Development of recurrent facial palsy during plasmapheresis in Guillain-Barré syndrome: a case report

Introduction: Guillain-Barré syndrome is an immune-mediated polyneuropathy that is routinely initially treated with either intravenous immunoglobulin or plasmapheresis. To the best of our knowledge, no association between plasmapheresis treatment and acute onset of facial neuropathy has been reported. Case presentation: A 35-year-old Caucasian man with no significant prior medical history developed ascending motor weakness and laboratory findings consistent with a diagnosis of Guillain-Barré syndrome. Plasmapheresis was initiated. Acute facial palsy developed during the plasma exchange that subsequently resolved and then acutely recurred during the subsequent plasma exchange. Conclusion: To the best of our knowledge, no prior cases of acute facial palsy developing during plasmapheresis treatment are known. Although facial nerve involvement is common in typical Guillain-Barré syndrome, the temporal association with treatment, near-complete resolution and later recurrence support the association. The possible mechanism of plasmapheresis-induced worsening of peripheral nerve function in Guillain-Barré syndrome is unknown

The Caenorhabditis elegans vab-10 spectraplakin isoforms protect the epidermis against internal and external forces

Morphogenesis of the Caenorhabditis elegans embryo is driven by actin microfilaments in the epidermis and by sarcomeres in body wall muscles. Both tissues are mechanically coupled, most likely through specialized attachment structures called fibrous organelles (FOs) that connect muscles to the cuticle across the epidermis. Here, we report the identification of new mutations in a gene known as vab-10, which lead to severe morphogenesis defects, and show that vab-10 corresponds to the C. elegans spectraplakin locus. Our analysis of vab-10 reveals novel insights into the role of this plakin subfamily. vab-10 generates isoforms related either to plectin (termed VAB-10A) or to microtubule actin cross-linking factor plakins (termed VAB-10B). Using specific antibodies and mutations, we show that VAB-10A and VAB-10B have distinct distributions and functions in the epidermis. Loss of VAB-10A impairs the integrity of FOs, leading to epidermal detachment from the cuticle and muscles, hence demonstrating that FOs are functionally and molecularly related to hemidesmosomes. We suggest that this isoform protects against forces external to the epidermis. In contrast, lack of VAB-10B leads to increased epidermal thickness during embryonic morphogenesis when epidermal cells change shape. We suggest that this isoform protects cells against tension that builds up within the epidermis

Maximizing efficiency of rumen microbial protein production.

Rumen microbes produce cellular protein inefficiently partly because they do not direct all ATP toward growth. They direct some ATP toward maintenance functions, as long-recognized, but they also direct ATP toward reserve carbohydrate synthesis and energy spilling (futile cycles that dissipate heat). Rumen microbes expend ATP by vacillating between (1) accumulation of reserve carbohydrate after feeding (during carbohydrate excess) and (2) mobilization of that carbohydrate thereafter (during carbohydrate limitation). Protozoa account for most accumulation of reserve carbohydrate, and in competition experiments, protozoa accumulated nearly 35-fold more reserve carbohydrate than bacteria. Some pure cultures of bacteria spill energy, but only recently have mixed rumen communities been recognized as capable of the same. When these communities were dosed glucose in vitro, energy spilling could account for nearly 40% of heat production. We suspect that cycling of glycogen (a major reserve carbohydrate) is a major mechanism of spilling; such cycling has already been observed in single-species cultures of protozoa and bacteria. Interconversions of short-chain fatty acids (SCFA) may also expend ATP and depress efficiency of microbial protein production. These interconversions may involve extensive cycling of intermediates, such as cycling of acetate during butyrate production in certain butyrivibrios. We speculate this cycling may expend ATP directly or indirectly. By further quantifying the impact of reserve carbohydrate accumulation, energy spilling, and SCFA interconversions on growth efficiency, we can improve prediction of microbial protein production and guide efforts to improve efficiency of microbial protein production in the rumen

Biallelic Loss-of-Function Variants in BICD1 Are Associated with Peripheral Neuropathy and Hearing Loss

Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control. Pathogenic variants in known disease genes associated with hearing loss and peripheral neuropathy were excluded. A homozygous frameshift variant in the BICD1 gene, c.1683dup (p.(Arg562Thrfs*18)), was identified in the proband and segregated with hearing loss and peripheral neuropathy in the family. The BIDC1 RNA analysis from patient fibroblasts showed a modest reduction in gene transcripts compared to the controls. In contrast, protein could not be detected in fibroblasts from a homozygous c.1683dup individual, whereas BICD1 was detected in an unaffected individual. Our findings indicate that bi-allelic loss-of-function variants in BICD1 are associated with hearing loss and peripheral neuropathy. Definitive evidence that bi-allelic loss-of-function variants in BICD1 cause peripheral neuropathy and hearing loss will require the identification of other families and individuals with similar variants with the same phenotype

The effect of corporate governance on stock repurchases: evidence from Sweden

Research Question/Issue: The paper examines whether corporate governance differences affect firms' stock repurchasing behaviour. Previous hypotheses on stock repurchases, well-supported by US data, are based on assumptions of managerial autonomy that might not be descriptive in corporate governance systems characterised by influential controlling shareholders such as the Swedish. Firm-level corporate governance arrangements may also affect firms' incentives to repurchase stock. Research Findings/Insights: Stock-repurchasing patterns among Swedish firms differ from those previously observed among US firms. The findings indicate that Swedish firms do not repurchase stock to distribute excess cash, signal undervaluation or fend off takeovers. Stock repurchases are made in addition to dividends and thus do not substitute for them. Firm-level corporate governance arrangements directly affect stock repurchasing behaviour. Firms without a dominant controlling owner seem to use stock repurchases to increase leverage. The existence of a dominant controlling shareholder diminishes the propensity for stock repurchases, while cross listing on a US or UK stock market increases that propensity. Theoretical/Academic Implications: The findings suggest that corporate governance differences affect stock repurchasing behaviour. The agency-theoretical view of the firm, on which the leading hypotheses on stock repurchases are based, accurately predicts stock repurchases only in certain institutional and governance settings. Practitioner/Policy Implications: The study suggests that differences in national and firm-level corporate governance must be taken into account in order to accurately assess outcomes of regulatory reforms and/or harmonisation attempts

Consanguinity and Intimate Partner Violence

Why is marriage between relatives common throughout the world? Consanguineous marriage was commonplace throughout human history, but became increasingly rare in the developed world beginning in the 1800’s. For large swaths of the world from Morocco to Indonesia, it is still ubiquitous.This project investigates the theory that women use consanguineous marriage to mitigate their exposure to Intimate Partner Violence. Marrying relatives, particularly first cousins, provides women with an ex ante information gathering mechanism and an ex post behavior enforcement mechanism, both of which serve to lower the amount of violence women are exposed to.Observational data taken from USAID’s Demographic and Health Surveys confirms the expected result that consanguinity and Intimate Partner Violence are negatively correlated in three of the four countries studied—Pakistan, Egypt, and Jordan. In India, however, the two are positively linked. Relying on previous literature, I speculate that the reason behind this divergence lies in dowry practices in India

Development of recurrent facial palsy during plasmapheresis in Guillain-Barré syndrome: a case report

Abstract Introduction Guillain-Barré syndrome is an immune-mediated polyneuropathy that is routinely initially treated with either intravenous immunoglobulin or plasmapheresis. To the best of our knowledge, no association between plasmapheresis treatment and acute onset of facial neuropathy has been reported. Case presentation A 35-year-old Caucasian man with no significant prior medical history developed ascending motor weakness and laboratory findings consistent with a diagnosis of Guillain-Barré syndrome. Plasmapheresis was initiated. Acute facial palsy developed during the plasma exchange that subsequently resolved and then acutely recurred during the subsequent plasma exchange. Conclusion To the best of our knowledge, no prior cases of acute facial palsy developing during plasmapheresis treatment are known. Although facial nerve involvement is common in typical Guillain-Barré syndrome, the temporal association with treatment, near-complete resolution and later recurrence support the association. The possible mechanism of plasmapheresis-induced worsening of peripheral nerve function in Guillain-Barré syndrome is unknown.</p

Clinical evolution of pure upper motor neuron disease/dysfunction (PUMMD)

Introduction: PLS is defined as pure upper motor neuron disease/dysfunction (PUMND) beyond 48 months after symptom onset. We know little about its early stages, but such knowledge would help to identify the mechanisms underlying PLS and ALS and determine why PLS patients seem to be protected against lower MND (LMND). Methods: We reviewed 622 MND cases during a 4-year period and identified 34 patients with PUMND (5.4%). Results: Among 23 cases with follow-up data/electromyograms (EMGs; 2 had only 1 EMG), 13 (57%) remained classified as PUMND, and 8 (35%) developed LMND (mean, 51.4 months after onset). Of these 8, LMND developed in 3 after 48 months from symptom onset. Patients with PUMND and LMND were more functionally impaired (P = 0.02). Separately, we identified 5 patients with PUMND who developed LMND long after 48 months (range, 50-127 months). Conclusions: PLS belongs to the ALS spectrum, and perhaps all cases eventually develop LMND. © 2012 Wiley Periodicals, Inc

Lack of effect on ambulation of dalfampridine-ER (4-AP) treatment in adult SMA patients

SMA is a genetically determined motor system disorder that results in muscle weakness, selective motor neuron death, muscle atrophy, and impaired functional mobility. In SMA model systems, long-term treatment with 4-aminopyridine (4-AP) has been shown to improve motor function. To assess tolerability and preliminary efficacy of 4-AP on walking ability, endurance and EMG in adult ambulatory SMA patients, we conducted a double blind, placebo control, crossover pilot study with dalfampridine (4-AP, 10 mg BID). The study is comprised of a short-term (2 weeks) treatment arm with 1-week washout and a long-term (6 weeks) treatment arm with a 2-week washout. The primary outcome measure, for which the study was powered, was the 6 min walk test (6MWT, distance and percent fatigue); secondary outcome measures were the Hammersmith Functional Motor Scale Expanded (HFMSE), Manual Muscle Testing (MMT), Myometry with Hand held Dynamometry, HHD) and Quantitative Gait Analyses. We performed electrophysiology, including CMAP and H-reflex, during the short-term treatment trial. The mean age of the 11 participants enrolled was 37.7 +/- 11.9 years; 54.5% were male. Dalfampridine was safe and well tolerated and no patient suffered a serious adverse event related to treatment. We observed no statistically significant positive effects of dalfampridine treatment on our primary functional motor outcome (6MWT distance, fatigue). Dalfampridine had a positive effects on H-reflex and H/M ratio but not on CMAP amplitude. The effect on the H-reflex is of interest, as it suggests dalfampridine may enhance neuronal activity, an effect observed in SMA Drosophila and mouse models at doses (mg/kg) not recommended for clinical use. Larger studies with dalfampridine in SMA patients are needed to confirm our findings, especially in light of studies in other populations showing drug effects in only a subset of patients. (c) 2020 Published by Elsevier B.V