Effects of Exercise-Diet Therapy on Cognitive Function in Healthy Elderly People Evaluated by Deep Learning Based on Basic Blood Test Data.

BACKGROUND: Recent studies reported that vascular cognitive impairment in the elderly caused by arteriosclerosis plays an important role in cognitive disorders in both vascular dementia and Alzheimer's disease. In addition, systemic metabolic disorders such as oxygen metabolism dysfunction could be risk of dementia. Based on these findings, we have developed a deep neural network-based screening test (DNN-based test) of cognitive function using basic blood test data, which allowed prediction of cognitive function expressed by Mini Mental State Examination (MMSE) scores. AIM: Here, we investigated whether the DNN-based test could be applicable to assessment of the effects of exercise-diet on cognitive function. METHODS: We studied the following two groups: (1) seven subjects of the local fitness gym (68.6 ± 3.2 years old). We evaluated cognitive function by the DNN-based test using blood data before and after the intervention (for 3 months). These results were compared with the measured MMSE score. (2) we studied a total of 230 subjects (67.9 ± 7.4 years old) who were members of the Tsuminory health class (Apple classroom). We assessed cognitive function by the DNN-based test before and after the intervention (for 2 months). We compared the predicted MMSE scores by the DNN-based test before and after the 2-month intervention. RESULTS: In the first group, the MMSE score predicted by the DNN-based test increased from 27.1 ± 0.8 to 27.6 ± 0.7 after the intervention period (p = 0.024). The measured MMSE score also increased after exercise, but not significant (P = 0.28). In the second group, the exercise-diet therapy increased the predicted MMSE scores in 189 cases (p < 0.001). In contrast, the therapy significantly reduced the mean MMSE score (p < 0.001). DISCUSSION: The MMSE score predicted by the DNN-based test were increased by exercise-diet therapy in most subjects. The DNN-based test may be useful to monitor the effect of exercise-diet therapy on cognitive function aged people.

Effects of 20-Minute Intensive Exercise on Subjects with Different Working Memory Bases.

Continuous moderate-intensity aerobic exercise improves cognitive function including working memory (WM). We aimed to determine the differences in the effects of exercise on WM based on pre-exercise WM function and oxyhemoglobin (O2Hb) changes. We enrolled 12 healthy adult males who, after a 4-min rest and warm-up, performed a 20-min exercise regime at a workload corresponding to 50% of maximal oxygen consumption. They performed a pre- and postexercise two-back test, and the reaction times were recorded. Near-infrared spectroscopy was used to monitor the O2Hb concentration in the left prefrontal cortex during the exercise. Based on the pre-exercise reaction time, the subjects were allocated into either a fast group (FG) or a slow group (SG). The pre- and postexercise changes in the reaction time and time-to-peak O2Hb were compared. Further, we determined the relationship between the change in the reaction time and time-to-peak O2Hb. There was no significant change in the reaction time of the FG; however, that in the SG decreased significantly. The time-to-peak O2Hb in the FG was significantly less than that in the SG. These results showed differences in the changes of reaction time and O2Hb changes between the FG and SG.

Relationship Between Cognitive Dysfunction and Systemic Metabolic Disorders in Elderly: Dementia Might be a Systematic Disease.

Vascular cognitive impairment (VCI) plays an important role in dementia in elderly people, and refers to the contribution of vascular pathology to the entire spectrum of cognitive disorders, ranging from mild cognitive impairment to severe dementia, as well as the pathological spectrum, from 'pure' Alzheimer disease through degrees of vascular comorbidity to 'pure' vascular dementia. In the present study, we investigated the relationship between cognitive dysfunction and systemic metabolic disorders, by employing deep learning (DL). We studied 202 patients (73.4 ± 13.0 years), 94.6% of whom were undergoing treatment for lifestyle diseases, and 68.8% of whom had a history of cerebrovascular disorder. We evaluated cognitive dysfunction by performing a Mini Mental State Examination (MMSE). We performed general blood examination, including Complete Blood Count and Basic Metabolic Panel, and measured cerebral blood oxygenation in the prefrontal cortex (PFC) using time-resolved near infrared spectroscopy (TNIRS). We then used deep neural networks to assess the MMSE scores of the subjects based on the TNIRS parameters and the blood examination data, independently. Next, we compared predicted MMSE scores based on the TNIRS and the blood examination. There was a significant positive correlation between the TNIRS parameters and the blood examination data (r = 0.6, p < 0.01). These observations suggest that cognitive dysfunction in patients with VCI may be caused by combinations of systemic metabolic disorders such as energy and oxygen metabolisms and cerebral circulatory disturbance due to arteriosclerosis resulting from lifestyle-related diseases.

Thoracoscopic esophagectomy with extended lymph node dissection in the left lateral position: technical feasibility and oncologic outcomes.

The aim of this study was to estimate the technical and oncologic feasibility of video-assisted thoracoscopic radical esophagectomy (VATS) in the left lateral position. From January 2003 to December 2011, 132 patients with esophageal cancer underwent VATS. The mean duration of the thoracic procedure and the entire procedure was 294 ± 88 and 623 ± 123 minutes, respectively. Mean blood loss during the thoracic procedure and the entire procedure was 313 ± 577 and 657 ± 719 g, respectively. The mean number of dissected thoracic lymph nodes was 32.6 ± 12.9. There were four in-hospital deaths (3.0%); two patients (1.5%) died of acute respiratory distress syndrome and two patients (1.5%) died of tumor progression. Postoperative unilateral or bilateral recurrent laryngeal nerve (RLN) palsy, or pneumonia was found in 33 (25.0%), 21 (15.9%), and 27(20.5%) patients, respectively. The patients were divided into the first 66 patients who underwent VATS (Group 1) and the subsequent 66 patients (Group 2). The numbers of cases who underwent neoadjuvant or induction chemotherapy for T4 tumor and intrathoracic anastomosis were higher in Group 2 than in Group 1. The duration of the procedure, amount of blood loss, and the number of dissected thoracic lymph nodes were not different between the two groups. The total number of dissected lymph nodes was higher in Group 2 than in Group 1 (72.6 ± 27.8 vs. 62.6 ± 21.6, P = 0.023). The rate of bilateral RLN palsy was less in Group 2 than in Group 1 (7.6% vs. 24.2%, P = 0.042). The mean follow-up period was 38.7 months. Primary recurrence consisted of hematogenous, lymphatic, peritoneal dissemination, pleural dissemination, and locoregional in 15 (11.3%), 20 (15.1%), 3 (2.3%), 4 (3.0%), and 5 patients (3.8%), respectively. The rate of regional lymph node recurrence within the dissection field was only 4.5%. The prognosis of patients with lymph node metastasis was significantly poorer than that of patients without lymph node metastasis. However, the prognosis of the 11 cases that had metastasis only around RLNs was similar to that of node-negative cases. Thirteen patients with pathological remnant tumor (R1 or R2) did not survive longer than 5 years at present. The overall 5-year survival rate of stage I, II, and III disease after curative VATS was 82.2%, 77.0%, and 52.3%, respectively. Expansion of VATS criteria for patients after induction chemotherapy for T4 tumor or thoracoscopic anastomosis did not adversely affect the surgical results by experience. Although the VATS procedure is accompanied by a certain degree of morbidity including RLN palsy and pulmonary complications, VATS has an excellent locoregional control effect. In addition, the favorable survival after VATS shows that the procedure is oncologically feasible.

Granulocyte and monocyte adsorption apheresis as an effective treatment for Reiter disease.

Reiter disease (RD) is characterized by a triad of sterile arthritis, urethritis and conjunctivitis. The conditions occur concomitantly or sequentially, and are associated with mucocutaneous features such as circinate balanitis and stomatitis. Arthritis usually occurs in attacks followed by recovery, but it sometimes progresses to permanent damage of the affected joints. Because the symptoms of this disorder are attributable to activated neutrophils, we assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) in a 73-year-old man with RD who had skin rashes on his penis, scrotum and right hand, with severe arthralgia. The patient's skin rash and joint pain responded dramatically to five sessions of GCAP delivered at intervals of 5 days. We present a detailed description of the patient and discuss the mechanisms of GCAP, and suggest that GCAP may be useful for treating RD.

[Video-assisted thoracic surgery for pneumothorax in patients over fifty years of age].

BACKGROUND: Pneumothorax in middle-aged and elderly patients has various different features from young patients. We set out to investigate the outcome and usefulness of video-assisted thoracic surgery (VATS) in this group. PATIENTS AND METHODS: From January 1993 to August 2010, 168 patients underwent a total of 178 thoracoscopic surgeries. There were 160 men and 8 women with mean age of 67 (range, 50 to 85). The average duration of thoracic drainage before surgery was 7.4 days. We excised only responsible lesions as minimum degree of dissection as possible. When patients have intractable air leakage and chest computed tomography (CT) indicates severe pleural adhesions, pleurography should be performed to locate the site of air leakage and determine surgical approaches. One hundred and seventy patients were treated with the lateral approach, while 8 patients were successfully treated with the anterior approach. One hundred and fifty-one patients were treated with VATS alone, and 27 patients were treated with the combination of VATS and small thoracotomy. The duration of chest tube drainage, hospital stay, post-operative complication, outcome and recurrence were assessed. RESULTS: The air leakages stopped and all patients except for 2 patents were discharged without drainage tubes. Postoperative drainage time was 4.5 +/- 3.4 days. Postoperative hospital stay was 9.9 +/- 13.9 days. One patient died caused by perioperative myocardial infarction. Seventeen patients died of other diseases. Seven patients needed local hospital treatments and the recurrence rate was 3.9%. CONCLUSION: VATS for pneumothorax in patients over 50 years old is very useful by appropriate perioperative managements.

Genomic signatures of the evolution of defence against its natural enemies in the poisonous and medicinal plant Datura stramonium (Solanaceae).

Tropane alkaloids and terpenoids are widely used in the medicine and pharmaceutic industry and evolved as chemical defenses against herbivores and pathogens in the annual herb Datura stramonium (Solanaceae). Here, we present the first draft genomes of two plants from contrasting environments of D. stramonium. Using these de novo assemblies, along with other previously published genomes from 11 Solanaceae species, we carried out comparative genomic analyses to provide insights on the genome evolution of D. stramonium within the Solanaceae family, and to elucidate adaptive genomic signatures to biotic and abiotic stresses in this plant. We also studied, in detail, the evolution of four genes of D. stramonium-Putrescine N-methyltransferase, Tropinone reductase I, Tropinone reductase II and Hyoscyamine-6S-dioxygenase-involved in the tropane alkaloid biosynthesis. Our analyses revealed that the genomes of D. stramonium show signatures of expansion, physicochemical divergence and/or positive selection on proteins related to the production of tropane alkaloids, terpenoids, and glycoalkaloids as well as on R defensive genes and other important proteins related with biotic and abiotic pressures such as defense against natural enemies and drought.

Prospective randomized controlled study on the effects of perioperative administration of a neutrophil elastase inhibitor to patients undergoing video-assisted thoracoscopic surgery for thoracic esophageal cancer.

Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of neutrophil elastase (NE) and is effective in reducing acute lung injury associated with systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative acute lung injury in patients undergoing thoracoscopic esophagectomy and radical lymphadenectomy. Twenty-two patients with thoracic esophageal cancer underwent video-assisted thoracoscopic esophagectomy with extended lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given methylprednisolone immediately before surgery. Postoperative clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial oxygen pressure/fraction of inspired oxygen ratio, white blood cell count, serum C-reactive protein level, plasma cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the sivelestat-treated group than in the control group (P= 0.007). The median arterial oxygen pressure/fraction of inspired oxygen ratio of the sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum C-reactive protein levels, plasma interleukin-1beta, tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6, surfactant protein-A, or surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of lung injury. Plasma interleukin-8 levels were significantly lower in the sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative hypoxia, partially suppressed postoperative hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic esophagectomy.

Learning of thoracoscopic radical esophagectomy: how can the learning curve be made short and flat?

Attainment of proficiency in video-assisted thoracoscopic radical esophagectomy (VATS) for thoracic esophageal cancer requires much experience. We have mastered this procedure safely under the direction of an experienced surgeon. After adoption of the procedure, the educated surgeon directed induction of this surgical procedure at another institution. We evaluated the efficacy of instruction during the induction period by comparing the results at the two institutions in which VATS had been newly induced. We defined the induction period as the time from the beginning of VATS to the time when the last instruction was carried out. From January 2003 to December 2007, 53 patients were candidates for VATS at Kanazawa University (institution 1). Of these, 46 patients underwent curative VATS by a single operator. We divided this period into three parts: the induction period of VATS, post-induction period, and proficient period when the educated surgeon of institution 1 directed the procedure at Maebashi Red Cross Hospital (institution 2). At institution 1, 12 VATS were scheduled, and nine procedures (75%) (group A) including eight instructions were completed during the induction period (from January 2003 to August 2004). Thereafter, VATS was performed without instruction. In the post-induction period, nine VATS were scheduled, and eight procedures (88.8%) (group B) were completed from September 2004 to August 2005. Subsequently, 32 VATS were scheduled, and 29 procedures (90.6%) (group C) were completed during the proficient period (from September 2005 to December 2007). The surgeon at Maebashi Red Cross Hospital (institution 2) started to perform VATS under the direction of the surgeon who had been educated at institution 1 from September 2005. VATS was completed in 13 (76.4%) (group D) of 17 cases by a single surgeon including seven instructions during the induction period at institution 2 from September 2005 to December 2007. No lethal complication occurred during the induction period at both institutions. We compared the results of VATS among four groups from the two institutions. There were no differences in the background and clinicopathological features among the four groups. The number of dissected lymph nodes and amount of thoracic blood loss were similar in the four groups (35 [22-52] vs 41 [26-53] vs 32 [17-69] vs 29 [17-42] nodes, P = 0.139, and 170 [90-380] vs 275 [130-550] vs 220 [10-660] vs 210 [75-543] g, P = 0.373, respectively). There was no difference in the duration of the thoracic procedure during the induction period at the two institutions. However, the duration of the procedure was significantly shorter in the proficient period of institution 1 (group C: 266 [195-555] minutes) than in the induction period of both institutions (group A: 350 [280-448] minutes [P = 0.005] and group D: 345 [270-420] mL [P = 0.002]). There were no surgery-related deaths in any of the groups. The incidence of postoperative complications did not differ among the four groups. Thoracoscopic radical esophagectomy can be mastered quickly and safely with a flat learning curve under the direction of an experienced surgeon. The educated surgeon can instruct surgeons at another institution on how to perform thoracoscopic esophagectomy. The operation time of thoracoscopic surgery is shortened by experience.

Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes.

AIMS/HYPOTHESIS: Maternal diabetes during pregnancy increases the risk of congenital malformations such as neural tube defects (NTDs). Although the mechanism of this effect is uncertain, it is known that levels of nitric oxide synthase (NOS) and nitric oxide are elevated in embryos of a mouse model of diabetes. We postulated that overproduction of nitric oxide causes diabetes-induced congenital malformations and that inhibition of inducible NOS (iNOS) might prevent diabetic embryopathy. METHODS: Mice were rendered hyperglycaemic by intraperitoneal injection of streptozotocin. The incidence of congenital malformations including NTDs was evaluated on gestational day 18.5. We assessed the involvement of iNOS in diabetes-induced malformation by administering ONO-1714, a specific inhibitor of iNOS, to pregnant mice with streptozotocin-induced diabetic mice and by screening mice with iNOS deficiency due to genetic knockout (iNos(-/-)). RESULTS: ONO-1714 markedly reduced the incidence of congenital anomalies, including NTDs, in fetuses of a mouse model of diabetes. It also prevented apoptosis in the head region of fetuses, indicating that iNOS is involved in diabetes-related congenital malformations. Indeed, no NTDs were observed in fetuses of diabetic iNos(-/-) mice and the incidence of other malformations was also markedly reduced. CONCLUSIONS/INTERPRETATION: We conclude that increased iNOS activity during organogenesis plays a crucial role in the pathogenesis of diabetes-induced malformations and suggest that inhibitors of iNOS might help prevent malformations, especially NTDs, in diabetic pregnancy.