Clinical Features and Management of Stenotrophomonas Maltophilia Keratitis.

INTRODUCTION: Stenotrophomonas maltophilia keratitis is an uncommon infectious disease of the cornea. The clinical features, antibiotic susceptibility, and clinical outcomes of S. maltophilia keratitis were investigated in this study. METHODS: Between January 2015 and February 2020, the medical records of 16 patients with culture-proven S. maltophilia-associated infectious keratitis were retrospectively reviewed. Clinical data were analyzed regarding risk factors, clinical presentation, antibiotic susceptibility, and clinical outcomes. RESULTS: The average age of the patients was 56.24 ± 24.84 years. The most common risk factors for S. maltophilia keratitis were trauma (6/16, 37.5%), use of contact lenses (6/16, 37.5%), and herpes simplex virus keratitis (3/16, 18.8%), which caused ocular instability. Regarding the antibiotic sensitivities, most isolates (15/16, 93.8%) were susceptible to fluoroquinolones, 87.5% (14/16) of them to aminoglycosides, and 81.3% (13/16) of them to beta-lactams. Patients were classified into two groups according to the initial antibiotic eye drops, and there were significant differences in the final visual acuity between two groups: mixed fluoroquinolone, beta-lactam, aminoglycoside group, and mixed beta-lactam and aminoglycoside groups (p = 0.039). CONCLUSION: Ocular infection due to S. maltophilia is an opportunistic infection followed by instability of the ocular surface. In cases of S. maltophilia infection, mixed use of fluoroquinolone, beta-lactam, and aminoglycoside should be considered for treatment of choice.

Non-melanoma skin cancer as a clinical marker for internal malignancies: a nationwide population-based cohort study.

INTRODUCTION: Non-melanoma skin cancers (NMSCs) are the most common cancers in the world, but the risk of internal malignancy in patients with NMSC has not been well investigated. OBJECTIVES: We aimed to assess the risk of internal malignancy in patients with NMSC compared with controls without NMSC in Korean population. METHODS: This nationwide cohort study, compared 27 259 NMSC patients with 54 518 matched controls without NMSC, 40 years or older using the data from Korea Health Insurance Review and Assessment Service from 2007 to 2016. The first 2 years were washout period, and we followed the patients for 8 years to observe the development of any internal malignancies after a diagnosis of NMSC. The Cox proportional hazard model was used to determine the hazard ratios (HRs) for developing internal malignancies. RESULTS: The overall risk of internal malignancies at all sites was 2727.7 and 1392.4 per 100 000 person-years for the patients with NMSC and controls, respectively. The risk was significantly higher in the patients with NMSC (HR 1.866, 95% confidence interval [CI] 1.768-1.970). Bone cancer showed the highest risk (HR 12.745, 95% CI 6.288-25.834), followed by nasal cavity and larynx (HR 10.279, 95% CI 6.178-7.103), oral cavity and pharynx (HR 10.211, 95% CI 7.375-14.137), anus and anal canal (HR 8.147, 95% CI 3.893-17.051) and cervical (HR 5.900, 95% CI 3.694-9.423) cancers with risks greater than fivefold higher in NMSC patients compared with the controls. The risks of cancers of the thorax, oesophagus, breast, lung, stomach, thyroid gland and non-Hodgkin's lymphoma were also statistically higher in the patients with NMSC. In contrast, the risks of cancers of the colon and rectum were found to be significantly decreased in the patients with NMSC (HR 0.765, 95% CI 0.657-0.890). CONCLUSION: Patients with NMSC require careful screening and follow-up for internal malignancy.

Cultural Stigma Manifested in Official Suicide Death in South Korea.

This article examines the cultural sources of underreported suicide deaths in South Korea. It analyzes two sets of suicide data compiled by two different government agencies. Noting the considerable undercounting of suicide deaths compiled by the National Statistical Office, it explores how the underreporting is linked to the Confucian norm of familism. Despite an effort to improve the quality of official suicide data, a reform in the death system is needed in order to gather accurate data for a better understanding of the increased suicides as well as for the development of more effective suicide prevention and intervention strategies.

Effects of dietary supplementation of bacteriophages against enterotoxigenic Escherichia coli (ETEC) K88 on clinical symptoms of post-weaning pigs challenged with the ETEC pathogen.

The present study was performed to investigate the effects of dietary supplementation of bacteriophages (phages) against enterotoxigenic Escherichia coli (ETEC) K88 as a therapy against the ETEC infection in post-weaning pigs. Two groups of post-weaning pigs aged 35 days, eight animals per group, were challenged with 3.0 × 1010 colony forming units of ETEC K88, a third group given the vehicle. The unchallenged group and one challenged group were fed a basal nursery diet for 14 days while the remaining challenged group was fed the basal diet supplemented with 1.0 × 107 plaque forming units of the phage per kg. Average daily gain (ADG), goblet cell density and villous height:crypt depth (VH:CD) ratio in the intestine were less in the challenged group than in the unchallenged group within the animals fed the basal diet (p < 0.05); the reverse was true for rectal temperature, faecal consistency score (FCS), E. coli adhesion score (EAS) in the intestine, serum interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) concentrations and digesta pH in the stomach, caecum and colon. The ETEC infection symptom within the challenged animals was alleviated by the dietary phage supplementation (p < 0.05) in ADG, FCS, EAS in the jejunum, serum TNF-α concentration, digesta pH in the colon, goblet cell density in the ileum and colon and VH:CD ratio in the ileum. Moreover, the infection symptom tended to be alleviated (p < 0.10) by the phage supplementation in rectal temperature, EAS in the ileum and caecum, and VH:CD ratio in the duodenum and jejunum. However, EAS in the colon, digesta pH in the stomach and caecum, and goblet cell density in the jejunum did not change due to the dietary phage. Overall, results indicate that the phage therapy is effective for alleviation of acute ETEC K88 infection in post-weaning pigs.

Exogenous administration of DLK1 ameliorates hepatic steatosis and regulates gluconeogenesis via activation of AMPK.

BACKGROUND/OBJECTIVES: Activation of Notch signaling pathologically enhances lipogenesis and gluconeogenesis in the liver causing non-alcoholic fatty liver disease (NAFLD) and diabetes. Delta-like 1 homolog (DLK1), an imprinted gene that can modulate adipogenesis and muscle development in mice, was found as an inhibitory regulator of Notch signaling. Therefore, we investigated the metabolic effect of exogenous DLK1 in vitro and in vivo. SUBJECTS/METHODS: A soluble DLK1 peptide was generated with fusion between a human Fc fragment and extracellular domain of DLK1. Male db/db mice were randomly assigned to two groups: vehicle treated and DLK1-treated group (25 mg kg(-1), intraperitoneal injection, twice a week for 4 weeks). Primary mice hepatocytes and HepG2 cells were used for in vitro experiments. RESULTS: After 4 weeks of DLK1 administration, hepatic triglyceride content and lipid droplets in liver tissues, as well as serum levels of liver enzymes, were markedly decreased in db/db mice. DLK1 treatment induced phosphorylation of AMPK and ACC and suppressed nuclear expression of SREBP-1c in the mouse liver or hepatocytes, indicating regulation of fatty acid oxidation and synthesis pathways. Furthermore, DLK1-treated mice showed significantly lower levels of fasting and random glucose, with improved glucose and insulin tolerance compared with the vehicle-treated group. Macrophage infiltration and proinflammatory cytokine levels in the epididymal fat were decreased in DLK1-treated db/db mice. Moreover, DLK1 suppressed glucose production from hepatocytes, which was blocked after co-administration of an AMPK inhibitor, compound C. DLK1-treated hepatocytes and mouse liver tissues showed lower PEPCK and G6Pase expression. DLK1 triggered AKT phosphorylation followed by cytosolic translocation of FOXO1 from the nucleus in hepatocytes. CONCLUSIONS: The present study demonstrated that exogenous administration of DLK1 reduced hepatic steatosis and hyperglycemia via AMPK activation in the liver. This result suggests that DLK1 may be a novel therapeutic approach for treating NAFLD and diabetes.

Cell cycle-dependent Cdc25C phosphatase determines cell survival by regulating apoptosis signal-regulating kinase 1.

Cdc25C (cell division cycle 25C) phosphatase triggers entry into mitosis in the cell cycle by dephosphorylating cyclin B-Cdk1. Cdc25C exhibits basal phosphatase activity during interphase and then becomes activated at the G2/M transition after hyperphosphorylation on multiple sites and dissociation from 14-3-3. Although the role of Cdc25C in mitosis has been extensively studied, its function in interphase remains elusive. Here, we show that during interphase Cdc25C suppresses apoptosis signal-regulating kinase 1 (ASK1), a member of mitogen-activated protein (MAP) kinase kinase kinase family that mediates apoptosis. Cdc25C phosphatase dephosphorylates phospho-Thr-838 in the activation loop of ASK1 in vitro and in interphase cells. In addition, knockdown of Cdc25C increases the activity of ASK1 and ASK1 downstream targets in interphase cells, and overexpression of Cdc25C inhibits ASK1-mediated apoptosis, suggesting that Cdc25C binds to and negatively regulates ASK1. Furthermore, we showed that ASK1 kinase activity correlated with Cdc25C activation during mitotic arrest and enhanced ASK1 activity in the presence of activated Cdc25C resulted from the weak association between ASK1 and Cdc25C. In cells synchronized in mitosis following nocodazole treatment, phosphorylation of Thr-838 in the activation loop of ASK1 increased. Compared with hypophosphorylated Cdc25C, which exhibited basal phosphatase activity in interphase, hyperphosphorylated Cdc25C exhibited enhanced phosphatase activity during mitotic arrest, but had significantly reduced affinity to ASK1, suggesting that enhanced ASK1 activity in mitosis was due to reduced binding of hyperphosphorylated Cdc25C to ASK1. These findings suggest that Cdc25C negatively regulates proapoptotic ASK1 in a cell cycle-dependent manner and may play a role in G2/M checkpoint-mediated apoptosis.

Characteristics of nonbalding scalp zones of androgenetic alopecia in East Asians.

BACKGROUND: Hair is known to persist on the occipital and part of the temporal scalp in patients with androgenetic alopecia (AGA), but no quantified data about the follicular changes in such areas exist. AIM: To evaluate the hair characteristics in nonbalding scalp areas in East Asian patients with AGA. METHODS: In total, 265 participants [211 patients with AGA and 50 healthy controls (HCs)] were enrolled. The patients were divided by the Basic and Specific (BASP) classification [four basic types (L, M, C, and U) and two special types (V and F)], and the hair in the occipital region and two sites of the temporal region were analysed by computer-assisted phototrichography. Hair density, hair width, number of each follicular unit, ratio of single to compound hairs and ratio of terminal to vellus hairs were examined. RESULTS: In the temporal region, a statistically significant (P < 0.05) decrease in hair density was observed in patients with C, U or F subtypes, and a significant (P < 0.05) decrease in hair thickness was observed in patients with the U subtype compared with HCs. In the mastoid and occipital areas, both hair density and hair thickness was significantly (P < 0.05) decreased in patients with the U subtype compared with HCs. Within each classification, hairs became generally thinner as the hair loss progressed. CONCLUSIONS: Hair density and hair thickness of known nonbalding scalp regions showed some differences depending on the severity and the BASP subtypes in East Asian people with male pattern baldness.

Use of permanent marker to deposit a protection layer against FIB damage in TEM specimen preparation.

Permanent marker deposition (PMD), which creates permanent writing on an object with a permanent marker, was investigated as a method to deposit a protection layer against focused ion beam damage. PMD is a simple, fast and cheap process. Further, PMD is excellent in filling in narrow and deep trenches, enabling damage-free observation of high aspect ratio structures with atomic resolution in transmission electron microscopy (TEM). The microstructure, composition, gap filling ability and planarization of the PMD layer were studied using dual beam focused ion beam, transmission electron microscopy, energy dispersive X-ray spectroscopy and electron energy loss spectroscopy. It was found that a PMD layer is basically an amorphous carbon structure, and that such a layer should be at least 65 nm thick to protect a surface against 30 keV focused ion beam damage. We suggest that such a PMD layer can be an excellent protection layer to maintain a pristine sample structure against focused ion beam damage during transmission electron microscopy specimen preparation.

Rising youth suicide and the changing cultural context in South Korea.

BACKGROUND: South Korean society faces a serious challenge in the increasing rates of youth suicidal behavior. There is a need both to gain a better understanding of the causes of this behavior and to develop strategies for responding to this critical public health issue. AIMS: This article analyzes how psychological, sociopsychological, and subcultural factors influence suicidal proneness among Korean youth as well as makes suggestions for developing social policies that could reduce Korean youth suicidal behaviors. METHOD: Correlation and multivariate regression analyses on suicide proneness and depression were employed using a sample of 172 South Korean youths (aged 18-24) selected from the 2009 General Social Survey collected through face-to-face interviews. RESULTS: Young people's suicidal proneness is associated with depression, a tolerant attitude toward suicide, strained family relations, living in rural areas, being female, and being closely related to survivors of suicide or potential suicides. CONCLUSION: The findings from this study reveal the significance of social and cultural factors as influences on recent youth suicidal behavior in Korea. The analysis suggests that the underlying risk factors of suicidal behavior are embedded in the changing social and cultural context of Korean society. Thus, suicide prevention efforts should involve more than merely treating any underlying psychiatric disorders.

Identification of a pivotal endocytosis motif in c-Met and selective modulation of HGF-dependent aggressiveness of cancer using the 16-mer endocytic peptide.

Since c-Met has an important role in the development of cancer, it is considered as an attractive target for cancer therapy. Although molecular mechanisms for oncogenic property of c-Met have been actively investigated, regulatory elements for c-Met endocytosis and its effect on c-Met signaling remain unclear. In this study, we identified a pivotal endocytic motif in c-Met and tested it for selective modulation of HGF-induced c-Met response. Using various chimeric constructs with the cytoplasmic tail of c-Met, we were able to demonstrate that a dileucine motif located in the C-terminus of c-Met acts to regulate its endocytosis. Synthetic peptide Ant-3S, consisting of antennapedia-derived protein transduction domain (designated as Ant) and c-Met-derived 16 amino-acids (designated as 3S, spanning amino-acids 1378 to 1393), rapidly moved into cancer cells and disrupted c-Met trafficking. Importantly, an extension of c-Met retention time on the membrane by Ant-3S peptide significantly decreased phosphorylation-dependent c-Met signal transduction. Additionally, the peptide effectively inhibited HGF-induced cell growth, scattering and migration. The underlying molecular mechanism for these observations has been investigated and revealed that the dileucine motif interacts with endocytic machinery, including adaptin ß and caveolin-1, for sustained and enhanced signal transduction. Finally, Ant-3S peptide specifically blocked internalization of interleukin-2 receptor α-subunit/3S chimeric protein, but not the other receptors, including Glut4, Glut8 and transferrin receptor. Such results indicate the presence of a selective endocytic assembly for c-Met. It also suggests a potential for c-Met-specific anti-cancer therapy using the identified endocytic motif in this study.

Rural and urban suicide in South Korea.

Suicide rates in 2005 in South Korea were higher in rural areas than in urban areas. Those in rural areas more often used pesticides and chemicals as a method for suicide, and there was a greater proportion of men and the elderly, both groups at higher risk for suicide in South Korea. These three factors may account for the high rural suicide rate in South Korea.

Towards a reassessment of the role of divorce in suicide outcomes: evidence from five Pacific Rim populations.

The connection between divorce and suicide risk in Asia is unclear. To understand the contribution of cultural transitions to suicide among the divorced, we compare age- and sex-specific suicide rates among divorced men and women from five Pacific Rim populations: Hong Kong, Taiwan, Japan, South Korea and the state of Victoria in Australia. On a cultural spectrum, we consider Hong Kong and Taiwan to lie between the more individualistic Australian culture and the more collectivistic Japanese and Korean cultures. Coefficients of aggravation (COA) are also compared. Suicide rates were found to be higher among the divorced than among other marital status groups in all five populations, but this difference was small in Victoria. The effect of divorce was significantly greater for men than for women only in Japan and South Korea. In the other populations, divorced men and women were at equal risk. Age trends in suicide rates for the divorced groups differed across populations. The COAs for the divorced group aged 40 or younger in the East Asian populations were higher than the COAs for older divorced groups, though this was not the case in the Victorian population. Suicide patterns among the divorced in the East Asian populations can be understood in terms of the legacy of Confucian traditions. Gender differences in Japan and South Korea may reflect either gender inequality (male dominance in formal interactions and emotional dependence in domestic life within a deteriorating Confucian family support system) or unique socio-cultural factors among married women. Divorced East Asian groups aged 40 or younger may be at a higher risk of suicide due to individual-level cultural ambivalence combined with a desire for systemic-level emotional interdependence. Social welfare regimes in the four East Asian populations need to fill the vacancy left by retreating traditional family systems. Research implications are discussed.

A critical step for JNK activation: isomerization by the prolyl isomerase Pin1.

c-Jun N-terminal kinase (JNK) is activated by dual phosphorylation of both threonine and tyrosine residues in the phosphorylation loop of the protein in response to several stress factors. However, the precise molecular mechanisms for activation after phosphorylation remain elusive. Here we show that Pin1, a peptidyl-prolyl isomerase, has a key role in the JNK1 activation process by modulating a phospho-Thr-Pro motif in the phosphorylation loop. Pin1 overexpression in human breast cancer cell lines correlates with increased JNK activity. In addition, small interfering RNA (siRNA) analyses showed that knockdown of Pin1 in a human breast cancer cell line decreased JNK1 activity. Pin1 associates with JNK1, and then catalyzes prolyl isomerization of the phospho-Thr-Pro motif in JNK1 from trans- to cis-conformation. Furthermore, Pin1 enhances the association of JNK1 with its substrates. As a result, Pin1(-/-) cells are defective in JNK activation and resistant to oxidative stress. These results provide novel insights that, following stress-induced phosphorylation of Thr in the Thr-Pro motif of JNK1, JNK1 associates with Pin1 and undergoes conformational changes to promote the binding of JNK1 to its substrates, resulting in cellular responses from extracellular signals.

Suicide among foreign residents of Japan.

The suicide rate of Koreans living in Japan is twice as high as that of Koreans in South Korea. Reasons for this high suicide rate are discussed, including effects of economic crises and discrimination.

Martyrs' last letters: are they the same as suicide notes?

Of the 800,000 suicides worldwide every year, a small number fall under Emile Durkheim's term of altruistic suicides. Study on martyrdom has been limited. There has to date, for example, been no systematic empirical study of martyr letters. We examined 33 letters of Korean self-immolators, compared with 33 suicide notes of a matched sample of more common suicides. An analysis of intrapsychic factors (suicide as unbearable pain, psychopathology) and interpersonal factors (suicide as murderous impulses and need to escape) revealed that, although one can use the same psychological characteristics or dynamics to understand the deaths, the state of mind of martyrs is more extreme, such that the pain is reported to be even more unbearable. Yet, there are differences, such as there was no ambivalence in the altruistic notes. It is concluded that intrapsychic and interpersonal characteristics are central in understanding martyrs, probably equal to community or societal factors. More forensic study is, however, warranted.

Limb lengthening with a submuscular locking plate.

Ten patients, who were unsuitable for limb lengthening over an intramedullary nail, underwent lengthening with a submuscular locking plate. Their mean age at operation was 18.5 years (11 to 40). After fixing a locking plate submuscularly on the proximal segment, an external fixator was applied to lengthen the bone after corticotomy. Lengthening was at 1 mm/day and on reaching the target length, three or four screws were placed in the plate in the distal segment and the external fixator was removed. All patients achieved the pre-operative target length at a mean of 4.0 cm (3.2 to 5.5). The mean duration of external fixation was 61.6 days (45 to 113) and the mean external fixation index was 15.1 days/cm (13.2 to 20.5), which was less than one-third of the mean healing index (48 days/cm (41.3 to 55). There were only minor complications. Lengthening with a submuscular locking plate can successfully permit early removal of the fixator with fewer complications and is a useful alternative in children or when nailing is difficult.

Far upstream element-binding protein-1, a novel caspase substrate, acts as a cross-talker between apoptosis and the c-myc oncogene.

Far upstream element-binding protein-1 (FBP-1) binds to an upstream element of the c-myc promoter and regulates the c-myc mRNA level. Earlier, FBP-1 was identified as a candidate substrate of caspase-7. Here, we report that FBP-1 is cleaved by executor caspases, both in vitro and during apoptosis. Cleavage occurs at the caspase consensus site (DQPD(74)) located within the classical bipartite nuclear localization signal sequence. In cells subjected to apoptotic stimuli, the caspase-mediated cleavage of FBP-1 leads to its decreased presence in the nucleus, concomitant with the marked downregulation of c-Myc and its various target proteins. By contrast, cells transfected with a non-cleavable mutant of FBP-1 (D74A) maintain higher levels of c-Myc and are protected from apoptosis. On the basis of these results, we suggest that the oncogenic potential of c-Myc is 'switched off' after apoptosis induction as a consequence of the caspase-mediated cleavage of FBP-1.