The neuropathological study of myelin oligodendrocyte glycoprotein in the temporal lobe of schizophrenia patients

2018 ◽  
Vol 30 (4) ◽  
pp. 232-240 ◽  
Author(s):  
Tomoyasu Marui ◽  
Youta Torii ◽  
Shuji Iritani ◽  
Hirotaka Sekiguchi ◽  
Chikako Habuchi ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Superior Temporal Gyrus ◽  
Middle Layer ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Postmortem Brain ◽  
Duration Of Illness ◽  
Long Duration ◽  
Stratum Lucidum ◽  
Postmortem Brains

AbstractObjectiveRecent studies based on the neuroimaging analysis, genomic analysis and transcriptome analysis of the postmortem brain suggest that the pathogenesis of schizophrenia is related to myelin-oligodendrocyte abnormalities. However, no serious neuropathological investigation of this protein in the schizophrenic brain has yet been performed. In this study, to confirm the change in neuropathological findings due to the pathogenesis of this disease, we observed the expression of myelin-oligodendrocyte directly in the brain tissue of schizophrenia patients.MethodsMyelin oligodendrocyte glycoprotein (MOG) was evaluated in the cortex of the superior temporal gyrus (STG) and the hippocampus in 10 schizophrenic and nine age- and sex-matched normal control postmortem brains.ResultsThe expression of MOG was significantly lower in the middle layer of the neocortex of the STG and stratum lucidum of CA3 in the hippocampus in the long-term schizophrenic brains (patients with ≥30 years of illness duration) than in the age-matched controls. Furthermore, the thickness of MOG-positive fibre-like structures was significantly lower in both regions of the long-term schizophrenic brains than in the age-matched controls.ConclusionThese findings suggest that a long duration of illness has a marked effect on the expression of MOG in these regions, and that myelin-oligodendrocyte abnormalities in these regions may be related to the progressive pathophysiology of schizophrenia.

Management and Outcome in Anorexia Nervosa

1983 ◽  
Vol 143 (3) ◽  
pp. 282-287 ◽  
Author(s):  
H. G. Morgan ◽  
Joan Purgold ◽  
Jill Welbourne
Keyword(s):  
Anorexia Nervosa ◽  
Evaluation Procedure ◽  
Factors Associated ◽  
Poor Outcome ◽  
Duration Of Illness ◽  
Long Duration ◽  
Special Clinic ◽  
Chronic Morbidity

SummaryThe outcome of 78 patients with anorexia nervosa treated in a special clinic is described, using a standardized follow-up technique. The findings are compared with two previous studies which utilized an identical evaluation procedure. Certain predictors of poor outcome already identified by previous studies (long duration of illness before referral, previous personality problems, difficulties in relationship between family and patient) are confirmed. The findings suggest that early intervention may be an important component of effective treatment. The possible advantages of long term continuity of outpatient care are also discussed and the need for careful scrutiny of criteria for hospital admission emphasized.It is concluded that chronic morbidity due to anorexia nervosa represents an important topic for further research. There is need for further identification of factors associated with chronicity, some of which may be secondary repercussions of the illness itself, and prospective evaluation of treatment programmes which focus on predictors of poor outcome.

CHANGES IN BLOOD PROTEOME OF COSMONAUTS WITH MICRO- AND MACROVASCULAR INJURIES DUE TO G-LOADS AT THE FINAL STAGE OF LONG-DURATION SPACE MISSIONS

2020 ◽  
Vol 54 (5) ◽  
pp. 5-14
Author(s):  
L.Kh. Pastushkova ◽  
◽  
K.S. Kireev ◽  
I.M. Larina ◽  
◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Soft Tissues ◽  
Blood Rheology ◽  
Landing Site ◽  
Space Missions ◽  
Vascular Injuries ◽  
New Approach ◽  
Long Duration ◽  
Integrated Response

The integrated response of the human proteome to re-entry g-loads following long-term space missions was studied in 13 male cosmonauts at the age of 44 ± 6 years. Examination at the landing site discovered local petechial hemorrhages into soft tissues of the back and lower legs. The paper presents a new approach to evaluation of petechia and soft tissue hemorrhages in cosmonauts on return to Earth. Proteomic analysis was performed with the use of LC-MS. Bioinformation analysis was made using Perseus, PubMed, Uniprot and ANDSystem software. Nine out of 19 significantly different (p < 0.05) proteins were related to vascular injuries directly. We described proteins with a primarily protecting effect against endothelial cells apoptosis and augmentation of vascular permeability, proteins that are responsible for blood rheology and proteins antagonistic to the main triggers of ischeamia-reperfusion injuries of the lungs, liver and other parenchymal organs.

scholarly journals Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma

2021 ◽  
Author(s):  
Chao Wang ◽  
Min Shi ◽  
Lei Zhang ◽  
Jun Ji ◽  
Ruyan Xie ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Genomic Analysis ◽  
Molecular Characteristics ◽  
Immune Microenvironment ◽  
Term Survival ◽  
Long Term Survival ◽  
Tumor Immune Microenvironment ◽  
Genetic Features ◽  
Multiple Recurrences

Abstract Objective To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD). Methods The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized. Results High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer. Conclusions The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.

Timing, Storage, and Comparison of Stimulus Duration Engage Discrete Anatomical Components of a Perceptual Timing Network

2008 ◽  
Vol 20 (12) ◽  
pp. 2185-2197 ◽  
Author(s):  
Jennifer T. Coull ◽  
Bruno Nazarian ◽  
Franck Vidal
Keyword(s):  
Stimulus Duration ◽  
Brain Activity ◽  
Temporal Discrimination ◽  
Superior Temporal Gyrus ◽  
Motor Preparation ◽  
Long Term Memory ◽  
Temporal Encoding ◽  
Perceptual Timing ◽  
The Right

The temporal discrimination paradigm requires subjects to compare the duration of a probe stimulus to that of a sample previously stored in working or long-term memory, thus providing an index of timing that is independent of a motor response. However, the estimation process itself comprises several component cognitive processes, including timing, storage, retrieval, and comparison of durations. Previous imaging studies have attempted to disentangle these components by simply measuring brain activity during early versus late scanning epochs. We aim to improve the temporal resolution and precision of this approach by using rapid event-related functional magnetic resonance imaging to time-lock the hemodynamic response to presentation of the sample and probe stimuli themselves. Compared to a control (color-estimation) task, which was matched in terms of difficulty, sustained attention, and motor preparation requirements, we found selective activation of the left putamen for the storage (“encoding”) of stimulus duration into working memory (WM). Moreover, increased putamen activity was linked to enhanced timing performance, suggesting that the level of putamen activity may modulate the depth of temporal encoding. Retrieval and comparison of stimulus duration in WM selectively activated the right superior temporal gyrus. Finally, the supplementary motor area was equally active during both sample and probe stages of the task, suggesting a fundamental role in timing the duration of a stimulus that is currently unfolding in time.

Cigarette smoking in long-term schizophrenia

2006 ◽  
Vol 21 (4) ◽  
pp. 219-223 ◽  
Author(s):  
R.K.R. Salokangas ◽  
T. Honkonen ◽  
E. Stengård ◽  
A.-M. Koivisto ◽  
J. Hietala
Keyword(s):  
Cigarette Smoking ◽  
Institutional Care ◽  
Male Gender ◽  
Hospital Treatment ◽  
Women Patients ◽  
Heavy Smoking ◽  
Duration Of Illness ◽  
Lower Education ◽  
Great Health

AbstractPurposeCigarette smoking is a great health problem and prevalent among subjects with schizophrenia. Our aim was to investigate the prevalence and associations of cigarette smoking in patients with long-term schizophrenia.MethodsSeven hundred and sixty schizophrenia patients were interviewed and their cigarette smoking was recorded.ResultsSmoking was more prevalent men than in women patients. In logistic regression analysis, male gender, duration of illness (DUI) from 10 to 19 years, being divorced or separated, lower education and high daily doses of neuroleptics (DDN) associated significantly with regular smoking. Heavy smoking associated, in men, with hospital treatment.ConclusionsIn schizophrenia patients, smoking is associated with long DUI, high DDN and institutional care. Interventions for cessation and/or reduction of cigarette smoking should be a part of the treatment for patients with schizophrenia.

scholarly journals Long-Term Microgravity Effects on Isometric Handgrip and Precision Pinch Force with Visual and Proprioceptive Feedback

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Ilario Puglia ◽  
Michele Balsamo ◽  
Marco Vukich ◽  
Valfredo Zolesi
Keyword(s):  
Maximum Voluntary Contraction ◽  
Space Station ◽  
Voluntary Contraction ◽  
Force Output ◽  
Isometric Handgrip ◽  
Short Term ◽  
Space Flights ◽  
Pinch Force ◽  
Long Duration

The study and analysis of human physiology during short- and long-duration space flights are the most valuable approach in order to evaluate the effect of microgravity on the human body and to develop possible countermeasures in prevision of future exploratory missions and Mars expeditions. Hand performances such as force output and manipulation capacity are fundamental for astronauts’ intra- and extravehicular activities. Previous studies on upper limb conducted on astronauts during short-term missions (10 days) indicated a temporary partial reduction in the handgrip maximum voluntary contraction (MVC) followed by a prompt recovery and adaptation to weightlessness during the last days of the mission. In the present study, we report on the “Crew’s Health: Investigation on Reduced Operability” (CHIRO) protocol, developed for handgrip and pinch force investigations, performed during the six months increment 7 and increment 8 (2003-2004) onboard International Space Station (ISS). We found that handgrip and pinch force performance are reduced during long-term increments in space and are not followed by adaptation during the mission, as conversely reported during short-term increment experiments. The application of protocols developed in space will be eligible to astronauts during long-term space missions and to patients affected by muscle atrophy diseases or nervous system injury on Earth.

Patients with steroid-refractory toxicity following immune checkpoint inhibitors: Frequent hospitalizations and long duration of illness.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2655-2655
Author(s):  
Mia Bothwell ◽  
Aaron Cheng ◽  
Leyre Zubiri ◽  
Meghan Mooradian ◽  
Yevgeniy R. Semenov ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Academic Medical Center ◽  
Complete Response ◽  
Second Line ◽  
Duration Of Illness ◽  
Long Duration ◽  
Steroid Refractory

2655 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer with significantly improved outcomes, but these agents have a unique spectrum of toxicities known as immune-related adverse events (irAEs). The recommended treatment for non-endocrine toxicities is steroid based. However, a subset of patients (pts) is steroid-refractory and requires second-line immunosuppression. There is very little evidence regarding this population. In this retrospective study we report the 1) incidence 2) type of treatment used 3) natural history and 4) potential predictors of steroid-refractory irAE at a major academic medical center. Methods: The Research Patient Database Registry at Mass General Brigham was used to identify pts treated with an ICI from 1/5/2017 to 6/1/2019. Pharmaceutical records identified a subset of the cohort received a second-line immunosuppressive agent within a 15-month period after ICI. For pts with steroid-refractory irAE additional information was collected: demographics, ICI regimen, type/#/and severity of irAE, clinical characteristics, # of admissions, length of stay (LOS), amount and duration of steroid therapy, second line immunosuppression type, treatment discontinuation rates, response, and outcome of re-challenge. Multivariate logistic regressions were used to predict risk of refractory toxicity and study the association of different variables (age, sex, race, marital status, cancer and ICI types) with refractory toxicities. Results: We identified 61 pts (1.4%) with steroid-refractory irAEs (48 colitis, 4 myocarditis, 6 pneumonitis, 3 neurologic) out of the total ICI cohort (N=4,325). 60.7% received ICI monotherapy. 24.6% received ICI in the adjuvant setting. Median length of steroid duration was 68 days with max of 1135 days. Despite use of second line immunosuppression, 25.8% of pts were never able to discontinue steroids. Majority of pts (72.1%) had at least one hospitalization with median LOS of 7.5 days. 93.4% of pts permanently discontinued the ICI responsible for the irAE. Thirteen pts (21.3%) were later re-challenged with ICI and 7 (53.8%) of these developed a subsequent irAE. Anti-CTLA-4 therapy was associated with a 10-fold risk of refractory toxicity compared to PD-1 (p<.05). Best tumor response was complete response in 21.3% and partial response in 26.2%. Among different cancer types, melanoma was most strongly associated with refractory events (OR 2.97 in comparison to thoracic malignancy). Conclusions: Refractory toxicity is uncommon but leads to high rates of ICI discontinuation, frequent hospitalizations, and a long duration of illness with exposure to prolonged and high-doses of steroids. There is an urgent need for further investigation into predictive factors for steroid-refractory toxicity given that ICI is being used more frequently and in earlier lines of treatment.

scholarly journals Effect on lipid profile due to prolong Valproic acid intake

2021 ◽  
Vol 15 (7) ◽  
pp. 1497-1499
Author(s):  
Rao. S Aziz ◽  
Usman Saeed ◽  
Liaqat Ali ◽  
Muhammad Arshad ◽  
Roman Abbas ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Lipid Profile ◽  
Total Cholesterol ◽  
Cholesterol Oxidase ◽  
Venous Blood ◽  
Case Group ◽  
Long Duration ◽  
And Control ◽  
Relationship Of

Background: Valproic acid (VA) serve as the antimigraine , anti-mental disturbances agent and antiepileptic medicine. After using va, metabolic rearrangements seen in patients that include alteration in lipoproteins levels; Aim: To discuss the effects of VA after using for long duration on total levels of cholesterol in adult. Methods: About Eighty candidates participated and they were divided into two groups namely, case group (40 candidates) and control groups (40 candidates). All the candidates were asked for collection of venous blood sample in order to determine total cholesterol serum level among them via aid of enzymatic cholesterol oxidase phenol 4-aminoantipyrine peroxidase. Results: By the aid of the logistic regression analysis, the relationship of the long-term VA treatment and the level of total cholesterol was obtained. With respect to our analysis, there is a co relation between total levels of cholestrol and long term usage of VA (P=0.003). Conclusions: In a net shell, by using VA for long duration, the total level of cholesterol in adults reduces. Keywords: Lipid profile, side effects, total cholesterol, valproic acid

scholarly journals Long-term bedrest study and astronaut training

2016 ◽  
Author(s):  
Edwin Mulder ◽  
Alexandra Noppe ◽  
Ulrich Limper
Keyword(s):  
Bed Rest ◽  
Dual Purpose ◽  
Planetary Environments ◽  
Exercise Regimen ◽  
Long Duration ◽  
Astronaut Training ◽  
Health Support ◽  
Art Research ◽  
Induced Changes

In the context of space physiology, research is being conducted to understand the physiological effects from radiation, hypogravity, spaceflight and planetary environments. The goal is to identify new methods to address the unique challenges in medical treatment, human factors, and behavioral health support on future exploration missions. As crew size is small and time is limited during actual missions, space agencies resort to addressing the effects of space travel in analog environments that have features similar to those of spaceflight. Head-down tilt bed rest (HDBR), for instance, is one of the established terrestrial models used to simulate some of the physiological changes experienced during spaceflight under weightless conditions and is therefore considered a valuable testbed to prepare for future long-duration exploration missions. HDBR studies are performed in extremely-well controlled laboratory settings, offering the possibility to test the effects of – what is in essence - physical inactivity and fluid shift. However, HDBR studies have a dual purpose, as they are also invaluable for the development, testing and validation of countermeasures aimed at mitigating microgravity-induced changes to the human body. With respect to the latter, the consensus is that short-term bed rest studies (< 14 days) serve foremost as a first screening of potential promising countermeasures, particularly for the cardiovascular system. Screening of preventative procedures and protocols for the muscular system requires at least mid-term (14 -28 days), whereas studies aiming to validate countermeasures for bone require long-term HDBR studies, in the order of 60-90 days. Hitherto the preferred countermeasure during spaceflight has been physical exercise. The presentation will therefore provide a short overview of the current onboard exercise regimen and will, in light of this, outline the scientific background and aims of the ongoing 60-day HDBR study at the :envihab (from the words ‘Environment’ and ‘Habitat’), the DLR Institute of Aerospace Medicine’s state-of-the-art research facility.

scholarly journals Targeting B cells to modify MS, NMOSD, and MOGAD

2020 ◽  
Vol 8 (1) ◽  
pp. e919
Author(s):  
Jonas Graf ◽  
Jan Mares ◽  
Michael Barnett ◽  
Orhan Aktas ◽  
Philipp Albrecht ◽  
...  
Keyword(s):  
B Cell ◽  
Case Series ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Clinical Development ◽  
B Cell Depletion ◽  
Phase 2 ◽  
Proven Efficacy ◽  
Advanced Stages ◽  
Related Proteins

Ocrelizumab, rituximab, ofatumumab, ublituximab, inebilizumab, and evobrutinib are immunotherapies that target various B cell–related proteins. Most of these treatments have proven efficacy in relapsing and progressive forms of MS and neuromyelitis optica spectrum disease (NMOSD) or are in advanced stages of clinical development. Currently, ocrelizumab and inebilizumab are licensed for treatment of MS and NMOSD, respectively. This part of the review focuses on monoclonal antibody B cell–depleting strategies in NMOSD and the emerging related myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G–associated disease (MOGAD). Case series and phase 2/3 studies in these inflammatory disorders are assessed. The safety profile of long-term B-cell depletion in MS, NMOSD, and MOGAD will be highlighted. Finally implications of the current coronavirus disease 2019 pandemic on the management of patients with these disorders and the use of B cell–depleting agents will be discussed.

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