Circulating plasma MicroRNA in patients with active acromegaly

Author(s):  
Alexander Lutsenko ◽  
Zhanna Belaya ◽  
Alexey Nikitin ◽  
Alexander Solodovnikov ◽  
Anastasia Lapshina ◽  
...  

Abstract Context Excessive production of growth hormone causes marked multiorgan changes in patients with acromegaly, which may involve epigenetic mechanisms. Objective To evaluate differences in circulating microRNAs (miRNAs) associated with chronic growth hormone overproduction in adults. Design and setting A cross-sectional case-control study was conducted at a tertiary medical center. Participants We enrolled 12 consecutive patients with acromegaly along with 12 age and gender matched controls in the discovery phase of the study and then extended this cohort to 47 patients with acromegaly and 28 healthy controls for the validation study. Main Outcome Measures Plasma microRNAs were quantified by next-generation sequencing (NGS) in the discovery phase. Levels of selected miRNAs were validated on extended cohorts using RT-qPCR, compared between groups and correlated with clinical parameters. Results Based on NGS data, we selected three plasma miRNAs downregulated in patients with acromegaly compared to healthy controls: miR-4446-3p –1.317 (p=0.001), miR-215-5p –3.040 (p=0.005), miR-342-5p –1.875 (p=0.013) without multiplicity correction for all three miRNAs. These results were confirmed by RT-qPCR in the validation phase for two miRNAs out of three: miR-4446-3p (p <0.001, p-adj <0.001), AUC 0.862 (95% CI 0.723-0.936) p<0.001 and miR-215-5p (p <0.001, p-adj <0.001), AUC 0.829 (95% CI 0.698-0.907) p<0.001 to differentiate patients with acromegaly from healthy controls. Conclusions In a two-phase experiment using two different techniques we found and validated the downregulation of plasma miR-4446-3p and miR-215-5p in patients with acromegaly compared to healthy subjects, which makes them promising biomarkers for further research.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1386.2-1387
Author(s):  
P. E. Bermudez Bermejo ◽  
R. Jimenez-Soto ◽  
A. Sanchez Rodríguez ◽  
A. Turrent ◽  
D. Mercado Velasco ◽  
...  

Background:Nailfold capillaroscopy is a relatively easy-to-access, low-cost clinical tool that could help identify early coagulopathy in subjects with SARS-CoV-2, but specific findings vs. controls and its possible prognostic role has not been studied.Objectives:To describe capillaroscopic findings and their usefulness in patients with COVID-19 compared to healthy controls.Methods:We designed a cross-sectional study, carried out in a single care center for critical patients with SARS-CoV-2 pneumonia at the ABC Medical Center, Mexico City, which included patients from an intensive care unit (ICU) and internal medicine ward from March to April 2020. Demographic, biochemical and clinical features were collected. All patients signed the informed consent and the study was approved by the hospital ethics committee. All patients underwent nail capillary imaging of the 3 central fingers of each hand with a portable microscope with 60-100x magnification coupled to a smartphone with 7 megapixel images in an immersion medium. Capillaroscopy was performed in patients who did not have fever or hypothermia, or need vasopressors at the time of evaluation. Control subjects are healthy subjects matched on age and sex from a database of healthy controls without rheumatic diseases. Image evaluation of COVID-19 patients was performed in a blinded way for their characteristics. Prior to the analysis of the images, a pilot test was obtained with 4 rheumatologists in random cases, obtaining an acceptable global agreement in the visualization of capillaries and specific alterations of the nail bed. (Kappa = 0.58, p = 0.0019). Obtained data from capillaroscopies were used to be compared between severe and moderate cases of SARS-CoV-2 pneumonia. Additionally, we compared the findings against a healthy population in order to establish a reference.Results:We included data from 27 patients and 32 controls with similar demographic features. Patients with COVID-19 patients had a mean age of 43 +/- 13.8 years, 63% female. Comorbidities were present in 44.4% with: type II Diabetes Mellitus 18.5%, systemic arterial hypertension 18.5%, and rheumatoid arthritis 3.7%. The mean length of stay time was 13 +/- 7.1 days, 48.1% were admitted to the ICU, and 40.7% required invasive mechanical ventilation. In the capillaroscopic review remarkable findings of patients vs. controls were hemosiderin deposits (33 vs 12.5%, p=0.05), less frequently observable capillaries (77 vs 100%, p=0.005), any abnormality in capillaries (25.9 vs. 6.3%, p=0.03). Of notice, specific findings in COVID-19 patients were capillary tortuosities in 19%, dilatation in 9.5%, serpentine pattern in 4.8%, bush pattern in 9.5% and decreased density in only 4.8% of the cases. No avascular areas or capillaries of neoformation were observed. Finally, the presence of hemosiderin was associated with worse presentation and risk factors for severe COVID-19: Male sex 66.7 vs. 27.8%, (p = 0.024); Admission to ICU 77% vs 33% (p = 0.029); BMI > 30 kg/m2 66.7 vs. 27.8% (p = 0.053). And risk for ICU admission OR = 7.0 (95% CI 1.098 - 44.6). No significant associations were found for abnormalities in capillary morphology.Conclusion:We present one of the first reports of nailfold capillaroscopic findings in patients with COVID-19 and the first to compare to healthy controls. Previous data on this regard suggests the presence of endothelial dysfunction and microvascular complications such as micro hemorrhage or micro thrombosis. Further studies may confirm these findings and prognostic value for worse outcomes in COVID-19 patients.References:[1]Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–13.[2]Cutolo M, Cortes S. capillaroscopic patterns in rheumatic diseases. Acta Reumatol Port. 2007 Jan-Mar;32(1):29-36.[3]Natalello G, De Luca G, Gigante L, et al. Nailfold capillaroscopy findings in patients with coronavirus disease 2019: Broadening the spectrum of COVID-19 microvascular involvement. Microvasc Res. 2021;133:104071.Disclosure of Interests:None declared


1998 ◽  
Vol 18 (4) ◽  
pp. 410-414 ◽  
Author(s):  
Nicholas Apostolidis ◽  
Themis Paradellis ◽  
Andreas Karydas ◽  
Andreas Manouras ◽  
Nicholas Katirtzoglou ◽  
...  

Background Strontium is known to affect calcium metabolism both experimentally and in clinical studies on conditions other than end-stage renal failure (ESRF) and continuous ambulatory peritoneal dialysis (CAPD). Objective To investigate Sr metabolism in relation to that of Ca in ESRF patients undergoing CAPD, and the possible influence of the duration of treatment. Design Cross-sectional observational study. Setting University medical center and Institute of Nuclear Physics. Patients Twenty-four patients on CAPD; 14 chronic renal failure (CRF) patients not on dialysis, and 52 healthy controls. Measurements Calcium and Sr content of serum, urine or dialysate effluent, and selected dietary products. Results Calcium and Sr are absorbed by the intestinal tract of healthy subjects with equal efficiency. Serum Ca levels were considerably lower in CRF patients than in healthy subjects and patients on CAPD (p < 0.001). Serum Sr was significantly higher in both CAPD and CRF patients than in healthy controls (p < 0.001). The Sr/Ca ratio in the sera of the healthy subjects was defined by the preferential excretion of Sr over Ca by the kidney. This preferential excretion was lost during renal failure. During treatment there was a tendency for the uptake of both Ca and Sr to increase. Conclusions Strontium is accumulated in the body during renal failure and CAPD cannot restore normal levels. Considering the varying effects of different doses of Sr on bone metabolism experimentally, it would be interesting to determine by further studies the possible significance of the observed Sr accumulation for renal bone disease.


2018 ◽  
Vol 51 (06) ◽  
pp. 251-256 ◽  
Author(s):  
Theresa Dembler-Stamm ◽  
Jana Fiebig ◽  
Andreas Heinz ◽  
Jürgen Gallinat

Abstract Introduction Sexual dysfunction figures prominently in patients with schizophrenia; however, medication effects may play a role. The objective of this case control study was to assess differences in the presence of sexual dysfunction in unmedicated patients with schizophrenia versus healthy controls. Methods Sexual dysfunction was assessed using the Derogatis Inventory for Sexual Function self-rating in a cross-sectional design controlling for age and gender effects. A brief sexual anamnesis was applied to describe the psychosocial background of the mostly male sample further. Results Results show a significant difference with patients reporting more problems in most domains and with a significant correlation between severity of psychosis (Positive and Negative Syndrome Scale total scores) and the impairment of orgasm experience. The study revealed reduced sexual activities and less pleasure during sexual activities of patients. Discussion This study implies that schizophrenia has an impact on the presence of sexual dysfunction and that sexual dysfunction is partly independent of antipsychotic treatment. Since the sample consisted mostly of first-episode males, conclusions might only be valid for this subgroup.


Author(s):  
Johannes J. Kovarik ◽  
Anna K. Kämpf ◽  
Fabian Gasser ◽  
Anna N. Herdina ◽  
Monika Breuer ◽  
...  

This study aimed to determine the specific cytokine profile in peripheral blood during the early onset of COVID-19 infection. This was a cross-sectional exploratory, single center study. A total of 55 plasma samples were studied. Serum samples of adults showing symptoms of COVID-19 infection who were tested positive for SARS-CoV-2 infection (CoV+, n=18) at the COVID-19 outpatient clinic of the Medical University of Vienna were screened for immune activation markers by Luminex technology. Additionally, age and gender-matched serum samples of patients displaying COVID-19 associated symptoms, but tested negative for SARS-CoV-2 (CoV-, n=16) as well as healthy controls (HC, n=21) were analyzed. COVID-19 positive (CoV+) patients showed a specific upregulation of BLC (141; 74-189 pg/mL), SCD30 (273; 207-576 pg/mL), MCP-2 (18; 12-30 pg/mL) and IP-10 (37; 23-96 pg/mL), compared to patients with COVID19-like symptoms but negative PCR test (CoV-), BLC (61; 22-100 pg/mL), sCD30L (161; 120-210 pg/mL), MCP-2 (8; 5-12 pg/mL) and IP-10 (9; 6-12 pg/mL) and healthy controls (HC) (BLC 22; 11-36 pg/mL, sCD30 74; 39-108 pg/mL, MCP-2 6; 3-9. pg/mL, IP-10 = 8; 5-13). The markers APRIL, sIL-2R, IL7, MIF, MIP-1b, SCF, SDF-1a, sTNF-RII were elevated in both CoV+ and CoV- patient groups compared to healthy controls. HGF, MDC and VEGF-A were elevated in CoV- but not CoV+ compared to healthy controls. BLC, sCD30, MCP-2 and IP-10 are specifically induced during early stages of COVID-19 infection and might constitute attractive targets for early diagnosis and treatment of this disease.


2021 ◽  
pp. 103985622110227
Author(s):  
Xiaoyu Zhu ◽  
Jia Zhou ◽  
Yu Zhu ◽  
Feng Yan ◽  
Xiaole Han ◽  
...  

Objective: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have been used as markers of inflammation in mental illness. However, these indices have not been widely used in schizophrenia research in Chinese participants. Our aim was to use these ratios to explore the relationship between schizophrenia and inflammation. Methods: In this retrospective cross-sectional study, we collected total blood cell counts of 549 patients with schizophrenia and 930 healthy controls at Beijing Huilongguan Hospital in October 2019. We analyzed the subjects’ platelet, lymphocyte, monocyte, and neutrophil counts; compared the calculated NLR, MLR, and PLR between patients and healthy controls; and evaluated the correlations with age and gender. Results: Platelet and lymphocyte counts were significantly lower, while NLR and MLR were significantly higher, in patients with schizophrenia compared to healthy controls. Additionally, monocyte count, lymphocyte count, MLR, and NLR were different between male and female subjects. Conclusion: This study supports the inflammatory hypothesis of schizophrenia in the Chinese population.


2018 ◽  
Vol 47 ◽  
pp. 50-59 ◽  
Author(s):  
L. García-Álvarez ◽  
J.R. Caso ◽  
M.P. García-Portilla ◽  
L. de la Fuente-Tomás ◽  
L. González-Blanco ◽  
...  

AbstractBackgroundImmune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear.Main aimTo identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC).MethodsCross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)].Statistical analysisANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD.ResultsPro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040).ConclusionsThis study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.


2003 ◽  
Vol 8 (3) ◽  
pp. 131-147 ◽  
Author(s):  
Gian Vittorio Caprara ◽  
Mariagiovanna Caprara ◽  
Patrizia Steca

Three cross-sectional studies examined stability and change in personality over the course of life by measuring the relations linking age to personality traits, self-efficacy beliefs, values, and well-being in large samples of Italian male and female participants. In each study, relations between personality and age were examined across several age groups ranging from young adulthood to old age. In each study, personality constructs were first examined in terms of mean group differences accrued by age and gender and then in terms of their correlations with age across gender and age groups. Furthermore, personality-age correlations were also calculated, controlling for the demographic effects accrued by marital status, education, and health. Findings strongly indicated that personality functioning does not necessarily decline in the later years of life, and that decline is more pronounced in males than it is in females across several personality dimensions ranging from personality traits, such as emotional stability, to self-efficacy beliefs, such as efficacy in dealing with negative affect. Findings are discussed in terms of their implications for personality theory and social policy.


2019 ◽  
pp. 68-73
Author(s):  
Trong Nghia Nguyen ◽  
Thi Nhan Nguyen ◽  
Thi Dua Dao

Background: The metabolic syndrome is a constellation of cardiometabolic risk factors that tend to cluster together in affected individuals more often than predicted by chance. The presence of the metabolic syndrome substantially increases the risk of developing type 2 diabetes and cardiovascular disease, and is associated with a range of adverse clinical outcomes, many of which are closely associated with aging. Current estimates suggest that approximately 20 - 25% of the world’s population is affected by the metabolic syndrome. The prevalence of the metabolic syndrome rises with age and more than 45% of people aged over 60 years have the metabolic syndrome. Recent studies show that low vitamin D status is very common in the world and this is a risk factor of metabolic syndrome. Objective: (1) Plasma 25-hydroxyvitamin D concentration in subjects with metabolic syndrome. (2) Cut off value of plasma 25-hydroxyvitamin D concentration for predicting metabolic syndrome. Material and method: A cross-sectional study with control group on 318 adult subjects for health examinations at International Medical Center at Hue Central Hospital, including 139 subjects with metabolic syndrome and control group of 179 healthy subjects. Metabolic syndrome was defined according to the IDF, NHLBI, AHA, WHF, IAS, IASO (2009). Plasma hydroxyvitamin D concentration was measured using chemiluminescent microparticle immunoassay. Reciever operating characteristic (ROC) curve were generated to assess sensitivity and specificity for different cut off value of 25-hydroxyvitamin D concentration for predicting metabolic syndrome. Results: Plasma 25-hydroxyvitamin D concentration in subjects with metabolic syndrome was 26.4 ng/ml, incidence of plasma 25-hydroxyvitamin D deficiency (59.7%) was significantly higher than in control group (23.5%) (p < 0.001). The optimal cut off point for 25-OH-D concentration for predictor of metabolic syndrome as 26.4 ng/ml (AUC=0.657, sensitivity=53.4%, specificity=71.6%). Conclusion: In 139 subjects with metabolic syndrome, the plasma 25-hydroxyvitamin D concentration was 26.4 ng/ml and the incidence of 25-hydroxyvitamin D deficiency in the metabolic syndrome group was 59.7%. The optimal cut off point for plasma 25-hydroxyvitamin D concentration for predictor of metabolic syndrome as 26.4 ng/ml. Key words: Metabolic syndrome, 25-hydroxyvitamin D


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