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Purpose In this study, we determined whether there were significant differences in procedure time, radiation dose, fluoroscopy time, and total contrast media dose when unruptured wideneck bifurcation aneurysms (WNBAs) were treated with the Woven EndoBridge (WEB) device and stent-assisted coil (SAC) embolization. Materials and Methods The WEB device and SAC embolization (14:17) were used to treat 31 cases of internal carotid artery bifurcation, anterior communicating artery, middle cerebral artery bifurcation, and basilar bifurcation aneurysms between August 2021 and December 2022. The procedure time, radiation dose, fluoroscopy time, and total contrast medium dose between the 2 treatment groups were compared and analyzed. In the WEB device group, the results between operators were compared, and the follow-up radiologic outcomes were investigated. Results The procedure and fluoroscopy times were significantly shorter in the WEB device group. Radiation and total contrast media dose were also significantly smaller in the WEB device, but there was no significant difference in results between operators. The follow-up radiological outcome showed adequate occlusion in 83.3% (10/12) of cases. Conclusion The WEB device can be used as an alternative treatment method among the available endovascular treatment methods for WNBAs to reduce radiation exposure and the dose of contrast media when used adequately with appropriate indications.

Summary: The human body reacts to tissue damage by generating damage-associated molecular patterns (DAMPs) that activate sterile immune responses. To date, little is known about how DAMPs are removed to avoid excessive immune responses. Here, we show that proteasomal dysfunction induces the release of mitochondrial DNA (mtDNA) as a DAMP that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway and is subsequently degraded through the N-degron pathway. In the resolution phase of sterile immune responses, DNA-dependent protein kinase (DNA-PK) senses cytosolic mtDNA and activates N-terminal (Nt-) arginylation by ATE1 R-transferases. The substrates of Nt-arginylation include the molecular chaperone BiP/GRP78 retrotranslocated from the endoplasmic reticulum (ER). R-BiP, the Nt-arginylated species of BiP, is associated with cytosolic mtDNA to accelerate its targeting to autophagic membranes for lysosomal degradation. Thus, cytosolic mtDNA activates the N-degron pathway to facilitate its own degradation and form a negative feedback loop, by which the cell can turn off sterile immune responses at the right time.

Background Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity. Methods A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared. Results Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered. Conclusion The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

Abstract Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory disorders of the central nervous system (CNS) with similar characteristics. The differential diagnosis between MS and NMOSD is critical for initiating early effective therapy. In this study, we developed a deep learning model to differentiate between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) using brain magnetic resonance imaging (MRI) data. The model was based on a modified ResNet18 convolution neural network trained with 5-channel images created by selecting five 2D slices of 3D FLAIR images. The accuracy of the model was 76.1%, with a sensitivity of 77.3% and a specificity of 74.8%. Positive and negative predictive values were 76.9% and 78.6%, respectively, with an area under the curve of 0.85. Application of Grad-CAM to the model revealed that white matter lesions were the major classifier. This compact model may aid in the differential diagnosis of MS and NMOSD in clinical practice.

Single embryo transfer (SET) is a technique used in assisted reproductive treatment (ART) that is used to promote singleton pregnancies. To date, there are five reported cases of dizygotic twin pregnancies with mothers who underwent SET. Here, we present a sixth case of a dichorionic, diamniotic twin pregnancy with sex discordance. The patient is a 34-year-old woman with unexplained secondary infertility who underwent in vitro fertilization (IVF) and frozen-thawed embryo transfer from a SET. The ultrasonographic images from the first and second trimester scans identified dichorionic, diamniotic twin gestations. The delivery was full term and postnatal genetic testing confirmed 46, XX, and 46, XY offspring. Pathology reports of the placental and membrane findings reported diamniotic, dichorionic twins. There was no zygosity testing conducted, thus it is unknown if the twins are monozygotic or dizygotic. Two possible etiologies for sex-discordant twins, in this case, are concurrent natural conception via breakthrough ovulation at the time of SET, or discordant postzygotic nondisjunction of a single embryo. Multiple gestations may still occur in the setting of SET and zygosity testing in these instances would better elucidate our understanding of this occurrence. Moreover, improved data on the zygosity of multiple gestations following SET may enhance patient counseling.

Extracellular vesicles play an important role in intercellular communication, with the potential to serve as biomaterials for nanocarriers. Combining such extracellular vesicles and liposomes results in advanced drug delivery carriers. In this study, we attempted to fabricate hybrid vesicles using a membrane fusion method and incorporated an anticancer drug. As a result, we successfully prepared nanosized uniform hybrid vesicles and evaluated their physicochemical characteristics and intracellular uptake mechanisms via endocytosis in various cell lines. Compared to liposomes, the hybrid vesicles showed better physical properties and a relatively higher reduction in cell viability, which was presumably dependent on the specific cell type. These findings suggest that fusion-based hybrid vesicles offer a novel strategy for delivering therapeutic agents and provide insights into the types of extracellular vesicles that are useful in fabricating hybrid vesicles to develop an advanced drug delivery system.

Abstract Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two representative chronic inflammatory demyelinating disorders of the central nervous system. We aimed to determine and compare the alterations of white matter (WM) connectivity between MS, NMOSD, and healthy controls (HC). This study included 68 patients with relapsing–remitting MS, 50 with NMOSD, and 26 HC. A network-based statistics method was used to assess disrupted patterns in WM networks. Topological characteristics of the three groups were compared and their associations with clinical parameters were examined. WM network analysis indicated that the MS and NMOSD groups had lower total strength, clustering coefficient, global efficiency, and local efficiency and had longer characteristic path length than HC, but there were no differences between the MS and NMOSD groups. At the nodal level, the MS group had more brain regions with altered network topologies than did the NMOSD group when compared with the HC group. Network alterations were correlated with Expanded Disability Status Scale score and disease duration in both MS and NMOSD groups. Two distinct subnetworks that characterized the disease groups were also identified. When compared with NMOSD, the most discriminative connectivity changes in MS were located between the thalamus, hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and inferior and superior temporal gyri. In conclusion, MS patients had greater network dysfunction compared to NMOSD and altered short connections within the thalamus and inferomedial temporal regions were relatively spared in NMOSD compared with MS.

Abstract The proper estimation of prestressing force (PF) distribution is critical to ensure the safety and serviceability of prestressed concrete (PSC) structures. Although the PF distribution can be theoretically calculated based on certain predictive equations, the resulting accuracy of the theoretical PF needs to be further validated by comparison with reliable test data. Therefore, a Smart Strand with fiber optic sensors embedded in a core wire was developed and applied to a full-scale specimen and two long-span PSC girder bridges in this study. The variation in PF distribution during tensioning and anchoring was measured using the Smart Strand and was analyzed by comparison with the theoretical distribution calculated using the predictive equations for short-term prestress losses. In particular, the provisions for anchorage seating loss and elastic shortening loss were reviewed and possible improvements were proposed. A new method to estimate the amount of anchorage slip based on real PF distributions revealed that the general assumption of 3–6-mm slip falls within a reasonable range. Finally, the sensitivity of the PF distribution to a few of the variables included in the equation of the elastic shortening loss was examined. The study results confirmed that the developed Smart Strand can be used to improve the design parameters or equations in PSC structures by overcoming the drawbacks of conventional sensing technologies.

Abstract Although fatigue is a major symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), the underlying mechanism remains unclear. We explored the relationship between subcortical structures and fatigue severity to identify neural substrates of fatigue in NMOSD. Clinical characteristics with brain magnetic resonance imaging were evaluated in forty patients with NMOSD. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) questionnaire (a higher score indicates less fatigue). We assessed the correlation between subcortical structures and fatigue severity using surface-based shape analysis. Most of the enrolled patients showed fatigue (72.5%; mean FACIT-fatigue score, 34.8 ± 10.8). The FACIT-fatigue score was negatively correlated with Expanded Disability Status Scale and Beck Depression Inventory scores (r = − 0.382, p = 0.016; r = − 0.578, p

Abstract Backgrounds Alzheimer’s disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. Objectives We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer’s disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood–derived MSCs (hUCB-MSCs). Methods We recruited nine mild-to-moderate Alzheimer’s disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 107 cells/2 mL), and six patients received a high dose (3.0 × 107 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study. Results After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed. Conclusions Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy. Trial registration ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017

Abstract We investigated the effect of education on the edge efficiency in resting state functional networks (RSFNs) in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease dementia (ADD). We collected the data of 57 early aMCI, 141 late aMCI, 173 mild ADD, and 39 moderate-to-severe ADD patients. We used years of education as a proxy for cognitive reserve. We measured edge efficiency for each edge in RSFNs, and performed simple slope analyses to discover their associations with education level among the four groups. In the late aMCI, a sub-network that had hub nodes in the right middle frontal gyrus and the right posterior cingulate gyrus, showed a positive association between RSFN edge efficiency and education (threshold = 2.5, p = 0.0478). There was no negative effect of education on the RSFN edge efficiency. In the early aMCI, mild ADD, and moderate-to-severe ADD, there were no sub-networks showing positive or negative correlation between education and RSFN edge efficiency. There was a positive effect of higher education on RSFN edge efficiency in the late aMCI, but not in the early aMCI or ADD. This indicates that in late aMCI, those who have higher education level have greater ability to resist collapsed functional network.

The purpose of this study is to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) to improve the oral absorption of poorly water-soluble olaparib. Through the solubility test of olaparib in various oils, surfactants and co-surfactants, pharmaceutical excipients were selected. Self-emulsifying regions were identified by mixing the selected materials at various ratios, and a pseudoternary phase diagram was constructed by synthesizing these results. The various physicochemical properties of microemulsion incorporating olaparib were confirmed by investigating the morphology, particle size, zeta potential, drug content and stability. In addition, the improved dissolution and absorption of olaparib were also confirmed through a dissolution test and a pharmacokinetic study. An optimal microemulsion was generated in the formulation of Capmul® MCM 10%, Labrasol® 80% and PEG 400 10%. The fabricated microemulsions were well-dispersed in aqueous solutions, and it was also confirmed that they were maintained well without any problems of physical or chemical stability. The dissolution profiles of olaparib were significantly improved compared to the value of powder. Associated with the high dissolutions of olaparib, the pharmacokinetic parameters were also greatly improved. Taken together with the results mentioned above, the microemulsion could be an effective tool as a formulation for olaparib and other similar drugs.

Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aβ) and lacune with cognitive function in patients with mild cognitive impairment (MCI).Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB) PET for 3 years. The mediation effect of subcortical structure on the association of PiB or lacunes with cognitive function was analyzed using mixed effects models.Results: Volume changes in the amygdala and hippocampus partially mediated the effect of PiB changes on memory function (direct effect = −0.168/−0.175, indirect effect = −0.081/−0.077 for amygdala/hippocampus) and completely mediated the effect of PiB changes on clinical dementia rating scale sum of the box (CDR-SOB) (indirect effect = 0.082/0.116 for amygdala/hippocampus). Volume changes in the thalamus completely mediated the effect of lacune on memory, frontal executive functions, and CDR-SOB (indirect effect = −0.037, −0.056, and 0.047, respectively).Conclusions: Our findings provide a better understanding of the distinct role of subcortical structures in the mediation of the relationships of amyloid or vascular changes with a decline in specific cognitive domains.

PURPOSEEarly enhancement and a washout pattern are reported to be the characteristic imaging features of Warthin tumor (WT). The purpose of this study was to evaluate the enhancement patterns of basal cell adenoma (BCA) and myoepithelioma (ME) of the parotid gland on two-phase computed tomography (CT), compared with WT.METHODSWe retrospectively evaluated two-phase CT examinations of histologically proven 19 BCAs, 12 MEs, and 23 WTs of the parotid gland. In all patients, CT scans were obtained at early and delayed phases with scanning delays of 40 and 180 s, respectively. We measured the attenuation values on each phase of CT scans and calculated washout attenuation and relative percentage enhancement washout ratio. From the data acquired, we statistically compared the enhancing characteristics among three tumor groups.RESULTSBased on the results of washout attenuation and relative percentage enhancement washout ratio, 15 (79%) of 19 BCAs, 9 (75%) of 12 MEs, and 23 (100%) of 23 WTs demonstrated a washout pattern of enhancement on two-phase CT scans. Despite variations of the individual tumors, both parameters revealed no significant difference among three tumor groups.CONCLUSIONBCAs and MEs of the parotid gland frequently show early enhancement and a washout pattern on two-phase CT, which can be indistinguishable from WTs in the majority of cases.

Abstract Objective To investigate the whole-brain resting-state functional connectivity in patients with chronic migraine (CM) using a data-driven method. Methods We prospectively recruited patients with either episodic migraine (EM) or CM aged 18–60 years who visited the headache clinic of the Samsung Medical Center from July 2016 to December 2017. All patients underwent 3 T MRI using an identical scanner. Patients were considered interictal if they did not have a migraine headache at the day and ± 1 days of functional MRI acquisition. Using the group-independent component analysis (ICA), connectivity analysis with a weighted and undirected network model was performed. The between-group differences in degree centrality (DC) values were assessed using 5000 permutation tests corrected with false discovery rate (FDR). Results A total of 62 patients (44 EM and 18 CM) were enrolled in this study. Among the seven functionally interpretable spatially independent components (ICs) identified, only one IC, interpreted as the pain matrix, showed a significant between-group difference in DC (CM > EM, p = 0.046). This association remained significant after adjustment for age, sex, migraine with aura (MWA), allodynia, depression, and anxiety (p = 0.038). The pain matrix was functionally correlated with the hypothalamus (p = 0.040, EM > CM) and dorsal raphe nucleus (p = 0.039, CM > EM) with different levels of strength in EM and CM. Conclusion CM patients have a stronger connectivity in the pain matrix than do EM patients. Functional alteration of the pain network might play a role in migraine chronification.

The aim of this study was to develop a four-component self-nanoemulsifying drug delivery system (FCS) to enhance the solubility and dissolution of pazopanib hydrochloride (PZH). In the solubility test, PZH showed a highly pH-dependent solubility (pH 1.2 > water >> pH 4.0 and pH 6.8) and was solubilized at 70 °C in the order Kollisolv PG (5.38%, w/w) > Kolliphor RH40 (0.49%) > Capmul MCM C10 (0.21%) and Capmul MCM C8 (0.19%), selected as the solubilizer, the surfactant, and the oils, respectively. In the characterization of the three-component SNEDDS (TCS) containing Kolliphor RH40/Capmul MCM C10, the particle size of dispersion was very small (95% at 120 min) at four different pHs with 1% polysorbate 80, whereas the raw PZH and Kollisolv PG solution showed a pH-dependent poor dissolution rate (about 40% at 120 min), specifically at pH 6.8 with 1% polysorbate 80. In conclusion, PZH-loaded FCS in this work demonstrated enhanced solubility and a consistent dissolution rate regardless of medium pH.

Biodegradable nanoparticles (NPs) are preferred as drug carriers because of their effectiveness in encapsulating drugs, ability to control drug release, and low cytotoxicity. Although poly(lactide co-glycolide) (PLGA)-based NPs have been used for controlled release strategies, they have some disadvantages. This study describes an approach using biodegradable polyhydroxyalkanoate (PHA) to overcome these challenges. By varying the amount of PHA, NPs were successfully fabricated by a solvent evaporation method. The size range of the NPS ranged from 137.60 to 186.93 nm, and showed zero-order release kinetics of paclitaxel (PTX) for 7 h, and more sustained release profiles compared with NPs composed of PLGA alone. Increasing the amount of PHA improved the PTX loading efficiency of NPs. Overall, these findings suggest that PHA can be used for designing polymeric nanocarriers, which offer a potential strategy for the development of improved drug delivery systems for sustained and controlled release.

Compared to other types of sensors, fiber optic sensors have improved accuracy and durability. Recently, the Smart Strand was developed to maximize the advantages of fiber optic sensors for measuring the cable forces in prestressed concrete structures or cable-supported bridges. The Smart Strand has fiber Bragg gratings (FBGs) embedded in a core wire of the seven-wire strand. Similar to other sensors, the strain measured at an FBG is affected by temperature; therefore, the temperature effect that is not related to the mechanical strain should be compensated for or corrected in the long-term measurement subjected to temperature variation. However, a temperature compensation procedure for the FBG has yet to be established, and relevant studies have used different formulas for the compensation. Moreover, when the FBG sensors are packaged with a certain material—such as fiber reinforced polymer—for protection, it is important to consider the interaction between the FBG, packaging material, and host material during thermal behavior. Therefore, this study proposed a reasonable procedure for temperature compensation for the FBG sensors embedded in packaging material and host material. In particular, the thermal sensitivity of the Smart Strand was intensively investigated. The proposed theoretical formulas were validated through comparison with data obtained from various specimens in a temperature-controlled chamber. Finally, the procedure was applied to correct the data measured using the Smart Strands in a 20-m-long full-scale specimen for about a year, thus resulting in a realistic trend of the long-term prestressing force.

Abstract Background The protective effect of education has been well established in Alzheimer’s disease, whereas its role in patients with isolated cerebrovascular diseases remains unclear. We examined the correlation of education with cortical thickness and cerebral small vessel disease markers in patients with pure subcortical vascular mild cognitive impairment (svMCI) and patients with pure subcortical vascular dementia (SVaD). Methods We analyzed 45 patients with svMCI and 47 patients with SVaD with negative results on Pittsburgh compound B positron emission tomographic imaging who underwent structural brain magnetic resonance imaging. The main outcome was cortical thickness measured using surface-based morphometric analysis. We also assessed the volumes of white matter hyperintensities (WMH) and numbers of lacunes as other outcomes. To investigate the correlation of education with cortical thickness, WMH volume, and number of lacunes, multiple linear regression analyses were performed after controlling for covariates, including Mini Mental State Examination, in the svMCI and SVaD groups. Results In the SVaD group, higher education was correlated with more severe cortical thinning in the bilateral dorsolateral frontal, left medial frontal, and parahippocampal areas, whereas there was no correlation of education with cortical thickness in the svMCI group. There was no correlation between education and cerebral small vessel disease, including WMH and lacunes, in both patients with svMCI and patients with SVaD. Conclusions Our findings suggest that the compensatory effects of education on cortical thinning apply to patients with SVaD, which might be explained by the cognitive reserve hypothesis.

Migraineurs show an increased load of white matter hyperintensities (WMHs) and more rapid deep WMH progression. Previous methods for WMH segmentation have limited efficacy to detect small deep WMHs. We developed a new fully automated detection pipeline, DEWS (DEep White matter hyperintensity Segmentation framework), for small and superficially-located deep WMHs. A total of 148 non-elderly subjects with migraine were included in this study. The pipeline consists of three components: 1) white matter (WM) extraction, 2) WMH detection, and 3) false positive reduction. In WM extraction, we adjusted the WM mask to re-assign misclassified WMHs back to WM using many sequential low-level image processing steps. In WMH detection, the potential WMH clusters were detected using an intensity based threshold and region growing approach. For false positive reduction, the detected WMH clusters were classified into final WMHs and non-WMHs using the random forest (RF) classifier. Size, texture, and multi-scale deep features were used to train the RF classifier. DEWS successfully detected small deep WMHs with a high positive predictive value (PPV) of 0.98 and true positive rate (TPR) of 0.70 in the training and test sets. Similar performance of PPV (0.96) and TPR (0.68) was attained in the validation set. DEWS showed a superior performance in comparison with other methods. Our proposed pipeline is freely available online to help the research community in quantifying deep WMHs in non-elderly adults. Keywords: Deep white matter hyperintensity, Automated detection, Migraine

Abstract Although the association between apolipoprotein E (APOE) genotype and disease progression is well characterized in patients with Alzheimer’s disease, such a relationship is unknown in patients with subcortical vascular cognitive impairment. We evaluated whether APOE genotype is associated with disease progression in subcortical vascular mild cognitive impairment (svMCI) patients. We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3 homozygotes, and 11 APOE2 carriers). Patients were annually followed-up with brain MRI and neuropsychological tests for three years and underwent a second Pittsburgh compound B (PiB)-PET at a mean interval of 32.3 months. Amyloid-ß burden was quantified by PiB standardized uptake value ratio (SUVR), and the amount of small vessel disease was quantified by number of lacune and small vessel disease score on MRI. We also measured cortical thickness. During the three years of follow-up, compared to the APOE3 homozygotes, there was less increase in PiB SUVR among APOE2 carriers (p = 0.023), while the APOE genotype did not show significant effects on small vessel disease progression. APOE2 carriers also showed less cortical thinning (p = 0.023) and a slower rate of cognitive decline (p = 0.009) compared to those with APOE3 homozygotes. Our findings suggest that, in svMCI patients, APOE2 has protective effects against amyloid-ß accumulation, cortical thinning, and cognitive decline.

PURPOSE:Nasopharyngeal inflammatory pseudotumor (NIPT) is hard to differentiate from infiltrating nasopharyngeal carcinoma (NPC) on conventional magnetic resonance imaging (MRI). The purpose of this study is to determine whether discrepant lesion sizes estimated on T1- and fat-suppressed T2-weighted images can help distinguish between NIPT and NPC.METHODS:We retrospectively reviewed MRI data of histologically proven 14 NIPTs and 18 infiltrating NPCs. We measured the area of the lesion on contrast-enhanced T1-weighted, unenhanced T1-weighted, and fat-suppressed T2-weighted images by placing the largest possible polygonal region-of-interest within the lesion at the same level. Using lesion size measured on contrast-enhanced T1-weighted image as the reference, we calculated and compared area ratio of T1 (ART1) and area ratio of T2 (ART2) between NIPTs and NPCs. For validation, we also undertook a double-blinded study by two reviewers and assessed the diagnostic performance and interobserver agreement.RESULTS:For NIPTs, ART2 (median, 0.48; range, 0.18–0.97) was statistically significantly less than ART1 (median, 1.01; range, 0.80–1.99), while these values were not significantly different for NPCs. The interobserver agreement in differentiating between NIPT and NPC was good, with a sensitivity of 93% and a specificity of 83%–94%.CONCLUSION:In contrast to NPCs, NIPTs appear smaller on fat-suppressed T2-weighted images than on T1-weighted images. This discrepancy in the lesion size estimated on T1-weighted and fat-suppressed T2-weighted images may provide a simple and consistent way to differentiate between NIPTs and NPCs on conventional MRI.

Probiotics offer various health benefits. Lactobacillus plantarum has been used for decades to enhance human intestinal mucosal immunity and improve skin barrier integrity. Extracellular vesicles (EVs) derived from eukaryotic or prokaryotic cells have been recognized as efficient carriers for delivery of biomolecules to recipient cells, and to efficiently regulate human pathophysiology. However, the mechanism underlying the beneficial effects of probiotic bacteria-derived EVs on human skin is unclear. Herein, we investigated how L. plantarum-derived EVs (LEVs) exert beneficial effects on human skin by examining the effect of LEVs on cutaneous immunity, particularly on macrophage polarization. LEVs promoted differentiation of human monocytic THP1 cells towards an anti-inflammatory M2 phenotype, especially M2b, by inducing biased expression of cell-surface markers and cytokines associated with M2 macrophages. Pre- or post-treatment with LEVs under inflammatory M1 macrophage-favouring conditions, induced by LPS and interferon-γ, inhibited M1-associated surface marker, HLA-DRα expression. Moreover, LEV treatment significantly induced expression of macrophage-characteristic cytokines, IL-1β, GM-CSF and the representative anti-inflammatory cytokine, IL-10, in human skin organ cultures. Hence, LEVs can trigger M2 macrophage polarization in vitro, and induce an anti-inflammatory phenomenon in the human skin, and may be a potent anti-inflammatory strategy to alleviate hyperinflammatory skin conditions.

Background: Progressed tissue culture techniques have allowed us to easily obtain mass products of tissue-cultured mountain ginseng over 100 yr old (TCMG-100). We investigated the effects of TCMG-100 extract on erectile function using in vitro and in vivo studies. Methods: To examine the relaxation effects and mechanisms of action of TCMG-100 on rabbit cavernosal strips evaluated in an organ bath. To investigate the long-term treatment effect of TCMG-100, 8-wk administration was performed. After administration of TCMG-100, intracavernosal pressure, cyclic guanosine monophosphate and nitric oxide (NO) levels of cavernosal tissue, serum testosterone level, histological observation of collagen fiber, endothelium, smooth muscle cell, and transforming growth factor-β1 were investigated. Results: TCMG-100 extract displayed dose-dependent relaxation effects on precontracted rabbit corporal smooth muscle. The TCMG-100-induced relaxation was significantly reduced by removing the endothelium, and treatment with an NO synthase inhibitor or NO scavenger. Eight weeks of TCMG-100 administration increased intracavernosal pressure in a rat model. The levels of cyclic guanosine monophosphate and NO in the corpus callosum and serum testosterone level were also increased by TCMG-100 treatment. Furthermore, histological evaluation of collagen, smooth muscle, and endothelium showed increases in endothelium and smooth muscle, and a decrease in transforming growth factor-β1 expression. Conclusion: These relaxation effects on corporal smooth muscle and increased erectile function suggest that TCMG-100 might be used as an alternative herbal medicine to improve erectile function.

PURPOSE:Invasive fungal sinusitis (IFS) has rarely been reported to develop from non-IFS. The purpose of this study was to disclose the nature of the extrasinonasal infiltrative process in the presence of a sinonasal fungus ball (FB).METHODS:We retrospectively reviewed the medical records, computed tomography, magnetic resonance images of 13 patients with sinonasal FB and the extrasinonasal infiltrative process. Based on histology and clinical course, we divided the extrasinonasal infiltrative process into IFS and the nonfungal inflammatory/infectious process (NFIP). The images were analyzed with particular attention to the presence of cervicofacial tissue infarction (CFTI).RESULTS:Of the 13 patients, IFS was confirmed in only one, while the remaining 12 were diagnosed to have presumed NFIP. One patient with IFS died shortly after diagnosis. In contrast, all 12 patients with presumed NFIP, except one, survived during a mean follow-up of 17 months. FB was located in the maxillary sinus (n=4), sphenoid sinus (n=8), and both sinuses (n=1). Bone defect was found in five patients, of whom four had a defect in the sphenoid sinus. Various sites were involved in the extrasinonasal infiltrative process, including the orbit (n=10), intracranial cavity (n=9), and soft tissues of the face and neck (n=7). CFTI was recognized only in one patient with IFS.CONCLUSION:In most cases, the extrasinonasal infiltrative process in the presence of sinonasal FB did not seem to be caused by IFS but probably by NFIP. In our study, there were more cases of invasive changes with the sphenoid than with the maxillary FB.

This paper presents a multi-functional strand capable of introducing prestressing force in prestressed concrete (PSC) girders and sensing their static and dynamic behavior as well. This innovative strand is developed by replacing the core steel wire of the strand used in PSC structures with a carbon fiber-reinforced polymer (CFRP) wire with a built-in optical Fiber Bragg Grating (FBG) sensor. A full-scale girder specimen was fabricated by applying this multi-function strand to check the possibility of tracking the change of prestressing force at each construction stage. Moreover, dynamic data could be secured during dynamic loading tests without installing accelerometers and made it possible to obtain the natural frequencies of the structure. The results verified the capability to effectively manage the prestressing force in the PSC bridge structure by applying the PC strand with a built-in optical sensor known for its outstanding practicability and durability.

This study intends to verify analytically and experimentally the performance of a new type of prestressed concrete (PSC) I-girder for its application as railway bridge. Since the girder-type railway bridge develops relatively low torsional rigidity, there is risk for the dynamic responses to amplify due to the superposition of the torsional mode and flexural mode. The superposition of the torsional and flexural modes as well as the dynamic stability of the railway bridge were examined through dynamic analysis. Three-dimensional modelling was built to be suitable for carrying out moving load analysis. Four different span lengths of 30, 35, 40 and 45 m adopted considering the most applied span length currently and future lengthening of the span length. Moreover, a full-scale girder specimen with span length of 35 m was fabricated and subjected to dynamic loading. The measured dynamic responses were then compared to the analytic values. Finally, the ultimate bearing capacity of the specimen was verified by static loading test.

ObjectiveIn vivo visualization of intracranial atherosclerotic plaque has been performed only with high-resolution magnetic resonance imaging (HRMR). We investigated whether atherosclerotic plaque of the basilar artery (BA) can be identified in conventional magnetic resonance imaging (MRI).MethodsPatients with acute ischemic stroke who had BA stenosis ("symptomatic BAA") were retrospectively recruited using the prospective stroke registry. In the HRMR databank, subjects without BA stenosis were recruited and classified as those with silent plaque ("silent BAA") and without any plaque ("normal controls"). Outer diameter of the BA and T2 plaque sign (an eccentric or complete obscuration of normal flow-void) within the BA were assessed by two blinded raters using conventional T2 MRI.ResultsSeventy-five patients with symptomatic BAA, 40 with asymptomatic BAA, and 36 normal controls were included in the study. Maximal BA diameter was significantly larger in symptomatic BAA patients with 70% stenosis (all pConclusionsOur data suggest that BA atherosclerosis can be detected by conventional MRI. When the use of HRMR is limited, conventional MR imaging may give additive information to clinicians.

The aim of this study was to develop a coenzyme Q10 (CoQ10) microemulsion system with improved solubility, penetration, and wound healing efficacy. Based on the pseudo-ternary diagram, microemulsions containing isopropyl myristate (IPM), Cremophor EL®, and Transcutol® HP were selected and confirmed to be nanosized (w/w %) demonstrated a higher permeation efficacy compared to microemulsions with S/CoS ratio of 3:1 or 4:1 (w/w %). Additionally, the CoQ10-loaded microemulsion with an S/CoS ratio of 2:1 demonstrated a relatively rapid wound healing effect in keratinocytes and fibroblasts. Overall, these data suggest that a microemulsion based on IPM, Cremophor EL®, and Transcutol® HP could be an effective vehicle for the topical administration of CoQ10 and could be utilized for the application of other therapeutic agents that have difficulty in penetrating the skin.

Background: In neuromyelitis optica spectrum disorder (NMOSD), brain involvement is common and cognitive dysfunction is frequently found. The study investigated alterations of white matter (WM) connectivity using graph theory and correlations with cognitive dysfunction in patients with NMOSD.Methods: We prospectively enrolled patients with NMOSD (N = 14) and age- and sex-matched healthy controls (N = 21). Structural connections between any pair of the 90 cortical and subcortical regions were established using diffusion tensor imaging and graph theory. Network-based statistics was employed to assess differences in WM connectivity between the NMOSD and healthy control groups. We further investigated the relationship between the topological network characteristics and cognitive test performances.Results: WM network analysis showed decreased total strength of brain networks and two disrupted sub-networks in patients with NMOSD. The first featured six hub nodes in the rectus, hippocampus, calcarine, cuneus, and precuneus with the left-sided predominance. The second had six hub nodes in the orbitomiddle frontal, post-central, superior parietal, superior, and middle temporal, and caudate with the right-sided predominance. Compared to healthy controls, NMOSD patients showed poor performance on tests for attention/working memory and processing speed, visuospatial processing, and executive function, which were associated with significant decreases in nodal clustering coefficient, local efficiency, and regional efficiency in the disrupted sub-networks (all p < 0.05).Conclusions: The data show the overall WM disruption and the relationship between poor cognitive function and sub-network alterations identified by the network analysis in NMOSD patients. We suggest that cognitive dysfunction is related to dysconnectivity of WM network including default mode network in NMOSD.

Prestressed concrete (PSC) is one of the most reliable, durable and widely used construction materials, which overcomes the weakness of concrete in tension by the introduction of a prestress force. Smart strands enabling measurement of the prestress force have recently been developed to maintain PSC structures throughout their lifetime. However, the smart strand cannot give a representative indication of the whole prestress force when used in multi-strand systems since each strand sustains a different prestress force. In this paper, the actual distribution of the prestress force in a multi-strand system is examined using elastomagnetic (EM) sensors to develop a method for tracking representative indicators of the prestress force using smart strands.

The N-end rule pathway is a proteolytic system in which single N-terminal amino acids of proteins act as a class of degrons (N-degrons) that determine the half-lives of proteins. We have previously identified a family of mammals N-recognins (termed UBR1, UBR2, UBR4/p600, and UBR5/EDD) whose conserved UBR boxes bind N-degrons to facilitate substrate ubiquitination and proteasomal degradation via the ubiquitin-proteasome system (UPS). Amongst these N-recognins, UBR1 and UBR2 mediate ubiquitination and proteolysis of short-lived regulators and misfolded proteins. Here, we characterized the null phenotypes of UBR4-deficient mice in which the UBR box of UBR4 was deleted. We show that the mutant mice die around embryonic days 9.5-10.5 (E9.5-E10.5) associated with abnormalities in various developmental processes such as neurogenesis and cardiovascular development. These developmental defects are significantly attributed to the inability to maintain cell integrity and adhesion, which significantly correlates to the severity of null phenotypes. UBR4-loss induces the depletion of many, but not all, proteins from the plasma membrane, suggesting that UBR4 is involved in proteome-wide turnover of cell surface proteins. Indeed, UBR4 is associated with and required to generate the multivesicular body (MVB) which transiently store endocytosed cell surface proteins before their targeting to autophagosomes and subsequently lysosomes. Our results suggest that the N-recognin UBR4 plays a role in the homeostasis of cell surface proteins and, thus, cell adhesion and integrity.

Zinc is an important trace metal in immune systems, and zinc transporters are involved in many immune responses. Recent advances have revealed the structural and biochemical bases for zinc transport across the cell membrane, with clinical implications for the regulation of zinc homeostasis in immune cells like dendritic cells, T cells, B cells, and mast cells. In this review, we discuss the function, structure, and transport aspects of two major mammalian zinc transporter types, importers and exporters. First, Zrt-/Irt-like proteins (ZIPs) mediate the zinc influx from the extracellular or luminal side into the cytoplasm. There are 14 ZIP family members in humans. They form a homo- or heterodimer with 8 transmembrane domains and extra-/intracellular domains of various lengths. Several ZIP members show specific extracellular domains composed of two subdomains, a helix-rich domain and proline-alanine-leucine (PAL) motif-containing domain. Second, ZnT (zinc transporter) was initially identified in early studies of zinc biology; it mediates zinc efflux as a counterpart of ZIPs in zinc homeostasis. Ten family members have been identified. They show a unique architecture characterized by a Y-shaped conformation and a large cytoplasmic domain. A precise, comprehensive understanding of the structures and transport mechanisms of ZIP and ZnT in combination with mice experiments would provide promising drug targets as well as a basis for identifying other transporters with therapeutic potential.

PurposeWe present our experiences of intra-arterial tirofiban injection through a deployed Solitaire stent as a rescue therapy after failed mechanical thrombectomy in patients with acute ischemic stroke.Materials and MethodsData on 18 patients treated with adjunctive tirofiban injection through a temporarily deployed Solitaire stent after failed mechanical thrombectomy were retrospectively reviewed. Solitaire stent was used as a primary thrombectomy device in 16 of 18 patients. Two patients received manual aspiration thrombectomy initially. If initial mechanical thrombectomy failed, tirofiban was injected intra-arterially through the deployed Solitaire stent and then subsequent Solitaire thrombectomy was performed.ResultsFourteen patients had occlusions in the middle cerebral artery, 2 in the distal internal carotid artery, and 2 in the basilar artery. Successful recanalization was achieved in 14 patients (77.7%) after intra-arterial injection of tirofiban and subsequent Solitaire thrombectomy. Three patients without successful recanalization after rescue method received angioplasty with stenting. Overall, successful recanalization (TICI grades 2b and 3) was achieved in 17 (94.4%) of 18 patients. Periprocedural complications occurred in 5 patients: distal migration of emboli in 5 patients and vessel perforation in 1. Three patients died. Good functional outcome (mRS ≤ 2) was achieved in 9 patients (50.0%) at 3 months.ConclusionRescue intra-arterial injection of tirofiban through a temporarily deployed Solitaire stent may facilitate further recanalization in cases of failed mechanical thrombectomy in patients with acute ischemic stroke.

Prestressed Concrete Wire and Strand (PC) strands are the most used materials to introduce prestress in a Pre-Stressed Concrete (PSC) structure. However, it is difficult to evaluate the final prestress force of the PC strand after prestressing or its residual prestress force after completion of the structure on site. This impossibility to assess eventual loss of prestress of the PC strand has resulted in a number of serious accidents and even in the collapse of several structures. This situation stresses the necessity to maintain the prestress force residual or after prestressing for the evaluation of the health of the concrete structure throughout its lifespan. Recently, several researchers have studied methods enabling one to verify the prestress force by inserting an optical fiber sensor inside the strand but failed to provide simple techniques for the fabrication of these devices to fulfill measurement performance from the design prestress to failure. Moreover, these methods require the additional installation of electrical resistance strain gages, displacement sensors and load cells on the outer surface of the structure for long-term precise measurement. This paper proposes a method enabling one to evaluate precisely and effectively the prestress force of the PC strand and intends to verify the applicability of the proposed method on actual concrete structures. To that end, an innovative PC strand is developed by embedding a Fiber Bragg Grating (FBG) sensor in the core wire of the PC strand so as to enable short term as well as long term monitoring. The measurement performance of the developed strand is then evaluated experimentally and the reliability of the monitoring data is assessed.

Purpose: This study aimed to evaluate the ultrasonographic findings for various types of vascular closure devices (VCDs) immediately after the angiographic procedure and at 6-month follow-up. Methods: We included 18 VCDs including Angio-Seal (n=4), FemoSeal (n=8), ExoSeal (n=3), Perclose (n=2), and StarClose (n=1) in this study. Four patients were implanted with 2 VCDs at the each side of bilateral femoral arteries, while the remaining 8 patients were inserted 1 VCD at the right femoral artery. Ultrasonography was performed within 10 days and at approximately 6 months after the angiographic procedure. Ultrasonographic morphology of the attached VCD and its relationship with the arterial wall were analyzed. Results: Initial ultrasonography revealed the attached VCD as the relevant unique structure with successful deployment and hemostasis. Follow-up ultrasonography demonstrated partial absorption of hemostatic materials in cases of Angio-Seal (n=3), FemoSeal (n=5), and ExoSeal (n=3), changes in the soft tissue surrounding the femoral artery in case of Angio-Seal (n=1), arterial intimal hyperplasia in cases of FemoSeal (n=3), and no gross changes as compared with the initial ultrasonographic findings in cases of Perclose (n=2) and StarClose (n=1). Conclusion: Initial ultrasonographic evaluation reflected the unique structure of each VCD, with most of them being easily distinguishable. Follow-up ultrasonography revealed various changes in the affected vessels.

PurposeAn intracranial aneurysm, with or without subarachnoid hemorrhage (SAH), is a relevant health problem. The rupture of an intracranial aneurysm is a critical concern for individual health; even an unruptured intracranial aneurysm is an anxious condition for the individual. The aim of this guideline is to present current and comprehensive recommendations for the management of intracranial aneurysms, with or without rupture.Materials and MethodsWe performed an extensive literature search, using Medline. We met in person to discuss recommendations. This document is reviewed by the Task Force Team of the Korean Society of Interventional Neuroradiology (KSIN).ResultsWe divided the current guideline for ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms (UIAs). The guideline for RIAs focuses on diagnosis and treatment. And the guideline for UIAs focuses on the definition of a high-risk patient, screening, principle for treatment and selection of treatment method.ConclusionThis guideline provides practical, evidence-based advice for the management of patients with an intracranial aneurysm, with or without rupture.

PurposeThe purpose of this study was to analyze the results of an immediate and mid-term angiographic and clinical follow-up of endovascular treatment for paraclinoid aneurysms.Materials and MethodsFrom January 2002 to December 2012, a total of 113 consecutive patients (mean age: 56.2 years) with 116 paraclinoid saccular aneurysms (ruptured or unruptured) were treated with endovascular coiling procedures. Clinical and angiographic outcomes were retrospectively evaluated.ResultsNinety-three patients (82.3%) were female. The mean size of the aneurysm was 5.5 mm, and 101 aneurysms (87.1%) had a wide neck. Immediate catheter angiography showed complete occlusion in 40 aneurysms (34.5%), remnant sac in 51 (43.9%), and remnant neck in 25 (21.6%). Follow-up angiographic studies were performed on 80 aneurysms (69%) at a mean period of 20.4 months. Compared with immediate angiographic results, follow-up angiograms showed no change in 38 aneurysms, improvement in 37 (Fig. 2), and recanalization in 5. There were 6 procedure-related complications (5.2%), with permanent morbidity in one patient.ConclusionOut study suggests that properly selected patients with paraclinoid aneurysms can be successfully treated by endovascular means.

D-allulose, a C-3 epimer of D-fructose, is a rare monosaccharide used as a food ingredient or a sweetener. In the present study, the in vitro metabolic stability of D-allulose was examined in biorelevant media, that is, simulated gastric fluid (SGF) and fasted state simulated intestinal fluid (FaSSIF) containing digestive enzymes, and in cryopreserved human and rat hepatocytes. The hepatocyte metabolic stabilities of D-allulose were also investigated and compared with those of fructose and erythritol (a sugar-alcohol with no calorific value). D-allulose was highly stable in SGF (97.8% remained after 60 min) and in FaSSIF (101.3% remained after 240 min), indicating it is neither pH-labile nor degraded in the gastrointestinal tract. D-allulose also exhibited high levels of stability in human and rat hepatocytes (94.5−96.8% remained after 240 min), whereas fructose was rapidly metabolized (43.1−52.6% remained), which suggested these two epimers are metabolized in completely different ways in the liver. The effects of D-allulose on glucose and fructose levels were negligible in hepatocytes. Erythritol was stable in human and rat hepatocytes (102.1−102.9% remained after 240 min). Intravenous pharmacokinetic studies in rats showed D-allulose was eliminated with a mean half-life of 72.2 min and a systemic clearance of 15.8 mL/min/kg. Taken together, our results indicate that D-allulose is not metabolized in the liver, and thus, unlikely to contribute to hepatic energy production.

Hemangioblastoma is a benign and highly vascular tumor. Complete surgical resection of highly vascular tumor such as hemangioblastoma may be challenging due to excessive bleeding. Preoperative embolization of these lesions may decrease the intraoperative blood loss and facilitate excision. We report three cases of cerebellar hemangioblastomas that were embolized using Onyx.

We report our experience using Onyx for embolization of dural arteriovenous fistula (DAVF) under dual lumen balloon catheter flow arrest. Transfemoral cerebral angiography revealed a superior sagittal sinus (SSS) DAVF that was supplied via multiple branches of the external carotid arteries, the right anterior cerebral arteries, and the meningeal branches of the internal carotid artery. There was no anterograde venous drainage through the SSS, and venous drainage was almost retrograde through the medullary and cortical veins. Under general anesthesia, a transvenous approach was utilized to place the microcatheter close to the fistula site. After intravenous embolization with various coils, DAVF was partially occluded; Balloon catheter gained access to the DAVF via the right middle meningeal artery. We injected Onyx through the Scepter C catheter, after which DAVF was nearly completely occluded. Balloon-assisted Onyx embolization is a feasible and effective approach for the management of DAVF.

Development of de novo aneurysm or aneurysm regrowth after complete clipping of an intracranial aneurysm is rare. We report coiled cases of de novo aneurysm and aneurysm regrowth. We retrospectively reviewed 107 cases of intracranial aneurysm coiling performed in our hospital, identifying five cases of coiled aneurysm that were de novo aneurysm or aneurysm regrowth. In all the cases, total or near total occlusion was seen. There were no complications related to the procedure. In two of the three patients with ruptured aneurysms, consciousness level on admission was stupor. When the patient was discharged after the treatment, one of them had 4 of the modified Rankin Scale. The other one had 5 on discharge. The rest three patients had 0. As for a de novo aneurysm or a regrowth of aneurysm, coiling may be considered when clipping is difficult.

The purpose of this study was to demonstrate the potential alterations in structural network properties related to physical activity (PA) in healthy elderly. We recruited 76 elderly individuals with normal cognition from Samsung Medical Center in Seoul, Korea. All participants underwent the Cambridge Neuropsychological Test Automated Battery and 3.0T brain magnetic resonance imaging (MRI). Participants were subdivided into quartiles according to the International Physical Activity Questionnaire scores, which represents the amount of PA. Through graph theory based analyses, we compared global and local network topologies according to PA quartile. The higher PA group demonstrated better performance in speed processing compared to the lower PA group. Regional nodal strength also significantly increased in the higher PA group, which involved the bilateral middle frontal, bilateral inferior parietal, right medial orbitofrontal, right superior and middle temporal gyri. These results were further replicated when the highest and the lowest quartile groups were compared in terms of regional nodal strengths and local efficiency. Our findings that the regional nodal strengths associated with the attentional network were increased in the higher PA group suggest the preventive effects of PA on age-related cognitive decline, especially in attention.

The purpose of this study was to investigate if multi-domain cognitive training, especially robot-assisted training, alters cortical thickness in the brains of elderly participants. A controlled trial was conducted with 85 volunteers without cognitive impairment who were 60 years old or older. Participants were first randomized into two groups. One group consisted of 48 participants who would receive cognitive training and 37 who would not receive training. The cognitive training group was randomly divided into two groups, 24 who received traditional cognitive training and 24 who received robot-assisted cognitive training. The training for both groups consisted of daily 90-min-session, five days a week for a total of 12 weeks. The primary outcome was the changes in cortical thickness. When compared to the control group, both groups who underwent cognitive training demonstrated attenuation of age related cortical thinning in the frontotemporal association cortices. When the robot and the traditional interventions were directly compared, the robot group showed less cortical thinning in the anterior cingulate cortices. Our results suggest that cognitive training can mitigate age-associated structural brain changes in the elderly.ClnicalTrials.gov NCT01596205.

The recently developed smart strand offers the possibility of measuring the prestress force of the tendon from jacking and all along its service life. In the present study, a method estimating the force distribution in all the tendons of a prestressed concrete (PSC) girder installed with one smart strand is proposed. The force distribution in the prestressed tendons is formulated by the friction and the anchorage slip, and is obtained through an optimization process with respect to the compatibility conditions and equilibrium of the forces in the section of the PSC girder. The validation of the proposed method through a numerical example and experiment shows that it can be used to estimate the force developed in the tendon.

The recently developed smart strand can be used to measure the prestress force in the prestressed concrete (PSC) structure from the construction stage to the in-service stage. The higher cost of the smart strand compared to the conventional strand renders it unaffordable to replace all the strands by smart strands, and results in the application of only a limited number of smart strands in the PSC structure. However, the prestress forces developed in the strands of the multi-strand system frequently adopted in PSC structures differ from each other, which means that the prestress force in the multi-strand system cannot be obtained by simple proportional scaling using the measurement of the smart strand. Therefore, this study examines the prestress force distribution in the multi-strand system to find the correlation between the prestress force measured by the smart strand and the prestress force distribution in the multi-strand system. To that goal, the prestress force distribution was measured using electromagnetic sensors for various factors of the multi-strand system adopted on site in the fabrication of actual PSC girders. The results verified the possibility to assume normal distribution for the prestress force distribution per anchor head, and a method computing the mean and standard deviation defining the normal distribution is proposed. This paper presents a meaningful finding by proposing an estimation method of the prestress force based upon field-measured data of the prestress force distribution in the multi-strand system of actual PSC structures.

The kidney filter represents a unique assembly of podocyte epithelial cells that tightly enwrap the glomerular capillaries with their complex foot process network. While deficiency of the polarity proteins Crumbs and aPKC result in impaired podocyte foot process architecture, the function of basolateral polarity proteins for podocyte differentiation and maintenance remained unclear. Here we report, that Scribble is expressed in developing podocytes, where it translocates from the lateral aspects of immature podocytes to the basal cell membrane and foot processes of mature podocytes. Immunogold electron microscopy reveals membrane associated localisation of Scribble predominantly at the basolateral site of foot processes. To further study the role of Scribble for podocyte differentiation Scribble(flox/flox) mice were generated by introducing loxP-sites into the Scribble introns 1 and 8 and these mice were crossed to NPHS2.Cre mice and Cre deleter mice. Podocyte-specific Scribble knockout mice develop normally and display no histological, ultrastructural or clinical abnormalities up to 12 months of age. In addition, no increased susceptibility to glomerular stress could be detected in these mice. In contrast, constitutive Scribble knockout animals die during embryonic development indicating the fundamental importance of Scribble for embryogenesis. Like in podocyte-specific Scribble knockout mice, the development of podocyte foot processes and the slit diaphragm was unaffected in kidney cultures from constitutive Scribble knockout animals. In summary these results indicate that basolateral polarity signaling via Scribble is dispensable for podocyte function, highlighting the unique feature of podocyte development with its significant apical membrane expansions being dominated by apical polarity complexes rather than by basolateral polarity signaling.

The labyrinth is the highly vascularized part of the rodent placenta that allows efficient transfer of gases, nutrients, wastes, and other molecules between the maternal and embryonic circulations. These two blood compartments are separated by blastocyst-derived trophoblasts and endothelial cells with an intervening basement membrane that contains laminin and other typical basement membrane components. Previously we reported that the labyrinth of laminin α5 knockout (LMα5-/-) embryos exhibits reduced vascularization and detachment of endothelial cells from the basement membrane, which normally contains LMα5. As very little is known about the origin of this vascular basement membrane, we investigated the cellular requirements for LMα5 expression in the mouse placental labyrinth. By fluorescence-activated cell sorting and RT-PCR we confirmed that both endothelial cells and trophoblasts normally express LMα5. Using Cre-loxP technology and doxycycline-mediated gene expression, we generated genetically mosaic placentas in which either the trophoblasts or the endothelial cells, but not both, expressed LMα5. We found that the overall architecture of the labyrinth was normal as long as one of these two cell types expressed LMα5, even if it was transgene-derived human laminin α5. These results suggest that laminin trimers containing α5 that are synthesized and secreted by endothelium or by trophoblasts are capable of integrating into the basement membrane and promoting normal vascularization of the placenta. Additional studies showed that endothelium-expressed human LMα5 can support vascularization of the kidney glomerulus, consistent with previous studies using a tissue grafting approach.

Purpose: This study aimed to evaluate the quality of artificial intelligence (AI)/machine learning (ML) studies on hemorrhagic stroke using the Minimum Information for Medical AI Reporting (MINIMAR) and Minimum Information About Clinical Artificial Intelligence Modeling (MI-CLAIM) frameworks to promote clinical application. Materials and Methods: PubMed, MEDLINE, and Embase were searched for AI/ML studies on hemorrhagic stroke. Out of the 531 articles found, 29 relevant original research articles were included. MINIMAR and MI-CLAIM scores were assigned by two experienced radiologists to assess the quality of the studies. Results: We analyzed 29 investigations that utilized AI/ML in the field of hemorrhagic stroke, involving a median of 224.5 patients. The majority of studies focused on diagnostic outcomes using computed tomography scans (89.7%) and were published in computer science journals (48.3%). The overall adherence rates to reporting guidelines, as assessed through the MINIMAR and MI-CLAIM frameworks, were 47.6% and 46.0%, respectively. In MINIMAR, none of the studies reported the socioeconomic status of the patients or how missing values had been addressed. In MI-CLAIM, only two studies applied model-examination techniques to improve model interpretability. Transparency and reproducibility were limited, as only 10.3% of the studies had publicly shared their code. Cohen's kappa between the two radiologists was 0.811 and 0.779 for MINIMAR and MI-CLAIM, respectively. Conclusion: The overall reporting quality of published AI/ML studies on hemorrhagic stroke is suboptimal. It is necessary to incorporate model examination techniques for interpretability and promote code openness to enhance transparency and increase the clinical applicability of AI/ML studies. [ABSTRACT FROM AUTHOR]