Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

     

IgA Nephropathy-Associated Uveitis: A Case Presentation

ABSTRACT

Purpose: To describe a case of bilateral panuveitis in the setting of IgA nephropathy.

Methods: Retrospective review of clinical records, fundus, and optical coherence tomographic (OCT) images, and fluorescein angiography.

Results: A 36-year-old female presented with IgA nephropathy and contemporaneous ocular manifestations of one-year duration. Clinical exam demonstrated bilateral panuveitis, 3+ anterior chamber (AC) cell in the right eye (OD), and 0.5+ AC cell in the left eye (OS). Funduscopic exam demonstrated diffuse yellow drusenoid deposits bilaterally (OU), accentuated on fundus autofluorescence as focal areas of hyperautofluorescence. Deposits correlated with retinal pigment epithelium hyper-reflectivity on OCT, and choroidal hypo-fluorescence on fluorescein angiography. The patient was managed with oral prednisone.

Conclusion: IgA nephropathy is a systemic autoimmune disease that may be associated with uveitis. Immunosuppression with corticosteroids appears to be an effective therapy.     

The Association Between Physical Activity and Cataracts Among 17,777 People Aged 15–69 Years Residing in Spain

ABSTRACT

Purpose

The aim of the present study was to assess the association between levels of physical activity (PA) and the presence of cataracts in people aged 15–69 years residing in Spain.     

Increasing the rate of the hydrogen evolution reaction in neutral water with protic buffer electrolytes

Electrocatalytic generation of H₂ is challenging in neutral pH water, where high catalytic currents for the hydrogen evolution reaction (HER) are particularly sensitive to the proton source and solution characteristics. A tris(hydroxymethyl)aminomethane (TRIS) solution at pH 7 with a [2Fe-2S]-metallopolymer electrocatalyst gave catalytic current densities around two orders of magnitude greater than either a more conventional sodium phosphate solution or a potassium chloride (KCl) electrolyte solution. For a planar polycrystalline Pt disk electrode, a TRIS solution at pH 7 increased the catalytic current densities for H₂ generation by 50 mA/cm² at current densities over 100 mA/cm² compared to a sodium phosphate solution. As a special feature of this study, TRIS is acting not only as the primary source of protons and the buffer of the pH, but the protonated TRIS ([TRIS-H]⁺) is also the sole cation of the electrolyte. A species that is simultaneously the proton source, buffer, and sole electrolyte is termed a protic buffer electrolyte (PBE). The structure–activity relationships of the TRIS PBE that increase the HER rate of the metallopolymer and platinum catalysts are discussed. These results suggest that appropriately designed PBEs can improve HER rates of any homogeneous or heterogeneous electrocatalyst system. General guidelines for selecting a PBE to improve the catalytic current density of HER systems are offered.

Molecular hydrogen (H₂), a clean-burning and energy-dense fuel source, has been widely discussed as an attractive way to store intermittent energy from solar and wind through water electrolysis (1, 2). Current commercial electrolyzers can be separated into two categories based on their operating pH. The first are acidic polymer electrolyte membrane electrolyzers that work best with rare and expensive platinum-based electrocatalysts for the hydrogen evolution reaction (HER) (3). The second are strongly alkaline electrolyzers that suffer from caustic basic reaction conditions (4). Neutral pH conditions with inexpensive catalysts composed of Earth-abundant elements are a target for practical solar-to-hydrogen fuel devices due to lower cost and fewer safety concerns (5), but achieving fast rates with mild overpotentials under neutral conditions remains a challenge (6–12). In the pH range from 5 to 9, the electrocatalytic activity of platinum (Pt) itself does not conform to the expected thermodynamic potential shift with pH dependence of −59 mV/pH (13). This is due to the low concentration of the hydronium ion in this pH range and a transition to water as the primary reactant, which has a higher thermodynamic requirement for hydrogen evolution (13). Studies of electrocatalysts using buffers to maintain the pH in this range and ionic salts such as potassium chloride (KCl) to provide ionic strength to ensure high solution conductivity have shown that the buffer can aid the HER activity, presumably by acting as a proton donor (6, 14–18). To extend the scope of water-soluble electrocatalysts, biopolymers and bioinspired metallopolymer catalysts have also been studied (7, 12, 17–26). Bren and coworkers recently reported particularly enlightening studies of the effects of buffer pK_a and structure on the mechanism of the hydrogen evolution reaction for cobalt minienzymes (17, 18).We recently reported a new metallopolymer catalyst system built around a customized [2Fe-2S] catalyst site with a bridging aryldithiolato ligand which exhibits remarkable catalytic activity, air stability, and chemical stability (21). The electrocatalytic mechanism of the [2Fe-2S] catalysts with aryldithiolato ligands is known from previous studies and these catalysts operate at rates of 10⁵ s⁻¹ and faster (27–30). The readily synthesized and water-soluble metallopolymer composed of tertiary amine side-chain groups, PDMAEMA-g-[2Fe-2S] (Fig. 1), approached the current density of Pt operating in neutral water under the same conditions and matched the Faradaic yield (97 ± 3%) (21). Although the detailed structural and mechanistic causality of these profound improvements for these metallopolymer electrocatalysts remain subjects of study, the nature of this molecular system is ideal for studying solution effects on the HER reaction at neutral pH for complexes that are normally insoluble in water. In the course of characterizing these electrocatalysts, solutions containing tris(hydroxymethyl)aminomethane (TRIS) at pH 7 were discovered to be exceptionally advantageous to the catalytic rate. In contrast to the few previous studies of TRIS buffer with electrocatalysts (14, 15, 18), we utilized TRIS at a high concentration. At pH 7, TRIS is sufficiently in the cationic protonated form that additional electrolyte such as KCl is not needed for conductance. This important distinction from conventional studies allows TRIS to simultaneously play the roles of pH buffer, proton source, and sole electrolyte. There is precedence in employing buffers in a manner in which they are the sole electrolyte (7, 31–34). Referring to such species simply as a “buffer” or as an “electrolyte” is inadequate in representing the three functions including proton source. For the purposes of this paper we term a species that serves all three functions a protic buffer electrolyte (PBE). In the following discussion, a TRIS PBE solution is one in which [TRIS-H]⁺Cl⁻ is the sole electrolyte and the cation is a proton source, and a sodium phosphate PBE solution is one in which Na⁺[H₂PO₄]⁻ is the sole electrolyte and the anion is a proton source.Open in a separate windowFig. 1.(A) Depiction of the 2e⁻ electrocatalytic HER with POEGMA-g-[2Fe-2S] and/or PDMAEMA-g-[2Fe-2S] metallopolymers using TRIS or sodium phosphate protic buffer electrolytes at pH 7. (B) Image of POEGMA-g-[2Fe-2S] with MW = 14,216 grown in silico. The [2Fe-2S] active site is in the center of the polymer, blue represents the polymer backbone, and the rest are the oligo(ethylene glycol) side chains. See SI Appendix for the details of modeling and a larger image.One of the key unanswered questions for these new catalyst systems is whether the metallopolymer composition (i.e., amine side-chain groups) or the PBEs are more important to afford this outstanding catalytic activity. Herein we study the effects of PBEs by comparing the HER performances of a standard platinum catalyst and a [2Fe-2S] metallopolymer catalyst in TRIS PBE solutions, sodium phosphate PBE solutions, and a KCl electrolyte solution without a PBE. For this study, nonionic water-soluble metallopolymers were used, which were made using oligo(ethylene glycol) side-chain groups on the polymer to avoid the possibility of contributing effects of the protonated amino groups of PDMAEMA-g-[2Fe-2S] referred to earlier. The metallopolymer catalyst used in this work is designated as POEGMA-g-[2Fe-2S] (Fig. 1). We previously reported that this water-soluble metallopolymer was largely inactive for H₂ electrocatalysis at neutral pH in phosphate buffer (22). The current findings suggest that the use of electrolytes composed of inexpensive cationic organic proton donors can be readily applied to any homogeneous or heterogeneous electrocatalyst system as a facile means to enhance HER activity.     

Heart-type fatty acid-binding protein: an overlooked cardiac biomarker

Abstract

Cardiac troponins (cTn) are currently the standard of care for the diagnosis of acute coronary syndromes (ACS) in patients presenting to the emergency department (ED) with chest pain (CP). However, their plasma kinetics necessitate a prolonged ED stay or overnight hospital admission, especially in those presenting early after CP onset. Moreover, ruling out ACS in low-risk patients requires prolonged ED observation or overnight hospital admission to allow serial measurements of c-Tn, adding cost. Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury with putative advantages over cTn. Being present in abundance in the myocellular cytoplasm, it is released rapidly (<1?h) after the onset of myocardial injury and could potentially play an important role in both earlier diagnosis of high-risk patients presenting early after CP onset, as well as in risk-stratifying low-risk patients rapidly. Like cTn, H-FABP also has a potential role as a prognostic marker in other conditions where the myocardial injury occurs, such as acute congestive heart failure (CHF) and acute pulmonary embolism (PE). This review provides an overview of the evidence examining the role of H-FABP in early diagnosis and risk stratification of patients with CP and in non-ACS conditions associated with myocardial injury.

• Key messages

• Heart-type fatty acid-binding protein is a biomarker that is elevated early in myocardial injury

• The routine use in the emergency department complements the use of troponins in ruling out acute coronary syndromes in patients presenting early with chest pain

• It also is useful in risk stratifying patients with other conditions such as heart failure and acute pulmonary embolism.

     

Assessing the impact of capacity building for HIV activists in Europe and Central Asia

ABSTRACT

STEP-UP is a capacity building and training programme for HIV community activists in Europe and Central Asia, led by the European AIDS Treatment Group (EATG). The programme aims to empower a new cohort of HIV activists each year to engage more deeply in HIV activism at local and national levels addressing key themes such as HIV treatment literacy, prevention technologies, living with HIV, project development, clinical trials, patient participation, advocacy and policy landscapes. The expected outcome of the project is that trainees become activists with knowledge of both policy and science who advocate for change to policy and or practice. To assess the impact of the programme on individual graduates, their organisations and the communities they work with, EATG conducted an evaluation of the programme for the period of 2013–2017. The methods used during the assessment were: a desk review of information about the programme; interviews with implementers and trainees; a focus group with trainees; inputs from national and regional networks, activists and references given by trainees; and an online survey of trainees. This article evaluates the lessons learnt and forms a set of recommendations to implement in the design of future editions of STEP-UP.     

Effects of boron-containing compounds on immune responses: review and patenting trends

Introduction: Boron-containing compounds induce effects on immune responses. Such effects are interesting to the biomedical field for the development of therapeutic tools to modulate the immune system.

Areas covered: The scope of BCC use to modify immune responses is expanding, mainly with regard to inflammatory diseases. The information was organized to demonstrate the breadth of reported effects. BCCs act as modulators of innate and adaptive immunity, with the former including regulation of cluster differentiation and cytokine production. In addition, BCCs exert effects on inflammation induced by infectious and noninfectious agents, and there are also reports regarding their effects on mechanisms involving hypersensitivity and transplants. Finally, the authors discuss the beneficial effects of BCCs on pathologies involving various targets and mechanisms.

Expert opinion: Some BCCs are currently used as drugs in humans. The mechanisms by which these BCCs modulate immune responses, as well as the required structure–activity relationship for each observed mechanism of action, should be clarified. The former will allow for the development of improved immunomodulatory drugs with extensive applications in medicine. Patenting trends involve claims concerning the synthesis and actions of identified molecules with a defined profile regarding cytokines, cell differentiation, proliferation, and antibody production.     

Role of Anatomical Patella Replacement on Anterior Knee Pain

Background

Anterior knee pain (AKP) remains a complex issue affecting patient satisfaction after total knee arthroplasty. Several radiographic parameters have been shown to be causative factors with various designs. The aim of this study is to evaluate the known radiographic parameters of AKP and clinical outcomes (ie, AKP) in the setting of a modern prosthesis with an anatomic patella button.

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.