Publications by authors named "Min Chu"

217 Publications

Correction to: Burden of migraine and unmet needs from the patients' perspective: a survey across 11 specialized headache clinics in Korea.

J Headache Pain 2021 Jun 11;22(1):56. Epub 2021 Jun 11.

Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, South Korea.

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http://dx.doi.org/10.1186/s10194-021-01270-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194232PMC
June 2021

Validity and reliability of the self-administered Visual Aura Rating Scale questionnaire for migraine with aura diagnosis: A prospective clinic-based study.

Headache 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Objective: To assess the validity and reliability of the self-administered Visual Aura Rating Scale (VARS) questionnaire using a hospital-based sample in a cross-sectional setting.

Background: Visual aura is the most common type of aura manifesting in 98%-99% of migraine with aura (MA). The VARS is a diagnostic rating scale used to quantify the cardinal characteristics of MA and has shown high sensitivity and specificity in the diagnosis of visual aura.

Methods: We translated the VARS into Korean and constructed a five-item self-administered questionnaire based on the VARS. We consecutively recruited first-visit patients with migraine at the neurology clinics of two university hospitals. The scoring of the self-administered VARS questionnaire was the same as that for the original VARS. We assessed criterion validity and internal consistency reliability. The diagnosis of migraine and aura was assigned by two headache neurologists based on a comprehensive clinical assessment using the International Classification of Headache Disorders, 3rd edition.

Results: A total of 240 participants with migraine were enrolled. Of these, 55 (22.9%) had MA. All participants with MA had visual aura. Receiver operating characteristic curve analysis revealed that a cutoff score of 3 provided the highest rate of correct identification of patients ([200/240], 83.3%), with a sensitivity of 96.4% (95% confidence interval [CI], 84.5%-99.6%) and specificity of 79.5% (95% CI, 72.9%-85.0%). Cronbach's alpha coefficient was 0.852.

Conclusion: The self-administered VARS questionnaire is a valid and reliable instrument for the screening of visual aura in patients with migraine in neurology outpatient clinics.
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http://dx.doi.org/10.1111/head.14133DOI Listing
June 2021

Bi-directional regulation functions of lanthanum-substituted layered double hydroxide nanohybrid scaffolds activating osteogenesis and inhibiting osteoclastogenesis for osteoporotic bone regeneration.

Theranostics 2021 3;11(14):6717-6734. Epub 2021 May 3.

The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.

Osteoporotic patients suffer symptoms of excessive osteoclastogenesis and impaired osteogenesis, resulting in a great challenge to treat osteoporosis-related bone defects. Based on the positive effect of rare earth elements on bone metabolism and bone regeneration, we try to prove the hypothesis that the La dopants in lanthanum-substituted MgAl layered double hydroxide (La-LDH) nanohybrid scaffolds simultaneously activate osteogenesis and inhibit osteoclastogenesis. A freeze-drying technology was employed to construct La-LDH nanohybrid scaffolds. The osteogenic and anti-osteoclastogenic activities of La-LDH nanohybrid scaffolds were evaluated by using ovariectomized rat bone marrow stromal cells (rBMSCs-OVX) and bone marrow-derived macrophages (BMMs) as cell models. The bone regeneration ability of the scaffolds was investigated by using critical-size calvarial bone defect model of OVX rats. La-LDH nanohybrid scaffolds exhibited three-dimensional macroporous structure, and La-LDH nanoplates arranged perpendicularly on chitosan organic matrix. The La dopants in the scaffolds promote proliferation and osteogenic differentiation of rBMSCs-OVX by activating Wnt/β-catenin pathway, leading to high expression of ALP, Runx-2, COL-1 and OCN genes. Moreover, La-LDH scaffolds significantly suppressed RANKL-induced osteoclastogenesis by inhibiting NF-κB signaling pathway. As compared with the scaffolds without La dopants, La-LDH scaffolds provided more favourable microenvironment to induce new bone in-growth along macroporous channels. La-LDH nanohybrid scaffolds possessed the bi-directional regulation functions on osteogenesis and osteoclastogenesis for osteoporotic bone regeneration. The modification of La dopants in bone scaffolds provides a novel strategy for osteoporosis-related bone defect healing.
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http://dx.doi.org/10.7150/thno.56607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171081PMC
May 2021

Global Gene Expression of T Cells Is Differentially Regulated by Peritoneal Dendritic Cell Subsets in an IL-2 Dependent Manner.

Front Immunol 2021 17;12:648348. Epub 2021 May 17.

Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.

Dendritic cells (DCs) in peripheral tissues may have a unique role to regulate innate and adaptive immune responses to antigens that enter the tissues. Peritoneal cavity is the body compartment surrounding various tissues and organs and housing diverse immune cells. Here, we investigated the specialized features of classical DC (cDC) subsets following the intraperitoneal injection of a model antigen ovalbumin (OVA). Peritoneal cDC1s were superior to cDC2s in activating OVA-specific CD8 T cells, while both cDCs were similar in stimulating OVA-specific CD4 T cells. Each peritoneal cDC subset differentially regulated the homing properties of CD8 T cells. CD8 T cells stimulated by cDC1s displayed a higher level of lung-homing receptor CCR4, whereas those stimulated by cDC2s prominently expressed various homing receptors including gut-homing molecules CCR9 and α4β7. Also, we found that cDC1s played a dominating role over cDC2s in controlling the overall gene expression of CD8 T cells. Soluble factor(s) emanating from CD8 T cells stimulated by peritoneal cDC1s were responsible for mediating this dominance of cDC1s, and we identified IL-2 as a soluble factor regulating the global gene expression of T cells. Collectively, our study indicates that different peritoneal cDC subsets effectively diversify T cell responses by altering the level of cytokines, such as IL-2, in the milieu.
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http://dx.doi.org/10.3389/fimmu.2021.648348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165281PMC
May 2021

Family Caregiver Suffering in Caring for Patients with Amyotrophic Lateral Sclerosis in Korea.

Int J Environ Res Public Health 2021 05 6;18(9). Epub 2021 May 6.

Seoul Women's College of Nursing, Seoul 03617, Korea.

The purpose of this study was to describe the meaning of the suffering experience of Korean ALS family caregivers. This is a descriptive phenomenological study that included ten participants using convenience sampling with maximum variation in a tertiary hospital in Seoul, South Korea. Colaizzi's data analysis method was used to inductively determine themes and formulate meanings. The three main themes derived from analysis were: "frustration with seeing a patient suffering", "burnout at the cost of a life of dedication", and "desperate need for help". Caregivers experience high levels of suffering, which can come in various forms depending on the circumstances of the particular patient and family. Especially, distress from seeing a loved one suffering was another aspect of suffering in Korean ALS caregivers, reflecting strong family ties. At the same time, patients are in desperate need of help and support from their families. Thus, it is essential to provide care to lessen the causes of distress and meet the needs of not only patients, but also caregivers through family-centered care to improve overall quality of life for all involved.
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http://dx.doi.org/10.3390/ijerph18094937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125242PMC
May 2021

Burden of migraine and unmet needs from the patients' perspective: a survey across 11 specialized headache clinics in Korea.

J Headache Pain 2021 May 24;22(1):45. Epub 2021 May 24.

Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, South Korea.

Background: Migraine is a neurological, primary headache disorder affecting more than 1 billion people worldwide, with a multi-faceted burden that can significantly impact the everyday life of a patient, both during and between attacks. However, studies on patient awareness, burden, and clinical management of migraine in Korea are limited and outdated. The aim of this study was to comprehensively investigate the current difficulties and unmet needs that Korean patients with migraine encounter from their perspective.

Methods: A total of 207 patients with episodic or chronic migraine aged between 15 and 76 years, completed a survey designed to cover the following topics: diagnosis, understanding of the disease, treatment experience, disability, and quality of life. Patients were recruited by their neurologists from 11 specialized headache clinics in Korea and completed the survey between 22 July and 19 August 2019. Validated scales such as the Migraine Disability Assessment (MIDAS) questionnaire and Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) were used to assess levels of disability and quality of life, respectively, in patients.

Results: On average, it took 10.1 years from onset of symptoms to diagnosis and a mean of 3.9 hospitals were visited for treatment prior to the patient's current hospital. There was a lack of understanding among respondents about migraine, with 55.6% believing that unilateral headache is a unique feature of migraine compared with other headache disorders. On average, high levels of disability and poor quality of life were reported by patients, as assessed by MIDAS and MSQv2.1, respectively, but only 23.7% had regularly taken preventive medication in the past. Overall satisfaction with previous doctor-patient relationships was reported by 29.5% of respondents, and satisfaction with preventive and acute medications by only 40.8% and 27.1% of the respondents, respectively.

Conclusion: Korean patients with migraine experience significant disability and reduced quality of life as a result of the disease and have clear unmet needs in terms of diagnosis, understanding of the disease, and disease management including treatment.
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http://dx.doi.org/10.1186/s10194-021-01250-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146656PMC
May 2021

Novel PSEN1 and PSEN2 Mutations Identified in Sporadic Early-onset Alzheimer Disease and Posterior Cortical Atrophy.

Alzheimer Dis Assoc Disord 2021 May 11. Epub 2021 May 11.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background/purpose: Sporadic early-onset Alzheimer disease (sEOAD) and its visual variant, posterior cortical atrophy (PCA), have a disease onset at less than 65 years of age with no familial aggregation. The etiology and genetic basis of these diseases remain poorly understood. Our study aimed to identify additional mutations or variants associated with sEOAD and PCA and to further examine their genetic and phenotypic spectrums.

Methods: We performed whole-exome sequencing and analyzed the clinical and neuroimaging features of mutation carriers with 29 patients having sEOAD and 25 having PCA.

Results: Nine rare damaging variants were identified in 4 patients with sEOAD and 3 with PCA. A novel mutation (p.A136V) in PSEN1 was identified in a patient with sEOAD and a likely pathogenic variant (p.M239T) was identified for PSEN2 in a patient with PCA. In addition, 7 rare damaging variants were detected in other genes related to neurodegenerative diseases. The patient carrying the PSEN1 p.A136V mutation presented with typical clinical and imaging features of sEOAD, and the PCA patient with the PSEN2 p.M239T mutation presented with visuospatial impairment as the initial symptom.

Conclusion: Our study expands the PSEN1 mutation spectrum of sEOAD and highlights the importance of screening PSEN1 and/or PSEN2 mutations in PCA patients.
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http://dx.doi.org/10.1097/WAD.0000000000000438DOI Listing
May 2021

The Upregulation of a Novel Long Noncoding RNA AK097647 Promotes Enterovirus 71 Replication and Decreases IFN-λ1 Secretion.

Intervirology 2021 May 5:1-9. Epub 2021 May 5.

Shenzhen Institute of Wuhan University, Shenzhen, China.

Background: Enterovirus 71 (EV71) infects millions of children every year in China and has become a challenge to public health. However, there is no effective treatment for EV71 infection. Long noncoding RNAs (lncRNAs) have been found to play various roles in virus replication and infection.

Objective: We aimed to explore the role of a novel long noncoding RNA AK097647 (lncRNA-AK097647) during EV71 infection.

Methods: To assess the role of lncRNA-AK097647 during EV71 infection, siRNAs were used to silence lncRNA-K097647 expression. RT-qPCR assay and Western blotting were applied to measure the mRNA and protein levels of EV71 VP1 and the phosphorylation of NF-κB. ELISA was used to detect the level of IFN-λ1 expression.

Results: The novel lncRNA-AK097647 was upregulated in human rhabdomyosarcoma cells and the blood of hand, foot, and mouth disease patients infected with EV71, as demonstrated by RT-qPCR. Interestingly, RNAi-mediated knockdown of lncRNA-AK097647 dramatically increased the level of IFN-λ1 expression, resulting in the suppression of EV71 replication. In contrast, overexpression of lncRNA-AK097647 decreased the level of IFN-λ1 expression and resulted in increased EV71 replication. In addition, we found that lncRNA-AK097647 could inhibit the phosphorylation of NF-κB.

Conclusion: These results suggest a novel mechanism by which EV71 evades the IFN-mediated host antiviral response by increasing lncRNA-AK097647 expression.
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http://dx.doi.org/10.1159/000515903DOI Listing
May 2021

Smoking History and Clinical Features of Cluster Headache: Results from the Korean Cluster Headache Registry.

J Clin Neurol 2021 Apr;17(2):229-235

Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea.

Background And Purpose: Epidemiologic data suggest that cluster headache (CH) is significantly associated with cigarette smoking. The aim of this study was to determine differences in features between patients with a smoking history and those who are never-smokers, using data from a prospective multicenter registry.

Methods: Data used in this study were obtained from the Korean Cluster Headache Registry that collected data from consecutive patients diagnosed with CH. We compared clinical and demographic features between ever-smokers (current or former smokers) and never-smokers.

Results: This study enrolled 250 patients who were diagnosed with CH, of which 152 (60.8%) were ever-smokers and 98 (39.2%) were never-smokers. The age at CH onset was significantly lower in the never-smoker group than in the ever-smoker group [27.1±12.9 years vs. 30.6±10.9 years (mean±standard deviation), =0.024]. Seasonal rhythmicity (58.1% vs. 44.7%, =0.038) and triptan responsiveness (100% vs. 85.1%, =0.001) were higher in never-smokers, while other clinical features such as pain severity, duration, attack frequency, and associated autonomic symptoms did not differ significantly between the groups. The male-to-female ratio was markedly higher in ever-smokers (29.4:1) than in never-smokers (1.7:1).

Conclusions: Most of the clinical features did not differ significantly between patients with a smoking history and never-smokers. However, the age at CH onset, sex ratio, and seasonal rhythmicity were significantly associated with smoking history.
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http://dx.doi.org/10.3988/jcn.2021.17.2.229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053542PMC
April 2021

The Impact of Practice Environment and Resilience on Burnout among Clinical Nurses in a Tertiary Hospital Setting.

Int J Environ Res Public Health 2021 03 3;18(5). Epub 2021 Mar 3.

Interdisciplinary Program of Arts & Design Technology, College of Nursing, Chonnam National University, 160 Baekseoro, Donggu, Gwangju 61469, Korea.

The purpose of this study was to examine practice environment, resilience, and burnout and to identify the impacts of practice environment and resilience on burnout among clinical nurses working at a tertiary hospital. A cross-sectional secondary data analysis was conducted using a convenience sample of 199 nurses. The nurses completed survey questionnaires regarding practice environment, resilience, and burnout. The majority of the nurses were below the age of 30, single, and worked in medical-surgical wards. Approximately, 92% of the nurses reported moderate to high burnout, with a mean practice environment score of 2.54 ± 0.34 and resilience score of 22.01 ± 5.69. Practice environment and resilience were higher in the low level of burnout than in the moderate to high level of burnout. After controlling for demographic and occupational characteristics, resilience and nursing foundations for quality of care were significant predictors of burnout (OR = 0.71, = 0.001; OR = 0.01, = 0.036, respectively), explaining 65.7% of the variance. In a mixed practice environment, increased resilience and nursing foundations for quality of care lowered nurses' burnout. Our findings suggest that interventions focused on enhancing individual resilience and practice environment and building better nursing foundations for quality of care should be developed and provided to alleviate burnout in clinical nurses working at tertiary hospitals. Nursing and hospital administrators should consider the importance of practice environment and resilience in nurses in developing interventions to decrease burnout.
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http://dx.doi.org/10.3390/ijerph18052500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967630PMC
March 2021

Clinical features of cluster headache without cranial autonomic symptoms: results from a prospective multicentre study.

Sci Rep 2021 Mar 25;11(1):6916. Epub 2021 Mar 25.

Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Keun Jae Bong-gil 7, Hwaseong, 18450, Gyeonggi-do, Korea.

Although cranial autonomic symptoms (CAS) are typical in cluster headache (CH), some individuals with CH show no CAS during their headache attacks. Probable cluster headache (PCH) is a subtype of CH that fulfils all but one criterion of CH. This study aimed to investigate the frequency and clinical features of CH and PCH without CAS in comparison to those with CAS. We analysed data from the Korea Cluster Headache Registry, a prospective multicentre registry involving data from 16 hospitals. Of the 216 participants with CH and 26 with PCH, 19 (8.8%) and 7 (26.9%), respectively, did not have CAS. Participants with CH without CAS exhibited less severe anxiety (General Anxiety Disorder-7 score, median [interquartile range], 2.0 [1.0-6.0] vs 8.0 [3.0-12.0], p = 0.001) and depression (Patient Health Questionnaire-9 score, 3.0 [1.0-7.0] vs 7.0 [3.0-11.0], p = 0.042) than those with CAS. Among participants with PCH, headache intensity was less severe in participants without CAS than in those with CAS (numeric rating scale, 8.0 [7.0-8.0] vs 9.5 [8.0-10.0], p = 0.015). In conclusion, a significant proportion of participants with CH and PCH did not have CAS. Some clinical features of CH and PCH differed based on the presence of CAS.
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http://dx.doi.org/10.1038/s41598-021-86408-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994319PMC
March 2021

SFTSV Infection Induced Interleukin-1β Secretion Through NLRP3 Inflammasome Activation.

Front Immunol 2021 23;12:595140. Epub 2021 Feb 23.

State Key Laboratory of Virology, School of Health Sciences, Wuhan University, Wuhan, China.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus that causes hemorrhagic fever. Previous studies showed that SFTSV-infected patients exhibited elevated levels of pro-inflammatory cytokines like interleukin-1β (IL-1β), indicating that SFTSV infection may activate inflammasomes. However, the detailed mechanism remains poorly understood. Herein, we found that SFTSV could stimulate the IL-1β secretion in the infected human peripheral blood mononuclear cells (PBMCs), human macrophages, and C57/BL6 mice. We demonstrate that the maturation and secretion of IL-1β during SFTSV infection is mediated by the nucleotide and oligomerization domain, leucine-rich repeat-containing protein family, pyrin-containing domain 3 (NLRP3) inflammasome. This process is dependent on protease caspase-1, a component of the NLRP3 inflammasome complex. For the first time, our study discovered the role of NLRP3 in response to SFTSV infection. This finding may lead to the development of novel drugs to impede the pathogenesis of SFTSV infection.
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http://dx.doi.org/10.3389/fimmu.2021.595140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940371PMC
February 2021

Exercise in Treatment of Migraine Including Chronic Migraine.

Curr Pain Headache Rep 2021 Feb 25;25(3):14. Epub 2021 Feb 25.

Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 03722, South Korea.

Purpose Of Review: With this review, we aimed to investigate the effect of exercise on migraine and explored the possibility of exercise as a treatment option for migraine.

Recent Findings: A close association of physical activity and exercise with migraine has been reported in clinical and population-based studies. Recent randomized controlled trials investigating the effect of aerobic exercise as a migraine-preventive treatment have revealed a notable improvement in migraine symptoms. Data on the effect of anaerobic exercise and exercise for flexibility, coordination, and relaxation on migraine are currently insufficient to make any recommendations. Possible pathways for the attenuation of migraine by exercise include the endogenous opioid and cannabinoid systems, brain-derived neurotrophic factor, inflammation, and behavioral/psychological factors. Regarding efficacy, side effects, and health benefits, aerobic exercise is a potentially beneficial strategy in the preventive treatment of migraine. Further studies are needed to delineate an evidence-based exercise program for migraine treatment.
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http://dx.doi.org/10.1007/s11916-020-00929-wDOI Listing
February 2021

Prevalence and characteristics of cutaneous allodynia in probable migraine.

Sci Rep 2021 Jan 28;11(1):2467. Epub 2021 Jan 28.

Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03772, Republic of Korea.

Cutaneous allodynia (CA) is a pain in response to non-nociceptive stimulation and a marker of central sensitisation. Probable migraine (PM) is a migraine subtype that fulfils all but one criterion of migraine. Headache intensity and the disability of individuals with PM are similar or lower than individuals with migraine. This study compared CA prevalence and characteristics of PM and migraine using a nationally representative sample in Korea. The Allodynia Symptom Checklist-12 (ASC-12) was used to assess CA (ASC-12 score ≥ 3). PM and migraine prevalence were 11.6% and 5.0%, respectively. CA prevalence did not significantly differ between PM and migraine (14.5% vs. 16.0%, p = 0.701). Participants with PM with CA reported a higher monthly headache frequency (3.3 ± 4.3 vs. 1.8 ± 3.6, p = 0.044), more severe headache intensity (Visuals Analogue Scale, 6.0 [4.0-7.0] vs. 5.0 [3.0-6.0], p = 0.002), and higher impact of headache (Headache Impact Test-6, 56.3 ± 7.2 vs. 48.3 ± 8.0, p < 0.001) than those without CA. Multiple regression analyses revealed that headache frequency and intensity, anxiety, and depression were significant factors for CA in participants with PM. In conclusion, CA prevalence among participants with PM and migraine were comparable. Anxiety, depression, and headache frequency and intensity were significant factors for CA in participants with PM.
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http://dx.doi.org/10.1038/s41598-021-82080-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844001PMC
January 2021

Prevalence, Disability, and Management Patterns of Migraine in Korea: Nationwide Survey Data from 2009 and 2018.

J Clin Neurol 2021 Jan;17(1):77-85

Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background And Purpose: Identifying changes in the prevalence, disability, and management patterns of migraine is important for reducing the burden of this disease. However, data on the changes in these variables are scarce.

Methods: We compared data obtained in the 2009 Korean Headache Survey and the 2018 Korean Sleep-Headache Survey.

Results: The 1-year migraine prevalence did not differ significantly between 2018 and 2009 [5.2% (114/2,200) vs. 6.0% (91/1,507), =0.492]. The number of days with missed activity due to headache during the previous 3 months was larger in the 2018 survey than in the 2009 survey [1.1±2.9 vs. 0.3±1.0 days (mean±standard deviation), =0.013]. The number of days with reduced productivity during the previous 3 months did not differ significantly between the two surveys (0.8±2.8 vs. 1.4±1.4 days, =0.679). The proportion of subjects with a substantial-to-severe headache impact (Headache Impact Test-6 score ≥56) was marginally larger in the 2018 survey than in the 2009 survey [42.1% (48/114) vs. 29.7% (27/91), =0.066]. The rate of lifetime medical consultations did not differ between the 2018 and 2009 surveys [34.2% (39/114) vs. 30.8% (28/91), =0.615].

Conclusions: Migraine prevalence was stable over the 9-year period between the surveys, but disability due to missed activity was greater in 2018 than in 2009 in Korea.
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http://dx.doi.org/10.3988/jcn.2021.17.1.77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840323PMC
January 2021

The Effect of Psychiatric Comorbidities on Headache-Related Disability in Migraine: Results From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

Headache 2020 Sep 16;60(8):1683-1696. Epub 2020 Aug 16.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

Objective: To examine the influences of depression and anxiety on headache-related disability in people with episodic migraine or chronic migraine.

Background: Depression and anxiety are common comorbidities in people with migraine, especially among those with chronic migraine.

Methods: This cross-sectional analysis of data from the longitudinal, internet-based Chronic Migraine Epidemiology and Outcomes Study assessed sociodemographic and headache features, and headache-related disability (Migraine Disability Assessment Scale). Four groups were defined based on scores from validated screeners for depression (9-item Patient Health Questionnaire) and anxiety (7-item Generalized Anxiety Disorder Scale): depression alone, anxiety alone, both, or neither.

Results: Respondents (N = 16,788) were predominantly women (74.4% [12,494/16,788]) and white (84.0% [14,044/16,788]); mean age was 41 years. Depression was more likely in persons with chronic migraine vs episodic migraine (56.6% [836/1476] vs 30.0% [4589/15,312]; P < .001), as were anxiety (48.4% [715/1476] vs 28.1% 4307/15,312]; P < .001) and coexisting depression and anxiety (42.0% [620/1476] vs 20.8% [3192/15,312]; P < .001). After controlling for headache frequency and other covariates, depression alone, and anxiety alone were associated with 56.0% (rate ratio [RR], 1.56; 95% confidence interval [CI], 1.46-1.66) and 39.0% (RR, 1.39; 95% CI, 1.30-1.50) increased risks of moderate/severe migraine-related disability (both P < .001), respectively; the combination had an even greater effect on risk of moderate/severe disability (79.0% increase; RR, 1.79; 95% CI, 1.71-1.87; P < .001).

Conclusions: Depression alone and anxiety alone are associated with greater headache-related disability after controlling for sociodemographic and headache features. Coexisting depression and anxiety are more strongly associated with disability than either comorbidity in isolation. Interventions targeting depression and anxiety as well as migraine itself may improve headache-related disability in people with migraine.
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http://dx.doi.org/10.1111/head.13914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496280PMC
September 2020

Risk Factors for Severe Residual Headache in Cerebral Venous Thrombosis.

Stroke 2021 Jan 7;52(2):531-536. Epub 2021 Jan 7.

China-America Institute of Neuroscience (K.J., C.Z., L.W., W.L., M.J., M.C., D.W., X.J.), Xuanwu Hospital, Capital Medical University, Beijing, China.

Background And Purpose: Which factors will influence the presence of severe residual headache after cerebral venous thrombosis (CVT) is unclear. The purpose of this study was to identify risk factors for severe residual headache in a large single-center cohort of patients with CVT.

Methods: We consecutively included eligible patients with CVT from a prospective stroke registry. Severe residual headache was defined as a residual headache attack requiring bed rest or hospital admission within 1 month before the last follow-up visit. We identified the risk factors of severe residual headache in all survivors and in those with favorable functional outcome (a modified Rankin Scale score, 0-2).

Results: A total of 325 patients' data were analyzed. At the last follow-up (median 13 months), 43 patients (13.2%) reported severe headache. In the multivariable analysis, isolated intracranial hypertension (odds ratio [OR], 3.309 [95% CI, 1.434-7.634]; =0.005), CVT recurrence (OR, 4.722 [95% CI, 1.639-13.602]; =0.004), and no recanalization (OR, 10.158 [95% CI, 4.194-24.600]; <0.001) were independently associated with severe headache. Severe headache was more frequent in patients with unfavorable outcome (11/25 [44.0%] versus 32/300 [10.7%]; <0.001). In patients with favorable outcome, the risk factors for severe headache were isolated intracranial hypertension (OR, 3.236 [95% CI, 1.268-8.256]; =0.014) and no recanalization (OR, 7.863 [95% CI, 3.120-19.812]; <0.001).

Conclusions: Isolated intracranial hypertension, CVT recurrence, and no recanalization increased the risk for severe residual headache after CVT.
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http://dx.doi.org/10.1161/STROKEAHA.120.029820DOI Listing
January 2021

Identification of Yak's Alternative Spliceosomes and Bioinformatic Analysis of TLR4 Protein Structure and Function.

Animals (Basel) 2020 Dec 26;11(1). Epub 2020 Dec 26.

Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.

In this study, the yak's gene alternative spliceosomes were investigated using PCR amplification and cloning to improve disease-resistance in yak and promote efficient utilization of yak's resources. qRT-PCR was used to determine the expression levels of two alternatively spliced transcripts of the gene in seven distinct tissues. To predict the function of proteins expressed by each spliceosome, bioinformatic analysis of yak's TLR4 protein structure and function was performed, which led to the identification of two alternative spliceosomes of yak's gene. The TLR4-X1 sequence length was 2526 bp, and it encoded full-length TLR4 protein (841 amino acids). The sequence length of the exon-2 deleted TLR4-X2 sequence was 1926 bp, and it encoded truncated TLR4 protein (641 amino acids). TLR4-X2 sequence was consistent with the predicted sequence of the gene in GenBank. Each tissue showed significantly different expression levels of these two alternative spliceosomes. As per the bioinformatic analysis of the structure and function of TLR4 protein, deletion of exon-2 in the gene resulted in frameshift mutations of the reading frame in the corresponding protein, which altered its ligand-binding and active sites. Besides, biological property such as substrate specificity of truncated TLR4 protein was also altered, leading to altered protein function. This study has laid a theoretical foundation for exploring the role of two variants of the gene in yak's disease resistance. Besides, this study's data could be analyzed further to explore the molecular mechanism associated with disease-resistance in the yak.
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http://dx.doi.org/10.3390/ani11010032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823342PMC
December 2020

Copy number variation of the HPGDS gene in the Ashidan yak and its associations with growth traits.

Gene 2021 Mar 26;772:145382. Epub 2020 Dec 26.

Key Laboratory of Yak Breeding Engineering Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China. Electronic address:

Copy number variation (CNV) is a structural variation at the submicroscopic level of the genome, which can affect gene-related phenotypes by changing genes dosage and transcript structure. Hematopoietic prostaglandin D synthase (HPGDS) is a member whose functions are closely related to weight gain and inflammatory diseases of the glutathione S-transferase (GSTs) family. In this study, the growth characteristics (body weight, withers height, body length, and chest girth) of 336 Ashidan yaks were monitored at four stages (6 months, 12 months, 18 months, and 30 months). In addition, CNV of the HPGDS gene was detected, discovered relationships of CNV with growth traits, and explored the level of gene expression. Based on the statistical analysis by IBM SPSS software, significant correlations were observed between HPGDS-CNV and body weight in 12-month-old yak (P < 0.01), 18-month-old yak (P < 0.001) and 30-month-old yak (P < 0.001) and body length in 18-month-old yak (P < 0.05) and 30-month-old yak (P < 0.05), respectively. Additionally, the individuals with gain copy number type performed better in body weight and body length than those with normal or loss copy number type. To our best of knowledge, this is the first time to make efforts to probe into the role of HPGDS-CNV and its interaction with livestock growth traits. Our results suggested that the CNV of the HPGDS gene may be an active candidate gene for the marker-assisted selection (MAS) of yaks.
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http://dx.doi.org/10.1016/j.gene.2020.145382DOI Listing
March 2021

The complete mitochondrial genome sequence and phylogenetic analysis of Sibu yak ().

Mitochondrial DNA B Resour 2019 Dec 9;5(1):46-47. Epub 2019 Dec 9.

Key Laboratory for Yak Breeding Engineering of Gansu Province, Lanzhou, PR China.

Sibu yak is famous for its excellent breed in Tibet and has become a magic way for local herdsmen to get rich. The Sibu yak, however, has been identified as an endangered bovine species. In this study, the complete mitochondrial genome of Sibu yak () was sequenced. The complete mitochondrial genome is a circular molecule with 16,324 bp in length, including 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes, and a non-coding control region (D-loop). The entire nucleotide composition is A(33.70%), T(27.27%), C(25,81%), G(13.21%), respectively. Except that ND6 and 7 tRNAs (tRNA-Glu,tRNA-Pro,tRNA-Cys, tRNA-Tyr, tRNA-Ala, tRNA-Asn, and tRNA-Gln) are encoded on the light strand, the remaining genes are encoded on the heavy strand. As a valuable resource, we have compared it to related Bos species to understand the evolutionary history of Sibu yak.
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http://dx.doi.org/10.1080/23802359.2019.1693929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720976PMC
December 2019

Characterization of the complete mitochondrial genome of the Tianjun yak ().

Mitochondrial DNA B Resour 2019 Nov 20;4(2):4120-4121. Epub 2019 Nov 20.

Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, People's Republic of China.

Tianjun yak () is a yak breed with strong adaptation to the high-elevation, cold and anoxic environments. Its complete mitochondrial genome is 16,323 bp long with an asymmetric base composition, and harbors the 37 typical mitochondrial genes and one noncoding control region. The PCGs are initiated with the typical ATA or ATG codons, and are terminated with TAA, TAG or the incomplete stop codon T--. Phylogenetic analysis suggests that Tianjun yak is most closely related to the polled yak.
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http://dx.doi.org/10.1080/23802359.2019.1692716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707699PMC
November 2019

Characterisation of the complete mitochondrial genome of the Jinchuan Yak ().

Mitochondrial DNA B Resour 2019 Nov 8;4(2):3856-3857. Epub 2019 Nov 8.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Jinchuan yak was a newly discovered yak breed, not only possesses a large proportion of multi-ribs but also exhibits many good characteristics. However, there is limited information about its overall genetic structure. In this study, we assembled the mitochondrial genome for Jinchuan yak (), the results show that the mitochondrial genome is 16,324bp long with an A + T-biased base composition (61.0% A + T) and harbours the typical set of 37 mitochondrial genes and 1 non-coding control region. The PCGs start with the typical ATA or ATG codons and are terminated with TAA, TAG or the incomplete stop codon T. Phylogenetic analysis suggests that Jinchuan yak is most closely related to Datong yak and Sunan yak.
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http://dx.doi.org/10.1080/23802359.2019.1681312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707553PMC
November 2019

Transcriptome Analysis Reveals the Potential Role of Long Non-coding RNAs in Mammary Gland of Yak During Lactation and Dry Period.

Front Cell Dev Biol 2020 25;8:579708. Epub 2020 Nov 25.

Key Lab of Yak Breeding Engineering, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China.

The mammary gland is a remarkably dynamic organ of milk synthesis and secretion, and it experiences drastic structural and metabolic changes during the transition from dry periods to lactation, which involves the expression and regulation of numerous genes and regulatory factors. Long non-coding RNA (lncRNA) has considered as a novel type of regulatory factors involved in a variety of biological processes. However, their role in the lactation cycle of yak is still poorly understood. To reveal the involved mechanism, Ribo-zero RNA sequencing was employed to profile the lncRNA transcriptome in mammary tissue samples from yak at two physiological stages, namely lactation (LP) and dry period (DP). Notably, 1,599 lncRNA transcripts were identified through four rigorous steps and filtered through protein-coding ability. A total of 59 lncRNAs showed significantly different expression between two stages. Accordingly, the results of qRT-PCR were consistent with that of the transcriptome data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that target genes of differentially expressed lncRNAs (DELs) were involved in pathways related to lactation, such as ECM-receptor interaction, PI3K-Akt signaling pathway, biosynthesis of amino acids and focal adhesion etc. Finally, we constructed a lncRNA-gene regulatory network containing some well known candidate genes for milk yield and quality traits. This is the first study to demonstrate a global profile of lncRNA expression in the mammary gland of yak. These results contribute to a valuable resource for future genetic and molecular studies on improving milk yield and quality, and help us to gain a better understanding of the molecular mechanisms underlying lactogenesis and mammary gland development of yak.
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http://dx.doi.org/10.3389/fcell.2020.579708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723986PMC
November 2020

Secondary Structural Transformation of Bovine Lactoferricin Affects Its Antibacterial Activity.

Probiotics Antimicrob Proteins 2021 Jun 14;13(3):873-884. Epub 2020 Nov 14.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.

Lactoferricin (Lfcin) is a potent antibacterial peptide derived from lactoferrin by pepsin hydrolysis. It was hypothesized that structural transformation of Lfcin could affect its antibacterial function through forming and breaking of intramolecular disulfide bond. To prove this hypothesis, bovine Lfcin (bLfcin) and its two derivatives, bLfcin with a disulfide bond (bLfcin DB) and bLfcin with a mutation C36G (bLfcin C36G), were synthesized, purified, and identified. The circular dichroism (CD) spectra of the peptides were detected in solutions with different ionic and hydrophobic strength. Then, the secondary structure contents of the peptides were calculated on the basis of the CD spectra. The antibacterial activity of the peptides against Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 14028, Shigella flexneri ATCC 12022, and Staphylococcus aureus ATCC 25923 was evaluated. The results showed that bLfcin and bLfcin C36G had similar percentages of secondary structure in water, while bLfcin and bLfcin DB had similar ratios of secondary structure under less hydrophobic conditions. The synthetic peptides exhibited antibacterial activity against all the tested bacteria, except for S. aureus ATCC 25923. bLfcin demonstrated higher antibacterial activity compared with its derivatives. The results suggested that bLfcin could transform its structure under alterative ionic strengths and hydrophobic conditions, and the transformation of structures was beneficial to enhancing the antibacterial function.
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http://dx.doi.org/10.1007/s12602-020-09726-8DOI Listing
June 2021

Endophytic bacterial communities and spatiotemporal variations in cotton roots in Xinjiang, China.

Can J Microbiol 2020 Nov 12. Epub 2020 Nov 12.

Xinjiang Academy of Agricultural Sciences, 74608, Urumqi, China, 830091.

Endophytic bacteria may be important for plant health and other ecologically relevant functions of cotton. However, the endophytic bacterial community structure and diversity in cotton is still poorly characterized. We investigated the community structure of endophytic bacteria in cotton roots growing in Xinjiang, China, using the Illumina amplicon sequencing. A total of 60.84 M effective sequences of 16S rRNA gene V3 region were obtained from cotton samples. These sequences revealed huge amount of operational taxonomic units (OTUs) in cotton, that is, 81-338 OTUs in a cotton sample, at 3% cutoff level and sequencing depth of 50000 sequences. We identified 23 classes from the resulting 2,723,384 sequences. Gammaproteobacteria were the dominant class in all cottons, followed by Alphaproteobacteria, Actinobacteria and Bacilli. A marked difference in the diversity of endophytic bacteria in cotton for different growth periods was evident. The greatest number of OTUs was detected during seedling (654 OTUs) and budding (381 OTUs). Endophytic bacteria diversity was reduced during flowering (350 OTUs) and boll-opening (351 OTUs). 217 OTUs were common to all four periods. There were more tags of Pantoea in Shihezi than other locations. While there were more tags of Erwinia in Hami than other locations. The dynamics of endophytic bacteria communities were influenced by plant growth stage. These results show the complexity of the bacterial populations present in inner tissues of cotton.
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http://dx.doi.org/10.1139/cjm-2020-0249DOI Listing
November 2020

Sex differences in the association between chronotype and risk of depression.

Sci Rep 2020 10 28;10(1):18512. Epub 2020 Oct 28.

Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Information on sex differences in the association between chronotype and depression is scarce. We aimed to investigate these differences using data from the Korea National Health and Nutrition Examination Survey in 2016. Chronotypes were categorised based on mid-sleep time on free days corrected by sleep debt accumulated on workdays (MSFsc): early type, < mean MSFsc - 1 standard deviation (SD); intermediate type, between mean MSFsc - 1 SD and MSFsc + 1 SD; and late type, > mean MSFsc + 1 SD. A Patient Health Questionnaire-9 score of ≥ 10 indicated depression. Among 5550 non-shift working adults aged 19-80 years, the prevalence rates of depression in the early, intermediate, and late chronotype groups were 7.4%, 4.5%, and 9.3%, respectively. Women with late chronotype (odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.8-4.7) showed a higher risk of depression than women with intermediate chronotype after adjusting for covariates. Women with early chronotype did not show a significant difference in depression risk (OR = 1.3, 95% CI = 0.9-2.0). In conclusion, late chronotype is associated with an increased risk of depression in women but not in men. Early chronotype is not associated with depression in women or men.
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http://dx.doi.org/10.1038/s41598-020-75724-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595163PMC
October 2020

Effect of intramolecular disulfide bond of bovine lactoferricin on its molecular structure and antibacterial activity against Trueperella pyogenes separated from cow milk with mastitis.

BMC Vet Res 2020 Oct 23;16(1):401. Epub 2020 Oct 23.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, 730050, Lanzhou, China.

Background: Lactoferricin (Lfcin) is an antimicrobial activity center of lactoferrin, produced by hydrolysis from the N-terminal of lactoferrin. It was hypothesized that the intramolecular disulfide bond in Lfcin could affect its antibacterial function through influencing its molecular structure. To prove this hypothesis, bovine Lfcin (bLfcin) and its two derivatives, bLfcin with an intramolecular disulfate bond (bLfcin DB) and bLfcin with a mutation C36G (bLfcin C36G), were synthesized, purified, and identified. The circular dichroism spectra of the peptides were detected in solutions with different ionic and hydrophobic strength. The antibacterial activity of the peptides against Trueperella pyogenes, separated from cow milk with mastitis, were determined.

Results: The secondary structure of bLfcin DB showed more β-turn and less random coil than the other peptides in HO, similar ratios of secondary structures with bLfcin and bLfcin C36G under ionic conditions, and close percentages of secondary structure with bLfcin under hydrophobic conditions. The synthetic peptides exhibited strong antimicrobial activity against T. pyogenes isolates, T. pyogenes ATCC 19,411, and E. coli ATCC 25,922. The antimicrobial activities of the three peptides were greater against T. pyogenes than against E. coli, and bLfcin DB exhibited higher antibacterial activity compared with its derivatives.

Conclusions: The intramolecular disulfide bond could change the molecular structure of bLfcin under alternative ionic strengths and hydrophobic effects, and the formation of the disulfide bond is beneficial to executing the antibacterial function of bLfcin.
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http://dx.doi.org/10.1186/s12917-020-02620-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585202PMC
October 2020

Clinical characteristics of pre-attack symptoms in cluster headache: A large series of Korean patients.

Cephalalgia 2021 Feb 21;41(2):227-236. Epub 2020 Oct 21.

Department of Neurology, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea.

Background: Previous studies have reported notable differences in demographic and clinical features of cluster headache between Western and Asian populations, including lower prevalence of the chronic type and in women. Recently, prodromal symptoms of migraine and pre-attack symptoms of cluster headache have drawn attention regarding their potential pathophysiological implications and pre-emptive treatment. However, pre-attack symptoms of cluster headache have not been studied in the Asian population.

Methods: A total of 136 patients with cluster headache (21 first-onset, 110 episodic, and five chronic cases) were recruited in this multi-center study between October 2018 and December 2019. We evaluated the characteristics of pre-attack symptoms in a current bout using a structured questionnaire. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with presence of pre-attack symptoms.

Results: Pre-attack symptoms were reported in 71.3% of our patients with cluster headache. When present, pre-attack symptoms occurred at a median of 20 minutes (range 1-120) before the attack. The prevalence of local and painful, local and painless sensory, autonomic, and general symptoms was 58.8%, 14.7%, 11.0%, and 30.1%, respectively. Multivariable logistic regression analysis revealed that higher number of bouts was associated with higher prevalence of pre-attack symptoms (OR = 1.464,  = 0.044).

Conclusions: Pre-attack symptoms were frequently observed in Korean patients with cluster headache, which was consistent with previous Western studies.
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http://dx.doi.org/10.1177/0333102420966983DOI Listing
February 2021

Nasal pain as an aura: Amygdala origin?

Seizure 2020 Dec 7;83:13-16. Epub 2020 Oct 7.

Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: Nasal pain, as an epileptic aura, has been poorly recognized. This study aims to demonstrate clinical features of patients with epilepsy who have nasal pain as an aura.

Methods: We retrospectively investigated consecutive patients who visited the epilepsy clinic of tertiary hospital from April 2000 to September 2019. All included patients underwent epilepsy-dedicated, high-resolution magnetic resonance imaging (MRI) examinations. All MRI studies were analyzed by visual inspection.

Results: Seven patients who presented nasal pain as an aura, were identified. Four patients reported nasal pain as the first aura. Four patients had right amygdala enlargement (isolated amygdala enlargement in three patients; amygdala enlargement in addition to hippocampal sclerosis in one patient), and one patient with compression of an internal carotid-posterior communicating artery aneurysm to right amygdala on brain MRI. Interictal epileptiform or ictal discharges on EEG were found in the right temporal region in five patients. In all four patients with amygdala enlargement, amygdala enlargement was ipsilateral to EEG anomalies. In all patients, nasal pain was accompanied by ictal semiological features, such as autonomic, olfactory, abdominal, or psychic auras, and focal impaired awareness seizures, which are typically associated with mesial temporal lobe epilepsy.

Conclusions: Our findings suggest that nasal pain can occur as an epileptic aura in patients with temporal lobe epilepsy with probable involvement of the amygdala.
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http://dx.doi.org/10.1016/j.seizure.2020.09.028DOI Listing
December 2020

Therapeutic role of melatonin in migraine prophylaxis: Is there a link between sleep and migraine?

Prog Brain Res 2020 10;255:343-369. Epub 2020 Jun 10.

Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Melatonin is a ubiquitously distributed molecule that possesses diverse functions. Melatonin plays a key role in the endogenous circadian rhythms of humans via light stimulation in the hypothalamus. In addition, melatonin has roles in the opioid system, the nitric oxide pathway, free radical scavenging, inflammation, and antinociception. Melatonin is nontoxic and relatively safe. Recently, exogenous melatonin has been shown to have significant effects in the treatment of migraine. Further, it has demonstrated efficacy in the treatment of sleep disorders, including insomnia, circadian rhythm sleep-wake disorders, parasomnias, and sleep breathing disorders. Sleep disorders are commonly reported by those who experience migraine, and migraine and sleep disorders have been reported to be closely associated in cross-sectional studies. Longitudinal studies have shown that some sleep disorders and migraine show bidirectional comorbidities. Therefore, the identification and treatment of sleep disorders is important when treating migraine. Melatonin represents a promising treatment strategy for both disorders, especially when these conditions are combined.
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http://dx.doi.org/10.1016/bs.pbr.2020.05.014DOI Listing
June 2020