This review considers a minimally invasive ab interno approach to glaucoma filtration surgery. Glaucoma filtration surgery can be defined as an attempt to lower intraocular pressure (IOP) by the ...surgical formation of an artificial drainage pathway from the anterior chamber to the subconjunctival space. Subconjunctival drainage of aqueous fluid has been a cornerstone of glaucoma surgery for more than a century. Varying techniques have been deployed to provide access to this space. Yet, despite numerous innovations in filtering surgery to achieve safe IOP reduction, too many short-term and long-term complications are associated with this surgery. This article describes the development of a new, soft, and permanent ab interno collagen implant (XEN gel stent) to optimize aqueous drainage to the subconjunctival space. Specific characteristics are critical in designing such an implant. Determining the optimum size of the device lumen to avoid hypotony while maximizing long-term outflow is crucial. Other topics discussed include material, length, diameter, flexibility, stability, and biocompatibility of the implant. Preclinical and human eye testing shows that the implant does not seem to occlude inside the lumen and the implant material does not appear to cause tissue reaction in the eye. The ab interno placement of the stent offers an alternative for lowering IOP with a minimally invasive procedure, minimum conjunctival tissue disruption, restricted flow to avoid hypotony, and long-term safety.
Dr. Lewis received financial support from Aquesys, Inc. as a consultant.
The terrestrial carbon sink has been large in recent decades, but its size and location remain uncertain. Using forest inventory data and long-term ecosystem carbon studies, we estimate a total ...forest sink of 2.4 ± 0.4 petagrams of carbon per year (Pg C year -1 ) globally for 1990 to 2007. We also estimate a source of 1.3 ± 0.7 Pg C year -1 from tropical land-use change, consisting of a gross tropical deforestation emission of 2.9 ± 0.5 Pg C year -1 partially compensated by a carbon sink in tropical forest regrowth of 1.6 ± 0.5 Pg C year -1 . Together, the fluxes comprise a net global forest sink of 1.1 ± 0.8 Pg C year -1 , with tropical estimates having the largest uncertainties. Our total forest sink estimate is equivalent in magnitude to the terrestrial sink deduced from fossil fuel emissions and land-use change sources minus ocean and atmospheric sinks.
The proteasome processes proteins to facilitate immune recognition and host defense. When inherently defective, it can lead to aberrant immunity resulting in a dysregulated response that can cause ...autoimmunity and/or autoinflammation. Biallelic or digenic loss-of-function variants in some of the proteasome subunits have been described as causing a primary immunodeficiency disease that manifests as a severe dysregulatory syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE). Proteasome maturation protein (POMP) is a chaperone for proteasome assembly and is critical for the incorporation of catalytic subunits into the proteasome. Here, we characterize and describe POMP-related autoinflammation and immune dysregulation disease (PRAID) discovered in two unrelated individuals with a unique constellation of early-onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and autoimmunity. We also begin to delineate a complex genetic mechanism whereby de novo heterozygous frameshift variants in the penultimate exon of POMP escape nonsense-mediated mRNA decay (NMD) and result in a truncated protein that perturbs proteasome assembly by a dominant-negative mechanism. To our knowledge, this mechanism has not been reported in any primary immunodeficiencies, autoinflammatory syndromes, or autoimmune diseases. Here, we define a unique hypo- and hyper-immune phenotype and report an immune dysregulation syndrome caused by frameshift mutations that escape NMD.
Guillain‐Barré syndrome (GBS) is an inflammatory polyradiculoneuropathy associated with numerous viral infections. Recently, there have been many case reports describing the association between ...coronavirus disease‐2019 (COVID‐19) and GBS, but much remains unknown about the strength of the association and the features of GBS in this setting. We reviewed 37 published cases of GBS associated with COVID‐19 to summarize this information for clinicians and to determine whether a specific clinical or electrodiagnostic (EDx) pattern is emerging. The mean age (59 years), gender (65% male), and COVID‐19 features appeared to reflect those of hospitalized COVID‐19 patients early in the pandemic. The mean time from COVID‐19 symptoms to GBS symptoms was 11 days. The clinical presentation and severity of these GBS cases was similar to those with non–COVID‐19 GBS. The EDx pattern was considered demyelinating in approximately half of the cases. Cerebrospinal fluid, when assessed, demonstrated albuminocytologic dissociation in 76% of patients and was negative for severe acute respiratory distress syndrome–coronavirus‐2 (SARS‐CoV‐2) in all cases. Serum antiganglioside antibodies were absent in 15 of 17 patients tested. Most patients were treated with a single course of intravenous immunoglobulin, and improvement was noted within 8 weeks in most cases. GBS‐associated COVID‐19 appears to be an uncommon condition with similar clinical and EDx patterns to GBS before the pandemic. Future studies should compare patients with COVID‐19–associated GBS to those with contemporaneous non–COVID‐19 GBS and determine whether the incidence of GBS is elevated in those with COVID‐19.
Copper nanoparticles (Cu‐NPs) have a wide range of applications as heterogeneous catalysts. In this study, a novel green biosynthesis route for producing Cu‐NPs using the metal‐reducing bacterium, ...Shewanella oneidensis is demonstrated. Thin section transmission electron microscopy shows that the Cu‐NPs are predominantly intracellular and present in a typical size range of 20–40 nm. Serial block‐face scanning electron microscopy demonstrates the Cu‐NPs are well‐dispersed across the 3D structure of the cells. X‐ray absorption near‐edge spectroscopy and extended X‐ray absorption fine‐structure spectroscopy analysis show the nanoparticles are Cu(0), however, atomic resolution images and electron energy loss spectroscopy suggest partial oxidation of the surface layer to Cu2O upon exposure to air. The catalytic activity of the Cu‐NPs is demonstrated in an archetypal “click chemistry” reaction, generating good yields during azide‐alkyne cycloadditions, most likely catalyzed by the Cu(I) surface layer of the nanoparticles. Furthermore, cytochrome deletion mutants suggest a novel metal reduction system is involved in enzymatic Cu(II) reduction and Cu‐NP synthesis, which is not dependent on the Mtr pathway commonly used to reduce other high oxidation state metals in this bacterium. This work demonstrates a novel, simple, green biosynthesis method for producing efficient copper nanoparticle catalysts.
A novel green biosynthesis route for the production of functional copper nanoparticles (Cu‐NPs) using a metal‐reducing bacterium is reported. Detailed characterization reveals well‐dispersed Cu(0) nanoparticles with a thin, stable Cu2O surface layer. The catalytic activity of the biogenic Cu‐NPs is demonstrated for a range of “click chemistry” azide‐alkyne cycloaddition reactions, and the commercial potential of this approach discussed.
OBJECTIVE:We aimed to explore the diagnosis and misdiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) and to identify pitfalls that erroneously lead to a misdiagnosis.
METHODS:A ...retrospective study of 59 consecutive patients referred with a diagnosis of CIDP was performed. Patients were classified as having or not having CIDP according to European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria. Diagnostic and treatment data were compared in the 2 groups.
RESULTS:Forty-seven percent of patients referred with a diagnosis of CIDP failed to meet minimal CIDP diagnostic requirements. All misdiagnosed patients who satisfied EFNS/PNS clinical criteria would be considered atypical as defined by the EFNS/PNS. CSF cytoalbuminologic dissociation was present in 50% of those without CIDP, although protein elevations were generally mild. Nerve conduction studies in patients without CIDP were heterogeneous, but generally showed demyelinating features better explained by a process other than CIDP. Patients frequently reported improvements after being treated with immunotherapy, even if the CIDP diagnosis was incorrect.
CONCLUSIONS:CIDP misdiagnosis is common. Over-reliance on subjective patient-reported perception of treatment benefit, liberal electrophysiologic interpretation of demyelination, and placing an overstated importance on mild or moderate cytoalbuminologic dissociation are common diagnostic errors. Utilization of clear and objective indicators of treatment efficacy might improve our ability to make informed treatment decisions.
As a syndrome with typical and atypical cases, chronic inflammatory demyelinating polyneuropathy (CIDP) has been a difficult disorder to diagnose and treat. The pathophysiologic basis for CIDP has ...not been established, contributing to the challenges in dealing with these patients. However, as one of only a handful of treatable peripheral neuropathies, there has been a tendency to diagnose CIDP to attempt a therapeutic intervention. We are also aware that there has also been overtreatment of some patients. This combination of overdiagnosis and prolonged treatment has been a concern. This chapter will review these challenges and discuss recent findings that will lead to improved diagnosis and treatment.
The factors leading to misdiagnosis of CIDP were explored in a cohort of patients referred to a neuromuscular center. On a more positive note, the identification of two disorders with antibodies directed at paranodal constituents has excited the field. Treatment options have increased and been clarified. Pulse corticosteroids have been compared with oral prednisone and with intravenous immunoglobulin. The clinical trial of subcutaneous immunoglobulin in CIDP has shown both efficacy and a very low side effect profile adding to our therapeutic options.
The current review will identify recent developments that show both the challenges and the exciting growth in our ability to diagnose and treat CIDP.
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