Cell-type-specific hypothalamic pathways to brainstem drive context-dependent strategies in response to stressors.

Adaptive behavioral responses to stressors are critical for survival. However, which brain areas orchestrate switching the appropriate stress responses to distinct contexts is an open question. This study aimed to identify the cell-type-specific brain circuitry governing the selection of distinct behavioral strategies in response to stressors. Through novel mouse behavior paradigms, we observed distinct stressor-evoked behaviors in two psycho-spatially distinct contexts characterized by stressors inside or outside the safe zone. The identification of brain regions activated in both conditions revealed the involvement of the dorsomedial hypothalamus (DMH). Further investigation using optogenetics, chemogenetics, and photometry revealed that glutamatergic projections from the DMH to periaqueductal gray (PAG) mediated responses to inside stressors, while GABAergic projections, particularly from tachykinin1-expressing neurons, played a crucial role in coping with outside stressors. These findings elucidate the role of cell-type-specific circuitry from the DMH to the PAG in shaping behavioral strategies in response to stressors. These findings have the potential to advance our understanding of fundamental neurobiological processes and inform the development of novel approaches for managing context-dependent and anxiety-associated pathological conditions such as agoraphobia and claustrophobia.

Antimicrobial properties of glass-ionomer cement incorporated with nano-hydroxyapatite against mutans streptococci and lactobacilli under orthodontic bands: An in vivo split-mouth study.

Background: Fixed orthodontic appliances enhance dental plaque accumulation. Glass ionomer (GI) is among the most popular orthodontic cement. It possesses antibacterial properties; however, its antibacterial activity may not be sufficient for caries prevention. Although evidence shows that the addition of 8wt% nano-hydroxyapatite (nHA) may enhance the antibacterial properties of GI, no clinical study has been conducted in this respect. Thus, this study aimed to assess the subgingival accumulation of Streptococcus mutans (S. mutans) and Lactobacillus acidophilus (L. acidophilus) around orthodontic bands cemented with conventional GI and GI reinforced with 8wt% nHA. Materials and Methods: This split-mouth clinical trial was conducted on 20 patients requiring a lingual arch. The patients were randomly assigned to two groups. In group 1, the right molar band was cemented with pure Fuji I (GC), and the left was cemented with Fuji I containing 8wt% nHA. In group 2, the right molar band was cemented with Fuji I containing 8wt% nHA, and the left was cemented with Fuji I. After 3 months, subgingival sampling was performed by sterile paper points. S. mutans and L. acidophilus were cultured on MSB and MRS agar, and colonies were counted by a colony counter. Data were analyzed by independent samples t-test using SPSS 25 at a 0.05 level of significance. Results: The mean counts of S. mutans, aerobic and anaerobic lactobacilli, and total bacterial around orthodontic bands cemented with Fuji I containing 8wt% nHA were significantly lower than those around orthodontic bands cemented with pure Fuji I (P < 0.05). Conclusion: The addition of 8wt% nHA to GI cement can enhance its antibacterial properties for the cementation of orthodontic bands, decrease the accumulation of cariogenic bacteria, and probably decrease the incidence of caries in orthodontic patients.

Nanotechnology and nano-sized tools: Newer approaches to circumvent oncolytic adenovirus limitations.

Oncolytic adenoviruses (OAds), engineered Ads preferentially infect and lyse tumor cells, have attracted remarkable attention as immunotherapy weapons for the treatment of various malignancies. Despite hopeful successes in preclinical investigations and translation into clinical phases, they face some challenges that thwart their therapeutic effectiveness, including low infectivity of cancer cells, liver sequestration, pre-existing neutralizing antibodies, physical barriers to the spread of Ads, and immunosuppressive TME. Nanotechnology and nano-sized tools provide several advantages to overcome these limitations of OAds. Nano-sized tools could improve the therapeutic efficacy of OAds by enhancing infectivity and cellular uptake, targeting and protecting from pre-existing immune responses, masking and preventing liver tropism, and co-delivery with other therapeutic agents. Herein, we reviewed the constructs of various OAds and their application in clinical trials, as well as the limitations they have faced. Furthermore, we emphasized the potential applications of nanotechnology to solve the constraints of OAds to improve their anti-tumor activities.

Flexibility and inflexibility in an Iranian sample: psychometric properties of MPFI based on the Hexaflex model.

OBJECTIVES: Acceptance and Commitment Therapy (ACT) emphasizes the importance of psychological flexibility in promoting emotional, psychological, and social well-being, while also acknowledging rigidity as a precursor to psychological disorders. Analyzing the psychometric qualities based on the multidimensional Hexaflex model is critical for determining the efficiency of therapeutic interventions. Thus, the purpose of this study is to investigate the psychometric features of the Multidimensional Psychological Flexibility Inventory (MPFI) within the context of the Hexaflex model in a group of Iranian university students. METHODS: Exploratory and confirmatory factor analyses were used in this study to evaluate the psychometric features of the flexibility/inflexibility scale (MPFI) in a sample of Iranian university students. FINDINGS: In the exploratory factor analysis involving a sample of 300 students, six factors were identified for flexibility and six for inflexibility (56.3% males and 43.7% females). In the confirmatory factor analysis with a sample of 388 participants, the results validated 60 items across a total of six flexibility and inflexibility factors. This outcome can serve as a robust estimate for flexibility, inflexibility, the second-order model, and the final model. Cronbach's alpha values for various components, including acceptance, present-moment awareness (or contact with the present moment), self as context, cognitive defusing, values, committed action, total flexibility, experiential avoidance, lack of present-moment awareness, self as content, fusion, lack of contact with values, inaction, and total inflexibility, were reported as follows: 0.818, 0.869, 0.862, 0.904, 0.935, 0.935, 0.942, 0.895, 0.839, 0.883, 0.904, 0.912, 0.941, and 0.941, respectively. CONCLUSIONS: The Farsi version of the MPFI for university students has great psychometric qualities, making it a reliable assessment instrument for the ACT.

Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope.

To relieve the limitations of the human papillomavirus (HPV) vaccines based on L1 capsid protein, vaccine formulations based on RG1 epitope of HPV L2 using various built-in adjuvants are under study. Herein, we describe design and construction of a rejoined peptide (RP) harboring HPV16 RG1 epitope fused to TLR4/5 agonists and a tetanus toxoid epitope, which were linked by the (GGGS)3 linker in tandem. In silico analyses indicated the proper physicochemical, immunogenic and safety profile of the RP. Docking analyses on predicted 3D model suggested the effective interaction of TLR4/5 agonists within RP with their corresponding TLRs. Expressing the 1206 bp RP-coding DNA in E. coli produced a 46 kDa protein, and immunization of mice by natively-purified RP in different adjuvant formulations indicated the crucial role of the built-in adjuvants for induction of anti-RG1 responses that could be further enhanced by combination of TLR7 agonist/alum adjuvants. While the TLR4/5 agonists contributed in the elicitation of the Th2-polarized immune responses, combination with TLR7 agonist changed the polarization to the balanced Th1/Th2 immune responses. Indeed, RP + TLR7 agonist/alum adjuvants induced the strongest immune responses that could efficiently neutralize the HPV pseudoviruses, and thus might be a promising formulation for an inexpensive and cross-reactive HPV vaccine.

Immunogenicity evaluation of a novel virus-like particle vaccine candidate against SARS-CoV-2 in BALB/c.

The coronavirus disease (COVID-19) pandemic has imposed deployment of an effective vaccine as a worldwide health priority. The new variants of SARS-CoV-2 have also brought serious concerns due to virus eradiation hesitancy. In this study, we evaluated the protective immune system activity of a recombinant viral vector-based vaccine candidate encoding a fusion spike, membrane and nucleocapsid proteins, Spike (528-1273aa)-M-N, in BALB/c via two different routes of delivery, intranasal and subcutaneous. The immune responses were then assessed through specific SARS-CoV-2 antibodies, interleukin and granzyme B secretion. The outcomes showed that the IgG titer and IgA secretion was higher in intranasal route in comparison with the subcutaneous, and what is more, a higher titer of IL-4 was detected through the intranasal route, whereas IFN-γ was highly induced via the subcutaneous route. The cytotoxic cell activities were mostly achieved via subcutaneous route immunization. Vaccination with the target antigen is immunogenic and led to induction of specific antibodies. Both humoral and cellular immunity arms were well activated in immunized mice, especially through intranasal route with detectable IgA and IgG. Therefore, implication of the platform as a potential vaccine candidate has potential as a future prophylactic vaccine that guarantees further investigations for the assessment of its immunogenicity in humans.

Adherence to a healthy diet and odds of metabolic syndrome: A cross-sectional study.

INTRODUCTION: Metabolic syndrome (MetS) is a major health concern around the world. Dietary factors, including diet quality, play a significant role in its pathophysiology. Healthy Eating Index (HEI) is a tool used as a valid measurement of the individual's diet quality. We aimed at investigating the relationship between diet quality as assessed by HEI-2015 and the risk of MetS and its components in a cross-sectional sample of suburban individuals from PERSIAN Kavar cohort study (PKCS), Fars province, Iran. METHODS: 2225 individuals meeting the eligibility criteria participated in the study. The relevant data were obtained from the baseline phase of PKCS. MetS was defined according to cut-offs presented by the National Cholesterol Education Program Adult Treatment Panel III (ATP III). HEI-2015 was calculated for the included individuals. Odds ratios were estimated. P-values <0.05 were considered as significant. RESULTS: The overall prevalence of MetS was 27.3%. Individuals with lower HEI-2015 scores had higher odds for MetS and its components. We observed that those who were categorized as the top HEI-2015 tertile had 42% (OR: 0.58; 95% CI: 0.38-0.90) lower odds of high blood pressure in the overall population. Also, the odds of high serum triacylglycerol was lower (OR: 0.72; 95% CI: 0.57-0.90) in those with the highest HEI-2015 scores. CONCLUSION: We found that higher dietary quality measured by HEI will decrease the risk of developing MetS, hypertension, and hypertriglyceridemia among Iranian adults. However, future interventional studies are required to further elucidate the issue.

Antimicrobial properties of glass-ionomer cement incorporated with zinc oxide nanoparticles against mutans streptococci and lactobacilli under orthodontic bands: An in vivo split-mouth study.

Background: The aim of this study was to assess the effect of incorporation of zinc oxide nanoparticles (ZnO-NPs) to glass-ionomer cement (GIC) (Fuji II SC, GC Corp., Tokyo, Japan) on subgingival accumulation of mutans streptococci and lactobacilli under orthodontic bands. Materials and Methods: In order to conduct this in vivo split-mouth study, 20 patients aged between 7 and 10 years who required lingual holding arch on their mandibular first molars were divided into two groups. In one group, Fuji II SC GIC was used for cementation of the right molar band, and the same cement containing 2 wt% ZnO-NPs was used for the left one. The opposite was performed for the second group while the operator was blinded to the cement types. Subgingival microbial sampling was performed 16 weeks after cementation of lingual arch. Mutans streptococci and lactobacilli colony counts were compared. Paired t-test was used to compare the two cement groups. Data were analyzed using SPSS version 21, and P ≤ 0.05 was considered statistically significant. Results: The mean colony counts of mutans streptococci, lactobacilli, and total bacterial count in Fuji II SC containing ZnO-NPs were significantly lower than the corresponding values in plain Fuji II SC group. Conclusion: Incorporation of ZnO-NPs into GIC reveals antimicrobial features against mutans streptococci and lactobacilli under orthodontic bands.

Validation of a Transcriptome-Based Assay for Classifying Cancers of Unknown Primary Origin.

INTRODUCTION: Cancers assume a variety of distinct histologies, and may originate from a myriad of sites including solid organs, hematopoietic cells, and connective tissue. Clinical decision-making based on consensus guidelines such as the National Comprehensive Cancer Network (NCCN) is often predicated on a specific histologic and anatomic diagnosis, supported by clinical features and pathologist interpretation of morphology and immunohistochemical (IHC) staining patterns. However, in patients with nonspecific morphologic and IHC findings-in addition to ambiguous clinical presentations such as recurrence versus new primary-a definitive diagnosis may not be possible, resulting in the patient being categorized as having a cancer of unknown primary (CUP). Therapeutic options and clinical outcomes are poor for patients with CUP, with a median survival of 8-11 months. METHODS: Here, we describe and validate the Tempus Tumor Origin (Tempus TO) assay, an RNA-sequencing-based machine learning classifier capable of discriminating between 68 clinically relevant cancer subtypes. Model accuracy was assessed using primary and/or metastatic samples with known subtype. RESULTS: We show that the Tempus TO model is 91% accurate when assessed on both a retrospectively held out cohort and a set of samples sequenced after model freeze that collectively contained 9210 total samples with known diagnoses. When evaluated on a cohort of CUPs, the model recapitulated established associations between genomic alterations and cancer subtype. DISCUSSION: Combining diagnostic prediction tests (e.g., Tempus TO) with sequencing-based variant reporting (e.g., Tempus xT) may expand therapeutic options for patients with cancers of unknown primary or uncertain histology.

Exploring potential barriers in equitable access to pediatric diagnostic imaging using machine learning.

In this work, we examine magnetic resonance imaging (MRI) and ultrasound (US) appointments at the Diagnostic Imaging (DI) department of a pediatric hospital to discover possible relationships between selected patient features and no-show or long waiting room time endpoints. The chosen features include age, sex, income, distance from the hospital, percentage of non-English speakers in a postal code, percentage of single caregivers in a postal code, appointment time slot (morning, afternoon, evening), and day of the week (Monday to Sunday). We trained univariate Logistic Regression (LR) models using the training sets and identified predictive (significant) features that remained significant in the test sets. We also implemented multivariate Random Forest (RF) models to predict the endpoints. We achieved Area Under the Receiver Operating Characteristic Curve (AUC) of 0.82 and 0.73 for predicting no-show and long waiting room time endpoints, respectively. The univariate LR analysis on DI appointments uncovered the effect of the time of appointment during the day/week, and patients' demographics such as income and the number of caregivers on the no-shows and long waiting room time endpoints. For predicting no-show, we found age, time slot, and percentage of single caregiver to be the most critical contributors. Age, distance, and percentage of non-English speakers were the most important features for our long waiting room time prediction models. We found no sex discrimination among the scheduled pediatric DI appointments. Nonetheless, inequities based on patient features such as low income and language barrier did exist.

Association of plant-based dietary patterns with metabolic syndrome: baseline results from the Persian Kavar cohort study (PKCS).

Plant-based diets (PBDs) have gained a positive reputation among experts as a solution to combat the epidemic of MetS. A total of 2225 healthy Iranian individuals aged 35-70 years were considered eligible to be included in this cross-sectional investigation. Various dietary, anthropometric, and biochemical assessments were conducted using standard, valid methods/tools. Relevant PBD scores were calculated using three a posteriori indices, including the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). Our findings showed that women with the highest adherence to hPDI had a lower chance of MetS. Also, participants in the top tertiles of hPDI were more likely to have a lower risk of low serum HDL-c and abnormal glucose homeostasis. Additionally, a significant increasing trend was observed for low serum HDL-c across tertiles of uPDI. Our observations suggest that healthful-rich plant foods may have a protective effect against MetS, especially in women.

INTERDEPENDENCE OF SKIN AND UTERUS IN PERSIAN MEDICINE

Persian Medicine, which flourished in the Islamic Golden Age (9th to 12th century AD), considers the human body a unified whole whose organs are in constant interaction and equilibrium with each other. The skin is one of these interdependent organs that play an important role in protecting internal organs, and as an excretion route, it can expel substances that are not consumed by the body. Alternatively, the uterus, a vital organ in pregnancy, excretes excess body material during menstruation to maintain a woman's health. This narrative study discussed the importance of aligning the structure and function of these two organs based on the main textbooks of Persian Medicine, especially those written during this historical period. Likewise, electronic databases were used for investigating related articles. The skin and uterus are two excretory organs. When the secretion of excess material through menstruation is physiologically or pathologically impaired, the body transfers these substances to the skin as the organ associated with the uterus. Thus, the clinical manifestations of some skin diseases can be a sign of imbalance in the function of the uterus and its related organs. Consequently, the structural and functional similarities of both organs can provide a new guide in the approach to their participatory diseases in the integration of Persian and conventional medicine.

Bioengineered synthesis of phytochemical-adorned green silver oxide (Ag2O) nanoparticles via Mentha pulegium and Ficus carica extracts with high antioxidant, antibacterial, and antifungal activities.

Silver oxide nanoparticles have various biomedical and pharmaceutical applications. However, conventional nanofabrication of Ag2O is associated with the use of toxic chemicals and organic solvents. To circumvent this hurdle, herein silver oxide quantum dots (Ag2O-QDs) were synthesized quickly (3 min) via the use of ultrasonic irradiation and plant-extract. Additionally, due to ultrasonic irradiation's effect on cell-wall destruction and augmentation of extraction efficiency, ultrasonic was also used in the preparation of Mentha pulegium and Ficus carica extracts (10 min, r.t) as natural eco-friendly reducing/capping agents. The UV-Vis result indicated a broad absorption peak at 400-500 nm. TEM/SEM analysis showed that ultrasound introduced a uniform spherical particle and significantly reduced particle size compared to the conventional heating method (∼ 9 nm vs. ∼ 100 nm). Silver and oxygen elements were found in the bio-synthesized Ag2O by EDS. The FTIR and phenol/flavonoid tests revealed the presence of phenol and flavonoid associated with the nanoparticles. Moreover, nanoparticles exhibited antioxidant/antibacterial/antifungal activities. The MIC and MBC results showed the Ag2O QDs synthesized with M. pulegium extract have the highest antibacterial activity against E. coli (MBC = MIC:15.6 ppm), which were significantly different from uncoated nanoparticles (MBC = MIC:500 ppm). The data reflects the role of phyto-synthesized Ag2O-QDs using ultrasonic-irradiation to develop versatile and green biomedical products.

Very rapid synthesis of highly efficient and biocompatible Ag2Se QD phytocatalysts using ultrasonic irradiation for aqueous/sustainable reduction of toxic nitroarenes to anilines with excellent yield/selectivity at room temperature.

There are many problems associated with the synthesis of nanocatalysts and catalytic reduction of nitroarenes - e.g., high temperatures, costs, long reaction/synthesis process times, the toxicity of chemicals/solvents, undesirable byproducts, the toxic/harmful wastes, low efficiency/selectivity, etc. This study represents an attempt to overcome these challenges. To this purpose, biocompatible and highly efficient Ag2Se quantum dots (QDs) catalysts with antibacterial activity were synthesized in a very rapid (30 sec, rt), simple, inexpensive, sustainable/green, and one-pot strategy in water using ultrasonic irradiation. Characterization of the QDs was performed using different techniques. UV-Vis absorption and fluorescence spectroscopic studies showed an absorption peak at 480-550 nm and a maximum emission peak around 675 nm, which confirmed the successful synthesis of Ag2Se QDs via the applied biosynthetic method. Subsequently, catalytic reduction of nitroarenes by them was carried out under safe conditions (H2O, rt, air atmosphere) in âˆ¼ 60 min with excellent yield and selectivity (>99%). Their catalytic activity in the reduction of various toxic nitroarenes to aminoarenes under green conditions was investigated. Thus, a rapid and safe ultrasound-based method was employed to prepare stable and green Ag2Se QDs phyto-catalysts with unique properties, including exquisite monodispersity in shape (orthorhombic) and size (∼7 nm), air-stability, and good purity and crystallinity. Importantly, instead of various toxic chemicals, the plant extract obtained by rapid ultrasonic method (10 min, rt) was used as natural reducing, capping, and stabilizing agents. Moreover, antibacterial assays results showed that Ag2Se-QDs catalysts at low concentrations (ppm) have high activity against all tested bacteria, especially E. coli (MIC:31.25 ppm, MBC:125 ppm) which were significantly different from those of Fig extract (MIC = MBC:500 ppm). The data reflect the role of these bio-synthesized Ag2Se-QDs catalysts in the development of versatile and very safe catalysts with biomedical properties.

The Role of Bloodletting and Cupping in Severe Acute Urticaria and Angioedema as Skin Emergencies in Persian Medicine.

Objectives: Some dermatological diseases can be life-threatening. Urticaria and angioedema are common reasons for patients to seek treatment at an emergency department. Severe, generalized urticaria and angioedema can endanger patients' lives by involving the airways and causing anaphylactic shock. The humor-based Persian Medicine (PM) concepts of Shara and Mashara, referring to two kinds of skin lesions, have similarities to urticaria and angioedema, respectively. This article aims to provide scientific evidence regarding the application of PM as an early intervention strategy in the emergency management of urticaria and angioedema. Methods: This was a narrative review of PM studies identified by searching medical databases using search terms related to these diseases, as well as risk-associated keywords such as "fatal", "death", "life-threatening", "emergency", "cupping", and "bloodletting". Data were then compared, interpreted, and analyzed. Results: PM scholars consider the human body as a unified whole and believe in an inner power (Nature) which stems from the body. When the presence of excessive hot substances cause an imbalance of bodily humors, Nature directs their heated vapors sharply toward the skin, thus causing Shara and Mashara. If there is a high risk of inflammation spreading to vital organs under severe conditions, urgent manual interventions are crucial. Conclusion: In serious conditions of urticaria and angioedema, Fasd or bloodletting and Hijama can be effective in speeding up the control of lesions and reducing morbidity and mortality. Consequently, the development of integrated Persian and conventional medicines may provide new therapeutic pathways for skin emergencies.

Co-administration of rotavirus nanospheres VP6 and NSP4 proteins enhanced the anti-NSP4 humoral responses in immunized mice.

Inconveniences associated with the efficacy and safety of the World Health Organization (WHO) approved/prequalified live attenuated rotavirus (RV) vaccines, sounded for finding alternative non-replicating modals and proper RV antigens (Ags). Herein, we report the development of a RV candidate vaccine based on the combination of RV VP6 nanospheres (S) and NSP4112-175 proteins (VP6S + NSP4). Self-assembled VP6S protein was produced in insect cells. Analyses by western blotting and transmission electron microscopy (TEM) indicated expression of VP6 trimer structures with sizes of ≥140 kDa and presence of VP6S. Four group of mice were immunized (2-dose formulation) intra-peritoneally (IP) by either¨VP6S + NSP4¨ or each protein alone (VP6S or NSP4112-175) emulsified in aluminium hydroxide or control. Results indicated that VP6S + NSP4 formulation induced significant anti-VP6 IgG (P < 0.001) and IgA (P < 0.05) as well as anti-NSP4 IgG (P < 0.001) and enhancement of protective immunity. Analyses of anti-VP6S and anti-NSP4 IgG subclass (IgG1 and IgG2a) showed IgG1/IgG2a ≥6 and IgG1/IgG2a ≥3 ratios, respectively indicating Th2 polarization of immune responses. The combination of VP6S + NSP4 proteins emulsified in aluminum hydroxide adjuvant might present a dual universal, efficient and cost-effective candidate vaccine against RV infection.

The Effect of Occupational Stress and Concerns about the COVID-19 Pandemic on Secondary Traumatic Stress Syndrome among Iranian Frontline Nurses: A Mediating Model.

Objective: With the increasing effects of stress caused by the COVID-19 pandemic and occupational stress on the mental health of frontline nurses, it is imperative to further investigate how these stresses affect nurses' mental health and secondary traumatic stress syndrome. This research aimed to investigate the relationship of nurses' occupational stress and concerns about COVID-19 with secondary traumatic stress syndrome, and also to investigate the mediating effect that concerns about the COVID-19 pandemic have on the relationship between nurses' occupational stress and secondary traumatic stress syndrome. Method : A cross-sectional design was adopted. The population of the study was defined as all front-line nurses in Shiraz hospitals, from which 225 nurses of two corona care hospitals were selected using convenience sampling. The degree of secondary traumatic stress, concerns about the COVID-19, and nurses' occupational stress were assessed using Bride's Secondary Traumatic Stress Scale (STSS), an adopted version of Level of Concerns about the COVID-19 questionnaire, and the Nurses' Occupational Stressor Scale (NOSS) among Hospital-based Healthcare Workers. Structural equation modeling (SEM) was used to examine the relationships among variables. Results: Results showed that nurses' occupational stresses presented a direct effect on nurses' level of concern about the COVID-19 pandemic (ß = 0.85, P < 0.001), and concern about the COVID-19 pandemic was directly related to front-line nurse's secondary traumatic stress syndrome (ß = 0.83, P < 0.001). In addition, nurses' level of concern about the COVID-19 pandemic fully mediated the effects of nurses' occupational stresses on their secondary traumatic stress (ß = 0.70, P < 0.001). This indirect effect has explained 68% of the variance in nurses' secondary traumatic stress. Conclusion: These results emphasized the indirect effect of nurses' occupational stresses on secondary traumatic stress syndrome via mediating the level of concern about COVID-19. Therefore, to reduce the secondary traumatic stress of nurses who have dealt directly with COVID-19 patients, it seems necessary to pay serious attention to the sources of their occupational stress, which probably existed even before this pandemic and increased their concerns in pandemic conditions.

Heterologous administration of HPV16 E7 epitope-loaded nanocomplexes inhibits tumor growth in mouse model.

The nanostructured complexes can result in enhanced vaccine efficacy by facilitating the distribution and uptake of antigens by antigen-presenting cells (APCs), thereby stimulating immune responses. Here, we hypothesized that either directly coating of nanoadjuvants including aluminum phosphate (AlPO4) and adenovirus (Ad) with a modified HPV16 E7 MHC-I specific epitope, RAHYNIVTF49-57, or mixing the CpG oligodeoxynucleotide (CpG-ODN) with the cationic epitope to form nanocomlexes, and their combinational therapy would enhance their anti-tumor effects in a TC-1 mouse model. The positively-charged HPV16 E7 epitope was attracted to the oppositely-charged adjuvants by electrostatic interaction to generate epitope/adjuvant nanocomplexes. We showed that coating the nanosized adjuvants with the cationic epitope increased the particles' surface charge without significant change in their size. We then tested the cellular immunogenicity and therapeutic efficacy of nanocomplexes by measuring IL-10 and IFN-γ production, the expression of CD107a as a marker of CTL response, and tumor growth inhibition. The nanocomplexes were administered either in homologous or heterologous prime-boost regimens, and heterologous immunizations including Ad/Pep-CpG/Pep, CpG/Pep-Ad/Pep, Ad/Pep-Alum/Pep, and Alum/Pep-Ad/Pep induced significantly higher levels of IL-10, IFN-γ, and CD107a-expressing CD8 T cells compared with homologous administrations. Furthermore, the tumor growth was significantly suppressed in mice receiving nanostructured complexes in the heterologous immunizations. Our study highlights the potential of the heterologous prime-boost administration of the epitope-coated nanostructures as an effective immunization strategy.