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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.
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Fibras Musculares Esqueléticas , Miositis por Cuerpos de Inclusión , Humanos , Miositis por Cuerpos de Inclusión/metabolismo , Miositis por Cuerpos de Inclusión/genética , Miositis por Cuerpos de Inclusión/patología , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Diferenciación Celular , Anciano , Femenino , Masculino , Células Cultivadas , Transcriptoma , Mioblastos/metabolismo , Mioblastos/patología , Biopsia , Perfilación de la Expresión Génica , Persona de Mediana EdadRESUMEN
BACKGROUND: Inclusion body myositis (IBM) is a progressive myopathy occurring in patients over 45 years of age, with heterogeneous and variable clinical features. This study aimed to determine the influence of autoantibodies, gender, and age of onset on the clinical features of IBM. METHODS: Medical records and muscle histology findings of 570 participants with suspected IBM were reviewed. Various characteristics of patients who met the 2011 ENMC IBM diagnostic criteria were compared based on the presence of anti-cytosolic 5'-nucleotidase 1 A (cN1A) autoantibodies, gender, age of onset, and disease duration. RESULTS: Of the 353 patients who met the criteria, 41.6% were female. The mean age at onset was 64.6 ± 9.3 years, and the mean duration from onset to diagnosis was 5.7 ± 4.7 years. 196 of the 353 patients (55.5%) were positive for anti-cN1A autoantibodies and 157 were negative. Logistic regression showed that patients with anti-cN1A autoantibodies had a higher frequency of finger flexion weakness. Multiple regression showed that patients with later age of onset had shorter disease duration, lower BMI, and lower serum CK levels. Male patients had a higher frequency of onset with finger weakness and female patients had a lower BMI. CONCLUSION: Autoantibodies, gender, age of onset, and disease duration may influence the clinical presentation of IBM, highlighting the need for a precision medicine approach that considers these factors along with the underlying mechanisms of the disease.
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Background: Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, conducting a QOL survey with patients is difficult. Therefore, we conducted a QOL survey with physicians. Specifically, this study aimed to clarify how physicians assess QOL in patients with pancreatic cancer by conducting a survey and comparing the results between physicians and the general public. Methods: A survey was conducted by interviewing physicians administering chemotherapy to patients for recurrent/metastatic pancreatic cancer. This method is similar to that of the QOL survey conducted among the general public. Responses were evaluated using the composite time trade-off (cTTO) and the visual analog scale (VAS) for 11 pancreatic cancer status scenarios (survey scenarios). These scenarios consisted of patients' health states as well as the types and grades of adverse events (AEs). Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). In addition, we conducted a survey using the EuroQol 5 Dimensions 5-Level (EQ-5D-5l) as reference values. Results: Twenty physicians responded to the survey. SD had the highest mean QOL value for both assessment methods (Physicians: 0.78, General public: 0.63), whereas PD had the lowest mean QOL value (Physicians: 0.15, General public: -0.12). The physicians assigned higher QOL values on both the VAS and cTTO than the general public did in all survey scenarios. Conclusions: The QOL values obtained from physicians were consistent with the degree of status in any assessment scenarios. Based on the differences in the QOL survey results between physicians and the general public, physicians tended to assign higher QOL values than the general public in cTTO and VAS assessments.
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Various studies have attempted to improve the milk yield and composition in dairy animals. However, no study has examined the effects of milking at different times on milk yield and composition. Therefore, this study aimed to compare the yield, composition, and antimicrobial components of milk obtained from milking at different times in lactating goats. Eight goats were milked once daily at different times for three consecutive weeks (first week: 06:00 h; second week: 09:00 h; and third week: 12:00 h). The light ranged from 06:30 to 19:00 h. Milk and blood samples were collected once a day during milking time. Milking at 09:00 h resulted in a significantly higher milk yield than that obtained after milking at 06:00 and 12:00 h. Prolactin levels in plasma and the fat, Na+, ß-defensin, and S100A7 (antimicrobial component) levels in milk were the lowest in the 09:00 h milking. These results indicate that milk yield, composition, and antimicrobial components can be affected by milking time, which may be related to the altered concentration of prolactin in the blood. These findings provide a rational basis for achieving maximal milk production with strong immunity by changing to a more effective milking time.
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Cabras , Lactancia , Leche , Prolactina , beta-Defensinas , Animales , Cabras/fisiología , Femenino , Leche/química , Prolactina/sangre , Factores de Tiempo , beta-Defensinas/análisis , Industria Lechera/métodos , Sodio/sangre , Sodio/análisis , Antiinfecciosos/análisisRESUMEN
This study examined the effects of low frequency milking on the concentrations of antimicrobial components in goat milk. Sixteen goats were divided into two groups of eight each: milking once every 2 d three times (for six days, three times group) or five times (for 10 days, five times group). On other days, milking was performed once daily. Milk was collected, and milk yield, somatic cell count (SCC), and the concentrations of some antimicrobial proteins such as lactoferrin (LF), S100A7, IgA, and sodium ions (Na+) in milk were measured. Milk yield significantly decreased in both the groups during the low-milking frequency period, followed by an increase above the low frequency milking period in both groups. In contrast, SCC and LF concentrations in milk increased in both groups during the low frequency milking period. The concentration of S100A7 in milk temporarily decreased after the low frequency milking period, followed by a significant increase. The S100A7 concentration during this period was higher in the five times group than in the three times group. These results indicated that low frequency milking induced a gradual decrease in milk yield and a concomitant increase in antimicrobial components, such as LF and S100A7, in milk. This increase in the antimicrobial components may be useful in preventing mastitis.
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Industria Lechera , Cabras , Lactancia , Lactoferrina , Leche , Animales , Leche/química , Femenino , Lactoferrina/análisis , Industria Lechera/métodos , Inmunoglobulina A/análisis , Mastitis/veterinaria , Proteína A7 de Unión a Calcio de la Familia S100 , Recuento de Células/veterinaria , Sodio/análisisRESUMEN
Sporadic inclusion body myositis (sIBM) is an intractable and progressive skeletal muscle disease of unknown etiology. Muscle biopsy typically reveals endomysial inflammation, invasion of mononuclear cells into non-necrotic fibers, and rimmed vacuoles, suggesting that inflammation and degeneration co-exist in the pathomechanism. According to a nationwide survey conducted by a research team of the Ministry of Health, Labor, and Welfare, the number of patients is increasing in Japan as well. The clinical progression shows a slow and chronic deterioration. sIBM is usually diagnosed five years after onset. Muscle weakness and atrophy in the quadriceps, wrist flexors, and finger flexors are typical neurological findings of sIBM. Dysphagia and asymmetric weakness are often found. Serum creatine kinase is usually below 2,000 IU/L. sIBM is generally refractory to current therapy, such as steroids or immunosuppressants. Understanding the pathomechanism of sIBM is crucial for developing effective therapeutic strategies.
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Miositis por Cuerpos de Inclusión , Miositis por Cuerpos de Inclusión/terapia , Miositis por Cuerpos de Inclusión/diagnóstico , Miositis por Cuerpos de Inclusión/patología , Humanos , Progresión de la EnfermedadRESUMEN
BACKGROUND: Hallux valgus and hallux rigidus are disorders affecting the first ray and are associated with hypermobility of this structure. This study aimed to investigate the three-dimensional mobility of each joint of the first ray between feet with hallux valgus or hallux rigidus and healthy feet using weightbearing and nonweightbearing computed tomography (CT). METHODS: This case-control study analyzed 17 feet of 11 healthy volunteers (control group), 16 feet of 16 patients with hallux valgus (HV group), and 16 feet of 11 patients with hallux rigidus (HR group). First, nonweightbearing foot CT imaging was performed in the supine position on a loading device with no load applied, with the legs extended and the ankle in the neutral position. Next, a load equivalent to body weight was applied for weightbearing CT imaging. Distal bone displacement relative to the proximal bone was quantified three-dimensionally under both conditions. RESULTS: In the HV group, the talonavicular joint showed significantly greater eversion (P = 00.011) compared with the control group and significantly greater dorsiflexion (P = 00.027) and eversion (P < 00.01) compared with the HR group. In the medial cuneiform joint, the HV group showed significantly greater eversion (P < 00.01) and abduction (P = 00.011) than the control group. For the first tarsometatarsal joint, the HV group showed significantly greater dorsiflexion (P = 00.014), inversion (P = 00.028), and adduction (P < 00.01) than the control group, and greater inversion (P < 00.01) and adduction (P < 00.01) than the HR group. Dorsiflexion of the first tarsometatarsal joint was significantly greater in the HR group compared with the control group (P = 00.026). CONCLUSION: Hypermobility of the first ray appears to be three-dimensional: in hallux valgus, it is centered at the first tarsometatarsal joint, while in hallux rigidus it is mainly in the sagittal plane at the first tarsometatarsal joint only. This difference may explain the different deformities ultimately observed in each condition.
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The components of milk from beef cows remain to be elucidated. This study examined the differences in the antimicrobial components of milk between dairy and beef cows. Quarter milk was collected from both Japanese Black (beef type) and Holstein (dairy type) cows to compare the concentrations of antimicrobial components. The concentration of lingual antimicrobial peptide (LAP) was higher, whereas that of the other antimicrobial components (lactoferrin, S100A7, and S100A8) was lower in beef cows than in dairy cows. Overall, these results indicate that the differences in antimicrobial components between beef and dairy cows may be associated with the difference in the prevalence of mastitis between them.
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Antiinfecciosos , Enfermedades de los Bovinos , Mastitis Bovina , Femenino , Bovinos , Animales , Leche , Antiinfecciosos/farmacología , Prevalencia , Mastitis Bovina/epidemiología , Lactancia , Recuento de Células/veterinariaRESUMEN
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive multisystem neurologic disorder caused by biallelic intronic repeats in RFC1. Although the phenotype of CANVAS has been expanding via diagnostic case accumulation, there are scant pedigree analyses to reveal disease penetrance, intergenerational fluctuations in repeat length, or clinical phenomena (including heterozygous carriers). We identified biallelic RFC1 ACAGG expansions of 1000 ~ repeats in three affected siblings having sensorimotor neuronopathy with spinocerebellar atrophy initially presenting with painful muscle cramps and paroxysmal dry cough. They exhibit almost homogeneous clinical and histopathological features, indicating motor neuronopathy. Over 10 years of follow-up, painful intractable muscle cramps ascended from legs to trunks and hands, followed by amyotrophy and subsequent leg pyramidal signs. The disease course combined with the electrophysical and imagery data suggest initial and prolonged hyperexcitability and the ensuing spinal motor neuron loss, which may progress from the lumbar to the rostral anterior horns and later expand to the corticospinal tract. Genetically, heterozygous ACAGG expansions of similar length were transmitted in unaffected family members of three successive generations, and some of them experienced muscle cramps. Leukocyte telomere length assays revealed comparatively shorter telomeres in affected individuals. This comprehensive pedigree analysis demonstrated a non-anticipating ACAGG transmission and high penetrance of manifestations with a biallelic state, especially motor neuronopathy in which muscle cramps serve as a prodromal and disease progress marker. CANVAS and RFC1 spectrum disorder should be considered when diagnosing lower dominant motor neuron disease, idiopathic muscle cramps, or neuromuscular hyperexcitability syndromes.
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Calambre Muscular , Linaje , Proteína de Replicación C , Humanos , Calambre Muscular/genética , Masculino , Femenino , Proteína de Replicación C/genética , Adulto , Persona de Mediana Edad , Japón , Enfermedad de la Neurona Motora/genética , Vestibulopatía Bilateral/genética , Ataxias Espinocerebelosas/genética , Expansión de las Repeticiones de ADN/genética , Pueblos del Este de AsiaRESUMEN
We investigated the antimicrobial components in cow milk at dry off and postpartum and their contribution in preventing new high SCC at quarter level. Milk samples from 72 quarters of 19 lactating cows were collected at last milking before dry off and at 7 d after parturition. Milk yield of each cow was recorded and SCC, IgG, IgA, lactoferrin, lingual antimicrobial peptide (LAP), and S100A7 concentrations in each quarter milk sample were measured. The postpartum milk yield was significantly higher than that at dry off. The IgG, IgA and lactoferrin concentrations in milk at dry off were significantly higher than those at postpartum, whereas the LAP concentration was lower. Quarters with SCC < 300 000 cells/ml at both dry off and postpartum were classified as persistent low SCC (PL) whereas those that rose above that same threshold postpartum were classified as new high SCC (NH). At dry off, IgG and LAP concentrations in milk were significantly higher in PL than in NH. These results suggest that high LAP concentrations during the dry period may contribute toward the prevention of new high SCC.
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Inmunoglobulina A , Inmunoglobulina G , Lactancia , Lactoferrina , Leche , Periodo Posparto , Animales , Bovinos , Femenino , Leche/química , Lactoferrina/análisis , Lactancia/fisiología , Recuento de Células/veterinaria , Inmunoglobulina G/análisis , Inmunoglobulina A/análisis , Mastitis Bovina/prevención & control , beta-DefensinasRESUMEN
The aim of this study was to examine the effects of milking cessation under different inflammatory conditions on the changes in antimicrobial components in milk and the process of mammary gland involution. Twenty udder halves were divided into two groups: those with (LPS) and without (control) lipopolysaccharide infusion, followed by cessation of milking for 8 weeks. Milk samples were collected weekly. Udder tissue was collected 4 weeks after milking cessation to measure the area of the lobule and connective tissue. After milking cessation, the somatic cell count (SCC) in the control group increased, whereas that in the LPS group did not. Lactoferrin (LF) and cathelicidin (Cath)-2 concentrations increased in both groups, whereas only LF was significantly lower in the LPS group than in the control group at week 4. The Cath-7 and S100A8 concentrations were significantly lower in the LPS group than in the control group. The lobule area was higher, and the connective tissue area was lower in the LPS group than in the control group. These results indicate that inflammation at milking cessation decreased the concentrations of some antimicrobial components and interfered with mammary gland involution. Therefore, animals with mastitis should recover prior to the onset of the dry period.
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Antiinfecciosos , Enfermedades de las Cabras , Femenino , Animales , Leche , Lactancia , Lipopolisacáridos/farmacología , Glándulas Mamarias Animales , Cabras , Antiinfecciosos/farmacología , Inflamación/veterinaria , Recuento de Células/veterinariaRESUMEN
This report examines delayed leukoencephalopathy as a postoperative complication after the use of flow diverter (FD) devices for endovascular cerebral aneurysm treatment. A case involving a 78-year-old female treated with a pipeline embolization device for a left internal carotid artery aneurysm is presented. Despite adherence to dual anti-platelet therapy, the patient developed intermittent headaches and memory issues 3 months post-operation. MRI revealed T1-enhancing foci and T2 hyperintense signal abnormalities in the left cerebral hemisphere, without new ischemic lesions, indicating potential embolic events or foreign body reactions. Following aphasia, a change from clopidogrel to prasugrel and the initiation of steroid pulse therapy led to the resolution of symptoms and MRI abnormalities over 6 months. This case underscores the reversibility of delayed leukoencephalopathy with appropriate intervention.
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Enfermedades de las Arterias Carótidas , Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma Intracraneal , Femenino , Humanos , Anciano , Aneurisma Intracraneal/terapia , Aneurisma Intracraneal/cirugía , Embolización Terapéutica/efectos adversos , Stents/efectos adversos , Enfermedades de las Arterias Carótidas/terapia , Imagen por Resonancia Magnética , Resultado del TratamientoRESUMEN
In lactating mammary glands, tight junctions (TJs) prevent blood from mixing with milk and maintain epithelial cell polarity, which is important for milk production. This study aimed to investigate the effect of sodium acetate and sodium butyrate (SB) stimulation direction on the TJ barrier function, which is measured with regard to transepithelial electrical resistance and fluorescein flux, in goat mammary epithelial cells. The expression and localization of the TJ proteins claudin-3 and claudin-4 were examined using Western blotting and immunofluorescence. SB treatment in the lower chamber of cell culture inserts adversely affected the TJ barrier function, whereas sodium acetate barely had any effect, regardless of stimulation direction. In addition, SB treatment in the lower chamber significantly upregulated claudin-3 and claudin-4, whereas TJ proteins showed intermittent localization. Moreover, SB induced endoplasmic reticulum (ER) stress. ARC155858, a monocarboxylate transporter-1 inhibitor, alleviated the adverse impact of SB on TJs and the associated ER stress. Interestingly, sodium ß-hydroxybutyrate, a butyrate metabolite, did not affect the TJ barrier function. Our findings indicate that sodium acetate and SB influence the TJ barrier function differently, and excessive cellular uptake of SB can disrupt TJs and induce ER stress.
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Cabras , Uniones Estrechas , Animales , Femenino , Ácido Butírico/farmacología , Claudina-3 , Claudina-4/genética , Lactancia , Acetato de Sodio , Células Epiteliales , Proteínas de Transporte de MembranaRESUMEN
OBJECTIVE: Multisystem proteinopathy (MSP) is an inherited disorder in which protein aggregates with TAR DNA-binding protein of 43 kDa form in multiple organs. Mutations in VCP, HNRNPA2B1, HNRNPA1, SQSTM1, MATR3, and ANXA11 are causative for MSP. This study aimed to conduct a nationwide epidemiological survey based on the diagnostic criteria established by the Japan MSP study group. METHODS: We conducted a nationwide epidemiological survey by administering primary and secondary questionnaires among 6235 specialists of the Japanese Society of Neurology. RESULTS: In the primary survey, 47 patients with MSP were identified. In the secondary survey of 27 patients, inclusion body myopathy was the most common initial symptom (74.1%), followed by motor neuron disease (11.1%), frontotemporal dementia (FTD, 7.4%), and Paget's disease of bone (PDB, 7.4%), with no cases of parkinsonism. Inclusion body myopathy occurred most frequently during the entire course of the disease (81.5%), followed by motor neuron disease (25.9%), PDB (18.5%), FTD (14.8%), and parkinsonism (3.7%). Laboratory findings showed a high frequency of elevated serum creatine kinase levels and abnormalities on needle electromyography, muscle histology, brain magnetic resonance imaging, and perfusion single-photon emission computed tomography. INTERPRETATION: The low frequency of FTD and PDB may suggest that FTD and PDB may be widely underdiagnosed and undertreated in clinical practice.
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Demencia Frontotemporal , Enfermedad de la Neurona Motora , Enfermedades Musculares , Trastornos Parkinsonianos , Humanos , Demencia Frontotemporal/genética , Demencia Frontotemporal/patología , Japón/epidemiología , Proteína que Contiene Valosina/genética , Proteínas de Unión al ARN , Proteínas Asociadas a Matriz NuclearRESUMEN
The patient was 57 years old when he was diagnosed with amyotrophic lateral sclerosis (ALS) at 1 year after developing bulbar symptoms. At 58 years old, he stated that he was considering donating his kidney to his son suffering from diabetic nephropathy. We confirmed the patient's intentions through repeated interviews before his death at 61 years old. Nephrectomy was performed 30 min after his cardiac death. Organ donation spontaneously proposed by an ALS patient should be considered in order to meet the requests of patients who want their families and other patients to live longer, thereby imparting a beneficial legacy through their deaths.
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Esclerosis Amiotrófica Lateral , Obtención de Tejidos y Órganos , Masculino , Humanos , Persona de Mediana Edad , Esclerosis Amiotrófica Lateral/cirugía , Autopsia , RiñónRESUMEN
OBJECTIVE: Multisystem proteinopathy type 3 (MSP3) is an inherited, pleiotropic degenerative disorder caused by a mutation in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which can affect the muscle, bone, and/or nervous system. This study aimed to determine detailed histopathological features and transcriptomic profile of HNRNPA1-mutated skeletal muscles to reveal the core pathomechanism of hereditary inclusion body myopathy (hIBM), a predominant phenotype of MSP3. METHODS: Histopathological analyses and RNA sequencing of HNRNPA1-mutated skeletal muscles harboring a c.940G > A (p.D314N) mutation (NM_031157) were performed, and the results were compared with those of HNRNPA1-unlinked hIBM and control muscle tissues. RESULTS: RNA sequencing revealed aberrant alternative splicing events that predominantly occurred in myofibril components and mitochondrial respiratory complex. Enrichment analyses identified the nuclear pore complex (NPC) and nucleocytoplasmic transport as suppressed pathways. These two pathways were linked by the hub genes NUP50, NUP98, NUP153, NUP205, and RanBP2. In immunohistochemistry, these nucleoporin proteins (NUPs) were mislocalized to the cytoplasm and aggregated mostly with TAR DNA-binding protein 43 kDa and, to a lesser extent, with hnRNPA1. Based on ultrastructural observation, irregularly shaped myonuclei with deep invaginations were frequently observed in atrophic fibers, consistent with the disorganization of NPCs. Additionally, regarding the expression profiles of overall NUPs, reduced expression of NUP98, NUP153, and RanBP2 was shared with HNRNPA1-unlinked hIBMs. INTERPRETATION: The shared subset of altered NUPs in amyotrophic lateral sclerosis (ALS), as demonstrated in prior research, HNRNPA1-mutated, and HNRNPA1-unlinked hIBM muscle tissues may provide evidence regarding the underlying common nuclear pore pathology of hIBM, ALS, and MSP.
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Esclerosis Amiotrófica Lateral , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B , Enfermedades Musculares , Humanos , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/metabolismo , Esclerosis Amiotrófica Lateral/genética , Poro Nuclear/metabolismo , Poro Nuclear/patología , Músculo Esquelético/metabolismo , Cuerpos de Inclusión/metabolismo , Cuerpos de Inclusión/patología , Enfermedades Musculares/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Complejo Poro Nuclear/metabolismoRESUMEN
Objectives: As social restrictions of COVID-19 are being eased worldwide, preventing SARS-CoV-2 transmission among staff members and customers in dining facilities is essential to continuously running business because restaurants and bars are high-risk locations for COVID-19 outbreaks. In 2021, COVID-19 outbreaks occurred at restaurants or bars in Asahikawa city, Japan two weeks after the launch of a promotional campaign for local dining facilities. We investigated this event to assess the association between the promotional campaign and the occurrence of SARS-CoV-2 infection. Study design: Cohort study. Methods: We assessed the association between the occurrence of COVID-19 cases in the restaurants and bars and their participation in the campaign by calculating risk ratio and 95% confidence interval. Results: Cases were identified among workers or customers in 4.0% (4/101) of the participating restaurants or bars and in 1.2% (39/3257) of the non-participating restaurants or bars. The risk ratio was 3.3 (95% confidence interval 1.2-9.0). Conclusion: The association between the occurrence of SARS-CoV-2 infection in the restaurants or bars and participation in the campaign is undeniable. Promotional campaigns to vitalize dining facilities should be accompanied by enhanced infection prevention measures, especially ventilation.
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This study aimed to evaluate the effect of orally administered lipopolysaccharide (LPS) derived from Pantoea agglomerans (LPSpa) on innate immune functions, including the concentrations of antimicrobial components and interleukin (IL)-10 in goat milk, for the prevention of goat mastitis. Twelve Tokara goats were divided into two groups of six goats. Goats in the LPSpa and control groups were orally administrated with 0.4 g/kg dextrin with or without 0.02 mg/kg LPSpa for 7 days (day 0-6), respectively. After treatment (i.e., day 7), 1 µg LPS from Escherichia coli O111 (LPSec) was infused into one side of the udder in both groups to induce mastitis. Milk from all sides of the udder, saliva, and feces were collected on days 0 and 7. After LPSec infusion into the udders, milk was collected from the infused side of the udder on days 8, 10, and 12. Milk yields and somatic cell counts were recorded during the examination period. The concentrations of immunoglobulin (Ig) A in saliva, feces, and milk and the concentrations of lactoferrin, goat ß defensin-1 (GBD1), S100A7, and IL-10 in milk were measured. After LPSpa oral administration, the concentrations of GBD-1 and IL-10 in the milk of the LPSpa group were significantly higher on day 7 than those in the control group, and the concentration of IgA in the feces tended to be higher than that in the control group. After LPSec intramammary infusion, S100A7 concentration on day 12 was significantly lower in the LPSpa group than in the control group. These findings suggest that the oral administration of LPSpa may prevent mastitis by increasing the concentration of GBD1 in milk.
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Enfermedades de las Cabras , Mastitis , Pantoea , Femenino , Animales , Lipopolisacáridos/farmacología , Interleucina-10 , Leche , Inmunidad Innata , Administración Oral , Escherichia coli , Cabras , Glándulas Mamarias Animales , Mastitis/veterinariaRESUMEN
Distal myopathy with rimmed vacuoles (DMRV), also known as GNE myopathy, is a rare disease affecting the distal muscles, such as the tibialis anterior muscle. The GNE gene, which codes for a key enzyme in the sialic acid biosynthesis pathway, is mutated in a homozygous or compound heterozygous manner, and the lack of sialic acid in skeletal muscle is the critical underlying mechanism in DMRV pathogenesis. DMRV mouse models were established, and supplementation with sialic acid improved the phenotypes of the models. A phase 1 clinical trial using aceneuramic acid was conducted at Tohoku University Hospital, Japan, followed by trials using a slow-release product. A phase II/III study, subsequent extended trial, and confirmatory trial were also conducted. Regulatory approval is currently under review.