Discovery of putative salivary biomarkers for Sjögren's syndrome using high resolution mass spectrometry and bioinformatics

The purpose of the current study was to determine if saliva contains biomarkers that can be used as diagnostic tools for Sj?gren's syndrome (SjS). Twenty seven SjS patients and 27 age-matched healthy controls were recruited for these studies. Unstimulated glandular saliva was collected from the Wharton's duct using a suction device. Two μl of salvia were processed for mass spectrometry analyses on a prOTOF 2000 matrix-assisted laser desorption/ionization orthogonal time of flight (MALDI O-TOF) mass spectrometer. Raw data were analyzed using bioinformatic tools to identify biomarkers. MALDI O-TOF MS analyses of saliva samples were highly reproducible and the mass spectra generated were very rich in peptides and peptide fragments in the 750-7,500 Da range. Data analysis using bioinformatic tools resulted in several classification models being built and several biomarkers identified. One model based on 7 putative biomarkers yielded a sensitivity of 97.5%, specificity of 97.8% and an accuracy of 97.6%. One biomarker was present only in SjS samples and was identified as a proteolytic peptide originating from human basic salivary proline-rich protein 3 precursor. We conclude that salivary biomarkers detected by high-resolution mass spectrometry coupled with powerful bioinformatic tools offer the potential to serve as diagnostic/prognostic tools for SjS.     

Persistence of autoreactive myelin oligodendrocyte glycoprotein (MOG)-specific T cell repertoires in MOG-expressing mice

Experimental autoimmune encephalomyelitis, an experimental murine model for multiple sclerosis, is induced by stimulation of myelin-specific T lymphocytes. Myelin oligodendrocyte glycoprotein (MOG), a minor component of myelin proteins, is a potent autoantigen which contributes extensively to the anti-myelin response. In the present work, immunoscope analyses and sequencing of the oligoclonal expansions revealed anti-MOG Valpha and Vbeta public repertoires in lymphocytes infiltrating the CNS of wild-type (WT) mice. Moreover, a subset of CNS-infiltrating CD4+ T lymphocytes bearing the public Vbeta8.2 segment have an inflammatory phenotype strongly suggesting that it is encephalitogenic. We then observed that, in lymph node cells of MOG-deficient and WT animals, the Valpha and Vbeta public repertoires expressed by MOG-specific T cells are identical in both strains of mice and correspond to those found in the CNS of WT animals. These findings indicate that the MOG immunodominant determinant is unable to induce tolerance by deletion, and public anti-MOG T cell repertoires are selected for, regardless of the presence of MOG in the thymus and peripheral organs.     

Trends in private and public health insurance for adolescents

Context  Previous studies (1984-1995) of adolescent health insurance have shown little change in the proportion with coverage. Federally mandated expansions in Medicaid were offset by declines in private coverage. Further expansions of Medicaid and implementation of the State Children's Health Insurance Program (SCHIP) have opened new avenues for increasing coverage rates. Objectives  To assess the current health insurance status of adolescents, the demographic and socioeconomic correlates of insurance coverage, and document recent changes in public and private coverage rates. Design, Setting, and Participants  We analyzed data on 12 995 adolescents aged 10 to 18 years, who had been included in the 2002 National Health Interview Survey. We conducted multivariate analyses to assess the independent association of age, sex, race, poverty status, family structure, family size, and region on the likelihood of having insurance coverage. Results are compared with previously published findings on adolescent health insurance coverage spanning 1984 to 1995. Main Outcome Measure  Insurance coverage for adolescents. Results  An estimated 12.2% of adolescents were uninsured in 2002, which is a decrease from 14.1% in 1995 (P<.003). The decrease occurred entirely because of an expansion of public coverage and is concentrated among children in poor (<100% of the federal poverty level) and near-poor (100%-199% of the federal poverty level) families. A substantial decrease in the differences between poor and higher-income groups occurred between 1995 and 2002 due to gains in coverage for adolescents in poor and near-poor families and losses in coverage among those in middle- and upper-income families (=" BORDER="0">200% of the federal poverty level). Specifically, the proportion of adolescents in poor families without coverage declined from 27.4% in 1995 to 19.7% in 2002 (P<.001). The proportion of adolescents in near-poor families without coverage declined from 24.8% in 1995 to 19.2% in 2002 (P<.002). In contrast, the proportion of adolescents in middle- and higher-income families without insurance increased from 4.1% in 1995 to 6.3% in 2002 because availability of insurance through the private market declined (P<.001). Conclusions  A modest but significant reduction in the percentage of adolescents without insurance has occurred since 1995, largely as a result of expansions in public coverage. An even larger reduction in the proportion of adolescents without coverage would have occurred, if not for a reduction in private coverage for adolescents in middle- and higher-income families.      

Dynamic spring-mediated cranioplasty in a rabbit model

Since the beginning of craniofacial surgery, there has been an ongoing search for surgical techniques to enhance outcome while, at the same time, decreasing the invasiveness of the surgical treatment of craniofacial deformities. The purpose of this study was to test a recently reported minimally invasive treatment modality, the dynamic spring, in a rabbit calvarial model for efficacy and safety. Specifically, the results of spring cranioplasty on skull growth, the underlying brain, and adjacent bone were to be assessed. The study population consisted of 36 7-week-old New Zealand white rabbits. The rabbits were divided into four treatment groups (9 rabbits each): control, sham surgery, stainless steel springs, and memory metal springs. Postoperative analysis included weekly radiographs to evaluate movement of amalgam markers placed at standardized locations. Additionally, 16 rabbits (4 from each group) were killed at 14 days after surgery, and postmortem histological analysis was done. The remaining rabbits were followed until they were adults and were then killed and similarly analyzed. No morbidity or mortality occurred in the immediate perioperative period secondary to the surgery. Postmortem histological analysis of all study animals revealed no intracranial, subcutaneous, or skin infections and no technical complications related to the surgery. Statistical analysis using ANOVA and pair-wise comparisons between treatment groups revealed a statistically significant difference (P < 0.05) between the marker movement in the spring groups versus the sham and control groups. There were no significant differences between the sham and control groups or between the two spring groups. In conclusion, this study confirms the efficacy and safety of the dynamic spring in a rabbit model.     

Clinical outcomes and risk factors for severe COVID-19 in patients with haematological disorders receiving chemo- or immunotherapy

Haematology patients receiving chemo- or immunotherapy are considered to be at greater risk of COVID-19-related morbidity and mortality. We aimed to identify risk factors for COVID-19 severity and assess outcomes in patients where COVID-19 complicated the treatment of their haematological disorder. A retrospective cohort study was conducted in 55 patients with haematological disorders and COVID-19, including 52 with malignancy, two with bone marrow failure and one immune-mediated thrombotic thrombocytopenic purpura (TTP). COVID-19 diagnosis coincided with a new diagnosis of a haematological malignancy in four patients. Among patients, 82% were on systemic anti-cancer therapy (SACT) at the time of COVID-19 diagnosis. Of hospitalised patients, 37% (19/51) died while all four outpatients recovered. Risk factors for severe disease or mortality were similar to those in other published cohorts. Raised C-reactive protein at diagnosis predicted an aggressive clinical course. The majority of patients recovered from COVID-19, despite receiving recent SACT. This suggests that SACT, where urgent, should be administered despite intercurrent COVID-19 infection, which should be managed according to standard pathways. Delay or modification of therapy should be considered on an individual basis. Long-term follow-up studies in larger patient cohorts are required to assess the efficacy of treatment strategies employed during the pandemic.     

Atrial fibrillation in the Wolff-Parkinson-White syndrome: ECG recognition and treatment in the ED

Estimated to occur in 0.1% to 0.3% of the population, Wolff-Parkinson-White syndrome (WPW) is a condition where atrial impulses bypass the atrioventricular node and activate the ventricular myocardium directly via an accessory pathway. Clinical clues to the diagnosis include a young patient with previous episodes of palpitations, rapid heart rate, or syncope. Although several different rhythm presentations are possible, atrial fibrillation is a not infrequent dysrhythmia seen in the WPW patient. Electrocardiographic features suggestive of WPW atrial fibrillation include irregularity of the rhythm; a very rapid ventricular response; presence of a delta wave; and a wide, bizarre QRS complex. Stable patients suspected of having this condition should not receive agents that predominantly block atrioventricular conduction, but they may be treated with procainamide or ibutilide. If instability is present, electrical cardioversion is required.