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Background: Traumatic brain injury (TBI) is considered a major cause of death globally, resulting from trauma. Decompressive craniectomy (DC) may improve functional outcomes in patients with TBI and its associated complications. This study was designed to determine safety and efficacy of DC in improving clinical outcomes in TBI patients compared to standard therapy., Methods: A systematic search was conducted across six electronic databases to identify relevant randomized controlled trials (RCTs) examining decompressive craniotomy (DC) and traumatic brain injury (TBI) from database inception until March 2021. The pooled risk ratio was estimated for categorical outcomes, while the pooled standardized mean difference with a 95% confidence interval was calculated for continuous outcomes. Statistical analysis software, including RevMan 5.4 and STATA version 17, was employed to perform this meta-analysis. The protocol for this study is registered with the OSF registry, ensuring transparency and reproducibility., Results: A total of 656 studies were screened, and five RCTs involving 665 subjects (334 in the DC group and 331 in the control group) were included in this meta-analysis. Our meta-analysis revealed a non-significant trend towards a higher rate of favorable clinical outcomes in subjects who underwent DC compared to those in the medical treatment (MT) group (risk ratio (RR) 1.20, 95% confidence interval (CI) 0.70 to 2.08, P = 0.50). In contrast, the mortality rate was significantly lower in patients treated with DC compared to those receiving MT alone (RR 0.58, 95% CI 0.47 to 0.73, P < 0.001). Additionally, intracranial pressure (ICP) levels were significantly lower in subjects who underwent DC compared to those receiving MT alone (standardized mean difference (SMD): - 0.87, 95% CI - 1.58 to - 0.16, P = 0.02). Furthermore, there was a statistically significant reduction in the duration of stay in the DC group compared to the MT alone group (SMD: - 1.18, 95% CI - 1.49 to - 0.86, P < 0.001)., Conclusion: This study presents evidence suggesting that DC is linked to a lower mortality rate, decreased ICP, and shorter hospital stays among patients with moderate to severe TBI. However, it did not show a significant impact on improving favorable clinical outcomes., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: An ethics statement is not applicable because this study is based exclusively on published literature., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Interleukin-1-receptor-associated kinase 4 (IRAK4) possesses a crucial function in the toll-like receptor (TLR) signaling pathway, and the dysfunction of this molecule could lead to various infectious and immune-related diseases in addition to cancers. IRAK4 genetic variants have been linked to various types of diseases. Therefore, we conducted a comprehensive analysis to recognize the missense variants with the most damaging impacts on IRAK4 with the employment of diverse bioinformatics tools to study single-nucleotide polymorphisms' effects on function, stability, secondary structures, and 3D structure. The residues' location on the protein domain and their conservation status were investigated as well. Moreover, docking tools along with structural biology were engaged in analyzing the SNPs' effects on one of the developed IRAK4 inhibitors. By analyzing IRAK4 gene SNPs, the analysis distinguished ten variants as the most detrimental missense variants. All variants were situated in highly conserved positions on an important protein domain. L318S and L318F mutations were linked to changes in IRAK4 secondary structures. Eight SNPs were revealed to have a decreasing effect on the stability of IRAK4 via both I-Mutant 2.0 and Mu-Pro tools, while Mu-Pro tool identified a decreasing effect for the G198E SNP. In addition, detrimental effects on the 3D structure of IRAK4 were also discovered for the selected variants. Molecular modeling studies highlighted the detrimental impact of these identified SNP mutant residues on the druggability of the IRAK4 ATP-binding site towards the known target inhibitor, HG-12-6, as compared to the native protein. The loss of important ligand residue-wise contacts, altered protein global flexibility, increased steric clashes, and even electronic penalties at the ligand-binding site interfaces were all suggested to be associated with SNP models for hampering the HG-12-6 affinity towards IRAK4 target protein. This given model lays the foundation for the better prediction of various disorders relevant to IRAK4 malfunction and sheds light on the impact of deleterious IRAK4 variants on IRAK4 inhibitor efficacy.

Salinity and cadmium (Cd) contamination of soil are serious environmental issues threatening food security. This study investigated the role of salicylic acid (SA) and potassium (K) in enhancing the resilience of quinoa against the combined stress of salinity and Cd. Quinoa plants were grown under NaCl (0, 200 mM) and Cd (0, 100 µM) stress, with the addition of 0.1 mM SA and 10 mM K, separately or in combination. The joint stress of Cd and NaCl caused >50% decrease in plant growth, chlorophyll contents, and stomatal conductance compared to the control plants. The higher accumulation of Na and Cd reduced the uptake of K in quinoa tissues. The joint stress of salinity and Cd caused an 11-fold increase in hydrogen peroxide and 13-fold increase in thiobarbituric acid reactive substances contents, and caused a 61% decrease in membrane stability. An external supply of 0.1 mM SA and 10 mM K helped plants to better adapt to salinity and Cd stress with less of a reduction in plant biomass (shoot 19% and root 24%) and less accumulation of Na and Cd in plant tissues. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) were enhanced by 11-fold, 10-fold, 7.7-fold, and 7-fold, respectively, when SA and K were applied together to the plants subjected to the joint stress of Cd and salinity. Based on the values of the bioconcentration factor (>1), the translocation factor (<1), and the higher tolerance index, it was clear that Cd-contaminated, salty soils could be stabilized with quinoa under the combined supply of SA and K.

Background : Mammalian WD-repeat protein 12 (WDR12), a family member of proteins containing repeats of tryptophan-aspartic acid (WD), is a potential homolog of yeast Ytm1p and consists of seven repeats of WD. Aim of the study : This study aims to investigate the potential oncogenic effects of WDR12 in various human malignancies throughout a pan-cancer analysis that has been carried out to examine the various patterns in which this gene is expressed and behaves in tumor tissues. Methods : Herein, we used The Cancer Genome Atlas (TCGA) and various computational tools to explore expression profiles, prognostic relevance, genetic mutations, immune cell infiltration, as well as the functional characteristics of WDR12 in multiple human cancers. Results : We found that WDR12 was inconsistently expressed in various cancers and that variations in WDR12 expression predicted survival consequences for cancer patients. Furthermore, we observed a significant correlation between WDR12 gene mutation levels and the prognosis of some tumors. Furthermore, significant correlations were found between WDR12 expression patterns and cancer-associated fibroblast (CAF) infiltration, myeloid-derived suppressor cells (MDSCs), tumor mutation burden, microsatellite instability and immunoregulators. Ultimately, pathway enrichment analysis revealed that WDR12-related pathways are involved in carcinogenesis. Conclusions : The findings of our study are stisfactory, demonstrating that WDR12 could serve as a promising reliable prognostic biomarker, as well as a therapeutic target for novel cancer therapeutic approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Eid, Eldeen, Soltan, Al-Shraim, Aldehri, Alqahtani, Alsharif, Albogami, Jafri, Fayad, Park, Bibi, Behairy, Kim and Zaki.)

Fornix deep brain stimulation (DBS) has the ability to refurbish memory functions in animal models with experimental dementia. One of the possible underlying mechanisms is the acute increase of acetylcholine in the hippocampus. Another suggested hypothesis is neuroplasticity. Recent work in rats has shown that acute fornix DBS can modulate neurotrophic factors as well as synaptic plasticity markers on the short-term. Here, we want to test the hypothesis that acute fornix DBS can also lead to long-term effects on neuroplasticity. Rats received DBS at 100 Hz, 100 μA and 100 μs pulse width for 4 h with electrodes placed bilaterally in the fornix. Seven weeks after stimulation, rats were sacrificed. BDNF, p-CREB, SV2 and synaptophysin immunohistochemistry was performed for their brains. No differences were found in the number of BDNF, p-CREB or SV2 positive cells for fornix DBS rats when compared to sham. Surprisingly, the density of synaptophysin immunoreactive presynaptic boutons was significantly decreased in the CA1 and CA3 subregion of the hippocampus for DBS rats. Therefore, fornix DBS might induce long-term depression related mechanisms., (Copyright © 2018. Published by Elsevier B.V.)

Background: Dementia is among the leading causes of severe and long-term disability worldwide, decreasing the quality of life of individuals and families. Moreover, it induces an enormous economic burden on societies. The most prevalent cause of dementia is Alzheimer's disease (AD). Because current treatment options for AD are limited, deep brain stimulation (DBS) has been considered., Methods: The aim of this review is to survey the current understanding regarding the effects of DBS in AD and possibly shed light on the mechanisms of DBS in AD. We searched PubMed and Cochrane for various studies in English literature describing DBS in patients with AD and relevant preclinical studies. All related studies published from December 2013 to March 2017 were included in this review., Results: Our understanding of the neural circuitry underlying learning and memory in both rodent models and human patients has grown over the past years and provided potential therapeutic targets for DBS such as the fornix and the nucleus basalis of Meynert. Clinical results indicate that DBS is most beneficial for patients who are in the early stages of AD. Potential mechanisms of action of DBS in AD comprise long-term structural plasticity, including hippocampal enlargement as well as enhanced neurotransmitter release., Conclusion: It is still premature to conclude that DBS can be used in the treatment of AD, and the field will wait for the results of ongoing and future clinical trials., Competing Interests: There are no conflicts of interest.