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Category: biotech/medical – Page 46

Pallidus internus versus subthalamic nucleus deep brain stimulation for Meige syndrome: a randomized, controlled, double-blind multicenter trial

The aim of this randomized, controlled, double-blind multicenter trial was to compare the safety and efficacy of globus pallidus internus (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Meige syndrome (MeS). Additionally, the authors explored the optimal site of DBS and identified predictors of clinical outcomes.

The primary outcome was improvement in motor function as assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The secondary outcomes included mood, global cognitive function, and quality of life (QOL). The optimal stimulation site for DBS was investigated using Lead-DBS.

A total of 62 patients with MeS were randomized to receive GPi-DBS (n = 31) or STN-DBS (n = 31), and all completed the 1-year follow-up. In the GPi-DBS group, the mean improvement rates in BFMDRS movement scores were 54.9%, 57.3%, and 59.7% at 3, 6, and 12 months, respectively. In the STN-DBS group, the corresponding rates were 57.1%, 59.0%, and 59.9%. There was no significant difference in the efficacy of motor symptoms, depression, anxiety, and QOL between the two groups during follow-up. The total electrical energy delivered in the GPi-DBS group was significantly greater than that in the STN-DBS group. The adverse event rates were comparable between the GPi-DBS (16.1%) and STN-DBS (12.9%) groups (p 0.99). The “sweet spot” for GPi-DBS was found to be located in the posterolateral dorsal pallidum (ρ = 0.76, p = 0.001), while the sweet spot for STN-DBS was found to be situated in the dorsal subthalamic nucleus (ρ = 0.66, p = 0.005).

Bayesian probabilistic density mapping of the decussating dentato-rubro-thalamic tract to predict clinical tremor improvement in MRgFUS

OBJECTIVE Magnetic resonance–guided focused ultrasound (MRgFUS) is increasingly recognized as an effective treatment option for patients with medication-refractory essential tremor (ET). Indirect coordinates of the ventral intermediate nucleus of the thalamus, as well as the dentato-rubro-thalamic tract (DRTT) originating from the ipsilateral dentate nucleus, known as the “nondecussating DRTT” (nd-DRTT), are commonly used as targets for sonication. Anatomically, the DRTT originating from the contralateral dentate nucleus, referred to as the “decussating DRTT” (d-DRTT), constitutes the predominant component of the two fiber populations. However, the d-DRTT is rarely visualized using conventional diffusion tensor imaging (DTI) because of the technical challenges associated with resolving crossing fiber orientations. Probabilistic tractography enables the differentiation of crossing fibers, thus allowing for visualization of both the d-DRTT and nd-DRTT. Authors of this study aimed to evaluate whether the d-DRTT delineated by probabilistic tractography represents an anatomical target more important than indirect coordinates or the nd-DRTT. METHODS Consecutive patients with medically refractory ET who underwent unilateral MRgFUS thalamotomy at a single institution between May 2022 and August 2024 were analyzed. Tremor severity was assessed using the Clinical Rating Scale for Tremor Part B, and the percentage improvement at 3 months after treatment was calculated as an indicator of functional recovery. Probabilistic tractography of the DRTT was performed post hoc using preoperative diffusion MRI and Bayesian modeling (BedpostX) and probabilistic tracking (ProbtrackX). The distances between the sonicated lesion as detected on postoperative MRI and each of the following were compared: indirect coordinates, nd-DRTT, and d-DRTT. Subgroup analysis was performed on patients with a peak lesion temperature ≥ 55°C. Pearson correlation was used to assess the relationships between distance metrics and clinical outcomes. RESULTS Probabilistic tractography successfully visualized the d-DRTT in all 28 patients included in the study. The d-DRTT was more lateral than both the indirect coordinate and the nd-DRTT (p < 0.01 for both), with a nonsignificant tendency for a more anterior position relative to the nd-DRTT (p = 0.054). Among the patients with a peak lesion temperature ≥ 55°C, the distance between the sonicated lesion and the d-DRTT showed a strong correlation with clinical outcomes, whereas that between the lesion and nd-DRTT showed a moderate correlation; the indirect coordinates showed no significant correlation. CONCLUSIONS Probabilistic tractography successfully visualized the d-DRTT, and its location appears to capture the “tremor-relevant” neural pathway more accurately than either the indirect coordinate or the nd-DRTT.

Efficacy and Safety of VMAT2 Inhibitors in the Treatment of Huntington DiseaseA Meta-Analysis of Randomized Clinical Trials

In patients with Huntington disease, vesicular monoamine transporter 2 inhibitors (VMAT2is) treatment improved chorea without significant changes in adverse effects or depressive symptoms.

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Hidden mosquito viruses emerge as RNA immune signals map global infections

Aedes aegypti, commonly known as the yellow fever mosquito, is a highly adapted, invasive mosquito species recognized as a major global health threat that acts as the primary vector for several severe diseases, most notably dengue fever, as well as yellow fever, chikungunya and Zika virus. Local government agencies conduct routine molecular surveillance of these mosquitoes to detect and track viruses. However, they are primarily limited to using conventional reverse transcription polymerase chain reaction methodologies, which can only detect known pathogens that have already been identified and for which specific genetic primers have been developed.

Recent research efforts applying high-throughput RNA sequencing have led to a large expansion in the mosquito virome (the entire collection of viruses contained within mosquitoes). However, questions remain as to how persistent insect viruses are within mosquito colonies, how insect viruses interact with mosquito immune responses and how frequently insect viruses can be transmitted.

A new study by Boston University Chobanian & Avedisian School of Medicine researchers looked at the mosquitoes’ immune response to discover many more insect viruses and they hope to someday use the mosquitoes’ own immune system to battle some of the most pervasive and antagonistic human viruses. The findings are published in the journal Nature Communications.

Abstract: Proposing a no-nonsense strategy for the treatment of dominant neurodevelopmental disorders:

Xiaochang Zhang & team introduce exon annotation for nonsense-mediated mRNA (EANMD) and report on alternatively spliced exons in the brain that trigger mRNA decay, noting modulation of such exons in disease-causal genes can potentially treat neurodevelopmental disorders.

Address correspondence to: Xiaochang Zhang, University of Chicago, Cummings Life Science Center 507A, 920 E. 58th St., Chicago, Illinois 60,637, USA. Phone: 773.834.5369; Email: [email protected].

Vitamin D Receptor Polymorphisms and Diabetes Risk

Among adults with Prediabetes, vitamin D3 supplementation was associated with lower diabetes risk only in those with specific ApaI vitamin D receptor genotypes.

This genetic association analysis of the D2d study suggests that genetic variation in the VDR, specifically the ApaI polymorphism, is associated with diabetes risk at higher intratrial 25(OH)D levels and is associated with response to 4,000 IU/d of vitamin D3 supplementation among adults with prediabetes. Participants carrying the ApaI AA genotype did not experience a reduction in diabetes risk, either when achieving higher intratrial 25(OH)D concentrations or while being treated with 4,000 IU/d of vitamin D3. In contrast, those carrying the ApaI CC and AC genotypes, representing 71% of the D2d study population, had progressively lower risk of type 2 diabetes at intratrial 25(OH)D levels of 40 ng/mL or higher. Participants with these genotypes randomized to vitamin D3 had a 19% reduction in the risk of progression to diabetes compared with placebo, whereas those with ApaI AA alleles did not respond to treatment with vitamin D3. The BsmI polymorphism also appeared to play a role in the association between the achieved intratrial 25(OH)D level and diabetes risk, as expected given the high linkage disequilibrium of ApaI and BsmI (D’ = 1.0 and r2 = 1.0) among people of European ancestry.15 Because there was a near complete overlap between participants carrying the nonresponsive Bsml TT genotype and those carrying the nonresponsive ApaI AA genotype, knowing the ApaI genotype alone was sufficient to identify individuals who were likely—or unlikely—to respond to supplementation with 4,000 IU/d of vitamin D3. These exploratory genetic association findings support our hypothesis that a common VDR variant modulates the link between high intratrial 25(OH)D levels and diabetes risk, and the association between relatively high-dose vitamin D3 supplementation and diabetes risk among adults with prediabetes. The distributions of alleles of the 3 polymorphisms in the D2d study were similar to those reported in the UK Biobank of participants with prediabetes.5 Consistent with the UK Biobank study and other studies,5,16,17 the 25(OH)D levels achieved during the D2d trial did not differ significantly among participants with different VDR polymorphisms.

In the UK Biobank study, among adults with prediabetes and a median 25(OH)D level of 19.2 ng/mL (a value below our referent range of 20–29.9 ng/mL), there was a stepwise decrease in the risk of diabetes at 25(OH)D levels of lower than 10 (the study’s referent), 10 to 20, 20 to 30, and 30 ng/mL or higher.5 Risk reduction was present in all VDR genotypes of the 4 examined polymorphisms (ApaI, BsmI, TaqI, and FokI), but it was more prominent among those carrying the T allele of BsmI. There were too few participants in the D2d study with sufficiently low 25(OH)D levels to address this range of the 25(OH)D spectrum. Conversely, there were too few participants with sufficiently high 25(OH)D levels in the UK Biobank study to address the question posed in our study. To our knowledge, no other high-dose vitamin D trials among adults with prediabetes have examined how VDR polymorphisms may modify the effect of vitamin D supplementation on diabetes risk.

Our exploratory findings, if confirmed, hold promise for high-dose vitamin D3 as a targeted, personalized approach to reducing the risk of type 2 diabetes among selected adults with prediabetes. The magnitude of the observed risk reduction among participants with AC and CC alleles of the ApaI polymorphism, if confirmed in an independent clinical trial, would have clinical implications for the management of prediabetes. In the original report of the D2d trial,2 the HR for conversion to type 2 diabetes with vitamin D supplementation was 0.88 (95% CI, 0.72−1.04). The HR decreased to 0.81 (95% CI, 0.66−0.99) in our exploratory analysis when genetically nonresponsive participants (those with AA alleles of the ApaI polymorphism, comprising 29.5% of all participants) were excluded. If confirmed, a 19% risk reduction in conversion to type 2 diabetes with vitamin D3 supplementation would not be trivial. First, assessment of a single VDR polymorphism is inexpensive and now widely available.

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