Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans.

Post-traumatic stress disorder (PTSD) is one of the most widespread and disabling psychiatric disorders among combat veterans. Substantial interindividual variability in susceptibility to PTSD suggests the presence of different risk factors for this disorder. Twin and family studies confirm genetic factors as important risk factors for PTSD. In addition to genetic factors, epigenetic factors, especially DNA methylation, can be considered as a potential mechanism in changing the risk of PTSD. So far, many genetic and epigenetic association studies have been conducted in relation to PTSD. In genetic studies, many single nucleotide polymorphisms have been identified as PTSD risk factors. Meanwhile, the variations in catecholamines-related genes, serotonin transporter and receptors, brain-derived neurotrophic factor, inflammatory factors, and apolipoprotein E are the most prominent candidates. CpG methylation in the upstream regions of many genes is also considered a PTSD risk factor. Accurate identification of genetic and epigenetic changes associated with PTSD can lead to the presentation of suitable biomarkers for susceptible individuals to this disorder. This study aimed to delineate prominent genetic variations and epigenetic changes associated with post-traumatic stress disorder in military veterans who have experienced combat, focusing on genetic and epigenetic association studies.

Smartwatches in healthcare medicine: assistance and monitoring; a scoping review.

Smartwatches have become increasingly popular in recent times because of their capacity to track different health indicators, including heart rate, patterns of sleep, and physical movements. This scoping review aims to explore the utilisation of smartwatches within the healthcare sector. According to Arksey and O'Malley's methodology, an organised search was performed in PubMed/Medline, Scopus, Embase, Web of Science, ERIC and Google Scholar. In our search strategy, 761 articles were returned. The exclusion/inclusion criteria were applied. Finally, 35 articles were selected for extracting data. These included six studies on stress monitoring, six on movement disorders, three on sleep tracking, three on blood pressure, two on heart disease, six on covid pandemic, three on safety and six on validation. The use of smartwatches has been found to be effective in diagnosing the symptoms of various diseases. In particular, smartwatches have shown promise in detecting heart diseases, movement disorders, and even early signs of COVID-19. Nevertheless, it should be emphasised that there is an ongoing discussion concerning the reliability of smartwatch diagnoses within healthcare systems. Despite the potential advantages offered by utilising smartwatches for disease detection, it is imperative to approach their data interpretation with prudence. The discrepancies in detection between smartwatches and their algorithms have important implications for healthcare use. The accuracy and reliability of the algorithms used are crucial, as well as high accuracy in detecting changes in health status by the smartwatches themselves. This calls for the development of medical watches and the creation of AI-hospital assistants. These assistants will be designed to help with patient monitoring, appointment scheduling, and medication management tasks. They can educate patients and answer common questions, freeing healthcare providers to focus on more complex tasks.

Can gamified surgical sets improve surgical instrument recognition and student performance retention in the operating room? A multi-institutional experimental crossover study.

INTRODUCTION: Surgery requires a high degree of precision, speed, and concentration. Owing to the complexity of the modern world, traditional methods cannot meet these requirements. Therefore, in this study, we investigated students' diagnostic skills in the Operating Room in the context of surgical instruments by using gamification of surgical instruments and a crossover design. METHOD: The study design was a multi-institutional quasi-experimental crossover and involved a three-arm intervention (with gender-specific block randomisation: Group A, B, and C) with a pre-test and three post-tests. A total of 90 students fell into three groups of 30 participants each. The surgical sets were learned for one semester through game-based instruction and traditional teaching, and then three OSCE tests were administered with time and location differences. Using one-way ANOVA, OSCE results were compared in the game, traditional, and control groups. The effectiveness of the intervention was tested in each group by repeated measures. RESULT: The pretest scores of all three groups did not differ significantly. In the OSCE tests, both groups, A and B, performed similarly. However, these tests showed a significant difference in grouping between training through games and training in the traditional way. There was no significant difference between OSCE tests 2 and 3 in the game-based training group, indicating that what was learned was retained, while in the traditional method training group, OSCE 3 test scores declined significantly. Furthermore, repeated measures showed the effectiveness of game-based training. CONCLUSION: In this study, gamification has turned out to be very effective in helping learners learn practical skills and leading to more sustainable learning.

Does the rubella immunoglobulin G affect the severity of COVID- 19? : Rubella immunoglobulin G and COVID- 19.

OBJECTIVE & AIM: The coronavirus disease, so far (COVID-19) has brought about millions of infections and fatalities throughout the world. Our aim was to determine the correlation between rubella IGG titers with the severity COVID-19.  MATERIALS & METHODS: This study was conducted among COVID-19 confirmed patients over 18 years of age. The disease severity levels were categorized by WHO interim guidance. The rubella-specific IgG antibody-titer spectrum was measured (within first 48 h of hospitalization) by enzyme-linked immunosorbent assay (ELISA). RESULT: In a study of 46 inpatients with varying COVID-19 disease severity (mild, moderate, severe, and critical), we observed a negative correlation between rubella IgG antibody titers and COVID-19 severity (P-Value = 0.017), There was an interaction between COVID-19 vaccination history and rubella IGG on severity COVID-19 (P-Value = 0.0015). There was an interaction between age group under 44 years (including national measles- rubella (MR) vaccination in Iran) and rubella IGG titers on severity COVID-19 too (p-value = 0.014). CONCLUSION: In conclusion, MR vaccination seems to have a positive effect in reducing the severity of the disease, emphasizing that, the important and separate effect of the IGG rubella (due to natural or extrinsic immunity) titers is determining.

Normal spirometry prediction equations for the Iranian population.

BACKGROUND: This study aimed to establish normative spirometric equations in a healthy population of Iranian children and adults, and compare these equations with those developed by the Caucasian Global Lung Initiative (GLI) for the first time. METHODS: Spirometric data from healthy Iranian aged 4-82 years sampled in 2019 were used to derive reference equations using the generalized additive model for location (mu), shape (lambda), and scale (sigma). RESULTS: A total of 418 females and 204 males were included in the study. Applying the GLI standards for the Iranian population resulted from the Z scores of FEV1, FVC, FEV1/FVC, and FEF25-75% was not different from zero. Based on the newly calculated LLN, eleven individuals showed significant values below the LLN for FEV1/FVC. In all age groups, this frequency was less than 5%, except for men over 70 years of age, which was 12.5%. There are significant differences between new data and GLI for Caucasian data. CONCLUSION: It is recommended that the values and equations generated from this study should be used by physicians and technicians in their routine practice for the diagnosis and assessment of pulmonary disorders.

The viability of SARS-CoV-2 on solid surfaces.

The COVID-19 pandemic had a major impact on life in 2020 and 2021. One method of transmission occurs when the causative virus, SARS-CoV-2, contaminates solids. Understanding and controlling the interaction with solids is thus potentially important for limiting the spread of the disease. We review work that describes the prevalence of the virus on common objects, the longevity of the virus on solids, and surface coatings that are designed to inactivate the virus. Engineered coatings have already succeeded in producing a large reduction in viral infectivity from surfaces. We also review work describing inactivation on facemasks and clothing and discuss probable mechanisms of inactivation of the virus at surfaces.

Nothotylenchus andrassy n. sp. (Nematoda: Anguinidae) from Northern Iran.

Nothotylenchus andrassy n. sp. is described and illustrated from moss ( Sphagnum sp.) based on morphology and molecular analyses. Morphologically, this new species is characterized by a medium body size, six incisures in the lateral fields, and a delicate stylet (8-9 µm long) with clearly defined knobs. Pharynx with fusiform, valveless, non-muscular and sometimes indistinct median bulb. Basal pharyngeal bulb elongated and offset from the intestine; a long post-vulval uterine sac (55% of vulva to anus distance); and elongate, conical tail with pointed tip. Nothotylenchus andrassy n. sp. is morphologically similar to five known species of the genus, namely Nothotylenchus geraerti , Nothotylenchus medians , Nothotylenchus affinis , Nothotylenchus buckleyi , and Nothotylenchus persicus . The results of molecular analysis of rRNA gene sequences, including the D2-D3 expansion region of 28S rRNA, internal transcribed spacer (ITS) rRNA and partial 18S rRNA gene are provide for the new species.

Energy metabolism in skin cancers: A therapeutic perspective.

Skin cancers are the most common cancers worldwide. The incidence of common skin cancers, including basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs) and melanomas, continues to rise by 5 to 7% per year, mainly due to ultraviolet (UV) exposure and partly because of aging. This suggests an urgent necessity to improve the level of prevention and protection for skin cancers as well as developing new prognostic and diagnostic markers of skin cancers. Moreover, despite innovative therapies especially in the fields of melanoma and carcinomas, new therapeutic options are needed to bypass resistance to targeted therapies or treatment's side effects. Since reprogramming of cellular metabolism is now considered as a hallmark of cancer, some of the recent findings on the role of energy metabolism in skin cancer initiation and progression as well as its effect on the response to targeted therapies are discussed in this review. This article is part of a Special Issue entitled Mitochondria in cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.

Postoperative endodontic pain of three different instrumentation techniques in asymptomatic necrotic mandibular molars with periapical lesion: a prospective, randomized, double-blind clinical trial.

OBJECTIVES: The purpose of this prospective, randomized, double-blind study was to compare postoperative pain of root canal treatment in patients with asymptomatic mandibular molar teeth with necrotic pulp and periapical lesion using three different instrumentation techniques: hand, multi-file rotary (ProTaper Universal), and reciprocating single-file (Wave-One) instrumentation techniques. MATERIALS AND METHODS: Ninety-six patients who fulfilled specific inclusion criteria were assigned to three groups according to the root canal instrumentation technique used: Hand (G1), ProTaper Universal (G2), and Wave-One (G3). One-visit root canal treatment was carried out, and the severity of the postoperative pain was assessed by the Heft-Parker visual analogue scale 6, 12, 18, 24, 48, and 72 h after treatment. Data were analyzed by Kruskal-Wallis, χ 2, Cochrane Q, one-way ANOVA, and Spearman's correlation analyses (α = 0.05). RESULTS: The patients in group 3 reported significantly lower postoperative pain levels at 6, 12, and 18 h compared with the patients in the two other groups (P < .05). In addition, the patients in group 2 reported significantly lower postoperative pain levels at 6 and 12 h compared with the patients in group 1 (P < .05). There were no significant differences in postoperative pain between the three groups at other time intervals (P > .05). The analgesic consumption was significantly higher in group 1 (P < .05), but no difference was seen between the two other groups (P > .05). CLINICAL RELEVANCE: Postoperative pain was significantly lower in patients undergoing root canal instrumentation with the Wave-One file compared with the ProTaper Universal and hand files.

Population-based metabolic syndrome risk score and its determinants: The Isfahan Healthy Heart Program.

BACKGROUND: Metabolic syndrome (MetSy), an important predisposing factor for the most of noncommunicable diseases, has become a global pandemic. Given different definitions used for the MetSy, recently using a score termed "continuous MetSy risk score (CMetSyS)" is recommended. The aim of this study was to provide a CMetSyS in a population-based sample of Iranian adults and to assess its determinants. MATERIALS AND METHODS: We used the data of the baseline survey of a community trial entitled "the Isfahan health heart program." The MetSy was defined according to the Revised National Cholesterol Education Program Third Adult Treatment Panel. All probable predictive models and their predictive performance were provided using leave-one-out cross-validated logistic regression and the receiver operation characteristic curve methods. Multiple linear regression was performed to assess factors associated with the CMetSyS. RESULTS: The study population consisted of 8313 persons (49.9% male, mean age 38.54 ± 15.86 years). The MetSy was documented in 1539 persons (21.86%). Triglycerides and waist circumference were the best predictive components, and fasting plasma glucose had the lowest area under curve (AUC). The AUC for our best model was 95.36 (94.83-95.83%). The best predictive cutoff for this risk score was -1.151 with 89% sensitivity and 87.93% specificity. CONCLUSION: We provided four population-based leave-one-out cross-validated risk score models, with moderate to perfect predictive performance to identify the MetSy in Iranian adults. The CMetSyS had significant associations with high sensitive C-reactive protein, body mass index, leisure time, and workplace physical activity as well as age and gender.

Evaluation of the T helper 17 cell specific genes and the innate lymphoid cells counts in the peripheral blood of patients with the common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by a deficiency in the immune system with a heterogeneous collection of disorders resulting in antibody deficiency and recurrent infections. T helper 17 (Th17) cells promote B-cell survival and synergize with the B-cell activating factor to induce their differentiation into the plasma cells. A sub-population of innate lymphoid cells (ILCs) also produces interleukin 17 (IL-17). This study aimed to measure the Th17 specific genes and ILCs counts in the CVID patients in comparison with control subjects. MATERIALS AND METHODS: Total messenger ribonucleic acid (mRNA) was extracted from the whole blood samples of 10 CVID patients and 10 healthy individuals. IL-17, retinoic acid receptor-related orphan receptor C2 (RORC2), IL-23R, and IL-9 gene expression were measured using the quantitative reverse transcriptase-polymerase chain reaction. Count of lineage negative/CD127(+)/CD90(+) ILCs in the blood samples was performed by the flow cytometry method. RESULTS: The transcript levels of IL-17 and RORC2 in CVID patients was strongly lower than control subjects (P = 0.049 and P = 0.046, respectively), but slight reduction in the IL-23R expression (P = 0.252) have seen in the CVID patients. Accordingly, the number of ILCs decreased significantly (P = 0.04). Interestingly, IL-9 mRNA level was more significantly in the CVID patients (P = 0.001). CONCLUSION: The results presented in this study show that the Th17 cell specific genes expression (as the determiner Th17 cells) and ILCs (another lymphoid source of IL-17) are decreased in patients with CVID and this could be an explanation for the defect of their humoral immune response. In addition, elevation of the IL-9 gene expression may shed a new light into the way toward the understanding of the mechanism of autoimmunity in the CVID patients.

Infectious Diarrhea Risks as a Public Health Emergency in Floods; a Systematic Review and Meta-Analysis.

Introduction: Infectious diarrhea, a significant global health challenge, is exacerbated by flooding, a consequence of climate change and environmental disruption. This comprehensive study aims to quantify the association between flooding events and the incidence of infectious diarrhea, considering diverse demographic, environmental, and pathogen-specific factors. Methods: In this systematic review and meta-analysis, adhering to PROSPERO protocol (CRD42024498899), we evaluated observational studies from January 2000 to December 2023. The analysis incorporated global data from PubMed, Scopus, Embase, Web of Science, and ProQuest, focusing on the relative risk (RR) of diarrhea post-flooding. The study encompassed diverse variables like age, sex, pathogen type, environmental context, and statistical modeling approaches. Results: The meta-analysis, involving 42 high-quality studies, revealed a substantial increase (RR = 1.40, 95% CI [1.29-1.52]) in the incidence of diarrhea following floods. Notably, bacterial and parasitic diarrheas demonstrated higher RRs (1.82 and 1.35, respectively) compared to viral etiologies (RR = 1.15). A significant sex disparity was observed, with women exhibiting a higher susceptibility (RR = 1.55) than men (RR = 1.35). Adults (over 15 years) faced a greater risk than younger individuals, highlighting age-dependent vulnerability. Conclusion: This extensive analysis confirms a significant correlation between flood events and increased infectious diarrhea risk, varying across pathogens and demographic groups. The findings highlight an urgent need for tailored public health interventions in flood-prone areas, focusing on enhanced sanitation, disease surveillance, and targeted education to mitigate this elevated risk. Our study underscores the critical importance of integrating flood-related health risks into global public health planning and climate change adaptation strategies.

Metformin reduces the clonal fitness of Dnmt3aR878H hematopoietic stem and progenitor cells by reversing their aberrant metabolic and epigenetic state.

Clonal hematopoiesis (CH) arises when a hematopoietic stem cell (HSC) acquires a mutation that confers a competitive advantage over wild-type (WT) HSCs, resulting in its clonal expansion. Individuals with CH are at an increased risk of developing hematologic neoplasms and a range of age-related inflammatory illnesses1-3. Therapeutic interventions that suppress the expansion of mutant HSCs have the potential to prevent these CH-related illnesses; however, such interventions have not yet been identified. The most common CH driver mutations are in the DNA methyltransferase 3 alpha (DNMT3A) gene with arginine 882 (R882) being a mutation hotspot. Here we show that murine hematopoietic stem and progenitor cells (HSPCs) carrying the Dnmt3aR878H/+ mutation, which is equivalent to human DNMT3AR882H/+, have increased mitochondrial respiration compared with WT cells and are dependent on this metabolic reprogramming for their competitive advantage. Importantly, treatment with metformin, an oral anti-diabetic drug with inhibitory activity against complex I in the electron transport chain (ETC), reduced the fitness of Dnmt3aR878H/+ HSCs. Through a multi-omics approach, we discovered that metformin acts by enhancing the methylation potential in Dnmt3aR878H/+ HSPCs and reversing their aberrant DNA CpG methylation and histone H3K27 trimethylation (H3K27me3) profiles. Metformin also reduced the fitness of human DNMT3AR882H HSPCs generated by prime editing. Our findings provide preclinical rationale for investigating metformin as a preventive intervention against illnesses associated with DNMT3AR882 mutation-driven CH in humans.

CO2 laser conditioning of porcelain surfaces for bonding metal orthodontic brackets.

Bonding to porcelain remains to be a challenge in orthodontic treatments. The objective of this study was to evaluate the effect of CO2 laser conditioning of porcelain surfaces on shear bond strength (SBS) of orthodontic brackets. Eighty feldspathic porcelain specimens were divided into four groups of 20. In each group, half of the porcelain surfaces were deglazed, while the others remained glazed. The specimens in groups 1 to 3 were treated with a fractional CO2 laser for 10 s using 10 mJ of energy, frequency of 200 Hz and powers of 10 W (group 1), 15 W (group 2) and 20 W (group 3). In group 4, a 9.6 % hydrofluoric (HF) acid gel was used for 2 min. A silane coupling agent was applied before bracket bonding, and the SBS was measured with a universal testing machine after 24 h. Deglazing caused significant increase in SBS of laser treated porcelain surfaces (p < 0.05), but had no significant effect on SBS when HF acid was used for etching (p = 0.137). ANOVA revealed no significant difference in SBS values of the study groups when glazed surfaces were compared (p = 0.269). However, a significant between group difference was found among the deglazed specimens (p < 0.001). Tukey test revealed that the bond strengths of 10 W and 15 W laser groups were significantly higher than that of the HF acid group (p < 0.05). Laser conditioning with a fractional CO2 laser can be recommended as a suitable alternative to hydrofluoric acid for deglazed feldspathic porcelain.

Super-enhanced evaporation of droplets from porous coatings.

HYPOTHESIS: The addition of a thin, hydrophilic, porous, coating to an impermeable solid will lead to more rapid evaporation of liquid droplets that impinge on the solid. The droplet will imbibe quickly, but the progress normal to the interface will be limited to the thickness of the coating, and therefore the liquid will spread laterally into a broad disk to expose a large liquid-vapor interface for evaporation. EXPERIMENTS: Liquid droplets of volume 2.5-25 µL were placed on solids and then both the mass and area of each droplet were monitored over time. We compared data for smooth, impermeable hydrophilic glass to the same glass that was coated in thin (35-109 µm) porous, hydrophilic-glass layer fabricated from glass beads. FINDINGS: The droplet was imbibed (wicked) into the coating within seconds, and the liquid spread laterally to form a thin, broad, disk. Critically, evaporation of a droplet was enhanced by a factor of 7-8 on the thin coating. The evaporation rate was not proportional to the reciprocal thickness of the coating. The ability to enhance evaporation of small droplets on a solid may have practical applications, for example, in speeding the death of microbes.

Inverse correlation between vitamin D and CRP levels in alopecia areata: A pilot study.

INTRODUCTION: Alopecia areata (AA) is an autoimmune non-scarring hair loss. The role of micronutrients such as iron, zinc, and vitamins, especially vitamin D, on the natural hair cycle is well defined in literature. This study aims to evaluate the correlation between vitamin D and CRP levels in patients with alopecia areata. METHODS: This cross-sectional study was performed from beginning of October 2020 until end of December 2021. Alopecia areata patients over 18 years of age gave their written consent to participate in the study. The severity of the patients' disease was assessed using the Severity of Alopecia Tool. Serum vitamin D and CRP levels were measured and CBC and LFT were also performed. RESULTS: There were significant differences between the patients with the localized form of AA and its universal form in the following variables: Vitamin D levels, SALT score, WBC, ALKP, and CRP. There was also a significant inverse correlation between CRP and vitamin D levels (p < 0.0001). CONCLUSION: Vitamin D deficiency is associated with higher CRP levels, and patients with low serum vitamin D and high CRP levels are at a higher risk of developing the universalis form of AA; therefore, these patients should undergo more aggressive treatments.

Low-temperature acclimation related with developmental regulations of polyamines and ethylene metabolism in wheat recombinant inbred lines.

Winter survival is determined by complicated developmental regulations enabling wheat to adjust their transcriptome and metabolome to develop low temperature (LT) tolerance. The aim of the study was to clarify the metabolic responses developmentally regulated in six F6 recombinant inbred lines from a cross between Pishtaz (spring parent) and Mironovskaya 808 (winter parent). Spring genotypes, including pishtaz, RILs 4006 and 4014 showed lower LT tolerance, PAs (except the spermin), GABA and proline contents and DPPH• scavenging capacity. In these genotypes, genes and enzymes involved in the pathways of PAs and GABA degradation and ethylene biosynthesis were more active than other genotypes. RILs 4012 and 4016 with short vernalization displayed higher tolerance and lower H2O2 content compared to Pishtaz. Strong vernalization requirements in winter and facultative genotypes (Mironovskaya 808 parent and RILs 4003 and 4005) results in up-regulation of the metabolites and genes involved in PAs and GABA biosynthesis pathways (particularly when vernalization fulfillment occurred) to establish high tolerance as compared to genotypes without vernalization requirement. LT tolerance in all genotypes significantly decreased after vernalization fulfillment in February. Results indicated that LT tolerance was partly validated from developmental regulation of PAs, GABA, and ethylene metabolism during venalization and LT acclimation.

Dietary and Sleep Quality Association in Hemodialysis Patients.

Background: Poor sleep quality is a common issue among patients with end-stage renal disease (ESRD) who undergo dialysis. Nutritional habits are associated with sleep hygiene in patients undergoing dialysis. The objective of this study was to examine the potential correlation between nutritional status and sleep quality in individuals receiving hemodialysis treatment. Materials and Methods: This cross-sectional study included 160 hemodialysis patients. A food frequency questionnaire (FFQ) was used to measure food intake in participants. The Persian-validated version of the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Patients were classified as poor or good sleepers with a PSQI score of <5 and >5, respectively. Results: Eighty-four percent of hemodialysis patients had bad sleep hygiene. There was a significant association between sleep quality and educational status and age (P < 0.001). Poor sleepers were older (61.65 years versus 51.12) and less educated (31.1% versus 4%). However, there was no significant difference in the intake of micro- and macronutrients between poor and good sleepers (P > 0.05). Conclusion: The results of this study suggest that sleep quality has no significant relationship with nutrient intake in hemodialysis patients. Demographic factors, such as age and educational status, have played a more effective role than nutritional factors in patients' sleep quality.

Crossover design in triage education: the effectiveness of simulated interactive vs. routine training on student nurses' performance in a disaster situation.

INTRODUCTION: This study investigates the effectiveness of incorporating simulated interactive guidelines in nursing students' performance during disaster situations, compared to routine training. METHOD: This study was a crossover design with pre-and post-tests for two groups. Each group consisted of 60 students selected using the census method. SIG and routine (Face-to-Face) training sessions were conducted as a crossover design. Triage knowledge questionnaires were used in the pretest to assess triage knowledge. An OSCE test was administered in the posttest to assess student performance, followed by a triage skills questionnaire. Both questionnaires were highly reliable, as indicated by Cronbach's alpha coefficients (0.9 and 0.95, respectively). Statistical analysis was performed using SPSS version 26 software at a significance level 0.05. RESULT: The chi-square test showed that the two groups were homogeneous regarding age. Regarding knowledge level, both groups were homogeneous before the intervention (P = 0.99). Nevertheless, the results of the OSCE test showed that the students in Group A had a higher level of skill than the students in Group B (93% versus 70%). Also, 18% of the students in group B had low skills. DISCUSSION: The study found that student outcomes improved in both groups receiving SIG, suggesting that interaction and simulation improve learning. However, gamification is an ideal precursor to learning and not a substitute for education. Therefore, gamification should not be used as a stand-alone teaching method. CONCLUSIONS: The crossover study found that simulators and games should not be considered stand-alone teaching methods but can contribute to learning sustainability when used alongside instruction.

Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study.

BACKGROUND: COVID-19 is a respiratory illness caused by SARS-CoV-2. Pharmaceutical companies aim to control virus spread through effective drugs. This study investigates chromone compound derivatives' ability to inhibit viral entry and prevent replication. METHOD: This study investigated the inhibitory effect of chromone-embedded peptidomimetics and furopyrimidines on 7BZ5 from Severe Acute Respiratory Syndrome CoV-2, Homo sapiens, and 6LU7 from Bat SARS-like CoV using molecular docking. The crystal structure of these proteins was obtained from the Protein Data Bank, and the inhibition site was determined using ligand binding interaction options. The 3D structure was protonated and energetically minimised using MOE software. Chromone derivatives were designed in three dimensions, and their energy was minimised using MOE 2019. The molecular drug-likeness was calculated using SwissADME, Lipinski and Benigni-Bossa's rule, and toxicity was calculated using Toxtree v3.1.0 software. Compounds with pharmacological properties were selected for molecular docking, and interactions were assessed using MOE 2019. MD simulations of Mpro-ch-p complexes were performed to evaluate root mean square fluctuations (RMSF) and measure protein stability. RESULT: The pharmacokinetic tests revealed that chromone derivatives of the peptidomimetic family have acceptable pharmacokinetic activity in the human body. Some compounds, such as Ch-p1, Ch-p2, Ch-p6, Ch-p7, Ch-p12, and Ch-p13, have pronounced medicinal properties. Molecular docking revealed high affinity for binding to SARS-CoV-2 protease. Ch-p7 had the highest binding energy, likely due to its inhibitory property. A 10 ns molecular dynamics study confirmed the stability of the protein-ligand complex, resulting in minimal fluctuations in the system's backbone. The MM-GBSA analysis revealed free energies of binding of - 19.54 kcal/mol. CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.