We investigated the associations between negative life events, social support, depressive and hostile symptoms, and suicide risk according to gender in multinational Asian patients with major depressive disorder (MDD). A total of 547 outpatients with MDD (352 women and 195 men, mean age of 39.58±13.21 years) were recruited in China, South Korea, Malaysia, Singapore, Thailand, and Taiwan. All patients were assessed with the Mini-International Neuropsychiatric Interview, the Montgomery-Asberg Depression Rating Scale, the Symptoms Checklist 90-Revised, the Multidimensional Scale of Perceived Social Support, and the List of Threatening Experiences. Negative life events, social support, depressive symptoms, and hostility were all significantly associated with suicidality in female MDD patients. However, only depressive symptoms and hostility were significantly associated with suicidality in male patients. Depression severity and hostility only partially mediated the association of negative life events and poor social support with suicidality in female patients. In contrast, hostility fully mediated the association of negative life events and poor social support with suicidality in male patients. Our results highlight the need of in-depth assessment of suicide risk for depressed female patients who report a number of negative life events and poor social supports, even if they do not show severe psychopathology.

Several studies have linked teachers' personality characteristics and sense of efficacy to stress. However, investigating the relationship between these three constructs in this context was limited. This study aims to investigate the relationship between personality, sense of efficacy and perceived stress among Korean teachers. A total of 137 teachers working in elementary, middle, and high schools located in Seoul, South Korea were recruited for the study. The participants were administered Temperament and Character Inventory, Teacher's Sense of Efficacy Scale (TSES), and Perceived Stress Scale. The TSES was negatively correlated with harm avoidance and positively correlated with persistence, self-directedness, cooperativeness, and self-transcendence. Perceived stress was positively correlated with harm avoidance and negatively correlated with persistence and self-directedness. The path analysis showed that harm avoidance directly predicted perceived stress (β=0.37, 95% CI=0.21-0.53, p=0.002), and self-directedness and persistence predicted one's sense of efficacy (β=0.18, 95% CI=0.01-0.39 and β=0.31, 95% CI=0.10-0.47), which predicted perceived stress (β=-0.21, 95% CI=-0.39 to -0.02). The results of the present study indicate that harm avoidance might be associated with stress-proneness, while persistence, self-directedness, and sense of efficacy might act as protective resources against stress in Korean teachers.

Plasmodium falciparum malaria remains one of the world's foremost health problems, primarily in highly endemic regions such as Sub-Saharan Africa, where it is responsible for substantial morbidity, mortality and economic losses. Malaria is a significant cause of severe disease and death in pregnant women and newborns, with pathogenesis being associated with expression of a unique variant of the multidomain Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) called VAR2CSA. Here, we characterize the polymorphism of the DBL3X domain of VAR2CSA and identify regions under selective pressure among placental parasites from women living in endemic western Kenya. In addition to significant levels of polymorphism, our analysis reveals evidence for diversification through intra-segmental recombination and novel mutations that likely contributed to the high number of unique VAR2CSA sequence types identified in this study. Interestingly, we also identified a number of critical residues that may be implicated in immune evasion through switching (or toggling) to alternative amino acids, including an arginine residue within the predicted binding pocket in subdomain III, which was previously implicated in binding to placental CSA. Overall, these findings are important for understanding parasite diversity in pregnant women and will be useful for identifying epitopes and variants of DBL3X to be included in a vaccine against placental malaria.

The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014-2018. Of the 2,865 samples successfully sequenced before treatment (day of enrollment) and on the day of treatment failure, 29 (1.0%) samples contained 11 unique nonsynonymous mutations and 83 (2.9%) samples contained 27 unique synonymous mutations. Two samples from Kenya contained the S522C mutation, which has been associated with delayed parasite clearance; however, no samples contained validated or candidate artemisinin-resistance mutations.

The hippocampus, which engages in the process of consolidating long-term memories and learning, shows active development during childhood and adolescence. The hippocampus also functionally influences attention. Based on the influence of hippocampal function on attention, it was expected that the volume of the hippocampus would be associated with the difference in attention during childhood and adolescence, in which the brain develops actively. Thus, this study examined the association between hippocampal volume and attention metrics measured by the continuous performance test (CPT) in 115 children and adolescents (mean age = 12.43 ± 3.0, 63 male and 52 female). In association studies with both auditory and visual attention, we found that the bilateral hippocampal volumes showed negative relationships with auditory omission errors. A smaller volume of the left hippocampus also led to a longer auditory response time. However, visual attention did not show any significant relationship with the hippocampal volume. These findings were consistent even after adjusting for the effects of the related covariates (e.g., age, insomnia, and depression). Taken together, this study suggested that the increase in hippocampal volume during childhood and adolescence was associated significantly with better auditory attention.

Screening of the antiviral and virucidal activities of ethanol extracts from plants endemic to the Republic of Korea revealed the inhibitory activity of a 70% ethanol extract of the whole plant of A. pseudoglehnii (APE) against influenza virus infection. Two chlorophyll derivatives, ethyl pheophorbides a and b, isolated as active components of APE, exerted virucidal effects with no evident cytotoxicity. These compounds were effective only under conditions of direct incubation with the virus, and exerted no effects on the influenza A virus (IAV) surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Interestingly, virucidal activities of ethyl pheophorbides a and b were observed against enveloped but not non-enveloped viruses, suggesting that these compounds act by affecting the integrity of the viral membrane and reducing infectivity.

Intracellular C-terminal cleavage of the amyloid precursor protein (APP) is elevated in the brains of Alzheimer's disease (AD) patients and produces a peptide labeled APP-C31 that is suspected to be involved in the pathology of AD. But details about the role of APP-C31 in the development of the disease are not known. Here, this work reports that APP-C31 directly interacts with the N-terminal and self-recognition regions of amyloid-β40 (Aβ40 ) to form transient adducts, which facilitates the aggregation of both metal-free and metal-bound Aβ40 peptides and aggravates their toxicity. Specifically, APP-C31 increases the perinuclear and intranuclear generation of large Aβ40 deposits and, consequently, damages the nucleus leading to apoptosis. The Aβ40 -induced degeneration of neurites and inflammation are also intensified by APP-C31 in human neurons and murine brains. This study demonstrates a new function of APP-C31 as an intracellular promoter of Aβ40 amyloidogenesis in both metal-free and metal-present environments, and may offer an interesting alternative target for developing treatments for AD that have not been considered thus far.

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Few studies have sought to identify, in a regionally unbiased way, the precise cortical and subcortical regions that are affected by white matter abnormalities in attention-deficit/hyperactivity disorder (ADHD). This study aimed to derive a comprehensive, whole-brain characterization of connectomic disturbances in ADHD.

Cyclospora cayetanensis is a human parasite transmitted via ingestion of contaminated food or water. Cases of C. cayetanensis infection acquired in the United States often go unexplained, partly because of the difficulties associated with epidemiologic investigations of such cases and the lack of genotyping methods. A Multilocus Sequence Typing (MLST) method for C. cayetanensis based on five microsatellite loci amplified by nested PCR was described in 2016. The MLST loci had high variability, but many specimens could not be assigned a type because of poor DNA sequencing quality at one or more loci. We analyzed Cyclospora-positive stool specimens collected during 1997-2016 from 54 patients, including 51 from the United States. We noted limited inter-specimen variability for one locus (CYC15) and the frequent occurrence of unreadable DNA sequences for two loci (CYC3 and CYC13). Overall, using the remaining two loci (CYC21 and CYC22), we detected 17 different concatenated sequence types. For four of five clusters of epidemiologically linked cases for which we had specimens from >1 case-patient, the specimens associated with the same cluster had the same type. However, we also noted the same type for specimens that were geographically and temporally unrelated, indicating poor discriminatory power. Furthermore, many specimens had what appeared to be a mixture of sequence types at locus CYC22. We conclude that it may be difficult to substantially improve the performance of the MLST method because of the nucleotide repeat features of the markers, along with the frequent occurrence of mixed genotypes in Cyclospora infections.

Plasmodium falciparum resistance to artemisinin has emerged in the Greater Mekong Subregion and now poses a threat to malaria control and prevention. Recent work has identified mutations in the kelch propeller domain of the P. falciparum K13 gene to be associated artemisinin resistance as defined by delayed parasite clearance and ex vivo ring stage survival assays. Species specific primers for the two most prevalent human malaria species, P. falciparum and P. vivax, were designed and tested on multiple parasite isolates including human, rodent, and non- humans primate Plasmodium species. The new protocol described here using the species specific primers only amplified their respective species, P. falciparum and P. vivax, and did not cross react with any of the other human malaria Plasmodium species. We provide an improved species specific PCR and sequencing protocol that could be effectively used in areas where both P. falciparum and P. vivax are circulating. To design this improved protocol, the kelch gene was analyzed and compared among different species of Plasmodium. The kelch propeller domain was found to be highly conserved across the mammalian Plasmodium species.

The recent emergence of artemisinin resistance in the Greater Mekong Subregion poses a major threat to the global effort to control malaria. Tracking the spread and evolution of artemisinin-resistant parasites is critical in aiding efforts to contain the spread of resistance. A total of 417 patient samples from the year 2007, collected during malaria surveillance studies across ten provinces in Thailand, were genotyped for the candidate Plasmodium falciparum molecular marker of artemisinin resistance K13. Parasite genotypes were examined for K13 propeller mutations associated with artemisinin resistance, signatures of positive selection, and for evidence of whether artemisinin-resistant alleles arose independently across Thailand. A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F). Notably, the R575K and S621F mutations have previously not been reported in Thailand. The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders. It appears these two haplotypes may have independent evolutionary origins. In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

The influence of childhood adversity on depression is modulated by genetic vulnerability. The apolipoprotein E ε4 (APOE-ε4) allele is a strong genetic risk factor for Alzheimer's disease (AD). Because late-life depressive symptoms could be a part of the preclinical course of AD, the APOE-ε4 allele may contribute to depression in old age.

Refusing to attend school is a serious problem that could lead to psychopathology. We aimed to: (1) prospectively observe the actual development of school refusal behavior according to a history of separation anxiety symptoms (SAS) and (2) explore factors for predicting school refusal behavior in children who were just beginning primary school. The participants were 277 children, aged 6-7 years, who were expected to enter primary school in 2 months. The parents were surveyed about the child׳s history of SAS and their behavior. The children were questioned about anxiety symptoms. The children were surveyed about whether school refusal behavior developed or not after they entered primary school. Of the 248 children who responded to the follow-up survey, 7.66% of children met the criteria for school refusal behavior during the 3 months after entering school. We found no significant differences in the occurrence of school refusal behavior according to the children׳s SAS history. Familial risk factors for school refusal behavior included low parental educational level and a working mother. School refusal behavior by first graders cannot be fully explained by the expression of SAS and could be implicated in a more complex psychopathology.

People with depression often suffer from comorbid, chronic physical diseases. Little is known about how demographic characteristics such as age and sex influence the prevalence of chronic physical diseases comorbid with depression. Therefore, this study aimed to explore the age and sex differences in the prevalence of diverse, chronic physical diseases comorbid with depression.

Based on the National Epidemiological Survey of Psychiatric Disorders in South Korea conducted in 2006, we examined the prevalence, clinical correlations, comorbidities, and suicidal tendencies of pathological gamblers in the community.

We examined a functional model of acquired capability for suicide, which was elaborated from the "Interpersonal-Psychological Theory of Suicide".

Cancer diagnosis is associated with an increased suicide risk, particularly within the first 1 year after diagnosis of cancer. Abnormal function of the hypothalamic-pituitary-adrenal axis has been implicated in the pathophysiology of depression and suicide. We examined genetic associations of the functional Bcl-1 polymorphism of (rs41423247) neuron-specific glucocorticoid receptor (NR3C1) gene, with death by suicide in cancer patients. Suicides occurring within a year of cancer diagnosis ('early suicide') were considered separately from those suicides during the second or subsequent year ('late suicide') after cancer diagnosis.

This study identified factors affecting changes in depression of 64 North Korean refugee youths (NKRYs) aged 13 to 23 years (40 female) using follow-up data over a three-year period. We collected intrapersonal factors (emotional regulation strategies, resilience, quality of life) and external factors (psychological and practical support, family adaptation, and cohesion) to understand the preventative and risk factors affecting changes in depression. The trend of depression symptoms significantly increased, and the proportion of people classified as depressed (cut-off score = 21) increased steadily from 45.3% to 59.4% in the third year. In addition, we conducted a panel regression analysis, which showed that individual internal factors had a statistically significant effect on changes in depression. Specifically, expressive suppression of emotions was shown to increase depression over time. Resilience and life satisfaction were significant factors reducing depression in this study. On the other hand, external factors were not significantly related to changes over time in depression of NKRYs. Interventions for NKRYs at risk of depression are necessary and should include ways to enhance resilience and life satisfaction, and foster ego strength by recognizing emotions and promoting healthy emotional expression.

Cyclospora cayetanensis is an intestinal parasite responsible for the diarrheal illness, cyclosporiasis. Molecular genotyping, using targeted amplicon sequencing, provides a complementary tool for outbreak investigations, especially when epidemiological data are insufficient for linking cases and identifying clusters. The goal of this study was to identify candidate genotyping markers using a novel workflow for detection of segregating single nucleotide polymorphisms (SNPs) in C. cayetanensis genomes. Four whole C. cayetanensis genomes were compared using this workflow and four candidate markers were selected for evaluation of their genotyping utility by PCR and Sanger sequencing. These four markers covered 13 SNPs and resolved parasites from 57 stool specimens, differentiating C. cayetanensis into 19 new unique genotypes.