Autonomic disorders and myocardial 123I-metaiodobenzylguanidine scintigraphy in Huntington's disease.

BACKGROUND: Huntington's disease (HD) patients often present with abnormal modulation of blood pressure and heart rate. We investigated whether cardiac autonomic innervation assessed by 123I-metaiodobenzylguanidine (MIBG) imaging is impaired in HD patients, in comparison with controls (Ctrl). METHODS: Fifteen patients (6 F and 9 M) were assessed by the motor section of the Unified HD Rating Scale, the Total Function Capacity, and the scale for outcomes in Parkinson's disease-autonomic (SCOPA-AUT) questionnaire. All patients and 10 Ctrl (5 F and 5 M) underwent 123I-MIBG imaging. From planar images, the early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR) were calculated. RESULTS: We did not find significant differences in early and late H/M ratios and WR between the two groups. At individual level, three patients showed reduced early and/or late H/M ratios. The most common autonomic complaints were gastrointestinal and genitourinary disorders. SCOPA-AUT questionnaire score results positively correlated with the disease duration and WR. CONCLUSIONS: Our study indicates that myocardial postganglionic sympathetic innervation is essentially preserved or only minimally involved in HD. These findings suggest that the cardiovascular dysfunction might be mainly due to the impairment of brain areas associated with the regulation and modulation of the heart function.

Muscle Mass as a Biomarker for Health Status and Function in Pediatric Individuals with Neuromuscular Disabilities: A Systematic Review.

This systematic review aims to investigate the relationship between muscle mass and specific health outcomes in pediatric populations with neuromuscular disorders. A search was performed for any relevant studies published in English from 1996 to 2023 in five databases. To be included in this analysis, articles must have had participants with an average age ≤21, focus on children with neuromuscular disabilities, and primarily examine relationships between muscle mass and any functional or health outcomes measure. Studies including typically developing children were used to contrast and enhance findings. Thirty-two studies were included, with 10,129 unique individuals represented: seventeen studies focused on healthy/typically developing children; seven on children with cerebral palsy; three on children with Duchenne muscular dystrophy; two on children with sarcopenia; and one study each on children with osteoporosis, congenital muscular dystrophy, and other various neurologic disorders. Thirteen studies assessed functional outcomes, ten assessed bone outcomes, and nine assessed other cardiovascular/metabolic outcomes. All of the included studies demonstrated relationships between muscle mass and respective outcomes in varying measures. The results of this review demonstrate that there is a consistently recognized relationship between muscle mass and important health outcomes in children, supporting clinically targeting muscle mass as a means to optimize desired outcomes.

Formal Single Atom Editing of the Glycosylated Natural Product Fidaxomicin Improves Acid Stability and Retains Antibiotic Activity.

Fidaxomicin (Fdx) constitutes a glycosylated natural product with excellent antibacterial activity against various Gram-positive bacteria but is approved only for Clostridioides difficile infections. Poor water solubility and acid lability preclude its use for other infections. Herein, we describe our strategy to overcome the acid lability by introducing acid-stable S-linked glycosides. We describe the direct, diastereoselective modification of unprotected Fdx without the need to avoid air or moisture. Using our newly established approach, Fdx was converted to the single atom exchanged analogue S-Fdx, in which the acid labile O-glycosidic bond to the noviose sugar was replaced by the acid stable S-glycosidic bond. Studies of the antibacterial activity of a structurally diverse set of thioglycoside derivatives revealed high potency of acyl derivatives of S-Fdx against Clostridioides difficile (MIC range: 0.12-4 µg/mL) and excellent potency against Clostridium perfringens (MIC range: 0.06-0.5 µg/mL).

Allylic Carbocyclic Inhibitors Covalently Bind Glycoside Hydrolases.

Allylic cyclitols were investigated as covalent inhibitors of glycoside hydrolases by chemical, enzymatic, proteomic, and computational methods. This approach was inspired by the C7 cyclitol natural product streptol glucoside, which features a potential carbohydrate leaving group in the 4-position (carbohydrate numbering). To test this hypothesis, carbocyclic inhibitors with leaving groups in the 4- and 6- positions were prepared. The results of enzyme kinetics analyses demonstrated that dinitrophenyl ethers covalently inhibit α-glucosidases of the GH13 family without reactivation. The labeled enzyme was studied by proteomics, and the active site residue Asp214 was identified as modified. Additionally, computational studies, including enzyme homology modeling and density functional theory (DFT) calculations, further delineate the electronic and structural requirements for activity. This study demonstrates that previously unexplored 4- and 6-positions can be exploited for successful inhibitor design.

Lower Prevalence of Chronic Pain in Manifest Huntington's Disease: A Pilot Observational Study.

Pain is a minor problem compared with other Huntington Disease (HD) symptoms. Nevertheless, in HD it is poorly recognized and underestimated. So far, no study evaluated the presence of chronic pain in HD. The aim of this pilot study was to evaluate the presence and features of chronic pain in a cohort of HD gene carriers. An observational cross-sectional study was conducted in a cohort of HD gene carriers compared to not gene carriers (n.134 HD subjects, n.74 not gene mutation carriers). A specific pain interview, alongside a neurological, cognitive and behavioural examination, was performed in order to classify the type of pain, subjective intensity. A significant prevalence of "no Pain" in HD was found, which tended to increase with HD progression and a reduced frequency of pain in the last 3 months. A clear difference was found between manifest and premanifest HD in terms of intensity of pain, which did not change significantly with HD progression; however, a tendency emerges to a progressive reduction. No significant group difference was present in analgesic use, type and the site of pain. These findings could support a lower prevalence of chronic pain in manifest HD. Prevalence and intensity of chronic pain seem directly influenced by the process of neurodegeneration rather than by an incorrect cognitive and emotional functioning.

Minimizing cotton retention in neurosurgical procedures: which imaging modality can help?

Cotton balls are used in neurosurgical procedures to assist with hemostasis and improve vision within the operative field. Although the surgeon can reshape pieces of cotton for multiple intraoperative uses, this customizability and scale also places them at perpetual risk of being lost, as blood-soaked cotton balls are visually similar to raw brain tissue. Retained surgical cotton can induce potentially life-threatening immunologic responses, impair postoperative imaging, lead to a textiloma or misdiagnosis, and/or require reoperation. This study investigated three imaging modalities (optical, acoustic, and radiographic) to find the most effective method of identifying foreign bodies during neurosurgery. First, we examined the use of dyes to increase contrast between cotton and surrounding parenchyma (optical approach). Second, we explored the ability to distinguish surgical cotton on or below the tissue surface from brain parenchyma using ultrasound imaging (acoustic approach). Lastly, we analyzed the ability of radiography to differentiate between brain parenchyma and cotton. Our preliminary testing demonstrated that dark-colored cotton is significantly more identifiable than white cotton on the surface level. Additional testing revealed that cotton has noticeable different acoustic characteristics (eg, speed of sound, absorption) from neural tissue, allowing for enhanced contrast in applied ultrasound imaging. Radiography, however, did not present sufficient contrast, demanding further examination. These solutions have the potential to significantly reduce the possibility of intraoperative cotton retention both on and below the surface of the brain, while still providing surgeons with traditional cotton material properties without affecting the surgical workflow.