In silico evaluation of a new compound incorporating 4(3H)-quinazolinone and sulfonamide as a potential inhibitor of a human carbonic anhydrase.

The present study investigates the potential of a new compound containing sulfonamide and 4(3H)-quinazolinone to inhibit the hCA-IIX enzyme using in silico methods. Density functional theory-based calculations of electronic properties have been addressed through the analysis of frontier molecular orbitals, molecule electrostatic potential, and IR and UV-vis spectroscopy data. A molecular electrostatic potential analysis predicts that the target protein will be most inhibited by the sulfonamide groups since it has the highest potential spots for electrophile and nucleophile attack. The investigated compound exhibited good ADMET properties and satisfied the Lipinski rule of drug likeness. The hCA-IIX protein binding affinity with the proposed compound was determined by molecular docking analysis, which revealed a stable conformation with more negative binding energy (-12.19 kcal/mol) than the standard AZA drug (-7.36 kcal/mol). Moreover, a molecular dynamics study confirmed the docking results through trajectory analysis. The RMSD and RMSF both showed convergence and no significant fluctuations during the simulation time, which revealed a stable interaction within the active domain of the target protein. According to these findings, the proposed compound has a good pharmacological nature and could potentially be an efficient drug against hCAIX enzymes.

Screening of IL-22 first and second introns and FOXP3 second exon for SNPs and mutations with potential role in the susceptibility of SLE in selected population.

OBJECTIVE: The main objective of performing this study was the mutational analysis of Forkhead box family member (FoxP3) and Interleukin-22 (IL-22) genes and their associations with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: A total of sixty blood samples were collected from SLE patients from different hospitals in Lahore. Proforma was based on American College of Rheumatology (ACR) criteria. The total time for this research was one year (2018-2019). DNA was extracted, and FoxP3 and IL-22 genes were polymerized through PCR and further sequenced through the Sanger Sequencing method. Chromas version 2.6.6 was used for the similarity index of sequences. NG_060763 and NG_007392.1 were used as Reference Sequences of IL-22 and FoxP3 genes, respectively. RESULTS: Three already identified Single Nucleotide Polymorphisms (SNPs) in the IL-22 gene i.e., rs2227491, rs2227485, and rs2227513, were confirmed in the sequencing results of SLE patients. Results showed that there were nine novel mutations (27.27%) in the case of the IL-22 gene in the studied genotyped samples. These SNPs had remarkably increased allele T frequency in rs2227485 and allele C frequency in rs2227491 and rs2227513. On the other hand, in the case of FoxP3 gene exon 2, there was an addition of T at position 10 in the intronic portion, thus not involved in the progression of the disease. CONCLUSIONS: The importance of cytokine-mediated signaling pathways, such as the IL-22 gene, is thus established. Novel variants in the IL-22 gene likely contributed significantly to the development of this autoimmune disorder. The current study found that the dysregulation of the inflammatory markers in SLE is not related to the FoxP3 gene, even though FoxP3 is implicated in the tolerance process.

Tubermycin B coated on Galactosylated Chitosan Nanoparticles synthesized by eco-friendly method ameliorates intracellular free radical production and reduces oxidative stress, reducing phosphorylation of IKKα/ß/pIкBα/NF-кB pathway.

OBJECTIVE: The objective of the current study was to investigate the cytotoxic potentials of Galactosylated Chitosan Nanoparticles. Specifically, the study aimed to develop Tubermycin B coated on Galactosylated Chitosan Nanoparticles using a new green method that replaces sodium borohydride in the reduction process. MATERIALS AND METHODS: The study synthesized Tubermycin B coated on Galactosylated Chitosan Nanoparticles through a new green method. The cytotoxicity of these nanoparticles was evaluated in a mice intestinal tract model that had been induced with chlorpyrifos, which causes oxidative stress-related enterotoxicity. Multiple activities, including the apoptosis of intestinal macrophages and the activation of Ikappa α/ß kinase (IKKα/ß), were examined as indicators of the nanoparticles' efficacy. The stability of the synthesized Chitosan Nanoparticles was also assessed. Additionally, the encapsulation efficiency of Boscia angustifalia and Boscia senegalensis extracts within the nanoparticles was determined. RESULTS: The results of the study showed that Tubermycin B coated on Galactosylated Chitosan Nanoparticles effectively alleviated the oxidative stress-related enterotoxicity in the mice intestinal tract induced by chlorpyrifos. The nanoparticles prevented the apoptosis of intestinal macrophages and inhibited the activation of IKKα/ß. The synthesized chitosan nanoparticles exhibited high stability. The encapsulation efficiency of Boscia angustifalia extract was recorded as 46.58%, whereas for Boscia senegalensis extract, it was 9.77%. The nanoparticles showed no cytotoxicity at all tested concentrations and demonstrated a medium-level anticancer effect. CONCLUSIONS: Based on the findings, it can be concluded that Tubermycin B coated on Galactosylated Chitosan Nanoparticles has the potential to alleviate oxidative stress-related enterotoxicity in the mice intestinal tract. The nanoparticles showed high stability and exhibited a medium-level anticancer effect. Furthermore, the study demonstrated that Boscia angustifalia extract exhibited higher anti-hepatitis C virus antibodies (anti-HCV) activity compared to Boscia senegalensis extract in an in-vitro system. Therefore, Boscia angustifalia could be considered a promising candidate for the development of an anti-HCV drug for future in-vivo studies.

Examining the prevalence of obesity in school children through an on-site obesity outpatient clinics survey based on student's lifestyles.

OBJECTIVE: The purpose of this study was to identify the prevalence of obesity, overweight, and risk factors in pediatric patients attending outpatient clinics at a public sector hospital in the central province of Saudi Arabia. SUBJECTS AND METHODS: This cross-sectional study was conducted in Riyadh, the capital of Saudi Arabia, between January 2022 and October 2022. The target population was aged 6-15 years. We conducted on-site obesity assessments utilizing questionnaire-based interviews with patients attending outpatient clinics. Data collection was carried out with the help of parents, where required. Using BMI growth charts for Saudi children and teenagers, the weight, height, and body mass index (BMI) of subjects were computed. RESULTS: A total of 576 responses with a response rate of 64% were received and included in the study. In the current study, the majority (41.1%) of the patients were aged between 11 and 12 years old, followed by 37.0% of the students aged between 13 and 15 years old, and 21.9% of students aged between 8 and 10 years old. In the current study, 54.2% of the patients had normal weight, 15.6% of patients were underweight, 16.7% of patients were overweight, and 13.5% were obese. In this study, the prevalence of overall obesity was 2.3 times more prevalent in children aged 11 to 12 years (OR=2.30; p=0.03), followed by ~2 times higher levels in children aged 13 to 15 years (OR=2.30; p=0.03). Moreover, 2.11 times higher prevalence of obesity (OR=2.11; p=0.77) in those who regularly took food (especially lunch) from the school cafeteria. A significant ~2.5 high obesity level was recorded for students who consumed fizzy/soft drinks four or more times per week (OR=2.38; p=0.007). CONCLUSIONS: Saudi Arabia still has a high rate of overweight and obesity among children of school-going age, which is a significant public health issue. To properly address and control this issue, policies at the national, local, and individual levels must be implemented. Notably, there was also a high prevalence of being underweight, and this issue needs to be brought up as well.

Analysis of SARS-CoV-2 genomic surveillance data during the Delta and Omicron waves at a Saudi tertiary referral hospital.

BACKGROUND: Studying the genomic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may help determine outbreak clusters and virus transmission advantages to aid public health efforts during the pandemic. Thus, we tracked the evolution of SARS-CoV-2 by variant epidemiology, breakthrough infection, and patient characteristics as the virus spread during the Delta and Omicron waves. We also conducted phylogenetic analyses to assess modes of transmission. METHODS: Nasopharyngeal samples were collected from a cohort of 900 patients with positive polymerase chain reaction (PCR) test results confirming COVID-19 disease. Samples underwent real-time PCR detection using TaqPath assays. Sequencing was performed with Ion GeneStudio using the Ion AmpliSeq™ SARS-CoV-2 panel. Variant calling was performed with Torrent Suite™ on the Torrent Server. For phylogenetic analyses, the MAFFT tool was used for alignment and the maximum likelihood method with the IQ-TREE tool to build the phylogenetic tree. Data were analyzed using SAS statistical software. Analysis of variance or t tests were used to assess continuous variables, and χ2 tests were used to assess categorical variables. Univariate and multivariate logistic regression analyses were preformed to estimate odds ratios (ORs). RESULTS: The predominant variants in our cohort of 900 patients were non-variants of concern (11.1 %), followed by Alpha (4.1 %), Beta (5.6 %), Delta (21.2 %), and Omicron (58 %). The Delta wave had more male than female cases (112 vs. 78), whereas the Omicron wave had more female than male cases (311 vs. 208). The oldest patients (mean age, 43.4 years) were infected with non-variants of concern; the youngest (mean age, 33.7 years), with Omicron. Younger patients were mostly unvaccinated, whereas elderly patients were mostly vaccinated, a statistically significant difference. The highest risk for breakthrough infection by age was for patients aged 30-39 years (OR = 12.4, CI 95 %: 6.6-23.2), followed by patients aged 40-49 years (OR = 11.2, CI 95 %: 6.1-23.1) and then 20-29 years (OR = 8.2, CI 95 %: 4.4-15.4). Phylogenetic analyses suggested the interaction of multiple cases related to outbreaks for breakthrough infections, healthcare workers, and intensive care unit admission. CONCLUSION: The findings of this study highlighted several major public health ramifications, including the distribution of variants over a wide range of demographic and clinical variables and by vaccination status.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it’s role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review / Glicogênio sintase quinase-3 (GSK-3), uma enzima mágica: seu papel no diabetes mellitus e na homeostase da glicose: interações com fluoroquinolonas. Uma mini-revisão

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer’s disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: its role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimers disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it's role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review / Glicogênio sintase quinase-3 (GSK-3), uma enzima mágica: seu papel no diabetes mellitus e na homeostase da glicose: interações com fluoroquinolonas. Uma mini-revisão

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis ​​pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Protective effect of barbigerone against ethanol-induced ulcers via the interleukins/ICAM-1/Bcl-2 pathway.

OBJECTIVE: The objective of the study was to assess the protective effects of barbigerone in ethanol-induced gastric ulcers in rats. MATERIALS AND METHODS: Male Wistar rats (180±20 g) were used in the study (n=06). The rats were randomly divided into different groups, i.e., the normal group, ethanol control, and barbigerone 10 and 20 mg/kg group. Various biochemical parameters were assessed - total acidity and pH values, oxidative stress biomarkers such as superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and catalase (CAT) along with markers, i.e., tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, intercellular adhesion molecule-1 (ICAM-1) and expression of B-Cell Leukemia/Lymphoma 2 (Bcl-2). Also, histopathology was performed. RESULTS: Treatment with barbigerone in the ethanol-induced-ulcer rats restored the levels of biochemical parameters such as SOD, GSH, MDA, CAT, and markers expression, including TNF-α, IL-6, IL-1ß, ICAM-1, and Bcl-2 with protected against cellular necrosis. CONCLUSIONS: Barbigerone protective effects can be attributed to its ability to reduce oxidative stress and inflammation, as well as promote gastroprotection against ethanol-induced ulcers in rats.

Green synthesis of gold nanaoparticles using Delphinium Chitralense tuber extracts, their characterization and enzyme inhibitory potential.

Green synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

Green synthesis of gold nanaoparticles using Delphinium Chitralense tuber extracts, their characterization and enzyme inhibitory potential

Abstract Green synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

Resumo A síntese verde foi introduzida como uma alternativa à síntese química devido às graves consequências. As nanopartículas metálicas sintetizadas através da abordagem verde têm diferentes aplicações farmacêuticas, médicas e agrícolas. O presente estudo seguiu uma rota verde e simples para a preparação de nanopartículas de ouro potencialmente bioativas (Au NPs). As NPs de Au foram preparadas via abordagem de síntese verde usando a porção alcaloide básica bruta do tubérculo de Delphinium chitralense. As NPs de Au sintetizadas verdes foram caracterizadas por microscopia eletrônica de transmissão (TEM), microscopia eletrônica de varredura (MEV), difração de raios X (DRX), infravermelho com transformada de Fourier (FTIR) e espectrofotômetro UV-Visível. A análise morfológica mostra que as NPs de Au possuem geometria cúbica com tamanhos diferentes. A análise espectroscópica UV-Vis confirmou a síntese de Au NPs enquanto a XRD provou sua fase cristalina pura. O Au NPs mostrou inibição dependente da dose promissora de AChE e BChE em comparação com a droga bruta e padrão.

Green synthesis of gold nanaoparticles using Delphinium Chitralense tuber extracts, their characterization and enzyme inhibitory potential / Síntese verde de nanaopartículas de ouro utilizando extratos de tubérculos Delphinium chitralense, sua caracterização e potencial inibitório enzimático

Greeen synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

A síntese verde foi introduzida como uma alternativa à síntese química devido às graves consequências. As nanopartículas metálicas sintetizadas através da abordagem verde têm diferentes aplicações farmacêuticas, médicas e agrícolas. O presente estudo seguiu uma rota verde e simples para a preparação de nanopartículas de ouro potencialmente bioativas (Au NPs). As NPs de Au foram preparadas via abordagem de síntese verde usando a porção alcaloide básica bruta do tubérculo de Delphinium chitralense. As NPs de Au sintetizadas verdes foram caracterizadas por microscopia eletrônica de transmissão (TEM), microscopia eletrônica de varredura (MEV), difração de raios X (DRX), infravermelho com transformada de Fourier (FTIR) e espectrofotômetro UV-Visível. A análise morfológica mostra que as NPs de Au possuem geometria cúbica com tamanhos diferentes. A análise espectroscópica UV-Vis confirmou a síntese de Au NPs enquanto a XRD provou sua fase cristalina pura. O Au NPs mostrou inibição dependente da dose promissora de AChE e BChE em comparação com a droga bruta e padrão.

Adolescents' Usage and Attitude Toward Contact Lenses: A Descriptive Study In Saudi Arabia.

AIMS: The aim of this study was to explore adolescents' (11-20 years) usage of, beliefs in, attitudes toward, and barriers to contact lens use in Riyadh, Saudi Arabia. METHOD: The study recruited 1252 healthy participants from 20 highly populated schools. The schools were selected at random from middle and high schools in Riyadh. A self-administered contact lens questionnaire was used directed towards glasses usage and contact lens knowledge, usage, attitudes, and barriers. RESULT: A total of 726 of the 1252 participants had refractive errors, and 47% of those wore glasses. The proportion of non-compliance was 24%. One of the main reasons of non-compliance was cosmetic appearance (26%). Fewer than 10% were offered contact lenses for refractive error correction. One hundred and fifty-nine participants used contact lenses, and most obtained them without proper professional consultation. About 90% of contact lens-wearing participants did not sleep with the lenses and about 50% had no complications wearing them. CONCLUSION: The percentage of contact lens users was relatively low. A substantial number of older adolescents and females were found to wear contact lenses, although without proper professional consultation. Knowledge of and attitudes toward contact lenses among adolescents were in acceptable levels. These results gave indications that contact lens usage in adolescents can be achievable and valuable for refractive error correction, especially for those who are non-compliant with glasses.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it's role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review.

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Investigation of dosimetric impact of organ motion in static and dynamic conditions for three stereotactic ablative body radiotherapy techniques: 3D conformal radiotherapy, intensity modulated radiation therapy, and volumetric modulated arc therapy by using presage 3D dosimeters.

AIM: To investigate the use of PRESAGE 3D dosimeters to quantify the dosimetric variation between the static and dynamic conditions of three stereotactic ablative body radiotherapy techniques. MATERIALS AND METHODS: An in-house custom-designed thorax dynamic phantom was designed to simulate the tumor motion in two directions (i.e., superior/inferior (Z-axis) and anterior/posterior (Y-axis)). The PRESAGE dosimeter was attached to the moving arm of the phantom and irradiated in two scenarios (static and dynamic) using three stereotactic ablative body radiotherapy (SABR) techniques: 3D conformal radiotherapy (3D CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). RESULTS: The highest differences in the mean volume measurements between the two conditions were noticed in IMRT (0.14 cm3) and 3D CRT (0.13 cm3). The mean volume measurements of the VMAT showed the lowest difference between the static and dynamic conditions of 0.10 cm3. The gamma analysis for 3%, 3-mm criterion showed passing rates of < 1 for 3D CRT, IMRT, and VMAT. CONCLUSION: This study quantify the dosimetric variations which are caused by the tumor motion in lung cases. In the SABR of the lung for QA purposes, this could help in identifying the prescription dose coverage due to tumor movement and correlate with the planned dose using 3D dosimeters like PRESAGE.

Comparative analysis of margin status in breast conservation surgery and its correlation with subsequent re-excision findings.

PURPOSE: Breast-conservation surgery (BCS) has become a standard treatment option for invasive breast carcinoma (IBC) and ductal carcinoma in situ (DCIS). The strongest predictor of local recurrence remains the surgical margin status. We evaluated the margin positivity by quantifying the tumor on positive margins and analyzing the histologic factors including type and extent in determining the likelihood of residual disease upon re-excision. METHOD: Retrospective analysis of 210 BCS performed at Mount Sinai Medical Center from the period of January 2011 - December 2017 revealed that 58 had IBC, DCIS, or both, with positive margins that were followed by re-excision. RESULT: The margins had IBC in 18 (31%), DCIS in 32 (55.2%) and both in 8 (13%) cases. Thirty-eight cases (65.5%) were free of carcinoma on re-excision. Of 40 cases with margins positive for DCIS, 16 (40%) had residual DCIS. Of 26 cases with IBC at the margins, and 5 had residual disease (19%). This difference was statistically significant (p = 0.002). Of 21 cases with extensive DCIS, 12 had residual disease (p = 0.02) as compared to only 4 out of 19 without extensive DCIS. None of the cases with clinging/micro-papillary DCIS had residual disease, while 51% of the other types (solid, cribriform, come-do) had residual disease (p = 0.02). The area of DCIS as measured on the involved margin correlated with the amount of residual disease on re-excision (p = 0.03). CONCLUSION: Margins positive for DCIS are more likely to have residual disease on re-excision in comparison to margins positive for only IBC. The type and extent of DCIS appears to influence the likelihood of residual disease.

Evaluation of dose calculation algorithms using different density materials for in-field and out-of-field conditions.

AIM: The accuracy of the dose calculation is vital in the stereotactic ablative body radiotherapy (SABR) technique to achieve clinically effective dose distribution for better tumor control. Multiple commercial radiotherapy treatment planning systems (TPS) were implemented with different algorithms, such as Acuros XB in Eclipse and Superposition in XiO. The aim of this study is to investigate five different dose calculation algorithms, namely, pencil beam convolution (PBC), Acuros XB, AAA implemented in an Eclipse system, collapsed cone convolution (CCC) algorithm implemented in Mobius3D and superposition algorithms implemented in the XiO system, and then validate the results against measurements using an Institute of Physical Sciences in Medicine (IPSM) phantom with different density materials for in-field and out-of- field conditions. MATERIAL AND METHODS: The IPSM phantom was used to investigate the dose calculation algorithm performances in four different densities (water, lung, ribs, and dense bone) using different beam configurations, including small beam fields utilised in lung SABR. Five commercial algorithms implemented in two TPS (Eclipse and XiO) and one plan check (M3D) system were used for in-field and out-of-field measurement. RESULTS: In the in-field condition, the Acuros XB algorithm had lower mean differences than the measured dose by the IC ranging from -0.46 to 0.24 for all the densities. In the out-of-field condition, the results of eclipse system: AAA, PBC and Acuros XB algorithms demonstrated underdose point's measurements by -40% for all densities except for AAA calculations in lung density (overdosed by 40%). The measured points of the superposition algorithms were overestimated to the actual dose less than 30% in water, lung and dense bone. At the same densities, the CCC algorithms showed relatively the lowest differences in percentage compared to the superposition algorithms. CONCLUSION: Our results showed that the Acuros XB and superposition algorithms are closer to the actual measured dose than AAA, PBC and CCC for majority of the field conditions for water-equivalent, lung, rib and dense bone densities. The CCC algorithm resulted in a better agreement with the measurement of the out-of-field points compared with the other algorithms.

Pulsed UV laser-induced modifications in optical and structural characteristics of alpha-irradiated PM-355 SSNTD.

Pre- and postalpha-exposed PM-355 detectors were irradiated using UV laser with different number of pulses (100, 150, 200, 300, and 400). UV laser beam energy of 20mJ per pulse with a pulse width of 9ns was incident on an area of 19.6mm2 of the samples. XRD spectra indicated that for both reference and UV-irradiated samples, the structure is amorphous, but the crystallite size increases upon UV irradiation. The same results were obtained from SEM analysis. Optical properties of PM-355 polymeric solid-state nuclear track detectors were also investigated. Absorbance measurements for all PM-355 samples in the range of 200-400nm showed that the absorption edge had a blue shift up to a certain value, and then, it had an oscillating behavior. Photoluminescence spectra of PM-355 at 250nm revealed a decrease in the broadband peak intensity as a function of the number of UV pulses, while the wavelengths corresponding to the peaks had random shifts.

Synergistic interaction between lipid-loading and doxorubicin exposure in Huh7 hepatoma cells results in enhanced cytotoxicity and cellular oxidative stress: implications for acute and chronic care of obese cancer patients.

There has been a dramatic increase in the number of clinically obese individuals in the last twenty years. This has resulted in an increasingly common scenario where obese individuals are treated for other diseases, including cancer. Here, we examine interactions between lipid-induced steatosis and doxorubicin treatment in the human hepatoma cell line Huh7. The response of cells to either doxorubicin, lipid-loading or a combination were examined at the global level by DNA microarray, and for specific endpoints of cytotoxicity, lipid-loading, reactive oxygen species, anti-oxidant response systems, and apoptosis. Both doxorubicin and lipid-loading caused a significant accumulation of lipid within Huh7 cells, with the combination resulting in an additive accumulation. In contrast, cytotoxicity was synergistic for the combination compared to the individual components, suggesting an enhanced sensitivity of lipid-loaded cells to the acute hepatotoxic effects of doxorubicin. We demonstrate that a synergistic increase in reactive oxygen species and deregulation of protective anti-oxidant systems, most notably metallothionein expression, underlies this effect. Transcriptome analysis confirms synergistic changes at the global level, and is consistent with enhanced pro-inflammatory signalling in steatotic cells challenged with doxorubicin. Such effects are consistent with a potentiation of progression along the fatty liver disease spectrum. This suggests that treatment of obese individuals with doxorubicin may increase the risk of both acute (i.e. hepatotoxicity) and chronic (i.e. progress of fatty liver disease) adverse effects. This work highlights the need for more study in the growing therapeutic area to develop risk mitigation strategies.

Peroxidase and polyphenol oxidase activity in moderate resistant and susceptible Vicia faba induced by Aphis craccivora (Hemiptera: Aphididae) infestation.

Two faba bean, Vicia faba L., cultivars, Gazira2 and Misr1, representing cultivars moderately resistant and susceptible to aphids, were analyzed for peroxidase (POD) and polyphenol oxidase (PPO) activities induced by cowpea aphid, Aphis craccivora Koch. infestation. Two tissue types (whole plant [WP] and detached leaf [DL]), two infestation status (infested and uninfested), and three aphid infestation durations (1, 3, and 5 d) were considered in POD and PPO data analysis. Factorial analysis showed that only cultivar factor has a significant effect on both POD and PPO activity, especially on the first day after aphid infestation (P: 0.0003 and 0.001, respectively). Tissue type has no significant effect, indicating either DL or WP can be used for measuring POD and PPO activities. While the unsignificant different of infestation status reflecting a constitutive resistant character in Gazira2. Mann-Whitney U-test showed that POD and PPO activities in Gazira2 were higher significantly when compared with Misr1 with P value 0.0006 and 0.0015 for POD and PPO, respectively. Repeated measures analysis indicates that the POD and PPO activities on Gazira2 were significantly higher when compared with Misr1. Additionally, POD activity changed significantly over the time in 1, 3, and 5 d after aphid infestation. We concluded that higher activity of POD and PPO in cultivar Gazira2 is strongly associated with their resistant characters.