Traumatic brain injury is one of the leading causes of mortality and morbidity in the world with no current pharmacological treatment. The role of BDNF in neural repair and regeneration is well ...established and has also been the focus of TBI research. Here, we review experimental animal models assessing BDNF expression following injury as well as clinical studies in humans including the role of BDNF polymorphism in TBI. There is a large heterogeneity in experimental setups and hence the results with different regional and temporal changes in BDNF expression. Several studies have also assessed different interventions to affect the BDNF expression following injury. Clinical studies highlight the importance of BDNF polymorphism in the outcome and indicate a protective role of BDNF polymorphism following injury. Considering the possibility of affecting the BDNF pathway with available substances, we discuss future studies using transgenic mice as well as iPSC in order to understand the underlying mechanism of BDNF polymorphism in TBI and develop a possible pharmacological treatment.
The present study reports on how peer modelling with collaborative ground rules may contribute to the pair dynamics of one intermediate‐level English L2 learner when interacting with peers of the ...same as well as higher proficiency levels. The study was one‐semester long (i.e., nine sessions) and our pair talk data were collected from an intact class where pair members were involved in performing narrative tasks. In this study, we focused on how one intermediate (i.e., core) learner as listener interacted in core‐intermediate and core‐advanced pairs in the opening talk of narrative tasks across sessions. Each session, adult Teaching English as a Foreign Language (TEFL) students narrated their short stories to three different interlocutors and also listened to three short stories of their classmates while recording their voices. On the fifth session, students viewed a staged peer modelling demonstration with built‐in collaborative ground rules. The peer modelling was intended to demonstrate to the learners how best to perform the task to their mutual benefit. We transcribed pair talk data from the focused pairs and analysed them for instances of changes in pair dynamics and quantity of collaborative features based on Storch's framework. The results indicated that both core‐intermediate and core‐advanced pairs demonstrated more collaborative pair dynamics after the peer modelling session; the core‐advanced pairs made greater improvement in terms of instances and number of collaborative features. Trends in our data support peer modelling as one effective pedagogical technique to raise learners’ awareness and to assist them in creating quality learning opportunities in their pair interaction. Our findings are discussed in terms of its implications for the integration of peer modelling in pair work tasks in language learning settings.
چکیده
در دهههای اخیر، تحقیقات به امر مشارکت بین زبانآموزان در طول فرآیند یادگیری زبان دوم به عنوان یک اصل اساسی در روش تدریس توجه فراوانی کرده است. ولی با وجود اهمیت فراوان مشارکت بینابینی در امر یادگیری، برخی تحقیقات انجام شده در این زمینه نشان دادهاست که صرف انجام فعالیت آموزشی به صورت گروهی بدون آگاهی در مورد چگونگی انجام موثر آن لزوما منجر به یادگیری مورد انتظار در زبانآموزان نمی گردد. با توجه به این مسئله ، هدف مطالعهی حاضر بررسی نقش آموزش اصول تعامل از طریق مدلسازی با استفاده از همتایان در ساختار مشارکت است. داده های این پژوهش در طول یک نیمسال تحصیلی از زبانآموزی با سطح زبانی متوسط درحین تعامل با افرادی با سطح زبانی مشابه و یا بالاتر جمع آوری شده است. مطابق برنامهی کلاس، این زبانآموز، همانند سایرین، سه مرتبه راوی داستانک خود و سه مرتبه شنونده روایتهای کوتاه داستانی همتایانش به صورت رودررو بود. در جلسه ی پنجم، اصول تعامل با هدف افزایش فرصت یادگیری از طریق مدلسازی با استفاده از همتایان در کلاس به نمایش گذاشته شد. داده های ضبط شدهی قبل و بعد از نمایش مدلسازی این زبانآموز بر اساس مدل گفتگوکاوی مورد تجزیه و تحلیل قرار گرفت. نتایج نشان می دهد که ساختار مشارکتی این زبانآموز با افرادی با سطوح زبانی مشابه و بالاتر تغییرات چشمگیری داشته است بطوریکه بعد از ارائه ی مدلسازی ساختار مشارکت وی شکل تعاملیتری به خود گرفت. یافته های این تحقیق، مدلسازی با استفاده از همتایان را به عنوان روشی مناسب جهت آموزش اصول ساختار تعامل معرفی می کند که میتواند فرصت یادگیری بهتر و مناسبتری را برای زبانآموزان فراهم کند.
Excellent thermal and mechanical properties and high chemical resistance with low shrinkage of epoxy resins open a wide window of various industrial applications, including coatings, paints, ...adhesive, etc. Despite their excellent properties, epoxy resins are brittle and have a low resistance to the initiation and growth of cracks. To overcome this drawback, different kinds of reinforcements, including liquid rubbers, core–shell rubber particles, dendritic polymers, block copolymers, thermoplastics, rigid particles, etc., have been used to improve the fracture toughness of epoxy resin systems. This paper briefly introduces each reinforcement separately and mainly presents an in-depth review of the progress of the last decade in the field of toughening of epoxy resins using core–shell rubber particles. This review paper also refers to the results of the research papers published on the effect these rubber particles on the mechanical properties of epoxy resins, as well as explains different toughening mechanisms of epoxy resins. Researchers first focused on the use of core–shell rubber particles containing different cores and shells. They then used core–shell rubber particles along with rigid fillers such as silica to offset the slight diminish in mechanical properties, as well as the glass transition temperature. In recent years, some research teams have used core–shell rubber particles and block copolymers simultaneously and have achieved fascinating results.
Graphical abstract
•Critically illness polyneuropathy/myopathy (CIN/CIM) was more prevalent in COVID-19 ICU patients with severe illness.•Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) ...levels were higher in the CIN/CIM group and GFAp correlated with motor nerve amplitudes.•COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care.
The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW).
An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients.
111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes.
CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness.
COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM.
Chitosan, de-acetylated form of chitin and the amino polysaccharide, is one of the most suitable biopolymer with vast possibilities of chemical modifications for novel properties and nano-medicine ...generations in biomedical fields. The primary amine groups in chitosan are responsible for its various properties such as cationic nature, controlled drug release, muco-adhesion, in situ gelation, antimicrobial and permeation enhancement.
Chitosan nanoparticles (NPs) are commonly used as drug carriers since they have good biocompatibility, biodegradability and loading capacity. These NPs also show low toxicity and can be readily modified by simple reactions. Chitosan NPs are widely used as drug delivery systems since they are able to load a wide range of natural and chemical agents including proteins, oligosaccharide, and anticancer drugs. In additions, chitosan NPs can be applied via various routes of administration as nasal, intravenous, oral and ocular.
NPs can potentially target specific tissues; hence, cell specific targeting of NPs seems to be a promising way to increase local drug concentration, prevent non-specific interactions and decrease the toxicity and side effects of systemic administration. Targeted delivery can be achieved by modifying NPs using peptides, antibodies, aptamer or small molecules. These strategies of targeting NPs not only cause the lower dosage of required drugs, but also lead them achieving to the receptors.
The present review aims to show the features of chitosan NPs which are rapidly developing field of nanotechnology and their potential applications in targeted drug delivery. This review presents a broad view of chitosan NPs, discussing their types such as antibody, magnetic and pH sensitive conjugated chitosan.
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•Chitosan is a widely used biopolymer with active amino groups.•Chitosan can act as compatible and effective biomaterials and shows antimicrobial activity.•Chitosan based targeted drug carriers can be considered as a promising way for cancer therapy.
In the present work, molecular docking methodology in combination with quantitative structure–activity relationship (QSAR) was employed to predict the inhibition activity of 87 structurally diverse ...pyrimidine-based derivatives as phosphodiestrae10A (PDE10A) inhibitors due to their potential in the treatment of schizophrenia. In this method, compounds in their preferred enzyme-docked conformations were utilized to derive interaction-based quantitative descriptors in order to explain reported PDE10A inhibitory activities. Multiple linear regression (MLR), artificial neural network (ANN), and least square support vector regression (LS-SVR) were exploited to developing the structure-based quantitative structure–activity relationship models. Among these models, LS-SVR model showed more satisfactory statistical parameters with regard to both internal (
R
train
= 0.951,
Q
2
= 0.804, RMSE
train
= 0.494) and external validation (
R
test
= 0.941, RMSE
test
= 0.549) test results. Information from the most relevant descriptors suggests that incorporating steric effect, electronegativity, and the number of substituted aromatic carbon correlate the activity with structural features of the studied compounds. Molecular docking analysis of the most potent inhibitor explored that hydrogen bond formation and hydrophobicity participated in the binding interaction of PDE10A complex active pocket which these findings are in line with those obtained from QSAR model. The reliability assessment of compounds predictions was checked by model applicability domain (AD) analysis.
Irradiation can induce multiple inhibitory and stimulatory effects on the immune system. In recent studies, it has been noted that administration of radiation with various doses and fractionation ...plans may influence on immune responses in microenvironment of tumor. But in radiobiology, the Biologically Effective Dose (BED) formula has been designed for calculating isoeffect doses in different regimens of daily clinical practice. In other words, BED has also been used to predict the effects of fractionation schedules on tumor cells.
In our study, three different regimens with BEDs of 40 gray (Gy) were analyzed in BALB/c mice. These included conventional fractionated radiotherapy (RT) (3Gyx10), high-dose hypofractionated RT (10Gyx2), and single ablative high-dose RT (15Gyx1).
As BED predicts, all three similarly decreased tumor volumes and increased survival times relative to controls, but after high dose exposure in ablative group, the expression of IFNγ was increased following high infiltration of CD8 cells into the tumor microenvironment. When anti-PDL-1 was combined with RT, single ablative high-dose radiation enhanced antitumor activity by increasing IFNγ in tumors and CD8+ tumor-infiltrating lymphocytes; as a result, this combining therapy had enhanced antitumor activity and lead to control tumor volume effectively and improve significantly survival rate and finally the recurrence of tumor was not observed.
Results show distinct radiation doses and fractionation schemes with same BED have different immunogenic response and these findings can provide data helping to design regimens of radiation combined with immune checkpoint blockers (ICBs).
A high proportion of patients with coronavirus disease 2019 (COVID-19) experience post-acute COVID-19, including neuropsychiatric symptoms. Objective signs of central nervous system (CNS) damage can ...be investigated using CNS biomarkers such as glial fibrillary acidic protein (GFAp), neurofilament light chain (NfL) and total tau (t-tau). We have examined whether CNS biomarkers can predict fatigue and cognitive impairment 3-6 months after discharge from the intensive care unit (ICU) in critically ill COVID-19 patients. Fifty-seven COVID-19 patients admitted to the ICU were included with analysis of CNS biomarkers in blood at the ICU and at follow up. Cognitive dysfunction and fatigue were assessed with the Montreal Cognitive Assessment (MoCA) and the Multidimensional Fatigue inventory (MFI-20). Elevated GFAp at follow-up 3-6 months after ICU discharge was associated to the development of mild cognitive dysfunction (p = 0.01), especially in women (p = 0.005). Patients who experienced different dimensions of fatigue at follow-up had significantly lower GFAp in both the ICU and at follow-up, specifically in general fatigue (p = 0.009), physical fatigue (p = 0.004), mental fatigue (p = 0.001), and reduced motivation (p = 0.001). Women showed a more pronounced decrease in GFAp compared to men, except for in mental fatigue where men showed a more pronounced GFAp decrease compared to women. NfL concentration at follow-up was lower in patients who experienced reduced motivation (p = 0.004). Our findings suggest that GFAp and NfL are associated with neuropsychiatric outcome after critical COVID-19.Trial registration The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).
Abstract
Study Objectives
The evolution of sleep bruxism manifestations and their co-occurrence with separation anxiety in early childhood remain unclear. Our threefold aim was to: (1) describe ...developmental sleep bruxism trajectories in early childhood, (2) investigate co-occurrences between trajectories of sleep bruxism and separation anxiety, and (3) determine whether distinct trajectories of separation anxiety increase the risk of presenting sleep bruxism during the first year of elementary school.
Methods
This study is part of the Québec Longitudinal Study of Child Development. Sleep bruxism scores were assessed from age 1.5 to 7 years with the Self-Administered Questionnaire for Mother (n = 1946). Separation anxiety scores were measured from age 1.5 to 6 years with the Interviewer-Completed Computerized Questionnaire (n = 2045).
Results
We identified four sleep bruxism trajectories from age 1.5 to 6 years: High-Increasing sleep bruxism at age 1.5 (14.1%), High-Increasing sleep bruxism at age 4 (18.3%), Low-Persistent sleep bruxism (12.1%), and Never-Persistent sleep bruxism (55.5%); and four separation anxiety trajectories from age 1.5 to 6 years: Low-Persistent separation anxiety (60.2%), High-Increasing separation anxiety (6.9%), High-Decreasing separation anxiety (10.8%), and Low-Increasing separation anxiety (22.1%). Sleep bruxism and separation anxiety trajectories were weakly associated (X2 = 37.84, p < 0.001). Compared with preschoolers belonging to the Low-Persistent separation anxiety trajectory, preschoolers in the High-Increasing separation anxiety trajectory had almost double the risk of presenting sleep bruxism at age 7 (95% CI = 1.25–3.22, p = 0.04).
Conclusion
When separation anxiety issues are detected in early childhood, it would be useful to target sleep bruxism during the first year of elementary school.
How Can a Punch Knock You Out? Hånell, Anders; Rostami, Elham
Frontiers in neurology,
10/2020, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
Several hypotheses have been put forth over time to explain how consciousness can be so rapidly lost, and then spontaneously regained, following mechanical head trauma. The knockout punch in boxing ...is a relatively homogenous form of traumatic brain injury and can thus be used to test the predictions of these hypotheses. While none of the hypotheses put forth can be considered fully verified, pore formation following stretching of the axonal cell membrane, mechanoporation, is a strong contender. We here argue that the theoretical foundation of mechanoporation can be strengthened by a comparison with the experimental method electroporation.
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