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High light (HL) is a common environmental stress directly imposes photoinhibition on the photosynthesis apparatus. Breeding plants for tolerance against HL is therefore highly demanded. Chlorophyll fluorescence (ChlF) is a sensitive indicator of stress in plants and can be evaluated using OJIP transients. In this study, we compared the ChlF features of plants exposed to HL (1200 μmol m -2  s -1 ) with that of control plants (300 μmol m -2  s -1 ). To extract the most reliable ChlF features for discrimination between HL-stressed and non-stressed plants, we applied three artificial neural network (ANN)-based algorithms, namely, Boruta, Support Vector Machine (SVM), and Recursive Feature Elimination (RFE). Feature selection algorithms identified multiple features but only two features, namely the maximal quantum yield of PSII photochemistry (F V /F M ) and quantum yield of energy dissipation (ɸ D0 ), remained consistent across all genotypes in control conditions, while exhibited variation in HL. Therefore, considered reliable features for HL stress screening. The selected features were then used for screening 14 tomato genotypes for HL. Genotypes were categorized into three groups, tolerant, semi-tolerant, and sensitive genotypes. Foliar hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) contents were measured as independent proxies for benchmarking selected features. Tolerant genotypes were attributed with the lowest change in H 2 O 2 and MDA contents, while the sensitive genotypes displayed the highest magnitude of increase in H 2 O 2 and MDA by HL treatment compared to the control. Finally, a F V /F M higher than 0.77 and ɸ D0 lower than 0.24 indicates a healthy electron transfer chain (ETC) when tomato plants are exposed to HL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Cancer is still the most challenging disease and is responsible for many deaths worldwide. Considerable research now focuses on targeted therapy in cancer using natural components to improve anti-tumor efficacy and reduce unfavorable effects. Lactoferrin is an iron-binding glycoprotein found in body fluids. Increasing evidence suggests that lactoferrin is a safe agent capable of inducing anti-cancer effects. Therefore, we conducted a study to evaluate the effects of the exosomal form of bovine milk lactoferrin on a human MDA-MB-231 breast cancer cell line., Methods: The exosomes were isolated from cancer cells by ultracentrifugation and incorporated with bovine milk lactoferrin through the incubation method. The average size of the purified exosome was determined using SEM imaging and DLS analysis. The maximum percentage of lactoferrin-loaded exosomes (exoLF) was achieved by incubating 1 mg/ml of lactoferrin with 30 µg/ml of MDA-MB-231 cells-derived exosomes. Following treatment of MDA-MB-231 cancer cells and normal cells with 1 mg/ml exoLF MTT assay applied to evaluate the cytotoxicity, PI/ annexin V analysis was carried out to illustrate the apoptotic phenotype, and the real-time PCR was performed to assess the pro-apoptotic protein, Bid, and anti-apoptotic protein, Bcl-2., Results: The average size of the purified exosome was about 100 nm. The maximum lactoferrin loading efficiency of exoLF was 29.72%. MTT assay showed that although the 1 mg/ml exoLF treatment of MDA-MB-231 cancer cells induced 50% cell growth inhibition, normal mesenchymal stem cells remained viable. PI/ annexin V analysis revealed that 34% of cancer cells had late apoptotic phenotype after treatment. The real-time PCR showed an elevated expression of pro-apoptotic protein Bid and diminished anti-apoptotic protein Bcl-2 following exoLF treatment., Conclusion: These results suggested that exoLF could induce selective cytotoxicity against cancer cells compared to normal cells. Incorporating lactoferrin into the exosome seems an effective agent for cancer therapy. However, further studies are required to evaluate anti-tumor efficacy and the underlying mechanism of exoLF in various cancer cell lines and animal models., (© 2023. The Author(s).)

Hematopoietic stem cell transplantation (HSCT) is a life-saving therapy for various hematologic disorders. Due to the bone marrow suppression and its long recovery period, secondary infections, like cytomegalovirus (CMV), Epstein-Bar virus (EBV), and adenovirus (AdV), are the leading causes of morbidity and mortality in HSCT cases. Drug resistance to the antiviral pharmacotherapies makes researchers develop adoptive T cell therapies like virus-specific T cell therapy. These studies have faced major challenges such as finding the most effective T cell expansion methods, isolating the expected subtype, defining the functionality of the end-cell population, product quality control, and clinical complications after the injection. This review discusses the viral infections after HSCT, T cells characteristics during chronic viral infection, application of virus-specific T cells (VSTs) for refractory infections, standard methods for producing VSTs and their limitation, clinical experiences on VSTs, focusing on outcomes and side effects that can be helpful in decision-making for patients and further researches., Competing Interests: None., (©2023 The Authors.)

BACKGROUND Acute aortic insufficiency can be secondary to multiple conditions, including infective endocarditis, aortic root pathologies (eg, dissection, aortitis), or traumatic injury. Aortitis involves a broad spectrum of disorders characterized by inflammatory changes in the aortic wall. This pathology can be subsequently classified depending on its etiology into inflammatory and infectious causes. Large-vessel vasculitis (giant-cell arteritis, Takayasu arteritis, and IgG4-related vasculitis) is the most common non-infectious causes of aortitis. Giant-cell aortitis usually lacks the classic clinical findings of giant-cell arteritis such as headache, visual symptoms, or jaw claudication, which can be a diagnostic challenge. However, clinicians should have a high index of suspicion, since this pathology can evolve into potentially life-threatening conditions, including aortic aneurysm, aortic wall rupture, and aortic acute dissection. CASE REPORT We present a case of a 76-year-old woman who presented to the Emergency Department (ED) with shortness of breath associated with orthopnea, paroxysmal nocturnal dyspnea, and mild productive cough with white sputum. A transthoracic echocardiogram demonstrated reduced left ventricular ejection fraction, dilated left ventricle, and severe aortic insufficiency. Cardiac catheterization revealed mild non-obstructive coronary arteries and severe aortic regurgitation. The surgical pathology report of the portion of the aorta was consistent with giant-cell aortitis. CONCLUSIONS In this article, we present a case of giant-cell aortitis as an unusual etiology of acute aortic insufficiency, which is most probably under-detected in clinical practice. In addition to describing the case, we aim to highlight the importance of proper ascending aorta evaluation in patients presenting with new-onset aortic regurgitation and heart failure to prevent associated morbidity and mortality.

Background: Over the past few years, mesenchymal stromal cells (MSCs) have attracted a great deal of scientific attention owing to their promising results in the treatment of incurable diseases. However, there are several concerns about their possible side effects after direct cell transplantation, including host immune response, time-consuming cell culture procedures, and the dependence of cell quality on the donor, which limit the application of MSCs in clinical trials. On the other hand, it is well accepted that the beneficial effects of MSCs are mediated by secretome rather than cell replacement. MSC secretome refers to a variety of bioactive molecules involved in different biological processes, specifically neuro-regeneration., Main Body: Due to the limited ability of the central nervous system to compensate for neuronal loss and relieve disease progress, mesenchymal stem cell products may be used as a potential cure for central nervous system disorders. In the present study, the therapeutic effects of MSC secretome were reviewed and discussed the possible mechanisms in the three most prevalent central nervous system disorders, namely Alzheimer's disease, multiple sclerosis, and Parkinson's disease. The current work aimed to help discover new medicine for the mentioned complications., Conclusion: The use of MSC-derived secretomes in the treatment of the mentioned diseases has encouraging results, so it can be considered as a treatment option for which no treatment has been introduced so far., (© 2023. The Author(s).)

Competing Interests: Conflict of Interest The authors declare that no competing interests exist.

Background: Sodium arsenate (Na 3As0 4, Sodium As) is an important toxic substance that leads to nephrotoxicity. Due to having bioactive molecules, such as polyphenols and tyrosol, olive oil plays a significant role in scavenging free radicals. This study aimed to investigate the effects of olive oil and tyrosol on As-induced nephrotoxicity., Methods: In our study, 42 adult male BALB/c mice were randomly divided into six groups: control (normal saline), olive oil (0.4 ml/d, gavage), tyrosol (5 mg/kg/d), Sodium As (15 mg/kg), olive oil + Sodium As, and tyrosol + Sodium As (olive oil and tyrosol received one hour before Sodium As). Drugs were administreted once daily for 30 consecutive days. On the 31 st day of the study, oxidative stress parameters in kidney tissue, FRAP in plasma, renal function parameters in serum, and histopathological assays were performed., Results: Sodium As-induced renal damage as characterized by a significant increase of creatinine and BUN ( P < 0.001) and histopathological changes. Also, Sodium As markedly altered oxidative stress biomarkers such as a significant increase in MDA ( P < 0.001) and significantly decreased in FRAP and GSH ( P < 0.01). Olive oil and tyrosol administration significantly improved the renal antioxidant defense system and decreased MDA concentration, markedly preserving the tissue structure and functional markers of kidney. However, these effects were more effective for tyrosol than olive oil., Conclusions: Our results suggest that olive oil and tyrosol can be used as a protective agent in preventing Sodium As-induced nephrotoxicity due to antioxidant property., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 International Journal of Preventive Medicine.)

Background: Interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have gained interest as diagnostic biomarkers of traumatic brain injury (TBI), but factors affecting their blood levels in patients with moderate-to-severe TBI are largely unknown., Objective: To investigate the trajectories of IL-10 and H-FABP between TBI patients with and without extracranial injuries (ECI); to investigate if there is a correlation between the levels of IL-10 and H-FABP with the levels of inflammation/infection markers C-reactive protein (CRP) and leukocytes; and to investigate if there is a correlation between the admission level of H-FABP with admission levels of cardiac injury markers, troponin (TnT), creatine kinase (CK), and creatine kinase MB isoenzyme mass (CK-MBm)., Materials and Methods: The admission levels of IL-10, H-FABP, CRP, and leukocytes were measured within 24 h post-TBI and on days 1, 2, 3, and 7 after TBI. The admission levels of TnT, CK, and CK-MBm were measured within 24 h post-TBI., Results: There was a significant difference in the concentration of H-FABP between TBI patients with and without ECI on day 0 (48.2 ± 20.5 and 12.4 ± 14.7 ng/ml, p = 0.02, respectively). There was no significant difference in the levels of IL-10 between these groups at any timepoints. There was a statistically significant positive correlation between IL-10 and CRP on days 2 (R = 0.43, p < 0.01) and 7 (R = 0.46, p = 0.03) after injury, and a negative correlation between H-FABP and CRP on day 0 (R = -0.45, p = 0.01). The levels of IL-10 or H-FABP did not correlate with leukocyte counts at any timepoint. The admission levels of H-FABP correlated with CK (R = 0.70, p < 0.001) and CK-MBm (R = 0.61, p < 0.001), but not with TnT., Conclusion: Inflammatory reactions during the early days after a TBI do not significantly confound the use of IL-10 and H-FABP as TBI biomarkers. Extracranial injuries and cardiac sources may influence the levels of H-FABP in patients with moderate-to-severe TBI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Niiranen, Chiollaz, Takala, Voutilainen, Tenovuo, Newcombe, Maanpää, Tallus, Mohammadian, Hossain, van Gils, Menon, Hutchinson, Sanchez and Posti.)

This paper proposes a revised version of the robust generalized maximum likelihood (GM)-type unscented KALMAN filter (GM-UKF) for the state estimation of gene regulatory networks (GRNs) in the presence of different types of deviations from assumptions. As known, the parameters and the power of the assumed noises within the GRN model may change abruptly as a result of jump behavior and bursting process in transcription and translation phases. Moreover, there may be outlying samples among genomic measurement data. Some other outliers may also occur in the model dynamics. The outliers may be misinterpreted by the filtering method if not detected and downweighted. To deal with all such deviations, a robust GM-UKF is designed that includes some modifications to address the challenges in calculating the projection statistics in GRNs such as the nonlinear behavior and the natural distance of the states. The proposed filter is compared to four Bayesian filters, i.e., the conventional UKF, the H ∞ -UKF, the downweighting UKF (DW-UKF), and a modified version of the GM-UKF, the so-called maximum-likelihood UKF(M-UKF). The outcome results demonstrate that the GM-UKF outperforms other methods for all outlier types while the H ∞ -UKF is appropriate for the changes in noise powers.

Objectives: This study aimed to evaluate the cardiometabolic abnormalities in women with normal-weight obesity (NWO) in comparison with lean, overweight, and obese women., Methods: This cross-sectional study evaluated the assessment of cardiometabolic abnormalities of women with NWO compared to lean, overweight, and obese women. NWO was defined as a BMI < 25 kg.m -2 and a BFP higher than 30%. Anthropometric variables, cardiometabolic abnormality markers (fasting blood glucose (FBG), blood pressure (BP), lipid profile, insulin resistance, and high-sensitivity C-reactive protein (hs-CRP)), and liver enzymes were also examined., Results: Significant differences were observed in HDL concentrations between NWO, lean, and obese participants ( p < 0.05). There were no significant differences in FBG, insulin resistance, liver enzymes, or cholesterol between groups ( p > 0.05). The prevalence of the abnormal metabolic phenotype was higher in NWO compared to the lean group (4.0% and 24.1%, respectively; p < 0.05). Women with type 2 and 3 obesity had abnormal metabolic profiles (60.9% and 73.9%, respectively) compared to NWO participants ( p < 0.01). The NWO group had a significantly higher incidence of cardiometabolic abnormalities compared to the lean participants ( p < 0.05), while the type 2 and 3 obese individuals had significantly higher incidences compared to the NWO group ( p < 0.001 and p < 0.001, respectively)., Conclusions: Individuals with NWO had a significantly higher incidence of cardiometabolic abnormalities when compared to lean participants. These abnormalities strongly relate to BFP and waist circumferences.

Background & Objective: Interleukin-6 (IL-6) is involved in inflammation and has a significant role in chronic lymphocytic leukemia (CLL) progression. Accordingly, IL-6 level may increase in CLL-affected patients compared to healthy individuals. The -174G>C single nucleotide polymorphism (SNP) in IL-6 promoter region has been related to differences in IL-6 transcription. Therefore, we investigated the possible association of IL-6 polymorphism with CLL., Methods: We examined the -174G>C SNP in IL-6 gene and studied its possible relationship with CLL in affected patients and in healthy controls using Amplification Refractory Mutation System- polymerase chain reaction genotyping method. IL-6 plasma level was measured in both studied groups., Results: According to the results, IL-6 mean plasma concentration was increased significantly in the CLL patients compared to the controls. However, 174G>C genotype of the IL-6 gene was not associated with CLL. Furthermore, there were no significant differences in the distribution of allele and genotype frequencies between the CLL-affected patients and the controls ( P >0.05)., Conclusion: Our study showed that -174G>C SNP in promotor of IL-6 gene could not be considered a risk factor for CLL. Larger prospective studies should be performed to confirm our results., Competing Interests: None.

Detection of microstructural white matter injury in traumatic brain injury (TBI) requires specialised imaging methods, of which diffusion tensor imaging (DTI) has been extensively studied. Newer fibre alignment estimation methods, such as constrained spherical deconvolution (CSD), are better than DTI in resolving crossing fibres that are ubiquitous in the brain and may improve the ability to detect microstructural injuries. Furthermore, automatic tract segmentation has the potential to improve tractography reliability and accelerate workflow compared to the manual segmentation commonly used. In this study, we compared the results of deterministic DTI based tractography and manual tract segmentation with CSD based probabilistic tractography and automatic tract segmentation using TractSeg. 37 participants with a history of TBI (with Glasgow Coma Scale 13-15) and persistent symptoms, and 41 healthy controls underwent deterministic DTI-based tractography with manual tract segmentation and probabilistic CSD-based tractography with TractSeg automatic segmentation.Fractional anisotropy (FA) and mean diffusivity of corpus callosum and three bilateral association tracts were measured. FA and MD values derived from both tractography methods were generally moderately to strongly correlated. CSD with TractSeg differentiated the groups based on FA, while DTI did not. CSD and TractSeg-based tractography may be more sensitive in detecting microstructural changes associated with TBI than deterministic DTI tractography. Additionally, CSD with TractSeg was found to be applicable at lower b-value and number of diffusion-encoding gradients data than previously reported., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent advances in adoptive cell therapy have considerably changed the paradigm of cancer immunotherapy. Although current immunotherapies could cure many patients with multiple myeloma (MM), relapsed/refractory MM (RR/MM) is still challenging in some cases. Natural killer (NK) cells are innate immune cells that exert effective cytotoxic activity against malignant cells like myeloma cells. In addition to their antitumor properties, NK cells do not induce graft versus host disease following transplantation. Therefore, they provide a promising approach to treating RR/MM patients. Currently, attempts have been made to produce large-scale and good manufacturing practices (GMP) of NK cells. Ex vivo expanded/activated NK cells derived from the own patient or allogenic donors are potential options for NK cell therapy in MM. Besides, novel cell-based products such as NK cell lines and chimeric antigen receptor (CAR)-NK cells may provide an off-the-shelf source for NK cell therapy. Here, we summarized NK cell activity in the MM microenvironment and focused on different NK cell therapy methods for MM patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Objectives. The active factor along with light exercise can reduce static muscle work and increase muscle flexibility and endurance. Accordingly, this study aimed to design and prototype a new active footrest, implemented in conventional sitting workstations, and to test its usability among office workers. Methods. The steps taken to design and prototype the active footrest were: selection of an exercise appropriate for goals of ergonomic interventions; idea development; selection of the best conceptual design; design with SOLIDWORKS version 2016; and fabrication of a prototype. Afterward, usability of the active footrest prototype was assessed among 20 office workers (10 females) using field data by the system usability scale. Results. Upon completion of the design steps, the active footrest prototype was prototyped by taking into account design criteria (e.g., functionality, inclusive design, easy application and reduction of additional body movement), anthropometric data and mechanical properties. The participants rated the usability of the active workstation as 89 ± 8.21 (out of 100), indicating good usability results. Conclusion. In this study, an active footrest was designed and prototyped to perform knee extension exercise with the capability of being implemented in conventional sitting workstations.

Type 1 diabetes (T1D) is an autoimmune disease resulting from the demolition of β-cells that are responsible for producing insulin in the pancreas. Treatment with insulin (lifelong applying) and islet transplantation (in rare cases and severe diseases), are standards of care for T1D. Pancreas or islet transplantation have some limitations, such as lack of sufficient donors and longtime immune suppression for preventing allograft rejection. Recent studies demonstrate that autologous hematopoietic stem cells (HSC) can regenerate immune tolerance against auto-antigens. Taking advantage of this feature, autologous HSC transplantation (auto-HSCT) is likely the only treatment for T1D that is associated with lasting and complete remission. None of the other evaluated immunotherapies worldwide had the clinical efficacy of auto-HSCT. Therapy with auto-HSCT is insulin-independent rather than reducing insulin needs or delaying loss of insulin production. This review provided the latest findings in auto-HSCT for treatment of T1D., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background and Aims: COVID-19 pandemic has generated a rise in psychological distress, such as illness anxiety disorder, apart from its negative physical effects. This study intends to the evaluation of illness anxiety disorder rate following the prevalence of COVID-19 in Iran and its associated factors., Methods: In this study, 634 people were studied. The data collection method was performed via the virtual networks using a questionnaire, with the sampling method being convenient and nonprobable with the method of snowball. Evans illness anxiety disorder questionnaire was utilized in this investigation. The logistic regression model and the χ 2 were used to evaluate the data., Results: The prevalence of illness anxiety disorder was 12.1%. The chance to have an illness anxiety disorder in the people whose relatives had a history of COVID-19 was 5.32 times, and in those who had a relative with a history of COVID-19 had higher (odds ratio = 1.27). But, this connection in people who worked or studied in nonmedical fields, is several times more than those who are busy in the medical fields. In individuals of 30 years and older, the chance of patients in single people compared to married people was 5.20 times higher, but under the age of 30 years, the chance of illness anxiety disorder in single people was 0.91., Conclusion: COVID-19 pandemic, also to the physical effects, may have psychological implications for people. Therefore, reducing the individual and social activities in terms of this disease, along with measures related to physical problems, diagnosis, timely treatment and proper psychological consequences, including illness anxiety disorder can be very fruitful., Competing Interests: There is no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Purpose: Radiotherapy is one of the most important therapeutic options used to treat cancers. Radiation effects can be improved using nanoparticles and chemotherapeutic drugs as radiosensitizing agents. The aim of the present study was to evaluate the effects of folic acid-conjugated gold nanoparticles (GNP-F) in combination with doxorubicin (DOX) and x-Ray irradiation in colorectal cancer (CRC) cell line (HT-29). Methods: The cell viability assay (WST-1) was performed to study the cytotoxic effects of different concentrations of DOX and GNP-F after 24 and 48 hours treatments. Then, the effects of the GNP-F, X-Ray irradiation, and DOX drug in single and combined treatments were examined after 24 and 48 hours treatment with effective doses. Likewise, the caspase 3 gene expression ratio and the caspase 3 activity were assessed after 48 h treatment. Moreover, the malondialdehyde (MDA) level was determined in treated and untreated cells. Results: When GNP-F (at a concentration of 70 μM) was combined with X-ray irradiation (2 Gy) and DOX drug, induced more cytotoxic effects compared to the control group. The results of cell viability assay showed that GNP-F + X-Ray in combination with a low concentration of DOX (0.25 × IC50) enhanced the cytotoxic effects of cells compared to related single treatments. Caspase 3 gene expression ratio and caspase 3 activity increased in double and triple combination treatments in comparison with the single groups. Moreover, the MDA level increased in triple combination compared to the single treatments. Conclusion: Our findings confirmed the potential anti-cancer effects of the GNP-F and DOX in combination with X-Ray irradiation in CRC cells., Competing Interests: The authors declared no conflict of interest., (©2022 The Authors.)

Increasing evidence strongly support that the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the development of COVID-19-associated central nervous system (CNS) manifestations. The presence of SARS-CoV-2 viral protein in the brainstem, which includes cardiovascular control centers, has been documented previously. Given the changes in autonomic nervous system function evaluated by heart rate variability (HRV) metrics, which are observed even prior to clinical signs, the potential effect of SARS-CoV-2 on the autonomic nervous system (ANS) center is likely. The integral parts of the brain renin-angiotensin system, as ACE2 enzyme, are highly expressed in the brainstem, which may also be involved in baroreflex sensitivity, playing an important role in HRV. SARS-CoV-2 may bind to ACE2 in order to enter the host brainstem cell and change baroreflex sensitivity due to the altered ratio of the concentration of angiotensin II (Ag II) to angiotensin (1-7). In this article, we discussed the information on the possibility that the SARS-CoV-2 viral particle by disrupting the homeostasis of the brain renin-angiotensin system even without brainstem neuropathological changes, may affect the function of the ANS center in the brainstem. SARS-CoV-2 could influence ANS function before affecting the immune system. It is possible that the altered HRV parameters imply the potential neurotropic characteristics of SARS-CoV-2. Therefore, this potential feature should be taken into account in diagnostic and therapeutic approaches for COVID-19 patients., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Poor sperm quality in oligoasthenoteratospermia patients negatively affects assisted reproductive technology outcomes. Therefore, the development of sperm media is necessary to improve sperm parameters. This study investigated the effect of GM-CSF via PI3K/AKT pathway on sperm quality in OAT patients. Semen samples were collected from 20 OAT patients, and each sample was divided into two groups: Experiment and Control. In the experimental group, the samples were incubated with medium containing GM-CSF, and control samples were incubated without GM-CSF. Sperm parameters, mitochondrial membrane potential, acrosome reaction and DFI were studied; in addition, gene expression of PI3KR1, PI3KCA, GLUT1, GLUT3 and AKT1 was analysed, evaluation of PAKT/TAKT, and expression of GLUT 1, 3 was examined; subsequent fertilization rate and embryo quality were assessed. Our data showed that GM-CSF supplementation could significantly increase motility, mitochondrial activity, gene expression of PI3KCA, AKT1, the protein level of PAKT/TAKT and expression of GLUT 1, 3 while it decreases DNA fragmentation. The fertilization rate and embryo quality significantly improved in the treatment group. LY294002 had adverse effects on sperm motility and the PAKT/TAKT ratio. GM-CSF can improve in vitro sperm quality and could be a suitable supplement to sperm media for OAT patients., (© 2022 Wiley-VCH GmbH.)

Pharmaceutical development of biosimilars is primarily focused on meeting the regulatory requirements for analytical comparability of the product's critical quality attributes (CQAs), concerning safety and efficacy, to those of the originator drug of interest. To this end, the early adoption of a systematic science-based approach, as guided by quality-by-design (QbD) principles, is crucial due to the blind starting point where the same insights of an originator developer into the challenges of a given biopharmaceutical and its manufacturing process are lacking. In this study, we devised a pharmaceutical QbD-guided approach to undertake the biosimilar development of Pembrolizumab (Keytruda®), the ace of therapeutic monoclonal antibodies (mAbs) in terms of approved indications and market sales, and its manufacturing process development. Quality target product profile (QTPP) for Pembrolizumab biosimilar product was assembled using publicly available information on Keytruda®. Upon preliminary analyses of four different lots of Keytruda®, the product CQAs and their acceptable ranges of specification were determined via risk assessment based on the relevant pharmaceutical development quality guidelines, particularly those of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The development and clone selection of Chinese Hamster Ovary (CHO) DG44 cell line was performed using DHFR expression vectors and Methotrexate (MTX) selective pressure. The CHO clone stably expressing relatively higher mAb titer (∼1200 mg/l) in small-scale shake-flask cultures, with the highest similarity of the CQAs charge variants contents (CVCs), N-glycan profile, and biological potency to those of Keytruda® reference standard was selected as the lead clone and the produced Pembrolizumab candidate was named PSG-024. The upstream process (USP) and downstream process (DSP) developments for production were started with the process evaluation screening experiments for the identification of critical process parameters (CPPs) founded upon the prior knowledge on different process stages, input process parameters (iPPs), output process parameters (oPPs), and their impacts on product CQAs. Thereby, screening experiments of USP fed-batch cell culture in 5-liter bioreactor resulted in improvement of PSG-024 expression titer to 2060 ± 70 mg/l and selection of the iPPs feed amount (A), glucose setpoint (B), culture temperature (C), and agitation rate (D) for the optimization design of experiments (DoEs) mainly focused on the CQA acidic CVC and the oPPs mAb expression yield. The USP optimization DoEs using response surface methodology (RSM) yielded valid prediction models and optimal conditions of A = 35%, B = 4.5 g/l, C = 37 °C, and D = 160-220 rpm, which resulted in the final PSG-024 expression titer of 3170 ± 40 mg/l without an excessive rise in acidic CVC. The DSP screening experiments led to achieving the mAb recovery rates of 94% ± 3% and 71.5% ± 3.5% for affinity (capture) and cation-exchange (polishing) chromatography stages, respectively. The capture eluate buffer and viral inactivation conditions were optimized to prevent mAb eluate turbidity and protein aggregation. Moreover, the polishing stage optimization DoEs via one-factor-at-a-time method focused on wash and elution steps for control of the acidic CVC CQA and achieving >80% mAb recovery rate. By shifting to Step elution from the primary salt gradient method and considering an additional intermediate wash step, the maximum mAb recovery of 87% ± 1.5% was achievable while maintaining the CQA acidic CVC within the acceptable range. The consistency of final analytical comparability of PSG-024 demonstrated the effectiveness of the adopted pharmaceutical QbD approach for Pembrolizumab biosimilar development, paving the way for the technology transfer to the client to proceed further development., (Copyright © 2022. Published by Elsevier B.V.)

Diffuse axonal injury (DAI) is a common neuropathological manifestation of traumatic brain injury (TBI), presenting as traumatic alterations in the cerebral white matter (WM) microstructure and often leading to long-term neurocognitive impairment. These WM alterations can be assessed using diffusion tensor imaging (DTI). Cerebral microbleeds (CMBs) are a common finding on head imaging in TBI and are often considered a visible sign of DAI, although they represent diffuse vascular injury. It is poorly known how they associate with long-term white matter integrity. This study included 20 patients with TBI and CMBs, 34 patients with TBI without CMBs, and 11 controls with orthopedic injuries. DTI was used to assess microstructural WM alterations. CMBs were detected using susceptibility-weighted imaging (SWI) and graded according to their location in the WM and total lesion load was counted. Patients underwent SWI within 2 months after injury. DTI and clinical outcome assessment were performed at an average of eight months after injury. Outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The Glasgow Coma Scale (GCS) and length of post-traumatic amnesia (PTA) were used to assess clinical severity of the injury. We found that CMB grading and total lesion load were negatively associated with fractional anisotropy (FA) and positively associated with mean diffusivity (MD). Patients with TBI and CMBs had decreased FA and increased MD compared with patients with TBI without CMBs. CMBs were also associated with worse clinical outcome. When adjusting for the clinical severity of the injury, none of the mentioned associations were found. Thus, the difference in FA and MD is explained by patients with TBI and CMBs having more severe injuries. Our results suggest that CMBs are not associated with greater WM alterations when adjusting for the clinical severity of TBI. Thus, CMBs and WM alterations may not be strongly associated pathologies in TBI., Competing Interests: VN reports a grant from Roche Pharmaceuticals, outside the submitted work. DM reports grants from GlaxoSmithKline and personal fees from NeuroTraumaSciences, Pfizer, Calico, PressuraNeuro, Lantmannen, Integra Neurosciences, Gryphon, and Cortirio, outside the submitted work. JP has received a speaker's free from the Finnish Medical Association. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dahl, Tenovuo, Posti, Hirvonen, Katila, Frantzén, Maanpää, Takala, Löyttyniemi, Tallus, Newcombe, Menon, Hutchinson and Mohammadian.)

Objective: In this study, by using clinical and paraclinical characteristics, we have aimed to predict the severity of the disease in hospitalized COVID-19 children., Method: This cross-sectional study was conducted on medical records about epidemiologic data, underlying diseases, symptoms, and laboratory tests from March to October, 2020, on 238 hospitalized confirmed COVID-19 paediatric cases in several children's hospitals of Tehran, Ahwaz, Isfahan, and Bandar Abbas., Results: From 238 patients, 140 (59%) were male and most of them were in the age group of 1 to 5 years (34.6%). Among all hospitalized patients, 38% had an underlying disease and in total, 5% of cases were expired., Conclusion: Determining patient severity is essential for appropriate clinical decision making; our results showed that in hospitalized pediatric patients, by using several variables such as SGOT, CRP, ALC, LDH, WBC, O 2 sat, and ferritin, we can use clinical and paraclinical characteristics for predicting the severity of COVID-19., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Shahnaz Armin et al.)

Background: There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting., Methods: Adult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011-2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13-15 was classified as mild (mTBI); GCS 9-12 as moderate (moTBI) and GCS 3-8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed., Results: Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls., Conclusions: S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting., Competing Interests: Competing interests: DM reports grants from European Union, during the conduct of the study; grants, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Pfizer, personal fees from NeuroTrauma Sciences, personal fees from Calico, grants and personal fees from PressuraNeuro, grants and personal fees from Integra Neurosciences, grants and personal fees from Lantmannen, outside the submitted work; VFJN reports grants from Roche, outside the submitted work; HZ reports that he has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg (BBS), which is a part of the GU Ventures Incubator Program; KB served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg (BBS), which is a part of the GU Ventures Incubator Program., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

We investigated the topology of structural brain connectivity networks and its association with outcome after mild traumatic brain injury, a major cause of permanent disability. Eighty-five patients with mild traumatic brain injury underwent magnetic resonance imaging (MRI) twice, about three weeks and eight months after injury, and 30 age-matched orthopedic trauma control subjects were scanned. Outcome was assessed with Extended Glasgow Outcome Scale on average eight months after injury. We performed constrained spherical deconvolution-based probabilistic streamlines tractography on diffusion MRI data and parcellated cortical and subcortical gray matter into 84 regions based on T1-weighted data to reconstruct structural brain connectivity networks weighted by the number of streamlines. Graph theoretical methods were employed to measure network properties in both patients and controls, and correlations between these properties and outcome were calculated. We found no global differences in the network properties between patients with mild traumatic brain injury and orthopedic control subjects at either stage. We found significantly increased betweenness centrality of the right pars opercularis in the chronic stage compared with control subjects, however. Further, both global and local network properties correlated significantly with outcome. Higher normalized global efficiency, degree, and strength as well as lower small-worldness were associated with better outcome. Correlations between the outcome and the local network properties were the most prominent in the left putamen and the left postcentral gyrus. Our results indicate that both global and local network properties provide valuable information about the outcome already in the acute/subacute stage and, therefore, are promising biomarkers for prognostic purposes in mild traumatic brain injury.

Purpose: Apatinib has been utilized in colon cancer therapies but its efficiency and molecularmechanism are not fully understood. Chemotherapy in combination with non-toxic compoundscan be an effective treatment strategy for cancer. Consequently, this study was carried out toevaluate the effects of apatinib and piperine on colorectal cancer (CRC) cell line and theirpotential anti-cancerous mechanisms in vitro. Methods: The effects of apatinib and piperine on HCT-116 CRC cells were detected byassessing cell viability using MTT assay. The potential cytotoxic mechanisms of apatinib andpiperine were investigated by evaluating MDM-2 gene expression ratio using real-time PCRassay. Moreover, the glutathione peroxidase (GPX) activity and nitric oxide (NO) levels wereassessed by colorimetric assays. Results: The proliferation rate of CRC cells decreased by increasing the concentrations ofpiperine or apatinib. When HCT-116 cells were treated with different concentrations of apatinibin combination with piperine, the synergistic effects were observed (combination index < 1).In HCT-116 cells treated with apatinib and piperine at the concentrations of 0.5×IC50 and0.2×IC50, the MDM-2 gene expression was downregulated and NO levels increased comparedto the untreated control cells and related single treatments. In addition, GPX activity significantlydecreased in combination treatment at 0.5×IC50 concentration of both agents versus singletreatments. Conclusion: Apatinib in combination with piperine could significantly inhibit the growth ofCRC cells. These cytotoxic effects were induced by regulation of MDM-2 gene expression andinhibition of antioxidant marker., (©2022 The Authors.)

Introduction: In this study, the cytotoxic and anti-cancer effects of Irinotecan as a conventional chemotherapeutic agent compared to 17-(allyl amino)-17-demethoxygeldanamycin (17-AAG) as possible radiosensitizers in the HCT-116 cell line were investigated. Methods: HCT-116 cells were treated with various concentrations of irinotecan and 17-AAG and also irradiated with a 2-Gy of X-ray radiation. Then, the cell viability was examined by a water-soluble tetrazolium-1 assay after 24 hours. For single therapies and double and triple combination cases, IC 50 , 0.5×IC 50 and 0.25×IC 50 concentrations of each drug were selected respectively for a terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay and other tests. In treated and untreated cells, the caspase 3 and Bcl-2 gene expression ratios were evaluated by the real-time PCR method. Likewise, caspase 3 activity was detected with a colorimetric assay. Results: In all combined treatments, including 17-AAG- radiation, irinotecan - radiation, irinotecan -17-AAG, and irinotecan-17-AAG-radiation, decreased cellular viability and increased TUNEL positive cells were presented versus the control group ( P  < 0.05). There were increased TUNEL positive cells in the triple combination, in concentrations of 0.25×IC 50 of each drug, in comparison with single and double agent treatments. Moreover, in triple combination, the caspase 3 mRNA level and caspase 3 activity increased versus related single treatments. Likewise, in the irinotecan-17-AAG-radiation combined treatment and the 17-AAG-radiation double treatment, the Bcl-2 gene expression level decreased in comparison with single therapies. Conclusion: It can be indicated that the combination of chemo-radiotherapy versus single treatments has significant anti-cancer effects., (Copyright © 2022 J Lasers Med Sci.)

Cognitive demand and mental workload assessment are essential for the optimal interaction of human-machine systems. The aim of this study was to investigate the cognitive demands and mental workload as well as the relationship between them among the mining control room operators. This cross-sectional study was performed on 63 control room operators of a large mining plant located in Iran. Cognitive demands and mental workload were assessed using cognitive task analysis (CTA) and NASA Task Load Index (NASA-TLX), respectively and the analysis was performed using SPSS version 21. Independent samples T-test, Mann-Whitney U test and multivariate linear regression were used for data analysis. Twelve cognitive demands were extracted after observing the tasks and conducting semi-structured interviews with the control room staff. The mean scores of total cognitive demands and MWL were 6.60 and 72.89, respectively, and these two indicators showed a positive and significant correlation (r = 0.286; P = 0.023). The participants' demographic characteristics such as age, education, and work experience did not affect mental workload, but the two cognitive demands (memory and defect detection) affected MWL. High cognitive demands and mental workload indicate poor interaction between humans and machines. Due to the effect of memory load and defect detection on mental workload, it is recommended to assign cognitive tasks based on memory and defect detection to the machine to reduce the mental workload and improve human-machine interaction., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Vertical stiffness has been highlighted as a potential determinant of performance and may be estimated across a range of different performance tasks. The aim of the current study was to investigate the relationship between vertical stiffness determined during 9 different hopping tests and performance of vertical jumps. Twenty healthy, active males performed vertical hopping tests with three different strategies (self-selected, maximal, and controlled) and three different limb configurations (bilateral, unilateral preferred, and unilateral non-preferred), resulting in nine different variations, during which vertical stiffness was determined. In addition, participants performed squat jump (SQJ) and countermovement jump (CMJ) during which jump height, CMJ stiffness, and eccentric utilization ratio (EUR) were determined. Vertical stiffness in bilateral and unilateral preferred tasks performed with a self-selected and maximal, but not controlled, strategy was associated with stiffness in the CMJ ( r  = 0.61-0.64; p  < 0.05). However, stiffness obtained during unilateral preferred and non-preferred hopping with self-selected strategy was negatively associated with performance in SQJ and CMJ tasks ( r  = -0.50 to -0.57; p  < 0.05). These findings suggest that high levels of vertical stiffness may be disadvantageous to static vertical jumping performance. In addition, unilateral hopping with a self-selected strategy may be the most appropriate task variation if seeking to determine relationships with vertical jumping performance. Highlights Stiffness obtained during unilateral hopping with a preferred strategy was negatively associated with vertical jumping performancesStiffness obtained during hopping with preferred and maximal strategies was associated with stiffness obtained during a countermovement jumpIn this population, hopping stiffness may therefore be reflective of an individual's countermovement jump strategyHigh levels of stiffness may be disadvantageous to static-start vertical jumping.

Acute myeloblastic leukemia (AML) is one of the most common types of blood malignancies that results in an AML-associated high mortality rate each year. Several causes have been reported as prognostic factors for AML in children and adults, the most important of which are cytogenetic abnormalities and environmental risk factors. Following the discovery of numerous drugs for AML treatment, leukemic cells sought a way to escape from the cytotoxic effects of chemotherapy drugs, leading to treatment failure. Nowadays, comprehensive studies have looked at the role of extracellular vesicles (EVs) secreted by AML blasts and how the microenvironment of the tumor changes in favor of cancer progression and survival to discover the mechanisms of treatment failure to choose the well-advised treatment. Reports show that malignant cells secrete EVs that transmit messages to adjacent cells and the tumor's microenvironment. By secreting EVs, containing immune-inhibiting cytokines, AML cells inactivate the immune system against malignant cells, thus ensuring their survival. Also, increased secretion of EVs in various malignancies indicates an unfavorable prognostic factor and the possibility of drug resistance. In this study, we briefly reviewed the challenges of treating AML with a glance at the EVs' role in this process. It is hoped that with a deeper understanding of EVs, new therapies will be developed to eliminate the relapse of leukemic cells., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Repeated allogeneic blood transfusions in thalassemia major patients stimulate the patient's immune system to generate antibodies against foreign erythrocyte antigens. This study was carried out to systematically review the findings of available studies about the prevalence of alloantibodies and autoantibodies, as well as the type of causative antigens among transfusion-dependent thalassemia patients in Iran., Methods: Electronic search was conducted on Medline, PubMed, Cochrane, EMBASE, ScienceDirect, and Persians databases. All relevant articles published from January 1990 to July 2018 were included. Abstracts of conference booklets which that been published in the last 5 years were also included in the meta-analysis. The search language was restricted to English and Persian. The quality of studies was evaluated according to a checklist developed by authors, and Cochrane Risk of Bias Assessment Tool was used to evaluate the risk of bias., Results: Twenty-three relevant articles met all the inclusion criteria. The prevalence of alloimmunization was 13%. Our study showed that anti-D (25%) and anti-K (25%) were most prevalent among Iranian β-thalassemia patients. Data analysis shows the autoantibody prevalence to be 1% among 3787 patients. Meta-regression revealed that the prevalence of alloantibodies increases with each year as the average age of the study population increases., Conclusion: The prevalence of red blood cell (RBC) alloantibodies in transfused Iranian β-thalassemia patients was high. Appropriate preventive strategies such as RBC phenotyping for patients before beginning transfusion and using extended RBC donor-recipient matching, specifically for Rh and Kell system, could be implemented to avoid complications in thalassemia patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Asian Journal of Transfusion Science.)

Background: The population-based survival rate is affected by the quality and effectiveness of health care systems. Overall, the survival of prostate cancer (PC) patients has improved over the past two decades worldwide. This study aimed to determine the overall survival rate and correlate it with the prognostic factors in patients with PC diagnosed in Kurdistan province., Methods: In a retrospective cohort study, 410 PC patients registered in Kurdistan province population-based cancer registry from March 2011 to 2018 were recruited. Kaplan-Meier method and log-rank test were used to analyze the overall survival rates of PC patients. A Multivariate Cox regression model was used to determine adjusted hazard ratios for different variables., Results: Of 410 patients with PC, 263 (64.1%) died within seven years due to the disease. The 1, 3, and 5 years survival rates were 93, 64.1, and 40.7%, respectively. According to the results of multiple Cox regression, the following factors were significantly related to PC survival: age at diagnosis (≥81-years old) (HR=2.23, 95% CI: 1.23-4.42) and 71-80 years old was (HR=1.26, 95% CI: 1.12-2.31), occupation (employee) (HR=0.42, 95% CI: 0.20-0.87), educational level: academic (HR=0.78, 95% CI: 0.64-0.91), AJCC stage of disease (HR=2.18, 95% CI: 1.9-3.68), Gleason score ≥ 9 (HR=7.12, 95% CI: 5.35-10.28), and Gleason score= 8 (HR=4.16, 95% CI: 2.50-6.93). There was less mortality rate among the patients who had received active care, radical prostatectomy, radiotherapy, combined treatment, and orchiectomy had a lower mortality rate than those who received no treatment (P<0.05)., Conclusions: This study demonstrated that factors such as age at diagnosis, level of education, occupation, AJCC stage of disease, Gleason score, and type of treatments were influential factors in the survival of PC patients in Kurdistan province and needed more attention., (© 2021. The Author(s).)

The field of robot-assisted physical rehabilitation and robotics technology for providing support to the elderly population is rapidly evolving. Lower limb robot aided rehabilitation and assistive technology have been a focus for the engineering community during the last three decades as several robotic lower limb exoskeletons have been proposed in the literature as well as some being commercially available. Numerous manufacturing techniques and materials have been developed for lower limb exoskeletons during the last two decades, resulting in the design of a variety of robot exoskeletons for gait assistance for elderly and disabled people. One of the most important aspects of developing exoskeletons is the selection of the most appropriate proper material. The material selection strongly influences the overall weight and performance of the exoskeleton robot. The most suitable fabrication method for material is also an important parameter for the development of lower limb robot exoskeletons. In addition to the materials and manufacturing methods, the actuation method plays a vital role in the development of these robot exoskeletons. Even though various materials, manufacturing methods and actuators are reported in the literature for these lower limb robot exoskeletons, there are still avenues of improvement in these three domains. In this review, we have examined various lower limb robotic exoskeletons, concentrating on the three main aspects of material, manufacturing, and actuation. We have focused on the advantages and drawbacks of various materials and manufacturing practices as well as actuation methods. A discussion on future directions of research is provided for the engineering community covering the material, manufacturing and actuation methods.

Background: Breastfeeding self-efficacy is an important motivational factor in the continuity of lactation in mothers with preterm infants., Objective: The study aimed to determine the effect of continuous supportive telephone counselling on improving breastfeeding self-efficacy in mothers with late preterm infants., Material and Methods: This randomized, controlled study was carried out with 65 eligible mothers (control n = 32, intervention n = 33) recruited in Ahvaz, Iran, in 2020. The eligible women were allocated into two groups- intervention and control-according to the block design. Data were measured monthly up to four months after discharge using the Dennis Breastfeeding Self-Efficacy Questionnaire. The control group received only routine care. Continuous supportive telephone counselling was provided for the intervention group members daily for 14 days after neonatal discharge. Data were analyzed using chi-square, repeated measures analysis of variance, independent t-test, and paired t-test at the significant level of 0.05. Statistical analysis was performed using the SPSS 16.0 software (SPSS Inc., Chicago, IL, USA)., Results: The overall score in breastfeeding self-efficacy showed a statistically significant difference between the two study groups during the four months after discharge compared to the pre-intervention stage (P = 0.001). In the intervention group, the mean score of breastfeeding self-efficacy increased from 33.18 to 53.48, and in the control group it decreased from 31.17 to 28.56., Conclusion: The results showed that continuous supportive telephone counselling can improve breastfeeding self-efficacy in mothers with preterm infants. The approach seems to be an acceptable basis for designing intervention programs in this field., (© 2021 Mohammadian Marzieh et al. published by Sciendo.)

Background: The repetitive and prolonged exertion of grip and pinch strength are current among carpet weaver tasks. The three objectives of this study were (1) to investigate the relationship between symptoms of musculoskeletal disorders and grip and pinch strength of carpet weavers in carpet weaving workshops in Kerman province, (2) to compare the grip and pinch strength of carpet weavers with normal values, and (3) to identify the relationship between hand postures of carpet weavers during work and force exertion., Methods: In this cross-sectional study, grip strength and key, tip and palmar pinch strengths of 101 female carpet weavers aged 20 to 71 years were measured in Kerman province, in 2018. Nordic Musculoskeletal Questionnaire (Extended version) was also used to evaluate musculoskeletal disorders., Results: Bivariate and multivariate linear regression analyses showed that participants who suffered from musculoskeletal disorders had lower grip and pinch strength than others and this decrease was statistically significant in upper back, wrists/hands, and knees. Moreover, there was a significant difference between grip and three types of pinch strength of carpet weavers and normal values. Furthermore, for both hands, the grip strength in the position recommended by American Society of Hand Therapists was significantly greater than that in the normal position carpet weavers usually adopt., Conclusion: Based on the results, the high prevalence of musculoskeletal disorders has led to a significant decrease in the grip and pinch strength of carpet weavers. Therefore, it is necessary to undertake ergonomic interventions in designing the carpet weaving workstation., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Occupational and Environmental Medicine.)

GABA (gamma-aminobutyric acid) and melatonin are endogenous compounds that enhance plant responses to abiotic stresses. The response of Vicia faba to different stressors (salinity (NaCl), poly ethylene glycol (PEG), and sulfur dioxide (SO 2 )) was studied after priming with sole application of GABA and melatonin or their co-application (GABA + melatonin). Both melatonin and GABA and their co-application increased leaf area, number of flowers, shoot dry and fresh weight, and total biomass. Plants treated with GABA, melatonin, and GABA + melatonin developed larger stomata with wider aperture compared to the stomata of control plants. The functionality of the photosynthetic system was improved in primed plants. To investigate the photosynthetic functionality in details, the leaf samples of primed plants were exposed to different stressors, including SO 2 , PEG, and NaCl. The maximum quantum yield of photosystem II (PS II) was higher in the leaf samples of primed plants, while the non-photochemical quenching (NPQ) of primed plants was decreased when leaf samples were exposed to the stressors. Correlation analysis showed the association of initial PI abs with post-stress F V /F M and NPQ. Stressors attenuated the association of initial PI abs with both F V /F M and NPQ, while priming plants with GABA, melatonin, or GABA + melatonin minimized the effect of stressors by attenuating these correlations. In conclusion, priming plants with both GABA and melatonin improved growth and photosynthetic performance of Vicia faba and mitigated the effects of abiotic stressors on the photosynthetic performance.

In this study, a modified mesoporous adsorbent (MSU-S) impregnated by aluminum was used to remove the aromatic sulfur compounds from n-decane as the model fuel. Physical and chemical properties of as-synthesized adsorbent were investigated by XRD (X-Ray Diffraction), SEM (Scanning Electron Microscopy), FTIR (Fourier Transform Infrared spectroscopy) and BET (Brunauer-Emmett-Teller) method. Adsorptive desulfurization of model fuel was studied through batch and continues processes under mild temperature and normal atmospheric pressure. The equilibrium adsorption was modeled by Langmuir, Temkin, and Freundlich and the kinetics of adsorption was studied through first, second and intraparticle diffusion models. It was figured out that Temkin and the pseudo-second-order model were best fitting the adsorption equilibrium and describing the kinetics, respectively.

We aimed to investigate the possible anticancer effects of radiation in combination with 17-allylamino-17-demethoxy geldanamycin (17-AAG) and silver graphene quantum dot (SQD) in breast cancer (BC) cells. MCF-7 BC cells treated with, or without, different concentrations of 17-AAG and synthesized SQD and cellular viability detected. The growth inhibitory effects of low concentrations of 17-AAG with minimally toxic concentration of SQD in combination with 2 Gy of X-ray radiation were examined. The apoptosis induction assessed by acridine orange/ethedium bromide staining. Likewise, the levels of lactate, hydrogen peroxide (H 2 O 2 ), nitric oxide (NO) were evaluated. The relative gene expression levels of Bax and Bcl-2 were detected by real-time polymerase chain reaction and the Bax/Bcl-2 expression ratio was determined. Moreover, the protein expression of epidermal growth factor receptor (EGFR) was assessed by western blot analysis. Treatment with low concentrations of 17-AAG and SQD at a minimally toxic concentration promoted inhibition of BC cell growth and induced apoptosis. In addition, significant reduction in cell viability was seen in triple combination versus all double and single treatments. Indeed 17-AAG and SQD in combined with radiation significantly increased the H 2 O 2 and NO versus single and double treated cases. In addition, triple combination treatment showed decreased lactate level in compared tomonotherapies. EGFR protein expression levels were found to decreased in all double and triple combined cases versus single treatments. Additionally, in double and triple treatments, Bax/Bcl2 ratio were higher in compared to single treatments. Treatment with low concentrations of 17-AAG and SQD at a minimally toxic concentration tends to induce anticancer effects and increase the radiation effects when applied with 2 Gy of radiation versus radiation monotherapy., (© 2020 Wiley Periodicals LLC.)

Mild traumatic brain injury (mTBI) can have long-lasting consequences. We investigated white matter (WM) alterations at 6-12 months following mTBI using diffusion tensor imaging (DTI) and assessed if the alterations associate with outcome. Eighty-five patients with mTBI underwent diffusion-weighted magnetic resonance imaging (MRI) on average 8 months post-injury and patients' outcome was assessed at the time of imaging using the Glasgow Outcome Scale-Extended (GOS-E). Additionally, 30 age-matched patients with extracranial orthopedic injuries were used as control subjects. Voxel-wise analysis of the data was performed using a tract-based spatial statistics (TBSS) approach and differences in microstructural metrics between groups were investigated. Further, the susceptibility of the abnormalities to specific fiber orientations was investigated by analyzing the first eigenvector of the diffusion tensor in the voxels with significant differences. We found significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) in patients with mTBI compared with control subjects, whereas no significant differences were observed in axial diffusivity (AD) between the groups. The differences were present bilaterally in several WM regions and correlated with outcome. Moreover, multiple clusters were found in the principal fiber orientations of the significant voxels in anisotropy, and similar orientation patterns were found for the diffusivity metrics. These directional clusters correlated with patients' functional outcome. Our study showed that mTBI is associated with WM changes at the chronic stage and these alterations occur in several WM regions. In addition, several significant clusters of WM alterations in specific fiber orientations were found and these clusters were associated with outcome.

Background: Blood biomarkers may enhance outcome prediction performance of head computed tomography scores in traumatic brain injury (TBI). Objective: To investigate whether admission levels of eight different protein biomarkers can improve the outcome prediction performance of the Helsinki computed tomography score (HCTS) without clinical covariates in TBI. Materials and methods: Eighty-two patients with computed tomography positive TBIs were included in this study. Plasma levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein, heart fatty acid-binding protein, interleukin 10 (IL-10), neurofilament light, S100 calcium-binding protein B, and total tau were measured within 24 h from admission. The patients were divided into favorable (Glasgow Outcome Scale-Extended 5-8, n = 49) and unfavorable (Glasgow Outcome Scale-Extended 1-4, n = 33) groups. The outcome was assessed 6-12 months after injury. An optimal predictive panel was investigated with the sensitivity set at 90-100%. Results: The HCTS alone yielded a sensitivity of 97.0% (95% CI: 90.9-100) and specificity of 22.4% (95% CI: 10.2-32.7) and partial area under the curve of the receiver operating characteristic of 2.5% (95% CI: 1.1-4.7), in discriminating patients with favorable and unfavorable outcomes. The threshold to detect a patient with unfavorable outcome was an HCTS > 1. The three best individually performing biomarkers in outcome prediction were Aβ40, Aβ42, and neurofilament light. The optimal panel included IL-10, Aβ40, and the HCTS reaching a partial area under the curve of the receiver operating characteristic of 3.4% (95% CI: 1.7-6.2) with a sensitivity of 90.9% (95% CI: 81.8-100) and specificity of 59.2% (95% CI: 40.8-69.4). Conclusion: Admission plasma levels of IL-10 and Aβ40 significantly improve the prognostication ability of the HCTS after TBI., (Copyright © 2020 Posti, Takala, Raj, Luoto, Azurmendi, Lagerstedt, Mohammadian, Hossain, Gill, Frantzén, van Gils, Hutchinson, Katila, Koivikko, Maanpää, Menon, Newcombe, Tallus, Blennow, Tenovuo, Zetterberg and Sanchez.)

Background: The immune response is influenced by the administration of omega-3 polyunsaturated fatty acids (PUFA). Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) are affected by PUFA. The combination of evening primrose/hemp seed oil (EPO/HSO) has essential fatty acids (EFAs) for human optimal health due to the favorable ratio of omega-6/omega-3 and antioxidantal properties. The study was conducted to evaluate the effects of EPO/HSO on improving the membrane fatty acids composition of spleen and blood cells and immunologic factors in compared to rapamycin (RAPA) in the EAE model., Methods and Materials: Chronic-EAE was induced by induction of MOG in C57BL/6J mice (female, age: 6-8 weeks, weight 18-21). Mice were assigned to 5 groups (6/group) to evaluate the therapeutic effects of EPO/HSO supplement in comparison with rapamycin: A group; EPO/HSO + RAPA, B group; RAPA, C group; EPO/HSO. Results were compared to two control groups (EAE and naive). The fatty acid profile of the spleen and blood cell membrane was evaluated. Real-time-polymerase chain reaction was used for the evaluate the genes expression levels of interleukin (IL) -4, IL-5, and IL-13 in lymphocytes. Also, IL-4 of serum was evaluated by enzyme-linked immunosorbent assay (ELISA)., Results: Our findings indicated that EPO/HSO therapy significantly increased the percentage of essential fatty acids in cell membrane of the spleen and blood. The relative expression of IL-4, IL-5, and IL-13 genes in lymphocytes and serum level of IL-4 was significantly increased in the HSO/EPO treated group versus other groups., Conclusion: These results point to potential therapeutic effects on the repair of the structure of cell membranes and suppression of inflammation by EPO/HSO in EAE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Change in the lower extremity alignments in the frontal plane and muscle activation patterns have been associated with lower extremity injuries. Therefore, to prevent injuries, many therapeutic protocols focus on find ways to correct dynamic knee valgus (DKV)., Methods: Thirty-one recreational male cyclists with DKV (26.4 ± 4.5 years, 176.63 ± 7.51 cm, 75.81 ± 9.29 kg, 23.20 ± 4.15 kg/m2) volunteered to participate in this study. Simultaneous recordings of kinematic and electromyography data were performed on ten consecutive pedal cycles which began during the last 30 seconds of each four test condition: with band at 0.5 kg workload, with band at 2 kg workload, without band at 0.5 kg workload, and without band at 2 kg workload. The paired t-test was used for statistical analysis (p < 0.05)., Results: The results indicated significant differences in VM (band = 0.029, no band = 0.031) and VL (band = 0.015, no band = 0.035) activation between workloads in each condition. Also there were significant differences in Gmed activation (0.5kg = 0.001, 2kg = 0.037), onset of Gmed (0.5kg = 0.048, 2kg = 0.012), offset of Gmed (0.5kg = 0.048, 2kg = 0.015), TFL activation (0.5kg = 0.001, 2kg = 0.041) and offset of TFL (0.5kg = 0.078, 2kg = 0.005) between the band and no band conditions. There was no different significant in VM/VL ratio between in each of four testing conditions (p > 0.05). The Gmed/TFL ratio was significantly greater in band condition than no band at both 0.5 (p = 0.045) and 2 kg (p = 0.001) workload. Knee abduction angle was affected by the band loop during the pedaling at two different workloads (0.5 kg: p = 0.047, 2 kg: p = 0.021) but mean (p = 0.027) and peak (p = 0.033) knee abduction angle significantly increased with increasing workload during the pedaling with band loop., Conclusions: pedaling with the band loop can be considered as an effective method to increase the Gmed, Gmed/TFL ratio and control of DKV but increasing the workload during pedaling must be done with caution to prevent DKV., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Parkinson's disease (PD) is a prevalent neurodegenerative illness. It has been believed that oxidative stress (OS) is an important factor in the advancement of PD. This investigation attempts to evaluate the relations between blood trace elements, ferritin, and transferrin concentrations as well as the levels of protein and gene expression of ceruloplasmin (CP), Nrf-2, and HO-1 in patients suffering PD., Methods: The serum concentrations of variables were assessed in 110 PD patients group and 110 normal subjects. Furthermore, we applied qRT-PCR as well as western blot (WB) analysis to measure the levels of gene and protein, respectively., Results: Considerable differences were detected in the serum concentrations of copper (Cu), iron (Fe), and zinc (Zn), when healthy and patient groups were compared. Nevertheless, the levels of Se, ferritin, and transferrin were not significantly different between the two groups. qRT-PCR and WB data analysis revealed significant differences of CP, Nrf-2, and HO-1at genes expression and protein levels when comparing the two PD patients and control groups., Conclusion: The results of the current work revealed that blood levels of Cu, Fe, and Zn were significantly higher in subjects who had PD. In addition, it was found that the levels of protein and gene expression CP, Nrf-2, and HO-1 were markedly higher in PD group than in non-PD subjects. Indeed, in this study, the results showed that the antioxidant content of the body can be linked to PD., (Copyright © 2020 Elsevier B.V. All rights reserved.)