Proteomics Analysis of Proteotoxic Stress Response in In-Vitro Human Neuronal Models.

Heat stroke, a hazardous hyperthermia-related illness, is characterized by CNS injury, particularly long-lasting brain damage. A root cause for hyperthermic neurological damage is heat-induced proteotoxic stress through protein aggregation, a known causative agent of neurological disorders. Stress magnitude and enduring persistence are highly correlated with hyperthermia-associated neurological damage. We used an untargeted proteomic approach using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify and characterize time-series proteome-wide changes in dose-responsive proteotoxic stress models in medulloblastoma [Daoy], neuroblastoma [SH-SY5Y], and differentiated SH-SY5Y neuron-like cells [SH(D)]. An integrated analysis of condition-time datasets identified global proteome-wide differentially expressed proteins (DEPs) as part of the heat-induced proteotoxic stress response. The condition-specific analysis detected higher DEPs and upregulated proteins in extreme heat stress with a relatively conservative and tight regulation in differentiated SH-SY5Y neuron-like cells. Functional network analysis using ingenuity pathway analysis (IPA) identified common intercellular pathways associated with the biological processes of protein, RNA, and amino acid metabolism and cellular response to stress and membrane trafficking. The condition-wise temporal pathway analysis in the differentiated neuron-like cells detects a significant pathway, functional, and disease association of DEPs with processes like protein folding and protein synthesis, Nervous System Development and Function, and Neurological Disease. An elaborate dose-dependent stress-specific and neuroprotective cellular signaling cascade is also significantly activated. Thus, our study provides a comprehensive map of the heat-induced proteotoxic stress response associating proteome-wide changes with altered biological processes. This helps to expand our understanding of the molecular basis of the heat-induced proteotoxic stress response with potential translational connotations.

Association of Coagulopathy and Inflammatory Biomarkers with Severity in SARS-CoV-2-Infected Individuals of the Al-Qunfudhah Region of Saudi Arabia.

BACKGROUND: Identifying prognosticators/predictors of COVID-19 severity is the principal focus for early prediction and effective management of the disease in a time-bound and cost-effective manner. We aimed to evaluate COVID-19 severity-dependent alteration in inflammatory and coagulopathy biomarkers. METHODS: A hospital-dependent retrospective observational study (total: n = 377; male, n = 213; and female, n = 164 participants) was undertaken. COVID-19 exposure was assessed by performing real-time PCR on nasopharyngeal (NP) swabs. Descriptive and inferential statistics were applied for both continuous and categorical variables using Rstudio-version-4.0.2. Pearson correlation and regression were executed with a cut-off of p < 0.05 for evaluating significance. Data representation by R-packages and ggplot2. RESULTS: A significant variation in the mean ± SD (highly-sever (HS)/moderately severe (MS)) of CRP (HS/MS: 102.4 ± 22.9/21.3 ± 6.9, p-value < 0.001), D-dimer (HS/MS: 661.1 ± 80.6/348.7 ± 42.9, p-value < 0.001), and ferritin (HS/MS: 875.8 ± 126.8/593.4 ± 67.3, p-value < 0.001) were observed. Thrombocytopenia, high PT, and PTT exhibited an association with the HS individuals (p < 0.001). CRP was correlated with neutrophil (r = 0.77), ferritin (r = 0.74), and WBC (r = 0.8). D-dimer correlated with platelets (r = -0.82), PT (r = 0.22), and PTT (r = 0.37). The adjusted odds ratios (Ad-OR) of CRP, ferritin, D-dimer, platelet, PT, and PTT for HS compared to MS were 1.30 (95% CI -1.137, 1.50; p < 0.001), 1.048 (95% CI -1.03, 1.066; p < 0.001), 1.3 (95% CI -1.24, 1.49, p > 0.05), -0.813 (95% CI -0.734, 0.899, p < 0.001), 1.347 (95% CI -1.15, 1.57, p < 0.001), and 1.234 (95% CI -1.16, 1.314, p < 0.001), respectively. CONCLUSION: SARS-CoV-2 caused alterations in vital laboratory parameters and raised ferritin, CRP, and D-dimer presented an association with disease severity at a significant level.

Formulation and evaluation of simvastatin cubosomal nanoparticles for assessing its wound healing effect.

Wound healing is one of the most challenging medical circumstances for patients. Pathogens can infect wounds, resulting in tissue damage, inflammation, and disruption of the healing process. Simvastatin was investigated recently, as a wound healing agent that may supersede the present therapies for wounds. Our goal in this paper is to focus on formulation of simvastatin cubosomes for topical delivery, as a potential approach to improve simvastatin skin permeation. By this technique its wound healing effect could be improved. Cubosomes were prepared using the top-down method and the prepared cubosomes were characterized by several techniques. The most optimal simvastatin cubosomal formulation was then included in a cubogel dosage form using different gelling agents. The results showed that the average particle size of the prepared cubosomes was 113.90 ± 0.58 nm, the entrapment efficiency was 93.95 ± 0.49% and a sustained simvastatin release was achieved. The optimized formula of simvastatin cubogel displayed pseudoplastic rheological behavior. This same formula achieved enhancement in drug permeation through excised rat skin compared to free simvastatin hydrogel with flux values of 46.18 ± 2.12 mcg cm-2 h-1 and 25.92 ± 3.45 mcg cm-2 h-1 respectively. Based on the in-vivo rat studies results, this study proved a promising potential of simvastatin cubosomes as wound healing remedy.

Prevalence and Associated Factors of Eating Disorders Among Female Students at Jazan University, Kingdom of Saudi Arabia: A Survey Study.

BACKGROUND AND OBJECTIVE: Concerns about the incidence of eating disorders (EDs) among university students are spreading throughout the world. In Saudi Arabia, little is known about the prevalence and associated factors of EDs among female university students. Thus, this study investigated the prevalence, common types, and potential associated factors of EDs among female students of Jazan University.  Methods: A cross-sectional survey was conducted between August 31, 2020, and November 2, 2020. The snowball technique was used to recruit female students via an electronic survey distributed in Arabic. The survey collected information about demographic characteristics, and SCOFF (Sick, Control, One, Fat, Food) and Eating Attitudes Test (EAT-26) scales. Cronbach's alpha for the SCOFF and EAT-26 scales was calculated to be 0.78 and 0.58, respectively, in this study. RESULTS: A total of 566 female students participated in the survey, with a mean age of 22.12 ± 2.93 years. The results showed that 47.9% of participants were at risk for EDs based on SCOFF scores, while 26.5% were at risk based on EAT-26 scores. The most common types of EDs were bulimia nervosa and binge eating disorder. Furthermore, the study identified several sociodemographic characteristics, including year of study (p = 0.042), college type (p = 0.004), body weight (p = 0.001), and BMI (p = 0.001), that are significantly associated with EDs. However, no significant relationships were observed between marital status (p = 0.103), age (p = 0.147), and height (p = 0.509) with SCOFF scores. Some students reported frequent binge eating, purging, or laxative/diet pill misuse. CONCLUSIONS: The study revealed a moderate to high prevalence of risk for EDs among female university students in Jazan, Saudi Arabia, associated with higher study years, college majors, and body weight and BMI. Dangerous ED behaviors reported by some students signal an urgent need for resources to identify and support those suffering from these disorders. Targeted interventions and services may help address this critical issue on campuses and support vulnerable students in need. Continued research and public health action are needed to curb the spread of these disorders.

Impact of porous microsponges in minimizing myotoxic side effects of simvastatin.

Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV microsponges that have the potential to minimize the myotoxicity accompanying the oral administration of the drug. SV microsponges were prepared by exploiting the emulsion solvent evaporation technique. The % entrapment efficiency (%EE) of the drug approached 82.54 ± 1.27%, the mean particle size of SV microsponges ranged from 53.80 ± 6.35 to 86.03 ± 4.79 µm in diameter, and the % cumulative drug release (%CDR) of SV from microsponges was significantly higher than that from free drug dispersion much more, the specific surface area of the optimized microsponges formulation was found to be 16.6 m2/g revealed the porosity of prepared microsponges. Histological and glycogen histochemical studies in the skeletal muscles of male albino rats revealed that microsponges were safer than free SV in minimizing myotoxicity. These findings were proven by Gene expression of Mitochondrial fusion and fission (Mfn1) & (Fis1) and (Peroxisome proliferator-activated receptor gamma co-activator 1α) PGC-1α. Finally, our study ascertained that SV microsponges significantly decreased the myotoxicity of SV.

Profiling the Hsp70 Chaperone Network in Heat-Induced Proteotoxic Stress Models of Human Neurons.

Heat stroke is among the most hazardous hyperthermia-related illnesses and an emerging threat to humans from climate change. Acute brain injury and long-lasting brain damage are the hallmarks of this condition. Hyperthermic neurological manifestations are remarkable for their damage correlation with stress amplitude and long-term persistence. Hyperthermia-induced protein unfolding, and nonspecific aggregation accumulation have neurotoxic effects and contribute to the pathogenesis of brain damage in heat stroke. Therefore, we generated heat-induced, dose-responsive extreme and mild proteotoxic stress models in medulloblastoma [Daoy] and neuroblastoma [SH-SY5Y] and differentiated SH-SY5Y neuronal cells. We show that heat-induced protein aggregation is associated with reduced cell proliferation and viability. Higher protein aggregation in differentiated neurons than in neuroblastoma precursors suggests a differential neuronal vulnerability to heat. We characterized the neuronal heat shock response through RT-PCR array analysis of eighty-four genes involved in protein folding and protein quality control (PQC). We identify seventeen significantly expressed genes, five of which are Hsp70 chaperones, and four of their known complementing function proteins. Protein expression analysis determined the individual differential contribution of the five Hsp70 chaperones to the proteotoxic stress response and the significance of only two members under mild conditions. The co-expression analysis reveals significantly high co-expression between the Hsp70 chaperones and their interacting partners. The findings of this study lend support to the hypothesis that hyperthermia-induced proteotoxicity may underlie the brain injury of heat stroke. Additionally, this study presents a comprehensive map of the Hsp70 network in these models with potential clinical and translational implications.

Anticancer, anti-proliferative activity of Avicennia marina plant extracts.

PURPOSE: Medical halophytes plants are potent sources of bioactive secondary metabolite components used against different diseases. Avicenniamarina one of the typical halophytes plant species used in folk medicine to treat smallpox, rheumatism, and ulcer. Despite the richness of A.marina with polyphenolic, flavonoids, terpenoid, and terpene, contents remain poorly investigated against cancer types. Consequently, to explore the function-composition relationship of A.marina hexane leaves crude extract, the current study designed to investigate the cytotoxicity, apoptotic and antiproliferative impacts on the colon (HCT-116), liver (HepG2), and breast (MCF-7) cancer cell lines. MATERIALS AND METHODS: Therefore, the cytotoxicity impact screening carried out by Sulforhodamine-B assay. While, the initiation of the apoptosis evaluated by chromatin condensing, early apoptosis, late apoptosis and the formation and appearance of apoptotic bodies. On the other hand, the flow cytometry used to identify the phase of inhibition where the determined IC50 value used. While, the chemical composition of the hexane extract was detected using liquid chromatography-mass spectrometry/mass spectrometry. RESULTS: Revealed that hexane extract showed a weak induction of apoptosis despite the formation of apoptotic bodies and the high cell inhibitory effect on all tested cell lines with IC50 values (23.7 ± 0.7, 44.9 ± 0.93, 79.55 ± 0.57) µg/ml on HCT-116, HepG2, and MCF-7, respectively. Furthermore, it showed the ability to inhibit cell cycle in G0/G1 for HCT-116, S phase for HepG2, and MCF-7. CONCLUSION: In the light of these results, the current study suggests that A.marina leaves hexane extract may be considered as a candidate for further anticancer drug development investigations.

Bond Strength of Orthodontic Brackets to Temporary Crowns: In Vitro Effects of Surface Treatment.

BACKGROUND: The number of patients seeking orthodontic treatment has been consistently increasing. During orthodontic treatment, it is recommended to place the provisional restoration and to delay the final restoration until completion of orthodontic treatment. Recurrent bracket debonding necessitates orthodontists to prepare the bonding area with special measures. OBJECTIVE: This study aimed to evaluate the effect of different grit sizes of diamond burs and sandblasting surface treatment on the shear bond strength of orthodontic brackets to provisional crowns. MATERIALS AND METHODS: A total of 75 discs were fabricated from a bisacrylic composite and divided into 5 groups (n = 15) according to surface treatment by black, blue, and green diamond burs and sandblasting in addition to a control group. Metal orthodontic brackets were bonded to discs in a standardized conventional manner. All specimens were subjected to thermocycling with 5000 cycles of alternating 5°C and 55°C waterbaths. The shear bond strength test was performed using a universal testing machine. A scanning electron microscope (SEM) was used to analyze the surface treatment effect and features of debonded surfaces. The amount of composite resin left on the specimen surfaces was analyzed and classified with the adhesive remnant index. One-way ANOVA was performed at α = 0.05. RESULTS: The shear bond strength of specimens treated with sandblasting was significantly higher than that of the control group under thermal aging conditions (p=0.022), as well as blue burs (p=0.001), while no significant differences were found between different grit diamond burs and the controls (p > 0.05). CONCLUSION: Under thermocycling conditions, sandblasting of provisional crowns increases the bond strength of orthodontic brackets.

Mutation Profiling of Intracranial Myxopapillary Ependymoma by Next Generation DNA Sequencing.

OBJECTIVES: Primary intracranial myxopapillary ependymomas (MPE) are very rare. In order to determine genomic changes in an intracranial MPE, we analyzed its mutation patterns by next generation DNA sequencing. METHODS: Tumor DNA was sequenced using an Ion PI v3 chip on Ion Proton instrument and the data were analyzed by Ion Reporter 5.6. RESULTS: In this tumor, NGS generated 6,298, 354 mapped reads using the Ion PI v3 Chip. The average reads per amplicon was 29,365, 100% of amplicons had at least 500 reads and the amplicons read end-to-end were 97.58%. In this tumor, NGS data analysis identified 12 variants, of which two were missense mutations, seven were synonymous mutations and three were intronic variants. Missense mutation in c.395G>A; in exon 4 of the IDH1 gene, and a missense mutation in c.215C>G; in exon 4 of the TP53 gene were found in this tumor were previously reported. The known synonymous mutations were found in this tumor were, in exon 14 of FGFR3 in c.1953G>A; in exon 12 of PDGFRA in c.1701A>G; in exon 18 of PDGFRA c.2472C>T; in exon 20 of EGFR in c.2361G>A; in exon 13 of RET in c.2307G>T; in exon 16 of APC in c.4479G>A; and in exon 2 of MET in c.534C>T. Additionally, a known intronic variant was identified in KDR and a known acceptor site splice variant in FLT3 (rs2491231) and a SNP in the 3 ' -UTR of the CSF1R gene (rs2066934) were also identified. Except, the frequency of IDH1 variant, the frequencies of other variants were high, and the p-values were significant and Phred scores were high for all of these mutations. CONCLUSIONS: The variants reported in this tumor have not been detected in myxopapillary grade I ependymoma tumor by NGS analysis previously and we therefore report these variants in this case for the first time.

EGFRvIII expression and isocitrate dehydrogenase mutations in patients with glioma.

Molecular pathology and personalized medicine are still being evolved in Saudi Arabia, and genetic testing for the detection of mutations as cancer markers have not been established in the diagnostics laboratories in Saudi Arabia. The aim of the present study was to determine the prevalence of isocitrate dehydrogenase (IDH1 and IDH2) mutations and epidermal growth factor receptor variant (EGFRv)III transcript expression in Saudi Arabian patients with glioma. Out of 117 brain tumors tested by reverse transcription-quantitative PCR for EGFRvIII, 41 cases tested positive. In the glioblastoma (GBM) category, 28/55 tumors were positive, in astrocytoma tumors 5/22, and in oligodendrogliomas 4/13 cases were positive respectively. EGFRvIII transcript was sequenced by capillary electrophoresis to demonstrate the presence of EGFRvIII-specific junction where exons 2-7 were deleted. In the present study 106 tumors were sequenced for IDH1 exon-4 mutations using the capillary sequencing method. The most common substitution missense mutation c.395G>A was found in 16 tumors. In the case of adamantinomatous craniopharyngioma, a novel missense mutation in c.472C>T was detected in IDH2 gene. Using next-generation sequencing (NGS), 74 tumors were sequenced for the IDH1 gene, and a total of 8 missense variants were identified in 36 tumors in a population of Saudi Arabia. The missense mutation (c.395G>A) was detected in 29/36 of tumors. A novel intronic mutation in c.414+9T>A was found in 13 cases in the IDH1 gene. In addition, one case exhibited a novel synonymous mutation in c.369A>G. Eleven tumors were found to have compound mutations in the IDH1 gene. In IDH2 gene, out of a total of 16 variants found in 6 out of 45 tumors, nine were missense, five were synonymous and one was intronic. This is the first report from Saudi Arabian laboratories analyzing glioma tumors for EGFRvIII expression, and the first study from Saudi Arabia to analyze IDH mutations in gliomas using the capillary and NGS methods.

Chemo-Mechanical Approach to Improve Repair Bond Strength of Denture Teeth.

BACKGROUND: Detachment of acrylic teeth from denture base material is a common complication in dentistry which accounts for 26-30% of repair cases. This study aimed to evaluate the effect of alumina-blasting, silane coupling agent, and thermal cycling on the shear bond strength of repaired teeth to denture base. MATERIALS AND METHODS: Specimens (140) of repaired teeth to denture bases were fabricated and divided into 14 groups: 7 groups before thermal cycling and 7 groups after thermal cycling (n = 10). The groups were divided according to surface treatment into no treatment (control), treatment of the base (B), the tooth (T), or both (BT). Each group was further subdivided according to the surface treatment method into alumina-blasting or alumina-blasting and silane coupling agent. After treatment, acrylic discs and teeth were fixed in a jig, and the repair procedure was done. Half the specimens were thermally cycled. Shear bond strength was measured using a universal testing machine. ANOVA and Tukey HSD tests were performed at α = 0.05. RESULTS: Surface treatment significantly improved the bond strength compared to the control group (P < 0.001). Comparing surface treatments, alumina-blasting with silane coupling agent treatment resulted in significantly higher strength compared to alumina-blasting alone (P < 0.001). The BT group treated with alumina-blasting and silane coupling agent showed the highest significant shear bond strength (23.91 ± 0.96 MPa) (P < 0.001). Significant drop in strength value was observed in all groups after thermal cycling (P < 0.004) except the BT group treated with alumina-blasting (P=0.096). CONCLUSION: Surface treatment using alumina-blasting with silane coupling agent for denture base and tooth increased repair strength.

Adamantinomatous Craniopharyngioma in an Adult: A Case Report with NGS Analysis.

PURPOSE: Several recent studies have documented CTNNB1 and BRAF mutations which are mutually exclusive for adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) tumors. This discovery is helpful in the development of novel targeted therapies in successful clinical trials with BRAF mutations in PCP cases. However, no such targeted therapy is available yet for ACP. Here, we report novel mutations, which are not previously reported, in a case of an adult ACP using NGS analysis. RESULTS: Patient DNA was sequenced using Ion PI v3 chip on Ion Proton. A total of 16 variants were identified in this tumor by NGS analysis, out of which four were missense mutations, seven were synonymous mutations, and five were intronic variants. In CTNNB1 gene a known missense mutation in c.101G>T; in TP53 a known missense mutation in c.215C>G; and two known missense variants in PIK3CA, viz., in c.1173A>G; in exon 7, and in c.3128T>C; in exon 21, were found, respectively. Seven synonymous mutations were detected in this tumor, viz., in IDH1 (rs11554137), in FGFR3 (rs7688609), in PDGFRA (rs1873778), in APC (COSM3760869), in EGFR (rs1050171), in MET (rs35775721), and in RET (rs1800861), respectively. Three known, intronic variants were found in genes, such as PIK3CA, KDR, and JAK3, respectively. Also, a 3'-UTR and a splice site acceptor site variant in CSF1R and FLT3 genes were found in this tumor. We have shown allele coverage, allele ratio, and p-value, for all these mutations. The p-values and Phred quality score were significantly high for these variants. CONCLUSION: As reported in previous studies, in ACP tumors we found a CTNNB1 mutation by NGS analysis. The PIK3CA variants we detected were not known previously in ACP tumors. Finding the PIK3CA mutations in the ACP tumors may help develop targeted therapy for a subset of craniopharyngiomas with PIK3CA activating mutations. Clinical trials are in progress with specific PIK3CA inhibitors in advanced stages of many cancers.

Effect of SiO2 Nanoparticles Addition on the Flexural Strength of Repaired Acrylic Denture Base.

OBJECTIVE: The objective of this study was to evaluate the effect of nano-SiO2 addition on the flexural strength (FS) of repaired acrylic denture base. MATERIALS AND METHODS: Heat-polymerized acrylic resin specimens were fabricated in dimensions of (65 × 10 × 2.5 ± 0.1 mm3 ) and then sectioned and prepared, creating repair gap with butt (90 degrees) and bevel (45 degrees) repair surface designs forming two main groups according to joint design. Further subdivision was done into four groups (n = 10) according to nano-SiO2 concentration: one unmodified group and three modified groups (0.25, 0.5, and 0.75 wt %) in the autopolymerized repair resin. Each pair of a specimen was assembled in a mold and repaired according to manufacturer's recommendations. STATISTICAL ANALYSIS: Three-point bending test was done to measure FS, followed by scanning electron microscope (SEM) examination for fracture surface analysis. Data were analyzed using ANOVA and Tukey's post hoc test (α = 0.05). RESULTS: The addition of nano-SiO2 significantly improved FS of repaired acrylic resin in comparison to the unmodified group (p ˂ 0.05). For butt joint, significant differences between nano-SiO2 reinforced groups were noticed (p ˂ 0.05), while reinforced beveled groups did not differ significantly (p ˃ 0.05). Bevel design remarkably increased FS compared with butt design per respective filler concentration. From the SEM images, improved FS was presented with a homogeneous distribution of nano-SiO2 within polymethyl methacrylate. CONCLUSION: Nano-SiO2 addition to repair resin and 45 degree-beveled repair surface increased FS of repaired acrylic resin.

A Novel Approach to Improve Repair Bond Strength of Repaired Acrylic Resin: An in Vitro Study on the Shear Bond Strength.

PURPOSE: To evaluate the combined effect of mechanical surface treatment with intermediate bonding agents (methyl methacrylate [MMA] and silane coupling agents) and ZrO2 nanoparticle (nano-ZrO2 ) addition to repair material on the shear bond strength (SBS) of repaired denture bases. MATERIALS AND METHODS: Heat-polymerized acrylic resin was used to fabricate 130 cylindrical blocks (15 mm × 10 mm) and divided into a control group without treatment (C, n = 10), and 3 repair groups (n = 40/group) divided into specimens treated with alumina blasting alone (AB), specimens blasted with alumina combined with silane coupling agent (AB + SCA), or combined with MMA-based composite bonding agent (AB + MA). Treated groups were further subdivided according to nano-ZrO2 concentrations into 0 wt%, 2.5 wt%, 5 wt%, and 7.5 wt% added to repair resin powder. Repair resin monomer and polymer were combined and packed on the repair area and then placed in a pressure pot at 37°C for 15 minutes for polymerization. Shear bond test was performed using a universal testing machine. Scanning electron microscopy (SEM) was used to examine the effect of surface modifications on repair surfaces and to evaluate the topography of fracture surfaces. Tukey-Kramer multiple-comparison test was used to detect significant differences between groups (p ≤ 0.05). RESULTS: SBS (MPa) of specimens treated with alumina blasting and application of intermediate agents were significantly higher than the control group (p < 0.05), while no significant differences were found between AB and control group (p > 0.05). Nano-ZrO2 addition significantly increased SBS except for AB, and 5%, 7.5% MA (p > 0.05). SEM evaluation showed that alumina blasting created rougher and more porous surfaces, while SCA and MA reduced the irregularities and fissures. CONCLUSION: Application of bonding agents to repair surfaces after alumina blasting improved the repair bond strength and proved to be a possible new adhesive method for denture repair. Moreover, nano-ZrO2 addition in combination with surface treatment improved the repair bond strength.

Comparative Effect of Glass Fiber and Nano-Filler Addition on Denture Repair Strength.

PURPOSE: To evaluate and compare the effects of glass fiber (GF), Zirconium oxide nanoparticles (nano-ZrO2 ), and silicon dioxide nanoparticles (nano-SiO2 ) addition on the flexural strength and impact strength of repaired denture base material. MATERIALS AND METHODS: Heat-polymerized acrylic resin specimens were fabricated. All specimens were sectioned centrally and beveled creating 2.5 mm repair gap except for 10 controls. Specimen grouping (n = 10/group) was done according to filler concentration of 0%, 0.25%, 0.5%, and 0.75% of auto-polymerized acrylic powder. Modified resin was mixed, packed in the repair gap, polymerized, finished and polished. Three-point bending test and Charpy type impact testing were done. Data were analyzed using one-way-ANOVA and Post-Hoc Tukey test (α = 0.05). RESULTS: All additives significantly increased flexural strength and impact strength (p < 0.05). Within the modified subgroups, no significant differences were found for GF. Significant increase for nano-ZrO2 and significant decrease for nano-SiO2 as the concentration of additive increased were noted for both flexural strength and impact strength. Highest flexural strength was found with 0.75%-nano-ZrO2 (69.59 ± 2.52MPa) and the lowest was found with 0.75%-nano-SiO2 (53.82 ± 3.10MPa). The 0.25%-nano-SiO2 showed the highest impact strength value (2.54 ± 0.21 kJ/m2 ) while the lowest impact strength value was seen with 0.75%-nano-SiO2 (1.54 ± 0.17 kJ/m2 ). CONCLUSION: Nano-filler effect was concentration dependent and its addition to repair resin increased the flexural and impact strengths. The incorporation of 0.75%-ZrO2 or 0.25%-SiO2 into repair resin proved to be a promising technique to enhance repair strength and avoid repeated fractures.

Next generation DNA sequencing of atypical choroid plexus papilloma of brain: Identification of novel mutations in a female patient by Ion Proton.

Choroid plexus papilloma (CPP) is a rare benign tumor of the central nervous system that is usually confined to the cerebral ventricles. According to the World Health Organization, CPP corresponds to a grade I atypical CPP (a-CPP); however, it can become more aggressive and reach grade II, which can rarely undergo malignant transformation into a choroid plexus carcinoma (grade III). To the best of our knowledge, identification of these tumors mutations by next generation DNA sequencing (NGS) has not been yet reported. In the present study, NGS analysis of an a-CPP case was performed. Data were analyzed using Advaita Bioinformatics i-VariantGuide and Ion Reporter 5.6 programs. The results from NGS identified 12 novel missense mutations in the following genes: NOTCH1, ATM, STK36, MAGI1, DST, RECQL4, NUMA1, THBS1, MYH11, MALT1, SMARCA4 and CDH20. The PolyPhen score of six variants viz., DST, RECQL4, NUMA1, THBS1, MYHI1 and SMARCA4 were high, which suggested these variants represents pathogenic variants. Two novel insertions that caused frameshift were also found. Furthermore, two novel nonsense mutations and 14 novel intronic variants were identified in this tumor. The novel missense mutation detected in ATM gene was situated in c.5808A>T; p. (Leu1936Phe) in exon 39, and a known ATM mutation was in c.5948A>G; p. (Asn1983Ser). These novel mutations had not been reported in previous database. Subsequently, the quality statistics of these variants, including allele coverage, allele ratio, P-value, Phred quality score, sequencing coverage, PolyPhen score and alleles frequency was performed. For all variants, P-value was highly significant and the Phred quality score was high. In addition, the results from sequencing coverage demonstrated that 97.02% reads were on target and that 97.88% amplicons had at least 500 reads. These findings may serve at determining new strategies to distinguish the types of choroid plexus tumor, and at developing novel targeted therapies. Development of NGS technologies in the Kingdom of Saudi Arabia may be used in molecular pathology laboratories.

Utilization of lithium incorporated mesoporous silica for preventing necrosis and increase apoptosis in different cancer cells.

There are many molecules used as a drug carrier. TUD-1 is a newly synthesized mesoporous silica (SM) molecule possess two important features; consists of mesoporous so it is very suitable to be drug carrier in addition to that it has the ability to induce apoptosis in cancer cells. However, the effect of TUD-1 appears to act as cell death inducer, regardless of whether it is necrosis or apoptosis. Unfortunately, recent studies indicate that a proportion of cells undergo necrosis rather than apoptosis, which limits the use of TUD-1 as a secure treatment. On the other hand, lithium considered as necrosis inhibitor element. Hence, the current study based on the idea of producing a new Li-TUD-1 by incorporated mesoporous silica (TUD-1 type) with lithium in order to produce a new compound that has the ability to activate apoptosis by mesoporous silica (TUD-1 type) and at the same time can inhibit the activity of necrosis by lithium. Herein, lithium incorporated in TUD-1 mesoporous silica by using sol-gel technique in one-step synthesis procedure. Moreover, lithium incorporated in TUD-1 with different loading in order to form different active sites such as isolated lithium ions, nanoparticles of Li2O, and bulky crystals of Li2O. The ability of the new compounds to induce apoptosis and prevent necrosis was evaluated on three different types of cancer cell lines, which are; liver HepG-2, breast MCF-7, and colon HCT116. The obtained results show that Li-TUD-1 has the ability to control necrosis and thus reduce the side effects of treatments containing silica in the case of lithium added to them, especially in chronic cases. This opinion has demonstrated by the significant increase in the IC50 value and cell viability compared to control groups. Consequently, the idea is new, so it needs more develop and test with materials that have a more apoptotic impact than silica to induce apoptosis without induction of necrosis.

Catalyst-Free Vertical ZnO-Nanotube Array Grown on p-GaN for UV-Light-Emitting Devices.

One-dimensional (1D) structures-based UV-light-emitting diode (LED) has immense potential for next-generation applications. However, several issues related to such devices must be resolved first, such as expensive material and growth methods, complicated fabrication process, efficiency droop, and unavoidable metal contamination due to metal catalyst that reduces device efficiency. To overcome these obstacles, we have developed a novel growth method for obtaining a high-quality hexagonal, well-defined, and vertical 1D Gd-doped n-ZnO nanotube (NT) array deposited on p-GaN films and other substrates by pulsed laser deposition. By adopting this approach, the desired high optical and structural quality is achieved without utilizing metal catalyst. Transmission electron microscopy measurements confirm that gadolinium dopants in the target form a transparent in situ interface layer to assist in vertical NT formation. Microphotoluminescence (PL) measurements of the NTs reveal an intense ZnO band edge emission without a defect band, indicating high quality. Carrier dynamic analysis via time-resolved PL confirms that the emission of n-ZnO NTs/p-GaN LED structure is dominated significantly by the radiative recombination process without efficiency droop when high carrier density is injected optically. We developed an electrically pumped UV Gd-doped ZnO NTs/GaN LED as a proof of concept, demonstrating its high internal quantum efficiency (>65%). The demonstrated performance of this cost-effective UV LED suggests its potential application in large-scale device production.

Quality of life assessment of breast cancer patients in Saudi Arabia.

BACKGROUND: To assess the quality of life (QOL) of females with breast cancer in Saudi Arabia and its association with patients' demographic, social, and clinical data. MATERIALS AND METHODS: This analytical cross-sectional study was conducted among breast cancer patients attending King Abdullah Medical City, Makkah. Participants were asked to complete a self-administered structured questionnaire. We utilized the validated Arabic version of the European Organization for Research and Treatment of Cancer QOL-C30 (EORTC-QOL-C30) and breast cancer module QLQ-BR23 (EORTC-QOL-BR-23). Data were analysed using SPSS; mean and standard deviation computed for continuous variables, and percentages for categorical variables. Student's t-test performed to compare mean scores for various groups. RESULTS: Eighty-eight women participated in the study. The participants had a mean global health score of 64.0, standard deviation (SD) = 27.7. Of the functional scales, role functioning scored the highest (mean 71.2, SD = 31), while social and emotional functioning scored the lowest, (mean 57 SD = 35.8) and (mean 59.5 SD = 32), respectively. On the symptom scales, the most troubling symptoms were fatigue and insomnia, (mean 48.86 SD = 29.4) and (mean = 48, SD = 35), respectively. On the disease-specific tool (QLQ-BR23), body image and future perspective scored the lowest with a mean of 60.2 SD = 35 and 42.0 SD = 39.6, respectively. The most distressing symptom was hair loss (mean 61.56 SD = 41). CONCLUSIONS: Our population showed an acceptable overall global health score. However, they scored low on the important functional and symptoms domains. This study implies that patient age, social, and physical factors were possible determinants of global health and QOL scores. The healthcare system of Saudi Arabia should, therefore, address all these different aspects of QOL of breast cancer survivors.

Cell Cycle Arrest in Different Cancer Cell Lines (Liver, Breast, and Colon) Induces Apoptosis under the Influence of the Chemical Content of Aeluropus lagopoides Leaf Extracts.

Natural products, especially secondary metabolites produced by plants under stressed conditions, are shown to have different pharmacological impacts from one to another. Aeluropus lagopoides is one of the common halophyte plants that survive under stressed conditions, and has been used for healing wounds and as a painkiller. The bioactivity and the chemical composition of this plant have been poorly investigated. Consequently, the chemical components of A. lagopoides leaves were extracted using hexane (nonpolar), ethyl acetate (semi-polar), and n-butanol (polar) to extract the most extensive variety of metabolites. The cytotoxicity and anticancer impact of extracted secondary metabolites were evaluated against breast (MCF-7), colon (HCT-116), and liver (HepG2) cancer cell lines using a SulphoRhodamine-B (SRB) test. Their mechanisms of action were verified by observing the appearance of apoptotic bodies using the fluorescent microscope, while their antiproliferative impacts were evaluated using a flow cytometer. Results revealed that secondary metabolites extracted using hexane and ethyl acetate had the highest cytotoxicity and thus the greatest anticancer activity effect on HepG2 with IC50 (24.29 ± 0.85 and 11.22 ± 0.679 µg/mL, respectively). On the other hand, flow cytometer results showed that secondary metabolites could inhibit the cell cycle in the G0/G1 phase. To ascertain the chemical composition⁻function relationship, the extracts were analyzed using LC-MS/MS. Accordingly, A. lagopoides hexane and ethyl acetate extracts may contain agents with anticancer potential.