Search results for: traumatic brain injury.

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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Authors: Yi-Feng Kao, Huey-Jine Chai, Chin-I Chang, Yi-Chen Chen, June-Ru Chen

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Microglia is a macrophage that resides in brain, and overactive microglia may result in brain neuron damage or inflammation. In this study, the phospholipids was extracted from squid skin and manufactured into a liposome (SQ liposome) to mimic apoptotic body. We then evaluated anti-inflammatory effects of SQ liposome on mouse microglial cell line (BV-2) by lipopolysaccharide (LPS) induction. First, the major phospholipid constituents in the squid skin extract were including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine and 19.3% of other phospholipids by HPLC-UV analysis. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the squid skin extract were 11.8 and 28.7%, respectively. The microscopic images showed that microglia cells can engulf apoptotic cells or SQ-liposome. In cell based studies, there was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/mL. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significant suppressed (P < 0.05) by pretreated 0.03~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (P < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.

Keywords: apoptotic mimicry, neuroinflammation, microglia, squid processing by-products

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Authors: Alireza Pishgahi, Mohammad Rahbar, Javad Shokri, Shahla Dareshiri, Yaghoub Salekzamani, Fariba Eslamian

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Background and Objectives: Hypertrophic scars are one of the complications following a burn injury. Intralesional corticosteroid injection is an invasive method for treatment of this complication. We had design a single blinded randomized control trial to deliver dexamethasone by phonophoresis and evaluate its efficacy on hypertrophic burn scars characteristics. Material and Methods: 56 cases of hypertrophic burn scar due to burn injury allocated randomly to dexamethasone and control group. Individuals in case group received 10 sessions of dexamethasone 0.4% phonophoresis. Patients in control group had placebo phonophoresis (ultrasound with normal routine aquatic gel without any dexamethasone) with the same protocol. At the beginning of study and one week after last session, hypertrophic scar characteristics and pruritus were measured by ‘Vancouver Scar Scale’, and ‘5-D Pruritus Scale’ respectively in both groups. Results: Despite mild improvement in Vancouver Scar Scale score one week after intervention in dexamethasone phonophoresis group in comparison to control subjects, but this difference was not significant (p=0.08). Pruritus score perceived subjectively were significantly lower one week after intervention in dexamethasone groups in comparison to control subjects (p=0.00). Conclusion: Dexamethasone phonophoresis is a safe and effective treatment method for burn hypertrophic scar pruritus, but its efficacy for scar characteristics improvement needs to be evaluated by larger studies with long-term follow-up period.

Keywords: dexamethasone, hypertrophic scar, phonophoresis, pruritus

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Authors: Alexandra K. Diem, Giles Richardson, Roxana O. Carare, Neil W. Bressloff

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Alzheimer's disease (AD) is the most common form of dementia and although it has been researched for over 100 years, there is still no cure or preventive medication. Its onset and progression is closely related to the accumulation of the neuronal metabolite Aβ. This raises the question of how metabolites and waste products are eliminated from the brain as the brain does not have a traditional lymphatic system. In recent years the rapid uptake of Aβ into cerebral artery walls and its clearance along those arteries towards the lymph nodes in the neck has been suggested and confirmed in mice studies, which has led to the hypothesis that interstitial fluid (ISF), in the basement membranes in the walls of cerebral arteries, provides the pathways for the lymphatic drainage of Aβ. This mechanism, however, requires a net reverse flow of ISF inside the blood vessel wall compared to the blood flow and the driving forces for such a mechanism remain unknown. While possible driving mechanisms have been studied using mathematical models in the past, a mechanism for net reverse flow has not been discovered yet. Here, we aim to address the question of the driving force of this reverse lymphatic drainage of Aβ (also called perivascular drainage) by using multi-scale numerical and analytical modelling. The numerical simulation software COMSOL Multiphysics 4.4 is used to develop a fluid-structure interaction model of a cerebral artery, which models blood flow and displacements in the artery wall due to blood pressure changes. An analytical model of a layer of basement membrane inside the wall governs the flow of ISF and, therefore, solute drainage based on the pressure changes and wall displacements obtained from the cerebral artery model. The findings suggest that an active role in facilitating a reverse flow is played by the components of the basement membrane and that stiffening of the artery wall during age is a major risk factor for the impairment of brain lymphatics. Additionally, our model supports the hypothesis of a close association between cerebrovascular diseases and the failure of perivascular drainage.

Keywords: Alzheimer's disease, artery wall mechanics, cerebral blood flow, cerebral lymphatics

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Authors: Naim Izet Kajtazi

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Context: The third ventricle colloid cyst (CC) is a benign growth usually located in the third ventricle and can cause various neurological symptoms, including sudden death. Modern surgical interventions may still result in a wide range of complications and cerebral venous thrombosis (CVT) is among them. Process: A 38-year-old female with an existing diagnosis of diabetes mellitus (DM) and hypothyroidism and a six-month history of headaches, blurred vision, and vomiting presented to our clinic three days after the headaches became excessively severe. Neurological examination on admission revealed bilateral papilledema without any associated focal neurological deficits. Brain computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of a third ventricle colloid cyst and associated non-communicating hydrocephalus involving the lateral ventricles. As a result, the patient underwent emergency bilateral external ventricular drainage (EVD) insertion followed by a third ventricular CC excision under neuronavigation through a right frontal craniotomy. Twelve days post-operatively, the patient developed further headaches, followed by a generalized tonic-clonic seizure that led to no postictal neurological deficits. Nonetheless, computed tomography venography of the brain revealed extensive thrombosis of the superior sagittal sinus, inferior sagittal sinus, right sigmoid sinus, and right internal jugular vein. A newly diagnosed CVT was treated with intravenous heparin. The patient was discharged with warfarin, which was discontinued after 12 months. Ten years after her illness, she remained stable and free from any neurological deficits but still suffered from mild chronic headaches. Outcome: Ten years after her illness, she remained stable and free from any neurological deficits but still suffered from mild chronic headaches. Relevance: A preoperative venous study should be performed in all cases to gain a better understanding of the venous anatomy. We advocate meticulous microsurgical techniques to protect the venous system surrounding the foramen of Monro and reduce the amount of retraction during surgery.

Keywords: CVT, seizures, third ventricle colloid cyst, MRI of brain

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Authors: Sang Chul Lee, Gi-Young Park, Dong Rak Kwon

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Objective: The aim of this study was to investigate regenerative effects of ultrasound (US)-guided injection with human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and/or polydeoxyribonucleotide (PDRN) injection in a chronic traumatic full-thickness rotator cuff tendon tear (FTRCTT) in a rabbit model. Material and Methods: Rabbits (n = 32) were allocated into 4 groups. After a 5-mm sized FTRCTT just proximal to the insertion site on the subscapularis tendon was created by excision, the wound was immediately covered by silicone tube to prevent natural healing. After 6 weeks, 4 injections (0.2 mL normal saline, G1; 0.2 mL PDRN, G2; 0.2 mL UCB-MSCs, G3; and 0.2 mL UCB-MSCs with 0.2ml PDRN, G4) were injected into FTRCTT under US guidance. We evaluated gross morphologic changes on all rabbits after sacrifice. Masson’s trichrome, anti-type 1 collagen antibody, bromodeoxyuridine, proliferating cell nuclear antigen, vascular endothelial growth factor and platelet endothelial cell adhesion molecule stain were performed to evaluate histological changes. Motion analysis was also performed. Results: The gross morphologic mean tendon tear size in G3 and 4 was significantly smaller than that of G1 and 2 (p < .05). However, there were no significant differences in tendon tear size between G3 and 4. In G4, newly regenerated collagen type 1 fibers, proliferating cells activity, angiogenesis, walking distance, fast walking time, and mean walking speed were greater than in the other three groups on histological examination and motion analysis. Conclusion: Co-injection of UCB-MSCs and PDRN was more effective than UCB-MSCs injection alone in histological and motion analysis in a rabbit model of chronic traumatic FTRCTT. However, there was no significant difference in gross morphologic change of tendon tear between UCB-MSCs with/without PDRN injection. The results of this study regarding the combination of UCB-MSCs and PDRN are worth additional investigations.

Keywords: mesenchymal stem cell, umbilical cord, polydeoxyribonucleotides, shoulder, rotator cuff, ultrasonography, injections

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Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

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Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

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Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

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Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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Authors: Mohammad Tahir Yousafzai, Nighat Nisar, Rehana Khalil

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The aim of this study is to assess the practices of sharp injuries and factors leading to it among medical practitioners in slum areas of Karachi, Pakistan. A cross sectional study was conducted in slum areas of Landhi Town Karachi. All medical practitioners (317) running the private clinics in the areas were asked to participate in the study. Data was collected on self administered pre-tested structured questionnaires. The frequency with percentage and 95% confidence interval was calculated for at least one sharp injury (SI) in the last one year. The factors leading to sharp injuries were assessed using multiple logistic regressions. About 80% of private medical practitioners consented to participate. Among these 87% were males and 13% were female. The mean age was 38±11 years and mean work experience was 12±9 years. The frequency of at least one sharp injury in the last one year was 27%(95% CI: 22.2-32). Almost 47% of Sharp Injuries were caused by needle recapping, less work experience, less than 14 years of schooling, more than 20 patients per day, administering more than 30 injections per day, reuse of syringes and needle recapping after use were significantly associated with sharp injuries. Injection practices were found inadequate among private medical practitioners in slum areas of Karachi, and the frequency of Sharp Injuries was found high in these areas. There is a risk of occupational transmission of blood borne infections among medical practitioners warranting an urgent need for launching awareness and training on standard precautions for private medical practitioners in the slum areas of Karachi.

Keywords: injection practices, private practitioners, sharp injuries, blood borne infections

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Authors: Hossein Barri Ghazani

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Transfusion-related acute lung injury is the main reason of transfusion-related death, and it’s assigned to white blood cell reactive antibodies present in the blood product (anti-HLA class I and class II or anti granulocyte antibodies). TRALI may occur in the COVID-19 patients who are treated by convalescent plasma. The rate of TRALI’s reactions is the same in both males and females and can happen in all age groups. TRALI’s occurrence is higher for people who receive plasma from female donors because the parous female donors have multiple HLA antibodies in their plasma. Patients with chronic liver disease have an augmented risk of transfusion-related acute lung injuries from plasma containing blood products like FFP and PRP. The condition of TRALI suddenly starts with a non‐cardiogenic pulmonary Edema, often accompanied by marked systemic hypovolemic and hypotension. The conditions occur during or within a few hours of transfusion. Chest X-ray shows a nodular penetration or bats’ wing pattern of Edema which can be seen in acute respiratory distress syndrome as well. TRALI can occur with any type of blood products and can occur with as little as one unit. The blood donor center should be informed of the suspected TRALI reactions when the symptoms of TRALI are observed. After a review of the clinical data, the donors must be screened for granulocyte and HLA antibodies. The diagnosis and management of TRALI is not simple and is best done with a professional team and a specialty skilled nurse experienced with the upkeep of these patients.

Keywords: TRALI, transfusion-related death, anti-granulocyte antibodies, anti-HLA antibodies, COVID-19

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Authors: Sonia Boscenco, Zihan Wang, Euclides José de Mendoça Filho, João Paulo Hoppe, Irina Pokhvisneva, Geoffrey B.C. Hall, Michael J. Meaney, Patricia Pelufo Silveira

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Entropy can be described as a measure of the number of states of a system, and when used in the context of physiological time-based signals, it serves as a measure of complexity. In functional connectivity data, entropy can account for the moment-to-moment variability that is neglected in traditional functional magnetic resonance imaging (fMRI) analyses. While brain fMRI resting state entropy has been associated with some pathological conditions like schizophrenia, no investigations have explored the association between brain entropy measures and individual differences in child behavior in healthy children. We describe a novel exploratory approach to evaluate brain fMRI resting state data in two child cohorts, and MAVAN (N=54, 4.5 years, 48% males) and GUSTO (N = 206, 4.5 years, 48% males) and its associations to child behavior, that can be used in future research in the context of child exposures and long-term health. Following rs-fMRI data pre-processing and Shannon entropy calculation across 32 network regions of interest to acquire 496 unique functional connections, partial correlation coefficient analysis adjusted for sex was performed to identify associations between entropy data and Strengths and Difficulties questionnaire in MAVAN and Child Behavior Checklist domains in GUSTO. Significance was set at p < 0.01, and we found eight significant associations in GUSTO. Negative associations were found between two frontoparietal regions and cerebellar posterior and oppositional defiant problems, (r = -0.212, p = 0.006) and (r = -0.200, p = 0.009). Positive associations were identified between somatic complaints and four default mode connections: salience insula (r = 0.202, p < 0.01), dorsal attention intraparietal sulcus (r = 0.231, p = 0.003), language inferior frontal gyrus (r = 0.207, p = 0.008) and language posterior superior temporal gyrus (r = 0.210, p = 0.008). Positive associations were also found between insula and frontoparietal connection and attention deficit / hyperactivity problems (r = 0.200, p < 0.01), and insula – default mode connection and pervasive developmental problems (r = 0.210, p = 0.007). In MAVAN, ten significant associations were identified. Two positive associations were found = with prosocial scores: the salience prefrontal cortex and dorsal attention connection (r = 0.474, p = 0.005) and the salience supramarginal gyrus and dorsal attention intraparietal sulcus (r = 0.447, p = 0.008). The insula and prefrontal connection were negatively associated with peer problems (r = -0.437, p < 0.01). Conduct problems were negatively associated with six separate connections, the left salience insula and right salience insula (r = -0.449, p = 0.008), left salience insula and right salience supramarginal gyrus (r = -0.512, p = 0.002), the default mode and visual network (r = -0.444, p = 0.009), dorsal attention and language network (r = -0.490, p = 0.003), and default mode and posterior parietal cortex (r = -0.546, p = 0.001). Entropy measures of resting state functional connectivity can be used to identify individual differences in brain function that are correlated with variation in behavioral problems in healthy children. Further studies applying this marker into the context of environmental exposures are warranted.

Keywords: child behaviour, functional connectivity, imaging, Shannon entropy

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Authors: Gustavo Axel Elizalde-Velázquez

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Metformin is the first line of oral therapy to treat type II diabetes and is also employed as a treatment for other indications, such as polycystic ovary syndrome, cancer, and COVID-19. Recent data suggest it is the aspirin of the 21st century due to its antioxidant and anti-aging effects. However, increasingly current articles indicate its long-term consumption generates mitochondrial impairment. Up to date, it is known metformin increases the biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, but further information related to brain damage after its consumption is missing. Bearing in mind the above, this work aimed to establish whether or not chronic exposure to metformin may alter swimming behavior and induce neurotoxicity in Danio rerio adults. For this purpose, 250 Danio rerio grown-ups were assigned to six tanks of 50 L of capacity. Four of the six systems contained 50 fish, while the remaining two had 25 fish (≈1 male:1 female ratio). Every system with 50 fish was allocated one of the three metformin treatment concentrations (1, 20, and 40 μg/L), with one system as the control treatment. Systems with 25 fish, on the other hand, were used as positive controls for acetylcholinesterase (10 μg/L of Atrazine) and oxidative stress (3 μg/L of Atrazine). After four months of exposure, a mean of 32 fish (S.D. ± 2) per group of MET treatment survived, which were used for the evaluation of behavior with the Novel Tank test. Moreover, after the behavioral assessment, we aimed to collect the blood and brains of all fish from all treatment groups. For blood collection, fish were anesthetized with an MS-222 solution (150 mg/L), while for brain gathering, fish were euthanized using the hypothermic shock method (2–4 °C). Blood was employed to determine CASP3 activity and the percentage of apoptotic cells with the TUNEL assay, and brains were used to evaluate acetylcholinesterase activity, oxidative damage, and gene expression. After chronic exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. To the best of our understanding, this is the first study that delivers evidence of oxidative impairment, apoptosis, AChE alteration, and overexpression of B- amyloid-related genes in the brain of fish exposed to metformin.

Keywords: AChE inhibition, CASP3 activity, NovelTank test, oxidative damage, TUNEL assay

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Authors: Habib Alah Dadgar, Nasim Norouzbeigi

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The precise definition margin of high and low-grade gliomas is crucial for treatment. We aimed to assess the feasibility of assessment of the resection legions with post-operative positron emission tomography (PET) using [18F]O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). Four patients with the suspicion of high and low-grade were enrolled. Patients underwent post-operative [18F]FET-PET, pre-operative magnetic resonance imaging (MRI) and CT for clinical evaluations. In our study, three patients had negative response to recurrence and progression and one patient indicated positive response after surgery. [18F]FET-PET revealed a legion of increased radiotracer uptake in the dura in the craniotomy site for patient 1. Corresponding to the patient history, the study was negative for recurrence of brain tumor. For patient 2, there was a lesion in the right parieto-temporal with slightly increased uptake in its posterior part with SUVmax = 3.79, so the study was negative for recurrence evaluation. In patient 3 there was no abnormal uptake with negative result for recurrence of brain tumor. Intense radiotracer uptake in the left parietal lobe where in the MRI there was a lesion with no change in enhancement in the post-contrast image is indicated in patient 4. Assessment of the resection legions in high and low-grade gliomas with [18F]FET-PET seems to be useful.

Keywords: FET-PET, CT, glioma, MRI

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Authors: Khalida Douibi, Rodrigo Balp, Solène Le Bars

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In the medical field, applications related to human experiments are frequently linked to reduced samples size, which makes the training of machine learning models quite sensitive and therefore not very robust nor generalizable. This is notably the case in Brain-Computer Interface (BCI) studies, where the sample size rarely exceeds 20 subjects or a few number of trials. To address this problem, several resampling approaches are often used during the data preparation phase, which is an overly critical step in a data science analysis process. One of the naive approaches that is usually applied by data scientists consists in the transformation of the entire database before the resampling phase. However, this can cause model’ s performance to be incorrectly estimated when making predictions on unseen data. In this paper, we explored the effect of data leakage observed during our BCI experiments for device control through the real-time classification of SSVEPs (Steady State Visually Evoked Potentials). We also studied potential ways to ensure optimal validation of the classifiers during the calibration phase to avoid overfitting. The results show that the scaling step is crucial for some algorithms, and it should be applied after the resampling phase to avoid data leackage and improve results.

Keywords: data leackage, data science, machine learning, SSVEP, BCI, overfitting

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Authors: Ron Dick, P. S. D. V. Prasadarao, Glenn Coltman

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Agenesis of the corpus callosum (ACC) is a failure to develop corpus callosum - the large bundle of fibers of the brain that connects the two cerebral hemispheres. It can occur as a partial or complete absence of the corpus callosum. In the general population, its estimated prevalence rate is 1 in 4000 and a wide range of genetic, infectious, vascular, and toxic causes have been attributed to this heterogeneous condition. The diagnosis of ACC is often achieved by neuroimaging procedures. Though persons with ACC can perform normally on intelligence tests they generally present with a range of neuropsychological and social deficits. The deficit profile is characterized by poor coordination of motor movements, slow reaction time, processing speed and, poor memory. Socially, they present with deficits in communication, language processing, the theory of mind, and interpersonal relationships. The present paper illustrates the role of neuropsychological assessment with implications to psychosocial management in a case of agenesis of the corpus callosum. Method: A 27-year old left handed Caucasian male with a history of ACC was self-referred for a neuropsychological assessment to assist him in his employment options. Parents noted significant difficulties with coordination and balance at an early age of 2-3 years and he was diagnosed with dyspraxia at the age of 14 years. History also indicated visual impairment, hypotonia, poor muscle coordination, and delayed development of motor milestones. MRI scan indicated agenesis of the corpus callosum with ventricular morphology, widely spaced parallel lateral ventricles and mild dilatation of the posterior horns; it also showed colpocephaly—a disproportionate enlargement of the occipital horns of the lateral ventricles which might be affecting his motor abilities and visual defects. The MRI scan ruled out other structural abnormalities or neonatal brain injury. At the time of assessment, the subject presented with such problems as poor coordination, slowed processing speed, poor organizational skills and time management, and difficulty with social cues and facial expressions. A comprehensive neuropsychological assessment was planned and conducted to assist in identifying the current neuropsychological profile to facilitate the formulation of a psychosocial and occupational rehabilitation programme. Results: General intellectual functioning was within the average range and his performance on memory-related tasks was adequate. Significant visuospatial and visuoconstructional deficits were evident across tests; constructional difficulties were seen in tasks such as copying a complex figure, building a tower and manipulating blocks. Poor visual scanning ability and visual motor speed were evident. Socially, the subject reported heightened social anxiety, difficulty in responding to cues in the social environment, and difficulty in developing intimate relationships. Conclusion: Persons with ACC are known to present with specific cognitive deficits and problems in social situations. Findings from the current neuropsychological assessment indicated significant visuospatial difficulties, poor visual scanning and problems in social interactions. His general intellectual functioning was within the average range. Based on the findings from the comprehensive neuropsychological assessment, a structured psychosocial rehabilitation programme was developed and recommended.

Keywords: agenesis, callosum, corpus, neuropsychology, psychosocial, rehabilitation

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Authors: S. El Ballal, H. El Sabbagh, M. Abd El Gaber, A. Eisa, A. Al Gamal

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Cadmium is one of the most harmful heavy metals able to induce severe injury. In this study, sixty four male Sprague Dawley rats weighing (70-80 gm) were used. Rats were divided into 4 groups each group of 16 rats. Group A: served as control and received commercial ration and distilled water Group B: cadmium chloride was administered orally in water at dose of 300 ppm cadmium (560 mg/L as CdCl2). Group C: Animals received cadmium in drinking water in addition to administration of N-acetylcysteine (NAC) orally at a dose of 150 mg/kg body weight, equivalent to 1500 ppm in food. Group D: Animals received cadmium in drinking water in addition to administration of alpha lipoic acid (ALA) orally at a dose of 150 mg/kg body weight, equivalent to 1500 ppm in food. The experiment was continued for 2 months. Collection of blood and tissue samples was performed at 2, 4, 6, 8 weeks. Blood sample were collected for serum biochemical analysis including malondialdehyde (MDA), total antioxidants, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, urea and uric acid. Tissue specimens were collected for histopathological examination including liver, kidney, brain and testis. Histopathological examination revealed that cadmium choloride induces pathological alterations which increased in severity with time. The use of NAC and ALA can ameliorate toxic effect of CdCl2. The results showed significant decrease MDA and significant increase total antioxidants in group C and D compared to group B, Liver enzymes include AST and ALT showed significant decrease. Regarding to results of total protein and albumin, they revealed significant increase. Urea and uric acid showed significant decrease. From our study we conclude that NAC and ALA have protective effect against cadmium toxicity.

Keywords: ALA, cadmium, histopathology, NAC

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Authors: Elizabeth Howarth, Dawn Green, Sean Connolly, Geena Vabulas, Sara Smolley

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Through the EU Horizon 2020 Nuvoic Project, the project team recruited 70 individuals in the UK and Ireland to test the Voiceitt speech recognition app and provide user feedback to developers. The app is designed for people with dysarthric speech, to support communication with unfamiliar people and access to speech-driven technologies such as smart home equipment and smart assistants. Participants with atypical speech, due to a range of conditions such as cerebral palsy, acquired brain injury, Down syndrome, stroke and hearing impairment, were recruited, primarily through organisations supporting disabled people. Most had physical or learning disabilities in addition to dysarthric speech. The project team worked with individuals, their families and local support teams, to provide access to the app, including through additional assistive technologies where needed. Testing was user-led, with participants asked to identify and test use cases most relevant to their daily lives over a period of three months or more. Ongoing technical support and training were provided remotely and in-person throughout the testing period. Structured interviews were used to collect feedback on users' experiences, with delivery adapted to individuals' needs and preferences. Informal feedback was collected through ongoing contact between participants, their families and support teams and the project team. Focus groups were held to collect feedback on specific design proposals. User feedback shared with developers has led to improvements to the user interface and functionality, including faster voice training, simplified navigation, the introduction of gamification elements and of switch access as an alternative to touchscreen access, with other feature requests from users still in development. This work offers a case-study in successful and inclusive co-design with the disabled community.

Keywords: co-design, assistive technology, dysarthria, inclusive speech recognition

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Authors: Teja Joshi

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Laterality has shown to play a role in performance as well as injuries especially in unilateral sports disciplines. Uniquely, Artistic Gymnastics involves combination of unilateral, bilateral and complex multi-planer elements as well as gymnastics specific rotational preference. Therefore, this study was conducted to explore if any such preferences are associated with number of injuries in artistic gymnasts. To explore the association between lateral preferences, rotational preferences and injuries incidence in artistic gymnastics. Artistic gymnasts above 16 years of age, were invited to participate in an online survey. The survey included consent, lateral preference inventory, injury data collection according to anatomical locations and rotational preference for selected gymnastics elements performed on the floor exercise. SPSS version 24 was used to analyse Non-parametric data using Kruskal-Wallis (K- independent test) test. Multiple regression was performed to identify the predictor for injuries and their side in gymnasts. Total number of injuries per gymnast was associated with handedness (p value-0.049) and no significant association was noted for footdness (p value-0.207), eyedness (p value-0.491) and eardness (p value-0.798). Additionally, rotational preferences did not influence number of injuries (p value-0.521). In multiple regression, eyedness was identified as a predicting factor to determine the number of injuries. Rotational preferences were neither determined as a national strategy nor a product of lateral preference. Dominant hand had higher number of injuries in artistic gymnasts. Rotational preference is independent of laterality, number of injuries and nationality.

Keywords: sports injury, rotational preference, gymnastics, handedness

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Authors: Somojit Saha, Rohit K. Chatterjee, Sarit K. Das, Avijit Kar

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A new force field is designed for propagation of the parametric contour into deep narrow cortical fold in the application of knowledge based reconstruction of cerebral cortex from MR image of brain. Designing of this force field is highly inspired by the Generalized Gradient Vector Flow (GGVF) model and markedly differs in manipulation of image information in order to determine the direction of propagation of the contour. While GGVF uses edge map as its main driving force, the newly designed force field uses the map of distance between zero valued pixels and their nearest non-zero valued pixel as its main driving force. Hence, it is called Zero-Non-Zero Distance (ZNZD) force field. The objective of this force field is forceful propagation of the contour beyond spurious convergence due to partial volume effect (PVE) in to narrow sulcal fold. Being function of the corresponding non-zero pixel value, the force field has got an inherent property to determine spuriousness of the edge automatically. It is effectively applied along with some morphological processing in the application of cortical reconstruction to breach the hindrance of PVE in narrow sulci where conventional GGVF fails.

Keywords: deformable model, external force field, partial volume effect, cortical reconstruction, MR image of brain

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Authors: Chan Yan Nok

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The present study is a qualitative study based on the coping experiences of six Hong Kong Chinese mothers who had childhood trauma from their first-person perspective. Expanding the perspective beyond the dominant discourse of “inter-generation transmission of trauma”, this study explores the experiences and meanings of child trauma embedded in their narratives through the process of thematic analysis and narrative analysis. The interviewees painted a nuanced picture of their process of coping and trauma resolution. First, acknowledgement; second, feel safe and start to tell the story of trauma; third, feel the feelings and expression of emotions; fourth, clarifying and coping with the impacts of trauma; fifth, integration and transformation; and sixth, using their new understanding of experience to have a better life. It was seen that there was no “end” within the process of trauma resolution. Instead, this is an ongoing process with positive healing trajectory. Analysis of the stories of the mothers revealed recurrent themes around continuous self-reflective awareness in the process of trauma coping. Rather than being necessarily negative and detrimental, childhood trauma could highlight the meanings of being a mother and reveal opportunities for continuous personal growth and self-enhancement. Utilizing the sense of inadequacy as a core driver in the trauma recovery process while developing a heightened awareness of the unfinished business embedded in their “automatic pattern” of behaviors, emotions, and thoughts can help these mothers become more flexible to formulate new methods in facing future predicaments. Future social work and parent education practices should help mothers deal with unresolved trauma, make sense of their impacts of childhood trauma and discover the growth embedded in the past traumatic experience. They should be facilitated in “acknowledging the reality of the trauma”, including understanding their complicated emotions arising from the traumatic experiences and voicing their struggles. In addition, helping these mothers to be aware of short-term and long-term trauma impacts (i.e., secondary responses to the trauma) and explore their effective coping strategies in “overcoming secondary responses to the trauma” are crucial for their future positive adjustment and transformation. Through affirming their coping abilities and lessons learnt from past experiences, mothers can reduce feelings of shame and powerlessness and enhance their parental capacity.

Keywords: childhood trauma, coping, mothers, self-awareness, self-reflection, trauma resolution

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Authors: Qian Liu, Steve Furber

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To explore how the brain may recognize objects in its general,accurate and energy-efficient manner, this paper proposes the use of a neuromorphic hardware system formed from a Dynamic Video Sensor~(DVS) silicon retina in concert with the SpiNNaker real-time Spiking Neural Network~(SNN) simulator. As a first step in the exploration on this platform a recognition system for dynamic hand postures is developed, enabling the study of the methods used in the visual pathways of the brain. Inspired by the behaviours of the primary visual cortex, Convolutional Neural Networks (CNNs) are modeled using both linear perceptrons and spiking Leaky Integrate-and-Fire (LIF) neurons. In this study's largest configuration using these approaches, a network of 74,210 neurons and 15,216,512 synapses is created and operated in real-time using 290 SpiNNaker processor cores in parallel and with 93.0% accuracy. A smaller network using only 1/10th of the resources is also created, again operating in real-time, and it is able to recognize the postures with an accuracy of around 86.4% -only 6.6% lower than the much larger system. The recognition rate of the smaller network developed on this neuromorphic system is sufficient for a successful hand posture recognition system, and demonstrates a much-improved cost to performance trade-off in its approach.

Keywords: spiking neural network (SNN), convolutional neural network (CNN), posture recognition, neuromorphic system

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Authors: Rika Susanti, Eryati Darwin, Dedi Afandi, Yanwirasti, Syahruddin Said, Noverika Windasari, Zelly Dia Rofinda

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Introduction: Blunt head trauma is one of the leading causes of death associated with murders and other deaths involved in criminal acts. Creatine kinase (CKBB) levels have been used as a biomarker for blunt head trauma. Therefore, it is now used as an alternative to an autopsy. The aim of this study is to investigate CKBB levels in cerebrospinal fluid (CSF) and post-mortem serum in order to deduce the cause and time of death. Method: This investigation was conducted through post-test–only group design involving deaths caused by blunt head trauma, which was compared to deaths caused by ketamine poisoning. Results: There were eight treatment groups, each consisting of six adult rats (Rattus norvegicus) Sprague-Dawley strain. Examinations were done at 0 hours, 1 hour, 2 hours, and 3 hours post-mortem, which followed by brain tissue observation. Data were then analyzed statistically with a repeated-measures general linear model. Conclusion: There were increases in the level of CKBB in CSF and postmortem serum in both blunt head trauma and ketamine poisoning treatment groups. However, there were no significant differences between these two groups.

Keywords: blunt head trauma, CKBB, the cause of death, estimated time of death

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Authors: Wenqiu Cao

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Suicide prevention is a global problem that needs to be taken seriously. Investigating the mechanisms of suicide in major depressive disorder (MDD) separately through neuroimaging technology is essential for effective suicide prevention. And it’s particularly urgent in geriatric depressive patients since older adults are more likely to use rapidly deadly means, and suicidal behavior is more lethal for older adults. The current study reviews five studies related to suicide in geriatric MDD that uses neuroimaging methodology in order to analyze the relevant neurobiological mechanisms. The majority of the studies found significant white matter and grey matter reduction or lesion widespread in multiple brain regions, including the frontal and parietal regions, the midbrain, the external capsule, and the cerebellum. Regarding the cognitive impairment in geriatric MDD, the reward signals were found weakened in the paralimbic cortex. The functional magnetic resonance imaging (fMRI) studies also found hemodynamic changes in the right dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in late-life MDD patients with suicidal ideation. Future studies should consider the age of depression onset, more accurate measurements of suicide, larger sample size, and longitudinal design.

Keywords: brain imaging, geriatric major depressive disorder, suicidality, suicide

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Authors: Nadia Zahra Karimi Khiavi, Amir Ghiami Rad

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Due to the high likelihood of injuries in karate, karatekas' injuries warrant special treatment. This study explores the prevalence of karate injuries in East Azerbaijan, Iran and provides a model for karatekas to use in the prevention of such injuries. This study employs a descriptive approach. Male and female participants with a brown belt or above in either control or non-control styles in East Azerbaijan province are included in the study's statistical population. A statistical sample size of 100 people was computed using the tools employed (smartpls), and the samples were drawn at random from all clubs in the province with the assistance of the Karate Board in order to give a model for the prevention of karate injuries. Information was gathered by means of a survey that made use of the Standard Questionnaire for Australian Sports Medicine Injury Reports. The information is presented in the form of tables and samples, and descriptive statistics were used to organise and summarise the data. Control and non-control independent t-tests were conducted using SPSS version 20, and structural equation modelling (pls) was utilised for injury prevention modelling at a 0.05 level of significance. The results showed that the most common areas of injury among the control groups were the upper limbs (46.15%), lower limbs (34.61%), trunk (15.38%), and head and neck (3.84%). The most common types of injuries were broken bones (34.61%), sprain or strain (23.13%), bruising and contusions (23.13%), trauma to the face and mouth (11.53%), and damage to the nerves (69.69%). Uncontrolled committees are most likely to sustain injuries to the head and neck (33.33%), trunk (25.92%), upper limbs (22.22%), and lower limbs (18.51%). The most common injuries were to the mouth and face (33.33%), dislocations and fractures (22.22%), aspirin and strain (22.22%), bruises and contusions (18.51%), and nerves (70%), in that order. Among those who practice control kata, injuries to the upper limb account for 45.83%, the lower limb for 41.666%, the trunk for 8.33%, and the head and neck for 4.166%. The most common types of injuries are dislocations and fractures (41.66 per cent), aspirin and strain (29.16 per cent), bruising and bruises (16.66 per cent), and nerves (12.5%). Injuries to the face and mouth were not reported among those practising the control kata. By far, the most common sites of injury for those practising uncontrolled kata were the lower limb (43.74%), upper limb (39.13%), trunk (13.14%), and head and neck (4.34%). The most common types of injuries were dislocations and fractures (34.82%), aspirin and strain (26.08%), bruises and contusions (21.73%), mouth and face (13.14%), and nerves. Teaching the concepts of cooling and warming (0.591) and enhancing the degree of safety in the sports environment (0.413) were shown to play the most essential roles in reducing sports injuries among karate practitioners of controlling and uncontrolled styles, respectively. Use of common sports gear (0.390), Modification of training programme principles (0.341), Formulation of an effective diet plan for athletes (0.284), Evaluation of athletes' physical anatomy, physiology, chemistry, and physics (0.247).

Keywords: sports injuries, karate, prevention, cooling and warming

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Authors: Matthew J. I. Woolley, Gemma J. M. Read, Paul M. Salmon, Natassia Goode

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The significance of high consequence, workplace failures within construction continues to resonate with a combined average of 12 fatal incidents occurring daily throughout Australia, the United Kingdom, and the United States. Within the Australian construction domain, more than 35 serious, compensable injury incidents are reported daily. These alarming figures, in conjunction with the continued occurrence of fatal and serious, occupational injury incidents globally suggest existing approaches to incident analysis may not be achieving required injury prevention outcomes. One reason may be that, incident analysis methods used in construction have not kept pace with advances in the field of safety science and are not uncovering the full range system-wide contributory factors that are required to achieve optimal levels of construction safety performance. Another reason underpinning this global issue may also be the absence of information surrounding the construction operating and project delivery system. For example, it is not clear who shares the responsibility for construction safety in different contexts. To respond to this issue, to the author’s best knowledge, a first of its kind, control structure model of the construction industry is presented and then used to analyse a fatal construction incident. The model was developed by applying and extending the Systems Theoretic and Incident Model and Process method to hierarchically represent the actors, constraints, feedback mechanisms, and relationships that are involved in managing construction safety performance. The Causal Analysis based on Systems Theory (CAST) method was then used to identify the control and feedback failures involved in the fatal incident. The conclusions from the Coronial investigation into the event are compared with the findings stemming from the CAST analysis. The CAST analysis highlighted additional issues across the construction system that were not identified in the coroner’s recommendations, suggested there is a potential benefit in applying a systems theory approach to incident analysis in construction. The findings demonstrate the utility applying systems theory-based methods to the analysis of construction incidents. Specifically, this study shows the utility of the construction control structure and the potential benefits for project leaders, construction entities, regulators, and construction clients in controlling construction performance.

Keywords: construction project management, construction performance, incident analysis, systems thinking

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Authors: A/Prof Marjan Khajehei

Abstract:

In the last century, the role of fathers in the birth has changed exponentially. Before the 1970s, the principal view was that birth was a female business and not a man’s place. Changing cultural and professional attitudes around the emotional bond between a man and a woman, family structure and the more proactive involved role of men in the family have encouraged fathers’ attendance at birth. There is evidence that fathers’ support can make birthing less traumatic for some women and can make couples closer. This has made some clinicians to believe the fathers should be more involved throughout the birth process. Some clinicians even go further and ask the fathers to watch the medical procedures, such as inserting vaginal speculum, forceps or vacuum, episiotomy and stitches. Although birth can unfold like a beautiful picture captured by birth photographers, with fathers massaging women’s backs by candle light and the miraculous moment of birth, it can be overshadowed by less attractive images of cervical mucous, emptying bowels and the invasive medical procedures. What happens in the birth room and the fathers’ reaction to the graphic experience of birthing can be unpredictable. Despite the fact that most men are absolutely thrilled to be in the delivery room, for some men, a very intimate body part can become completely desexualised, and they can experience psychological and sexual scarring. They see someone they cherish dramatically sliced open and can then associate their partners with a disturbing scene, and it can dramatically affect their relationships. While most women want the expectant fathers by their side for this life-changing event, not all of them may be happy for their partners to watch the perineum to be cut or stitched or when large blades of forceps are inserted inside the vagina. Anecdotal reports have shown that consent is not sought from the labouring women as to whether they want their partners to watch these procedures. The majority of research1, 2, 3 focuses on men’s and women’s retrospective attitudes towards their birth experience. However, the effect of witnessing invasive procedures during childbirth on a man's attraction to his partner, while she is most vulnerable, and also an increased risk of post-traumatic stress disorder in fathers have not been widely investigated. There is a lack of sufficient research investigating whether women need to be asked for their consent before inviting their partners to closely watch medical procedures during childbirth. Future research is required to provide a basis for better awareness and involve the consumers to understanding the men’s and women’s experience and their expectations for labour and birth.

Keywords: birth, childbirth, father, labour, men, women

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Authors: Shiva Rezaei, Seyed Jalal Hosseinimehr, Abbasali Karimpour Malekshah, Mansooreh Mirzaei, Fereshteh Talebpour Amiri, Mehryar Zargari

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Objective(s): Cyclophosphamide (CP), as an antineoplastic drug, is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA), as a natural phenylpropanoid, has antioxidant, anti-inflammatory, and anti-cancer properties. Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Keywords: apoptosis, cyclophosphamide, liver injury, inflammation, oxidative stress, sinapic acid

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Authors: Hye Jin Kim, Hwa Sung Shin

Abstract:

Ischemic stroke means the caused brain damage due to neurological defects, occurring occlusion of cerebral vascular resulting in thrombus or embolism. t-PA (tissue Plasminogen Activator) is the only thrombolytic agent passed the FDA (Food and Drug Administration). However, t-PA directly dissolves the thrombus (direct activity) through fibrinolysis, showing side effects such as re-occlusion. In this study, we evaluated the thrombolytic activities of the serine protease extracted from lugworms inhabiting tidal flats. The new serine protease identified as 38 kDa by SDS-PAGE was not toxic to brain endothelial cells line (hCMEC/D3). Also, the plasmin synthesis inhibition activity (indirect activity) of the new serine protease was confirmed through fibrin zymography assay and fibrin plate assay. It was higher than direct activity as compared to u-PA (urokinase Plasminogen Activator). The activities were found to be maintained at a wide range of temperature (4-70 ℃) and pH 7-10 compared to previous thrombolytic agents from the azocasein assay. In addition, the new serine protease has shown anticoagulant activity from fibrinogenolytic activity assay. In conclusion, the serine protease in lug worms inhabiting the tidal flats could be considered a promising thrombolytic candidate for the treatment of ischemic stroke.

Keywords: alkaline serine protease, bifunctional thrombolytic activity, fibrinolytic activity, ischemic stroke, lug worms

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Authors: Saleh N. Maodaa

Abstract:

Background: Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated. Objective: This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation. Methods: Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks, and blood and testes samples were collected. Results: Pb intoxication impaired the pituitary-testicular axis (PTA), manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2 Conclusion: These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.

Keywords: pituitary-gonadal axis, cytokines, DNA damage, apoptosis

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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