Impact of various intensities and frequencies of non-occupational physical activity on the risk of dementia among physically independent older adults: the Japan Gerontological Evaluation Study.

OBJECTIVES: The aim of this study was to investigate the association between different intensities and frequencies of non-occupational physical activity (PA) and the risk of dementia among Japanese older adults. STUDY DESIGN: This was a prospective cohort study. METHODS: A total of 2194 participants aged ≥65 years from the Japan Gerontological Evaluation Study were followed up between 2010 and 2016. The standardised dementia scale of the long-term care insurance system was used to identify incident dementia, whereas non-occupational PA (<2 or ≥2 times/week on each intensity: light, moderate and vigorous) was assessed using a questionnaire. Cox regression was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia. RESULTS: After adjustment for sociodemographic and medical characteristics, the following frequencies and intensities of non-occupational PA, compared with no non-occupational PA at all, were associated with a reduced risk of dementia: light PA ≥2 times/week (HR = 0.61, 95% CI: 0.38-0.97), moderate PA <2 times/week (HR = 0.46, 95% CI: 0.28-0.76), moderate PA ≥2 times/week (HR = 0.57, 95% CI: 0.36-0.91), vigorous PA <2 times/week (HR = 0.40, 95% CI: 0.21-0.74) and vigorous PA ≥2 times/week (HR = 0.29, 95% CI: 0.15-0.57). In the sex-specific analysis, moderate PA <2 times/week and vigorous PA ≥2 times/week were associated with a reduced risk of dementia in men, whereas light and moderate PA ≥2 times/week and all frequencies of vigorous PA were associated with a reduced risk of dementia in women. CONCLUSIONS: Practicing non-occupational PA was associated with a reduced risk of dementia among Japanese older adults.

Diffuse pollution monitoring and modelling of small urban watershed in Brazil Cerrado.

The stormwater runoff carries different pollutants that can reduce the quality of receiving waters due to diffuse pollutant loads. This research was aimed at evaluating the concentration of pollutants in stormwater and the application of SWMM (Storm Water Management Model) to an urban catchment in Lake Paranoá watershed to carry out the simulation of flow discharge with the hydraulic model, and subsequently to estimate the loads conveyed to the lake in ordinary events of precipitation. This study was carried out based on rainfall and runoff monitoring during events. It was confirmed that this model's results fit well in simulation of this type of watershed, leading to high value of the Nash-Sutcliffe coefficient after calibration but, as expected, precipitation distribution is a very important factor for calibration. Concerning water quality, it was observed that the event mean concentration values of suspended solids and chemical oxygen demand were high, indicating that the diffuse pollution is an important source of pollution of the receiving waters. The monitoring and modelling of stormwater are essential to identify diffuse pollution discharge, in searching for a sustainable solution.

Cancer survivors exhibit a different relationship between muscle strength and health-related quality of life/fatigue compared to healthy subjects.

We investigated the difference in relationship between muscle strength and quality of life (QOL)/fatigue in long-term cancer survivors and healthy subjects. Thirty-six cancer survivors and 29 healthy subjects were assessed for body composition and bone status at the calcaneus using the Osteo Sono Assessment Index. Muscle strength was evaluated via handgrip and knee extensor strength. Health-related QOL was assessed using the Medical Outcome Study 36-item Short-Form Health Survey. Fatigue was measured using the brief fatigue inventory. Cancer survivors exhibited lower QOL scores in the physical functioning, physical role function, bodily pain and general health domains (p < .05). Grip and knee extension muscle strength in cancer survivors was positively correlated with the physical function and bodily pain of QOL (p < .05). The usual fatigue subscale score was only significantly higher in cancer survivors than in healthy subjects (p < .05). However, there were no correlations between muscle strength and fatigue in cancer survivors. Our results showed that muscle strength was an important factor for improving QOL in cancer survivors. We believe that the findings of this study will be relevant in the context of planning rehabilitation for cancer survivors.

Hydrodynamic characteristics of a membrane oxygenator: modeling of pressure-flow characteristics and their influence on apparent viscosity.

The viscosity obtained from pressure-flow characteristics of an oxygenator may help to detect factors that change oxygenator resistance. The objective of this study was to model pressure-flow characteristics of a membrane oxygenator with an integrated arterial filter and to quantify their influence on apparent viscosity of non-Newtonian fluids. One Newtonian fluid (glycerin solution) and two non-Newtonian fluids (whole bovine blood and a human red blood cell suspension) were perfused through an oxygenator and their pressure-flow characteristics examined systematically. Four resistance parameters for the pressure gradient characteristics approximation equation were obtained by the least squares method from the relational expression of pressure-flow characteristics and viscosity. For all three fluids, a non-linear flow to pressure change was observed with a coefficient of determination of almost 1 by exponential approximation. The glycerin solution had a higher pressure gradient (10-70%) than the other fluids; the apparent viscosity of the non-Newtonian fluids was around 35% lower than the static one measured by a torsional oscillation viscometer. Overall, our study demonstrated that the influence on the apparent viscosity of non-Newtonian fluids can be quantified by pressure gradient differences in a membrane oxygenator with an integrated arterial filter.

Preliminary development and evaluation of the support system for care of mechanically ventilated patients.

BACKGROUND: We wanted to demonstrate the feasibility of a novel computer-assisted ventilator alarm system, the support system for care of mechanically ventilated patients (SCMVP), to detect gas leaks and provide graphical information on the site of the leak in a manikin model. METHODS: We tested six leakage scenarios. Four scenarios were applied to both the respiratory circuits with the SCMVP and without the SCMVP (conventional system), and two scenarios were each specific to one of the systems. Fifteen registered nurses were asked to manage three scenarios each (two mutual and one system-specific scenario). Time to identify the site of the leak was measured and compared between the two systems. RESULTS: The SCMVP showed significantly shorter time for troubleshooting in one of the four mutual scenarios and shorter accumulated time for troubleshooting in the four mutual scenarios [18.0 (range, 14.5-19.5) and 48.5 (9.0-180.0) s, respectively] compared with the conventional system [76.0 (47.0-133.8) and 82.5 (16.0-180.0) s, respectively]. In the mutual scenarios, SCMVP resulted in significantly more frequent incidences of successful troubleshooting within 30 s and less frequent incidences of troubleshooting requiring >180 s [43.3% (13/30) and 6.7% (2/30), respectively] compared with the conventional system [13.3% (4/30) and 30% (9/30), respectively]. CONCLUSIONS: The SCMVP can facilitate rapid and successful recognition of the site of leak in a respiratory circuit in a simulation environment.

Development of loop-mediated isothermal amplification assay for the detection of Pythium myriotylum.

UNLABELLED: This study reports the development of a loop-mediated isothermal amplification (LAMP) reaction for the detection of Pythium myriotylum. The primer set targeting the ITS sequence of P. myriotylum worked most efficiently at 60°C and allowed the detection of P. myriotylum DNA within 30 min by fluorescence monitoring using a real-time PCR instrument. The peak denaturing temperature of amplified DNA was about 87·0°C. In specificity tests using eight Pythium myriotylum strains, 59 strains from 39 species of Pythium, 11 Phytophthora strains and eight other soil-borne pathogens, LAMP gave no cross-reactions. The detection limit was 100 fg of genomic DNA, which was as sensitive as PCR. LAMP could detect P. myriotylum in hydroponic solution samples, and the results coincided with those of the conventional plating method in almost all cases. The LAMP method established in this study is a simple and sensitive tool for the detection of P. myriotylum. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the first LAMP assay for the detection of Pythium myriotylum. The primer set designed from ITS region of P. myriotylum can detect the pathogen in field sample with a fast and convenient method. Analysis of the annealing curve of the LAMP reaction products increases the reliability of the LAMP diagnosis. This study shows that the diagnostic method using the LAMP assay is useful for monitoring P. myriotylum in the field.

Integrin α3 is overexpressed in glioma stem-like cells and promotes invasion.

BACKGROUND: Glioma stem-like cell (GSC) properties are responsible for gliomagenesis and recurrence. GSCs are invasive but its mechanism remains to be elucidated. Here, we attempted to identify the molecules that promote invasion in GSCs. METHODS: Neurospheres and CD133⁺ cells were collected from glioblastoma (GBM) specimens and glioma cell lines by sphere-formation method and magnetic affinity cell sorting, respectively. Differential expression of gene candidates, its role in invasion and its signaling pathway were evaluated in glioma cell lines. RESULTS: Neurospheres from surgical specimens attached to fibronectin and laminin, the receptors of which belong to the integrin family. Integrin α3 was overexpressed in CD133⁺ cells compared with CD133⁻ cells in all the glioma cell lines (4 out of 4). Immunohistochemistry demonstrated the localisation of integrin α3 in GBM cells, including invading cells, and in the tumour cells around the vessels, which is believed to be a stem cell niche. The expression of integrin α3 was correlated with migration and invasion. The invasion activity of glioma cells was linked to the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. CONCLUSION: Our results suggest that integrin α3 contributes to the invasive nature of GSCs via ERK1/2, which renders integrin α3 a prime candidate for anti-invasion therapy for GBM.

Dose escalation study of carboplatin-pemetrexed followed by maintenance pemetrexed for elderly patients with advanced nonsquamous nonsmall-cell lung cancer.

BACKGROUND: This study was designed to determine the recommended dose of carboplatin-pemetrexed in elderly (≥75 years old), chemotherapy-naive patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received escalated doses of carboplatin and pemetrexed every 3 weeks for four cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed. RESULTS: The combination of carboplatin at an area under the concentration-time curve (AUC) of 5, and 500 mg/m(2) pemetrexed, was determined to be the recommended dose for elderly patients with advanced nonsquamous NSCLC. Of 17 patients, 10 received a median of five cycles of pemetrexed maintenance therapy without unexpected or cumulative toxic effects. The study had an overall response rate of 47.1%. The median progression-free survival time was 142 days (95% confidence interval [CI] 68-216 days) and the median overall survival time was 461 days (95% CI 168-754 days). CONCLUSIONS: This combination was a tolerable and effective regimen, and recommended dose (RD) was carboplatin [area under the curve (AUC) of 5]/pemetrexed (500 mg/m(2)) every 3 weeks, in chemotherapy-naïve, elderly (≥75 years old) patients with advanced nonsquamous NSCLC.

Genetic variation of Gongylonema pulchrum from wild animals and cattle in Japan based on ribosomal RNA and mitochondrial cytochrome c oxidase subunit I genes.

The gullet worm (Gongylonema pulchrum) has been recorded from a variety of mammals worldwide, including monkeys and humans. Due to its wide host range, it has been suggested that the worm may be transmitted locally to any mammalian host by chance. To investigate this notion, the ribosomal RNA gene (rDNA), mainly regions of the internal transcribed spacers (ITS) 1 and 2, and a cytochrome c oxidase subunit I (COI) region of mitochondrial DNA of G. pulchrum were characterized using parasites from the following hosts located in Japan: cattle, sika deer, wild boars, Japanese macaques, a feral Reeves's muntjac and captive squirrel monkeys. The rDNA nucleotide sequences of G. pulchrum were generally well conserved regardless of their host origin. However, a few insertions/deletions of nucleotides along with a few base substitutions in the ITS1 and ITS2 regions were observed in G. pulchrum from sika deer, wild boars and Japanese macaques, and those differed from G. pulchrum in cattle, the feral Reeves's muntjac and captive squirrel monkeys. The COI sequences of G. pulchrum were further divided into multiple haplotypes and two groups of haplotypes, i.e. those from a majority of sika deer, wild boars and Japanese macaques and those from cattle and zoo animals, were clearly differentiated. Our findings indicate that domestic and sylvatic transmission cycles of the gullet worm are currently present, at least in Japan.

Formation and evolution of carbonaceous asteroid Ryugu: Direct evidence from returned samples.

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide-bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu's parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of <1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate that Ryugu's parent body formed ~2 million years after the beginning of Solar System formation.

Natural history of lymph pumping pressure after pelvic lymphadenectomy.

Lower limb lymphedema is difficult to prevent and diagnose early because its natural history is unclear. Therefore, the aim of this study was to clarify its pathogenesis and to identify risk factors that may lead to early diagnosis. In 29 patients, aged 25 to 74 years with cervical, uterine, or ovarian cancer who underwent pelvic lymphadenectomy, indocyanine green fluorescence lymphangiography was performed with an infrared camera system, and lymph pumping pressure was measured indirectly preoperatively, and one, two, three, and six months postoperatively. Of these 29 patients, 22 (75.9%) completed the examinations. In the non-lymphedema group, the average lymph pumping pressure did not change significantly at postoperative follow-up compared with preoperative values. On the other hand, lymph pumping pressure increased at various time points in five patients who developed early lymphatic changes with dermal diffusion at the level of the proximal femur. An increase in lymph flow path resistance due to pelvic lymphadenectomy resulted in an initial increase in lymph pumping pressure, followed by a subsequent decrease, in the early lymphatic changes group. This trend in the pressure change signifies that the lymph vessels became dysfunctional as they were overwhelmed by the overload condition and this feature may be a clinically useful signal for the early diagnosis of developing lymphedema.

Evaluation of the efficacy of orange roughy (Hoplostetbus atlanticus) oil in subjects with dry skin.

Moisturizers have beneficial effects in treating dry skin. The objective of this study was to evaluate the effect of orange roughy (Hoplostethus atlanticus) oil, a marine-derived wax ester, on skin dryness in comparison with a reference commercially available petrolatum-based moisturizer (Vaseline) and untreated control. Subjects (n = 24) with moderate to severe skin dryness at the lower limb of legs (Study 1) and with certain degree of skin dryness on the face and the forearms (n = 22, Study 2) were treated twice a day for 42 consecutive days with the test products in randomized clinical trials. Transepidermal water loss (TEWL) was measured at the beginning and the end of Study 1, whereas skin hydration was measured at the beginning, after 3 and 6 weeks of the application (the end of the study) in Study 2. Changes in the skin dryness were assessed by a dermatologist using a video microscopy. In Study 1, the dryness score of skin applied with orange roughy oil improved significantly (P < 0.01) in 6 weeks. The skin looked smooth with no or little dry scaly skin. Orange roughy oil was evaluated with a 60% efficacy in treating skin dryness by the expert, which comparable to that of petrolatum (68%). No significant change in TEWL was found either in orange roughy oil or petrolatum treatment, although the values showed a tendency to improve in both cases. Similarly, the results of the skin capacitance in Study 2 showed a significant improvement of the skin symptoms after 3 and 6 weeks. These results showed that the performance of orange roughy oil in treating skin dryness was comparable to that of petrolatum.

Toll-like receptor 4-dependent adjuvant activity of Kakkon-to extract exists in the high molecular weight polysaccharide fraction.

Kakkon-to, a traditional herbal medicine (Kampo formula), has been used historically in China and Japan for the treatment of infectious diseases such as influenza and the common cold. However, the biological mechanism of its therapeutic action has not yet been elucidated. In this study, we investigated the immunological function of Kakkon-to and found that the high molecular weight fraction of the extract activated macrophages in vitro. This fraction was found to be composed primarily of saccharides and in vitro intensively stimulated mouse peritoneal macrophages that produce Th1 inflammatory cytokines such as tumor necrosis factor α (TNFalpha), interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6). The fraction did not activate macrophages from C3H/HeJ lacking Toll-like receptor 4 (TLR4) or MyD88-deficient mice, indicating that macrophage activation by the fraction was mediated by TLR4. The route of administration of the fraction into mice regulated the kinetics of TNFalpha production in immune organs. Intravenous administration induced TNFalpha production in the four target organs of spleen, liver, lung, and Peyer’s patch; however, the most abundant production occurred in the liver and peaked at 30-60 min post administration. Peritoneal administration induced similar kinetics but the most abundant production occurred in the spleen. In contrast, oral administration induced TNFalpha production in the liver, lung, and Peyer’s patch, but not in the spleen. Although liver and lung are TNFalpha-abundant organs, production peaks in these organs occurred later than in Peyer’s patch. We also found that the fraction induced antibody production as an adjuvant against a specific antigen ovalbumin (OVA) when administered simultaneously and subcutaneously in a dose-dependent manner. Interestingly, the fraction induced IgG-class antibody in response to low doses of the antigen, which induced only IgM-class antibody when administered alone, suggesting that the fraction induces a class switch of immunoglobulin as an adjuvant in vivo. The high molecular weight fraction of Kakkon-to extract could be applicable as a potent immunostimulating drug and adjuvant.

Transient and mild reduction of consciousness during febrile illness in children.

We have studied the clinical and neuroimaging characteristics of transient and mild reduction of consciousness during febrile illness in children. We retrospectively evaluated 58 children admitted with mild reduction of consciousness within 12 h during febrile illness. 53 patients (91%) had delirious behavior, and 5 (9%) had no delirious behavior. We also compared the clinical characteristics, brain magnetic resonance imaging (MRI) findings, and electroencephalography (EEG) findings between patients with and without delirious behavior, and no statistically significant differences were observed in any of them between the 2 patient groups (P≥0.05). MRI was performed 0-4 days after onset in 23 patients. Reversible splenial or callosal and white matter lesions were observed in 2 of 3 patients without delirious behavior vs. 4 of 20 patients with delirious behavior on diffusion-weighted images. EEG was performed 0-3 days after onset in 29 patients. Transient abnormal findings were observed in 3 of 4 patients without delirious behavior vs. 11 of 25 patients with delirious behavior. In conclusion, we consider that transient and mild reduction of consciousness during febrile illness is a unique clinical group that is constituted by children both with and without delirious behavior.

TL antigen as a transplantation antigen recognized by TL-restricted cytotoxic T cells.

In contrast to broadly expressed classical class I antigens of the major histocompatibility complex, structurally closely related TL antigens are expressed in a highly restricted fashion. Unlike classical class I antigens, TL antigens are not known to be targets of cytotoxic T cells or to mediate graft rejection. Whereas classical class I antigens function as antigen-presenting molecules to T cell receptors (TCR), the role of TL is yet to be defined. To elucidate the function of TL, we have derived transgenic mice expressing TL in most tissues including skin by introducing a TL gene, T3b of C57BL/6 mouse origin, driven by the H-2Kb promoter. By grafting the skin of transgenic mice, we demonstrate that TL can serve as a transplantation antigen and mediate a TCR-alpha/beta+ CD8+ cytotoxic T cell response. This T cell recognition of TL does not require antigen presentation by H-2 molecules. Furthermore, we show that C57BL/6 F1 mice develop CD8+ T cells that are cytotoxic for C57BL/6 TL+ leukemia cells, providing further support for the concept that aberrantly expressed nonmutated proteins such as TL can be recognized as tumor antigens.

Is response rate increment obtained by molecular targeted agents related to survival benefit in the phase III trials of advanced cancer?

BACKGROUND: It remains unclear whether response rate (RR) is related to survival benefit in phase III trials of advanced cancer treated with molecular targeted agents (MTA) in combination with standard therapies. MATERIALS AND METHODS: We carried out a systematic search of PubMed for randomized phase III trials of four solid tumors examining the efficacy of MTA when added to a standard therapy. We examined whether there were any associations between RR increment obtained by the addition of targeted agents (DeltaRR) and survival benefit in phase III trials. RESULTS: We identified 26 phase III trials of MTA with a total of 21 156 patients and 29 experimental arms of MTA. Studies which showed significant survival benefit had higher DeltaRR compared with those which did not show significant benefit. In the receiver operating characteristic curve analysis, using a 7% gain as threshold value for DeltaRR allowed assessment of survival benefit with high sensitivity and specificity. There were also significant relationships between DeltaRR and hazard ratios for overall survival and progression-free survival in the linear regression analysis. CONCLUSION: RR increment obtained by the addition of MTA to a standard therapy may be useful to predict survival benefit in clinical phase III trials of advanced cancer.

Microendoscopic resection of lumbar discal cysts.

INTRODUCTION: A lumbar discal cyst is a relatively rare cystic lesion that communicates with lumbar intervertebral discs. Surgical resection of the cyst is the reported treatment of choice. In this study, the authors report the minimally invasive surgical resection of lumbar discal cysts using a microendoscopy. PATIENTS AND METHODS: Seven male patients with lumbar discal cysts underwent microendoscopic resections (mean age: 25.1+/-3.2 years and the mean follow-up period: 27.9 months). During the surgeries, the cysts were subtotally resected in a piecemeal fashion, and the fistulas forming the communications between the cysts and the corresponding intervertebral discs were coagulated using a bipolar coagulator. RESULTS: All the patients obtained relief from their pain after surgery, and no recurrences occurred during a mean follow-up period of 28 months. The mean operation time was 72.6+/-20.2 min, and the mean blood loss was 44.4+/-13.7 grams. No intra- or peri-operative complications were noted in any of the patients. CONCLUSIONS: Microendoscopic resection appears to be a minimally invasive and feasible surgical option for the treatment of lumbar discal cysts.

Metabolic Syndrome and Cognitive Function: Cross-Sectional Study on Community-Dwelling Non-Demented Older Adults in Japan.

AIM: This is a cross-sectional study of relation between metabolic syndrome and cognitive function in community-dwelling non-demented older adults in Japan. We examine the effect of metabolic syndrome and its components on global cognitive function. We also aim to clarify differences of specific cognitive domains between the subjects with and without metabolic syndrome. METHODS: We studied 2150 subjects aged between 60 and 90 years whose scores on mini mental state examination (MMSE) were over 23 points. We analyzed difference in MMSE scores between the subjects with and without metabolic syndrome. Logistic regression analysis was performed with MMSE score as the dependent variable and metabolic syndrome components as the independent variable adjusted with age. We also examined differences in attention, logical memory, and verbal and category fluency between the subjects with and without metabolic syndrome. RESULTS: MMSE scores were not significantly different between subjects with and without metabolic syndrome. In logistic regression analysis, the score of MMSE was significantly negatively associated with triglycerides in males and significantly negatively associated with abdominal circumference in females. Subjects with metabolic syndrome showed significantly lower performance of attention tasks compared to subjects without metabolic syndrome. CONCLUSIONS: Our results suggest that in community-dwelling non-demented Japanese older adults, attention but not global cognitive function may be impaired by metabolic syndrome. Inverted association between some components of metabolic syndrome and global cognitive function indicate necessity of further studies on the relation between undernutrition and cognitive function.