Design, synthesis, and molecular dynamics simulation studies of some novel kojic acid fused 2-amino-3-cyano-4H-pyran derivatives as tyrosinase inhibitors.

A novel series of kojic acid fused 2-amino-3-cyano-4H-pyran derivatives were synthesized via a multicomponent reaction involving kojic acid, benzyloxy benzaldehyde, and malonitrile as tyrosinase inhibitors. Subsequently, the structures of the compounds were characterized using FT-IR, 1H-, and 13C-NMR spectroscopic analyses. The designed compounds fall into three series: (1) 4-benzyloxy-phenyl kojopyran 6a-e, (2) 3-benzyloxy- phenyl kojopyran derivatives 6f-j, and (3) 4-benzyloxy-3-methoxy-phenyl kojopyran derivative 6 k-o. The assessment of tyrosinase inhibition activity was conducted using L-Dopa as the substrate. Among synthesized compounds, 2-amino-4-(4-((4-fluorobenzyl)oxy)phenyl)-6-(hydroxymethyl)-8-oxo-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile (6b) demonstrated the highest antityrosinase activity with a competitive inhibition pattern (IC50 = 7.69 ± 1.99 µM) as compared to the control agent kojic acid (IC50 = 23.64 ± 2.56 µM). Since compound 6b was synthesized as a racemic mixture, in silico studies were performed for both R and S enantiomers. The R- enantiomer showed critical interactions compared with the S-enantiomer. Specifically, it established hydrogen bonds and hydrophobic interactions with crucial and highly conserved amino acids within the enzyme's binding site in the target protein. Moreover, the molecular dynamics simulations revealed that compound 6b demonstrated significant interactions with essential residues of the binding site, resulting in a stable complex throughout the entire simulation run. The drug-like and ADMET properties predictions showed an acceptable profile for compound 6b. Thus, it can serve as a drug candidate to develop more potent antityrosinase agents due to its low toxicity and its high inhibition activity.

Stewardship; The Missing Loop of Rehabilitation in the Health System: A Policy Brief.

Providing optimal rehabilitation services for people with disabilities has always been recognized as a major concern of health systems in all countries. Stewardship is one of the biggest challenges to provide rehabilitation services to people with disabilities in Iran. We advocate the Ministry of Health & Medical Education (MoHME) to take the lead as a steward of rehabilitation services in Iran, while the dedicated sections in the MoHME need to be determined, with a clear list of responsibilities and affiliations.

Novel Pyrano[3,2-c]quinoline-1,2,3-triazole Hybrids as Potential Anti-Diabetic Agents: In Vitro α-Glucosidase Inhibition, Kinetic, and Molecular Dynamics Simulation.

In this study, a novel series of pyrano[3,2-c]quinoline-1,2,3-triazole hybrids 8a-o were synthesized and evaluated against the α-glucosidase enzyme. All compounds showed significant in vitro inhibitory activity (IC50 values of 1.19 ± 0.05 to 20.01 ± 0.02 µM) compared to the standard drug acarbose (IC50 = 750.0 µM). Among them, 2-amino-4-(3-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile (compound 8k) demonstrated the best inhibitory effect toward α-glucosidase (IC50 = 1.19 ± 0.05 µM) with a competitive pattern of inhibition. Since compound 8k was synthesized as a racemic mixture, molecular docking and dynamics simulations were performed on R- and S-enantiomers of compound 8k. Based on the molecular docking results, both R- and S-enantiomers of compound 8k displayed significant interactions with key residues including catalytic triad (Asp214, Glu276, and Asp349) in the enzyme active site. However, an in silico study indicated that S- and R-enantiomers were inversely located in the enzyme active site. The R-enantiomer formed a more stable complex with a higher binding affinity to the active site of α-glucosidase than that of the S- enantiomer. The benzyl ring in the most stable complex ((R)-compound 8k) was located in the bottom of the binding site and interacted with the enzyme active site, while the pyrano[3,2-c]quinoline moiety occupied the high solvent accessible entrance of the active site. Thus, the synthesized pyrano[3,2-c]quinoline-1,2,3-triazole hybrids seem to be promising scaffolds for the development of novel α-glucosidase inhibitors.

Are women with preterm labour at risk for negative birth experience? a comparative cross-sectional study from Iran.

BACKGROUND: The unpredictable nature of preterm labour can be a stressful experience for the mother. The occurrence of preterm birth can lead to the failure of the mother's previous expectations regarding the process of labour and birth leading to negative perception towards birth. METHODS: This descriptive-analytical cross-sectional study was conducted in Tabriz, Iran. We employed convenience sampling to recruit eligible mothers with term birth (314 women) and preterm birth (157 women). Childbirth Experience Questionnaire 2.0, Preterm Birth Experiences and Satisfaction Scale, and Delivery Fear Scale were used to measure the woman's fear of delivery during labour and birth experience. Data were analysed by general linear model. RESULTS: The prevalence of negative birth experience in the term and preterm birth groups was 31.8% and 14.3%, respectively. The results of the multivariable general linear model, after the adjustment of demographic and obstetric characteristics, showed that there was no statistically significant difference between the two groups of mothers with term and preterm birth [ß (95% CI): -0.06 (-0.22 to 0.09); p = 0.414] in terms of childbirth experience. However, the fear of delivery had a significant relationship with the childbirth experience [-0.02 (-0.03 to -0.01); p < 0.001]. CONCLUSION: There was no statistically significant difference in terms of women's childbirth experience between the mothers with term and preterm births. The fear of delivery during labour was the predictor of childbirth experience. In order to improve women's childbirth experience, interventions should be made to reduce their fear during labour.

Investigation of biological activities of two cultivars of Cicer arietinum proteins mass associated with Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with some known classical factors. Cicer arietinum (Leguminosae) is a source of protein for humans and contains albumin, globulin, glutelin, and prolamin. The protein content of two cultivars of C. arietinum, Hashem and Mansour, was isolated to evaluate their inhibition activity against acetylcholinesterase (AChE), butyrylcholine esterase (BChE), and ß-amyloid peptide (ßA) aggregation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and molecular docking were also applied to evaluate the content and determine the potential of each chickpea protein to interact with AChE, respectively. Obtained data showed that proteins from both cultivars could inhibit AChE with IC50 of 17.73 (0.03) and 22.20 (0.06) µg/mL, respectively, with no activity on BChE. The 50 µg/mL protein concentration of each cultivar suppressed ßA accumulation (Mansour: 25.66% and Hashem: 21.69%) and showed biometal chelating activity. SDS-PAGE analysis revealed relatively different protein patterns, though the Mansour cultivar contained some protein bands with molecular weights of 18, 24, and 70 kDa were estimated to belong to vicilin and legumin, which were absent in the Hashem protein mass. Molecular docking showed that legumin and especially vicilin have good potential to interact with AChE. The chickpea proteins showed inhibitory activity against AChE, which might be due to the vicilin and legumin fractions. The characterization of the inhibitory effect of each protein band could be promising in finding new therapeutic peptide candidates to treat Alzheimer's in the future, although more experimental work is needed in this issue.

Synthesis of Novel Pyrimido[4,5-b] Quinolines Containing Benzyloxy and 1,2,3-Triazole Moieties by DABCO as a Basic Catalyst.

DABCO was used as a basic and inexpensive catalyst for the synthesis of some new benzyloxy pyrimido[4,5-b]quinoline derivatives and 1,2,3- triazole-fused pyrimido[4,5-b]quinolines by the one-pot multi-component reaction of various benzyloxy benzaldehydes or benzylic -1,2,3-triazol-4-yl-methoxy benzaldehydes with dimedone and 6-amino-1,3-dimethyluracil at 90 °C under the solvent-free condition.

Urinary incontinence and related quality of life among elderly women in Tabas, South Khorasan, Iran.

BACKGROUND: Urinary incontinence (UI) is one of the most common problems in old age that is often seen in women, which causes not only physical problems but also psychological, social, economic problems and poor quality of life. The aim of the present study was to evaluate the UI and related quality of life (QoL) in elderly women. METHODS: This cross-sectional study enrolled 369 women over 60 years old and living in Tabas city, Iran who were selected by cluster random sampling method. The instruments included the International Consultation on Incontinence Questionnaire-Short Form, the International Consultation on Incontinence Questionnaire Urinary Incontinence Quality of Life Module, and a demographic questionnaire. Data analysis was carried out using independent t-test, chi-square, and logistic regression in SPSS software. RESULTS: The UI prevalence among participants was 24.9% and stress urinary incontinence was the most common type (40.2% of all elderly patients). The mean UI-related QoL score was 38.04 ± 11.67 from the score range of 22-76. There was a significant positive correlation between UI-related QoL score and UI score (r = 0.585, p < 0.001). Age, body mass index (BMI), constipation, history of cesarean section, hypertension, and the use of angiotensin receptor blockers are factors increasing the odds of having UI in this study population. CONCLUSION: Aging, some chronic diseases, high BMI, and the use of some drugs are related to UI prevalence. Also, it is associated with lower QOL among elderly women. Designing appropriate intervention programs, controlling chronic diseases, training in the proper use of drugs, and also some physical exercises can be effective in controlling and improving this common syndrome of old age and promoting their QoL.

Ultrasound-assisted synthesis of kojic acid-1,2,3-triazole based dihydropyrano[3,2-b]pyran derivatives using Fe3O4@CQD@CuI as a novel nanomagnetic catalyst.

The magnetic nanoparticles coated with carbon quantum dot and copper (I) iodide (Fe3O4@CQD@CuI) were used as eco-friendly heterogeneous Lewis / Brønsted acid sites and Cu (I) nanocatalysts. In the first step, it was applied in the synthesis of kojic acid-based dihydropyrano[3,2-b]pyran derivatives in a three-component reaction and in the second step, as a recyclable catalyst for the synthesis of kojic acid-1,2,3-triazole based dihydropyrano[3,2-b]pyran derivatives in the CuI-catalyzed azide/alkyne cycloaddition (CuAAC) reaction. The catalyst was characterized fully by using the different techniques including fourier transform infrared spectroscopy (FT-IR), elemental mapping analysis, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray spectroscopy (EDX), transmission electron microscopy (TEM), thermal gravimetric (TG) and value-stream mapping (VSM) methods. The final synthesized derivatives were identified by 1H- and 13C-NMR spectroscopy.

Factors affecting nurses' retention in Iranian hospitals.

AIM: This research was conducted to study the factors affecting nurses' retention in Iranian hospitals. BACKGROUND: Health care systems should pay attention to their human resources' retention to deliver health care services and maintain their organizational values. This issue becomes more significant when we consider the human and financial limitations in place. METHOD: Data were analysed using conventional qualitative content analysis based on the model developed by Elo and Kyngäs. Forty-two managers and nurses were selected by purposive sampling. Data were obtained through 45 semi-structured interviews until data saturation was reached. RESULTS: The data analysis resulted in four main categories and 17 subcategories. The main categories included dignity and respect, ethics and spirituality, empathy, and flourishing. The main theme extracted was 'maternal management'. CONCLUSION: The present study proposes 'maternal management' as a strategy to increase the retention of nurses.

Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: in vitro and in vivo biological activities against Alzheimer's disease.

Alzheimer's disease (AD) is now ranked as the third leading cause of death after heart disease and cancer. There is no definite cure for AD due to the multi-factorial nature of the disease, hence, multi-target-directed ligands (MTDLs) have attracted lots of attention. In this work, focusing on the efficient cholinesterase inhibitory activity of tacrine, design and synthesis of novel arylisoxazole-tacrine analogues was developed. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition assay confirmed high potency of the title compounds. Among them, compounds 7l and 7b demonstrated high activity toward AChE and BChE with IC50 values of 0.050 and 0.039 µM, respectively. Both compounds showed very good self-induced Aß aggregation and AChE-induced inhibitory activity (79.4 and 71.4% for compound 7l and 61.8 and 58.6% for compound 7b, respectively). Also, 7l showed good anti-BACE1 activity with IC50 value of 1.65 µM. The metal chelation test indicated the ability of compounds 7l and 7b to chelate biometals (Zn2+, Cu2+, and Fe2+). However, they showed no significant neuroprotectivity against Aß-induced damage in PC12 cells. Evaluation of in vitro hepatotoxicity revealed comparable toxicity of compounds 7l and 7b with tacrine. In vivo studies by Morris water maze (MWM) task demonstrated that compound 7l significantly reversed scopolamine-induced memory deficit in rats. Finally, molecular docking studies of compounds 7l and 7b confirmed establishment of desired interactions with the AChE, BChE, and BACE1 active sites.

Novel tacrine-based acetylcholinesterase inhibitors as potential agents for the treatment of Alzheimer's disease: Quinolotacrine hybrids.

A new series of quinolotacrine hybrids including cyclopenta- and cyclohexa-quinolotacrine derivatives were designed, synthesized, and assessed as anti-cholinesterase (ChE) agents. The designed derivatives indicated higher inhibitory effect on the acetylcholinesterase (AChE) with IC50 values of 0.285-100 µM compared to butyrylcholinesterase (BChE) with IC50 values of > 100 µM. Of these compounds, cyclohexa-quinolotacrine hybrids displayed a little better anti-AChE activity than cyclopenta-quinolotacrine hybrids. Compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c'] diquinolin-6-one (6m) including 3-hydroxyphenyl and cyclohexane ring moieties exhibited the best AChE inhibitory activity with IC50 value of 0.285 µM. The kinetic and molecular docking studies indicated that compound 6m occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE as a mixed inhibitor. Using neuroprotective assay against H2O2-induced cell death in PC12 cells, the compound 6h illustrated significant protection among the assessed compounds. In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these quinolotacrine hybrids can be very encouraging AChE inhibitors to treat Alzheimer's disease. A novel series of quinolotacrine hybrids were designed, synthesized, and evaluated against AChE and BChE enzymes as potential agents for the treatment of AD. The hybrids showed good to significant inhibitory activity against AChE (0.285-100 µM) compared to butyrylcholinesterase (BChE) with IC50 values of > 100 µM. Among them, compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c'] diquinolin-6-one (6 m) bearing 3-hydroxyphenyl moiety and cyclohexane ring exhibited the highest anti-AChE activity with IC50 value of 0.285 µM. The kinetic and molecular docking studies illustrated that compound 6 m is a mixed inhibitor and binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE.

Pullulan films loading saffron extract encapsulated in nanoliposomes; preparation and characterization.

Nanoencapsulation of saffron extract (SE) components into the rapeseed lecithin nanoliposomes were performed by sonication of their aqueous dispersions as a green process. Dynamic light scattering (DLS) results exhibited that empty and SE loaded nanoliposomes (SENL) had average sizes in range of 118-138 nm, negative zeta potentials (-32.0 to -46.8 mV) and polydispersity index (PDI) less than 0.3 during storage for 28 days at 4 °C. Encapsulation efficiency of crocin was approximately 30%. The 70% of crocin released from SENLs within 5 h in PBS solution. Pullulan-based films were fabricated by incorporation of empty and SE loaded nanoliposomes into pullulan solution through casting method. The mechanical resistance and thermal stability of the films reduced by addition of nanoliposomes. FTIR and thermal characterizations indicated that SE was successfully encapsulated in the nanoliposomes and film matrix with high thermal stability. Incorporation of nanoliposomes enhanced the oxygen barrier properties of the films, while it didn't significantly affect the water vapor permeability (WVP) of the films. The obtained edible films or coatings can provide additional benefits due to unique flavor and color of saffron. In addition, the utilization of SE, can provide benefits for health-allegation from SE antioxidant capacity.

Computational drug repurposing study of antiviral drugs against main protease, RNA polymerase, and spike proteins of SARS-CoV-2 using molecular docking method.

OBJECTIVES: The new Coronavirus (SARS-CoV-2) created a pandemic in the world in late 2019 and early 2020. Unfortunately, despite the increasing prevalence of the disease, there is no effective drug for the treatment. A computational drug repurposing study would be an appropriate and rapid way to provide an effective drug in the treatment of the coronavirus disease of 2019 (COVID-19) pandemic. In this study, the inhibitory potential of more than 50 antiviral drugs on three important proteins of SARS-CoV-2, was investigated using the molecular docking method. METHODS: By literature review, three important proteins, including main protease, RNA-dependent RNA polymerase (RdRp), and spike, were selected as the drug targets. The three-dimensional (3D) structure of protease, spike, and RdRp proteins was obtained from the Protein Data Bank. Proteins were energy minimized. More than 50 antiviral drugs were considered as candidates for protein inhibition, and their 3D structure was obtained from Drug Bank. Molecular docking settings were defined using Autodock 4.2 software and the algorithm was executed. RESULTS: Based on the estimated binding energy of docking and hydrogen bond analysis and the position of drug binding, five drugs including, indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, had the highest inhibitory potential for all three proteins. CONCLUSIONS: According to the results, among the mentioned drugs, saquinavir and lopinavir showed the highest inhibitory potential for all three proteins compared to the other drugs. This study suggests that saquinavir and lopinavir could be included in the laboratory phase studies as a two-drug treatment for SARS-CoV-2 inhibition.

Investigation of anti-Alzheimer's activity of aqueous extract of areca nuts (Areca catechu L): in vitro and in vivo studies / Investigación de la actividad anti-Alzheimer del extracto acuoso de nueces de areca (Areca catechu L): estudios in vitro e in vivo

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Sever cognitive and memory impairments, huge increase in the prevalence of the disease, and lacking definite cure have absorbed worldwide efforts to develop therapeutic approaches. Since many drugs have failed in the clinical trials due to multifactorial nature of AD, symptomatic treatments are still in the center attention and now, nootropic medicinal plants have been found as versatile ameliorators to reverse memory disorders. In this work, anti-Alzheimer's activity of aqueous extract of areca nuts (Areca catechu L.) was investigated via in vitro and in vivo studies. It depicted good amyloid ß (Aß) aggregation inhibitory activity, 82% at 100 µg/mL. In addition, it inhibited beta-secretase 1 (BACE1) with IC50 value of 19.03 µg/mL. Evaluation of neuroprotectivity of the aqueous extract of the plant against H2O2-induced cell death in PC12 neurons revealed 84.5% protection at 1 µg/mL. It should be noted that according to our results obtained from Morris Water Maze (MWM) test, the extract reversed scopolamine-induced memory deficit in rats at concentrations of 1.5 and 3 mg/kg.

La enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo relacionado con la edad. Los severos deterioros cognitivos y de la memoria, el enorme aumento de la prevalencia de la enfermedad y la falta de una cura definitiva han absorbido los esfuerzos mundiales para desarrollar enfoques terapéuticos. Dado que muchos fármacos han fallado en los ensayos clínicos debido a la naturaleza multifactorial de la EA, los tratamientos sintomáticos siguen siendo el centro de atención y ahora, las plantas medicinales nootrópicas se han encontrado como mejoradores versátiles para revertir los trastornos de la memoria. En este trabajo, se investigó la actividad anti-Alzheimer del extracto acuoso de nueces de areca (Areca catechu L.) mediante estudios in vitro e in vivo. Representaba una buena actividad inhibidora de la agregación de amiloide ß (Aß), 82% a 100 µg/mL. Además, inhibió la beta-secretasa 1 (BACE1) con un valor de CI50 de 19,03 µg/mL. La evaluación de la neuroprotección del extracto acuoso de la planta contra la muerte celular inducida por H2O2 en neuronas PC12 reveló una protección del 84,5% a 1 µg/mL. Cabe señalar que, de acuerdo con nuestros resultados obtenidos de la prueba Morris Water Maze (MWM), el extracto revirtió el déficit de memoria inducido por escopolamina en ratas a concentraciones de 1,5 y 3 mg/kg.

Convention on the rights of persons with disabilities: Qualitative exploration of barriers to the implementation of articles 25 (health) and 26 (rehabilitation) in Iran.

Background: The International Convention on the Rights of Persons with Disabilities (CRPD) is the most important International Document for recognizing the rights of persons with disabilities, including the right to health and rehabilitation. Islamic Republic Iran acceded to the Convention in 2008, but still has a long way to go to achieve its desired status and in line with the objectives of the convention. This study aimed to identify the barriers to the implementation of articles 25 and 26 of the CRPD in Iran. Methods: This study was performed using conventional content analysis. Twenty-one individuals were recruited by purposive sampling with maximum variation and were continued until saturation. Data were gathered through in-depth, semi-structured interviews from June 2018 to May 2019. MAXQDA version 10 was used for analyzing data. Results: The resulting data analysis yielded 860 initial or open codes. The concepts were categorized into 27 subcategories and 7 categories. Main categories were included: "Structure inefficiency", "lack of comprehensive rehabilitation program", "inadequate awareness", "neglected economy of people with disabilities", "weak access to services", "cultural challenges" and "disregard for new technologies". Conclusion: The findings showed that the executive structures in the country have a lot of problems with health and rehabilitation programs for people with disabilities. It seems understanding the barriers to implementation of articles 25 and 26 of the international CRPD empowers officials in the field and improve services by providing a better view of the disabled. Nevertheless, it is recommended for policymakers to consider rehabilitation as a main element of the health system.

Design, Synthesis, and Molecular Docking of Some Novel Tacrine Based Cyclopentapyranopyridine- and Tetrahydropyranoquinoline-Kojic Acid Derivatives as Anti-Acetylcholinesterase Agents.

A novel series of tacrine based cyclopentapyranopyridine- and tetrahydropyranoquinoline-kojic acid derivatives were designed, synthesized, and evaluated as anti-cholinesterase agents. The chemical structures of all target compounds were characterized by 1 H-NMR, 13 C-NMR, and elemental analyses. The synthesized compounds mostly inhibited acetylcholinesterase enzyme (AChE) with IC50 values of 4.18-48.71 µM rather than butyrylcholinesterase enzyme (BChE) with IC50 values of >100 µM. Among them, cyclopentapyranopyridine-kojic acid derivatives showed slightly better AChE inhibitory activity compared to tetrahydropyranoquinoline-kojic acid. The compound 10-amino-2-(hydroxymethyl)-11-(4-isopropylphenyl)-7,8,9,11-tetrahydro-4H-cyclopenta[b]pyrano[2',3' : 5,6]pyrano[3,2-e]pyridin-4-one (6f) bearing 4-isopropylphenyl moiety and cyclopentane ring exhibited the highest anti-AChE activity with IC50 value of 4.18 µM. The kinetic study indicated that the compound 6f acts as a mixed inhibitor and the molecular docking studies also illustrated that the compound 6f binds to both the catalytic site (CS) and peripheral anionic site (PAS) of AChE. The compound 6f showed moderate neuroprotective properties against H2 O2 -induced cytotoxicity in PC12 cells. The theoretical ADME study also predicted good drug-likeness for the compound 6f. Based on these results, the compound 6f seems to be a very promising AChE inhibitor for the treatment of Alzheimer's disease.

Design, synthesis, biological evaluation, and docking study of novel dual-acting thiazole-pyridiniums inhibiting acetylcholinesterase and ß-amyloid aggregation for Alzheimer's disease.

New compounds containing thiazole and pyridinium moieties were designed and synthesized. The potency of the synthesized compounds as selective inhibitors of acetylcholinesterase (AChE), and ß-amyloid aggregation (Aß) was evaluated. Compounds 7d and 7j showed the best AChE inhibitory activities at the submicromolar concentration range (IC50 values of 0.40 and 0.69 µM, respectively). Most of the novel compounds showed moderate to low inhibition of butyrylcholinesterase (BChE), which is indicative of their selective inhibitory effects towards AChE. Kinetic studies using the most potent compounds 7d and 7j confirmed a mixed-type of AChE inhibition mechanism in accordance with the docking results, which shows their interactions with both catalytic active (CAS) and peripheral anionic (PAS) sites. The specific binding of 7a, 7j, and 7m to PAS domain of AChE was also confirmed experimentally. In addition, 7d and 7j were able to show ß-amyloid self-aggregation inhibitory effects (20.38 and 42.66% respectively) stronger than donepezil (14.70%) assayed at 10 µM concentration. Moreover, compounds 7j and 7m were shown to be effective neuroprotective agents in H2O2-induced oxidative stress on PC12 cells almost similar to those observed for donepezil. The ability of 7j to pass blood-brain barrier was demonstrated using the PAMPA method. The results presented in this work provide useful information about designing novel anti-Alzheimer agents.

Perceived professional preparedness of senior nursing students' questionnaire: Development and psychometric evaluation.

BACKGROUND: Nursing students' perceptions of their professional preparedness help them perform their independent nursing role with self-confidence. OBJECTIVES: To develop and psychometric testing of an instrument, the "Perceived Professional Preparedness of senior Nursing Students" questionnaire. DESIGN: Mixed-method exploratory study. METHODS: We conducted this study in two phases: (1) development of initial questionnaire through interview and literature review; (2) evaluation of psychometric properties of the instrument to introduce a reliable, valid tool. SETTINGS AND PARTICIPANTS: We assessed qualitative and quantitative face validity of initial questionnaire by administering it to 10 nursing students. Then, a panel of 10 nursing specialists determined the Content Validity Index. After modifying items, we assessed the construct validity of the 45-item questionnaire. A sample of 159 senior nursing students completed the questionnaire, and we conducted exploratory and confirmatory factor analysis using this data. To assess the test-retest reliability, 30 students completed the instrument twice with a two-week time interval. RESULTS: The Content Validity Index with the modified Kappa coefficient was calculated as ≥0.72, which is considered satisfactory. In exploratory factor analysis using the maximum likelihood method and varimax rotation, we extracted 19 items in four factors. This structure included 61.91% of the total variance. The factors were clinical competency, evidence-based practice, framework-oriented performance, and patient-centered care. Cronbach's alpha coefficient and McDonald's omega values higher than 0.70 and inter-class correlation coefficient above 0.90 for all factors confirmed reliability. Confirmatory factor analysis indicated a suitable fitting of the final developed model. CONCLUSION: The developed questionnaire is a valid, reliable tool to assess the perceived preparedness of senior nursing students for transition to the clinical setting. Further psychometric testing for this questionnaire on larger populations and in different contexts is suggested.

Design, synthesis, and evaluation of novel cinnamic acid-tryptamine hybrid for inhibition of acetylcholinesterase and butyrylcholinesterase.

BACKGROUND: Acetylcholine deficiencies in hippocampus and cortex, aggregation of ß-amyloid, and ß-secretase over activity have been introduced as main reasons in pathogenesis of Alzheimer's disease. METHODS: Colorimetric Ellman's method was used for determination of IC50 value in AChE and BChE inhibitory activity. The kinetic studies, neuroprotective and ß-secretase inhibitory activities, evaluation of inhibitory potency on ß-amyloid (Aß) aggregations induced by AChE, and docking study were performed for prediction of the mechanism of action. RESULT AND DISCUSSION: A new series of cinnamic acids-tryptamine hybrid was designed, synthesized, and evaluated as dual cholinesterase inhibitors. These compounds demonstrated in-vitro inhibitory activities against acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). Among of these synthesized compounds, (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dimethoxyphenyl)acrylamide (5q) demonstrated the most potent AChE inhibitory activity (IC50 = 11.51 µM) and (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(2-chlorophenyl)acrylamide (5b) were the best anti-BChE (IC50 = 1.95 µM) compounds. In addition, the molecular modeling and kinetic studies depicted 5q and 5b were mixed type inhibitor and bound with both the peripheral anionic site (PAS) and catalytic sites (CAS) of AChE and BChE. Moreover, compound 5q showed mild neuroprotective in PC12 cell line and weak ß-secretase inhibitory activities. This compound also inhibited aggregation of ß-amyloid (Aß) in self-induced peptide aggregation test at concentration of 10 µM. CONCLUSION: It is worth noting that both the kinetic study and the molecular modeling of 5q and 5b depicted that these compounds simultaneously interacted with both the catalytic active site and the peripheral anionic site of AChE and BChE. These findings match with those resulted data from the enzyme inhibition assay. Graphical abstract A new series of cinnamic-derived acids-tryptamine hybrid derivatives were designed, synthesized and evaluated as butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) inhibitors and neuroprotective agents. Compound 5b and 5q, as the more potent compounds, interacted with both the peripheral site and the choline binding site having mixed type inhibition. Results suggested that derivatives have a therapeutic potential for the treatment of AD.

Proteomic and genomic biomarkers for Non-Small Cell Lung Cancer: Peroxiredoxin, Haptoglobin, and Alpha-1 antitrypsin.

BACKGROUND: The development of lung cancer is a multifactorial process that involves the environmental and genetic factors. The mortality rate of this cancer is higher than breast, colorectal, and prostate cancers. In this study, we try to analyze the proteome of patients with Non-Small Cell Lung Cancer (NSCLC) and compare it with the healthy samples. METHODS: This study has compared 30 lung tissue samples from patients with NSCLC and 30 healthy samples using proteomics and RT-PCR. Hence, tissue samples were obtained from the surgical ward in sterile conditions, and then, protein extraction applied to them. At the next stage, two-dimensional electrophoresis and mass spectrometry LCMS/MS were performed for protein isolation and sequencing, respectively. RESULTS: The proteome analysis identified more than 40 differences in proteomic pattern of normal lung tissues compared to lung tissues with NSCLC. Peroxiredoxin, Haptoglobin, and Alpha-1 antitrypsin proteins were identified. Molecularly, it has also been shown that the two main proteins of Peroxiredoxin-2 and Alpha-1 antitrypsin were upregulated, and the expression of Haptoglobin protein was downregulated in cancer tissue. CONCLUSION: The results of this study showed that there are some differences in term of protein content between the normal and cancerous lung tissues. Further studies are needed to evaluate these proteins that investigate whether these proteins can candidate as biomarkers to use in the early diagnosis of patients with NSCLC.