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1.
BMJ Open ; 14(4): e077686, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684248

RESUMEN

OBJECTIVE: To describe the characteristics of patients who sought medical attention for headache and those who did not. DESIGN: This observational study used a cross-sectional online survey and linked medical claims data. SETTING: Data from an online self-administered questionnaire survey conducted in November 2020 as well as linked medical claims data spanning December 2017 and November 2020 were provided by DeSC Healthcare Inc. PARTICIPANTS: Of 21 480 respondents aged 19-74 years whose sex and age data matched the claims data, 7311 reported experiencing headache. MEASURES: Outcomes included participant characteristics, status of medical attention seeking, medication use, quality of life (QOL) measured by Migraine-Specific QOL (MSQ) questionnaire V.2.1 and headache intensity. RESULTS: Of the 7311 respondents with headache, 735 sought medical attention and 6576 did not. Compared with those who did not seek medical attention, those who sought medical attention had more frequent headaches (median: 5 days/3 months vs 10 days/3 months in those who did not vs those who sought medical attention, respectively) had lower MSQ score (mean (SD) MSQ total score: 87.6 (13.0) vs 77.1 (18.1)) and were likely to experience moderately severe to severe headache (19.0% (1252/6576) vs 41.2% (303/735)) without headache medication. The inability to tolerate headache (36.5% (268/735)) was a common reason for seeking medical attention. Since the pain was not severe enough, 35.3% (2323/6576) of patients did not seek medical attention. Furthermore, a subgroup of respondents experiencing headache for ≥15 days were uncertain about which hospital or department to attend. CONCLUSIONS: Patients typically seek help when the pain becomes unbearable. Still, some of them did not seek medical attention while they were experiencing headache for ≥15 days per month. Therefore, it is important to raise awareness and encourage seeking early medical attention before symptoms and associated burdens become too severe to be managed effectively.


Asunto(s)
Cefalea , Aceptación de la Atención de Salud , Calidad de Vida , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Transversales , Adulto , Japón/epidemiología , Anciano , Cefalea/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto Joven
2.
Cell Rep ; 43(1): 113634, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-38194969

RESUMEN

Neurodevelopmental disorders, such as intellectual disability (ID), epilepsy, and autism, involve altered synaptic transmission and plasticity. Functional characterization of their associated genes is vital for understanding physio-pathological brain functions. LGI3 is a recently recognized ID-associated gene encoding a secretory protein related to an epilepsy-gene product, LGI1. Here, we find that LGI3 is uniquely secreted from oligodendrocytes in the brain and enriched at juxtaparanodes of myelinated axons, forming nanoscale subclusters. Proteomic analysis using epitope-tagged Lgi3 knockin mice shows that LGI3 uses ADAM23 as a receptor and selectively co-assembles with Kv1 channels. A lack of Lgi3 in mice disrupts juxtaparanodal clustering of ADAM23 and Kv1 channels and suppresses Kv1-channel-mediated short-term synaptic plasticity. Collectively, this study identifies an extracellular organizer of juxtaparanodal Kv1 channel clustering for finely tuned synaptic transmission. Given the defective secretion of the LGI3 missense variant, we propose a molecular pathway, the juxtaparanodal LGI3-ADAM23-Kv1 channel, for understanding neurodevelopmental disorders.


Asunto(s)
Epilepsia , Proteómica , Animales , Ratones , Axones/metabolismo , Epilepsia/metabolismo , Plasticidad Neuronal , Oligodendroglía/metabolismo , Proteínas/metabolismo
3.
Front Neurol ; 14: 1231351, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38090268

RESUMEN

Purpose: The study aimed to validate and compare coding algorithms for identifying people with migraine within the Japanese claims database. Methods: This study used the administrative claim database provided by DeSC Healthcare, Inc., that was linked to the results of an online survey administered to adult users of the health app "kencom®." The ability of the 12 algorithms to detect migraines using diagnostic records alone or with prescription records was evaluated based on sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs). We used a migraine diagnosis judged based on respondents' self-reported symptoms according to the diagnostic criteria of the International Classification of Headache Disorders, version 3 (ICHD-3), as true. Results: Of the 21,480 individuals, 691 had migraine according to the ICHD-3 criteria. The 12 algorithms had a sensitivity of 5.4-8.8%, specificity of 98.8-99.6%, PPVs of 19.2-32.5%, and NPVs of 96.9-97.0%. Algorithm 9 (migraine diagnostic records more than once AND at least one prescription record for migraine prophylaxis or triptans in the same month as diagnosis) produced the highest PPV, whereas Algorithm 2 (at least one diagnostic record of migraine or tension-type headache) had the highest sensitivity. Similar trends were observed when using the ID-Migraine or 4-item migraine screener, instead of the ICHD-3 criteria, for case ascertainment. Conclusion: Strict algorithms, such as Algorithm 9, yielded a higher PPV but a lower sensitivity, and such algorithms may be suitable for studies estimating the relative risk. Conversely, algorithms based on a single diagnostic record, such as Algorithm 2, had a higher sensitivity and may be suitable for studies estimating the prevalence/incidence of disease. Our findings will help select a desirable algorithm for migraine studies using a Japanese claim database.

4.
iScience ; 26(11): 108177, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38107876

RESUMEN

Mammalian embryos differentiate into the inner cell mass (ICM) and trophectoderm at the 8-16 cell stage. The ICM forms a single cluster that develops into a single fetus. However, the factors that determine differentiation and single cluster formation are unknown. Here we investigated whether embryos could develop normally without gravity. As the embryos cannot be handled by an untrained astronaut, a new device was developed for this purpose. Using this device, two-cell frozen mouse embryos launched to the International Space Station were thawed and cultured by the astronauts under microgravity for 4 days. The embryos cultured under microgravity conditions developed into blastocysts with normal cell numbers, ICM, trophectoderm, and gene expression profiles similar to those cultured under artificial-1 g control on the International Space Station and ground-1 g control, which clearly demonstrated that gravity had no significant effect on the blastocyst formation and initial differentiation of mammalian embryos.

5.
Mov Disord ; 38(12): 2145-2150, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37986211

RESUMEN

Schematic illustration of cortically induced dynamic activity changes of the output nuclei of the basal ganglia (the internal segment of the globus pallidus, GPi and the substantia nigra pars reticulata, SNr) in the healthy and diseased states. The height of the dam along the time course controls the expression of voluntary movements. Its alterations could cause a variety of movement disorders, such as Parkinson's disease and hyperkinetic disorders. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Trastornos del Movimiento , Enfermedad de Parkinson , Humanos , Ganglios Basales , Globo Pálido , Sustancia Negra
6.
Cell Rep Med ; 4(10): 101208, 2023 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-37774703

RESUMEN

Dyskinesia is involuntary movement caused by long-term medication with dopamine-related agents: the dopamine agonist 3,4-dihydroxy-L-phenylalanine (L-DOPA) to treat Parkinson's disease (L-DOPA-induced dyskinesia [LID]) or dopamine antagonists to treat schizophrenia (tardive dyskinesia [TD]). However, it remains unknown why distinct types of medications for distinct neuropsychiatric disorders induce similar involuntary movements. Here, we search for a shared structural footprint using magnetic resonance imaging-based macroscopic screening and super-resolution microscopy-based microscopic identification. We identify the enlarged axon terminals of striatal medium spiny neurons in LID and TD model mice. Striatal overexpression of the vesicular gamma-aminobutyric acid transporter (VGAT) is necessary and sufficient for modeling these structural changes; VGAT levels gate the functional and behavioral alterations in dyskinesia models. Our findings indicate that lowered type 2 dopamine receptor signaling with repetitive dopamine fluctuations is a common cause of VGAT overexpression and late-onset dyskinesia formation and that reducing dopamine fluctuation rescues dyskinesia pathology via VGAT downregulation.


Asunto(s)
Discinesia Inducida por Medicamentos , Trastornos Parkinsonianos , Ratones , Animales , Agonistas de Dopamina/efectos adversos , Levodopa/efectos adversos , Dopamina , Antiparkinsonianos/efectos adversos , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/patología , Discinesia Inducida por Medicamentos/etiología , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/patología , Oxidopamina/efectos adversos , Ácido gamma-Aminobutírico/efectos adversos
7.
Front Aging Neurosci ; 15: 1221341, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37441679

RESUMEN

Zonisamide (ZNS; 1,2-benzisoxazole-3-methanesulfonamide) was initially developed and is commonly used as an anticonvulsant drug. However, it has also shown its beneficial effects on Parkinson's disease (PD), a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the midbrain. Recent clinical studies have suggested that ZNS can also have beneficial effects on L-DOPA-induced dyskinesia (LID), which is a major side effect of long-term L-DOPA treatments for PD. In the present study, we examined the behavioral effects of ZNS on LID in PD model mice. Acute ZNS treatment did not have any observable behavioral effects on LID. Contrastingly, chronic ZNS treatment with L-DOPA delayed the peak of LID and reduced the severity of LID before the peak but increased the duration of LID in a dose-dependent manner of ZNS compared to PD model mice treated with L-DOPA alone. Thus, ZNS appears to have both beneficial and adverse effects on LID.

8.
BMC Neurol ; 23(1): 80, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36809985

RESUMEN

BACKGROUND: Limited epidemiological data are available for headache disorders in Japan, and no recent studies have reported the impact of several primary headache disorders in Japan. This study aimed to report the up-to-date epidemiological data and impact of primary headaches on daily activities as well as the use of medical care, clinical features, and pain severity/activity impairment using nationwide data in Japan. METHODS: We used anonymized online survey data coupled with medical claims data, from individuals aged 19-74 years old, that were provided by DeSC Healthcare Inc. The outcomes included the prevalence of migraine, tension-type headache, cluster headache, and other headache types stratified by age and sex, use of medical care, clinical features, medication use, and severity of pain/activity impairment. All outcomes were examined separately for each headache type. This is the second paper reported concurrently with this research. RESULTS: The study population comprised 691/1,441/21/5,208 individuals with migraine/tension-type headache/cluster headache/other headache types, respectively. The prevalence of migraine and tension-type headache was higher in women than in men but was similar for cluster headache (male vs. female, 1.7% vs. 7.4%, 5.3% vs. 10.8%, and 0.1% vs. 0.1%, respectively). The percentage of individuals with migraine, tension-type headache, cluster headache who had not seen a doctor was 81.0%, 92.0%, 57.1%, respectively. The common headache triggers were fatigue in migraine and tension-type headache, and weather-related phenomena and turning of the seasons in migraine. Common activities refrained from or reduced by headaches were "operating a computer or smartphone", "drinking alcohol", and "going to crowded places" in all three headache types and housework-related activities in women. Among individuals taking medicines, 16.8%, 15.8%, 47.6% with migraine, tension-type headache, and cluster headache reported moderate to severe pain, respectively, and 12.6%, 7.7%, 19.0% reported moderate to severe disability, respectively. CONCLUSIONS: This study found various triggers of headache attacks, and daily activities refrained from or reduced by headaches. Additionally, this study suggested that the disease burden in people possibly experiencing tension-type headaches, many of whom had not seen a doctor. The study findings are of clinical value for the diagnosis and treatment of primary headaches.


Asunto(s)
Cefalalgia Histamínica , Trastornos Migrañosos , Cefalea de Tipo Tensional , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Japón , Cefalea/epidemiología , Trastornos Migrañosos/tratamiento farmacológico
9.
Life Sci Space Res (Amst) ; 36: 138-146, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36682823

RESUMEN

Functional relationships between endogenous levels of plant hormones in the growth and development of shoots in etiolated Alaska pea and etiolated Golden Cross Bantam maize seedlings under different gravities were investigated in the "Auxin Transport" experiment aboard the International Space Station (ISS). Comprehensive analyses of 31 species of plant hormones of pea and maize seedlings grown under microgravity (µg) in space and 1 g conditions were conducted. Principal component analysis (PCA) and a multiple regression analysis with the dataset from the plant hormone analysis of the etiolated pea seedlings grown under µg and 1 g conditions in the presence and absence of 2,3,5-triiodobenzoic acid (TIBA) revealed endogenous levels of auxin correlated positively with bending and length of epicotyls. Endogenous cytokinins correlated negatively with them. These results suggest an interaction of auxin and cytokinins in automorphogenesis and growth inhibition of etiolated Alaska pea epicotyls grown under µg conditions in space. Less polar auxin transport with reduced endogenous levels of auxin increased endogenous levels of cytokinins, resulting in changing the growth direction of epicotyls and inhibiting growth. On the other hand, almost no close relationship between endogenous plant hormone levels and growth and development in etiolated maize seedlings grown was observed under µg conditions in space, as per Schulze et al. (1992). However, endogenous levels of IAA in the seedlings grown under µg conditions in space were significantly higher than those grown on Earth, similar to the cases of polar auxin transport already reported.


Asunto(s)
Vuelo Espacial , Ingravidez , Reguladores del Crecimiento de las Plantas , Plantones , Zea mays , Pisum sativum , Ácidos Indolacéticos/farmacología , Citocininas
10.
J Cardiol ; 82(1): 35-42, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36587792

RESUMEN

BACKGROUND: The impact of tolvaptan on the long-term outcomes of patients with heart failure (HF) remains inconclusive. We evaluated patients requiring long-term congestion management for the time to rehospitalization for HF (HF rehospitalization), the time to in-hospital death and explored the factors that may influence the outcomes. METHODS: Using data (April 2008 to September 2019) from a medical claims database, patients with HF prescribed tolvaptan (tolvaptan cohort) and those prescribed loop diuretics before tolvaptan was introduced to the hospital (furosemide cohort) were compared. Patients with HF who experienced ≥2 HF hospitalizations and ≥1 tolvaptan or loop diuretic prescription during and after HF hospitalization were included. Data of patients with serum creatinine and estimated glomerular filtration rate were analyzed for time to HF rehospitalization and in-hospital death within 1 year after the second discharge and factors that may influence the outcomes. RESULTS: Among the 1931 and 631 tolvaptan and furosemide cohort patients, respectively, time to HF rehospitalization was not significantly different (p = 0.0921); time to in-hospital death was significantly longer in the tolvaptan cohort than in the furosemide cohort (p = 0.0005). Age, serum sodium, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were identified as factors for both outcomes (p < 0.05). CONCLUSIONS: Tolvaptan did not significantly affect time to HF rehospitalization. However, further worsening of the condition leading to death may be delayed, and time to in-hospital death may be prolonged in patients treated with tolvaptan, indicating its usefulness for long-term congestion management.


Asunto(s)
Furosemida , Insuficiencia Cardíaca , Humanos , Tolvaptán , Antagonistas de los Receptores de Hormonas Antidiuréticas , Estudios Retrospectivos , Japón/epidemiología , Mortalidad Hospitalaria , Benzazepinas/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/inducido químicamente , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico
12.
PLoS One ; 17(10): e0270781, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36206235

RESUMEN

Whether mammalian embryos develop normally under microgravity remains to be determined. However, embryos are too small to be handled by inexperienced astronauts who orbit Earth on the International Space Station (ISS). Here we describe the development of a new device that allows astronauts to thaw and culture frozen mouse 2-cell embryos on the ISS without directly contacting the embryos. First, we developed several new devices using a hollow fiber tube that allows thawing embryo without practice and observations of embryonic development. The recovery rate of embryos was over 90%, and its developmental rate to the blastocyst were over 80%. However, the general vitrification method requires liquid nitrogen, which is not available on the ISS. Therefore, we developed another new device, Embryo Thawing and Culturing unit (ETC) employing a high osmolarity vitrification method, which preserves frozen embryos at -80°C for several months. Embryos flushed out of the ETC during thawing and washing were protected using a mesh sheet. Although the recovery rate of embryos after thawing were not high (24%-78%) and embryonic development in ETC could not be observed, thawed embryos formed blastocysts after 4 days of culture (29%-100%) without direct contact. Thus, this ETC could be used for untrained astronauts to thaw and culture frozen embryos on the ISS. In addition, this ETC will be an important advance in fields such as clinical infertility and animal biotechnology when recovery rate of embryos were improved nearly 100%.


Asunto(s)
Blastocisto , Vitrificación , Animales , Criopreservación/métodos , Embrión de Mamíferos , Femenino , Congelación , Mamíferos , Ratones , Nitrógeno , Embarazo
13.
Cell Rep ; 40(10): 111309, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36070693

RESUMEN

Dysfunctional dopamine signaling is implicated in various neuropsychological disorders. Previously, we reported that dopamine increases D1 receptor (D1R)-expressing medium spiny neuron (MSN) excitability and firing rates in the nucleus accumbens (NAc) via the PKA/Rap1/ERK pathway to promote reward behavior. Here, the results show that the D1R agonist, SKF81297, inhibits KCNQ-mediated currents and increases D1R-MSN firing rates in murine NAc slices, which is abolished by ERK inhibition. In vitro ERK phosphorylates KCNQ2 at Ser414 and Ser476; in vivo, KCNQ2 is phosphorylated downstream of dopamine signaling in NAc slices. Conditional deletion of Kcnq2 in D1R-MSNs reduces the inhibitory effect of SKF81297 on KCNQ channel activity, while enhancing neuronal excitability and cocaine-induced reward behavior. These effects are restored by wild-type, but not phospho-deficient KCNQ2. Hence, D1R-ERK signaling controls MSN excitability via KCNQ2 phosphorylation to regulate reward behavior, making KCNQ2 a potential therapeutical target for psychiatric diseases with a dysfunctional reward circuit.


Asunto(s)
Dopamina , Canal de Potasio KCNQ2 , Trastornos Mentales , Proteínas del Tejido Nervioso , Animales , Dopamina/metabolismo , Canal de Potasio KCNQ2/metabolismo , Trastornos Mentales/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Fosforilación , Receptores de Dopamina D1/metabolismo , Recompensa
14.
Cereb Cortex Commun ; 3(2): tgac022, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35769971

RESUMEN

Functional magnetic resonance imaging (fMRI) is a promising approach for the simultaneous and extensive scanning of whole-brain activities. Optogenetics is free from electrical and magnetic artifacts and is an ideal stimulation method for combined use with fMRI. However, the application of optogenetics in nonhuman primates (NHPs) remains limited. Recently, we developed an efficient optogenetic intracortical microstimulation method of the primary motor cortex (M1), which successfully induced forelimb movements in macaque monkeys. Here, we aimed to investigate how optogenetic M1 stimulation causes neural modulation in the local and remote brain regions in anesthetized monkeys using 7-tesla fMRI. We demonstrated that optogenetic stimulation of the M1 forelimb and hindlimb regions successfully evoked robust direct and remote fMRI activities. Prominent remote activities were detected in the anterior and posterior lobes in the contralateral cerebellum, which receive projections polysynaptically from the M1. We further demonstrated that the cerebro-cerebellar projections from these M1 regions were topographically organized, which is concordant with the somatotopic map in the cerebellar cortex previously reported in macaques and humans. The present study significantly enhances optogenetic fMRI in NHPs, resulting in profound understanding of the brain network, thereby accelerating the translation of findings from animal models to humans.

15.
Otol Neurotol ; 43(6): 657-665, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35761457

RESUMEN

OBJECTIVE: Cholesteatoma is occasionally accompanied by excessive calcification and presumably has different osteogenic dynamics compared to noncholesteatomous chronic otitis media. Cholesteatoma-related sclerotic lesions through the temporal bone can pose manipulatory difficulties, possibly leading to worse surgical outcomes or complications. Therefore, we compared surgical outcomes of cholesteatomas with and without sclerotic lesions. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center. PATIENTS: Consecutive ears with acquired cholesteatomas requiring primary resection between January 2009 and December 2019. The ears followed up for <1 year were excluded. INTERVENTIONS: Tympanoplasty with/without mastoidectomy. MAIN OUTCOME MEASURES: Prevalence and location of sclerotic lesion, comorbid fistulae, postoperative air-bone gap, recidivism, and complications. RESULTS: Overall, 19 (6.4%) of 299 ears had sclerotic lesions. More than two-thirds (68.4%) of sclerotic lesions were located adjacent to the lateral semicircular canal (LSC). Among ears with sclerotic lesions adjacent to the LSC, 46.2% had a comorbid fistula in the LSC. The prevalence of labyrinth fistula was significantly greater in ears with sclerotic lesions (42.1%) than in ears without sclerotic lesions (5.0%) (p < 0.0001, Fisher's exact test). Sensorineural hearing deterioration was significantly higher in ears with sclerotic lesions than in ears without (p = 0.0004, Fisher's exact test). Multivariate logistic regression analysis demonstrated that the presence of sclerotic lesions was a significant prognostic factor for residual disease (odds ratio [95% confidence interval]: 6.820 [2.055-22.633], p = 0.0017). CONCLUSIONS: Surgeons should be conscious of preoperative identification of sclerotic lesions adjacent to one of the semicircular canals, possibly leading to postoperative sensorineural hearing deterioration or residual cholesteatoma.


Asunto(s)
Colesteatoma del Oído Medio , Colesteatoma , Fístula , Colesteatoma/complicaciones , Colesteatoma/cirugía , Colesteatoma del Oído Medio/complicaciones , Colesteatoma del Oído Medio/cirugía , Fístula/cirugía , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Timpanoplastia
16.
J Headache Pain ; 23(1): 70, 2022 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-35733104

RESUMEN

BACKGROUND: Migraine is a chronic disease characterized by episodic headache attacks. No recent studies have, however been conducted on the epidemiology of migraine or the treatment landscape in Japan. This study was conducted as a fact-finding survey using medical claims data and an online survey on migraine and headaches, conducted among members of health insurance associations with the objective of gaining an understanding of migraine prevalence and the treatment status in Japan. METHODS: The study methodology utilized a unique approach of combined data sources. The data sources used in this study are medical claims data and linked online survey data provided by DeSC Healthcare Inc (DeSC). The primary outcomes (from survey responses) were: the overall number and proportion of migraine patients; and the overall prevalence of migraine, stratified by age and sex. The secondary outcomes (from survey responses) were use of medical care; and clinical features/headache symptoms. The analysis population included all individuals who had response data for surveys conducted by DeSC. The online survey data and medical claims data were summarized. RESULTS: The data population comprised 21,480 individuals. On the basis of the survey results, including probable cases, the overall prevalence of migraine was 3.2%. The highest prevalence of migraine was observed in patients aged 30-39 years. The prevalence of migraine in women was 4.4 times higher than in men. The percentage of migraine patients who had not been seen by a doctor was 81.0%. More than 80% of patients were taking over-the-counter drugs and 4.8% took prescription medicines only. Approximately 52.9% of patients considered that the intensity of pain symptoms was severe. Moreover, the majority of patients (72.9%) considered that the impairment of daily life activities was of moderate or severe degree. CONCLUSIONS: In Japan, the percentage of people with migraine who did not receive medical attention is as high as 80%. Additionally, the majority of patients tend to endure symptoms and continue with everyday activities. With innovative treatment approaches becoming available it is necessary to disseminate information that migraine is not a simple headache but an illness that requires medical treatment and consultation.


Asunto(s)
Trastornos Migrañosos , Femenino , Cefalea/epidemiología , Humanos , Seguro de Salud , Japón/epidemiología , Masculino , Trastornos Migrañosos/diagnóstico , Prevalencia
17.
Sci Data ; 8(1): 159, 2021 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-34183680

RESUMEN

Cynomolgus macaque (Macaca fascicularis) and common marmoset (Callithrix jacchus) have been widely used in human biomedical research. Long-standing primate genome assemblies used the human genome as a reference for ordering and orienting the assembled fragments into chromosomes. Here we performed de novo genome assembly of these two species without any human genome-based bias observed in the genome assemblies released earlier. We assembled PacBio long reads, and the resultant contigs were scaffolded with Hi-C data, which were further refined based on Hi-C contact maps and alternate de novo assemblies. The assemblies achieved scaffold N50 lengths of 149 Mb and 137 Mb for cynomolgus macaque and common marmoset, respectively. The high fidelity of our assembly is also ascertained by BAC-end concordance in common marmoset. Our assembly of cynomolgus macaque outperformed all the available assemblies of this species in terms of contiguity. The chromosome-scale genome assemblies produced in this study are valuable resources for non-human primate models and provide an important baseline in human biomedical research.


Asunto(s)
Callithrix/genética , Mapeo Contig , Macaca fascicularis/genética , Animales , Cromosomas , Orden Génico
18.
Sci Adv ; 7(24)2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34117068

RESUMEN

Space radiation may cause DNA damage to cells and concern for the inheritance of mutations in offspring after deep space exploration. However, there is no way to study the long-term effects of space radiation using biological materials. Here, we developed a method to evaluate the biological effect of space radiation and examined the reproductive potential of mouse freeze-dried spermatozoa stored on the International Space Station (ISS) for the longest period in biological research. The space radiation did not affect sperm DNA or fertility after preservation on ISS, and many genetically normal offspring were obtained without reducing the success rate compared to the ground-preserved control. The results of ground x-ray experiments showed that sperm can be stored for more than 200 years in space. These results suggest that the effect of deep space radiation on mammalian reproduction can be evaluated using spermatozoa, even without being monitored by astronauts in Gateway.

19.
Neuropsychiatr Dis Treat ; 17: 821-833, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33776438

RESUMEN

PURPOSE: This study aimed to describe real-world treatment patterns and medication adherence among patients with bipolar disorder (BD) in Japan. PATIENTS AND METHODS: Adult patients with a BD diagnosis were identified between July 2013 and February 2018, using an employment-based health insurance claims database from the JMDC Inc. Treatment patterns of target drugs (mood stabilizers, antipsychotics) and adherence (measured by the proportion of days covered [PDC]) were assessed during the first- through third-year follow-up. Adherence was also assessed for patient subgroups. RESULTS: The analyzed population included 13,788 patients with BD. They were mostly prescribed sodium valproate, lithium, or aripiprazole (range: 21.1-27.4%) across 3 years of follow-up, whereas lamotrigine was prescribed to 11.2-12.8% of patients. Benzodiazepines (70-87%) and antidepressants (52-71%) were commonly prescribed during all three follow-up periods. The mean PDC among all patients with BD was 0.51 during the first and increased to 0.61 during the third year. The mean PDC was 0.42 (first year) in patients aged <30 years and 0.49 in those aged 30-40 years. The PDC was 0.44-0.61 (depending on the drug class) in those who were prescribed a single-class target drug and 0.68-0.83 in those prescribed two drug classes concomitantly. CONCLUSION: This study documented generally low medication adherence among patients with BD, and those at young age. These patients may require more attention.

20.
Hepatol Res ; 51(6): 682-693, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33710718

RESUMEN

AIM: Prognosis of liver cirrhosis patients is poor when ascites is present and liver function is impaired, but such up-to-date information from a large-scale, real-world setting is limited in Japan. We aimed to investigate the hospital mortality of Japanese liver cirrhosis inpatients. METHODS: This retrospective cohort study included data on liver cirrhosis inpatients between January 2011 and September 2018 extracted from an administrative claims database. The outcome was in-hospital mortality. The 1- and 3-year cumulative survival rates were examined for liver cirrhosis etiology, Child-Pugh classification, or ascites presence/absence using Kaplan-Meier analysis. The survival up to 1 year for tolvaptan prescription/nonprescription was examined. RESULTS: We analyzed the data of 57 769 inpatients. Survival rates did not substantially differ among etiologies, with a better prognosis for alcohol etiology and poorer prognosis for hepatitis C virus. According to the Child-Pugh classification, the 1- and 3-year survival rates were 90.2% and 75.3% for grade A, 73.5% and 53.9% for grade B, and 41.9% and 28.9% for grade C, respectively. Patients without ascites had a higher survival rate (83.2% and 67.0% at 1 and 3 years, respectively) than those with ascites (51.9% and 36.3%, respectively). Based on examining matched patients with ascites using a propensity score, prognosis was poor in general but was better at 6 months (58.1%) or similar at 1 year (47.1%) in patients prescribed tolvaptan compared to those not prescribed tolvaptan (54.8% and 47.5%, respectively). CONCLUSIONS: Poorer prognosis was suggested in inpatients with cirrhosis who had a worse Child-Pugh grade and ascites.

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