Impact of COVID-19-Induced Academic Stress on Insomnia and Suicidal Ideation among Taiwanese Health Trainees and Junior Doctors.

BACKGROUND Clinical training for allied health trainees (AHTs) and postgraduate-year (PGY) doctors needed to go online during the outbreak of coronavirus disease 2019 (COVID-19), which may have caused academic stress and consequent outcomes among this cohort. MATERIAL AND METHODS To evaluate academic-related stress, clinical confidence, psychological distress, and insomnia, an online survey-based study was conducted among Taiwanese AHTs and PGY doctors between July and December, 2022, during the COVID-19 pandemic. The survey included the 21-item Depression, Anxiety, and Stress Scale (DASS-21), the Insomnia Severity Index (ISI), and self-designed questions. It was distributed using convenience sampling and snowball sampling and was completed by 522 participants. RESULTS Structural equational modelling showed that academic stress was negatively associated with clinical confidence (standardized coefficient [ß]=-0.382, p<0.001). Clinical confidence was negatively associated with psychological distress (ß=-0.397, p<0.001), which was associated with insomnia (ß=0.648, p<0.001). Additionally, clinical confidence and psychological distress were the significant mediators. Results indicated that higher academic stress was associated with higher level of insomnia via the mediation of clinical confidence and psychological distress. CONCLUSIONS Academic stress related to changes in clinical training may have led to insomnia among AHTs and PGY doctors during the pandemic. Factors to reduce academic stress should be investigated to promote good mental health while providing sufficient clinical training, especially during events that can cause increased stress (eg, epidemics, pandemics).

Phytohormones in postharvest storage of fruit and vegetables: mechanisms and applications.

As a ubiquitous and essential part of phytophysiology, phytohormones have attracted tremendous attention for effective regulation of development and senescence of agricultural products. However, the postharvest mechanisms of phytohormones have not been thoroughly understood. This review provides an overview of common phytohormones for extending the shelf life of fruit and vegetables. The modulation principles are discussed in detail based on defence gene expression activation, sensitivity of senescence-related phytohormones inhibition, antioxidant enzymes activity stimulation, and cell membrane integrity maintenance. The applications of jasmonates, salicylic acids, cytokinins, gibberellins, polyamines, and brassinosteroids in preserving fruit and vegetables based on defence signaling network stimulation, senescence-related phytohormones expression or sensitivity repression, as well as antioxidant system enhancement and cell membrane integrity sustentation are introduced. The challenges and problems to be solved are discussed, and new trends of expanding lifespan by combining phytohormones with other treatments are also suggested. Although phytohormones have been demonstrated to have promising efforts in maintaining agricultural products, more novel and effective combination treatments should be developed to complement each other.

Developments of mathematical models for simulating vacuum cooling processes for food products - a review.

Vacuum cooling is a rapid cooling method widely used in cooling some food products. Simulating the vacuum cooling process with mathematical models helps to acquire a more intuitive understanding and optimize the whole cooling process. However, there is no review summarizing the mathematical models of vacuum cooling. In this review, heat and mass transfer process during vacuum cooling, types of mathematical models for vacuum cooling, and numerical methods including finite difference method, finite element method and finite volume method used for process simulation are introduced in details. The food products used in numerical simulation study of vacuum cooling generally include liquid food, vegetables and cooked meat. The ranges of application of various numerical methods are also discussed. Moreover, heat and mass transfer coefficients have a great influence on the accuracy of the model, and are generally provided by the literature. The investigations presented in this review invariably demonstrate that mathematical modeling can provide good prediction of key information of vacuum cooling process, and has a great potential to improve vacuum cooling process in the food industry. However, more efforts are still needed to realize the industrial translation of laboratory results.

Synthesis of S-linked NeuAc-α(2-6)-di-LacNAc bearing liposomes for H1N1 influenza virus inhibition assays.

S-NeuAc-α(2-6)-di-LacNAc (5) was efficiently synthesized by a [2+2] followed by a [1+4] glycosylation, and later conjugated with 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE) to form both single-layer and multi-layer homogeneous liposomes in the presence of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol. These liposomes were found to be weak inhibitors in both the influenza virus entry assay and the hemagglutination inhibition assay. The single layer liposome was found to more efficiently interfere with the entry of the H1N1 influenza virus into MDCK cells than the multilayer liposome containing 5.

S-Linked sialyloligosaccharides bearing liposomes and micelles as influenza virus inhibitors.

An efficient, homogeneous synthesis of phospholipid conjugation of S-Neu5Acα2-6Galß1-4GluNAcß1-3 (3) and its 6-sulphate analogue 4 has been developed. The self-assembled micelles and liposomes of these trisaccharides formed in solution were found to be inhibitors interfering with the entry of the H1N1 influenza virus into MDCK cells. Compound 3 bearing a liposome and a micelle displayed superior inhibitory activity than its 6-sulfate congener 4 in both the virus neutralization assay and the hemagglutination inhibition assay.

The effect of social support and resource support on emotional exhaustion, insomnia, and suicidal ideation among allied health trainees and post-graduate year doctors in Taiwan.

BACKGROUND: COVID-19-related stigmatization refers to COVID-19-related judgements by others that devalue the individual. Such stigmatization towards healthcare workers may cause psychological burden and negative consequences. Such stigmatization may have particularly overwhelmed allied health trainees (AHTs) and post-graduate year doctors (PGYDs) because they just started their medical career. Social support and resource support have been reported to benefit psychological health and reduce stigmatization. Therefore, the present study used a cross-sectional study design to investigate the association between perceived stigma, self-stigma, psychological distress, and negative outcomes (including emotional exhaustion, insomnia and suicidal ideation) among AHTs and PGYDs in Taiwan. METHODS: An online survey distributed between July and December, 2022 received 522 responses. Variables were assessed using the 21-item Depression, Anxiety and Stress Scale, Insomnia Severity Index and a series of self-designed questions to assess social support, resource support, perceived stigma, self-stigma, emotional exhaustion, and suicidal ideation. RESULTS: Structural equation modeling showed that perceived stigma was associated with self-stigma (standardized coefficient [ß] = 0.428, p < 0.001), and self-stigma was associated with psychological distress (ß = 0.197, p < 0.001), as well as being associated with emotional exhaustion, insomnia, and suicidal ideation (ß = 0.349, 0.556 and 0.212, all p-values < 0.001). While social support and resource support were negatively associated with perceived stigma (ß= - 0.175 and - 0.152, p < 0.01), additional associations were found between social support and emotional exhaustion (ß= - 0.093, p < 0.001), as well as between resource support and insomnia (ß= - 0.120, p < 0.001). CONCLUSIONS: The results showed that COVID-19 related stigmatization was correlated to the detrimental consequences of emotional exhaustion, insomnia and suicidal ideation. Clear paths regarding the associations of social support and resource support with the three negative associations were found as the possible solutions. Strategies to reduce the stigmatization and these negative outcomes, or improve the psychological health will benefit AHTs and PGYDs in maintaining a healthy mental status.

Tyrosol and its analogues inhibit alpha-melanocyte-stimulating hormone induced melanogenesis.

Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV) irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), 2-hydroxyphenylacetic acid (7), or salidroside (11) resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5) and 2-hydroxyphenylacetic acid (7) suppressed MC1R expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) inhibited α-MSH induced TRP-1 expression, but salidroside (11) did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) at concentrations below 4 mM and salidroside (11) at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.

COVID-19-Related Self-Stigma, Post-Traumatic Stress Disorder, Insomnia, and Smartphone Addiction Among Frontline Government Workers with COVID-19 Pandemic Control Duties.

Purpose: The duties related to COVID-19 control and prevention may have caused psychological stress for the individuals in charge (eg, frontline government workers) and have reportedly led to mental health issues, such as insomnia and post-traumatic stress disorder (PTSD). However, the prevalence of these COVID-19-related disorders and their associated factors remain unclear. Therefore, the purpose of the present study was to investigate the prevalence rates of insomnia, PTSD, COVID-19-related self-stigma, and smartphone addiction, along with the identification of risk factors and protective factors for Taiwan frontline government workers with COVID-19 pandemic control duties. Methods: The survey was carried out with 151 participants between September and October 2021. All participants completed the Fear of COVID-19 Scale (assessing fear of COVID-19), Self-Stigma Scale (assessing self-stigma during the COVID-19 pandemic), Smartphone Application-Based Addiction Scale (assessing the risk of smartphone addiction), Insomnia Severity Index (assessing insomnia), Impacts of Event Scale-6 (assessing PTSD), and a self-designed set of questions assessing trait resilience. Results: The results showed that the prevalence rate was 31.1% for insomnia and 33.8% for PTSD. Furthermore, service duration (adjusted odds ratio [AOR] = 0.93; 95% confidence interval [CI] = 0.86, 0.999) and trait resilience (AOR = 0.19; 95% CI = 0.08, 0.46) were protective factors and fear of COVID-19 (AOR = 1.91; 95% CI = 1.02, 3.57) was a risk factor for insomnia. Fear of COVID-19 (AOR = 2.63; 95% CI = 1.35, 5.14), self-stigma (AOR = 3.62; 95% CI = 1.19, 11.02), and smartphone addiction (AOR = 1.09, 95% CI = 1.001, 1.19) were risk factors, and trait resilience was a protective factor (AOR = 0.58; 95% CI = 0.29, 1.17) for PTSD. Conclusion: The findings demonstrated a high prevalence of insomnia and PTSD. Risk-reducing strategies and protective factor promotion strategies are recommended to help reduce the symptoms of insomnia and PTSD among Taiwan frontline government workers.

COVID-19-Related Variables and Its Association with Anxiety and Suicidal Ideation: Differences Between International and Local University Students in Taiwan.

PURPOSE: The present study examined the differences between international and local university students in Taiwan regarding COVID-19-related variables, anxiety, and suicidal ideation. PARTICIPANTS AND METHODS: An online cross-sectional survey (sent via an online link in an email) was carried out comprising university students (n=529). The students were assessed on measures (including validated psychometric instruments) of perceived susceptibility to COVID-19, perceived sufficiency of resources, sources of COVID-19 information, perceived satisfaction with support, anxiety and suicidal ideation. RESULTS: Local students had higher susceptibility to COVID-19 (p<0.001) but decreased sufficiency with resources (p<0.001) and anxiety (p<0.001) compared with international students. Staying with family members, satisfaction with support, and information seeking were the factors that predicted anxiety among international students (all p-values<0.05), while information seeking predicted local students' anxiety (p<0.001). Furthermore, staying with family members, susceptibility to COVID-19, and sufficiency with resources were the factors that predicted suicidal ideation among international students (all p-values<0.05), while being a male and satisfaction with support predicted suicidal ideation among local students (all p-values<0.05). CONCLUSION: International students displayed different COVID-19-related challenges compared with local students. More specifically, international students as compared with local students had lower susceptibility to COVID-19 and higher anxiety. Therefore, healthcare providers should pay more attention to international students' psychological health and awareness regarding impacts of COVID-19 on health.

Learning From Each Other in the Management of Natural Disaster and COVID-19 Pandemic: A Case Study in Taiwan.

In response to the COVID-19 pandemic, Taiwan has been one of the best performers in the world with extremely low infections and deaths. This success can be attributed to the long experiences dealing with natural disasters and communicable diseases. However, with different disastrous characteristics, the disaster management systems for communicable diseases and natural disasters are very different in terms of laws, plans, frameworks, and emergency operations. Taking the response to COVID-19 pandemic as a study subject, we found that disaster management for communicable diseases can be improved through a comparison with natural disasters, and vice versa. First, having wider and longer impacts than natural disasters, the plans and framework for communicable diseases in Taiwan focus more on national and regional scales. Local governments would need more capacity support including budgets and training to conduct investigations and quarantine during the COVID-19 pandemic. Second, for quick response, the emergency operation for communicable diseases was designed to be more flexible than that for natural disasters by giving the commander more authority to adjust to the circumstances. The commanding system requires a more objective consultation group to prevent arbitrary decisions against the COVID-19 pandemic. Finally, risk governance is important for communicable diseases as well as for natural disasters. Additional efforts should be made to enhance vulnerability assessment, disaster reduction, and risk communication for shaping responses and policies in an efficient and coordinating way.

Community Outbreak Moderates the Association Between COVID-19-Related Behaviors and COVID-19 Fear Among Older People: A One-Year Longitudinal Study in Taiwan.

Although health behavior theories indicate that fear is effective in activating preventive behaviors, the question of whether COVID-19 severity moderates the association between fear of COVID-19 and preventive behaviors remains unclear. The present study investigated the association between the fear of COVID-19 and preventive behaviors during the COVID-19 community outbreak of two severity levels in Taiwan. Data were obtained regarding the fear of COVID-19 and practice of preventive behaviors from 139 older people (mean age = 71.73 years; 30.2% men) through in-person interviews during a mild COVID-19 outbreak period (baseline assessment). Data from 126 of the 139 participants were obtained again through a telephone interview during a severe COVID-19 outbreak period (follow-up assessment). A significant increase in the fear of COVID-19 (d = 0.39, p < 0.001) and a decrease in preventive behaviors (d = 0.63, p < 0.001) were found in the follow-up assessment. The association between fear of COVID-19 and preventive behaviors was not significant at baseline (r = -0.07, p > 0.05) but became significant at the follow-up assessment (r = 0.32, p < 0.001). The severity of a COVID-19 outbreak may alter older people's psychological status and related behaviors.

Induction of Terminal Oxidases of Electron Transport Chain in Broccoli Heads under Controlled Atmosphere Storage.

Controlled atmosphere (CA) storage, that is, at low O2 and high CO2 concentrations, effectively extends the shelf life of horticultural products. The influence of CA storage (O2/CO2: 2.5%/6.0% or 2.5%/0.0%) and in normal air (both at 1 °C for 21 d) on the physicochemical (O2 uptake, mass loss and L-ascorbate) and biological properties of broccoli (Brassica oleracea var. italica, Plenck, 1794) via amounts and activities of terminal oxidases of the electron transport chain was investigated. Mass loss, a sensitive index of freshness for broccoli heads under CA, was significantly lower under CA than under normoxia (p < 0.05). Mass loss was depressed 7 d earlier under CA, including 6.0% CO2 than under CA without CO2. High CO2 effectively depressed the degradation of L-ascorbate. During storage, the activity of the alternative oxidase (AOX) was lower under CA than in normal air (p < 0.05), while the amount of cytochrome c oxidase (COX), and the AOX/COX activity ratio (based on oxygen isotope discrimination), were not affected during storage. Our results indicate that CA storage effectively retained the freshness of broccoli heads by depressing the induction of AOX. However, depression of AOX amount was not associated with CO2 around broccoli heads.

Influence of a Modified Atmosphere on the Induction and Activity of Respiratory Enzymes in Broccoli Florets during the Early Stage of Postharvest Storage.

Modified atmosphere packaging and controlled atmosphere storage (hypoxia conditions) extend shelf lives of horticultural products by depressing the O2 uptake rate. We investigated the relationship between atmospheres and alternative oxidase (AOX) to cytochrome c oxidase (COX) activities (on the basis of oxygen isotope discrimination) and the relative amounts of two respiratory enzymes, AOX and COX, during the early stage of storage. Broccoli florets, with high O2 uptake rates, were stored under hypoxia and normoxia at 25 °C. O2 uptake rates, weight loss, and yellowing of broccoli florets were significantly lower when stored under hypoxia than when stored under normoxia. Significantly more AOX proteins were produced during storage under normoxia, but COX proteins were more consistent than those of AOX proteins. Hypoxia may depress the expression of AOX and prolong the shelf life. Oxygen isotope discrimination was elevated under hypoxia after 50.5 h. AOX production in broccoli was controlled more by changing atmospheres than by COX.

Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer.

While aberrant JAK/STAT signaling is crucial to the development of gastric cancer (GC), its effects on epigenetic alterations of its transcriptional targets remains unclear. In this study, by expression microarrays coupled with bioinformatic analyses, we identified a putative STAT3 target gene, NR4A3 that was downregulated in MKN28 GC daughter cells overexpressing a constitutively activated STAT3 mutant (S16), as compared to an empty vector control (C9). Bisulphite pyrosequencing and demethylation treatment showed that NR4A3 was epigenetically silenced by promoter DNA methylation in S16 and other GC cell lines including AGS cells, showing constitutive activation of STAT3. Subsequent experiments revealed that NR4A3 promoter binding by STAT3 might repress its transcription. Long-term depletion of STAT3 derepressed NR4A3 expression, by promoter demethylation, in AGS GC cells. NR4A3 re-expression in GC cell lines sensitized the cells to cisplatin, and inhibited tumor growth in vitro and in vivo, in an animal model. Clinically, GC patients with high NR4A3 methylation, or lower NR4A3 protein expression, had significantly shorter overall survival. Intriguingly, STAT3 activation significantly associated only with NR4A3 methylation in low-stage patient samples. Taken together, aberrant JAK/STAT3 signaling epigenetically silences a potential tumor suppressor, NR4A3, in gastric cancer, plausibly representing a reliable biomarker for gastric cancer prognosis.

Galactosylated liposome as a dendritic cell-targeted mucosal vaccine for inducing protective anti-tumor immunity.

Mucosal surfaces contain specialized dendritic cells (DCs) that are able to recognize foreign pathogens and mount protective immunity. We previously demonstrated that intranasal administration of targeted galactosylated liposomes can elicit mucosal and systemic antibody responses. In the present study, we assessed whether galactosylated liposomes could act as an effective DC-targeted mucosal vaccine that would be capable of inducing systemic anti-tumor immunity as well as antibody responses. We show that targeted galactosylated liposomes effectively facilitated antigen uptake by DCs beyond that mediated by unmodified liposomes both in vitro and in vivo. Targeted galactosylated liposomes induced higher levels of pro-inflammatory cytokines than unmodified liposomes in vitro. C57BL/6 mice thrice immunized intranasally with ovalbumin (OVA)-encapsulated galactosylated liposomes produced high levels of OVA-specific IgG antibodies in their serum. Spleen cells from mice receiving galactosylated liposomes were restimulated with OVA and showed significantly augmented levels of IFN-γ, IL-4, IL-5 and IL-6. In addition, intranasal administration of OVA-encapsulated beta-galactosylated liposomes resulted in complete protection against EG7 tumor challenge in C57BL/6 mice. Taken together, these results indicate that nasal administration of a galactosylated liposome vaccine mediates the development of an effective immunity against tumors and might be useful for further clinical anti-tumoral applications.

Synthesis of a chlorogenin glycoside library using an orthogonal protecting group strategy.

Naturally occurring spirostanol saponins bear a chacotriose, α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranose residue as the oligosaccharide moiety which is believed to be important for biological activity. Herein the development of a concise, combinatorial method for the synthesis of two series of glycan variants at the 2' and/or 4' positions of chacotriose is described and the structure-activity relationships of the glycone part at 3-OH of chlorogenin investigated. These compounds were found to be weakly-cytotoxic toward leukemia cell lines CCRF and HL-20, indicating that the chacotriose moiety is important for anticancer activity.

Application of galactose-modified liposomes as a potent antigen presenting cell targeted carrier for intranasal immunization.

The mucosal immune system produces secretory IgA (sIgA) as the first line of defense against invasion by foreign pathogens. Our aim was to develop a galactose-modified liposome as a targeted carrier which can be specifically recognized by macrophage, one of the most important antigen presenting cells. First, galactose was covalently conjugated with 1,2-didodecanoyl-sn-glycero-3-phosphoethanolamine (DLPE) to give a targeted ligand, a galactosyl lipid. The galactosyl lipid was then incorporated into a liposomal bilayer to form a galactosylated liposome carrier. Further, the ovalbumin (OVA) was encapsulated into the galactosylated liposome carriers and mice were intranasally immunized. Confocal laser scanning microscopy and flow cytometry analysis showed that the targeted galactosylated liposome carrier had a higher uptake rate than unmodified liposomes. The targeted galactosylated liposome induced higher levels of tumor necrosis factor-α and interleukin-6 production than unmodified liposomes (P<0.05). Furthermore, 6-week-old BALB/c female mice immunized with the OVA-encapsulated targeted galactosylated liposome had significantly higher OVA-specific s-IgA levels in the nasal and lung wash fluid (P<0.05). In addition, the targeted galactosylated liposome simultaneously augmented the serum IgG antibody response. In summary, the OVA-encapsulated targeted galactosylated liposome induced significantly higher mucosal IgA and systemic IgG antibody titers and is a potential antigen delivery carrier for further clinical applications.

High-throughput simultaneous analysis of five urinary metabolites of areca nut and tobacco alkaloids by isotope-dilution liquid chromatography-tandem mass spectrometry with on-line solid-phase extraction.

BACKGROUND: Areca nut and tobacco are commonly used drugs worldwide and have been frequently used in combination. We describe the use of on-line solid-phase extraction and isotope-dilution liquid chromatography-tandem mass spectrometry for the simultaneous measurement of five major urinary metabolites of both areca nut and tobacco alkaloids, namely, arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine. METHODS: Automated purification of urine was accomplished with a column-switching device. After the addition of deuterium-labeled internal standards, urine samples were directly analyzed within 13 minutes. This method was applied to measure urinary metabolites in 90 healthy subjects to assess areca nut/tobacco exposure. Urinary time course of arecoline, arecaidine, and N-methylnipecotic acid was investigated in five healthy nonchewers after oral administration of areca nut water extracts. RESULTS: The limits of detection were 0.016 to 0.553 ng/mL. Interday and intraday imprecision were <10%. Mean recoveries of five metabolites in urine were 97% to 114%. Mean urinary concentrations of arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine in regular areca nut chewers also smokers were 23.9, 5,816, 1,298, 2,635, and 1,406 ng/mg creatinine, respectively. Time course study revealed that after administration of areca nuts extracts, the major urinary metabolite was arecaidine with a half-life of 4.3 hours, followed by N-methylnipecotic acid with a half-life of 7.9 hours, and very low levels of arecoline with a half-life of 0.97 hour. CONCLUSIONS: This on-line solid-phase extraction liquid chromatography-tandem mass spectrometry method firstly provides high-throughput direct analysis of five urinary metabolites of areca nut/tobacco alkaloids. IMPACT: This method may facilitate the research into the oncogenic effects of areca nut/tobacco exposure.