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M. Zamfirov

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Jul 2026

Whole-Body Vibration After Compressive Spinal Cord-Injury in Rats Restores Dorsal Horn Synaptic Relations and Alleviates Pain-Associated Behavior.

Spinal cord injury (SCI) induces neuronal loss and demyelination, leading to maladaptive neuronal circuits that drive persistent central neuropathic pain (PCNP). While pharmacological, psychological, and physiotherapeutic approaches have been applied, including whole-body vibration (WBV), synaptic-level mechanisms of WBV remain largely unexplored. Here, we assessed the post-SCI pain-associated behavior index (PAB, based on established behavioral criteria) and compared synapse counts (SYN+, VGLUT1+, ChAT+, VGAT+), CGRP+- and SER+-structures, as well as astrocytic and microglial populations in the lumbar dorsal horn following thoracic SCI in WBV-treated and untreated rats. Animals received WBV from postoperative week 3 to 12, and outcomes were compared with non-treated controls. PAB was consistently reduced in WBV-treated animals. STED-microscopy quantification showed that WBV increased the linear density of VGAT + and VGLUT1 + perisomatic terminals, as well as the number of SER + fibers. Conversely, WBV reduced CGRP + structures in the dorsal horn, decreased the density of CGRP + perisomatic and axo-axonic synapses, and lowered astrocytic and microglial populations. Our data indicate that the WBV-induced frequent (15-30 Hz) muscle contractions and proprioceptive impulses contribute to spasticity modulation (via VGAT-related mechanisms) and attenuation of post-SCI hyperalgesia (CGRP-associated). Together with the reduced astro- and microglia amounts, the described synaptic alterations are considered essential prerequisites for better motor recovery. These findings provide preclinical evidence for the functional benefits of WBV in an animal SCI model and warrant further investigations to determine mechanisms underpinning this non-invasive, low-cost and easily applicable rehabilitation approach.

Svenja Rink-Notzon, Martin Krueger, M. Zamfirov et al. · 1 citation
Open access Jul 2026

Risk Beyond the Variant: A Composite Metric for Autism Gene Pathogenicity

Background: Variant-based pathogenicity predictors such as REVEL evaluate missense variants in isolation, discarding the gene-length and allele-frequency context needed to compare collections of genes. Methods: We introduce a composite gene-level metric integrating Hardy–Weinberg heterozygosity, coding-sequence length, and REVEL scores. The metric returns a single value per gene expressing variant burden per unit of coding sequence within a given cohort, so that the ratio between a case and a control cohort quantifies gene-level enrichment. It was evaluated on 55 high-confidence autism genes, defined as the intersection of three large-scale ASD sequencing studies, against the 1000 Genomes reference. Results: It identifies elevated pathogenic burden in 48 of 55 genes, removes gene-length and variant-count confounds, and substantially outperforms naive gene-level aggregation of REVEL scores. Bootstrap resampling and a label-permutation control confirm the enrichment is stable and not an artefact of the scoring construction. Conclusions: The metric allows genes to be ranked within a set and aggregate burden to be compared across gene sets. We present it as a complementary gene-level layer for case–control and gene-set comparisons, with a nonlinear successor outlined as future work.

Beloslava Malakova, Simeon Karpuzov, Dobromir Tsolyov et al. · 0 citations