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Needle Aponeurotomy of Dupuytren’s Contracture Causing 4th Digital Neuropathy (P7-11.013)
No full textCytotoxic Lesions of the Corpus Collosum (CLOCC) in an Adult With Type-B Influenza Infection (P2-2.008)
No full textRegulation of Mutant Huntingtin Mitochondrial Toxicity by Phosphomimetic Mutations within Its N-Terminal Region.
No full textHuntington\u27s disease (HD), a neurodegenerative disease, affects approximately 30,000 people in the United States, with 200,000 more at risk. Mitochondrial dysfunction caused by mutant huntingtin (mHTT) drives early HD pathophysiology. mHTT binds the translocase of the mitochondrial inner membrane (TIM23) complex, inhibiting mitochondrial protein import and altering the mitochondrial proteome. The 17 aa HTT N-terminal sequence (N17) acts as a regulatory domain in HD pathogenesis; phosphomimetic modification of serines 13 and 16 of the N17 domain impacts subcellular localization and degradation and ameliorates toxicity in mouse and cell models of HD. Using cellular and mouse (either sex) HD models, we investigated the mechanisms by which HTT phosphorylation affects intracellular localization. We demonstrate that introducing phosphomimetic mutations within the mHTT fragment N17 domain decreased TIM23 binding affinity and reduced inhibition of mHTT-mediated mitochondrial protein import. BACHD-SD mice expressing full-length mHTT harboring the same two N17 phosphomimetic mutations have an ameliorated HD-like phenotype as compared with mice expressing mHTT. Consistent with reduced toxicity in vivo, we found that the amount of full-length mHTT in the brain mitochondria of BACHD-SD transgenic mice is less when the mHTT has two phosphomimetic mutations. To complement the relevance of the phosphomimetic HTT findings, endogenous N17 phospho-mHTT is less likely to translocate to the mitochondria compared with nonphosphorylated mHTT. We demonstrate that phosphorylation of mHTT at serines 13 and 16 is critical for negatively regulating mHTT mitochondrial targeting and that reducing mHTT mitochondrial localization and binding to TIM23 results in amelioration of mHTT-induced mitochondrial and neuronal toxicity
Miniaturized Workflow for Transcriptomic Profiling of Urinary Extracellular RNA during Pregnancy.
No full textUrine contains extracellular RNA (exRNA) carried by extracellular vesicles (EVs) and other biomolecular complexes. There is currently a need for studies focused on female cohorts to develop new methods for non-invasive analysis of biofluids to create reference profiles and for identification of biomarkers of reproductive and pregnancy disorders. The objective of this study was therefore to identify optimal methods for transcriptomic profiling of urine by testing different exRNA isolation and scalable library preparation methods that enable detection of biomarkers that reflect pregnancy-associated changes in the placenta and maternal tissues. RNA was extracted from pooled and individual urine samples obtained from normal non-pregnant and pregnant females, as well as males, using input volumes of either 0.6 mL, 1 mL, or 4 mL. Samples were extracted using methods that focused either on isolating vesicular (EV-associated) or total (EV-associated and non EV-associated) exRNA. Small RNA libraries (n=208) were prepared using the NEBNext Small RNA Library Prep kit and long RNA libraries (n=97) were prepared using the SMART-Seq v4 Ultra Low Input RNA or the SMARTer Stranded Total RNA-Seq Kit v2 Pico Input kits (Takara). Principal component analysis showed that the greatest source of variance amongst technical replicates of small RNA libraries (n=176 which passed quality control) was exRNA isolation method, and amongst long RNA libraries (n=97 which passed quality control) was library preparation method. Long RNA libraries prepared from exRNA extracted using miRCURY showed that the SMART-Seq v4 method yielded significantly more uniquely mapped reads compared to the Pico v2 method (
Standardizing the large-volume tap test for evaluating idiopathic normal pressure hydrocephalus: a systematic review.
No full textINTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the clinical triad of gait, cognitive, and urinary dysfunction associated with ventriculomegaly on neuroimaging. Clinical evaluation before and after CSF removal via large volume lumbar puncture (the tap test ) is used to determine a patient\u27s potential to benefit from shunt placement. Although clinical guidelines for iNPH exist, a standardized protocol detailing the procedural methodology of the tap test is lacking.
EVIDENCE ACQUISITION: Using PRISMA guidelines, a systematic review of PubMed and Embase identifying studies of the tap test in iNPH was performed, centered on four clinical questions (volume of CSF to remove, type of needle for lumbar puncture, which clinical assessments to utilize, and timing of assessments). A modified Delphi approach was then applied to develop a consensus standardized tap test protocol for the evaluation of idiopathic normal pressure hydrocephalus.
EVIDENCE SYNTHESIS: Two hundred twenty-two full-text articles encompassing a total of 80,322 participants with iNPH met eligibility and were reviewed. Variations in the tap test protocol resulted in minimal concordance among studies. A standardized protocol of the tap test was iteratively developed over a two-year period by members of the International Parkinson and Movement Disorders Society Normal Pressure Hydrocephalus Study Group until expert consensus was reached.
CONCLUSIONS: The literature shows significant variability in the procedural methodology of the tap test. The proposed protocol was subsequently developed to standardize clinical management, improve patient outcomes, and better align future research in idiopathic normal pressure hydrocephalus
Breath-Holding Spells
No full textFlodine, T. E., Shah, M., & Mendez, M. D. (2023). Breath-Holding Spells. In StatPearls. StatPearls Publishing
