Linear ubiquitin chains: NF-κB signalling, cell death and beyond.

Ubiquitylation is a versatile post-translational modification. Met1-linked linear ubiquitin chains are involved in nuclear factor-κB signalling and cell death, and dysfunctions in linear ubiquitylation underlie chronic inflammation. Recent identification of deubiquitylating enzymes and binding domains that are specific for linear ubiquitin chains suggests new physiological roles for linear ubiquitin chains. Moreover, the ligase required for linear ubiquitylation has a crucial role in the pathogenesis of some malignancies. Structural and functional analyses of the conjugation and deconjugation of linear ubiquitin chains have enabled the development of new probes to study the roles of linear chain ubiquitylation.

Iron-induced NCOA4 condensation regulates ferritin fate and iron homeostasis.

Iron is not only essential but also a toxic trace element. Under iron repletion, ferritin maintains cellular iron homeostasis by storing iron to avoid iron toxicity. Under iron depletion, the ferritin-specific autophagy adaptor NCOA4 delivers ferritin to lysosomes via macroautophagy to enable cells to use stored iron. Here, we show that NCOA4 also plays crucial roles in the regulation of ferritin fate under iron repletion. NCOA4 forms insoluble condensates via multivalent interactions generated by the binding of iron to its intrinsically disordered region. This sequesters NCOA4 away from ferritin and allows ferritin accumulation in the early phase of iron repletion. Under prolonged iron repletion, NCOA4 condensates can deliver ferritin to lysosomes via a TAX1BP1-dependent non-canonical autophagy pathway, thereby preventing relative iron deficiency due to excessive iron storage and reduced iron uptake. Together, these observations suggest that the NCOA4-ferritin axis modulates intracellular iron homeostasis in accordance with cellular iron availability.

Impact of autonomic symptoms on the clinical course of Parkinson's disease.

PURPOSE: Patients with Parkinson's disease (PD) exhibit various degrees of autonomic symptoms, which may be associated with Lewy body pathology distributed extensively in the autonomic nervous system. We hypothesized that the severity of autonomic symptoms reflects the severity of PD-related pathology, resulting in poor outcomes. The purpose of this study was to evaluate the impact of autonomic symptoms on PD progression. METHODS: We conducted a follow-up study among consecutive patients with PD at Dokkyo Medical University Hospital. Patients underwent comprehensive baseline evaluations and were classified into high and low autonomic symptom groups using the Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT). The Kaplan‒Meier survival curves were used to analyze the time to discontinuation of their visits because of PD-related endpoints and to evaluate the association with high SCOPA-AUT scores. RESULTS: Of the 101 patients, 74 (73%) met the inclusion criteria. During the follow-up period (mean 1654 days), 22/74 patients reached PD-related endpoints (death, 4; hospitalization, 9; nursing home institutionalization, 9). PD patients with high SCOPA-AUT scores reached the endpoints faster than those with low SCOPA-AUT scores. A high SCOPA-AUT score, including gastrointestinal, urinary, and thermoregulation domains; high motor symptom scores; and low specific binding ratios (SBRs) on 123I FP-CIT-SPECT (DAT-SPECT) were associated with reaching PD-related endpoints. A high SCOPA-AUT score was associated with reaching the endpoints even after adjustment for covariates. CONCLUSIONS: Patients with high autonomic symptom scores had a greater risk of reaching PD-related endpoints than patients with low autonomic symptom scores.

Effects of communication delay in the dual cockpit remote robotic surgery system.

PURPOSE: To evaluate the impact of dual cockpit telesurgery on proctors and operators, and acceptable levels of processing delay for video compression and restoration. METHODS: Eight medical advisors and eight trainee surgeons, one highly skilled per group, performed gastrectomy, rectal resection, cholecystectomy, and bleeding tasks on pigs. Using the Medicaroid surgical robot hinotori™, simulated delay times (0 ms, 50 ms, 100 ms, 150 ms, and 200 ms) were inserted mid-surgery to evaluate the tolerance level. Operative times and dual cockpit switching times were measured subjectively using 5-point scale questionnaires (mSUS [modified System Usability Scale], and Robot Usability Score). RESULTS: No significant difference was observed in operative times between proctors and operators (proctor: p = 0.247, operator: p = 0.608) nor in switching times to the dual cockpit mode (p = 0.248). For each survey setting, proctors tended to give lower ratings to delays of ≥ 150 ms. No marked difference was observed in the operator evaluations. On the postoperative questionnaires, there were no marked differences in the mSUS or Robot Usability Score between the proctors and operators (mSUS: p = 0.779, Robot Usability Score: p = 0.261). CONCLUSION: Telesurgery using a dual cockpit with hinotori™ is practical and has little impact on surgical procedures.

Effectiveness of three calcitonin gene-related peptide monoclonal antibodies for migraine: A 12-month, single-center, observational real-world study in Japan.

BACKGROUND: Real-world data on the effectiveness of calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in migraine patients are needed. METHODS: We performed a single-center, real-world study with an observation period of up to 12 months (mean 7.5 ± 3.4 months) after CGRP mAb administration. A total of 228 Japanese patients with episodic or chronic migraine (age, 45.9 ± 13.2 years; 184F; 45 erenumab; 60 galcanezumab; 123 fremanezumab) who were treated with CGRP mAbs for at least three months were ultimately included in this study. RESULTS: In the total cohort, after CGRP mAb treatment, mean monthly migraine days decreased by 7.2 ± 4.8, 8.3 ± 4.7, and 9.5 ± 5.0 at three, six and 12 months, respectively. The ≥50% monthly migraine day reduction rates at three, six and 12 months were 48.2%, 61.0% and 73.7%, respectively. In the logistic regression analysis, the presence of osmophobia and fewer baseline monthly migraine days contributed to ≥50% responders at three, six and 12 months. The ≥50% responders at three or six months were useful in predicting ≥50% responders at 12 months. In subgroups of patients with difficult-to-treat migraine (those with medication overuse headache or psychiatric comorbidities) and previous CGRP mAb users, monthly migraine days were substantially reduced over 12 months. There was no difference in monthly migraine day reduction over 12 months among three different CGRP mAbs. Adverse reactions were observed in 28 (12.3%) patients, with injection site reactions being the most common (n = 22) though generally mild in severity. CONCLUSION: This real-world study confirmed the efficacy and safety of three different CGRP mAbs for prophylactic treatment of patients with migraine.

Loss of height predicts fall risk in elderly Japanese: a prospective cohort study.

INTRODUCTION: The purpose of this study was to explore whether height loss is associated with future falls and whether the combination of height loss and fall experience is associated with future falls. MATERIALS AND METHODS: In this prospective observational study, a total of 765 individuals (354 men, 411 women) agreed to join the study. Baseline data on demographics, comorbidities, physical performance, and previous falls were assessed. Height loss was calculated as the difference between the self-reported height at a younger age and the current height and was divided into two groups: < 2 cm and ≥ 2 cm. Approximately 15 months after the baseline evaluation, follow-up questionnaires were used to assess the fall history. Participants were classified as either "non-fallers" or "fallers." Multiple logistic regression was used to evaluate the association between falls and each factor and to obtain adjusted odds ratio estimates. RESULTS: The follow-up questionnaire was returned by 668 participants, 74 of whom (11.1%) fell at least once during the observation period. Multiple logistic regression analysis found that height loss of > 2 cm was a significant predictor of future falls, even after adjusting for other factors. Additionally, the combination of height loss and previous falls was a risk factor for falls. CONCLUSIONS: We suggest that height loss of ≥ 2 cm is a predictor of future falls in older adults, and the combination of height loss and fall experiences may be a useful screening tool for determining fall risk.

Comparison of methylprednisolone pulse vs conventional dexamethasone for adult cases of COVID-19 requiring oxygen; a Japanese retrospective cohort study.

BACKGROUND: Although dexamethasone is an effective treatment in cases of coronavirus disease 2019 (COVID-19) requiring oxygen, the efficacy of methylprednisolone pulse is unclear. We compared the characteristics and outcomes of methylprednisolone pulse to those of dexamethasone. METHODS: We conducted a retrospective cohort study on adult COVID-19 cases requiring oxygen and no invasive mechanical ventilation treated with methylprednisolone pulse (1 g/day for 3 days) or dexamethasone (6 mg/day orally or 6.6 mg/day intravenously for ≥5 days). The primary outcome was intensive care unit (ICU) admission. The secondary outcomes were hospital mortality, length of hospital stay (LoS), duration of oxygen requirement, and requirement for hospital transfer, vasopressor(s), intubation, extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapy (CRRT). RESULTS: Twenty two cases of methylprednisolone pulse and 77 cases of dexamethasone were included. Mask ventilation was more common in the methylprednisolone pulse group (P < 0.001). The proportion of ICU admissions was similar between both groups (P = 0.635). The secondary outcomes of hospital mortality and the requirement for hospital transfer, vasopressor(s), intubation, and CRRT were similar between groups. No cases received ECMO. Median LoS (P = 0.006) and duration of oxygen requirement (P = 0.004) were longer in the methylprednisolone pulse group. CONCLUSIONS: The proportion of ICU admissions was similar between the methylprednisolone pulse and the dexamethasone group. However, more cases in the methylprednisolone pulse group required mask ventilation than in the dexamethasone group, suggesting that some cases benefited from methylprednisolone pulse.

Development of a Biomarker-Based Scoring System Predicting Early Recurrence of Resectable Pancreatic Duct Adenocarcinoma.

BACKGROUND: Resectable pancreatic ductal adenocarcinoma (R-PDAC) often recurs early after radical resection, which is associated with poor prognosis. Predicting early recurrence preoperatively is useful for determining the optimal treatment. PATIENTS AND METHODS: One hundred and seventy-eight patients diagnosed with R-PDAC on computed tomography (CT) imaging and undergoing radical resection at Hirosaki University Hospital from 2005 to 2019 were retrospectively analyzed. Patients with recurrence within 6 months after resection formed the early recurrence (ER) group, while other patients constituted the non-early recurrence (non-ER) group. Early recurrence prediction score (ERP score) was developed using preoperative parameters. RESULTS: ER was observed in 45 patients (25.3%). The ER group had significantly higher preoperative CA19-9 (p = 0.03), serum SPan-1 (p = 0.006), and CT tumor diameter (p = 0.01) compared with the non-ER group. The receiver operating characteristic (ROC) curve analysis identified cutoff values for CA19-9 (133 U/mL), SPan-1 (78.2 U/mL), and preoperative tumor diameter (23 mm). When the parameter exceeded the cutoff level, 1 point was given, and the total score of the three factors was defined as the ERP score. The group with an ERP score of 3 had postoperative recurrence-free survival (RFS) of 5.5 months (95% CI 3.02-7.98). Multivariate analysis for ER-related perioperative and surgical factors identified ERP score of 3 [odds ratio (OR) 4.63 (95% CI 1.82-11.78), p = 0.0013] and R1 resection [OR 3.20 (95% CI 1.01-10.17), p = 0.049] as independent predictors of ER. CONCLUSIONS: For R-PDAC, ER could be predicted by the scoring system using preoperative serum CA19-9 and SPan-1 levels and CT tumor diameter, which may have great significance in identifying patients with poor prognoses and avoiding unnecessary surgery.

Anti-LGI1 encephalitis recurring 3 years after the first episode: a case report.

BACKGROUND: Patients with antibodies against leucine-rich glioma-inactivated 1 (LGI1) present with limbic encephalitis, which is clinically characterized by a subacute disturbance of memory and behavior, often experience seizures. Most patients have a monophasic course, often with hyponatremia. CASE PRESENTATION: Herein, we report a 67-year-old Japanese male presenting with involuntary neck movement, abnormal behavior and apraxia. He was disoriented to time and place and occasionally unable to follow directions. Laboratory tests revealed the patient had hyponatremia (131 mEq/L). Cerebrospinal fluid (CSF) analysis showed that the cell count (1/µL) and protein content (33 mg/dL) were in the normal ranges. Electroencephalography showed transient theta bursts in the right frontal lobe. Magnetic resonance imaging (MRI) of the brain demonstrated hyperintensities in the medial temporal lobe and basal forebrain on fluid-attenuated inversion recovery (FLAIR) without gadolinium enhancement. Anti-voltage-gated potassium channel (Anti-VGKC) complex antibodies were below the reference level for limbic encephalitis. Although the diagnosis was unknown, intravenous methylprednisolone therapy was effective. Three years later, the patient began to speak incoherently and became disoriented to time. FLAIR MRI of the brain revealed recurrence in the left medial temporal lobe. The patient's serum sodium level was 131 mEq/L. After intravenous methylprednisolone therapy, he regained alertness. A CSF sample stored at the time of the first attack was assayed and the patient was found to be LGI1-positive and CASPR-2-negative, and the diagnosis of anti-LGI1 encephalitis was made. CONCLUSIONS: Monitoring serum sodium levels and the preserved samples from the first episode were useful for diagnosis.

Sick sinus syndrome as the initial manifestation of neuromyelitis optica spectrum disorder: a case report.

BACKGROUND: Sick sinus syndrome (SSS) is known to occur due to lesions in the medulla oblongata. Although medullary lesions have occurred in patients with neuromyelitis optica spectrum disorder (NMOSD), there are few reports of SSS associated with NMOSD. We report a patient with NMOSD who developed refractory nausea, vomiting and SSS as the initial manifestation. CASE PRESENTATION: A 77-year-old female developed refractory nausea and frequent episodes of syncope. The patient was diagnosed with SSS because sinus pauses lasting five to six seconds were observed, and pacemaker implantation was performed. Two months later, she was referred to our hospital because of limb weakness and sensory impairment that progressed over a month. The patient was confirmed to have muscle weakness; manual muscle testing revealed grade 4 in the upper extremities and grade 3 in the lower extremities. Tendon reflexes were diminished, while no pathological reflexes were present. Thermal and pain sensations were impaired in the upper and lower extremities, and vibration sensation was impaired in both lower extremities. Bladder and rectal disturbances were also noted. Optic neuritis was not detected. T2-weighted magnetic resonance imaging (MRI) showed high-intensity lesions in the dorsal part of the medulla oblongata and C3-6 cervical cord. Her serum was positive for antibodies against aquaporin 4, and a diagnosis of NMOSD was made. She was treated with two courses of an intravenous methylprednisolone pulse and one course of plasma exchange. Then, she was transferred to another hospital for rehabilitation. CONCLUSIONS: Because SSS is a life-threatening complication, clinicians should be aware of the possibility that medullary lesions in NMOSD can cause SSS as the initial manifestation.

Linear Hydrocarbon Chain Growth from a Molecular Diruthenium Carbide Platform.

The formation of linear hydrocarbon chains by sequential coupling of C1 units on the metal surface is the central part of the Fischer-Tropsch (F-T) synthesis. Organometallic complexes have provided numerous models of relevant individual C-C coupling events but have failed to reproduce the complete chain lengthening sequence that transforms a linear Cn hydrocarbon chain into its Cn+1 homologue in an iterative fashion. In this work, we demonstrate stepwise growth of linear Cn hydrocarbon chains and their conversion to their Cn+1 homologues via consecutive addition of CH2 units on a molecular diruthenium carbide platform. The chain growth sequence is initiated by the formation of a µ-η1:η1-C═CH2 ligand from a C + CH2 coupling between the µ-carbido complex [(Cp*Ru)2(η-NPh)(µ-C)] (1; Cp* = η5-C5Me5) and Ph2SCH2. Then, the chain propagates via a general C═CHR + CH2 coupling and subsequent hydrogen-assisted isomerization of the resulting allene ligand µ-η1:η3-H2C═C═CHR to a higher vinylidene homologue µ-η1:η1-C═CH(CH2)R. By repeating this reaction sequence, up to C6 chains have been synthesized in a stepwise fashion. The key step of this chain homologation sequence is the selective hydrogenation of the µ-η1:η3-allene unit to the corresponding µ-alkylidene ligand. Isotope labeling and computational studies indicate that this transformation proceeds via the hydrogenation of the allene ligand to a terminal alkene form and its isomerization to the µ-alkylidene ligand facilitated by the coordinatively unsaturated diruthenium platform.

Use of a Novel Fluorescent Catheter to Locate the Ureters during Total Laparoscopic Hysterectomy.

Ureteral injury can occur during total laparoscopic hysterectomy. This report documents our experience in using the near-infrared ray catheter (NIRC), a newly developed fluorescent ureteral catheter made of material that contains a fluorescent dye to improve visualization of the ureters. We have used the device in 3 patients between 40 and 50 years of age (mean, 46.3 ± 4.5 years) undergoing total laparoscopic hysterectomy and bilateral salpingectomy for uterine myomas. The time of catheter insertion ranged from 4 minutes and 9 seconds to 10 minutes and 57 seconds. A number of intraoperative procedures were performed near the ureters, namely, identification and ligation of the uterine arteries, dissection of the cardinal ligament, incision of the vaginal canal, and suturing of the vaginal stump. The abovementioned fluorescent ureteral catheter appears green on a monitor when illuminated by near-infrared light, and this facilitated real-time confirmation of the ureter positions, increasing surgical safety. The patients were followed up for 6 months postoperatively, and no urinary tract infection or injury was found. Prophylactic use of the fluorescent ureteral catheter may improve visualization of the ureters in patients considered to be at high risk of ureteral injury, such as those expected to exhibit ureteral deviation due to severe adhesions or an enlarged uterus and when the surgeon has little experience in laparoscopic surgery.

[Significance of Neoadjuvant Chemotherapy before Colorectomy and Hepatectomy].

BACKGROUND: We discuss the significance of neoadjuvant chemotherapy for resectable simultaneous liver metastases in our department. SUBJECT: We examined 73 cases of resectable simultaneous colorectal liver metastases surgeries occurred in our department from 2000 to 2019. RESULTS: There were 13 patients in the chemotherapy before colorectomy group(before colorectomy group), 24 patients in the chemotherapy before hepatectomy group(before hepatectomy group), and 36 patients in the no chemotherapy group(no chemo group). Five-year overall survival in Grade A/B was 77.8%/100% in the before colorectomy group, 50.0%/42.4% in the before hepatectomy group and 45.6%/66.2% in the no chemo group. Three-year progression-free survival in Grade A/B was 51.9%/50.0% in the before colorectomy group, 16.7%/40.4% in the before hepatectomy group and 46.5%/55.6% in the no chemo group. Six patients in the before colorectomy group had no local recurrence, lymph node recurrence, or peritoneal dissemination. CONCLUSION: Patients in the before colorectomy group were expected to have prolonged survival. There was no local recurrence, lymph node recurrence, or peritoneal dissemination in the before colorectomy group, suggesting the possibility of controlling them.

[A Case of Stage â £ Gastric Cancer with Para-Aortic Lymph Node Metastasis, and Multiple Liver, Lung, and Bone Metastases Leading to Conversion Therapy].

We report a case of unresectable gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases leading to conversion therapy. A 70s-year-old man visited previous doctor with epigastralgia. He was diagnosed as stage Ⅳ gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases by upper gastrointestinal endoscopy, contrast enhanced computer tomography(CT), and positron emission tomography(PET). After a regimen consisting of 6 courses of capecitabine plus cisplatin plus trastuzumab, para-aortic lymph node metastasis and liver, lung, and bone metastases were absent in CT and PET images. So, he visited our department for surgery treatment. We judged curative resection could be achieved for gastric cancer. Total gastrectomy, D2 and paraaortic lymphadenectomy, and cholecystectomy were performed. The histopathological examination of the resected specimen revealed the efficacy of chemotherapy was Grade 2b. The patient was discharge 14 days after the operation, and capecitabine plus trastuzumab was started as adjuvant chemotherapy, and the patient remains alive without recurrence 11 months after surgical treatment.

[A Case of Two Stage taTME for Perforated Rectal Cancer during Chemotherapy].

The patient was a 57-year-old male. He was diagnosed with locally advanced rectal cancer infiltrating the left levator ani muscle. Chemotherapy(S-1 plus L-OHP plus bevacizumab regimen)was started for the purpose of obtaining a negative circumferential radial margin. After the second course, he presented with perforation of the sigmoid colon for which an emergency operation was performed. The perforation was located 5 centimeters above the tumor in the sigmoid colon. We performed partial resection of the sigmoid colon to repair the perforation and create a sigmoid colostomy. CT, after the initial S-1 plus L-OHP plus bevacizumab chemotherapy regimen, revealed tumor shrinkage. Following 2 more courses of chemotherapy( S-1 plus L-OHP regimen), we performed transanal total mesenteric excision(taTME)as curative surgery. R0 resection was achieved. The combined transanal and laparoscopic approach was highly effective for a patient with pan-peritonitis.

[A Case of Descending Colon and Rectal Cancer with Acute Myeloid Leukemia Performed Robot‒Assisted Hartmann's Procedure].

The case is a 68‒year‒old male, who had been diagnosed with acute myeloid leukemia(AML)prior to rectal cancer surgery, was referred to our hospital for treatment in July 2019. We planned to treat the AML first, and then the colorectal cancer. After completion of 1 course of CAG therapy(cytarabine, aclarubicin, G‒CSF), his white blood cell count increased sufficiently, so he underwent a robot‒assisted Hartmann operation in October. A second course of CAG therapy was started 15 days postoperatively. However, he was then diagnosed with exacerbation of the AML; remission induction therapy (daunorubicin, cytarabine)was started in November. In December, he developed a fever and abdominal pain, and on CT scan, it was discovered that an abscess had formed around the rectal resection site. Myelosuppression from AML led to prolonged sepsis; and by January 2020, the sepsis was systemic. His actual cause of death was given as circulatory failure. We report this, because only a few cases on the treatment of overlapping AML and colorectal cancers can be found in the literature.

Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis.

We applied combination antibiotic therapy to treat vertebral osteomyelitis and a psoas abscess caused by glycopeptide-intermediate (MIC, 2 µg/ml) and daptomycin-nonsusceptible (>2 µg/ml) methicillin-resistant Staphylococcus aureus The Etest synergy test showed the largest synergistic effects for imipenem/cilastatin and fosfomycin. Whole-gene sequencing showed amino acid changes in SA0802, SA1193 (mprF), and SA1531 (ald). Four weeks of combination treatment using imipenem/cilastatin (1.5 g per day) and fosfomycin (4.0 g per day) resulted in clinical improvement.

The one-leg portion of the Stand-Up Test predicts fall risk in aged individuals: A prospective cohort study.

BACKGROUND: Falls are a primary cause of physical disability in older adults, making them a major public health problem. Locomotive syndrome risk assessments have proven to be simple to administer, practical, and useful as screening tools in detecting decreased mobility in middle-aged and elderly adults. The current prospective study investigated whether these tests were associated with future falls among elderly Japanese. METHODS: This study was a two-year prospective observational study. A total of 1800 individuals (aged 65-79 years) who were without certification of long-term care or physical disability were initially invited through letters to participate in the study. Of these, 499 individuals (225 men, 274 women) agreed to participate and underwent baseline assessments. Demographic information, body function physical performance measurements, and locomotive syndrome risk tests [Stand-Up Test (SUT), Two-Step Test (TST), and the 25-question Geriatric Locomotive Function Scale (GLFS-25)] were assessed. Following baseline evaluation, we sent a follow-up questionnaire to assess fall history in the past two years. Participants were classified as either "non-fallers" or "fallers" (denoted by one or more falls). Multiple logistic regression was used to evaluate the association between falls and each factor by providing adjusted odds ratio estimates. RESULTS: The follow-up questionnaire was returned by 399 participants, 54 of whom (13.5%) fell at least once during the two-year observation period. The multiple logistic regression analysis revealed that difficulty with standing on one leg from a 40-cm-high seat (a portion of the SUT) was a significant predictor of future falls (odds ratio = 2.20, 95%CI = 1.04-4.69, p = 0.04). A history of falling was also a risk factor of falls. CONCLUSION: Our results suggest that standing on one leg from a 40-cm-high seat is predictive of falling in older adults, even after adjustment for previous falls and other confounding variables.

Association of Built Environments With Frequency of Going Outdoors Among Older Community-Dwelling Adults in Japan.

Built environmental factors are important for encouraging outdoor activity among community-dwelling older adults. A total of 214 participants aged 59-94 years were recruited from local cities in Japan. A mixed-effects multivariate linear regression model was conducted for the analysis. Parks that are easy to get to and car availability were positively associated with the number of days per week with any outdoor exposure. Further, the ability to conduct activities of daily living had a significant effect on the use of safe parks and walking areas and the number of days per week with outdoor time. The findings suggest that subjectively assessed neighborhood-built environments, such as readily available safe parks, walking areas, and car availability, are important for encouraging outdoor activity among older community-dwelling adults in Japan. For those with a limited ability to conduct daily activities, the safeness of parks and walking areas are most important.

[Improvement of QOL by Surgery in Two Patients for Brain Metastasis from Esophageal Carcinoma with Paralysis-A Report of Two Cases].

Brain metastasis from esophageal cancer is rare. Symptoms such as paralysis caused a decline in quality of life(QOL)and activity of daily life(ADL)and required emergency treatment. We report 2 cases in which QOL was improved by emergency resection for brain metastasis from esophageal carcinoma with paralysis. Case 1: A 50's male was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N2M0, Stage Ⅲ). Brain metastasis was detected owing to development of left hemiparesis. Craniotomy and tumorectomy were performed, left hemiparesis was improved. He died 10 months after diagnosis of brain metastasis due to progression of other metastatic lesions. Case 2: A 61-year-old female was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N1M0, Stage Ⅲ). She developed right hemiparesis 5 months after esophagectomy, admitted to our hospital. Brain and lung metastases were detected, craniotomy and tumorectomy and were performed, right hemiparesis was improved. Although systemic chemotherapy was administered, she died 10 months after diagnosis of brain metastasis due to progression of lung metastasis. Conclusion: Aggressive surgical treatments for brain metastasis were one good treatment option to maintain QOL and ADL.