Assisting the diagnosis of Graves’ hyperthyroidism with pattern recognition methods and a set of three routine tests parameters, and their correlations with free T4 levels: Extension to male patients

In our previous paper, we proposed a novel screening method that aids the diagnosis of female patients with Graves’ hyperthyroidism via two types of neural networks and the use of routine test data. This method can be applied by non-specialists during physical checkups at a low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists; i.e., to improve patients’ QOL. In this report, we investigate whether the screening method is also applicable to males since sex differences exist in routine test data. The values of 14 routine test parameters for 78 subjects with definite diagnoses (31 patients with Graves’ hyperthyroidism and 48 healthy volunteers) were adopted as training data, and 133 individuals who had also undergone the same routine tests at Tohoku University Hospital were screened for Graves’ hyperthyroidism using our method. The present examination of our screening method in males showed its high screening ability with the set of parameters used (low serum creatinine, elevated alkaline phosphatase, and low total cholesterol). It was also found that there is strong multiple correlation between a set of three parameters and serum free thyroxine (FT4) in male patients with Graves’ hyperthyroidism. A formula for FT4 consisting of three parameters was obtained, and this can be utilized in place of the true FT4 value. This result also supports the usefulness of our screening method.     

MicroRNA‐146a and microRNA‐146b deficiency correlates with exacerbated disease activity,and their longitude increment relates to etanercept response in psoriasis patients

BackgroundMicroRNA (miR)‐146a and miR‐146b regulate autoimmunity, inflammation, and keratinocytes proliferation to engage in psoriasis pathology. The current study aimed to investigate their correlation with disease risk and clinical features, and the linkage of their longitudinal changes with clinical response to etanercept in psoriasis patients.MethodsPlasma samples were collected from 84 moderate‐to‐severe psoriasis patients who underwent etanercept treatment (at baseline (M0), 1 month (M1), 3 months (M3), and 6 months (M6)), 80 disease controls and 80 health controls (both after enrollment); afterward, miR‐146a and miR‐146b expressions were detected by RT‐qPCR. Furthermore, PASI75 and PASI90 responses were assessed in psoriasis patients.ResultsBoth miR‐146a and miR‐146b were decreased in psoriasis patients compared with disease controls and health controls (all p < 0.001), which also distinguished psoriasis patients from disease controls and health controls by receiver‐operating characteristic analyses. Furthermore, miR‐146a positively correlated with miR‐146b in psoriasis patients (p < 0.001) and disease controls (p = 0.005) but not in healthy controls (p = 0.062). In psoriasis patients, miR‐146a negatively related to psoriatic body surface area (p = 0.011) and PASI score (p = 0.003); miR‐146b negatively linked with PASI score (p = 0.020). At M1, M3, and M6 after etanercept treatment, PASI75 response rate was 14.3%, 32.1%, and 69.0%, respectively; PASI90 response rate was 1.2%, 17.9%, and 36.9%, respectively. During etanercept treatment, both miR‐146a and miR‐146b elevated gradually over time and their longitude increments were associated with PASI75 response (all p < 0.001).ConclusionMiR‐146a and miR‐146b might serve as indicators for optimizing etanercept application and improving treatment outcomes in psoriasis patients.     

RSV下呼吸道感染患儿血清miR-146a、 miR-155的表达及意义

目的 探讨呼吸道合胞病毒(RSV)下呼吸道感染患儿血清微小RNA-146a(miR-146a)、miR-155的表达及意义.方法 选取该院97例RSV下呼吸道感染患儿作为试验组,同时随机选取101例健康儿童作为对照组.检测2组肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-10、超敏C-反应蛋白(hs-C...     

miR‐216a promotes breast cancer cell apoptosis by targeting PKCα

Breast cancer (BC) is the most common cause of death in women throughout the world. MicroRNAs (miRNAs, miR) have been identified as key regulators in carcinogenesis of several cancers, including BC. MicroRNA‐216a (miR‐216a) is downregulated in several cancers. Here, we evaluated the effects of miRNA‐216a on breast cancer cells and the underlying mechanisms. miR‐216a level was quantified by real‐time RT‐PCR. Cell viability was analyzed by MTT assay. Wound‐healing assay was performed for detection of cell migration. Apoptosis was detected by TUNEL and caspase‐3 activity assay. Moreover, the level of protein expression was determined by Western blot. We found that miR‐216a expression was remarkably decreased in both human BC tissues and MCF‐7 cells. miR‐216a overexpression dramatically suppressed the migration and promoted the apoptosis in cultured MCF‐7 cells. We validated PKCα (protein kinase C alpha, PRKCA) as a direct target of miR‐216a. Knockdown of PKCα induced apoptosis and inhibited migration in cultured MCF‐7 cells which were reversed by miR‐216a inhibitor. Moreover, the level of miR‐216a is negatively correlated with PKCα in cell lines. Our results collectively suggest that miR‐216a suppressed migration and promoted apoptosis in breast cancer cells by targeting PKCα. These findings indicate that manipulation of miR‐216a expression may represent a novel therapeutic strategy in the treatment of breast cancer.     

Aneurysmal bone cyst of the proximal femur concomitant with Graves’ disease and Moyamoya disease: report of a rare case

Aneurysmal bone cyst is a type of benign bone pathology with expansile and osteolytic features whose etiology remains unclear. Graves’ disease is an autoimmune disease characterized by diffuse goiter and hyperthyroidism. Moyamoya disease is a progressive cerebral vasculopathy. It has been reported that Graves’ disease and Moyamoya disease share a similar etiology involving cytokines and autoimmune and genetic factors. There are no previous reports regarding the relationship between aneurysmal bone cyst and Graves’ disease. Here, we present the rare case of a 25-year-old woman with suspected aneurysmal bone cyst of the left proximal femur and a definite preoperative diagnosis of Graves’ disease, in whom lesion resection combined with left total hip replacement was indicated. Biopsy confirmed the diagnosis of aneurysmal bone cyst. Three days postoperatively, the patient developed acute ischemic cerebral infarction owing to Moyamoya disease, which was subsequently confirmed. This case elucidates the potential interaction among aneurysmal bone cysts, Graves’ disease, and Moyamoya disease and provides lessons regarding appropriate perioperative preparation for patients with Graves’ disease who require surgery to avoid potential severe complications.     

Evaluation of analytic and clinical performance of two immunoassays for detecting thyroid‐stimulating receptor antibody in the diagnosis of Graves’ disease

ObjectiveTo evaluate the analytical and clinical performance of two immunoassays for diagnosis of Graves’ disease (GD), the Immulite thyroid‐stimulating immunoglobulin (TSI), and Elecsys Anti‐TSH receptor (TSHR) assay.MethodsPrecision and analytical measurement range were assessed using pooled samples of patients. The comparison between the two methods was evaluated using 579 clinical samples, and receiver operating characteristic (ROC) curves were drawn using the final diagnosis as reference. Clinical sensitivity and specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the two tests.ResultsThe repeatability and intermediate imprecision coefficient of variation (CV%) of the TSI assay were 3.8% and 4.1% at 0.95 IU/L, and 3.5% and3.6% at 19.5 IU/L, respectively. The assays were linear over a range 0.27–38.5 IU/L. There was a high correlation between the quantitative results of the two methods (correlation coefficient r = 0.930). The cut‐off value obtained by ROC analysis for TSI assay was 0.7 IU/L with sensitivity of 93.7% and specificity of 85.1%. An overall qualitative agreement of 91.5% between two methods was observed. Among 44 patients with discordant qualitative results, the TSI assay provided more satisfactory results consistent with clinical diagnoses.ConclusionThe TSI assay showed excellent analytical performance and provided a high PPV for GD.     

Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16‐week,randomized and placebo‐controlled trial

What is known: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer’s disease (AD). Objective: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. Methods: Forty‐six patients with probable AD were screened for a 16‐week, double‐blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale‐cognitive subscale (ADAS‐cog), and clinical dementia rating scale‐sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16‐week study. Results: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS‐cog: F = 4·12, d.f. = 1, P = 0·04; CDR: F = 4·12, d.f. = 1, P = 0·04). There were no significant differences in the two groups in terms of observed adverse events. What is new and conclusion: This double‐blind, placebo‐controlled study suggests that at least in the short‐term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for.     

Comparative performance of ELISA and dot blot assay for TSH‐receptor antibody detection in Graves’ disease

BackgroundGraves’ disease (GD) is an autoimmune disease, and it accounts for major cases of hyperthyroidism. Antibody against thyroid‐stimulating hormone receptor/TSHR (TRAb) is responsible for hyperthyroidism and is considered as a diagnostic marker for GD. Therefore, we developed a recombinant protein of human TSHR‐169 (hTSHR‐169), which was specifically recognized TRAb in the serum of GD patients and then compare the diagnostic performance between ELISA and dot blot of TRAb tests for their ability to diagnose GD.Methods20 GD patients and 20 healthy individuals from the Indonesian population were enrolled. TRAb concentration and density were quantified. Comparative analysis was performed using receiver‐operating curve (ROC) analysis.ResultsFor dot blot assay, the minimum concentration to detect TRAb requiring 100 ng of antigen with antiserum diluted at 1:60. For diagnosing GD, the ELISA yielded a higher AUC compared with the dot blot assay (0.95 and 0.85, respectively). Using the recommended cutoff values, the efficiency of both assays was examined by comparing the specificity and sensitivity of the assays to the clinical diagnosis. The ELISA showed 80% and 95%, while the dot blot assay showed 70% and 95% sensitivity and specificity, respectively.ConclusionAlthough the dot blot assay exhibited lower performance than the ELISA method, the dot blot assay is a simple and rapid diagnostic assay that is suitable for diagnosing GD in rural areas, in which healthcare facilities sometimes are not accessible.     

The lower expression of circulating miR‐210 and elevated serum levels of HIF‐1α in ischemic stroke; Possible markers for diagnosis and disease prediction

Background Stroke, either due to ischemia or hemorrhage, causes acute neurological damages to the brain. There is shortage of reliable biomarkers for ischemic stroke (IS), and we therefore investigated the serum concentrations of microRNA‐210 (miR‐210) and hypoxia inducible factor‐1α (HIF‐1α), as possible diagnostic and/or prognostic markers for IS.MethodsSerum samples were acquired from 52 IS patients and their healthy counterparts at five time points: upon admission, 24 and 48 h after admission, upon discharge and 3 months later. Serum levels of miR‐210 and HIF‐1α were respectively analyzed using real time RT‐PCR and ELISA. Diagnostic and prognostic accuracy tests were performed to assess the value of suggested biomarkers.ResultsIS patients demonstrated higher levels of serum HIF‐1α and lower miR‐210 in comparison to the healthy subjects. MiR‐210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF‐1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR‐210 and lower levels of HIF‐1α were associated with better survivals in IS patients.ConclusionsSerum miR‐210 is a weak diagnostic marker of IS. Serum HIF‐1α is a better biomarker in diagnosing IS patients but further work in larger groups, including those with hemorrhagic stroke is necessary to confirm its diagnostic utility. Similarly, the prognostic potentiality of miR‐210 and HIF‐1α was acceptable but needs bigger sample size and longer follow‐up to be statistically confirmed.     

Coronavirus disease 2019 (COVID‐19) as a potential trigger for benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is a rare disease characterized by recurrent severe itching and jaundice. Coronavirus disease 2019 (COVID‐19) is a multisystemic acute viral disease and the liver is frequently affected. Here, we wanted to present a BRIC case triggered by COVID‐19 infection, discussing it together with current information.     

Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease

Gait disorders form one component of the axial disorders observed in Parkinson’s disease (PD). Indeed, short steps with a forward‐leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late‐stage therapeutics – levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non‐dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leading to a major motor impact. The pedunculopontine nucleus (PPN) and lateral pontine tegmentum (rich in acetylcholine) are both involved in gait. Degenerative damage to the serotoninergic raphe nuclei appears to be less severe, although serotonin‐dopamine interactions are numerous and complex. Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area.     

Altered expression of serum miR‐106a,miR‐19b,miR‐17, and PTEN in patients with idiopathic membranous nephropathy

BackgroundTo find new diagnostic markers for idiopathic membranous nephropathy (IMN) and also conduct preliminary explorations into the possible pathogenesis of IMN by comparing the expression of microRNA‐451a (miR‐451a), miR‐106a, miR‐19b, miR‐17, and phosphatase and tensin homolog (PTEN) protein in the serum of patients with IMN and healthy controls.MethodsThe expression levels of miR‐451a, miR‐106a, miR‐19b, and miR‐17 in the serum of patients in the IMN group (n = 55, age: 50.2 ± 12.1 years) and the control group (n = 58, age 47.4 ± 13.1 years) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR), and the concentration of serum PTEN protein was determined by enzyme‐linked immunosorbent assay (ELISA).ResultsCompared with the control group, the expression of miR‐106a, miR‐19b, and miR‐17 was decreased significantly in the IMN group, whereas PTEN protein concentration was increased significantly in the IMN group. The areas under the receiver operating characteristic curve (AUC) of serum miR‐106a, miR‐19b, miR‐17, and PTEN were 0.66 (95% confidence interval [CI], 0.56–0.76), 0.81 (95% CI, 0.73–0.89), 0.69 (95% CI, 0.59–0.79), and 0.86 (95% CI, 0.79–0.93), respectively. The level of serum PTEN protein was negatively correlated with the expression of miR‐106a and miR‐19b. PTEN concentration was positively correlated with serum urea (Urea), creatinine (Crea), cystatin C (Cysc), 24 h urine total protein (24 h‐UP) and negatively correlated with albumin (Alb) and estimated glomerular filtration rate (eGFR).ConclusionsMiR‐106a, miR‐19b, miR‐17, and PTEN are involved in the pathogenesis of IMN and may become new biomarkers for the diagnosis of IMN.