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There are two types of uncertainty in a system to be controlled: parameter errors and unstructured uncertainty. Conventional ℋ∞ control synthesis in the presence of unstructured uncertainty has been developed on the basis of frequency-domain criteria using the state-space method. It is difficult to consider the sensitivity to parameter errors in the frequency domain, however. In this paper, the authors propose an ℋ ∞ controller design method which can cope with parameter errors by introducing a trajectory sensitivity model into the conventional ℋ ∞ controller design method. It is also shown that the obtained controller is equivalent to a dynamic state feedback controller whose order becomes high. Thus, controller reduction is adopted. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to assess the importance of KL-6 level in evaluating the status of stabilized chronic pneumonia in children in the severe motor and intellectual disabilities-medical care-dependent ( SMID-MCD) category. Methods A total of 20 SMID-MCD children were enrolled in this study. Serum KL-6, white blood cell count, C-reactive protein, chest computed tomography ( CT) and other factors related to respiratory complications were analyzed in all children under stable respiratory conditions. Results Mean age was 5.8 ± 1.0 years (mean ± SE). Serum KL-6 was significantly higher in those SMID-MCD children with abnormal CT than in those with normal CT: 316 ± 39 U/mL versus 190 ± 11, respectively ( P = 0.0075). Conclusions Measures of serum KL-6 level provide valuable information for determining the respiratory management of SMID-MCD children with occult chronic pneumonia. [ABSTRACT FROM AUTHOR]

Background: Deep vein thrombosis and its progression to pulmonary thromboembolism is a major source of mortality in patients with neuromuscular disease. Furthermore, ventilator use poses a high risk of DVT to patients. Methods: Hospitalized patients with neuromuscular disease who underwent tracheotomy with positive pressure ventilation (TPPV) had DVT evaluated in the lower extremities by ongoing whole leg venous ultrasonography. Patients who were diagnosed with DVT underwent a second ultrasonography 1 month later. The attending physicians decided on therapeutic measures. All patients were followed during the study period. Results: Eight of 33 patients had DVT. The site of DVT formation was the iliac veins in three cases, femoral veins in two cases, and calf veins in three cases. All of the patients with DVT were asymptomatic. There was no difference in the clinical future between patients with DVT and those without DVT. Progression of DVT was not observed in the second ultrasonographic examination 1 month later. All patients with DVT had an excellent prognosis after a follow‐up period of 9 months. Conclusion: The prevalence of DVT in patients with neuromuscular disease who undergo TPPV might be high. Further large studies on this issue are required because the clinical significance of this DVT is uncertain. [ABSTRACT FROM AUTHOR]

This study sought to present clinical and outcome data of patients with idiopathic childhood occipital epilepsy of Gastaut, to validate previously reported characteristics of this epilepsy. The study group was comprised of 12 affected children (three boys and nine girls), with a median age of onset at 10.3 years. Common ictal manifestations included elementary visual hallucinations (75.0%), blindness or blurring of vision (50.0%), headache (50.0%), and secondarily generalized tonic-clonic seizures (58.3%). Interictal electroencephalography revealed occipital spike-wave paroxysms reactive to eye closure and opening in all patients, accompanied by spike-wave activity in the extra-occipital areas in four (33.3%), and by generalized spike-wave discharges in two (16.7%). One patient exhibited the onset of occipital lobe seizures 1 year after manifesting absence epilepsy. Seizure remission occurred in 81.8% of cases, in half of which medication was discontinued by late adolescence. This study confirmed the previously delineated electroclinical features of epilepsy syndrome, with additional aspects including the frequent association of generalized tonic-clonic seizures and atypical evolution from childhood absence epilepsy. [Copyright &y& Elsevier]

α-Synuclein is a presynaptic protein involved in the pathogenesis of several neurodegenerative diseases, such as Parkinson's disease. Pyk2/related adhesion focal tyrosine kinase (RAFTK) tyrosine kinase is an upstream regulator of Src family kinases in the central nervous system that is involved in α-synuclein phosphorylation. The present study reports the cloning and characterization of a novel adaptor protein, Pyk2/RAFTK-associated protein (PRAP), that specifically binds to Pyk2/RAFTK and inhibits α-synuclein tyrosine phosphorylation. PRAP contains a coiled-coil domain, a pleckstrin homology domain, and a SH3 domain; the SH3 domain binds to the proline-rich domain of Pyk2/RAFTK. PRAP was observed to be present throughout the brain, including substantia nigra dopaminergic neurons, in which it localized to the cytoplasm. PRAP was found to function as a substrate for Src family kinases, such as c-Src or Fyn, but not for Pyk2/RAFTK. Hyperosmotic stress induced phosphorylation of tyrosine 125 of α-synuclein via Pyk2/ RAFTK, which acted through Src family kinases. Such phosphorylation was inhibited by PRAP expression, suggesting that PRAP negatively regulates α-synuclein phosphorylation following cell stress. In conclusion, PRAP functions as a downstream target for Pyk2/ RAFTK and plays a role in α-synuclein phosphorylation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Levels of circulating soluble thrombomodulin (sTM), an anticoagulant factor, are associated with the severity and progression of arteriosclerotic diseases. However, the role of elevated sTM levels remains to be clarified in patients on dialysis. As the calcification propensity time T50 is a novel marker of arterial calcification, we aimed to determine the association between sTM and T50 in patients on hemodialysis (HD). Methods: This cross-sectional study included 49 adult patients on maintenance HD. Correlation analysis was performed to test the association between T50 and patient characteristics. Linear regression was used to evaluate the association between T50 and sTM. Results: Partial correlation analysis showed a strong association between T50 and glycated albumin, phosphorous, and sTM levels (partial correlation coefficient: r [partial] = -0.359, p = 0.023; r [partial] = -0.579, p < 0.001; and r [partial] = 0.346, p = 0.029, respectively). Multivariate linear regression analysis revealed that only sTM level was significantly and positively associated with T50 (β = 0.288; t = 2.27; p = 0.029; 95% confidence interval, 0.082-1.403). Conclusions: sTM is independently and positively associated with the propensity time for calcification, suggesting that sTM could be a good marker of arterial calcification progression in patients on HD.

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

The gut microbiota has nutritional and protective functions. In patients with end-stage renal disease, changes in the gut microbiota disrupt their protective functions. Probiotics help maintain normal bowel function. However, their role in patients with end-stage renal disease is controversial. We investigated whether Clostridium butyricum affects the nutrition and immune function of patients with end-stage renal disease undergoing maintenance dialysis between 2014 and 2015; thirty-seven patients were included. The patients were divided into two groups: one in which C. butyricum was administered and one in which it was not. One tablet of the probiotics, which contained 20 mg of C. butyricum , was administered orally three times daily for 2 years in the C. butyricum group. The 16S rRNA genes were sequenced from stool samples of 14 (37.8%) patients in the C. butyricum group and 23 (62.2%) patients in the control group. The differences in the gut microbiota of the two groups were analyzed. The α-diversity index indicated that the C. butyricum group had significantly more operational taxonomic units and higher albumin and transferrin levels than the control group. The effector to target cell ratio was significantly higher in the C. butyricum group. In addition, interleukin-6 levels were significantly lower in the C. butyricum group, and inflammation was less severe in this group. The patients undergoing maintenance dialysis with C. butyricum had abundant gut microbiota. They also had a good nutritional status, low systemic inflammation, and a good immunological status., (©2022 BMFH Press.)

Background: Increasing the blood flow rate (BFR) is a useful method for increasing Kt/V and the clearance for low molecular solutes. Hemodialysis patients are often anemic due to hypoerythropoiesis and their chronic inflammatory state. Hepcidin, a hormone that regulates iron homeostasis, is considered as an indicator of iron deficiency in patients with end-stage renal disease. This study aimed to investigate the effects of an increased BFR during hemodialysis on serum hepcidin levels and anemia., Methods: Between April 2014 and March 2016, 22 chronic dialysis patients (11 men [50.0 %]; mean [± standard deviation] age, 72 ± 12 years) undergoing maintenance hemodialysis treatment, thrice weekly, were enrolled and followed prospectively for 24 months. In April 2014, the BFR was 200 mL/min; in April 2015 this was increased to 400 mL/min, which was within acceptable limits. The dialysate flow rate remained stable at; 500mlL/min. Blood samples were collected in March 2015 and 2016. The primary endpoint was the comparison of the amounts of erythropoiesis-stimulating agent (ESA) required., Results: The increased BFR increased the Kt/V and contributed to significantly decreased urea nitrogen (UN) (p = 0.015) and creatinine (Cr) (p = 0.005) levels. The dialysis efficiency was improved by increasing the BFR. Ferritin (p = 0.038), hepcidin (p = 0.041) and high-sensitivity interleukin-6 (p = 0.038) levels were also significantly reduced. The ESA administered was significantly reduced (p = 0.004) and the Erythropoietin Resistant Index (ERI) significantly improved (p = 0.031). The reduction rates in UN (p < 0.001), Cr (p < 0.001), and beta-2 microglobulin (p = 0.017) levels were significantly greater post the BFR increase compared to those prior to the BFR increase. However, hepcidin was not affected by the BFR change., Conclusions: Increasing BFR was associated with hemodialysis efficiency, and led to reduce inflammatory cytokine interleukin-6, but did not contribute to reduce C-reactive protein. This reduced hepcidin levels, ESA dosage and ERI. Hepcidin levels were significantly correlated with ferritin levels, and it remains to be seen whether reducing hepcidin leads to improve ESA and iron availability during anemia management.

Objective : Patients with severe motor and intellectual disabilities (SMID) often develop complications, including paralysis of the extremities due to abnormal muscular tonicity. Furthermore, the incidence of sudden death, which may be caused by pulmonary thromboembolism (PTE), is approximately 4.2%. Deep vein thrombosis (DVT) is attracting attention as an embolic source. In this study, DVT was confirmed in SMID patients by lower extremity venous ultrasound. The oral anticoagulant, warfarin, and novel oral anticoagulant, edoxaban tosilate hydrate, were administered, and their efficacies and safeties were evaluated. Materials and Methods : DVT patients were randomly allocated to warfarin and edoxaban groups. The frequency of hemorrhagic events and incidence of adverse events were investigated to evaluate efficacy and safety. Results : DVT was detected in 14 (8.4%) out of 167 patients. Four (0.067/person-month) hemorrhagic events occurred in the warfarin group from subcutaneous hemorrhage due to bruises caused by postural changes. Three (0.042/person-month) events occurred in the edoxaban group due to nasal hemorrhage caused by tracheal aspiration. There was no significant difference (p=0.5383) between groups. Conclusion : No significant differences were observed in hemorrhagic events between SMID patients with DVT treated with warfarin and edoxaban., Competing Interests: Disclosure StatementMashio Nakamura and Yukihiro Koretsune received honoraria from Daiichi Sankyo Company, Limited. The other authors do not have any conflicts of interest to declare., (Copyright © 2019 Annals of Vascular Diseases.)

Sudden death in patients with severe motor and intellectual disabilities (SMID) is sometimes caused in part by pulmonary thromboembolism (PTE), and deep venous thrombosis (DVT) has drawn attention as a possible embolic source. Warfarin, which is a conventional therapeutic agent, is not easy to control appropriately, and daily management can be especially difficult in SMID patients. On the other hand, edoxaban tosilate hydrate, which has been newly approved for insurance coverage for the treatment of DVT, is not listed in the Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism and Deep Vein Thrombosis (DVT-PTE guidelines). The aim of this study is to evaluate the efficacy and safety of anticoagulation therapy (warfarin vs. edoxaban) in DVT treatment in SMID patients by means of an open-label, randomized controlled trial. The primary endpoint is the incidence of hemorrhagic events during 12 months of follow up.

Sudden death associated with patients with severe motor and intellectual disabilities (SMID) have been thought to be caused in part by venous thromboembolism (VTE), but actual situation of VTE in SMID is not clear. We examined the prevalence and location of deep venous thrombosis (DVT), and the relation of the development of crural veins in 16 patients with SMID, using ultrasonography. The maximum diameter of soleal vein was 1.6±0.5 mm. In most cases, DVT was found in the femoral veins. We could not detect thrombus in the soleal veins. In the present study, the detection ratio of DVT was high in patients with SMID who had restricted mobility capability and were bedridden, and we found the veins centrally from popliteal veins in DVT in SMID, not soleal veins, as the initial sites of the DVT. In the literature, the mean diameter of soleal veins, in healthy adults is 6.7±1.8 mm, that in contrast in SMID being smaller. Underdevelopment of intramuscular veins is possibly related to the mechanism of DVT in SMID. In the current guidelines for the management of VTE, there is limited in scope of ambulatory adults and no application cases who exhibit to SMID restricted mobility of the lower extremities and are bedridden associated with cerebral palsy and developmental motor disabilities, and such patients have associated high risk of the complications of DVT. According to our present study, it is necessary to provide appropriate guidelines for DVT in SMID considering characteristic features. (This is a translation of Jpn J Phlebol 2017; 28: 29-34.).

Most of the existing results on the decentralized stabilization of large-scale systems consider systems in the input-output-decentralized form, i.e., systems whose input and output matrices are block diagonal. The controller synthesis for such systems is less involved than that for input-output-centralized ones. In this paper, a transformation is proposed for the input-output decentralization of the generic large-scale system. Using the transformed system, a sufficient condition for failure-tolerant performance stabilization of the original large-scale system in a desirable performance region under decentralized linear output feedback is established. The problem is then reformulated as a constrained nonlinear optimization problem. The proposed methodology results in the optimal reconciliation of failure-tolerant performance stabilization of the overall system, and reliability and low actuator gains of the isolated subsystems. The effectiveness of the proposed approach is demonstrated by an example.