Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Impaired physical function in patients with idiopathic inflammatory myopathies: results from the multicentre COVAD patient-reported e-survey.

OBJECTIVES: The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs. METHODS: Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease. RESULTS: A total of 1057 IIM patients, 3635 non-IIM AIRD patients and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs [36.3 (95% CI 35.5, 37.1) vs 41.3 (95% CI 40.2, 42.5) vs 46.2 (95% CI 45.8, 46.6), P < 0.001], irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis. CONCLUSION: Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.

The Role of Environmental Factors in the Development of Idiopathic Inflammatory Myopathies: a Narrative Review.

PURPOSE OF REVIEW: This review aims to evaluate recent findings on the role of environmental factors in the development and clinical presentation of idiopathic inflammatory myopathies (IIMs). RECENT FINDINGS: A targeted literature review was conducted to identify reports relevant to the association between environmental factors and IIMs published over the past three years. There has been an increasing number of publications dealing with the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination with the development of IIMs, highlighting the significant role of the antiviral immune response in the pathogenesis of the disease. Traditional environmental factors associated with the pathogenic process of IIM subclassifications included drugs such as statins and immune checkpoint inhibitors, ultraviolet radiation, smoking, air pollutants, and vitamin D deficiency. Correlations of seasonality and residence with the onset of certain IIM subtypes suggest a potential role of environmental triggers in the pathogenic process. An interplay between genetic predisposition and various environmental factors might contribute to the development of IIMs as well as the heterogeneous clinical and serological presentation of IIMs. The growing evidence on the role of environmental factors in the development of IIMs provides important clues to elucidate the pathophysiology of these disease entities. The mechanisms underlying the interactions between genetic predisposition and environmental factors should be investigated in the future.

Delayed adverse events following COVID-19 vaccination in patients with systemic sclerosis and other autoimmune diseases: a substudy of the COVAD-2 cohort.

Data on short-term safety of COVID-19 vaccination in patients with systemic sclerosis (SSc) were explored previously in the first COVID-19 vaccination in autoimmune diseases (COVAD) survey conducted in 2021. However, delayed adverse events (ADEs) (occurring > 7 days post-vaccination) are poorly characterized in these patients with SSc. In this study, we analysed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HCs) using data from the second COVAD study conducted in 2022. The COVAD-2 study was a cross-sectional, patient self-reported global e-survey conducted from February to June 2022. Data on demographics, SSc/SAID disease characteristics, COVID-19 infection history, and vaccination details including delayed ADEs as defined by the Centre for Disease Control were captured and analysed. Among 17,612 respondents, 10,041 participants fully vaccinated against COVID-19 were included for analysis. Of these, 2.6% (n = 258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines. Among patients with SSc, 18.9% reported minor, while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These frequencies were comparable to those of the ADEs reported by other patients with SAIDs and HCs. However, patients with SSc reported a higher frequency of difficulty in breathing than HCs [OR 2.3 (1.0-5.1), p = 0.042]. Patients with diffuse cutaneous SSc experienced minor ADEs [OR 2.1 (1.1-4.4), p = 0.036] and specifically fatigue more frequently [OR 3.9 (1.3-11.7), p = 0.015] than those with limited cutaneous SSc. Systemic sclerosis patients with concomitant myositis reported myalgia more frequently [OR 3.4 (1.1-10.7), p = 0.035], while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR 5.5 (1.5-20.2), p = 0.009] and dizziness [OR 5.9 (1.3-27.6), p = 0.024] than patients with SSc alone. A diagnosis of SSc did not confer a higher risk of delayed post-COVID-19 vaccine-related ADEs overall compared with other SAIDs and HCs. However, the diffuse cutaneous phenotype and coexisting autoimmune conditions including myositis and thyroid disease may increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post-COVID-19 vaccination period.

Gender differences in patient experience in idiopathic inflammatory myopathies: Sub analysis from the COVAD dataset.

OBJECTIVES: We aimed to investigate gender-based differences in idiopathic inflammatory myopathies (IIMs), with a particular focus on patient-reported outcomes, utilizing data obtained through the international COVID-19 vaccination in autoimmune disease (COVAD) e-survey. METHODS: Patient-reported outcomes including fatigue, pain, and physical function were extracted from the COVAD database and compared between genders, adjusting for demographics and IIM subgroups by multivariable analysis. Inclusion body myositis (IBM) was analysed separately because of substantial differences in outcomes. RESULTS: 1197 complete responses from patients with IIMs as of 31 August 2021 were analysed. Seventy percent were women. Women were younger (58 [48-68] vs. 69 [58-75] years old, median [IQR], p < 0.001) and more likely to suffer from autoimmune multimorbidity, defined as three or more autoimmune diseases in an individual patient (11.4% vs. 2.8%, p < 0.001). In non-IBM IIMs, fatigue visual analogue scale scores were higher in women (5 [3-7] vs. 4 [2-6], median [IQR], p = 0.004), whereas no significant gender-based differences were noted in IBM. Multivariable analysis in non-IBM IIMs revealed women, residence in high-income countries, overlap myositis, and autoimmune multimorbidity were independently associated with increased fatigue. CONCLUSIONS: Women with IIMs suffer from autoimmune multimorbidity and experience increased fatigue compared to men.

Density Functional Study on Compounds to Accelerate the Electron Capture Decay of 7Be.

In radionuclide compounds undergoing electron capture (EC) decay, the electron density at the nucleus (ρ(0)) and half-life of the nucleus are inversely proportional. Thus, the decay can be accelerated by changing the chemical or physical conditions. A previous study reported a 1.1-1.5% reduction in the half-life of 7Be encapsulated in C60 compared with 7Be metal. However, 7Be was inserted into the fullerene using the rebound energy of the nuclear reaction, which may not be a practical method. This paper elucidates the mechanism of ρ(0) change in various Be compounds from density functional calculations and attempts to propose better systems that show faster EC decay (larger ρ(0)) and/or that are easier to generate than Be in C60. In typical Be compounds, ρ(0) decreases because Be donates electrons to other atoms through chemical bonds and, thus, is not effective. Among the various Be-encapsulated fullerenes (C20-C180), the largest increase in ρ(0) was obtained for C50 fullerene, but the magnitude was almost similar to that of C60. As new systems, we propose Be-encapsulated rare gas solids, which would be generated only by applying high pressure. An increase in ρ(0) from Be metal in the range 2-10%, which depends on the lattice constant, is obtained.

Identification of human herpes virus 1 encoded microRNAs in biopsy samples of lower esophageal sphincter muscle during peroral endoscopic myotomy for esophageal achalasia.

Esophageal achalasia is a rare chronic debilitating disorder characterized by incomplete lower esophageal sphincter (LES) relaxation and abnormal peristalsis as a result of myenteric plexus degeneration. Although complex interactions among immunity, viruses and inheritance have been proposed, its causes remain unknown. MicroRNAs (miRs) play crucial roles in the regulation of gene expression during pathophysiological processes. Certain viruses such as herpes simplex virus (HSV) encode miRs derived from their own genomes. To determine the underlying relationship of miRNAs to achalasia, we analyzed the expression profile of miRNAs using biopsy samples obtained from LES muscle during peroral endoscopic myotomy. Peroral LES muscle biopsy sampling was uneventfully carried out in our case series of achalasia. Control biopsy tissues were also obtained from LES muscle of patients without symptoms relating to abnormal esophageal motility whose esophagogastric junction was surgically excised. RNA was extracted from biopsy specimens and analyzed using a microarray. Differentially expressed miRNAs in achalasia patients compared to controls were identified and analyzed using reverse transcription quantitative polymerase chain reaction. HSV-1-derived hsv1-miR-H1 and -H18 was significantly overexpressed in achalasia cohorts compared to controls. Correlations between the expression levels of viral miR and the patients' clinical characteristics including achalasia morphological type, dilatation grading, and disease duration were not identified. Further studies with a larger sample size are needed to replicate the current heuristic identification of neurotropic viral miRs and unravel their functional significance in order to provide new insight linking neurodegenerative etiology in achalasia.

In vitro platform of allogeneic stem cell-derived cardiomyocyte transplantation for cardiac conduction defects.

Aims: The aim of the present study is to develop in vitro experimental analytical method for the electrophysiological properties of allogeneic induced pluripotent stem cell-derived cardiomyocytes (CMs) in cardiac conduction defect model. Methods and results: Cardiomyocytes were derived from rat induced pluripotent stem cells CMs (riPSC-CMs) using an embryoid body-based differentiation method with the serial application of growth factors including activin-A, bone morphogenetic protein 4 (BMP-4), and inhibitor of wnt production 2 (IWP-2). Flow cytometry analysis showed that 74.0 ± 2.7% of riPSC-CMs expressed cardiac troponin-T (n = 3). Immunostaining analysis revealed organized sarcomeric structure in riPSC-CMs and the expression of connexin 43 between riPSC-CMs and neonatal rat ventricular CMs (NRVMs). Ca2+ transient recordings revealed the simultaneous excitement of riPSC-CMs and NRVMs, and prolonged Ca2+ transient duration of riPSC-CMs as compared with NRVMs (731 ± 15.9 vs. 610 ± 7.72 ms, P < 0.01, n = 3). Isolated NRVMs were cultured in two discrete regions to mimic cardiac conduction defects on multi-electrode array dish, and riPSC-CMs were seeded in the channel between the two discrete regions. Membrane potential imaging with di-8-ANEPPS discerned the propagation of the electrical impulse from one NRVM region to the other through a riPSC-CM pathway. This pathway had significantly longer action potential duration as compared with NRVMs. Electrophysiological studies using a multi-electrode array platform demonstrated the longer conduction time and functional refractory period of the riPSC-CM pathway compared with the NRVM pathway. Conclusion: Using an in vitro experimental system to mimic cardiac conduction defect, transplanted allogeneic riPSC-CMs showed electrical coupling between two discrete regions of NRVMs. Electrophysiological testing using our platform will enable electrophysiological screening prior to transplantation of stem cell-derived CMs.

Mycophenolate mofetil therapy for two cases of antiphospholipid antibody-associated chorea.

Chorea is associated with involuntary movement and may occur via an autoimmune mechanism. Until now, we treated immune-mediated chorea with glucocorticoids and cyclophosphamide as the efficacy of mycophenolate mofetil (MMF) therapy for this condition was unknown. Here, we report two cases of antiphospholipid antibody (aPL)-associated chorea that were cured by MMF. Measurement of aPL could help for future management of chorea patients. This report provides new insight into the beneficial effects of MMF on aPL-associated chorea.

Effectiveness of elcatonin for alleviating pain and inhibiting bone resorption in patients with osteoporotic vertebral fractures.

Elderly patients with osteoporotic vertebral fractures often experience severe pain that reduces their quality of life (QOL). Calcitonin, a bone resorption inhibitor, has been reported to alleviate pain in such patients; however, few clinical studies have demonstrated this effect. The objective of this study was to compare changes in pain scores, activities of daily living (ADL), QOL, bone resorption, bone mineral density (BMD), and fracture healing among patients with new vertebral fractures who received different treatment modalities. We conducted an open-label, multicenter, randomized, parallel control group study comprising 107 female patients ≥55 years old with acute back pain from vertebral fracture. All subjects received either intramuscular injections of elcatonin, a derivative of calcitonin, or an oral nonsteroidal antiinflammatory drug (NSAID) combined with an active vitamin D3 (VD3) analogue for 6 months. The pain was assessed using a visual analogue scale, and ADL and QOL were assessed using questionnaires. BMD was measured using dual-energy X-ray absorptiometry. A two-tailed significance level of 5% was used. The elcatonin IM group had significantly higher QOL score at 2 weeks and later, and significantly lower VAS and ADL scores than those in the NSAID + VD3 group at 1 month and later. The elcatonin IM group had significantly reduced TRACP-5b levels compared with those in the NSAID + VD3 group at 3 months and later and significantly higher percent changes in BMD than the NSAID + VD3 group. These results suggest that elcatonin significantly alleviated pain, inhibited bone resorption, and improved ADL, QOL, and BMD compared with NSAID + VD3.

Acute encephalopathy with biphasic seizures and late reduced diffusion in Kawasaki disease.

Herein we describe the case of a 7-month-old girl with Kawasaki disease (KD) in whom status epilepticus with fever developed on day 3 and cluster of seizures on day 6 of illness, followed by severe disturbance of consciousness afterward. Diffusion-weighted magnetic resonance imaging on day 6 of illness showed diffuse high signals in the bilateral subcortical white matter, while electroencephalogram indicated low-voltage slow waves. This indicated acute encephalopathy with biphasic seizures and late reduced diffusion (AESD); severe neurological sequelae remained. This is the first report of AESD as a complication of KD.

Effectiveness of monotherapy and combined therapy with calcitonin and minodronic acid hydrate, a bisphosphonate, for early treatment in patients with new vertebral fractures: An open-label, randomized, parallel-group study.

BACKGROUND: Evidence related to the effectiveness of combination drug therapy for the treatment of osteoporosis is currently considered insufficient. Therefore, this study was performed to clarify the effects of monotherapy, and combination therapy, with a bisphosphonate (minodronic acid hydrate), a bone resorption inhibitor, and calcitonin (elcatonin), which is effective for the alleviation of pain due to vertebral fractures in osteoporotic patients. METHODS: Study participants comprised of 51 female subjects with post-menopausal osteoporosis, whose main complaint was acute lower back pain caused by vertebral fractures. Subjects were randomly allocated into three groups and then administered with either intramuscular injections of elcatonin at a dose of 20 units weekly, minodronic acid hydrate at a dose of 1 mg daily, or a combination of these two drugs. As primary endpoints, time-dependent changes in levels of pain were assessed using a visual analog scale from baseline to 6 months of duration. In addition, we examined the effects of monotherapies, and a combination therapy on bone resorption, with changes in bone mineral density at 4 sites and advanced hip assessment parameters from baseline to 6 months. A two-tailed significance level of 5% was used for hypothesis testing. RESULTS: Elcatonin monotherapy showed some alleviation of pain immediately after any vertebral fractures, which was more than in the minodronic acid hydrate monotherapy group. In addition, the minodronic acid hydrate monotherapy group experienced more effective inhibited bone resorption than the elcatonin monotherapy group. In the combination therapy, the efficacy for alleviating pain and inhibiting bone resorption was equivalent to the effect observed in the elcatonin and minodronic acid hydrate monotherapy groups respectively, with further improved values of bone mineral density observed in the femoral neck and lumbar vertebrae, and in parameters of advanced hip assessment compared with both monotherapy groups. CONCLUSIONS: Combination therapy with elcatonin and minodronic acid hydrate appears to be an effective treatment for osteoporosis patients with lower back pain, caused by fresh vertebral fractures.

Combination of panobinostat with ponatinib synergistically overcomes imatinib-resistant CML cells.

The major mechanism of imatinib (IM) resistance of CML is the reactivation of ABL kinase either through BCR-ABL gene amplification or mutation. We investigated the cytotoxicity of a pan-ABL tyrosine kinase inhibitor, ponatinib, and a pan-histone deacetylase inhibitor, panobinostat, against IM-resistant CML cells in vitro. Two different IM-resistant cell lines, K562/IM-R1 and Ba/F3/T315I were evaluated in comparison with their respective, parental cell lines, K562 and Ba/F3. K562/IM-R1 overexpressed BCR-ABL due to gene amplification. Ba/F3/T315I was transfected with a BCR-ABL gene encoding T315I-mutated BCR-ABL. Ponatinib inhibited the growth of both K562/IM-R1 and Ba/F3/T315I as potently as it inhibited their parental cells with an IC50 of 2-30 nM. Panobinostat also similarly inhibited the growth of all of the cell lines with an IC50 of 40-51 nM. This was accompanied by reduced histone deacetylase activity, induced histone H3 acetylation, and an increased protein level of heat shock protein 70, which suggested disruption of heat shock protein 90 chaperone function for BCR-ABL and its degradation. Importantly, the combination of ponatinib with panobinostat showed synergistic growth inhibition and induced a higher level of apoptosis than the sum of the apoptosis induced by each agent alone in all of the cell lines. Ponatinib inhibited phosphorylation not only of BCR-ABL but also of downstream signal transducer and activator of transcription 5, protein kinase B, and ERK1/2 in both K562/IM-R1 and Ba/F3/T315I, and the addition of panobinostat to ponatinib further inhibited these phosphorylations. In conclusion, panobinostat enhanced the cytotoxicity of ponatinib towards IM-resistant CML cells including those with T315I-mutated BCR-ABL.

Muscarinic Receptor Binding in Rat Bladder Urothelium and Detrusor Muscle by Intravesical Solifenacin.

Solifenacin is an antimuscarinic agent used to treat symptoms of overactive bladder. Pharmacologically significant amounts of solifenacin were excreted in the urine of humans taking a clinical dose of this drug. The aim of this study is to measure muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats following the intravesical instillation of solifenacin. Muscarinic receptors were measured by radioreceptor assay using [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS), a selective radioligand of muscarinic receptors. Solifenacin showed concentration-dependent inhibition of specific [(3)H]NMS binding in the bladder urothelium and detrusor muscle of rats, with no significant difference in Ki values or Hill coefficients between these tissues. Following the intravesical instillation of solifenacin, there was significant muscarinic receptor binding (increase in Kd for specific [(3)H]NMS binding) in the bladder urothelium and detrusor muscle of rats. Similar bladder muscarinic receptor binding was observed by the intravesical instillation of oxybutynin, but not with trospium. In conclusion, the present study has demonstrated that solifenacin binds muscarinic receptors not only in the detrusor muscle but also in the bladder urothelium with high affinity. These bladder muscarinic receptors may be significantly affected by solifenacin excreted in the urine.

Tyrosine-kinase inhibitors to treat radioiodine-refracted, metastatic, or recurred and progressive differentiated thyroid carcinoma [Review].

Differentiated thyroid carcinoma (DTC) is generally indolent in nature and, even though it metastasizes to distant organs, the prognosis is normally excellent. In contrast, the overall survival (OS) of patients with radioactive iodine (RAI)-refractory and progressive metastases is dire, because no effective therapies have been available to control the metastatic lesions. However, recently, administration of tyrosine-kinase inhibitors (TKIs) has become a new line of therapy for RAI-refractory and progressive metastases. Previous studies have reported significant improvement regarding the progression-free survival rates of patients with metastatic lesions. However, TKIs cause various severe adverse events (AEs) that damage patients' quality of life and can even be life-threatening. Additionally, metastatic lesions may progress significantly after stopping TKI therapy. Therefore, it is difficult to determine who is a candidate for TKI therapy, as well as how and when physicians start and stop the therapy. The present review, created by Committee of pharmacological therapy for thyroid cancer of the Japanese Society of Thyroid Surgery (JSTS) and the Japan Association of Endocrine Surgeons (JAES) describes how to appropriately use TKIs by describing what we do and do not know about treatment using TKIs.

Eosinophilic enteritis due to cow's milk allergy: Possible cause of anastomosis failure following repair of focal intestinal perforation.

Reports of cow's milk allergy (CMA) after neonatal gastrointestinal surgery have recently increased. In recent years it has been suggested that the development of CMA after gastrointestinal surgery in newborn infants is due to an immune function. In addition, the development of CMA might be synergistically exacerbated by congenital abnormalities of the intestinal mucosa, general conditional changes and local damage to the intestine by invasive surgery, and poor pre- or post-surgical nutrition. CMA manifests as a variety of symptoms, such as mild vomiting and bloody stool, decreased activity, poor oral intake, and ileus. CMA may also rarely cause gastrointestinal perforation. Here, we report the case of a newborn infant who developed CMA following repair of focal small intestinal perforation, in which eosinophilic enteritis was suspected to be a possible cause of anastomosis leakage.

[Comparison of Contrast to Noise Ratio and Signal Difference to Noise Ratio Based on QA and QC Guidelines in CR Mammography].

The measurement methods of contrast to noise ratio (CNR) and signal difference to noise ratio (SDNR) in digital mammography are different among several quality assurance (QA) guidelines, that is, the type of pixel value (PV), phantom shape, location of aluminum plate, and the size of region of interest (ROI) principally differ in data acquisition. We compared CNR (SDNR) obtained from three QA guidelines. They are the European Reference Organisation for Quality Assured Breast Screening and Diagnostic Services (EUREF), the International Electrotechnical Commission (IEC), and the International Atomic Energy Agency (IAEA). In EUREF and IEC, CNR was calculated using linearized pixel value (LPV). In IAEA, because the type of pixel value to use in SDNR was not specified, SDNR was calculated using PV and LPV, and CNR was calculated using LPV. Target/filter combinations are molybdenum/molybdenum (Mo/Mo) and molybdenum/rhodium (Mo/Rh). Applied various tube voltages are 25, 30, and 35 kV, and various phantom thicknesses are 20, 45, and 70 mm of polymethyl methacrylate (PMMA). The PV-SDNR of IAEA showed the largest value among the three methods, following LPV-CNR of IEC, LPV-CNR of EUREF at 20 mm PMMA thickness. In IAEA, SDNR changed by the kind of pixel value (PV or LPV). When CNR is calculated, every researcher should describe the type of guidelines, the kind of pixel value, and formula for calculation.

[Influence of Detector Radiation Damage on CR Mammography Quality Control].

Recently, radiation damage to the detector apparatus employed in computed radiography (CR) mammography has become problematic. The CR system and the imaging plate (IP) applied to quality control (QC) program were also used in clinical mammography in our hospital, and the IP to which radiation damage has occurred was used for approximately 5 years (approximately 13,000 exposures). We considered using previously acquired QC image data, which is stored in a server, to investigate the influence of radiation damage to an IP. The mammography unit employed in this study was a phase contrast mammography (PCM) Mermaid (KONICA MINOLTA) system. The QC image was made newly, and it was output in the film, and thereafter the optical density of the step-phantom image was measured. An input (digital value)-output (optical density) conversion curve was plotted using the obtained data. The digital values were then converted to optical density values using a reference optical density vs. digital value curve. When a high radiation dose was applied directly, radiation damage occurred at a position on the IP where no object was present. Daily QC for mammography is conducted using an American College of Radiology (ACR) accreditation phantom and acrylic disc, and an environmental background density measurement is performed as one of the management indexes. In this study, the radiation damage sustained by the acrylic disc was shown to differ from that of the background. Thus, it was revealed that QC results are influenced by radiation damage.

Interactive effects of a common γ-glutamyltransferase 1 variant and low high-density lipoprotein-cholesterol on diabetic macro- and micro-angiopathy.

BACKGROUND: We investigated the clinical relevance of a common variant, rs4820599, in the γ-glutamyltransferase (GGT)1 gene, associated with the serum GGT level, in Japanese type 2 diabetes mellitus (T2DM) subjects. METHODS: We conducted a retrospective longitudinal study (4.9 ± 2.5 years) including 352 T2DM patients (T2DM subjects) and a cross-sectional study including 796 health screening program participants (general subjects). A real-time TaqMan allelic discrimination assay was used to identify the genotypes. Risk factors for a high brachial-ankle pulse wave velocity (baPWV) (≥1750 cm/sec) or diabetic retinopathy (DR) were determined using a generalized estimating equations approach, receiver operating characteristic (ROC) analysis or Cox proportional hazards model, etc. RESULTS: The frequency of the GGT1 G allele was 20.8% in the T2DM subjects, and no associations were found between the GGT1 genotype and risk of T2DM. The mean log GGT values in the T2DM and general subjects were significantly higher among G allele carriers than non-carriers. The G allele and a low HDL-C level were identified to be risk factors for a high baPWV in the T2DM subjects [odds ratio (OR) 1.80, P = 0.008; OR 1.71, P = 0.03; respectively), and a significant interactive effect between these factors was found on the risk of a high baPWV and DR. The HDL-C level at baseline was a significant predictor of a high baPWV only in G allele carriers according to the ROC analysis. This result regarding baPWV in the T2DM subjects was replicated in the general population. Meanwhile, the GGT1 genotype was not associated with the risk of DR, although it affected the principal factors involved in the risk of DR, and a low HDL-C level was also found to be a risk factor for DR only in G allele carriers. CONCLUSIONS: We herein describe for the first time the significant interactive effects of the GGT1 G allele and a low HDL-C level on a high baPWV and DR. These findings may encourage future clinical trials comparing the efficacy of agents increasing the HDL-C levels among the GGT1 genotypes. However, well-designed studies in larger cohorts are needed to confirm our results.