Search

Abstract: The effects of nickel and carbon concentrations on the wear resistance of Fe–xNi–yC (x =14–20wt.%, y =0.6–1.0wt.%) were investigated with respect to strain energy initiation of the martensitic transformation and hardness. The strain energy needed to initiate the martensitic transformation increased with increasing carbon and nickel concentrations, except in 1.0wt.% C alloys. The wear resistance of the material decreased with increasing carbon concentration up to 0.9wt.% C. This effect is most likely due to decrement of the martensite volume fraction with increasing carbon concentration induced by the incremental strain energy required to begin the martensitic transformation. In the case of 1.0wt.% C, the improved wear resistance may be due to carbide precipitation. [Copyright &y& Elsevier]

Background: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM.Objective: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments.Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI.Results: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer's disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD.Conclusion: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM. [ABSTRACT FROM AUTHOR]

• A gallium-doped reduced graphene oxide (Ga-rGO) material by a MOCVD system has been demonstrated. • It is investigated the effect of doping level on Ga bonding in rGO layer controlled via the pulsed mode of doping conditions. • The Dirac point for the Ga-rGO devices shifted in the positive direction towards positive gate voltages on pulsed mode. • The Ga-doped rGO layer demonstrates tunable electrical and structural properties by applying the doping-modulation process. In this study, we develop a gallium-doped reduced graphene oxide (Ga-rGO) material with desirable electrical properties by a metal-organic chemical vapor deposition system using the pulsed mode technique. The effect of doping level on Ga bonding in rGO layer controlled via the pulsed mode of doping conditions, such as dopant source injection and interruption durations, is investigated using the X-ray photoelectron spectroscopy (XPS). The XPS data indicated that the pulsed mode of doping conditions resulted in a higher Ga composition and a larger O–Ga bonding portion in the Ga-rGO layer. Additionally, the Dirac point of Ga-rGO layer with the pulsed mode was observed to shift toward positive voltage in the bottom-gate field effect transistor device, leading to a p -type behavior. The higher work function of Ga-rGO affected the Schottky contact between the Ga-rGO layer and n -type Si leading to lower fermi-energy level in the energy-band structure. Consequently, this work proposes a simplistic approach of Ga doping in graphene materials that can modulate the tunable electrical properties. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicated an association between Alzheimer's disease (AD) dementia and air particulate matter (PM) with aerodynamic diameter <10μm (PM10), as well as smaller PM. Limited information, however, is available for the neuropathological links underlying such association.Objective: This study aimed to investigate the relationship between long-term PM10 exposure and in vivo pathologies of AD using multimodal neuroimaging.Methods: The study population consisted of 309 older adults without dementia (191 cognitively normal and 118 mild cognitive impairment individuals), who lived in Republic of Korea. Participants underwent comprehensive clinical assessments, 11C-Pittsburg compound B (PiB) positron emission tomography (PET), and magnetic resonance imaging scans. A subset of 78 participants also underwent 18F-AV-1451 tau PET evaluation. The mean concentration of PM with aerodynamic diameter <10μm over the past 5 years (PM10mean) collected from air pollution surveillance stations were matched to each participant's residence.Results: In this non-demented study population, of which 62% were cognitively normal and 38% were in mild cognitive impairment state, exposure to the highest tertile of PM10mean was associated with increased risk of amyloid-β (Aβ) positivity (odds ratio 2.19, 95% confidence interval 1.13 to 4.26) even after controlling all potential confounders. In contrast, there was no significant associations between PM10mean exposure and tau accumulation. AD signature cortical thickness and white matter hyperintensity volume were also not associated with PM10mean exposure.Conclusion: The findings suggest that long-term exposure to PM10 may contribute to pathological Aβ deposition. [ABSTRACT FROM AUTHOR]

Background: An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aβ) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aβ deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain.Methods and Findings: The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1-13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1-13 SDs/week) was significantly associated with a lower Aβ positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163-0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history.Conclusions: In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aβ deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the relationships of cerebral amyloid beta (Aβ) deposition and neurodegeneration (ND) with subjective memory complaints (SMCs) in cognitively normal (CN) individuals, focusing specially on the modulating effects of vascular risk (VR) on those relationships. Participants and methods: A total of 230 CN elderly individuals underwent comprehensive clinical assessments including the Subjective Memory Complaints Questionnaire (SMCQ), VR assessment, and multimodal brain imaging including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose-PET, and magnetic resonance imaging. Results: We found a significant overall positive association between cerebral Aβ retention and SMCQ score. In addition, we found a significant cerebral Aβ retention × VR interaction effect on the SMCQ score. Subgroup analyses showed that the Aβ–SMC association was found only in VR-negative, and not in VR-positive, individuals. We found no relationship between ND and SMCQ. Conclusion: Our findings suggest that SMC in CN elderly individuals reflects early accumulation of Aβ in the brain. Given the modulating effect of VR on the Aβ–SMC relationship, SMC can be used as a meaningful marker of early Aβ deposition in individuals without VR. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to investigate the relationship of hypertension with beta-amyloid (Aβ) and neurodegeneration biomarkers of Alzheimer's disease (AD) and the modulating effect of apolipoprotein E-ε4 (APOE4). In total, 259 cognitively normal (CN) and 79 AD dementia older adults received clinical assessments including the evaluation for the presence of hypertension, [11C]-Pittsburgh-compound-B–positron emission tomography, magnetic resonance imaging, and APOE genotyping. We used a clinical stage-specific approach, separately focusing on CN and AD dementia stages. For the CN group, individuals with hypertension showed reduced AD signature cortical thickness compared with those without hypertension. Subsequent subgroup analyses showed that hypertension was associated with reduced AD signature cortical thickness only in APOE4 noncarriers, whereas hypertension was associated with elevated Aβ deposition in APOE4 carriers. Meanwhile, regardless of APOE4 status, AD dementia patients with hypertension had significantly lower Aβ deposition than those without hypertension. In conclusion, the findings suggest that hypertension contributes to AD primarily through the reduction of brain reserve. In case of APOE4 carriers, however, hypertension seems to additionally facilitate AD process through amyloid-dependent pathway. Highlights • Hypertension (HTN) is related to Alzheimer's disease (AD)-related neuronal injury. • HTN may contribute to AD mainly through the reduction of brain reserve. • HTN may additionally facilitate beta-amyloid deposition in APOE4 carrier. [ABSTRACT FROM AUTHOR]

One of the hallmarks of Alzheimer's disease is abnormal deposition of tau proteins in the brain. Although plasma tau has been proposed as a potential biomarker for Alzheimer's disease, a direct link to brain deposition of tau is limited. Here, we estimated the amount of in vivo tau deposition in the brain by PET imaging and measured plasma levels of total tau (t-tau), phosphorylated tau (p-tau, T181) and amyloid-β1-42. We found significant correlations of plasma p-tau, t-tau, p-tau/amyloid-β1-42, and t-tau/amyloid-β1-42 with brain tau deposition in cross-sectional and longitudinal manners. In particular, t-tau/amyloid-β1-42 in plasma was highly predictive of brain tau deposition, exhibiting 80% sensitivity and 91% specificity. Interestingly, the brain regions where plasma t-tau/amyloid-β1-42 correlated with brain tau were similar to the typical deposition sites of neurofibrillary tangles in Alzheimer's disease. Furthermore, the longitudinal changes in cerebral amyloid deposition, brain glucose metabolism, and hippocampal volume change were also highly associated with plasma t-tau/amyloid-β1-42. These results indicate that combination of plasma tau and amyloid-β1-42 levels might be potential biomarkers for predicting brain tau pathology and neurodegeneration. [ABSTRACT FROM AUTHOR]

We introduce a novel structure of ZnO nanorods (NRs) grown on ZnO NRs (ZnO NRs/NRs) via a facile, low-cost, and environmentally friendly synthesis for galactose biosensor application. The galactose oxidase enzyme (GalOx) is immobilized on the ZnO NR/NR surface to form the novel electrode structure (GalOx|ZnO NRs/NRs). The GalOx|ZnO NR/NR electrode has a linear detection range of current density from 11.30 μA/mm2 to 18.16 μA/mm2 over a galactose concentration range from 40 mM to 230 mM, indicating the increment of electrode sensitivity up to 60.7%. The ZnO NR/NR morphology with a high surface area to volume ratio has a great contribution to the electrochemical performance of galactose biosensor. Our results propose a straightforward approach to fabricate architecturally ZnO-based nanostructure for biosensor application. [ABSTRACT FROM AUTHOR]

Abstract: Selective growth by metal-organic chemical vapor deposition (MOCVD), and electrochemical etching of a heavily Si-doped GaN (n+-GaN) interlayer were employed to obtain air-gaps embedded in a u-GaN layer. As confirmed by Raman spectroscopy, the introduction of an n+-GaN, which was later etched to obtain air-gaps, also enhanced the strain-compliance of GaN epilayer on sapphire substrate. An enhanced electroluminescence emission was observed from the light-emitting diodes (LEDs) fabricated on the air-gap embedding template. Using theoretical LED simulation, it was discerned that the increase in optical emission from the LED was caused predominantly by the redirection of photons at GaN/air-gap interface. Finite-difference time domain (FDTD) simulation method was employed to understand the mechanism of optical emission enhancement and its spatial variation over the LED surface. [Copyright &y& Elsevier]

Background: Recently, the field of gene-gene or gene-environment interaction research appears to have gained growing interest, although it is seldom investigated in Alzheimer’s disease (AD). Hence, the current study aims to investigate interaction effects of the key genetic and environmental risks—the apolipoprotein ε4 allele (APOE4) and family history of late-onset AD (FH)—on AD-related brain changes in cognitively normal (CN) middle-aged and older adults. Methods: [11C] Pittsburg compound-B (PiB) positron emission tomography (PET) imaging as well as [18F] fluoro-2-deoxyglucose (FDG) PET that were simultaneously taken with T1-weighted magnetic resonance imaging (MRI) were obtained from 268 CNs from the Korean Brain Aging Study for Early Diagnosis and Prediction of AD (KBASE). Composite standardized uptake value ratios were obtained from PiB-PET and FDG-PET images in the AD signature regions of interests (ROIs) and analyzed. Voxel-wise analyses were also performed to examine detailed regional changes not captured by the ROI analyses. Results: A significant synergistic interaction effect was found between the APOE4 and FH on amyloid-beta (Aβ) deposition in the AD signature ROIs as well as other regions. Synergistic interaction effects on cerebral glucose metabolism were observed in the regions not captured by the AD signature ROIs, particularly in the medial temporal regions. Conclusions: Strong synergistic effects of APOE4 and FH on Aβ deposition and cerebral glucose metabolism in CN adults indicate possible gene-to-gene or gene-to-environment interactions that are crucial for pathogenesis of AD involving Aβ. Other unspecified risk factors—genes and/or environmental—that are captured by the positive FH status might either coexpress or interact with APOE4 to alter AD-related brain changes in CN. Healthy people with both FH and APOE4 need more attention for AD prevention. [ABSTRACT FROM AUTHOR]

The upper airway, particularly the nasal and oral mucosal epithelium, serves as a primary barrier for microbial interactions throughout life. Specialized niches like the anterior nares and the tooth are especially susceptible to dysbiosis and chronic inflammatory diseases. To investigate host-microbial interactions in mucosal epithelial cell types, we reanalyzed our single-cell RNA sequencing atlas of human oral mucosa, identifying polybacterial signatures (20% Gram-positive, 80% Gram-negative) within both epithelial- and stromal-resident cells. This analysis revealed unique responses of bacterial-associated epithelia when compared to two inflammatory disease states of mucosa. Single-cell RNA sequencing, in situ hybridization, and immunohistochemistry detected numerous persistent macromolecules from Gram-positive and Gram-negative bacteria within human oral keratinocytes (HOKs), including bacterial rRNA, mRNA and glycolipids. Epithelial cells with higher concentrations of 16S rRNA and glycolipids exhibited enhanced receptor-ligand signaling in vivo . HOKs with a spectrum of polybacterial intracellular macromolecular (PIM) concentrations were challenged with purified exogenous lipopolysaccharide, resulting in the synergistic upregulation of select innate ( CXCL8 , TNFSF15 ) and adaptive ( CXCL17 , CCL28 ) epikines. Notably, endogenous lipoteichoic acid, rather than lipopolysaccharide, directly correlated with epikine expression in vitro and in vivo . Application of the Drug2Cell algorithm to health and inflammatory disease data suggested altered drug efficacy predictions based on PIM detection. Our findings demonstrate that PIMs persist within mucosal epithelial cells at variable concentrations, linearly driving single-cell effector cytokine expression and influencing drug responses, underscoring the importance of understanding host-microbe interactions and the implications of PIMs on cell behavior in health and disease at single-cell resolution., Competing Interests: Competing interests: The authors had access to the study data and reviewed and approved the final manuscript. Although the authors view each of these as noncompeting financial interests, KMB, QTE, BFM, BTR, TW, and AH are all active members of the Human Cell Atlas. Furthermore, KMB is a scientific advisor at Arcato Laboratories; additionally, KMB and TW are co-inventors on provisional patents regarding the MAPCELL methodology (ADA Science & Research Institute). All other authors declare no competing interests.

Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, this study aims to investigate the anti-obesity and anti-diabetic effects of bioactive compounds derived from a Meretrix lusoria Protamex enzymatic hydrolysate (MLP) fraction (≤1 kDa) through a 6-week treatment (150 mg/kg or 300 mg/kg, administered once daily) in leptin receptor-deficient db/db mice. The MLP treatment significantly decreased the body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels while also exhibiting a beneficial effect on hepatic and serum marker parameters in db/db mice. A histological analysis revealed a reduction in hepatic steatosis and epididymal fat following MLP treatment. Furthermore, poor glucose tolerance was improved, and hepatic antioxidant enzyme activities were elevated in MLP-treated mice compared to db/db control mice. Western blot analysis showed an increased expression of the AMPK protein after MLP treatment. In addition, the expression of lipogenic genes decreased in db/db mice. These findings indicate that bioactive peptides, which are known to regulate blood glucose levels, lipid metabolism, and adipogenesis, could be beneficial functional food additives and pharmaceuticals.

Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation., (© 2024. The Author(s).)

Fibroblasts are ubiquitous mesenchymal cells that exhibit considerable molecular and functional heterogeneity. Besides maintaining stromal integrity, oral fibroblast subsets are thought to play an important role in host-microbe interaction during injury repair, which is not well explored in vivo. Here, we characterize a subset of fibroblast lineage labeled by paired-related homeobox-1 promoter activity (Prx1Cre + ) in oral mucosa and skin and demonstrate these fibroblasts readily respond to microbial products to facilitate the normal wound healing process. Using a reporter mouse model, we determined that Prx1Cre + fibroblasts had significantly higher expression of toll-like receptors 2 and 4 compared to other fibroblast populations. In addition, Prx1 immunopositive cells exhibited heightened activation of inflammatory transcription factor NF-κB during the early wound healing process. At the cytokine level, CXCL1 and CCL2 were significantly upregulated by Prx1Cre + fibroblasts at baseline and upon LPS stimulation. Importantly, lineage-specific knockout to prevent NF-κB activation in Prx1Cre + fibroblasts drastically impaired both oral and skin wound healing processes, which was linked to reduced macrophage infiltration, failure to resolve inflammation, and clearance of bacteria. Together, our data implicate a pro-healing role of Prx1-lineage fibroblasts by facilitating early macrophage recruitment and bacterial clearance., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Wound healing is a complex, highly regulated process and is substantially disrupted by diabetes. We show here that human wound healing induces specific epigenetic changes that are exacerbated by diabetes in an animal model. We identified epigenetic changes and gene expression alterations that significantly reduce reepithelialization of skin and mucosal wounds in an in vivo model of diabetes, which were dramatically rescued in vivo by blocking these changes. We demonstrate that high glucose altered FOXO1-matrix metallopeptidase 9 (MMP9) promoter interactions through increased demethylation and reduced methylation of DNA at FOXO1 binding sites and also by promoting permissive histone-3 methylation. Mechanistically, high glucose promotes interaction between FOXO1 and RNA polymerase-II (Pol-II) to produce high expression of MMP9 that limits keratinocyte migration. The negative impact of diabetes on reepithelialization in vivo was blocked by specific DNA demethylase inhibitors in vivo and by blocking permissive histone-3 methylation, which rescues FOXO1-impaired keratinocyte migration. These studies point to novel treatment strategies for delayed wound healing in individuals with diabetes. They also indicate that FOXO1 activity can be altered by diabetes through epigenetic changes that may explain other diabetic complications linked to changes in diabetes-altered FOXO1-DNA interactions., Article Highlights: FOXO1 expression in keratinocytes is needed for normal wound healing. In contrast, FOXO1 expression interferes with the closure of diabetic wounds. Using matrix metallopeptidase 9 as a model system, we found that high glucose significantly increased FOXO1-matrix metallopeptidase 9 interactions via increased DNA demethylation, reduced DNA methylation, and increased permissive histone-3 methylation in vitro. Inhibitors of DNA demethylation and permissive histone-3 methylation improved the migration of keratinocytes exposed to high glucose in vitro and the closure of diabetic skin and mucosal wounds in vivo. Inhibition of epigenetic enzymes that alter FOXO1-induced gene expression dramatically improves diabetic healing and may apply to other conditions where FOXO1 has a detrimental role in diabetic complications., (© 2023 by the American Diabetes Association.)

Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Up-regulation of the nuclear factor κB (NF-κB) pathway may lead to the development of chronic inflammatory disorders of the skin, but its role during the early events remains unclear. Through analysis of single-cell RNA sequencing data via iterative random forest leave one out prediction, an explainable artificial intelligence method, we identified an immunoregulatory role for a unique paired related homeobox-1 (Prx1) + fibroblast subpopulation. Disruption of Ikkb -NF-κB under homeostatic conditions in these fibroblasts paradoxically induced skin inflammation due to the overexpression of C-C motif chemokine ligand 11 (CCL11; or eotaxin-1) characterized by eosinophil infiltration and a subsequent T H 2 immune response. Because the inflammatory phenotype resembled that seen in human atopic dermatitis (AD), we examined human AD skin samples and found that human AD fibroblasts also overexpressed CCL11 and that perturbation of Ikkb -NF-κB in primary human dermal fibroblasts up-regulated CCL11. Monoclonal antibody treatment against CCL11 was effective in reducing the eosinophilia and T H 2 inflammation in a mouse model. Together, the murine model and human AD specimens point to dysregulated Prx1 + fibroblasts as a previously unrecognized etiologic factor that may contribute to the pathogenesis of AD and suggest that targeting CCL11 may be a way to treat AD-like skin lesions.

This study aimed to explore the moderating effects of the frequently used cognitive reserve (CR) proxies [i.e., education, premorbid intelligence quotient (pIQ), occupational complexity (OC), and lifetime cognitive activity (LCA)] on the relationships between various in vivo Alzheimer's disease (AD) pathologies and cognition. In total, 351 [268 cognitively unimpaired (CU), 83 cognitive impaired (CI)] older adults underwent multi-modal brain imaging to measure AD pathologies and cognitive assessments, and information on CR proxies was obtained. For overall participants, only education moderated the relationship between Aβ deposition and cognition. Education, pIQ, and LCA, but not OC, showed moderating effect on the relationship between AD-signature cerebral hypometabolism and cognition. In contrast, only OC had a moderating effect on the relationship between cortical atrophy of the AD-signature regions and cognition. Such moderation effects of the CR proxies were similarly observed in CI individuals, but most of them were not in CU individuals. The findings suggest that the proposed CR proxies have different moderating effects on the relationships between specific AD pathologies and cognition., (Copyright © 2021. Published by Elsevier Inc.)

There is significant interest in understanding the cellular mechanisms responsible for expedited healing response in various oral tissues and how they are impacted by systemic diseases. Depending upon the types of oral tissue, wound healing may occur by predominantly re-eptihelialization, by re-epithelialization with substantial new connective tissue formation, or by a a combination of both plus new bone formation. As a result, the cells involved differ and are impacted by systemic diaseses in various ways. Diabetes mellitus is a prevalent metabolic disorder that impairs barrier function and healing responses throughout the human body. In the oral cavity, diabetes is a known risk factor for exacerbated periodontal disease and delayed wound healing, which includes both soft and hard tissue components. Here, we review the mechanisms of diabetic oral wound healing, particularly on impaired keratinocyte proliferation and migration, altered level of inflammation, and reduced formation of new connective tissue and bone. In particular, diabetes inhibits the expression of mitogenic growth factors whereas that of pro-inflammatory cytokines is elevated through epigenetic mechanisms. Moreover, hyperglycemia and oxidative stress induced by diabetes prevents the expansion of mesengenic cells that are involved in both soft and hard tissue oral wounds. A better understanding of how diabetes influences the healing processes is crucial for the prevention and treatment of diabetes-associated oral complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Backgroud: Recurrent hemarthrosis following total knee arthroplasty (TKA) is a rare complication. Its pathophysiology and standard treatments have not yet been established. In this study, we report 7 cases of recurrent hemarthrosis after TKA in which failure of the initial conservative treatment was followed by angiographic embolization; in 1 of the 7 cases, arthroscopic electrocauterization was also performed after treatment failure with selective embolization., Methods: From January 2015 to May 2018, 7 patients visited our hospital due to recurrent hemarthrosis after TKA. Their medical records and serologic test results were reviewed to check for the presence of any bleeding disorder and history of anticoagulant use. Implant malalignment and instability were checked using X-ray. In all cases, the conservative treatment failed, so interventional angiography with selective embolization was performed, which was also followed by arthroscopic electrocauterization if the outcome was unsatisfactory., Results: The interval between TKA and the onset of hemarthrosis ranged from 3 to 76 months (average, 34.1 months). There was no coagulopathy and instability. All patients underwent conservative treatment at an interval of 4.3 months and the rate of relapse was 3.1 on average. On the interventional angiography, 6 cases showed vascular blush, and 1 case had pulsatile bleeding. The average duration for interventional angiography was 90.9 minutes. The average length of follow-up was 38.8 months. Embolization was successfully performed in 4 cases. In 2 of 3 failed cases, the symptoms improved without further treatment. In the remaining 1 failed case, the patient had a relapse of hemarthrosis, so an arthroscopic procedure was performed, which led to identification of the suspicious bleeding point by using preoperative angiographic findings. Electrocauterization was performed and active bleeding was stopped. All cases with recurrent hemarthrosis achieved improvement., Conclusions: Interventional angiography was used to aid in the diagnosis of recurrent hemarthrosis, and therapeutic selective embolization provided satisfactory clinical results. Even if selective embolization fails, interventional angiography may be helpful for further surgical procedures because it reveals vascular blush of a bleeding site. Therefore, interventional angiography and selective embolization should be considered to be a useful treatment for recurrent hemarthrosis after TKA., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2021 by The Korean Orthopaedic Association.)

Objective: Anosognosia is a common phenomenon in individuals with dementia. Anosognosia Questionnaire for dementia (AQ-D) is a well-known scale for evaluating anosognosia. This study aimed to establish a Korean version of the AQ-D (AQ-D-K) and to evaluate the reliability and validity of the AQ-D-K in patients with Alzheimer's disease (AD) dementia., Methods: We translated the original English version of AQ-D into Korean (AQ-D-K). Eighty-four subjects with very mild or mild AD dementia and their caregivers participated. Reliability of AQ-D-K was assessed by internal consistency and one-month test-retest reliability. Construct validity and concurrent validity were also evaluated., Results: Internal consistencies of the AQ-D-K patient form and caregiver form were high (Cronbach alpha 0.95 and 0.93, respectively). The test-retest reliability of AQ-D-K measured by intra-class correlation coefficient was 0.84. Three factors were identified: 1) anosognosia of instrumental activity of daily living; 2) anosognosia basic activity of daily living; and 3) anosognosia of depression and disinhibition. AQ-D-K score was significantly correlated with the clinician-rated anosognosia rating scale (ARS), center for epidemiological studies-depression scale (CES-D) and state-trait anxiety inventory (STAI)., Conclusion: The findings suggest that the AQ-D-K is a reliable and valid scale for evaluating anosognosia for AD dementia patients using Korean language.

Background: Despite known associations between low blood hemoglobin level and Alzheimer's disease (AD) or cognitive impairment, the underlying neuropathological links are poorly understood. We aimed to examine the relationships of blood hemoglobin levels with in vivo AD pathologies (i.e., cerebral beta-amyloid [Aβ] deposition, tau deposition, and AD-signature degeneration) and white matter hyperintensities (WMHs), which are a measure of cerebrovascular injury. We also investigated the association between hemoglobin level and cognitive performance, and then assessed whether such an association is mediated by brain pathologies. Methods: A total of 428 non-demented older adults underwent comprehensive clinical assessments, hemoglobin level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Episodic memory score and global cognition scores were also measured. Results: A lower hemoglobin level was significantly associated with reduced AD-signature cerebral glucose metabolism (AD-CM), but not Aβ deposition, tau deposition, or WMH volume. A lower hemoglobin level was also significantly associated with poorer episodic memory and global cognition scores, but such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a moderating effect. Conclusion: The present findings suggest that low blood hemoglobin in older adults is associated with cognitive decline via reduced brain metabolism, which seems to be independent of those aspects of AD-specific protein pathologies and cerebrovascular injury that are reflected in PET and MRI measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Byun, Yi, Lee, Jeon, Ko, Joung, Jung, Lee, Sohn, Lee, Kim and Lee.)

Background: Despite known associations of lower serum uric acid (UA) with Alzheimer's disease (AD) dementia or AD-related cognitive impairment, little is known regarding the underlying patho-mechanisms. We aimed to examine the relationships of serum UA with in vivo AD pathologies including cerebral beta-amyloid (Aβ) and tau deposition, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensities (WMH). We also investigated the association between serum UA and cognitive performance, and then assessed whether such an association is mediated by the brain pathologies., Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessments, measurement of serum UA level, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging scans. Mini-Mental State Examination (MMSE) and word list recall (WLR) test scores were used to measure cognitive performance., Results: Serum UA level was significantly associated with AD-CM, but not with Aβ deposition, tau deposition, or WMH volume. Serum UA levels also had significant association with WLR and marginal association with MMSE; such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a mediating effect., Conclusion: The findings of the present study indicate that there is an association of low serum UA with AD-related cerebral hypometabolism, and whether this represents a causal relationship remains to be determined., (Copyright © 2020 Kim, Byun, Yi, Lee, Jeon, Ko, Jung, Lee, Lee, Sohn, Lee, Shin, Kim and Lee.)

Purpose: Diabetes mellitus has been shown to delay osseointegration of titanium dental implants. This study tested the hypothesis that serum derived from diabetes negatively affects osteoblast adhesion to polystyrene and titanium surfaces, partly through the presence of advanced glycation end products (AGEs)., Materials and Methods: Twenty-four Sprague-Dawley rats were divided into three groups: normoglycemic control, streptozotocin-induced diabetic group, and diabetic group treated with the AGE inhibitor aminoguanidine. Polystyrene or titanium disks were preincubated in serum derived from each group. Human osteoblasts transfected with green fluorescent protein (GFP) were cultured, and the number of adherent osteoblasts was quantified. High-pressure liquid chromatography (HPLC) was used to fractionate eluates, which were further characterized by western blot with AGE antibody and adhesion assays. In parallel, sera derived from healthy patients, patients with controlled diabetes, and patients with uncontrolled diabetes were utilized for osteoblast adhesion assay and western blot., Results: Diabetic serum significantly reduced the number of adherent osteoblast and osteoblast aggregates on titanium disks, whereas aminoguanidine-treated serum rescued the effect of diabetes on the number of adherent osteoblast aggregates. Fractionated diabetic serum revealed distinct AGE bands at ~100 kDa and 44 kDa, whereas healthy serum did not express any. In human serum samples, both controlled and uncontrolled diabetes led to a significant reduction in the number of adherent osteoblasts on polystyrene and titanium surfaces compared with normoglycemic serum. This correlated with presence of AGEs in western blot in diabetic but not in healthy serum., Conclusion: Osteoblast adhesion on the titanium surface was greatly reduced by the exposure of serum derived from diabetic rats or humans. Recovery of osteoblast aggregates by aminoguanidine treatment suggests that AGEs played a role in this negative effect. The correlating presence of AGEs from the fractionated sera of diabetic rats or humans and impaired osteoblast adhesion on the titanium surface further supports this role.

This study aimed to investigate whether the midlife cognitive activity and physical activity moderate the relationship between apolipoprotein Eε4 (APOE4) and in vivo Alzheimer's disease (AD) pathologies. In total, 287 non-demented older adults (mean age 72 years) from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer's disease cohort were included. Participants underwent a comprehensive clinical assessment including the evaluation for midlife CA and physical activity, [ 11 C]-Pittsburgh-Compound-B-positron emission tomography (PET), [ 18 F]-fluorodeoxyglucose PET, structural magnetic resonance imaging (MRI), and APOE genotyping. We used linear regression and regression-based mediated-moderation models for statistical analyses. Neither midlife cognitive activity nor physical activity moderated the effect of APOE4 on β-amyloid (Aβ) retention itself. Midlife cognitive activity significantly moderated the effect of APOE4 on hippocampal volume [ B (SE) = - 627.580 (252.327), t = -2.488, p = 0.014]: APOE4 carriers had smaller hippocampal volume than non-carriers at relatively high cognitive activity state ( p = 0.004), but not at relatively low cognitive activity condition ( p = 0.937). Midlife physical activity significantly moderated the effect of Aβ retention, which was closely related to APOE4, on AD-signature region cerebral glucose metabolism [AD-CM; B (SE) = 0.004 (0.002), t = 2.030, p = 0.043]: higher Aβ accumulation was associated with lower AD-CM in relatively low physical activity condition ( p < 0.001), whereas no such association was observed in relatively high physical activity state ( p = 0.791). The findings suggest that high midlife cognitive activity may accelerate hippocampal atrophy induced by APOE4, whereas high midlife physical activity may delay AD-related cerebral hypometabolism by weakening the influence of APOE4-associated Aβ retention., (Copyright © 2020 Jeon, Byun, Yi, Lee, Ko, Sohn, Lee, Ryu, Lee, Shin, Kim, Kang, Sohn and Lee.)

Type 1 diabetes (T1D) imposes a significant health burden by negatively affecting tissue regeneration during wound healing. The adverse effect of diabetes is attributed to high levels of inflammation, but the cellular mechanisms responsible remain elusive. In this study, we show that intrinsic skeletal stem cells (SSCs), a subset of mesenchymal stem cells, are essential for resolution of inflammation to occur during osseous healing by using genetic approaches to selectively ablate SSCs. T1D caused aberrant nuclear factor-κB (NF-κB) activation in SSCs and substantially enhanced inflammation in vivo. Constitutive or tamoxifen-induced inhibition of NF-κB in SSCs rescued the impact of diabetes on inflammation, SSC expansion, and tissue formation. In contrast, NF-κB inhibition in chondrocytes failed to reverse the effect of T1D. Mechanistically, diabetes caused defective proresolving macrophage (M2) polarization by reducing TGF-β1 expression by SSCs, which was recovered by NF-κB inhibition or exogenous TGF-β1 treatment. These data identify an underlying mechanism for altered healing in T1D and demonstrate that diabetes induces NF-κB hyperactivation in SSCs to disrupt their ability to modulate M2 polarization and resolve inflammation., (© 2019 by the American Diabetes Association.)

Background: Although previous studies have suggested that insulin plays a role in brain function, it still remains unclear whether or not insulin has a region-specific association with neuronal and synaptic activity in the living human brain. We investigated the regional pattern of association between basal blood insulin and resting-state cerebral glucose metabolism (CMglu), a proxy for neuronal and synaptic activity, in older adults., Method: A total of 234 nondiabetic, cognitively normal (CN) older adults underwent comprehensive clinical assessment, resting-state 18F-fluodeoxyglucose (FDG)-positron emission tomography (PET) and blood sampling to determine overnight fasting blood insulin and glucose levels, as well as apolipoprotein E (APOE) genotyping., Results: An exploratory voxel-wise analysis of FDG-PET without a priori hypothesis demonstrated a positive association between basal blood insulin levels and resting-state CMglu in specific cerebral cortices and hippocampus, rather than in non-specific overall cerebral regions, even after controlling for the effects of APOE e4 carrier status, vascular risk factor score, body mass index, fasting blood glucose, and demographic variables. Particularly, a positive association of basal blood insulin with CMglu in the right posterior hippocampus and adjacent parahippocampal region as well as in the right inferior parietal region remained significant after multiple comparison correction. Conversely, no region showed negative association between basal blood insulin and CMglu., Conclusions: Our finding suggests that basal fasting blood insulin may have association with neuronal and synaptic activity in specific cerebral regions, particularly in the hippocampal/parahippocampal and inferior parietal regions., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: This study aimed to identify health-related quality of life (HRQoL) and its determinants in outpatients with acute coronary syndrome (ACS) after percutaneous coronary intervention., Methods: A cross-sectional design was used and a total of 124 Korean participants was enrolled. The HRQoL (physical limitations, treatment satisfaction, and disease perception), symptom experience (frequency, severity, and distress), physiological (left ventricular ejection fraction and lipids), psychological (depression and anxiety), and situational (social support) factors were measured, selected on the basis of the theory of unpleasant symptoms. The HRQoL was assessed by using the Seattle Angina Questionnaire-Korean, designed to evaluate disease-specific health outcomes in patients with coronary artery disease. Descriptive statistics and multiple linear regression analyses were conducted., Results: The mean age of the participants was 61.73 years. The HRQoL was moderate. Among the HRQoL domains, disease perception showed the lowest level. The most intense symptoms that were experienced by the participants were fatigue, shortness of breath, and chest discomfort. More than half of the participants had depression and anxiety. The determinants of worse HRQoL were severe symptom experience, higher depression, higher low-density lipoprotein cholesterol, a lower educational level, and lower social support., Conclusion: This study proposes a comprehensive approach to health care that incorporates symptom experience, as well as the physiological, psychological, and situational aspects based on the theory of unpleasant symptoms, to improve the HRQoL among outpatients with ACS. Nurses should play a key role to help patients with ACS to deal with the symptoms, low-density lipoprotein cholesterol, and depression and to promote social support, particularly in less-educated patients, in order to improve their HRQoL., (© 2018 Japan Academy of Nursing Science.)

The objective of this case series was to describe surgical approaches that can be used to efficiently and effectively treat peri-implantitis as measured by positive changes in clinical parameters. A total of 32 patients with 45 implants were treated surgically to eliminate peri-implantitis. Baseline clinical parameters measured prior to surgery were compared to those made 6 months postsurgery to evaluate the efficacy of each procedure. Implants demonstrating signs of peri-implantitis were treated by one of three approaches: (1) regenerative surgery, (2) osseous resective surgery, or (3) apically repositioned flap surgery. In all instances, the exposed implant surfaces were debrided and decontaminated. Relative to baseline values, regenerative surgery yielded statistically significant changes in probing depth (PD) (7.21 ± 0.27 mm to 4.09 ± 0.14 mm) and percentage of sites exhibiting bleeding on probing (BoP) (100.0% ± 0.0% to 10.6% ± 3.3%) as measured at the 6-month recall visit (P ≤ .05). The decrease in probing depth was not dependent on the type of graft material used (P ≤ .05). Resective surgery yielded statistically significant changes in PD (5.86 ± 0.23 mm to 3.63 ± 0.14 mm) and the percentage of sites exhibiting BoP (100.0% ± 0.0% to none) (P ≤ .05). Finally, the implants treated via apically repositioned flap surgery demonstrated statistically significant decreases (P ≤ .05) in both PD (6.79 ± 0.27 mm to 4.32 ± 0.16 mm) and BOP (100.0% ± 0.0% to 14.3% ± 6.7%) (P ≤ .05). Regenerative, resective, and apically positioned flap surgery can be utilized to successfully treat peri-implantitis.

Background: Although increased cognitive activity (CA), both current and past, is known to be associated with a decreased occurrence of Alzheimer's disease (AD) dementia in older adults, the exact neural mechanisms underlying the association between CA during different stages of life and human dementia remain unclear. Therefore, we investigated whether CA during different life stages is associated with cerebral amyloid-beta (Aβ) pathology and AD-related neurodegeneration in non-demented older adults. Methods: Cross-sectional analyses of data collected between April 2014 and March 2016 from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort. In total, 321 community-dwelling, non-demented older adults were involved in this study. Cerebral Aβ deposition and Aβ positivity were measured using 11 C-Pittsburgh compound B (PiB)-positron emission tomography (PET). AD-signature region cerebral glucose metabolism (AD-CMglu) and AD-signature region neurodegeneration (AD-ND) positivity were measured using 18 F-fluorodeoxyglucose (FDG)-PET. In addition, CA in early, mid, and late life was systematically evaluated using a structured questionnaire. Results: Of the 321 participants, 254 were cognitively normal (CN) and 67 had mild cognitive impairment (MCI). The mean age of participants was 69.6 years old [standard deviation (SD) = 8.0]. Higher early-life CA (CA early ) was associated with significantly increased AD-CMglu ( B = 0.035, SE = 0.013, P = 0.009) and a decreasing trend of AD-ND positivity (OR = 0.65, 95% CI 0.43-0.98, P = 0.04) but was not associated with Aβ deposition or positivity. We observed no association between midlife CA (CA mid ) and any AD-related brain changes. Late-life CA (CA late ) showed an association with both global Aβ deposition and AD-CMglu, although it was not statistically significant. Sensitivity analyses controlling for current depression or conducted only for CN individuals revealed similar results. Conclusion: Our results suggest that CA in early life may be protective against late-life AD-related neurodegeneration, independently of cerebral Aβ pathology.

Diabetes increases the likelihood of fracture, interferes with fracture healing and impairs angiogenesis. The latter may be significant due to the critical nature of angiogenesis in fracture healing. Although it is known that diabetes interferes with angiogenesis the mechanisms remain poorly defined. We examined fracture healing in normoglycemic and streptozotocin-induced diabetic mice and quantified the degree of angiogenesis with antibodies to three different vascular markers, CD34, CD31 and Factor VIII. The role of diabetes-enhanced inflammation was investigated by treatment of the TNFα-specific inhibitor, pegsunercept starting 10days after induction of fractures. Diabetes decreased both angiogenesis and VEGFA expression by chondrocytes. The reduced angiogenesis and VEGFA expression in diabetic fractures was rescued by specific inhibition of TNF in vivo. In addition, the TNF inhibitor rescued the negative effect of diabetes on endothelial cell proliferation and endothelial cell apoptosis. The effect of TNFα in vitro was enhanced by high glucose and an advanced glycation endproduct to impair microvascular endothelial cell proliferation and tube formation and to stimulate apoptosis. The effect of TNF, high glucose and an AGE was mediated by the transcription factor FOXO1, which increased expression of p21 and caspase-3. These studies indicate that inflammation plays a major role in diabetes-impaired angiogenesis in endochondral bone formation through its effect on microvascular endothelial cells and FOXO1., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The reliability of X-ray radiography for diagnosing nasal bone fractures (NBFs) remains controversial. Recent studies show that, for determining the orientation and location of the displaced/depressed fracture, nasal sonography is as accurate as facial computed tomography. This retrospective study compared conductor-assisted nasal sonography (CANS) to conventional diagnostic tools and reported subjective patient satisfaction and discomfort after closed reduction combined with tube technique., Methods: This retrospective study reports the results of 329 refinement treatments for nasal bone fracture (including 199 men and 130 women) performed from 2005 to 2011. All patients were assessed with CANS and completed a survey immediately prior to removing the packing. Questionnaires were adapted from the nasal obstruction symptom evaluation (NOSE) scale., Results: The study found that CANS has a 97.2% rate of accuracy in diagnosing NBF. The visual analog scale scores of nasal obstruction, nasal congestion, sleep disturbance, trouble breathing, and inability to move air through the nose were analyzed. The experimental group scores were significantly different from the control group for all scores (p < 0.001)., Conclusion: Compared to conventional methods, CANS is more accurate for detecting NBF. We recommend its use as an alternative tool for diagnosing a nasal fracture. Because the tube technique balances pressure between the nasopharynx and middle ear during swallowing, patient comfort is enhanced. Application of these modifications can improve accuracy in diagnosing NBF and can improve the quality of NBF treatment., (Copyright © 2014. Published by Elsevier Taiwan.)

Aims/hypothesis: Diabetes interferes with bone formation and impairs fracture healing, an important complication in humans and animal models. The aim of this study was to examine the impact of diabetes on mesenchymal stem cells (MSCs) during fracture repair., Methods: Fracture of the long bones was induced in a streptozotocin-induced type 1 diabetic mouse model with or without insulin or a specific TNFα inhibitor, pegsunercept. MSCs were detected with cluster designation-271 (also known as p75 neurotrophin receptor) or stem cell antigen-1 (Sca-1) antibodies in areas of new endochondral bone formation in the calluses. MSC apoptosis was measured by TUNEL assay and proliferation was measured by Ki67 antibody. In vitro apoptosis and proliferation were examined in C3H10T1/2 and human-bone-marrow-derived MSCs following transfection with FOXO1 small interfering (si)RNA., Results: Diabetes significantly increased TNFα levels and reduced MSC numbers in new bone area. MSC numbers were restored to normal levels with insulin or pegsunercept treatment. Inhibition of TNFα significantly reduced MSC loss by increasing MSC proliferation and decreasing MSC apoptosis in diabetic animals, but had no effect on MSCs in normoglycaemic animals. In vitro experiments established that TNFα alone was sufficient to induce apoptosis and inhibit proliferation of MSCs. Furthermore, silencing forkhead box protein O1 (FOXO1) prevented TNFα-induced MSC apoptosis and reduced proliferation by regulating apoptotic and cell cycle genes., Conclusions/interpretation: Diabetes-enhanced TNFα significantly reduced MSC numbers in new bone areas during fracture healing. Mechanistically, diabetes-enhanced TNFα reduced MSC proliferation and increased MSC apoptosis. Reducing the activity of TNFα in vivo may help to preserve endogenous MSCs and maximise regenerative potential in diabetic patients.

Background: Distal fingertip replantation is associated with good functional and aesthetic results. Venous anastomosis is the most challenging procedure. For replantation with an artery anastomosis-only procedure (no venous anastomosis), some protocols have been designed to relieve venous congestion involve anticoagulation and the creation of wounds for persistent bleeding. This report presents the authors' experience of fingertip survival after artery anastomosis-only replantation with no persistent external bleeding., Methods: Twelve Tamai zone I fingertip total amputation patients who underwent artery anastomosis-only replantations were recruited from February 2009 to June 2012. Nerve repair was performed if identified. The patients were not subjected to conventional external bleeding methods. Both the blood color on pinprick and fingertip temperature difference between the replanted and uninjured digits were used as indicators of deteriorated venous congestion., Results: The replanted digits of 11 patients survived. The only failed replant exhibited an average temperature difference of more than 6°C compared with the uninjured digits and consistently exhibited darker blood during the pinprick test. All other replants exhibited average temperature differences of less than 6°C., Conclusions: In these Tamai zone I artery anastomosis-only replantations, fingertips survived without the use of external bleeding method, indicating that external bleeding is probably not obligatory for survival of artery anastomosis-only replanted digits distal to Tamai zone I. An increasing temperature difference between the replanted and uninjured digits and darker blood on pinprick may be used as indicators of deteriorating congestion signs., (© 2014 Wiley Periodicals, Inc.)

For many animals, hunger promotes changes in the olfactory system in a manner that facilitates the search for appropriate food sources. In this video article, we describe an automated assay to measure the effect of hunger or satiety on olfactory dependent food search behavior in the adult fruit fly Drosophila melanogaster. In a light-tight box illuminated by red light that is invisible to fruit flies, a camera linked to custom data acquisition software monitors the position of six flies simultaneously. Each fly is confined to walk in individual arenas containing a food odor at the center. The testing arenas rest on a porous floor that functions to prevent odor accumulation. Latency to locate the odor source, a metric that reflects olfactory sensitivity under different physiological states, is determined by software analysis. Here, we discuss the critical mechanics of running this behavioral paradigm and cover specific issues regarding fly loading, odor contamination, assay temperature, data quality, and statistical analysis.

Indigo carmine is a blue dye that is widely applied to localise ureteral orifices. It is generally believed to be a safe, biologically inert substance, and hypotensive reactions are extremely rare. However, we experienced three cases of indigo carmine-induced hypotension within a period of two weeks.

Background: The major disadvantage of rocuronium is the withdrawal movement associated with its injection. The analgesic effect of perioperative gabapentin has been evaluated. We investigated the effects of gabapentin on the withdrawal movement induced by rocuronium injection., Methods: 86 ASA physical status I or II patients, aged 18-69 years who were scheduled to undergo elective surgery with general anesthesia were enrolled. Patients were randomly allocated into two groups to receive either gabapentin 600 mg or placebo 2 hours prior to surgery. The patient's response to rocuronium injection was graded using a 4-point scale., Results: The incidence of withdrawal movement after rocuronium administration was significantly lower in the gabapentin group (55.0% in the control group vs 28.6% in the gabapentin group). The number of patients with generalized response indicating severe pain, was 9 (22.5%) in the control group and 3 (7.1%) in the gabapentin group., Conclusions: Pretreatment with a single oral dose of gabapentin 600 mg reduced the incidence and severity of withdrawal movement after rocuronium administration.

Tracheal compression by vascular anomalies in adults is uncommon and most related reports are of children. A 79-year-old woman without any respiratory history underwent a lumbar spine surgery under general anesthesia. She suddenly developed airway obstruction after a position change from supine to prone. A fiberoptic bronchoscopy showed the obstruction of endotracheal tube. The obstruction was relieved after we changed the depth of endotracheal tube and supported the patient's neck with a cotton roll. The surgery ended without any other event and the patient recovered safely. A computed tomography revealed the rightward tracheal deviation and tortuous innominate artery contact with trachea. The patient didn't manifest any respiratory related symptoms during postoperative period, and she was discharged without any treatment.

Methemoglobinemia is an uncommon but potentially fatal disorder. Most cases have no adverse clinical consequence and require no treatment, but methemoglobinemia is often overlooked as a cause of low oxygen saturation, and often mistaken for the more common causes of hypoxia by anesthesiologists despite simple bedside tests that indicate the presence of this treatable abnormality. We present a 68-year-old female patient who underwent gastrectomy for advanced gastric cancer with bleeding. In the preoperative period, the patient showed cyanosis and oxygen saturation was 85% by pulse oximeter, but oxygen saturation by arterial blood gas analysis was 100%. After tracheal intubation, the methemoglobin level was 18.3%. Ascorbic acid and methylene blue were administered. During preanesthetic evaluation, the patient had not informed the anesthesiologist that she had been taking dapsone.

A 48-year-old healthy woman was admitted in our hospital for elective hemorrhoidectomy. She developed sudden headache and chest pain, and showed sinus bradycardia, arrhythmia and hypotension forty minutes after spinal anesthesia with 0.5% hyperbaric bupivacaine. An EKG showed ST depression and an transthoracic echocardiogram performed in PACU demonstrated mild LV dysfunction with hypokinesia of LV inferolateral wall. An coronary angiography on postoperative day 1 revealed normal coronary vessel and akinesia of LV inferior wall. Levels of CK-MB and Troponin I were mildly elevated. With medical therapy, the patient's symptoms improved and recovered without any complication.

In order to investigate the potential of a Sanguisorba officinalis root extract as an active ingredient for wrinkle-care cosmetics, we measured its free radical scavenging activity, elastase inhibitory activity, expression of MMP-1 (matrix metalloprotease-1) in vitro, and type I collagen synthesis in normal human fibroblast cells. To isolate the main components from the S. officinalis root extract, we purified the extract by solvent fractionation, column chromatography, and recrystallization. The active component was identified as ziyuglycoside I by a spectroscopic analysis. Ziyuglycoside I increased the expression of type I collagen in a dose-dependent manner (by up to 71.3% at 50 muM). A clinical study of a formulation containing ziyuglycoside I, which involved visual evaluation and image analysis, showed a significantly different effect (p<0.05) of the test formulation from that of the placebo. This result suggests that ziyuglycoside I isolated from S. officinalis root extract could be used as an active ingredient for cosmetics.

In order to search for new active cosmetic ingredients of natural origin, we screened about 60 plants collected from Jeju Island, which is located in the southernmost part of the Republic of Korea. We investigated their free radical scavenging activity, elastase inhibition activity, and reduction of MMP-1 mRNA expression for the development of anti-aging ingredients as raw materials for use in cosmetics. In the free radical scavenging capacity assay, 12 extracts, including Typha orientalis (seed) and Torreya nucifera (leaf), showed significant free radical scavenging activity (up to SC(50)<30 microg/ml). Among these extracts, Nymphaea tetragona (rhizome) extract showed the highest free radical scavenging activity (SC(50)=4.7 microg/ml). In the anti-elastase inhibition assay, seven extracts, including Typha orientalis (seed) and Persicaria hydropiper (whole plant), showed high inhibitory activity (>50% at 100 mug/ml). Among these extracts, Persicaria hydropiper (whole plant) extract showed the highest elastase inhibition activity (IC(50) = 46.7 mug/ml). In the MMP-1 expression assay using RT-PCR, Typha orientalis (seed), Pyrrosia hastata (root), and Capsicum annum (whole plant) showed slightly lower inhibition activity than EGCG, which was used as a control. Furthermore, four extracts, including Persicaria hydropiper (whole plant), Filipendula glaberrima (root), Nymphaea tetragona (root), and Camellia japonica (leaf), completely inhibited the expression of MMP-1 in human fibroblast cells. The results showed that four of the 60 plant extracts may hold potential for use as natural active ingredients for anti-aging cosmetics.

Polychlorinated biphenyls (PCBs), a group of persistent and widespread environmental pollutants, are considered to be immunotoxic, carcinogenic, and to induce apoptosis. However, the cellular mechanisms underlying the action of PCBs have not been established. Here, we investigated the effects of PCBs on the induction of cyclooxygenase-2 (COX-2). Among the several congeners examined, only 2,2',4,6,6'-pentachlorobiphenyl (PeCB) specifically increased the COX-2 promoter activity, and the levels of COX-2 mRNA and protein, and thereby enhanced prostaglandin E2 (PGE2) synthesis in Rat-1 cells. By conducting mutation analyses of the COX-2 promoter and its transcription factor, we found that the CRE site in COX-2 promoter and c-Jun are important for increased COX-2 promoter activity induced by 2,2',4,6,6'-PeCB. In addition, 2,2',4,6,6'-PeCB-stimulated COX-2 induction was reduced by the specific MAPK kinase (MEK) inhibitor, PD98059, and in p53-deficient cells, implying that COX-2 induction requires the activation of ERK1/2 MAPK and p53. The selective COX-2 inhibitor, NS-398, potentiated the 2,2',4,6,6'-PeCB-induced mitochondrial apoptotic pathway involved in Bcl-xL attenuation, cytochrome c release and the subsequent activation of caspase-3. Furthermore, the cell death was prevented by PGE2 treatment, suggesting that 2,2',4,6,6'-PeCB-induced apoptosis is restricted by prostaglandin upregulation by COX-2. Taken together, these results demonstrate that 2,2',4,6,6'-PeCB-induced COX-2 expression may be an important compensatory mechanism for abating 2,2',4,6,6'-PeCB toxicity.

Lysophosphatidic acid (LPA) activates a family of cognate G protein-coupled receptors and is involved in various pathophysiological processes. However, it is not clearly understood how these LPA receptors are specifically coupled to their downstream signaling molecules. This study found that LPA(2), but not the other LPA receptor isoforms, specifically interacts with Na(+)/H(+) exchanger regulatory factor2 (NHERF2). In addition, the interaction between them requires the C-terminal PDZ domain-binding motif of LPA(2) and the second PDZ domain of NHERF2. Moreover, the stable expression of NHERF2 potentiated LPA-induced phospholipase C-beta (PLC-beta) activation, which was markedly attenuated by either a mutation in the PDZ-binding motif of LPA(2) or by the gene silencing of NHERF2. Using its second PDZ domain, NHERF2 was found to indirectly link LPA(2) to PLC-beta3 to form a complex, and the other PLC-beta isozymes were not included in the protein complex. Consistently, LPA(2)-mediated PLC-beta activation was specifically inhibited by the gene silencing of PLC-beta3. In addition, NHERF2 increases LPA-induced ERK activation, which is followed by cyclooxygenase-2 induction via a PLC-dependent pathway. Overall, the results suggest that a ternary complex composed of LPA(2), NHERF2, and PLC-beta3 may play a key role in the LPA(2)-mediated PLC-beta signaling pathway.

This study was carried out to evaluate the application of food irradiation technology as a method for reducing milk allergies. Bovine alpha-casein (ACA) and beta-lactoglobulin (BLG) were used as milk proteins. Using milk-hypersensitive patients' immunoglobulin E (IgE) and rabbit IgGs individually produced to ACA and BLG, the changes of allergenicity and antigenicity of irradiated proteins were observed by competitive indirect enzyme-linked immunosorbent assay. Allergenicity and antigenicity of the irradiated proteins were changed with different slopes of the inhibition curves. The disappearance of the band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and increase of the turbidity showed that solubility of the proteins decreased by radiation, and this decrease might be caused by agglomeration of the proteins. These results indicated that epitopes on milk allergens were structurally altered by gamma irradiation.