Search results for: hepatic impairment

Authors: Manea A. I. Alqrad, Alaa Sirwi, Sabrin R. M. Ibrahim, Hossam M. Abdallah, Gamal A. Mohamed

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Phytochemical study of the methanolic extract of the air dried powdered of the parts of Viscum schemperi Engl. (Family: Viscaceae) using different chromatographic techniques led to the isolation of five compounds: -amyrenone (1), betulinic acid (2), (3β)-olean-12-ene-3,23-diol (3), -oleanolic acid (4), and α-oleanolic acid (5). Their structures were established based on physical, chemical, and spectral data. Anti-inflammatory and anti-apoptotic activities of oleanolic acid in a mouse model of acute hepatorenal damage were assessed. This study showed the efficacy of oleanolic acid to counteract thioacetamide-induced hepatic and kidney injury in mice through the reduction of hepatocyte oxidative damage, suppression of inflammation, and apoptosis. More importantly, oleanolic acid suppressed thioacetamide-induced hepatic and kidney injury by inhibiting NF-κB/TNF-α-mediated inflammation/apoptosis and enhancing SIRT1/Nrf2/Heme-oxygenase signalling pathway. These promising pharmacological activities suggest the potential use of oleanolic acid against hepatorenal damage.

Keywords: oleanolic acid, viscum schimperi, thioacetamide, SIRT1/Nrf2/NF-κB, hepatorenal damage

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Authors: Milan N. A. Van Der Kuil, Anne M. A. Visser-Meily, Andrea W. M. Evers, Ineke J. M. Van Der Ham

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Navigation ability is essential for autonomy and mobility in daily life. In patients with acquired brain injury, navigation impairment is frequently impaired; however, in this study, we tested the effectiveness of a serious gaming training protocol as a tool for cognitive rehabilitation to reduce navigation impairment. In total, 38 patients with acquired brain injury and subjective navigation complaints completed the experiment, with a partially blind, randomized control trial design. An objective navigation test was used to construct a strengths and weaknesses profile for each patient. Subsequently, patients received personalized compensation training that matched their strengths and weaknesses by addressing an egocentric or allocentric strategy or a strategy aimed at minimizing the use of landmarks. Participants in the experimental condition received psychoeducation and a home-based rehabilitation game with a series of exercises (e.g., map reading, place finding, and turn memorization). The exercises were developed to stimulate the adoption of more beneficial strategies, according to the compensatory approach. Self-reported navigation ability (wayfinding questionnaire), participation level, and objective navigation performance were measured before and after 1 and 4 weeks after completing the six-week training program. Results indicate that the experimental group significantly improved in subjective navigation ability both 1 and 4 weeks after completion of the training, in comparison to the score before training and the scores of the control group. Similarly, goal attainment showed a significant increase after the first and fourth week after training. Objective navigation performance was not affected by the training. This navigation training protocol provides an effective solution to address navigation impairment after acquired brain injury, with clear improvements in subjective performance and goal attainment of the participants. The outcomes of the training should be re-examined after implementation in a clinical setting.

Keywords: spatial navigation, cognitive rehabilitation, serious gaming, acquired brain injury

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Authors: Akbar Darouie, Mamak Joulaie

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In regard of phonological skills development importance and its influence on other aspects of language, this study has been performed. Determination of some phonological indexes in children with hearing impairment and comparison with hearing children was the objective. A sample of convenience was selected from a rehabilitation center and a kindergarten in Karaj, Iran. Participants consisted of 12 hearing impaired and 12 hearing children (age range: 5 years and 6 months to 6 years and 6 months old). Hearing impaired children suffered from severe to profound hearing loss while three of them were cochlear implanted and the others were wearing hearing aids. Conversational speech of these children was recorded and 50 first utterances were selected to analyze. Percentage of consonant correct (PCC) and vowel correct (PVC), initial and final consonant omission error, cluster consonant omission error and syllabic structure variety were compared in two groups. Data were analyzed with t test (version 16th SPSS). Comparison between PCC and PVC averages in two groups showed a significant difference (P< 0/01). There was a significant difference about final consonant emission error (P<0/001) and initial consonant emission error (P<0/01) too. Also, the differences between two groups on cluster consonant omission were significant (P<0/001). Therefore, some changes were seen in syllabic structures in children with hearing impairment compared to typical group. This study demonstrates some phonological differences in Farsi language between two groups of children. Therefore, it seems, in clinical practices we must notice this issue.

Keywords: hearing impairment, phonology, vowel, consonant

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Authors: A. C. Facin, M. C. Maronezi , M. P. Menezes, G. L. Montanhim, L. Pavan, M. A. R. Feliciano, R. P. Nociti, R. A. R. Uscategui, P. C. Moraes

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The incidence of brachycephalic syndrome (BS) in the clinical routine of small animals has increased significantly giving the higher proportion of brachycephalic pets in the last years and has been considered as an animal welfare problem. The treatment of BS is surgical and the clinical signs related can be considerably attenuated. Nevertheless, the systemic effects of the BS are still poorly reported and little is known about these when the surgical correction is not performed early. Affected dogs are more likely to develop cardiopulmonary, gastrointestinal and sleep disorders in which the chronic hypoxemia plays a major role. This syndrome is compared with the obstructive sleep apnea (OSA) in humans, both considered as causes of systemic and metabolic dysfunction. Among the several consequences of the BS little is known if the syndrome also affects the hepatic tissue of brachycephalic patients. Elastography is a promising ultrasound technique that evaluates tissue elasticity and has been recently used with the purpose of diagnosis of liver fibrosis. In medicine, it is a growing concern regarding the hepatic injury of patients affected by OSA. This prospective study hypothesizes if there is any consequence of BS in the hepatic parenchyma of brachycephalic dogs that don’t receive any surgical treatment. This study was conducted following the approval of the Animal Ethics and Welfare Committee of the Faculdade de Ciências Agrárias e Veterinárias, UNESP, Campus Jaboticabal, Brazil (protocol no 17944/2017) and funded by Sao Paulo Research Foundation (FAPESP, process no 2017/24809-4). The methodology was based in ARFI elastography using the ACUSON S2000/SIEMENS device, with convex multifrequential transducer and specific software as well as clinical evaluation of the syndrome, in order to determine if they can be used as a prognostic non-invasive tool. On quantitative elastography, it was collected three measures of shear wave velocity (meters per second) and depth in centimeters in the left lateral, left medial, right lateral, right medial and caudate lobe of the liver. The brachycephalic patients, 16 pugs and 30 french bulldogs, were classified using a previously established 4-point functional grading system based on clinical evaluation before and after a 3-minute exercise tolerance test already established and validated. The control group was based on the same features collected in 22 beagles. The software R version 3.3.0 was used for the analysis and the significance level was set at 0.05. The data were analysed for normality of residuals and homogeneity of variances by Shapiro-Wilks test. Comparisons of parametric continuous variables between breeds were performed by using ANOVA with a post hoc test for pair wise comparison. The preliminary results show significant statistic differences between the brachycephalic groups and the control group in all lobes analysed (p ≤ 0,05), with higher values of shear wave velocities in the hepatic tissue of brachycephalic dogs. In this context, the results obtained in this study contributes to the understanding of BS as well as its consequences in our patients, reflecting in evidence that one more systemic consequence of the syndrome may occur in brachycephalic patients, which was not related in the veterinary literature yet.

Keywords: airway obstruction, brachycephalic airway obstructive syndrome, hepatic injury, obstructive sleep apnea

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Authors: Nyla Anjum, Humaira Bano

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Disability, regardless of its type and nature limits one or two significant life activities. These limitations constitute risk factors for suicide. Rate and intensity of problem upsurges in critical age of adolescence. Researches in the field of mental health over look problem of suicide among persons with disability. Aim of the study was to investigate prevalence and risk factors for suicide among adolescents with disability. The study constitutes purposive sample of 106 elements of both gender with four major categories of disability: hearing impairment, physical impairment, visual impairment and intellectual disabilities. Face to face interview technique was opted for data collection. Other variable are: socio-economic status, social and family support, provision of services for persons with disability, education and employment opportunities. For data analysis independent sample t-test was applied to find out significant differences in gender and One Way Analysis of variance was run to find out differences among four types of disability. Major predictors of suicide were identified with multiple regression analysis. It is concluded that ideation, plans and attempts of suicide among adolescents with disability is a multifaceted and imperative concern in the area of mental health. Urgent research recommendations contains valid measurement of suicide rate and identification of more risk factors for suicide among persons with disability. Study will also guide towards prevention of this pressing problem and will bring message of happy and healthy life not only for persons with disability but also for their families. It will also help to reduce suicide rate in society.

Keywords: suicide, risk factors, adolescent, disability, mental health

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Authors: Vakhtang Nozadze, Luiza Arutinova, Khatuna Martskvishvili

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The social empowerment of most needed individuals is a challenging issue, especially for developing countries. The current study explores the effects of visual impairment on individuals’ satisfaction with different aspects of life (i.e. education, job, income, family) and coping strategies. Furthermore, the difference between groups according to health status is revealed. Other demographic variables (education, employment, and marital status) is also considered. The cross-sectional design and self-reported questionnaires were adopted. Seventy-two visually impaired males and females (age range 13-66) and seventy healthy individuals participated in the study. The results reveal the importance of health status on the accessibility of social amenities, individuals’ satisfaction with life, and a diversity of coping strategies, irrespective of the age. The research has an important implication for social integration research and policy.

Keywords: coping strategies, life satisfaction, social integration, visual impairment

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Authors: M. Aghili, S. Tabarestani, C. Freytes, M. Shojaie, M. Cabrerizo, A. Barreto, N. Rishe, R. E. Curiel, D. Loewenstein, R. Duara, M. Adjouadi

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A major challenge in medical studies, especially those that are longitudinal, is the problem of missing measurements which hinders the effective application of many machine learning algorithms. Furthermore, recent Alzheimer's Disease studies have focused on the delineation of Early Mild Cognitive Impairment (EMCI) and Late Mild Cognitive Impairment (LMCI) from cognitively normal controls (CN) which is essential for developing effective and early treatment methods. To address the aforementioned challenges, this paper explores the potential of using the eXtreme Gradient Boosting (XGBoost) algorithm in handling missing values in multiclass classification. We seek a generalized classification scheme where all prodromal stages of the disease are considered simultaneously in the classification and decision-making processes. Given the large number of subjects (1631) included in this study and in the presence of almost 28% missing values, we investigated the performance of XGBoost on the classification of the four classes of AD, NC, EMCI, and LMCI. Using 10-fold cross validation technique, XGBoost is shown to outperform other state-of-the-art classification algorithms by 3% in terms of accuracy and F-score. Our model achieved an accuracy of 80.52%, a precision of 80.62% and recall of 80.51%, supporting the more natural and promising multiclass classification.

Keywords: eXtreme gradient boosting, missing data, Alzheimer disease, early mild cognitive impairment, late mild cognitive impair, multiclass classification, ADNI, support vector machine, random forest

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Authors: Monica Gonzalez Machorro

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Dementia is hard to diagnose because of the lack of early physical symptoms. Early dementia recognition is key to improving the living condition of patients. Speech technology is considered a valuable biomarker for this challenge. Recent works have utilized conventional acoustic features and machine learning methods to detect dementia in speech. BERT-like classifiers have reported the most promising performance. One constraint, nonetheless, is that these studies are either based on human transcripts or on transcripts produced by automatic speech recognition (ASR) systems. This research contribution is to explore a method that does not require transcriptions to detect early Alzheimer’s disease (AD) and mild cognitive impairment (MCI). This is achieved by fine-tuning a pre-trained ASR model for the downstream early AD and MCI tasks. To do so, a subset of the thoroughly studied Pitt Corpus is customized. The subset is balanced for class, age, and gender. Data processing also involves cropping the samples into 10-second segments. For comparison purposes, a baseline model is defined by training and testing a Random Forest with 20 extracted acoustic features using the librosa library implemented in Python. These are: zero-crossing rate, MFCCs, spectral bandwidth, spectral centroid, root mean square, and short-time Fourier transform. The baseline model achieved a 58% accuracy. To fine-tune HuBERT as a classifier, an average pooling strategy is employed to merge the 3D representations from audio into 2D representations, and a linear layer is added. The pre-trained model used is ‘hubert-large-ls960-ft’. Empirically, the number of epochs selected is 5, and the batch size defined is 1. Experiments show that our proposed method reaches a 69% balanced accuracy. This suggests that the linguistic and speech information encoded in the self-supervised ASR-based model is able to learn acoustic cues of AD and MCI.

Keywords: automatic speech recognition, early Alzheimer’s recognition, mild cognitive impairment, speech impairment

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Authors: Toumi Farah, Charallah Salima

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In the Algerian Sahara, goat farming is predominant, and it’s associated with other types of breeding, particularly camel and sheep; it also constitutes a significant proportion of breeding exclusively goat. This Saharan goat is a small ruminant with a black dress with white’s spots, hanging ears, and a coat more or less long. It is known for its hardiness and resistance to adverse conditions of arid zones and its perfect ecophysiological adaptation to harsh environmental conditions. However, pregnancy alterations, particularly abortion, degrade its productivity and cause economic losses, having both direct and indirect effects on animal production, like the costs of veterinary interventions and the reconstitution of livestock. The purpose of this work is to study the histological aspect of the liver of goats’ aborted living under nomadic herds in the region of Béni-Abbès (30° 7' N, 2° 10 'O). The organs were collected in physiological serum, rinsed, and then fixed with formaldehyde (37°, diluted at 10%). After that, these samples were processed for a topographic study. The morphometric study of the liver was performed by using an image analysis and processing software "Image J"; the various measurements obtained are intended to specify the supposed stage of development according to the body weight. The histological structure of the liver shows that the hepatic parenchyma consists of vascular conjunctive spaces surrounded by Glisson’s capsule. The sinusoids and hepatic portal vein are full of red blood cells, representing sinusoidal congestion and a thrombosed vein. At high magnification, the blood vessels show the presence of vascular thrombosis and haemorrhage in some areas of the hepatic parenchyma. Morphometric analysis shows that the number of liver parenchymal cells and the diameter of liver vessels vary according to the stage of development. The results obtained will provide details of the anatomical and cellular elements that can be used in the diagnosis of early or late abortion and late embryonic death. It would be interesting to find, by immunohistochemistry, some inflammatory markers useful for monitoring the progress of pregnancy and bioindicators of fetomaternal distress.

Keywords: aborting goat, arid zone, liver, histopathology

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Authors: Ammar Amsyar Abdul Haddi, Mohd Hasni Jaafar

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Heavy metals are elements naturally presented in the environment that can cause adverse effect to health. But not much literature was found on effects toward lung function, where impairment of lung function may lead to various lung diseases. The objective of the study is to explore the lung function impairment, urinary heavy metal level, and its associated factors among the community in Klang valley, Malaysia. Sampling was done in Kuala Lumpur suburb public and housing areas during community events throughout March 2019 till October 2019. respondents who gave the consent were given a questionnaire to answer and was proceeded with a lung function test. Urine samples were obtained at the end of the session and sent for Inductively coupled plasma mass spectrometry (ICP-MS) analysis for heavy metal cadmium (Cd) and lead (Pb) concentration. A total of 200 samples were analysed, and of all, 52% of respondents were male, Age ranging from 18 years old to 74 years old with a mean age of 38.44. Urinary samples show that 12% of the respondent (n=22) has Cd level above than average, and 1.5 % of the respondent (n=3) has urinary Pb at an above normal level. Bivariate analysis show that there was a positive correlation between urinary Cd and urinary Pb (r= 0.309; p<0.001). Furthermore, there was a negative correlation between urinary Cd level and full vital capacity (FVC) (r=-0.202, p=0.004), Force expiratory volume at 1 second (FEV1) (r = -0.225, p=0.001), and also with Force expiratory flow between 25-75% FVC (FEF25%-75%) (r= -0.187, p=0.008). however, urinary Pb did not show any association with FVC, FEV1, FEV1/FVC, or FEF25%-75%. Multiple linear regression analysis shows that urinary Cd remained significant and negatively affect FVC% (p=0.025) and FEV1% (p=0.004) achieved from the predicted value. On top of that, other factors such as education level (p=0.013) and duration of smoking(p=0.003) may influencing both urinary Cd and performance in lung function as well, suggesting Cd as a potential mediating factor between smoking and impairment of lung function. however, there was no interaction detected between heavy metal or other influencing factor in this study. In short, there is a negative linear relationship detected between urinary Cd and lung function, and urinary Cd is likely to affects lung function in a restrictive pattern. Since smoking is also an influencing factor for urinary Cd and lung function impairment, it is highly suggested that smokers should be screened for lung function and urinary Cd level in the future for early disease prevention.

Keywords: lung function, heavy metals, community

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Authors: Atitallah Sofien, Bouyahia Olfa, Attar Souleima, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Ciliopathies are a spectrum of diseases that have in common a defect in the synthesis of ciliary proteins. It is a rare cause of neonatal cholestasis. Clinical presentation varies extremely, and the main affected organs are the kidneys, liver, and pancreas. Methodology: This is a descriptive case report of a newborn who was admitted for exploration of neonatal cholestasis in the Paediatric Department C at the Children’s Hospital of Tunis, where the investigations concluded with a rare genetic mutation. Results: This is the case of a newborn male with no family history of hepatic and renal diseases, born to consanguineous parents, and from a well-monitored uneventful pregnancy. He developed jaundice on the second day of life, for which he received conventional phototherapy in the neonatal intensive care unit. He was admitted at 15 days for mild bronchiolitis. On clinical examination, intense jaundice was noted with normal stool and urine colour. Initial blood work showed an elevation in conjugated bilirubin and a high gamma-glutamyl transferase level. Transaminases and prothrombin time were normal. Abdominal sonography revealed hepatomegaly, splenomegaly, and undifferentiated renal cortex with bilateral medullar micro-cysts. Kidney function tests were normal. The infant received ursodeoxycholic acid and vitamin therapy. Genetic testing showed a homozygous mutation in the DCDC2 gene that hadn’t been documented before confirming the diagnosis of renal-hepatic ciliopathy. The patient has regular follow-ups, and his conjugated bilirubin and gamma-glutamyl transferase levels have been decreasing. Conclusion: Genetic testing has revolutionized the approach to etiological diagnosis in pediatric cholestasis. It enables personalised treatment strategies to better enhance the quality of life of patients and prevent potential complications following adequate long-term monitoring.

Keywords: cholestasis, newborn, ciliopathy, DCDC2, genetic

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Authors: Aikaterini Tavoulari

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This research aims to address the types of repetitive behaviours (RBs) observed by adults in children with vision impairment (VI) or autism spectrum disorder (ASD), the explanations the adults employ to interpret these behaviours, and the impact RBs have on the child, the caregiver, the professional and society. The underlying reason for this is an attempt to discover any potential differences between two different disabilities in a comparative fashion. The study is based on the interpretivism paradigm and follows a qualitative approach. A comparative case study design based on the ecological systems theory (EST) is adopted. Thirty-five caregivers and accredited professionals were recruited (17 for the VI group, out of whom 8 were caregivers and 9 were professionals, and 18 for the ASD group, out of whom 9 were caregivers and 9 were professionals). Following the completion of a pilot study, all participants were interviewed regarding one specific child – their own child/student – via semi-structured interviews. During the interviews, the researcher used a research diary as a methodological tool and video elicitation as a facilitation tool. A cross-case analysis was conducted, and data were analysed according to the method of thematic analysis. A link has been indicated between VI and ASD, which concerns perceptions about the socially constructed manner in which an RB is perceived. ASD is perceived by the participants as a disability with challenging characteristics, such as an RB. The ASD group perceived RB as linked to ableism, social stigmatisation, and taboo, in contrast to VI, where the existence of RB seems to be a consequence of sensory loss. Bi-directionality of EST seems to have been lost completely, and the macrosystem seems to drive the interactions between the ecological systems.

Keywords: ableism, social stigma, disability, repetitive behaviour, vision impairment, autism spectrum disorder, perceptions

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Authors: Etim, Victoria Enefiok, Dada, Oluseyi Akintunde, Bassey Okon

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Phonological disorder is a serious and disturbing issue to many parents and teachers. Efforts towards resolving the problem have been undermined by other specific disabilities which were hidden to many regular and special education teachers. It is against this background that this study was motivated to provide data on the prevalence of phonological disorders in children with specific language impairment (CWSLI) as the first step towards critical intervention. The study was a survey of 15 CWSLI from St. Louise Inclusive schools, Ikot Ekpene in Akwa Ibom State of Nigeria. Phonological Processes Diagnostic Scale (PPDS) with 17 short sentences, which cut across the five phonological processes that were examined, were validated by experts in test measurement, phonology and special education. The respondents were made to read the sentences with emphasis on the targeted sounds. Their utterances were recorded and analyzed in the language laboratory using Praat Software. Data were also collected through friendly interactions at different times from the clients. The theory of generative phonology was adopted for the descriptive analysis of the phonological processes. Data collected were analyzed using simple percentage and composite bar chart for better understanding of the result. The study found out that CWSLI exhibited the five phonological processes under investigation. It was revealed that 66.7%, 80%, 73.3%, 80%, and 86.7% of the respondents have severe deficit in fricative stopping, velar fronting, liquid gliding, final consonant deletion and cluster reduction, respectively. It was therefore recommended that a nationwide survey should be carried out to have national statistics of CWSLI with phonological deficits and develop intervention strategies for effective therapy to remediate the disorder.

Keywords: language disorders, phonology, phonological processes, specific language impairment

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Authors: Suchana Marahatta, Sabina Bhattarai, Bishnu Hari Paudel, Dilip Thakur

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Background: Every year thousands of patients develop nerve damage and disabilities as a result of leprosy which can be prevented by early detection and treatment. So, early detection and treatment of nerve function impairment is of paramount importance in leprosy. Objectives: To assess the electrophysiological pattern of the peripheral nerves in leprosy patients and to compare it with clinical assessment tools. Materials and Methods: In this comparative cross-sectional study, 74 newly diagnosed leprosy patients without reaction were enrolled. They underwent thorough evaluation for peripheral nerve function impairment using clinical tests [i.e. nerve palpation (NP), monofilament (MF) testing, voluntary muscle testing (VMT)] and nerve conduction study (NCS). Clinical findings were compared with that of NCS using SPSS version 11.5. Results: NCS was impaired in 43.24% of leprosy patient at the baseline. Among them, sensory NCS was impaired in more patients (32.4%) in comparison to motor NCS (20.3%). NP, MF, and VMT were impaired in 58.1%, 25.7%, and 9.4% of the patients, respectively. Maximum concordance of monofilament testing and sensory NCS was found for sural nerve (14.7%). Likewise, the concordance of motor NP and motor NCS was the maximum for ulnar nerve (14.9%). When individual parameters of the NCS were considered, amplitude was found to be the most frequently affected parameter for both sensory and motor NCS. It was impaired in 100% of cases with abnormal NCS findings. Conclusion: Since there was no acceptable concordance between NCS findings and clinical findings, we should consider NCS whenever feasible for early detection of neuropathy in leprosy. The amplitude of both sensory nerve action potential (SNAP) and compound nerve action potential (CAMP) could be important determinants of the abnormal NCS if supported by further studies.

Keywords: leprosy, nerve function impairment, neuropathy, nerve conduction study

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Authors: B. Sadek, N. Khan, D. Łażewska, K. Kieć-Kononowicz

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The effects of the non-imidazole histamine H3 receptor (H3R) antagonist DL77 in passive avoidance paradigm (PAP) and novel object recognition (NOR) task in MK801-induced cognitive deficits associated with schizophrenia (CDS) in adult male rats, and applying donepezil (DOZ) as a reference drug were investigated. The results show that acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) significantly improved MK801-induced (0.1 mg/kg, i.p.) memory deficits in PAP. The ameliorating activity of DL77 (5 mg/kg, i.p.) in MK801-induced deficits was partly reversed when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL, 10 mg/kg, i.p.) or with the antimuscarinic antagonist scopolamine (SCO, 0.1 mg/kg, i.p.), but not with the CNS penetrant H1R antagonist pyrilamine (PYR, 10 mg/kg, i.p.). Moreover, the memory enhancing effect of DL77 (5 mg/kg, i.p.) in MK801-induced memory deficits in PAP was strongly reversed when rats were pretreated with a combination of ZOL (10 mg/kg, i.p.) and SCO (1.0 mg/kg, i.p.). Furthermore, the significant ameliorative effect of DL77 (5 mg/kg, i.p.) on MK801-induced long-term memory (LTM) impairment in NOR test was comparable to the DOZ-provided memory-enhancing effect, and was abrogated when animals were pretreated with the histamine H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to provide procognitive effect on MK801-induced short-term memory (STM) impairment in NOR test. In addition, DL77 (5 mg/kg) did not alter anxiety levels and locomotor activity of animals naive to elevated-plus maze (EPM), demonstrating that improved performances with DL77 (5 mg/kg) in PAP or NOR are unrelated to changes in emotional responding or spontaneous locomotor activity. These results provide evidence for the potential of H3Rs for the treatment of neurodegenerative disorders related to impaired memory function, e.g. CDS.

Keywords: histamine H3 receptor, antagonist, learning, memory impairment, passive avoidance paradigm, novel object recognition

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Authors: B. Medani Amna, M. A. Elbadwi Samia, E. Amin Ahmed

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Variable plants present in nature are used by simple rural and urban people, researchers and drug manufacturers for medicinal purposes. Garad is one of the most commonly used in Sudan for both treatment and prophylaxis of infections in the respiratory, urinogenital tracts and the skin. Water exctracts from Acacia nilotica bods were used in this very experiment to test for their toxicity to Nubian goats at two dose rates under proper experimental conditions. The clinical, pathological, haematological and biological changes in Nubian goats given daily oral doses of 1 and 5 g/kg body weight of Acacia nilotica to two groups of test goats. The goats of the control group were undosed with Acacia nilotica.Other than the dose co-related mortality rates, the clinical signs were observed to be salivation, staggered gait, intermittent loss of voice and low appetite. On histopathological testing, the main lesions were hepatic centrolobular necrosis and fatty changes associated with the significant changes in GGT and ALP are indicating hepatic dysfunction.Renal malfunction is indicated by haemorrhages in addition to the change in the urea concentration. The congested, haemorrhagic, emphysematous, edematous and cyanotic lungs may contribute to the development of dyspnea. Acacia nilotica poisoning may lead to an immunosuppression pointed out by the lymphocyte infiltration. On evaluation of the above results, Acacia nilotica was considered toxic to Nubian goats at the above mentioned doses. Future work for Acacia nilotica was forwarded and practical implications of the result were highlighted.

Keywords: Acaia nilotica, toxicity data, Nubian goats, Garad

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Authors: Izabella Szollosi, Klara Marton

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Aphasia can be defined as a weakness in accessing linguistic information. Accessing linguistic information is strongly related to information processing, which in turn is associated with the cognitive control system. According to the literature, a deficit in the cognitive control system interferes with language processing and contributes to non-fluent speech performance. The aim of our study was to explore this hypothesis by investigating how cognitive control interacts with language performance in participants with non-fluent aphasia. Cognitive control is a complex construct that includes working memory (WM) and the ability to resist proactive interference (PI). Based on previous research, we hypothesized that impairments in domain-general (DG) cognitive control abilities have negative effects on language processing. In contrast, better DG cognitive control functioning supports goal-directed behavior in language-related processes as well. Since stroke itself might slow down information processing, it is important to examine its negative effects on both cognitive control and language processing. Participants (N=52) in our study were individuals with non-fluent Broca’s aphasia (N = 13), with transcortical motor aphasia (N=13), individuals with stroke damage without aphasia (N=13), and unimpaired speakers (N = 13). All participants performed various computer-based tasks targeting cognitive control functions such as WM and resistance to PI in both linguistic and non-linguistic domains. Non-linguistic tasks targeted primarily DG functions, while linguistic tasks targeted more domain specific (DS) processes. The results showed that participants with Broca’s aphasia differed from the other three groups in the non-linguistic tasks. They performed significantly worse even in the baseline conditions. In contrast, we found a different performance profile in the linguistic domain, where the control group differed from all three stroke-related groups. The three groups with impairment performed more poorly than the controls but similar to each other in the verbal baseline condition. In the more complex verbal PI condition, however, participants with Broca’s aphasia performed significantly worse than all the other groups. Participants with Broca’s aphasia demonstrated the most severe language impairment and the highest vulnerability in tasks measuring DG cognitive control functions. Results support the notion that the more severe the cognitive control impairment, the more severe the aphasia. Thus, our findings suggest a strong interaction between cognitive control and language. Individuals with the most severe and most general cognitive control deficit - participants with Broca’s aphasia - showed the most severe language impairment. Individuals with better DG cognitive control functions demonstrated better language performance. While all participants with stroke damage showed impaired cognitive control functions in the linguistic domain, participants with better language skills performed also better in tasks that measured non-linguistic cognitive control functions. The overall results indicate that the level of cognitive control deficit interacts with the language functions in individuals along with the language spectrum (from severe to no impairment). However, future research is needed to determine any directionality.

Keywords: cognitive control, information processing, language performance, non-fluent aphasia

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Authors: Mrunal Phatak, Suvarna Raut

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Introduction: Thyroid hormone is important for the normal function of the auditory system. Hearing impairment can occur insidiously in subclinical hypothyroidism. The present study was undertaken with the aims of evaluating audiological tests like tuning fork tests, pure tone audiometry, brainstem evoked auditory potentials (BAEPs), and auditory reaction time (ART) in hypothyroid women and in age and sex matched controls so as to evaluate the effect of thyroid hormone on hearing. The objective of the study was to investigate hearing status by the audiological profile in hypothyroidism (group 1) and healthy controls ( group 2) to compare the audiological profile between these groups and find the correlation of levels of TSH, T3, and T4 with the above parameters. Material and methods: A total sample size of 124 women in the age group of 30 to 50 years was recruited and divided into the Cases group comprising of 62 newly diagnosed hypothyroid women and the Control group having 62 women with normal thyroid profile. Otoscopic examination, tuning fork tests, Pure tone audiometry tests (PTA). Brain Stem Auditory Evoked Potential (BAEP) and Auditory Reaction Time (ART) were done in both ears, i.e. total 248 ears of all subjects. Results: By BAEPs, hearing impairment was detected in total 64 ears (51.61%). A significant increase was seen in Wave V latency, IPL I-V, and IPL III-V, and the decrease was seen in the amplitude of Wave I and V in both the ears in cases. Positive correlation of Wave V latency of Right and Left ears is seen with TSH levels (p < 0.001) and a negative correlation with T3 (>0.05) and with T4 (p < 0.01). Negative correlation of wave V amplitude of Right and Left ears is seen with TSH levels (p < 0.001), and a significant positive correlation is seen with T3 and T4. Pure tone audiometry parameters showed hearing impairment of conductive (31.29%), sensorineural (36.29%), as well as the mixed type (15.32%). Hearing loss was mild in 65.32% of ears and moderate in 17.74% of ears. Pure tone averages (PTA) were significantly increased in cases than in controls in both the ears. Significant positive correlation of PTA of Right and Left ears is seen with TSH levels (p<0.05). Negative correlation with T3 and T4 is seen. A significant increase in HF ART and LF ART is seen in cases as compared to controls. Positive correlation of ART of high frequency and low frequency is seen with TSH levels and a negative correlation with T3 and T4 (p > 0.05). Conclusion: The abnormal BAEPs in hypothyroid women suggest an impaired central auditory pathway. BAEP abnormalities are indicative of a nonspecific injury in the bulbo-ponto-mesencephalic centres. The results of auditory investigations suggest a causal relationship between hypothyroidism and hearing loss. The site of lesion in the auditory pathway is probably at several levels, namely, in the middle ear and at cochlear and retrocochlear sites. Prolonged ART also suggests the impairment in central processing mechanisms. The results of the present study conclude that the probable reason for hearing impairment in hypothyroidism may be delayed impulse conduction in acoustic nerve up to the level of the midbrain (IPL I-V, III-V), particularly inferior colliculus (wave V). There is also impairment in central processing mechanisms, as shown by prolonged ART.

Keywords: deafness, pure tone audiometry, brain stem auditory evoked potential, hyopothyroidism

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Authors: D. M. El-Tanbouly, R. M. Abdelsalam, A. S. Attia, M. T. Abdel-Aziz

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Lipopolysaccharide (LPS) endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium, a well-known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS induced- endotoxima in mice. Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced one hour after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and three hours thereafter plasma was separated, animals were sacrificed and their livers were isolated. LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and myeloperoxidase (MPO) activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations through its anti-inflammatory and antioxidant potentials. Mg, therefore, could be regarded as an effective strategy for prevention of liver damage associated with septicemia.

Keywords: LPS, liver damage, magnesium, septicemia

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Authors: Girgis Younan, Ikram Eltayeb

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Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

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Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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Doxorubicin (DOX), an anthracycline antibiotic is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w. day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein, and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In conclusion, it can be supposed that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings.

Keywords: doxorubicin, purslane, hepatotoxicity, antioxidants

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Authors: H. M. Imam, H. M. Rezk, A. F. Tohamy

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Background: Human umbilical cord blood (HUCB) is considered as a unique source for stem cells. HUCB contain different types of progenitor cells which could differentiate into hepatocytes. Aims: To investigate the potential of rat's liver damage repair using human umbilical cord mesenchymal stem cells (hUCMSCs). We investigated the feasibility for hUCMSCs in recovery from liver damage. Moreover, investigating fibrotic liver repair and using the CCl4-induced model for liver damage in the rat. Methods: Rats were injected with 0.5 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. hUCMSCs were injected into the rats through the tail vein; Stem cells were transplanted at a dose of 1×106 cells/rat after 72 hours of CCl4 injection without receiving any immunosuppressant. After (6 and 8 weeks) of transplantation, blood samples were collected to assess liver functions (ALT, AST, GGT and ALB) and level of Procollagen III as a liver fibrosis marker. In addition, hepatic tissue regeneration was assessed histopathologically and immunohistochemically using antihuman monoclonal antibodies against CD34, CK19 and albumin. Results: Biochemical and histopathological analysis showed significantly increased recovery from liver damage in the transplanted group. In addition, HUCB stem cells transdifferentiated into functional hepatocytes in rats with hepatic injury which results in improving liver structure and function. Conclusion: Our findings suggest that transplantation of hUCMSCs may be a novel therapeutic approach for treating liver fibrosis. Therefore, hUCMSCs are a potential option for treatment of liver cirrhosis.

Keywords: carbon tetra chloride, liver fibrosis, mesenchymal stem cells, rat

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Authors: A. L. I. Prasanna, E. Liyanage, S. A. Rajaratne, K. P. A. P. Kariyawasam, A. A. J. Rajaratne

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Maintaining or improving the muscle strength of the injured body part is essential to optimize performance among disabled athletes. General conditioning and strengthening exercises might be ineffective if not sufficiently intense enough or targeted for each participant’s specific impairment. Specific strengthening programme, targeted to the affected body part, are essential to improve the strength of impaired muscles and increase in strength will help reducing the impact of disability. Methods: The muscle strength of hip, knee and ankle joints was assessed in a group of randomly selected disabled athletes, using the Medical Research Council (MRC) grading. Those having muscle strength of grade 4 or less were selected for this study (24 in number) and were given and a custom made exercise program designed to strengthen their hip, knee or ankle joint musculature, according to the muscle or group of muscles affected. Effectiveness of the strengthening program was assessed after a period of 3 months. Results: Statistical analysis was done using the Minitab 16 statistical software. A Mann-Whitney U test was used to compare the strength of muscle group before and after exercise programme. A significant difference was observed after the three month strengthening program for knee flexors (Left and Right) (P =0.0889, 0.0312) hip flexors (left and right) (P=0.0312, 0.0466), hip extensors (Left and Right) (P=0.0478, 0.0513), ankle plantar flexors (Left and Right) (P=0.0466, 0.0423) and right ankle dorsiflexors (P= 0.0337). No significant difference of strength was observed after the strengthening program in the knee extensors (left and right), hip abductors (left and right) and left ankle dorsiflexors. Conclusion: Impairment specific exercise programme appear to be beneficial for disabled athletes to significantly improve the muscle strength of the affected joints.

Keywords: muscle strengthening programme, disabled athletes, physiotherapy, rehabilitation sciences

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Authors: Chiagoziem A. Otuechere, Ebenezer O. Farombi

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The protective effect of dichloromethane: methanol extract of Pterocarpus mildbraedii (PME), a widely consumed Nigerian leafy vegetable, on the toxicity of propanil was investigated in male rats. Animals were distributed into eight groups of five each. Group 1 served as control and received normal saline while rats in groups 2, 3, and 4 received 100 mg/kg, 200 mg/kg, and 400 mg/kg extract doses respectively. Group 5 rats were orally administered 200 mg/kg propanil while groups 6, 7, and 8 rats were given propanil plus extract. Oral administration of propanil elicited a 14.8%, 5%, 122%, and 78% increase in the activity of serum enzymes; alanine aminotransferase (AST), alanine aminotransferase(ALT), Alkaline phoshatase (ALP) and Gamma glutamyl transferase (ﻻGT). There were also increase in Lactate dehydrogenase (LDH) activity, direct bilirubin and lipid peroxidation levels. Furthermore, PME significantly attenuated the marked hepatic oxidative damage that accompanied propanil treatment. The extract significantly decreased LDH activity and bilirubin levels following propanil treatment. Furthermore, propanil-induced alterations in the activities of antioxidant enzymes: Superoxide dismutase (SOD), catalase (CAT) and glutathione s-transferase (GST) in these rats were modulated by the extract. The percentage DPPH Radical Scavenging Activity of the extract was determined as 55% and compared to those of Gallic acid (49%). Hepatic histology examination further confirmed the damage to the liver as it revealed severe periportal cellular infiltration of the hepatocytes. These biochemical and morphological alterations were attenuated in rats pre-treated with 100 mg/kg and 200 mg/kg doses of the extract. These results suggest that PME possesses protective effect against propanil-induced hepatotoxicity.

Keywords: antioxidant, hepatoprotection, Pterocarpus mildbraedii, propanil

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Authors: Mehdi Sheikhi, Marjan Nassiri-Asl, Esmail Abbasi, Mahsa Shafiee

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Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. The present study aimed to investigate the effects of vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), a flavonoid found in such plants as tartary buckwheat sprouts, wheat leaves phenolome, Mimosa pudica Linn and Passiflora spp, on scopolamine-induced memory impairment in rats. To achieve this goal, we assessed the effects of vitexin on memory retrieval in the presence or absence of scopolamine using a step-through passive avoidance trial. In the first part of the study, vitexin (25, 50, and 100 μM) was administered intracerebroventricularly (i.c.v.) before acquisition trials. In the second part, vitexin, at the same doses, was administered before scopolamine (10 μg, i.c.v.) and before the acquisition trials. During retention tests, vitexin (100 μM) in the absence of scopolamine significantly increased the stepthrough latencies compared to scopolamine. In addition, vitexin (100 μM) significantly reversed the shorter step-through latencies induced by scopolamine (P < 0.05). These results indicate that vitexin has a potential role in enhancing memory retrieval. A possible mechanism is modulation of cholinergic receptors; however, other mechanisms may be involved in its effects in acute exposure.

Keywords: flavonoid, memory retrieval, passive avoidance, scopolamine, vitexin

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Authors: Jiping Cai, Ningzhi Wangyang, Jun Shao

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Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality that leads to structural and functional damage in several parts of the brain, such as cranial nerves, optic nerve tract or other circuitry involved in vision and occipital lobe, depending on its location and severity. As a result, the function associated with vision processing and perception are significantly affected and cause blurred vision, double vision, decreased peripheral vision and blindness. Here two cases complaining of monocular vision loss (actually temporal hemianopia) due to traumatic chiasmal syndrome after frontal head injury were reported, and were compared the findings with individual case reports published in the literature. Reported cases of traumatic chiasmal syndrome appear to share some common features, such as injury to the frontal bone and fracture of the anterior skull base. The degree of bitemporal hemianopia and visual loss acuity have a variable presentation and was not necessarily related to the severity of the craniocerebral trauma. Chiasmal injury may occur even in the absence bony chip impingement. Isolated bitemporal hemianopia is rare and clinical improvement usually may not occur. Mechanisms of damage to the optic chiasm after trauma include direct tearing, contusion haemorrhage and contusion necrosis, and secondary mechanisms such as cell death, inflammation, edema, neurogenesis impairment and axonal damage associated with TBI. Beside visual field test, MRI evaluation of optic pathways seems to the strong objective evidence to demonstrate the impairment of the integrity of visual systems following TBI. Therefore, traumatic chiasmal syndrome should be considered as a differential diagnosis by both neurosurgeons and ophthalmologists in patients presenting with visual impairment, especially bitemporal hemianopia after head injury causing frontal and anterior skull base fracture.

Keywords: bitemporal hemianopia, brain injury, optic chiasma, traumatic chiasmal syndrome.

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Authors: Ryo Shikimoto, Hidehito Niimura, Hisashi Kida, Kota Suzuki, Yukiko Miyasaka, Masaru Mimura

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Introduction: In Japan, the most aged country in the world, it is important to explore predictive factors of cognitive function among the elderly. Coping behavior relieves chronic stress and improves lifestyle, and consequently may reduce the risk of cognitive impairment. One of the most widely investigated frameworks evaluated in previous studies is approach-oriented and avoidance-oriented coping strategies. The purpose of this study is to investigate the relationship between cognitive function and coping strategies among elderly residents in urban areas of Japan. Method: This is a part of the cross-sectional Arakawa geriatric cohort study for 1,099 residents (aged 65 to 86 years; mean [SD] = 72.9 [5.2]). Participants were assessed for cognitive function using the Mini-Mental State Examination (MMSE) and diagnosed by psychiatrists in face-to-face interviews. They were then investigated for their each coping behaviors and coping strategies (approach- and avoidance-oriented coping) using stress and coping inventory. A multiple regression analysis was used to investigate the relationship between MMSE score and each coping strategy. Results: Of the 1,099 patients, the mean MMSE score of the study participants was 27.2 (SD = 2.7), and the numbers of the diagnosis of normal, mild cognitive impairment (MCI), and dementia were 815 (74.2%), 248 (22.6%), and 14 (1.3%), respectively. Approach-oriented coping score was significantly associated with MMSE score (B [partial regression coefficient] = 0.12, 95% confidence interval = 0.05 to 0.19) after adjusting for confounding factors including age, sex, and education. Avoidance-oriented coping did not show a significant association with MMSE score (B [partial regression coefficient] = -0.02, 95% confidence interval = -0.09 to 0.06). Conclusion: Approach-oriented coping was clearly associated with neurocognitive function in the Japanese population. A future longitudinal trial is warranted to investigate the protective effects of coping behavior on cognitive function.

Keywords: approach-oriented coping, cognitive impairment, coping behavior, dementia

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Authors: Ramandeep Kaur, Makula Ajitha

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Fluvastatin has been reported for increasing bone mineral density in osteoporosis since last decade. Systemically administered drug undergoes extensive hepatic first-pass metabolism, thus very small amount of drug reaches the bone tissue which is highly insignificant. The present study aims to deliver fluvastatin in the form of nanoemulsion (NE) gel directly to the bone tissue through transdermal route thereby bypassing hepatic first pass metabolism. The NE formulation consisted of isopropyl myristate as oil, tween 80 as surfactant, transcutol as co-surfactant and water as the aqueous phase. Pseudoternary phase diagrams were constructed using aqueous titration method and NE’s obtained were subjected to thermodynamic-kinetic stability studies. The stable NE formulations were evaluated for their droplet size, zeta potential, and transmission electron microscopy (TEM). The nano-sized formulations were incorporated into 0.5% carbopol 934 gel matrix. Ex-vivo permeation behaviour of selected formulations through rat skin was investigated and compared with the conventional formulations (suspension and emulsion). Further, in-vivo pharmacokinetic study was carried using male Wistar rats. The optimized NE formulations mean droplet size was 11.66±3.2 nm with polydispersity index of 0.117. Permeation flux of NE gel formulations was found significantly higher than the conventional formulations i.e. suspension and emulsion. In vivo pharmacokinetic study showed significant increase in bioavailability (1.25 fold) of fluvastatin than oral formulation. Thus, it can be concluded that NE gel was successfully developed for transdermal delivery of fluvastatin for the treatment of osteoporosis.

Keywords: fluvastatin, nanoemulsion gel, osteoporosis, transdermal

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Authors: Farah Diab, Mohamad Khalil, Francesca Storace, Francesca Baldini, Piero Portincasaa, Giulio Lupidi, Laura Vergani

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Thymbra spicata is a thyme-like plant belonging to the Lamiaceae family that shows a global distribution, especially in the eastern Mediterranean region. Leaves of T. spicata contain large amounts of phenols such as phenolic acids (rosmarinic acid), phenolic monoterpenes (carvacrol), and flavonoids. In Lebanon, T. spicata is currently used as a culinary herb in salad and infusion, as well as for traditional medicinal purposes. Carvacrol (5-isopropyl-2-methyl phenol), the most abundant polyphenol in the organic extract and essential oils, has a great array of pharmacological properties. In fact, carvacrol is largely employed as a food additive and neutraceutical agent. Our aim is to investigate the beneficial effects of T. spicata ethanolic extract (TE) and its main component, carvacrol, using in vitro models of hepatic steatosis and endothelial dysfunction. As a further point, we focused on investigating if and how the binding of carvacrol to albumin, the physiological transporter for drugs in the blood, might be altered by the presence of high levels of fatty acids (FAs), thus impairing the carvacrol bio-distribution in vivo. For that reason, hepatic FaO cells treated with exogenous FAs such as oleate and palmitate mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured lipid accumulation, free radical production, lipoperoxidation, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin with/without high levels of long-chain FAs was assessed by absorption and emission spectroscopies. Our findings show that both TE and carvacrol (i) counteracted lipid accumulation in hepatocytes by decreasing the intracellular and extracellular lipid contents in steatotic FaO cells; (ii) decreased oxidative stress in endothelial cells by significantly reducing lipoperoxidation and free radical production, as well as, attenuating the nitric oxide release; (ii) high levels of circulating FAs reduced the binding of carvacrol to albumin. The beneficial effects of TE and carvacrol on both hepatic and endothelial cells point to a nutraceutical potential. However, high levels of circulating FAs, such as those occurring in metabolic disorders, might hinder the carvacrol transport, bio-distribution, and pharmacodynamics.

Keywords: carvacrol, endothelial dysfunction, fatty acids, non-alcoholic fatty liver diseases, serum albumin

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Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

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Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

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