Restoration of RPGR expression in vivo using CRISPR/Cas9 gene editing.

Mutations in the gene for Retinitis Pigmentosa GTPase Regulator (RPGR) cause the X-linked form of inherited retinal degeneration, and the majority are frameshift mutations in a highly repetitive, purine-rich region of RPGR known as the OFR15 exon. Truncation of the reading frame in this terminal exon ablates the functionally important C-terminal domain. We hypothesized that targeted excision in ORF15 by CRISPR/Cas9 and the ensuing repair by non-homologous end joining could restore RPGR reading frame in a portion of mutant photoreceptors thereby correcting gene function in vivo. We tested this hypothesis in the rd9 mouse, a naturally occurring mutant line that carries a frameshift mutation in RPGRORF15, through a combination of germline and somatic gene therapy approaches. In germline gene-edited rd9 mice, probing with RPGR domain-specific antibodies demonstrated expression of full length RPGRORF15 protein. Hallmark features of RPGR mutation-associated early disease phenotypes, such as mislocalization of cone opsins, were no longer present. Subretinal injections of the same guide RNA (sgRNA) carried in AAV sgRNA and SpCas9 expression vectors restored reading frame of RPGRORF15 in a subpopulation of cells with broad distribution throughout the retina, confirming successful correction of the mutation. These data suggest that a simplified form of genome editing mediated by CRISPR, as described here, could be further developed to repair RPGRORF15 mutations in vivo.

Post-COVID-19 effect on biochemical parameters in children: Should we take heed?

The aim of this research is to analyze the potential impact of the COVID-19 infection on the serum biochemical concentration of children 6 months after recovery from the infection. The study included 72 children with a median age of 11 years. The case group consisted of 37 children who had contracted COVID-19 6 months prior to the analysis. They reported no other pre- or post-covid chronic or systemic diseases. The control group consisted of 35 children who had no prior record of COVID-19 infection. The analysis showed a substantial variation (P = 0.026) in the mean urea values (mmol/L) between the case group (4.513 ± 0.839) and the control group (5.425 ± 1.173). However, both groups' urea levels were within the normal range of their age group. No statistical differences were found analyzing the variations between the two groups in the levels of LDH, AST, ALT, BiliT, GGT, AlbBCG2, CRP, CK, AlKP, UA, Phos, Crea2, Gluc, Ca, Na, K, Cl, TP, TC, TG, and HDL (P > 0.05). The DMFT score was substantially greater (P < 0.002) in the infected team (5.38 ± 2.841) in comparison to the non-infected group (2.6 ± 2.257). The study indicates that COVID-19 infection does not leave biochemical alterations among children who did not have pre-existing conditions. The biochemical analysis suggests that children recover better than adults from COVID-19. Furthermore, it calls for investigating non-lethal COVID-19 infection as a tool to discover underlying conditions. The DMFT score shows a correlation between COVID-19 infection and caries. However, the nature of the correlation is yet to be investigated.

"Scie-losophy" a teaching and learning framework for the reconciliation of the P4C and the scientific method.

Today's students face new challenges that demand high levels of intelligence and meta-thinking skills. Science-based educational pedagogies like STEM, 5E's, and discovery-based education have earned a strong reputation for nurturing children's reasoning and critical thinking skills. However, there's a need for them to be more open and conceptual in order to better prepare students for modern life's challenges. The realms of philosophical and scientific-based educational models currently dominate the educational arena. In retrospect, both models have inherent values that would benefit learners. It is beneficial to examine both methods to develop a teaching framework that fosters higher-order thinking, metacognition, and problem-solving skills. The objective of this paper is to delve into the essenceof the philosophy for children (P4C) method in comparison with the scientific method and their impact onstudents' learning. Using the six reasoning strands, I will systematically compare the two models for strengths and similarities. Throughout this comparison, I aim to maintain objectivity by by drawing on references and practical experience, avoiding any undue bias in favor of one model over the other. Subsequently, by applyingTrompenaars Hampden-Turner™ dilemmas reconciliation model, I will propose the Scie-losophy model, which represents reconciliation between the two methods for the benefit of the learner and the greater good of society. •Currently, philosophical, and scientific-based education models dominate the educational arena. Both models have inherent values that would benefit learners.•Adopting one approach above the other will yield less than optimal results. I strongly discourage following a saturated educational system in which one of the two methods is used exclusively.•I propose a model that represents reconciliation between the two methods for the benefit of the learner and the interest of society.

Correlation of serum biochemical parameters and saliva pH in healthy individuals.

Saliva has the potential to work alongside needles in standard medical diagnosis. Yet the number of studies aimed at deciphering the biochemical communication between saliva and the rest of the body's systems is still very limited. The aim of this study is to investigate the interfluid interaction between saliva and serum by determining the correlation between saliva pH and serum biochemical parameters under mild conditions. Ultimately, using saliva may provide a stress-free diagnostic tool, but more ambitiously, the pH of saliva could present a genuine cost-effective screening tool that may immensely benefit areas with limited access to health care and diagnostic labs. Saliva and blood samples were collected from 43 randomly selected children (7-12 years), living in Jeddah, free from obesity and chronic or systemic body and mouth diseases. A complete serum biochemical analysis was performed, and the salivary pH of all samples was measured immediately at the time of collection. The correlations between saliva pH and serum biochemical parameters were investigated using Univariate and multiple linear regression models. Our results showed that pH has a weak significant positive correlation with total protein and a negative weak significant correlation with urea. Weak correlations suggest the existence of more serum factors to be investigated for their effect on the pH using a stepwise multiple linear regression. The multiple linear models' calculated saliva pH values were close to the measured values, demonstrating its possible capacity to predict saliva pH using serum parameters. The regression model's successful prediction of saliva pH using serum biochemicals reflects the significant correlations between the body fluids' parameters and invites more research to elucidate these relationships.