229 research outputs found

    Young athlete with sudden cardiac arrest treated with therapeutic hypothermia

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    Reported herein is a coronary anomaly that occurred in a young adolescent athlete who presented with cardiopulmonary arrest. The patient was resuscitated and treated with therapeutic hypothermia. The patient had no associated neurological complications at follow up. Enhanced computed tomography of the heart indicated an anomalous left main coronary artery originating from the right coronary sinus and coursing between the aorta and the pulmonary artery. The patient underwent surgical intervention with coronary artery bypass grafting to prevent symptom recurrence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100297/1/ped12144.pd

    Pex14p phosphorylation regulates peroxisome import

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    Peroxisomal matrix proteins are imported into peroxisomes via membrane-bound docking/translocation machinery. One central component of this machinery is Pex14p, a peroxisomal membrane protein involved in the docking of Pex5p, the receptor for peroxisome targeting signal type 1 (PTS1). Studies in several yeast species have shown that Pex14p is phosphorylated in vivo, whereas no function has been assigned to Pex14p phosphorylation in yeast and mammalian cells. Here, we investigated peroxisomal protein import and its dynamics in mitotic mammalian cells. In mitotically arrested cells, Pex14p is phosphorylated at Ser-232, resulting in a lower import efficiency of catalase, but not the majority of proteins including canonical PTS1 proteins. Conformational change induced by the mitotic phosphorylation of Pex14p more likely increases homomeric interacting affinity and suppresses topological change of its N-terminal part, thereby giving rise to the retardation of Pex5p export in mitotic cells. Taken together, these data show that mitotic phosphorylation of Pex14p and consequent suppression of catalase import are a mechanism of protecting DNA upon nuclear envelope breakdown at mitosis

    Association between the quality of life and asymptomatic episodes of paroxysmal atrial fibrillation in the J-RHYTHM II study

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    AbstractBackgroundParoxysmal atrial fibrillation (AF) patients have a reduced quality-of-life (QoL) despite the fact that the majority of AF episodes are asymptomatic. Asymptomatic AF is likely to be associated with substantial morbidity and mortality rates similar to those with symptomatic AF, whereas its effect on the QoL has not yet been clarified.PurposeWe studied the specific contribution of asymptomatic AF episodes to reducing the QoL.MethodsWe assessed the QoL in 233 patients with paroxysmal AF and hypertension (age 64.9±9.7 years, 71% male) enrolled in the Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) using an AF-specific QoL questionnaire (AFQLQ). The AFQLQ comprised 3 components: AFQLQ1, the frequency and duration of symptoms; AFQLQ2, severity of symptoms; and AFQLQ3, limitations in daily activities and mental anxiety. Higher scores indicated a better QoL. Each patient transmitted electrocardiograms for 30s daily at a predetermined time as well as whenever arrhythmia-related symptoms were experienced. We examined the relationship between the 3 AFQLQ components and frequency of symptomatic and asymptomatic AF episodes (days/month) during 12 months of follow-up.ResultsThe symptomatic and asymptomatic AF frequencies were 0.9±3.1 days/month and 1.5±3.5 days/month, respectively. AFQLQ1 negatively correlated with the symptomatic AF frequency (Spearman's correlation coefficient: r=−0.332, p<0.001). AFQLQ2 and AFQLQ3 correlated with both the symptomatic AF frequency (r=−0.27, p<0.001 and r=−0.265, p<0.001, respectively) and asymptomatic AF frequency (r=−0.197, p<0.01 and r=−0.229, p<0.005, respectively).ConclusionThe asymptomatic AF episode frequency correlates with a reduced QoL in patients with paroxysmal AF, suggesting that there would be psychological benefits to its reduction

    Initial periodontal treatment affects nucleotide-binding domain leucine-rich repeat-containing protein 3 inflammasome priming in peripheral blood mononuclear cells

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    Objective: Accumulating evidence suggests an association between periodontitis and several systemic diseases, such as atherosclerosis. In the lesions of these diseases, nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and caspase-1 form inflammasome complex, which leads to the functional maturation of interleukin (IL)-1β via cleavage of caspase-1 in macrophages. IL-1β plays a critical role in the etiology of these diseases; however, inflammasome priming?specifically, IL-1β and NLRP3 upregulation?is necessary for effective IL-1β production. We investigated the effect of initial periodontal treatment on the inflammasome priming of peripheral blood mononuclear cells (PBMCs). Methods: Twenty-two patients with chronic periodontitis were enrolled in this study and given initial periodontal treatment. Peripheral blood samples were collected at baseline and re-evaluation (41.1 ± 29.1 d after the treatment), and the relative expression of IL-1β, and three inflammasome components, ASC, NLRP3 and Caspase-1, mRNA was determined using quantitative reverse transcription PCR. PBMCs were stimulated with silica crystals, and the IL-1β secretion was measured via enzyme-linked immunosorbent assay. Results: Probing pocket depth and bleeding on probing (BOP) were significantly improved after the treatment. Expression of IL-1β and ASC in the PBMCs decreased after the treatment. PBMCs stimulated with silica crystals secreted IL-1β. The treatment attenuated IL-1β secretion by PBMCs in low BOP percentages group whereas IL-1β secretion was increased in high BOP percentages group. Conclusion: Periodontal treatment altered the inflammasome priming status of the PBMCs, however, the effects on systemic diseases need to be further investigated

    CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells

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    Collapsin response mediator protein 5 (CRMP5) is one of the CRMP members that expresses abundantly in the developing brain. To examine the in vivo function of CRMP5, we generated crmp5-deficient (crmp5(-/-)) mice. Anti-calbindin immunofluorescence studies of crmp5(-/-) mice revealed aberrant dendrite morphology; specifically, a decrease in the size of soma and diameter of primary dendrite of the cerebellar Purkinje cells at postnatal day 21 (P21) and P28, but not at P14. Coincidentally, CRMP5 is detected in Purkinje cells at P21 and P28 from crmp5(+/-) mice. In cerebellar slices of crmp5(-/-) mice, the induction of long-term depression of excitatory synaptic transmission between parallel fibers and Purkinje cells was deficient. Given that brain-derived neurotrophic factor (BDNF) plays major roles in dendritic development, we tried to elucidate the possible roles of CRMP5 in BDNF signaling. The effect of BDNF to induce dendritic branching was markedly attenuated in cultured crmp5(-/-) neurons. Furthermore, CRMP5 was tyrosine phosphorylated when coexpressed with neurotrophic tyrosine kinase receptor type 2 (TrkB), a receptor for BDNF, in HEK293T cells. These findings suggest that CRMP5 is involved in the development, maintenance and synaptic plasticity of Purkinje cells

    Apolipoprotein E and clusterin inhibit the early phase of amyloid-β aggregation in an in vitro model of cerebral amyloid angiopathy

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    Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid-β (Aβ) deposition, which leads to lobar hemorrhage and dementia. Biological molecules affecting the development of CAA have not been fully characterized. In this study, we performed proteome analysis of biopsied leptomeningeal and cortical vessels obtained from 6 CAA patients and 5 non-CAA patients who underwent surgery for large lobar hemorrhages. We found that 6 proteins, including Aβ, apolipoprotein E (apoE), clusterin (CLU), albumin, complement C4 and vitronectin were significantly upregulated in the vessels of CAA patients as compared to non-CAA patients. ApoE and CLU were found in all CAA patients. We next examined the effects of apoE and CLU on the early phase of Aβ aggregation, using a simple yet powerful in vitro model of CAA, which recapitulates the intramural periarterial drainage pathway model. We found that physiological concentrations of apoE and CLU delayed the initiation time of amyloid growth kinetics in a concentration-dependent manner. These data indicate that apoE and CLU may act as extracellular chaperones to inhibit Aβ amyloid deposition in CAA

    Percutaneous Endoscopic Gastrostomy, Duodenostomy and Jejunostomy

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    Although enteral feeding by nasal gastric tube is popular for the patients who have a swallowing disability and require long-term nutritional support, but have intact gut, this tube sometimes causes aspiration pneumonia or esophageal ulcer. For these patients, conventional techniques for performance of a feeding gastrostomy made by surgical laparotomy have been used so far. However, these patients are frequently poor anesthetic and operative risks. Percutaneous endoscopic gastrostomy (PEG) which can be accomplished with local anesthesia and without the necessity for laparotomy has become popular in the clinical treatment for these patients. PEG was performed in 31 cases, percutaneous endoscopic duodenostomy (PED) in 1 case, and percutaneous endoscopic jejunostomy (PEJ) in 2 cases. All patients were successfully placed, and no major complication and few minor complications (9%) were experienced in this procedure. After this procedure, some patients could discharge their sputa easily and their pneumonia subsided. PED and PEJ for the patients who had previously received gastrostomy could also be done successfully with great care. Our experience suggests that PEG, PED, and PEJ are rapid, safe, and useful procedures for the patients who have poor anesthetic or poor operative risks

    Acetaldehyde Removal from Indoor Air through Chemical Absorption Using L-Cysteine

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    The irreversible removal of acetaldehyde from indoor air via a chemical reaction with amino acids was investigated. To compare effectiveness, five types of amino acid (glycine, l-lysine, l-methionine, l-cysteine, and l-cystine) were used as the reactants. First, acetaldehyde-laden air was introduced into aqueous solutions of each amino acid and the removal abilities were compared. Among the five amino acids, l-cysteine solution showed much higher removal efficiency, while the other amino acids solutions didn’t show any significant differences from the removal efficiency of water used as a control. Next, as a test of the removal abilities of acetaldehyde by semi-solid l-cysteine, a gel containing l-cysteine solution was put in a fluororesin bag filled with acetaldehyde gas, and the change of acetaldehyde concentration was measured. The l-cysteine-containing gel removed 80% of the acetaldehyde in the air within 24 hours. The removal ability likely depended on the unique reaction whereby acetaldehyde and l-cysteine rapidly produce 2-methylthiazolidine-4-carboxylic acid. These results suggested that the reaction between acetaldehyde and l-cysteine has possibilities for irreversibly removing toxic acetaldehyde from indoor air

    Impact of a learning health system on acute care and medical complications after intracerebral hemorrhage

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    Introduction: Patients with stroke often experience pneumonia during the acute stage after stroke onset. Oral care may be effective in reducing the risk of stroke‐associated pneumonia (SAP). We aimed to determine the changes in oral care, as well as the incidence of SAP, in patients with intracerebral hemorrhage, following implementation of a learning health system in our hospital. Methods: We retrospectively analyzed the data of 1716 patients with intracerebral hemorrhage who were hospitalized at a single stroke center in Japan between January 2012 and December 2018. Data were stratified on the basis of three periods of evolving oral care: period A, during which conventional, empirically driven oral care was provided (n = 725); period B, during which standardized oral care was introduced, with SAP prophylaxis based on known risk factors (n = 469); and period C, during which oral care was risk‐appropriate based on learning health system data (n = 522). Logistic regression analysis was performed to evaluate associations between each of the three treatment approaches and the risk of SAP. Results: Among the included patients, the mean age was 71.3 ± 13.6 years; 52.6% of patients were men. During the course of each period, the frequency of oral care within 24 hours of admission increased (P < .001), as did the adherence rate to oral care ≥3 times per day (P < .001). After adjustment for confounding factors, a change in the risk of SAP was not observed in period B; however, the risk significantly decreased in period C (odds ratio 0.61; 95% confidence interval 0.43‐0.87) compared with period A. These associations were maintained for SAP diagnosed using strict clinical criteria or after exclusion of 174 patients who underwent neurosurgical treatment. Conclusions: Risk‐appropriate care informed by the use of learning health system data could improve care and potentially reduce the risk of SAP in patients with intracerebral hemorrhage in the acute stage
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