The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult-Onset Hypophosphatasia.

Hypophosphatasia (HPP) is an inherited disease caused by variants of the ALPL gene encoding tissue-nonspecific alkaline phosphatase. Adult-onset HPP (adult HPP), known as a mild form of HPP, develops symptoms involving osteomalacia after the age of 18 years. Asfotase alfa (AA) is a modulated recombinant human alkaline phosphatase (ALP) that has been established as a first-line therapy for severe forms of HPP, such as perinatal and infantile forms. We described a 64-year-old female who presented with pseudofractures in bilateral femur diaphyses and impaired mobility. Low serum ALP activity and a high concentration of urine phosphoethanolamine indicated the diagnosis of HPP, which was confirmed by the identification of a homozygous variant in the ALPL gene (c.319G > A; p.Val107Ile). An in vitro transfection experiment to measure the ALP activity of this novel variant protein was performed, resulting in 40% of the residual enzymatic activity compared with the wild type. AA was initiated to facilitate the union of pseudofracture and to improve mobility. After 6 months, radiographic images revealed the disappearance of fracture lines, and improvement of ambulatory ability was confirmed by the 6-minute walk test (525 to 606 m). The EQ-5D-5L index was also improved (0.757 to 0.895). Within a follow-up period, the levels of urine pyrophosphate corrected by urine creatinine (uPPi/Cre) declined in parallel with the level of plasma PPi (plasma PPi: 6.34 to 1.04 µM, uPPi/Cre: 226.8 to 75.4 nmol/mg). The beneficial effect of AA on pseudofracture healing in adult HPP was presented, although the application of AA should be restricted to patients exhibiting relatively severe manifestations. In addition, a novel pathogenic variant of the ALPL gene was identified with the supportive result of functional analysis. Furthermore, when monitoring patients with HPP treated with AA, uPPi/Cre might be a convenient substitute for plasma PPi, which requires immediate filtration after blood sampling. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Domestic violence victimization among Chinese women and its relevance to their economic power.

Introduction: This study conducted a survey of domestic violence victimization among women in China. Previously little research has been conducted on the subject of domestic violence against Chinese women as well as its relevance to their own economic power. Methods: Using online questionnaires, this study collected data about 412 women with current or previous marital status who came from four income brackets in Beijing and Shanghai. Results: It revealed that the proportions of physical, emotional, economic, and sexual violence they experienced were about 27.91%, 62.38%, 21.12%, and 30.10%, respectively. Women belonging to the highest income bracket faced almost the same risk of domestic violence compared with other income groups. Furthermore, there was a slight upward tendency in physical and emotional violence victimization in the highest-income group. The binary logistic regression analysis showed that adverse childhood experiences, arguments between couples due to different opinions regarding gender ideologies, and the approval level for specific gender ideologies were common significant factors across different income brackets. When all income brackets were considered, a higher income was tested as a protective factor with regard to sexual violence. As for the income gap between couples, women whose incomes were "once higher than that of the husband but now lower/almost the same" or "always higher than that of the husband" faced a higher risk of physical violence than women whose incomes were "always lower than/almost the same as that of the husband." Discussion: This study not only revealed the reality of domestic violence victimization in China but also suggested that more attention should be paid to high-income women's domestic violence victimization as well as the importance of helping them both through academia and domestic violence support institutions.

Physical Therapy for a Multiple Myeloma Patient with COVID-19: A Case Report.

Background: This case report describes the successful management of rehabilitation therapy for a hematological malignancy patient who was receiving chemotherapy and had coronavirus disease 2019 (COVID-19). Case: A 76-year-old man receiving chemotherapy for relapsed refractory multiple myeloma (MM) presented to our hospital with fever and dyspnea and was hospitalized with a diagnosis of COVID-19. Physical therapy (20 min/day, 5 days/week) was started on day 6 of hospitalization while the patient was receiving oxygen therapy. Conditioning exercises and movement exercises were performed in an isolation room, and blood counts, fracture susceptibility, and respiratory status were monitored. The patient was severely immunocompromised and required 34 days of isolation due to persistent severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection. Physical function was assessed by manual muscle testing of the lower extremities and by the extent of lower extremity fatigue and dyspnea on exertion, as assessed using the Borg scale. Motor capacity was assessed using the de Morton Mobility Index (DEMMI) score and the Barthel Index (BI). Muscle weakness and severe dyspnea developed 4 days after physical therapy was started. However, physical therapy led to improvements in DEMMI score and BI. The patient was discharged home on day 43 with home medical care. Discussion: Careful management of MM and COVID-19 facilitated safe treatment with physical therapy. The patient's physical function improved with a carefully planned physical therapy program. Moreover, the patient required prolonged isolation due to persistent viral shedding; however, as a result of the treatment, which was coordinated between physicians and nurses, the patient could be discharged home.

A Review of Climate Security Discussions in Japan.

This review paper provides preliminary analysis and answers to three key questions that were identified by synthesizing qualitative evidence from climate security research in Japan. The questions identified are: (1) Has Japan participated in the global climate security debate at all? (2) Why did climate security struggle to become a major political theme in Japan until 2020? (3) Why did Japan explicitly start dealing with climate security as a policy issue in 2020? We identify and discuss four key reasons relative to the second question. The review provides key details (and general parameters) of these questions that have been overlooked by not only Japanese researchers but also climate security research conducted between 2017 and 2022 in Europe and the United States. Climate security suddenly became a trending topic among Japanese researchers and political elites in 2020; we find evidence that future studies could provide important and more robust insight if an analysis of the above questions is supported by interview data obtained from Japanese government officials. In doing so, researchers will be able to provide valuable insight into the possibility (and extent) that inter-ministerial rivalry between key ministries has impeded domestic progress on climate security action. Furthermore, three separate projects on climate security have been commissioned and recently implemented in Japan. These form the basis for this first systematic literature review of 34 papers and the related research reports resulting from these projects. These papers and reports were retrieved from the electronic databases of Google Scholar, ProQuest, and the National Institute for Environmental Studies in April 2022. While the main limitation of this review paper is that readers are expected to connect these questions to their own experiences at the global level, we reduce the possibility of presenting biased information by identifying and verifying missing details. For example, we had difficulty identifying the method used in one of the co-authored papers and contacted the corresponding author. In summary, sustained discussion in academia and high-politics settings should eventually lead to a greater awareness about climate security.

Effect of Exercise Instructions With Ambulatory Accelerometer in Japanese Patients With Type 2 Diabetes: a Randomized Control Trial.

This study aimed to investigate the effects of physical therapists' exercise instructions in Japanese patients with type 2 diabetes. Thirty-six participants were recruited from the outpatient clinic at Matsushita Memorial Hospital, Osaka, Japan from June 2020 to September 2020 and were randomly assigned to either the non-intervention or intervention group. The intervention group received exercise instructions from physical therapists for 30 min at baseline (week 0) and at week 4 by referring to ambulatory accelerometer records. Laboratory parameters, physical activity, body composition, motor skill, and transtheoretical model were assessed in both the groups at baseline (week 0) and week 8. In week 8, patients in the intervention group had a statistically significant reduction in HbA1c levels compared with those in the non-intervention group (7.3% [6.8-%-7.9%] vs. 7.4% [7.3%-7.7%], P = 0.04). The number of steps per day (P = 0.001), energy expenditure (P = 0.01), lower extremity muscle strength (P = 0.002), and 6-min walk test results (P = 0.04) were significantly increased in the intervention group compared with those in the non-intervention group in week 8. The transtheoretical model varied between baseline (week 0) and week 8 only in the intervention group (P < 0.001). Thus, outpatient exercise instructions from physical therapists could improve glycemic control owing to physical activity by improving motor skills and changing the transtheoretical model in Japanese patients with type 2 diabetes.

Response of brain-derived neurotrophic factor to combining cognitive and physical exercise.

PURPOSE: Brain-derived neurotrophic factor (BDNF) is well known for its potential to promote brain plasticity. It has been proposed that combining cognitive and physical exercise (CCPE) may have the potential to generate more synergistic benefits in cognitive function than either cognitive exercise (CE) or physical exercise (PE) alone. The purpose of this study was to examine acute responses of peripheral BDNF levels and cognitive performance to CE, PE, and CCPE. METHODS: Thirteen healthy adult men participated in four experimental sessions; a 30-min CE, a 30-min cycling PE at an intensity of 60% peak oxygen uptake, a 30-min CCPE at the same intensity as PE, and a 30-min session of complete rest. Plasma BDNF levels and cognitive performance were measured before and after each session. RESULTS: Both PE and CCPE significantly increased plasma BDNF levels (p < .05). CE led to no significant increase (p ≥ .05), and there was no significant difference in peripheral BDNF levels between PE and CCPE (p ≥ .05). No session induced a significant change in cognitive performance (p ≥ .05). CONCLUSIONS: Our study suggests that CE and PE have different responses of peripheral BDNF levels and that CCPE had no additional or synergistic effect on peripheral BDNF levels compared with PE alone. This study offers further insights into the potential mechanisms underlying the respective roles of CE, PE, and CCPE for peripheral BDNF levels and cognitive performance.

Effect of Neuromuscular Electrical Stimulation on Brain-derived Neurotrophic Factor.

Brain-derived neurotrophic factor (BDNF) has been considered an essential mediator responsible for the beneficial effects of physical activity in preventing cognitive impairment. This study aimed at examining the effects of a single bout of neuromuscular electrical stimulation (NMES) on levels of BDNF in the plasma and on cognitive performance in healthy adult men. Thirteen healthy adult men participated in three experimental sessions. The first session was 30 min of NMES to both legs, the second was 30 min of cycling exercise at the intensity of 60% peak oxygen uptake, and the third was 30 min of complete rest. Blood was examined for plasma BDNF levels and glucose concentrations, and cognitive performance tests were performed before and after each session. A single bout of NMES significantly increased plasma BDNF levels (p<0.05), which were equivalent to the amount of plasma BDNF released during the exercise session (p>0.05). However, there were no significant changes in cognitive performance between the sessions (p>0.05). The present study found that a single bout of NMES significantly increased plasma BDNF to levels normally present during moderate voluntary exercise. Therefore, NMES could serve as an alternative method of exercise, and might shed light on individuals for whom voluntary physical exercise is contraindicated.