Metabolomics evaluation of the photochemical impact of violet-blue light (405 nm) on ex vivo platelet concentrates.

INTRODUCTION: Microbicidal violet-blue light in the visible spectrum (405 nm) has been under evaluation for pathogen inactivation in ex vivo human plasma and platelets (PLTs) stored in plasma. Results to date have demonstrated that several blood-borne infectious disease-causing pathogens can be successfully reduced to significantly low levels in the light-treated plasma and PLTs. METHOD: In order to evaluate whether the microbicidal 405 nm light is safe for the treatment of PLT concentrates for pathogen inactivation, LC/MS-based metabolomics analyses were performed to evaluate the overall impact of 405 nm violet-blue light treatment on ex vivo PLT concentrates suspended in plasma and on plasma itself, and to identify metabolome changes in intra-platelet and extra-cellular medium (i.e., plasma). RESULTS: The metabolomics data identified that platelet activating factors (PAFs), agonists and prostaglandins, which can influence PLT basic functions such as integrity, activation, and aggregation potential were unaltered, suggesting that 405 nm light illumination is safe regarding PLT basic functions. Distinct increases in hydroxyl fatty acids and aldehydes, as well as decreases in antioxidant metabolites indicated that reactive oxygen species (ROS) were generated at high levels after only one hour of exposure to 405 nm light. Distinctly changed endogenous photosensitizer metabolites after 1 h of light exposure provided good evidence that 405 nm light was an effective microbicide acting through ROS mechanism and no external additive photosensitizers were required.

Functional consequences and health-care seeking behaviour for recurrent non-specific low back pain in Zimbabwean adolescents: a cross-sectional study.

PURPOSE: The purpose of the study was to investigate the consequences of recurrent non-specific low back pain in Zimbabwean adolescents. Recurrent non-specific low back pain is a common cause of adult disability in low-income countries. However, its impact in adolescents has been a matter of debate in the literature. METHODS: A survey was conducted using a cluster sample of 544 school children between the ages of 13 and 19 years. The school children were randomly selected from government-administered secondary schools in Harare, Zimbabwe. RESULTS: Parental and students' response rate were 90.3 and 97.8 %, respectively. Almost a third (28.8 %) of school children reported recurrent symptoms (CI 27.8-31.6). However, the majority (84 %) of these cases were unknown to parents. Twenty-seven percent reported having sought medical treatment. On the nine-item Hanover Low Back Pain Disability Questionnaire, 71.2 % of school children had at least one activity of daily living compromised by recurrent NSLBP, especially sports participation. However, severe disability was reported in 28 % of the adolescents. Health-care seeking behaviour was not associated with the level of disability [χ (2)(1) = 0.36, p = 0.55]. CONCLUSION: Although most parents are unaware, recurrent NSLBP is common in Zimbabwean school children. However, treatment is rarely sought for the symptoms. A preponderance of adolescents with recurrent NSLBP experiences some degree of functional consequences, although severe disability is rare. There is need to raise awareness of the condition in schools and to parents. Spinal health educational programmes may need to be implemented to avert the functional consequences. Further studies are needed in the future to investigate the coping strategies for pain in adolescents.

Comprehensive in silico analysis of prolactin receptor (PRLR) gene nonsynonymous single nucleotide polymorphisms (nsSNPs) reveals multifaceted impact on protein structure, function, and interactions.

This study delves into the functional and structural implications of non-synonymous single nucleotide polymorphisms (nsSNPs) within the Prolactin Receptor (PRLR) gene. Thirteen deleterious nsSNPs were identified through bioinformatics tools, with SIFT predicting 168 out of 395 nsSNPs as detrimental, exhibiting tolerance index (TI) scores ranging from 0 to 0.05. Polyphen2 assigned likelihood scores >0.99 to all 13 nsSNPs, indicating high probability of harm, while Panther scores classified most nsSNPs as 'probably damaging', with specific mutations like W218R scoring 0.74, suggesting a higher impact. Stability analysis using DDG I-Mutant and DDG Mupro consistently predicted decreased stability for all mutations, with CUPSAT indicating mutations like V125G and W218R significantly decreasing stability. Structural analysis through DynaMut predicted destabilization for all mutations except L196I and L292H. MutPred2 highlighted structural alterations for all nsSNPs except L196I, L293V, R315W, and S353N. Domain analysis revealed key mutations within essential functional domains, with five nsSNPs located within Fibronectin type-III domains. Bayesian analysis through ConSurf identified 9 critical residues, with 11 nsSNPs exhibiting notably high conservation. STRING analysis unveiled a complex interaction network, indicating involvement in vital biological processes like lactation. Molecular dynamics (MD) simulations, spanning 100 nanoseconds, elucidated structural dynamics induced by detrimental missense SNPs. Post-translational modification (PTM) analysis identified specific mutations, such as R351, involved in methylation, while S353 was implicated in phosphorylation and glycosylation. These findings offer comprehensive insights into the molecular and phenotypic effects of deleterious nsSNPs in the PRLR gene, crucial for selective breeding.Communicated by Ramaswamy H. Sarma.

Aesthetic and Functional Consequences of Spreader Graft without Suturing To the Upper Lateral Nasal Cartilage: A Randomized Double-Blinded Clinical Trial.

Background: Considering the importance of the spreader graft technique in order to prevent collapse and airway retention and the importance of its effect on the dorsal aesthetic line and nasal width, in this study we compared the outcome of suturing spreader graft to septum _upper lateral cartilageas the classic technique to suturing spreader graft only to septum. Methods: This comparative observational study was conducted on 50 consecutive patients referred to Rhinoplasty Department in 15 khordad Hospital from 2019 - 2020 . The study participants were randomly assigned into two groups which scheduling the new spreader graft technique without suturing the upper lateral cartilage (n = 25) or the frequent spreader graft technique with suturing to both septum and upper lateral nasal cartilage (n = 25). The nasal obstruction degree, the status and health-related quality of life, patients' satisfaction, and subjective mental image of the nasal structure were the study endpoint. The patients were followed-up for six months. Results: The two groups were matched for gender and age. Although all study endpoints significantly improved in both groups, but the six-month trend of the change in each parameter was different in the two groups with superior improvement in those who planned for spreader graft technique without suturing the upper lateral cartilage. Conclusion: In patients scheduling for selective rhinoplasty, new procedural technique including spreader graft without suturing to upper lateral cartilage can lead to more postoperative favorable outcome with regard to patients' satisfaction of the procedure, lack of obstructive symptoms, aesthetic feature, and health-related quality of life as compared to suturing to both septum and upper lateral cartilage.

The psychosocial work environment, musculoskeletal disorders and their functional consequences among pediatric healthcare providers.

OBJECTIVE: The goal of this study was to examine the association between aspects of the psychosocial work environment and prevalence of musculoskeletal disorders (MSDs) and associated functional consequences among pediatric healthcare providers. BACKGROUND: The psychosocial work demands make pediatric care providers susceptible to MSDs and subsequent functional consequences, but research on this at-risk group is lacking. METHODS: Randomly selected pediatric registered nurses, behavioral health specialists, and patient care assistants (N = 569) completed a survey assessing psychosocial factors, MSDs, and functional consequences (e.g., missing work). Logistic regression was used to assess associations between psychosocial factors and outcomes. RESULTS: The analysis yielded moderate-to-strong, significant associations between psychosocial environment factors and MSDs and their functional consequences. The odds of MSDs increased nearly three-fold in the highest quartile of the psychosocial summary score vs. the lowest (OR: 2.7, 95% CI: 1.6-4.5). The highest quartiles of the psychosocial environment measures were significantly associated with functional consequences of MSDs. CONCLUSION: Results confirm knowledge about the association between the psychosocial environment and MSDs and demonstrates the association also exists among pediatric providers. Our study highlights the importance of studying the functional consequences of MSDs, which characterize the impact of MSD burden at work and elsewhere.

Methods of epigenome editing for probing the function of genomic imprinting.

The curious patterns of imprinted gene expression draw interest from several scientific disciplines to the functional consequences of genomic imprinting. Methods of probing the function of imprinting itself have largely been indirect and correlational, relying heavily on conventional transgenics. Recently, the burgeoning field of epigenome editing has provided new tools and suggested strategies for asking causal questions with site specificity. This perspective article aims to outline how these new methods may be applied to questions of functional imprinting and, with this aim in mind, to suggest new dimensions for the expansion of these epigenome-editing tools.

Structural and functional consequences of succinate dehydrogenase subunit B mutations.

Mitochondrial dysfunction, due to mutations of the gene encoding succinate dehydrogenase (SDH), has been implicated in the development of adrenal phaeochromocytomas, sympathetic and parasympathetic paragangliomas, renal cell carcinomas, gastrointestinal stromal tumours and more recently pituitary tumours. Underlying mechanisms behind germline SDH subunit B (SDHB) mutations and their associated risk of disease are not clear. To investigate genotype-phenotype correlation of SDH subunit B (SDHB) variants, a homology model for human SDH was developed from a crystallographic structure. SDHB mutations were mapped, and biochemical effects of these mutations were predicted in silico. Results of structural modelling indicated that many mutations within SDHB are predicted to cause either failure of functional SDHB expression (p.Arg27*, p.Arg90*, c.88delC and c.311delAinsGG), or disruption of the electron path (p.Cys101Tyr, p.Pro197Arg and p.Arg242His). GFP-tagged WT SDHB and mutant SDHB constructs were transfected (HEK293) to determine biological outcomes of these mutants in vitro. According to in silico predictions, specific SDHB mutations resulted in impaired mitochondrial localisation and/or SDH enzymatic activity. These results indicated strong genotype-functional correlation for SDHB variants. This study reveals new insights into the effects of SDHB mutations and the power of structural modelling in predicting biological consequences. We predict that our functional assessment of SDHB mutations will serve to better define specific consequences for SDH activity as well as to provide a much needed assay to distinguish pathogenic mutations from benign variants.

Glial Tau Pathology in Tauopathies: Functional Consequences.

Tauopathies are a class of neurodegenerative diseases characterized by the presence of hyperphosphorylated and aggregated tau pathology in neuronal and glial cells. Though the ratio of neuronal and glial tau aggregates varies across diseases, glial tau aggregates can populate the same degenerating brain regions as neuronal tau aggregates. While much is known about the deleterious consequences of tau pathology in neurons, the relative contribution of glial tau pathology to these diseases is less clear. Recent studies using a number of model systems implicate glial tau pathology in contributing to tauopathy pathogenesis. This review aims to highlight the functional consequences of tau overexpression in glial cells and explore the potential contribution of glial tau pathology in the pathogenesis of neurodegenerative tauopathies.