Expression of Epithelial-Mesenchymal Transition Markers in Epidermal Layer of Atopic Dermatitis.

The epithelial-mesenchymal transition (EMT) is a phenomenon, in which epithelial cells acquire a mesenchymal cell phenotype. It is important during wound healing; however, chronic inflammation leads to excessive EMT and causes tissue barrier dysfunction with hyperplasia. EMT is induced by several cytokines, such as interleukin (IL)-4 and IL-13. Additionally, IL-4 and IL-13 are known to increase in atopic dermatitis (AD) characterized by intense itching and eczema. Therefore, we assumed that there was commonality between the respective EMT and AD phenotypes. Herein, we evaluated EMT marker expression in AD skin and demonstrated that EMT-maker Snai1 and Twist expression were increased in AD mice model and patients with AD. Moreover, the epithelial-marker keratin 5 and mesenchymal marker Vimentin were co-expressed in the skin epidermis of mice with AD, suggesting the existence of hybrid epithelial-mesenchymal (E/M) cells possessing both epithelial and mesenchymal characteristics. In fact, we found that ΔNp63a, a stabilizing factor for hybrid E/M cells, was upregulated in the skin epidermis of the AD model mouse. Interestingly, increased expression of EMT markers was observed even at a nonlesion site in a patient with AD without initial inflammation or scratching. Therefore, EMT-like phenomena may occur independently of wound healing in skin of patients with AD.

Molecular basis of the unique osmoregulatory strategy in the inshore hagfish, Eptatretus burgeri.

Hagfishes are characterized by omo- and iono-conforming nature similar to marine invertebrates. Conventionally, hagfishes had been recognized as the most primitive living vertebrate that retains plesiomorphic features. However, some of the "ancestral" features of hagfishes, such as rudimentary eyes and the lack of vertebrae, have been proven to be deceptive. Similarly, by the principle of maximum parsimony, the unique body fluid regulatory strategy of hagfishes seems to be apomorphic, since the lamprey, another cyclostome, adopts osmo- and iono-regulatory mechanisms as in jawed vertebrates. Although hagfishes are unequivocally important upon discussing the origin and evolution of the vertebrate osmoregulatory system, the molecular basis for the body fluid homeostasis in hagfishes has been poorly understood. In the present study, we explored this matter in the inshore hagfish, Eptatretus burgeri, by analyzing the transcriptomes obtained from the gill, kidney and muscle of the animals acclimated to distinct environmental salinities. Together with the measurement of parameters in the muscular fluid compartment, our data indicate that the hagfish possesses an ability to conduct free amino acids (FAAs)-based osmoregulation at a cellular level, which is in coordination with the renal and branchial FAA absorption. We also revealed that the hagfish does possess the orthologs of the known osmoregulatory genes, and that the transepithelial movement of inorganic ions in the hagfish gill and kidney is more complex than previously thought. These observations pose a challenge to the conventional view that the physiological features of hagfishes have been inherited from the last common ancestor of the extant vertebrates.

Human IGF2 Gene Epigenetic and Transcriptional Regulation: At the Core of Developmental Growth and Tumorigenic Behavior.

Regulation of the human IGF2 gene displays multiple layers of control, which secures a genetically and epigenetically predetermined gene expression pattern throughout embryonal growth and postnatal life. These predominantly nuclear regulatory mechanisms converge on the function of the IGF2-H19 gene cluster on Chromosome 11 and ultimately affect IGF2 gene expression. Deregulation of such control checkpoints leads to the enhancement of IGF2 gene transcription and/or transcript stabilization, ultimately leading to IGF-II peptide overproduction. This type of anomaly is responsible for the effects observed in terms of both abnormal fetal growth and increased cell proliferation, typically observed in pediatric overgrowth syndromes and cancer. We performed a review of relevant experimental work on the mechanisms affecting the human IGF2 gene at the epigenetic, transcriptional and transcript regulatory levels. The result of our work, indeed, provides a wider and diversified scenario for IGF2 gene activation than previously envisioned by shedding new light on its extended regulation. Overall, we focused on the functional integration between the epigenetic and genetic machinery driving its overexpression in overgrowth syndromes and malignancy, independently of the underlying presence of loss of imprinting (LOI). The molecular landscape provided at last strengthens the role of IGF2 in cancer initiation, progression and malignant phenotype maintenance. Finally, this review suggests potential actionable targets for IGF2 gene- and regulatory protein target-degradation therapies.

Phylogenetic and functional properties of hagfish neurohypophysial hormone receptors distinct from their jawed vertebrate counterparts.

Vertebrate neurohypophysial hormones, i.e., vasopressin- and oxytocin-family peptides, exert versatile physiological actions via distinct G protein-coupled receptors. The neurohypophysial hormone receptor (NHR) family was classically categorized into four subtypes (V1aR, V1bR, V2R and OTR), while recent studies have identified seven subtypes (V1aR, V1bR, V2aR, V2bR, V2cR, V2dR and OTR; V2aR corresponds to the conventional V2R). The vertebrate NHR family were diversified via multiple gene duplication events at different scales. Despite intensive research effort in non-osteichthyes vertebrates such as cartilaginous fish and lamprey, the molecular phylogeny of the NHR family has not been fully understood. In the present study, we focused on the inshore hagfish (Eptatretus burgeri), another group of cyclostomes, and Arctic lamprey (Lethenteron camtschaticum) for comparison. Two putative NHR homologs, which were previously identified only in silico, were cloned from the hagfish and designated as ebV1R and ebV2R. In vitro, ebV1R, as well as two out of five Arctic lamprey NHRs, increased intracellular Ca2+ in response to exogenous neurohypophysial hormones. None of the examined cyclostome NHRs altered intracellular cAMP levels. Transcripts of ebV1R were detected in multiple tissues including the brain and gill, with intense hybridization signals in the hypothalamus and adenohypophysis, while ebV2R was predominantly expressed in the systemic heart. Similarly, Arctic lamprey NHRs showed distinct expression patterns, underscoring the multifunctionality of VT in the cyclostomes as in the gnathostomes. These results and exhaustive gene synteny comparisons provide new insights into the molecular and functional evolution of the neurohypophysial hormone system in vertebrates.

Cell cycle control by the insulin-like growth factor signal: at the crossroad between cell growth and mitotic regulation.

In proliferating cells and tissues a number of checkpoints (G1/S and G2/M) preceding cell division (M-phase) require the signal provided by growth factors present in serum. IGFs (I and II) have been demonstrated to constitute key intrinsic components of the peptidic active fraction of mammalian serum. In vivo genetic ablation studies have shown that the cellular signal triggered by the IGFs through their cellular receptors represents a non-replaceable requirement for cell growth and cell cycle progression. Retroactive and current evaluation of published literature sheds light on the intracellular circuitry activated by these factors providing us with a better picture of the pleiotropic mechanistic actions by which IGFs regulate both cell size and mitogenesis under developmental growth as well as in malignant proliferation. The present work aims to summarize the cumulative knowledge learned from the IGF ligands/receptors and their intracellular signaling transducers towards control of cell size and cell-cycle with particular focus to their actionable circuits in human cancer. Furthermore, we bring novel perspectives on key functional discriminants of the IGF growth-mitogenic pathway allowing re-evaluation on some of its signal components based upon established evidences.

Factors affecting patient safety culture in a university hospital under the universal health insurance system: A cross-sectional study from Japan.

We conducted a cross-sectional study of patient safety culture aimed at examining the factors that influence patient safety culture in university hospitals under a universal health insurance system. The Hospital Survey on Patient Safety Culture developed by the Agency for Healthcare Research and Quality was used. The survey was distributed to 1066 hospital employees, and 864 responded. The confirmatory factor analysis showed a good fit of the results to the 12-composites model. The highest positive response rates were for "(1) Teamwork within units" (81%) and "(2) Supervisor/manager expectations and actions promoting patient safety" (80%), and the lowest was for "(10) Staffing" (36%). Hayashi's quantification theory type 2 revealed that working hours per week had the greatest negative impact on patient safety culture. Under a universal health insurance system, workload and human resources might have a significant impact on the patient safety culture.

INF2-mediated actin filament reorganization confers intrinsic resilience to neuronal ischemic injury.

During early ischemic brain injury, glutamate receptor hyperactivation mediates neuronal death via osmotic cell swelling. Here we show that ischemia and excess NMDA receptor activation cause actin to rapidly and extensively reorganize within the somatodendritic compartment. Normally, F-actin is concentrated within dendritic spines. However, <5 min after bath-applied NMDA, F-actin depolymerizes within spines and polymerizes into stable filaments within the dendrite shaft and soma. A similar actinification occurs after experimental ischemia in culture, and photothrombotic stroke in mouse. Following transient NMDA incubation, actinification spontaneously reverses. Na+, Cl-, water, and Ca2+ influx, and spine F-actin depolymerization are all necessary, but not individually sufficient, for actinification, but combined they induce activation of the F-actin polymerization factor inverted formin-2 (INF2). Silencing of INF2 renders neurons vulnerable to cell death and INF2 overexpression is protective. Ischemia-induced dendritic actin reorganization is therefore an intrinsic pro-survival response that protects neurons from death induced by cell edema.

Tilapia prolactin cells are thermosensitive osmoreceptors.

Prolactin (PRL) cells within the rostral pars distalis (RPD) of euryhaline and eurythermal Mozambique tilapia, Oreochromis mossambicus, rapidly respond to a hyposmotic stimulus by releasing two distinct PRL isoforms, PRL188 and PRL177. Here, we describe how environmentally relevant temperature changes affected mRNA levels of prl188 and prl177 and the release of immunoreactive prolactins from RPDs and dispersed PRL cells. When applied under isosmotic conditions (330 mosmol/kgH2O), a 6°C rise in temperature stimulated the release of PRL188 and PRL177 from both RPDs and dispersed PRL cells under perifusion. When exposed to this same change in temperature, ∼50% of dispersed PRL cells gradually increased in volume by ∼8%, a response partially inhibited by the water channel blocker, mercuric chloride. Following their response to increased temperature, PRL cells remained responsive to a hyposmotic stimulus (280 mosmol/kgH2O). The mRNA expression of transient potential vanilloid 4, a Ca2+-channel involved in hyposmotically induced PRL release, was elevated in response to a rise in temperature in dispersed PRL cells and RPDs at 6 and 24 h, respectively; prl188 and prl177 mRNAs were unaffected. Our findings indicate that thermosensitive PRL release is mediated, at least partially, through a cell-volume-dependent pathway similar to how osmoreceptive PRL release is achieved.

A Novel Function of Sphingosylphosphorylcholine on the Inhibitory Effects of Acetylcholinesterase Activity.

Acetylcholine (ACh), a quaternary ammonium cation, is known as one of the itch inducer in atopic dermatitis (AD), an inflammatory skin disease with intense itching. Previous research has reported accumulation of ACh in lesional site of AD patients. Generally, ACh is metabolized by cholinesterase (ChE). Therefore, one of the causes of ACh accumulation may be the suppression of ChE activity. Increased levels of the multifunctional bioactive sphingolipid sphingosylphosphorylcholine (SPC) have also been detected in AD. Since SPC possesses a quaternary ammonium cation, like ACh, it is possible that SPC affects the activity of ChE catalyzing ACh metabolization. We investigated whether SPC influences the activity of ChE by performing enzymatic analysis of ChE in the presence of SPC. We found that SPC strongly suppressed acetylcholinesterase (AChE) activity, but the suppression of butyrylcholinesterase by SPC was quite low. The Michaelis constant (Km) of AChE in the presence of SPC increased, and the maximum velocity (Vmax) decreased, indicating that SPC acts as mixed-type inhibitor for AChE. The analysis of SPC analogs clarified the importance of both the quaternary ammonium cation and the carbon chain length of SPC for the AChE inhibitory effect and showed that SPC was unique in AChE inhibition among the sphingolipids in this study. These findings indicate a novel function of SPC on AChE inhibition. Thus, the inhibition activity of SPC may be a factor in the increase of ACh in AD.

Proteolytic Processing, Maturation, and Unique Synteny of the Streptomyces Hemagglutinin SHA.

SHA is an l-rhamnose- and d-galactose-binding lectin that agglutinates human group B erythrocytes and was first purified almost 50 years ago. Although the original SHA-producing Streptomyces strain was lost, the primary structure of SHA was more recently solved by mass spectrometry of the archived protein, which matched it to a similar sequence in the Streptomyces lavendulae genome. Using genomic and protein biochemical analyses, this study aimed to identify SHA-secreting Streptomyces strains to further investigate the expression and binding activities of these putative proteins. Of 67 strains genetically related to S. lavendulae, 17 secreted pro-SHAs in culture. Seven SHA homologues were purified to homogeneity and then subjected to liquid chromatography-high-resolution multistage mass spectrometry (LC-MS/MS) and hemagglutination (HA) assays. Processing of pro-SHAs occurred during and after purification, indicating that associated proteases converted pro-SHAs into mature SHAs with molecular masses and HA activities similar to that of the archived SHA. Previously, the SHA monomer was shown to have two carbohydrate binding sites. The present study, however, found no HA activity in pro-SHAs, suggesting that pro-SHAs have only one binding site. Genetically, the SHA gene resides in conserved syntenic regions. The published genomes of 1,234 Streptomyces strains were analyzed, revealing 18 strains with SHA genes, 16 of which localized to a unique syntenic region. The SHA syntenic region consists of ∼17 open reading frames (ORFs) and is specific to S. lavendulae-related strains. Notably, a lipoprotein gene excludes SHA from the synteny in some strains, suggesting that horizontal gene transfer events during the course of evolution shaped the distribution of SHA genes. IMPORTANCE Lectins are extremely useful molecules for the study of glycans and carbohydrates. Here, we show that homologous genes encoding the l-rhamnose- and d-galactose-binding lectins, SHAs, are present in multiple bacterial strains, genetically related to Streptomyces lavendulae. SHA genes are expressed as precursor pro-SHA proteins that are truncated and mature into fully active lectins with two carbohydrate binding sites, which exhibit hemagglutination activity for type B red blood cells. The SHA gene is located within a conserved syntenic region, hinting at specific but yet-to-be-discovered biological roles of this carbohydrate-binding protein for its soil-dwelling microbial producer.

Lipopolysaccharide Preconditioning Augments Phagocytosis of Malaria-Parasitized Red Blood Cells by Bone Marrow-Derived Macrophages in the Liver, Thereby Increasing the Murine Survival after Plasmodium yoelii Infection.

Malaria remains a grave concern for humans, as effective medical countermeasures for Plasmodium infection have yet to be developed. Phagocytic clearance of parasitized red blood cells (pRBCs) by macrophages is an important front-line innate host defense against Plasmodium infection. We previously showed that repeated injections of low-dose lipopolysaccharide (LPS) prior to bacterial infection, called LPS preconditioning, strongly augmented phagocytic/bactericidal activity in murine macrophages. However, whether LPS preconditioning prevents murine Plasmodium infection is unclear. We investigated the protective effects of LPS preconditioning against lethal murine Plasmodium infection, focusing on CD11bhigh F4/80low liver macrophages, which are increased by LPS preconditioning. Mice were subjected to LPS preconditioning by intraperitoneal injections of low-dose LPS for 3 consecutive days, and 24 h later, they were intravenously infected with pRBCs of Plasmodium yoelii 17XL. LPS preconditioning markedly increased the murine survival and reduced parasitemia, while it did not reduce tumor necrosis factor (TNF) secretions, only delaying the peak of plasma gamma interferon (IFN-γ) after Plasmodium infection in mice. An in vitro phagocytic clearance assay of pRBCs showed that the CD11bhigh F4/80low liver macrophages, but not spleen macrophages, in the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11bhigh F4/80low liver macrophages from LPS-preconditioned mice to control mice significantly improved survival after Plasmodium infection. We conclude that LPS preconditioning stimulated CD11bhigh F4/80low liver macrophages to augment the phagocytic clearance of pRBCs, which may play a central role in resistance against Plasmodium infection.

Primary leiomyoma of the ureter: a case report.

BACKGROUND: Only 14 cases of leiomyoma with ureteral origin have been reported previously. Such primary leiomyomas often present as hydronephrosis, making the diagnosis difficult. Radical nephroureterectomy is often performed because of the possible diagnosis of a malignant tumor. We report the 15th case of primary leiomyoma with a ureteral origin. CASE PRESENTATION: A 51-year-old Japanese man presented with a chief complaint of asymptomatic gross hematuria with a history of hypertension. Enhanced computed tomography showed a tumor at the upper part of the right ureter that appeared to be the cause of hydronephrosis and contracted kidney; no retroperitoneal lymphadenopathy and distal metastasis were observed. A well-defined 20-mm (diameter) defect was identified at the upper of the right ureter on retrograde pyelogram with no bladder cancer on cystoscopy. Urine cytology and right divided renal urine cytology findings were negative. Laparoscopic nephroureterectomy was performed, and the extracted tumor measured 20 × 13 mm. Histopathological examination revealed primary leiomyoma with no recurrence 16 months after the operation. CONCLUSIONS: Preoperative examination with the latest available ureteroscopic technology can help preserve renal function in the case of benign tumors by enabling preoperative ureteroscopic biopsy or intraoperative rapid resection. Moreover, nephroureterectomy is recommended in the case of preoperative suspicion of ureteral malignant tumors.

Local administration of anti-hepatocyte growth factor-neutralizing antibody reverts naturally occurring periodontitis.

OBJECTIVES: Periodontitis is a chronic inflammatory process associated with the loss of tooth-supporting tissue. The imbalance of epithelial-mesenchymal signaling is considered to drive disease progression, and hepatocyte growth factor (HGF) is one of the main mediators of this interaction. The aim of this study was to validate the role of HGF in the pathogenesis of periodontitis and to evaluate the effects of anti-HGF neutralizing antibodies. METHODS: Gingival tissues from cynomolgus monkeys, which naturally develop severe periodontitis, were isolated to establish an in vitro periodontitis model. Periodontitis-affected monkeys were treated by gingival injection of anti-HGF neutralizing antibodies. The therapeutic effects were documented by clinical examination (probing depth and bleeding on probing), histological examination of tissue, and reevaluation of gingival fibroblasts in the in vitro model. RESULTS: Periodontitis-affected monkeys contain periodontitis-associated fibroblasts (PAFs) with a pro-inflammatory phenotype that induced pronounced collagen degradation in vitro. This degradation was effectively inhibited by anti-HGF-neutralizing antibodies. Locally administered anti-HGF antibody to monkey gingiva clinically improved the severity of periodontitis. This was also reflected in the tissue histology with lower inflammatory cell infiltrates in treated gingiva than in non-treated gingiva. Moreover, fibroblasts isolated from anti-HGF-treated gingiva demonstrated reduced collagen degradation capacity. CONCLUSIONS: Our study confirmed the central role of HGF in the pathogenesis of severe periodontitis in relevant in vitro and in vivo models. The positive effect of anti-HGF treatment provides a strong rationale for the use of anti-HGF-neutralizing antibodies for the treatment of human periodontitis.

Targeting hepatocyte growth factor in epithelial-stromal interactions in an in vitro experimental model of human periodontitis.

Periodontitis is a chronic inflammatory disease leading to progressive connective tissue degradation and loss of the tooth-supporting bone. Clinical and experimental studies suggest that hepatocyte growth factor (HGF) is involved in the dysregulated fibroblast-epithelial cell interactions in periodontitis. The aim of this study was to explore effects of HGF to impact fibroblast-induced collagen degradation. A patient-derived experimental cell culture model of periodontitis was applied. Primary human epithelial cells and fibroblasts isolated from periodontitis-affected gingiva were co-cultured in a three-dimensional collagen gel. The effects of HGF neutralizing antibody on collagen gel degradation were tested and transcriptome analyses were performed. HGF neutralizing antibody attenuated collagen degradation and elicited expression changes of genes related to extracellular matrix (ECM) and cell adhesion, indicating that HGF signaling inhibition leads to extensive impact on cell-cell and cell-ECM interactions. Our study highlights a potential role of HGF in periodontitis. Antagonizing HGF signaling by a neutralizing antibody may represent a novel approach for periodontitis treatment.

The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells.

Homer is a postsynaptic scaffold protein, which has long and short isoforms. The long form of Homer consists of an N-terminal target-binding domain and a C-terminal multimerization domain, linking multiple proteins within a complex. The short form of Homer only has the N-terminal domain and likely acts as a dominant negative regulator. Homer2a, one of the long form isoforms of the Homer family, expresses with a transient peak in the early postnatal stage of mouse cerebellar granule cells (CGCs); however, the functions of Homer2a in CGCs are not fully understood yet. In this study, we investigated the physiological roles of Homer2a in CGCs using recombinant adenovirus vectors. Overexpression of the Homer2a N-terminal domain construct, which was made structurally reminiscent with Homer1a, altered NMDAR1 localization, decreased NMDA currents, and promoted the survival of CGCs. These results suggest that the Homer2a N-terminal domain acts as a dominant negative protein to attenuate NMDAR-mediated excitotoxicity. Moreover, we identified a novel short form N-terminal domain-containing Homer2, named Homer2e, which was induced by apoptotic stimulation such as ischemic brain injury. Our study suggests that the long and short forms of Homer2 are involved in apoptosis of CGCs.

Frequency-dependent effects of EEG phase resetting on reaction time.

There is trial-to-trial variability in the reaction time to stimulus presentation. Since this variability exists even in an identical stimulus condition, it reflects the internal neural dynamics of the brain. To understand the neural dynamics that influence the reaction time, we conducted an electroencephalogram (EEG) experiment in which participants were asked to press a response button as quickly as possible when a stimulus was visually presented. Phase-locking factor analysis revealed that phase resetting in two frequency bands, which appeared 0.2 s after the stimulus presentation, characterized the reaction time. The combination of the theta band phase resetting in the left parietal region and the delta band phase resetting mainly in the posterior region was associated with the fastest reaction time, whereas delta band phase resetting without theta band phase resetting was associated with the faster reaction time. The results indicated that there were frequency-dependent effects in the relationships between the EEG phase resetting and reaction time.

Age-Dependent Decline in Salinity Tolerance in a Euryhaline Fish.

Euryhaline teleost fish are characterized by their ability to tolerate a wide range of environmental salinities by modifying the function of osmoregulatory cells and tissues. In this study, we experimentally addressed the age-related decline in the sensitivity of osmoregulatory transcripts associated with a transfer from fresh water (FW) to seawater (SW) in the euryhaline teleost, Mozambique tilapia, Oreochromis mossambicus. The survival rates of tilapia transferred from FW to SW were inversely related with age, indicating that older fish require a longer acclimation period during a salinity challenge. The relative expression of Na+/K+/2Cl- cotransporter 1a (nkcc1a), which plays an important role in hyposmoregulation, was significantly upregulated in younger fish after SW transfer, indicating a clear effect of age in the sensitivity of branchial ionocytes. Prolactin (Prl), a hyperosmoregulatory hormone in O. mossambicus, is released in direct response to a fall in extracellular osmolality. Prl cells of 4-month-old tilapia were sensitive to hyposmotic stimuli, while those of >24-month-old fish did not respond. Moreover, the responsiveness of branchial ionocytes to Prl was more robust in younger fish. Taken together, multiple aspects of osmotic homeostasis, from osmoreception to hormonal and environmental control of osmoregulation, declined in older fish. This decline appears to undermine the ability of older fish to survive transfer to hyperosmotic environments.

Optimization and validation of diffusion MRI-based fiber tracking with neural tracer data as a reference.

Diffusion-weighted magnetic resonance imaging (dMRI) allows non-invasive investigation of whole-brain connectivity, which can reveal the brain's global network architecture and also abnormalities involved in neurological and mental disorders. However, the reliability of connection inferences from dMRI-based fiber tracking is still debated, due to low sensitivity, dominance of false positives, and inaccurate and incomplete reconstruction of long-range connections. Furthermore, parameters of tracking algorithms are typically tuned in a heuristic way, which leaves room for manipulation of an intended result. Here we propose a general data-driven framework to optimize and validate parameters of dMRI-based fiber tracking algorithms using neural tracer data as a reference. Japan's Brain/MINDS Project provides invaluable datasets containing both dMRI and neural tracer data from the same primates. A fundamental difference when comparing dMRI-based tractography and neural tracer data is that the former cannot specify the direction of connectivity; therefore, evaluating the fitting of dMRI-based tractography becomes challenging. The framework implements multi-objective optimization based on the non-dominated sorting genetic algorithm II. Its performance is examined in two experiments using data from ten subjects for optimization and six for testing generalization. The first uses a seed-based tracking algorithm, iFOD2, and objectives for sensitivity and specificity of region-level connectivity. The second uses a global tracking algorithm and a more refined set of objectives: distance-weighted coverage, true/false positive ratio, projection coincidence, and commissural passage. In both experiments, with optimized parameters compared to default parameters, fiber tracking performance was significantly improved in coverage and fiber length. Improvements were more prominent using global tracking with refined objectives, achieving an average fiber length from 10 to 17 mm, voxel-wise coverage of axonal tracts from 0.9 to 15%, and the correlation of target areas from 40 to 68%, while minimizing false positives and impossible cross-hemisphere connections. Optimized parameters showed good generalization capability for test brain samples in both experiments, demonstrating the flexible applicability of our framework to different tracking algorithms and objectives. These results indicate the importance of data-driven adjustment of fiber tracking algorithms and support the validity of dMRI-based tractography, if appropriate adjustments are employed.

Clinical Trial of Low Irritative Skin Care Cosmetics in Japanese Subjects with Dry Skin.

PURPOSE: To evaluate whether MediQOL, which was developed as a care cosmetic for sensitive skin, causes a change in skin condition for subjects with dry skin requiring moisture retention. SUBJECTS AND METHODS: This study includes 20 Japanese subjects with dry skin who required moisture retention, as identified by a dermatologist. The subjects used the novel MediQOL products twice a day for four consecutive weeks. A skin evaluation was performed by a dermatologist, and each subject completed a questionnaire prior to the study period and after two and four weeks of MediQOL use. RESULTS: After four weeks of MediQOL use, alleviation of skin dryness, redness, and itchiness was observed in the subjects. The water/oil content of the skin also improved during the study period. CONCLUSION: Four weeks of MediQOL use resulted in the alleviation of skin dryness, redness, and itchiness and balanced the water/oil content of the skin. MediQOL is expected to be effective in improving the condition of various skin types, including oily, mixed, and sensitive skin as well as dry skin.