Anisotropic spin-orbit torque generation in epitaxial SrIrO3 by symmetry design.

Spin-orbit coupling (SOC), the interaction between the electron spin and the orbital angular momentum, can unlock rich phenomena at interfaces, in particular interconverting spin and charge currents. Conventional heavy metals have been extensively explored due to their strong SOC of conduction electrons. However, spin-orbit effects in classes of materials such as epitaxial 5d-electron transition-metal complex oxides, which also host strong SOC, remain largely unreported. In addition to strong SOC, these complex oxides can also provide the additional tuning knob of epitaxy to control the electronic structure and the engineering of spin-to-charge conversion by crystalline symmetry. Here, we demonstrate room-temperature generation of spin-orbit torque on a ferromagnet with extremely high efficiency via the spin-Hall effect in epitaxial metastable perovskite SrIrO3 We first predict a large intrinsic spin-Hall conductivity in orthorhombic bulk SrIrO3 arising from the Berry curvature in the electronic band structure. By manipulating the intricate interplay between SOC and crystalline symmetry, we control the spin-Hall torque ratio by engineering the tilt of the corner-sharing oxygen octahedra in perovskite SrIrO3 through epitaxial strain. This allows the presence of an anisotropic spin-Hall effect due to a characteristic structural anisotropy in SrIrO3 with orthorhombic symmetry. Our experimental findings demonstrate the heteroepitaxial symmetry design approach to engineer spin-orbit effects. We therefore anticipate that these epitaxial 5d transition-metal oxide thin films can be an ideal building block for low-power spintronics.

A study of the microbiological profile of filler-induced skin necrosis.

Skin necrosis is one of the most severe complications following filler injections, and can result in permanent aesthetic defects. Although an increasing number of studies have addressed the management of dermal filler complications, no study has described the spectrum of microbial pathogens. The aim of this study was to delineate the bacterial profile and prognostic factors of filler-related skin necrosis by reviewing the clinical and microbiological features of these patients. A retrospective medical record review of patients undergoing treatment for skin necrosis induced by fillers was conducted. In total, 10 cases were identified, with injection sites being the nasolabial fold (70%; n = 7), nasal dorsum (20%; n = 2) and nasal tip (10%; n = 1). Reviewing the culture results, the true culture-positive rate was found to be 50% after cases of contamination were excluded. To avoid permanent sequelae, all physicians should be aware of possible secondary infections when treating filler-induced skin necrosis.

Mask-induced dermatoses during the COVID-19 pandemic: a questionnaire-based study in 12 Korean hospitals.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, various adverse skin reactions to long-term mask wearing have been reported. AIM: To assess the clinical features of mask-induced dermatoses and to recommend prevention and treatment options. METHODS: From April to August 2020, questionnaires including topics such as demographic information, pre-existing skin disorders, reported mask-related symptoms, daily mask-wearing duration and frequency, types of masks used and whether the participant was a healthcare worker, were distributed to patients in 12 hospitals. Dermatologists assessed skin lesions, confirmed diagnosis and recorded treatments. RESULTS: Itchiness was the most frequent symptom, mostly affecting the cheeks. The most common skin disease was new-onset contact dermatitis (33.94%), followed by new-onset acne (16.97%) and worsening of pre-existing acne (16.97%). Daily wearing of masks was significantly (P = 0.02) associated with new-onset contact dermatitis. More than half of patients with pre-existing skin problems experienced disease worsening while wearing masks. Longer duration of wearing (> 6 h/day, P = 0.04) and use of cotton masks (P < 0.001) significantly increased acne flare-up. Healthcare workers had a higher incidence of skin disease. Skin lesions were generally mild and well tolerated with topical treatment. The study had some limitations: the effect of seasonal characteristics and other risk factors were not assessed, and the patients were visiting dermatological clinics and had interest in their skin status, thus, there may have been selection bias. CONCLUSION: Mask-induced/-triggered dermatoses contribute to increase the dermatological burden during the pandemic.

Vesicular glutamate transporter-immunopositive axons that coexpress neuropeptides in the rat and human dental pulp.

AIM: To examine the type of vesicular glutamate transporter (VGLUT)-immunopositive (+) axons that coexpress neuropeptides in the rat and human dental pulp, which may help understand peripheral mechanism of pulpal inflammatory pain in rats and humans. METHODOLOGY: The trigeminal ganglia (TG) and the dental pulp of the maxillary molar teeth from three male Sprague-Dawley rats weighing 300-330 g and dental pulps of three healthy human (male) maxillary premolar teeth from three 16 to 28-year-old patients extracted for orthodontic treatment were used. The type of VGLUT + axons that coexpress substance P (SP)- and/or calcitonin gene-related peptide (CGRP) and parvalbumin in the rat TG and in the axons of the rat and the human dental pulp was examined by double fluorescence immunohistochemistry and quantitative analysis. Results were analyzed using one-way anova and the Kruskal-Wallis test. RESULTS: SP and CGRP were expressed in many human VGLUT1 + pulpal axons but not in the rat VGLUT1 + TG neurons and pulpal axons (P < 0.05). SP and CGRP were expressed in a considerable number of human VGLUT2 + pulpal axons and also in many rat TG neurons and pulpal axons. The fraction of VGLUT1 + axons expressing parvalbumin was about three times higher in the rat than in the human dental pulp (P < 0.05). CONCLUSIONS: These findings suggest that the types of VGLUT + axons, which release neuropeptides, may be different between the rat and the human dental pulp, raising a possibility that peripheral mechanism of pulpal inflammatory pain may be different between rats and humans.

Prenylflavonoids isolated from Macaranga tanarius stimulate odontoblast differentiation of human dental pulp stem cells and tooth root formation via the mitogen-activated protein kinase and protein kinase B pathways.

AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.

Comparison of the diagnostic performance of the 2017 and 2018 versions of LI-RADS for hepatocellular carcinoma on gadoxetic acid enhanced MRI.

AIM: To compare the diagnostic performance of the 2017 (v2017) and 2018 versions (v2018) of the Liver Imaging-Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) using gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) and to evaluate the effect in v2018. MATERIALS AND METHODS: Treatment-naive patients at high-risk for HCC who underwent Gd-EOB-MRI were included. The LI-RADS categories were assigned according to v2017 and v2018. The diagnostic performances were compared between v2017 and v2018 according to the size and combination of imaging features. RESULTS: A total of 117 patients with 137 observations were identified, including 89 HCCs; 76.2% (64/84) of observations with threshold growth were re-classified as subthreshold growth when using v2018 instead of v2017. The final categories changed in nine (14%) cases. For the combination of LR-5/LR-5V, there were no significant differences in sensitivity and specificity between the two versions (sensitivity, 64% versus 58.4%; specificity, 87.5% versus 85.4%; all p>0.05). For the combination of LR-4 and LR-5/5V, the diagnostic performance of v2018 was inferior to that of v2017 when considering only major features (accuracy, 86.1% versus 80.3%, respectively; p=0.013), particularly in observations measuring 10-20 mm, but was comparable after adding the ancillary features (accuracy, 86.9% versus 86.1%, respectively; p=1.00). CONCLUSION: In LI-RADS v2018, although a considerable number of observations re-classified subthreshold growth, changes in the assigned categories were insignificant; overall diagnostic performance was comparable to that of v2017, but v2018 might emphasise the value of ancillary features in combination with major features for determining the probability of HCC.

A simple and efficient method of generating HCMV pp65-specific T cells using overlapping peptides.

The methods for expansion of human cytomegalovirus (HCMV)-specific T lymphocytes are limited due to the complex culture process, long culture duration, and human leukocyte antigen (HLA) restriction. Here, we report that in vitro stimulation with pp65 kDa phosphoprotein (pp65)-derived overlapping synthetic peptides rapidly generates large numbers of HCMV-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) regardless of HLA type. Treatment of PBMCs from healthy volunteers expressing HLA-A*02:01 or HLA-A*24:02 with 138 pp65 overlapping peptides (OLP) resulted in an expansion of HCMV pp65 NLVPMVATV (NLV) pentamer-specific CD8+ T lymphocytes that expressed interferon (IFN)-γ, but the pp65 NLV peptide did not generate HCMV-specific CD8+ T lymphocytes in PBMCs obtained from an HLA-A*24:02 donor due to HLA restriction. The OLP-induced T lymphocytes specific for HCMV derived from PBMCs of HLA-A*02:01- and HLA-A*24:02-expressing donors showed effective cytolytic responses against target cells loaded with OLP or the NLV epitope, but pp65 NLV peptide-induced T lymphocytes did not. Phenotypic analyses demonstrated that OLP increased the frequency of CD3+ CD8+ cells, but not CD3+ CD4+, CD14+, or CD56+ cells, in donor PBMCs. Thus, this study provides evidence that in vitro stimulation with OLP efficiently generates sufficient numbers of HCMV pp65-specific cytotoxic T lymphocytes for adoptive cell therapy. Keywords: human cytomegalovirus; cytotoxic T lymphocyte; overlapping peptides; pp65; cytotoxicity.

Low rates of osteoporosis treatment after hospitalization for hip fracture in Hawaii.

We evaluated osteoporosis treatment and DEXA utilization rates of patients who were admitted for hip fracture in a single healthcare system in Hawaii from 2015 to 2016. We found that osteoporosis treatment and DEXA utilization rates were low, highlighting a critical gap in osteoporosis care after admission for hip fracture. INTRODUCTION: The objective of this study was to evaluate osteoporosis care after an admission for hip fracture at three community hospitals within a single healthcare system in Hawaii. METHODS: A retrospective chart review was conducted (n = 428) of patients ≥ 50 years and hospitalized for hip fractures between January 1, 2015, and May 31, 2016, at three major hospitals within Hawaii Pacific Health, a large healthcare system in Hawaii. Basic demographics were collected, and medications prescribed were quantified and described within 1 year of hip fracture. Logistic regression was used to evaluate the association between collected variables and the odds of osteoporosis treatment. RESULTS: Only 115 (26.9%) patients were prescribed a medication for osteoporosis as a secondary prevention within a year of hospitalization for hip fracture. DEXA scans were performed in 137 (32.0%) patients. Most of the treated patients were prescribed oral bisphosphonates. Treatment facility, female gender, and higher BMI were found to be predictive factors for osteoporosis treatment. CONCLUSION: The use of osteoporosis medication for secondary prevention after admission for hip fracture in Hawaii is low. Efforts need to be made to improve treatment rates, especially among males.

Identification of small droplets of photosynthetic squalene in engineered Synechococcus elongatus PCC 7942 using TEM and selective fluorescent Nile red analysis.

To identify microbial squalene that has been widely used in various industrial applications, intracellular formation of photosynthetic squalene was investigated using the previously engineered Synechococcus elongatusPCC 7942 strain. Unlike the proposed localization of squalene in the membrane bilayer, small droplets were identified in the cytoplasm of S. elongatusPCC 7942 as squalene using transmission electron microscopy analysis. Determination of the diameters of the squalene droplets with manual examination of 1016 droplets in different squalene-producing strains indicated larger squalene droplets in larger cells. Based on the observation of a sole droplet of squalene in a cyanobacterium, fluorescent Nile red was used for the selective staining of squalene. The fluorescent intensities were correlated with squalene contents determined using gas chromatography-mass spectrometry. Photosynthetic squalene was identified as a small droplet in S. elongatusPCC 7942, and this noninvasive quantitative method could be useful to promote high-throughput strain development for squalene production. SIGNIFICANCE AND IMPACT OF THE STUDY: Engineering of Cyanobacteria has focused on sustainable production of squalene by converting CO2 . Before improving the photosynthetic squalene production, we characterized formation of squalene, showing small droplets in the cytoplasm instead of single granule. Based on the finding and the analysis, this study has provided valuable evidences how further metabolic engineering strategies should apply to enhance the production yield.

Oral cancer: A multicenter study.

BACKGROUND: To determine the prevalence and clinicopathologic features of the oral cancer patients. MATERIAL AND METHODS: Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. RESULTS: Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. CONCLUSIONS: Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.

Interferon-inducible T-cell alpha chemoattractant (ITAC) induces the melanocytic migration and hypopigmentation through destabilizing p53 via histone deacetylase 5: a possible role of ITAC in pigment-related disorders.

BACKGROUND: Cell migration plays a major role in the immune response and in tumorigenesis. Interferon-inducible T-cell alpha chemoattractant (ITAC) elicits a strong chemotactic response from immune cells. OBJECTIVES: To examine the effect of ITAC on melanocyte migration and pigmentation and its involvement in related disorders, and to investigate potential key players in these processes. METHODS: Human melanocytes or melanoma cells were treated with ITAC and a migration assay was carried out. Global gene expression analysis was performed to find genes regulated by ITAC treatment. The function of key players involved in ITAC-induced cellular processes was addressed using knockdown or overexpression experiments in combination with ITAC treatment. ITAC expression in the inflammation-associated hypopigmentary disorder, vitiligo, was examined. RESULTS: Among CXCR3 ligands, only ITAC induced melanocyte migration. ITAC treatment upregulated the expression of histone deacetylase 5 (HDAC5) and downregulated that of p53, a known target of HDAC5. Through knockdown or overexpression of HDAC5 and p53, we confirmed that HDAC5 mediates ITAC-induced migration by decreasing levels of p53 via deacetylation. In addition, ITAC treatment could decrease pigmentation in a p53- and HDAC5-dependent manner. Finally, the increased migration of human melanoma cells by ITAC treatment and the increased ITAC expression in the epidermis of vitiligo skin were verified. CONCLUSIONS: This study provides in vitro evidence for the migratory and hypopigmentation effects of ITAC on melanocytic cells, gives translational insights into the roles of ITAC in pathological conditions, and suggests that HDAC5 and its substrate p53 are potent targets for regulating ITAC-induced cellular processes.

Value of unenhanced MRI with diffusion-weighted imaging for detection of primary small (≤20 mm) solid pancreatic tumours and prediction of pancreatic ductal adenocarcinoma.

AIM: To determine the diagnostic performance of unenhanced magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI; NonMRI) for the detection of primary small (≤20 mm) pancreatic solid tumours and prediction of pancreatic ductal adenocarcinoma (PDAC) in comparison with pancreatic computed tomography (CT; PanCT) and pancreatic MRI with magnetic resonance cholangiopancreatography (PanMRI). METHODS AND MATERIALS: The institutional review board approved this retrospective study and waived the requirement for informed consent. A total of 126 patients who underwent PanCT and PanMRI, including 94 small (≤20 mm) pancreatic tumours (51 PDACs, 34 neuroendocrine tumours [NETs], nine solid pseudopapillary tumours [SPTs]), and 32 patients with a normal pancreas, comprised the study population. Two observers assessed three sets of images: PanCT, PanMRI and NonMRI (T1- and T2-weighted images and DWI). Receiver operating characteristic curve analysis and diagnostic accuracy using the area under the receiver operating characteristic curve (Az) were used for statistical analysis. RESULTS: On NonMRI and PanMRI, all of tumours except one NET were detected, but eight tumours (six NETs, one PDAC, one SPT) were not detected on PanCT (p<0.01). For prediction of PDAC, the Az value of the NonMRI (0.884 for observer 1; 0.930 for observer 2) was comparable with PanCT (0.922; 0.924; p>0.05), and inferior to PanMRI (0.930; 0.977; p<0.05), but all of 51 PDACs were considered as probable or definite PDAC on NonMRI by both observers. CONCLUSION: NonMRI showed better performance than PanCT, and competitive performance to PanMRI for the detection of primary small solid pancreatic tumours, and showed reasonable sensitivity for prediction of PDACs compared with PanCT and PanMRI.

Efficacy and safety of non-invasive body tightening with high-intensity focused ultrasound (HIFU).

BACKGROUND: Noninvasive skin-tightening devices have become increasingly popular in response to increasing demand for improvements in skin laxity and tightening with minimal risk and recovery time. OBJECTIVE: We evaluated the efficacy and safety of HIFU for skin tightening in the face and body. METHODS: A total of 32 Korean subjects enrolled in this prospective clinical trial. The subjects were treated with HIFU to both cheeks, lower abdomen, and thigh. Skin elasticity was measured before and after treatment using a Cutometer (CT575, Courage and Khazaka® , Cologne, Germany). Three blinded, experienced dermatologists evaluated paired pre- and post-treatment (week 4 and 12) photographs according to the Global Aesthetic Improvement Scale (GAIS). Participants also completed self-assessments using GAIS. Subjects rated their pain on a numeric rating scale (NRS) immediately, 7 days, 4 weeks, and 12 weeks after treatment. RESULTS: Skin elasticity measured via a Cutometer was significantly improved 12 weeks after treatment at all treated sites (P<.05). Both IGAIS and SGAIS showed significant improvements 12 weeks after treatment. Immediately after treatment the mean NRS score was 3.00±1.586, but no pain was reported at 4 and 12 weeks post-treatment. No serious adverse effects were observed during the follow-up period. CONCLUSION: HIFU safely and effectively improves skin elasticity and clinical contouring of the face and body.

Improved methods for evaluating pre-clinical and histological effects of subcutaneous fat reduction using high-intensity focused ultrasound in a porcine model.

BACKGROUND: Non-invasive body sculpting procedures are becoming increasingly popular. High-intensity focused ultrasound (HIFU) treatment is a non-surgical fat reduction procedure that permanently destroys unwanted abdominal fat. Despite its increasing popularity, evaluation methods for the procedure have not yet been fully developed. AIMS: The objective of this study was to develop evaluation methods for HIFU for non-surgical, permanent fat reduction in the anterior abdomen using a porcine model. METHODS: The abdomens of female pigs (Sus scrofa, n = 7) were treated with a HIFU device (SCIZER™ , Classys Inc, Seoul, Korea). We examined treatment effects using photography, ultrasound, gross and microscopic pathology, and serum lipid and liver function level analysis, carbon tracer test, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure. RESULTS: HIFU treatment effectively reduced abdominal fat in a porcine model; it accurately treated the target subcutaneous fat layer and the subcutaneous fat was reduced effectively via ultrasonic measurement after HIFU treatment. On histological staining (H&E, toluidine blue, oil red O and immunohistochemistry), we found that subcutaneous fat reduction occurred effectively via accurate treatment of the targeted subcutaneous fat layer. On hematological assay, there were changes within normal range, and values remained stable after 48 h. Via carbon tracer test, the migration of activated macrophages was identified within the axillary lymph node (LN). PPAR-delta, a protein defined by immunohistochemistry staining, was overexpressed in the early stage on days 1 and 7, but a gradual decreasing pattern was confirmed. CONCLUSION: We successfully used a HIFU device for body contouring and fat reduction in a pre-clinical study. These results provide that the essential clues toward the effective evaluation, guiding selection of the appropriate diagnostic investigations.

Solid pseudopapillary neoplasm of the pancreas with liver metastasis initially misinterpreted as benign haemorrhagic cyst.

Solid pseudopapillary neoplasm (SPN) of the pancreas is considered a low-malignant neoplasm with a good prognosis. However, 5% to 15% of patients with SPNs develop metastatic disease, most commonly in the liver. Metastatic hepatic malignancies that show pseudocystic features are rare. Here we describe the case of a middle-aged female with a cystic liver metastasis from SPN. To the best of our knowledge, SPN with a single cystic liver metastasis has not been described, although these tumours frequently undergo haemorrhagic-cystic degeneration. Thus, in these patients the marked cystic change could be misinterpreted as a benign lesion.

Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia.

BACKGROUND: The use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression. PATIENTS AND METHODS: We assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples. RESULTS: Fifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders. CONCLUSION: This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL. TRIAL REGISTRATION: clinicaltrials.gov, NCT01004497.

Passive Q-switching of microchip lasers based on Ho:YAG ceramics.

A Ho:YAG ceramic microchip laser pumped by a Tm fiber laser at 1910 nm is passively Q-switched by single- and multi-layer graphene, single-walled carbon nanotubes (SWCNTs), and Cr2+:ZnSe saturable absorbers (SAs). Employing SWCNTs, this laser generated an average power of 810 mW at 2090 nm with a slope efficiency of 68% and continuous wave to Q-switching conversion efficiency of 70%. The shortest pulse duration was 85 ns at a repetition rate of 165 kHz, and the pulse energy reached 4.9 µJ. The laser performance and pulse stability were superior compared to graphene SAs even for a different number of graphene layers (n=1 to 4). A model for the description of the Ho:YAG laser Q-switched by carbon nanostructures is presented. This modeling allowed us to estimate the saturation intensity for multi-layered graphene and SWCNT SAs to be 1.2±0.2 and 7±1 MW/cm2, respectively. When using Cr2+:ZnSe, the Ho:YAG microchip laser generated 11 ns/25 µJ pulses at a repetition rate of 14.8 kHz.

High intensity focused ultrasound as a potential new modality for the treatment of pigmentary skin disorder.

BACKGROUND/PURPOSE: The clinical skin tightening benefits of high intensity focused ultrasound (HIFU) have been established, but its mechanism of action in pigmented skin disorders remains unknown. We macroscopically and histopathologically investigated dermatological changes after HIFU at different exposure doses in a UVB-induced guinea pig model of hyperpigmentation. METHODS: We applied HIFU irradiation at 0.1 and 0.2 J/cm(2) to UVB-induced spotty hyperpigmentation in guinea pig skin. The therapeutic effects of HIFU were judged based on gross appearance using photography, dermoscopy, and chromametry during a period of 3 weeks after HIFU irradiation. Histological assessments were performed using Fontana-Masson staining 1 day before and 3 weeks after HIFU irradiation. RESULTS: Macroscopically, UVB-induced hyperpigmentation was significantly reduced 2 weeks after HIFU with 0.2 J/cm(2) , and 3 weeks after HIFU with 0.1 J/cm(2) . Histopathologically, the heavy deposition of melanin in the epidermis induced by UVB exposure was reduced 3 weeks after HIFU irradiation. CONCLUSION: We confirmed that HIFU has a positive effect on UVB-induced hyperpigmentation as well as mechanical destructive activity. We suggest that HIFU may be useful as an alternative modality for human patients suffering from skin pigmentary conditions.

Tightening effects of high-intensity focused ultrasound on body skin and subdermal tissue: a pilot study.

BACKGROUND: High-intensity focused ultrasound (HIFU) has been introduced as a new treatment modality for skin tightening through application mainly to the face and neck. OBJECTIVES: This pilot study assessed the efficacy and safety of HIFU for body tightening in Asian females. METHODS: Six Asian female adults were enrolled in this pilot study. All subjects were treated with HIFU to the both cheek, upper arm, lower abdomen, thigh and calf using the following probes: 7 MHz, 1.5 mm focal depth; 2 MHz, 3.0 mm focal depth; 2 MHz, 4.5 mm focal depth; 2 MHz, 6.0 mm focal depth and 2 MHz, 9.0 mm focal depth. Three blinded independent dermatologists assessed results using the Investigator Global Aesthetic Improvement Scale (GAIS) using paired pre- and post-treatment (week 4) standardized photographs. Also, we evaluated skin elasticity at all treated sites using a cutometer. Participants used the subject GAIS to assess their clinical improvement after treatment and rated their pain using a visual analogue scale (VAS) immediately, 1 and 4 weeks after treatment. RESULTS: The three blinded evaluators judged all treated sites as showing clinical improvement 4 weeks after treatment. Skin elasticity measured via cutometer was significantly improved 4 weeks after treatment at all treated sites (P < 0.05). All patients scored themselves subjectively as more than 'improved' on the GAIS. Immediately after treatment the mean VAS score was 5.17 ± 2.48, but no pain was reported at weeks 1 and 4. No permanent adverse effects were observed during the follow-up period. CONCLUSION: For body tightening, we applied HIFU using transducers with a lower frequency and deep focal depth to effectively deliver ultrasound energy to skin tissues. HIFU appears to be a safe and effective treatment modality for dermal and subdermal tightening.