Patterns of Ankle Fractures Based on Radiographs and CT Images of 1000 Consecutive Patients.

Objectives: The knowledge of different types of ankle fractures based on plain radiographs and computed tomography (CT) images can help improve patients' management. Methods: This cross-sectional study assessed the plain radiographs and CT images of 1,000 consecutive patients observed in an emergency department between March 2015 and March 2020. Fractures were labeled as uni-, bi-, or trimalleolar. Malleolar fractures were classified into medial, lateral, and posterior ones based on Herscovici, Danis-Weber, and Mason and Molloy classifications, respectively. Bi- and trimalleolar fractures, on the other hand, were categorized according to the Lauge-Hansen classification. Results: This study included 1,000 patients with 1,003 ankle fractures. Of them, 901 were adults (mean±SD age: 41.6±16.7, male: 567 [62.9%]) with 904 fractures. In total, 53% of adult patients were 18 to 39 years old. Considering unilateral ankle fractures, the medial malleolar fracture was the most common unimalleolar fracture (62.6%), with Herscovici C being the most frequent subtype (65.3%). On the other hand, the most common type of lateral malleolar fracture was Danis-Weber type B (65.5%). There were also 209 (23.3%) bimalleolar and 114 (12.7%) trimalleolar fractures, 5.8% (16 fractures) of which could not be classified based on the Lauge-Hansen classification. Unimalleolar fractures were also observed in 87 (87.9%) children, with the medial malleolar fracture being the most common type (89.7%). Conclusion: Medial malleolar fractures were the most frequent malleoli in patients observed in the emergency department under study. Among bi- and trimalleolar ankle fractures, supination-external rotation and pronation-external rotation injuries were the most common patterns. The Lauge-Hansen classification was not applicable in 5.8% of bi- and trimalleolar fractures.

Design, synthesis, computational study and cytotoxic evaluation of some new quinazoline derivatives containing pyrimidine moiety.

Quinazoline derivatives, as an important category of heterocyclic compounds, have received much attention for the design and development of new drugs due to their various pharmacological properties. Besides, there is a great deal of evidence showing pyrimidine analogs as anticancer agents. Thus, in the present study, for the design of new target compounds with cytotoxic activity, we focused on various quinazolinone and pyrimidine hybrids. A new series of quinazoline-pyrimidine hybrid derivatives (6a-6n) have been designed and synthesized as novel antiproliferative agents. All the synthesized compounds characterized based on their IR, NMR and Mass spectroscopic data. Antiproliferative activities of the new compounds were evaluated against three human cancer cell lines (MCF-7, A549, SW-480). The compounds were found to have appropriate potential with IC50 values ranging from 2.3 ± 5.91 to 176.5 ± 0.7 µM against the tested cell lines. Compound 6n exerted the highest antiproliferative activity with IC50 values of 5.9 ± 1.69 µM, 2.3 ± 5.91 µM and 5.65 ± 2.33 µM against A549, SW-480 and MCF-7 respectively. The results indicated that 6n could induce apoptosis in A549 cell line in a dose dependent manner and arrest in the S phase of cell cycle. Docking studies were also done to investigate the detailed binding pattern of the synthesized compounds against EGFR. Furthermore, molecular dynamic simulation and binding free energy calculation have been done to rescore initial docking pose of the synthesized compounds using ensemble-based MMGB/PBSA free energy method. According to the results, free energy calculation confirmed biological activity of compounds and also, Arg 817 and Lys 721 residues had the pivotal role in the high potency of 6n. Finally, the drug likeness and in silico ADME study were also predicted.

6-Bromoquinazoline Derivatives as Potent Anticancer Agents: Synthesis, Cytotoxic Evaluation, and Computational Studies.

A series of 6-bromoquinazoline derivatives (5a-j) were synthesized. Cytotoxic effectiveness of compounds was done against two cancerous cell lines (MCF-7 and SW480) by standard MTT method. Fortunately, all of the compounds showed desirable activity in reducing the viability of the studied cancerous cell lines with IC50 value in the range of 0.53-46.6 µM. Compound 5b with a fluoro substitution at meta position of the phenyl moiety showed stronger activity than cisplatin with IC50 =0.53-1.95 µM. Studies on the hit compound (5b) through apoptosis assay illustrated that it could induce apoptosis in MCF-7 cell lines in dose dependent manner. Molecular docking study was done to investigate the detailed binding modes and interactions with EGFR as a plausible mechanism. The drug- likeness was predicted. To survey the reactivity of compounds, DFT calculation was performed. Taken together, 6-bromoquinazoline derivatives, especially 5b can be considered as hit compounds to rational drug designing as antiproliferative agents.

Adolescent Mental Health Literacy Questionnaire: Investigating Psychometric Properties in Iranian Female Students.

Objectives: Mental Health Literacy (MHL) is an important factor in promoting mental health. Assessing this structure is required for early recognition and intervention in mental health problems. To date, there was no tool to assess it among Iranian adolescents, so this study was aimed at examining the psychometric properties of the Persian version of the Adolescent Mental Health Literacy Questionnaire (AMHLQ) among Iranian female students. Method: The study instrument was a Persian version of the AMHLQ prepared through a translation and back-translation process. In this cross-sectional study, 275 female students completed the AMHLQ, and the Adolescent Strengths, and Difficulties Questionnaire (SDQ). Results: Findings of content, construct validity tests, Cronbach's alpha, and split-half coefficient demonstrated that the AMHLQ had satisfactory validity and suitable reliability. The exploratory factor analysis showed four dimensions of the AMHLQ: (1) knowledge of mental health problems (α = 0.89); (2) erroneous beliefs/stereotypes (α = 0.89); (3) help-seeking and first aid skills (α = 0.86); and (4) self-help strategies (α = 0.74). Conclusion: The findings showed that the tool was confirmed by questions and subscales, and this questionnaire was a valid and reliable tool in assessing level differences of MHL and in determining the impact of programs designed to improve MHL in Iranian female adolescents.

Anti-COVID-19 and antidiabetic activities of new oleanane and ursane-type triterpenoids from Salvia grossheimii: an in-silico approach.

Salvia grossheimii is a perennial herb with antidiabetic and cytotoxic constituents. In continuation of our study on S. grosshiemii to identify the bioactive phytochemicals, we have reported the characterization of seven undescribed triterpenoids. The aerial parts of the plant were extracted in dichloromethane and its constituents were isolated using chromatography techniques. The structures of compounds were identified using 1D, 2D NMR, and ESI-MS spectral data. Seven new oleanane- and ursane-type triterpenoids (1-7) were identified in S. grossheimii. The structures of 1-7 were characterized as; 2α-hydroxy-3ß-acetoxy-olean-9(11),12-diene (1), 2α-acetoxy-3ß-hydroxy-olean-9(11),12-diene (2), 3ß-acetoxy-olean-18-ene,2α,11α-diol (3), 2α-hydroxy-3ß-acetoxy-urs-9(11),12-diene (4), 2α-acetoxy-3ß-hydroxy-urs-9(11),12-diene (5), 2α,3ß-diacetoxy-urs-12-ene-11α,20ß-diol (6), 2α,3ß-diacetoxy-urs-9(11),12-diene-20ß-ol (7). Triterpenoids (2, 5, and 7) were intramolecular transesterification or dehydration products of their corresponding isomers or allylic alcohol in the C rings, respectively, produced in-situ during NMR spectroscopy. Virtual screening of 1-7 was performed with molecular docking analysis to identify the potential SARS-CoV-2 and α-glucosidase inhibitors using the smina molecular docking algorithm. The best binding energy values (kcal/mol) against COVID-19 main protease Mpro were calculated for 6 (-8.77) and 7 (-8.68), and the higher binding affinities toward human α-glucosidase were obtained for 2 (-9.39) and 6 (-8.63). This study suggests S. grossheimii as a rich source of bioactive triterpenoids and introduces new natural compounds. Considering the high binding energy values of 2, 6, and 7, these structures could be candidates for anti-COVID-19 and antidiabetic drug development in the future.

A Meta-Analysis of the Effectiveness of Cognitive Rehabilitation in Improving Memory Function in Patients With Posttraumatic Stress Disorder.

ABSTRACT: Posttraumatic stress disorder (PTSD) may have a detrimental effect on a patient's memory function. Memory problems are common after PTSD and can cause problems with a patient's day-to-day life. Cognitive rehabilitation is considered an effective treatment for patients with PTSD who want to improve cognitive memory. We searched keywords in electronic databases to find studies that looked into the effect of cognitive rehabilitation on memory function in patients with PTSD. This report is based on data from four studies with double-blind and placebo-controlled experiments totaling 198 participants. Effect size estimates were calculated using a mixed-effects meta-analysis for memory function. During cognitive rehabilitation, patients with PTSD demonstrated gains in memory in a variety of ways. Our results pointed to the need for further research into the most promising interventions for improving memory function in patients with PTSD. Furthermore, well-designed studies with large sample sizes are needed to confirm our results and determine the magnitude of the problem.

Phytochemical Analysis and Biological Activity of Salvia compressa Vent.

Background: Salvia extracts have various biological activities and are rich sources of bioactive metabolites. Objectives: We identified five phytochemicals from S. compressa extract and assessed its biological properties. Methods: The plant's shoots were extracted using dichloromethane, and the constituents were isolated using column chromatography. High-resolution NMR spectroscopy characterized the chemical structures of the compounds (1 - 5). The cytotoxic effect of the extract was examined against MCF-7 cells by MTT reduction assay, while cisplatin was tested as a reference cytotoxic compound. The antibacterial activity was assessed using nutrient broth micro-dilution (NBMD), and chloramphenicol was used as the positive control. Results: Citrostadienol (1), ß-sitosterol (2), two glyceride esters of linolenic, linoleic, and palmitic acids (3, 4), and geraniol (5) were isolated from S. compressa for the first time. The extract showed activity against MCF-7 breast cancer cells and reduced cell viability to 68.2 ± 13.1% compared to the control drug at the concentration of 50 µg/mL, while it was not active against seven test bacteria. Conclusions: The anti-complementary activity of the isolated steroids suggests S. compressa for future anti-inflammatory research.

Cytotoxic furanosesquiterpenoids and steroids from Ircinia mutans sponges.

CONTEXT: Ircinia mutans Wilson (Irciniidae) is a sponge with antimicrobial and cytotoxic constituents. OBJECTIVE: Our objective was to characterise the cytotoxic constituents of two seasonal collections of I. mutans. MATERIALS AND METHODS: The sponges were extracted in methanol-dichloromethane and their constituents were purified and characterised using column chromatography, GC-MS, 1 D and 2 D NMR. Anti-proliferative activities of the compounds, were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay (0.25-100 µg/mL, 72 h) against leukaemia (MOLT-4), breast (MCF-7) and colon cancer (HT-29) human cells. RESULTS: Three furanosesquiterpoids; furodysin (1), ent-furodysinin (2) and furoircin (3) and ten sterols were characterised in I. mutans, for the first time. Cholesterol (4), cholesta-5, 7-dien-3ß-ol (5) and ergosterol (6) were determined in the sponge from the winter collections, while cholesta-5, 22-dien-3ß-ol (7), 24-methyldesmosterol (8), campesterol (9), stigmasterol (10), γ-ergostenol (11), chondrillasterol (12) and γ-sitosterol (13) were detected in the summer samples. The steroids from the winter collection exhibited cytotoxic activity with IC50 values of 13.0 ± 0.9, 11.1 ± 1.7 and 1.1 ± 0.4 µg/mL, against the mentioned cancer cell lines, respectively, while those from the summer sample, showed greater activity, IC50 = 1.1 ± 0.2 µg/mL against MOLT-4. The purified steroids showed potent MOLT-4 cytotoxic activity, IC50 values = 2.3-7.8 µg/mL. DISCUSSION AND CONCLUSION: The present study suggests that I. mutans is a rich source of cytotoxic steroids, and introduces 3 as new natural product. Considering the high cytotoxic activity of the steroids, these structures could be candidates for anticancer drug development in future research.

miRNA96 expression level within red blood cells is probably associated with RSL indicators during the storage of red blood cell units.

BACKGROUND AND OBJECTIVES: Many biochemical and hematological changes occur during the storage of RBC units. Collectively, these changes are known as RSLs. Previous studies found miRNA96 as non-coding RNA that its expression level changed during RBC storage. However, its correlation with mechanical and biochemical RSL indicators is not yet determined. Therefore, this study aimed to assess possible correlations between miRNA96a and some RSLs indicators to clarify its biomarker capability for evaluating the storage quality of RBC units. MATERIALS AND METHODS: Samples were collected from ten leuko-reduced RBC units on days 0, 14, 28, and 42 of storage. miRNA96 gene expression level and RSLs indicators including hemolysis, mechanical fragility index (MFI), total antioxidant capacity (TAC), lipid peroxidation (TBARs), thiol groups, and RBC indices were measured on the days mentioned above. RESULTS: Significant correlations were found between the changes in miRNA96 expression level and the levels of hemolysis, TAC, TBARs, and MFI indices (p values < 0.05). The donors were classified into the high risk group and low risk group, according to four important characteristics and lifestyle habits (smoking, physical activity, age, and BMI). The high risk group had a significantly lower rate of hemolysis, free hemoglobin, MFI, TAC, and a higher rate of lipid peroxidation compared to low risk group (p values < 0.05). CONCLUSION: The finding suggested that upregulation of miRNA96 could prevent hemolysis of RBCs, despite the accumulation of oxidative injuries in them. The miRNA96 expression level was probably a potential predictor for mechanical and biochemical RSL indicators.

Antidiabetic and cytotoxic polyhydroxylated oleanane and ursane type triterpenoids from Salvia grossheimii.

Two polyhydroxylated oleanane and seven ursane triterpenoids were isolated from aerial parts of Salvia grossheimii. The chemical structures of the undescribed triterpenoids (1-6) were characterized using 1 and 2 D NMR and ESI-MS spectral data as; 2α, 3ß, 11α -trihydroxy-olean-12- ene (1), 2α, 3ß, 11α-trihydroxy-olean-18-ene (2), 2α- acetoxy-urs-12-ene-3ß, 11α, 20ß-triol (3), 3-keto-urs-12-ene-1ß, 11α, 20ß -triol (4), 2α, 3ß-diacetoxy-urs-12-ene-1ß, 11α, 20ß -triol (5), and 3ß-acetoxy-urs-12-ene-1ß, 11α, 20ß -triol (6). All compounds were evaluated for the in vitro α-glucosidase inhibitory and cytotoxic activities against MCF-7 human cancer cell line. Compounds 1, 2, 4, and 6 showed in vitro α-glucosidase inhibitory activity with IC50 = 43.6-198.4 µM, which were more potent than the antidiabetic medicine, acarbose. The remaining compounds; 3, and 7-9 showed potent cytotoxic activity (IC50 = 6.2-31.9 µM) against the cancerous cell line, while the potent α-glucosidase inhibitors were inactive. Molecular docking analysis and kinetic studies were applied to investigate the structure activity relationships and mechanisms of the human and Saccharomyces cerevisiae α-glucosidase inhibitory of the purified compounds. Comparing the high cytotoxicity and α-glucosidase inhibitory of the oleanane and ursane type triterpenoids suggest them as potential lead compounds for further research in anticancer and antidiabetic research.

Effectiveness of theory-based diabetes self-care training interventions; a systematic review.

BACKGROUND: Permanent compliance of self-care behaviors is a challenging issue in managing chronic diseases like diabetes. The evidence supports theory-based intervention in promoting self-care behaviors. However, no systematic review was done to monitor these interventions and compare more effective constructs. This study was conducted to investigate the studies using self-care theories and introducing the most effective theories. METHODS: This is a systematic review study during which some scientific databases including Scopus, Elsevier, Google scholar and PubMed were searched by using some key words like self-care or self-management, diabetes, theory or model. English articles from the start of 2013 up to the end of November 2020 were monitored. RESULTS: 20 articles were selected and studied based on eight theories which they used. These theories were: Social support theory, Health Belief Model, Heath Belief Model and Empowerment Theory, Empowerment Theory, Self-efficacy Theory, precede-proceed model, Self-regulation Theory, behavioral theory and Social Cognitive Theory. CONCLUSION: Four theories appeared to be more effective for the target behavior of present research: Social Support Theory and the combination of Empowerment Theory and Health Belief Model, Social Cognitive Theory and Self Efficacy Theory. Taken together, the findings of this systematic review suggest that interventions that go beyond individual determinants (such as changing knowledge and attitudes) to determinants of upper cognitive, motor, and social levels (such as the development of skills and competencies) they have led to raised self-care outcomes.

Ecological Roles and Biological Activities of Specialized Metabolites from the Genus Nicotiana.

Species of Nicotiana grow naturally in different parts of the world and have long been used both medicinally and recreationally by human societies. More recently in our history, Nicotiana tabacum has attracted interest as one of the most economically important industrial crops. Nicotiana species are frequently investigated for their bioactive natural products, and the ecological role of their specialized metabolites in responses to abiotic stress or biotic stress factors like pathogens and herbivores. The interest of tobacco companies in genetic information as well as the success of a few wild tobacco species as experimental model organisms have resulted in growing knowledge about the molecular biology and ecology of these plants and functional studies of the plant's natural products. Although a large number of reviews and books on biologically active natural products already exists, mostly from N. tabacum, we focus our attention on the ecological roles and biological activity of natural products, versus products from cured and processed material, in this Review. The studied compounds include alkaloids, aromatic compounds, flavonoids, volatiles, sesquiterpenoids, diterpenes alcohols, and sugar esters from trichomes of the plants, and recently characterized acyclic hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). In this Review (1800s-2017), we describe the above-mentioned classes of natural products, emphasizing their biological activities and functions as they have been determined either in bioassay-guided purification approaches or in bioassays with plants in which the expression of specific biosynthetic genes has been genetically manipulated. Additionally, a review on the history, taxonomy, ecology, and medicinal application of different Nicotiana species growing around the globe presented in this Review may be of interest for pharmacognosists, natural products, and ecological chemists.

A comparative QSAR analysis and molecular docking studies of phenyl piperidine derivatives as potent dual NK1R antagonists/serotonin transporter (SERT) inhibitors.

Depression is a critical mood disorder that affects millions of patients. Available therapeutic antidepressant agents are associated with several undesirable side effects. Recently, it has been shown that Neurokinin 1 receptor (NK1R) antagonists can potentiate the antidepressant effects of serotonin-selective reuptake inhibitors (SSRIs). In this study, a series of phenyl piperidine derivatives as potent dual NK1R antagonists/serotonin transporter (SERT) inhibitors were applied to quantitative structure-activity relationship (QSAR) analysis. A collection of chemometrics methods such as multiple linear regression (MLR), factor analysis-based multiple linear regression (FA-MLR), principal component regression (PCR), and partial least squared combined with genetic algorithm for variable selection (GA-PLS) were applied to make relations between structural characteristics and NK1R antagonism/SERT inhibitory of these compounds. The best multiple linear regression equation was obtained from GA-PLS and MLR for NK1R and SERT, respectively. Based on the resulted model, an in silico-screening study was also conducted and new potent lead compounds based on new structural patterns were designed for both targets. Molecular docking studies of these compounds on both targets were also conducted and encouraging results were acquired. There was a good correlation between QSAR and docking results. The results obtained from validated docking studies indicate that the important amino acids inside the active site of the cavity that are responsible for essential interactions are Glu33, Asp395 and Arg26 for SERT and Ala30, Lys7, Asp31, Phe5 and Tyr82 for NK1R receptors.

Cytotoxic activity and chemical constituents of Anthemis mirheydari.

Context The genus Anthemis L. (Asteraceae) comprises about 195 species which are widely used in the pharmaceutical, cosmetic and food industries. Objective Anthemis mirheydari Iranshar, an endemic plant from Iran, was investigated for its cytotoxic properties and chemical constituents. Materials and methods The whole parts of the plant (320 g) were extracted by dichloromethane and methanol for four days, successively. The cytotoxic activity of both dichloromethane and methanol extracts were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric methods against three human cancer cell lines including LS180, MCF-7 and MOLT-4. Different concentrations (10-100 µg/mL) of the plant extracts were tested to obtain IC50 values. The dichloromethane extract of A. mirheydari was subjected to silica gel-column and thin layer chromatography for purification of its chemical constituents and the isolated compounds were further tested against MOLT-4 cells. The structures of the pure compounds were elucidated using different spectral data including nuclear magnetic resonance and electron impact mass spectra. Results The IC50 values of the dichloromethane extract were 30.8 ± 6.7, 25.2 ± 6.5 and 8.6 ± 1.1 µg/mL (means ± standard error) for the above-mentioned cell lines, respectively. Two triterpenoids, taraxasterol (1) and pseudotaraxasterol (2), one sterol, ß-sitosterol (3) and one coumarin, 7-methoxycoumarin (4) were isolated from the extract. The IC50 of the mixture of compounds 1 and 2 as well as compounds 3 and 4 were higher (>100 µM) than that reported for the dichloromethane extract against MOLT-4 cells. Conclusion The dichloromethane extract was the most active one among the tested material.

Enhanced delivery of gentamicin to infection foci due to Staphylococcus aureus using gold nanorods.

Bacterial infections continue to be one of the major causes of morbidity and mortality. Although many methods for diagnosing and treating of infectious diseases currently exist, there is an urgent need for new and improved approaches for bacterial destruction. The present study focuses on the conjugation of gold nanorods (GNRs) with gentamicin via the Nanothink acid linker and its application in delivery of gentamicin to infection foci due to Staphylococcus aureus. The interaction between gentamicin and gold nanorods was confirmed by FT-IR spectroscopy. The high performance liquid chromatography (HPLC) and atomic absorption spectroscopy analyses showed that 2050 gentamicin molecules were attached to each gold nanorod. The minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of gentamicin-GNRs conjugate showed the enhancement of antibacterial effect of gentamicin. The biodistribution study demonstrated localization of the complex at the site of Staphylococcal infection with high sensitivity in mouse model.

Phytochemical Investigation on Euphorbia macrostegia (Persian wood spurge).

Euphorbia macrostegia or Persian wood spurge is one of the seventeen endemic plants of this genus in Iran. Three triterpenoids, 24-methylenecycloartan-3ß-ol (1), butyrospermol (2) and cycloartenol (3) and three diglycerides, 1,2-di-O-α-linolenoyl-sn-glycerol (4), 1-O-linoleoyl-3-O-palmitoyl-sn-glycerol (5) and 1-O-α-linolenoyl-2-O-palmitoyl-sn-glycerol (6) were isolated from the hexane soluble part of methanol-dichloromethane extracts of the aerial parts of Euphorbia macrostegia Boiss. The structures of all compounds were elucidated using different spectroscopy methods including, (1)H NMR, (13)C NMR, HSQC, HMBC, EI-MS and IR. The triterpenes and the unsaturated fatty acids moieties of the diglycerides isolated from the plant were reported previously to have analgesic, anticancer, bactericidal and antifungal activity. Here, we show that E. macrostegia is a new source for the above mentioned biologically active compounds.

Generalized relation between relative entropy and dissipation for nonequilibrium systems.

Recently, Kawai, Parrondo, and Van den Broeck [Phys. Rev. Lett. 98, 080602 (2007)] have related dissipation to time-reversal asymmetry. We generalized the result by considering a protocol where the physical system is driven away from an initial thermal equilibrium state with temperature ß0 to a final thermal equilibrium state at a different temperature. We illustrate the result using a model with an exact solution, i.e., a particle in a moving one-dimensional harmonic well.