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Background: Alcohol consumption has been considered as a modifiable risk factor for dementia development and alcohol-related brain damage may further impair cognitive abilities in dementia patients. This study aimed to find out the differences in cognitive function according to current alcohol drinking in patients with self-perceived memory decline, including subjective cognitive decline (SCD), mild cognitive impairment (MCI) and early Alzheimer-type dementia (ATD).Methods: From May 2018 to December 2019, retrospective chart review was performed in patients who visited CHA Bundang Medical Center for cognitive decline. A two-way analysis of variance with interaction test were used to analyze the impact of alcohol consumption on cognitive function between groups.Results: A total of 147 patients was classified into three groups of SCD (n=30), MCI (n=53), and ATD (n=64), and each group was divided into two subgroups of alcohol users and alcohol non-users, according to the current status of alcohol consumption. Between SCD, MCI and ATD groups, scores of clock drawing test and Go/No-go test were significantly lower in current alcohol users of ATD groups compared to the SCD and MCI groups (p

BACKGROUND Recent studies suggest that high levels of serum uric acid of very early life are a result of the in-utero environment and may lead to elevated blood pressure (BP) in adulthood. However, serum uric acid levels can change throughout life. We investigated the effect of serum uric acid levels in childhood on the BP tracking and analysed BP according to changes in serum uric acid levels in early life. METHODS A total of 449 children from the Ewha Birth and Growth Cohort study underwent at least 2 follow-up examinations. Data were collected across 3 check-up cycles. Serum uric acid levels, BP, and anthropometric characteristics were assessed at 3, 5, and 7 years of age. RESULTS Children with a serum uric acid level higher than the median values had significantly increased systolic BP (SBP) and diastolic BP at 3 years of age. Baseline serum uric acid levels measured at 3 years of age, significantly affected subsequent BP in the sex and body mass index adjusted longitudinal data analysis (P < 0.05). Considering the changing pattern of serum uric acid over time, subjects with high uric acid levels at both 3 and 5 years of age had the highest SBP at 7 years of age. CONCLUSIONS These findings suggest the importance of maintaining an adequate level of serum uric acids from the early life. Appropriate monitoring and intervention of uric acid levels in a high-risk group can reduce the risk of a future increased BP.

Spontaneous regression of malignant tumors is rare especially of lung tumor and biological mechanism of such remission has not been addressed. We report the case of a 79-year-old Korean patient with non-small cell lung cancer, squamous cell cancer with a right hilar tumor and multiple lymph nodes, lung to lung metastasis that spontaneously regressed without any therapies. He has sustained partial remission state for one year and eight months after the first histological diagnosis.

This study was conducted to examine the effects of alterations in water temperature (WT) on biochemical and immunological factors in the hemolymph of the abalones, Haliotis gigantea and H. discus discus. The abalone were exposed to various WT; 18, 20, 22, 24, 26 and for 96 hours. In biochemical factors, total-protein (TP), glucose, magnesium (Mg), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were not significant changes in hemolymph of H. gigantea and H. discus discus. But calcium was significantly increased by high WT (). In immunological factor, The phenoloxidase (PO) activity was decreased in hemolymph of H. gigantea and H. discus discus exposed to high temperature () compared to the control (P

Clostridium difficile infection (CDI) is a common cause of antibiotic-associated diarrhea with an increase in severity and frequency in the recent times. CDI can be refractory and relapses, especially in the elderly or patients with significant comorbidities. Conventional treatments with antibiotics often fail to cure the infection. Even when successfully treated, recurrent infection is common. Some studies have reported that fecal transplantation may be effective and safe for the treatment of recurrent and intractable CDI. We present two CDI cases (one recurrent and one refractory) which were treated successfully by fecal transplantation using enema.

Atypical adenomatous hyperplasia (AAH) has been considered to be a precursor lesion of bronchioloalveolar carcinoma (BAC) and pulmonary adenocarcinoma. It usually coexists with BAC and/or an adenocarcinoma. Chest computed tomography reveals multiple well-defined nodules with ground-glass opacity. Usually, AAH does not exceed 10 mm in size. AAH with extensive involvement on one side of the lung field or one that is larger than 2 cm has not been previously reported. We herein report a case of a 71-year-old nonsmoking female with lung AAH of larger than 2 cm.

The cutaneous manifestations of chronic active Epstein-Barr virus (EBV) infection can be diverse. Among them, hydroa vacciniforme-like eruption is one of the best-known features. Although rare, mucosal ulcers have been reported to be associated with EBV as a result of primary infection or immune suppression. We describe a 65-year-old female with recurrent necrotic papulovesicles on the face and both arms for 2 years. She also complained of recurrent oral and genital mucosal ulcers developing simultaneously with skin eruptions. They appeared periodically during the spring and summer and were triggered or aggravated by sun exposure. Skin biopsies from the face and genitalia showed identical findings with dense lymphocytic infiltrations. In addition, in situ hybridization revealed EBV-positive lymphoid cells in both specimens. To our knowledge, this is the first case of serologically and pathologically proven chronic active EBV infection presenting hydroa vacciniforme-like eruption and orogenital ulcers at the same time in one patient.

Context: Recently, an arginine-to-cysteine homozygous mutation at position 25 in mature PTH was reported in a Korean patient with hypoparathyroidism. Objective: To clarify whether the high bone mass phenotype observed in this patient was related to the hypoparathyroidism itself or to chronic elevation of mutant PTH. Methods: A series of in vitro and in vivo experiments were performed in MC3T3E1, ROS 17/2.8, and SAOS2 cells treated with human (h)PTH(1–34), Cys25hPTH(1–34), Ala1Cys25hPTH(1–34), and Bpa1Cys25hPTH(1–34). The peptides were then sc delivered to ovariectomized mice as daily single injections. Results: Compared with hPTH(1–34) and Ala1Cys25hPTH(1–34), treatment with Cys25hPTH(1–34) or Bpa1Cys25hPTH(1–34) resulted in decreases in the cAMP response and promoter-cAMP-response element luciferase reporter activity. Although the cAMP response was sustained with hPTH(1–34) in MC3T3E1 cells, such response was not observed with the other mutated peptides. Meanwhile, all PTH analogues exhibited ERK phospho...

Dear Editor: Cold-inducible RNA-binding proteins (CIRP) are a kind of RNA binding protein associated with diverse cellular responses including cell growth, proliferation, and apoptosis1. CIRP are induced by various cellular stresses in addition to cold exposure such as ultraviolet (UV) radiation and hypoxia1,2. Recently, their proto-oncogenic functions have been suggested, but a detailed expression pattern in skin tumor has not been reported3,4,5. Therefore, we aimed to simply observe the expression pattern of CIRP in photo-damaged epidermis of actinic keratosis (AK), squamous cell carcinoma (SCC) and normal skin by immunohistochemical staining. Five samples of normal skin were obtained from 5 healthy individuals undergoing cosmetic surgery. Among them, 3 were taken from the back and 2 from the face. Specimens of AK and SCC were obtained from the faces of 5 patients who underwent excisional surgery. SCC samples were confined to that which developed after long-standing AK. Clinically and pathologically active lesions were taken as the samples. In all cases, informed consent was obtained from patients according to the ethics committee of the Chonnam National University Hospital. Serial paraffin sections of each specimen were stained with monoclonal antibodies specific for CIRP (Proteintech Group, Chicago, IL, USA) at a dilution of 1 : 100 according to the manufacturers' protocols. The expression of CIRP in epidermal keratinocytes was scored semi-quantitatively by two dermatologists. Nuclear and cytoplasmic staining were assessed separately. We considered both staining intensity and the ratio of positively stained cells in comparison with adjacent stromal cells, lymphocytes, and sebaceous and eccrine glands. No staining was cited as 0, weaker staining than stromal cells as 1, similar to stromal cells as 2, and stronger as 3. Statistical analysis was performed using the chi-square test and Wilcoxon's rank sum test to compare the expression pattern (SPSS ver. 17.0; SPSS Inc., Chicago, IL, USA). In normal skin specimens, CIRP expression was more evident in nuclei than in cytoplasm throughout the epidermal keratinocytes (Fig. 1). However, in specimens from the face, the most sun exposed area, cytoplasmic CIRP staining intensity was increased compared to that in specimens from the back, a less-sun exposed area. In the case of AK, nuclear CIRP expression was decreased while cytoplasmic expression was maintained or rather increased. And in the most pathologic spots of SCC, CIRP expression was significantly decreased both in the nuclei and cytoplasm. Statistical analysis revealed significantly decreased expression of CIRP in nuclei of AK and consequent SCC compared with normal skin. There was no statistically significant difference in cytoplasmic staining intensity among them (Fig. 2). Fig. 1 Cold-inducible RNA-binding protein (CIRP) expression is evident in the nuclei of epidermal keratinocytes in normal skin from back (CIRP immunohistochemical stain, ×200). Fig. 2 Expression patterns of Cold-inducible RNA-binding protein (CIRP). Representative pictures of five cases in each normal skin from face (A), actinic keratosis (AK) (B), and squamous cell carcinoma (SCC) (C) (A~C: CIRP immunohistochemical stain, ×200). ... In previous studies of human cancer, the majority of endometrial carcinoma showed decreased staining intensity4. However, staining intensity was increased in several other human tumors, such as colon and prostate cancer5. These conflicting results may come from the early inducing mechanism of CIRP. CIRP regulates gene expression at the level of translation1,3. Therefore, the exact cellular function of CIRP remains unknown at the moment and the expression pattern in cancer cells could vary according to the state of the tumor. The increased cytoplasmic CIRP expression we observed in sun-exposed areas might be explained by relocalization of CIRP that was triggered by UV exposure2. We observed a significant decrease of nuclear CIRP expression in AK and SCC compared with normal skin. Further studies are needed to elucidate the relationship between CIRP and UV radiation and consequent tumorigenesis in the skin.

Sclerostin, encoded by the Sost gene, is mainly produced by osteocytes in bone and antagonizes the Wnt/β-catenin signaling pathway, which is a requisite for bone formation. Currently, human anti-sclerostin antibodies are being tested in phase III clinical trials. In addition, serum sclerostin levels are reported to be associated with bone mineral density and fracture risk in normal individuals; however, the correlation between serum sclerostin and bone mass remains controversial. To study the effects of the continuous exposure of exogenous sclerostin on bone, a ΦC31 integrase system, which has the characteristics of site-specificity and efficiency, was applied for the delivery of the Sost gene in this study. We injected Sost-attB plasmid with or without ΦC31 integrase plasmid into the mouse tail vein using a hydrodynamic-based method. The site-specific integration of the Sost gene into the mouse genome was confirmed by examining a pseudo-attP site on the hepatic genomic DNA. Sclerostin was expressed in the hepatocytes, secreted into the blood flow, and maintained at high concentrations in the mice with both Sost-attB plasmid and ΦC31 integrase plasmid injections, which was observed by serial measurement. Moreover, the mice with long-term high levels of serum sclerostin showed trabecular bone loss on micro-CT analysis. Peripheral B cell populations were not affected. Our results suggested that sclerostin could be expressed in the liver and sustained successfully at high levels in the blood by using the ΦC31 integrase system, leading to trabecular bone loss. These findings may help to further ascertain the effects of sclerostin introduced exogenously on the skeleton.

Epithin/PRSS14, a type II transmembrane serine protease, plays critical roles in cancer metastasis. Previously, we have reported that epithin/PRSS14 undergoes ectodomain shedding in response to phorbol myristate acetate (PMA) stimulation. In this study, we show that transforming growth factor-β (TGF-β) induces rapid epithin/PRSS14 shedding through receptor mediated pathway in 427.1.86 thymoma cells. Tumor necrosis factor-α converting enzyme (TACE) is responsible for this shedding. Amino acid sequence encompassing the putative shedding cleavage site of epithin/PRSS14 exhibit strong homology to the cleavage site of l-selectin, a known TACE substrate. TACE inhibitor, TAPI-0 and TACE siRNA greatly reduced TGF-β-induced epithin/PRSS14 shedding. TGF-β treatment induces translocation of intracellular pool of TACE to the membrane where epithin/PRSS14 resides. These findings suggest that TGF-β induces epithin/PRSS14 shedding by mediating translocation of epithin/PRSS14 sheddase, TACE, to the membrane.

The tumor suppressor, QM has been cloned and characterized from eukaryotic organisms including humans, vertebrates, invertebrates, plants and yeast. However, no study on Pieris rapae QM (PrQM) has been reported to date. In this study, cDNA encoding a putative QM protein (PrQM) was obtained from expressed sequence tags (ESTs) of the Pieris rapae cDNA library. Phylogenetic analysis of PrQM showed high similarity of amino acid sequence with other putative homologues identified from Heliothis virescens (95%), Bombyx mori (92%), Plutella xylostella (92%), Drosophila melanogaster (89%) and Polyrhachis vicina (85%), indicating that QM is highly conserved among insects. Semi-quantitative PCR datasets revealed that PrQM transcripts are highly expressed in head, silk gland, integument and fat body, with pronounced expression observed during the egg stage. The coding region of the PrQM gene was cloned into the pET28 (+) expression vector and the recombinant protein purified by His-tag affinity chromatography was used for antibody production. Western blotting with the anti-PrQM antibody detected a single band corresponding to the expected molecular weight of both endogenous (26 kDa) and recombinant (29 kDa) PrQM. Furthermore, immunohistochemical and confocal microscopic analysis with the anti-PrQM antibody showed that the QM gene is highly expressed in the cytoplasm of fat body, gut and Malpighian tubules in virus-uninfected control larvae, but down-regulated at 4 days post Pieris rapae granulovirus (PiraGV) infection. These data show that PrQM is negatively regulated upon virus infection and suggests a putative immunomodulatory function.

This paper proposes a novel detection and tracking scheme for large-scale phenomena, called continuous objects, in wireless sensor networks, such as wild fire and bio-chemical material. Unlike previous works, the scheme takes into account a two-tier grid structure in order to achieve flexible and reliable detection and tracking. Firstly, for flexibility, the scheme constructs a coarse-grained grid structure and then, once a continuous object appears, fine-grained grid structures are established within coarse-grained grid cells only around the continuous object. The fine-grained grid structures could be constructed with dynamic grid cell size according to various requirements. Secondly, for reliability, minute grid cells of the fine-grained grid structures are able to provide detailed shape of boundary of the continuous object; to quickly deal with diffusion of the continuous object the scheme prepares the fine-grained grid structures into next coarse-grained grid cells toward diffusion direction of the continuous object.

Compared to the vigorous development of targeted drugs and some of them are already become one of the best treatment of choices in lung adenocarcinoma, squamous lung carcinoma has no definite targets and treatment outcome is not yet superior to lung adenocarcinoma. Demonstration of initial carcinogenesis is benefitial in two aspects: cancer prevention and development of its targets. Studying preneoplastic lesions of bronchus can answer those questions. Preneoplastic lesion, which is considered to have malignant potential, may develop into invasive cancer by escaping from host immune response. CD274 (programmed death-ligand 1, PD-L1) interacts with PD-1, is known to inhibit CD8+ cytotoxic T lymphocyte and induce apoptosis and, also to promote the differentiation of CD4+ T cells into regulatory T cells, so finally evade immune surveillance. We hypothesized that PD-L1 may work as an immune evader in preneoplastic lesion during its carcinogenesis. We performed white light and/or autofluorescence bronchoscopy in patients who have risk factor(s) of lung cancer or are suspected to have a lung cancer. Interestingly, PD-L1 was also overexpressed in preneoplastic lesions especially in severe dysplasia of the bronchus. This finding implies overexpression of PD-L1 can involve at early step of carcinogenesis. Further studies are needed to demonstrate the role of PD-L1 in preneoplastic bronchial lesion potential to develop invasive cancer. Citation Format: Hee Sun Park, Bo Mi Park, Dong Il Park, Chung Jae Uk, Jae Young Moon, Jung Sung Soo, Choong Sik Lee, Ju Ock Kim, Sun Young Kim, Jaseok Peter Koo. Programmed death-ligand 1 is overexpressed in bronchial preneoplastic lesions: can it be a risk indicator. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-092. doi:10.1158/1538-7445.AM2015-LB-092

A 43-year-old man presented to our hospital with generalized skin papulonodular and pruriginous eruptions. Clinical examination revealed grouped and scattered pruritic papules and nodules on his legs, arms, and trunk (Figure 1). The patient had type 2 diabetes mellitus and hypertension, with no history of allergy or dermatitis. The papules first appeared on the lower legs when the patient began treatment with peritoneal dialysis, 2 years earlier. The papules gradually disseminated to the legs, arms, back, and chest. We performed a skin biopsy, and the biopsy findings indicated pseudo-epitheliomatous acanthosis, hyperkeratosis, and vascular hyperplasia of the upper dermis with mild inflammatory perivascular infiltration—symptoms that are characteristic of prurigo nodularis (Supplementary Figure S1 online). Prurigo nodularis is an unusual disorder of unknown etiology that could result from the accumulation of an unidentified pruritogenic, poorly dialyzable uremic substance in hemodialysis patients.1 No data are available on this condition in peritoneal dialysis patients. Therefore, nephrologists should consider prurigo nodularis when this skin lesion is observed. It is notoriously resistant to therapy,2 and is characterized by extremely pruritic nodules with well-defined clinical symptoms and histopathological findings. The patient was treated with a gradually tapered 16-mg dose of oral methylprednisolone, oral antibiotics, oral antihistamines, and cryotherapy. This treatment led to a temporary amelioration in the clinical symptoms, which later recurred. The patient has been on the wait list for a kidney transplantation, which is known to be the most effective treatment for uremic pruritus–associated prurigo nodularis.

In this paper, we describe 72-year-old female patient without evidence of malignant disease presented with significantly elevated serum carbohydrate antigen (CA) 19-9 levels by respiratory infections. She was diagnosed with respiratory infections due to Mycobacterium avium complex and Pseudomonas aeruginosa. The serum CA 19-9 levels remarkably increased (1,453-5,300 U/mL; reference range

The tumor suppressor, QM, has been cloned and characterized from various model organisms such as human, plant and invertebrates. Yet, it has not been seriously investigated for its role in conjunction with antiviral mechanisms involving innate insect immunity. From the expressed sequence tag (ESTs) project, conducted with larval cDNA library of cabbage butterfly, Pieris rapae, a partial fragment (718 bp) of QM homologue, termed PrQM containing 660 bp long open reading frame (ORF) encoding protein of 219 amino acids was identified. In silico analysis of PrQM ORF revealed the presence of ribosomal protein L10a/L10e type domain. Phylogenetic analysis of the P. rapae QM-like protein showed high amino acid sequence similarity with other PrQM polypeptides identified from Heliothis virescenes (95%), Plutella rapae (92%), Bombyx mori (92%), Drosophila melanogaster (89%), and Polyrhachis vicina (85%). The butterfly QM has the closest phylogenetic relationship to a moth (Hv) QM homologue. Further investigations revealed the expression of PrQM at all developmental stages, with pronounced presence at the egg stage. In addition, spatial pattern analysis indicated its high expression in the head, salivary gland, integument and fat body with visible presence in Malpighian tubule and gut. Time course expression studies conducted after immune-challenge with lipoteichoic acid (LTA) showed the induction of PrQM mRNA at 12 h and 24 h after challenge and also in response to granulovirus (GV). Results of this investigation therefore suggest possible role of QM-like proteins from Pieris rapae to be involved in innate antiviral immune responses. Further elucidation on the precise function of PrQM during antiviral immune responses by using RNA interference remains a viable research front.

It has been reported that QM may have antiviral function in invertebrate. However, it has not been seriously investigated whether insect QM plays a critical role in antiviral immunity against nucleopolyhedrosis virus (NPV). In this context, in silico identification and comparative analysis of Spodopetera exigua QM cDNA was conducted. As expected, it is highly conserved protein. To further examine whether entomopathogenic NPV up-regulates the level of SeQM mRNA, budded virus (AcMNPV-BV) was infected to the 3rd instar larvae. Real-time PCR analysis of SeQM in virus-infected larvae with poly I:C was conducted and potential significance of SeQM was discussed. It remains to elucidate the precise function of SeQM during antiviral immune responses by using RNA interference.

Becker's nevus is a relatively common acquired focal epidermal melanotic hypermelanosis usually found in the region of the shoulder girdle of young men. Various skeletal malformations and cutaneous dermatoses have been reported in Becker's nevus. Osteoma cutis is a rare disorder characterized by compact bone formation in the dermis or subcutaneous tissue. Secondary ossification on nevi has been reported, but not with Becker's nevus. Herein, we report a case of Becker's nevus with accompanying osteoma cutis in an 18-year-old female.