Neurorehabilitation with vagus nerve stimulation: a systematic review.

Objective: To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). Methods: Data sources: PubMed, EMBASE, SCOPUS, and Cochrane. Study selection: Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery. Data extraction: Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically. Data synthesis: Twenty-nine studies were included; 11 were animal models of stroke, TBI, and SCI, and eight involved humans with stroke. While there was heterogeneity in methods of delivering VNS with respect to rehabilitation therapy in animal studies and human non-invasive studies, a similar methodology was used in all human-invasive VNS studies. In animal studies, pairing VNS with rehabilitation therapy consistently improved motor outcomes compared to controls. Except for one study, all human invasive and non-invasive studies with controls demonstrated a trend toward improvement in motor outcomes compared to sham controls post-intervention. However, compared to non-invasive, invasive VNS, studies reported severe adverse events such as vocal cord palsy, dysphagia, surgical site infection, and hoarseness of voice, which were found to be related to surgery. Conclusion: Our review suggests that VNS (non-invasive or invasive) paired with rehabilitation can improve motor outcomes after stroke in humans. Hence, VNS human studies are needed in these populations (referring to SCI and TBI?) or just SCI. There are risks related to device implantation to deliver invasive VNS compared to non-invasive VNS. Future human comparison studies are required to study and quantify the efficacy vs. risks of paired VNS delivered via different methods with rehabilitation, which would allow patients to make an informed decision. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=330653.

Maturation-dependent changes in the size, structure and seeding capacity of Aß42 amyloid fibrils.

Many proteins self-assemble to form amyloid fibrils, which are highly organized structures stabilized by a characteristic cross-ß network of hydrogen bonds. This process underlies a variety of human diseases and can be exploited to develop versatile functional biomaterials. Thus, protein self-assembly has been widely studied to shed light on the properties of fibrils and their intermediates. A still open question in the field concerns the microscopic processes that underlie the long-time behaviour and properties of amyloid fibrillar assemblies. Here, we use atomic force microscopy with angstrom-sensitivity to observe that amyloid fibrils undergo a maturation process, associated with an increase in both fibril length and thickness, leading to a decrease of their density, and to a change in their cross-ß sheet content. These changes affect the ability of the fibrils to catalyse the formation of new aggregates. The identification of these changes helps us understand the fibril maturation processes, facilitate the targeting of amyloid fibrils in drug discovery, and offer insight into the development of biocompatible and sustainable protein-based materials.

Differences in pharmacologic and demographic factors in male and female patients with vascular dementia, Alzheimer's disease, and mixed vascular dementia.

Background: Increasing evidence suggests that demographic and pharmacologic factors may play a significant role in the epidemiology of dementia. Sex differences in prevalence also depend on dementia subtypes, such as Alzheimer's dementia (AD), vascular dementia (VaD), and mixed vascular-Alzheimer's dementia (MVAD). Therefore, studies are needed to investigate sex-specific differences, and identify potential therapeutic targets for both sexes. Methods: Data was collected from the Prisma Health-Upstate Alzheimer's registry from 2016 to 2021 for 6,039 VaD patients, 9,290 AD patients, and 412 MVAD patients. A logistic regression was used to determine demographic and pharmacological factors associated with gender differences in patients with VaD, AD, and MVAD. Results: In patients with VaD, African Americans (OR = 1.454, 95% CI, 1.257-1.682, p < 0.001) with increasing age (OR = 1.023, 95% CI, 1.017-1.029, p < 0.001), treated with aripiprazole (OR = 4.395, 95% CI, 2.880-6.707, p < 0.001), were associated with females, whereas patients treated with galantamine (OR = 0.228, 95% CI, 0.116-0.449, p < 0.001), memantine (OR = 0.662, 95% CI, 0.590-0.744, p < 0.001), with a history of tobacco (OR = 0.312, 95% CI, 0.278-0.349, p < 0.001), and ETOH (OR = 0.520, 95% CI, 0.452-0.598, p < 0.001) were associated with males. Among AD patients, African Americans (OR = 1.747, 95% CI, 1.486-2.053, p < 0.001), and Hispanics (OR = 3.668, 95% CI, 1.198-11.231, P = 0.023) treated with buspirone (OR = 1.541, 95% CI, 1.265-1.878, p < 0.001), and citalopram (OR = 1.790, 95% CI, 1.527-2.099, p < 0.001), were associated with females, whereas patients treated with memantine (OR = 0.882, 95% CI, 0.799-0.974, p = 0.013), and with a history of tobacco (OR = 0.247, 95% CI, 0.224-0.273, p < 0.001), and ETOH (OR = 0.627, 95% CI, 0.547-0.718, p < 0.001) were associated with male AD patients. In patients with MVAD, rivastigmine (OR = 3.293, 95% CI, 1.131-9.585, p = 0.029), memantine (OR = 2.816, 95% CI, 1.534-5.168, p < 0.001), and risperidone (OR = 10.515, 95% CI, 3.409-32.437, p < 0.001), were associated with females while patients with an increased length of stay (OR = 0.910, 95% CI, 0.828-1.000, p = 0.049), with a history of tobacco (OR = 0.148, 95% CI, 0.086-0.254, p < 0.001) and ETOH use (OR = 0.229, 95% CI, 0.110-0.477, p < 0.001) were more likely to be associated with males. Conclusions: Our study revealed gender differences and similarities in the demographic and pharmacological factors of VaD, AD, and MVAD. Prospective studies are needed to determine the role of demographic and pharmacological factors in reducing sex-based disparities among VaD, AD, and MVAD patients.