Antisense-Mediated Transcript Knockdown Triggers Premature Transcription Termination.

Antisense oligonucleotides (ASOs) that trigger RNase-H-mediated cleavage are commonly used to knock down transcripts for experimental or therapeutic purposes. In particular, ASOs are frequently used to functionally interrogate long noncoding RNAs (lncRNAs) and discriminate lncRNA loci that produce functional RNAs from those whose activity is attributable to the act of transcription. Transcription termination is triggered by cleavage of nascent transcripts, generally during polyadenylation, resulting in degradation of the residual RNA polymerase II (Pol II)-associated RNA by XRN2 and dissociation of elongating Pol II. Here, we show that ASOs act upon nascent transcripts and, consequently, induce premature transcription termination downstream of the cleavage site in an XRN2-dependent manner. Targeting the transcript 3' end with ASOs, however, allows transcript knockdown while preserving Pol II association with the gene body. These results demonstrate that the effects of ASOs on transcription must be considered for appropriate experimental and therapeutic use of these reagents.

Depression and posttraumatic stress disorder in adolescents with nonsuicidal self-injury: comparisons of the psychological correlates and suicidal presentations across diagnostic subgroups.

BACKGROUND: Nonsuicidal self-injury (NSSI) combined with suicide ideation increases the risk of suicidal behaviors. Depression and posttraumatic stress disorder (PTSD) are comorbidities of NSSI compounding this relationship. The present study compared diagnostic subgroups of NSSI based on current depression and PTSD on psychological correlates (i.e., vulnerabilities and impairment) and suicidal presentations (i.e., suicidal cognitions and behaviors) in a psychiatric sample of adolescents. METHODS: Eighty-seven adolescents meeting DSM-5 criteria for NSSI and 104 age-range-matched nonclinical controls (NC) participated. Participants completed self-report measures on psychological vulnerabilities and impairment (e.g., emotion regulation difficulties, negative cognitions). Adolescents with NSSI also completed clinical interviews on psychiatric diagnoses and a recent self-injurious behavior (SIB). Scores on the psychological correlates of NSSI were compared between adolescents with NSSI and NC, and across three diagnostic subgroups of NSSI (A: NSSI+/depression-/PTSD-, n = 14; B: NSSI+/depression+/PTSD-, n = 57; C: NSSI+/depression+/PTSD+, n = 14). Differences between NSSI diagnostic subgroups were tested on the motives for SIB and accompanying suicidal presentations (e.g., desire, intent, motive, lethality). RESULTS: Common comorbidities of NSSI included depression, panic disorder, generalized anxiety disorder, and PTSD. The NSSI subgroup classification was significantly associated with panic disorder, which was controlled for in the subsequent group comparisons. Overall, adolescents who engage in NSSI with vs. without depression reported more psychological vulnerabilities and impairment and a greater degree of suicidal thoughts/desire in SIB (i.e., groups B, C >A), which remained significant after controlling for panic disorder. An increased odds of the suicidal motive for SIB was found in adolescents with all three conditions (i.e., group C: NSSI+/depression+/PTSD+) compared to those with NSSI but neither depression nor PTSD (i.e., group A: NSSI+/depression-/PTSD-); however, this was not significant after controlling for panic disorder. CONCLUSIONS: Psychological underpinnings of adolescent NSSI in clinical contexts may be largely associated with concurrent depression. Suicidal motives in adolescents who engage in NSSI in the presence of depression and PTSD may be confounded by the co-occurrence of panic disorder. This study warrants the importance of attending to the comorbid depression with NSSI in adolescents as it is related to an increase in suicidal desire accompanying SIB.

Investigation of the Subtypes of Nonsuicidal Self-Injury Based on the Forms of Self-Harm Behavior: Examining Validity and Utility via Latent Class Analysis and Ecological Momentary Assessment.

BACKGROUND: This study aimed to empirically derive and validate subtypes of nonsuicidal self-injury (NSSI) based on the forms of self-harm behavior. METHODS: Sixty young adults who exhibited repetitive NSSI completed a clinical interview and baseline measures, followed by a two-week ecological momentary assessment (EMA). A latent class analysis was administered to identify NSSI subtypes based on the forms of self-harm behavior. The subtypes were then compared to baseline clinical and EMA variables, including emotions and urges to self-harm. RESULTS: The best-fitting model supported two subtypes: 1) substance abuse and suicide attempt subtype and 2) cutting and scratching subtype. The substance abuse and suicide attempt subtype reported a higher rate of engaging in lifetime suicide plans and suicide attempts and a higher number of lifetime suicide attempts. They also showed significantly higher severity of self-harm behavior, borderline personality traits, anger, posttraumatic symptoms, and difficulties in emotion regulation when compared to the cutting and scratching subtype. However, there was no inter-subtype difference in self-esteem. In the EMA data, anger toward others, feeling of rejection, loneliness, and helplessness were significantly high in the substance abuse and suicide attempt subtype. The variability of anger toward others was also higher in this subtype compared to the cutting and scratching subtype. Finally, in the two-week research period, the substance abuse and suicide attempt group showed a higher rate of reported urges to self-harm with or without suicidal intent. CONCLUSION: Findings support the validity of the subtypes based on the forms of self-harm behavior, suggesting the clinical utility of addressing heterogeneity within individuals exhibiting self-harm for assessment and treatment.

Outbred Mice with Streptozotocin-Induced Diabetes Show Sex Differences in Glucose Metabolism.

Outbred mice (ICR) with different genotypes and phenotypes have been reported to be more suitable for scientific testing than inbred mice because they are more similar to humans. To investigate whether the sex and genetic background of the mice are important factors in the development of hyperglycemia, we used ICR mice and divided them into male, female, and ovariectomized female (FOVX) groups and treated them with streptozotocin (STZ) for five consecutive days to induce diabetes. Our results show that fasting blood glucose and hemoglobin A1c (HbA1c) levels were significantly higher in diabetes-induced males (M-DM) and ovariectomized diabetes-induced females (FOVX-DM) than in diabetes-induced females (F-DM) at 3 and 6 weeks after STZ treatment. Furthermore, the M-DM group showed the most severe glucose tolerance, followed by the FOVX-DM and F-DM groups, suggesting that ovariectomy affects glucose tolerance in female mice. The size of pancreatic islets in the M-DM and FOVX-DM groups was significantly different from that of the F-DM group. The M-DM and FOVX-DM groups had pancreatic beta-cell dysfunction 6 weeks after STZ treatment. Urocortin 3 and somatostatin inhibited insulin secretion in the M-DM and FOVX-DM groups. Overall, our results suggest that glucose metabolism in mice is dependent on sex and/or genetic background.

Long-term adjuvant metronomic chemotherapy in a dog with recurrent maxillofacial osteosarcoma.

Osteosarcoma (OSA) is the most common malignant bone tumour in dogs; however, OSA of the maxilla is uncommon compared to appendicular OSA. Oral melanoma also commonly occurs in dogs with frequent distant metastasis. The role of adjuvant chemotherapy has been questioned in maxillary OSA and melanoma. A 17-year-old English Cocker Spaniel was referred with a growing mass on the right maxilla and a right lower lip mass. Osteosarcoma was diagnosed after partial maxillectomy, and the right lower lip mass was diagnosed as oral melanoma. Metronomic chemotherapy (MC) was performed, and the number of doses was tapered due to side effects at 5 weeks after initiation of MC. After 130 weeks of MC, chemotherapy was suspended due to kidney disease. After the suspension of chemotherapy, findings suggesting recurrence and metastasis were detected. The dog suddenly died 193 weeks after surgery, which was 8-14 times longer than the expected survival time. To the best of our knowledge, this is the first case report of successful long-term combination therapy, including surgery and MC, in a dog with maxillary OSA and lip melanoma. Our results show that the survival time can be greatly extended if MC is performed with proper management.

Allergenic characterization of Bomb m 4, a 30-kDa Bombyx mori lipoprotein 6 from silkworm pupa.

BACKGROUND: Silkworm pupa (SWP) food anaphylaxis has been described frequently in Asian countries. However, false-positive reactions by skin pricks and serum IgE (sIgE) tests to the extract complicate diagnosis, requiring identification of clinically relevant major allergens. OBJECTIVES: In this study, we characterized a novel SWP allergen, Bomb m 4, a 30-kDa lipoprotein, and evaluated its diagnostic sensitivity. METHODS: Bomb m 4 was identified by a proteomic analysis. This recombinant (r)Bomb m 4 was overexpressed in Escherichia coli, and the IgE reactivity by ELISA was compared with other reported allergenic proteins: Bomb m 1 (arginine kinase), 27-kDa glycoprotein, Bomb m 3 (tropomyosin) using the serum samples from 17 SWP allergic patients and 11 asymptomatic sensitized subjects. RESULTS: rBomb m 4-specific IgE was recognized by all 17 SWP allergic patients. The 27-kDa glycoprotein and Bomb m 1 sIgE were found in 35.3% and 0%, respectively, in the SWP allergic patients. ELISA sIgE reactivity increased significantly, when 4 M urea was added in serum samples. However, only 16% inhibition of sIgE reactivity to the whole SWP extract was exhibited by rBomb m 4, whereas more than 93% of self-inhibition of rBomb m 4 sIgE was obtained, possibly due to the low abundance of Bomb m 4 in the extract. Three linear epitopes (81-95, 191-205 and 224-238 residues) of rBomb m 4 were identified. These epitopes are shown to be released by pepsin digestion. Receiver operator characteristic (ROC) analysis showed the highest diagnostic value of Bomb m 4 followed by Bomb m 1, 27-kDa glycoprotein and Bomb m 3. CONCLUSION: Bomb m 4 is the major allergen of SWP allergic patients. It has cryptic epitopes which are exposed to IgE antibodies with digestive enzymes. This recombinant Bomb m 4 allergen permits exact diagnosis of SWP allergy.

Pak2 kinase promotes cellular senescence and organismal aging.

Cellular senescence defines an irreversible cell growth arrest state linked to loss of tissue function and aging in mammals. This transition from proliferation to senescence is typically characterized by increased expression of the cell-cycle inhibitor p16INK4a and formation of senescence-associated heterochromatin foci (SAHF). SAHF formation depends on HIRA-mediated nucleosome assembly of histone H3.3, which is regulated by the serine/threonine protein kinase Pak2. However, it is unknown if Pak2 contributes to cellular senescence. Here, we show that depletion of Pak2 delayed oncogene-induced senescence in IMR90 human fibroblasts and oxidative stress-induced senescence of mouse embryonic fibroblasts (MEFs), whereas overexpression of Pak2 accelerated senescence of IMR90 cells. Importantly, depletion of Pak2 in BubR1 progeroid mice attenuated the onset of aging-associated phenotypes and extended life span. Pak2 is required for expression of genes involved in cellular senescence and regulated the deposition of newly synthesized H3.3 onto chromatin in senescent cells. Together, our results demonstrate that Pak2 is an important regulator of cellular senescence and organismal aging, in part through the regulation of gene expression and H3.3 nucleosome assembly.

Factors Related to Anxiety and Depression Among Adolescents During COVID-19: A Web-Based Cross-Sectional Survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak and subsequent disease-containment measures (such as school closures) significantly affected the lives of adolescents. We evaluated the mental-health status and factors associated with anxiety and depression among South Korean adolescents. METHODS: A nationwide online survey was conducted to evaluate the mental-health status of South Korean adolescents during the COVID-19 pandemic. In total, 570 adolescents aged 13-18 years were surveyed between May 27 and June 11, 2021. The participants completed the Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9) to determine anxiety and depression symptoms, respectively. Stepwise logistic regression models were constructed to determine factors related to anxiety and depression. RESULTS: Among the study participants, 11.2% and 14.2% had anxiety and depression, respectively. The results suggested that several factors, such as the experience of COVID-19 infection and quarantine of oneself, a family member or an acquaintance, physical and mental health problems, and fear of one's local community being discriminated against as a COVID-19 area were related to anxiety and depression. CONCLUSION: The present study identified COVID-19-related factors associated with anxiety and depression among adolescents, and provides insights regarding potential interventions to improve the mental health of adolescents. To promote the mental health of adolescents during the COVID-19 pandemic, special attention should be paid to individuals with physical or mental-health problems, and efforts should be made to reduce the negative social and emotional impacts of infection-control measures.

Different outcomes of multiple sialadenitis involving the submandibular and zygomatic salivary glands in a Welsh Corgi dog.

A ten-year-old indoor, castrated male Cardigan Welsh Corgi (Canis familiaris) presented with the chief complaints of chronic vomiting, retching, hypersalivation, and bilateral submandibular masses for two months. The systemic examinations, including serum chemistry, radiography, ultrasonography, and fluoroscopy, were unremarkable. A fine-needle aspiration revealed bilateral submandibular sialadenitis. Broad-spectrum antibiotics with phenobarbital were prescribed to alleviate the ptyalism. Thereafter, the left submandibular glands were normalised, and the right submandibular glands decreased to half their size. Three weeks later, the animal had an emergency visit because of a sudden left exophthalmos. Computed tomography and magnetic resonance imaging revealed enlarged left zygomatic and right mandibular salivary glands. The affected glands were surgically removed; the histopathologic examination confirmed non-septic sialadenitis, and the patient was finally diagnosed with idiopathic sialadenitis. Vomiting continued after the gland removal and the dog required a gradual increase in the phenobarbital dosage and an additional antiepileptic drug (potassium bromide) to manage the symptoms. The patient died eight months later from an unknown cause. This case report of bilateral submandibular sialadenitis concurrent with unilateral zygomatic sialadenitis in a Welsh Corgi dog suggests that when multiple salivary glands are involved, the response to anti-epileptic drugs and the prognosis is poor compared to that involving a single salivary gland.

O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence.

The histone chaperone HIRA complex, consisting of histone cell cycle regulator (HIRA), Ubinuclein1 (UBN1), and calcineurin binding protein 1 (CABIN1), deposits histone variant H3.3 to genic regions and regulates gene expression in various cellular processes, including cellular senescence. How HIRA-mediated nucleosome assembly of H3.3-H4 is regulated remains not well understood. Here, we show that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of serine or threonine residues, interacts with UBN1, modifies HIRA, and promotes nucleosome assembly of H3.3. Depletion of OGT or expression of the HIRA S231A O-GlcNAcylation-deficient mutant compromises formation of the HIRA-H3.3 complex and H3.3 nucleosome assembly. Importantly, OGT depletion or expression of the HIRA S231A mutant delays premature cellular senescence in primary human fibroblasts, whereas overexpression of OGT accelerates senescence. Taken together, these results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence.

The effect of word imagery on priming effect under a preconscious condition: an fMRI study.

Semantic priming is affected by the degree of association and how readily a word is imagined. In the association effect, activity in the perisylvian structures including the bilateral inferior frontal gyrus, the left middle temporal gyrus, and the supramarginal gyrus was correlated. However, little is known about the brain regions related to the effect of imagery word under the preconscious condition. Forty word pairs for high (HA)-, low (LA)-, and nonassociation (NA), nonword (NW) conditions were presented. Each 40 association word pairs (HA and LA) included 20 high (HI) and 20 low (LI) imagery prime stimuli, using a visually presented lexical decision task. A trial consisted of 30 ms prime, 30 ms mask, 500 ms probe, and 2-8 s stimulus onset asynchrony. Brain activation was measured using functional magnetic resonance imaging during word discrimination. Behavioral data indicated that the shortest response time (RT) was given for HA words, followed by LA and NA, and NW showed the longest RT (P < 0.01). RT was faster in HI than LI within HA, but not LA conditions (P < 0.01). Functional neuroimaging showed that differential brain regions for high imagery (HI) and low imagery (LI) words within low prime-target word association were observed in the left precuneus, left posterior cingulate gyrus, and right cuneal cortex. The present findings demonstrate that the effect of the degree of imagery on semantic priming occurs during the early stage of language processing, indicating an "automatic imagery priming effect." Our paradigm may be useful to explore semantic deficit related to imagery in various psychiatric disorders.

Having mentors and campus social networks moderates the impact of worries and video gaming on depressive symptoms: a moderated mediation analysis.

BACKGROUND: Easy access to the internet has spawned a wealth of research to investigate the effects of its use on depression. However, one limitation of many previous studies is that they disregard the interactive mechanisms of risk and protective factors. The aim of the present study was to investigate a resilience model in the relationship between worry, daily internet video game playing, daily sleep duration, mentors, social networks and depression, using a moderated mediation analysis. METHODS: 6068 Korean undergraduate and graduate students participated in this study. The participants completed a web-based mental health screening questionnaire including the Beck Depression Inventory (BDI) and information about number of worries, number of mentors, number of campus social networks, daily sleep duration, daily amount of internet video game playing and daily amount of internet searching on computer or smartphone. A moderated mediation analysis was carried out using the PROCESS macro which allowed the inclusion of mediators and moderator in the same model. RESULTS: The results showed that the daily amount of internet video game playing and daily sleep duration partially mediated the association between the number of worries and the severity of depression. In addition, the mediating effect of the daily amount of internet video game playing was moderated by both the number of mentors and the number of campus social networks. CONCLUSIONS: The current findings indicate that the negative impact of worry on depression through internet video game playing can be buffered when students seek to have a number of mentors and campus social networks. Interventions should therefore target individuals who have higher number of worries but seek only a few mentors or campus social networks. Social support via campus mentorship and social networks ameliorate the severity of depression in university students.

Digital Phenotyping for Real-Time Monitoring of Nonsuicidal Self-Injury: Protocol for a Prospective Observational Study.

BACKGROUND: Nonsuicidal self-injury (NSSI) is a major global health concern. The limitations of traditional clinical and laboratory-based methodologies are recognized, and there is a pressing need to use novel approaches for the early detection and prevention of NSSI. Unfortunately, there is still a lack of basic knowledge of a descriptive nature on NSSI, including when, how, and why self-injury occurs in everyday life. Digital phenotyping offers the potential to predict and prevent NSSI by assessing objective and ecological measurements at multiple points in time. OBJECTIVE: This study aims to identify real-time predictors and explain an individual's dynamic course of NSSI. METHODS: This study will use a hybrid approach, combining elements of prospective observational research with non-face-to-face study methods. This study aims to recruit a cohort of 150 adults aged 20 to 29 years who have self-reported engaging in NSSI on 5 or more days within the past year. Participants will be enrolled in a longitudinal study conducted at 3-month intervals, spanning 3 long-term follow-up phases. The ecological momentary assessment (EMA) technique will be used via a smartphone app. Participants will be prompted to complete a self-injury and suicidality questionnaire and a mood appraisal questionnaire 3 times a day for a duration of 14 days. A wrist-worn wearable device will be used to collect heart rate, step count, and sleep patterns from participants. Dynamic structural equation modeling and machine learning approaches will be used. RESULTS: Participant recruitment and data collection started in October 2023. Data collection and analysis are expected to be completed by December 2024. The results will be published in a peer-reviewed journal and presented at scientific conferences. CONCLUSIONS: The insights gained from this study will not only shed light on the underlying mechanisms of NSSI but also pave the way for the development of tailored and culturally sensitive treatment options that can effectively address this major mental health concern. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53597.

Redox, mutagenic and structural studies of the glutaredoxin/arsenate reductase couple from the cyanobacterium Synechocystis sp. PCC 6803.

The arsenate reductase from the cyanobacterium Synechocystis sp. PCC 6803 has been characterized in terms of the redox properties of its cysteine residues and their role in the reaction catalyzed by the enzyme. Of the five cysteines present in the enzyme, two (Cys13 and Cys35) have been shown not to be required for catalysis, while Cys8, Cys80 and Cys82 have been shown to be essential. The as-isolated enzyme contains a single disulfide, formed between Cys80 and Cys82, with an oxidation-reduction midpoint potential (E(m)) value of -165mV at pH 7.0. It has been shown that Cys15 is the only one of the four cysteines present in Synechocystis sp. PCC 6803 glutaredoxin A required for its ability to serve as an electron donor to arsenate reductase, while the other three cysteines (Cys18, Cys36 and Cys70) play no role. Glutaredoxin A has been shown to contain a single redox-active disulfide/dithiol couple, with a two-electron, E(m) value of -220mV at pH 7.0. One cysteine in this disulfide/dithiol couple has been shown to undergo glutathionylation. An X-ray crystal structure, at 1.8Å resolution, has been obtained for glutaredoxin A. The probable orientations of arsenate reductase disulfide bonds present in the resting enzyme and in a likely reaction intermediate of the enzyme have been examined by in silico modeling, as has the surface environment of arsenate reductase in the vicinity of Cys8, the likely site for the initial reaction between arsenate and the enzyme.

Induced interpretation bias affects free recall and episodic memory bias in social anxiety.

The combined effect of each cognitive bias, interpretation, attention, and memory bias, is known to play a causal role in the etiology and maintenance of social anxiety. However, little is known about how each type of bias (i.e., interpretation, memory bias) acts during social anxiety. The present study aimed to investigate whether experimentally induced interpretation bias using the cognitive bias modification (CBM) paradigm would influence free recall and episodic memory biases in a Korean sample. A total of 61 participants were randomly assigned to either a positive (n = 30) or negative (n = 31) CBM group. The study used CBM scenarios that were auditory-specific and focused on social anxiety symptoms. The results showed that interpretation biases could be induced, and they resulted in training congruent state mood and memory biases on both free-recall memory and autobiographical memory, which partly confirmed the combined cognitive biases hypothesis proposed by Hirsch, Clark (1).

A Latent Class Analysis of Suicidal Behaviors in Adolescents.

OBJECTIVE: The purpose of the present study was to identify adolescents' suicide subgroups using five indicators (depression, anxiety, suicide ideation, and planned and attempted suicide), and explore the distinctive features of each subgroup. METHODS: This study included 2,258 teenagers from four schools. Both adolescents and their parents, who voluntarily agreed to participate in the study, completed a series of self-reported questionnaires on depression, anxiety, suicide, self-harm, self-esteem, impulsivity, childhood maltreatment, and deviant behaviors. The data were analyzed using latent class analysis, a person-centered method. RESULTS: Four classes were detected: "high risk for suicide without distress," "high risk for suicide with distress," "low risk for suicide with distress," and "healthy." The "high risk for suicide with distress" class was the most severe on all evaluated psychosocial risk factors, namely, impulsivity, low self-esteem, self-harming behaviours, deviant behaviour problems, and childhood maltreatment, followed by "high risk for suicide without distress." CONCLUSION: This study identified two high risk subgroups for adolescent' suicidality, "high risk for suicide with or without distress." Both high risk subgroups for suicide showed higher scores for all psychosocial risk factors than low risk subgroups for suicide. Our findings suggest that special attention needs to be paid to the latent class "high risk for suicide without distress," as this group's "cry for help" might be relatively difficult to detect. Specific interventions for each group (e.g., distress safety plans for "suicidal potential with or without emotional distress") need to be developed and implemented.

Time-Series Trends of Depressive Levels of Korean Adults During the 2020 COVID-19 Pandemic in South Korea.

OBJECTIVE: This study aimed to observe the changes in people's depressive levels over 9 months since the coronavirus disease of 2019 (COVID-19) outbreak as well as to identify the predictors of people's depressive levels including COVID-19 infection fear in the context of South Korea in 2020. METHODS: For these purposes, four cross-sectional surveys were periodically implemented from March to December 2020. We randomly recruited 6,142 Korean adults (aged 19 to 70) by using a quota survey. Along with descriptive analysis, which included a one-way analysis of variance and correlations, multiple regression models were built to identify the predictors of people's depressive levels during the pandemic. RESULTS: Overall, people's depressive levels and fear of COVID-19 infection gradually increased since the COVID-19 outbreak. In addition to demographic variables (i.e., being a female, young age, unemployed, and living alone) and the duration of the pandemic, people's COVID-19 infection fear was associated with their depressive levels. CONCLUSION: To ameliorate these rising mental health issues, access to mental health services should be secured and expanded, particularly for individuals who present greater vulnerabilities due to socioeconomic characteristics that may affect their mental health.

COVID-19 Pandemic-Related Job Loss Impacts on Mental Health in South Korea.

OBJECTIVE: The economic hardship brought by the coronavirus disease-2019 (COVID-2019) pandemic has caused mental health problems among people of different socioeconomic status (SES). As social support helps to buffer these problems, we investigated the association between job loss related to COVID-19 and depression, anxiety, and suicidal thoughts; the differences in the effects according to SES; and the mediating effects of social support. METHODS: The effects of COVID-19-related job loss on depression, anxiety, and suicidal thoughts among 1,364 people were investigated through semi-structured and self-administered questionnaires: Patient Health Questionnaire-9, General Anxiety Disorder-7, and the Functional Social Support Questionnaire. Logistic regression and subgroup analyses were performed to assess the association between job loss and mental health status, and the moderating effects of income and educational levels. Moreover, the mediating effects of perceived social support on the association between job loss and depression, anxiety, and suicidal thoughts were analyzed. RESULTS: COVID-19-related job loss increased the risk of depression and suicidal thoughts. Adults with lower income and education level were at higher risk of depression, anxiety, and suicidal thoughts; perceived social support level had significant mediating effects on the association between job loss and depression/anxiety; and income level had significant moderating effects on this mediating pathway. CONCLUSION: COVID-19-related job loss were likely to be significantly associated with negative mental health outcomes, especially among individuals with low income and education levels. As social support had buffering effects on such outcomes, related government policies in cooperation with the governance of communities and stakeholders must be prepared.

Proteolytic assay-based screening identifies a potent inhibitor of anthrax lethal factor.

Anthrax lethal factor (LF), a Zn(2+)-dependent metalloprotease, is a key virulence component of anthrax toxin. Here, we used proteolytic assay-based screening to identify novel LF inhibitors from a naturally extracted chemical library. The screening identified four compounds that inhibited in vitro proteolytic activity of LF with an IC(50) of low micromolar range (11-20 µM). Three of these compounds were toxic to the mouse macrophage-like cell line, RAW 264.7. Compound 200 was non-toxic, however, and successfully protected Raw 264.7 cells from a lethal toxin challenge with an IC(50) of 39.2 µM. We also identified possible binding modes of compound 200 by molecular docking.

Hemostatic Analysis of Simulated Gloydius ussuriensis Envenomation Using Canine Blood: A Comparison of Thromboelastography and Classical Coagulation Tests.

Snake envenomation may lead to venom-induced consumptive coagulopathy (VICC), usually diagnosed by classical coagulation tests (CCTs), such as prothrombin time (PT) and activated partial thromboplastin time (aPTT). However, the results of CCTs are frequently normal in the initial stages, which may delay anti-venom treatments. Thromboelastography (TEG) is a point-of-care and real-time diagnostic tool that enables a comprehensive assessment of the coagulation process. This in vitro study aimed to determine concentration-dependent changes in canine blood caused by Gloydius ussuriensis (G. ussuriensis) envenomation using TEG and CCTs. Lyophilized G. ussuriensis venom was reconstructed using mouse intravenous lethal dose 50 (LD50iv) and serially diluted to 25% LD50iv, 50% LD50iv, and 75% LD50iv to reproduce VICC at different concentrations. Normal saline was used for the control. We compared TEG values of the reaction time (R), kinetic time (K), rate of clot formation (α-angle), maximum amplitude (MA), fibrinolysis at 30 min (LY30), and global strength of the clot (G) with those of PT, aPTT, fibrinogen, and platelet counts (PLTs). Most TEG parameters, except R and LY30, demonstrated statistically significant changes compared with the control at all concentrations. CCTs, except PLTs, revealed significant changes at ≥50% LD50iv. Thus, TEG could be a useful diagnostic strategy for early VICC and preventing treatment delay.