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Fahad Albalawi,1,2,* Mohd Zobir Hussein,2,* Sharida Fakurazi,3,4 Mas Jaffri Masarudin5 1Department of Medical Laboratory and Blood Bank, King Fahad Specialist Hospital-Tabuk, Tabuk, Saudi Arabia; 2Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 3Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 4Natural Medicine and Product Research Laboratory Institute of Bioscience, Serdang, Selangor, Malaysia; 5Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia*These authors contributed equally to this workCorrespondence: Mohd Zobir Hussein Email mzobir@upm.edu.myAbstract: The emergence of nanotechnology as a key enabling technology over the past years has opened avenues for new and innovative applications in nanomedicine. From the business aspect, the nanomedicine market was estimated to worth USD 293.1 billion by 2022 with a perception of market growth to USD 350.8 billion in 2025. Despite these opportunities, the underlying challenges for the future of engineered nanomaterials (ENMs) in nanomedicine research became a significant obstacle in bringing ENMs into clinical stages. These challenges include the capability to design bias-free methods in evaluating ENMs’ toxicity due to the lack of suitable detection and inconsistent characterization techniques. Therefore, in this literature review, the state-of-the-art of engineered nanomaterials in nanomedicine, their toxicology issues, the working framework in developing a toxicology benchmark and technical characterization techniques in determining the toxicity of ENMs from the reported literature are explored.Keywords: engineered nanomaterials, nanomedicine, nanotoxicology, particle tracking analysis, asymmetric flow field-flow fractionation, Taylor dispersion analysis

The application of Model-Free Predictive Control (MFPC) in power electronic systems has garnered increasing attention. In this paper, MFPC control based on replacing the classical factory model with an ultra-local model (ULM) is studied. Generally, the Integral Sliding Mode Observer (ISMO) is used to estimate the unknown part in the ULM where the non-physical factor in the ULM is selected with approximate values ​​ranging from the nominal value of the system which is contrary to the concept of MFPC control. In this research, an improved adaptive integral sliding mode observer (AISMO) based MFPC (AISMO-MFPC ) is proposed to estimate this factor with the unknown function in the ULM equation. The new observer design enables the estimation of this factor based on the current error, which allows for independent prposedcontrol of the system parameters.To obtain the lowest current ripple, the concept of active vector execution time (AVET ) has been incorporated into the proposed control where two vectors are selected in the sampling period to minimize the cost function instead of selecting a single vector. ULM is also used to calculate AVET which facilitates the implementation of the imposed control. The combination of the proposed AISMO-MFPC and AVET gives faster system response and reduces the current ripple and lower harmonics, especially in case of mismatch parameters. Finally, the effectiveness of the proposed control is confirmed under various conditions by the presented simulation and experimental results., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

An adequate bedload prediction is a challenging task in hydraulic engineering because of the complex sediment transport processes and corresponding environmental factors. The current study introduces a novel comparative ensemble approach using metaheuristic machine learning (ML) models to enhance the accuracy of bedload prediction using data from laboratory flume experiments. To uncover key insights in bedload transport prediction, several models are employed, such as K-Nearest Neighbours (KNN), Extra Trees Regressor (ETR), Linear Regression (LR), Random Forest (RF), Bagging Regressor (BR), and XGBoost (XGB). The coefficient of determination (R 2 ) and root mean square error (RMSE) values vary between various models; however, XGB showed R 2  = 0.99 and RMSE = 0.11. The sensitivity analysis emphasizes the crucial role of the Shields parameter in bedload prediction, while the SHAP analysis highlights the substantial influence of the XGB model in enhancing predictive accuracy. The REC curves show that BR, XGB, and RF, outperformed KNN and LR models. Furthermore, a graphical user interface has also been developed to facilitate user interaction with the predictive models, allowing for easier visualization, analysis, and interpretation of bedload transport predictions. Additionally, k-fold cross-validation was performed to assess the performance, consistency and robustness of the ML models. Thus, it can be concluded from the current study that the utilization of ML algorithms can improve accuracy, providing valuable insights for hydraulic engineers and highlighting the importance of ML models in civil engineering practices, particularly in bedload transport prediction., (© 2024. The Author(s).)

Background: Oral Submucous Fibrosis (OSMF) is an oral potentially malignant disorder (OPMD) that commonly occurs in the South Asian population as there is high usage of areca nut. There has been extensive research on the pathogenesis and treatment of this condition. It is well-established in the scientific literature that mast cells (MC) have a definitive role in several inflammatory disorders. OSMF being a chronic inflammatory disorder, is also expected to have increased MCs. Hence, this review aims to evaluate the role of MCs in the pathogenesis of OSMF., Methods: A systematic search of articles was performed by two of the authors independently in PubMed, Scopus, Embase, Web of Science, and Google Scholar using the appropriate keywords and Boolean terms. The risk of bias was assessed using the Modified Newcastle-Ottawa Scale. The meta-analysis was performed with R studio software (Version: 4.4.0, Year: 2024, Company: The R foundation for statistical computing)., Results: The search retrieved 36 studies, of which 16 were suitable for the review. There is evidence for a marked increase in the number of MCs in OSMF than the normal mucosa upon analyzing the retrieved articles. However, when comparing the grades of OSMF, there are variations in the reports. As all the retrieved articles were case-control studies, the risk of bias was analyzed using the Modified New Castle Ottawa Scale. All the studies scored in the good category (Score 6-9). The pooled effect size shows the Standard Mean Deviation (SMD) to be 0.09, 95% confidence interval (CI) [-0.18;0.37] to lie on either side of no effect. Hence the role of MCs in OSMF has not been established because of homogeneity and consistent sampling error., Conclusion: Our systematic review does suggest a definitive role of mast cells in the progression of OSMF. However, there is a lack of methodological rigor in the included studies. This may contribute to diluting the results., (© 2024. The Author(s).)

Cytokine IL-1β is an early component of inflammatory cascades, with both priming and activation steps required before IL-1β release. Here, the P2X7 receptor (P2X7R) for ATP was shown to both prime and release IL-1β from retinal microglial cells. Isolated retinal microglial cells increased expression of Il1b when stimulated with endogenous receptor agonist extracellular ATP; ATP also rapidly downregulated expression of microglial markers Tmem119 and Cd206. Changes to all three genes were reduced by specific P2X7R antagonist A839977, implicating the P2X7R. Microglial cells expressed the P2X7R on ramifications and responded to receptor agonist BzATP with robust and rapid rises in intracellular Ca 2+ . BzATP increased expression of IL-1β protein colocalizing with CX3CR1-GFP in retinal wholemounts consistent with microglial cells. ATP also triggered release of IL-1β from isolated retinal microglia into the bath; release was inhibited by A839977 and induced by BzATP, supporting a role for the P2X7R in release as well as priming. The IL-1β release triggered by ATP was substantially greater from microglial cells compared to astrocytes from the optic nerve head region. Il1b expression was increased by a transient rise in intraocular pressure and Il1b levels remained elevated 10 days after a single IOP elevation. In summary, this study suggests the P2X7 receptor can both prime IL-1β levels in microglial cells and trigger its release. The P2Y12R was previously identified as a chemoattractant for retinal microglia, suggesting the recruitment of the cells towards the source of released extracellular ATP could position microglia for P2X7R receptor, enabling both priming and release of IL-1β.

The use of electronic cigarettes, or "e-cigarettes", among youths has sparked worries about the possibility of nicotine dependence as a serious public health issue. Dental practitioners play a critical role in helping their patients quit smoking. Dental schools across the globe have policies encouraging their students to help patients quit smoking. Current research, however, indicates that a significant portion of dental students smoke combustible cigarettes and use e-cigarettes. According to studies, using e-cigarettes has resulted in the subsequent initiation of combustible cigarette smoking among its users. The aim of this study was to determine the association between the use of electronic cigarettes and the subsequent initiation of combustible cigarette smoking among dental students who were not attitudinally susceptible to smoking combustible cigarettes. A longitudinal cohort study was conducted among 121 study participants who were never combustible cigarette users and were attitudinally non-susceptible to smoking at baseline. At baseline, 66 (54.6%) study participants were categorized as e-cigarette users who were attitudinally non-susceptible to combustible cigarette smoking, and 55 (45.4%) study participants were categorized as non-users who were attitudinally non-susceptible to combustible cigarette smoking. The initiation of combustible cigarette smoking was assessed at 6- and 12-month intervals. Binomial regression analysis of the outcome at the end of one-year follow-up, when analyzed with independent variables, revealed a significant influence of e-cigarette use on taking up combustible cigarette smoking [Relative Risk: 9.395; 95% CI: 3.03-29.04]. Chi-squared analysis of independent variables revealed e-cigarette use to be significantly associated with fathers' education level ( p = 0.00), parental cigarette smoking status ( p = 0.00), cigarette smoking among friends ( p = 0.00), and family income ( p = 0.00). E-cigarette users are more likely to believe it to be healthier ( p = 0.00) than combustible smoking. In the present study, e-cigarette usage demonstrated a significant influence on taking up combustible cigarette smoking among its users. Educational institutions should implement stringent policies and regulations to prevent health professionals from using these products.

Automatic age estimation has garnered significant interest among researchers because of its potential practical uses. The current systematic review was undertaken to critically appraise developments and performance of AI models designed for automated estimation using dento-maxillofacial radiographic images. In order to ensure consistency in their approach, the researchers followed the diagnostic test accuracy guidelines outlined in PRISMA-DTA for this systematic review. They conducted an electronic search across various databases such as PubMed, Scopus, Embase, Cochrane, Web of Science, Google Scholar, and the Saudi Digital Library to identify relevant articles published between the years 2000 and 2024. A total of 26 articles that satisfied the inclusion criteria were subjected to a risk of bias assessment using QUADAS-2, which revealed a flawless risk of bias in both arms for the patient-selection domain. Additionally, the certainty of evidence was evaluated using the GRADE approach. AI technology has primarily been utilized for automated age estimation through tooth development stages, tooth and bone parameters, bone age measurements, and pulp-tooth ratio. The AI models employed in the studies achieved a remarkably high precision of 99.05% and accuracy of 99.98% in the age estimation for models using tooth development stages and bone age measurements, respectively. The application of AI as an additional diagnostic tool within the realm of age estimation demonstrates significant promise.

Background: Receiving a cancer diagnosis can be extremely stressful for patients, as it is a life-threatening disease. However, when this topic is discussed or researched, the psychological state of cancer patients is often ignored or forgotten. The study aimed to measure the levels of hopelessness and social support among cancer patients. It also aimed to assess the relationship between different demographic variables, hopelessness, and social support of these patients., Methods: The study followed a cross-sectional quantitative design. The setting included Princess Norah Oncology Center, at King Abdul-Aziz Medical City, Jeddah.   A convenience sampling technique including 300 cancer patients was followed. Data collection included a demographic questionnaire, the Beck Hopelessness Scale (BHS), and the Multidimensional Scale of Perceived Social Support (MSPSS).  Ethical principles of anonymity and confidentiality were followed., Results: The total number of respondents was 300, with 50% being male and 50% being female. The mean age of patients was 52.6±14.83 years. The most prevalent types of cancer were breast cancer (21.4%), colorectal (15.2%), and lymphoma (12.1%) respectively. Most of the patients were married (71.3%). The mean value of the BHS was 4.5, whereas the mean value of the MSPSS was 67.7. Moreover, the type of cancer showed a significant association between family support and total social support. In colorectal cancer patients, the total social support (71.2 ± 20.1) and family support (26.2 ± 5.0) provided was the highest followed by leukemia (70.3 ± 15.5 and 25.2 ± 5.1) and breast cancer (68.3-± 20.3. and 24.3 ± 6.8)., Conclusion: The findings of the present study suggest that the levels of hopelessness in cancer patients are moderate, and the levels of social support received by participants are high. In addition, the relationship between the levels of hopelessness and the levels of social support received is inversely proportional.

Cigarette smoking has been considered a major public health concern due to its serious impact on health. However, smokers intending to quit may find long-term abstinence challenging. When smoking an electronic cigarette (EC), users can experience a sensation and taste similar to that of smoking a combustible cigarette. Therefore, manufacturers promote these products as a viable substitute for combustible cigarettes. However, several researchers report the serious health impacts experienced by EC users. Therefore, this review aims to examine the health impacts of EC use. Based on the findings of the research papers reported in the literature, the role of EC as a smoking cessation tool is unclear. Several researchers have also reported a significant association between EC usage among non-smokers at baseline and the future initiation of combustible cigarette smoking. EC use significantly impacts user health. The nicotine that is present in EC e-liquids can elevate blood pressure, resulting in blood vessel constriction and an increase in heart rate, ultimately leading the body to an ischemic condition, resulting in myocardial infarction (MI), stroke, and increased arterial stiffness. Researchers report a higher likelihood of prediabetes among EC users; its usage was associated with higher OR of having asthma attacks and higher OR of reporting depression and has an impact on birth outcomes among pregnant women. Men using EC are more likely to report erectile dysfunction than non-users. EC also has a significant impact on oral health, which includes periodontal diseases, mucosal lesions, irritation in the mouth and throat, reduced salivary flow, and an increased risk of developing cancer. The physical injury resulting from exploding EC is another health concern. The frequently burned areas included the hands, face, genitalia, and thighs. Marketers promote EC as an alternative to combustible cigarettes and a tool for quitting smoking. However, the Food and Drug Administration has not approved them for smoking cessation. EC can have a serious impact on the health of their users; hence, the findings of this paper have several implications, including the need for regulation of the sales and marketing of these products and educating the users on the impact of these products on their health and safety., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Khanagar et al.)

Objective: Craniofacial growth and development are more than a scientific curiosity; it is of tremendous interest to clinicians. Insights into the genetic etiology of cleft lip and palate development are essential for improving diagnosis and treatment planning. The purpose of this systematic review was to utilize a zebrafish model to highlight the role of the IRF6 gene in cleft lip and palate development in humans., Data: This review adhered to the guidelines outlined in the PRISMA statement. Nine studies were included in the analysis., Sources: This study used major scientific databases such as MEDLINE, EMBASE, Web of Science, and the Zebrafish Information Network and yielded 1275 articles. Two reviewers performed the screening using COVIDENCE™ independently, and a third reviewer resolved any conflicts., Study Selection: After applying the inclusion and exclusion criteria and screening, nine studies were included in the analysis. The Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE's) risk-of-bias tool was used to assess the quality of the included studies., Results: The main outcome supports the role of the IRF6 gene in zebrafish periderm development and embryogenesis, and IRF6 variations result in cleft lip and palate development. The overall SYRCLE risk of bias was low-medium., Conclusion: In conclusion, this review indicated the critical role of the IRF6 gene and its downstream genes ( GRHL3, KLF17, and ESRP1/2 ) in the development of cleft lip and palate in zebrafish models. Genetic mutation zebrafish models provide a high level of insights into zebrafish craniofacial development., Clinical Relevance: this review provides a productive avenue for understanding the powerful and conserved zebrafish model for investigating the pathogenesis of human cleft lip and palate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

There are various techniques and designs for springs used in orthodontic treatment, including frictionless methods for closing spaces. However, there is limited explicit evidence to support the superiority of one method over another. This review aims to investigate the available evidence and highlight the advantages of these different methods. This review contained six papers, and information such as study design, spring design, applied force systems, variables studied, follow-up period, and records were extracted. All of the studies focused on canine retraction with the Ladanyi spring showing the highest rate of movement (1.8 mm per month) among all springs for upper canine retraction. The Gjessing and T-loop springs outperformed the Reverse Closing Loop and Ricketts spring, respectively, substantially. In terms of tip control, the T-loop spring showed a clear advantage over the modified Marcotte spring with a difference of 1.2° vs. 6.6° per 3 months. Additionally, it was observed that the Reverse Closing Loop caused a significant loss of anchorage during canine retraction with a medial movement of 2.4 mm. When comparing wire types, no significant differences were found between TMA and Nitinol, while stainless steel was found to be less effective in terms of movement rate and tip control. However, the results indicated that there was no clear evidence that one specific technique was definitively preferable to another; therefore, there is an urgent need for more studies with proper study designs to produce more robust conclusions.

Chitosan nanoparticles (CS NPs) showed promising results in drug, vaccine and gene delivery for the treatment of various diseases. The considerable attention towards CS was owning to its outstanding biological properties, however, the main challenge in the application of CS NPs was faced during their size-controlled synthesis. Herein, ionic gelation reaction between CS and sodium tripolyphosphate (TPP), a widely used and safe CS cross-linker for biomedical application, was exploited. The development of nanodelivery platform, namely Sorafenib-loaded chitosan nanoparticles (SF-CS NPs), was constructed in order to improve SF drug delivery to human Hepatocellular Carcinoma (HepG2) cell lines. The NPs were artificially fabricated using an ionic gelation technique. A number of CS NPs that had been loaded with an SF were prepared using different concentrations of sodium tripolyphosphate (TPP). These concentrations were 2.5, 5, 10, and 20 mg/mL, and they are abbreviated as SF-CS NPs 2.5, SF-CS NPs 5.0, SF-CS NPs 10, and SF-CS NPs 20 respectively. DLS, FTIR, XRD, HRTEM, TGA, and FESEM with EDX and TEM were used for the physiochemical characterisation of SF-CS NPs. Both DLS and HRTEM techniques demonstrated that smaller particles were produced when the TPP content was raised. In a PBS solution with a pH of 4.5, the SF exhibited efficient release from the nanoparticles, demonstrating that the delivery mechanism is effective for tumour cells. The cytotoxicity investigation showed that their anticancer effect against HepG2 cell lines was significantly superior than that of free SF. In addition, the nanodrug demonstrated an absence of any detectable toxicity to normal adult human dermal fibroblast (HDFa) cell lines. This is a step towards developing a more effective anticancer medication delivery system with sustained-release characteristics, which will ultimately improve the way cancer is managed., (© 2023. The Author(s).)

A new era in 3-dimensional analysis has begun with the use of cone-beam computed tomography (CBCT) in orthodontics, which promises to provide a more thorough understanding of the craniofacial skeletal architecture. This study aimed to investigate the correlation between the transverse basal arches discrepancy and dental compensation by utilizing CBCT width analysis. An observational study was conducted to retrospectively review 88 CBCT scans of patients presented to dental clinics from 2014 to 2020 obtained from the Planmeca Romexis x-ray system at three centers. Dental compensation data across normal and narrow maxillae were analyzed and a Pearson correlation was used to find the relationship between molar inclination and width difference. Significant maxillary molar compensation differences were observed between the normal maxilla and narrow maxilla group, where the amount of dental compensation (164.73 ± 10.15) was higher in the narrow maxilla group. A significant negative correlation (r = -0.37) was observed between width difference and maxillary molar inclination. Maxillary molars were tipped buccally to compensate for the reduced maxillary arch width. These findings are important to determine the amount of needed maxillary expansion taking into account the buccal inclination while treating cases.

Objective: This study aims to evaluate three types of manual toothbrushes [Cross action (CA), Flat trim (FT), and orthodontic type (OT)] in terms of efficacy in plaque removal in patients undergoing fixed orthodontic treatment., Background: Manual toothbrushes are an essential part of oral hygiene for primary prevention. Plaque control, however, can be influenced by a number of individual and material-related factors. Individual factors include the presence of fixed orthodontic appliances on tooth surfaces, such as brackets and bands, which create difficulties with oral hygiene and lead to plaque formation. The evidence for the effectiveness of advanced bristle designs (multilevel, criss-cross) of the manual toothbrush alone in removing plaque in patients undergoing orthodontic therapy is limited., Methods: The experiment followed the Consolidated Standards of Reporting Trials (CONSORT) guidelines. This was a three treatment, three-period crossover clinical trial with a single brushing exercise. Thirty subjects were randomized to one of the three treatment sequences of different bristle designs: (CA, FT, and OT). The primary outcome measure was the difference in the plaque scores (baseline minus post-brushing) at each study period, as determined by the Turesky-Modified Quigley-Hein Plaque Index., Results: Of the thirty-four subjects enrolled in the study, thirty of the subjects met the inclusion criteria and completed all three periods of the study. The mean age was 19.5 ± 1.52 years, with a range of 18-23 years. The differences between treatments in plaque score reduction after brushing were statistically significant (p-value < .001). The treatment differences were statistically significant (p-value < .001) favoring the FT toothbrush over the OT and CA types of toothbrush designs. On the contrary, the difference between the OT and CA types was not statistically significant., Conclusions: Plaque was significantly removed by the conventional FT toothbrush after a single brushing compared to the OT and CA types., (© 2023. The Author(s).)

Atherosclerotic cardiovascular disease (ACVD) is the leading cause of death worldwide. Although current therapies, such as statins, have led to a marked reduction in morbidity and mortality from ACVD, they are associated with considerable residual risk for the disease together with various adverse side effects. Natural compounds are generally well-tolerated; a major recent goal has been to harness their full potential in the prevention and treatment of ACVD, either alone or together with existing pharmacotherapies. Punicalagin (PC) is the main polyphenol present in pomegranates and pomegranate juice and demonstrates many beneficial actions, including anti-inflammatory, antioxidant, and anti-atherogenic properties. The objective of this review is to inform on our current understanding of the pathogenesis of ACVD and the potential mechanisms underlying the beneficial actions of PC and its metabolites in the disease, including the attenuation of dyslipidemia, oxidative stress, endothelial cell dysfunction, foam cell formation, and inflammation mediated by cytokines and immune cells together with the regulation of proliferation and migration of vascular smooth muscle cells. Some of the anti-inflammatory and antioxidant properties of PC and its metabolites are due to their strong radical-scavenging activities. PC and its metabolites also inhibit the risk factors of atherosclerosis, including hyperlipidemia, diabetes mellitus, inflammation, hypertension, obesity, and non-alcoholic fatty liver disease. Despite the promising findings that have emerged from numerous in vitro, in vivo, and clinical studies, deeper mechanistic insights and large clinical trials are required to harness the full potential of PC and its metabolites in the prevention and treatment of ACVD.

Aim and Objective: To report on the prevalence and patterns of orofacial clefts (OFC) among Saudi Arabian children by analyzing the results of the studies that have been reported in the literature., Materials and Methods: A data search was carried out for the articles that had reported on the prevalence of OFC among the Saudi Arabian population in databases like Web of Science, PubMed, Google Scholar, Scopus, and Saudi Digital Library. Articles that were published over the last 15 years were included in this study, following which 13 studies were assessed for qualitative data. Newcastle-Ottawa Quality Assessment Scales for cross-sectional studies were used for analyzing the methodological quality of these studies., Results: The prevalence of OFC was within the range of 0.65-1.9/1,000 live births. The highest was witnessed in the Medina region. Parent's consanguinity was the most common risk factor in OFC cases in the included studies. OFC was found to be higher among the male population in comparison with the female., Conclusion: The prevalence of OFC in Saudi Arabian children follows the global patterns of OFC. Isolated cleft lip (CL) and cleft palate (CP) are the most common forms of OFC. The prevalence of orofacial anomalies was reported more among children born to parents who had consanguineous marriages. Considering the higher rate of consanguinity among this population, there is an urgent need of developing educational and counseling programs to address the genetic consequences., How to Cite This Article: Albalawi F Alsaeed S, Alalola B, et al. Prevalence and Patterns of Orofacial Clefts among Children from Different Regions of Saudi Arabia: A Systematic Review. Int J Clin Pediatr Dent 2023;16(1):124-130., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Background Palatal rugae patterns are useful in the field of forensic dentistry. Ethnicity has a significant effect on the development and final morphological pattern of palatal rugae. This study focused on a morphological analysis of the palatal rugae in a Saudi population to determine if any differences based on age and gender could support identifying an individual. Materials and methods This cross-sectional study conducted at the College of Dentistry, King Saud bin Abdul Aziz University for Health Sciences, was undertaken to evaluate 496 dental casts from the participant database of Saudi nationals from Riyadh. The rugae were delineated using a sharp graphite pencil under adequate light and magnification. The rugae patterns were classified based on the length, shape, and direction of the rugae by two observers as per Thomas and Kotze's criteria. Results The asymptotic chi-square McNemar test indicated bilateral symmetry for all the characteristics of the palatal rugae, except for the backward and forward directions of the rugae. Two-way analysis of variance (ANOVA) revealed a statistically significant interaction between the effects of age group and gender on the primary rugae count (F(3, 488) = 7.466, p <0.05)). In addition, age had a statistically significant effect on the fragmentary rugae (p <0.05), and gender had a statistically significant effect on the circular and backward patterns of the rugae (p<0.05). The females had a higher incidence of backward-directed rugae and the males had more circular rugae. No other significant difference was evident, based on gender. The logistic regression analyses showed a significant association between the circular (OR=1.298; 95% CI= 1.061-1.588) and backward (OR= 0.898; 95% CI= 0.828-0.975) palatal rugae and gender. Also, there was a significant association of the fragmentary palatal rugae (PR) (OR=1.274; 95% CI= 1.084-1.498) with the age group younger than 16 years. Conclusion In a Saudi Arabian ethnic group, the varying type of length of the palatal rugae patterns can be used to identify the age group while the direction and shape can be used to determine gender, although with limited accuracy. Post-mortem identification may benefit from using them along with other reliable forensic tools. There is a need to conduct continued research on diverse populations and ethnic groups in order to evaluate the PR potential in forensic dentistry., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alshammari et al.)

Background The purpose of this study was to investigate the distal extension of the palatal rugae area as an anatomical constraint on the harvesting of palatal soft tissue grafts in a Saudi Arabian population. Additionally, factors that could affect or predict the extension were considered. Methods Three hundred seventy-four (374) dental casts from Saudi nationals currently residing in Riyadh (170 males and 204 females) were included. Two independent observers used a standardized probe to measure the posterior extent of the rugae on each stone cast bilaterally on a horizontal base. A sharp graphite pencil was used to mark the measurements from the origin of the rugae to their terminal ends on the cast, and a magnification lens was used to identify them. Using this technique, the most posterior extension of the rugae was marked and then analyzed. The normal approximation test for binomial distribution was used to determine the proportion of the subjects with rugael extensions beyond the mesial end of the upper second premolar, and logistic regression was used to see the association of this extension with other factors. Results The asymptotic chi-squared (p = 0.0002) McNemar tests revealed that the posterior distal extension of the rugae was not the same on both sides. A normal approximation test for the left side with 95% confidence intervals (CIs) with the "rugael extension proximal to the mesial end of the upper second premolar" category considered "success" found that the proportion of upper second premolars with rugael extensions proximal to the mesial end was not significantly different to the proportion of rugael extensions beyond the mesial end of the upper second premolars (95% CI: 48.69%-58.79%, p = 0.147). Conversely, the proportion of the upper second premolars with rugael extensions proximal to the mesial end was significantly lower than that beyond the mesial end on the right (95% CI: 35.92%-45.89%, p = 0.00004). Gender, age, and palatal shape did not significantly affect the posterior extension of palatal rugae. Conclusions The palatal rugae on the left side of a sample of the Saudi Arabian population do not considerably extend beyond the upper second premolar mesial aspect, which may provide reliable soft tissue grafts for esthetic mucogingival surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alshammari et al.)

Obstructive sleep apnea (OSA) is a serious and often underreported condition, despite its highly prevalent distribution. Primary care physicians (PCPs) play an integral role in screening and managing patients with a high risk of developing OSA. This northern Saudi Arabian cross-sectional survey assessed the knowledge and attitude towards OSA among 264 randomly selected PCPs using the OSA Knowledge and Attitude (OSAKA) questionnaire. Among the participating PCPs, 43.9% and 45.1% had low scores in the knowledge and attitude categories, respectively. More than three-fourths (78%) of them recognized that an overnight sleep study is the gold standard for diagnosing OSA. Regarding referral, 39.4% of the OSA patients encountered by the PCPs were referred to ENT specialists, while 21% were referred to sleep clinics, and 18.2% were referred to pulmonologists. Nearly half (50.8%) of the participants recognized OSA as an important clinical disease, and 56.8% were confident in caring for OSA patients. Spearman's correlation of the current study identified a positive correlation between knowledge scores and attitude scores (rho-0.151, p = 0.017). It is important to improve PCPs' knowledge regarding OSA and the necessity for referral through different training methods. Furthermore, the study findings emphasize the need to include appropriate OSA programs and continuing medical education for PCPs.

Background: The 2021 American College of Rheumatology (ACR) rheumatoid arthritis (RA) guideline considers the specific context of the United States which differs from that of Saudi Arabia in many aspects that may impact recommendations. The objective of this project was to adapt a set of prioritized recommendations from the 2021 ACR guideline for the treatment of rheumatoid arthritis RA for the context of Saudi Arabia, by the Saudi Society for Rheumatology (SSR)., Methods: The process followed the GRADE-ADOLOPMENT methodology, and the reporting adhered to the RIGHT-Ad@pt checklist. Working groups included a coordination group and a 19-member panel representing different stakeholder groups. The Evidence to Decision (EtD) tables included evidence on health effects from the source guideline and contextual information from the Saudi setting., Results: The panel prioritized and adapted five recommendations from the source guideline. The process led to modifying two out of the five prioritized recommendations, all listed here. In naive patients with low disease activity, methotrexate (MTX) is conditionally recommended over sulfasalazine (SSZ) (modified direction); hydroxychloroquine (HCQ) is conditionally recommended over SSZ (unmodified). Initiation of csDMARDs with short-term glucocorticoids is conditionally recommended over csDMARDs alone in naive patients with moderate to high disease activity (modified direction). Switch to subcutaneous MTX is conditionally recommended over addition/switch to alternative DMARD(s) in patients taking oral MTX who are not at target (unmodified). Discontinuation of MTX is conditionally recommended over gradual discontinuation of the bDMARD or tsDMARD for patients taking MTX plus a bDMARD or tsDMARD who wish to discontinue a DMARD (unmodified)., Conclusion: Rheumatologists practicing in Saudi Arabia can use the adoloped recommendations generated by this project while adopting the rest of the recommendations from the 2021 ACR guidelines., (© 2022. The Author(s).)

Background: This study aimed to assess sleep medicine physicians' knowledge and attitudes toward the role of oral appliances (OAs) in managing obstructive sleep apnea (OSA) in Saudi Arabia., Methods: An online questionnaire was administered to the registered physicians practicing sleep medicine (otolaryngology, internal medicine, pulmonology, and family medicine) in Saudi Arabia. The questionnaire included 26 questions under five domains. All the collected data were analyzed using descriptive statistics and Chi-square tests., Results: One hundred sleep physicians (43% Saudi, 75% male) from Saudi Arabia participated in this study. Almost 43% of participants reported inadequate knowledge of the treatment of OSA patients using OAs. Half of the participants were unaware of how OAs work in managing OSA. Most physicians (62%) never referred the patient for treatment of OSA using OAs, whereas 4% referred at least one patient every month. The majority (60%) believed that there are barriers to referring a case for OA treatment, mainly the lack of knowledge of the suitable cases (60%) and the lack of qualified dentists in this area (43%)., Conclusion: Most sleep physicians reported poor knowledge of OA indications and mechanism of use, with most never referring a case for OA therapy.

Evolution in the fields of science and technology has led to the development of newer applications based on Artificial Intelligence (AI) technology that have been widely used in medical sciences. AI-technology has been employed in a wide range of applications related to the diagnosis of oral diseases that have demonstrated phenomenal precision and accuracy in their performance. The aim of this systematic review is to report on the diagnostic accuracy and performance of AI-based models designed for detection, diagnosis, and prediction of dental caries (DC). Eminent electronic databases (PubMed, Google scholar, Scopus, Web of science, Embase, Cochrane, Saudi Digital Library) were searched for relevant articles that were published from January 2000 until February 2022. A total of 34 articles that met the selection criteria were critically analyzed based on QUADAS-2 guidelines. The certainty of the evidence of the included studies was assessed using the GRADE approach. AI has been widely applied for prediction of DC, for detection and diagnosis of DC and for classification of DC. These models have demonstrated excellent performance and can be used in clinical practice for enhancing the diagnostic performance, treatment quality and patient outcome and can also be applied to identify patients with a higher risk of developing DC.

The cultural microbiomes of 27 bacteria colonies were isolated from Mugil cephalus for analysis of the antibacterial and antagonistic activities. A potent probiotic bacterium was characterized using16S r RNA sequencing. The potent strain was added to fish diet to perform the challenge test and to study the growth and immunological parameter. The extracellular proteins from the probiotic were collected and characterized using MALDI TOF/TOF. Out of G27, G9 strain inhibited all the five pathogenic strains. An isolated bacterium was identified as Bacillus subtilis PRBD09 with accession number KF765648. After 35 days of feeding period B. subtilis PRBD09 enhance the both cellular and humoral immune responses, which responsible for survive of the Mugil cephalus against Aeromonas hydrophila infection. The MALDI TOF sample 08 and 09 were recognized as hypothetical proteins based on the MALDI TOF sample. A cytidinedeaminase was found in samples 10, 11, and 12. Extracellular proteins may be involved for the immunological increase in Mugil cephalus against Aeromonas hydrophila, according to the current research., (© 2022. The Author(s).)

This paper focuses on robustness and sensitivity analysis for sensor fault diagnosis of a voltage source converter based microgrid model. It uses robust control parameters such as minimum sensitivity parameter (H-), maximum robustness parameter (H∞), and compromised both (H-/H∞), being incorporated in the sliding mode observer theory using the game theoretic saddle point estimation achieved through convex optimization of constrained LMIs. The approach used works in a way that the mentioned robust control parameters are embedded in Hamilton-Jacobi-Isaacs-Equation (HJIE) and are also used to determine the inequality version of HJIE, which is, in terms of the Lyapunov function, faults/disturbances and augmented state/output estimation error as its variables. The stability analysis is also presented by negative definiteness of the same inequality version of HJIE, and additionally, it also gives linear matrix inequalities (LMIs), which are optimized using iterative convex optimization algorithms to give optimal sliding mode observer gains enhanced with robustness to maximal preset values of disturbances and sensitivity to minimal preset values of faults. The enhanced sliding mode observer is used to estimate states, faults, and disturbances using sliding mode observer theory. The optimality of sliding mode observer gains for sensitivity of the observer to minimal faults and robustness to maximal disturbance is a game theoretic saddle point estimation achieved through convex optimization of LMIs. The paper includes results for state estimation errors, faults' estimation/reconstruction, fault estimation errors, and fault-tolerant-control performance for current and potential transformer faults. The considered faults and disturbances in current and potential transformers are sinusoidal nature composite of magnitude/phase/harmonics at the same time.

The study's purpose was to find and create a nourishing fruit juice made from avocado to suit nutritional and health demands. In this regard, the avocado juice was formulated using a statistical technique, and its biochemical and phytochemical characteristics were evaluated. Statistically formulated fruit juice was evaluated for its sensory characteristics, proximate composition, nutrients and vitamins, total phenols and flavonoids, and for its antioxidant ability, in addition to a shelf-life test. The optimal amount of all ingredients included in the mathematical model for the preparation of the juice was 150 g of Persea americana (Avocado) fruit pulp, 12.5 g of honey and 100 mL of water. In fact, the composition of avocado juice was found to have higher phenolic (910.36 ± 0.215 mg EAG g -1 /mL) and flavonoid (56.32 ± 1.26 mg QE g -1 / mL) amounts. DPPH, ABTS and FRAP antioxidant assays tended to be high compared with a standard. The shelf-life analysis indicated that the processed avocado juice (V7) had a long shelf life. In view of all these merits, a statistically formulated recipe for avocado fruit juice was recommended for the formulation of the most preferred health drink.

There has been tremendous spread of antimicrobial resistance globally, mainly due to the excessive and unnecessary use of antibiotics, making the situation alarming. This has created a need for the development of alternative strategies to selectively target the bacterial pathogenicity without exerting selection pressure for the development of antimicrobial resistance. Targeting quorum sensing (QS)-mediated virulence and biofilms by nontoxic natural products is gaining importance as new control strategy to combat the virulence and biofilms of pathogenic bacteria. In this study, the crude extract of Plumbago zeylanica was fractioned in different solvents using liquid-liquid partitioning to obtain the most bioactive fraction. The inhibitory effect of the bioactive extract of P. zeylanica on QS at sub-minimum inhibitory concentrations (MICs) was studied against Chromobacterium violaceum 12472, Pseudomonas aeruginosa PAO1, and Serratia marcescens MTCC 97. Biofilm inhibition was studied using microtiter plate assay, scanning electron microscopy, and confocal laser scanning microscopy. Major phytocompounds detected were cinnamaldehyde dimethyl acetal, plumbagin, asarone, 4-chromanol, phthalic acid, palmitic acid, ergost-5-en-3-ol, stigmasterol, and β-sitosterol. The violacein production in C. violaceum 12472 was reduced by >80% in the presence of P. zeylanica hexane fraction (PZHF; 200 μg/ml). The most active PZHF inhibited QS-mediated virulence factors of P. aeruginosa PAO1 such as pyocyanin, pyoverdin, rhamnolipid production, motility, etc., significantly at sub-MICs. Similarly, PZHF showed 59 to 76% inhibition of biofilm formation of above test pathogens. The findings revealed that active fraction of P. zeylanica was effective against the QS-regulated functions and biofilms development of Gram -ve pathogenic bacteria., (© 2021 Wiley Periodicals LLC.)

Background: The identification of endogenous signals that lead to microglial activation is a key step in understanding neuroinflammatory cascades. As ATP release accompanies mechanical strain to neural tissue, and as the P2X7 receptor for ATP is expressed on microglial cells, we examined the morphological and molecular consequences of P2X7 receptor stimulation in vivo and in vitro and investigated the contribution of the P2X7 receptor in a model of increased intraocular pressure (IOP)., Methods: In vivo experiments involved intravitreal injections and both transient and sustained elevation of IOP. In vitro experiments were performed on isolated mouse retinal and brain microglial cells. Morphological changes were quantified in vivo using Sholl analysis. Expression of mRNA for M1- and M2-like genes was determined with qPCR. The luciferin/luciferase assay quantified retinal ATP release while fura-2 indicated cytoplasmic calcium. Microglial migration was monitored with a Boyden chamber., Results: Sholl analysis of Iba1-stained cells showed retraction of microglial ramifications 1 day after injection of P2X7 receptor agonist BzATP into mouse retinae. Mean branch length of ramifications also decreased, while cell body size and expression of Nos2, Tnfa, Arg1, and Chil3 mRNA increased. BzATP induced similar morphological changes in ex vivo tissue isolated from Cx3CR1 +/GFP mice, suggesting recruitment of external cells was unnecessary. Immunohistochemistry suggested primary microglial cultures expressed the P2X7 receptor, while functional expression was demonstrated with Ca 2+ elevation by BzATP and block by specific antagonist A839977. BzATP induced process retraction and cell body enlargement within minutes in isolated microglial cells and increased Nos2 and Arg1. While ATP increased microglial migration, this required the P2Y12 receptor and not P2X7 receptor. Transient elevation of IOP led to microglial process retraction, cell body enlargement, and gene upregulation paralleling changes observed with BzATP injection, in addition to retinal ATP release. Pressure-dependent changes were reduced in P2X7 -/- mice. Death of retinal ganglion cells accompanied increased IOP in C57Bl/6J, but not P2X7 -/- mice, and neuronal loss showed some association with microglial activation., Conclusions: P2X7 receptor stimulation induced rapid morphological activation of microglial cells, including process retraction and cell body enlargement, and upregulation of markers linked to both M1- and M2-type activation. Parallel responses accompanied IOP elevation, suggesting ATP release and P2X7 receptor stimulation influence the early microglial response to increased pressure., (© 2021. The Author(s).)

In this article, a zirconia-based nano-catalyst (Nano-ZrO 2 ), with intermolecular C-N bond formation for the synthesis of various benzimidazole-fused heterocycles in a concise method is reported. The robustness of this reaction is demonstrated by the synthesis of a series of benzimidazole drugs in a one-pot method. All synthesized materials were characterized using 1 HNMR, 13 CNMR, and LC-MS spectroscopy as well as microanalysis data. Furthermore, the synthesis of nano-ZrO 2 was processed using a standard hydrothermal technique in pure form. The crystal structure of nano-ZrO 2 and phase purity were studied, and the crystallite size was calculated from XRD analysis using the Debye-Scherrer equation. Furthermore, the antimicrobial activity of the synthesized benzimidazole drugs was evaluated in terms of Gram-positive, Gram-negative, and antifungal activity, and the results were satisfactory.

Epilepsy is a neurological disorder ranked as the second most serious neurological disease known to humanity, after stroke. Inter-ictal spiking is an abnormal neuronal discharge after an epileptic seizure. This abnormal activity can originate from one or more cranial lobes, often travels from one lobe to another, and interferes with normal activity from the affected lobe. The common practice for Inter-ictal spike detection of brain signals is via visual scanning of the recordings, which is a subjective and a very time-consuming task. Motivated by that, this article focuses on using machine learning for epileptic spikes classification in magnetoencephalography (MEG) signals. First, we used the Position Weight Matrix (PWM) method combined with a uniform quantizer to generate useful features from time domain and frequency domain through a Fast Fourier Transform (FFT) of the framed raw MEG signals. Second, the extracted features are fed to standard classifiers for inter-ictel spikes classification. The proposed technique shows great potential in spike classification and reducing the feature vector size. Specifically, the proposed technique achieved average sensitivity up to 87% and specificity up to 97% using 5-folds cross-validation applied to a balanced dataset. These samples are extracted from nine epileptic subjects using a sliding frame of size 95 samples-points with a step-size of 8 sample-points.

Introduction: Rapid diagnosis of M. tuberculosis directly from sputum samples is a challenging process. This study aimed to design and evaluate a multiplex-PCR method for direct diagnosis of M. tuberculosis from sputum specimens., Materials and Methods: 46 suspected tuberculosis patients and 25 apparently healthy individuals were enrolled in the study. Sputa were collected from the study population and processed by cold ZN stain. DNA was extracted from each sample and processed by Multiplex PCR and Genotype Mycobacteria CM., Results: Out of the 46 Tuberculosis suspected patients, 22 (47.8%) revealed positive Acid fast ba- cilli (AFB), while 19 (41.3%) showed positive by both multiplex PCR and Genotype Mycobacte- ria CM. The overall sensitivity of multiplex PCR and smear microscopy were 100% while the specificity were 100, and 86.3%, respectively., Conclusion: Multiplex PCR method using two different sets of primers in combination with other diagnostic tools such as X-Rays and smear Microscopy are cheap, rapid and reliable methods for the diagnosis of M. tuberculosis from clinical samples and are able to identify most of the smear positive cases with valuable accuracy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Polyadenylation signals (PAS) are found in most protein-coding and some non-coding genes in eukaryotes. Their accurate recognition improves understanding gene regulation mechanisms and recognition of the 3'-end of transcribed gene regions where premature or alternate transcription ends may lead to various diseases. Although different methods and tools for in-silico prediction of genomic signals have been proposed, the correct identification of PAS in genomic DNA remains challenging due to a vast number of non-relevant hexamers identical to PAS hexamers. In this study, we developed a novel method for PAS recognition. The method is implemented in a hybrid PAS recognition model (HybPAS), which is based on deep neural networks (DNNs) and logistic regression models (LRMs). One of such models is developed for each of the 12 most frequent human PAS hexamers. DNN models appeared the best for eight PAS types (including the two most frequent PAS hexamers), while LRM appeared best for the remaining four PAS types. The new models use different combinations of signal processing-based, statistical, and sequence-based features as input. The results obtained on human genomic data show that HybPAS outperforms the well-tuned state-of-the-art Omni-PolyA models, reducing the classification error for different PAS hexamers by up to 57.35% for 10 out of 12 PAS types, with Omni-PolyA models being better for two PAS types. For the most frequent PAS types, 'AATAAA' and 'ATTAAA', HybPAS reduced the error rate by 35.14% and 34.48%, respectively. On average, HybPAS reduces the error by 30.29%. HybPAS is implemented partly in Python and in MATLAB available at https://github.com/EMANG-KAUST/PolyA&#95;Prediction&#95;LRM&#95;DNN., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The local anesthetics lidocaine and articaine are among the most widely used drugs in the dentist's arsenal, relieving pain by blocking voltage-dependent Na + channels and thus preventing transmission of the pain signal. Given reports of infrequent but prolonged paresthesias with 4% articaine, we compared its neurotoxicity and functional impairment by screening cultured neural SH-SY5Y cells with formulations used in patients (2% lidocaine + 1:100,000 epinephrine or 4% articaine + 1:100,000 epinephrine) and with pure formulations of the drugs. Voltage-dependent sodium channels Na(v)1.2 and Na(v)1.7 were expressed in SH-SY5Y cells. To test the effects on viability, cells were exposed to drugs for 5 minutes, and after washing, cells were treated with the ratiometric Live/Dead assay. Articaine had no effect on the survival of SH-SY5Y cells, while lidocaine produced a significant reduction only when used as pure powder. To determine reversibility of blockage, wells were exposed to drugs for 5 minutes and returned for medium for 30 minutes, and the calcium elevation induced by depolarizing cells with a high-potassium solution was measured using the calcium indicator Fura-2. High potassium raised calcium in control SH-SY5Y cells and those treated with articaine, but lidocaine treatment significantly reduced the response. In conclusion, articaine does not damage neural cells more than lidocaine in this in vitro model. While this does not question the safety of lidocaine used clinically, it does suggest that articaine is no more neurotoxic, at least in the in vitro setting.

Cross-reactions between innate immunity, lysosomal function, and purinergic pathways may link signaling systems in cellular pathologies. We found activation of toll-like receptor 3 (TLR3) triggers lysosomal ATP release from both astrocytes and retinal pigmented epithelial (RPE) cells. ATP efflux was accompanied by lysosomal acid phosphatase and beta hexosaminidase release. Poly(I:C) alkalinized lysosomes, and lysosomal alkalization with bafilomycin or chloroquine triggered ATP release. Lysosomal rupture with glycyl-L-phenylalanine-2-naphthylamide (GPN) eliminated both ATP and acid phosphatase release. Secretory lysosome marker LAMP3 colocalized with VNUT, while MANT-ATP colocalized with LysoTracker. Unmodified membrane-impermeant 21-nt and "non-targeting" scrambled 21-nt siRNA triggered ATP and acid phosphatase release, while smaller 16-nt RNA was ineffective. Poly(I:C)-dependent ATP release was reduced by TBK-1 block and in TRPML1 -/- cells, while TRPML activation with ML-SA1 was sufficient to release both ATP and acid phosphatase. The ability of poly(I:C) to raise cytoplasmic Ca 2+ was abolished by removing extracellular ATP with apyrase, suggesting ATP release by poly(I:C) increased cellular signaling. Starvation but not rapamycin prevented lysosomal ATP release. In summary, stimulation of TLR3 triggers lysosomal alkalization and release of lysosomal ATP through activation of TRPML1; this links innate immunity to purinergic signaling via lysosomal physiology, and suggests even scrambled siRNA can influence these pathways.

Inflammatory responses play a key role in many neural pathologies, with localized signaling from the non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune signaling and can link neural insult to chronic inflammation. The NLRP3 inflammasome requires two stages to contribute: priming and activation. The priming stage involves upregulation of inflammasome components while the activation stage results in the assembly and activation of the inflammasome complex. The priming step can be rate limiting and can connect insult to chronic inflammation, but our knowledge of the signals that regulate NLRP3 inflammasome priming in sterile inflammation is limited. This study examined the link between mechanical strain and inflammasome priming in neural systems. Transient non-ischemic elevation of intraocular pressure increased mRNA for inflammasome components IL-1 β , NLRP3, ASC , and CASP1 in rat and mouse retinas. The elevation was greater 1 day after the insult, with the rise in IL-1β most pronounced. The P2X7 receptor was implicated in the mechanosensitive priming of IL-1β mRNA in vivo , as the antagonist Brilliant Blue G (BBG) blocked the increased expression, the agonist BzATP mimicked the pressure-dependent rise in IL-1β, and the rise was absent in P2X7 knockout mice. In vitro measurements from optic nerve head astrocytes demonstrated an increased expression of IL-1 β following stretch or swelling. This increase in IL-1 β was eliminated by degradation of extracellular ATP with apyrase, or by the block of pannexin hemichannels with carbenoxolone, probenecid, or 10panx1 peptide. The rise in IL-1 β expression was also blocked by P2X7 receptor antagonists BBG, A839977 or A740003. The rise in IL-1 β was prevented by blocking transcription factor NFκB with Bay 11-7082, while the swelling-dependent fall in NFκB inhibitor IκB-α was reduced by A839977 and in P2X7 knockout mice. In summary, mechanical trauma to the retina primed NLRP3 inflammasome components, but only if there was ATP release through pannexin hemichannels, and autostimulation of the P2X7 receptor. As the P2X7 receptor can also trigger stage two of inflammasome assembly and activation, the P2X7 receptor may have a central role in linking mechanical strain to neuroinflammation.

Mechanical strain in neural tissues can lead to the up-regulation and release of multiple cytokines including interleukin 6 (IL-6). In the retina, the mechanosensitive release of ATP can autostimulate P2X7 receptors on both retinal ganglion cell neurons and optic nerve head astrocytes. Here, we asked whether the purinergic signaling contributed to the IL-6 response to increased intraocular pressure (IOP) in vivo, and stretch or swelling in vitro. Rat and mouse eyes were exposed to non-ischemic elevations in IOP to 50-60 mmHg for 4 h. A PCR array was used to screen cytokine changes, with quantitative (q)PCR used to confirm mRNA elevations and immunoblots used for protein levels. P2X7 antagonist Brilliant Blue G (BBG) and agonist (4-benzoyl-benzoyl)-ATP (BzATP) were injected intravitreally. ELISA was used to quantify IL-6 release from optic nerve head astrocytes or retinal ganglion cells. Receptor identity was confirmed pharmacologically and in P2X7 -/- mice, acute elevation of IOP altered retinal expression of multiple cytokine genes. Elevation of IL-6 was greatest, with expression of IL1rn, IL24, Tnf, Csf1, and Lif also increased more than twofold, while expression of Tnfsf11, Gdf9, and Tnfsf4 were reduced. qPCR confirmed the rise in IL-6 and extracellular ATP marker ENTPD1, but not pro-apoptotic genes. Intravitreal injection of P2X7 receptor antagonist BBG prevented the pressure-dependent rise in IL-6 mRNA and protein in the rat retina, while injection of P2X7 receptor agonist BzATP was sufficient to elevate IL-6 expression. IOP elevation increased IL-6 in wild-type but not P2X7R knockout mice. Application of mechanical strain to isolated optic nerve head astrocytes increased IL-6 levels. This response was mimicked by agonist BzATP, but blocked by antagonists BBG and A839977. Stretch or BzATP led to IL-6 release from both astrocytes and isolated retinal ganglion cells. The mechanosensitive up-regulation and release of cytokine IL-6 from the retina involves the P2X7 receptor, with both astrocytes and neurons contributing to the response., (© 2017 International Society for Neurochemistry.)

DEAF1 encodes a transcriptional binding factor and is a regulator of serotonin receptor 1A. Its protein has a significant expression in the neurons of different brain regions and is involved in early embryonic development. In addition, its role in neural tube development is evident from the knockout mouse as many homozygotes have exencephaly. Heterozygous mutations of this gene have been linked to intellectual disability in addition to the gene's involvement in major depression, suicidal tendencies, and panic disorder. In this clinical report, we describe two children from a consanguineous family with intellectual disability, microcephaly, and hypotonia. The brain MRI of both patients showed bilateral and symmetrical white matter abnormalities, and one of the patients had a seizure disorder. Using whole exome sequencing combined with homozygosity mapping, a homozygous p.R226W (c.676C>T) mutation in DEAF1 was found in both patients. Furthermore, sequencing analysis confirmed complete segregation in tested family members and absence of the mutation in control cohort (n = 650). The mutation is located in a highly conserved structural domain that mediates DNA binding and therefore regulates transcriptional activity of its target molecules. This study indicates, for the first time to our knowledge, a hereditary role of DEAF1 in white matter abnormalities, microcephaly and syndromic intellectual disability., (© 2014 Wiley Periodicals, Inc.)