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• What is the primary question addressed by this study? Are there specific anxiety symptoms associated with Alzheimer's disease pathologies, amyloid-β and tau, in cognitively unimpaired older adults? • What is the main finding of this study? Greater amyloid-β deposition was associated with higher levels of self-reported worry but not global anxiety, independent of subjective and objective cognition and depression. No associations were found between regional tau deposition and either worry or global anxiety. • What is the meaning of the finding? These findings implicate worry as an early, specific behavioral marker and possible therapeutic target in preclinical AD. Anxiety disorders and subsyndromal anxiety symptoms are highly prevalent in late life. Recent studies support that anxiety may be a neuropsychiatric symptom during preclinical Alzheimer's disease (AD) and that higher anxiety is associated with more rapid cognitive decline and progression to cognitive impairment. However, the associations of specific anxiety symptoms with AD pathologies and with co-occurring subjective and objective cognitive changes have not yet been established. Baseline data from the A4 and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies were analyzed. Older adult participants (n = 4,486) underwent assessments of anxiety (State-Trait Anxiety Inventory–6 item version [STAI]), and cerebral amyloid-beta (Aβ; 18F-florbetapir) PET and a subset underwent tau (18F-flortaucipir) PET. Linear regressions estimated associations of Aβ in a cortical composite and tau in the amygdala, entorhinal, and inferior temporal regions with STAI-Total and individual STAI item scores. Models adjusted for age, sex, education, marital status, depression, Apolipoprotein ε4 genotype, and subjective and objective cognition (Cognitive Function Index-participant; Preclinical Alzheimer Cognitive Composite). Greater Aβ deposition was significantly associated with higher STAI-Worry, adjusting for all covariates, but not with other STAI items or STAI-Total scores. In mediation analyses, the association of Aβ with STAI-Worry was partially mediated by subjective cognition with a stronger direct effect. No associations were found for regional tau deposition with STAI-Total or STAI-Worry score. Greater worry was associated with Aβ but not tau deposition, independent of subjective and objective cognition in cognitively unimpaired (CU) older adults. These findings implicate worry as an early, specific behavioral marker and a possible therapeutic target in preclinical AD. [ABSTRACT FROM AUTHOR]

Studies have confirmed that anxiety, especially worry and rumination, are associated with increased risk for cognitive decline, including Alzheimer's disease and related dementias (ADRD). Hippocampal atrophy is a hallmark of ADRD. We investigated the association between hippocampus and its subfield volumes and late-life global anxiety, worry, and rumination, and emotion regulation strategies. We recruited 110 participants with varying worry severity who underwent magnetic resonance imaging and clinical interviews. We conducted cross-sectional regression analysis between each subfield and anxiety, worry, rumination, reappraisal, and suppression while adjusting for age, sex, race, education, cumulative illness burden, stress, neuroticism, and intracranial volume. We imputed missing data and corrected for multiple comparisons across regions. Greater worry was associated with smaller subiculum volume, whereas greater use of reappraisal was associated with larger subiculum and CA1 volume. Greater worry may be detrimental to the hippocampus and to subfields involved in early ADRD pathology. Use of reappraisal appears protective of hippocampal structure. Worry and reappraisal may be modifiable targets for ADRD prevention. • How is late-life anxiety and its phenotypes associated with hippocampal subfields? • We found that severe worry was associated with smaller subiculum volumes. • We additionally found that reappraisal was associated with larger subfield volumes. • Worry and reappraisal may be modifiable targets for Alzheimer's prevention. [ABSTRACT FROM AUTHOR]

Individuals with chronic pain due to knee osteoarthritis (OA) are insufficiently physically active, and alterations of facilitatory and inhibitory nociceptive signaling are common in this population. Our objective was to examine the association of these alterations in nociceptive signaling with objective accelerometer-based measures of physical activity in a large observational cohort. We used data from the Multicenter Osteoarthritis Study. Measures of peripheral and central pain sensitivity included pressure pain threshold at the knee and mechanical temporal summation at the wrist, respectively. The presence of descending pain inhibition was assessed by conditioned pain modulation (CPM). Physical activity was quantitatively assessed over 7 days using a lower back-worn activity monitor. Summary metrics included steps/day, activity intensity, and sedentary time. Linear regression analyses were used to evaluate the association of pain sensitivity and the presence of descending pain inhibition with physical activity measures. Data from 1873 participants was analyzed (55.9% female, age = 62.8 ± 10.0 years). People having greater peripheral and central sensitivity showed lower step counts. CPM was not significantly related to any of the physical activity measures, and none of the exposures were significantly related to sedentary time. In this cohort, greater peripheral and central sensitivity were associated with reduced levels of objectively-assessed daily step counts. Further research may investigate ways to modify or treat heightened pain sensitivity as a means to increase physical activity in older adults with knee OA. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Are late-life anxiety phenotypes associated with cerebrovascular burden as measured by white matter hyperintensities (WMH)? • What is the main finding of this study? Greater WMH burden is associated with lower global anxiety and worry severity but not rumination in late-life. Executive function may play a significant role in this finding for individuals with advanced age and/or WMH accumulation. • What is the meaning of the finding? Late-life anxiety phenotypes share a complex relationship with white matter hyperintensity burden, executive function, and age that requires longitudinal studies to disentangle. We investigated the relationship between anxiety phenotypes (global anxiety, worry, and rumination) and white matter hyperintensities (WMH), with special consideration for the roles of age and executive function (EF). Our hypotheses were 1) anxiety phenotypes would be associated with WMH and 2) EF would moderate this relationship. Cross-sectional. Participants were recruited from the local community (Pittsburgh, PA). We recruited 110 older adults (age ≥ 50) with varying worry severity and clinical comorbidity. Not applicable. Demographics (age, sex, race, education), clinical measures (cumulative illness burden, global anxiety, worry, and rumination), EF, and WMH quantified with magnetic resonance imaging. Lower global anxiety and worry severity were significantly correlated with higher WMH volume, though the global anxiety relationship was not significant after controlling for age. Rumination as not associated with WMH burden. EF was not correlated with either global anxiety, worry, rumination, or WMH. However, in those with advanced age and/or greater WMH burden, there was an association between worry and EF as well as EF and WMH. Longitudinal studies are needed in order to clarify the complex interactions between anxiety phenotypes, WMH, and EF. [ABSTRACT FROM AUTHOR]

To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t -test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p <0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the risk of ankle OA onset after an incidence of sprain, relative to the risk of onset in healthy population, and to investigate the effect of gender, age, BMI, and exercise on the development of ankle OA after sprain.Design: Retrospective cohort study.Methods: Using a sample cohort dataset from 2002 to 2013 provided by the Korean National Health Insurance Sharing Service, we calculated the mean survival time and cumulative incidence rate in sprained and healthy populations using Kaplan-Meier analysis. A Cox proportional hazards model was used to analyze the adjusted hazard ratio (HR) of sprain for the development of OA with 95% confidence intervals (CIs). Adjusted HRs of gender, age, BMI, and exercise (yes/no) were analyzed in the sprained group.Results: Among the selected population of 195,393 individuals, 40,876 (20.9%) were diagnosed with an ankle sprain, and 1543 (3.85%) of those individuals developed ankle OA. Of the 154,517 healthy individuals (79.1%), 4062 (2.66%) cases had progressed to OA. The sprained group had 46% (HR, 1.46; 95% CI, 1.38-1.55) greater rate of progression to ankle OA than did healthy individuals. In the sprain group, individuals who were female, obese, and overweight had 40% (HR, 1.40; 95% CI, 1.26-1.55), 43% (HR, 1.43; 95% CI, 1.12-1.82), and 22% (HR, 1.22; 95% CI, 1.10-1.35) higher incidence to develop ankle OA, respectively, compared to those who were male, underweight and normal.Conclusions: This study found that ankle sprain was a significant risk factor for a diagnosis of early OA. Female gender and high BMI increased the incidence of ankle OA after sprain. [ABSTRACT FROM AUTHOR]

Research reveals that murine lymphomas respond to cancer treatment through a senescence process controlled by p53 and p16(sup)INK4a genes as shown by poor response to chemotherapy by tumors containing mutations in the genes. Data indicate a connection between cellular senescence and treatment outcome in cancer management.

Background: Social cognition indicates the cognitive processes involved in perceiving, interpreting, and processing social information. Although it is one of the six core DSM-5 cognitive domains for diagnosing neurocognitive disorders, it is not routinely assessed in older adults. The Reading the Mind in the Eyes Test assesses Theory of Mind, the social cognition mechanism which forms the root of empathy.Objectives: To describe the distribution of, and factors associated with, scores on a 10-item version of Reading the Mind in the Eyes Test (RMET-10) in older adults.Design: Population-based cross-sectional study.Setting: Small-town communities in Pennsylvania.Participants: Adults aged 66-105 years (N = 902, mean age = 76.6).Measurements: The assessment included RMET-10, demographics, cognitive screening, literacy, depression symptoms, anxiety symptoms, cognitive composites derived from a neuropsychological test battery, Social Norms Questionnaire, and Clinical Dementia Rating (CDR).Results: RMET-10 score was normally distributed in our overall study sample. Normative RMET-10 scores among those rated as CDR = 0 were calculated by age, sex, and education. RMET-10 score was significantly higher with younger age, higher education, white race, higher cognitive screening scores, literacy, social norms scores, higher scores in all five domains in cognitive composites, and lower CDR. RMET-10 score was also significantly higher with fewer depression and anxiety symptoms after adjusting for demographics.Conclusions: The RMET is a potentially useful measure of social cognition for use in the research assessment of older adults. With appropriate calibration it should also have utility in the clinical setting. [ABSTRACT FROM AUTHOR]

People with knee osteoarthritis walk with excessive muscle co-contraction that can accelerate disease progression. Central pain sensitization is common in people with knee osteoarthritis and may be related to walking patterns. The objective of this study was to examine the relation of central pain sensitization with muscle co-contraction during walking in people with knee osteoarthritis. This study reports secondary analysis from baseline data of two clinical trials (n = 90 participants with knee osteoarthritis). The presence of central pain sensitization was measured by mechanical temporal summation at the patella and the wrist. Quadriceps and hamstrings activation was assessed using surface electromyography during walking at self-selected and fast paces. Muscle co-contraction indices for vastus medialis-medial hamstrings and vastus lateralis-lateral hamstrings muscle pairs were calculated during stance phases. Co-contraction outcomes were compared between people with and without mechanical temporal summation at each site, adjusting for age, sex, and body mass index. People with mechanical temporal summation at the knee had greater vastus lateralis-lateral hamstrings co-contraction while walking at a fast pace (P = 0.04). None of the other differences was statistically significant, but the overall trends and effect sizes indicated greater co-contraction in people with temporal summation at the knee irrespective of gait phase, walking speed, or muscle pairs. Central pain sensitization, assessed as mechanical temporal summation at the knee, is related to greater knee muscle co-contraction during fast walking in people with knee osteoarthritis. Thus, mitigating central sensitization may be an interventional target to reduce muscle co-contraction for people with knee osteoarthritis. • Greater temporal summation of pain is related to greater muscular co-contraction during walking. • Central sensitization could be one mechanism altering motor function in knee osteoarthritis. • Reducing pain sensitization may potentially help normalizing motor function. [ABSTRACT FROM AUTHOR]

Background: Maternal depression and suicidal ideation (SI) predict adolescent SI. However, the influence of paternal psychopathology is less clear. This study examines how parental psychopathology contributes to adolescent SI.Methods: Data from a cross-sectional, nationwide, population-based survey was used. It assessed 4,073 adolescents (12-18 years) and their parents identified through random sampling of the non-institutionalized population in Korea. Stress, depressed mood, and SI of parents and adolescents were assessed using multivariate logistic regression to determine the association of adolescents' SI with parental stress, depressed mood, and SI.Results: Adolescents who reported SI were more likely to be girls, have shorter sleep duration, more stress, and a depressed mood than were adolescents without SI. Logistic regression analysis showed estimated odds ratios for SI of 1.444 (p < .05), 1.485 (p < .05) and 1.801 (p < .05) for girls who had mothers with stress, depressed mood, and SI, respectively, and 2.113 (p < .05) and 3.091 (p < .05) for girls who had fathers with depressed mood and SI, respectively. Boys' SI was associated with father's depressed mood (OR: 2.608, p < .05).Limitations: Cross-sectional design and use of self-report measures.Conclusions: Girls' SI was related to both parents' stress, depressed mood, and SI except for father's stress, and boys' SI was related to father's depressed mood. Evaluations and therapeutic interventions for adolescents with SI should consider both adolescents and their parents, and family-based interventions could be one method for adolescent suicide prevention. [ABSTRACT FROM AUTHOR]

Highlights • Suggestion of a novel lift-generating disk type wind power system. • Integrated simulation of proposed system using Modelica. • Verification of Modelica simulation result by wind tunnel test data. • Prediction of power generation of actual scale model by similarity law. Abstract Wind power generation research and application technology have received much attention in the development of renewable energy. However, the traditional blade-rotating type wind power system has a number of drawbacks such as natural landscaping damage, flow-induced noise, and shadow flickering problems. In this paper, we propose a lift-generating disk-type blade power generation mechanism that can effectively generate wind power even with a simple structure considering the problems of the existing systems. Data on the lift force in relation to the shape of the designed blade were derived through a computational fluid dynamics simulation, and the Modelica language was used to model the integrated multi-physics wind power system. Then, a wind tunnel test was conducted using a small-scale model of the disk-type blade created to verify the simulation. The experimental results were in good agreement with the simulated results. Thus, we validated the modeling of the wind power system and applied the law of similarity to obtain the generator power output prediction results for the actual scale model. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Ulceration is a serious consequence of diabetes that can lead to disability in patients with diabetes. One of the risk factors for ulceration is high foot pressure. The thickness of the pedal soft tissue is important because it has a cushioning effect. Soft tissue atrophy causes elevation in the plantar pressure, which, in turn, causes ischemia. Therefore, we investigated the severity of pedal soft tissue atrophy caused by diabetes and aging. From February 2009 to February 2016, we examined the feet of 261 patients treated in our hospital using magnetic resonance imaging. We divided the patients enrolled in the study into 2 groups. The first group included 52 patients with diabetes but without peripheral arterial disease and the second group included 47 patients without diabetes. We measured the vertical distances under all patients' metatarsal heads using T1-weighted magnetic resonance imaging and measured the pedal soft tissue thickness using the PACS workstation (m-view). We compared the soft tissue thicknesses of the 2 groups and performed statistical analyses of the relationships between these data and other parameters using 2-way analysis of variance. The soft tissue under the first to fourth metatarsal heads was thinner in the diabetic patients than in the nondiabetic patients (first metatarsal, 6.4 versus 8.69; second metatarsal, 8.85 versus 10.64; third metatarsal, 8.15 versus 9.21; fourth metatarsal, 7.38 versus 8.54; p  < .05). Aging had no effect on pedal soft tissue atrophy in either group. In conclusion, our study confirmed that diabetic patients experience more severe plantar soft tissue atrophy than nondiabetic patients. We have developed a standard procedure to enable the prediction of pedal soft tissue atrophy severity in diabetic patients. [ABSTRACT FROM AUTHOR]

Purpose To investigate the dosimetric effects due to interfractional changes in catheter position and variation in patient's anatomy during the course of interstitial high-dose-rate (HDR) brachytherapy. Methods and Materials A total of 15 patients with either cervical or vaginal cancer underwent interstitial HDR brachytherapy. Interstitial catheters and fiducials were placed under fluoroscopy and intraoperative 3T MRI to confirm the desired catheter placement for adequate target volume coverage. Single plan was generated from first-fraction CT fused with the MRI and used for all fractions of treatment. CT image was acquired before each treatment and registered to the first-fraction CT. Displacement of fiducials and catheters was calculated for each fraction and its effects on dosimetric parameters such as dose covering 90% for high-risk clinical target volume and intermediate-risk clinical target volume and dose to the 2 cm 3 of the volume for bladder, rectum, sigmoid, and bowel were studied. Results Average movements of fiducials and catheters were 1.6 mm (range: 0.1–7.1 mm) and 1.7 mm (range: 0.1–4.5 mm), respectively. Overall, deviation of the delivered dose to the target in each fraction was insignificant for all patients ( p -value: 0.66 for high-risk clinical target volume and 0.87 for intermediate-risk clinical target volume). The mean dose to organs at risk showed maximum difference up to 0.9, 2.7, 1.6, and 2.1 Gy for bladder, rectum, sigmoid, and bowel, respectively ( p -value: 0.88, 0.34, 0.68, and 0.85 for bladder, rectum, sigmoid, and bowel, respectively). Conclusions The interfractional dosimetric variation for both target and organs at risk was within clinically acceptable limit throughout the entire course of interstitial HDR-Syed brachytherapy. Only 6% of cases performed replanning, which could be readily identified using CT imaging. [ABSTRACT FROM AUTHOR]

Background The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for adults aged ≥65 years. To evaluate functional immune response against the additional 11 serotypes that are included in PPSV23, but not the 13-valent pneumococcal conjugate vaccine (PCV13), serotype-specific anti-pneumococcal antibodies were examined using an opsonophagocytic assay (OPA). Methods Participants ≥65 years of age that were naïve to the pneumococcal vaccine were enrolled. They were divided into two groups according to their age: group 1 (N = 30; aged 65–74 years) and group 2 (N = 32; aged ≥75 years). The functional antibody response prior to and 4 weeks post-immunization with PPSV23 was determined, using a multiplexed OPA (MOPA) for 11 pneumococcal serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F). Results Geometric mean OPA titers (GMTs) to 11 serotypes were significantly increased in both groups post-immunization compared to those prior to immunization. The GMTs for all serotypes were not significantly different between the two groups after immunization. The proportion of subjects with OPA titers post-immunization of ≥8 and ≥64 was 93–100% and 80–100% for the 11 serotypes, respectively, while subjects with a ≥4-fold increase in OPA titers ranged from 9 to 90% for the 11 serotypes. Conclusions This study revealed that PPSV23 vaccination induced significant functional immune responses to 11 non-PCV13 serotypes in older adults. The MOPA has been shown to be a useful tool for future application in evaluating new PCVs in older adults. The clinical trial registration number is KCT 0001963 (CRIS, https://cris.nih.go.kr/cris/en/ ). [ABSTRACT FROM AUTHOR]

This study investigated the effect of lemongrass essential oil (LGEO) on the infectivity and viral replication of norovirus. Murine norovirus 1 (MNV-1), a surrogate of human norovirus, was preincubated with LGEO and then used to infect RAW 264.7 cells in a plaque reduction assay. LGEO exhibited a significant reduction in MNV-1 plaque formation in both time- and dose-dependent manners. The quantification of viral genome by quantitative real-time PCR showed similar results in line with those of the plaque reduction assay. It was revealed that citral, a single compound in LGEO, showed dramatic reduction in MNV-1 infectivity (−73.09% when using a treatment of 0.02%, v/v). The inhibitory activity of LGEO on viral replication was further investigated in HG23 cells that harbored a human norovirus replicon. LGEO treatment significantly reduced viral replication in HG23 cells, which suggests that LGEO may have dual inhibitory activities that inactivate viral coat proteins required for viral infection and suppress norovirus genome replication in host cells. In animal experiments, oral administration of murine norovirus preincubated with LGEO significantly suppressed virus infectivity in vivo. Collectively, these results suggest that LGEO, in particular the LGEO component citral, inactivates the norovirus and its subsequent replication in host cells. Thus, LGEO shows promise as a method of inhibiting norovirus within the food industry. [ABSTRACT FROM AUTHOR]

• Hyperthermal erosion of nanocomposites by atomic oxygen and nitrogen molecule was compared for the first time. • Optimum reactive simulation condition to mimic disintegration under low earth orbital environment was provided. • Atomic oxygen bombardment showed reaction-assisted disintegration and desorption of nanocomposites. • Attack of nitrogen molecules showed comparable surface erosion to the atomic oxygen bombardment without active reaction. • Erosion yield of nanocomposites comparable to the in-flight experiment could be obtained. Against the hyperthermal atomic oxygen (AO) bombardment, mitigation of the surface recession has been the main issue in designing surface shielding materials in low earth orbital (LEO) environment. Meanwhile, the role of nitrogen molecules (N 2) in LEO and sub-LEO on disintegration of the shielding materials has rarely been studied despite their abundance and non-negligible colliding energy. This study for the first time compared the surface chemistry and disintegration of Kapton polyimide-based nanocomposites under AO and N 2 bombardment conditions using a reactive molecular dynamics (MD) simulation. The heat transfer from the surface to the behind layer and the associated boundary condition for the bombardment simulation were primarily discussed to provide the optimum bombardment simulation setup. Polyhedral oligomeric silsesquioxane (POSS), carbon nanotube (CNT) and graphene were respectively blended with Kapton to evaluate the damage mitigation efficacy. The addition of all types of additives to Kapton induced a notable thermo-protection effect. AO bombardment resulted in a sequential disintegration of oxidation and desorption, whereas the surface recession of nanocomposites by exposure to N 2 collision was mainly caused by physical desorption. It was also noteworthy that the surface recession caused by N 2 bombardment was comparable to that by AO attack at the same fluence. [Display omitted]. [ABSTRACT FROM AUTHOR]

Social cognition is the cognitive domain that processes social information, the means by which we make sense of ourselves in relation to others and our environments. Impaired social cognition is associated with functional dependence on others and can have dire social consequences leading to social isolation, increasing the risk for morbidity and mortality. Social cognition is be impaired in neurodegenerative disorders including Alzheimer's disease (AD). The most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) include social cognition as one of six core domains of neurocognitive function, alongside memory, executive control, complex attention, language, and visuospatial/perceptuomotor function, that can be impaired in the neurocognitive disorders. We have previously reported population-based norms from older adults on two social cognition measures, the Social Norms Questionnaire [SNQ-22], assessing social perception, and the 10-question version of the Reading the Mind in the Eyes Test [RMET-10], measuring Theory of Mind (ToM). Here, we report on the utility of a social cognition composite measure comprising the SNQ-22 and the RMET-10. Participants are 902 adults from a population-based cohort in Pennsylvania. The mean age is 76.6 years (SD 8.06). We created a social cognition composite comprising standardized z-scores on the Social Norms Questionnaire and the 10-item Reading the Mind in the Eyes Test. We described its distribution in the population-based sample of older adults, its association with demographic factors, other cognitive and behavioral measures, the Clinical Dementia Rating (CDR®). We compared sensitivity, specificity, and the area under the curve of social cognition to those of other cognitive domains for mild cognitive impairment (MCI). We calculated the impact of including social cognition as a sixth cognitive domain on the estimated prevalence of (cohort proportion classified as) neuropsychologically defined MCI. Better social cognition was associated with younger age, female sex, higher education, better general cognition (MMSE), fewer depressive symptoms, and lower Clinical Dementia Rating (CDR). Adjusting for demographics, associations with higher MMSE and fewer depressive symptoms, anxiety symptoms, and subjective cognitive complaints remained significant. The sensitivity and specificity of social cognition for CDR = 0.5 were comparable to those of the traditional five cognitive domains. Including social cognition as the sixth domain of cognition resulted in a 5% increase in the estimated prevalence of MCI. Better social cognition was associated with younger age, female sex, higher education, better general cognition (MMSE), fewer depressive symptoms, and lower Clinical Dementia Rating (CDR). Adjusting for demographics, associations with higher MMSE and fewer depressive symptoms, anxiety symptoms, and subjective cognitive complaints remained significant. We found that social cognition had sensitivity, specificity for CDR that was comparable to those of the five conventional cognitive domains of attention, executive functions, language, memory, and visuospatial function. The AUC values in the 0.6 – 0.7 range, which were comparable to the reported values in the literature. Considering neuropsychologically defined MCI, the inclusion of social cognition as the sixth domain of cognition resulted in about 5% of the sample becoming newly classified as MCI. These individuals differed from those already classified as MCI only in having higher MMSE scores; but they differed from those still classified as normal in having more anxiety symptoms, lower reading levels, and impairment in the CDR domain of home and hobbies. It appears a worthwhile consideration for standard cognitive assessments in older adults to routinely include brief objective assessments of the social cognition domain. The word reported here was supported in part by research grant # R37AG023657 from the National Institute on Aging, National Institutes of Health, US Department of Health and Human Services. [ABSTRACT FROM AUTHOR]

p38 mitogen-activated protein kinase (MAPK) is a promising target for the development of therapeutics for various immunological diseases. We designed and synthesized aminothiazole-based p38 MAPK inhibitors of with IC 50 values ranging from 0.1 to 2 μM by means of the structure-based de novo design of phenyl-(2-phenylamino-thiazol-5-yl)-methanone scaffold. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further investigation as anti-inflammatory drugs. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are discussed in detail. [ABSTRACT FROM AUTHOR]

Summary Background Frontalis hypertonicity has long been implicated in patients with significant dermatochalasia or blepharoptosis, as evidenced by eyebrow changes that occur after the resection of redundant skin or after blepharoptosis operation. However, whether upper blepharoplasty affects the forehead muscle has not been reported. Thus, this study investigated electrophysiology of the frontalis muscle and eyebrow morphology in a population of patients undergoing double-eyelid blepharoplasty. Method Patients wishing to undergo upper blepharoplasty were recruited for this prospective study between June 2011 and February 2012. The subjects were excluded for complaints of visual obstruction, trauma history, and for any underlying medical condition that would affect eyebrow height or electromyogram (EMG) findings. Eyebrow morphology was ascertained in a standardized photogrammetric evaluation, and the frontalis muscle activity was recorded with needle EMG. These assessments were carried out at preoperation and at 2 weeks, 3 months, and 6 months. Root-mean-square (RMS) indices of various facial expressions were used to normalize the frontalis activity values across individuals. Results Thirteen patients with a mean age of 55.5 years were recruited. No statistical significance was observed for eyebrow heights at various assessment points. However, EMG recordings have demonstrated a gradual decrease in the proportional RMS index of the frontalis muscle activity. This difference was statistically significant between preoperation and 6 months postoperation ( p < 0.05). Conclusion Upper blepharoplasty was associated with gradual decreases in the frontalis muscle activity. A longer follow-up study is needed to evaluate whether this decreased tonicity results in morphologic changes such as decreased forehead wrinkles and depressed eyebrows. This research indicates that upper blepharoplasty has the potential to interfere with those human–computer interaction designs with facial EMG readings as an input. [ABSTRACT FROM AUTHOR]

Using total suspended solid (TSS) removal efficiency and hydraulic retention time (HRT) as design parameters a design guideline of a settling basin in a constructed wetland (CW) was suggested; as well as management of sediment and particle in the settling basin. The CW was designed to treat the piggery wastewater effluent from a wastewater treatment plant during dry days and stormwater runoff from the surrounding paved area during wet days. The first settling basin (FSB) in the CW was theoretically designed with a total storage volume (TSV) of 453 m 3 and HRT of 5.5 hr. The amount of sediment and particles settled at the FSB was high due to the sedimentation and interception of plants in the CW. Dredging of sediments was performed when the retention rate at the FSB decreased to approximately 80%. Findings showed that the mean flow rate was 21.8 m 3 /hr less than the designed flow rate of 82.8 m 3 /hr indicating that the FSB was oversize and operated with longer HRT (20.7 hr) compared to the design HRT. An empirical model to estimate the length of the settling basin in the CW was developed as a function of HRT and desired TSS removal efficiency. Using the minimum tolerable TSS removal efficiency of 30%, the length of the FSB was estimated to be 31.2 m with 11.8 hr HRT. [ABSTRACT FROM AUTHOR]

In the last few decades, changing socioeconomic and family structures have increasingly left children alone without adult supervision. Carefully prepared and limited periods of unsupervised time are not harmful for children. However, long unsupervised periods have harmful effects, particularly for those children at high risk for inattention and problem behaviors. In this study, we examined the influence of unsupervised time on behavior problems by studying a sample of elementary school children at high risk for inattention and problem behaviors. The study analyzed data from the Children's Mental Health Promotion Project, which was conducted in collaboration with education, government, and mental health professionals. The child behavior checklist (CBCL) was administered to assess problem behaviors among first- and fourth-grade children. Multivariate logistic regression analysis was used to evaluate the influence of unsupervised time on children's behavior. A total of 3,270 elementary school children (1,340 first-graders and 1,930 fourth-graders) were available for this study; 1,876 of the 3,270 children (57.4%) reportedly spent a significant amount of time unsupervised during the day. Unsupervised time that exceeded more than 2h per day increased the risk of delinquency, aggressive behaviors, and somatic complaints, as well as externalizing and internalizing problems. Carefully planned afterschool programming and care should be provided to children at high risk for inattention and problem behaviors. Also, a more comprehensive approach is needed to identify the possible mechanisms by which unsupervised time aggravates behavior problems in children predisposed for these behaviors. [Copyright &y& Elsevier]

The nitrogen changes and the nitrogen mass balance in a free water surface flow constructed wetland (CW) using the four-year monitoring data from 2008 to 2012 were estimated. The CW was composed of six cells in series that include the first settling basin (Cell 1), aeration pond (Cell 2), deep marsh (Cell 3), shallow marsh (Cell 4), deep marsh (Cell 5) and final settling basin (Cell 6). Analysis revealed that the NH + 4 -N concentration decreased because of ammonification which was then followed by nitrification. The NO − 2 -N and NO − 2 -N were also further reduced by means of microbial activities and plant uptake during photosynthesis. The average nitrogen concentration at the influent was 37,819 kg/year and approximately 45% of that amount exited the CW in the effluent. The denitrification amounted to 34% of the net nitrogen input, whereas the accretion of sediment was only 7%. The biomass uptake of plants was able to retain only 1% of total nitrogen load. In order to improve the nutrient removal by plant uptake, plant coverage in four cells (i.e., Cells 1, 3, 4 and 5) could be increased. [ABSTRACT FROM AUTHOR]

Abstract: A facile oxidative cleavage of cyclic 1,2-diketones 1 to dicarboxylic acids 3 with hydroperoxide generated in situ has been developed. In situ generation of hydroperoxide was effected by the oxidation of 4,4′-dichlorobenzhydrol 2f to 4,4′-dichlorobenzophenone 4f using sodium hydride under oxygen atmosphere. [Copyright &y& Elsevier]

Abstract: This study demonstrated that the surface crystallinity of carbon nanostructures is an additional independent factor that should be considered for the inhibition of cancer proliferation without activating reactive oxygen species (ROS). In addition, cytotoxic evaluation of both proliferating cancer cells and fully differentiated nerve cells (i.e. non-proliferative) showed selective cytotoxicity: single-walled and highly crystalline carbon nanostructures aggressively inhibited the proliferation of glioma cancer cells, but exhibited no notable cytotoxicity effects on differentiated nerve cells. Although single-wall carbon nanotubes have been shown to elicit potent proinflammatory responses by means of trigger ROS, our results demonstrated that highly crystalline carbon structures can be utilized as a selective antiproliferative agent against brain tumor cells without increasing the ROS level and without significant cytotoxic effects to adjacent nerve cells. [Copyright &y& Elsevier]

Abstract: Mitogen/extracellular signal-regulated kinase (MEK) and phosphoinositide 3-kinase (PI3Kα) are considered to be promising targets for the development of anticancer therapeutics. We report the first example of the successful application of structure-based virtual screening to identify novel inhibitors of MEK with IC50 values ranging from 1 to 25μM. One of the four newly identified MEK inhibitors was found to be also a potent inhibitor of PI3Kα with submicromolar inhibitory activity (IC50 =0.3μM). Because this dual inhibitor was screened for having desirable physicochemical properties as a drug candidate as well as the high inhibitory activities against MEK and PI3Kα, it warrants further development through structure–activity relationship (SAR) studies to optimize the inhibitory and anticancer activities. Structural features relevant to the stabilization of the dual inhibitor in the ATP-binding sites of MEK1 and PI3Kα are addressed in detail. [Copyright &y& Elsevier]

Abstract: Perfluorooctanoic acid (PFOA) has unique physical and chemical characteristics, water and oil repellency, thermal stability, and surfactant properties. PFOA has been regularly found in the blood of animals and humans worldwide, and has become an increasing concern because of its adverse effects in immune system. However, the role of PFOA in the allergic inflammation is not well-known. To further extend the immunotoxicity of PFOA, we examined the role of PFOA on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. PFOA dose- and time-dependently increased histamine release from mast cells and serum histamine by the induction of intracellular calcium. PFOA exacerbated the IgE-dependent local allergic reaction in the mouse allergy model. PFOA induced gene expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in mast cells. The inducing effect of PFOA on the pro-inflammatory cytokines was nuclear factor-κB, p38 mitogen-activated protein kinase, and caspase-1 dependent. Furthermore, the activation of cyclooxygenase-2 by PFOA suggests the induction of allergic inflammatory mediators by the PFOA. Our findings provide evidence that PFOA, the known immunotoxic agent, induces mast cell-derived allergic inflammatory reactions by histamine release and expression of pro-inflammatory cytokines. [Copyright &y& Elsevier]

Abstract: Mesoporous silica (MPS), synthesized via the supramolecular polymer templating method, is one of the most attractive nanomaterials for biomedical applications, such as drug delivery systems, labeling, and tissue engineering. The significant difference between MPS and general silica (colloidal silica) is the pore architectures, such as specific surface area and pore volume. The pore structures of nanomaterials have been considered to be one of the key conditions, causing nanotoxicity due to their different efficiency of cellular uptake and immune response. We first studied the influence of pore structural conditions of silica nanoparticles on both inflammation and apoptosis, in vitro and in vivo, by comparing MPS and colloidal silica, and defined underlying mechanisms of action. Both the MPS and colloidal silica nanoparticles are produced by almost similar synthetic conditions, except the use of polymer template for MPS. The specific surface area of colloidal silica and MPS was 40 and 1150 m2 g−1, respectively, while other conditions, including particle size (100 nm) and shape (spherical), were kept constant. In both MTT assay and FACS analysis, MPS nanoparticles showed significantly less cytotoxicity and apoptotic cell death than colloidal silica nanoparticles. MPS nanoparticles induced lower expression of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, in macrophages. The reduced inflammatory response and apoptosis elicited by MPS nanoparticles were resulting from the reduction of mitogen-activated protein kinases, nuclear factor-κB, and caspase 3. In addition, using the local lymph node assay, a standalone in vivo method for hazard identification of contact hypersensitivity, we showed that colloidal silica nanoparticles act as an immunogenic sensitizer and induce contact hypersensitivity but not MPS nanoparticles. In conclusion, the pore architecture of silica nanoparticles greatly influences their biocompatibility and should be carefully designed. The MPS nanoparticles exhibit better biocompatibility than colloidal silica and promise excellent potential usage in the field of biomedical and biotechnological applications. [Copyright &y& Elsevier]

Abstract: DA-9601 (Stillen™) is a novel anti-peptic formulation prepared from the ethanol extracts of Artemisia asiatica possessing anti-oxidative, anti-allergic and anti-inflammatory activities. However, their effect on atopic dermatitis (AD) has not been studied yet. In this study, we report that topical application of DA-9601 suppressed house dust mite extract (Dermatophagoides farinae extract, DFE) and 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in BALB/c mice model. We established atopic dermatitis model in BALB/c mice by repeated local exposure of DFE/DNCB to the ears. Repeated alternative treatment of DFE/DNCB caused AD-like lesions. DA-9601 reduced AD-like skin lesions based on ear thickness and histopathological analysis, and serum IgE levels. DA-9601 inhibited mast cell infiltration into the ear and elevation of serum histamine in AD model. In addition, DA-9601 suppressed DFE/DNCB-induced expression of IL-4, IL-13, IL-31, and TNF-α in the ears. Taken together, our results showed that topical application of DA-9601 exerts beneficial effects in animal model of AD, suggesting that DA-9601 might be a candidate for the treatment of AD. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The Lindera obtusiloba has been used in traditional medicine for the treatment of inflammation and dermatitis. In this study, we investigated the effect of topical application of Lindera obtusiloba water extract (LOWE) on the house dust mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). Materials and methods: We established AD model in BALB/c mice by repeated local exposure of DFE/DNCB to the ears. After a topical application of LOWE on the skin lesions, the epidermal thickness, mast cell infiltration, and serum immunoglobulin E (IgE) and histamine were measured. In addition, the gene expression of interleukin (IL)-4, IL-13, IL-31, and tumor necrosis factor (TNF)-α in the ears was assayed. Results: LOWE reduced AD symptoms based on ear thickness, histopathological analysis, and serum IgE levels. LOWE inhibited mast cell infiltration into the ear and elevation of serum histamine in AD model. Moreover, LOWE suppressed DFE/DNCB-induced expression of IL-4, IL-13, IL-31, and TNF-α in the ears. Conclusions: Our results showed that topical application of LOWE exerts beneficial effects in AD symptoms, suggesting that LOWE might be a candidate for the treatment of AD. [Copyright &y& Elsevier]

Abstract: Aims: Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredients in StillenTM, a drug for the gastric mucosal ulcers. Eupatilin has been known to possess anti-peptic, anti-cancer, and anti-allergy activity. In this report, we defined the effect of eupatilin on the endotoxin-induced inflammation in lipopolysaccharide (LPS)-stimulated macrophages. Main methods: Mouse J774A.1 cell line and mouse peritoneal macrophages were used. Gene expression and production of inflammatory mediators were determined by real-time PCR and Western blot. Key findings: Eupatilin dose-dependently suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO). Eupatilin decreased LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines such as cyclooxygenase-2, monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. In addition, this suppression of inflammatory mediators was nuclear factor (NF)-κB dependent. Significance: Our findings imply that eupatilin suppresses inflammatory responses by the inhibition of NF-κB signaling pathway, and downstream inflammatory mediators in endotoxin-stimulated macrophages. [Copyright &y& Elsevier]

Abstract: The immunotoxicity of implanted nanostructured titanium is a paramount issue for vascular, dental and orthopedic applications. However, it has been unclear whether implanted surface nanostructures can inhibit or aggrevate inflammatory responses. Herein, macrophage activation, as evidence of migration, on transparent flat and nanostructured titanium correlated with pro-inflammatory protein synthesis and cytokine release. Through the real-time monitoring of initial cytoskeleton variations, this study identified that macrophage movement was restricted on nanostructured titanium compared to flat titanium surfaces. Furthermore, nanostructured titanium elicited secretion of fewer pro-inflammatory enzyme molecules and cytokines, as well as reduced nitric oxide production. All results collectively indicated that initial macrophage activation can be mitigated by nanoscale surface topography alone, without modification of surface chemistry or stiffness. [Copyright &y& Elsevier]

Abstract: Phosphatidylinositol-3-kinase alpha (PI3Kα) is an important target in cancer due to the deregulation of the PI3K/AKT signaling pathway in many tumors. In this study, we designed [3,5-d]-7-azaindole analogs as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3,5-positions of azaindole, we developed the SAR (Structure–activity relationship) and identified a series of potent PI3Kα inhibitors. Representative azaindole derivatives showed activity in a cellular proliferation and apoptosis assays. Moreover, B3 exhibited strong antiangiogenic effects on cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: Effect of the addition of poly(lactic acid) (PLA) to cellulose acetate propionate (CAP) on the optical anisotropy is studied considering the morphology and molecular orientation. It is found that PLA is miscible with CAP when the amount of PLA is less than 3 wt.%. The dissolution of PLA chains having large intrinsic birefringence into CAP phase enhances the orientation birefringence of a stretched film, although the viscosity and thus the relaxation time of PLA is significantly shorter than those of CAP. The high level of orientation of PLA chains without relaxation is attained by the cooperative alignment with CAP chains. As a result, a retardation film having appropriate birefringence can be designed by polymer blends composed of biomass-based materials. When the amount of PLA is more than 3 wt.%, however, phase separation occurs. In the case of the blends with phase-separated morphology, the orientation birefringence is not greatly enhanced by blending PLA, because the molecular orientation of PLA in PLA phase relaxes immediately as compared with that of CAP. [ABSTRACT FROM AUTHOR]

Summary: Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive barrier in early cancer development, at least in part, via an oncogene-evoked DNA damage response (DDR). In contrast, Myc activation—although producing a DDR as well—is known to primarily elicit an apoptotic countermeasure. Using the Eμ-myc transgenic mouse lymphoma model, we show here in vivo that apoptotic lymphoma cells activate macrophages to secrete transforming growth factor β (TGF-β) as a critical non-cell-autonomous inducer of cellular senescence. Accordingly, neutralization of TGF-β action, like genetic inactivation of the senescence-related histone methyltransferase Suv39h1, significantly accelerates Myc-driven tumor development via cancellation of cellular senescence. These findings, recapitulated in human aggressive B cell lymphomas, demonstrate that tumor-prompted stroma-derived signals may limit tumorigenesis by feedback senescence induction. [Copyright &y& Elsevier]

Abstract: Eupatilin (5,7-dihydroxy-3′,4′,6-trimethoxyflavone), an extract from Artemisia asiatica Nakai, is a flavonoid of pharmacologically active ingredients. Eupatilin is known to possess anti-cancer, anti-inflammatory, and anti-oxidative activity. Recently, eupatilin has been reported to be effective in producing gastric mucosal as an anti-gastritis agents. However, the mechanism of protective action is still unknown. We studied cytoprotective actions of eupatilin on H2O2-induced cell death and its possible mechanisms of action in human gastric (AGS) cells. Eupatilin dose-dependently inhibited H2O2-induced apoptosis as indicated by co-staining with Annexin V and propidium iodide. Hydrogen peroxide provoked phosphorylation of extracellular regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), and activation of nuclear factor-κB (NF-κB). On the contrary, eupatilin decreased H2O2-induced activation of ERK, JNK and NF-κB. In addition, treatment of specific inhibitors for ERK, JNK, and NF-κB attenuated H2O2-induced apoptosis. Co-treatment of inhibitors and eupatilin was more effective in decreasing H2O2-induced apoptosis. Taken together, we suggest that eupatilin inhibits H2O2-induced apoptosis through the inhibition ERK, JNK, and NF-κB. [Copyright &y& Elsevier]

Abstract: The mast cell-mediated immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of aqueous extract of Amomum xanthiodes (Zingiberaceae) (AXE) on the mast cell-mediated allergy model and studied its possible mechanisms of action. AXE inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. AXE decreased immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis reaction. AXE reduced histamine release and intracellular calcium from rat peritoneal mast cells activated by compound 48/80. Furthermore, AXE decreased the activation of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase and c-jun N-terminal kinase, and downstream tumor necrosis factor (TNF)-α production in phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cells. Our findings provide evidence that AXE inhibits mast cell-derived allergic reactions, and that intracellular calcium, TNF-α, and p38 MAPK are involved in these effects. [Copyright &y& Elsevier]

Abstract: Nitric oxide (NO) is an important regulator of immune responses. Effects of cytokines, such as tumor necrosis factor (TNF)-α or IFN-γ, and bacterial products, such as lipopolysaccharide, on macrophage NO production have been well documented; however, the role of the extracellular matrix proteins, including collagen, in this process remains unclear. We previously reported that discoidin domain receptor 1 (DDR1), a nonintegrin collagen receptor, was expressed in human macrophages, and its activation facilitated their differentiation as well as cytokine/chemokine production. Here, we examined the role for DDR1 in collagen-induced NO production using the murine macrophage cell line J774 cells that endogenously express DDR1. Activation of J774 cells with collagen induced the expression of inducible NO synthase (iNOS) and NO production. Inhibition of DDR1, but not β1-integrins, abolished collagen-induced iNOS and NO production. Activation of J774 cells with collagen-activated nuclear factor-κB, p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) and a pharmacological inhibitor of each signaling molecule significantly reduced collagen-induced NO production. Thus, we have demonstrated, for the first time, that the interaction of DDR1 with collagen induces iNOS expression and subsequent NO synthesis in J774 cells through activation of NF-κB, p38 MAPK, and JNK and suggest that intervention of DDR1 signaling in macrophages may be useful in controlling inflammatory diseases in which NO plays a critical role. [Copyright &y& Elsevier]

Abstract: This study evaluated the efficacy and tolerability in the initiation treatment of Concerta® (OROS methylphenidate HCl) in Korean children with Attention-Deficit/Hyperactivity Disorder (AD/HD). One hundred and nineteen children with AD/HD were entered into a multi-center, open-label, four-week trial. The dosage of Concerta® was adjusted by the investigators based on symptoms and safety assessments performed on a weekly basis. The safety of the drug and its efficacy for attention, behavior, and cognitive function were assessed. The primary outcome measures for efficacy were the Parent and Teacher IOWA Conners Rating Scales, Peer Interaction Items, and the Clinical Global Impression Scale. Cognitive tests (Continuous Performance Test, Matched Familiar Figure Test, Verbal Fluency Test, and Trail Making Test) were included as the secondary outcome measures. In most participants, OROS methylphenidate was well tolerated. There were significant improvements in attention, behavior, and function as measured by parents, teachers, and investigators. The benefit of the initiation of OROS methylphenidate in children with AD/HD was shown on the cognitive tests as well. These data provide support for the benefit of the once-daily methylphenidate preparation, Concerta® in the treatment of Korean children with AD/HD. Children were initiated safely in this short-term trial, and its effectiveness was evident in the behavioral, as well as neuropsychological measurements. [Copyright &y& Elsevier]