Publications by authors named "Tetsuya Yamamoto"

619 Publications

Cognitive control affects motor learning through local variations in GABA within the primary motor cortex.

Sci Rep 2021 Sep 17;11(1):18566. Epub 2021 Sep 17.

Division of Cerebral Integration, Department of System Neuroscience, National Institute for Physiological Sciences (NIPS), 38 Nishigonaka, Myodaiji, Okazaki, Aichi, 444-8585, Japan.

The primary motor cortex (M1) is crucial for motor learning; however, its interaction with other brain areas during motor learning remains unclear. We hypothesized that the fronto-parietal execution network (FPN) provides learning-related information critical for the flexible cognitive control that is required for practice. We assessed network-level changes during sequential finger tapping learning under speed pressure by combining magnetic resonance spectroscopy and task and resting-state functional magnetic resonance imaging. There was a motor learning-related increase in preparatory activity in the fronto-parietal regions, including the right M1, overlapping the FPN and sensorimotor network (SMN). Learning-related increases in M1-seeded functional connectivity with the FPN, but not the SMN, were associated with decreased GABA/glutamate ratio in the M1, which were more prominent in the parietal than the frontal region. A decrease in the GABA/glutamate ratio in the right M1 was positively correlated with improvements in task performance (p = 0.042). Our findings indicate that motor learning driven by cognitive control is associated with local variations in the GABA/glutamate ratio in the M1 that reflects remote connectivity with the FPN, representing network-level motor sequence learning formations.
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http://dx.doi.org/10.1038/s41598-021-97974-1DOI Listing
September 2021

Vertebral fracture and splenomegaly in a head and neck cancer producing granulocyte colony-stimulating factor: A case report of systemic complications associated with a cytokine-producing solid tumor.

Mol Clin Oncol 2021 Oct 8;15(4):202. Epub 2021 Aug 8.

Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University, Kochi 783-8505, Japan.

Granulocyte colony-stimulating factor (G-CSF)-producing tumors are rare and are associated with a poor prognosis when they occur in the lungs and the head and neck region. Positron emission tomography/computed tomography has been reported to show systemic specific accumulation of fluorodeoxyglucose in these cases, but the systemic complications associated with the cytokines produced are not well known. We herein present the case of a G-CSF-producing maxillary sinus squamous cell carcinoma in a 73-year-old Japanese woman with a vertebral fracture and splenomegaly. These findings are known severe adverse events of high-dose recombinant human G-CSF treatment. The aim of the present study was to further discuss the hypothesis that cytokines produced by solid tumors may induce spinal vertebral fracture and splenomegaly.
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http://dx.doi.org/10.3892/mco.2021.2364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375029PMC
October 2021

Evaluation of a combination protocol of CT-first triage and active telemedicine methods by a selected team tackling COVID-19: An experimental research study.

J Infect Public Health 2021 Sep 18;14(9):1212-1217. Epub 2021 Aug 18.

Team COVID-19, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa, Yokohama 2360004, Japan; Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 2360004, Japan.

Background: Many health care workers around the world tackled with COVID-19, however sadly, the infection of many medical care workers were reported. To reduce the risk of infection, we launched selected team (Team COVID) of non-specialists and brought in active telemedicine method and computed tomography (CT)-first protocol. We describe our actual practice and the health status of medical doctors dealing with COVID-19 patients.

Methods: Between April 17, 2020 and May 24, 2020, 10 doctors worked with COVID-19 patients as part of Team COVID. The Team COVID doctors used a CT-first triage protocol for outpatients and telemedicine for inpatients and outpatients. We evaluated paired serum-specific antibodies for SARS-CoV-2 at the initial and end of the study duration and PCR results for SARS-CoV-2 at the end of the study duration. Furthermore, 36-item short-form of the Medical Outcome Study Questionnaire (SF-36) at the beginning and end of the study period were evaluated.

Results: Ten doctors worked as Team COVID: seven internal medicine doctors and three surgeons. During the study period, Team COVID treated 165 individuals in the outpatient clinic and isolated hospitalized patients for 315 person-days. There were no positive results of serum-specific antibody testing and PCR testing for SARS-CoV-2 in Team COVID doctors. Furthermore, the SF-36 showed no deterioration in physical and mental QOL status. No in-hospital infection occurred during the study period.

Conclusions: The Team COVID fulfilled the treatment using the active telemedicine and CT-first triage protocol without in hospital infection and excess stress. The combination strategy seems acceptable for both the protection and stress relief among the medical staff.
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http://dx.doi.org/10.1016/j.jiph.2021.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372458PMC
September 2021

Relationship between structural and functional changes in glaucomatous eyes: a multifocal electroretinogram study.

BMC Ophthalmol 2021 Aug 21;21(1):305. Epub 2021 Aug 21.

Department of Ophthalmology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-shi, Gifu, 501-1194, Japan.

Background: The nasal to temporal amplitudes ratio (N/T) of multifocal electroretinography (mfERG) scans measured within 5° of the macula can be used to detect glaucomatous change. The photopic negative response (PhNR) of mfERG elicited by a circular stimulus centered on the fovea was significantly reduced in eyes with glaucoma. The PhNR to B-wave ratio (PhNR/B) is the optimal measure of the PhNR. However, clinical superiority for evaluating glaucoma patients has not been determined between N/T and PhNR/B yet.

Methods: For morphological assessments, ganglion cell complex (GCC) in six regions and the average were measured by optical coherence tomography (OCT). For functional assessment, Humphrey visual fields (VF) with mean sensitivities (MT) and mfERG scans with parameters of N/T and the multifocal photopic negative response to B-wave ratio (mfPhNR/B) were measured. Sixty-nine eyes of 44 glaucoma patients were included and correlations between mfERG parameters and OCT or VF parameters were evaluated.

Results: The mean age of patients was 59.4 years. The mean deviation for all eyes obtained with the VF 30-2 and VF 10-2 was - 7.00 and - 6.31 dB, respectively. Significant correlations between GCC thickness or VF parameter and the N/T were found, especially in the inferior and inforotemporal retinal areas corresponding to superior and superonasal VF sectors (GCC vs N/T; coefficient = - 7.916 and - 7.857, and MT vs N/T; coefficient = - 4.302 and - 4.437, in the inferior and inforotemporal retinal areas, respectively, all p values < 0.05). However, similar associations were not obtained between mfPhNR/B and OCT or VF parameters. The mfPhNR/B only in the inferotemporal sector was significantly correlated with the average thickness of GCC (coefficient = 4.823, P = 0.012).

Conclusions: The N/T was correlated with GCC and VF in more numbers of measurement areas than the mfPhNR/B in the current study, however, a future study modifying the stimuli and amplitudes to obtain the spatial correspondence to OCT and VF measurement will be required to evaluate the value of mfERG.
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http://dx.doi.org/10.1186/s12886-021-02061-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379802PMC
August 2021

In vivo brain levels of acetylcholine and 5-hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement.

Eur J Neurosci 2021 Aug 3. Epub 2021 Aug 3.

Intercontinental Neuroscience Research Group.

The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that has been linked to the modulation of several physiological functions, including the sleep-wake cycle. The PPARα recognizes as endogenous ligands the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which in turn, if systemically injected, they exert wake-promoting effects. Moreover, the activation of PPARα by the administration of OEA or PEA increases the extracellular contents of neurotransmitters linked to the control of wakefulness; however, the role of PPARα activated by OEA or PEA on additional biochemicals related to waking regulation, such as acetylcholine (ACh) and 5-hydroxytryptamine (5-HT), has not been fully studied. Here, we have investigated the effects of treatments of OEA or PEA on the contents of ACh and 5-HT by using in vivo microdialysis techniques coupled to HPLC means. For this purpose, OEA or PEA were systemically injected (5, 10 or 30 mg/kg; i.p.), and the levels of ACh and 5-HT were collected from the basal forebrain, a wake-related brain area. These pharmacological treatments significantly increased the contents of ACh and 5-HT as determined by HPLC procedures. Interestingly, PPARα antagonist MK-886 (30 mg/kg; i.p.) injected before the treatments of OEA or PEA blocked these outcomes. Our data suggest that the activation of PPARα by OEA or PEA produces significant changes on ACh and 5-HT levels measured from the basal forebrain and support the conclusion that PPARα is a suitable molecular element involved in the regulation of wake-related neurotransmitters.
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http://dx.doi.org/10.1111/ejn.15409DOI Listing
August 2021

Cyclothymic Temperament is Associated with Poor Medication Adherence and Disordered Eating in Type 2 Diabetes Patients: A Case-Control Study.

Diabetes Ther 2021 Sep 31;12(9):2611-2624. Epub 2021 Jul 31.

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Kimitsu Chuo Hospital, Sakurai 1010, Kisarazu, Chiba, 292-0822, Japan.

Introduction: Poor medication adherence and disordered eating are major self-care problems in patients with type 2 diabetes that worsen glycemic control and increase the risk of developing severe diabetes complications. Affective temperament, which remains mostly unchanged throughout life, is speculated to predict poor treatment response and high comorbidity. The aim of this study was to explore the link between affective temperament and poor glycemic control due to insufficient self-care.

Methods: This single-center case-control study involved 77 outpatients divided into the 'poor glycemic control' group (n = 52) and the 'better glycemic control' group (n = 25) based on their mean glycated hemoglobin (HbA1c) levels over the past 12 months. All participants underwent one-on-one interviews during which they completed the following psychometric questionnaires: (1) the Mini-International Neuropsychiatric Interview 5.0.0; (2) the Temperament Evaluation of Memphis, Pisa, and San Diego Auto-questionnaire; (3) a researcher-designed single question for assessing subclinical stress-induced overeating; and (4) the Morisky Medication Adherence Scale. The difference between two continuous independent variables was determined using Student's t test. Discrete variables were compared using the Chi-square (χ) or Fisher's exact test. Multiple testing corrections were performed using the false discovery rate.

Results: Those outpatients in the poor glycemic control group exhibited significantly more stress-induced overeating (χ = 1.14, q statistic = 0.040) and poor medication adherence (t = 3.70, q = 0.034) than those in the better glycemic control group. However, there were no significant differences between the two groups in terms of affective temperaments, clinical eating disorders, or diabetes-specific distress. Patients with stress-induced overeating (t = - 2.99, p = 0.004) and poor medication adherence (t = - 4.34, p = 0.000) exhibited significantly higher scores for cyclothymic temperament than their counterparts.

Conclusion: Cyclothymic temperament is significantly associated with disordered eating and/or poor medication adherence in patients with type 2 diabetes and is possibly linked to poor glycemic control.
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http://dx.doi.org/10.1007/s13300-021-01121-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384994PMC
September 2021

Posterior Ankle Arthroscopy for Flexor Hallucis Longus Entrapment: A Case Report.

J Orthop Case Rep 2021 Apr;11(4):70-74

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan.

Introduction: Stenosing tenosynovitis is a chronic disorder frequently observed in finger triggering of a digit. Regarding the toes, although entrapment of the flexor hallucis longus (FHL) has already been reported in a few cases among sports players, the clinical condition is uncommon. Besides, the case without any specific causes is particularly rare.

Case Report: We report the case of a 26-year-old male with FHL entrapment. Even though he was unaware of any cause, he felt tenderness on the posteromedial side of his left ankle, and his great toe was locked in the flex position. Magnetic resonance imaging indicated effusion in the tendon sheath of the FHL and the possibility of a partial tear of the FHL. We hypothesized that the scar tissue secondary to the partial tear of the FHL may have been irritated at the retrotalar pulley below the sustentaculum tali, where the FHL glides. Therefore, posterior ankle arthroscopy was performed for the treatment of the FHL entrapment.

Conclusion: Orthopedic surgeons should list this pathology as a differential diagnosis of posterior ankle pain, even in non-athletes.
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http://dx.doi.org/10.13107/jocr.2021.v11.i04.2158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310630PMC
April 2021

Diffuse bone marrow uptake related to granulocyte colony-stimulating factor-producing maxillary sinus carcinoma on 4-borono-2-F-fluoro-L-phenylalanine positron emission tomography/computed tomography.

World J Nucl Med 2021 Apr-Jun;20(2):188-191. Epub 2020 Oct 23.

Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University, Nangoku, Kochi, Japan.

Granulocyte colony-stimulating factor (G-CSF) can be produced by tumor cells and is known to promote tumor growth, thereby potentially accelerating disease progression. Squamous cell carcinoma (SCC) at maxillary sinus is aggressive growth with poor prognosis. Maxillary sinus carcinomas are rare and can be clinically silent in the early stages or manifest with the same signs and symptoms of more common illnesses, leading to their delayed diagnosis of disease. Hypermetabolic uptake of F-fluorodeoxyglucose (F-FDG) but not of 4-borono-2-F-fluoro- L-phenylalanine (F-FBPA), in the bone marrow of patients with G-CSF-producing tumors without bone marrow involvement during positron emission tomography (PET), has been reported. The present case report describes our first experience of bone marrow uptake in PET/computed tomography examination usingF-FBPA, high uptake seen in the bone marrow of a patient with a G-CSF-secreting SCC of the maxillary sinus that it relapsed following chemoradiation therapy and surgical resection of the tumor.
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http://dx.doi.org/10.4103/wjnm.WJNM_80_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286009PMC
October 2020

Social isolation and its psychosocial factors in mild lockdown for the COVID-19 pandemic: a cross-sectional survey of the Japanese population.

BMJ Open 2021 07 14;11(7):e048380. Epub 2021 Jul 14.

Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima, Tokushima, Japan.

Objective: This study investigated the sociodemographic, behavioural and psychological characteristics of socially isolated individuals during the 'mild lockdown' period of COVID-19 in Japan.

Design: A cross-sectional study.

Setting: The seven prefectures where the emergency declaration was first applied in Japan.

Participants: We collected data on 11 333 individuals (52.4% women, 46.3±14.6 years) living in the seven prefectures where the emergency declaration was first applied. The online survey was performed between 11 May and 12 May 2020, in the final phase of the state of emergency.

Primary Outcome Measures: Lubben Social Network Scale (LSNS-6) RESULTS: We found that male sex (95% CI 1.60 to 1.98), middle age (95% CI 1.55 to 1.93) and lower income (eg, annual household income <2.0 million: 95% CI 2.29 to 3.54) predicted social isolation; being a student was a protective factor against social isolation (95% CI 0.26 to 0.62). In the comparisons of each item of the LSNS-6 by sociodemographic characteristics, men were more likely to have fewer people to talk to about their personal problems (95% CI -0.37 to -0.28) and to seek help from (95% CI -0.39 to -0.30), and the middle-aged group had a lower social network of friends. Additionally, social isolation was associated with decreased online interaction with familiar people (95% CI -1.28 to -1.13) and decreased optimistic thinking under mild lockdown (95% CI -0.97 to -0.86).

Conclusions: We identified the sociodemographic and psychological characteristics associated with social isolation under mild lockdown. These results are expected to be a useful resource for identifying which groups may require intervention to improve their social interactions in order to preserve their mental health during the pandemic.
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http://dx.doi.org/10.1136/bmjopen-2020-048380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282418PMC
July 2021

Primary central nervous system lymphoma: clinicopathological and genomic insights for therapeutic development.

Brain Tumor Pathol 2021 Jul 13;38(3):173-182. Epub 2021 Jul 13.

Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

Primary central nervous system lymphoma (PCNSL) is a highly aggressive, extra-nodal non-Hodgkin lymphoma that is confined to the central nervous system (CNS) and the eyes. Most PCNSLs arise in immunocompetent older patients and less frequently in immunocompromised patients with Epstein-Barr virus infection. Although a patient's initial response to chemotherapy and radiation therapy is favorable, the clinical outcome of PCNSL remains poor compared to that of systemic lymphoma. Radiation-induced neurotoxicity is also a critical problem for patients with PCNSL. Therefore, a novel therapeutic strategy is required to overcome these challenges. Recent studies have largely uncovered the genomic landscape and associated histopathological features of PCNSL. Based on this background, novel therapeutic agents, such as Bruton's tyrosine kinase inhibitors and immune checkpoint inhibitors, have been introduced for patients with PCNSL. Here, we provide an overview of the updated histopathological and genomic characterization of PCNSL and summarize the current therapeutic strategies. We also review current preclinical PCNSL models for translational research.
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http://dx.doi.org/10.1007/s10014-021-00408-zDOI Listing
July 2021

Assessing the treatment of cannabidiolic acid methyl ester: a stable synthetic analogue of cannabidiolic acid on c-Fos and NeuN expression in the hypothalamus of rats.

J Cannabis Res 2021 Jul 12;3(1):31. Epub 2021 Jul 12.

Institute for Drug Research, Medical Faculty, Hebrew University, Jerusalem, Israel.

Background: Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals.

Objective: To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated.

Methods: c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.).

Results: Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part.

Conclusion: HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep-wake cycle by engaging the hypothalamus.
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http://dx.doi.org/10.1186/s42238-021-00081-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276432PMC
July 2021

Response inhibition deficits are positively associated with trait rumination, but attentional inhibition deficits are not: aggressive behaviors and interpersonal stressors as mediators.

Psychol Res 2021 Jun 6. Epub 2021 Jun 6.

Graduate School of Technology, Industrial and Social Sciences, Tokushima University, 1-1, Minamijosanjima-cho, Tokushima, 770-8502, Japan.

Previous findings on relationships between inhibition that is a core executive function, and trait rumination have been inconsistent. This inconsistency could be overcome by investigating the association between rumination and the two subcomponents of inhibition: response inhibition and attentional inhibition. This study examined whether and how response inhibition and attentional inhibition were related to rumination as well as worry. University students in Japan (N = 213) conducted the Go/No-Go Task and the Modified Stroop Task. They also completed self-report measures of depression, trait rumination, trait worry, stressors, and aggressive behaviors. Results indicated that response inhibition deficits were positively associated with trait rumination, and this association was mediated by increases in aggressive behaviors and interpersonal stressors. The associations between these variables remained significant even after controlling for depression level. There were no significant direct or indirect associations between attentional inhibition deficits and rumination. These results suggest that response inhibition deficits, among the subcomponents of inhibition, have an indirect positive association with rumination through interpersonal processes. Results also showed nonsignificant differences between rumination and worry in the magnitude of correlation coefficients with the two subcomponents of inhibition. Therefore, it remains unclear whether the positive association with response inhibition is unique to rumination.
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http://dx.doi.org/10.1007/s00426-021-01537-yDOI Listing
June 2021

Real-world evaluation of a computed tomography-first triage strategy for suspected Coronavirus disease 2019 in outpatients in Japan: An observational cohort study.

Medicine (Baltimore) 2021 Jun;100(22):e26161

Team COVID-19, Yokohama City University Hospital.

Abstract: The Coronavirus disease 2019 pandemic continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with symptoms of Coronavirus disease 2019 are treated as suspected of the disease. Use of computed tomography findings in Coronavirus disease 2019 are expected to be a reasonable method for triaging patients, and computed tomography-first triage strategies have been proposed. However, clinical evaluation of a computed tomography-first triage protocol is lacking.The aim of this study is to investigate the real-world efficacy and limitations of a computed tomography-first triage strategy in patients with suspected Coronavirus disease 2019.This was a single-center cohort study evaluating outpatients with fever who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February and 5 May 2020. We treated according to the computed tomography-first triage protocol. The primary outcome was efficacy of the computed tomography-first triage protocol for patients with fever in an outpatient clinic. Efficacy of the computed tomography-first triage protocol for outpatients with fever was evaluated using sensitivity, specificity, positive predictive value, and negative predictive value. We conducted additional analyses of the isolation time of feverish outpatients and final diagnoses.In total, 108 consecutive outpatients with fever were examined at our hospital. Using the computed tomography-first triage protocol, 48 (44.9%) patients were classified as suspected Coronavirus disease 2019. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group considered less likely to have Coronavirus disease 2019 tested positive for the virus. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs 1037.0 minutes, P < .001).Our computed tomography-first triage protocol was acceptable for screening patients with suspected Coronavirus disease 2019. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is inadequate.
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http://dx.doi.org/10.1097/MD.0000000000026161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183760PMC
June 2021

The Role of Peroxisome Proliferator-Activated Receptor in Addiction: A Novel Drug Target.

Curr Top Med Chem 2021 ;21(11):964-975

Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, Division Ciencias de la Salud, Universidad Anahuac Mayab, Merida, Yucatan, Mexico.

The peroxisome proliferator activated receptors (PPARs) are a superfamily of well-recognized ligand-binding nuclear receptors comprising three isoforms: PPARα, PPARγ, and PPARβ/δ. In response to endogenous lipid messengers, PPARs trigger the transcription of genes related to a wider spectrum of physiological phenomena, including fatty acid oxidation, inflammation, adipogenesis, among many others. Thus, the importance of PPARs as putative protective therapy in health issues has increased the interest of studying these nuclear receptors, including the management of neurodegenerative disorders, multiple sclerosis, and likely addiction. In recent years, several pieces of evidence from animal models have demonstrated the promising role of PPARs as a critical element for interventions in addictive behaviors by reducing the reinforcing properties of addictive substances such as alcohol. However, there is a lack of data in the scope and has so far been unexplored the function of PPARs in additional drugs such as cannabis, opioids, methamphetamine, or cocaine. A similar scenario has been found for the management of binge-type eating disorders. Thus, here we review recent advances in understanding the relevance of the PPAR controlling addiction.
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http://dx.doi.org/10.2174/1568026621666210521165532DOI Listing
January 2021

Surfactant-Free Decellularization of Porcine Aortic Tissue by Subcritical Dimethyl Ether.

ACS Omega 2021 May 14;6(20):13417-13425. Epub 2021 May 14.

Department of Materials Process Engineering, Nagoya University, Nagoya 464-8603, Japan.

Porcine aortic tissue was decellularized by subcritical dimethyl ether (DME) used as an alternative to the surfactant sodium dodecyl sulfate. The process included three steps. For the first step, lipids were extracted from the porcine aorta using subcritical DME at 23 °C with a DME pressure of 0.56 MPa. Next, DME was evaporated from the aorta under atmospheric pressure and temperature. The second step involved DNA fragmentation by DNase, which was primarily identical to the common method. For the third step, similar to the common method, DNA fragments were removed by washing with water and ethanol. After 3 days of DNase treatment, the amount of DNA remaining in the porcine aorta was 40 ng/dry-mg, which was lower than the standard value of 50 ng/mg-dry. Hematoxylin and eosin staining showed that most cell nuclei were removed from the aorta. These results demonstrate that subcritical DME eliminates the need to utilize surfactants.
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http://dx.doi.org/10.1021/acsomega.1c01549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158793PMC
May 2021

Genomic and Pathological Characterization of Multiple Renal Cell Carcinoma Regions in Patient With Tuberous Sclerosis Complex: A Case Report.

Front Oncol 2021 12;11:691996. Epub 2021 May 12.

Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.

Tuberous sclerosis complex is a genetic disorder characterized by facial angiofibromas, intellectual disability, epilepsy, and tumor formation in multiple organs, including the kidney. Renal cell carcinoma occurs in 2%-4% of patients with tuberous sclerosis complex, often developing multiply and bilaterally. Renal cell carcinoma associated with this genetic disorder may include complex tumor heterogeneity caused by the spatially different mutational landscape. Herein, we report the case of a female patient with tuberous sclerosis complex who developed multiple renal tumors. A 44-year-old female patient with tuberous sclerosis complex developed three different histological types of tumor-angiomyolipoma, clear cell renal cell carcinoma, and papillary renal cell carcinoma-in the left kidney at first renal cell carcinoma recurrence. The papillary renal cell carcinoma was morphologically atypical, indicating that its occurrence was associated with the genetic disorder. Furthermore, whole-exome sequencing revealed distinct patterns of somatic mutation in the three tumor types, and the atypical papillary renal cell carcinoma possessed a different mutational landscape than that of typical papillary renal cell carcinomas. Our findings indicate that tumors associated with tuberous sclerosis complex may be diagnosed with careful pathological examination. Furthermore, somatic mutation profiles of these tumors revealed their unique features, providing important information for further understanding the mechanism of multiple tumor development in patients with tuberous sclerosis complex.
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http://dx.doi.org/10.3389/fonc.2021.691996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149899PMC
May 2021

The quantitative evaluation of anterior drawer test using an electromagnetic measurement system.

Sports Biomech 2021 May 20:1-12. Epub 2021 May 20.

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

The anterior drawer test (ADT) is the gold standard examination for the diagnosis of anterior talofibular ligamentinsufficiency,although there is noquantitative evaluation of ADT that is generally usable and reliable.An electromagnetic sensor (EMS)has been used to quantitatively evaluate joint kinematics, and has a high potential to be applied to the ankle joint. The aim of this study was to validatethe EMS measurement of the ADTin comparison to the fluoroscopic evaluationand to evaluate the reproducibility of the EMS measurement.Six feet were included,and an examinerperformed the ADT5 times for each foot while the anterior translation of the ankle jointwas quantitative evaluatedusing EMS and fluoroscope simultaneously. The anterior translation of the ankle joint during the ADT in EMS and in fluoroscope was 8.1 ± 5.7 mm and 3.6 ± 2.4 mm.Astrong correlation was observed between the measurements using EMS and fluoroscope (p < 0.01, the correlation coefficient = 0.91). Another 20 feet were included, and three examiners performed the ADT five times for each foot with the EMS measurement. The intra and inter-examiner reliability was 0.99 and 0.89.The EMS could quantify the anterior translation during the ADT which corresponds to fluoroscopic evaluation.
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http://dx.doi.org/10.1080/14763141.2021.1918754DOI Listing
May 2021

Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines.

Cancer Treat Rev 2021 Jul 16;98:102209. Epub 2021 Apr 16.

Department of Orthopaedic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi, Shizuoka, Japan.

Children and adolescents and young adults (AYAs) with cancer are often treated with a multidisciplinary approach. This includes use of radiotherapy, which is important for local control, but may also cause adverse events in the long term, including second cancer. The risks for limited growth and development, endocrine dysfunction, reduced fertility and second cancer in children and AYAs are reduced by proton beam therapy (PBT), which has a dose distribution that decreases irradiation of normal organs while still targeting the tumor. To define the outcomes and characteristics of PBT in cancer treatment in pediatric and AYA patients, this document was developed by the Japanese Society for Radiation Oncology (JASTRO) and the Japanese Society of Pediatric Hematology/Oncology (JSPHO).
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http://dx.doi.org/10.1016/j.ctrv.2021.102209DOI Listing
July 2021

Effects of Interoceptive Sensibility on Mental Health during the Coronavirus Disease 2019 Pandemic.

Int J Environ Res Public Health 2021 04 27;18(9). Epub 2021 Apr 27.

Unit of Public Health and Preventive Medicine, School of Medicine, Yokohama City University, Yokohama 236-0004, Japan.

The current coronavirus disease 2019 pandemic has been reported to influence interoceptive sensibility. This study focused on adaptive and maladaptive aspects of interoceptive sensibility and examined how each aspect of interoceptive sensibility affects depression, anxiety, and somatization symptoms under the mild lockdown in Japan, which was not enforceable and a non-punitive lockdown. We used data from 10,672 participants who lived in prefectures where the emergency declaration was first applied in Japan. Interoceptive sensibility was measured by the Multidimensional Assessment of Interoceptive Awareness (MAIA). The findings show that Noticing, a subscale of the MAIA, significantly contributed to the worsening of psychological and somatic symptoms (all s < 0.001). Conversely, Not-Distracting, Not-Worrying, Self-Regulation, and Trusting significantly contributed to the decrease of these symptoms (all s < 0.05). The findings suggest that two aspects of interoceptive sensibility affected mental health in different ways during the mild lockdown. Mindfulness and mindfulness-based interventions would be effective in terms of enhancing adaptive aspects of interoceptive sensibility.
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http://dx.doi.org/10.3390/ijerph18094616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123634PMC
April 2021

High uric acid induces liver fat accumulation via ROS/JNK/AP-1 signaling.

Am J Physiol Endocrinol Metab 2021 06 26;320(6):E1032-E1043. Epub 2021 Apr 26.

Department of Endocrinology, Xiang'an Hospital of Xiamen University, Xiamen, China.

Uric acid is the end metabolite derived from the oxidation of purine compounds. Overwhelming evidence shows the vital interrelationship between hyperuricemia (HUA) and nonalcoholic fatty liver disease (NAFLD). However, the mechanisms for this association remain unclear. In this study, we established a urate oxidase-knockout (Uox-KO) mouse model by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology. To study the correlation between HUA and NAFLD, human HepG2 hepatoma cells were treated in culture medium with high level of uric acid. In vivo, the Uox-KO mice spontaneously developed hyperuricemia and aberrant lipid-metabolism, concomitant with abnormal hepatic fat accumulation. HUA activated c-Jun N-terminal kinase (JNK) in vivo and in vitro. Furthermore, inhibiting JNK activation by a JNK-specific inhibitor, SP600125, decreased fat accumulation and lipogenic gene expression induced by HUA. Overexpression of the lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase 1 was via activation of JNK, which was blocked by the JNK inhibitor SP600125. HUA activated AP-1 to upregulate lipogenic gene expression via JNK activation. In addition, HUA caused mitochondrial dysfunction and reactive oxygen species production. Pretreatment with the antioxidant -acetyl-l-cysteine could ameliorate HUA-activated JNK and hepatic steatosis. These data suggest that ROS/JNK/AP-1 signaling plays an important role in HUA-mediated fat accumulation in liver. Hyperuricemia and nonalcoholic fatty liver disease are global public health problems, which are strongly associated with metabolic syndrome. In this study, we demonstrate that uric acid induces hepatic fat accumulation via the ROS/JNK/AP-1 pathway. This study identifies a new mechanism of NAFLD pathogenesis and new potential therapeutic strategies for HUA-induced NAFLD.
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http://dx.doi.org/10.1152/ajpendo.00518.2020DOI Listing
June 2021

Practical Arachnoid Anatomy for the Technical Consideration of Galen Complex Dissection: Cadaveric and Clinical Evaluation.

World Neurosurg 2021 07 19;151:e372-e378. Epub 2021 Apr 19.

Department of Neurosurgery, Yokohama City University, Yokohama, Japan.

Background: The occipital transtentorial approach (OTA) is a very useful but challenging approach to expose the pineal region because the deep-seated arachnoid membranes usually fold and extend over the great vein of Galen (GVG), leading to dense and poor visibility. In addition, the practical aspects of arachnoid anatomy are not well understood. We aimed to develop a safe surgical procedure for the OTA according to the practical aspects of arachnoid anatomy.

Methods: The procedure is shown through an illustrative video of surgery and cadaver. Five cadavers were analyzed for their arachnoid structures and the surgical procedures via the OTA, in strict compliance with legal and ethical requirements.

Results: All cadavers showed a 2-layered arachnoid structure-one belonging to the occipital lobe, and the other to the cerebellum. According to our cadaveric analysis, the arachnoid attachment of the tentorial apex can be peeled bluntly, with an average distance of 10.2 mm. For our clinical presentation, a pineal tumor with hydrocephalus was detected in a 14-year-old boy. While using the OTA and expanding the deep surgical field, we detached the membrane from the tentorial apex and bluntly peeled it to reveal the deep veins. Finally, gross total removal of the tumor was achieved.

Conclusions: A 2-layered arachnoid structure interposes the GVG from above and below the tentorium. The arachnoid membrane below the tentorium can be peeled off bluntly from the GVG to the attachment bundle limited by the penetrating veins. This detachment technique is useful for safe enlargement of the surgical field for the OTA.
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http://dx.doi.org/10.1016/j.wneu.2021.04.041DOI Listing
July 2021

Slow chromatin dynamics enhances promoter accessibility to transcriptional condensates.

Nucleic Acids Res 2021 05;49(9):5017-5027

Cluster of Excellence Physics of Life, TU Dresden, Dresden 01062, Germany.

Enhancers are DNA sequences at a long genomic distance from target genes. Recent experiments suggest that enhancers are anchored to the surfaces of condensates of transcription machinery and that the loop extrusion process enhances the transcription level of their target genes. Here, we theoretically study the polymer dynamics driven by the loop extrusion of the linker DNA between an enhancer and the promoter of its target gene to calculate the contact probability of the promoter to the transcription machinery in the condensate. Our theory predicts that when the loop extrusion process is active, the contact probability increases with increasing linker DNA length. This finding reflects the fact that the relaxation time, with which the promoter stays in proximity to the surface of the transcriptional condensate, increases as the length of the linker DNA increases. This contrasts the equilibrium case for which the contact probability between the promoter and the transcription machineries is smaller for longer linker DNA lengths.
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http://dx.doi.org/10.1093/nar/gkab275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136786PMC
May 2021

Paraspeckles are constructed as block copolymer micelles.

EMBO J 2021 Jun 22;40(12):e107270. Epub 2021 Apr 22.

Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.

Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization, distinguish them from typical liquid-liquid phase-separated condensates. We experimentally and theoretically investigated how the shape and organization of paraspeckles are determined. We identified the NEAT1_2 RNA domains responsible for shell localization of the NEAT1_2 ends, which determine the characteristic internal organization. Using the soft matter physics, we then applied a theoretical framework to understand the principles that determine NEAT1_2 organization as well as shape, number, and size of paraspeckles. By treating paraspeckles as amphipathic block copolymer micelles, we could explain and predict the experimentally observed behaviors of paraspeckles upon NEAT1_2 domain deletions or transcriptional modulation. Thus, we propose that paraspeckles are block copolymer micelles assembled through a type of microphase separation, micellization. This work provides an experiment-based theoretical framework for the concept that ribonucleoprotein complexes (RNPs) can act as block copolymers to form RNA-scaffolding biomolecular condensates with optimal sizes and structures in cells.
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http://dx.doi.org/10.15252/embj.2020107270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204865PMC
June 2021

The synthetic CB cannabinoid receptor selective agonists: Putative medical uses and their legalization.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Aug 17;110:110301. Epub 2021 Mar 17.

Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, Mexico; Intercontinental Neuroscience Research Group, Mexico. Electronic address:

More than 500 molecules have been identified as components of Cannabis sativa (C. sativa), of which the most studied is Δ-tetrahydrocannabinol (Δ-THC). Several studies have suggested that Δ-THC exerts diverse biological effects, ranging from fragmentation of DNA to behavioral disruptions. Currently, it is accepted that most of the pharmacological properties of Δ-THC engage the activation of the cannabinoid receptors, named CB and CB. Interestingly, multiple pieces of evidence have suggested that the cannabinoid receptors play an active role in the modulation of several diseases leading to the design of synthetic cannabinoid-like compounds. Advances in the development of synthetic CB cannabinoid receptor selective agonists as therapeutical approaches are, however, limited. This review focuses on available evidence searched in PubMed regarding the synthetic CB cannabinoid receptor selective agonists such as AM-1235, arachidonyl-2' chloroethylamide (ACEA), CP 50,556-1 (Levonantradol), CP-55,940, HU-210, JWH-007, JWH-018, JWH-200 (WIN 55,225), methanandamide, nabilone, O-1812, UR-144, WIN 55,212-2, nabiximols, and dronabinol. Indeed, it would be ambitious to describe all available evidence related to the synthetic CB cannabinoid receptor selective agonists. However, and despite the positive evidence on the positive results of using these compounds in experimental models of health disturbances and preclinical trials, we discuss evidence in regards some concerns due to side effects.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110301DOI Listing
August 2021

Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Type 1 Diabetes Mellitus on Body Composition and Glucose Variabilities: Single-Arm, Exploratory Trial.

Diabetes Ther 2021 May 18;12(5):1415-1427. Epub 2021 Mar 18.

Department of Diabetes, Endocrinology and Metabolism, Nippon Medical School, Chiba Hokusoh Hospital, Chiba, Japan.

Introduction: Sodium glucose co-transporter 2 (SGLT2) inhibitors are widely used in the management of type 2 diabetes mellitus; they prevent cardiovascular events and reduce fat mass. However, little is known about the effects of SGLT2 inhibitors on type 1 diabetes mellitus as an adjuvant to insulin therapy. Therefore, we aimed to elucidate the effects of SGLT2 inhibitors on body composition of patients with type 1 diabetes mellitus and assess blood glucose variability.

Methods: A single-center, single-arm, prospective, interventional study was performed on Japanese patients with type 1 diabetes mellitus who were not administered SGLT2 inhibitors prior to this study. These patients were equipped with flash glucose monitoring (FGM) and administered ipragliflozin 50 mg daily. Body composition was evaluated using bioelectrical impedance analysis, and glycemic variabilities were assessed using FGM before and after SGLT2 inhibitor treatment.

Results: After 52 weeks of treatment, the total fat mass tended to be reduced (- 9.10% from baseline, P = 0.098). In addition, skeletal muscle mass also decreased (- 2.98% from baseline, P = 0.023). Although the basal insulin dose was reduced, SGLT2 inhibitors decreased HbA1c levels. FGM revealed that glycemic variabilities were also reduced, and time within the target glucose range increased (51.7% vs. 62.5%, P = 0.004).

Conclusion: SGLT2 inhibitors have beneficial effects on glycemic variabilities and fat mass reductions in patients with type 1 diabetes mellitus. However, loss of skeletal muscle is a major concern; therefore, caution is required when using SGLT2 inhibitors in lean patients with type 1 diabetes mellitus.

Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN000042407).
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http://dx.doi.org/10.1007/s13300-021-01047-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099976PMC
May 2021

Neural substrates for sharing intention in action during face-to-face imitation.

Neuroimage 2021 06 16;233:117916. Epub 2021 Mar 16.

Division of Cerebral Integration, Department of System Neuroscience, National Institute for Physiological Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan. Electronic address:

Face-to-face imitation is a unique social interaction wherein a shared action is executed based on the feedback of the partner. Imitation by the partner is the feedback to the imitatee's action, resulting in sharing actions. The neural mechanisms of the shared representation of action during face-to-face imitation, the core of inter-subjectivity, are not well-known. Here, based on the predictive coding account, we hypothesized that the pair-specific forward internal model is the shared representation of action which is represented by the inter-individual synchronization of some portion of the mirror neuron system. Hyperscanning functional magnetic resonance imaging was conducted during face-to-face interaction in 16 pairs of participants who completed an immediate imitation task of facial expressions. Paired participants were alternately assigned to either an imitator or an imitatee who was prompted to express a happy, sad, or non-emotional face. While neural activation elicited by imitating and being imitated were distinct with little overlap, on-line imitative interaction enhanced inter-brain synchronization in the right inferior parietal lobule that correlated with the similarity in facial movement kinematic profile. This finding indicates a critical role of the right inferior parietal lobule in sharing representation of action as a pair-specific forward internal model through imitative interaction.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117916DOI Listing
June 2021

Influence of selected plane on the evaluation of tibial tunnel locations using a three-dimensional bone model in double-bundle anterior cruciate ligament reconstruction.

Knee 2021 Mar 5;29:298-304. Epub 2021 Mar 5.

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: The purpose of this study was to investigate the influence of a selected plane on the evaluation of tibial tunnel locations following anterior cruciate ligament reconstruction (ACLR) between two planes: the plane parallel to the tibial plateau (Plane A) and the plane perpendicular to the proximal tibial shaft axis (Plane B).

Methods: Thirty-four patients who underwent double-bundle ACLR were included. Three-dimensional model of tibia was created using computed tomography images 2 weeks postoperatively, and tibial tunnels of the anteromedial bundle (AMB) and posterolateral bundle (PLB) were extracted. To evaluate tibial tunnel locations, two planes (Planes A and B) were created. The locations of the tibial tunnel apertures of each bundle were evaluated using a grid method and compared between Planes A and B. The difference in coronal alignment between Planes A and B were also assessed.

Results: The AMB and PLB tunnel apertures in Plane A were significantly more laterally located than in Plane B (mean difference; AMB, 1.5%; PLB, 1.7%, P < 0.01). There were no significant differences in the anteroposterior direction between the planes. Coronal alignment difference between the planes was 16.8 ± 2.2°; Plane B was more valgus than Plane A.

Conclusion: Although tibial tunnel locations were not significantly influenced by the selected planes in the AP direction, subtle but statistically significant differences were found in the ML direction between the Planes A and B in double-bundle anterior cruciate ligament reconstruction. The findings suggest that both Planes A and B can be used in the assessment of tibial tunnel locations after anterior cruciate ligament reconstruction.
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http://dx.doi.org/10.1016/j.knee.2021.02.020DOI Listing
March 2021

Single-Institutional Experience of Chronic Intracranial Electroencephalography Based on the Combined Usage of Subdural and Depth Electrodes.

Brain Sci 2021 Feb 28;11(3). Epub 2021 Feb 28.

Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan.

Implantation of subdural electrodes on the brain surface is still widely performed as one of the "gold standard methods" for the presurgical evaluation of epilepsy. Stereotactic insertion of depth electrodes to the brain can be added to detect brain activities in deep-seated lesions to which surface electrodes are insensitive. This study tried to clarify the efficacy and limitations of combined implantation of subdural and depth electrodes in intractable epilepsy patients. Fifty-three patients with drug-resistant epilepsy underwent combined implantation of subdural and depth electrodes for long-term intracranial electroencephalography (iEEG) before epilepsy surgery. The detectability of early ictal iEEG change (EIIC) were compared between the subdural and depth electrodes. We also examined clinical factors including resection of MRI lesion and EIIC with seizure freedom. Detectability of EIIC showed no significant difference between subdural and depth electrodes. However, the additional depth electrode was useful for detecting EIIC from apparently deep locations, such as the insula and mesial temporal structures, but not in detecting EIIC in patients with ulegyria (glial scar). Total removal of MRI lesion was associated with seizure freedom. Depth electrodes should be carefully used after consideration of the suspected etiology to avoid injudicious usage.
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http://dx.doi.org/10.3390/brainsci11030307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000142PMC
February 2021

Severe acute respiratory syndrome coronavirus 2 prevalence in saliva and gastric and intestinal fluid in patients undergoing gastrointestinal endoscopy in coronavirus disease 2019 endemic areas: Prospective cross-sectional study in Japan.

Dig Endosc 2021 Feb 6. Epub 2021 Feb 6.

Department of, Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Kanagawa, Japan.

Objectives: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high-risk procedure in the coronavirus disease 2019 (COVID-19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in saliva and gastrointestinal fluids to which endoscopy medical staff are exposed.

Methods: The study was a single-center cross-sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital were registered. All patients provided 3 mL of saliva. For upper GIE, 10 mL of gastric fluid was collected through the endoscope. For lower GIE, 10 mL of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS-CoV-2 in saliva and gastrointestinal fluids. We also analyzed serum-specific antibodies for SARS-CoV-2 and patients' background information.

Results: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS-CoV-2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases.

Conclusions: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS-CoV-2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. The study was registered as UMIN000040587.
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http://dx.doi.org/10.1111/den.13945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014498PMC
February 2021

Natural Cannabinoids as Templates for Sleep Disturbances Treatments.

Adv Exp Med Biol 2021 ;1297:133-141

Intercontinental Neuroscience Research Group, Mérida, Yucatán, México.

The sleep-wake cycle is a complex composition of specific physiological and behavioral characteristics. In addition, neuroanatomical, neurochemical and molecular systems exerts influences in the modulation of the sleep-wake cycle. Moreover, homeostatic and circadian mechanisms interact to control the waking or sleeping states. As many other behaviors, sleep also develops pathological features that include several signs and symptoms corresponding to medical conditions known as sleep disorders.In addition to the neurobiological mechanisms modulating sleep, external elements also influence the sleep-wake cycle, including the use of Cannabis sativa (C. sativa). In this regard, and over the last decades, the interest of studying the pharmacology of Δ-tetrahydrocannabinol (Δ-THC), the principal psychoactive constituent of C. sativa, has been addressed. Moreover, in recent years, the focus of scientific interest has moved on to studying the second plant constituent with non-psychotropic pharmacological properties: Cannabidiol (CBD).The pharmacological and pharmaceutical interest of CBD has been focus of attention due to the accumulating body of evidence regarding the positive outcomes of using CBD for the treatment of several health issues, such as psychiatric and neurodegenerative disorders, epilepsy, etc. Since the most prominent sleep disruptions include excessive daytime sleepiness (EDS), current treatments include the use of drugs such as stimulants of antidepressants. Notwithstanding, side effects are commonly reported among the patients under prescription of these compounds. Thus, the search of novelty therapeutical approaches aimed to treat ESD may consider the use of cannabinoid-derived compounds, such as CBD. In this chapter, we will show experimental evidence regarding the potential role of CBD as a wake-inducing compound aimed to manage EDS.
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http://dx.doi.org/10.1007/978-3-030-61663-2_9DOI Listing
February 2021
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