Mild traumatic brain injury (mTBI) accounts for 70-90% of all diagnosed traumatic brain injuries (TBI) affecting approximately 50-300 per 100.000 individuals annually. Persistent post-concussion symptoms are reported in 15-80% of hospital admitted and outpatient treated populations, affecting labour market attachment, academic achievement, income, socio-economic status, social interactions, home management, leisure activities and cohabitation status.
The association between mTBI and long-term trends in cohabitation status, income, academic achievement and socio-economic status has not been thoroughly explored. Previous studies focus on children's academic performance after severe TBI and only few studies include early adulthood and patients with mTBI. Trends in divorce rates are frequently conducted on severe injuries or populations consisting of veterans. Additionally, all studies have failed to apply a national register based design.
Aim The aim of the study is to examine the long-term associations between mTBI and trends in cohabitation status, academic achievement and socio-economic status between pre-injury rates and observed rates at 5 years post-injury. The hypothesis was that by 5 years mTBI would be associated with increased odds of marital breakdown, decreasing academic achievement, decreasing income, decreasing socio-economic status compared to the general population in Denmark.
Methods:
The study is a national register based cohort study with 5 years follow-up of patients with mild traumatic brain injury from 2008 - 2012 in Denmark.
Population:
Patients between 18-60 years diagnosed with concussion (ICD-10 S06.0) were extracted from the Danish National Patient Register between (2003-2007). Patients with major neurological injuries and previous concussions at the index date and 5 years before the index date (1998-2007) were excluded. Patients who were not resident in Denmark 5 years before and during the inclusion period were also excluded (1998-2007).
Data will be retrieved from several national databases, including: the Danish national patient register, Danish Civil Registration System (CRS), the Danish Education Registers, the Income Statistics Register and the Employment Classification Module (AKM).
One control of the general population were matched for each case on sex, age and municipality.
Outcome measures are: Cohabitation status, Education, income and socio-economic status.

Start Date20 Sep 2018

Sponsor / Collaborator

University of Copenhagen

[+1]

NCT02134041 / Unknown statusNot ApplicableIIT

Observational Study for Amyloid Accumulation After Mild Traumatic Brain

We are extending the researches of Taiwan neurosurgery traumatic brain injury (TBI) database which is led by Professor WT Chiu in Taipei Medical University and will recruit mild TBI (mTBI) participants who have ever been registered in the database. This database has been established for over 15 years and contains the information of over 150000 patients. It is one of the largest TBI database in the world.
TBI usually results from traffic accidents, falls or violence events. Most of the victims are young people and the victims suffer from life-threatening and mental-physical deficits. Mild TBI (mTBI) usually was neglected before because its symptoms, signs are mild and mTBI patients usually were not obtained enough initial treatment. Therefore, mTBI might result in long-term cognitive and affective impairments, such as depression, indifference, anxiety, memory impairment, loss of attention and executive function. These late effects not only decrease the life quality of patients and their family but also increase the social and medical burden.
Recent epidemiology studies have pointed out that TBI would increase the risk for dementia, especially Alzheimer disease (AD) by 2-4 times. However, the association between TBI severity, number of repeats, genetic factors and onset of AD remains further investigation.
Amyloid-β (Aβ) plaques and neurofibrillary tangles are the pathological hallmarks for AD. Accumulation of Aβ is considered to be the first step of pathophysilogy of AD. Compelling researches have supported TBI accelerates the formation and accumulation of Aβ. These findings could link TBI with AD but the previous researches had limitations. There was lack of mTBI pathology data so the impacts of mTBI on Aβ accumulation were still obscure. By amyloid-PET, we could study the effects of mTBI on the accumulation of Aβ and this tool could be helpful for understanding the real impacts and pathophysiological mechanisms of mTBI on AD.

Start Date01 Oct 2012

Sponsor / Collaborator

Taipei Medical University

[+1]

CTRI/2012/02/002450 / CompletedNot Applicable

Double blind comparative randomized study to evaluate efficacy and safety of CP-010, Homeopathy drug as compare to Magnesium Phosphoricum in the management of sub-acute and chronic painful conditions.â?? - Nil

Start Date16 Feb 2012

Sponsor / Collaborator-

100 Clinical Results associated with C6 x Complement system proteins

100 Translational Medicine associated with C6 x Complement system proteins

0 Patents (Medical) associated with C6 x Complement system proteins

1,964

Literatures (Medical) associated with C6 x Complement system proteins

01 Jan 2025·Annals of Anatomy - Anatomischer Anzeiger

Revisiting the anatomy of the pectoral nerves and nerve loops of the brachial plexus in the goat (Capra hircus)

Article

Author: Kamali, Younes

BACKGROUNDThe anatomy of the pectoral nerves and the two nerve loops on the course of the axillary artery was revisited to complement current general descriptions as well as to argue whether the nerves contributing to the formation of the pectoral loop are the cranial pectoral nerves. Besides, the positional relationship between the scalene muscles and the nerve roots of the brachial plexus, which contribute to the nerves aimed in this study, was also examined at the same time as the dissection.METHODSTwenty brachial plexuses of 10 domestic adult goats (8 females and 2 males) were examined using gross dissection in this study.RESULTSIn many dissections (95 %), the last bundle of scalenus ventralis muscle was found to pass between the roots of C7 and C8, dividing the brachial plexus into the cranial (ventral) and caudal (dorsal) parts. Two pectoral nerves were noted to contribute to the formation of the first nerve loop around the axillary artery. The first pectoral nerve arose predominantly from the ventral branches of C6 and C7 in company with the n. musculocutaneus, while the second pectoral nerve arose directly from C8 in 70 % of the dissections or as the first branch of the n. thoracicus lateralis (C8, T1) in the remaining 30 %. After the nerve loop, the second pectoral nerve branched off to innervate the superficial surface of the m. pectoralis profundus toward its insertion. The m. subclavius was found to receive its innervation from several sources, including the ventral branches of the brachial plexus. Interestingly, in 4 of the 14 dissections a communication between the n. subclavius and the n. phrenicus heretofore not found in the animal anatomy literature was found. In 16 of the 20 dissections (60 %), the ramus muscularis proximalis of the n. musculocutaneus received the communicating branch(s) from the n. medianus at the site of the second nerve loop, ansa axillaris.CONCLUSIONThe second pectoral nerve contributing to the pectoral loop would be better described as the caudal pectoral nerve rather than the cranial pectoral nerve. Besides the evolutionary perspectives, understanding the findings of this study would be helpful for teaching veterinary anatomy.

01 Dec 2024·International Immunopharmacology

Amino acid metabolism-related genes as potential biomarkers and the role of MATN3 in stomach adenocarcinoma: A bioinformatics, mendelian randomization and experimental validation study

Article

Author: Zhu, Wenjun ; Fu, Min ; Yang, Feng ; Peng, Bi ; Chen, Ziqi ; Zhang, Qiang ; Li, Xiaoyu ; Hu, Guangyuan ; Liu, Yuanhui ; Zhang, Yuanyuan ; Luo, Na ; Tang, Wenhua ; Peng, Xiaohong ; Li, Qianxia ; Zhang, Yiling ; Zhang, Qing ; Chen, Xin

BACKGROUNDStomach adenocarcinoma (STAD) is a major contributor to cancer-related mortality worldwide. Alterations in amino acid metabolism, which is integral to protein synthesis, have been observed across various tumor types. However, the prognostic significance of amino acid metabolism-related genes in STAD remains underexplored.METHODSTranscriptomic gene expression and clinical data for STAD patients were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Amino acid metabolism-related gene sets were sourced from the Gene Set Enrichment Analysis (GSEA) database. A prognostic model was built using LASSO Cox regression based on the TCGA cohort and validated with GEO datasets (GSE84433, GSE84437, GSE84426). Kaplan-Meier analysis compared overall survival (OS) between high- and low-risk groups, and ROC curves assessed model accuracy. A nomogram predicted 1-, 3-, and 5-year survival. Copy number variations (CNVs) in model genes were visualized using data from the Xena platform, and mutation profiles were analyzed with "maftools" to create a waterfall plot. KEGG and GO enrichment analyses were performed to explore biological mechanisms. Immune infiltration and related functions were evaluated via ssGSEA, and Spearman correlation analyzed associations between risk scores and immune components. The TIDE database predicted immunotherapy efficacy, while FDA-approved drug sensitivity was assessed through CellMiner database. The role of MATN3 in STAD was further examined in vitro and in vivo, including amino acid-targeted metabolomic sequencing to assess its impact on metabolism. Finally, Mendelian randomization (MR) analysis evaluated the causal relationship between the model genes and gastric cancer.RESULTSIn this study, we developed a prognostic risk model for STAD based on three amino acid metabolism-related genes (SERPINE1, NRP1, MATN3) using LASSO regression analysis. CNV amplification was common in SERPINE1 and NRP1, while CNV deletion frequently occurred in MATN3. STAD patients were classified into high- and low-risk groups based on the median risk score, with the high-risk group showing worse prognosis. A nomogram incorporating the risk score and clinical factors was created to estimate 1-, 3-, and 5-year survival rates. Distinct mutation profiles were observed between risk groups, with KEGG pathway analysis showing immune-related pathways enriched in the high-risk group. High-risk scores were significantly associated with the C6 (TGF-β dominant) subtype, while low-risk scores correlated with the C4 (lymphocyte-depleted) subtype. Higher risk scores also indicated increased immune infiltration, enhanced immune functions, lower tumor purity, and poorer immunotherapy response. Model genes were linked to anticancer drug sensitivity. Manipulating MATN3 expression showed that it promoted STAD cell proliferation and migration in vitro and tumor growth in vivo. Metabolomic sequencing revealed that MATN3 knockdown elevated levels of 30 amino acid metabolites, including alpha-aminobutyric acid, glycine, and aspartic acid, while reducing (S)-β-Aminoisobutyric acid and argininosuccinic acid. MR analysis found a significant causal effect of NRP1 on gastric cancer, but no causal relationship for MATN3 or SERPINE1.CONCLUSIONIn conclusion, the amino acid metabolism-related prognostic model shows promise as a valuable biomarker for predicting the clinical prognosis, selecting immunotherapy and drug treatment for STAD patients. Furthermore, our study has shed light on the potential value of the MATN3 as a promising strategy for combating the progression of STAD.

01 Nov 2024·The Anatomical Record

Origin and distribution of the brachial plexus in red‐necked wallaby (Notamacropus rufogriseus, Marsupialia: Macropodidae)

Article

Author: Batur, Barış ; Yunus, Hasen Awel ; Bakıcı, Caner

AbstractNotamacropus rufogriseus (red‐necked wallaby) are in the family Macropodidae, which is the second largest family of marsupials after the family Didelphidae. This study was conducted with the aim of providing a detailed description of the origin and distribution of the brachial plexus in N. rufogriseus. Two‐year‐old male and 3‐year‐old female red‐necked wallabies were used for the study. The brachial plexus was formed by ventral rami of C4, C5, C6, C7, C8, and T1 spinal nerves. It is composed of three trunks that give rise to 12 principal nerves. The cranial trunk is formed by the combination of the rami C4–C7; the middle trunk is formed by the combination of the rami C6 and C7; and the caudal trunk is formed by the combination of the rami C8 and T1. Differences between left and right side of the plexus brachialis were not observed. C6 ventral spinal rami contribute the most to brachial plexus nerve formation, while C4 contributes the least. The formation and distribution of the plexus in N. rufogriseus exhibited more resemblance to the patterns observed in marsupial animals rather than placental mammals. Marsupial mammals demonstrate the involvement of C4 in the development of the brachial plexus. The formation and branching of the brachial plexus sequentially adapt in accordance with changes in their thoracic limb activities and innervation points. Anatomical data from brachial plexus studies optimizes thoracic limb clinical and surgical treatments. This work can provide baseline data for future marsupial brachial plexus studies and fill gaps in the scarce literature.

News (Medical) associated with C6 x Complement system proteins

04 Feb 2022

·www.biospace.com

UCB announces positive data in myasthenia gravis with zilucoplan phase 3 study results

UCB, a global biopharmaceutical company, today announced positive topline results from the RAISE (NCT04115293) triali evaluating its investigational treatment zilucoplan, a self-administered, subcutaneous (SC) peptide inhibitor of complement component 5 (C5 inhibitor), versus placebo in adults with generalized myasthenia gravis (gMG). The primary endpoint of the trial was met - a clinically meaningful and statistically significant improvement from baseline in Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 12 was observed for the zilucoplan treatment group vs placebo. All key secondary endpoints were also met, including statistically significant improvements from baseline in Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Composite (MGC) score and MG-QoL15r score at Week 12 for the zilucoplan treatment group vs placebo. The results show zilucoplan was well-tolerated and no major unexpected safety findings were identified compared to earlier zilucoplan studies. The incidence of serious treatment emergent adverse events (TEAEs) in the zilucoplan and placebo treatment arms was similar. The safety and efficacy of zilucoplan have not been established, and it is not approved for use in any indication by any regulatory authority worldwide. Based on these results, UCB plans to progress with regulatory filings for zilucoplan in gMG in the United States (US), European Union (EU) and Japan, beginning later this year. "gMG patients can experience varying and debilitating symptoms that impact their everyday lives in unique ways," said James F. Howard, MD, Distinguished Professor of Neuromuscular Disease, Chief, Neuromuscular Disorders Section, University of North Carolina School of Medicine and lead investigator in the RAISE trial. "These exciting results give us additional reason to believe that zilucoplan can offer an important step forward in addressing the unmet needs of people living with gMG. As we strive to improve the management of this complex and unpredictable disease, any new medicines will be welcomed by physicians to help us realize our goal of offering effective and flexible treatment approaches in gMG which are tailored to the needs of individual patients." These findings from RAISE build on the positive results from the Phase 3 MycarinG study evaluating UCB's investigational treatment rozanolixizumab, an SC-infused monoclonal antibody targeting the neonatal Fc receptor (FcRn) which also met its primary and secondary endpoints with statistical significance in gMG.ii UCB is currently the only company investigating two potential treatments with different mechanisms of action in gMG. Detailed results from both Phase 3 trials will be presented at forthcoming medical meetings in 2022. "While there has been recent progress in the treatment of MG, there is still a significant unmet need for new, effective treatment options that address the unpredictable, fluctuating symptoms of MG – some of which require urgent treatment or hospitalization – to improve patient outcomes and quality of life," said Raquel Pardo, Spanish Myasthenia Association (AMES), Spain. "New research into additional treatment options will be welcomed by the global MG community." Iris Loew-Friedrich, Executive Vice-President and Chief Medical Officer added: "This is the latest in a series of positive Phase 3 data announcements across UCB's product pipeline validating our patient value strategy and laying foundations for future sustainable growth. Today's results represent another significant milestone in UCB's efforts to bring transformational outcomes to those living with myasthenia gravis. Positive results for zilucoplan and rozanolixizumab – each with a different mechanism of action – bring us one step closer to achieving our ambition of delivering choice and flexibility for a broad range of patients and physicians at each step of their treatment journey, addressing significant unmet needs and offering unique patient value. We thank the MG community for their continued insights, partnership and participation in this study." About Generalized Myasthenia Gravis (gMG) Myasthenia gravis is a rare disease impacting almost 200,000 patients in the U.S., EU and Japan.iii,iv People living with gMG can experience a variety of symptoms, including drooping eyelids, double vision and difficulty swallowing, chewing and talking, as well as severe life- threatening weakness of the muscles of respiration.v-viviiviii gMG is a chronic and unpredictable auto-immune disease in which pathogenic autoantibodies can inhibit synaptic transmission at the neuro-muscular junction by targeting specific proteins on the post-synaptic membrane. This disrupts the ability of the nerves to stimulate the muscle and results in a weaker contraction. gMG can occur at any age and in any race, although previous studies have shown that women are more often impacted than men.ix Complement activation, a key mediator of antibody function, is recognized as an important driver of pathology in gMG. About the zilucoplan RAISE studyx,xi The RAISE study (Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis (NCT04115293)) is a multi-center, Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of zilucoplan in adult patients with gMG. Patients were randomized in a 1:1 ratio to receive daily subcutaneous (SC) doses of zilucoplan or placebo for 12 weeks. The study was designed to determine if complete complement inhibition can bring clinical benefit to people with gMG and if complement inhibition was effective across a broad spectrum of patients with acetylcholine receptor antibody positive (AChR Ab+) MG regardless of disease duration, prior treatment or response to previous therapies. The primary endpoint for RAISE study is change from baseline at Week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score, an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities. Secondary endpoints include change in the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Composite (MGC) and the Myasthenia Gravis Quality of Life 15 revised (MG-QoL15r) from baseline to Week 12; time to rescue therapy; the percentage with minimum symptom expression (MSE) (defined as MG-ADL of 0 or 1), the percentage with a ≥3-point reduction in MG-ADL and the percentage with a ≥5-point reduction in QMG, all measured at Week 12. About the rozanolixizumab MycarinG studyxii The MycarinG study (NCT03971422) is a completed multi-center, Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of rozanolixizumab in adult patients with gMG, with an open-label extension. The primary endpoint for the MycarinG study is change in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) score. Secondary endpoints include response rates, changes in the Myasthenia Gravis Composite (MGC) score, the Quantitative MG (QMG) score, patient-reported outcomes and adverse events (AEs). A preliminary analysis of results shows the trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful change from baseline in the MG-ADL total score at Day 43. All secondary endpoints were also met with statistical significance. Overall, rozanolixizumab was well tolerated and no new safety signals were identified.xiii About Zilucoplan11,xiv Zilucoplan targets complement component 5 (C5), a component of the terminal complement activation pathway, and binds to C5 with high affinity and specificity. This prevents its cleavage by C5 convertases into the complement components C5a and C5b. In addition, zilucoplan is understood to bind to the domain of C5 that corresponds to C5b and thereby block binding of C5b to complement component C6. Inhibition of C5 cleavage prevents the downstream assembly and activity of membrane attack complex (MAC). This dual mechanism of action of zilucoplan has the potential to prevent activation of the terminal complement pathway and downstream assembly and activity of MAC that can damage and destroy the postsynaptic membrane, disrupt ionic channel conductance and impair neuromuscular transmission. Zilucoplan is being investigated in the RAISE study, a multi-center, Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of zilucoplan in subjects with gMG. Further indications that are potentially addressable by zilucoplan include amyotrophic lateral sclerosis (ALS) and other tissue-based complement-mediated disorders with high unmet medical need. Zilucoplan was selected as one of the first drugs to be tested in a multi-center ALS platform study sponsored by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, Boston, MA. The safety and efficacy of zilucoplan have not been established and it is not currently approved for use in any indication by any regulatory authority worldwide. About Rozanolixizumab Rozanolixizumab is a subcutaneously infused humanized monoclonal antibody that specifically binds, with high affinity, to human neonatal Fc receptor (FcRn). It has been designed to block the interaction of FcRn and Immunoglobulin G (IgG), accelerating the catabolism of antibodies and reducing the concentration of pathogenic IgG autoantibodies.xv,xvi Rozanolixizumab is under clinical development with the aim of improving the lives of people with pathogenic IgG-autoantibody-driven autoimmune diseases, including gMG, primary immune thrombocytopenia (ITP), myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD) and autoimmune encephalitis (AIE) by driving removal of pathogenic IgG autoantibodies. The safety and efficacy of rozanolixizumab have not been established and it is not approved for use in any indication by any regulatory authority worldwide. About UCB in Rare Diseases At UCB, we don't just see patients or population sizes, we see people in need. Through decades of serving the neurology and immunology communities, we have improved lives with impactful medicines and by enhancing the social and emotional well-being of patients. As a continuation of our heritage, we are now expanding our efforts to tackle rare neurological and immunological diseases where current options offer little hope. Leading with gMG, UCB are progressing development programmes in a number of Rare Diseases, including ITP, MOG-AD and AIE. Alongside cutting-edge medicines, UCB are also exploring innovative non-drug solutions with the aim of delivering a holistic approach to care. About UCB UCB, Brussels, Belgium ( ) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 7,600 people in approximately 40 countries, UCB generated revenue of €5.3 billion in 2020. UCB is listed on Euronext Brussels (symbol: UCB). References i Data on file. UCB. February 2022. ii UCB Press Release, December 10. 2021 Accessed February 2022 iii Chen J, et al. Incidence, mortality, and economic burden of myasthenia gravis in China: A nationwide population-based study. Lancet Reg Health West Pac.2020;5:10063. iv Gilhus N. Myasthenia Gravis. N Engl J Med. 2016;375:2570-2581. v Lisak, RP. Best Practice Myasthenia gravis. BMJ Best Practice. 2021. Last accessed December 2021 vi Robertson NP, et al. Myasthenia gravis: a population based epidemiological study in Cambridgeshire, England. J Neurol Neurosurg Psychiatry. 1998;65:492-496. vii Kupersmith MJ et al. Development of generalized disease at 2 years in patients with ocular myasthenia gravis. Arch Neurol. 2003;60(2):243-248. viii Hansen JS, et al. Mortality in myasthenia gravis: A nationwide population-based follow-up study in Denmark. Muscle Nerve. 2016;53:73-77. ix Myasthenia Gravis Foundation of America. Clinical Overview of MG. . Accessed November 2021. x Clinical Trials.gov 'Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis (RAISE)': . Accessed November 2021. xi Howard JF, Jr., et al. JAMA Neurol 2020;77:582–92. xii Clinical Trials.gov 'A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis': Accessed February 2022. xiii Data on file. UCB. December 2021 xiv Ricardo A, et al. Blood 2015;126:939. xv Kiessling P, et al. The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017;9(414).eaan1208 xvi Smith B, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs.2018;10:1111-30.

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