The ER‐bound kinase/endoribonuclease (RNase), inositol‐requiring enzyme‐1 (IRE1), regulates the phylogenetically most conserved arm of the unfolded protein response (UPR). However, the complex ...biology and pathology regulated by mammalian IRE1 cannot be fully explained by IRE1’s one known, specific RNA target, X box‐binding protein‐1 (XBP1) or the RNA substrates of IRE1‐dependent RNA degradation (RIDD) activity. Investigating other specific substrates of IRE1 kinase and RNase activities may illuminate how it performs these diverse functions in mammalian cells. We report that macrophage IRE1 plays an unprecedented role in regulating phosphatidylinositide‐derived signaling lipid metabolites and has profound impact on the downstream signaling mediated by the mammalian target of rapamycin (mTOR). This cross‐talk between UPR and mTOR pathways occurs through the unconventional maturation of microRNA (miR) 2137 by IRE1’s RNase activity. Furthermore, phosphatidylinositol (3,4,5) phosphate (PI(3,4,5)P3) 5‐phosphatase‐2 (INPPL1) is a direct target of miR‐2137, which controls PI(3,4,5)P3 levels in macrophages. The modulation of cellular PI(3,4,5)P3/PIP2 ratio and anabolic mTOR signaling by the IRE1‐induced miR‐2137 demonstrates how the ER can provide a critical input into cell growth decisions.
Synopsis
miR‐2137 is a new RNA substrate of IRE1, the master regulator of the Unfolded Protein Response, and connects IRE1 to phosphatidylinositide‐derived signaling lipid metabolism and growth signaling.
Endoplasmic reticulum‐anchored IRE1’s endoribonuclease activity leads to maturation of a micro RNA, miR‐2137.
IRE1 plays an unprecedented role in regulating the metabolism of phosphatidylinositide‐derived signaling lipids in macrophages.
miR‐2137 is induced by high fat diet‐activated IRE1 in lipid‐laden, foamy macrophages that are found in atherosclerotic plaques and is blocked by an IRE1 endoribonuclease‐specific inhibitor, suggesting miR‐2137 could be a mediator of macrophage IRE1’s known pro‐atherogenic action.
miR‐2137 is a new RNA substrate of IRE1, the master regulator of the Unfolded Protein Response, and connects IRE1 to phosphatidylinositide‐derived signaling lipid metabolism and growth signaling.
Abstract Objectives This study was intended to identify general psychiatric symptoms in multiple sclerosis (MS) patients and to determine the distribution of these psychiatric symptoms by type of MS ...and degree of disability. Methods One hundred fifty-two volunteers, 76 MS patients and 76 healthy controls, matched in terms of age, gender, marital status, years spent in education and income, were included. Psychiatric symptoms were measured using the Symptom Checklist-90-R, Beck Depression Inventory, State–Trait Anxiety Inventory, Pittsburgh Sleep Quality Index, Padua Inventory, Rosenberg Self-Esteem Scale and Eating Attitude Test. Degree of disability was determined using the Expanded Disability Status Scale (EDSS). In addition to being compared between the patient and control groups, scale scores were also compared between groups established on the basis of relapsing–remitting or progressive forms of MS, neurological disability and ambulatory ability. Correlations were determined between EDSS scores and psychiatric scale scores. Results In addition to symptoms of depression, anxiety and sleep impairment in MS patients, we also determined that less studied symptoms such as somatization, obsession, compulsion, interpersonal sensitivity, anger–hostility, phobic anxiety, paranoid ideation, psychoticism, low self-esteem and distorted eating attitudes were also more frequent compared to the healthy controls. Some symptoms were also more prevalent in progressive MS patients compared to relapsing–remitting subjects. Symptoms increase as degree of disability rises and ambulatory capacity declines. Conclusion Depressive, anxious and sleep impairment symptoms are not the only ones seen in MS patients; other psychiatric symptoms are also common. Further studies are needed to investigate the frequency and causes of these little-investigated symptoms. As seen in patients with a progressive course and greater neurological disability, more psychiatric symptoms develop in patients with more severe disease.
Background & Objective: Personality traits are associated with mental health and quality of life in patients with multiple sclerosis (MS). The aim of this study was to determine personality traits in ...patients with MS and to examine the relationship between these traits and stigmatization, depression and quality of life.
Method: This descriptive, cross-sectional study included 80 MS patients and 96 healthy controls. Data were collected online between June and July 2022. Patient/person information form, Eysenck Personality Questionnaire Revised-Short Form (EPQ-RS), Neuro Quality of Life-Stigma Scale, Beck Depression Inventory and MS Quality of Life Scale-54 were used for data collection.
Results: When the age variable was controlled, it was found that the mean neuroticism subscale score was higher (p=0.003) and the mean extraversion subscale score was lower (p=0.018) than the control group. In addition, the mean extraversion score was found to be negatively correlated with stigmatization (p<0.05) and depression (p<0.01), and positively correlated with the physical sub-dimension of quality of life (p<0.01). Neuroticism and psychoticism sub-dimensions were positively correlated with stigmatization and depression and negatively correlated with all sub-dimensions of quality of life (p<0.01). In addition, regression analysis showed that depression significantly contributed to the physical health dimension of quality of life and neuroticism personality trait significantly contributed to the mental health dimension.
Conclusions: Neurotic personality traits were found to be more dominant in patients with MS. Moreover, all sub-dimensions of personality traits were associated with stigmatization, depression and quality of life. Therefore, personality traits should be considered in interventions to improve mental health and quality of life.
ObjectiveTo investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.MethodsData were obtained from the MSBase Registry. Term/preterm pregnancies conceived from ...2011-2019 were included (modern cohort). Annualised relapse rates (ARR) were calculated before, during and after pregnancy. Predictors of intrapartum and early postpartum (1st3 months) relapse were determined by clustered logistic and Cox regression analyses, respectively.ResultsWe included 1640 pregnancies from 1452 women. Disease-modifying therapy (DMT) used in the one-year preconception included natalizumab (n=219), fingolimod (n=147), dimethyl fumarate (DMF; n=57) and low-efficacy therapies (n=845). Preconception ARR by DMT class used before conception were: natalizumab, 0.29 (95% CI 0.22-0.37); fingolimod, 0.37 (0.28-0.49); DMF, 0.24 (0.13-0.41); low-efficacy, 0.29 (0.25-0.33); and none, 0.24 (0.19-0.31). Among women who used fingolimod or natalizumab, ARR increased during pregnancy. Intrapartum ARR decreased in preconception DMF, low-efficacy or no DMT groups. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month 0.60-0.95, p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 0.04-0.32, p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 0.41-0.91, p=0.016).ConclusionWomen with MS prescribed natalizumab or fingolimod preconception had higher rates of intrapartum and postpartum relapse. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 32-34 weeks gestation, with early re-initiation after delivery is an effective option to minimise relapse risks. Strategies of DMT use have to be balanced against potential foetal/neonatal complications.
Background. To investigate the frequency of restless leg syndrome (RLS), sleep quality impairment, depression, fatigue, and sleep behavior disorder and to determine the effects of surgery on these ...parameters in radiculopathy patients resistant to conservative treatment. Methods. The present study included 66 lumbar radiculopathy patients, who were resistant to conservative treatment and had indication of surgery. Five different questionnaires were performed to assess depression (the Beck Depression Inventory (BDI)), sleep quality (the Pittsburgh Sleep Quality Index (PSQI)), fatigue (the Fatigue Severity Scale (FSS)), and presence of RLS and rapid eye movement sleep behavior disorder (RBD). The same questionnaires were also performed on a control group (n=61). Results. Of the radiculopathy patients, 68.1% had RLS and 92.4% had fatigue. Of the controls, 16.4% had RLS and 59% had fatigue. RBD was present in 8 (12.1%) patients and 3 (4.9%) controls. The PSQI revealed that sleep quality was impaired in 46 (69.7%) patients and 35 (57.4%) controls (P>0.05). The number of individuals having substantial depression according to the BDI was significantly higher in the patients than in the controls. Conclusions. There was a significant increase in the frequency of RLS, which was significantly decreased in the postoperative period in the radiculopathy patients.
This study was conducted as a randomized controlled study to evaluate the effect of self-acupressure on fatigue in patients with Multiple Sclerosis (MS).
The sample of the study consisted of 123 ...patients (41 in the experiment group, 40 in the sham group, and 42 controls) who were admitted to a neurology clinic in a university hospital. To collect data a patient information form, Fatigue Severity Scale (FSS), Expanded Disability Status Scale (EDSS), and Mini-Mental Status Examination were used. Depressive mood and sleep quality, which may affect fatigue, were evaluated using the Beck Depression Scale (BDI-II) and Pittsburg Sleep Quality Index (PSQI), respectively. The patients in the experimental group were applied acupressure by use of LI4 (He Gu), SP6 (San Yin Jiao) and ST36 (Zu San Li) points.
The majority of patients were female (67.5%) and the mean age was 41.18. In addition, the mean BDI-II score of the patients was found to be 15.54, and the mean score of PSQI was 6.78 and the mean scores of these scales were similar in all groups. When the baseline FSS score means were examined, there was no significant difference among the groups (Acupressure:5.54 ± 0.87, Control:5.40 ± 0.92, and Sham:5.50 ± 0.99; p = 0.816). In the 4th week, there was a significant decrease in the mean score of fatigue of the experimental group compared to the other two groups (Acupressure:4.15 ± 1.09, Control:5.47 ± 1.11, Sham:5.34 ± 1.14, p < 0,001).
Our results suggest that acupressure might be an effective method to reduce fatigue in patients with MS.
•This study investigated the effect of self-acupressure on fatigue in patients with Multiple Sclerosis (MS).•The patients in the experimental group were applied acupressure by use of LI4, SP6, and ST36 points.•When the baseline FSS score means were examined, there was no significant difference among the groups.•In the 4th week, there was a significant decrease in the mean score of fatigue of the experimental group.•Our results suggest that acupressure might be an effective method to reduce fatigue in patients with MS.
•The fear of coronavirus and sleep quality were similar in patients and controls .•The anxiety and depression levels of the patients were higher than the controls.•Compared to the pre-pandemic, the ...sleep quality of the patients was impaired.•There was a deterioration in many sub-dimensions of quality of life (QoL).•Anxiety, depression and sleep problems were predictors of physical and mental QoL.
The COVID-19 outbreak, which has caused great fear and has affected many aspects of life even in healthy individuals, could become more threatening for people with multiple sclerosis (PwMS).
The aim of the present study was to evaluate depression, sleep and quality of life before and one year after the COVID-19 pandemic in PwMS and the association between the fear of COVID-19 and these parameters.
A total of 89 PwMS and 262 healthy controls were included in this descriptive cross-sectional study. The study compared the data collected before the pandemic with the data collected online approximately one year after the onset of the pandemic. The Fear of COVID-19 Scale (FCV-19S), the Worry and Anxiety Questionnaire (WAQ), the Beck Depression Inventory (BDI), the Pittsburgh Sleep Quality Index (PSQI) and the MS Quality of life scale (MSQoL-54) were used as data collection tools.
The mean age of the patients was 41.08 (±10.2) years; 62% were female and half (50.6%) of the patients were not working. The mean EDSS and the mean duration of diagnosis were found to be 1.33(±1.6) and 7.73(±6.1), respectively. The mean age of the control group was 38.08 (±11.4) and 51.5% were female. In both groups, social (PwMS 79.8% vs HC 89.3%) and psychological (PwMS 61.8% vs HC 51.9%) fields were found to have been affected by the COVID-19 pandemic most. Of the patients, 19% reported that the frequency of exacerbations increased during the pandemic. In the patient group, the fear of coronavirus (p=0.808) and the sleep quality (p=0.906) were found not to be different to those in control group; however, the anxiety (p=0.001) and depression (p=0.001) levels were determined to be significantly higher. Compared to the pre-pandemic period, the sleep quality of the patients was seen to be impaired during the pandemic (p<0.05); however, the depression scores were seen not to change (p>0.05). Although there were improvements in energy/vitality (p<0.001) and sexual function (p=0.002) scale scores, compared to the pre-pandemic period, deterioration in many sub-dimensions of quality of life was detected. Multiple regression analysis demonstrated that the anxiety, depression, and the sleep problems were predictors of both the physical health (p<0.001) and the mental health (p<0.001) sub-dimensions. The fear of coronavirus was determined not to have a significant effect on the quality of life (p>0.05).
It was determined that PwMS and were psychosocially affected by the COVID-19 pandemic, and had a significant deterioration in sleep quality at the end of a year spent with the pandemic. In addition, there was a deterioration in depression scores, although it was not statistically significant. Considering the fact that many subdimensions of quality of life, especially those associated with mental health, were impaired, it can be said that providing psychosocial support to patients is an important necessity.
Background & Objective: Patients with multiple sclerosis (PwMS) may experience discrimination and stigma. The aim of this study was to examine the relationship between stigma and the symptom burden ...in PwMS.
Methods: This cross-sectional descriptive study was conducted between June 2020 and September 2021 on MS patients enrolled in the neurology outpatient clinic of a university hospital in Turkiye. Multiple Sclerosis-Related Symptom Checklist and Neuroquality of Life (Neuro-QoL)-Stigma Scale were used to collect data.
Results: The mean age of the 195 study patients was 37.5 (± 9.7) years and 67.2% were female. One-fourth of the patients (26.2%) had a primary education level, and the unemployment rate was 9.7%. The patients reported that their private life (issues such as getting married, having boyfriend/girlfriend or problems in marital life) was affected the most (23.6%) by MS. The mean stigma burden scale scores of the patients were 37.9 (± 18.2). It was found that the stigma score of the patients was not significantly related to age, gender, education, and employment (p> 0.05); but was worse in divorced/widowed patients (p = 0.039); and was worse in patients who reported that their work, school, and private life were affected due to MS (p <0.05). The regression analysis showed that neuropsychiatric (p<0.001), urinary (p<0.001) and sensory (p=0.029) symptoms contributed the most to stigma.
Conclusions: A study on PwMS in Turkiye showed a mild level of stigma. The symptom burden of the patients correlated with the stigma level suggesting that effective symptom control may help reduce the stigma level of PwMS.
The incidence of early onset multiple sclerosis (EOMS) is increasing. We therefore aimed to compare the demographic, clinical, and magnetic resonance imaging features of early onset and adult onset ...multiple sclerosis patients. Furthermore, the effects of age of onset were evaluated for patients who reached an expanded disability status scale (EDSS) scores of six.
This was a retrospective study of MS patient medical charts between 1977 and 2021, which were registered in the MS database. Only patients with relapsing remitting MS longer than 1 year were included in the study. The patients included in the study were divided into the EOMS and adult onset MS (AOMS) groups. General demographic datas, clinical datas such as the characteristics of the first clinical period, the time between the first two attacks, the attack rate in the first 2 and 3 years, the treatment status, the EDSS at the first evaluation, the EDSS score at 6 month intervals, the time to reach an EDSS score of six, and magnetic resonance imaging features such brain and spinal T2 lesions were recorded.
Total of 3477 including 353 (10.2 %) EOMS and 3124 (89.8 %) AOMS patients were analyzed. There was no statistically significant difference in symptom patterns between the EOMS and AOMS groups ( p = 0.649). Supratentorial clinical features at first attack were more common in AOMS patients, while optic neuropathy at first attack was more common in EOMS patients. Using univariable analysis, clinical supratentorial features at first attack, clinical optic neuropathy at first attack, clinical spinal cord at fist attack, spinal cord lesions, first EDSS score, relapse in the first 3 years, and onset patterns in terms of age were found to be statistically significant risk factors. In multivariable-adjusted analysis, clinical supratentorial features at first attack, clinical spinal cord lesions at first attack, first EDSS scores relapses in the first 3 years, and onset patterns in terms of age were found to be independent risk factors for EDSS in reaching a score of six. Early treatment start was associated with reduced hazard rate of reaching an EDSS score of 6.
Onset pattern in terms of age was an independent prognostic factor for neurological disabilities in MS patients.
•Onset pattern in terms of age is an independent prognostic factor for neurological disability in MS.•AOMS patients have an increased risk of reaching an EDSS score of six compared to patients with EOMS.•EOMS may be slower to progression than AOMS, but moderate-to-severe disability is reached at a younger age in EOMS.•In EOMS patients, any DMTs should be started early to prevent neurological disabilities due to MS.
ABSTRACT Objective: In this study, it was aimed to investigate the effects of nutrition education given to persons with multiple sclerosis and their families on anthropometric and biochemical ...measurements and diet quality. Methods: Data from 51 persons with multiple sclerosis were analysed in this intervention study. The study was conducted with 3 groups. The education group consisted of only persons with multiple sclerosis, the family education group consisted of persons with multiple sclerosis and a family member living with them, and the control group consisted of persons with multiple sclerosis who had not received an education. Anthropometric and biochemical measurements and dietary quality assessments were made before (T1) and immediately after education (T2) and also 3 months after education (follow-up, T3). Results: The distribution of family education group diet quality scores showed a significant increase from “poor” to “needs improvement” at T3 compared to T1. The upper middle arm circumference measurements of the female control group were decreased at T2 and T3 from 29.0 (23-34) cm to 28.0 (22-31) cm and to 27.5 (22-31) cm. Women in family education group, levels of serum haemoglobin and haematocrit were higher than in control group at T2 and T3. Also, men in family education group, levels of alanine aminotransferase were lower than those in education group at follow up. Levels of total cholesterol and low-density lipoprotein cholesterol in education group were higher than those control group at T1, T2, and T3. Conclusion: This study indicates that nutrition education affects some biochemical and anthropometric measurements in persons with multiple sclerosis. Diet quality improved when receiving education together with families.
RESUMO Objetivo: Objetivou-se investigar os efeitos da educação nutricional dada a pessoas com esclerose múltipla e seus familiares, avaliação de medidas antropométricas, bioquímicas e da qualidade da dieta. Métodos: Dados de 51 participantes com esclerose múltipla foram analisados neste estudo de intervenção. O estudo foi dividido em 3 grupos, sendo o primeiro composto por indivíduos que obtiveram educação nutricional, o segundo, composto por indivíduos mais um membro da família que morava com eles e obtiveram educação nutricional, e o terceiro, grupo controle, composto por indivíduos que não obtiveram educação nutricional. Medidas antropométricas, bioquímicas e avaliações da qualidade da dieta foram feitas antes (T1) imediatamente após a educação nutricional (T2) e também 3 meses após a educação nutricional (T3). Resultados: A distribuição dos escores de qualidade da dieta do grupo de educação familiar mostrou um aumento significativo de “ruim” para “precisa melhorar” no T3 em comparação ao T1. As medidas da circunferência do braço médio do grupo controle feminino foram menores em T2 e T3 de 29,0 (23-34) cm para 28,0 (22-31) cm e para 27,5 (22-31) cm. Nas mulheres do grupo família, os níveis séricos de hemoglobina e hematocrito foram maiores do que no grupo controle em T2 e T3. Também nos homens do grupo família, os níveis de alanina aminotransferasa foram mais baixos do que os do grupo educação no seguimento. Os níveis de CT e LDL-C no grupo educação foram superiores aos do grupo controle em T1, T2 e T3. Conclusão: Este estudo observou que a educação nutricional afeta algumas medidas bioquímicas antropométricas em pessoas com esclerose múltipla. A qualidade da dieta melhorou quando recebeu educação junto com as famílias.
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