The role of education in health policy reform outcomes: evidence from Japan.

This study analyzes the role of education in the outcomes of the reform of the Japanese annual health checkup program. In April 2008, the annual checkup was redesigned to address concerns about metabolic syndrome. As the checkup is mandatory only for salaried workers, their participation rate is significantly higher than other workers; thus, they were most affected by the reform. Using institutional information, a difference-in-differences estimation was conducted with salaried workers as the treatment group and self-employed workers as the control group. We found that the reform caused significant changes in health behaviors and outcomes only among university graduates who were at a relatively high risk of metabolic syndrome. This highly educated group increased their physical activity, brought energy intake close to an ideal level, and achieved significant weight loss and BMI reduction to levels that minimize all-cause mortality among middle-aged Japanese. A secondary analysis implies that the difference in cognitive functioning test scores may be a critical factor in explaining the heterogeneous responses to the reform, suggesting that thoroughly well-articulated recommendations for healthy behaviors are needed in order to improve reform uptake.

Urinary titin N-fragment as a predictor of decreased skeletal muscle mass in patients with interstitial lung diseases.

This study aimed to examine the validity of urinary N-terminal titin fragment/creatinine (urinary N-titin/Cr) reflecting muscle damage biomarker in patients with interstitial lung disease. This retrospective study enrolled patients with interstitial lung disease. We measured urinary N-titin/Cr. Furthermore, we measured the cross-sectional areas of the pectoralis muscles above the aortic arch (PMCSA) and erector spinae muscles of the 12th thoracic vertebra muscles (ESMCSA) to assess muscle mass until 1 year. We examined the correlation between urinary N-titin/Cr and the change in muscle mass. We plotted receiver operating characteristic curves to estimate the cut-off points for urinary N-titin/Cr for distinguishing the greater-than-median and smaller-than-median reduction of muscle mass after 1 year. We enrolled 68 patients with interstitial lung disease. The median urinary N-titin/Cr value was 7.0 pmol/mg/dL. We observed significant negative correlations between urinary N-titin/Cr and changes in the PMCSA after 1 year (p < 0.001) and changes in the ESMCSA after 6 months (p < 0.001) and 1 year (p < 0.001). The cut-off points for urinary N-titin/Cr were 5.2 pmol/mg/dL and 10.4 pmol/mg/dL in the PMCSA and ESMCSA, respectively. In summary, urinary N-titin/Cr may predict muscle loss in the long-term and act as a clinically useful biomarker reflecting muscle damage.

Synthesis of a fully protected long-chain polyamine subunit of aculeine B using the photoremovable NPEC group.

Polyamines are ubiquitously found in nature. In this paper, we disclose our iterative coupling strategy for the synthesis of a structurally defined polymer of 1,3-propanediamine, and the polymer can be used for the synthesis of both the initially proposed structure and the revised structure of protoaculeine B isolated from a marine sponge. We first attempted the synthesis of polyamines using "the Ns strategy" but found that a polyamine with eleven Ns groups has solubility problems. We then examined the versatility of the photoremovable NPEC protecting group in polyamine synthesis. Finally, the synthesis of a suitably protected 12-mer polyamine was achieved employing the NPEC group for the temporary protection of a terminal amino group.

Association between hospital acquired disability and post-discharge mortality in patients after living donor liver transplantation.

BACKGROUND: Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital. METHODS: We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival. RESULTS: HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p < 0.001), and in the HAD/low SMI group, all-cause mortality was highest between the groups (log-rank: p < 0.001). In multivariable analysis, HAD was an independent risk factor for all-cause mortality (hazard ratio [HR]: 16.54; P < 0.001) and HAD/low SMI group (HR: 16.82; P = 0.002). CONCLUSION: HAD was identified as an independent risk factor for all-cause mortality suggesting that it could be a key component in determining prognosis after LDLT. Future larger-scale studies are needed to consider the overall new strategy of perioperative rehabilitation, including enhancement of preoperative physiotherapy programs to improve physical function.

Predictors of sedation period for critical illness patients focusing on early rehabilitation on the bed.

There are various interventions of rehabilitation on the bed, but these are time-consuming and cannot be performed for all patients. The purpose of this study was to identify the patients who require early mobilization based on the level of sedation. We retrospectively evaluated the data of patients who underwent physical therapy, ICU admission of > 48 h, and were discharged alive. Sedation was defined as using sedative drugs and a Richmond Agitation-Sedation Scale score of < - 2. Multiple regression analysis was performed using sedation period as the objective variable, and receiver operating characteristic (ROC) curve and Spearman's rank correlation coefficient were performed. Of 462 patients admitted to the ICU, the data of 138 patients were analyzed. The Sequential Organ Failure Assessment (SOFA) score and non-surgery and emergency surgery cases were extracted as significant factors. The ROC curve with a positive sedation period of more than 3 days revealed the SOFA cutoff score was 10. A significant positive correlation was found between sedation period and the initial day on early mobilization. High SOFA scores, non-surgery and emergency surgery cases may be indicators of early mobilization on the bed in the ICU.

Oxa-Michael-based divergent synthesis of artificial glutamate analogs.

Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, by oxa-Michael reaction as the key reaction from δ-hydroxyenone. The construction of the 1,3-dioxane skeleton, achieved through hemiacetal formation followed by oxa-Michael reaction from δ-hydroxyenone, was exploited to access structurally diverse heterotricyclic artificial glutamate analogs. On the other hand, formation of a novel tetrahydro-2H-pyranol skeleton was accomplished by the inverse reaction order: oxa-Michael reaction followed by hemiacetal formation. Thus, this study succeeded in showing that structural diversity in a compound collection can be acquired by interchanging the order of just two reactions. Among the skeletally diverse, heterotricyclic artificial glutamate analogs synthesized in this study, a neuronally active compound named TKM-50 was discovered in the mice in vivo assay.

A comparative study of the sarcopenia screening in older patients with interstitial lung disease.

BACKGROUND: The Asian Working Group for Sarcopenia 2019 (AWGS 2019) is the gold standard diagnostic criteria for sarcopenia in Asian populations. The calf circumference (CalF), the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) and the SARC-CalF questionnaires for sarcopenia screening have been used by AWGS 2019. The aim of this study was to assess accuracy of these three sarcopenia screening tools in patients with interstitial lung disease. METHODS: In this cross-sectional study, stable patients with interstitial lung disease were enrolled. The SARC-F, SARC-CalF, and CalF, used in patients with interstitial lung disease, were compared to the diagnostic criteria proposed by AWGS 2019. The accuracy of screening tools was compared using sensitivity and specificity. Moreover, areas under the receiver operating characteristic curves (AUC) were computed. RESULTS: Seventy eight patients were analyzed, and sarcopenia was identified in 25 (32.1%) patients with interstitial lung disease by the AWGS 2019 criteria. The sensitivity of the CalF was highest (96%) of the three screening tools, while the specificity was 60%. The sensitivity of SARC-F and SARC-CalF were 24% and 68%, while the specificity were 92% and 66%, respectively. The AUCs of CalF, SARC-F, and SARC-CalF in all patients were 0.78, 0.58, and 0.67, respectively. CONCLUSIONS: The CalF is most suitable for screening sarcopenia in patients with interstitial lung disease, while SARC-F and SARC-CalF are not.

Do macroeconomic shocks in the local labor market lead to child maltreatment and death?: Empirical evidence from Japan.

BACKGROUND: Japan is facing a rapid increase in the number of reported child maltreatment cases. Child maltreatment has long-term consequences for the victims, and unemployment rate is considered a strong predictor of it. However, only few studies have analyzed the causal relation between child maltreatment and the unemployment rate-particularly the effects of the latter on the former-in Japan. METHODS: Using prefecture-level longitudinal data from 2005 to 2016, we employed a fixed effects instrumental variable estimation. The estimation included a weighted average of the national unemployment rate across industries by industrial structures in 2005 as an instrument to identify the causal effects. RESULTS: The average local unemployment rate changed by approximately 50% from the peak to the bottom in the sample period. A 50% increase in local unemployment rates increased the number of reported child neglect cases and child deaths by 80% and 70% (statistically significant at the 5% level), respectively. Further, it increased cases of death due to external causes, unintentional injuries, and unintentional drowning by 146%, 217%, and 315% (statistically significant at the 5% level), respectively. CONCLUSION: The local unemployment rate is a risk factor for child maltreatment, resulting in children's death, especially as a result of unintentional drowning-the common cause of death due to child neglect. When the local unemployment rates rise, governments should allocate more financial and human resources for preventive measures to combat child deaths caused by neglect.

Role of Early Mobilization on the Clinical Course of Patients who Underwent Pancreaticoduodenectomy: A Retrospective Cohort Study.

The length of hospital stay is an important outcome measure in patients who have undergone pancreaticoduodenectomy. Although postoperative complications are known to adversely affect the length of hospital stay (LOS), the influence of early mobilization on LOS has not been clarified yet. This study aimed to examine the impact of the initial ambulation day, which is one of the components of early mobilization, on LOS after pancreaticoduodenectomy. We retrospectively enrolled patients who underwent pancreaticoduodenectomy between January 2013 and December 2017. Postoperative complications were evaluated using the Clavien-Dindo classification (CDC) system. Patients were divided into two groups based on the median LOS (early and late-discharge groups) and compared to determine their characteristics. Multivariate logistic regression analysis was performed with LOS as the dependent variable. Patients in the late-discharge group were significantly older, had an initial ambulation delay, and had higher rates of advanced disease stages and a CDC grade ≥ IIIa than those in the early discharge group. In the multivariate logistic regression analysis, CDC grade ≥ IIIa, initial ambulation day, and age were found to be significant independent factors associated with LOS. Our results demonstrated that not only postoperative complications, but also the initial ambulation day, could affect LOS after pancreaticoduodenectomy, emphasizing the importance of early ambulation for patients who undergo this surgery.

Respiratory Impairment, Limited Activity, and Pulmonary Rehabilitation in Patients with Interstitial Lung Disease.

Interstitial lung disease (ILD) is a diverse group of chronic lung conditions characterized by dyspnea, exercise-induced hypoxemia (EIH), and exercise intolerance. Since activity limitations and impaired health-related quality of life (HRQoL) in ILD are similar to those in other chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), pulmonary rehabilitation is also indicated for patients with ILD. This rehabilitation program mainly comprises exercise training and self-management education. Exercise training is the most important component of pulmonary rehabilitation. It significantly improves dyspnea and enhances exercise capacity and HRQoL in patients with ILD. The standard exercise prescription used for COPD is also effective for ILD. However, considering that disease progression and exercise-limiting factors are different in patients with COPD is necessary. Severe EIH, the adverse effects of corticosteroid administration, and comorbidities often lead to difficulty in employing a sufficient exercise intensity. Some modifications in the exercise prescription for individual patients or strategies to minimize EIH and dyspnea are required to optimize training intensity. Since EIH is common and severe in patients with ILD, supplemental oxygen should be provided. In advanced and more severe patients, who have difficulty in performing exercises, energy conservation techniques and the use of energy-saving devices to improve and maintain the patients' activities of daily living may be effective．.

Structure Revision of Protoaculeine B, a Post-translationally Modified N-Terminal Residue in the Peptide Toxin Aculeine B.

The structure of protoaculeine B, the N-terminal residue of the marine peptide toxin aculeine B, is revised to the cis-1,3-disubstituted tetrahydro-ß-carboline framework. We prepared two truncated model compounds that lack a long-chain polyamine using the one-step Pictet-Spengler reaction of tryptophan and compared their NMR, mass spectra, and chemical reactivity with those of the natural protoaculeine B. The synthetic models reproduced the profiles of the natural product well, which confirmed the appropriateness of the structure revision.

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs.

Herein, we report the enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational analysis by NMR, conformational calculation, and X-ray crystallography. A mice in vivo assay showed that (2R)-MC-27, with a six-membered oxacycle, is neuroactive, whereas the (2S)-counterpart is inactive. It was also found that TKM-38, with an eight-membered azacycle, is neuronally inactive, showing that the activity is controlled by the ring C.

Corticosteroids are associated with reduced skeletal muscle function in interstitial lung disease patients with mild dyspnea.

BACKGROUND: Interstitial lung diseases (ILDs) patients receiving steroid treatment tend to be immobilized by dyspnea and muscle weakness as the disease progresses. We therefore expected that steroid treatment for ILDs would have a greater effect on muscle function under severe dyspnea. To test this hypothesis, we evaluated whether the effect of corticosteroid treatment on peripheral muscle force and exercise capacity varied according to patients' dyspnea severity. METHODS: In this retrospective cross-sectional study of 87 ILD patients enrolled between 2008 and 2017, quadriceps force (QF), handgrip force (HF), and 6-min walk distance (6 MWD) were compared between a low (grades 0-2) and a high (grades 3-4) modified-Medical Research Council (mMRC) dyspnea scale score group. RESULTS: In patients with lower levels of dyspnea, corticosteroid treatments were associated with lower QF and HF (20.0 vs. 30.0 kgf, p = 0.01; 22.5 vs. 28.4 kgf, p = 0.03, respectively) values; however, no significant differences were observed between the corticosteroid and control subgroups in the high mMRC group (QF: 18.5 vs. 17.3 kgf, p = 0.64; HF: 21.0 vs. 17.1 kgf, p = 0.24, respectively). Analysis of covariance indicated that both corticosteroid treatment and mMRC dyspnea scale interacted with QF, HF, and 6 MWD. The effects of the corticosteroid treatment varied according to the level of dyspnea (interaction ß = 7.52, p = 0.034; interaction ß = 8.78, p = 0.048; interaction ß = 131.08, p < 0.001). CONCLUSIONS: Muscle weakness and exercise capacity in ILD patients in the low mMRC group were associated with corticosteroid treatment.

Total Synthesis of the Proposed Structure for Protoaculeine B, a Polycationic Marine Sponge Metabolite, with a Homogeneous Long-Chain Polyamine.

By establishing the procedures for sequential deprotections, reaction monitoring, purification, and handling, for the first time, we achieved the total synthesis of the proposed structure for protoaculeine B (2), which is a highly hydrophilic and polycationic amino acid. The NMR and mass spectra and chemical reactivity of the synthetic sample differed from those of natural protoaculeine B, which indicates the necessity for revision of the originally reported structure.

Factors Influencing Functional Exercise Capacity After Lung Resection for Non-Small Cell Lung Cancer.

Purpose: We investigated, in patients who underwent lung resection for non-small cell lung cancer (NSCLC), the magnitude of early limitation in functional exercise capacity and the associations with pre- and postoperative factors. Methods: Consecutive patients with preoperative clinical stage I to IIIA NSCLC who underwent lung resection were prospectively enrolled. We measured functional exercise capacity (6-minute walk distance [6MWD]) and skeletal muscle strength (handgrip [HF] and quadriceps force [QF]) within 2 days prior to surgery and on day 7 postoperatively. Results: Two hundred eighteen participants were recruited (median age 69 years) of whom 49 developed postoperative complications (POCs). 6MWD was markedly decreased (514 m vs 469 m, P < .001); HF and QF were slightly decreased following surgery. Multiple linear regression showed that preoperative vital capacity (P < .01), QF (P < .05), the duration of chest tube drainage (P < .001), and presence of POCs (P < .05) were significant predictors. However, intraoperative factors were not significantly associated with the decline in 6MWD. Conclusions: These results suggest that patients with preoperative impairments in pulmonary function and muscle strength, and those who require prolonged chest tube drainage or develop POCs are likely to have impaired exercise capacity. Therefore, individual assessment and follow-up of patients with such factors is indicated.

Effects of quadriceps muscle neuromuscular electrical stimulation in living donor liver transplant recipients: phase-II single-blinded randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of neuromuscular electrical stimulation on quadriceps muscle strength and thickness in liver transplantation patients. DESIGN: Phase-II, randomized, parallel-group, allocation-concealed, assessor-blinded, single-center controlled trial. SETTING: Inpatient rehabilitation sector. SUBJECTS: Patients following living donor liver transplantation. INTERVENTIONS: The quadriceps muscle stimulation and the control groups received bilateral muscle electrical stimulation on the quadriceps and tibialis anterior muscles, respectively. Neuromuscular electrical stimulation sessions in both groups were conducted for 30 minutes per session, once per day for five weekdays over four weeks by a physical therapist. MAIN MEASURES: Quadriceps muscle strength and quadriceps muscle thickness. RESULTS: Neuromuscular electrical stimulation was applied to the quadriceps muscles group ( n = 23) or the tibialis anterior muscle in the control group ( n = 22). The decrease in quadriceps muscle thickness differed significantly between both groups on postoperative day 30 (median -3 vs -8, P < 0.01). The changes in predicted quadriceps strength and 6 minutes walking distance were not significantly different between groups (quadriceps strength median -12% vs -5%, P = 0.40; 6 minutes walking distance median -18 vs -21 m, P = 0.74). CONCLUSION: Neuromuscular electrical stimulation of the quadriceps muscle for liver transplantation recipients was able to maintain the quadriceps muscle thickness after surgery. Future larger scale studies are needed to consider the effectiveness of neuromuscular electrical stimulation and how to incorporate this intervention in the overall strategy of the physical therapy program.

Effect of early mobilization on postoperative pulmonary complications in patients undergoing video-assisted thoracoscopic surgery on the esophagus.

BACKGROUND: Esophagectomy performed via thoracotomy is associated with a high rate of postoperative pulmonary complications. Video-assisted thoracoscopic surgery at the esophagus (VATS-E) can reduce the rate of postoperative pulmonary complications. VATS-E is being increasingly implemented owing to its benefits. This procedure makes early patient mobilization possible, because there is minimal thoracic wall invasion, and thus, less postoperative pain. This study aimed to identify the efficacy of early mobilization in patients undergoing VATS-E. METHODS: We retrospectively reviewed the patients who underwent VATS-E between November 2008 and October 2016. All the patients underwent preoperative physiotherapy and postoperative early mobilization for standard perioperative management. We examined the relation between early mobilization and the factors affecting postoperative pulmonary complications and the duration of physiotherapy with regard to the surgical outcome of VATS-E. RESULTS: A total of 118 patients who underwent VATS-E were assessed. The incidence of postoperative pulmonary atelectasis decreased with early mobilization, and earlier mobilization was associated with a better decrease (P < 0.001). Multiple logistic regression analysis identified the percentage of volume capacity [odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93-0.99] and initial walking (OR 1.82; 95% CI 1.40-2.48) as independent risk factors for postoperative pulmonary atelectasis. In addition, the presence or absence of atelectasis was found to reduce the necessary period of physiotherapy (P < 0.001). CONCLUSION: Our results indicated that early mobilization reduces the incidence of postoperative pulmonary atelectasis, which may also contribute to early recovery in patients who undergo VATS-E.

Studies on Aculeines: Synthetic Strategy to the Fully Protected Protoaculeine B, the N-Terminal Amino Acid of Aculeine B.

A synthetic strategy for accessing protoaculeine B (1), the N-terminal amino acid of the highly modified peptide toxin aculeine, was developed via the synthesis of the fully protected natural homologue of 1 with a 12-mer poly(propanediamine). The synthesis of mono(propanediamine) analog 2, as well as core amino acid 3, was demonstrated by this strategy. New amino acid 3 induced convulsions in mice; however, compound 2 showed no such activity.

Incidence of orthostatic hypotension and cardiovascular response to postoperative early mobilization in patients undergoing cardiothoracic and abdominal surgery.

BACKGROUND: In cardiothoracic and abdominal surgery, postoperative complications remain major clinical problems. Early mobilization has been widely practiced and is an important component in preventing complications, including orthostatic hypotension (OH) during postoperative management. We investigated cardiovascular response during early mobilization and the incidence of OH after cardiothoracic and abdominal surgery. METHODS: In this prospective observational study, we consecutively analyzed data from 495 patients who underwent elective cardiothoracic and abdominal surgery. We examined the incidence of OH, and the independent risk factors associated with OH during early mobilization after major surgery. Multivariate logistic regression was performed using various characteristics of patients to identify OH-related independent factors. RESULTS: OH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac, thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%) of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural anesthesia (OR 2.906; p < 0.001) were independently associated with OH on multivariate analysis. CONCLUSIONS: These results demonstrate that approximately 40% patients experience OH during early mobilization after cardiothoracic and abdominal surgery. Sex was identified as an independent factor for OH during early mobilization after all three types of surgeries, while epidural anesthesia was only identified after thoracic surgery. Therefore, the frequent occurrence of OH during postoperative early mobilization should be recognized. TRIAL REGISTRATION: University hospital Medical Information Network Center (UMIN-CTR) number UMIN000018632 . (Registered on 1st October, 2008).

A monocyclic neodysiherbaine analog: Synthesis and evaluation.

Monocyclic analog of neuroexcitatory neodysiherbaine has been designed and stereoselectively synthesized in 0.40% yield over total 24 steps starting from d-ribose, by employing domino aldol-Cannizzaro reaction and stereoselective aldol reaction for construction of two quaternary carbon stereogenic centers at C4 and C6 positions, respectively. The hyperactivity of neodysiherbaine in mice was found to deteriorate in the novel analog, upon intracerebroventricular injection.