Search results for: muscle atrophy

Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

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Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.

Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance

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Authors: Jelena Maletkovic

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Background: Endogenous Cushing’s syndrome is a rare disease, but iatrogenic or drug related Cushing syndrome from glucocorticoid products is commonly seen in clinical practice. With high dose and long term use of glucocorticoids, patients can develop isolated hypothalamic-pituitary-adrenal (HPA) suppression, or HPA axis suppression can be accompanied by overt iatrogenic Cushing’s syndrome. This is a rare case where severe Cushing’s syndrome developed from an unknown medication and was followed by severe and prolonged adrenal insufficiency and multiple potentially fatal complications. Case: This is a 37-year-old woman who is presented to Emergency Room (ER) with shortness of breath and chest pain. Four months prior to this presentation the patient was a generally healthy woman who was looking for improvement in her appearance and visited local Rejuvenation Clinic. After initial consultation with a nurse, she was contacted by a physician over the phone and was advised to start taking multiple injectable medications that will arrive by mail. Medications without any labels on bottles were delivered and the patient started daily intramuscular injections. Over the next two months, she noticed rounding of her face and swelling around her eyes. She gained 20 pounds, mostly abdominal fat and became extremely fatigued. Her muscles on legs were visibly decreasing in size and she felt significant muscle weakness. Unexplained bruising occurred. She started growing hair on face and developed secondary amenorrhea. New severe back pain started. She developed depression and headaches. Finally, over a few days, a number of red-purple stretch marks that were sensitive and painful appeared over her abdomen, upper part of arms and legs. She then became suspicious that these dramatic symptoms are caused by injectable medication and she discontinued injections. Over the next few days she presented to ER with low blood pressure and oxygen saturation of 75%. Studies revealed extensive pneumonia as well as multiple pulmonary emboli. Her white blood count was elevated with 32 000 and she also had acute kidney failure on admission. She was treated for sepsis and was also given stress dose steroids. Steroids were tapered over 48 hours and discontinued. After being discharged to home, on her first visit to endocrinology clinic she had undetectable ACTH of < 2pg/mL and undetectable 8am cortisol of < 0.2mcg/dL. She did not respond to an intramuscular injection of cosyntropin 250mcg and her repeated cortisol after 60 minutes was only 1mcg/dL. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone 20mg+10mg. It took close to 2 years of slow tapering for recovery of this patient’s HPA axis and resolve all the sequelae from Cushing’s syndrome. Conclusion: Misuse and abuse of glucocorticoids have been present almost since these medications were discovered. This is a rare case where not only severe Cushing’s syndrome in full clinical picture developed but also the patient suffered multiple potentially fatal complications and prolonged adrenal insufficiency. Visits to herbal, rejuvenation, esthetic, and similar clinics are becoming more and more popular and physicians need to be aware of possible non-benign nature of medications that their patients may be using.

Keywords: iatrogenic, Cushing's syndrome, adrenal crisis, steroid abuse

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Authors: Ikele Chika Bright, Mgbenka Bernard Obialo, Ikele Chioma Faith

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Icthyophthiriasis is a prevalent protozoan (ectoparasite) mostly affecting cultured and aquarium fishes. The majority of the chemotherapeutants lack efficacy for completely eliminating Ich parasite without affecting the environment and they are not safe for human health. The present work is focused on the evaluating different immersion treatments of African catfish (Clarias gariepinus) infected with ichthyophthiriasis and treated with a non-chemical and environmental friendly parasiticides Moringa oleifera. A total number of 800 apparently healthy parasites free (examined) post juvenile catfish were obtained from a reputable farm, disinfected with potassium permanganate in a quarantine tank to remove any possible external parasites. The fish were further challenged with approximately 44,000 infective stages of theronts which were obtained through serial passages by cohabitation. Seven groups (A-G) of post Juvenile were used for the experiment which was carried out into three stages; Dips (60minutes), short term treatment (24-96h) and prolong bath treatment (0-15 days). The concentrations selected were dependent on the outcome of the LC50 of the plant material from which dose-dependent factors were used to select various concentrations of the treatment. In Dips treatment, group D-G were treated with 1,500mg/L, 2500mg/L., 3500mg/L and 4500mg/L, short-term treatment was treated with 150mg/L, 250mg/L, 350mg/L and 450mg/L and prolong bath was treated with 15mg/L, 25mg/L, 35mg/L and 45mg/L of the plant extract whereas group A, B and C were normal control, Ich- infested not treated and Ich- infested treated with standard drug (Acriflavin), respectively. The various types of treatment applied with corresponding concentrations showed almost complete elimination of the adult parasites (trophonts) both in the gills and the body smear, thereby making M. oleifera a potential parasiticides. There were serious pathological alterations in the skin and gills which are usually the main point for Ich parasites invasion but no significant morphological characteristics was noted among the treated groups subjected to different immersion treatment patterns. Epitheliocystis, aneurysm, oedema, hemorrhage, and localization of the adult parasite in the gills were the overall common observations made in the gills whereas degeneration of muscle fibre, dermatitis, hemorrhage, oedema, abscess formation and keratinisation were observed in the skin. However, there are no pathological changes in the control group. Moreover, biochemical parameters such as urea, creatinine, albumin., globulin, total protein, ALT, AST), blood chemistry (sodium, chloride, potassium, bicarbonate), antioxidants (CAT, SOD, GPx, LPO), enzymatic activities (myeloperoxidase, thioreadoxin reductase), Inflammatory response (C-reactive protein), Stress markers (lactate dehydrogenase), heamatological parameters (RBC, PCV, WBC, HB and differential count), lipid profile (total cholesterol, tryglycerides , high density lipoprotein and low density lipoprotein) all showed various significant (P<0.05) and no significant (P>0.05) responses among the Ich-infested fish treated under three immersion treatments. It is suggested that M. oleifera may serve as an alternatives to chemotherapeutants for control of Ichthyophthiriasis in African catfish Clarias gariepinus.

Keywords: Icthyophthirius multifilis, immersion treatment, pathophysiology, African catfish

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

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

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

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Siti Rahayu, Khairulniza Mohd Puat, Kesavan R., Mohammad Harris A., Jalila, Kunalan G., Fazir Mohamad

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The greatest challenge has been in establishing and maintaining the dedicated nursing team. Continuity is served when nurses are assigned exclusively for managing wound, where they can continue to build expertise and skills. In addition, there is a growing incidence of chronic wounds and recognition of the complexity involved in caring for these patients. We would like to share 4 cases with different techniques of wound management. 1st case, 39 years old gentleman with underlying rheumatoid arthritis with chronic periprosthetic joint infection of right total knee replacement presented with persistent drainage over right knee. Patient was consulted for two stage revision total knee replacement. However, patient only agreed for debridement and retention of implant. After debridement, large medial and lateral wound was treated with Instillation Negative Pressure Wound Therapy Dressings. After several cycle, the wound size reduced, and conventional dressing was applied. 2nd case, 58 years old gentleman with underlying diabetes presented with right foot necrotizing fasciitis with gangrene of 5th toe. He underwent extensive debridement of foot with rays’ amputation of 5th toe. Post debridement patient was started on Instillation Negative Pressure Wound Therapy Dressings. After several cycle of VAC, the wound bed was prepared, and he underwent split skin graft over right foot. 3 rd case, 60 years old gentleman with underlying diabetes mellitus presented with right foot necrotizing soft tissue infection. He underwent rays’ amputation and extensive wound debridement. Upon stabilization of general condition, patient was discharge with regular wound dressing by same nurse and doctor during each visit to clinic follow up. After 6 months of follow up, the wound healed well. 4th case, 38-year-old gentleman had alleged motor vehicle accident and sustained closed fracture right tibial plateau. Open reduction and proximal tibial locking plate were done. At 2 weeks post-surgery, the patient presented with warm, erythematous leg and pus discharge from the surgical site. Empirical antibiotic was started, and wound debridement was done. Intraoperatively, 50cc pus was evacuated, unhealthy muscle and tissue debrided. No loosening of the implant. Patient underwent multiple wound debridement. At 2 weeks post debridement wound healed well, but the proximal aspect was unable to close immediately. This left the proximal part of the implant to be exposed. Patient was then put on VAC dressing for 3 weeks until healthy granulation tissue closes the implant. Meanwhile, antibiotic was change according to culture and sensitivity. At 6 weeks post the first debridement, the wound was completely close, and patient was discharge home well. At 3 months post operatively, patient wound and fracture healed uneventfully and able to ambulate independently. Complex wounds are too serious to be dealt with. Team managing complex wound need continuous support through the provision of educational tools to support their professional development, engagement with local and international expert, as well as highquality products that increase efficiencies in services

Keywords: VAC (Vacuum Assisted Closure), empirical- initial antibiotics, NPWT- negative pressure wound therapy, NF- necrotizing fasciitis, gangrene- blackish discoloration due to poor blood supply

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Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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Authors: J. van Soest, B. Bruneel, J. Smit, N. Williams, P. Swiegers

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Selenium (Se) is an essential trace mineral involved in reducing oxidative stress, enhancing immune status, improving reproduction, and regulating growth. During finishing period, selenium supplementation can be applied to improve meat quality. Dietary selenium can be provided in inorganic or organic forms. Specifically, L-selenomethionine (organic selenium) allows for selenium storage in animal protein which supports the animal during periods of high oxidative stress. The objective of this study was to investigate the effects of synthetically produced, single amino acid, L-selenomethionine (Excential Selenium 4000, Orffa Additives BV) on production parameters, health status, and meat quality of Bonsmara bull calves. 24 calves, 7 months of age, completed a 60-day initial growing period at a commercial feedlot, after which they were transported to research station Rumen-8 (Bethlehem, South-Africa). After a ten-day adaptation period, the bulls were allocated to a control (n=12) or treatment (n=12) group. Each group was divided over 3 pens based on weight. Both groups received Total Mixed Ration supplemented with 5.25 mg Se/head per day. The control group was supplemented with sodium selenite as Se source, whilst the treatment group was supplemented with L-selenomethionine (Excential Selenium 4000, Orffa Additives BV). Animals were limited to 10 kg feed intake per head per day to ensure similar Se intake. Treatment period lasted 1.5 months. A beta-adrenergic agonist was included in the feed for the last 30 days. During the treatment period, average daily gain, average daily feed intake, and feed conversion ratio were recorded. Blood parameters were measured at day 1, day 25, and before slaughter (day 47). After slaughter, carcass weight, dressing percentage, grading, and meat quality (pH, tenderness, colour, odour, purge, proximate analyses, acid detergent fibre, and neutral detergent fibre) were determined. No differences between groups were found in performance. A higher number of animals with cortisol levels below detection limit (27.6 nmol/l) was recorded for the treatment group. Other blood parameters showed no differences. No differences were found regarding carcass weight and dressing percentage. Important parameters of meat quality were significantly improved in the treatment group: instrumental tenderness at 14 days ageing was 2.8 and 3.4 for treatment and control respectively (P=0.010), and a 0.5% decrease in purge (of fresh samples) was shown, 1.5% and 2.0% for treatment group and control respectively (p=0.029). Besides, pH was shown to be numerically reduced in the treatment group. In summary, supplementation with L-selenomethionine as selenium source improved meat quality compared to sodium selenite. Lower instrumental tenderness (Warner Bratzler Shear Force, WBSF) was recorded for the treatment group. This indicates less tough meat and highest consumer satisfaction. Regarding purge, control was just below 2.0%, an important threshold for consumer acceptation. Treatment group scored 0.5% lower for purge than control, indicating higher consumer satisfaction. The lower pH in the treatment group could be an indication of higher glycogen reserves in muscle which could contribute to a reduced risk of Dark Firm Dry carcasses. More animals showed cortisol levels below detection limit in the treatment group, indicating lower levels of stress when animals receive L-selenomethionine.

Keywords: calves, meat quality, nutrition, selenium

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Authors: Mian Huang, Chi Ma, Junyu Lin, William Lu

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Introduction: Bone health attracts more attention recently and an intelligent question and answer (QA) chatbot for osteoporosis is helpful for science popularization. With Generative Pretrained Transformer (GPT) technology developing, we build an osteoporosis corpus dataset and then fine-tune LLaMA, a famous open-source GPT foundation large language model(LLM), on our self-constructed osteoporosis corpus. Evaluated by clinical orthopedic experts, our fine-tuned model outperforms vanilla LLaMA on osteoporosis QA task in Chinese. Three-dimensional quantitative computed tomography (QCT) measured bone mineral density (BMD) is considered as more accurate than DXA for BMD measurement in recent years. We develop an automatic Phantom-less QCT(PL-QCT) that is more efficient for BMD measurement since no need of an external phantom for calibration. Combined with LLM on osteoporosis, our PL-QCT provides efficient and accurate BMD measurement for our chatbot users. Material and Methods: We build an osteoporosis corpus containing about 30,000 Chinese literatures whose titles are related to osteoporosis. The whole process is done automatically, including crawling literatures in .pdf format, localizing text/figure/table region by layout segmentation algorithm and recognizing text by OCR algorithm. We train our model by continuous pre-training with Low-rank Adaptation (LoRA, rank=10) technology to adapt LLaMA-7B model to osteoporosis domain, whose basic principle is to mask the next word in the text and make the model predict that word. The loss function is defined as cross-entropy between the predicted and ground-truth word. Experiment is implemented on single NVIDIA A800 GPU for 15 days. Our automatic PL-QCT BMD measurement adopt AI-associated region-of-interest (ROI) generation algorithm for localizing vertebrae-parallel cylinder in cancellous bone. Due to no phantom for BMD calibration, we calculate ROI BMD by CT-BMD of personal muscle and fat. Results & Discussion: Clinical orthopaedic experts are invited to design 5 osteoporosis questions in Chinese, evaluating performance of vanilla LLaMA and our fine-tuned model. Our model outperforms LLaMA on over 80% of these questions, understanding ‘Expert Consensus on Osteoporosis’, ‘QCT for osteoporosis diagnosis’ and ‘Effect of age on osteoporosis’. Detailed results are shown in appendix. Future work may be done by training a larger LLM on the whole orthopaedics with more high-quality domain data, or a multi-modal GPT combining and understanding X-ray and medical text for orthopaedic computer-aided-diagnosis. However, GPT model gives unexpected outputs sometimes, such as repetitive text or seemingly normal but wrong answer (called ‘hallucination’). Even though GPT give correct answers, it cannot be considered as valid clinical diagnoses instead of clinical doctors. The PL-QCT BMD system provided by Bone’s QCT(Bone’s Technology(Shenzhen) Limited) achieves 0.1448mg/cm2(spine) and 0.0002 mg/cm2(hip) mean absolute error(MAE) and linear correlation coefficient R2=0.9970(spine) and R2=0.9991(hip)(compared to QCT-Pro(Mindways)) on 155 patients in three-center clinical trial in Guangzhou, China. Conclusion: This study builds a Chinese osteoporosis corpus and develops a fine-tuned and domain-adapted LLM as well as a PL-QCT BMD measurement system. Our fine-tuned GPT model shows better capability than LLaMA model on most testing questions on osteoporosis. Combined with our PL-QCT BMD system, we are looking forward to providing science popularization and early morning screening for potential osteoporotic patients.

Keywords: GPT, phantom-less QCT, large language model, osteoporosis

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Authors: Victoria L. Chester, Usha Kuruganti

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The forest industry is a major economic sector of Canada and also one of the most dangerous industries for workers. The use of mechanized mobile forestry harvesting machines has successfully reduced the incidence of injuries in forest workers related to manual labor. However, these machines have also created additional concerns, including a high machine operation learning curve, increased the length of the workday, repetitive strain injury, cognitive load, physical and mental fatigue, and increased postural loads due to sitting in a confined space. It is critical to obtain objective performance data for employers to develop appropriate work practices for this industry, however ergonomic field studies of this industry are lacking mainly due to the difficulties in obtaining comprehensive data while operators are cutting trees in the woods. The purpose of this study was to establish a measurement and experimental protocol to examine the effects of worker skill level and movement training speed (joystick crane speed) on harvesting performance using a forestry simulator. A custom wrist angle measurement device was developed as part of the study to monitor Euler angles during operation of the simulator. The device of the system consisted of two accelerometers, a Bluetooth module, three 3V coin cells, a microcontroller, a voltage regulator and an application software. Harvesting performance and crane data was provided by the simulator software and included tree to frame collisions, crane to tree collisions, boom tip distance, number of trees cut, etc. A pilot study of 3 operators with various skill levels was tested to identify factors that distinguish highly skilled operators from novice or intermediate operators. Dependent variables such as reaction time, math skill, past work experience, training movement speed (e.g. joystick control speeds), harvesting experience level, muscle activity, and wrist biomechanics were measured and analyzed. A 10-channel wireless surface EMG system was used to monitor the amplitude and mean frequency of 10 upper extremity muscles during pre and postperformance on the forestry harvest stimulator. The results of the pilot study showed inconsistent changes in median frequency pre-and postoperation, but there was the increase in the activity of the flexor carpi radialis, anterior deltoid and upper trapezius of both arms. The wrist sensor results indicated that wrist supination and pronation occurred more than flexion and extension with radial-ulnar rotation demonstrating the least movement. Overall, wrist angular motion increased as the crane speed increased from slow to fast. Further data collection is needed and will help industry partners determine those factors that separate skill levels of operators, identify optimal training speeds, and determine the length of training required to bring new operators to an efficient skill level effectively. In addition to effective and employment training programs, results of this work will be used for selective employee recruitment strategies to improve employee retention after training. Further, improved training procedures and knowledge of the physical and mental demands on workers will lead to highly trained and efficient personnel, reduced risk of injury, and optimal work protocols.

Keywords: EMG, forestry, human factors, wrist biomechanics

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Authors: Surbhi Kaura, Sachin Kandhari, Shahiduz Zafar

Abstract:

Chronic stroke, characterized by persistent motor deficits, often necessitates comprehensive rehabilitation interventions to improve functional outcomes and mitigate long-term dependency. Luna neurorobotic devices, integrated with EMG feedback systems, provide an innovative platform for facilitating neuroplasticity and functional improvement in stroke survivors. This retrospective study aims to investigate the impact of EMG-based Luna neurorobotic interventions on the strengthening of the affected side in chronic stroke patients. In rehabilitation, active patient participation significantly activates the sensorimotor network during motor control, unlike passive movement. Stroke is a debilitating condition that, when not effectively treated, can result in significant deficits and lifelong dependency. Common issues like neglecting the use of limbs can lead to weakness in chronic stroke cases. In rehabilitation, active patient participation significantly activates the sensorimotor network during motor control, unlike passive movement. This study aims to assess how electromyographic triggering (EMG-triggered) robotic treatments affect walking, ankle muscle force after an ischemic stroke, and the coactivation of agonist and antagonist muscles, which contributes to neuroplasticity with the assistance of biofeedback using robotics. Methods: The study utilized robotic techniques based on electromyography (EMG) for daily rehabilitation in long-term stroke patients, offering feedback and monitoring progress. Each patient received one session per day for two weeks, with the intervention group undergoing 45 minutes of robot-assisted training and exercise at the hospital, while the control group performed exercises at home. Eight participants with impaired motor function and gait after stroke were involved in the study. EMG-based biofeedback exercises were administered through the LUNA neuro-robotic machine, progressing from trigger and release mode to trigger and hold, and later transitioning to dynamic mode. Assessments were conducted at baseline and after two weeks, including the Timed Up and Go (TUG) test, a 10-meter walk test (10m), Berg Balance Scale (BBG), and gait parameters like cadence, step length, upper limb strength measured by EMG threshold in microvolts, and force in Newton meters. Results: The study utilized a scale to assess motor strength and balance, illustrating the benefits of EMG-biofeedback following LUNA robotic therapy. In the analysis of the left hemiparetic group, an increase in strength post-rehabilitation was observed. The pre-TUG mean value was 72.4, which decreased to 42.4 ± 0.03880133 seconds post-rehabilitation, with a significant difference indicated by a p-value below 0.05, reflecting a reduced task completion time. Similarly, in the force-based task, the pre-knee dynamic force in Newton meters was 18.2NM, which increased to 31.26NM during knee extension post-rehabilitation. The post-student t-test showed a p-value of 0.026, signifying a significant difference. This indicated an increase in the strength of knee extensor muscles after LUNA robotic rehabilitation. Lastly, at baseline, the EMG value for ankle dorsiflexion was 5.11 (µV), which increased to 43.4 ± 0.06 µV post-rehabilitation, signifying an increase in the threshold and the patient's ability to generate more motor units during left ankle dorsiflexion. Conclusion: This study aimed to evaluate the impact of EMG and dynamic force-based rehabilitation devices on walking and strength of the affected side in chronic stroke patients without nominal data comparisons among stroke patients. Additionally, it provides insights into the inclusion of EMG-triggered neurorehabilitation robots in the daily rehabilitation of patients.

Keywords: neurorehabilitation, robotic therapy, stroke, strength, paralysis

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