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Background:This project is an effort to understand how orders for IV immunoglobulin (IVIg) are documented and prescribed by physicians, and subsequently, how they are reviewed by insurance companies for the treatment of immune neuropathies. Methods:A panel of neuromuscular specialists reviewed case records from 248 IVIg-naive patients whose in-home IVIg infusion treatment was submitted to insurance for authorization. After reviewing a case record, 1 panelist was asked to make a diagnosis and to answer several questions about the treatment. A second panelist reviewed the original record and follow-up records that were obtained for reauthorization of additional treatments and was asked to determine whether the patient had responded to the treatment. Results:Our specialists believed that only 32.2% of 248 patients had an immune neuropathy and were appropriate candidates for IVIg therapy, whereas 46.4% had neuropathies that were not immune mediated. Only 15.3% of cases met electrodiagnostic criteria for a demyelinating neuropathy. Our specialists believed that 36.7% of 128 cases with follow-up records had responded to therapy. In cases in which the initial reviewer had predicted that there would be a response to IVIg, the second reviewer found that 54% had responded. This is compared with a 27% response rate when the first reviewer predicted that there would be no response (p = 0.019). Conclusions:Our expert review finds that the diagnosis of immune neuropathies made by providers, and subsequently approved for IVIg therapy by payers, is incorrect in a large percentage of cases. If payers include an expert in their review process, it would improve patient selection, appropriate use, and continuation of treatment with this expensive therapeutic agent.

As high-throughput methods become more common, training undergraduates to analyze data must include having them generate informative summaries of large datasets. This flexible case study provides an opportunity for undergraduate students to become familiar with the capabilities of R programming in the context of high-throughput evolutionary data collected using macroarrays. The story line introduces a recent graduate hired at a biotech firm and tasked with analysis and visualization of changes in gene expression from 20,000 generations of the Lenski Lab's Long-Term Evolution Experiment (LTEE). Our main character is not familiar with R and is guided by a coworker to learn about this platform. Initially this involves a step-by-step analysis of the small Iris dataset built into R which includes sepal and petal length of three species of irises. Practice calculating summary statistics and correlations, and making histograms and scatter plots, prepares the protagonist to perform similar analyses with the LTEE dataset. In the LTEE module, students analyze gene expression data from the long-term evolutionary experiments, developing their skills in manipulating and interpreting large scientific datasets through visualizations and statistical analysis. Prerequisite knowledge is basic statistics, the Central Dogma, and basic evolutionary principles. The Iris module provides hands-on experience using R programming to explore and visualize a simple dataset; it can be used independently as an introduction to R for biological data or skipped if students already have some experience with R. Both modules emphasize understanding the utility of R, rather than creation of original code. Pilot testing showed the case study was well-received by students and faculty, who described it as a clear introduction to R and appreciated the value of R for visualizing and analyzing large datasets. [ABSTRACT FROM AUTHOR]

Introduction/aims: Small fiber neuropathies (SFN) have been associated with two autoantibodies, trisulfated heparin disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR-3), and intravenous immune globulin (IVIG) has been suggested as a potential therapy. The study objective is to determine the efficacy of IVIG on nerve density, pain and neurologic examinations in patients with SFN associated with TS-HDS and FGFR-3 autoantibodies.Methods: This was a double-blind placebo-controlled pilot study. Subjects with SFN confirmed by history, examination, and skin biopsy with elevated autoantibodies to TS-HDS and/or FGFR-3 received IVIG (or blinded placebo) 2 grams/kg followed by 1 gram/kg every 3 wk for a total of 6 treatments. All subjects had Utah Early Neuropathy Scores (UENS), questionnaires and skin biopsies with quantitation of intra-epidermal nerve fiber density (IENFD) taken from adjacent sites at the distal leg at baseline and 6 mo later. The primary outcome was the change in IENFD over 6 mo.Results: Twenty subjects were enrolled; 17 completed treatment (8 IVIG, 9 placebo). Three did not have final data due to coronavirus disease 2019 (COVID-19). Skin biopsy IENFD improved by 0.5 ± 0.8 fibers/mm in the placebo group and improved by 0.6 ± 0.6 fibers/mm in the IVIG-treated group (p = NS).Over 24 wk the change in pain scores (11 point pain scale) was -1.9 ± 2.6 in the placebo group, and - 1.7 ± 0.9 in the IVIG group (p = NS), the UENS improved by 3.0 ± 5.8 in the placebo group and improved by 1.8 ± 3.9 in the IVIG group (p = NS).Discussion: This pilot study did not detect a benefit of treatment with IVIG in patients with SFN and autoantibodies to TS-HDS and FGFR-3. [ABSTRACT FROM AUTHOR]

Background: X‐linked dystonia parkinsonism (XDP) or "Lubag" is a genetic dystonia syndrome observed among Filipinos that can present with levodopa‐responsive parkinsonism and abnormal dopamine transporter (DAT) imaging. Objective: The aim of this study is to describe the results of skin biopsies for phosphorylated α‐synuclein (P‐SYN) in XDP. Method: This study used the retrospective chart review. Results: We report 6 patients who carried the XDP gene mutation with DAT imaging and skin biopsies to detect P‐SYN. Five had segmental or multifocal dystonia and parkinsonism: 4 were levodopa‐responsive and 1 non‐levodopa‐responsive. One patient was asymptomatic but had mild bradykinesia. Cutaneous P‐SYN and abnormal DAT scans were noted in the 4 levodopa‐responsive patients and 1 asymptomatic patient. Conclusion: We report for the first time the presence of cutaneous P‐SYN in XDP. Our findings suggest that XDP may be a hitherto‐undescribed synucleinopathy or that some XDP patients may have concurrent Parkinson's disease. [ABSTRACT FROM AUTHOR]

Introduction: Causes of small-fiber peripheral neuropathies (SFN) are often undefined. In this study we investigated associations of serum autoantibodies, immunoglobulin G (IgG) vs fibroblast growth factor receptor-3 (FGFR-3), and immunoglobulin M (IgM) vs trisulfated heparan disaccharide (TS-HDS) in cryptogenic SFN.Methods: One hundred fifty-five patients with biopsy-proven SFN and no identified cause for their neuropathy were blindly tested for serum IgM vs TS-HDS and IgG vs FGFR-3.Results: Forty-eight percent of SFN patients had serum antibodies, 37% with IgM vs TS-HDS and 15% with IgG vs FGFR-3. TS-HDS antibodies were more frequent in SFN patients than in controls (P = .0012). Both antibodies were more common in females, and with non-length-dependent nerve pathology. Nintey-two percent of patients with acute-onset SFN had serum IgM vs TS-HDS.Discussion: Autoantibodies directed against TS-HDS and FGFR-3 suggest an immune disorder in otherwise idiopathic SFN. Serum IgM vs TS-HDS may be a marker for SFN with an acute onset. [ABSTRACT FROM AUTHOR]

Leg autotomy can be a very effective strategy for escaping a predation attempt in many animals. In spiders, autotomy can be very common (5-40% of individuals can be missing legs) and has been shown to reduce locomotor speeds, which, in turn, can reduce the ability to find food, mates, and suitable habitat. Previous work on spiders has focused mostly on the influence of limb loss on horizontal movements. However, limb loss can have differential effects on locomotion on the nonhorizontal substrates often utilized by many species of spiders. We examined the effects of leg autotomy on maximal speed and kinematics while moving on horizontal, 45° inclines, and vertical (90°) inclines in the cellar spider Pholcus manueli, a widespread species that is a denizen of both natural and anthropogenic, three-dimensional microhabitats, which frequently exhibits autotomy in nature. Maximal speeds and kinematic variables were measured in all spiders, which were run on all three experimental inclines twice. First, all spiders were run at all inclines prior to autotomization. Second, half of the spiders had one of the front legs removed, while the other half was left intact before all individuals were run a second time on all inclines. Speeds decreased with increasing incline and following autotomy at all inclines. Autotomized spiders exhibited a larger decrease in speed when moving horizontally compared to on inclines. Stride length decreased at 90° but not after autotomy. Stride cycle time and duty factor increased after autotomy, but not when moving uphill. Results show that both incline and leg autotomy reduce speed with differential effects on kinematics with increasing incline reducing stride length, but not stride cycle time or duty factor, and vice versa for leg autotomy. The lack of a significant influence on a kinematic variable could be evidence for partial compensation to mitigate speed reduction. [ABSTRACT FROM AUTHOR]

We performed a randomized, double-blind phase I clinical trial for six months on the effects of oral L-serine in patients with ALS. The protocol called for enrollment of patients with a diagnosis of probable or definite ALS, age 18–85 years, disease duration of less than three years and forced vital capacity (FVC) ≥ 60%. Patients were randomly assigned to four different oral twice-daily dose regimens (0.5, 2.5, 7.5, or 15 g/dose). Blood, urine and CSF samples, ALS Functional Rating Scale-Revised (ALSFRS-R) scores and forced vital capacity (FVC) were obtained throughout the trial. Disease progression was compared with matched historical placebo controls from five previous ALS therapeutic trials. Of 20 patients enrolled, one withdrew before receiving study drug and two withdrew with gastro-intestinal problems. Three patients died during the trial. L-serine was generally well tolerated by the patients and L-serine did not appear to accelerate functional decline of patients as measured by slope of their ALSFRS-R scores. Based on this small study, L-serine appears to be generally safe for patients with ALS. [ABSTRACT FROM AUTHOR]

Because of the sedentary lifestyle of freshwater mussels, studies examining their movement capabilities are scarce. However, the ability to burrow into the substrate and the ability to remain stationary are likely crucial components of their behavioural repertoire. The performance of these different tasks is likely to be affected by the presence of the shell ornamentation characteristic of many mussel species. Previous studies have suggested that shell ornamentation results in a trade-off between burrowing ability and remaining stationary when an extrinsic force attempts to dislodge it from the substrate once buried. We examined the effect of morphology and shell ornamentation on burrowing performance and anchoring ability by artificially creating shell ornamentation on a relatively smooth-shelled species ( Potamilus alatus). Burrowing behaviours and performance and the force required to dislodge mussels (anchoring ability) were quantified with and without ornamentation. Interestingly, we found that the artificial shell ornamentation had no significant effect on burrowing behaviours and performance or dislodgement force. Burrowing and dislodgement, however, were both highly influenced by shell size and shape. All of the available information suggests that shell size, shape, and sculpture influence burrowing and anchoring in complex ways that needs further examination. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 111, 136-144. [ABSTRACT FROM AUTHOR]