Machine learning-based models to predict the need for neurosurgical intervention after moderate traumatic brain injury.

Background and Aims: Traumatic brain injury (TBI) is a widespread global health issue with significant economic consequences. However, no existing model exists to predict the need for neurosurgical intervention in moderate TBI patients with positive initial computed tomography scans. This study determines the efficacy of machine learning (ML)-based models in predicting the need for neurosurgical intervention. Methods: This is a retrospective study of patients admitted to the neuro-intensive care unit of Emtiaz Hospital, Shiraz, Iran, between January 2018 and December 2020. The most clinically important variables from patients that met our inclusion and exclusion criteria were collected and used as predictors. We developed models using multilayer perceptron, random forest, support vector machines (SVM), and logistic regression. To evaluate the models, their F1-score, sensitivity, specificity, and accuracy were assessed using a fourfold cross-validation method. Results: Based on predictive models, SVM showed the highest performance in predicting the need for neurosurgical intervention, with an F1-score of 0.83, an area under curve of 0.93, sensitivity of 0.82, specificity of 0.84, a positive predictive value of 0.83, and a negative predictive value of 0.83. Conclusion: The use of ML-based models as decision-making tools can be effective in predicting with high accuracy whether neurosurgery will be necessary after moderate TBIs. These models may ultimately be used as decision-support tools to evaluate early intervention in TBI patients.

Design of a novel multi-epitope vaccine candidate against Chlamydia trachomatis using structural and nonstructural proteins: an immunoinformatics study.

Chlamydia trachomatis (C. trachomatis) is an obligate intracellular bacterium which causes eye and sexually transmitted infections. During pregnancy, the bacterium is associated with preterm complications, low weight of neonates, fetal demise and endometritis leading to infertility. The aim of our study was design of a multi-epitope vaccine (MEV) candidate against C. trachomatis. After protein sequence adoption from the NCBI, potential epitopes toxicity, antigenicity, allergenicity, MHC-I and MHC-II binding, cytotoxic T lymphocytes (CTLs), Helper T lymphocytes (HTLs) and interferon-γ (IFN-γ)- induction were predicted. The adopted epitopes were fused together using appropriate linkers. In the next step, the MEV structural mapping and characterization, three-dimensional (3D) structure homology modeling and refinement were also performed. The MEV candidate interaction with the toll-like receptor 4 (TLR4) was also docked. The immune responses simulation was assessed using the C-IMMSIM server. Molecular dynamic (MD) simulation verified the structural stability of the TLR4-MEV complex. The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach demonstrated the MEV high affinity of binding to the TLR4, MHC-I and MHC-II. The MEV construct was also stable and water soluble and had enough antigenicity and lacked allergenicity with stimulation of T cells and B cells and INF-γ release. The immune simulation confirmed acceptable responses of both the humoral and cellular arms. It is proposed that in vitro and in vivo studies are needed to evaluate the findings of this study.Communicated by Ramaswamy H. Sarma.

Advanced simulations and screening to repurposing a 3C protease inhibitor against the rupintrivir-resistant human norovirus-induced gastroenteritis.

Human norovirus (HuNoV) causes acute viral gastroenteritis in all age groups, and dehydration and severe diarrhea in the elderly. The World Health Organization reports ∼1.45 million deaths from acute gastroenteritis annually in the world. Rupintrivir, an inhibitory medicine against the human rhinovirus C3 protease, has been reported to inhibit HuNoV 3C protease. However, several HuNoV 3C protease mutations have been revealed to reduce the susceptibility of HuNoV to rupintrivir. The structural details behind rupintrivir-resistance of these single-point mutations (A105V and I109V) are not still clear. Hence, in this study, a combination of computational techniques were used to determine the rupintrivir-resistance mechanism and to propose an inhibitor against wild-type and mutant HuNoV 3C protease through structure-based virtual screening. Dynamic structural results indicated the unstable binding of rupintrivir at the cleft binding site of the wild-type and mutant 3C proteases, leading to its detachment. Our findings presented that the domain II of the HuNoV 3C protease had a critical role in binding of inhibitory molecules. Binding energy computations, steered molecular dynamics and umbrella sampling simulations confirmed that amentoflavone, the novel suggested inhibitor, strongly binds to the cleft site of all protease models and has a good structural stability in the complex system along the molecular dynamic simulations. Our in silico study proposed the selected compound as a potential inhibitor against the HuNoV 3C protease. However, additional experimental and clinical studies are required to corroborate the therapeutic efficacy of the compound.

Design of a novel multi-epitope vaccine candidate against hepatitis C virus using structural and nonstructural proteins: An immunoinformatics approach.

Hepatitis C virus (HCV) infects the liver and causes chronic infection. Several mutations in the viral genome have been associated with drug resistance development. Currently, there is no approved vaccine against the HCV. The employment of computational biology is the primary and crucial step for vaccine design or antiviral therapy which can substantially reduce the duration and cost of studies. Therefore, in this study, we designed a multi-epitope vaccine using various immunoinformatics tools to elicit the efficient human immune responses against the HCV. Initially, various potential (antigenic, immunogenic, non-toxic and non-allergenic) epitope segments were extracted from viral structural and non-structural protein sequences using multiple screening methods. The selected epitopes were linked to each other properly. Then, toll-like receptors (TLRs) 3 and 4 agonists (50S ribosomal protein L7/L12 and human ß-defensin 2, respectively) were added to the N-terminus of the final vaccine sequence to increase its immunogenicity. The 3D structure of the vaccine was modeled. Molecular dynamics simulations studies verified the high stability of final free vaccines and in complex with TLR3 and TLR4. These constructs were also antigenic, non-allergenic, nontoxic and immunogenic. Although the designed vaccine traits were promising as a potential candidate against the HCV infection, experimental studies and clinical trials are required to verify the protective traits and safety of the designed vaccine.

Efflux dynamics of the antiseizure drug, levetiracetam, through the P-glycoprotein channel revealed by advanced comparative molecular simulations.

Understanding the precise mechanistic details of the possible binding and transport of antiseizure medications (ASMs) through the P-glycoprotein (P-gp) efflux pump is essential to find strategies for the treatment of patients with epilepsy resistant to ASMs. In the present work, conventional molecular dynamics, binding free energy calculations, steered molecular dynamics and umbrella sampling were applied to study the interactions of levetiracetam and brivaracetam with P-gp and their possible egress path from the binding site. Comparative results for the control drugs, zosuquidar and verapamil, confirmed their established P-gp inhibitory activity. Brivaracetam, a non-substrate of P-gp, demonstrated stronger static and dynamic interactions with the exporter protein, than levetiracetam. The potential of mean force calculations indicated that the energy barriers through the ligand export were the lowest for levetiracetam, suggesting the drug as a P-gp substrate with facile passage through the transporter channel. Our findings also stressed the contribution of nonpolar interactions with P-gp channel lining as well as with membrane lipid molecules to hamper the ASM efflux by the transmembrane exporter. Appropriate structural engineering of the ASMs is thus recommended to address drug-resistant epilepsy.

The Effect of Mesenchymal Stem Cells on the Expression of IDO and Qa2 Molecules in Dendritic Cells.

Purpose: Mesenchymal stem cells (MSCs) have been shown to reduce the activity of immune cells, including dendritic cells (DCs). But the exact mechanism of mesenchymal inhibition of DCs is still unknown. In this study, the effect of mesenchymal cells on the expression of indoleamine dioxygenase (IDO) and Qa2 molecules in DCs was evaluated. Methods: MSCs and DCs were respectively isolated from the bone marrow and spleen of BALB/c mice. Then DCs were co-cultured with MSCs in the present and absence of lipopolysaccharides (LPS). Then the expression of mRNA and protein of IDO and Qa2 molecules were investigated in DCs that were treated with MSCs. Results: The expression of IDO and Qa2 mRNA in DCs that were treated with MSCs did not significantly differ from the control group. The expression of IDO protein in DCs that were cocultured with MSCs (in 1:10 and 1:50 ratios) in absence of LPS was increased, although they were not statistically significant (P values: 0.24 and 0.18, respectively). The expression of Qa2 protein in DCs that were co-cultured with MSCs (in 1:10 and 1:50 ratios) in presence of LPS was increased, although they were not statistically significant (P-values: 0.09 and 0.33, respectively). Conclusion: Our results denied the possibility that MSCs led to the induction of tolerogenic DCs by increasing the expression of the IDO and Qa2 immunomodulatory molecules.

Breast cancer-linked lncRNA u-Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding.

Recently, it has been revealed that estrogen-related reproductive factors are linked with some early gene expression lesions associated with malignancy in clinically healthy breasts. Accordingly, the aim of the current study was to evaluate the association of expression levels of estrogen-related long noncoding RNAs (lncRNAs) upstream Eleanor (u-Eleanor) and HOX antisense intergenic RNA (HOTAIR) with the different patterns of reproductive factors in breast tissue of healthy women. The subjects of this study were 98 cancer-free women who had undergone cosmetic mammoplasty. The expression levels of u-Eleanor and HOTAIR were measured using quantitative real-time polymerase chain reaction. The results of the current study showed that the women without a history of breastfeeding had a high-level expression of u-Eleanor compared with the women with a breastfeeding duration greater than 6 to 24 months (P = 0.03) as well as the women with a breastfeeding duration of more than 24 months (P = 0.005). Furthermore, a higher expression of u-Eleanor was found in the women with a short breastfeeding duration for 1 to 6 months than that in the women with a breastfeeding duration of greater than 24 months (P = 0.02). In the same way, the results of correlation test (r = -0.258; P = 0.036) and multivariate regression model (ß = -0.321; P = 0.023) are indicative of a significant relationship of elevated expression of u-Eleanor with decreasing breastfeeding duration in the women. These findings could be important to identify the molecular mechanisms behind the relationship between a lack or short duration of the breastfeeding and the risk of breast cancer, which has previously been reported by epidemiological studies.

The Effect of Educational Intervention Based on BASNEF Model on Self-Medication Behavior of Type 2 Diabetic Patients.

BACKGROUND: Diabetes is one of the main reasons of the increase of morbidity and mortality around the world. Considering the burden of disease, self-medication can result in irrecoverable consequences. The aim of this study is to investigate the effect of educational intervention based on Beliefs, Attitudes, Subjective Norms and Enabling Factors (BASNEF) model on self-medication behaviors of type 2 diabetic patients in Fasa, Fars province, Iran, in 2017-2018. MATERIALS AND METHODS: In this quasi-experimental study, 200 type 2 diabetic patients under cover of the diabetes center of Fasa were investigated (100 patients for experimental group and 100 patients for control group). A questionnaire investigating demographic information and BASNEF Model constructs (knowledge, attitude, enabling factors, subjective norms, and behavioral intention) was used for evaluating self-medication behaviors of patients before and 3 months after intervention. RESULTS: The average age of experimental group was 53.25 ± 8.42 and the average age of control group was 54.18 ± 8.13. Three months after intervention, experimental group showed significant enhancement in knowledge, attitude, enabling factors, subjective norms, and behavioral intention and their self-medication behaviors reduced, while control group showed no significant changes in mentioned factors. CONCLUSION: The present study indicated the efficiency of BASNEF model on reduction of self-medication behaviors of diabetic patients. Hence, this model can act as a framework for designing and implementing educational interventions in this field.

Method development for determination of migrated phthalate acid esters from polyethylene terephthalate (PET) packaging into traditional Iranian drinking beverage (Doogh) samples: a novel approach of MSPE-GC/MS technique.

In the current study, a novel magnetic solid phase extraction (MSPE) technique combined with a gas chromatography/mass spectroscopy (GC/MS) was developed to determine the phthalate ester content of bottled Doogh samples. Doogh is a yogurt-based drinking beverage, which is frequently consumed in Middle East and Balkans. It is produced by stirring yogurt in Chern separation machine and consists of substances such as water, yogurt, and salt in addition to aqueous extracts of native herbs. The magnetic multi-walled carbon nanotubes (MWCNT-Fe3O4) were used as adsorbents of phthalate acid esters (PAEs) due to a superior adsorption capability of hydrophobic compounds. In this context, the quantity of the extractable migrated phthalate esters (dibutyl phthalate (DBP), dimethyl phthalate (DMP), butyl benzyl phthalate (BBP), diethyl phthalate (DEP), di-N-octyl phthalate (DNOP), and bis (2-ethylhexyl) phthalate (DEHP)) from polyethylene terephthalate (PET) bottles into Doogh samples was measured. The correlation between the concentration of migrated PAEs and some factors such as the type of Doogh (gaseous and without gas), difference in brand (five brands), volume (1500 and 300 mL), and the storage time also was investigated. The migration level into Doogh samples was increased by incorporating of gas as well as increasing the volume of PET bottles. Also, with elaborating of storage time, the migration of some phthalates such as DEHP (the mean from 2419.85 ng L-1 in the first week to 2716.15 ng L-1 in the second month), DEP, and total phthalate was increased. However, no significant difference in concentrations of migrated phthalate esters among different examined brands was noted. Finally, the concentration of migrated PAEs from bottle into all the examined Doogh samples was below the defined standards by EPA; 6 µg/L for DEHP in drinking water. Graphical abstract ᅟ.

Efecto de una intervención educativa basada en el modelo de creencias de salud en la automedicación de madres iraníes / Efeito de uma intervenção educativa baseada no modelo de crenças de saúde na automedicação de mães iranianas / Effect of an educational intervention based on the model of health beliefs in self-medication of Iranian mothers

Objective. This study sought to determine the effect of education based on the model of health beliefs in self-medication of women in Iran. Methods. Quasi-experimental study in a group of mothers (N = 90, 45 in the intervention group and 45 in the control group) users of health centers from the city of Fasa, province of Fars, southern Iran. Before and after the educational intervention (four training sessions in three months), a questionnaire was applied containing questions based on the model of health beliefs, on the components of knowledge, vulnerability, severity, benefits, and barriers perceived, and practices on self-medication. Results. Prior to the educational intervention, the level of knowledge, sensitivity, intensity, and benefits of self-medication were equal in both groups; however, after the educational intervention, it was observed that the intervention group improved in all components of evaluation and diminished barriers perceived and self-treatment practices. Conclusion. The educational intervention based on the model of health beliefs was effective in reducing self-medication practices in the group of mothers. Hence, this type of training is recommended in health centers to diminish the frequency of this practice.

Objetivo. Determinar los efectos de la educación basada en el modelo de creencias de salud en la automedicación de las mujeres en Irán. Métodos. Estudio cuasi-experimental en un grupo de madres (N = 90, 45 en el grupo de intervención y 45 en el grupo de control) usuarias de centros de salud de la ciudad de Fasa, provincia de Fars, al sur de Irán. Antes y después de la intervención educativa (cuatro sesiones de capacitación en tres meses) se aplicó un cuestionario que contenía preguntas basadas en el modelo de creencias de salud, sobre los componentes de conocimiento, vulnerabilidad, severidad, beneficios y barreras percibidas, y prácticas sobre automedicación. Resultados. Antes de la intervención educativa, el nivel de conocimiento, sensibilidad, intensidad y los beneficios de la automedicación fueron iguales en los dos grupos; sin embargo, después de la intervención educativa se observó que el grupo de intervención mejoró en todos los componentes de evaluación y disminuyó las barreras percibidas y las prácticas de autotratamiento. Conclusión. La intervención educativa basada en el modelo de creencias de salud fue efectiva en la reducción de prácticas de automedicación en el grupo de control. Por lo tanto, se recomienda realizar este tipo de capacitación en los centros de salud con el fin de disminuir la frecuencia de esta práctica.

Objetivo. Determinar o efeito da educação baseada no modelo de crenças de saúde na automedicação das mulheres no Irão. Métodos. Estudo quase-experimental num grupo de mães (N = 90, 45 no grupo de intervenção e 45 no grupo de controle) usuárias de centros de saúde da cidade de Fasa, província de Fars, ao sul do Irão. Antes e depois da intervenção educativa (quatro sessões de capacitação em três meses) se aplicou um questionário que tinha perguntas baseadas no modelo de crenças de saúde, sobre os componentes de conhecimento, vulnerabilidade, severidade, benefícios e barreiras percebidas, e práticas sobre automedicação. Resultados. Antes da intervenção educativa, o nível de conhecimento, sensibilidade, intensidade e os benefícios da automedicação foram iguais nos dos grupos; embora, depois da intervenção educativa, se observou que o grupo de intervenção melhorou em todos os componentes de avaliação e diminuiu as barreiras percebidas e as práticas de auto-tratamento. Conclusão. A intervenção educativa baseada no modelo de crenças de saúde foi efetiva na redução de práticas de automedicação no grupo de mães. Por tanto, se recomenda realizar este tipo de capacitação nos centros de saúde com o fim de diminuir a frequência desta prática.

Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice.

Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression.

Differences in Cardiovascular Responses to Alamandine in Two-Kidney, One Clip Hypertensive and Normotensive Rats.

BACKGROUND: Alamandine is a newly discovered component of the renin-angiotensin system, which regulates blood pressure. In this study, the effect of alamandine on cardiovascular parameters in two-kidney, one clip (2K1C) hypertensive rats and normotensive rats, and the possible roles of the angiotensin II type 1 receptor (AT1R) and the PD123319-sensitive receptors in mediating this effect was investigated.Methods and Results:The cardiovascular parameters were monitored for 10 min before the infusion of the drugs or saline, and for 30 min afterward. In the 2K1C hypertensive rats, alamandine caused brief increases in mean arterial pressure (MAP), left-ventricular systolic pressure (LVSP) and maximum rate of pressure change in the left ventricle (dP/dt(max)). This was followed by decreases in these parameters, which extended throughout the remainder of the infusion period. Losartan, an AT1R blocker, abolished alamandine's initial pressor effect and PD123319, which can block AT2R and Mas-related G protein-coupled receptor D (MrgD) receptors, partially decreased the late depressor effect. Left ventricular end-diastolic pressure (LVEDP) decreased during alamandine infusion; this effect was reduced by PD123319. In the normotensive rats, alamandine increased MAP, LVSP, dP/dt (max), and it decreased LVEDP during the infusion period. These effects of alamandine were reduced by losartan. CONCLUSIONS: The results of this investigation suggest that, under normal conditions, alamandine acts via AT1R, but in pathological conditions such as hypertension, its effect on PD123319-sensitive receptors masks its effect on AT1R.

Effect of an educational intervention based on the model of health beliefs in self-medication of Iranian mothers.

OBJECTIVES: This study sought to determine the effect of education based on the model of health beliefs in self-medication of women in Iran. METHODS: Quasi-experimental study in a group of mothers (N = 90, 45 in the intervention group and 45 in the control group) users of health centers from the city of Fasa, province of Fars, southern Iran. Before and after the educational intervention (four training sessions in three months), a questionnaire was applied containing questions based on the model of health beliefs, on the components of knowledge, vulnerability, severity, benefits, and barriers perceived, and practices on self-medication. RESULTS: Prior to the educational intervention, the level of knowledge, sensitivity, intensity, and benefits of self-medication were equal in both groups; however, after the educational intervention, it was observed that the intervention group improved in all components of evaluation and diminished barriers perceived and self-treatment practices. CONCLUSIONS: The educational intervention based on the model of health beliefs was effective in reducing self-medication practices in the group of mothers. Hence, this type of training is recommended in health centers to diminish the frequency of this practice.

Assessing whether measurement invariance of the KIDSCREEN-27 across child-parent dyad depends on the child gender: a multiple group confirmatory factor analysis.

This study aims to assess the measurement invariance (MI) of the KIDSCREEN-27 questionnaire across girl-parent and boy-parent dyad to clarify how child gender affects the agreement between children's and parents' perception of the meaning of the items in the questionnaire. The child self-reports and parent proxy-reports of the KIDSCREEN-27 were completed by 1061 child-parent dyad. Multiple group categorical confirmatory factor analysis (MGCCFA) was applied to assess MI. The non-invariant items across girl-parent dyad were mostly detected in the psychological well-being and the social support and peers domains. Moreover, the boys and their parents differed mainly in the autonomy and parent relation domain. Detecting different non-invariant items across the girl-parent dyad compared to the boy-parent dyad underlines the importance of taking the child's gender into account when assessing measurement invariance between children and their parents and consequently deciding about children's physical, psychological or social well-being from the parents' viewpoint.

Facile fabrication of uniform hollow silica microspheres using a novel biological template.

Biological templates, due to their ease of preparation and surface modifications can be a promising approach to fabricate hollow structures. In this study, for the first time, a biological template was used for the production of hollow silica microspheres. Silica was successfully deposited on Staphylococcus aureus cells surface using the Stöber method. The hollow silica spheres with a mesoporous shell of approximately 700nm in diameter were produced by applying this novel method.