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Understanding the interaction between macrophages and biomaterials is important for the creation of new biomaterials and the development of technologies to control macrophage function. Since macrophages are strongly adhesive, caution is required when performing in vitro evaluations. Similarly, when THP-1 cells, macrophage precursor cells, are differentiated into macrophages using phorbol-12-myristate-13-acetate (PMA), it becomes difficult to detach them from the adherent substrate, which has been a problem on investigation of immunological responses to biomaterials. In this study, the interaction of THP-1 cell-differentiated macrophages with biomaterials was analyzed based on a new method of seeding THP-1 cells. THP-1 cells were cultured in static and rotation culture without and with PMA. In undifferentiated THP-1 cells, there was no change in cellular function between static and rotation cultures. In rotation culture with PMA, THP-1 cells differentiated and formed macrophage aggregates. IL-1ß and MRC1 expression in macrophage aggregates was examined after differentiation and M1/M2 polarization. Macrophage aggregates in rotation culture tended to be polarized toward M2 macrophages compared with those in static culture. In the evaluation of the responses of macrophage aggregates to several kinds of polymeric materials, macrophage aggregates showed different changes in MRC1 expression over time at 30, 50, and 70 rpm. Rotation speed of 30 rpm was considered most appropriate condition in that it gave stable results with the same trend as obtained with static culture. The use of macrophage aggregates obtained by rotational culture is expected to provide new insights into the evaluation of inflammatory properties of biomaterials.
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BACKGROUND: Postpartum depression is experienced by approximately 10% of women and affects the health and development of their children. Although it is recommended that all mothers have the opportunity for early detection and intervention for postpartum depression, it is unclear whether early postpartum check-ups help to reduce postpartum depression. OBJECTIVE: The aim of this study was to assess the effect of 2-week postpartum check-ups on screening positive for postpartum depression in Japan. METHODS: This was a population-based cohort study that used the administrative database of Tsuyama, Japan. Participants were women who received postpartum home visits from a public health nurse in Tsuyama during the fiscal years 2017-2019. Data were obtained on participant's attendance at a 2-week postpartum check-up and their responses on the Edinburgh Postpartum Depression Scale. Owing to the initiation of a publicly funded postpartum check-up programme, participants were pseudo-randomly assigned to receive/not receive a 2-week postpartum check-up. We conducted instrumental variable estimation to assess the causal effects of the check-up on screening positive for postpartum depression. RESULTS: The characteristics of the 1,382 participants did not differ by fiscal year of childbirth. We found a 6.7% (95% confidence interval 2.2-11.2) reduction in the prevalence of screening positive for postpartum depression as an effect of 2-week postpartum check-ups among women received 1-month postpartum home visits. CONCLUSION: The results suggest that 2-week postpartum check-ups are effective in reducing the prevalence of screening positive for postpartum depression among 1-month postpartum women. Despite some limitations, early postpartum care could reduce postpartum depression.
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Menarche is delayed in patients with type 1 diabetic mellitus (T1DM) compared to non-diabetics. The purpose of this survey study was to define the age of onset of menarche in Japanese patients with T1DM, as well the secular trends in menarcheal age across the period of 1976-2020 and determine the effects of T1DM and disease management on that age. The study subjects (n = 155) were recruited from among Japanese T1DM patients who visited the outpatient clinic of the Department of Pediatrics, Osaka City University Hospital. The study subjects experienced menarche during 1976-2020. They were divided into the menarche-post-T1DM group (n = 117) and the menarche-pre-T1DM group (n = 38), in whom menarche occurred after or before the diagnosis of T1DM, respectively. The time of birth was also stratified into five decade/time bins extending from 1960s to 2000s. The subjects filled a questionnaire on menarche. Other clinical information was obtained from the medical records. The median age at menarche was 12.5 years (11.3-13.4) (25th-75th percentile) for the menarche-post-T1DM group and 11.8 years (10.9-13.0) for the menarche-pre-T1DM group (p = 0.024). Menarche occurred at a significantly younger age in recent years in the menarche-post-T1DM group (r = -0.209, p = 0.023), but no such trend was found in the control group. Analysis of data of subjects born after 1990 still showed significant delay associated with T1DM [post-T1DM group: 12.3 years (11.3-13.2), pre-T1DM group: 11.8 years (11.0-12.2), p = 0.045]. The results suggest that recent advances in insulin therapy seem to improve metabolism under T1DM but might have not enough impact on menarche in Japanese girls.
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Diabetes Mellitus Tipo 1 , Menarca , Fatores Etários , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Insulina/uso terapêutico , Japão/epidemiologia , Inquéritos e QuestionáriosRESUMO
Liposome surface coating has been studied to avoid the immunological responses caused by the complement system, and alternative materials to poly(ethylene glycol) (PEG) have been explored recently since the production of anti-PEG IgM antibodies has been found in humans. We previously reported a liposome coating with poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC))-conjugated lipids (PMPC-lipids) and demonstrated its protective effect on blood protein interactions. Here, we attempted to modify the liposome surface by exogenously adding PMPC-lipids, which were spontaneously incorporated into the outer membrane via hydrophobic interactions. The polymerization degree of the PMPC segment was regulated from 10 to 100. The incorporated ratio of PMPC-lipid increased with a decrease in the degree of PMPC polymerization. Due to surface modification with PMPC-lipids, increase in the length of the PMPC-chain increased the size of the liposomes. The modified liposomes were kept stable for 14 d in terms of their size, polydispersity, and surface properties, where approximately 70% of PMPC-lipids were incorporated into the liposome surface. We demonstrated that liposome surface modification with PMPC-lipids can inhibit protein adsorption when exposed to serum, regardless of the degree of polymerization of PMPC. In addition, the PMPC-lipid modified surface was not recognized by the anti-PEG IgM antibody, whereas PEG-lipid was recognized by the antibody. Thus, we successfully fabricated an inert liposome surface via spontaneous modification with PMPC-lipids, where only the outer bilayer surface was modified. This technique can be available for full loading of water-soluble active pharmaceutical ingredient inside the modified liposome.
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The use of amphiphilic molecules such as poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) enables incorporation into liposome surfaces by exogenous addition as a result of the self-assembly with lipids. This technique can be applicable for manipulation of both liposomes and cells. In this study, we aimed to characterize Tat peptide (YGRKKRRQRRR)-conjugated PEG-lipids when used to exogenously surface modify liposomes (size: ca. 100 nm). We earlier reported that cells, which were surface modified with Tat peptides conjugated to PEG-lipids could attach spontaneously to material surfaces without any chemical modification. Here, we synthesized different types of Tat-PEG-lipids by combining PEG of different molecular weights (5 and 40 kDa) with different lipids with three acyl chains (myristoyl, palmitoyl, and stearoyl, respectively) and then studied the spontaneous adsorption of modified liposomes onto a substrate surface induced by the different Tat-PEG-lipids. The amount of adsorbed liposomes strongly depended on the number of incorporated Tat-PEG-lipid moieties: a decrease in both the PEG and the acyl chain lengths led to adsorption of higher amounts of liposomes. Furthermore, when a collagenase-cleavable amino acid sequence was inserted between the Tat sequence and the PEG segment, adsorbed liposomes could be harvested from the substrate by collagenase treatment with no difference in desorption efficiency between the different Tat-PEG-lipids. Thus, Tat-PEG-lipid can be a suitable tool for the manipulation of liposomes and cells.
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Peptídeos Penetradores de Células , Lipossomos , Adsorção , Humanos , Fosfolipídeos , PolietilenoglicóisRESUMO
Mutations in dysferlin are responsible for a group of progressive, recessively inherited muscular dystrophies known as dysferlinopathies. Using recombinant proteins and affinity purification methods combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), we found that AMP-activated protein kinase (AMPK)γ1 was bound to a region of dysferlin located between the third and fourth C2 domains. Using ex vivo laser injury experiments, we demonstrated that the AMPK complex was vital for the sarcolemmal damage repair of skeletal muscle fibers. Injury-induced AMPK complex accumulation was dependent on the presence of Ca2+, and the rate of accumulation was regulated by dysferlin. Furthermore, it was found that the phosphorylation of AMPKα was essential for plasma membrane repair, and treatment with an AMPK activator rescued the membrane-repair impairment observed in immortalized human myotubes with reduced expression of dysferlin and dysferlin-null mouse fibers. Finally, it was determined that treatment with the AMPK activator metformin improved the muscle phenotype in zebrafish and mouse models of dysferlin deficiency. These findings indicate that the AMPK complex is essential for plasma membrane repair and is a potential therapeutic target for dysferlinopathy.
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Proteínas Quinases Ativadas por AMP/metabolismo , Disferlina/química , Disferlina/metabolismo , Metformina/administração & dosagem , Músculo Esquelético/lesões , Distrofia Muscular do Cíngulo dos Membros/tratamento farmacológico , Animais , Linhagem Celular , Modelos Animais de Doenças , Disferlina/genética , Humanos , Lasers/efeitos adversos , Metformina/farmacologia , Camundongos , Músculo Esquelético/metabolismo , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Mutação , Fosforilação , Domínios Proteicos , Sarcolema/metabolismo , Peixe-ZebraRESUMO
In this study, we designed and synthesized an implantable anti-CD25 antibody-immobilized polyethylene (CD25-PE) mesh to suppress tumor growth by removing regulatory T cells (Tregs). The PE mesh was graft-polymerized with poly(acrylic acid), and the anti-mouse CD25 antibody was then immobilized using the 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide reaction. Immobilization of the antibody on the PE mesh was confirmed by immunostaining. The CD25-PE mesh could effectively and selectively capture CD25-positive cells through antigen-antibody interactions when the CD25-PE mesh was incubated with a suspension of mouse spleen cells, including CD25-positive cells. In addition, implantation of the CD25-PE mesh into mice subcutaneously demonstrated the Treg-capturing ability of the CD25-PE mesh with only a weak inflammatory reaction. In tumor-bearing mice, tumor growth was suppressed by subcutaneous implantation of the CD25-PE mesh near the tumor for 1 week. These results suggested that the anti-CD25 antibody-immobilized material could capture Tregs in vivo and inhibit tumor proliferation in a limited tumor-bearing mouse model. Further research is needed to facilitate cancer immunotherapy using implantable anti-CD25 antibody-immobilized material as a Treg-capturing device.
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Dysferlinopathy is a group of autosomal recessive muscular dystrophies caused by variants in the dysferlin gene (DYSF), with variable proximal and distal muscle involvement. We performed DYSF gene analyses of 200 cases suspected of having dysferlinopathy (Cohort 1), and identified diagnostic variants in 129/200 cases, including 19 novel variants. To achieve a comprehensive genetic profile of dysferlinopathy, we analyzed the variant data from 209 affected cases from unrelated 209 families, including 80 previously diagnosed and 129 newly diagnosed cases (Cohort 2). Among the 90 types of variants identified in 209 cases, the NM_003494.3: c.2997G>T; p.Trp999Cys, was the most frequent (96/420; 22.9%), followed by c.1566C>G; p.Tyr522* (45/420; 10.7%) on an allele base. p.Trp999Cys was found in 70/209 cases (33.5%), including 20/104 cases (19.2%) with the Miyoshi muscular phenotype and 43/82 cases (52.4%) with the limb-girdle phenotype. In the analysis of missense variants, p.Trp992Arg, p.Trp999Arg, p.Trp999Cys, p.Ser1000Phe, p.Arg1040Trp, and p.Arg1046His were located in the inner DysF domain, representing in 113/160 missense variants (70.6%). This large cohort highlighted the frequent missense variants located in the inner DysF domain as a hotspot for missense variants among our cohort of 209 cases (>95%, Japanese) and hinted at their potential as targets for future therapeutic strategies.
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Disferlina/genética , Estudos de Associação Genética , Perfil Genético , Distrofia Muscular do Cíngulo dos Membros/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Adulto JovemRESUMO
Mutations in the PNPLA2 gene cause neutral lipid storage disease with myopathy (NLSDM) or triglyceride deposit cardiomyovasculopathy. We report a detailed case study of a 53-year-old man with NLSDM. The PNPLA2 gene was analyzed according to the reported method. We summarized the clinical, laboratory, and genetic information of 56 patients, including our patient and 55 other reported patients with homozygous or compound heterozygous mutations in the PNPLA2 gene. We found a novel homozygous mutation (c.194delC) in the PNPLA2 gene that resulted in frameshift. The patient suffered from normal-tension glaucoma and pulmonary cysts, symptoms that are relatively common in the elderly but were not previously reported for this disease. Our summary confirmed that Jordan's anomaly, polymorphonuclear leukocytes with lipid accumulation, was the most consistent finding of this disease. Because this disease is potentially treatable, our results may help rapid and correct diagnosis.
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Lipase/genética , Erros Inatos do Metabolismo Lipídico/genética , Doenças Musculares/genética , Mutação da Fase de Leitura , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Recent applications of decellularized tissue have included the use of hydrogels for injectable materials and three-dimensional (3D) bioprinting bioink for tissue regeneration. Microvascular formation is required for the delivery of oxygen and nutrients to support cell growth and regeneration in tissues and organs. The aim of the present study was to evaluate the formation of capillary networks in decellularized extracellular matrix (d-ECM) hydrogels. The d-ECM hydrogels were obtained from the small intestine submucosa (SIS) and the urinary bladder matrix (UBM) after decellularizing with sodium deoxycholate (SDC) and high hydrostatic pressure (HHP). The SDC d-ECM hydrogel gradually gelated, while the HHP d-ECM hydrogel immediately gelated. All d-ECM hydrogels had low matrix stiffness compared to that of the collagen hydrogel, according to a compression test. D-ECM hydrogels with various elastic moduli were obtained, irrespective of the decellularization method or tissue source. Microvascular-derived endothelial cells were seeded on d-ECM hydrogels. Few cells attached to the SDC d-ECM hydrogel with no network formation, while on the HHP d-ECM hydrogel, a capillary network structure formed between elongated cells. Long, branched networks formed on d-ECM hydrogels with lower matrix stiffness. This suggests that the capillary network structure that forms on d-ECM hydrogels is closely related to the matrix stiffness of the hydrogel.
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Módulo de Elasticidade , Células Endoteliais/fisiologia , Matriz Extracelular/química , Hidrogéis/química , Intestino Delgado/fisiologia , Neovascularização Fisiológica , Bexiga Urinária/fisiologia , Animais , Capilares , Proliferação de Células , Colágeno/química , Células Endoteliais/citologia , Intestino Delgado/citologia , Ratos , Ratos Wistar , Suínos , Engenharia Tecidual , Bexiga Urinária/citologiaRESUMO
One of the problems in dental implant treatment is the lack of periodontal ligament (PDL), which supports teeth, prevents infection, and transduces sensations such as chewiness. The objective of the present study was to develop a decellularized PDL for supporting an artificial tooth. To this end, we prepared mouse decellularized mandible bone with a PDL matrix by high hydrostatic pressure and DNase and detergent treatments and evaluated its reconstruction in vivo. After tooth extraction, the decellularized mandible bone with PDL matrix was implanted under the subrenal capsule in rat and observed that host cells migrated into the matrix and oriented along the PDL collagen fibers. The extracted decellularized tooth and de- and re-calcified teeth, which was used as an artificial tooth model, were re-inserted into the decellularized mandible bone and implanted under the subrenal capsule in rat. The reconstructed PDL matrix for the extracted decellularized tooth resembled the decellularized mandible bone without tooth extraction. This demonstrates that decellularized PDL matrix can reconstruct PDL tissue by controlling host cell migration, which could serve as a novel periodontal treatment approach.
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Matriz Extracelular , Regeneração Tecidual Guiada Periodontal , Ligamento Periodontal/fisiologia , Regeneração , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ligamento Periodontal/cirurgia , RatosRESUMO
Streptococcus pneumoniae is a main causative agent of serious invasive bacterial infections. However, concurrent infection with invasive pneumococcal disease (IPD) and viral infectious mononucleosis (IM) is rare. We report an infant with serotype 6C infection causing IPD occurring simultaneously with IM. A previously healthy 11-month-old girl referred to our hospital because of fever, leukopenia, and elevated C-reactive protein presented to us with disturbance of consciousness, tachycardia, tachypnea and agranulocytosis. Other findings included tonsillitis with purulent exudates and white spots, bilateral cervical adenopathy, and hepatosplenomegaly. We diagnosed her illness as sepsis and administered a broad-spectrum antibiotic, an antiviral agent, and granulocyte transfusions. After treatment was initiated, fever gradually decreased and general condition improved. IPD was diagnosed based upon isolation of S. pneumoniae of serotype 6C from blood cultures obtained on admission. Concurrently the girl had IM, based upon quantitation of Epstein-Barr viral DNA copies in blood and fluctuating serum antibody titers. Although simultaneous IPD and IM is a rare occurrence, this possibility is important to keep in mind.
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Agranulocitose/complicações , Febre/complicações , Mononucleose Infecciosa/complicações , Infecções Pneumocócicas/complicações , Streptococcus pneumoniae/isolamento & purificação , Agranulocitose/sangue , Agranulocitose/microbiologia , Agranulocitose/terapia , Antibacterianos/uso terapêutico , Proteína C-Reativa/análise , Citomegalovirus/isolamento & purificação , Feminino , Febre/sangue , Febre/tratamento farmacológico , Febre/microbiologia , Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Mononucleose Infecciosa/sangue , Mononucleose Infecciosa/microbiologia , Mononucleose Infecciosa/terapia , Transfusão de Leucócitos , Infecções Pneumocócicas/sangue , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/terapia , Reação em Cadeia da Polimerase , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/imunologiaAssuntos
Adenosina Trifosfatases/imunologia , Anticorpos/sangue , Calcinose/diagnóstico por imagem , Proteínas de Ligação a DNA/imunologia , Dermatomiosite/imunologia , Tomografia por Emissão de Pósitrons/métodos , Idoso , Calcinose/sangue , Calcinose/imunologia , Dermatomiosite/sangue , Feminino , Fluordesoxiglucose F18 , Humanos , Compostos RadiofarmacêuticosRESUMO
Background: The COVID-19 pandemic has impacted healthcare behaviors, leading to fewer pediatric visits in Japan and potentially fewer visits by adult patients. However, existing Japanese studies on treatment interruptions have generally relied on questionnaire-based methods. In this study, we assessed the impact of the pandemic on antihypertensive treatment interruption using real-world prescription data. Methods: We conducted an interrupted time series analysis using the National Health Insurance Database in Okayama Prefecture, Japan. Participants included individuals aged 40-69 years with at least one antihypertensive prescription between 2018 and 2020. Treatment interruption was defined as a 3-month or longer gap in prescriptions after medication depletion. We used segmented Poisson regression with models unadjusted and adjusted for seasonality and over-dispersion to assess monthly treatment interruptions before and after Japan's April 2020 emergency. Results: During the study period, 23.0% of 55,431 participants experienced treatment interruptions. Cyclical fluctuations in interruptions were observed. The crude analysis indicated a 1.2-fold increase in treatment interruptions following the pandemic; however, the adjusted models showed no significant changes. Even among higher-risk groups, such as women, younger adults, and those with shorter prescriptions, no significant alterations were observed. Conclusion: We found no significant impact of the COVID-19 pandemic on antihypertensive treatment interruption in Okayama Prefecture. The less severe outbreak in the area or increased use of telemedicine and extended prescriptions may have contributed to treatment continuity. Further research is needed using a more stable and comprehensive database, broader regional data, and detailed prescription records to validate and extend our findings.
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INTRODUCTION: Patients with Parkinson's disease (PD) may benefit from deep brain stimulation (DBS). Perifocal brain edema sometimes occurs after DBS surgery, but it is transient and does not affect the final prognosis. Transient deterioration of cognitive function has been reported in patients with frontal edema in the first postoperative week. This study aimed to investigate the effect of Goreisan in preventing edematous changes after DBS and determine the influence of edema on cognition. METHODS: We included 29 patients with PD who underwent bilateral subthalamic nucleus (STN) DBS and who were divided into 2 groups: those using (11 patients) and those not using Goreisan (18 patients). At 1 week postoperatively, all patients underwent magnetic resonance imaging. We measured the volume of edema either in the frontal white matter or STN on fluid-attenuated inversion recovery (FLAIR) images. Finally, brain edema, motor function, and cognitive function were compared between the groups with and without Goreisan. RESULTS: In the FLAIR image 1 week postoperatively, the average postoperative frontal subcortical edema (FE) volume of the group with Goreisan was significantly lower than that without Goreisan (2249 ± 2186 mm3, 6261 ± 7213 mm3, respectively, p = 0.023). Multivariate analysis with age, preoperative Mini-Mental State Examination (MMSE) score, FE, and peri-STN edema (SE) as factors, and MMSE at 1 week postoperatively as the dependent variable showed that preoperative MMSE score and SE were significant as associated factors. CONCLUSIONS: FE after DBS surgery may be alleviated using Goreisan. SE and preoperative MMSE scores were associated with MMSE scores 1 week postoperatively. TRIAL REGISTRATION: Not applicable.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/diagnóstico por imagem , Estimulação Encefálica Profunda/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Imageamento por Ressonância Magnética , Período Perioperatório , Cognição/fisiologiaRESUMO
Type 1 diabetes mellitus (T1DM) adversely affects gonadal function. This study aimed to define the characteristics and factors associated with menstrual cycle abnormalities and polycystic ovary syndrome (PCOS) in Japanese patients with T1DM. Our study enrolled 157 patients, including 55 with oligomenorrhea (prolonged menstrual cycle) and 102 without oligomenorrhea. LH/FSH ratio (p = 0.04) and total testosterone levels (p = 0.03) were significantly higher in the oligomenorrhea group than in the non-oligomenorrhea group. No significant differences were found between the two groups regarding age at menarche, age at T1DM diagnosis, treatment, glycated hemoglobin, or total daily insulin dose. Of the 55 patients in the oligomenorrhea group, 27 were diagnosed with PCOS based on the Rotterdam criteria. We concluded that female patients with T1DM, as well as abnormal menstrual cycles and hyperandrogenism, may suffer from undiagnosed PCOS and should be referred to a gynecologist for full assessment, diagnosis, and treatment.
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BACKGROUND: Strictly superficial cerebellar microbleeds and cerebellar superficial siderosis have been considered markers of advanced cerebral amyloid angiopathy (CAA), but there are few studies on cerebellar ischemic lesions in CAA. We investigated the presence of superficial small cerebellar infarct (SCI) ≤15 mm and its relation to magnetic resonance imaging (MRI) markers in patients with probable CAA. METHODS: Eighty patients with probable CAA were retrospectively evaluated. The presence of superficial SCIs was examined, along with cerebellar microbleeds and cerebellar superficial siderosis, using 3-T MRI. Lobar cerebral microbleeds, cortical superficial siderosis (cSS), enlargement of the perivascular space in the centrum semiovale, and white matter hyperintensity were assessed and the total CAA-small vessel disease (SVD) score was calculated. RESULTS: Nine of the 80 patients (11.3%) had a total of 16 superficial SCIs. By tentatively defining SCI <4 mm as cerebellar microinfarcts, 8 out of 16 (50%) superficial SCIs corresponded to cerebellar microinfarcts. The total CAA-SVD score was significantly higher in patients with superficial SCIs (p = 0.01). The prevalence of cSS (p = 0.018), cortical cerebral microinfarct (p = 0.034), and superficial cerebellar microbleeds (p = 0.006) was significantly higher in patients with superficial SCIs. The number of superficial cerebellar microbleeds was also significantly higher in patients with superficial SCIs (p = 0.001). CONCLUSIONS: Our results suggest that in patients with CAA, superficial SCIs (including microinfarcts) on MRI may indicate more severe, advanced-stage CAA. These preliminary findings should be verified by larger prospective studies in the future.
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Angiopatia Amiloide Cerebral , Doenças de Pequenos Vasos Cerebrais , Siderose , Humanos , Estudos Retrospectivos , Hemorragia Cerebral/epidemiologia , Estudos Prospectivos , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/epidemiologia , Imageamento por Ressonância Magnética/métodos , InfartoRESUMO
This study aimed to evaluate the feasibility and efficacy of individualized occupational therapy (IOT) plus group occupational therapy (GOT) as standard care for cognition compared to GOT alone, and to determine which IOT component has the greatest effect on cognitive outcome in patients with schizophrenia. This study was conducted at 14 clinical sites across Japan and enrolled recently hospitalized patients with schizophrenia. The IOT consisted of motivational interview, self-monitoring, individualized visits, craft activities, individualized psychoeducation, and discharge planning. Among the 68 patients who were randomized to the GOT + IOT group (n = 34) and GOT alone group (n = 34), 67 completed the trial (GOT + IOT group, n = 34; GOT alone group, n = 33). There were significant improvements in change from baseline to post-treatment between the groups in verbal memory, working memory, verbal fluency, attention, executive function domains, and the composite score of the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS composite score was significantly associated with the number of craft activity sessions. The addition of IOT to GOT has a favorable feasibility profile and efficacy for cognition in schizophrenia. Craft activity is the most effective IOT component in improving cognition.
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Terapia Ocupacional , Esquizofrenia , Humanos , Esquizofrenia/reabilitação , Esquizofrenia/terapia , Esquizofrenia/complicações , Esquizofrenia/fisiopatologia , Masculino , Feminino , Terapia Ocupacional/métodos , Adulto , Pessoa de Meia-Idade , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/reabilitação , Disfunção Cognitiva/terapia , Disfunção Cognitiva/fisiopatologia , Estudos de Viabilidade , Psicoterapia de Grupo , Avaliação de Resultados em Cuidados de Saúde , Psicologia do EsquizofrênicoRESUMO
Sporadic inclusion body myositis (sIBM) is a muscle disease in older people and is characterized by inflammatory cell invasion into intact muscle fibers and rimmed vacuoles. The pathomechanism of sIBM is not fully elucidated yet, and controversy exists as to whether sIBM is a primary autoimmune disease or a degenerative muscle disease with secondary inflammation. Previously, we established a method of collecting CD56-positive myoblasts from human skeletal muscle biopsy samples. We hypothesized that the myoblasts derived from these patients are useful to see the cell-autonomous pathomechanism of sIBM. With these resources, myoblasts were differentiated into myotubes, and the expression profiles of cell-autonomous pathology of sIBM were analyzed. Myoblasts from three sIBM cases and six controls were differentiated into myotubes. In the RNA-sequencing analysis of these "myotube" samples, 104 differentially expressed genes (DEGs) were found to be significantly upregulated by more than twofold in sIBM, and 13 DEGs were downregulated by less than twofold. For muscle biopsy samples, a comparative analysis was conducted to determine the extent to which "biopsy" and "myotube" samples differed. Fifty-three DEGs were extracted of which 32 (60%) had opposite directions of expression change (e.g., increased in biopsy vs decreased in myotube). Apolipoprotein E (apoE) and transmembrane protein 8C (TMEM8C or MYMK) were commonly upregulated in muscle biopsies and myotubes from sIBM. ApoE and myogenin protein levels were upregulated in sIBM. Given that enrichment analysis also captured changes in muscle contraction and development, the triggering of muscle atrophy signaling and abnormal muscle differentiation via MYMK or myogenin may be involved in the pathogenesis of sIBM. The presence of DEGs in sIBM suggests that the myotubes formed from sIBM-derived myoblasts revealed the existence of muscle cell-autonomous degeneration in sIBM. The catalog of DEGs will be an important resource for future studies on the pathogenesis of sIBM focusing on primary muscle degeneration.