L-carnitine fails to rescue chemotherapy injured ovaries by epigenetic changes of transcription factors.

Cyclophosphamide (CP), as an anti-cancer drug, is frequently used to treat various types of cancer. A decreased number of ovarian follicles impaired normal ovarian function, and subsequent premature ovarian failure (POF) presented as a side effect of cyclophosphamide usage. These events may eventually affect the fertility rate of individuals. The present study showed the effect of cyclophosphamide on ovarian reserves and the protective effect of L-carnitine (LC) as an antioxidant to prevent POF. To design the study, six to eight-week-old NMRI female mice were divided into three groups: control, cyclophosphamide (CP), and cyclophosphamide + L-carnitine (CP + LC). Mice received drugs intraperitoneally (IP) for 21 days. In the following 24 h after the last injection, both ovaries were used to evaluate the expression of Sohlh1 and Lhx8 genes by Real-time PCR. Furthermore, the alteration of Lhx8 promoter methylation was examined by Methylation-sensitive high-resolution melting analysis (MS-HRM). The present data showed the negative effect of CP on regulator genes of oogenesis including Sohlh1 and Lhx8. In addition, an examination of the epigenetic status of the Lhx8 gene showed a change in promoter methylation of this gene following cyclophosphamide injection. Although, L-carnitine is an effective antioxidant in relieving oxidative stress caused by cyclophosphamide and its damage, in the present study, however, the use of L-carnitine failed to protect the ovaries from changes caused by CP injection. So, using cyclophosphamide can alter the expression of folliculogenesis genes through its effects on epigenetic changes and may cause POF. The results of the present study showed that L-carnitine consumption can't protect the ovaries against the adverse effects of CP.

Insights into Targeted and Stimulus-Responsive Nanocarriers for Brain Cancer Treatment.

Brain cancers, especially glioblastoma multiforme, are associated with poor prognosis due to the limited efficacy of current therapies. Nanomedicine has emerged as a versatile technology to treat various diseases, including cancers, and has played an indispensable role in combatting the COVID-19 pandemic as evidenced by the role that lipid nanocarrier-based vaccines have played. The tunability of nanocarrier physicochemical properties -including size, shape, surface chemistry, and drug release kinetics- has resulted in the development of a wide range of nanocarriers for brain cancer treatment. These nanocarriers can improve the pharmacokinetics of drugs, increase blood-brain barrier transfer efficiency, and specifically target brain cancer cells. These unique features would potentially allow for more efficient treatment of brain cancer with fewer side effects and better therapeutic outcomes. This review provides an overview of brain cancers, current therapeutic options, and challenges to efficient brain cancer treatment. The latest advances in nanomedicine strategies are investigated with an emphasis on targeted and stimulus-responsive nanocarriers and their potential for clinical translation.

Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides.

Recent preclinical and clinical studies have focused on the active area of therapeutic peptides due to their high potency, selectivity, and specificity in treating a broad range of diseases. However, therapeutic peptides suffer from multiple disadvantages, such as limited oral bioavailability, short half-life, rapid clearance from the body, and susceptibility to physiological conditions (e.g., acidic pH and enzymolysis). Therefore, high peptide dosages and dose frequencies are required for effective patient treatment. Recent innovations in pharmaceutical formulations have substantially improved therapeutic peptide administration by providing the following advantages: long-acting delivery, precise dose administration, retention of biological activity, and improvement of patient compliance. This review discusses therapeutic peptides and challenges in their delivery and explores recent peptide delivery formulations, including micro/nanoparticles (based on lipids, polymers, porous silicon, silica, and stimuli-responsive materials), (stimuli-responsive) hydrogels, particle/hydrogel composites, and (natural or synthetic) scaffolds. This review further covers the applications of these formulations for prolonged delivery and sustained release of therapeutic peptides and their impact on peptide bioactivity, loading efficiency, and (in vitro/in vivo) release parameters.

Smart biomaterials: From 3D printing to 4D bioprinting.

This century is blessed with enhanced medical facilities on the grounds of the development of smart biomaterials. The rise of the four-dimensional (4D) bioprinting technology is a shining example. Using inert biomaterials as the bioinks for the three-dimensional (3D) printing process, static objects that might not be able to mimic the dynamic nature of tissues would be fabricated; by contrast, 4D bioprinting can be used for the fabrication of stimuli-responsive cell-laden structures that can evolve with time and enable engineered tissues to undergo morphological changes in a pre-planned way. For all the aptitude of 4D bioprinting technology in tissue engineering, it is imperative to select suitable stimuli-responsive biomaterials with cell-supporting functionalities and responsiveness; as a result, in this article, recent advances and challenges in smart biomaterials for 4D bioprinting are briefly discussed. An overview perspective concerning the latest developments in 4D-bioprinting is also provided.

Safety climate assessment: a survey in an electric power distribution company.

Introduction. This study aimed to investigate safety climate and its structural dimensions as well as establish a relationship between safety climate and demographic variables in a power distribution company. Method. This cross-sectional study included 200 workers. The safety climate questionnaire recommended by the UK Health and Safety Executive was applied containing 43 questions in 11 dimensions. Demographic information was also assessed. SPSS version 22.0 was applied to analyze the data. Results. In total, 179 workers participated in this survey. The response rate was high (89.5%). Safety climate had the highest correlation with the management commitment dimension (r = 0.754). The total score of safety climate in this company was 3.37 on a scale ranging from 1 to 5. Among safety climate factors, the highest score was for safety-related training (3.87) but work pressure had the lowest score (2.80). Among demographic variables, a significant relationship was observed between safety climate and age (r = 0.180). Conclusions. Management as an organizational power can exert great influence on the promotion of safety climate. Moreover, adopting efficient training programs and making a balance in workload for decreasing work pressure can improve safety climate.

Polymer-functionalization of carbon nanotube by in situ conventional and controlled radical polymerizations.

Functionalization of carbon nanotube (CNT) with polymers has drawn much attention due to its wide range of applications. Polymer-functionalized CNT could exhibit variety of properties, such as responsivity to environmental stimuli, ability of complexation with metal ions, increased dispersibility in different solvents, higher compatibility with polymer matrix, etc. Chemical and physical methods have been developed for the preparation of polymer-functionalized CNT. Polymer chains are chemically bonded to the CNT edge or surface in the chemical methods, which results in highly stable CNT/polymer composites. "Grafting to", "grafting from", and "grafting through" methods are the most common chemical methods for polymer-functionalization of CNT. In "grafting to" method, pre-fabricated polymer chains are coupled with the either functionalized or non-functionalized CNT. In "grafting from" and "grafting through" methods, CNT is functionalized by polymers simultaneously synthesized by in situ polymerization methods. Conventional free radical polymerization (FRP) and also controlled radical polymerization (CRP) are the most promising methods for in situ tethering of polymer brushes onto the surface of CNT due to their control over the grafting density, thickness, and functionality of the polymer brushes. The main focus of this review is on the synthesis of polymer-functionalized CNT via both the "grafting from" and "grafting through" methods on the basis of FRP and CRP routs, which is commonly known as in situ polymerizations. Finally, the most important challenges and applications of the in situ polymer grafting methods are discussed, which could be interesting for the future works.

Functional Prediction of Long Noncoding RNAs in Cutaneous Melanoma Using a Systems Biology Approach.

Cutaneous melanoma is the most aggressive type of skin cancer which its incidence has significantly increased in recent years worldwide. Thus, more investigations are required to identify the underlying mechanisms of melanoma malignant transformation and metastasis. In this context, long noncoding RNAs (lncRNAs) are a new type of noncoding transcripts that their dysregulations are associated with almost all cancers including melanoma. However, the precise functional roles of most of the significantly altered lncRNAs in melanoma have not yet been fully inspected. In this study, a comprehensive list of lncRNAs was interrogated across cutaneous melanoma samples to identify the significantly altered/dysregulated lncRNAs. To this end, lncRNAs were filtered in several steps and the selected lncRNAs projected to a bioinformatic and systems biology analysis using several publicly available databases and tools such as GEPIA and cBioPortal. According to our results, 30 lncRNAs were notably altered/dysregulated in cutaneous melanoma most of which were co-expressed with each other. Also, co-expression/alteration and differential expression analyses led to the selection of 12 out of these 30 lncRNAs as cutaneous melanoma key lncRNAs. Furthermore, functional demonstrated that these 12 lncRNAs might be involved in melanoma-relevant biological processes and pathways. In addition, the end result of our analyses demonstrated that these lncRNAs are associated with the clinicopathological features of melanoma patients. These 12 lncRNAs need to be further investigated in future studies to characterize their exact roles in melanoma development and to identify their potential for being used as drug targets and/or biomarkers for cutaneous melanoma.

Global precedence changes by environment: A systematic review and meta-analysis on effect of perceptual field variables on global-local visual processing.

Perceptual organization and, in particular, visual processing have been debated for many years. The global precedence effect in local-global visual processing, as introduced by David Navon, refers to the condition that global aspects of a scene are processed more rapidly than are local details. This perceptual dynamic is influenced by many factors that can be divided into two major categories: subjective or internal factors (e.g., age, disorder, culture) and the external factors called perceptual field variables (PFVs; e.g., stimulus size, eccentricity, sparsity). The aim of the current study was to identify the latter factors using a meta-analysis followed by a systematic literature review. In accordance of the standard framework suggested by PRISMA, 28 PFVs were observed through a literature search on articles published from 1982 to 2019, among which 10 factors have been qualified to be included in a meta-analysis. Subsequently, the random effects model proposed by Hedges and Olkin was used to estimate pooled effect sizes of PFVs. These effect sizes were used to compare and sort the PFVs on the basis of their intensity. According to Cohen's index, our analyses show that relevance, sparsity, and solidness type are categorized as small effects; visual field, level repetition, spatial frequency, and shape type are categorized as medium effects; and congruency, eccentricity, and size as large effect PFVs on global precedence.

Functionalization of carbon nanotubes by combination of controlled radical polymerization and "grafting to" method.

This paper reviews the recent advances in non-covalent and covalent tethering of small molecules and polymer chains onto carbon nanotube (CNT) and its derivatives. The functionalized CNT has recently attracted great attention because of an increasing number of its potential applications. In non-covalent functionalization of CNT, the sp2-hybridized network plays a crucial role. The non-covalent grafting of small molecules and polymers can mainly be carried out through hydrogen bonding and π-stacking interactions. In covalent functionalization of CNT, condensation, cycloaddition, and addition reactions play a key role. Polymer modification has been reported by using three main methods of "grafting from", "grafting through", and also "grafting to". The "grafting from" and "grafting through" rely on propagation of polymer chains in the presence of CNT modified with initiator and double bond moieties, respectively. In "grafting to" method, which is the main aim of this review, the pre-fabricated polymer chains are mainly grafted onto the surface using coupling reactions. The coupling reactions are used for grafting pre-fabricated polymer chains and also small molecules onto CNT. Recent studies on grafting polymer chains onto CNT via "grafting to" method have focused on the pre-fabricated polymer chains by conventional and controlled radical polymerization (CRP) methods. CRP includes reversible activation, atom transfer, degenerative (exchange) chain transfer, and reversible chain transfer mechanisms, and could result in polymer-grafted CNT with narrow polydispersity index of the grafted polymer chains. Based on the mentioned mechanisms, nitroxide-mediated polymerization, atom transfer radical polymerization, and reversible addition-fragmentation chain transfer are known as the three commonly used CRP methods. Such polymer-modified CNT has lots of applications in batteries, biomedical fields, sensors, filtration, solar cells, etc.

Synthesis of coumarin-containing multi-responsive CNC-grafted and free copolymers with application in nitrate ion removal from aqueous solutions.

Cellulose nanocrystals (CNC)-grafted and free copolymers were synthesized in three different ratios of DMAEMA and coumarin monomers (30:5, 40:7, and 50:10) through reversible addition-fragmentation chain transfer polymerization. These multi-responsive polymers to carbon dioxide (CO2), temperature, and light triggers can be used in nitrate ions removal from aqueous solutions. These amphiphilic copolymers were self-assembled to vesicular structures in water. Adsorption of nitrate ions was carried out by protonation of the CO2-responsive block with inserting of CO2. Proton nuclear magnetic resonance and thermogravimetric analysis were used to confirm the synthesis process. Responsivity to temperature, CO2, and light in addition to the adsorption of nitrate ions from aqueous solutions was studied by UV-vis spectroscopy and dynamic light scattering. By increasing the PDMAEMA content, the adsorption capacity has also increased. The CNC-grafted copolymers showed lower adsorption in comparison with the free copolymers. The CNC-grafted copolymers can be regenerated by light and filtration processes.

Polymer grafting on graphene layers by controlled radical polymerization.

In situ controlled radical polymerization (CRP) is considered as an important approach to graft polymer brushes with controlled grafting density, functionality, and thickness on graphene layers. Polymers are tethered with chain end or through its backbone to the surface or edge of graphene layers with two in situ polymerization methods of "grafting from" and "grafting through" and also a method based on coupling reactions known as "grafting to". The "grafting from" method relies on the propagation of polymer chains from the surface- or edge-attached initiators. The "grafting through" method is based on incorporation of double bond-modified graphene layers into polymer chains through the propagation reaction. The "grafting to" technique involves attachment of pre-fabricated polymer chains to the graphene substrate. Here, physical and chemical attachment approaches are also considered in polymer-modification of graphene layers. Combination of CRP mechanisms of reversible activation, degenerative (exchange) chain transfer, atom transfer, and reversible chain transfer with various kinds of grafting reactions makes it possible to selectively functionalize graphene layers. The main aim of this review is assessment of the recent advances in the field of preparation of polymer-grafted graphene substrates with well-defined polymers of controlled molecular weight, thickness, and polydispersity index. Study of the opportunities and challenges for the future works in controlling of grafting density, site-selectivity in grafting, and various topologies of the brushes with potential applications in stimuli-responsive surfaces, polymer composites, Pickering emulsions, coating technologies, and sensors is also considered.

Assessment of the expression level of miRNA molecules using a semi-quantitative RT-PCR approach.

Type 2 diabetes is one of the most prevalent diseases, which increases resistance to insulin in target tissues. The measurement of miRNAs quantity is a molecular approach for diagnosis of diabetes. miRNAs are small non-coding RNA strings of 21-23 long nucleotides that act as inhibitors in proteins translation. Several methods including Northern blot, qRT-PCR and Microarray have been used for diagnosis of miRNA molecules. Real time PCR is an expensive and accurate quantitative method that is widely used in miRNA studies. The miR-21 is an important miRNA in diabetes. In this study, for the first time, a semi-quantitative protocol was developed to quantify different amounts of a synthetic miR-21. In addition to semi-quantitative method, the miR-21 quantity was determined by quantitative method in several patients with type 2 diabetes and healthy people. The results indicated that there was a direct relationship between the amount of synthetic miR-21 and the intensity of the PCR bands. We also showed that the expression of miR-21 in people with type 2 diabetes increased compared to healthy people. The results were observed by both quantitative and semi-quantitative methods. The real-time RT-PCR was more sensitive than semi-quantitative PCR in identification of miRNAs. However, semi-quantitative PCR method benefited from higher simplicity and lower costs for defining general patterns of miRNA expression.

Survival analysis and functional annotation of long non-coding RNAs in lung adenocarcinoma.

Long non-coding RNAs (lncRNAs) are a subclass of non-protein coding transcripts that are involved in several regulatory processes and are considered as potential biomarkers for almost all cancer types. This study aims to investigate the prognostic value of lncRNAs for lung adenocarcinoma (LUAD), the most prevalent subtype of lung cancer. To this end, the processed data of The Cancer Genome Atlas LUAD were retrieved from GEPIA and circlncRNAnet databases, matched with each other and integrated with the analysis results of a non-small cell lung cancer plasma RNA-Seq study. Then, the data were filtered in order to separate the differentially expressed lncRNAs that have a prognostic value for LUAD. Finally, the selected lncRNAs were functionally annotated using a bioinformatic and systems biology approach. Accordingly, we identified 19 lncRNAs as the novel LUAD prognostic lncRNAs. Also, based on our results, all 19 lncRNAs might be involved in lung cancer-related biological processes. Overall, we suggested several novel biomarkers and drug targets which could help early diagnosis, prognosis and treatment of LUAD patients.

Behavioral and cognitive markers of mild cognitive impairment: diagnostic value of saccadic eye movements and Simon task.

BACKGROUND: Mild Cognitive Impairment (MCI) has been considered as a prodromal stage of Alzheimer disease (AD). Subtle changes in specific aspects of executive function like inhibitory control have been found in MCI. AIMS: We examined attentional and inhibitory control with the aim to distinguish between amnestic MCI patients and healthy controls. METHOD: Using neuropsychological, behavioral, and oculomotor function experiments, we examined executive function in 59 normal control, 49, multiple domain amnestic MCI (a-MCI) subjects, and 21 early stage AD patients using eye tracking and Simon task as measures of attentional control, to determine which saccade and behavioral tasks were sensitive enough to identify a-MCI. Saccades were investigated in gap and overlap pro-saccade and anti-saccade tasks. RESULTS: Scores on the Simon task were inversely correlated with general cognitive status and can distinguish a-MCI from controls with excellent specificity (AUC = 0.65 for reaction time and 0.59 for false responses). More importantly, our results showed that saccadic gains were affected in a-MCI and were the most sensitive measures to distinguish a-MCI from normal participants AST gap task AUC = 0.7, PST gap task AUC = 0.63, AST overlap task (AUC = 0.73). Moreover, these parameters were strongly correlated with neuropsychological measures. Using tests in parallel model, improved sensitivity up to 0.97. CONCLUSION: The present results enable us to suggest eye tracking along with behavioral data as a possible sensitive tools to detect a-MCI in preclinical stage.

The variation of mitochondrial NADH dehydrogenase subunit 4 (mtND4) and molecular dynamics simulation of SNPs among Iranian women with breast cancer.

Breast cancer is the second cause of death among women all around the world. One out of every eight women is diagnosed with breast cancer in Iran. There are many reasons for cancer, one of which is the mutations in the mitochondrial genome observed in most breast cancer studies. However, the aim of this study is to evaluate the genetic region of NADH dehydrogenase subunit 4 in patients with breast cancer. First, the genomic DNA was extracted from a tissue. The NADH dehydrogenase subunit 4 coding region was amplified by PCR, and then the SSCP was sequenced. After that, the molecular dynamics were employed. The association between the mutations and the prognostic factors such as ER, PR, HER-2, and age were statistically examined. The sequence of the ND4 area was determined in 24 suspected patients, and 15 nucleotide changes were reported. The role of this variations was investigated by in-silico. The harmful mutations were predicted based on some servers. The molecular dynamics results showed that there is a significant relationship between the mutant protein and the changes in the structural conformation. Our results showed that the mutation in the ND4 area plays an important role in developing breast cancer. So, it can be concluded that the mitochondrial NADH dehydrogenase analysis may help to detect breast cancer in the early stages.

Radial neuropathy following arterial line removal: A rare complication from a routine ICU procedure.

Radial artery thrombosis is a rare complication of cannulation. There are no reported cases of acute thrombosis and severe acute neuropathy in the setting of cannula discontinuation. We report a case of acute radial nerve mono-neuropathy following thrombosis after radial arterial line removal. The thrombus was immediately evident on exam and diagnostic imaging after cannula discontinuation. The patient was consented and promptly taken to OR for immediate repair. Mild radial neuropathy persisted despite immediate repair. Immediate recognition of signs and symptoms is essential for diagnosis and management, especially in the high-risk population.

Antibacterial glass-ionomer cement restorative materials: A critical review on the current status of extended release formulations.

Glass-ionomer cements (GICs) have been widely used for over forty years, because of their desirable properties in dentistry. The most important advantages of the GICs are associated with their ability to release long-term antimicrobial agents. However, GICs used as restorative materials have still lots of challenges due to their secondary caries and low mechanical properties. Recent studies showed that the fluoride-releasing activity of conventional GICs is inadequate for effectual antibacterial conservation in many cases. Therefore, many efforts have been proposed to modify the antibacterial features of GICs in order to prevent the secondary caries. Particularly, for achieving this goal GICs were incorporated into various biomaterials possessing antibacterial activities. The scope of this review is to assess systematically the extant researches addressing the antibacterial modifications in GICs in order to provide with an authoritative, at the same time in-depth understanding of controlled antibacterial release in this class of biomaterials. It also gives a whole perspective on the future developments of GICs and challenges related to antibacterial GICs.

Dow's fire and explosion index: a case-study in the process unit of an oil extraction factory.

INTRODUCTION: The incidence of fires and explosions have led to severe damage in many industries, primarily in industries' financial losses. This study was conducted to estimate losses due to fire and explosion and the impact of control measures on the number of losses applying Dow's Fire and Explosion Index. METHODS: This is a case study conducted in one of the process units of an oil extraction factory. Dow's Fire and Explosion Index Hazard classification guide, 7th edition, issued by the American Institute of Chemical Engineers was applied. Data were obtained mainly through interviews and consultation with experts, as well as reported operating parameters and process documents. RESULTS: The Dow Index of the processing unit was estimated to be 243.68, and the most probable base damage was approximately $4.15 million in 2008. The actual damages were estimated to be $2,863,500, and the number of lost work days to be 64.56 days. The interruption losses were estimated to be $15,817,200 and the total losses to the system to be $18.67 million. These results demonstrated that losses resulting from production interruptions are greater than losses due to the destruction of equipment. A series of corrections was then proposed and risk analysis was performed again to examine the effects of reforms. The comparison shows that by applying reforms the FEI can change to 86.62 and the total loss can reduce to $9.03 million. CONCLUSION: This study shows that Dow's Index is a systematic tool to examine the impact of control measures. It also enhances resource management considering an optimal insurance contract. Considering the priority of reducing damage factors, several correction actions were suggested, such as modifying the drainage system, installation of hexane detectors, an automatic sprinkler system, fire detectors on the cable tray, and finally, using the water spray washing on the tanks.

Discordance Between Physician Assessment and Patient-Reported Depressive Symptoms in Parkinson Disease.

OBJECTIVE: To assess concordance between physician assessment and patient-reported symptoms when screening for depression in Parkinson disease (dPD). BACKGROUND: Depression in Parkinson disease is highly prevalent (∼40%) and has a significant impact on quality of life and disability, yet physician recognition and treatment remain inadequate. METHODS: One thousand seventy-six patients with PD completed the Brief Symptom Inventory-18 (BSI-18), a screening questionnaire for psychiatric symptoms, which was compared to item #3 (depression) on the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: The mean BSI-18 depression score was 51.4 (9.7). Of the 170 (16%) patients screening positive for dPD on the BSI-18, 104 (61%) were not recognized as depressed by neurologists on the UPDRS. Factors associated with lower neurologist recognition included male gender, better mental health quality of life, and lack of antidepressant use. CONCLUSION: More than 60% of patients screening positive for depression on self-report were not recognized by neurologists on the UPDRS. A patient-reported screening tool for depression may improve recognition and management of dPD.