Association Between Community Contextual Factors and Stigma of Mental Illness in South Korea: a Multilevel Analysis.

This study examined the association of subjective and objective community contextual factors with stigma of mental illness in a sample of users of community mental health services centers in South Korea. Five hundred thirty-two persons with MI were surveyed on perceived stigma and experienced stigma, and on two subjective measures of community characteristics-perceived disorder and perceived collective efficacy of their neighborhood. Objective community indicators at the neighborhood level were collected from a government administrative data base. Multilevel statistical analysis was conducted to identify the effects of individual-level characteristics and community-level objective indicators on stigma. Perceived neighborhood disorder was associated with both perceived stigma and experienced stigma. Perceived collective efficacy was associated with perceived stigma but not experienced stigma. The proportion of persons with disabilities in the neighborhood, an objective community indicator, was associated with experienced stigma. Mental health practitioners and policy planners need to examine the relevance of neighborhood characteristics in the design of policy and practice interventions in order to enhance the social inclusion of persons with MI.

Amyloid Oligomers and Mature Fibrils Prepared from an Innocuous Protein Cause Diverging Cellular Death Mechanisms.

Despite significant advances, the molecular identity of the cytotoxic species populated during in vivo amyloid formation crucial for the understanding of neurodegenerative disorders is yet to be revealed. In this study lysozyme prefibrillar oligomers and fibrils in both mature and sonicated states have been isolated through an optimized ultrafiltration/ultracentrifugation method and characterized with various optical spectroscopic techniques, atomic force microscopy, and transmission electron microscopy. We examined their level and mode of toxicity on rat pheochromocytoma (PC12) cells in both differentiated and undifferentiated states. We find that oligomers and fibrils display cytotoxic capabilities toward cultured cells in vitro, with oligomers producing elevated levels of cellular injury toward undifferentiated PC12 cells (PC12(undiff)). Furthermore, dual flow cytometry staining experiments demonstrate that the oligomers and mature fibrils induce divergent cellular death pathways (apoptosis and secondary necrosis, respectively) in these PC12 cells. We have also shown that oligomers but not sonicated mature fibrils inhibit hippocampal long term potentiation, a form of synaptic plasticity implicated in learning and memory, in vivo. We conclude that our in vitro and in vivo findings confer a level of resistance toward amyloid fibrils, and that the PC 12-based comparative cytotoxicity assay can provide insights into toxicity differences between differently aggregated protein species.

Sources of social support and community integration among persons with serious mental illnesses in Korea.

BACKGROUND: Community integration is an important component of recovery for persons with serious mental illnesses (SMI). However, persons with SMI often experience barriers in using community resources, participating in community activities, and developing interactions with neighbors and other community members. AIMS: This study examines the association between different sources of social support, including family, friends and mental health services providers, and three dimensions of community integration. METHOD: A sample of 399 persons with SMI was interviewed from community-based mental health service agencies in South Korea. RESULTS: Family support and friendship support positively influenced all three aspects of community integration. More support from mental health professionals was associated with increased perceived accessibility to community resources but decreased involvement in community activities. CONCLUSION: Recommendations are made in supporting the role of natural networks and in advocating for a consumer-centered approach to service delivery.

Electrostatic interactions play an essential role in the binding of oleic acid with α-lactalbumin in the HAMLET-like complex: a study using charge-specific chemical modifications.

Human α-lactalbumin made lethal to tumor cells (HAMLET) and its analogs are partially unfolded protein-oleic acid (OA) complexes that exhibit selective tumoricidal activity normally absent in the native protein itself. To understand the nature of the interaction between protein and OA moieties, charge-specific chemical modifications of lysine side chains involving citraconylation, acetylation, and guanidination were employed and the biophysical and biological properties were probed. Upon converting the original positively-charged lysine residues to negatively-charged citraconyl or neutral acetyl groups, the binding of OA to protein was eliminated, as were any cytotoxic activities towards osteosarcoma cells. Retention of the positive charges by converting lysine residues to homoarginine groups (guanidination); however, yielded unchanged binding of OA to protein and identical tumoricidal activity to that displayed by the wild-type α-lactalbumin-oleic acid complex. With the addition of OA, the wild-type and guanidinated α-lactalbumin proteins underwent substantial conformational changes, such as partial unfolding, loss of tertiary structure, but retention of secondary structure. In contrast, no significant conformational changes were observed in the citraconylated and acetylated α-lactalbumins, most likely because of the absence of OA binding. These results suggest that electrostatic interactions between the positively-charged basic groups on α-lactalbumin and the negatively-charged carboxylate groups on OA molecules play an essential role in the binding of OA to α-lactalbumin and that these interactions appear to be as important as hydrophobic interactions.

Alternatively folded proteins with unexpected beneficial functions.

HAMLET (human α-lactalbumin made lethal to tumour cells) and its related partially unfolded protein-fatty acid complexes are novel biomolecular nanoparticles that possess relatively selective cytotoxic activities towards tumour cells. One of the key characteristics is the requirement for the protein to be partially unfolded, hence endowing native proteins with additional functions in the alternatively folded states. Beginning with the history of its discovery and development, the cellular targets that appear to be strongly correlated with tumour cell death are introduced in the present article.

The novel therapeutic potential of bovine α-lactalbumin made lethal to tumour cells (BALMET) and oleic acid in oral squamous cell carcinoma (OSCC).

BACKGROUND: Since the serendipitous discovery of bovine α-lactalbumin made lethal to tumour cells (BAMLET)/human α-lactalbumin made lethal to tumour cells there has been an increased interest in the ability of the two components, oleic acid and α-lactalbumin, to form anti-cancer complexes. Here we have investigated the in-vitro efficacy of the BAMLET complex in killing oral cancer (OC) cells, determined the active component of the complex and investigated possible biological mechanisms. MATERIALS AND METHODS: Two OC cell lines (±p53 mutation) and one dysplastic cell line were used as a model of progressive oral carcinogenesis. We performed cell viability assays with increasing BAMLET concentrations to determine the cytotoxic potential of the complex. We further analysed the individual components to determine their respective cytotoxicities. siRNA knockdown of p53 was used to determine its functional role in mediating sensitivity to BAMLET. Cell death mechanisms were investigated by flow cytometry, confocal microscopy and the lactate dehydrogenase assay. RESULTS: Our results show that BAMLET is cytotoxic to the OC and dysplastic cell lines in a time and dose-dependent manner. The cytotoxic component was found to be oleic acid, which, can induce cytotoxicity even when not in complex. Our results indicate that the mechanism of cytotoxicity occurs through multiple simultaneous events including cell cycle arrest, autophagy like processes with a minor involvement of necrosis. CONCLUSION: Deciphering the mechanism of cytotoxicity will aid treatment modalities for OC. This study highlights the potential of BAMLET as a novel therapeutic strategy in oral dysplastic and cancerous cells.

Correction to: Violence Victimization Among Adolescents from Culturally or Ethnically Diverse South Korean Families.

The original version of the article unfortunately contained a typo in corresponding author name. The corresponding author name is Gyungjoo Lee instead it was published incorrectly as Gyungoo Lee.

Violence Victimization Among Adolescents from Culturally or Ethnically Diverse South Korean Families.

This study compared the prevalence of violence victimization requiring hospital treatment among adolescents that are culturally or ethnically diverse and those that are South Korean living in South Korea. This study used a nationally representative data set of 63,376 adolescents obtained from the Korean Youth Risk Behavior Web-based Survey conducted in 2015 by the Korea Centers for Disease Control and Prevention. Hierarchical multivariable logistic regression was conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for violence victimization in each group of culturally diverse adolescents compared to that of adolescents with South Korean parents. The analysis showed that adolescents whose parents are both culturally or ethnically diverse had ORs of 18.64 (95% CI 11.28-30.81) for violent experience. To decrease the violent victimization of culturally diverse adolescents with a culturally or ethnically diverse parent, specific government policies and school strategies are needed.

Factors related to malnutrition in community-dwelling patients with schizophrenia.

PURPOSE: This study aims to identify demographic, clinical, and nutritional factors related to malnutrition in community-dwelling patients with schizophrenia. DESIGN AND METHODS: We used a descriptive cross-sectional design. Between June and July 2016, 188 community-dwelling patients with schizophrenia were included in this study. FINDINGS: Of the 188 participants, 4.3% were classified as malnourished, and 40.4% were at risk of malnutrition. Living status, body weight, and appetite were significant factors related to malnutrition in community-dwelling patients with schizophrenia. PRACTICE IMPLICATION: Assessment of nutritional status should be considered along with demographic and nutritional factors in community-dwelling patients with schizophrenia.

Peer support for persons with co-occurring disorders and community tenure: a survival analysis.

Individuals with co-occurring mental health and substance abuse diagnoses experience high rehospitalization rates. Consumer-delivered services are recognized as an important intervention for this population, but no studies have examined the extent to which such services are associated with enhanced community tenure and prevention of rehospitalizations. This longitudinal, comparison group study examines the effect of participation in The Friends Connection, a peer support program for individuals with co-occurring disorders, on 3-year rehospitalization patterns. Results from a survival analysis suggest that program participants have longer community tenure (i.e., periods of living in the community without rehospitalization) than a comparison group. Chi-square tests also indicate that significantly more people in the comparison group (73%) are rehospitalized in a 3-year period versus those in the Friends Connection group (62%). These results suggest that Friends Connection may facilitate community tenure and prevent rehospitalizations for a group that is at high-risk for rehospitalizations. The findings lend additional support of the potential effectiveness of peer support programs as part of a service delivery system that facilitates recovery of individuals with co-occurring disorders.

[The daily experiences of people with chronic schizophrenia].

PURPOSE: This research investigated the daily experiences of patients' lives to develop a formal theory that explains the lives of schizophrenic patients. METHOD: A grounded theory method(Strauss & Corbin, 1998) guided the data collection and analysis. Thirteen patients who were diagnosed with schizophrenia in regional communities participated. RESULT: The experiences of chronic schizophrenic patients are defined as "escaping from a fallen mine" comparing their suffering to that of entrapped miners trying to free themselves from a collapsed mine tunnel with much difficulty and without hope. In observing participant's time lines of having lived with chronic schizophrenia, it advances with "surrender", "collapse", "reaching out", "rising", "preparing to spring up", and "starting anew". CONCLUSION: The results of this study indicate that the experience of a chronic schizophrenic patient is like that of a miner caught under a fallen mine channel, who, without external help cannot escape the depths of the mine, but at the same time must have conviction and hope of rescue and avert fear to cooperate with outside help. The result indicates that family members, doctors and nurses as well as an institute's persistent and active support is most critical for the patient's adjustment to social life.

Outcomes of shelter use among homeless persons with serious mental illness.

OBJECTIVE: The purpose of this study was to examine the extent to which the use of case management services predicted public shelter use among homeless persons with serious mental illness after the termination of Access to Community Care and Effective Services and Supports (ACCESS), a five-year outreach and case management program. METHOD: The sample consisted of 475 Philadelphia ACCESS program participants. Client-level interview data and case manager service delivery records that were collected during the ACCESS intervention period were linked with administrative data on public shelter use for the 12-month period after the ACCESS program was terminated. By using Cox's proportional hazards model, multivariate analyses were conducted to test how the characteristics of the participants and the intensity of case management service use affected the rate of the first entry into a public shelter. RESULTS: Homeless individuals with serious mental illness who were younger, were African American, had fewer years of schooling, and had longer shelter stays during the ACCESS intervention period were more likely to enter shelters in the 12 months after the ACCESS program ended. Although use of vocational and supportive services was associated with a lower probability of shelter entry, use of housing assistance was associated with a higher probability of shelter entry. CONCLUSIONS: The study found that the total number of case management service contacts was not significantly associated with residential outcomes. Rather, the use of specific types of services was important in reducing the use of homeless shelters. These findings suggest that case management efforts should focus on developing vocational and psychosocial rehabilitation services to reduce the risk of recurrent homelessness among persons with serious mental illness.

Long-term effectiveness of the ACCESS program in linking community mental health services to homeless persons with serious mental illness.

This study examined the long-term effectiveness of the ACCESS (Access to Community Care and Effective Services and Supports) project on service utilization and continuity of care among homeless persons with serious mental illness. A 3-year longitudinal analysis, using Medicaid claims data, tracked behavioral health service utilization among 146 Medicaid-eligible participants in the Pennsylvania ACCESS program. Utilization patterns of inpatient, outpatient, and emergency department services for psychiatric and substance abuse treatment were examined during the year prior to, during, and one year after the implementation of the ACCESS project. Use of psychiatric ambulatory care significantly increased among intervention participants and remained greater following ACCESS intervention. Better continuity of care following hospitalization was achieved during and after the intervention. The number of days spent hospitalized significantly decreased during the intervention. These results suggest that the ACCESS intervention was effective in linking hard-to-reach homeless persons with serious mental illness to the community mental health service system, and that this effect was maintained after termination of the intervention.

Synthesis, characterization, in vitro antimicrobial, and U2OS tumoricidal activities of different coumarin derivatives.

BACKGROUND: Coumarin and its derivatives are biologically very active. It was found that the enhanced activities are dependent on the coumarin nucleus. Biological significance of these compounds include anti-bacterial, anti-thrombotic and vasodilatory, anti-mutagenic, lipoxygenase and cyclooxygenase inhibition, scavenging of reactive oxygen species, and anti-tumourigenic. Our interest in medicinal chemistry of dicoumarol compounds have been developed by keeping in view the importance of coumarins along with its derivatives in medicinal chemistry. All the synthesized compounds were fully characterized by spectroscopic and analytical techniques and were screened for antimicrobial and U2OS bone cancer activities. RESULTS: 4-hydroxycoumarin was derivatized by condensing with different aldehydes yielding the dicoumarol and translactonized products. Elemental analyses, ESI(+,-) MS, 1H and 13C{1H}-NMR, infrared spectroscopy and conductance studies were used to characterize the synthesized compounds which revealed the dicoumarol and dichromone structures for the compounds. The compounds were screened against U2OS cancerous cells and pathogenic micro organisms. The compounds with intermolecular H-bonding were found more active revealing a possible relationship among hydrogen bonding, cytotoxicity and antimicrobial activities. CONCLUSION: Coumarin based drugs can be designed for the possible treatment of U2OS leukemia.

New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells.

BACKGROUND: Enormous interest had been paid to the coordination chemistry of alkali and alkaline metal ions because of their role inside body viz; their Li(+)/Na(+) exchange inside the cell lead to different diseases like neuropathy, hypertension, microalbuminuria, cardiac and vascular hypertrophy, obesity, and insulin resistance. It has been presumed that alkali metal ions (whether Na(+) or K(+)) coordinated to chelating ligands can cross the hydrophobic cell membrane easily and can function effectively for depolarizing the ion difference. This unique function was utilized for bacterial cell death in which K(+) has been found coordinated valinomycin (antibiotic). RESULTS: Distinct sodium adduct (1) with dicoumarol ligand, 4-Hydroxy-3-[(4-hydroxy-2-oxo-4a,8a-dihydro-2H-chromen-3-yl)-phenyl-methyl]-chromen-2-one (L) is isolated from the saturated solution of sodium methoxide. Single crystal X-ray diffraction studies of the adduct reveals that sodium is in the form of cation attached to a methoxide, methanol and a dicoumarol ligand where carbonyl functional groups of the coumarin derivative are acting as bridges. The sodium compound (1) is also characterized by IR, (1)H-NMR, and (13)C{(1)H}-NMR spectroscopic techniques. The composition is confirmed by elemental analysis. DFT study for 1 has been carried out using B3LYP/6-13G calculations which shown the theoretical confirmation of the various bond lengths and bond angles. Both the compounds were studied subsequently for the U2OS tumoricidal activity and it was found that L has LD50 value of 200 µM whereas the sodium analog cytotoxicity did not drop down below 60%. CONCLUSION: A sodium analogue (1) with medicinally important dicoumarol ligand (L) has been reported. The crystal structure and DFT study confirm the formation of cationic sodium compound with dicoumarol. The ligand was found more active than the sodium analog attributed to the instability of 1 in solution state. Coumarin compound with sodium was observed to be less cytotoxic than the ligand, its LD50 value never dropped below 60%.

alpha-Lactalbumin, engineered to be nonnative and inactive, kills tumor cells when in complex with oleic acid: a new biological function resulting from partial unfolding.

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex consisting of partially unfolded protein and fatty acid and was first identified in casein fractions of human breast milk. The complex can be produced from its pure components through a modified chromatographic procedure where preapplied oleic acid binds with partially unfolded alpha-lactalbumin on the stationary phase in situ. Because native alpha-lactalbumin itself cannot trigger cell death, HAMLET's remarkable tumor-selective cytotoxicity has been strongly correlated with the conformational change of the protein upon forming the complex, but whether a recovery to the native state subsequently occurs upon entering the tumor cell is yet unclear. To this end, we utilize a recombinant variant of human alpha-lactalbumin in which all eight cysteine residues are substituted for alanines (rHLA(all-Ala)), rendering the protein nonnative and biologically inactive under all conditions. The HAMLET analogue formed from the complex of rHLA(all-Ala) and oleic acid (rHLA(all-Ala)-OA) exhibited equivalent strong tumoricidal activity against lymphoma and carcinoma cell lines and was shown to accumulate within the nuclei of tumor cells, thus reproducing the cellular trafficking pattern of HAMLET. In contrast, the fatty acid-free rHLA(all-Ala) protein associated with the tumor cell surface but was not internalized and lacked any cytotoxic activity. Structurally, whereas HAMLET exhibited some residual native character in terms of NMR chemical shift dispersion, rHLA(all-Ala)-OA showed significant differences to HAMLET and, in fact, was found to be devoid of any tertiary packing. The results identify alpha-lactalbumin as a protein with strikingly different functions in the native and partially unfolded states. We posit that partial unfolding offers another significant route of functional diversification for proteins within the cell.

Inhibition of HIV-1 reverse transcriptase and protease by phlorotannins from the brown alga Ecklonia cava.

The bioassay-directed isolation of a marine brown alga, Ecklonia cava, afforded four phlorotannin derivatives, eckol (1), 8,8'-bieckol (2), 8,4"'-dieckol (3), and phlorofucofuroeckol A (4). Among these compounds, 2 and 3 exhibited an inhibitory effect on human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease. Specifically, they inhibited the RT more potently than the protease. The inhibitory activity of compound 2 (IC(50), 0.51 microM) against HIV-1 RT was comparable to that of nevirapine (IC(50), 0.28 microM), a reference compound. An enzyme kinetic assay showed that this compound inhibited the RNA-dependent DNA synthesis activity of HIV-1 RT noncompetitively against dUTP/dTTP with a K(i) value of 0.78 microM. With respect to the homopolymeric template/primer, (rA)n(dT)15, 8,8'-bieckol (2) displayed an uncompetitive type of inhibition (K(i), 0.23 microM).