Normal Healthy Controls Research Articles

A novel molecular mechanism mediated by circCCDC134 regulates non-small cell lung cancer progression.

Circular RNA (circRNA) plays a crucial role in non-small cell lung cancer (NSCLC) progression. However, the role of circCCDC134 in NSCLC is still largely unknown. Quantitative real-time PCR was utilized for measuring circCCDC134, microRNA (miR)-625-5p and nuclear factor of activated T cell 5 (NFAT5) expression. Cell functions were evaluated by colony formation, EdU, transwell, and wound healing assays and flow cytometry. Glucose consumption, lactate production, and ATP level were determined to analyze cell glycolysis. Western blot analysis was used to detect protein expression. Animal experiments were performed to assess the effect of circCCDC134 on NSCLC tumor growth. RNA interaction was evaluated by dual-luciferase reporter assay and RIP assay. Exosomes were isolated from the serum of NSCLC patients and healthy normal controls. Highly expressed circCCDC134 was found in NSCLC tissues and cells, as well as in the serum exosomes of NSCLC patients. Downregulated circCCDC134 restrained NSCLC cell growth, metastasis and glycolysis. CircCCDC134 sponged miR-625-5p to regulate NFAT5. MiR-625-5p inhibitor abolished the regulation of circCCDC134 knockdown on NSCLC progression, and NFAT5 overexpression eliminated the effects of miR-625-5p on NSCLC cell behaviors. CircCCDC134 knockdown also inhibited NSCLC tumor growth. Our study revealed that circCCDC134 was involved in regulating NSCLC progression through the miR-625-5p/NFAT5 pathway, confirming that circCCDC134 might function as the diagnostic and therapeutic target for NSCLC.

Rapid Single-Step Immunochromatographic Assay for Angiostrongylus cantonensis Specific Antigen Detection.

Angiostrongylus cantonensis is the major etiological nematode parasite causing eosinophilic meningitis and/or eosinophilic meningoencephalitis in humans. The rapid global spread of Angiostrongylus cantonensis and the emerging occurrence of the infection have exposed the shortcomings of traditional/conventional diagnostics. This has spurred efforts to develop faster, simpler and more scalable platforms that can be decentralized for point-of-need laboratory testing. By far, the point-of-care immunoassays such as the lateral flow assay (LFA) are the best-placed. In this work, a LFA in the form of an immunochromatographic test device (designated AcAgQuickDx), based on the detection of a circulating Angiostrongylus cantonensis-derived antigen, was established using anti-31 kDa Angiostrongylus cantonensis antibody as the capture reagent and anti-Angiostrongylus cantonensis polyclonal antibody as the indicator reagent. The AcAgQuickDx was evaluated for its diagnostic potential with a total of 20 cerebrospinal fluids (CSF) and 105 serum samples from patients with angiostrongyliasis and other clinically related parasitic diseases, as well as serum samples from normal healthy subjects. Three of the ten CSF samples from serologically confirmed angiostrongyliasis cases and two of the five suspected cases with negative anti-Angiostrongylus cantonensis antibodies showed a positive AcAgQuickDx reaction. Likewise, the AcAgQuickDx was able to detect Angiostrongylus cantonensis specific antigens in four serum samples of the 27 serologically confirmed angiostrongyliasis cases. No positive reaction by AcAgQuickDx was observed in any of the CSF (n = 5) and serum (n = 43) samples with other parasitic infections, or the normal healthy controls (n = 35). The AcAgQuickDx enabled the rapid detection of active/acute Angiostrongylus cantonensis infection. It is easy to use, can be transported at room temperature and does not require refrigeration for long-term stability over a wide range of climate. It can supplement existing diagnostic tests for neuroangiostrongyliasis under clinical or field environments, particularly in remote and resource-poor areas.

Spirometric Lung Functions in Type 2 Diabetes Mellitus: A Hospital-Based Study.

Objective This cross-sectional case-control study was conducted with the aim to analyzespirometric lung functions in type 2 diabetes mellitus (T2DM) patients and to correlate the spirometric dysfunction with (a) duration of diabetes, b) metabolic control of diabetes, and c) microvascular complications of diabetes. Methods Pulmonary function tests (PFTs) were performed in 50 T2DM patients and 50 normal healthy controls aged <80 years by using an electronic spirometer. The PFTs recorded were as follows: forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1%, forced expiratory flow 25 (FEF25), forced expiratory flow 25-75 (FEF25-75), and peak expiratory flow rate (PEFR). The glycated hemoglobin (HbA1c) of all the patients was measured by affinity chromatography using the NycoCard HbA1C kit. The assessment of diabetic microvascular complications was performed as follows: peripheral neuropathy was done using Michigan Neuropathy Screening Instrument (MNSI), diabetic retinopathy using fundus examination, and diabetic nephropathy using solid phase/sandwich-format/immunometric assay using NycoCard U-albumin kit.PFTs of diabetic patients and controls were compared by applying an independent sample t-test. The correlation between FVC and FEV1, and HbA1c and duration of illness in diabetic patients was analyzed by applying the Pearsoncoefficient. Results The cases had low FVC (103.82 ±24.43 vs. 116.08 ±13.66), FEV1 (101.36 ±24.23 vs. 110.26 ±14.39), FEV1%(97.56 ±8.64 vs. 103.84 ±5.06),PEFR (101.52 ±27.18 vs. 116.96 ±14.96), and FEF 25-75 (73.56 ±29.19 vs. 98.40 ±14.45) compared to controls, and the difference was statistically significant. Asignificant negativecorrelation was found between spirometry parameters and duration of illness as well as HbA1c. Spirometric lung dysfunction also negatively correlated with microvascular complications of diabetes. Among various microvascular complications, retinopathy correlated best with various spirometric parameters. Conclusion Based on our findings, T2DM patients had a significant decrease in their spirometric indices. The pattern of spirometric dysfunction was suggestive of "mixedventilatory dysfunction". The studyresultshighlight the need to include PFTs in the periodic check-up as part of thecomprehensive management of diabetic patients. Hence, pulmonary function should be included in the periodic comprehensive diabetic check for the holistic management of these patients.

TLR7-MyD88-DC-CXCL16 axis results neutrophil activation to elicit inflammatory response in pustular psoriasis

Pustular psoriasis (PP) is a chronic inflammatory disease associated with multiple complications, often with hyperthermia and hypoproteinemia, and its continued progression can be life-threatening. Toll-like receptor 7 (TLR7) induces dendritic cell (DC) production of inflammatory factors that exacerbate the inflammatory response in PP. A membrane-bound chemokine expressed on DCs, CXC motif chemokine ligand 16 (CXCL16) is overexpressed in PP lesions, and neutrophils express its receptor CXC chemokine receptor 6 (CXCR6). There are few studies on the PP immune microenvironment and it is unclear whether TLR7 and CXCL16 can be used as targets in PP therapy. Skin tissue (n = 5) and blood (n = 20) samples were collected from PP and healthy normal controls. The skin tissue transcriptome was analyzed to obtain the differentially expressed genes, and the immune microenvironment was deciphered using pathway enrichment. Tissue sequencing analysis indicated that TLR7, CXCL16, DCs, and neutrophils were involved in the PP process. The enzyme-linked immunosorbent assay, reverse transcription–PCR, and scoring table results demonstrated that TLR7 induced DC secretion of CXCL16, which enabled neutrophil activation of the secretion of the inflammatory factors interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α). The co-culture of neutrophils with DCs treated with TLR7 inhibitor or TLR7 agonist demonstrated that TLR7 regulated neutrophil activation, migration, and apoptosis. We constructed imiquimod-induced psoriasis-like skin lesions in wild-type, Cd11c-Cre Myd88f/f, and Mrp8-Cre Cxcr6f/f mice. The mouse models suggested that TLR7 might influence DC release of CXCL16 and neutrophil proinflammatory effects by interfering with the myeloid differentiation primary response gene 88 (MyD88) signaling pathway. In conclusion, the TLR7–MyD88–DC–CXCL16 axis is an important mechanism that promotes neutrophil migration to PP skin lesions and stimulates the inflammatory response.

Altered structural covariance of locus coeruleus in individuals with significant memory concern and patients with mild cognitive impairment.

The locus coeruleus (LC) is the site where tau accumulation is preferentially observed pathologically in Alzheimer's disease (AD) patients, but the changes in gray matter co-alteration patterns between the LC and the whole brain in the predementia phase of AD remain unclear. In this study, we estimated and compared the gray matter volume of the LC and its structural covariance (SC) with the whole brain among 161 normal healthy controls (HCs), 99 individuals with significant memory concern (SMC) and 131 patients with mild cognitive impairment (MCI). We found that SC decreased in MCI groups, which mainly involved the salience network and default mode network. These results imply that seeding from LC, the gray matter network disruption and disconnection appears early in the MCI group. The altered SC network seeding from the LC can serve as an imaging biomarker for discriminating the patients in the potential predementia phase of AD from the normal subjects.

7T MRI Versus 3T MRI of the Brain in Professional Fighters and Patients With Head Trauma.

Many studies have investigated the imaging sequelae of repetitive head trauma with mixed results, particularly with regard to the detection of intracranial white matter changes (WMCs) and cerebral microhemorrhages (CMHs) on ≤3 Tesla (T) field magnetic resonance imaging (MRI). 7T MRI, which has recently been approved for clinical use, is more sensitive at detecting lesions associated with multiple neurological diagnoses. In this study, we sought to determine whether 7T MRI would detect more WMCs and CMHs than 3T MRI in 19 professional fighters, 16 patients with single TBI, versus 82 normal healthy controls (NHCs). Fighters and patients with TBI underwent both 3T and 7T MRI; NHCs underwent either 3T (n = 61) or 7T (n = 21) MRI. Readers agreed on the presence/absence of WMCs in 88% (84 of 95) of 3T MRI studies (Cohen's kappa, 0.76) and in 93% (51 of 55) of 7T MRI studies (Cohen's kappa, 0.79). Readers agreed on the presence/absence of CMHs in 96% (91 of 95) of 3T MRI studies (Cohen's kappa, 0.76) and in 96% (54 of 56) of 7T MRI studies (Cohen's kappa, 0.88). The number of WMCs detected was greater in fighters and patients with TBI than NHCs at both 3T and 7T. Moreover, the number of WMCs was greater at 7T than at 3T for fighters, patients with TBI, and NHCs. There was no difference in the number of CMHs detected with 7T MRI versus 3T MRI or in the number of CMHs observed in fighters/patients with TBI versus NHCs. These initial findings suggest that fighters and patients with TBI may have more WMCs than NHCs and that the improved voxel size and signal-to-noise ratio at 7T may help to detect these changes. As 7T MRI becomes more prevalent clinically, larger patient populations should be studied to determine the cause of these WMCs.

Investigating the interactions between regulatory T cells and cancer-associated fibroblasts and their role in lung cancer progression

Abstract The tumor microenvironment (TME) is a highly complex multicellular system and has been shown to play a fundamental role in dictating tumorigenesis. High expression of regulatory surface molecules, cytokines, and chemokines in fibroblast niches within lung tumor stroma, paired with their colocalization with tumor infiltrating lymphocytes (TILs), suggests that cancer-associated fibroblast (CAF) niches may alter the functional response of TILs and influence the anti-tumor immune response. Here, utilizing a transcriptomic approach, we have uncovered a distinct CAF population, which we term “iCAFs,” that is enriched for immunomodulatory gene signatures, T cell ligands, and chemoattractants. This population expresses a unique set of cell surface molecules that permit their identification and isolation from lung tumor tissue. Given the demonstrated importance of Tregs in suppressing anti-tumor immunity, we chose to evaluate how Tregs may be interacting with iCAFs within the TME of lung adenocarcinoma. We uncovered significant colocalization patterns of Foxp3 +Tregs with iCAF—a pattern which was found to be unique for Tregs when compared to conventional CD4 +Foxp3 −T cells. Moreover, the Treg to conventional CD4 +T cell ratio is significantly decreased in tumor tissue relative to normal adjacent tissue and healthy controls. Our analyses demonstrate that Tregs preferentially associate with iCAF populations within the tumor, leading us to hypothesize that interactions between Tregs and iCAFs may, in turn, influence Treg trafficking, phenotype and function within the TME. T32AI106711

Abstract #1406834: Study of Methylation Status and Expression of Vitamin D Receptor Gene in Polycystic Ovarian Syndrome Patients of Kashmiri Population

Downregulation of Vitamin D Receptor (VDR) gene expression resulting from epigenetics events, like methylation in promoter of VDR gene play an important role in pathogenesis, clinical and bio-chemical parameters of polycystic ovary syndrome, but the results from different studies are inconsistent. We aim to determine the methylation status of promoter of VDR gene and VDR gene expression analysis in addition to the co-relation between promoter methylation and expression profile of VDR genes in PCOS patients in Kashmiri Population. This study was a case control, comprising of 100 women with PCOS and 100 normal healthy control women aged between 15-45 years. PCOS patients were selected after proper diagnosis using Rotterdam criteria (2004) and obtaining written consent. DNA extraction was carried out by the non-enzymatic Salting out method and extracted DNA samples were subjected to bisulphite treatment using EZ DNA Methylation-Gold Kit (Zymo Research, Irvine, California) to produces a chemical conversion of unmethylated cytosine to uracil, which is detected as a thymine after PCR. Methylation specific PCR (MS-PCR) was performed following the bisulfite conversion, using pre-designed sets of methylated and unmethylated primers to confirm the prominence of methylation in the promoter VDR region and to specially acknowledge methylated and unmethylated VDR fragments. The VDR expression analysis was carried out following RNA extraction from the blood sample and processed ahead for cDNA synthesis using reverse transcriptase reaction and then relative expression analysis by RT-PCR using SYBR Green fluorescent dye. We found that vitamin D level among test group was significantly lower compared to controls (13.95±9.60 VS. 16.63±7.46; p=0.026). Methylation was significantly higher in test group compared to controls (84% vs 62%; p<0.0001) with OR of 3.21. Furthermore, there exists a significant difference between the average cyclic threshold (CT) value of VDR gene among test and control groups (24.64 vs. 26.14;p <0.0001). The average CT value corresponding to GAPDH (glyceraldehyde phosphate dehydrogenase) is 29.76 in test group and 32.11 in control group. The expression of VDR gene was 0.55 times down regulated in test group in comparison to controls. In the present study, we have comprehensively shown that VDR hypermethylation is significantly associated with reduced vitamin D level and decreased expression level of VDR gene among PCOS women. Increased VDR methylation in response to decreased vitamin D levels could be involved in the impairment of VDR mediated effects resulting in the peculiar clinical and bio-chemical derangements in patients of polycystic ovary syndrome. However, the enhanced ligand availability results in decreased receptor expression to maintain homeostasis of vitamin D signalling. Hence, this, inverse association could have a significant role in the altered gene expression of VDR and thereby effecting the cell response in PCOS patients.

Hepatálne zmeny obéznych pediatrických pacientov

Rationale: Non-alcoholic fatty liver disease (NAFLD) is emerging clinical issue in childhood and adolescent age. Present knowledge of NAFLD suggests an important role of genetic and environmental risk factors in the pathogenesis of the disease. Most of the patients are obese, however, NAFLD also occurs in the non-obese group and interestingly, in obese individuals it may be absent. The transabdominal ultrasound examination is the most widely used imaging method for NAFLD screening. Aim: The aim of the study was to assess the impact of paediatric obesity as the main risk factor in NAFLD development. Materials and methods: The degree of steatosis (represented by hepatorenal index) and hepatic parenchyma stiffness (represented by fibrosis liver index) were quantitatively evaluated using ultrasound device in a total of 240 paediatric and adolescent patients divided in subgroups according to age and weight criteria. Results from ultrasound examination were subsequently correlated with anthropometric and laboratory parameters. Results: Hepatorenal index (HRI) and liver fibrosis index (LFI) in healthy term neonates with normal birth weight was significantly lower compared to the control group of healthy normal weight children aged 10–18 years (p &lt;0.001). We did not observe an effect of gender on changes in HRI (p = 0.332) and LFI (p = 0.339) in teenage and adolescent controls. Regardless of gender, normal HRI values in paediatric heathy control group ranged from 1.02–1.23 (10th–90th percentile). The group of obese children aged 10–18 years had HRI and LFI values significantly higher in contrast with healthy normal weight controls. Obese individuals had liver stiffness proportional to BMI (p = 0.005, rs = 0.310), however, the steatosis degree remained unchanged (p = 0.357). Hepatic parenchyma stiffness also increased with waist circumference gain in corpulent patients (p &lt;0.01). Conclusion: Results of this study point to a significant association of obesity and NAFLD in paediatric population. The assessment of HRI and liver stiffness using ultrasound methods have been employed in the diagnosis of early stages of hepatic changes in obese children and adolescent patients at risk of NAFLD development. In addition to the early detection in these changes, ultrasound determination enables non-invasive and real-time assessment of dynamics of the disease and the effect of the administered therapy, which improves control over the disease. Keywords non-alcoholic fatty liver disease, obesity, hepatorenal index, real-time elastography, body roundness index, paediatric age, adolescent age

Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer cells (NK) and natural killer-T cells (NKT) in neuromyelitis optica spectrum disorder. (S50.003)

Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer cells (NK) and natural killer-T cells (NKT) in neuromyelitis optica spectrum disorder. (S50.003)

Consensus Definition of Blood Samples from the Subcategorized Normal Controls in the Korea Biobank Network.

A control group is defined as a group of people used for comparison. Depending on the type of study, it can be a group of healthy people or a group not exposed to risk factors. It is important to allow researchers to select the appropriate control participants. The Korea Biobank Project-sponsored biobanks are affiliated with the Korea Biobank Network (KBN), for which the National Biobank of Korea plays a central coordinating role among KBN biobanks. KBN organized several working groups to address new challenges and needs in biobanking. The "Normal Healthy Control Working Group" developed standardized criteria for three defined control groups, namely, normal, normal-plus, and disease-specific controls. Based on the consensus on the definition of a normal control, we applied the criteria for normal control participants to retrospective data. The main reason for exclusion from the "Normal-plus" group was blood test results beyond 5% of the reference range, including hypercholesterolemia. Subclassification of samples of normal controls by detailed criteria will help researchers select optimal normal controls for their studies.

Gut Microbiota and Serum Metabolites in Individuals with Class III Obesity Without Type 2 Diabetes Mellitus: Pilot Analysis.

Background: Gut microbial composition seems to change in association with prediabetes. The purpose of this prospective cross-sectional study was to compare the composition of gut microbiota and energy metabolites between individuals with class III obesity but without type 2 diabetes mellitus (OB) and healthy normal weight controls. Methods: The subjects of this prospective cross-sectional study were participants recruited from a previous clinical trial (No: NCT02325804), with intervention focused on weight loss. We recruited 19 OB [mean age ± standard deviation (SD) was 35.4 ± 7.0 years, mean body mass index (BMI) ± SD was 48.8 ± 6.7 kg/m2] and 23 controls (mean age ± SD was 31.7 ± 14.8 years, mean BMI ± SD was 22.2 ± 1.7 kg/m2). Their fecal microbiota was categorized using specific primers targeting the V1-V3 region of 16S rDNA, whereas serum metabolites were characterized by nuclear magnetic resonance spectroscopy. Multivariate statistical analysis and Random Forest models were applied to discriminate predictors with the highest variable importance. Results: We observed a significantly lower microbial α-diversity (P = 0.001) and relative abundance of beneficial bacterium Akkermansia (P = 0.001) and the short-chain fatty acid-producing bacteria Eubacterium hallii (P = 0.019), Butyrivibrio (P = 0.024), Marvinbryantia (P = 0.010), and Coprococcus (P = 0.050) and a higher abundance of the pathogenic bacteria Bilophila (P = 0.018) and Fusobacterium (P = 0.022) in OB compared with controls. Notably, the Random Forest machine learning analysis identified energy metabolites (citrate and acetate), HOMA-IR, and insulin as important predictors capable of discriminating between OB and controls. Conclusions: Our results suggest that changes in gut microbiota and in serum acetate and citrate are additional promising biomarkers before progression to Type 2 diabetes. The non-invasive manipulation of gut microbiota composition in OB through a healthy lifestyle, thus, offers a new approach for managing class III obesity and associated disorders. ClinicalTrials.gov identifier: NCT02325804.

Abstract 3339: Circulating long non-coding RNA HULC as an early indicator of hepatocellular carcinoma irrespective of etiology

Abstract Background: Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide and is highly prevalent in Asian countries. Long noncoding RNAs (lncRNAs) are non-coding transcripts with a size of more than 200 bases in length. Several studies reported that lncRNAs are highly deregulated in HCC and could be used as biomarkers for early diagnosis and prognostic purposes. In the present study, we measured the circulating lncRNA HULC as an early diagnostic marker for HCC with different etiology. Methods: Serum samples were collected from healthy controls, liver cirrhosis (LC), and HCC patients with different etiology and stored at -80°C until assay. Total RNA was extracted using Qiagen RNeasy kit and tested for RNA quantity and purity using NanoDrop spectrophotometer. The RNA extract that contains lncRNA HULC was transcribed into cDNA using a reverse transcription kit. Employing target specific primers for the lncRNA HULC, qRT-PCR was performed with the synthesized cDNA using Qiagen QuantiFast SYBR Green PCR kit on a Rotor-Gene qRT-PCR system. Results: Quantification of lncRNA HULC using qRT-PCR in the serum samples demonstrated significant increase in LC cases and in all HCC cases irrespective of etiology compared to the normal healthy controls. The highest concentration was observed in serum samples from HCC patients with hepatitis B virus (HBV) infection, which was about 8 fold higher compared to healthy controls. There was no significant difference between the mean HULC lncRNA levels in HCC patients with different etiology such as alcoholic cirrhosis, LC due to other reasons, hepatitis B and hepatitis C virus (HCV) infections, and HCC developed from other unknown causes. However, serum HULC lncRNA levels in LC cases without HCC was significantly lower compared to all HCC samples. Conclusions: The results of the present study demonstrated that there is a significant increase in HULC lncRNA levels in the serum samples of all HCC patients irrespective of etiology. Therefore, the circulating lncRNA HULC could be used as an early diagnostic biomarker for HCC before appearing other clinical symptoms. Citation Format: Joseph George, Mutsumi Tsuchishima, Mikihiro Tsutsumi. Circulating long non-coding RNA HULC as an early indicator of hepatocellular carcinoma irrespective of etiology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3339.

Assessment of Proinflammatory Cytokines Among Patients with Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant morbidity and mortality. This study was performed to assess the proinflammatory cytokines profile among MERS-CoV patients. A total of 46 MERS-CoV-infected patients (27 symptomatic and 19 asymptomatic) were assessed and compared with 52 normal healthy controls for plasma levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-17, IL-7, IL-6, interferon (IFN)-α, and IL-15 using a customized luminex kit. Whereas asymptomatic MERS-CoV patients and controls were no different; the mean plasma levels among MERS-CoV symptomatic patients were significantly higher than the normal controls: IL-1β (16.89 ± 1.23 vs. 12.80 ± 0.59 pg/mL; p < 0.001), TNF-α (14.04 ± 0.93 vs. 10.35 ± 0.29 pg/mL; p < 0.0001), IL-17 (14.3 ± 0.89 vs. 11.47 ± 0.61 pg/mL; p < 0.001), IL-7 (21.56 ± 1.00 vs. 16.31 ± 0.30 pg/mL; p < 0.0001), IL-6 (156.5 ± 37.90 vs. 18.60 ± 1.59 pg/mL; p < 0.0001), and IFN-α (68.73 ± 13.06 vs. 23.57 ± 1.05 pg/mL; p < 0.0001). The mean plasma levels of IL-7 (24.81 ± 1.63 vs. 19.79 ± 0.94 pg/mL; p < 0.01), IL-6 (312.7 ± 94.67 vs. 101.2 ± 25.67 pg/mL; p < 0.01), and IFN-α (89.00 ± 18.97 vs. 51.05 ± 8.68 pg/mL; p < 0.05) were significantly elevated among MERS-CoV symptomatic patients with fatal outcome compared with MERS-CoV symptomatic patients who survived. Only IL-7 was found to have a higher risk ratio of mortality (4.76, 95% confidence interval: 1.5-14.94; p < 0.01). No differences were observed in IL-15 levels among the groups. Significantly elevated proinflammatory cytokines among symptomatic MERS-CoV-infected patients may contribute to manifestations of cytokine storm frequently observed among critically ill MERS-CoV patients and IL-7 may serve as a marker for disease activity.

Serum Bile Acid Metabolites Predict the Therapeutic Effect of Mesalazine in Patients with Ulcerative Colitis.

Ulcerative colitis (UC) is a systematic chronic disease characterized by insufficient intestinal absorption, and mesalazine is a common medical treatment. In the present study, 20 normal healthy controls (NC group), 10 unmedicated UC patients (UC group), and 20 mesalazine-responsive and 20 mesalazine-nonresponsive UC patients were recruited. A total of 42 serum BA metabolites, including 8 primary bile acids and 34 secondary bile acids (SBAs), were quantitatively measured. Compared with the NC group, serum SBAs in the UC patients were significantly lower but increased after mesalazine therapy. Differences in the serum TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S metabolites were found between the UC and NC groups, with AUC values of 0.777, 0.800, 0.815, 0.775, and 0.740, respectively. Furthermore, we identified 12-keto LCA as a specific BA marker of UC and BA biomarkers of mesalazine responsiveness. It was concluded that serum SBAs were decreased in UC patients, and TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S might aid in the diagnosis of UC. The abundance of SBAs increased after the mesalazine therapy, and serum 12-keto LCA was identified as an alternative invasive biomarker associated with UC diagnosis and therapeutic response, thereby providing a new approach for the prediction of response to mesalazine therapy in UC patients.

Eye movement study in essential tremor patients and its clinical correlates.

Essential tremor (ET) encompasses a wide spectrum of motor and non-motor features. Eye movement abnormalities were first reported two decades ago as an atypical finding in ET. Today, a growing number of publications about eye movement abnormalities in neurodegenerative diseases have helped understand their pathophysiology and the basis of their phenotypic variability. Thus, addressing such aspect in ET may disentangle, based on the oculomotor network abnormalities, the dysfunctional brain pathways in ET. In this study, we aimed to describe neurophysiological eye movement abnormalities in ET and their clinical correlates in terms of cognition and other associated clinical signs. We conducted a cross-sectional study in a tertiary neurology referral center including consecutive ET patients and cognitively normal healthy controls (HC) matched for age and sex. The study protocol included the assessment of voluntary horizontal saccades, smooth pursuit, anti-saccades and saccadic intrusions. We assessed the associated motor signs, cognitive functions and the presence of rapid eye movement disorder (RBD). Sixty-two ET patients and 66 HC were enrolled in the study. Eye movement examination showed significant abnormalities in comparison with HC (46.7% vs 20%, p = 0.002). Prolonged saccadic latency (38.7%, p = 0.033) and altered smooth pursuit (38.7%, p = 0.033) were the most common abnormalities in ET patients. Anti-saccadic errors (16% vs 0% in HC, p = 0.034) correlated with the presence of rigidity (p = 0.046), bradykinesia (p = 0.001), cognitive dysfunction (p = 0.006), executive dysfunction (p = 0.0002), apraxia (p = 0.0001), altered verbal fluency (p = 0.013) and altered backward digit span (p = 0.045) along with the presence of RBD (p = 0.035). Square-wave jerks (11.5% vs 0% in HC, p = 0.0024) correlated with rest tremor. A distinctive phenotype of ET could emerge out of this study characterized by anti-saccadic errors and a sub-cortical cognitive profile, consecutive to the disruption of the cerebello-thalamo-cortical loop. Patients with anti-saccadic errors could be cognitively vulnerable and in need of a close monitoring of their cognitive efficiency during the disease's progression. They may as well convert to Parkinson disease if they present with parkinsonism, RBD and square-wave jerks and require, consequently, a close observation of their motor progression.

Could serum serotonin be used as a marker for portal vein invasion in patients with hepatocellular carcinoma?

Introduction: Hepatocellular carcinoma represents the sixth and the fourth cause of cancer in the world and Egypt, respectively. In Egypt, HCC mortality and morbidity is high. Serotonin is a precious neurotransmitter and vascular viable molecule. Serotonin plays an important role in hepatocytes mitosis and tumor genesis leading to hepatocellular carcinoma. Aim of Work: To investigate if serum serotonin can be used as a marker for portal vein invasion in patient with hepatocellular carcinoma. Methods: Cross-sectionla analytic study was performed in Suez Canal University Hospitals. The study included 90 participants; 10 normal healthy control individuals and 80 chronic liver disease patients divided into four groups ( 20 cirrhotic; 20 early HCC; 20 advanced HCC and 20 ablated HCC). All study groups were subjected to the following; history, clinical examination, and investigations including hematological, biochemical, serum Alpha fetoprotein and Serotonin levels) with pelviabdominal ultrasound and Triphasic computerized tomography. Results: Portal Vein Thrombosis (PVT), abnormal liver function tests, and AFP were positively correlate with serum serotonin level. In comparison between study groups, mean serum serotonin level was (117±84, 693±65,1613±37) for patients with normal, dilated, and portal vein invasion respectively with a statistically significant difference ( p value &lt;0.001).

Evaluation of the executive dysfunction in patients with bipolar disorder

IntroductionBipolar disorders (BD) associate impairments in cognitive functioning not restricted to acute mood episodes. The functional impact of these cognitive dysfunctions is significant in many cases, therefore, an extensive evaluation is granted for BD patients from this perspective. Executive dysfunction in BD has been reported, especially during mania and was associated with formal thought disorder, but multiple cognitive deficits may reflect an underlying pathologic process related to the mood disorder itself.ObjectivesTo assess the level of executive dysfunction in a sample of patients with type I BD (BDI) using structured measurement methods.MethodsFive patients diagnosed with BDI (two patients during manic episodes, one during the euthymic phase, and 2 during depressive episodes) were evaluated for working memory (n-back test), verbal fluency (Controlled Oral Word Association Test, COWAT) and verbal learning (Verbal Learning and Memory test, VLMT). All patients were adults, mean age of 35.5 years, and all were undergoing psychotropic treatment with antipsychotics and/or mood stabilizers. Also, five normal healthy controls, matched for age, were evaluated using the same test battery.ResultsAll five BDI patients presented dysfunctions (three at a trend level, and one at a significant level, p&lt;0. 01) in at least one cognitive domain, with three patients presenting modifications in all three tests that were administered vs. normal controls. The most affected domain was verbal learning, followed by working memory and verbal fluency. No individual in the control group had significant cognitive deterioration, on any outcome assessed.ConclusionsCognitive domains are altered in BDI patients, therefore, a test battery destined to quantify executive dysfunctions, independent of the presence of an acute mood episode or during the euthymic phase, may be useful for case management.Disclosure of InterestNone Declared

High-Throughput Peptide Arrays Identify Potential Diagnostic Autoantibody Signatures in Early-Stage Lung Adenocarcinoma.

Early diagnosis is critical to lung adenocarcinoma patients' survival but faces inadequacies in convenient early detection. We applied a comprehensive microarray of 130,000 peptides to detect "autoantibody signature" that is autoantibodies binding to mimotopes for early detection of stage 0-I LUAD. Plasma samples were collected from 147 early-stage lung adenocarcinoma (Early-LUAD), 108 benign lung disease (BLD), and 122 normal healthy controls (NHC). Clinical characteristics, low-dose CT (LDCT), and laboratory tests were incorporated into correlation analysis. We identified 143 and 133 autoantibody signatures, distinguishing Early-LUAD from NHC/BLD in the discovery cohort. Autoantibody signatures significantly correlated with age, stage, tumor size, basophil count, and IgM level (P < 0.05). The random forest models based on differential autoantibody signatures displayed AUC of 0.92 and 0.87 to discern Early-LUAD from NHC/BLD in the validation cohort, respectively. Compared with LDCT, combining autoantibody signature and LDCT improved the positive predictive value from 50% to 78.33% (P = 0.049). In addition, autoantibody signatures displayed higher sensitivity of 72.4% to 81.0% compared with the combinational tumor markers (cyfra21.1, NSE, SCC, ProGRP) with a sensitivity of 22.4% (P = 0.000). Proteins matched by differential peptides were enriched in cancer-related PI3K/Akt, MAPK, and Wnt pathways. Overlaps between matched epitopes and autoantibody signatures illustrated the underlying engagement of autoantibodies in immune recognition. Collectively, autoantibody signatures identified by a high-throughput peptide microarray have the potential to detect Early-LUAD, which could assist LDCT to better diagnose Early-LUAD. Novel sensitive autoantibody signatures can adjuvant LDCT to better diagnose LUAD at very early stage.

Study of Coagulation parameters in HIV patients and its relation to CD4 counts and ART status

Introduction: We started this study with a research question that whether prolonged APTT, prolonged PT and decreased platelet counts have any correlation with the patients having HIV, as compared to normal healthy controls and also do these changes go hand in hand with the level of CD4 count thus reflecting disease progression. We look for an answer to the question that, can these coagulation parameters be included in the routine testing and care of the HIV patients? Does the treatment have an effect on these parameters? Aims and Objectives: 1) To evaluate PT, APTT, and platelet count of HIV patients and compare them with normal healthy controls. 2) To analyse these parameters with respect to their CD4 count. Conclusion: In the present study the mean APTT value was prolonged which was statistically significant when compared to normal healthy controls. The mean PT value was not prolonged and the difference between HIV patients and controls was not statistically significant. Mean platelet count was not decreased, but the difference was statistically significant when compared to normal controls. The difference in mean APTT, PT and platelet count was not statistically significant when patients with CD4 count &lt;200cell/mm3 were compared with those having CD4 count &gt;200cells/mm3. Hence these parameters cannot be used for disease monitoring.