A 64-Year-Old Man With Multifocal Infiltrates.

CASE PRESENTATION: A 64-year-old previously healthy man presented with 8 weeks of progressive dyspnea on exertion and cough. Prior to presentation, the patient was able to bicycle > 60 miles per week and work full-time in a home improvement store. He was up-to-date with age-appropriate cancer screening and immunizations, and home medications included famotidine for reflux and nonsteroidal antiinflammatories for osteoarthritis, both as-needed. He had no significant respiratory exposure, aside from previous work as an electrician. His symptoms began in mid-February 2020 amid the coronavirus disease 2019 pandemic, although he had no known exposure to the virus.

Anti-MDA5 autoantibodies associated with juvenile dermatomyositis constitute a distinct phenotype in North America.

OBJECTIVE: Myositis-specific autoantibodies have defined distinct phenotypes of patients with juvenile myositis (JIIM). We assessed the frequency and clinical significance of anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody-associated JIIM in a North American registry. METHODS: Retrospective examination of the characteristics of 35 JIIM patients with anti-MDA5 autoantibodies was performed, and differences from other myositis-specific autoantibody groups were evaluated. RESULTS: Anti-MDA5 autoantibodies were present in 35/453 (7.7%) of JIIM patients and associated with older age at diagnosis, and lower serum creatine kinase and aldolase levels. Patients with anti-MDA5 autoantibodies had more frequent weight loss, adenopathy, arthritis, interstitial lung disease (ILD), and less frequent falling compared with anti-transcriptional intermediary factor 1 (TIF1), anti-nuclear matrix protein 2 (NXP2) and myositis-specific autoantibody/myositis-associated autoantibody-negative patients. They had a different season of diagnosis and less frequent mechanic's hands and ILD compared with those with anti-synthetase autoantibodies. Anti-MDA5 patients received fewer medications compared with anti-TIF1, and corticosteroid treatment was shorter compared with anti-TIF1 and anti-nuclear matrix protein 2 autoantibody groups. The frequency of remission was higher in anti-MDA5 than anti-synthetase autoantibody-positive JIIM. In multivariable analyses, weight loss, arthritis and arthralgia were most strongly associated with anti-MDA5 autoantibody-positive JIIM. CONCLUSION: Anti-MDA5 JIIM is a distinct subset, with frequent arthritis, weight loss, adenopathy and less severe myositis, and is also associated with ILD. Anti-MDA5 is distinguished from anti-synthetase autoantibody-positive JIIM by less frequent ILD, lower creatine kinase levels and differing seasons of diagnosis. Anti-MDA5 has comparable outcomes, but with the ability to discontinue steroids more rapidly and less frequent flares compared with anti-TIF1 autoantibodies, and more frequent remission compared with anti-synthetase JIIM patients.

Silicosis, sarcoidosis y esclerosis sistémica en un mismo paciente / Silicosis, sarcoidosis and systemic sclerosis in the same patient

No disponible

Assessing Performance of HRP2 Antigen Detection for Malaria Diagnosis in Mozambique.

Rapid diagnostic tests (RDTs) that detect the Plasmodium falciparum-specific histidine-rich protein 2 (PfHRP2) antigen are the primary methods for malaria diagnosis in Mozambique. However, these tests do not detect infections with non-falciparum malaria or Pfhrp2- and Pfhrp3-deleted P. falciparum parasites. To assess the appropriateness of conventional PfHRP2-only RDTs for malaria diagnosis in Mozambique, samples collected during a health facility survey conducted in three provinces of Mozambique were screened using antigen detection methods and further characterized by molecular techniques. Samples from 1,861 outpatients of all ages and symptoms attending 117 randomly selected public health facilities in 2018 were analyzed with an ultrasensitive bead-based immunoassay for the presence of PfHRP2, pan-Plasmodium aldolase (pAldo), and pan-Plasmodium lactate dehydrogenase (pLDH). The presence of PfHRP2 in patient blood detected using the bead-based assay was compared to the results of PfHRP2-based RDTs performed during the routine health facility consult and during the survey reexamination at the exit interview. Samples with discordant antigen profiles (negative for PfHRP2 but positive for pAldo and/or pLDH) were further characterized by photoinduced electron transfer PCR (PET-PCR). Using the bead-based laboratory assay as the gold standard, the sensitivities of the conventional RDTs administered during the routine health facility consult and the exit interview were 90% and 83%, respectively, and the specificities were 91% and 97%, respectively. Of 710 samples positive for at least one antigen, 704 (99.2%) were positive for PfHRP2. Six (0.8% of total) discordant samples lacked PfHRP2 but were positive for pAldo and/or pLDH; 3 of these (0.4% of total) were Plasmodium ovale monoinfections or coinfections where P. ovale was the dominant species. The remaining 3 discordant samples were negative by PET-PCR. The sensitivity and specificity of the conventional RDTs performed in the routine health facility consults and survey exit interviews were acceptable, and there was no evidence of Pfhrp2- and Pfhrp3-deleted parasites. Monoinfections with non-falciparum malaria species comprised <1% of the total malaria infections. Nearly all malaria antigen-positive patients had detectable PfHRP2, confirming that this antigen remains an appropriate malaria diagnostic target in the surveyed provinces.

Clearance dynamics of lactate dehydrogenase and aldolase following antimalarial treatment for Plasmodium falciparum infection.

BACKGROUND: Lingering post-treatment parasite antigen in blood complicates malaria diagnosis through antigen detection. Characterization of antigen clearance dynamics is important for interpretation of positive antigen detection tests. RESULTS: We used a bead-based serological assay to measure lactate dehydrogenase (LDH), aldolase (Aldo), and histidine-rich protein 2 (HRP2) levels in 196 children with Plasmodium falciparum malaria treated with effective antimalarials and followed for 28 to 42 days as part of therapeutic efficacy studies in Angola. Compared to pre-treatment levels, antigen concentrations two days after treatment declined by 99.7% for LDH, 96.3% for Aldo, and 54.6% for HRP2. After Day 2, assuming a first-order kinetics clearance model, half-lives of the antigens were 1.8 days (95% CI: 1.5-2.3) for LDH, 3.2 days (95% CI: 3.0-3.4) for Aldo, and 4.8 days (95% CI: 4.7-4.9) for HRP2. CONCLUSIONS: LDH and Aldo show substantially different clearance rates than HRP2, and their presence is largely indicative of active infection.

Comparative proteomic analysis of plasma of children with congenital heart disease.

Congenital heart disease is one of the largest class of birth defects. Eight subjects with ventricular septal defect (VSD, a kind of congenital heart disease) and 11 health children were enrolled in tandem mass tags label-based quantitative proteomic analysis to compare plasma proteins differentially abundance. A total of 66 proteins were significantly upregulated or downregulated in VSD patients compared with healthy children. These proteins were involved in pathways linked to platelet activation, fructose and mannose metabolism, complement and coagulation cascades, glycolysis/gluconeogenesis, regulation of actin cytoskeleton, and carbon metabolism. The amount of ten proteins changed significantly (p < 0.05) in newly recruited 30 VSD compared with 15 control children, which were validated by ELISA. The areas under the receiver operating characteristic curve values of fructose-bisphosphate aldolase B (ALDOB) and thymosin beta-4 (Tß4) were higher than those of other candidate proteins. ALDOB and Tß4 might be potential biomarkers applied for identifying VSD in the further works.

Diffusion-weighted magnetic resonance imaging is useful for assessing inflammatory myopathies.

INTRODUCTION: Short tau inversion recovery (STIR) sequences in whole-body MRI are usually used for detecting muscle edema (ME) in inflammatory myopathies. We evaluated b-value 800 diffusion-weighted imaging (b800 DWI). METHODS: Two radiologists independently and a consensus reader retrospectively reexamined 60 patients with inflammatory myopathies and 15 controls. For each participant, 78 muscles were analyzed with 3 sets of imaging acquisitions: T1-weighted (T1) turbo spin echo and STIR; T1 and DWI; and T1, STIR and DWI. Mean edema per patient was compared between sequences. Agreement was evaluated. RESULTS: Diffusion-weighted imaging detected more ME compared with STIR (P < 0.001). Agreement between readers was better with both sequences (k = 0.94) than with b800 DWI (k = 0.89) or STIR (k = 0.84) alone. DISCUSSION: Diffusion-weighted imaging is a valuable add-on for the study of inflammatory myopathies. Muscle Nerve 59:555-555, 2019.

Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress.

BACKGROUND: Stress precipitates mood disorders, characterized by a range of symptoms present in different combinations, suggesting the existence of disease subtypes. Using an animal model, we previously described that repetitive stress via restraint or immobilization induced depressive-like behaviors in rats that were differentially reverted by a serotonin- or noradrenaline-based antidepressant drug, indicating that different neurobiological mechanisms may be involved. The forebrain astrocyte protein aldolase C, contained in small extracellular vesicles, was identified as a potential biomarker in the cerebrospinal fluid; however, its specific origin remains unknown. Here, we propose to investigate whether serum small extracellular vesicles contain a stress-specific protein cargo and whether serum aldolase C has a brain origin. METHODS: We isolated and characterized serum small extracellular vesicles from rats exposed to restraint, immobilization, or no stress, and their proteomes were identified by mass spectrometry. Data available via ProteomeXchange with identifier PXD009085 were validated, in part, by western blot. In utero electroporation was performed to study the direct transfer of recombinant aldolase C-GFP from brain cells to blood small extracellular vesicles. RESULTS: A differential proteome was identified among the experimental groups, including aldolase C, astrocytic glial fibrillary acidic protein, synaptophysin, and reelin. Additionally, we observed that, when expressed in the brain, aldolase C tagged with green fluorescent protein could be recovered in serum small extracellular vesicles. CONCLUSION: The protein cargo of serum small extracellular vesicles constitutes a valuable source of biomarkers of stress-induced diseases, including those characterized by depressive-like behaviors. Brain-to-periphery signaling mediated by a differential molecular cargo of small extracellular vesicles is a novel and challenging mechanism by which the brain might communicate health and disease states to the rest of the body.

Hyaluronic acid in dermatomyositis and polymyositis: relationship with disease and cutaneous lesions.

BACKGROUND: There are scarce studies in the literature about hyaluronic acid in systemic autoimmune myopathies. OBJECTIVES: To analyze the serum level of hyaluronic acid in patients with dermatomyositis and polymyositis. METHODS: Cross-sectional study, single-center, that evaluated hyaluronic acid in 18 dermatomyositis and 15 polymyositis (Bohan and Peter criteria), newly diagnosed, with clinical and laboratory activity, with no previous drug treatment. The patients were also age-, gender- and ethnicity-matched to 36 healthy individuals. The hyaluronic acid was analyzed by ELISA/EIA kit anti-hyaluronic acid. RESULTS: There was a higher serum level of hyaluronic acid in patients with autoimmune myopathies, in relation to control group (P<0.05). Moreover, the serum level of this glycosaminoglycan was higher in dermatomyositis, when compared to polymyositis. Both groups were comparable with regard to demographic, clinical and laboratory data, except for the presence of skin lesions in the first group. STUDY LIMITATIONS: The presence of hyaluronic acid in cutaneous lesions, particularly of patients with dermatomyositis, was not analyzed neither quantified. In addition, due to disease rarity and the establishment of strict inclusion and exclusion criteria, there was a small sample in the present study. CONCLUSIONS: As an example of others systemic autoimmune diseases, it is possible that the hyaluronic acid is involved in the pathogenesis of autoimmune myopathies, and particularly when associated with cutaneous lesions.

Hyaluronic acid in dermatomyositis and polymyositis: relationship with disease and cutaneous lesions

Abstract: Background: There are scarce studies in the literature about hyaluronic acid in systemic autoimmune myopathies. Objectives: To analyze the serum level of hyaluronic acid in patients with dermatomyositis and polymyositis. Methods: Cross-sectional study, single-center, that evaluated hyaluronic acid in 18 dermatomyositis and 15 polymyositis (Bohan and Peter criteria), newly diagnosed, with clinical and laboratory activity, with no previous drug treatment. The patients were also age-, gender- and ethnicity-matched to 36 healthy individuals. The hyaluronic acid was analyzed by ELISA/EIA kit anti-hyaluronic acid. Results: There was a higher serum level of hyaluronic acid in patients with autoimmune myopathies, in relation to control group (P<0.05). Moreover, the serum level of this glycosaminoglycan was higher in dermatomyositis, when compared to polymyositis. Both groups were comparable with regard to demographic, clinical and laboratory data, except for the presence of skin lesions in the first group. Study limitations. The presence of hyaluronic acid in cutaneous lesions, particularly of patients with dermatomyositis, was not analyzed neither quantified. In addition, due to disease rarity and the establishment of strict inclusion and exclusion criteria, there was a small sample in the present study. Conclusions: As an example of others systemic autoimmune diseases, it is possible that the hyaluronic acid is involved in the pathogenesis of autoimmune myopathies, and particularly when associated with cutaneous lesions.

Effect of BCAA supplement timing on exercise-induced muscle soreness and damage: a pilot placebo-controlled double-blind study.

BACKGROUND: The aim of the present study was to compare the effects of branched-chain amino acid (BCAA) supplementation taken before or after exercise on delayed onset muscle soreness (DOMS) and exercise-induced muscle damage (EIMD). METHODS: Fifteen young men (aged 21.5±0.4 years) were given either BCAA (9.6 g·day-1) or placebo before and after exercise (and for 3 days prior to and following the exercise day) in three independent groups: the control group (placebo before and after exercise), the PRE group (BCAA before exercise and placebo after exercise), and the POST group (placebo before exercise and BCAA after exercise). Participants performed 30 repetitions of eccentric exercise with the non-dominant arm. DOMS, upper arm circumference (CIR), elbow range of motion (ROM), serum creatine kinase (CK), lactate dehydrogenase (LDH), and aldolase, BCAA, and ß-hydroxy-ß-methylbutyrate (3HMB) were measured immediately before and after the exercise and on the following 4 days. RESULTS: Serum BCAA and 3HMB concentrations increased significantly in the PRE group immediately after the exercise, recovering to baseline over the following days. In the days following the exercise day, DOMS, CIR, and ROM were significantly improved in the PRE group compared to the control group, with weaker effects in the POST group. Serum activities of CK, LDH, and aldolase in the days following the exercise day were significantly suppressed in the PRE group compared to control group. CONCLUSIONS: The present study confirmed that repeated BCAA supplementation before exercise had a more beneficial effect in attenuating DOMS and EIMD induced by eccentric exercise than repeated supplementation after exercise.

Spontaneous pneumomediastinum in dermatomyositis: a case series and literature review / Pneumomediastino espontâneo na dermatomiosite: uma série de casos e revisão de literatura

OBJECTIVES: To describe a case series of spontaneous pneumomediastinum in dermatomyositis and to review the literature. METHODS: This was a retrospective single-center case series, reporting 9 patients with pneumomediastinum and defined dermatomyositis, followed from 2005 to 2017. RESULTS: Median age of patients: 33 years; cutaneous and pulmonary involvement in all cases; constitutional symptoms in 88.8% of patients; involvement of the joints in 11.1%, gastrointestinal tract in 44.4%, and muscles in 77.7%; subcutaneous emphysema was observed in 55.5% and pneumothorax in 11.1%, respectively. Muscle weakness was observed in 77.7% of cases and with a median level of serum creatine phosphokinase of 124U/L. Drawing on results for our literature review, the overall analysis showed that the risk factors associated with spontaneous pneumomediastinum were: (a) a history of interstitial pneumopathy; (b) normal or low levels of muscle enzymes; (c) previous use of systemic glucocorticoid; (d) over 50% of patients had subcutaneous emphysema; (e) high mortality as a consequence of severity of the interstitial lung disease. CONCLUSIONS: Our case series revealed that pneumomediastinum is a rare complication in dermatomyositis that occurs in patients with a history of interstitial pneumopathy and may be accompanied by subcutaneous emphysema and pneumothorax.

OBJETIVOS: Descrever série de casos de pneumomediastino espontâneo em portadores de dermatomiosite e revisar a literatura. MÉTODOS: Trata-se de série de casos, único centro, relatando 9 pacientes com pneumomediastino e dermatomiosite definida, acompanhados de 2005 a 2017. RESULTADOS: A mediana da idade dos pacientes foi de 33 anos. Sintomas constitucionais estavam presentes em 88,8% dos pacientes. Houve acometimento cutâneo e pulmonar em todos os casos, acometimento das articulações em 11,1%, trato gastrointestinal em 44,4% e musculatura em 77,7% dos pacientes. Enfisema subcutâneo foi observado em 55,5% e pneumotórax em 11,1%, respectivamente. A fraqueza muscular foi observada em 77,7% dos casos, com um nível médio de creatinofosfoquinase sérica de 124U/L. Com base nos resultados da revisão da literatura, a análise geral mostrou que: os fatores de risco associados ao pneumomediastino espontâneo foram: história de pneumopatia intersticial, níveis normais ou baixos de enzimas musculares, uso prévio de glicocorticoide sistêmico; >50% dos pacientes tiveram enfisema subcutâneo; houve alta mortalidade como consequência da gravidade da doença pulmonar intersticial. CONCLUSÕES: Nossa série de casos revelou que o pneumomediastino é uma complicação rara na dermatomiosite e que ocorre em pacientes com história de pneumopatia intersticial e pode ser acompanhada por enfisema subcutâneo e pneumotórax.

Insulin resistance is increased in adult patients with dermatomyositis / Resistência insulínica aumentada em pacientes com dermatomiosite

OBJECTIVE: To evaluate insulinemia in glucocorticoid naïve patients with dermatomyositis and to evaluate insulin resistance using the homeostatic model assessment of insulin resistance (HOMA2-IR). METHODS: This cross-sectional study included 25 dermatomyositis, non-diabetic glucocorticoid naïve patients. The control group consisted of 50 volunteers matched for age, gender, ethnicity, weight and height. The HOMA2-IR index was calculated from baseline insulin and glucose data. The International Myositis Assessment & Clinical Studies Group (IMACS) parameters were used to evaluate disease status. RESULTS: Mean age of the patients was 43.5 years and these were predominantly females. Patients had low disease activity according to IMACS parameters. Higher body mass index and waist circumference were observed in the dermatomyositis group compared to the control group. Insulin level and HOMA2-IR were also higher in patients with dermatomyositis. Moreover, analyzing dermatomyositis alone, the HOMA2-IR index correlated positively with weight, body mass index and waist circumference and was independent on disease status parameters. CONCLUSIONS: Patients with dermatomyositis had higher values for basal insulinemia, insulin resistance, body mass index and waist circumference. Moreover, HOMA2-IR moderately correlated with these anthropometric parameters. These metabolic abnormalities are related to the development of metabolic syndrome, one of the main comorbidities observed in dermatomyositis.

OBJETIVO: Avaliar a insulinemia em pacientes com dermatomiosite virgens de glicocorticoide e avaliar a resistência insulínica, utilizando o modelo de avaliação da homeostase de resistência insulínica (HOMA2-IR). MÉTODOS: Este estudo transversal incluiu 25 pacientes com dermatomiosites, não-diabéticos e sem uso prévio de glicocorticoides. Para o grupo de controle, 50 voluntários foram pareados por idade, gênero, etnia, peso e estatura. O índice HOMA2-IR foi calculado a partir de dados basais de insulina e glicose. Os parâmetros do International Myositis Assessment & Clinical Studies Group (IMACS) foram utilizados para avaliar o status da doença. RESULTADOS: A méda de idade dos pacientes foi de 43,5 anos, predominantemente do sexo feminino. Os pacientes apresentaram baixa atividade de doença de acordo com os parâmetros do IMACS. O índice de massa corporal e a circunferência da cintura foram maiores no grupo da dermatomiosite em comparação com o grupo controle. O nível de insulina e o HOMA2-IR também foram maiores em pacientes com dermatomiosite. Além disso, analisando a dermatomiosite isoladamente, o índice HOMA2-IR correlacionou-se positivamente com o peso, o índice de massa corporal e a circunferência da cintura e foi independente dos parâmetros de status da doença. CONCLUSÕES: Pacientes com dermatomiosite apresentam valores mais elevados de insulinemia basal, resistência à insulina, índice de massa corporal e circunferência da cintura. Além disso, o HOMA2-IR está moderadamente correlacionado com esses parâmetros antropométricos. Essas anormalidades metabólicas estão relacionadas ao desenvolvimento da síndrome metabólica, uma das principais comorbidades observadas na dermatomiosite.

New astroglial injury-defined biomarkers for neurotrauma assessment.

Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs. Their levels increased over four orders of magnitude in severe TBI CSF. First post-injury week, ALDOC levels were markedly high and stable. Short-lived BLBP and PEA15 related to injury progression. ALDOC, BLBP and PEA15 appeared hyper-acutely and were similarly robust in severe and mild TBI blood; 25kD-GFAP-BDP appeared overnight after TBI and was rarely present after mild TBI. Using a human culture trauma model, we investigated biomarker kinetics. Wounded (mechanoporated) astrocytes released ALDOC, BLBP and PEA15 acutely. Delayed cell death corresponded with GFAP release and proteolysis into small GFAP-BDPs. Associating biomarkers with cellular injury stages produced astroglial injury-defined (AID) biomarkers that facilitate TBI assessment, as neurological deficits are rooted not only in death of CNS cells, but also in their functional compromise.

Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis.

New non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of the highest priority for global TB control. We performed in-depth proteomic analysis using the 4,000-plex SOMAscan assay on 1,470 serum samples from seven countries where TB is endemic. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled out for TB by culture and clinical follow-up. HIV coinfection was present in 34% of samples, and 25% were sputum smear negative. Serum protein biomarkers were identified by stability selection using L1-regularized logistic regression and by Kolmogorov-Smirnov (KS) statistics. A naive Bayes classifier using six host response markers (HR6 model), including SYWC, kallistatin, complement C9, gelsolin, testican-2, and aldolase C, performed well in a training set (area under the sensitivity-specificity curve [AUC] of 0.94) and in a blinded verification set (AUC of 0.92) to distinguish TB and non-TB samples. Differential expression was also highly significant (P < 10-20) for previously described TB markers, such as IP-10, LBP, FCG3B, and TSP4, and for many novel proteins not previously associated with TB. Proteins with the largest median fold changes were SAA (serum amyloid protein A), NPS-PLA2 (secreted phospholipase A2), and CA6 (carbonic anhydrase 6). Target product profiles (TPPs) for a non-sputum biomarker test to diagnose active TB for treatment initiation (TPP#1) and for a community-based triage or referral test (TPP#2) have been published by the WHO. With 90% sensitivity and 80% specificity, the HR6 model fell short of TPP#1 but reached TPP#2 performance criteria. In conclusion, we identified and validated a six-marker signature for active TB that warrants diagnostic development on a patient-near platform.

Muscle MRI at the time of questionable disease flares in Juvenile Dermatomyositis (JDM).

BACKGROUND: The course of JDM has improved substantially over the last 70 years with early and aggressive treatments. Yet it remains difficult to detect disease flares as symptoms may be mild; signs of rash and muscle weakness vary widely and are often equivocal; laboratory tests of muscle enzyme levels are often normal; electromyography and muscle biopsy are invasive. Alternative tools are needed to help decide if more aggressive treatment is needed. Our objective is to determine the effectiveness of muscle Magnetic Resonance Imaging (MRI) in detecting JDM flares, and how an MRI affects physician's decision-making regarding treatment. METHODS: This study was approved by the Institutional Review Board of Nationwide Children's Hospital. JDM patients were consulted between 1/2005 and 6/2015. MRIs were performed on both lower extremities without contrast sequentially: axial T1, axial T2 fat saturation, axial and coronal inversion recovery, and axial diffusion weighted. The physician decision that a JDM patient was in a flare was considered the gold standard. MRI results were compared with physician's decisions on whether a relapse had occurred, and if there was a concordance between the assessment methods. RESULTS: Forty-five JDM patients were studied. Eighty percent had weakness at diagnosis, 100% typical rash, and 73% typical nail-fold capillary changes. At diagnosis, muscle enzymes were compatible with JDM generally (CK 52%, LDH 62%, aldolase 72%, AST 54% abnormal). EMG was abnormal in 3/8, muscle biopsy typical of JDM in 10/11, and MRI abnormal demonstrating myositis in 31/40. Thirteen patients had a repeat MRI for possible flares with differing indications. Three repeat MRI's were abnormal, demonstrating myositis. There was moderate agreement about flares between MRI findings and physician's treatment decisions (kappa = 0.59). In each abnormal MRI case the physician decided to increase treatment (100% probability for flares). MRI was negative for myositis in 10 patients, by which 7/10 the physicians chose to continue or to taper the medications (70% probability for non-flares). CONCLUSION: A muscle MRI would facilitate objective assessments of JDM flares. When an MRI shows myositis, physicians tend to treat 100% of the time. When an MRI shows no myositis, physicians continued the same medications or tapered medications 70% of the time. Further studies would help confirm the utility and cost-effectiveness of MRI to determine JDM flares.

Electrochemical biosensor based on enzyme substrate as a linker: Application for aldolase activity with pectin-thionine complex as recognization element and signal amplification probe.

A new strategy to fabricate electrochemical biosensor is reported based on the linkage of enzyme substrate, thereby an electrochemical method to detect aldolase activity is established using pectin-thionine complex (PTC) as recognization element and signal probe. The linkage effect of fructose-1,6-bisphosphate (FBP), the substrate of aldolase, can be achieved via its strong binding to magnetic nanoparticles (MNPs)/aminophenylboronic acid (APBA) and the formation of phosphoramidate bond derived from its reaction with p-phenylenediamine (PDA) on the surface of electrode. Aldolase can reversibly catalyze the substrates into the products which have no binding capacity with MNPs/APBA, resulting in the exposure of the corresponding binding sites and its subsequent recognization on signal probe. Meanwhile, signal amplification can be accomplished by using the firstly prepared PTC which can bind with MNPs/APBA, and accuracy can be strengthened through magnetic separation. With good precision and accuracy, the established sensor may be extended to other proteins with reversible catalyzed ability.

Serum inflammatory markers after rupture retinal laser injury in mice.

BACKGROUND AND OBJECTIVE: To characterize the cellular, immunological, and inflammatory response to retinal photocoagulation of intense rupture laser lesions as a model of retinal degenerative diseases. MATERIALS AND METHODS: Seven C57BL/6 mice were irradiated using a 532-nm laser to induce 10 retinal burns per eye that ruptured Bruch's membrane. Blood was drawn from the saphenous vein before and 2 months after laser treatment. The serum was run on antigen microarrays with 85 molecular markers associated with retinal degenerative diseases. RESULTS: Rupture laser resulted in dramatic changes in the immunoglobulin reactivity of most inflammatory markers 2 months after laser injury. Approximately two-thirds increased expression and one-third decreased expression. Notable markers that were increased included complement C3, CRP, PKM2, and aldolase. CONCLUSION: Rupture laser injury causes a change in the serum inflammatory markers after 2 months similar to macular degeneration, diabetic retinopathy, and cancer-associated retinopathy. This animal model could be used as a biomarker for disease stage and activity in retinal degenerations.

Influence of autoimmune biomarkers on interstitial lung diseases: A tertiary referral center based case-control study.

BACKGROUND: The benefit of routinely measuring autoimmune biomarkers to evaluate patients with interstitial lung disease (ILD) remains debated outside specific contexts such as connective tissue disease (CTD). This study aimed at evaluating the influence of biomarkers on outcome on patients with ILD in a case-control study at a tertiary referral center. We hypothesized that patients with positive autoimmune biomarkers have increased odds of developing ILD even in the absence of CTD. METHODS: We reviewed the medical records of 3573 patients seen at the ILD clinic in Mayo Clinic Rochester between September 2001 and September 2006. We assessed their clinical course through June 25, 2013. We included patients with patterns of ILD most often associated with CTD (n = 1256) while excluding patients with other known causes of ILD. Controls (n = 2317) included cases seen at the ILD clinic without evidence of ILD. RESULTS: We identified 930 (26%) cases of ILD alone, 124 (3%) CTD alone, 326 (9%) ILD combined with CTD, and 2193 (61%) with no ILD or CTD. Positive antinuclear antibodies (ANA), rheumatoid factor and aldolase were associated with ILD. After adjustment for age, gender, race, smoking history and CTD, ANA remained an independent risk factor for ILD (OR 1.70, 95% CI 1.33-2.17). Among patients with ILD, the presence of CTD but not biomarker alone was associated with a better survival. CONCLUSION: In this study, the presence of positive biomarkers was associated with increased odds of ILD, even in the absence of overt CTD, but was not associated with a better outcome.