Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

BACKGROUND AND OBJECTIVES Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates. METHODS We identified patients with acetylcholine receptor antibody-positive (AChR$^{+}$) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses. We generated recombinant monoclonal antibodies (mAbs) corresponding to the B-cell receptors of the CLL phenotype B cells and screened them for autoantigen binding. RESULTS A computational immune cell screen revealed a subgroup of 5/38 patients with MG and 0/21 healthy controls who displayed a CLL-like B-cell phenotype. In follow-up hematologic flow cytometry, 2 of these 5 patients were diagnosed with an MBL. An additional patient with AChR$^{+}$ MG as a complication of manifest CLL presented at our neuromuscular clinic and was successfully treated with the anti-CD20 therapy obinutuzumab plus chlorambucil. We investigated the specificities of expanding CLL-like B-cell clones to assess a direct causal link between the 2 diseases. However, we observed no reactivity of the clones against the AChR, antigens at the neuromuscular junction, or other common autoantigens. DISCUSSION Our study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR$^{+}$ MG. CLASSIFICATION OF EVIDENCE This is a single case study and provides Class IV evidence that obinutuzumab is safe to use in patients with MG

The Effect of Zero Copayments on Medication Adherence in a Community Pharmacy Setting

Background: Prescription medication copayments can be a financial burden to many patients. When patients cannot afford their medications, they may become nonadherent, and as a result, this can lead to an increase in chronic disease complications and healthcare costs. Objective: The objective of this study was to determine if zero copayments have an effect on medication adherence in a community pharmacy. Methods: This retrospective cohort study examined the prescription refill records of patients who filled specific generic medications for hypertension, hyperlipidemia, and gastroesophageal reflux disease (GERD) in 2016 at the NSU Clinic Pharmacy. The adherence rates of patients with zero copayments were compared to the adherence rates of patients with copayments greater than $0. Adherence was determined by calculating the proportion of days covered (PDC). Patients were considered adherent if their PDC was greater than or equal to 80Results: GERD patients with no copayments had average PDC ratios of 87.4Conclusion: Overall, patients with$0 copayments had higher adherence rates than patients with copayments greater than $0. GERD patients with no copayments were significantly more adherent than GERD patients with copayments. However, no statistically significant difference was found between patients with or without copayments in the hyperlipidemia and hypertension cohorts. Further studies are recommended to analyze additional factors that may influence medication adherence.   Article Type: Original Researc

The N2K Consortium. VII. Atmospheric Parameters of 1907 Metal-Rich Stars: Finding Planet-Search Targets

We report high-precision atmospheric parameters for 1907 stars in the N2K low-resolution spectroscopic survey, designed to identify metal-rich FGK dwarfs likely to harbor detectable planets. 284 of these stars are in the ideal temperature range for planet searches, T_eff <= 6000K, and have a 10% or greater probability of hosting planets based on their metallicities. The stars in the low-resolution spectroscopic survey should eventually yield >60 new planets, including 8-9 hot Jupiters. Short-period planets have already been discovered orbiting the survey targets HIP 14801 and HD 149143.Comment: Accepted for publication in Astrophysical Journal Supplements. 24 pages, including 8 figures and one table. Two more tables will appear in ApJS online editio

Phone-based audience response system as an adjunct in orthodontic teaching of undergraduate dental students: a cross-over randomised controlled trial

Background: The advent of electronic teaching facilities improves tutor-student communication. This study aims to explore the effectiveness of Phone-Based Audience Response System (PB-ARS), as an adjunctive pedagogy tool to enhance the retention of orthodontic information by dental students; and to explore the students’ perception of PB-ARS. Methods: This cross-over clustered randomised control trial included 34 males who were in the final year of their undergraduate dental training. Participants were allocated to one of two event groups (G1 and G2) using computer-generated randomisation. Both groups simultaneously attended two different traditional lectures (L 1 and L2) a week apart. During L1, PB-ARS was used as an adjunct to conventional presentation to teach G1 participants, (PB-ARS group) while G2’s participants acted as a control group (CG), and were taught using a traditional presentation. In the second week (L2), the interventions were crossed-over. Participants from both groups completed pre- and post-lecture multiple-choice questionnaires (MCQ) to assess their short-term retention of information. Their performance in the final MCQ exam (10 weeks following L2) was tracked to assess the long-term retention of the information. Participants also completed post-lecture questionnaires to evaluate their perceptions. Results: Twenty-nine and 31 participants from the CG and PB-ARS group completed this trial, respectively. Although 87.5% of students in the PB-ARS group showed an improvement in their immediate post-lecture scores compared with 79.3% for the CG, it was statistically insignificant (p = 0.465). Similarly, the intervention showed an insignificant effect on the long-term retention of the knowledge (p = 0.560). There was a mildly but favourable attitude of students towards the use of PB-ARS. However, the difference in the overall level of satisfaction between both groups was statistically insignificant (p = 0.183). Conclusion: PB-ARS has a minimal and insignificant effect on the short- and long-term retention of orthodontic knowledge by male undergraduate dental students. PB-ARS was the preferred adjunct tool to conventional classroom teaching. Due to the limitations of this trial, a long-term randomised controlled trial with a larger sample size is recommended

Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors

Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections

Designing for the Infrastructure of the Supply Chain of Malay Handwoven Songket in Terengganu

The growing HCI interest in developing contexts and cultural craft practices is ripe to focus on their under-explored homegrown sociotechnical infrastructures. This paper explores the creative infrastructural actions embedded within the practices of songket's supply chain in Terengganu, Malaysia. We report on contextual interviews with 92 participants including preparation workers, weavers, designers, merchants, and customers. Findings indicate that increased creative infrastructural actions are reflected in these actors' resourcefulness for mobilizing information, materials, and equipment, and for making creative artifacts through new technologies weaved within traditional practices. We propose two novel approaches to design in this craft-based infrastructure. First, we explore designing for the social layer of infrastructure and its mutually advantageous exploitative relationships rooted in culture and traditions. Second, we suggest designing for roaming value-creation artifacts, which blend physical and digital materializations of songket textile design. Developed through a collaborative and asynchronous process, we argue that these artifacts represent less-explored vehicles for value co-creation, and that sociotechnical infrastructures as emerging sites of innovation could benefit from HCI research

A unified account of tilt illusions, association fields, and contour detection based on Elastica

As expressed in the Gestalt law of good continuation, human perception tends to associate stimuli that form smooth continuations. Contextual modulation in primary visual cortex, in the form of association fields, is believed to play an important role in this process. Yet a unified and principled account of the good continuation law on the neural level is lacking. In this study we introduce a population model of primary visual cortex. Its contextual interactions depend on the elastica curvature energy of the smoothest contour connecting oriented bars. As expected, this model leads to association fields consistent with data. However, in addition the model displays tilt-illusions for stimulus configurations with grating and single bars that closely match psychophysics. Furthermore, the model explains not only pop-out of contours amid a variety of backgrounds, but also pop-out of single targets amid a uniform background. We thus propose that elastica is a unifying principle of the visual cortical network