Normal Subjects Research Articles

Exosomal miRNAs Differentiate Chronic Total Occlusion from Acute Myocardial Infarction.

Although coronary artery occlusion can have a negative effect on the myocardium, chronic total occlusion (CTO) exhibits different clinical features from those of acute myocardial infarction (AMI). In this study, we identify the differential associations of exosomal miRNAs with CTO and AMI. Exosomes were isolated from the plasma obtained from coronary arteries of patients undergoing percutaneous coronary intervention to treat CTO (n = 29) and AMI (n = 24), followed by small RNA sequencing, target gene predictions, and functional enrichment analyses. Promising miRNA markers were validated using real-time PCR in 35 CTO, 35 AMI, and 10 normal subjects. A total of 205 miRNAs were detected in all subjects, and 20 and 12 miRNAs were upregulated and downregulated in CTO compared to AMI patients, respectively (|fold change| > 4, FDR q < 0.05). The target genes of miRNAs that were higher in CTO patients were associated with "regulation of cell cycle phase transition", "cell growth", and "apoptosis". The target genes of miRNAs that were lower in CTO patients were enriched in terms such as "muscle cell differentiation", "response to oxygen levels", and "artery morphogenesis". On qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p were significantly different between CTO and AMI patients. The miRNA expression levels accurately distinguished CTO from AMI patients with 79% specificity and 97% sensitivity. The miRNA contents of plasma exosomes were significantly different between CTO and AMI patients. The miRNAs may play important roles in CTO and AMI.

2D Shear Wave Elastography of Normal Thyroid Gland in Nepalese Population

Ultrasonography (USG) is modality of choice for normal, diffuse or nodular thyroid diseases. Two dimensional shear wave elastography (2D-SWE) is the latest innovation in USG techniques that allows real-time quantitative assessment of tissue stiffness using acoustic radiation force impulse (ARFI) induced by ultrafast focused US beam sequence (up to 20,000Hz) to record the propagation of the shear waves in real time and displays a map that represents the local elasticity values of tissues in real-time and in a quantitative manner without any compression of the organ. At times, there are difficulties in differentiating normal thyroid gland from diffuse thyroid disease based solely on gray scale USG for which 2D-SWE can be an adjunct. This study aims to establish 2D-SWE parameters for normal thyroid gland in Nepalese population. A cross sectional descriptive study was carried out with 2D SWE on all euthyroid patients with normal thyroid gland on B-mode USG at Department of Radiology, Nepal Medical College Teaching Hospital between December 2021 and November 2022. Tissue stiffness of normal thyroid gland was recorded and tabulated in terms of SMV units (m/s) according age and gender. Out of 100 subjects ( 52 females and 48 males) the youngest was 16 year female and oldest was 68 year female with mean age of 37.07 year (S.D = 11.58). Minimum mean velocity of 1.78 m/s was seen in 36 year old male and maximum of 3.40 m/s in 26 year old female. Mean of mean velocity was 2.36 m/s with (S.D= 0.34). Linear positive correlation was seen between shear wave velocities and age with no statistically significant difference between genders. This study had the most number of normal subjects (100) with almost equal gender distribution (52 females and 48 males) compared to previous studies in known literature. This study also analyzed correlation of shear wave velocity with age unlike other studies. Statistically significant correlation was seen between age and velocities in males only and also in mean velocities between age group 21-40 and 41-60 years (p-value= 0.037).

Functional Tests of the Abdominal Wall Muscles in Normal Subjects and in Patients with Diastasis and Oblique Inguinal Hernias in a Pilot Study.

To identify typical patterns of abdominal wall muscle activation in patients with diastasis recti and inguinal hernias compared to controls during the Valsalva maneuver, voluntary coughing, and physical activity. The study included 15 subjects: 5 with diastasis recti, 4 with inguinal hernias, and 6 healthy controls. The functions of rectus abdominis (RA) and external oblique (OE) muscles were measured by surface electromyography (sEMG). Using ultrasound, the thicknesses of the RA, OE, internal oblique (IO), and transversus abdominis (TA) muscles were assessed as well as the echo intensity (EI) of RA and OE. We found a significant effect of the type of abdominal wall pathology on the maximum sEMG amplitude (p = 0.005). There was a reliable trend in maximum sEMG amplitude, with the highest one in diastasis recti and a significantly lower one in inguinal hernias. Duncan's test showed a significant difference in muscle thickness, both on the right and left sides, between patients with diastasis and controls, but only on the left side between patients with diastasis and those with inguinal hernia (p < 0.05). The abdominal wall pathology results in a change in the function and structure of the abdominal muscles, which can be detected using electromyography and ultrasound examination. The presence of diastasis recti is accompanied by an increase in bioelectrical activity and a decrease in thickness.

Electronic Nose Analysis of Exhaled Breath Volatile Organic Compound Profiles during Normoxia, Hypoxia, and Hyperoxia.

This study investigates volatile organic compound (VOC) profiles in the exhaled breath of normal subjects under different oxygenation conditions-normoxia (FiO2 21%), hypoxia (FiO2 11%), and hyperoxia (FiO2 35%)-using an electronic nose (e-nose). We aim to identify significant differences in VOC profiles among the three conditions utilizing principal component analysis (PCA) and canonical discriminant analysis (CDA). Our results indicate distinct VOC patterns corresponding to each oxygenation state, demonstrating the potential of e-nose technology in detecting physiological changes in breath composition (cross-validated accuracy values: FiO2 21% vs. FiO2 11% = 63%, FiO2 11% vs. FiO2 35% = 65%, FiO2 21% vs. FiO2 35% = 71%, and p < 0.05 for all). This research underscores the viability of breathomics in the non-invasive monitoring and diagnostics of various respiratory and systemic conditions.

Photoreceptor outer segment reflectivity with ultrahigh resolution visible light optical coherence tomography in systemic hydroxychloroquine use.

To evaluate outer retinal organization in normal subjects and those using hydroxychloroquine (HCQ) with ultrahigh resolution visible light optical coherence tomography (VIS-OCT). Forty eyes of 22 adult subjects were recruited from a tertiary care retina practice including controls (20 eyes, 12 subjects, mean age 40±22yrs, mean logMAR BCVA 0.19, 90% female) and subjects with a history of HCQ use (20 eyes, 10 subjects, mean age 62±17yrs, mean logMAR BCVA 0.03, 67% female). Each subject was imaged using a custom-built VIS-OCT device (axial resolution 1.3μm) and FDA-approved OCT devices. Using VIS-OCT, control subjects demonstrate 5 and 6 hyperreflective bands in the foveal and parafoveal regions, respectively, between the outer nuclear layer and Bruch's membrane. These bands demonstrate intensity profiles complementary to the known histopathologic distribution of rods and cones. In comparison to controls, subjects taking HCQ demonstrate blunting of all bands, particularly bands 2-4. In all cases of suspected or known toxicity, VIS-OCT demonstrated attenuation of band 3i and in no cases was there attenuation of other bands that was more severe than band 3i, suggesting that changes in the reflectivity of Band 3i may be the earliest identifiable sign of HCQ toxicity. VIS-OCT of the outer retina demonstrates a unique outer retinal banding pattern corresponding to photoreceptor density profiles. There is a notable attenuation of the photoreceptor outer segment reflectivity profile associated with early HCQ toxicity. This finding may be an early, and possibly reversible, sign of HCQ toxicity, primarily impacting the cones.

Acoustics Features of Cervical Auscultation in Dysphagic and Dysphonic Individuals: A Preliminary Study.

The acoustics of cervical auscultation of swallowing, a potential objective tool for the swallowing assessment, has been explored in normal subjects. However, there needs to be more literature profiling the same in individuals with swallowing problems. The study estimated the acoustic features of swallowing sounds in individuals with swallowing and voice problems and compared them with the previous reported findings in literature. Eight individuals with dysphonia and dysphagia were recruited to analyse cervical auscultation using a vibration pickup conduction microphone attached to the cricoid region on the neck of each participant. The participants showed different acoustic wave morphologies for swallowing sounds, including multiple waves, which were absent in the normal waveforms. The mean intensity, peak intensity were as higher in the current study participants than normal values reported literature in previous, suggesting increased strain and effort in individuals with dysphagia. The duration parameters were comparatively longer than those reported in previous literature showing the prolonged pharyngeal stage. The morphological and acoustic characteristics of swallow sounds in dysphagic and dysphonic individuals are deviating from then normal patterns. The utilisation of these features will help comprehensive diagnosis of swallowing difficulties. The LTAS was found to be the appropriate way of estimating the frequency of the peak intensity than using the intensity contour in the spectrogram since the values calculated using LTAS are more representative of the parameters. The study was a preliminary attempt to explore the acoustic features in individuals with voice and swallowing problems.

Automatic Quantification of Abnormal Lung Parenchymal Attenuation on Chest Computed Tomography Images Using Densitometry and Texture-based Analysis.

To compare texture-based analysis using convolutional neural networks (CNNs) against lung densitometry in detecting chest computed tomography (CT) image abnormalities. A U-NET was used for lung segmentation, and an ensemble of 7 CNN architectures was trained for the classification of low-attenuation areas (LAAs; emphysema, cysts), normal-attenuation areas (NAAs; normal parenchyma), and high-attenuation areas (HAAs; ground-glass opacities, crazy paving/linear opacity, consolidation). Lung densitometry also computes (LAAs, ≤-950HU), NAAs (-949 to -700HU), and HAAs (-699 to -250HU). CNN-based and densitometry-based severity indices (CNN and Dens, respectively) were calculated as (LAA+HAA)/(LAA+NAA+HAA) in 812 CT scans from 176 normal subjects, 343 patients with emphysema, and 293 patients with interstitial lung disease (ILD). The correlation between CNN-derived and densitometry-derived indices was analyzed, alongside a comparison of severity indices among patient subgroups with emphysema and ILD, using the Spearman correlation and ANOVA with Bonferroni correction. CNN-derived and densitometry-derived severity indices (SIs) showed a strong correlation (ρ=0.90) and increased with disease severity. CNN-SIs differed from densitometry SIs, being lower for emphysema and higher for moderate to severe ILD cases. CNN estimations for normal attenuation areas were higher than those from densitometry across all groups, indicating a potential for more accurate characterization of lung abnormalities. CNN outputs align closely with densitometry in assessing lung abnormalities on CT scans, offering improved estimates of normal areas and better distinguishing similar abnormalities. However, this requires higher computing power.

Identification and evaluation of a serum microRNA panel to diagnose colorectal cancer patients.

Screening plays a crucial role in the early detection of colorectal cancer, greatly reducing mortality rates. The objective of this study was to identify a non-invasive diagnostic method utilizing serum microRNA expression for the diagnosis of colorectal cancer patients. The study consisted of three stages. In the first stage, 129 patients with colorectal cancer and 129 normal subjects were recruited as the training set for the development of a blood miRNA panel. The second stage involved recruiting 200 patients from each group as the validation cohort. Finally, a blinded study was conducted in the third stage, with 260 patients recruited to determine the predictive value of our miRNA panel. Serum samples were prospectively collected from colorectal cancer patients and normal subjects between 2017 and 2021 at Queen Mary Hospital in Hong Kong. Quantitative PCR was utilized to detect the serum levels of candidate microRNAs, and a multiple linear regression model was employed to formulate a serum microRNA panel for diagnosing colorectal cancer patients. The performance of the panel was evaluated using ROC analysis. Our study showed that the values of three pairs of serum microRNAs, namely miR-106b-5p/miR-1246, miR-106b-5p/miR-16 and miR-106b-5p/miR-21-5p, exhibited statistically significant differences between colorectal cancer patients and normal subjects. A serum microRNA panel formulated from these three pairs of microRNAs demonstrated high accuracy in diagnosing colorectal cancer patients from normal subjects, with an AUC of approximately 0.9. The serum miRNA test proved to be a feasible and promising non-invasive biomarker for the diagnosis of colorectal cancer patients in comparison to normal subjects.

HYPERCHOLESTEROLEMIA AS A CAUSATIVE RISK FACTOR FOR NON-ALCOHOLIC FATTY LIVER DISEASE.

Increased serum Cholesterol level is a known risk factor for cardiovascular diseases. Derangements in serum Cholesterol levels will affect normal hepatic Cholesterol homeostasis resulting in hypercholesterolemia. Non-Alcoholic fatty liver disease (NAFLD) initially asymptomatic but can lead to cirrhosis and hepatocellular carcinoma from mild steatosis to non-alcoholic steatohepatitis. The objective of this study is to find out hypercholesterolemia as a causative risk factor in NAFLD patients. This will help to prevent the development and progression of the disease. This cross-sectional study was conducted from 16th August 2021 to 16th August 2022 at Ayub Medical institute Abbottabad. Random sampling technique was used. Sample size was 100, in which 50 were diagnosed cases of liver disease and 50 normal subjects diagnosed on ultrasound. A questionnaire was designed. Subjects between 40-65 years age group were selected after informed consent and confidentiality. Data was collected from the out-patient department of medical and surgical unit and analysed with the help of SPSS-22.00. Chi-square test was used. Enzymatic kit method was used for serum cholesterol and triglycerides estimation. BMI was derived from the mass (weight) and height of the person. It was found that 48% study subjects with NAFLD shows high serum Cholesterol levels while 52% subjects with NAFLD were found within normal limits but 10% individuals with no fatty infiltration had high serum Cholesterol levels while 90% without NAFLD had shown normal serum Cholesterol levels. Significant p-value of <0.001 was found between presence of NAFLD and high serum Cholesterol levels. Significant association was also found among serum Cholesterol and serum Triglyceride levels showing strong association of serum cholesterol levels with NAFLD and raised serum triglycerides levels with p-value 0.001. Similarly, significant association was found between serum cholesterol levels and BMI with p-value ˂0.001. Highly significant association was found between Hypercholesterolemia and non-alcoholic fatty liver disease. It suggests hypercholesterolemia as a causative risk factor for NAFLD.

Functional correlation tensors in brain white matter and the effects of normal aging

Resting state correlations between blood oxygenation level dependent (BOLD) MRI signals from voxels in white matter (WM) are demonstrably anisotropic, so that functional correlation tensors (FCT) may be used to quantify the underlying microstructure of BOLD effects in WM tracts. However, the overall spatial distribution of FCTs and their metrics in specific populations has not yet been established, and the factors that affect their precise arrangements remain unclear. Changes in WM occur with normal aging, and these may be expected to affect FCTs. We hypothesized that FCTs exhibit a characteristic spatial pattern and may show systematic changes with aging or other factors. Here we report our analyses of the FCT characteristics of fMRI images of a large cohort of 461 cognitively normal subjects (190 females, 271 males) sourced from the Open Access Series of Imaging Studies (OASIS), with age distributions of 42 y/o – 95 y/o. Group averages and statistics of FCT indices, including axial functional correlations, radial functional correlations, mean functional correlations and fractional anisotropy, were quantified in WM bundles defined by the JHU ICBM-DTI-81 WM atlas. In addition, their variations with normal aging were examined. The results revealed a dimorphic distribution of changes in FCT metrics with age, with decreases of the functional correlations in some regions and increases in others. Supplementary analysis revealed that females exhibited significant age effects on a greater number of WM areas, but the interaction between age and sex was not significant. The findings demonstrate the reproducibility of the spatial distribution of FCT metrics and reveal subtle regional changes with age.

Clot waveform analysis to differentiate mild, moderate, and severe hemophilia A

Background Clot waveform analysis can be used to evaluate clot formation profiles. This waveform can be obtained from activated partial thromboplastin time (APTT) assays without additional reagents and shows different patterns in hemophilia patients with coagulation factor VIII (F VIII) deficiency or abnormality. Objective To determine the clot wave pattern and its process in clot formation phases (pre-coagulation, coagulation, and post-coagulation) in normal and hemophilia A subjects, analyze for possible correlations between clot wave parameters and F VIII activity, and obtain the pattern of coagulation curves in hemophilia subjects as a step to assess clot waveform analysis as a possible screening tool for hemophilia. Methods In this cross-sectional study, we performed clot wave analysis in 145 adult and pediatric subjects with hemophilia to obtain the clot wave pattern in this condition. Clot wave analysis was also done in 160 subjects with normal hemostasis to obtain reference clot wave parameters. Results In this study, the starting point of coagulation phase in normal subjects was between 30-40 seconds, with a shorter pre-coagulation phase and steeper slope. Hemophilia patients had a longer pre-coagulation phase and flatter slope, especially in severe hemophilia A patients, who had longer and more variable coagulation starting points (P&lt;0.001). The absolute values of maximum coagulation velocity (Min1), maximum coagulation acceleration (Min2), and maximum coagulation deceleration (Max2) of hemophilia A patients were also lower than those of normal hemostasis patients, with lower absolute value seen in severe than in mild-moderate hemophilia A patients. A moderate correlation was found between Min1, Min2, and Max2 with F VIII activity (P&lt;0.001). Conclusion Clot wave analysis may be considered as a method for screening hemophilia patients to distinguish mild-moderate and severe hemophilia A patients in health facilities that lack the ability to perform F VIII assays.

Magnetic Resonance Imaging Biomarkers of Muscle.

This review is focused on the current status of quantitative MRI (qMRI) of skeletal muscle. The first section covers the techniques of qMRI in muscle with the focus on each quantitative parameter, the corresponding imaging sequence, discussion of the relation of the measured parameter to underlying physiology/pathophysiology, the image processing and analysis approaches, and studies on normal subjects. We cover the more established parametric mapping from T1-weighted imaging for morphometrics including image segmentation, proton density fat fraction, T2 mapping, and diffusion tensor imaging to emerging qMRI features such as magnetization transfer including ultralow TE imaging for macromolecular fraction, and strain mapping. The second section is a summary of current clinical applications of qMRI of muscle; the intent is to demonstrate the utility of qMRI in different disease states of the muscle rather than a complete comprehensive survey.

A parafoveal retinal cones analysis using adaptive-optics retinal camera in patients with primary open angle glaucoma

ObjectivesTo study the density, spacing, and regularity of retinal cone photoreceptors using an Adaptive Optics (AO) retinal camera (Rtx1TM, Imagine Eyes, Orsay, France) in patients with Primary Open Angle Glaucoma (POAG) and to compare the outcomes with those of healthy age-matched control subjects.MethodsThe study included 43 eyes with POAG and 31 eyes of normal subjects. POAG patients were divided into three groups according to the severity of the visual field defect. The AO Rtx1TM was used to obtain images of the parafoveal cone mosaic to calculate cone values. Analysis was performed at two and four degrees of eccentricity from the fovea along the four meridians (nasal, temporal, superior, inferior).ResultsIn POAG eyes, the mean ± standard deviation (SD) cone density at 2° considering all meridians was significantly lower than in normal controls (23,058.6 ± 3532.0 cones/mm2, and 25,511.7 ± 3157.5 cones/mm2, respectively; p = 0.003). Cone spacing was 7.3 ± 0.5 µm in POAG and 7.0 ± 0.4 µm in normal controls (p = 0.005), and cone regularity was 90.5 ± 4.9% and 93.5 ± 1.9% in POAG and normal controls, respectively (p < 0.001). At 4° similar trends were observed. However, no significant differences were found among patients with different severity of POAG (p > 0.05).ConclusionsUsing AO Rtx1TM, significant differences in retinal photoreceptors mosaic pattern were found between POAG eyes and age-matched controls, indicating a reduction in photoreceptors in POAG. No significant differences in retinal photoreceptor values were found among the three POAG groups.

Quantitative analysis of peripapillary capillary volume using dense B-scan OCT angiography in normal and diabetic retina

BackgroundThe value of quantitatively analyzing peripapillary capillary volume (PPCV) distribution was explored in normal and diabetic retinopathy (DR) eyes using dense B-scan optical coherence tomography angiography (DB OCTA).MethodsThis was a cross-sectional observational study followed by prospective follow-up for those with DR, which enrolled 101 healthy subjects and 140 DR patients. Dense, automatic, real-time (DART) volume scans of DB OCTA were performed using a Spectralis HRA + OCT2. ImageJ and MATLAB were used to process and calculate PPCV distribution detected by DB OCTA.ResultsIn normal subjects, PPCV distribution were significantly correlated with the age and quadrant location (all P < 0.001). The PPCV distribution in each quadrant was significantly lower in severe nonproliferative DR patients than in normal subjects in all age groups (all P < 0.05, t-test). Compared to normal subjects, the PPCV distribution improved significantly in the pan-retinal photocoagulation treatment and surgery groups (all P < 0.001). No significant variation was observed in the anti-VEGF treatment group and normal subjects (P > 0.05). The PPCV distribution is significantly correlated with post-treatment best-corrected visual acuity in both the pan-retinal photocoagulation treatment and surgery groups (all P < 0.003) but not in the anti-VEGF treatment group (P = 0.940).ConclusionsQuantitative assessment of PPCV distribution using DB OCTA is valuable in prognosis evaluation of DR with pan-retinal photocoagulation and surgery.

Predicting Late Gadolinium Enhancement of Acute Myocardial Infarction in Contrast-Free Cardiac Cine MRI Using Deep Generative Learning.

Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is a standard technique for diagnosing myocardial infarction (MI), which, however, poses risks due to gadolinium contrast usage. Techniques enabling MI assessment based on contrast-free CMR are desirable to overcome the limitations associated with contrast enhancement. We introduce a novel deep generative learning method, termed cine-generated enhancement (CGE), which transforms standard contrast-free cine CMR into LGE-equivalent images for MI assessment. CGE features with multislice spatiotemporal feature extractor, enhancement contrast modulation, and sophisticated loss function. Data from 430 patients with acute MI from 3 centers were collected. After image quality control, 1525 pairs (289 patients) of center I were used for training, and 293 slices (52 patients) of the same center were reserved for internal testing. The 40 patients (401 slices) of the other 2 centers were used for external testing. The CGE robustness was further tested in 20 normal subjects in a public cine CMR data set. CGE images were compared with LGE for image quality assessment and MI quantification regarding scar size and transmurality. The CGE method produced images of superior quality to LGE in both internal and external data sets. There was a significant (P<0.001) correlation between CGE and LGE measurements of scar size (Pearson correlation, 0.79/0.80; intraclass correlation coefficient, 0.79/0.77) and transmurality (Pearson correlation, 0.76/0.64; intraclass correlation coefficient, 0.76/0.63) in internal/external data set. Considering all data sets, CGE demonstrated high sensitivity (91.27%) and specificity (95.83%) in detecting scars. Realistic enhancement images were obtained for the normal subjects in the public data set without false positive subjects. CGE achieved superior image quality to LGE and accurate scar delineation in patients with acute MI of both internal and external data sets. CGE can significantly simplify the CMR examination, reducing scan times and risks associated with gadolinium-based contrasts, which are crucial for acute patients.

Continuous muscle pump activation by neuromuscular electrical stimulation of the common peroneal nerve in the treatment of patients with venous leg ulcers: A position paper.

The standard treatment for patients with confirmed Venous Leg Ulcers (VLUs) is compression therapy to improve the function of the calf muscle pump. There is a significant cohort of patients who are unable to tolerate optimal compression therapy or indeed any level of compression therapy. In addition, there is a cohort of patients who can tolerate compression whose ulcers show little or no evidence of healing. There is a need for ways to further improve calf muscle pump function and to improve venous ulcer healing in these patients. Published data were reviewed on the use of Muscle Pump Activation (MPA) using common peroneal nerve neuromuscular electrical stimulation (NMES) to improve calf muscle pump function. There is physiological evidence that MPA can improve calf muscle pump function and venous return in both control subjects and in patients with venous disease. The use of MPA has also been shown to improve venous flow volume and venous flow velocity on ultrasound scanning in patients with venous disease. MPA has been shown to improve microcirculation in the skin using Laser Doppler and laser Doppler Speckle Contrast Imaging, in both normal subjects as well as in patients with venous disease and VLU. A recent randomized controlled trial of MPA plus compression therapy compared with compression therapy alone, found significantly faster rates of healing with the use of MPA in addition to compression therapy. There are indications for the use of MPA as an adjunctive treatment to enhance calf muscle pump function in patients with VLU: who cannot tolerate compression therapy who can only tolerate suboptimal, low-level compression whose ulcer healing remains slow or stalled with optimal compression.

P18: BDNF levels and affective disorders as a marker of vulnerability to developing cognitive impairment in the Chilean adult population

Summary: Disorders related to progressive cognitive decline constituting an important cause of global death and disability-adjusted life years because conditions are also associated to impairment of several brain functions, psychological and behavioral changes, regardless of economic status. Brain-derived neurotrophic factor (BDNF) is a neurotrophin highly relevant in memory, learning and neuroplasticity processes in adults. The amount of plasma BDNF has been considered to partly reflect its secretion in the brain. Its deficiency is associated with affective disorders and neurodegenerative pathologies such as Alzheimer disease and Parkinson’sdisease.The aim of this study was to identify quantifiable biomarkers (serum levels of BDNF) and clinical marker (state of depression and anxiety) that allow early detection of cognitive impairment risk. We made an analytic and transversal study with a representative sample (n:307) of the population over 50 years old in the south of Chile (X region). We determine the cognitive condition of the population by applying cognitive functionality tests, such as the minimental status examination (MMSE) test and identify demographic and psychosocial characteristics that constitute impairment cognitive risk. Subsequently, we determined depression status (scale of Yesavage) and anxiety status (Beck inventory), and finally we made a quantitative determination of human BDNF at the blood level using ELISA technique.Our results revealed that 26.7% of the participants exhibited some degree of cognitive impairment, being higher in women (55.7%) with average age of 70,7. A 18,2% of subjects manifested indicators of depression and 33,2% have a very hight level of anxiety. The correlation analysis revealed a significant positive correlation between MMSE test (p &lt; 0.001) and both BDNF plasma levels (p &lt; 0.001) and education level (p &lt; 0.001) scores. The results additionally indicated a negative correlation between cognitive functions and age range/anxiety state, suggesting low age level/hight level of anxiety in subjects with more pronounced cognitive decline (p &lt; 0.001),. In consistent, the results of our study point towards decreases plasma BDNF levels and hight levels of anxiety in cognitive impairment subjects compared with cognitive normal subjects, which may be due to the early and middle stages of neurodegeneration process.

Biomechanical effects of mandibular deviation on the temporomandibular joint in patients with mandibular prognathism under incisal occlusion

PurposeThe aim of this study was to investigate the biomechanical effects of mandibular deviation on the TMJ in patients with mandibular prognathism before and after orthognathic surgery using three-dimensional finite element analysis. MethodsEight patients with mandibular prognathism without deviation, eight patients with mandibular prognathism with deviation and sixteen normal subjects were recruited. Three-dimensional models of the maxillofacial were reconstructed using MIMICS. Nine muscle forces were used to simulate incisal occlusion and contact was used to simulate fossa-disc-condyle interactions. ResultsBefore surgery, the stress in the TMJ was generally greater in the Pre-MD&MP group than in the Pre-MD group; it was much greater in both groups than in the control group, ranging from about 2 to 12 times as great in the Pre-MD group and from about 5 to 64 times as great in the Pre-MD&MP group. After orthognathic surgeries, the stresses in the Post-MP&MD were significantly reduced by approximately 21.7 % to 93.4 %. And in the Post-MP group, the stresses were reduced by approximately 1.4 % to 51.1 %. ConclusionMandibular deviation exacerbated the abnormal stress distribution in the TMJ of patients with mandibular prognathism. Orthognathic surgeries could improve the stress distribution in patients with mandibular prognathism (with and without deviation). TMD was closely related to the stress levels of the TMJ.

The Early Perfusion Image Is Useful to Support the Visual Interpretation of Brain Amyloid-PET With 18F-Flutemetamol in Borderline Cases.

Visual interpretation of brain amyloid-β (Aβ) PET can be difficult in individuals with borderline Aβ burden. Coregistration with individual MRI is recommended in these cases, which, however, is not always available. This study evaluated coregistration with the early perfusion frames acquired immediately after tracer injection to support the visual interpretation of the late Aβ-frames in PET with 18F-flutemetamol (FMM). Fifty dual-time-window FMM-PET scans of cognitively normal subjects with 0 to 60 Centiloids were included retrospectively (70.1 ± 6.9 years, 56% female, MMSE score 28.9 ± 1.3, 42% APOE ɛ4 carrier). Regional Aβ load was scored with respect to a 6-point Likert scale by 3 independent raters in the 10 regions of interest recommended for FMM reading using 3 different settings: Aβ image only, Aβ image coregistered with MRI, and Aβ image coregistered with the perfusion image. The impact of setting, within- and between-readers variability, region of interest, and Aβ-status was tested by repeated-measure analysis of variance of the Likert score. The Centiloid scale ranged between 2 and 52 (interquartile range, 7-19). Support of visual scoring by the perfusion image resulted in the best discrimination between Aβ-positive and Aβ-negative cases, mainly by improved certainty of excluding Aβ plaques in Aβ-negative cases (P = 0.030). It also resulted in significantly higher between-rater agreement. The setting effect was most pronounced in the frontal lobe and in the posterior cingulate cortex/precuneus area (P = 0.005). The early perfusion image is a suitable alternative to T1-weighted MRI to support the visual interpretation of the late Aβ image in FMM-PET.

Osteocalcin: A potential marker to identify and monitor girls with rapidly progressive central precocious puberty.

To evaluate the suitability of serum osteocalcin (OC) as a marker to distinguish between rapidly and non-rapidly progressive central precocious puberty (RP-CPP and NRP-CPP), as well as its potential to assess growth rates following treatment with gonadotropin-releasing hormone agonist (GnRHa). Serum levels of OC were measured using enzyme-linked immunosorbent assays in girls diagnosed with either RP-CPP or NRP-CPP as well as in normal control subjects. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value for OC. Multivariate linear regression analysis was used to analyse the main influencing factors associated with OC. Serum OC levels were higher in the CPP girls when compared to normal controls (110.76 ± 43.69 vs 55.97 ± 20.96 ng/mL, P < 0.001). The level in the RP-CPP group was higher than the NRP-CPP group (153.28 ± 33.89 vs 88.33 ± 29.26 ng/mL, P < 0.001). The cut-off value of OC levels for distinguishing between RP-CPP and NRP-CPP was 107.05 ng/mL, the sensitivity was 94.7% and the specificity was 77.8%, which was superior to using the basal luteinising hormone (B-LH) levels, and the area under ROC curve (AUC) were 0.933 versus 0.695, respectively. Following 1-2 years of treatment with GnRHa for girls with CPP, both OC levels and the growth rates decreased to pre-pubertal values. B-LH levels, bone age and body weight were also significant factors, which affected OC levels. Serum OC levels may be a useful marker for distinguishing RP-CPP from NRP-CPP. In addition, it was also found to be a useful predictor for growth rate during GnRHa treatment.