Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Study of the K_{L}→π

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Search for K_{L}→π

A search for the rare decay K_{L}→π^{0}νν[over ¯] was performed. With the data collected in 2015, corresponding to 2.2×10^{19} protons on target, a single event sensitivity of (1.30±0.01_{stat}±0.14_{syst})×10^{-9} was achieved and no candidate events were observed. We set an upper limit of 3.0×10^{-9} for the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K_{L}→π^{0}X^{0} was also set as 2.4×10^{-9} at the 90% C.L., where X^{0} is an invisible boson with a mass of 135 MeV/c^{2}.

Adipochemokines induced by ultraviolet irradiation contribute to impaired fat metabolism in subcutaneous fat cells.

BACKGROUND: Adipose tissue is now appreciated as the pivotal regulator of metabolic and endocrine functions. Subcutaneous (SC) fat, in contrast to visceral fat, may protect against metabolic syndrome and systemic inflammation. We demonstrated that chronic as well as acute ultraviolet (UV) irradiation to the skin induces loss of underlying SC fat. UV-irradiated SC fat may produce chemokines or cytokines that modulate lipid homeostasis and secretion of adipokines. OBJECTIVES: To elucidate UV-induced specific adipochemokines implicated in UV-induced modulation of SC fat. METHODS: Primary cultured adipocytes were treated with conditioned medium from UV- or sham-irradiated skin cells. Young and older healthy participants provided SC fat from sun-exposed and sun-protected skin. Sun-protected skin from other participants was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. The functions of select adipochemokines involved in lipid metabolism were examined via short interfering RNA-mediated knockdown of cognate receptors. RESULTS: Specific adipochemokines, including C-X-C motif chemokine (CXCL) family members such as CXCL5/ENA-78, and C-C motif chemokine (CCL) family members such as CCL20/MIP-3α and CCL5/RANTES, were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via downregulation of lipogenic enzymes and sterol regulatory element-binding protein-1 through their respective cognate receptors, CXC chemokine receptor type (CXC-R)2, C-C chemokine receptor type (CCR)-6, and CCR-5. In addition, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat. CONCLUSIONS: These UV-induced adipochemokines may be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity.

Effect of goal-directed haemodynamic therapy in free flap reconstruction for head and neck cancer.

BACKGROUND: In free flap reconstruction for head and neck cancer, achieving a haemodynamic target using excessive fluid infusion is associated with decreased flap survival rates and extended hospital stays. We hypothesized that goal-directed haemodynamic therapy would improve flap survival rates and shorten hospitalization periods. METHODS: Patients scheduled for free flap reconstruction were randomly assigned to a goal-directed haemodynamic therapy group (n = 31) or a conventional haemodynamic therapy control group (n = 31). The control group received extra bolus fluid and ephedrine or norepinephrine to maintain a mean arterial pressure ≥ 65 mmHg. The goal-directed haemodynamic therapy group received a colloid solution as the extra bolus fluid to maintain a stroke volume variation < 12%; dobutamine, ephedrine, or norepinephrine was administered to maintain a cardiac index ≥ 2.5 l/min/m2 and mean arterial pressure ≥ 65 mmHg. Enhanced recovery after surgery protocols were not used except for fluid therapy. An otolaryngologist blinded to group assignments assessed flap outcomes and classified them as 'survival,' 'at risk' or 'failure.' RESULTS: The hospitalization period was not significantly different between the groups. The goal-directed haemodynamic therapy group had significantly shorter intensive care unit stays and a higher flap survival rate. The crystalloid volume was significantly lower in goal-directed haemodynamic therapy group. Reoperation rates, post-operative complications, and laboratory data including inflammatory markers were similar between the groups. CONCLUSION: Compared to conventional haemodynamic therapy, goal-directed haemodynamic therapy does not reduce hospitalization periods; it may, however, reduce the length of intensive care unit stays and increase flap survival rates. Further studies including multi-centre trials with larger sample sizes are warranted.

A method of evaluating facial pores using optical 2D images and analysis of age-dependent changes in facial pores in Koreans.

BACKGROUND: Enlarged facial pores and changes in pore area are of concern for cosmetic reasons. To evaluate pores, measuring tools based on 3D methodology are used. Yet, these methods are limited by their measuring ranges. In this study, we performed pore analysis by measuring the whole face using 2D optical images. We further sought to understand how the pores of Korean women change with age. MATERIALS AND METHODS: One hundred sixteen Korean female subjects aged 20-60 years were recruited for this study. Facial images were taken using the VISIA-CR® adjusted light source. Images were processed using Image-Pro Plus 9.2. Statistical significance was assumed when P < .05. RESULTS: The pore area, as indicated by pixel count, gradually increased in patients through their 40s, but decreased through their 50s and 60s. Facial pores generally exhibited directionality through the patients' 30s, but this isotropic feature was more prominent in their 50s. Pore elongation increased stepwise. The first increase occurred during the transition from patients' 30s to their 40s and the second increase occurred during the transition from patients' 50s to their 60s. This indicated that the pores deformed from a circular shape to a long elliptic shape over time. CONCLUSION: A new evaluation method using 2D optical images facilitates the analysis of pore distribution and elongation throughout the entire cheek. This is an improvement over an analysis of pores over a narrow region of interest.

Use of SkinFibrometer® to measure skin elasticity and its correlation with Cutometer® and DUB® Skinscanner.

BACKGROUND: Skin elasticity is an important indicator of skin aging. The aim of this study was to demonstrate that the SkinFibrometer® is appropriate for measuring skin biomechanical properties, and to correlate it with elasticity parameters measured using the Cutometer® and with dermis structural properties measured using DUB® Skinscanner. MATERIALS AND METHODS: Twenty-one individuals participated in this study. The skin of the cheek, around the eye, and the volar forearm were evaluated. To analyze correlations of elasticity parameters, the induration value against the indenter pressure of SkinFibrometer® and R, Q parameters of Cutometer® were compared. Dermal echogenicity using DUB® Skinscanner was compared with the induration value of SkinFibrometer® . RESULTS: The younger age group showed more firm and elastic skin properties compared to the older age group, and the elasticity values of the volar forearm were significantly higher than those of the cheek and around the eye region. Even though the measuring principle is different, both SkinFibrometer® and Cutometer® demonstrated the same trends of skin elasticity differences according to age and anatomical regions. There were significant correlations between the induration value of SkinFibrometer® , representing skin firmness, and R0, Q0 and R2, R5, R7, Q1, Q2 of Cutometer® , which represent skin firmness and resilience, respectively (P < .01). In addition, dermal echogenicity positively correlated with skin firmness determined by SkinFibrometer® (P < .01). CONCLUSION: We identified correlations between skin elasticity parameters evaluated by two different methods of suction and indentation, and demonstrated that the SkinFibrometer® is an objective, non-invasive evaluation tool for skin stiffness and elasticity.

Comparison of stratum corneum thickness between two proposed methods of calculation using Raman spectroscopic depth profiling of skin water content.

BACKGROUND/PURPOSE: The stratum corneum (SC) is the most important layer for the barrier function of skin, so investigation of the SC is very important in cosmetic and medical research. Here, we calculated the SC thickness using the depth profile of the skin's water concentration based on previously described methods, and then compared the results. METHODS: Seven Korean women in their 30s participated in this study. Raman spectroscopy was used to measure the in vivo depth profile of skin water concentration. A total of 21 areas were measured at forearm. Microsoft Excel 2007 was used to calculate SC thickness based on the slope and intersection methods. RESULTS: The slope method and the intersection method gave a forearm SC thickness calculated at 21.3 ± 2.6 µm and 17.6 ± 2.8 µm, respectively. There was a significant difference between the two calculation methods but the two methods showed strong correlation of SC thickness results (r = .899). CONCLUSION: Although there was a difference in calculated SC thickness of about 20% between the two methods, these results reveal that the two SC thickness calculation methods using Raman spectroscopy were suitable for measuring SC thickness, a finding consistent with other published results.

A new technique for evaluating heel xerosis grade and the effects of moisturizer on heel skin dryness.

BACKGROUND: Dryness-related heel skin problems are common; however, there are very few studies about heel skin dryness. The objective of this study was to develop new assessment methods for evaluating heel skin dryness, to clarify the characteristics associated with heal skin dryness, and assess the effectiveness of moisturizer use according to dryness severity. MATERIALS AND METHODS: We investigated the heel skin of 150 Korean women (aged 20-78 years). Heel skin images were taken using a DSLR camera and the distribution or severity of flakes, scaling, cracking, and fissures were visually assessed. Skin properties such as hydration, transepidermal water loss (TEWL), amount of dead skin cells, and efficacy of moisturizer were evaluated according to heel xerosis grade. Furthermore, as conventional evaluation methods for desquamation are not appropriate for heel skin, we developed new techniques using binarization of magnified images. RESULTS: Skin hydration tended to decrease and TEWL tended to increase as heel dryness grade increased. The amount of dead skin cells increased with increasing dryness grade using the new technique. Subjects in the severe dryness group achieved similar hydration levels as normal subjects at baseline after 3 hours of moisturizer application. CONCLUSION: Our new methods of visually classifying heel dryness and quantifying dead skin cells using magnified images effectively evaluated heel skin properties. As heel skin is prone to dryness, daily repetitive application of moisturizer might be helpful for hydrating dry heel skin, and ultimately preventing complications.

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.

BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

Effects of dietary mixture of garlic (Allium sativum), coriander (Coriandrum sativum) and probiotics on immune responses and caecal counts in young laying hens.

This study was conducted to evaluate the effects of a combined mixture of phytogenic extracts (garlic and coriander) and probiotics on growth performance and immune responses in laying hens based on the results of in vitro studies to screen for immunomodulatory potency of each ingredient. Several parameters of immunomodulatory potency were estimated using lamina propria leucocytes (LPLs) isolated from rat intestinal mucosa tissue. Results show that the combined mixture enhanced LPLs proliferation, increased LPL-mediated cytotoxicity against YAC-1 tumour cells, and decreased lipopolysaccharide (LPS)-induced cytokine production including tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in LPLs. For in vivo study, laying hens (n = 50/each diet group) were fed with control diet, a diet containing antibiotics (0.01% per kg feed) or the combined mixture (0.02% per kg feed) for 21 days. The dietary combined mixture improved egg production (p < 0.05) but not growth performance and carcass traits. Interestingly, the patterns of suppressing plasma IFN-γ productions during inflammation by LPS injection and decreasing caecal E. coli counts in the combined mixture group were comparable to those in the antibiotics group. Taken together, our results suggested that the 0.02% of combined mixture of phytogenic extracts and probiotics as ingredients has potential immunomodulatory effects in laying hens.

Cognitive impairments associated with morphological changes in cortical and subcortical structures in multiple system atrophy of the cerebellar type.

BACKGROUND AND PURPOSE: Patients with the cerebellar variant of multiple system atrophy (MSA-C) often show cognitive deficits in various cognitive domains. The association between morphometric changes in cortical and subcortical structures and cognitive impairments in MSA-C were investigated to explore the neural correlates responsible for cognitive deficits in MSA-C patients. METHODS: Using surface-based morphometry, region-of-interest cortical thickness and the volumes and shapes of subcortical structures were examined in 18 patients who fulfilled the criteria of probable MSA-C and were compared to 50 healthy controls. The association between regional changes and cognitive functions in MSA-C were investigated by applying linear regression analyses after controlling for confounding factors. RESULTS: Compared with controls, the patients with MSA-C showed significant cortical thinning in the fronto-temporo-parietal regions and volume reduction in subcortical structures with shape changes. Cerebellar volume had no significant effect on cortical and subcortical volumes. The severity of atrophic changes in the bilateral thalamus, the left cerebellum and the left pericalcarine gyrus were significantly correlated with attentional, executive and visuospatial dysfunctions. CONCLUSION: Cognitive impairment in MSA-C might result from functional disruption of the corticostriatal and pontocerebellar circuit mediated by primary cortical, cerebellar or thalamic pathology.

The brain-derived neurotrophic factor Val66Met polymorphism and degeneration of the corticospinal tract after stroke: a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: A common single nucleotide polymorphism, Val66Met, in the human brain-derived neurotrophic factor (BDNF) gene has a potential role in the pathogenesis and treatment of stroke. The relevance of the BDNF Val66Met polymorphism to long-term stroke outcomes was examined, specifically with respect to changes in corticospinal integrity. METHODS: Thirty-five stroke patients with unilateral motor weakness were genotyped within 2 weeks after onset (T1), and changes in the integrity of the ipsilesional corticospinal tract (CST) as well as alterations in motor function at 1 month (T2) and 3 months after onset (T3) were tracked. RESULTS: On the basis of the Fugl-Meyer assessment upper extremity score, carriers of the Met allele (Val/Met and Met/Met) showed poorer motor outcomes at T2 and T3 compared to carriers of only the Val allele (Val/Val). For both BDNF allele types, patients exhibited characteristic degeneration of the CST compared to healthy controls. There were no differences between the two genotypes with respect to time-dependent changes in diffusion-tensor-imaging-derived parameters of the CST. However, the two groups showed different relationships between motor outcomes and directional diffusivities according to the elapsed time after onset. Poorer motor function was associated with lower axial diffusivity values for the Val/Val genotype group in the sub-acute phase (T1 and T2) but with higher radial diffusivity values for the Val/Met and Met/Met genotype group in the early chronic phase (T3). CONCLUSIONS: Motor recovery in stroke patients may be affected by the BDNF Val66Met polymorphism, possibly through its effects on distinct pathological processes underlying corticospinal degeneration.

Incidence and risk factors for backpack palsy in young Korean soldiers.

OBJECTIVES: Backpack palsy (BPP) is a common aetiology of brachial plexopathy in military hospitals. We aimed to determine the incidence and risk factors of BPP in young Korean soldiers. METHODS: We identified enlisted patients who were diagnosed with BPP from a review of the medical records of all the Korean military hospitals in 2011 and 2012 and investigated their clinical findings and medical study results. To identify risk factors of BPP, we also surveyed, by questionnaire, healthy recruits of a company in a training centre who had just finished night marches. We divided them according to whether they had paresthaesia and/or weakness in their arm(s) during marching and compared their characteristics. RESULTS: The incidence of BPP in Korean soldiers was 29.7 per 100,000 person-years (95% CI 17.2 to 24.3). Body mass index (BMI) was significantly lower in patients with BPP than it was in healthy recruits. Among healthy recruits, those who had experienced paresthaesia and/or weakness during marching had a significantly lower BMI than did those who had not. CONCLUSIONS: We report the incidence of BPP in young Korean soldiers. A low BMI was a risk factor for BPP. These results may be helpful in establishing a strategy for the prevention of BPP in the setting of military training.

Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance. METHODS: We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab. RESULTS: Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting. CONCLUSIONS: Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer.

A case of panniculitis caused by Mycobacterium massiliense mimicking erythema induratum.

Among nontuberculosis mycobacteria (NTM), rapidly growing mycobacteria (RGM) are the most common causative agents of soft tissue infection. Mycobacterium massiliense, a new species of NTM, was isolated in 2004. Due to the lower virulence of RGM, M. massiliense infection is rare in the general population. Here, we report a case of multiple infective panniculitis, due to M. massiliense, mimicking erythema induratum in a patient with Cushing syndrome. The organism was identified using traditional mycobacterial culturing and staining methods as well as molecular approaches, including erythromycin ribosome transferase gene polymerase chain reaction. The patient was treated with clarithromycin for 9 months, based on antibiotic susceptibility testing.

Effect-site concentration of remifentanil for attenuating QTc interval prolongation following intubation in hypertensive female patients.

BACKGROUND: Haemodynamic changes after sympathetic stimuli like tracheal intubation are more pronounced in hypertensive patients than in normotensive patients. Heart rate (HR)-corrected QT (QTc) interval changes related to intubation may also be more prominent in hypertensive patients. We hypothesised that there would be a difference in the effect-site concentration (Ce) of remifentanil to attenuate QTc interval prolongation in normotensive and hypertensive patients following intubation. METHODS: Twenty-two normotensive and 22 hypertensive female patients (≥ 50 year) were enrolled and anaesthesised with remifentanil and propofol using a target-controlled infusion. All hypertensive patients received oral antihypertensive medications for > 6 months and took the medications in the morning of the surgery. The effective concentration of remifentanil Ce in 50% (EC50 ) and 95% of the population (EC95 ) required to maintain QTc interval prolongation < 15 ms following intubation was calculated using the isotonic regression and a bootstrapping approach following the Dixon's up-and-down method. RESULTS: Median duration of hypertension was 6 years. Isotonic regression revealed that the EC50 (83% confidence interval) of remifentanil Ce for reducing QTc interval prolongation following intubation was 3.8 (3.5-4.1) ng/ml in normotensive and 6.1 (5.8-6.2) ng/ml in hypertensive female patients. The EC95 (95% confidence interval) of remifentanil Ce was 4.4 (4.3-4.5) ng/ml in normotensive and 6.5 (6.4-6.5) ng/ml in hypertensive female patients. CONCLUSION: The Ce of remifentanil required to attenuate QTc interval prolongation following intubation was significantly higher in hypertensive patients than it was in normotensive patients. Thus, more caution should be taken related to QTc interval prolongation when intubating hypertensive patients.

A case of perforating dermatofibroma with floret-like giant cells.

Dermatofibromas are slow-growing solitary nodules, composed mostly of a dermal proliferation of spindle cells and epithelioid cells. Some dermatofibromas present with multinucleated giant cells, such as Touton, foreign body, and osteoclast-like cells. We report a case of dermatofibroma containing both Touton giant cells and floret-type cells. A 12-year-old boy presented with a 6-mm, firm, nontender, dusky-red to greyish dermal nodule on his left popliteal fossa. As suggested clinically by the central opening, perforation of the epidermis with partial extrusion of the dermal components, including macrophages and vertically oriented collagen bundles, via transepidermal elimination, were detected. In the upper dermis, collagen trapping and mostly epithelioid cells with many giant cells were seen, while the lower part contained mainly spindle cells in a storiform pattern. Multinucleated giant cells scattered in the upper dermis were mainly floret-type multinucleated giant cells with star-shaped cytoplasmic projections, associated with some Touton giant cells. To our knowledge, this is the first report of a perforating dermatofibroma with floret-type multinucleated giant cells.