Twist family BHLH transcription factor 1 is required for the maintenance of leukemia stem cell in MLL-AF9+ acute myeloid leukemia.

Leukemia stem cells (LSC) are a rare population capable of limitless self-renewal and are responsible for the initiation, maintenance, and relapse of leukemia. Elucidation of the mechanisms underlying the regulation of LSC function could provide novel treatment strategies. Here, we show that TWIST1 is extremely highly expressed in the LSC of MLL-AF9+ acute myeloid leukemia (AML), and its upregulation is positively regulated by KDM4C in a H3K9me3 demethylation-dependent manner. We further demonstrate that TWIST1 is essential for the viability, dormancy, and self-renewal capacities of LSC, and that it promotes the initiation and maintenance of MLL-AF9-mediated AML. In addition, TWIST1 directly interacts and collaborates with HOXA9 in inducing AML in mice. Mechanistically, TWIST1 exerts its oncogenic function by activating the WNT5a/RAC1 axis. Collectively, our study uncovers a critical role of TWIST1 in LSC function and provides new mechanistic insights into the pathogenesis of MLL-AF9+ AML.

Exosomes derived from human dermal fibroblasts (HDFn-Ex) alleviate DNCB-induced atopic dermatitis (AD) via PPARα.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Recently, exosomes have been considered as potential cell-free medicine for skin defects such as aging, psoriasis and wounds. The aim of this study was to investigate the effects of human dermal fibroblast-neonatal-derived exosome (HDFn-Ex) on AD. HDFn-Ex increased the expression of peroxisome proliferator activated receptor α (PPARα) and alleviated the 1-chloro-2,4-dinitrobenzene (DNCB)-mediated downregulation of filaggrin, involucrin, loricrin, hyaluronic acid synthase 1 (HAS1) and HAS2 in human keratinocyte HaCaT cells. However, these effects were inhibited by the PPARα antagonist GW6471. In the artificial skin model, HDFn-Ex significantly inhibited DNCB-induced epidermal hyperplasia and the decrease in filaggrin and HAS1 levels via a PPARα. In the DNCB-induced AD-like mouse model, HDFn-Ex administration reduced epidermis thickening and mast cell infiltration into the dermis compared to DNCB treatment. Moreover, the decreases in PPARα, filaggrin and HAS1 expression, as well as the increases in IgE and IL4 levels induced by DNCB treatment were reversed by HDFn-Ex. These effects were blocked by pre-treatment with GW6471. Furthermore, HDFn-Ex exhibited an anti-inflammatory effect by inhibiting the DNCB-induced increases in IκBα phosphorylation and TNF-α expression. Collectively, HDFn-Ex exhibited a protective effect on AD. Notably, these effects were regulated by PPARα. Based on our results, we suggest that HDFn-Ex is a potential candidate for treating AD by recovering skin barrier dysfunction and exhibiting anti-inflammatory activity.

Frequent Intraluminal Growth of Large Muscular Veins in Surgically Resected Colorectal Cancer Tissues: A 3-Dimensional Pathologic Reconstruction Study.

Although venous invasion (VI) is common in colorectal cancers (CRCs) and is associated with distant metastasis, the 3-dimensional (3D) microscopic features and associated mechanisms of VI are not well elucidated. To characterize the patterns of VI, 103 tissue slabs were harvested from surgically resected CRCs with ≥pT2. They were cleared using the modified immunolabeling-enabled 3D imaging of solvent-cleared organs method, labeled with multicolor fluorescent antibodies, including antibodies against cytokeratin 19, desmin, CD31, and E-cadherin, and visualized by confocal laser scanning microscopy. VI was classified as intravasation, intraluminal growth, and/or extravasation, and 2-dimensional and 3D microscopic features were compared. VI was detected more frequently in 3D (56/103 [54.4%]) than in conventional 2-dimensional hematoxylin and eosin-stained slides (33/103 [32%]; P < .001). When VI was present, it was most commonly in the form of intraluminal growth (51/56), followed by extravasation (13/56) and intravasation (5/56). The mean length of intraluminal growth was 334.0 ± 212.4 µm. Neoplastic cell projections extended from cancer cell clusters in the connective tissue surrounding veins, penetrated the smooth muscle layer, and then grew into and filled the venous lumen. E-cadherin expression changed at each invasion phase; intact E-cadherin expression was observed in the cancer cells in the venous walls, but its expression was lost in small clusters of intraluminal neoplastic cells. In addition, reexpression of E-cadherin was observed when cancer cells formed well-oriented tubular structures and accumulated and grew along the luminal side of the venous wall. In contrast, singly scattered cancer cells and cancer cells with poorly defined tubular structures showed loss of E-cadherin expression. E-cadherin expression was intact in the large cohesive clusters of extravasated cancer cells. However, singly scattered cells and smaller projections of neoplastic cells in the stroma outward of venous wall showed a loss of E-cadherin expression. In conclusion, VI was observed in more than half of the CRCs analyzed by 3D histopathologic image reconstruction. Once inside a vein, neoplastic cells can grow intraluminally. The epithelial-mesenchymal transition is not maintained during VI of CRCs.

TWIST1 preserves hematopoietic stem cell function via the CACNA1B/Ca2+/mitochondria axis.

Mitochondria of hematopoietic stem cells (HSCs) play crucial roles in regulating cell fate and preserving HSC functionality and survival. However, the mechanism underlying HSC regulation remains poorly understood. Here, we identify transcription factor TWIST1 as a novel regulator of HSC maintenance through modulation of mitochondrial function. We demonstrate that Twist1 deletion results in significantly decreased lymphoid-biased HSC frequency, markedly reduced HSC dormancy and self-renewal capacity, and skewed myeloid differentiation in steady-state hematopoiesis. Twist1-deficient HSCs are more compromised in tolerance of irradiation- and 5-fluorouracil-induced stresses and exhibit typical phenotypes of senescence. Mechanistically, Twist1 deletion induces transactivation of voltage-gated calcium channel (VGCC) Cacna1b, which exhausts lymphoid-biased HSCs, impairs genotoxic hematopoietic recovery, and enhances mitochondrial calcium levels, metabolic activity, and reactive oxygen species production. Suppression of VGCC by a calcium channel blocker largely rescues the phenotypic and functional defects in Twist1-deleted HSCs under both steady-state and stress conditions. Collectively, our data, for the first time, characterize TWIST1 as a critical regulator of HSC function acting through the CACNA1B/Ca2+/mitochondria axis and highlight the importance of Ca2+ in HSC maintenance. These observations provide new insights into the mechanisms for the control of HSC fate.

GADD45g acts as a novel tumor suppressor, and its activation suggests new combination regimens for the treatment of AML.

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy for which there is an unmet need for novel treatment strategies. Here, we characterize the growth arrest and DNA damage-inducible gene gamma (GADD45g) as a novel tumor suppressor in AML. We show that GADD45g is preferentially silenced in AML, especially in AML with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations and mixed-lineage leukemia (MLL)-rearrangements, and reduced expression of GADD45g is correlated with poor prognosis in patients with AML. Upregulation of GADD45g impairs homologous recombination DNA repair, leading to DNA damage accumulation, and dramatically induces apoptosis, differentiation, and growth arrest and increases sensitivity of AML cells to chemotherapeutic drugs, without affecting normal cells. In addition, GADD45g is epigenetically silenced by histone deacetylation in AML, and its expression is further downregulated by oncogenes FLT3-ITD and MLL-AF9 in patients carrying these genetic abnormalities. Combination of the histone deacetylase 1/2 inhibitor romidepsin with the FLT3 tyrosine kinase inhibitor AC220 or the bromodomain inhibitor JQ1 exerts synergistic antileukemic effects on FLT3-ITD+ and MLL-AF9+ AML, respectively, by dually activating GADD45g. These findings uncover hitherto unreported evidence for the selective antileukemic role of GADD45g and provide novel strategies for the treatment of FLT3-ITD+ and MLL-AF9+ AML.

Ball divergence for the equality test of crossing survival curves.

It is a very common problem to test survival equality using the right-censored time-to-event data in clinical research. Although the log-rank test is popularly used in various studies, it may become insensitive when the proportional hazards assumption is violated. As follows, there have a variety of statistical methods being proposed to identify the discrepancy between crossing survival curves or hazard functions. The omnibus tests against general alternatives are usually preferred due to their wide applicability to complicated scenarios in real applications. In this paper, we propose two novel statistics to estimate the ball divergence using the right-censored survival data, and then implement them in the equality test on survival time in two independent groups. The simulation analysis demonstrates their efficiency in identifying the survival discrepancy. Compared to the existing methods, our proposed methods present higher power in situations with complex distributions, especially when there is a scale shift between groups. Real examples illustrate its advantage in practical applications.

A comparison of dyeing efficacy between hair-oxidation-based and hair-coating-based shampoos for the treatment of gray hair.

BACKGROUND: The process of hair dyeing causes hair damage, and periodic re-dyeing is required for newly grown hair. To avoid these hassles, hair color shampoos have been developed and are widely used. In this study, we compared the effects of two hair color shampoos with different dyeing principles to analyze the function of hair color shampoos. We analyzed hair tresses treated by hair-oxidation- and hair-coating-based shampoos. MATERIALS AND METHODS: We measured the color, tensile properties, softness, elasticity, gloss, moisture content, and protein content of the hair tresses dyed with color shampoos. The hair structures were analyzed by scanning and transmission electron microscopies (SEM and TEM) and a hydroxy radical-based method. RESULTS: The shampoo based on hair coating enhanced the hair dyeing effect and roughness, whereas that based on hair oxidation improved the color retention and moisture content in the hair tresses. Frictional resistance, gloss, and elasticity of the hair tresses were similar for the two products. However, according to the results of the protein loss test, TEM, and hydroxyl radical staining, the shampoo based on hair oxidation showed a longer dyeing retention compared to that based on hair coating but caused cuticle damage. CONCLUSION: These results show that the two shampoos with different dyeing principles exhibit different hair dyeing abilities and hair health indices. Therefore, we recommend that hair color shampoos should be used according to the requirements of an individual.

Full-thickness skin rejuvenation by a novel dual-length microneedle radiofrequency device: A proof-of-concept study using human skin.

BACKGROUND: A novel dual-length microneedle radiofrequency (DLMR) device has been developed to achieve full-thickness skin rejuvenation by stimulating the papillary and reticular dermis simultaneously. This device's dual-level targeting concept need to be validated on human skin, although its clinical efficacy has been demonstrated in a previous study. OBJECTIVES: This study evaluated the dual-depth targeting capability and the ability to induce rejuvenation in each layer of vertical skin anatomy, that is, the epidermis, papillary dermis, and reticular dermis, using full-thickness human facial skin samples. METHODS: Human facial skin samples were obtained from 13 Asian patients who had facelift surgery. To validate the dual-depth targeting concept, DMLR-treated skin samples were analyzed using a digital microscope, thermal imaging, and hematoloxylin and eosin (H&E) staining immediately after DLMR application. On samples stained with H&E, Masson's tricrome, and Verhoeff-Van Gieson, histological observation and morphometric analysis were performed. Total collagen assay (TCA) and quantitative real-time polymerase chain reaction (qPCR) were used to assess changes in total collagen content and mRNA expression levels of collagen types I/III and vimentin, respectively. RESULTS: The DLMR device successfully induced thermal stimulation in the papillary and reticular dermis. The thickness, stacks, and dermal-epidermal junction convolution of the epidermis treated with DLMR were significantly increased. Collagen bundles in the dermis treated with DLMR exhibited a notable increase in thickness, density, and horizontal alignment. Dermal collagen levels were significantly higher in the morphometric and TCA data, as well as in the qPCR data for dermal matrix proteins. CONCLUSIONS: Our DLMR device independently and precisely targeted the papillary and reticular dermis, and it appears to be an effective modality for implementing full-thickness rejuvenation.

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size.

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

Pancreatic Cysts after Endoscopic Ultrasonography-Guided Ethanol and/or Paclitaxel Ablation Therapy: Another Mimic of Pancreatic Pseudocysts.

BACKGROUND: Endoscopic ultrasound-guided ablation (EUS-A) therapy is a minimally invasive procedure for pancreatic-cystic tumors in patients with preoperative comorbidities or in patients who are not indicated for surgical resection. However, histopathologic characteristics of pancreatic cysts after ablation have not been well-elucidated. METHODS: Here, we analyzed pathological findings of 12 surgically resected pancreatic cysts after EUS-A with ethanol and/or paclitaxel injection. RESULTS: Mean patient age was 49.8 ± 13.6 years with a 0.3 male/female ratio. Clinical impression before EUS-A was predominantly mucinous cystic neoplasms. Mean cyst size before and after ablation therapy was similar (3.7 ± 1.0 cm vs. 3.4 ± 1.6 cm; p = 0.139). Median duration from EUS-A to surgical resection was 18 (range, 1-59) months. Mean percentage of the residual neoplastic lining epithelial cells were 23.1 ± 37.0%. Of the resected cysts, 8 cases (67%) showed no/minimal (<5%) residual lining epithelia, while the remaining 4 cases (33%) showed a wide range of residual mucinous epithelia (20-90%). Ovarian-type stroma was noted in 5 cases (42%). Other histologic features included histiocytic aggregation (67%), stromal hyalinization (67%), diffuse egg shell-like calcification along the cystic wall (58%), and fat necrosis (8%). CONCLUSION: Above all, diffuse egg shell-like calcification along the pancreatic cystic walls with residual lining epithelia and/or ovarian-type stroma were characteristics of pancreatic cysts after EUS-A. Therefore, understanding these histologic features will be helpful for precise pathological diagnosis of pancreatic cystic tumor after EUS-A, even without knowing the patient's history of EUS-A.

MACULAR MICROVASCULATURE IN X-LINKED RETINOSCHISIS: Optical Coherence Tomography and Optical Coherence Tomography Angiography Study.

PURPOSE: The study aimed to evaluate the macular microvasculature of X-linked retinoschisis (XLRS) and identify correlations between vascular changes, structural changes, and functional outcome. METHODS: Genetically confirmed XLRS patients and heathy control subjects underwent complete ophthalmic examination, dilated funduscopic examination, optical coherence tomography, and optical coherence tomography angiography. Schisis distribution, outer plexiform layer discontinuation, photoreceptor layer thickness, and photoreceptor outer segment length were reviewed using optical coherence tomography. Vascular flow density and foveal thickness at foveal and parafoveal area were measured using optical coherence tomography angiography. RESULTS: A total of 17 eyes of 9 XLRS patients and 22 eyes of 11 control subjects were examined from July 2018 to August 2020. Flow density in the deep capillary plexus at foveal and parafoveal area decreased in XLRS patients compared with control subjects (P = 0.014 and 0.001, respectively), whereas foveal avascular zone area and perimeter remarkably increased (P = 0.015 and 0.001, respectively). Although outer and total retinal layers were significantly thicker in XLRS, inner retinal layer was thinner with reduced photoreceptor layer thickness and shortened photoreceptor outer segment length (P < 0.001 and P < 0.001, respectively). Foveal flow loss in deep capillary plexus, foveal avascular zone enlargement, thinner inner retina and photoreceptor layer thickness, and shortened photoreceptor outer segment length correlated with best-corrected visual acuity. CONCLUSION: X-linked retinoschisis eyes exhibit decreased flow density in the deep capillary plexus and variable foveal avascular zone with enlarged perimeter. Structural deterioration of the photoreceptor best reflects the degenerative changes, whereas microvascular alteration shows considerable correlation with functional outcome in XLRS.

Involvement of the p38 MAPK-NLRC4-Caspase-1 Pathway in Ionizing Radiation-Enhanced Macrophage IL-1ß Production.

Macrophages are abundant immune cells in the tumor microenvironment and are crucial in regulating tumor malignancy. We previously reported that ionizing radiation (IR) increases the production of interleukin (IL)-1ß in lipopolysaccharide (LPS)-treated macrophages, contributing to the malignancy of colorectal cancer cells; however, the mechanism remained unclear. Here, we show that IR increases the activity of cysteine-aspartate-specific protease 1 (caspase-1), which is regulated by the inflammasome, and cleaves premature IL-1ß to mature IL-1ß in RAW264.7 macrophages. Irradiated RAW264.7 cells showed increased expression of NLRC4 inflammasome, which controls the activity of caspase-1 and IL-1ß production. Silencing of NLRC4 using RNA interference inhibited the IR-induced increase in IL-1ß production. Activation of the inflammasome can be regulated by mitogen-activated protein kinase (MAPK)s in macrophages. In RAW264.7 cells, IR increased the phosphorylation of p38 MAPK but not extracellular signal-regulated kinase and c-Jun N-terminal kinase. Moreover, a selective inhibitor of p38 MAPK inhibited LPS-induced IL-1ß production and NLRC4 inflammasome expression in irradiated RAW264.7 macrophages. Our results indicate that IR-induced activation of the p38 MAPK-NLRC4-caspase-1 activation pathway in macrophages increases IL-1ß production in response to LPS.

RAPGEF2 mediates oligomeric Aß-induced synaptic loss and cognitive dysfunction in the 3xTg-AD mouse model of Alzheimer's disease.

AIMS: Amyloid-ß (Aß) oligomers trigger synaptic degeneration that precedes plaque and tangle pathology. However, the signalling molecules that link Aß oligomers to synaptic pathology remain unclear. Here, we addressed the potential role of RAPGEF2 as a novel signalling molecule in Aß oligomer-induced synaptic and cognitive impairments in human-mutant amyloid precursor protein (APP) mouse models of Alzheimer's disease (AD). METHODS: To investigate the role of RAPGEF2 in Aß oligomer-induced synaptic and cognitive impairments, we utilised a combination of approaches including biochemistry, molecular cell biology, light and electron microscopy, behavioural tests with primary neuron cultures, multiple AD mouse models and post-mortem human AD brain tissue. RESULTS: We found significantly elevated RAPGEF2 levels in the post-mortem human AD hippocampus. RAPGEF2 levels also increased in the transgenic AD mouse models, generating high levels of Aß oligomers before exhibiting synaptic and cognitive impairment. RAPGEF2 upregulation activated the downstream effectors Rap2 and JNK. In cultured hippocampal neurons, oligomeric Aß treatment increased the fluorescence intensity of RAPGEF2 and reduced the number of dendritic spines and the intensities of synaptic marker proteins, while silencing RAPGEF2 expression blocked Aß oligomer-induced synapse loss. Additionally, the in vivo knockdown of RAPGEF2 expression in the AD hippocampus prevented cognitive deficits and the loss of excitatory synapses. CONCLUSIONS: These findings demonstrate that the upregulation of RAPGEF2 levels mediates Aß oligomer-induced synaptic and cognitive disturbances in the AD hippocampus. We propose that an early intervention regarding RAPGEF2 expression may have beneficial effects on early synaptic pathology and memory loss in AD.

Microtubule-associated protein 2 mediates induction of long-term potentiation in hippocampal neurons.

Microtubule-associated protein (MAP) 2 has been perceived as a static cytoskeletal protein enriched in neuronal dendritic shafts. Emerging evidence indicates dynamic functions for various MAPs in activity-dependent synaptic plasticity. However, it is unclear how MAP2 is associated with synaptic plasticity mechanisms. Here, we demonstrate that specific silencing of high-molecular-weight MAP2 in vivo abolished induction of long-term potentiation (LTP) in the Schaffer collateral pathway of CA1 pyramidal neurons and in vitro blocked LTP-induced surface delivery of AMPA receptors and spine enlargement. In mature hippocampal neurons, we observed rapid translocation of a subpopulation of MAP2, present in dendritic shafts, to spines following LTP stimulation. Time-lapse confocal imaging showed that spine translocation of MAP2 was coupled with LTP-induced spine enlargement. Consistently, immunogold electron microscopy revealed that LTP stimulation of the Schaffer collateral pathway promoted MAP2 labeling in spine heads of CA1 neurons. This translocation depended on NMDA receptor activation and Ras-MAPK signaling. Furthermore, LTP stimulation led to an increase in surface-expressed AMPA receptors specifically in the neurons with MAP2 spine translocation. Altogether, this study indicates a novel role for MAP2 in LTP mechanisms and suggests that MAP2 participates in activity-dependent synaptic plasticity in mature hippocampal networks.

CENTRAL RETINAL VEIN OCCLUSION IN YOUNG PATIENTS: Clinical Characteristics and Prognostic Factors.

PURPOSE: To investigate the clinical characteristics and prognostic factors of young patients with central retinal vein occlusion (CRVO). METHODS: This retrospective cohort study involved treatment-naïve patients with CRVO. Medical records regarding basic demographics, predisposing factors, ocular characteristics, and treatments were reviewed and compared according to age at CRVO onset. RESULTS: We enrolled 263 patients, of whom 69 were younger patients. Younger patients had higher prevalence of nontraditional risk factors including physical or psychological stress (P = 0.032), hematologic abnormalities (P = 0.003), and better visual acuity at baseline and last visit (all P < 0.001) and were unlikely to undergo intravitreal injections (47.8 vs. 68.6%, P < 0.001) during follow-up. Younger patients had higher prevalence of paracentral acute middle maculopathy (28.1 vs. 4.7%, P < 0.001). Older age (odds ratio = 1.165, P = 0.028), male sex (odds ratio = 7.074, P = 0.034), coexisting renal disease (odds ratio = 7.845, P = 0.050), and poor baseline visual acuity (odds ratio = 16.069, P = 0.002) were significant risk factors for poor visual outcomes in young CRVO patients. CONCLUSION: Younger CRVO patients had a milder clinical course with fewer treatments and were more likely to have nontraditional risk factors than older patients.

Comparison of different energy response for lipolysis using a 1,060-nm laser: An animal study of three pigs.

BACKGROUND: Non-invasive body-sculpting procedures are becoming increasingly popular. The application of 1,060 nm of laser energy transcutaneously to hyperthermically induce the disruption of fat cells in the abdomen is a type of non-invasive procedure. AIMS: The purpose of this study was to compare the treatment results from two parameters of the same system, each with different energy output levels, in an in vivo porcine model to determine the most effective application. METHODS: Female pigs (n = 3) were used in this study. We examined the effects of the treatment using photography, ultrasonography, gross and microscopic pathology, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure. Blood chemistry analysis was performed before each session to check lipid levels and to monitor for any adverse changes in markers that may indicate liver damage. Biopsies were taken and routinely processed with hematoxylin and eosin and Oil Red O stains to examine for tissue damage at baseline and after each treatment. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assays were performed to check for apoptotic-related DNA damage. RESULTS: Ultrasonic imaging of the same area before and after the application of 1,060 nm of laser energy at outputs of 0.9 and 1.4 W/cm2 showed that the density of the fat layer changed immediately after irradiation due to the transient heat transfer in the fat layer. Preclinical evaluation was performed to obtain comparison data on the safety and efficacy of subcutaneous fat reduction after applying the different energy outputs of 0.9 and 1.4 W/cm2 . CONCLUSION: Based on our findings, we suggest that long-term histologic changes through the use of these devices suggest a comparative effectiveness of the treatment energy.

Evaluation of nail surface topography using a three-dimensional in vivo optical skin imaging system.

BACKGROUND: The analysis of nail surface topography is a subject of ever-increasing interest in dermatology, especially in cosmetic studies. However, there is no accurate and scientifically sound instrumental method that can identify and provide quantitative data on nail surface topography. MATERIALS AND METHODS: The right index fingers of 78 healthy individuals were examined. The severity of nail roughness was rated by two independent dermatologists on a scale of 1 to 3. Using the phaseshift rapid in vivo measurement of the skin (PRIMOS) system, three-dimensional microtopography was performed, and the roughness parameter values were calculated and evaluated. The relationship between clinical nail roughness grade and nail roughness parameter values obtained utilizing PRIMOS was evaluated. RESULTS: A moderate correlation was found between the roughness parameter values and the clinical roughness grade. Our study showed that an overall relationship exists between the nail roughness parameter values obtained using PRIMOS and clinically observed nail surface changes. CONCLUSION: With further studies, PRIMOS could be a valuable tool for clinicians and researchers for conducting an accurate and objective patient assessment in daily practice and demonstrating effectiveness of different therapies for nail dystrophy or evaluating cosmetic effects of various topical treatments in future clinical trials.

Fusion of subarachnoid hemorrhage data and computed tomography angiography data is helpful to identify the rupture source in patients with multiple intracranial aneurysms.

Determining the rupture source is imperative in patient with aneurysmal subarachnoid hemorrhage (SAH). About one third of SAH cases with multiple intracranial aneurysms cannot be certain of the rupture source according to the hemorrhage pattern. This study aims to identify of the rupture source in patients with multiple intracranial aneurysms by fusing SAH data and computed tomography angiography (CTA) data. This retrospective study included 52 aneurysmal SAH patients with multiple intracranial aneurysms. In the 52 patients, 36 had definitive hemorrhage patterns on computed tomography imaging. And the other 16 patients had non-definitive hemorrhage patterns, which were bewildered for us to determine the ruptured aneurysms. Fusion of SAH data and CTA data was performed to demonstrate the spatial relationship between the SAH with each aneurysm by using the 3D Slicer software. For the patients with definitive bleed patterns, all of the suspected ruptured aneurysms were confirmed to be accurate according to the surgical records. Interestingly, the suspected rupture sources were correct in 14 of 16 patients with non-definitive hemorrhage patterns. For all 52 patients with multiple intracranial aneurysms, the ruptured aneurysms were identified in 50 cases (96.2%). In conclusion, fusion of SAH data and CTA data can precisely demonstrate the spatial relationship between the SAH with each aneurysm, which is helpful to determine the ruptured aneurysm in patients with multiple intracranial aneurysms.

Improved Light Field Compression Efficiency through BM3D-Based Denoising Using Inter-View Correlation.

Multi-view or light field images have recently gained much attraction from academic and commercial fields to create breakthroughs that go beyond simple video-watching experiences. Immersive virtual reality is an important example. High image quality is essential in systems with a near-eye display device. The compression efficiency is also critical because a large amount of multi-view data needs to be stored and transferred. However, noise can be easily generated during image capturing, and these noisy images severely deteriorate both the quality of experience and the compression efficiency. Therefore, denoising is a prerequisite to produce multi-view-based image contents. In this paper, the structural characteristics of linear multi-view images are fully utilized to increase the denoising speed and performance as well as to improve the compression efficiency. Assuming the sequential processes of denoising and compression, multi-view geometry-based denoising is performed keeping the temporal correlation among views. Experimental results show the proposed scheme significantly improves the compression efficiency of denoised views up to 76.05%, maintaining good denoising quality compared to the popular conventional denoise algorithms.

Large tumor size, lymphovascular invasion, and synchronous metastasis are associated with the recurrence of solid pseudopapillary neoplasms of the pancreas.

BACKGROUND: Solid pseudopapillary neoplasms (SPNs) of the pancreas have low malignant potential. However, malignant SPNs are not fully understood. METHODS: To evaluate risk factors affecting malignant potential, the clinicopathologic features of 375 surgically resected SPNs were compared. RESULTS: Fifty (13.3%) had malignant histologic features. Twenty-seven and 22 had perineural and lymphovascular invasions, respectively. Adjacent organ invasion was noted in 9 cases. Recurrence occurred in 8 cases. The median recurrence time after surgical resection was 67 months and was associated with a higher pT category (P = 0.001), lymphovascular invasion (P < 0.001), and synchronous metastasis (P < 0.001). SPN patients with malignant histologic features had worse recurrence-free survival (RFS; 10-year survival rate, 73.2%) than those without malignant histologic features (96.3%; P = 0.01). Patients with a higher pT category (P = 0.04), synchronous metastasis (P < 0.01), and lymphovascular invasion (P < 0.01) had worse RFS. Lymphovascular invasion (P = 0.042) and a higher T category (P = 0.002) were poor prognostic factors for recurrence. CONCLUSION: Lymphovascular invasion and a higher T category were worse prognostic factors for recurrence in SPN patients with malignant histologic features. For SPN patients with malignant histologic features, a longer follow-up may be required.