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Neural Regeneration Research Jun 2024Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target...
Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury-specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research (in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc (AXER-204), fasudil, phosphatase and tensin homolog protein (PTEN) antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide, (-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.
PubMed: 38934397
DOI: 10.4103/NRR.NRR-D-24-00176 -
Heliyon Jun 2024Grapes are globally popular with wine production being one of the most well-known uses of grapes worldwide. Brazil has a growing wine industry, and the Serra Gaúcha...
Grapes are globally popular with wine production being one of the most well-known uses of grapes worldwide. Brazil has a growing wine industry, and the Serra Gaúcha region is a significant contributor to the country's wine production. Nonetheless, other states are increasing their relevance in this segment. Environmental factors and the soil microbiome (bacteria and fungi) heavily influence grape quality, shaping the crucial "" for wines. Here, soil quality was assessed through nutrient analysis and bacteria microbial diversity, which could significantly impact grape health and final wine attributes. Soil samples from São Paulo's vineyards, focusing on Syrah, Malbec, and Cabernet Sauvignon, underwent chemical and microbial analysis via 16S rRNA metabarcoding and highlighted significant differences in soil composition between vineyards. Statistical analyses including PCA and CAP showcased region-based separation and intricate associations between microbiota, region, and grape variety. Correlation analysis pinpointed microbial genera linked to specific soil nutrients. Random Forest analysis identified abundant bacterial genera per grape variety and the Network analysis revealed varied co-occurrence patterns, with Cabernet Sauvignon exhibiting complex microbial interactions. This study unveils complex relationships between soil microbiota, nutrients, and diverse grape varieties in distinct vineyard regions. Understanding how these specific microorganisms are associated with grapes can improve vineyard management, grape quality, and wine production. It can also potentially optimize soil health, bolster grapevine resilience against pests and diseases, and contribute to the unique character of wines known as .
PubMed: 38933974
DOI: 10.1016/j.heliyon.2024.e32283 -
Heliyon Jun 2024Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit.... (Review)
Review
Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit. Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms. Several reviews have been published regarding TMS-based ASD treatment, however, a systematic review on study characteristics, specific stimulating parameters, localization techniques, stimulated targets, behavioral outcomes, and neuroimage biomarker changes is lagged behind since 2018. Here, we performed a systematic search on literatures published after 2018 in PubMed, Web of Science, and Science Direct. After screening, the final systematic review included 17 articles, composing seven randomized controlled trial studies and ten open-label studies. Two studies are double-blind, while the other studies have a moderate to high risk of bias attributing to inadequate subject- and evaluator-blinding to treatment allocation. Five studies utilize theta-burst stimulation mode, and the others apply repetitive TMS with low frequency (five studies), high frequency (six studies), and combined low and high frequency stimulation (one study). Most researchers prioritize the bilateral dorsolateral prefrontal lobe as stimulation target, while parietal lobule, inferior parietal lobule, and posterior superior temporal sulci have also emerged as new targets of attention. One third of the studies use neuronavigation based on anatomical magnetic resonance imaging to locate the stimulation target. After TMS intervention, discernible enhancements across a spectrum of scales are evident in stereotyped behavior, repetitive behavior, and verbal social domains. A comprehensive review of literature spanning the last five years demonstrates the potential of TMS treatment for ASD in ameliorating the clinical core symptoms.
PubMed: 38933955
DOI: 10.1016/j.heliyon.2024.e32251 -
Frontiers in Genetics 2024The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: ), specifying the variant proline (P64) to histidine (H64), is known to...
INTRODUCTION
The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: ), specifying the variant proline (P64) to histidine (H64), is known to affect the protein's functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC).
MATERIALS AND METHODS
To deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome.
RESULTS
Firstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization.
CONCLUSION
Our study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies.
PubMed: 38933925
DOI: 10.3389/fgene.2024.1380495 -
Frontiers in Epidemiology 2024Despite several interventions on the control of cholera, it still remains a significant public health problem in Africa. According to the World Health Organization,...
INTRODUCTION
Despite several interventions on the control of cholera, it still remains a significant public health problem in Africa. According to the World Health Organization, 251,549 cases and 4,180 deaths (CFR: 2.9%) were reported from 19 African countries in 2023. Tools exist to enhance the surveillance of cholera but there is limited evidence on their deployment and application. There is limited evidence on the harmonization of the deployment of tools for the evaluation of cholera surveillance. We systematically reviewed available literature on the deployment of these tools in the evaluation of surveillance systems in Africa.
METHOD
Three electronic databases (PubMed, Medline and Embase) were used to search articles published in English between January 2012 to May 2023. Grey literature was also searched using Google and Google Scholar. Only articles that addressed a framework used in cholera surveillance in Africa were included. The quality of articles was assessed using the appropriate tools. Data on the use of surveillance tools and frameworks were extracted from articles for a coherent synthesis on their deployment.
RESULT
A total of 13 records (5 frameworks and 8 studies) were fit for use for this study. As per the time of the study, there were no surveillance frameworks specific for the evaluation of surveillance systems of cholera in Africa, however, five frameworks for communicable diseases and public health events could be adapted for cholera surveillance evaluation. None (0%) of the studies evaluated capacities on cross border surveillance, multisectoral one health approach and linkage of laboratory networks to surveillance systems. All (100%) studies assessed surveillance attributes even though there was no synergy in the attributes considered even among studies with similar objectives. There is therefore the need for stakeholders to harmoniously identify a spectrum of critical parameters and attributes to guide the assessment of cholera surveillance system performance.
PubMed: 38933896
DOI: 10.3389/fepid.2024.1353826 -
Frontiers in Nutrition 2024Crop yield and quality has increased globally during recent decades due to plant breeding, resulting in improved food security. However, climate change and shifts in... (Review)
Review
Crop yield and quality has increased globally during recent decades due to plant breeding, resulting in improved food security. However, climate change and shifts in human dietary habits and preferences display novel pressure on crop production to deliver enough quantity and quality to secure food for future generations. This review paper describes the current state-of-the-art and presents innovative approaches related to alien introgressions into wheat, focusing on aspects related to quality, functional characteristics, nutritional attributes, and development of novel food products. The benefits and opportunities that the novel and traditional plant breeding methods contribute to using alien germplasm in plant breeding are also discussed. In principle, gene introgressions from rye have been the most widely utilized alien gene source for wheat. Furthermore, the incorporation of novel resistance genes toward diseases and pests have been the most transferred type of genes into the wheat genome. The incorporation of novel resistance genes toward diseases and pests into the wheat genome is important in breeding for increased food security. Alien introgressions to wheat from e.g. rye and spp. have also contributed to improved nutritional and functional quality. Recent studies have shown that introgressions to wheat of genes from chromosome 3 in rye have an impact on both yield, nutritional and functional quality, and quality stability during drought treatment, another character of high importance for food security under climate change scenarios. Additionally, the introgression of alien genes into wheat has the potential to improve the nutritional profiles of future food products, by contributing higher minerals levels or lower levels of anti-nutritional compounds into e.g., plant-based products substituting animal-based food alternatives. To conclude, the present review paper highlights great opportunities and shows a few examples of how food security and functional-nutritional quality in traditional and novel wheat products can be improved by the use of genes from alien sources, such as rye and other relatives to wheat. Novel and upcoming plant breeding methods such as genome-wide association studies, gene editing, genomic selection and speed breeding, have the potential to complement traditional technologies to keep pace with climate change and consumer eating habits.
PubMed: 38933881
DOI: 10.3389/fnut.2024.1393357 -
Nanoscale Advances Jun 2024Nanostructuring in α-CuSe while optimizing carrier concentration holds the promise of realizing further high thermoelectric performance at near room temperature....
Nanostructuring in α-CuSe while optimizing carrier concentration holds the promise of realizing further high thermoelectric performance at near room temperature. Nevertheless, controlling the amounts of Cu vacancies, which work as acceptors, in nanostructures is considerably more intricate than in bulk materials. Hence, controlling the amounts of Cu vacancies while maintaining the α-phase and nanostructure shape poses a formidable challenge. In this study, we synthesized Cu Se nanowires (NWs) with various amounts of Cu vacancies at room temperature by the photoreduction method and investigated their thermoelectric properties. Cu Se NWs exhibited a comparable thermoelectric power factor to that of the polycrystalline films fabricated at higher temperature. The achievement of the high power factor despite low-temperature fabrication is attributed to the precise synthesis of Cu Se NWs with various amounts of Cu vacancies. We also investigated the reaction process of CuSe NWs in detail by observing the reaction intermediates. It was found that photoreduction occurred with Cu ions adsorbed on Se NWs, leading to the reaction of Cu ions and Se NWs without Cu deficiency. Namely, this photoreduction under the adsorbed conditions realized the control of Cu vacancies in Cu Se NWs.
PubMed: 38933852
DOI: 10.1039/d4na00156g -
Frontiers in Neuroscience 2024The Human Connectome Project (HCP) has become a keystone dataset in human neuroscience, with a plethora of important applications in advancing brain imaging methods and...
INTRODUCTION
The Human Connectome Project (HCP) has become a keystone dataset in human neuroscience, with a plethora of important applications in advancing brain imaging methods and an understanding of the human brain. We focused on tractometry of HCP diffusion-weighted MRI (dMRI) data.
METHODS
We used an open-source software library (pyAFQ; https://yeatmanlab.github.io/pyAFQ) to perform probabilistic tractography and delineate the major white matter pathways in the HCP subjects that have a complete dMRI acquisition ( = 1,041). We used diffusion kurtosis imaging (DKI) to model white matter microstructure in each voxel of the white matter, and extracted tract profiles of DKI-derived tissue properties along the length of the tracts. We explored the empirical properties of the data: first, we assessed the heritability of DKI tissue properties using the known genetic linkage of the large number of twin pairs sampled in HCP. Second, we tested the ability of tractometry to serve as the basis for predictive models of individual characteristics (e.g., age, crystallized/fluid intelligence, reading ability, etc.), compared to local connectome features. To facilitate the exploration of the dataset we created a new web-based visualization tool and use this tool to visualize the data in the HCP tractometry dataset. Finally, we used the HCP dataset as a test-bed for a new technological innovation: the TRX file-format for representation of dMRI-based streamlines.
RESULTS
We released the processing outputs and tract profiles as a publicly available data resource through the AWS Open Data program's Open Neurodata repository. We found heritability as high as 0.9 for DKI-based metrics in some brain pathways. We also found that tractometry extracts as much useful information about individual differences as the local connectome method. We released a new web-based visualization tool for tractometry-"Tractoscope" (https://nrdg.github.io/tractoscope). We found that the TRX files require considerably less disk space-a crucial attribute for large datasets like HCP. In addition, TRX incorporates a specification for grouping streamlines, further simplifying tractometry analysis.
PubMed: 38933816
DOI: 10.3389/fnins.2024.1389680 -
Frontiers in Veterinary Science 2024Intracapsular reconstruction (ICR) has long been recommended as a treatment for cranial cruciate ligament deficiency (CCLD) in dogs, but it has fallen out of favor due...
Intracapsular reconstruction (ICR) has long been recommended as a treatment for cranial cruciate ligament deficiency (CCLD) in dogs, but it has fallen out of favor due to its inferior long-term functional outcomes. These outcomes may be attributed to the poor stiffness and strength of the graft in the early period before ligamentization is completed. Additional placement of extracapsular sutures to mechanically protect the graft during the ligamentization process may be a viable method to address this problem. However, the biomechanical effect of this combined surgical approach remains unknown. This study aimed to evaluate the 3D kinematics of the CCLD stifle in dogs in response to ICR and combined extra- and intracapsular reconstruction (CEICR). Twelve hindlimbs were collected from nine cadavers of mature dogs. The limbs were tested using a custom-made testing apparatus that reproduces their sagittal plane kinematics during the stance phase. Four statuses of stifle joints were tested, namely, (a) cranial cruciate ligament (CCL) intact; (b) CCLD; (c) CCLD stifle stabilized by CEICR; and (d) CCLD stifle stabilized by ICR only. Three-dimensional stifle kinematics at the 5 instances of the stance phase were measured with an optoelectronic system. The results showed that ICR marginally corrects the increased adduction, internal rotation, and caudodistal stifle joint center displacement that occur as a result of CCLD. CEICR led to better restoration of the stifle kinematics, especially with respect to the internal rotation and cranial translation stabilities. Furthermore, CEICR only resulted in minor excessive restraints on other motion components. The findings indicated that the additional lateral fabellotibial suture offers immediate stability to the stifle, consequently lowering the risk of graft over-elongation in the short term postoperatively. Considering the propensity for the extracapsular suture to degrade over time, further studies are warranted to explore the long-term effects of the CEICR procedure.
PubMed: 38933704
DOI: 10.3389/fvets.2024.1336797 -
Trauma Surgery & Acute Care Open 2024The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials...
BACKGROUND
The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials focusing on traumatic injury. In the setting of prehospital traumatic injury trials, no literature currently exists analyzing the clinical implications of AEs and their associations with mortality and morbidity. We sought to analyze AEs from three prehospital hemorrhagic shock trials and characterize their time course, incidence, severity, associated clinical outcomes, and relatedness.
METHODS
We performed a secondary analysis of three prehospital randomized clinical trials. We analyzed AEs at both the patient level as well as the individual AE level. We categorized patients who had no AEs, a single documented AE and those with multiple events (>1 AE). We characterized AE timing, severity, relatedness and attributable mortality outcomes.
RESULTS
We included 1490 patients from the three harmonized clinical trials, with 299 (20.1%) individual patients having at least a single AE documented with 529 AEs documented overall as a proportion of patients had multiple events. Over 44% of patients had a death-related misclassified AE. Patients with at least a single documented AE had a significantly higher 28-day mortality (log-rank χ=81.27, p<0.001) compared with those without an AE documented. Patients with a single AE had a significant higher mortality than those with multiple AEs, potentially due to survival bias (log-rank χ=11.80, p=0.006). When relatedness of each individual AE was characterized, over 97% of AEs were classified as 'definitely not related' or 'probably not related' to the intervention.
CONCLUSIONS
AEs in hemorrhagic shock trials are common, occur early and are associated with mortality and survival bias. The potential for inaccurate reporting exists, and education and training remain essential for appropriate treatment arm comparison. The current results have important relevance to injury-related clinical trials.
TRIAL REGISTRATION NUMBERS
NCT01818427, NCT02086500 and NCT03477006.
LEVEL OF EVIDENCE
II.
PubMed: 38933603
DOI: 10.1136/tsaco-2024-001465