Category: Nevin Manimala

BMC Genomics. 2022 Dec 1;23(1):789. doi: 10.1186/s12864-022-09044-z.

ABSTRACT

BACKGROUND: The exact mechanism of atrial fibrillation (AF)-induced heart failure (HF) remains unclear. Proteomics and metabolomics were integrated to in this study, as to describe AF patients’ dysregulated proteins and metabolites, comparing patients without HF to patients with HF.

METHODS: Plasma samples of 20 AF patients without HF and another 20 with HF were analyzed by multi-omics platforms. Proteomics was performed with data independent acquisition-based liquid chromatography-tandem mass spectrometry (LC-MS/MS), as metabolomics was performed with LC-MS/MS platform. Proteomic and metabolomic results were analyzed separately and integrated using univariate statistical methods, multivariate statistical methods or machine learning model.

RESULTS: We found 35 up-regulated and 15 down-regulated differentially expressed proteins (DEPs) in AF patients with HF compared to AF patients without HF. Moreover, 121 up-regulated and 14 down-regulated differentially expressed metabolites (DEMs) were discovered in HF patients compared to AF patients without HF. An integrated analysis of proteomics and metabolomics revealed several significantly enriched pathways, including Glycolysis or Gluconeogenesis, Tyrosine metabolism and Pentose phosphate pathway. A total of 10 DEPs and DEMs selected as potential biomarkers provided excellent predictive performance, with an AUC of 0.94. In addition, subgroup analysis of HF classification was performed based on metabolomics, which yielded 9 DEMs that can distinguish between AF and HF for HF classification.

CONCLUSIONS: This study provides novel insights to understanding the mechanisms of AF-induced HF progression and identifying novel biomarkers for prognosis of AF with HF by using metabolomics and proteomics analyses.

PMID:36456901 | DOI:10.1186/s12864-022-09044-z

Neuroradiology. 2022 Dec 1. doi: 10.1007/s00234-022-03094-6. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to evaluate whether the heterogeneity of tuber imaging features, evaluated on the structural imaging and apparent diffusion coefficient (ADC) map, can facilitate detecting epileptogenic tubers before surgery in tuberous sclerosis complex (TSC) patients.

METHODS: Twenty-three consecutive patients, who underwent tuber resection at our institute, were retrospectively selected. A total of 125 tubers (39 epileptogenic, 86 non-epileptogenic) were used for the analysis. Tuber heterogeneity was evaluated, using a 5-point visual scale and standard deviation of ADC values (ADC_sd). A 5-point visual scale reflected the degree of T1/T2 prolongation, presence of internal cystic degeneration, and their spatial distribution within the tuber. These results were statistically compared between epileptogenic and non-epileptogenic groups, and their performance in predicting the epileptogenicity was also evaluated by receiver operating characteristic (ROC) analysis.

RESULTS: A 5-point visual scale demonstrated that more heterogeneous tubers were significantly more epileptogenic (p < 0.001). Multiplicity of internal cystic degeneration moderately correlated with epileptogenicity (p < 0.03) based on the comparison between class 4 and class 5 tubers. ADC_sd was significantly higher in epileptogenic tubers (p < 0.001). ROC curves revealed that a 5-point visual scale demonstrated higher area under the curve (AUC) value than ADC_sd (0.75 and 0.72, respectively).

CONCLUSION: Tuber heterogeneity may help identify the epileptogenic tubers in presurgical TSC patients. Visual assessment and standard deviation of ADC value, which are easier to implement in clinical use, may be a useful tool predicting epileptogenic tubers, improving presurgical clinical management for TSC patients with intractable epilepsy.

PMID:36456893 | DOI:10.1007/s00234-022-03094-6

Endocrine. 2022 Dec 2. doi: 10.1007/s12020-022-03273-8. Online ahead of print.

ABSTRACT

PURPOSE: Thirty years into the genomic era, this study sought to explore events that helped transform the clinical landscape of hereditary medullary thyroid cancer (MTC).

METHOD: This retrospective analysis of prospectively collected data included all RET carriers referred to a tertiary center for neck surgery that was performed between 1986 and 2021, using descriptive statistics and Poisson regression analysis.

RESULTS: Altogether, 496 RET carriers were referred for thyroidectomy (388 carriers) or neck reoperation (108 carriers). Of these, 44 carriers had highest risk mutations (p.Met918Thr), 164 carriers high risk mutations (p.Cys634Arg/Gly/Phe/Ser/Trp/Tyr/insHisGluLeuCys), 116 carriers moderate-high risk mutations (p.Cys609/611/618/620/630Arg/Gly/Phe/Ser/Tyr) and 172 carriers low-moderate risk mutations (p.Glu768Asp, p.Leu790Phe, p.Val804Leu/Met, or p.Ser891Ala). Three event clusters drove referral numbers upward: a string of first reports of causative RET mutations between 1993 and 1998; the international consensus guidelines for diagnosis and therapy of MEN type 1 and type 2 in 2001; and the revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma in 2015. Referrals for neck reoperation declined sluggishly over 30 years, ending in 2018. Index patients continued to be referred into 2021. Referrals for thyroidectomy, grouped in 5-year increments, peaked in 1996-2000 for carriers of highest and high risk mutations, and in 2006-2010 for carriers of moderate-high and low-moderate risk mutations, some 10 years later.

CONCLUSION: International management guidelines are critical in building and increasing the pressure towards screening of sporadic-appearing disease and offspring of known gene families by encompassing the complete disease spectrum early on.

PMID:36456885 | DOI:10.1007/s12020-022-03273-8

Graefes Arch Clin Exp Ophthalmol. 2022 Dec 2. doi: 10.1007/s00417-022-05923-z. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate differences in acquisition time, peripheral extension, and chromaticity between 3 different commercialized ultra-wide-field (UWF) fundus cameras.

METHODS: Patients were prospectively enrolled from 07/2021 to 11/2021. Patients underwent fundus photography with the following scanning protocols: (1) single shot with Silverstone (Optos, California), two-shot montage with Clarus 500 (Carl Zeiss, Dublin, CA), and three-shot montage with iCare EIDON FA with UWF module (CenterVue Spa, a company of iCare Finland Oy; Vantaa, Finland). Acquisition time was calculated as the interval between the beginning and the end of the acquisition. Peripheral extension was quantified as the average ratio between the total retinal pixel area and the optic nerve head (ONH) pixel area. The average chromaticity of all pixels in the red-green-blue (RGB) space was calculated.

RESULTS: Twenty-three eyes of 13 prospectively enrolled healthy controls were included in the study. Optos Silverstone had a higher total retina area/ONH area ratio (509.1 [480.9;559.3]) compared to Zeiss Clarus (442.0 [431.9;510.5], p = 0.02) and iCare EIDON (369.7 [345.3;387.8], p < 0.0001). Silverstone demonstrated the shortest acquisition time (median [interquartile range]: 32 [20;58.5] s) compared to Zeiss Clarus (42 [28.5;53.5] s, p = 0.6733) and iCare EIDON (72 [68.5;78] s, p = 0.0003). iCare EIDON demonstrated the lowest variability of acquisition time (9.5 s), compared to Zeiss Clarus (25 s) and Optos Silverstone (38.5 s). A statistically significant difference was found in the RGB distribution between each of the 3 devices (p < 0.001). iCare EIDON demonstrated an average barycenter position (RGB = [0.412, 0.314, 0.275]) that represented the best color balance of the image. Zeiss Clarus had a noticeable red shift at the expense of the blue and green channels (RGB = [0.515, 0.294, 0.191]). Optos Silverstone showed an absence of the blue channel (RGB = [0.621, 0.372, 0.007]) which results in a distortion of the color of the image.

CONCLUSION: Optos Silverstone and Zeiss Clarus required less time than iCare EIDON to acquire a comparable size image and captured larger areas of the retina than iCare EIDON. iCare EIDON provided more color-balanced retinal images with greater richness of color content than the other two devices.

PMID:36456861 | DOI:10.1007/s00417-022-05923-z

J Immigr Minor Health. 2022 Dec 1. doi: 10.1007/s10903-022-01434-5. Online ahead of print.

ABSTRACT

This study explored factors that mediate the relationship between subjective wellbeing and depression in a sample of West Indian American immigrants. An intersectional theoretical framework was used to identify the relative contribution of psychological stressors-perceived discrimination, financial strain and acculturative stress-that mediate the relationship between subjective wellbeing and depression. A geographically diverse sample was recruited by an online survey (N = 255), consisting of 138 men, 115 women, 173 Indo-West Indians and 82 Afro-West Indians. Path analysis was used to identify the relative contribution of psychological stressors. Acculturative stress and financial strain were both statistically significant predictors of depression. Financial strain was identified as the major mediator between subjective wellbeing and depression in West Indian Americans. West Indian Americans are vulnerable to financial strain and acculturative stress. These sources of psychological stress are important contributors to depression in the community. More research is needed to clarify these relationships.

PMID:36456840 | DOI:10.1007/s10903-022-01434-5

J Digit Imaging. 2022 Dec 1. doi: 10.1007/s10278-022-00738-0. Online ahead of print.

ABSTRACT

Retinal fundus images are non-invasively acquired and faced with low contrast, noise, and uneven illumination. The low-contrast problem makes objects in the retinal fundus image indistinguishable and the segmentation of blood vessels very challenging. Retinal blood vessels are significant because of their diagnostic importance in ophthalmologic diseases. This paper proposes improved retinal fundus images for optimal segmentation of blood vessels using convolutional neural networks (CNNs). This study explores some robust contrast enhancement tools on the RGB and the green channel of the retinal fundus images. The improved images undergo quality evaluation using mean square error (MSE), peak signal to noise ratio (PSNR), Similar Structure Index Matrix (SSIM), histogram, correlation, and intersection distance measures for histogram comparison before segmentation in the CNN-based model. The simulation results analysis reveals that the improved RGB quality outperforms the improved green channel. This revelation implies that the choice of RGB to the green channel for contrast enhancement is adequate and effectively improves the quality of the fundus images. This improved contrast will, in turn, boost the predictive accuracy of the CNN-based model during the segmentation process. The evaluation of the proposed method on the DRIVE dataset achieves an accuracy of 94.47, sensitivity of 70.92, specificity of 98.20, and AUC (ROC) of 97.56.

PMID:36456839 | DOI:10.1007/s10278-022-00738-0

Atherosclerosis. 2022 Nov 9;363:48-56. doi: 10.1016/j.atherosclerosis.2022.11.006. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The association between rheumatoid arthritis (RA) and blood lipid levels has often been described as paradoxical, despite the strong association between RA and cardiovascular disease (CVD) risk. We aimed to clarify the genetic architecture that would explain the relationship between RA and blood-lipid levels, while considering inflammation as measured by C-reactive protein (CRP).

METHODS: Genome-wide association study (GWAS) summary statistics were collected from the CHARGE Consortium and Global Lipids Genetics Consortium. Blood-lipid levels includes HDL-C, LDL-C, triglycerides (TG), and total cholesterol (TC). Causality was examined by assessing Mendelian Randomization (MR) analysis. Pleiotropy, the identification of shared causal variants between traits, was assessed by conducting colocalization analyses.

RESULTS: Using the MR Egger method, RA did not appear to causally predict alterations in lipid factors, rather the MR Egger intercept revealed that the genetic relationship between RA and HDL-C, LDL-C and TC may be explained by horizontal pleiotropy (p=0.003, 0.006, and 0.018, respectively). MR was suggestive of a horizontally pleiotropic relationship between CRP and lipid factors, while a causal relationship could not be ruled out. Recurring genes arising from shared causal genetic variants between RA and varying lipid factors included NAT2/PSD3, FADS2/FADS1, SH2B3, and YDJC.

CONCLUSIONS: Horizontal pleiotropy appears to explain the genetic relationship between RA and blood-lipid levels. In addition, blood-lipid levels appear to suggest a horizontally pleiotropic relationship to CRP, if not mediated through RA as well. Consideration of the pleiotropic genes between RA and blood lipid levels may aid in enhancing diagnostic means to predict CVD.

PMID:36455308 | DOI:10.1016/j.atherosclerosis.2022.11.006

Atherosclerosis. 2022 Nov 23;363:22-29. doi: 10.1016/j.atherosclerosis.2022.11.018. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The susceptibility of low-density lipoprotein (LDL) to aggregation predicts atherosclerotic cardiovascular disease. However, causes of interindividual variation in LDL lipid composition and aggregation susceptibility remain unclear. We examined whether the lipid composition and aggregation susceptibility of LDL reflect the lipid composition of the human liver.

METHODS: Liver biopsies and blood samples for isolation of LDL particles were obtained from 40 obese subjects (BMI 45.9 ± 6.1 kg/m², age 43 ± 8 years). LDL was isolated using sequential ultracentrifugation and lipidomic analyses of liver and LDL samples were determined using ultra-high performance liquid chromatography-mass spectrometry. LDL aggregation susceptibility ex vivo was analyzed by inducing aggregation by human recombinant secretory sphingomyelinase and following aggregate formation.

RESULTS: The composition (acyl carbon number and double bond count) of hepatic triglycerides, phosphatidylcholines, and sphingomyelins (SMs) was closely associated with that of LDL particles. Hepatic dihydroceramides and ceramides were positively correlated with concentrations of the corresponding SM species in LDL as well with LDL aggregation. These relationships remained statistically significant after adjustment for age, sex, and body mass index.

CONCLUSIONS: Lipid composition of LDL reflects that of the human liver in obese patients. Changes in hepatic sphingolipid metabolism may contribute to interindividual variation of LDL lipid composition and susceptibility to aggregation.

PMID:36455305 | DOI:10.1016/j.atherosclerosis.2022.11.018

Clin Neurol Neurosurg. 2022 Nov 25;224:107544. doi: 10.1016/j.clineuro.2022.107544. Online ahead of print.

ABSTRACT

OBJECTIVE: Eagle syndrome or styloid process syndrome is a clinical condition of complex aetiology. Since, as a consequence of vascular compression,due to the length of the styloid process and its nearness to the internal carotid artery,it can lead to vertigo. Vertigo may be the only symptom of stylocarotid syndrome and it is extremely challenging diagnose.To the best of our knowledge, this is the first study that measures the lengths of styloid process on the Croatian population’s,and possible influence of styloid process length on isolated vertigo of unknown aetiology.

METHODS: This study included 829 subjects who were divided into two groups.The first group was the control group, consisting of 800 subjects.The second group, study group, consisted of 29 subjects who suffered from the vertigo of unknown aetiology.

RESULTS: The statistically significant difference between the study and the control group was observed in the length of the styloid process, and in the closest distance of the styloid process from the carotid artery.

CONCLUSIONS: The prolonged styloid process and its close association with the internal carotid artery may affect vertigo of unknown aetiology and should be clinically and radiographically investigated in cases of unexplained vertigo as an isolated and only symptom within stylocarotid syndrome.

PMID:36455302 | DOI:10.1016/j.clineuro.2022.107544

ACS Chem Neurosci. 2022 Dec 1. doi: 10.1021/acschemneuro.2c00478. Online ahead of print.

ABSTRACT

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder in the U.S. α-Synuclein (α-Syn) preformed fibrils (PFFs) have been shown to propagate PD pathology in neuronal populations. However, little work has directly characterized the morphological changes on membranes associated with α-Syn PFFs at a cellular level. Scanning ion conductance microscopy (SICM) is a noninvasive in situ cell imaging technique and therefore uniquely advantageous to investigate PFF-induced membrane changes in neuroblastoma cells. The present work used SICM to monitor cytoplasmic membrane changes of SH-SY5Y neuroblastoma cells after incubation with varying concentrations of α-Syn PFFs. Cell membrane roughness significantly increased as the concentration of α-Syn PFFs increased. Noticeable protrusions that assumed a more crystalline appearance at higher α-Syn PFF concentrations were also observed. Cell viability was only slightly reduced, though statistically significantly, to about 80% but independent of the dose. These observations indicate that within the 48 h treatment period, PFFs continue to accumulate on the cell membranes, leading to membrane roughness increase without causing prominent cell death. Since PFFs did not induce major cell death, these data suggest that early interventions targeting fibrils before further aggregation may prevent the progression of neuron loss in Parkinson’s disease.

PMID:36455298 | DOI:10.1021/acschemneuro.2c00478