBI (MBI+), relative to those without (MBI‐).MethodsData from dementia‐free participants in three prospective cohort studies were pooled. MBI+ status was determined using the MBI‐checklist. Imaging data were acquired using 3T MRI. Seed‐based connectivity analyses were performed using the CONN toolbox. The DMN included the posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC), and lateral parietal (LP) regions, with the PCC as the seed. The SN included the anterior cingulate cortex (ACC), anterior insula (AI), rostral prefrontal cortex (RPFC), and supramarginal gyrus (SMG), with the ACC as the seed. FC maps of the DMN and SN were computed for each MBI group; difference maps were extracted to identify regions with significantly different connectivity across MBI groups. A threshold of p&lt;0.05 was used with false discovery rate correction for multiple comparisons at the cluster level; a p&lt;0.001 uncorrected for voxel level was used for group comparisons. All analyses were covaried for age, sex, years of education, and Montreal Cognitive Assessment scores.ResultsOf the 95 participants, 32 were MBI+ and 63 MBI‐ (mean age 71.7; 54.7% female). Within the DMN, MBI+ individuals had lower functional connectivity between the PCC and MPFC, compared to MBI‐ (β=‐0.15, p=0.004). Within the SN, MBI+ was associated with lower functional connectivity between the ACC and left AI (β=‐0.12, p=0.028).ConclusionOur findings suggest that in dementia‐free individuals, MBI is associated with decreased functional connectivity in networks disrupted in AD. This result lends additional support to MBI as a potential early marker of disease.

Abstract 10043: Plasma Metabolite Dimethylguanidino Valeric Acid and Risk of Incident Coronary Heart Disease Among Women

Introduction: Circulating dimethylguanidino valeric acid (DMGV) has been related to visceral adiposity and unhealthy obesogenic lifestyle factors, and recently emerged as an early marker of cardiovascular disease. Hypothesis: We tested whether circulating DMGV was associated with the risk of coronary heart disease (CHD) among women. We also investigated obesogenic diet/lifestyle factors and biomarkers associated with higher DMGV levels. Methods: This prospective nested case-control study included 1518 women (759 incident cases of fatal CHD and nonfatal myocardial infarction and 759 controls) from the Nurses’ Health Study (NHS). Incident cases of CHD were identified over 10-14 years of follow-up time. Obesogenic lifestyle factors (such as physical inactivity and dietary intakes), adiposity, and cardiometabolic abnormalities (hypertension, dyslipidemia, and diabetes) were assessed in the NHS and the Women's Lifestyle Validation Study (WLVS; n=723). Results: In the NHS, higher plasma DMGV levels were related to greater risk of CHD (P for linear relation=0.007) after controlling for demographic factors, family history of myocardial infarction, and postmenopausal hormone. Compared with women in the lowest quartile of DMGV levels, those in the highest quartile had a relative risk (RR) of 1.70 (95% CI: 1.25, 2.31) for CHD. The RR in the highest quartile was attenuated after controlling for obesogenic factors and adiposity. Obesogenic diet/lifestyle factors, adiposity, altered adipokine levels, and cardiometabolic abnormalities were significant factors related to higher plasma DMGV levels in the NHS and WLVS. Conclusions: Circulating DMGV may be a significant metabolite related to obesogenic diet quality, lifestyles, and cardiometabolic abnormalities among women. High DMGV levels were associated with an increased risk of incident CHD among women.

Surface-enhanced Raman spectroscopy (SERS) for protein determination in human urine

Excessive protein excretion in human urine is an early and sensitive marker of diabetic nephropathy, primary and secondary renal disease. Kidney problems, particularly chronic kidney disease, remain among the few growing causes of mortality in the world. Therefore, it is important to develop efficient, expressive, and low-cost method for protein determination. Surface-enhanced Raman spectroscopy (SERS) methods are potential candidates to achieve those criteria. In this paper, the SERS method was developed to distinguish patients with proteinuria and the healthy group. Two types of commercial gold nanoparticles with a diameter of 60 nm and 100 nm were employed to prepare substrates for the analysis of 78 samples of unique patients. Data analysis by the PCA-LDA algorithm, and the ROC curves, gave results for diagnostic figures of merits. Sensitivity, specificity, accuracy, and AUC were 0.79, 0.89, 0.85, and 0.90 for the set with 60 nm Au NPs, respectively. Sensitivity, specificity, accuracy, and AUC were 0.79, 0.98, 0.90, and 0.91 for the set with 100 nm Au NPs, respectively. The results show the potential of SERS spectroscopy in differentiating between patients with proteinuria and healthy individuals for clinical diagnostics.

Pacemaker implantation due to cardiac conduction disease in patients with subsequent cardiac sarcoidosis may be a marker of early disease and is associated with adverse 5-year clinical outcome

Abstract Background Sarcoidosis is a rare chronic granulomatous disease of unknown aetiology with potential multi-organ involvement and end-organ dysfunction. Cardiac sarcoidosis (CS) occurs in 5–10% of patients with sarcoidosis though an up to 25% prevalence has been reported by imaging and autopsy studies, suggesting undiagnosed silent disease. Progression of CS, especially if undiagnosed and untreated, may lead to heart failure, atrioventricular block (AVB), ventricular arrhythmias and sudden cardiac death. Aim We sought to determine whether signs of cardiac conduction disease (CCD) prior to the clinical diagnosis of sarcoidosis is associated with poor long-term prognosis in patients with imaging-confirmed cardiac involvement. Method All patients diagnosed with CS since January 1, 2000, at a tertiary centre (n=112) with either primary cardiac localisation (n=70) or cardiac involvement in otherwise primary non-cardiac sarcoidosis (n=42) as per imaging were included. Swedish pacemaker and ICD registry was used to identify patients who received cardiac implantable electronic device (CIED). CCD-related indications for CIED implant were defined as AVB, bi- or trifascicular block. Kaplan-Meier curve analysis and time-dependent Cox regression analysis were used for estimation of risk of death from any cause (primary endpoint), death or upgrade to cardiac resynchronization therapy (CRT, secondary endpoint) at 5 years after CS diagnosis, stratified for history of CIED implantation due to CCD. Hazard ratios were calculated in a univariate model and adjusted for age, gender and the use of implantable cardioverter-defibrillator (ICD). Results Mean age at CS diagnosis was 59±13 years (54% male). Forty-nine patients received CIED implant at a mean age of 54±13 years (14 pacemakers (29%), 14 primary prevention ICDs (29%), 13 secondary prevention ICDs (27%) and 8 CRT-D (16%)). The median time in years from CS diagnosis to CIED implant was for pacemaker −2.5 [IQR 8.5], primary ICD −0.3 [IQR 3.8], secondary ICD −4.0 [IQR 10.4] and CRT-D −0.03 [IQR 1.5]. CIED was implanted prior to CS diagnosis in 29 patients of whom 17 had CCD [MOU1] as the indication for implant. At 5-year follow-up in the CS cohort, 16 patients died and 2 underwent device upgrade to CRT (median 3.2 years [IQR 1.2]). CIED implant prior to CS diagnosis was associated with the primary (HRuni 3.5, 95% CI 1.2–10, p=0.021, Figure 1; HRadj 10.5, 95% CI 1.7–63, p=0.01) and the secondary (HR 3.5, 95% CI 1.2–10, p=0.019; HRadj 8.2, 95% CI 1.6–41.1, p=0.011) endpoints. Conclusion CIED implantation due to CCD can be an early manifestation of undiagnosed CS. It was observed in 15% of all patients with CS and was associated with adverse outcome. Identification of signs of CCD necessitating CIED implant in a middle-aged patient may motivate further diagnostic work-up aimed at timely detection of concealed CS. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Hjärt-Lung fondenAvtal om Läkarutbildning och Forskning

Quantitative bone imaging biomarkers and joint space analysis of the articular Fossa in temporomandibular joint osteoarthritis using artificial intelligence models.

Temporomandibular joint osteoarthritis (TMJ OA) is a disease with a multifactorial etiology, involving many pathophysiological processes, and requiring comprehensive assessments to characterize progressive cartilage degradation, subchondral bone remodeling, and chronic pain. This study aimed to integrate quantitative biomarkers of bone texture and morphometry of the articular fossa and joint space to advance the role of imaging phenotypes for diagnosis of Temporomandibular Joint Osteoarthritis (TMJ OA) in early to moderate stages by improving the performance of machine-learning algorithms to detect TMJ OA status. Ninety-two patients were prospectively enrolled (184 h-CBCT scans of the right and left mandibular condyles), divided into two groups: 46 control and 46 TMJ OA subjects. No significant difference in the articular fossa radiomic biomarkers was found between TMJ OA and control patients. The superior condyle-to-fossa distance (p < 0.05) was significantly smaller in diseased patients. The interaction effects of the articular fossa radiomic biomarkers enhanced the performance of machine-learning algorithms to detect TMJ OA status. The LightGBM model achieved an AUC 0.842 to diagnose the TMJ OA status with Headaches and Range of Mouth Opening Without Pain ranked as top features, and top interactions of VE-cadherin in Serum and Angiogenin in Saliva, TGF-β1 in Saliva and Headaches, Gender and Muscle Soreness, PA1 in Saliva and Range of Mouth Opening Without Pain, Lateral Condyle Grey Level Non-Uniformity and Lateral Fossa Short Run Emphasis, TGF-β1 in Serum and Lateral Fossa Trabeculae number, MMP3 in Serum and VEGF in Serum, Headaches and Lateral Fossa Trabecular spacing, Headaches and PA1 in Saliva, and Headaches and BDNF in Saliva. Our preliminary results indicate that condyle imaging features may be more important in regards to main effects, but the fossa imaging features may have a larger contribution in terms of interaction effects. More studies are needed to optimize and further enhance machine-learning algorithms to detect early markers of disease, improve prediction of disease progression and severity to ultimately better serve clinical decision support systems in the treatment of patients with TMJ OA.

Ultrasound Evaluation of Carotid Artery Intima-Media Thickness: Effective Early Marker of Carotid Artery Disease in Adult Head and Neck Cancer Patients After Neck Radiation?

Radiation is a recommended front-line treatment for many adult head and neck cancer (HNC) patients. Early identification of radiation-associated carotid artery disease (CAD), a well-known phenomenon, can minimize long-term sequelae. This integrative literature review assesses the use of ultrasound measured carotid artery intima-media thickness (IMT) as an early marker of CAD in adult HNC patients after neck radiation. A search of PubMed and Scopus databases in December 2020 yielded 475 unique articles published between January 2011 and December 2020, of which eight met inclusion criteria. Carotid IMT, measured by ultrasound, was significantly increased after neck radiation in all reviewed publications. Ultrasound was able to detect IMT measurements exceeding or at risk of exceeding pathologic IMT, indicating higher risk for future cardiovascular events. Findings suggest that radiation-associated carotid IMT increase occurs early and persists for years. Ultrasound adequately detects post-radiation carotid IMT changes and is a reliable early marker for radiation-associated CAD. Initiation of ultrasound screening should be considered prior to neck radiation for a baseline and at 1 year post treatment to optimize medical management.

Circulating Tumour Cells, Cell Free DNA and Tumour-Educated Platelets as Reliable Prognostic and Management Biomarkers for the Liquid Biopsy in Multiple Myeloma.

Simple SummaryEven though the presently employed biomarkers in the detection and management of multiple myeloma are demonstrating encouraging results, the mortality percentage of the malignancy is still elevated. Thus, searching for new diagnostic or prognostic markers is pivotal. Liquid biopsy allows the examination of circulating tumour DNA, cell-free DNA, extracellular RNA, and cell free proteins, which are released into the bloodstream due to the breakdown of tumour cells or exosome delivery. Liquid biopsy can now be applied in clinical practice to diagnose, and monitor multiple myeloma, probably allowing a personalized treatment of the disease.Liquid biopsy is one of the fastest emerging fields in cancer evaluation. Circulating tumour cells and tumour-originated DNA in plasma have become the new targets for their possible employ in tumour diagnosis, and liquid biopsy can define tumour burden without invasive procedures. Multiple Myeloma, one of the most frequent hematologic tumors, has been the target of therapeutic progresses in the last few years. Bone marrow aspirate is the traditional tool for diagnosis, prognosis, and genetic evaluation in multiple myeloma patients. However, this painful procedure presents a relevant drawback for regular disease examination as it requires an invasive practice. Moreover, new data demonstrated that a sole bone marrow aspirate is incapable of expressing the multifaceted multiple myeloma genetic heterogeneity. In this review, we report the emerging usefulness of the assessment of circulating tumour cells, cell-free DNA, extracellular RNA, cell-free proteins, extracellular vesicles, and tumour-educated platelets to evaluate the changing mutational profile of multiple myeloma, as early markers of disease, reliable predictors of prognosis, and as useful tools to perform less invasive monitoring in multiple myeloma.

Impact of Periodontitis on Glycemic Control and Metabolic Status in Diabetes Patients: Current Knowledge on Early Disease Markers and Therapeutic Perspectives.

Diabetes mellitus and periodontitis are two of the most common chronic diseases affecting the world's population, and they are intimately linked. For several years, in fact, it has been known that there is an interdependent relationship between the two diseases: Diabetes promotes the destruction of periodontal tissues, and periodontal disease negatively affects glycemic control. In relation to the control of dental plaque and oral dysbiosis responsible for periodontal disease, both nonsurgical and surgical therapy associated with proper home hygiene procedures have emerged as essential for good glycemic control. Moreover, several evidences suggest the essential role played by the control of periodontal disease in preventing the onset of the most common complications of diabetes: cardiovascular diseases, retinopathies, and other systemic diseases. The aim of this study is to update the current knowledge on the bi-univocal relationship between diabetes and periodontitis and the impact of therapy in the optimal management of these two disorders. From the information found in the literature, it has emerged that the correct treatment of periodontal disease in diabetic patients represents one of the main mechanisms and means currently established and valid to control periodontal disease and glucose metabolism and prevent the onset or development of diabetic complications.

Transthyretin cardiac amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure (HF) and mortality worldwide. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have shifted ATTR-CA from a rare and untreatable disease to a relatively prevalent condition that clinicians should consider on a daily basis. Amyloid fibril formation results from age-related failure of homoeostatic mechanisms in wild-type ATTR (ATTRwt) amyloidosis (non-hereditary form) or destabilizing mutations in variant ATTR (ATTRv) amyloidosis (hereditary form). Longitudinal large-scale studies in the United States suggest an incidence of cardiac amyloidosis in the contemporary era of 17 per 100 000, which has increased from a previous estimate of 0.5 per 100 000, which was almost certainly due to misdiagnosis and underestimated. The presence and degree of cardiac involvement is the leading cause of mortality both in ATTRwt and ATTRv amyloidosis, and can be identified in up to 15% of patients hospitalized for HF with preserved ejection fraction. Associated features, such as carpal tunnel syndrome, can preceed by several years the development of symptomatic HF and may serve as early disease markers. Echocardiography and cardiac magnetic resonance raise suspicion of disease and might offer markers of treatment response at a myocardial level, such as extracellular volume quantification. Radionuclide scintigraphy with 'bone' tracers coupled with biochemical tests may differentiate ATTR from light chain amyloidosis. Therapies able to slow or halt ATTR-CA progression and increase survival are now available. In this evolving scenario, early disease recognition is paramount to derive the greatest benefit from treatment.