Search results for: mitochondrial disorders

Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Pejman Taghibeikzadehbadr

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Background and Aim: PGC-1 alpha is a transcription factor that was first detected in brown adipose tissue. Since its discovery, PGC-1 alpha has been known to facilitate beneficial adaptations such as mitochondrial biogenesis and increased angiogenesis in skeletal muscle following aerobic exercise. Therefore, the purpose of this study was to investigate the expression of PGC-1 alpha isoforms in response to eccentric and concentric resistance training in healthy subjects. Materials and Methods: Ten healthy men were randomly divided into two groups (5 patients in eccentric group - 5 in eccentric group). Isokinetic contraction protocols included eccentric and concentric knee extension with maximum power and angular velocity of 60 degrees per second. The torques assigned to each subject were considered to match the workload in both protocols, with a rotational speed of 60 degrees per second. Contractions consisted of a maximum of 12 sets of 10 repetitions for the right leg, a rest time of 30 seconds between each set. At the beginning and end of the study, biopsy of the lateral broad muscle tissue was performed. Biopsies were performed in both distal and proximal directions of the lateral flank. To evaluate the expression of PGC1α-1 and PGC1α-4 genes, tissue analysis was performed in each group using Real-Time PCR technique. Data were analyzed using dependent t-test and covariance test. SPSS21 software and Exell 2013 software were used for data analysis. Results: The results showed that intra-group changes of PGC1α-1 after one session of activity were not significant in eccentric (p = 0.168) and concentric (p = 0.959) groups. Also, inter-group changes showed no difference between the two groups (p = 0.681). Also, intra-group changes of PGC1α-4 after one session of activity were significant in an eccentric group (p = 0.012) and concentric group (p = 0.02). Also, inter-group changes showed no difference between the two groups (p = 0.362). Conclusion: It seems that the lack of significant changes in the desired variables due to the lack of exercise pressure is sufficient to stimulate the increase of PGC1α-1 and PGC1α-4. And with regard to reviewing the answer, it seems that the compatibility debate has different results that need to be addressed.

Keywords: eccentric contraction, concentric contraction, PGC1α-1 و PGC1α-4, human subject

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Authors: Mariya Yeldhos, G. Hema, Sowmya Narayanan, L. Dhiviyalakshmi

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Insomnia is one of the most prevalent psychological disorders worldwide. Some of the deficiencies of the current treatments of insomnia are: side effects in the case of sleeping pills and high costs in the case of psychotherapeutic treatment. In this paper, we propose a device which provides a combination of audio visual entrainment and acupressure based compression therapy for insomnia. This device provides drug-free treatment of insomnia through a user friendly and portable device that enables relaxation of brain and muscles, with certain advantages such as low cost, and wide accessibility to a large number of people. Tools adapted towards the treatment of insomnia: -Audio -Continuous exposure to binaural beats of a particular frequency of audible range -Visual -Flash of LED light -Acupressure points -GB-20 -GV-16 -B-10

Keywords: insomnia, acupressure, entrainment, audio-visual entrainment

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Authors: Cristina Fernandez, Felix Amparano, John Tumberger, Stephani Stancil, Sarah Hampl, Brooke Sweeney, Amy R. Beck, Helena H Laroche, Jared Tucker, Eileen Chaves, Sara Gould, Matthew Lindquist, Lora Edwards, Renee Arensberg, Meredith Dreyer, Jazmine Cedeno, Alleen Cummins, Jennifer Lisondra, Katie Cox, Kelsey Dean, Rachel Perera, Nicholas A. Clark

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Background: Adolescents with obesity are at higher risk of disordered eating than the general population. Detection of eating disorders (ED) is difficult. Screening questionnaires may aid in early detection of ED. Our team’s prior efforts focused on increasing ED screening rates to ≥90% using a validated 10-question adolescent binge eating disorder screening questionnaire (ADO-BED). This aim was achieved. We then aimed to improve treatment plan initiation of patients ≥12 years of age who screen positive for BED within our WMC from 33% to 70% within 12 months. Methods: Our WMC is within a tertiary-care, free-standing children’s hospital. A3, an improvement framework, was used. A multidisciplinary team (physicians, nurses, registered dietitians, psychologists, and exercise physiologists) was created. The outcome measure was documentation of treatment plan initiation of those who screen positive (goal 70%). The process measure was ADO-BED screening rate of WMC patients (goal ≥90%). Plan-Do-Study-Act (PDSA) cycle 1 included provider education on current literature and treatment plan initiation based upon ADO-BED responses. PDSA 2 involved increasing documentation of treatment plan and retrain process to providers. Pre-defined treatment plans were: 1) repeat screen in 3-6 months, 2) resources provided only, or 3) comprehensive multidisciplinary weight management team evaluation. Run charts monitored impact over time. Results: Within 9 months, 166 patients were seen in WMC. Process measure showed sustained performance above goal (mean 98%). Outcome measure showed special cause improvement from mean of 33% to 100% (n=31). Of treatment plans provided, 45% received Plan 1, 4% Plan 2, and 46% Plan 3. Conclusion: Through a multidisciplinary improvement team approach, we maintained sustained ADO-BED screening performance, and, prior to our 12-month timeline, achieved our project aim. Our efforts may serve as a model for other multidisciplinary WMCs. Next steps may include expanding project scope to other WM programs.

Keywords: obesity, pediatrics, clinic, eating disorder

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Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

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Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

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Authors: Benghezel Hichem

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Thyroid dysfunction in hemodialysis subjects is represented mainly by hypothyroidism. The objective of our work is to determine the thyroid profile of our hemodialysis patients and to highlight the prevalence of different thyroid disorders. Methods: This is a retrospective study performed on a mono centric 2 months (February and March 2013) on 42 hemodialysis patients (11 male and 31 female). We made the dosage of thyroid hormones Thyrotropin (TSH) ((free thyroxin ) FT4 and free Triodothyronin ) FT3) by chemiluminescence immunoassay method on cobas 6000 Roche Diagnostics. The results: The prevalence of biological hypothyroidism was 18% (7% with a high TSH isolated and a mean +/- SD 9.44 +/- 6.29, 5% with high TSH, and with low FT4 a mean +/- SD is 8.18 +/- 0.53 for TSH and 9.69 +/- 0.22 for FT4, One patient with a high TSH, and low FT4, FT3. 4% of patients with a low T3 syndrome with a mean +/- SD of 3.93 +/- 0,3 for FT3), we notice that 5% of patients with hyperthyroidism TSH collapsed and mean +/- SD of TSH is 0.017 +/- 0,001. Conclusion: The biological Hypothyroidism is a common endocrine disorder in chronic hemodialysis.

Keywords: hypothyroidism, hemodialysis, thyréostimulin, free thyroxin, triodothyronin

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Authors: Jose A. Diaz-Olivares, Nafise Mahdavian, Farhad Abtahi, Kaj Lindecrantz, Abdelakram Hafid, Fernando Seoane

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Despite new recommendations and guidelines for the evaluation of occupational risk assessments and their prevention, work-related musculoskeletal disorders are still one of the biggest causes of work activity disruption, productivity loss, sick leave and chronic work disability. It affects millions of workers throughout Europe, with a large-scale economic and social burden. These specific efforts have failed to produce significant results yet, probably due to the limited availability and high costs of occupational risk assessment at work, especially when the methods are complex, consume excessive resources or depend on self-evaluations and observations of poor accuracy. To overcome these limitations, a pervasive system of risk assessment tools in real time has been developed, which has the characteristics of a systematic approach, with good precision, usability and resource efficiency, essential to facilitate the prevention of musculoskeletal disorders in the long term. The system allows the combination of different wearable sensors, placed on different limbs, to be used for data collection and evaluation by a software solution, according to the needs and requirements in each individual working environment. This is done in a non-disruptive manner for both the occupational health expert and the workers. The creation of this solution allows us to attend different research activities that require, as an essential starting point, the recording of data with ergonomic value of very diverse origin, especially in real work environments. The software platform is here presented with a complimentary smart clothing system for data acquisition, comprised of a T-shirt containing inertial measurement units (IMU), a vest sensorized with textile electronics, a wireless electrocardiogram (ECG) and thoracic electrical bio-impedance (TEB) recorder and a glove sensorized with variable resistors, dependent on the angular position of the wrist. The collected data is processed in real-time through a mobile application software solution, implemented in commercially available Android-based smartphones and tablet platforms. Based on the collection of this information and its analysis, real-time risk assessment and feedback about postural improvement is possible, adapted to different contexts. The result is a tool which provides added value to ergonomists and occupational health agents, as in situ analysis of postural behavior can assist in a quantitative manner in the evaluation of work techniques and the occupational environment.

Keywords: ergonomics, mobile technologies, risk assessment, smart textiles

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Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

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Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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Authors: Sundus Mona, Atif Adnan, Babar Ali, Fareeha Arshad, Allah Rakha

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Molecular diversity is the variation in the abundance of species. Forensic entomology is a neglected field in Pakistan. Insects collected from the crime scene should be handled by forensic entomologists who are currently virtually non-existent in Pakistan. Correct identification of insect specimen along with knowledge of their biodiversity can aid in solving many problems related to complicated forensic cases. Inadequate morphological identification and insufficient thermal biological studies limit the entomological utility in Forensic Medicine. Recently molecular identification of entomological evidence has gained attention globally. DNA barcoding is the latest and established method for species identification. Only proper identification can provide a precise estimation of postmortem intervals. Arthropods are known to be the first tourists scavenging on decomposing dead matter. The objective of the proposed study was to identify species by molecular techniques and analyze their phylogenetic importance with barcoded necrophagous insect species of early succession on human cadavers. Based upon this identification, the study outcomes will be the utilization of established DNA bar codes to identify carrion feeding insect species for concordant estimation of post mortem interval. A molecular identification method involving sequencing of a 658bp ‘barcode’ fragment of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene from collected specimens of unknown dipteral species from cadavers of Lahore was evaluated. Nucleotide sequence divergences were calculated using MEGA 7 and Arlequin, and a neighbor-joining phylogenetic tree was generated. Three species were identified, Chrysomya megacephala, Chrysomya saffranea, and Chrysomya rufifacies with low genetic diversity. The fixation index was 0.83992 that suggests a need for further studies to identify and classify forensically relevant insects in Pakistan. There is an exigency demand for further research especially when immature forms of arthropods are recovered from the crime scene.

Keywords: molecular diversity, DNA barcoding, species identification, forensically relevant

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Authors: James D. Beauchemin

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Introduction: The incarceration of people with mental illness and substance use disorders is a major public health issue with social, clinical, and economic implications. Yoga participation has been associated with numerous psychological benefits; however, there is a paucity of research examining impacts of yoga with incarcerated populations. The purpose of this study was to evaluate effectiveness of a six-week yoga intervention on several mental health-related variables, including emotion regulation, body awareness, and warnings of substance relapse among incarcerated females. Methods: This study utilized a pre-post, three-arm design, with participants assigned to intervention, therapeutic community, or general population groups. A between-group analysis of covariance (ANCOVA) was conducted across groups to assess intervention effectiveness using the Difficulties in Emotion Regulation Scale (DERS), Scale of Body Connection (SBC), and Warnings of Relapse (AWARE) Questionnaire. Results: ANCOVA results for warnings of relapse (AWARE) revealed significant between-group differences F(2, 80) = 7.15, p = .001; np2 = .152), with significant pairwise comparisons between the intervention group and both the therapeutic community (p = .001) and the general population (p = .005) groups. Similarly, significant differences were found for emotional regulation (DERS) F(2, 83) = 10.521, p = .000; np2 = .278). Pairwise comparisons indicated a significant difference between the intervention and general population (p = .01). Finally, significant differences between the intervention and control groups were found for body awareness (SBC) F(2, 84) = 3.69, p = .029; np2 = .081). Between-group differences were clarified via pairwise comparisons, indicating significant differences between the intervention group and both the therapeutic community (p = .028) and general population groups (p = .020). Implications: Study results suggest that yoga may be an effective addition to integrative mental health and substance use treatment for incarcerated women and contributes to increasing evidence that holistic interventions may be an important component for treatment with this population. Specifically, given the prevalence of mental health and substance use disorders, findings revealed that changes in body awareness and emotion regulation might be particularly beneficial for incarcerated populations with substance use challenges as a result of yoga participation. From a systemic perspective, this proactive approach may have long-term implications for both physical and psychological well-being for the incarcerated population as a whole, thereby decreasing the need for traditional treatment. By integrating a more holistic, salutogenic model that emphasizes prevention, interventions like yoga may work to improve the wellness of this population while providing an alternative or complementary treatment option for those with current symptoms.

Keywords: wellness, solution-focused coaching, college students, prevention

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Authors: Muhammad Wahb

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Physical activity is increasingly recognized as a significant factor in maintaining optimal health and preventing chronic diseases. This research scrutinizes the long-term health benefits of sustained physical activity, employing a systematic review of epidemiological studies and randomized control trials conducted over the past decade. The study illuminates the protective effects of regular physical activity against cardiovascular disease, obesity, diabetes, and mental health disorders, with a special focus on the mechanisms involved. Furthermore, the paper provides insights into how public health initiatives can effectively promote physical activity among diverse populations, contributing to improved community health outcomes.

Keywords: physical activity, long-term health benefits, chronic disease prevention, public health

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Authors: Ming-Dong Wang, Abigail F. Ruby, Michelle E. Ross

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Methylphenidate is a first-line treatment drug for attention deficit hyperactivity disorder (ADHD), a common mental health disorder in children and adolescents. Over the last several decades, the rate of children and adolescents using ADHD medication has been increasing in many countries. A recent study found that the prevalence of ADHD medication use among children aged 3-18 years increased in 13 different world regions between 2001 and 2015, where the absolute increase ranged from 0.02 to 0.26% per year. The goal of this study was to examine the use of methylphenidate in Canadian children and its associated adverse reactions. Methylphenidate use information among young Canadians aged 0-14 years was extracted from IQVIA data on prescriptions dispensed by pharmacies between April 2014 and June 2020. The adverse reaction information associated with methylphenidate use was extracted from the Canada Vigilance database for the same time period. Methylphenidate use trends were analyzed based on sex, age group (0-4 years, 5-9 years, and 10-14 years), and geographical location (province). The common classes of adverse reactions associated with methylphenidate use were sorted, and the relative risks associated with methylphenidate use as compared with two second-line amphetamine medications for ADHD were estimated. This study revealed that among Canadians aged 0-14 years, every 100 people used about 25 prescriptions (or 23,000 mg) of methylphenidate per year during the study period, and the use increased with time. Boys used almost three times more methylphenidate than girls. The amount of drug used was inversely associated with age: Canadians aged 10-14 years used nearly three times as many drugs compared to those aged 5-9 years. Seasonal methylphenidate use patterns were apparent among young Canadians, but the seasonal trends differed among the three age groups. Methylphenidate use varied from region to region, and the highest methylphenidate use was observed in Quebec, where the use of methylphenidate was at least double that of any other province. During the study period, Health Canada received 304 adverse reaction reports associated with the use of methylphenidate for Canadians aged 0-14 years. The number of adverse reaction reports received for boys was 3.5 times higher than that for girls. The three most common adverse reaction classes were psychiatric disorders, nervous system disorders and injury, poisoning procedural complications. The number one commonly reported adverse reaction for boys was aggression (11.2%), while for girls, it was a tremor (9.6%). The safety profile in terms of adverse reaction classes associated with methylphenidate use was similar to that of the selected control products. Methylphenidate is a commonly used pharmaceutical product in young Canadians, particularly in the province of Quebec. Boys used approximately three times more of this product as compared to girls. Future investigation is needed to determine what factors are associated with the observed geographic variations in Canada.

Keywords: adverse reaction risk, methylphenidate, prescription trend, use variation

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Authors: Kyeong-Ri Ko, Seong Bong Bae, Jang Sik Choi, Sung Bum Pan

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A simple method for testing the posture imbalance of the human body is to check for differences in the bilateral shoulder and pelvic height of the target. In this paper, to check for spinal disorders the authors have studied ways to establish a motion capture system to obtain and express motions of 4-joints, and to acquire data based on this system. The 4 sensors are attached to the both shoulders and pelvis. To verify the established system, the normal and abnormal postures of the targets listening to a lecture were obtained using the established 4-joint based motion capture system. From the results, it was confirmed that the motions taken by the target was identical to the 3-dimensional simulation.

Keywords: inertial sensor, motion capture, motion data acquisition, posture imbalance

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Authors: Harika Atmaca, Emir Bozkurt, Latife Merve Oktay, Selim Uzunoglu, Ruchan Uslu, Burçak Karaca

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Microarrays have been developed for highly parallel enzyme-linked immunosorbent assay (ELISA) applications. The most common protein arrays are produced by using multiple monoclonal antibodies, since they are robust molecules which can be easily handled and immobilized by standard procedures without loss of activity. Protein expression profiling with protein array technology allows simultaneous analysis of the protein expression pattern of a large number of proteins. Trabectedin, a tetrahydroisoquinoline alkaloid derived from a Caribbean tunicate, Ecteinascidia turbinata, has been shown to have antitumor effects. Here, we used a novel proteomic approach to explore the mechanism of action of trabectedin in prostate cancer cell line PC-3 by apoptosis antibody microarray. XTT cell proliferation kit and Cell Death Detection Elisa Plus Kit (Roche) was used for measuring cytotoxicity and apoptosis. Human Apoptosis Protein Array (R&D Systems) which consists of 35 apoptosis related proteins was used to assess the omic protein expression pattern. Trabectedin induced cytotoxicity and apoptosis in prostate cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL R2/DR5, TNF R1/TNFRSF1A, FADD were significantly increased by 4.0-, 21.0-, 4.20- and 11.5-fold by trabectedin treatment in PC-3 cells. Moreover, mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, and Cleaved Caspase-3 expressions were induced by 2.68-, 2.07-, 2.8-, and 4.5-fold and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 3.5- and 5.2-fold in PC-3 cells. Proteomic (antibody microarray) analysis suggests that the mechanism of action of trabectedin may be exerted via the induction of both intrinsic and extrinsic apoptotic pathways. The antibody microarray platform can be utilised to explore the molecular mechanism of action of novel anticancer agents.

Keywords: trabectedin, prostate cancer, omic protein expression profile, apoptosis

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Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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Authors: M. Y. Abubakar, Ipinjolu J. K., Yuzine B. Esa, Magawata I., Hassan W. A., Turaki A. A.

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Catfish (Heterobranchus spp.) is a major freshwater fish that are widely distributed in Nigeria waters and are gaining rapid aquaculture expansion. However, indiscriminate artificial crossbreeding of the species with others poses a threat to their biodiversity. There is a paucity of information about the genetic variability, hence this insight on the genetic variability is badly needed, not only for the species conservation but for aquaculture expansion. In this study, we tested the level of Genetic diversity, population differentiation and phylogenetic relationship analysis on 35 individuals of two populations of Heterobranchus bidorsalis and 29 individuals of three populations of Heterobranchus longifilis using the mitochondrial cytochrome c oxidase subunit I (mtDNA COI) gene sequence. Nucleotide sequences of 650 bp fragment of the COI gene of the two species were compared. In the whole 4 and 5 haplotypes were distinguished in the populations of H. bidorsalis & H. longifilis with accession numbers (MG334168 - MG334171 & MG334172 to MG334176) respectively. Haplotypes diversity indices revealed a range of 0.59 ± 0.08 to 0.57 ± 0.09 in H. bidorsalis and 0.000 to 0.001051 ± 0.000945 in H. longifilis population, respectively. Analysis of molecular variance (AMOVA) revealed no significant variation among H. bidorsalis population of the Niger & Benue Rivers, detected significant genetic variation was between the Rivers of Niger, Kaduna and Benue population of H. longifilis. Two main clades were recovered, showing a clear separation between H. bidorsalis and H. longifilis in the phylogenetic tree. The mtDNA COI genes studied revealed high gene flow between populations with no distinct genetic differentiation between the populations as measured by the fixation index (FST) statistic. However, a proportion of population-specific haplotypes was observed in the two species studied, suggesting a substantial degree of genetic distinctiveness for each of the population investigated. These findings present the description of the species character and accessions of the fish’s genetic resources, through gene sequence submitted in Genetic database. The data will help to protect their valuable wild resource and contribute to their recovery and selective breeding in Nigeria.

Keywords: AMOVA, genetic diversity, Heterobranchus spp., mtDNA COI, phylogenetic tree

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Authors: Misty Attwood, Helgi Schioth

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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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Authors: Alene Toulany, Elizabeth Dettmer, Seena Grewal, Kaley Roosen, Andrea Regina, Cathleen Steinegger, Kate Stadelman, Melissa Chambers, Lindsay Lochhead, Kelsey Gallagher, Alissa Steinberg, Andrea Leyser, Allison Lougheed, Jill Hamilton

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Obesity and psychiatric disorders occur together so frequently that the combination has been coined an epidemic within an epidemic. Youth living with obesity are at increased risk for trauma, depression, anxiety and disordered eating. Although symptoms of binge eating disorder are common in paediatric obesity management programs, they are often not identified or addressed within treatment. At The Hospital for Sick Children (SickKids), a tertiary care paediatric hospital in Toronto, Canada, adolescents with obesity are treated in an interdisciplinary outpatient clinic (1-2 hours/week). This intensity of care is simply not enough to help these extremely complex patients. Existing day treatment programs for eating, and psychiatric disorders are not well suited for patients with obesity. In order to address this identified care gap, a unique collaboration was formed between the obesity, psychiatry, and eating disorder programs at SickKids in 2015. The aim of this collaboration was to provide an enhanced treatment arm to our general psychiatry day hospital program that addresses both the mental health issues and the lifestyle challenges common to youth with obesity and binge eating. The program is currently in year-one of a two-year pilot project and is designed for a length of stay of approximately 6 months. All youth participate in daily group therapy, academics, and structured mealtimes. The groups are primarily skills-based and are informed by cognitive/dialectical behavioural therapies. Weekly family therapy and individual therapy, as well as weekly medical appointments with a psychiatrist and a nurse, are provided. Youth in the enhanced treatment arm also receive regular sessions with a dietitian to establish normalized eating behaviours and monthly multifamily meal sessions to address challenges related to behaviour change and mealtimes in the home. Outcomes that will be evaluated include measures of mental health, anthropometrics, metabolic status, and healthcare satisfaction. At the end of the two years, it is expected that we will have had about 16 youth participants. This model of care delivery will be the first of its kind in Canada and is expected to inform future paediatric treatment practices.

Keywords: adolescent, binge eating, mental illness, obesity

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Authors: Yun-Shan Tsai, Si-Ping Lin, En-Chieh Lin, Xin-Hong Chen, Shin-Yun Ho, Shin-Hong Huang, Ching-ju Hsieh

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Background and significance: Uncorrected refractive errors and cataracts are the main visually debilitating ophthalmological abnormalities in adult participants with intellectual disability (ID). However, not all adult participants with ID may receive a regular and timely ophthalmological assessment. Consequently, some of the ocular diseases may not be diagnosed until late, thereby causing unnecessary ocular morbidity. In addition, recent clinical practice and researches have also suggested that eye-care services for this group are neglected. Purpose: To investigate the unmet need for eye care services, clinical characteristics of cataract, visual function, surgical outcome and prognostic predictors in adult participants with ID at Taipei City Hospital in Taiwan. Methods: This is a one-year prospective clinical study. We recruited about 120 eyes of 60 adult participants with ID who were received cataract surgery. Caregivers of all participants received a questionnaire on current eye care services. Clinical demographic data, such as age, gender, and associated systemic diseases or syndromes, were collected. All complete ophthalmologic examinations were performed 1 month preoperatively and 3 months postoperatively, including ocular biometry, visual function, refractive status, morphology of cataract, associated ocular features, anesthesia methods, surgical types, and complications. Morphology of cataract, visual and surgical outcome was analyzed. Results: A total of 60 participants with mean age 43.66 ± 13.94 years, including 59.02% male and 40.98% female, took part in comprehensive eye-care services. The prevalence of unmet need for eye care services was high (about 70%). About 50% of adult participants with ID have bilateral cataracts at the time of diagnosis. White cataracts were noted in about 30% of all adult participants with ID at the time of presentation. Associated ocular disorders were included myopic maculopathy (4.54%), corneal disorders (11.36%), nystagmus (20.45%), strabismus (38.64%) and glaucoma (2.27%). About 26.7% of adult participants with ID underwent extracapsular cataract extraction whereas a phacoemulsification was performed in 100% of eyes. Intraocular lens implantation was performed in all eyes. The most common postoperative complication was posterior capsular opacification (30%). The mean best-corrected visual acuity was significantly improved from preoperatively (mean log MAR 0.48 ± 0.22) to at 3 months postoperatively (mean log MAR 0.045 ± 0.22) (p < .05). Conclusions: Regular follow up will help address the need for eye-care services in participants with ID. A high incidence of bilateral cataracts, as well as white cataracts, was observed in adult participants with ID. Because of early diagnosis and early intervention of cataract, the visual and surgical outcomes of cataract are good, but the visual outcomes are suboptimal due to associated ocular comorbidities.

Keywords: adult participants with intellectual disability, cataract, cataract surgery

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Authors: Roihatul Mutiah, Sukardiman, Aty Widyawaruyanti

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Calotropis gigantiea (L.) R. Br (Apocynaceae) commonly called as “Biduri” or “giant milk weed” is a well-known weed to many cultures for treating various disorders. Several studies reported that C.gigantea roots has anticancer activity. The main aim of this research was to isolate and identify an active marker compound of C.gigantea roots for quality control purpose of its extract in the development as anticancer natural product. The isolation methods was bioactivity guided column chromatography, TLC, and HPLC. Evaluated anticancer activity of there substances using MTT assay methods. Identification structure active compound by UV, 1HNMR, 13CNMR, HMBC, HMQC spectral and other references. The result showed that the marker active compound was identical as Calotropin.

Keywords: calotropin, Calotropis gigantea, anticancer, marker active

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Authors: Feng Guo

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Human brain organoids, 3D brain tissue cultures derived from human pluripotent stem cells, hold promising potential in modeling neuroinflammation for a variety of neurological diseases. However, challenges remain in generating standardized human brain organoids that can recapitulate key physiological features of a human brain. Here, this study presents a series of organoids-on-a-chip systems to generate better human brain organoids and model neuroinflammation. By employing 3D printing and microfluidic 3D cell culture technologies, the study’s systems enable the reliable, scalable, and reproducible generation of human brain organoids. Compared with conventional protocols, this study’s method increased neural progenitor proliferation and reduced heterogeneity of human brain organoids. As a proof-of-concept application, the study applied this method to model substance use disorders.

Keywords: human brain organoids, microfluidics, organ-on-a-chip, neuroinflammation

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Authors: Hakim Derradji, Abdelkader Yahi, Abdelmalek Sabrou, Nacer Tabet

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Introduction: Cystic lesions located in the sellar and suprasellar region cause a diagnostic and therapeutic problem, given their location and their impact on neighboring structures. The patient's symptomatology varies from a simple headache to serious visual and endocrine disorders, involving the functional prognosis, sometimes even the vital prognosis. Surgery in this region remains a therapeutic challenge, and several surgical techniques have been described and used. Material and Methods: We treated 15 patients during the period from 2015 to 2022, whose clinical, biological, radiological, and therapeutic characteristics will be presented in detail in this work, and in whom the surgical technique differs from one case to another. Conclusion: We will discuss in this work the different techniques used to treat these lesions and the different objectives to be achieved for each case, as well as the complications and our conduct to be taken per and post-operative.

Keywords: cystic lesions, adenomas, sellar and suprasellar region, neuroendoscopy

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Authors: Richard Vuijk, Arnoud Arntz

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Rationale: To our knowledge treatment of personality disorder comorbidity in adults with autism spectrum disorder (ASD) is understudied and is still in its infancy: We do not know if treatment of personality disorders may be applicable to adults with ASD. In particular, it is unknown whether patients with ASD benefit from experiential techniques that are part of schema therapy developed for the treatment of personality disorders. Objective: The aim of the study is to investigate the efficacy of a schema mode focused treatment with adult clients with ASD and comorbid personality pathology (i.e. at least one personality disorder). Specifically, we investigate if they can benefit from both cognitive-behavioral, and experiential interventions. Study design: A multiple baseline case series study. Study population: Adult individuals (age > 21 years) with ASD and at least one personality disorder. Participants will be recruited from Sarr expertise center for autism in Rotterdam. The study requires 12 participants. Intervention: The treatment protocol consists of 35 weekly offered sessions, followed by 10 monthly booster sessions. A multiple baseline design will be used with baseline varying from 5 to 10 weeks, with weekly supportive sessions. After baseline, a 5-week exploration phase follows with weekly sessions during which current and past functioning, psychological symptoms, schema modes are explored, and information about the treatment will be given. Then 15 weekly sessions with cognitive-behavioral interventions and 15 weekly sessions with experiential interventions will be given. Finally, there will be a 10-month follow-up phase with monthly booster sessions. Participants are randomly assigned to baseline length, and respond weekly during treatment and monthly at follow-up on Belief Strength of negative core beliefs (by VAS), and fill out SMI, SCL-90 and SRS-A 7 times during screening procedure (i.e. before baseline), after baseline, after exploration, after cognitive and behavioral interventions, after experiential interventions, and after 5- and 10- month follow-up. The SCID-II will be administered during screening procedure (i.e. before baseline), at 5- and at 10-month follow-up. Main study parameters: The primary study parameter is negative core beliefs. Secondary study parameters include schema modes, personality disorder manifestations, psychological symptoms, and social interaction and communication. Discussion: To the best of author’s knowledge so far no study has been published on the application of schema mode focused interventions in adult patients with ASD and comorbid PD(s). This study offers the first systematic test of application of schema therapy for adults with ASD. The results of this study will provide initial evidence for the effectiveness of schema therapy in treating adults with both ASD and PD(s). The study intends to provide valuable information for future development and implementation of therapeutic interventions for adults with both ASD and PD(s).

Keywords: adults, autism spectrum disorder, personality disorder, schema therapy

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Authors: Yusra Ibrahim

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Parental involvement in their children’s education and behavioral modification is important. This article provides a policy analysis that describes laws and public education regulations concerning justice-involved youth and youth at risk of delinquency in the United Arab Emirates. The article aims to clarify the UAE laws for parents and guardians regarding their involvement in addressing school violations and crimes committed by their children, particularly those with emotional and behavioral disorders, youths at risk for delinquency, and justice-involved youths. The article concludes with implications for parents, policymakers, and educators and suggests ways to improve services and support for these parents and their youth.

Keywords: justice-involved youth, parents, incarceration, incarcerated youth, United Arab Emirates.

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Authors: Elena E. Lyakso, Olga V. Frolova, Yuri N. Matveev, Aleksey S. Grigorev, Alexander S. Nikolaev, Viktor A. Gorodnyi

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The study of the children’s emotional sphere depending on age and psychoneurological state is of great importance for the design of educational programs for children and their social adaptation. Atypical development may be accompanied by violations or specificities of the emotional sphere. To study characteristics of the emotional state reflection in the voice and speech features of children, the perceptual study with the participation of adults and the automatic recognition of speech were conducted. Speech of children with typical development (TD), with Down syndrome (DS), and with autism spectrum disorders (ASD) aged 6-12 years was recorded. To obtain emotional speech in children, model situations were created, including a dialogue between the child and the experimenter containing questions that can cause various emotional states in the child and playing with a standard set of toys. The questions and toys were selected, taking into account the child’s age, developmental characteristics, and speech skills. For the perceptual experiment by adults, test sequences containing speech material of 30 children: TD, DS, and ASD were created. The listeners were 100 adults (age 19.3 ± 2.3 years). The listeners were tasked with determining the children’s emotional state as “comfort – neutral – discomfort” while listening to the test material. Spectrographic analysis of speech signals was conducted. For automatic recognition of the emotional state, 6594 speech files containing speech material of children were prepared. Automatic recognition of three states, “comfort – neutral – discomfort,” was performed using automatically extracted from the set of acoustic features - the Geneva Minimalistic Acoustic Parameter Set (GeMAPS) and the extended Geneva Minimalistic Acoustic Parameter Set (eGeMAPS). The results showed that the emotional state is worse determined by the speech of TD children (comfort – 58% of correct answers, discomfort – 56%). Listeners better recognized discomfort in children with ASD and DS (78% of answers) than comfort (70% and 67%, respectively, for children with DS and ASD). The neutral state is better recognized by the speech of children with ASD (67%) than by the speech of children with DS (52%) and TD children (54%). According to the automatic recognition data using the acoustic feature set GeMAPSv01b, the accuracy of automatic recognition of emotional states for children with ASD is 0.687; children with DS – 0.725; TD children – 0.641. When using the acoustic feature set eGeMAPSv01b, the accuracy of automatic recognition of emotional states for children with ASD is 0.671; children with DS – 0.717; TD children – 0.631. The use of different models showed similar results, with better recognition of emotional states by the speech of children with DS than by the speech of children with ASD. The state of comfort is automatically determined better by the speech of TD children (precision – 0.546) and children with ASD (0.523), discomfort – children with DS (0.504). The data on the specificities of recognition by adults of the children’s emotional state by their speech may be used in recruitment for working with children with atypical development. Automatic recognition data can be used to create alternative communication systems and automatic human-computer interfaces for social-emotional learning. Acknowledgment: This work was financially supported by the Russian Science Foundation (project 18-18-00063).

Keywords: autism spectrum disorders, automatic recognition of speech, child’s emotional speech, Down syndrome, perceptual experiment

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Authors: Sangram A. Sathe, Neha A. Madgulkar, Shruti S. Raut, S. P. Wadkar

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Transforaminal lumbar interbody fusion (TLIF) surgeries have nowadays became popular for treatment of degenerated spinal disorders. The interbody fusion technique like TLIF maintains load bearing capacity of the spine and a suitable disc height. Currently many techniques have been introduced to cure Spondylolisthesis. This surgery provides greater rehabilitation of degenerative spines. While performing this TLIF surgery existing methods use guideway, which is a troublesome surgery technique as the use of two separate instruments is required to perform this surgery. This paper presents a concept which eliminates the use of guideway. This concept also eliminates problems that occur like reverting the cage. The concept discussed in this paper also gives high accuracy while performing surgery.

Keywords: TLIF, spondylolisthesis, spine, instruments

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Authors: Mohamed Thani Ibouroi, Ali Cheha, Claudine Montgelard, Veronique Arnal, Dawiyat Massoudi, Guillelme Astruc, Said Ali Ousseni Dhurham, Aurelien Besnard

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The Livingstone's flying fox (Pteropus livingstonii) and the Comorian fruit bat (P.seychellensis comorensis) are two endemic fruit bat species among the mostly threatened animals of the Comoros archipelagos. Despite their role as important ecosystem service providers like all flying fox species as pollinators and seed dispersers, little is known about their ecologies, population genetics and structures making difficult the development of evidence-based conservation strategies. In this study, we assess spatial distribution and ecological niche of both species using Species Distribution Modeling (SDM) based on the recent Ensemble of Small Models (ESMs) approach using presence-only data. Population structure and genetic diversity of the two species were assessed using both mitochondrial and microsatellite markers based on non-invasive genetic samples. Our ESMs highlight a clear niche partitioning of the two sympatric species. Livingstone’s flying fox has a very limited distribution, restricted on steep slope of natural forests at high elevation. On the contrary, the Comorian fruit bat has a relatively large geographic range spread over low elevations in farmlands and villages. Our genetic analysis shows a low genetic diversity for both fruit bats species. They also show that the Livingstone’s flying fox population of the two islands were genetically isolated while no evidence of genetic differentiation was detected for the Comorian fruit bats between islands. Our results support the idea that natural habitat loss, especially the natural forest loss and fragmentation are the important factors impacting the distribution of the Livingstone’s flying fox by limiting its foraging area and reducing its potential roosting sites. On the contrary, the Comorian fruit bats seem to be favored by human activities probably because its diets are less specialized. By this study, we concluded that the Livingstone’s flying fox species and its habitat are of high priority in term of conservation at the Comoros archipelagos scale.

Keywords: Comoros islands, ecological niche, habitat loss, population genetics, fruit bats, conservation biology

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Authors: Georgia Saxami, Evangelia N. Kerezoudi, Evdokia K. Mitsou, Marigoula Vlassopoulou, Georgios Zervakis, Adamantini Kyriacou

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Autism Spectrum Disorder (ASD) is a complex group of developmental disorders of the brain, characterized by social and communication dysfunctions, stereotypes and repetitive behaviors. The potential interaction between gut microbiota (GM) and autism has not been fully elucidated. Children with autism often suffer gastrointestinal dysfunctions, while alterations or dysbiosis of GM have also been observed. Treatment with dietary components has been postulated to regulate GM and improve gastrointestinal symptoms, but there is a lack of evidence for such approaches in autism, especially for prebiotics. This study assessed the effects of Pleurotus eryngii mushroom (candidate prebiotic) and inulin (known prebiotic compound) on gut microbial composition, using faecal samples from autistic children in an in vitro batch culture fermentation system. Selected members of GM were enumerated at baseline (0 h) and after 24 h fermentation by quantitative PCR. After 24 h fermentation, inulin and P. eryngii mushroom induced a significant increase in total bacteria and Faecalibacterium prausnitzii compared to the negative control (gut microbiota of each autistic donor with no carbohydrate source), whereas both treatments induced a significant increase in levels of total bacteria, Bifidobacterium spp. and Prevotella spp. compared to baseline (t=0h) (p for all <0.05). Furthermore, this study evaluated the impact of fermentation supernatants (FSs), derived from P. eryngii mushroom or inulin, on the expression levels of tight junctions’ genes (zonulin-1, occludin and claudin-1) in Caco-2 cells stimulated by bacterial lipopolysaccharides (LPS). Pre-incubation of Caco-2 cells with FS from P. eryngii mushroom led to a significant increase in the expression levels of zonulin-1, occludin and claudin-1 genes compared to the untreated cells, the cells that were subjected to LPS and the cells that were challenged with FS from negative control (p for all <0.05). In addition, incubation with FS from P. eryngii mushroom led to the highest mean expression values for zonulin-1 and claudin-1 genes, which differed significantly compared to inulin (p for all <0.05). Overall, this research highlighted the beneficial in vitro effects of P. eryngii mushroom on the composition of GM of autistic children after 24 h of fermentation. Also, our data highlighted the potential preventive effect of P. eryngii FSs against dysregulation of the intestinal barrier, through upregulation of tight junctions’ genes associated with the integrity and function of the intestinal barrier. This research has been financed by "Supporting Researchers with Emphasis on Young Researchers - Round B", Operational Program "Human Resource Development, Education and Lifelong Learning."

Keywords: gut microbiota, intestinal barrier, autism spectrum disorders, Pleurotus Eryngii

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Authors: Garima Joshi, Ashima N. Wadhawan

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Neuropsychology in India is a fairly new field, having started only four decades back. Neuropsychology has come a long way since the establishment of the first department, from using western batteries for assessing patients to the development of highly reliable indigenous tools for assessing neuropsychological functioning. Clinical neuropsychology has risen as a discipline in the field of assessing and rehabilitating patients with various neurological conditions such as Traumatic Brain Injury, Stroke, Mild Cognitive Impairment, Alzheimer’s, Schizophrenia and other disorders with cognitive decline. The current review attempts to assimilate the history of the discipline in India, along with the current developments and future direction of the field and highlights the pursuit and undertakings of the scientists to provide culturally appropriate services, in terms of assessment and rehabilitation, to the Indian population.

Keywords: clinical neuropsychology, cognitive assessment, cognitive rehabilitation, neuropsychological test batteries in India

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Authors: J. Manuel Bello-López, Julieta Rojo-Medina

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Introduction: The transplant of Umbilical Cord Blood Units (UCBU) are a therapeutic possibility for patients with oncohaematological disorders, especially in children. In Mexico, 48.5% of oncological diseases in children 1-4 years old are leukemias; whereas in patients 5-14 and 15-24 years old, lymphomas and leukemias represent the second and third cause of death in these groups respectively. Therefore it is necessary to have more registries of UCBU in order to ensure genetic diversity in the country; the above because the search for appropriate a UCBU is increasingly difficult for patients of mixed ethnicity. Objective: To estimate the genetic diversity (polymorphisms) of Human Leucocyte Antigen (HLA) Class I (A, B) and Class II (DRB1) in UCBU cryopreserved for transplant at Cord Blood Bank of the NCBT. Material and Methods: HLA typing of 533 UCBU for transplant was performed from 2003-2012 at the Histocompatibility Laboratory from the Research Department (evaluated by Los Angeles Ca. Immunogenetics Center) of the NCBT. Class I HLA-A, HLA-B and Class II HLA-DRB1 typing was performed using medium resolution Sequence-Specific Primer (SSP). In cases of an ambiguity detected by SSP; Sequence-Specific Oligonucleotide (SSO) method was carried out. A strict analysis of populations genetic parameters were done in 5 representative UCBU populations. Results: 46.5% of UCBU were collected from Mexico City, State of Mexico (30.95%), Puebla (8.06%), Morelos (6.37%) and Veracruz (3.37%). The remaining UCBU (4.75%) are represented by other states. The identified genotypes correspond to Amerindian origins (HLA-A*02, 31; HLA-B*39, 15, 48), Caucasian (HLA-A*02, 68, 01, 30, 31; HLA-B*35, 15, 40, 44, 07 y HLA-DRB1*04, 08, 07, 15, 03, 14), Oriental (HLA-A*02, 30, 01, 31; HLA-B* 35, 39, 15, 40, 44, 07,48 y HLA-DRB1*04, 07,15, 03) and African (HLA-A*30 y HLA-DRB1*03). The genetic distances obtained by Cavalli-Sforza analysis of the five states showed significant genetic differences by comparing genetic frequencies. The shortest genetic distance exists between Mexico City and the state of Puebla (0.0039) and the largest between Veracruz and Morelos (0.0084). In order to identify significant differences between this states, the ANOVA test was performed. This demonstrates that UCBU is significantly different according to their origin (P <0.05). This is shown by the divergence between arms at the Dendogram of Neighbor-Joining. Conclusions: The NCBT provides UCBU in patients with oncohaematological disorders in all the country. There is a group of patients for which not compatible UCBU can be find due to the mixed ethnic origin. For example, the population of northern Mexico is mostly Caucasian. Most of the NCBT donors are of various ethnic origins, predominantly Amerindians and Caucasians; although some ethnic minorities like Oriental, African and pure Indian ethnics are not represented. The NCBT is, therefore, establishing agreements with different states of Mexico to promote the altruistic donation of Umbilical Cord Blood in order to enrich the genetic diversity in its files.

Keywords: cord blood, genetic diversity, human leucocyte antigen, transplant

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