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Tamami Kono,1 Akiyoshi Ogimoto,1 Kazuhisa Nishimura,1 Toshihiro Yorozuya,2 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension and Nephrology, 2Department of Anesthesiology and Resuscitology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan Abstract: A 32-year-old man with Duchenne muscular dystrophy (DMD) was admitted to the hospital because of worsening dyspnea and general fatigue. He had received medication therapy for cardiomyopathy with heart failure and home mechanical ventilation for respiratory failure. An electrocardiogram on admission showed intermittent third-degree atrioventricular block. Echocardiography showed global mild left ventricular systolic dysfunction with dyssynchrony (ejection fraction: 45%). He underwent implantation of a cardiac resynchronization therapy–defibrillator. His B-type natriuretic peptide level was improved after cardiac resynchronization therapy–defibrillator implantation, and he remains asymptomatic. The incidence of cardiomyopathy increases with age. By adulthood, 100% of patients have cardiac involvement. Keywords: cardiac resynchronization therapy, Duchenne muscular dystrophy, progression of cardiomyopathy, heart failure, arrhythmia

Abstract Background This study aimed to identify the factors relating to moderately increased albuminuria among middle-aged and older individuals in Japan. Methods We conducted specific health examinations in which we measured albuminuria levels, and administered a questionnaire survey to record participants’ lifestyles in western Tokushima Prefecture, Japan. A total of 1,660 people whose albuminuria was less than 300 mg/g creatinine (Cr) were analyzed. We divided participants into two groups—those with normal albuminuria ( 300 mg/gCr)—and compared their characteristics. To investigate all relevant factors, we conducted a multivariate logistic regression analysis. Results The moderately increased albuminuria group were significantly older and had, among them, significantly higher percentages of a body mass index (BMI) ≥ 25 kg/m2, diabetes, hypertension, and mild liver disorder (aspartate transaminase ≥ 31 U/L or alanine aminotransferase ≥ 31 U/L or gamma-glutamyl transferase ≥ 51 U/L). (p

HIP1-ALK is a relatively rare fusion pattern in ALK-rearranged NSCLC. Existing studies on the efficacy of ALK tyrosine kinase inhibitor (TKI) resistance mechanisms and treatment strategies in HIP1-ALK–rearranged lung cancer are limited. Here, we report the case of an 18-year-old man with HIP1-ALK–rearranged adenocarcinoma who developed BRAF V600E and V1180L mutations after ALK TKI therapy, in whom the administration of BRAF and MEK inhibitors was ineffective. Brigatinib was effective after chemotherapy with cytotoxic drugs. Development of effective treatments is desirable for rare variants of ALK-rearranged lung cancer after acquiring resistance to ALK TKIs.

Objective: Preserving core body temperature across a wide range of ambient temperatures requires adaptive changes of thermogenesis that must be offset by corresponding changes of energy intake if body fat stores are also to be preserved. Among neurons implicated in the integration of thermoregulation with energy homeostasis are those that express both neuropeptide Y (NPY) and agouti-related protein (AgRP) (referred to herein as AgRP neurons). Specifically, cold-induced activation of AgRP neurons was recently shown to be required for cold exposure to increase food intake in mice. Here, we investigated how consuming a high-fat diet (HFD) impacts various adaptive responses to cold exposure as well as the responsiveness of AgRP neurons to cold. Methods: To test this, we used immunohistochemistry, in vivo fiber photometry and indirect calorimetry for continuous measures of core temperature, energy expenditure, and energy intake in both chow- and HFD-fed mice housed at different ambient temperatures. Results: We show that while both core temperature and the thermogenic response to cold are maintained normally in HFD-fed mice, the increase of energy intake needed to preserve body fat stores is blunted, resulting in weight loss. Using both immunohistochemistry and in vivo fiber photometry, we show that although cold-induced AgRP neuron activation is detected regardless of diet, the number of cold-responsive neurons appears to be blunted in HFD-fed mice. Conclusions: We conclude that HFD-feeding disrupts the integration of systems governing thermoregulation and energy homeostasis that protect body fat mass during cold exposure.

Abstract Chronic obstructive pulmonary disease (COPD) may coexist with lung cancer, but the impact on prognosis is uncertain. Moreover, it is unclear whether pharmacological treatment for COPD improves the patient’s prognosis. We retrospectively investigated patients with advanced non-small-cell lung cancer (NSCLC) who had received chemotherapy at Kyoto University Hospital. Coexisting COPD was diagnosed by spirometry, and the association between pharmacological treatment for COPD and overall survival (OS) was assessed. Of the 550 patients who underwent chemotherapy for advanced NSCLC between 2007 and 2014, 347 patients who underwent spirometry were analyzed. Coexisting COPD was revealed in 103 patients (COPD group). The median OS was shorter in the COPD group than the non-COPD group (10.6 vs. 16.8 months). Thirty-seven patients had received COPD treatment, and they had a significantly longer median OS than those without treatment (16.7 vs. 8.2 months). Multivariate Cox regression analysis confirmed the positive prognostic impact of COPD treatment. Additional validation analysis revealed similar results in patients treated with immune checkpoint inhibitors (ICIs). Coexisting COPD had a significant association with poor prognosis in advanced NSCLC patients if they did not have pharmacological treatment for COPD. Treatment for coexisting COPD has the potential to salvage the prognosis.

Abstract Background Cardiac amyloidosis (CA) mimics left ventricular hypertrophy (LVH). It is treatable, but its prognosis is poor. A simple screening tool for CA would be valuable. CA is more precisely diagnosed with echocardiographic deformation parameters (e.g., relative apical sparing pattern [RASP]) than with conventional parameters. We aimed to 1) investigate incremental benefits of echocardiographic deformation parameters over established parameters for CA screening; 2) determine the resultant risk score for CA screening; and 3) externally validate the score in LVH patients. Methods We retrospectively studied 295 consecutive non-ischemic LVH patients who underwent detailed diagnostic tests. CA was diagnosed with biopsy or 99mTc-PYP scintigraphy. The base model comprised age (≥65 years [men], ≥70 years [women]), low voltage on the electrocardiogram, and posterior wall thickness ≥ 14 mm in reference to the literature. The incremental benefit of each binarized echocardiographic parameter over the base model was assessed using receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC). Results Fifty-four (18%) patients had CA. RASP showed the most incremental benefit for CA screening over the base model. After conducting multiple logistic regression analysis for CA screening using four variables (RASP and base model components), a score was determined (range, 0–4 points). The score demonstrated adequate discrimination ability for CA (AUC = 0.86). This result was confirmed in another validation cohort (178 patients, AUC = 0.88). Conclusions We developed a score incorporating RASP for CA screening. This score is potentially useful in the risk stratification and management of LVH patients.

Abstract Aims This study aimed to evaluate the changes in left ventricular remodelling with time in patients with hypertrophic cardiomyopathy (HCM) using thallium‐201 myocardial scintigraphy. Methods and results Forty‐eight patients with HCM participated in the study. The extent score (ES) and a newly devised index termed the ‘mean count change’ (MCC) were used to evaluate the myocardial perfusion defects. Using the amount of thallium‐201 uptake (TU), MCC (%) was calculated using the following formula: (last TU − initial TU)∕initial TU × 100. To confirm the site of the lesion, the left ventricle was divided into five segments: anterior, septal, inferior, lateral, and apex. Cardiovascular complications and deaths were recorded. The mean follow‐up period was 8.6 ± 2.0 years. ES increased from 17.4 ± 13.7% to 44.0 ± 22.3% (P

Deployment of electric vehicles (EVs) has been accelerated in many countries. However, for further deployment of EVs and their contribution to electrical power systems, various new services need to be implemented related to EVs and their charging, called “Place of Use” (PoU) services. The combined menu of the charging services has been proposed which bundles EV charging fees with home electricity bills. Settlement will be needed for such combined menu. This paper proposes the combined menu of EV charging with settlement of electricity. Technical feasibility of the settlement has been tested by EV charging testbed with the IoT-HUB technology. IoT-HUB is the virtual infrastructure which interconnects various connected devices and application by using “drivers” for each device. This paper also proposes a forecast method of EV charging demand for the settlement after the charging starts. The proposed method has reduced the forecast error of total charged energy compared to the simple method, but some of the forecast error has remained because of the variability of the charging time at the final step of state of charge.

Failure to deal with the issue of collective and social loss increases the risk of extreme nationalism. When taken too far, a repetition of manic defence can arise that manifests itself in the form of war. In this paper, the notion of the "inability to mourn" by the German Psychoanalysts A. and M. Mitshcerlich (1967) is discussed in relation to the problem of Japan's post World War II nationalism, and its silence on social matters. The process of confronting past atrocities committed by the state is then discussed from the perspective of structural theory. [ABSTRACT FROM AUTHOR]

Given their excellent superconducting properties, REBa2Cu3Oy (REBCO)-coated conductors (CCs) are anticipated to be utilized in a variety of magnet applications. To further increase the critical current density J c of these materials to levels needed for commercial applications, this study employs reel-to-reel (RTR) pulsed laser deposition (PLD) to fabricate REBCO+BaHfO3 (BHO) CCs. PLD creates BHO nanorods, which serve as flux-pinning defects. The material is subjected to O2+ irradiation to introduce more defects. The irradiation-induced defects serve as flux-pinning centers to the REBCO+BHO-nanorod CCs, increasing J c along the c axis and over a wide range of magnetic-field angles compared with conventional REBCO+BHO-nanorod CCs. Both nanorods and irradiation-induced defects are demonstrated to be effective pinning centers in this material. [ABSTRACT FROM AUTHOR]

Pure primary ovarian squamous cell carcinoma (SCC) is a rare histological type with a poor prognosis. Herein, we present the first reported case of advanced pure primary ovarian SCC with homologous recombination deficiency (HRD). A 65-yearold woman who underwent emergency surgery because of acute abdominal pain was diagnosed with SCC of the ovary and was referred to our department for further treatment. Thorough investigations revealed no signs of other primary sites of SCC except for the left ovary. Postoperative positron emission tomography-computed tomography showed residual tumor. Since pure primary ovarian SCC typically shows a poor response to chemotherapy, we decided to perform debulking surgery. Total abdominal hysterectomy, right salpingo-oophorectomy, pelvic lymphadenectomy, paraaortic lymphadenectomy, bowel resection and left partial ureterectomy were performed. Postoperatively, there was no residual tumor larger than 1 cm. Postoperatively, she developed pelvic infection that prolonged her hospital stay due to the need for antibiotics. However, there were no other perioperative complications and she was discharged. SCC with keratinization was observed on histopathological examination of metastatic lymph nodes. An HRD companion diagnostic test performed on the resected specimen was positive for HRD (score 57) and negative for BRCA 1/2 mutations. She received six courses of paclitaxel and carboplatin followed by maintenance therapy with niraparib, which is continuing. There are no signs of recurrence as of the one-year follow-up after surgery. We presented a rare case of advanced pure primary ovarian SCC with HRD. Complete surgical removal of HRD-positive pure primary ovarian SCC may lead to longterm survival with subsequent chemotherapy followed by maintenance therapy with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors. [ABSTRACT FROM AUTHOR]

Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration of oxytocin to rats can both prevent and treat diet-induced obesity.