Reprogramming macrophage by targeting VEGF and CD40 potentiates OX40 immunotherapy.

The low clinical response rate of checkpoint blockades, such as PD-1 and CTLA-4, highlighted the requirements of agonistic antibodies to boost optimal T cell responses. OX40, a co-stimulatory receptor on the T cells, plays a crucial role in promoting T cell survival and differentiation. However, the clinical efficacy of anti-OX40 agonistic antibodies was unimpressive. To explore the mechanism underlying the action of anti-OX40 agonists to improve the anti-tumor efficacy, we analyzed the dynamic changes of tumor-infiltrating immune cells at different days post-treatments using single-cell RNA-sequencing (scRNA-seq). In this study, we found that tumor-infiltrating regulatory T (Treg) cells were reduced after two rounds of anti-OX40 treatment, but the increase of infiltration and activation of CD8+ effector T cells, as well as M1 polarization in the tumor were only observed after three rounds of treatments. Moreover, our group first analyzed the antitumor effect of anti-OX40 treatments on regulating the macrophages and discovered the dynamic changes of vascular endothelial growth factor (VEGF) and CD40 signaling pathways on macrophages, indicating their possibility to being potential combination targets to improve the anti-OX40 agonists efficacy. The combination of VEGFR inhibitors or anti-CD40 agonist antibody with anti-OX40 agonists exhibited more remarkable inhibition of tumor growth. Therefore, the mechanism-driven combination of anti-OX40 agonists with VEGFR inhibitors or anti-CD40 agonists represented promising strategies.

Intestinal metabolite xylulose inhibits colorectal cancer by inducing apoptosis through the MAPK signalling pathway.

BACKGROUND: The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. RESULTS: We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. CONCLUSION: Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.

Genetically engineered membrane-based nanoengagers for immunotherapy of pancreatic cancer.

Modulating macrophages presents a promising avenue in tumor immunotherapy. However, tumor cells have evolved mechanisms to evade macrophage activation and phagocytosis. Herein, we introduced a bispecific antibody-based nanoengager to facilitate the recognition and phagocytosis of tumor cells by macrophages. Specifically, we genetically engineered two single chain variable fragments (scFv) onto cell membrane: anti-CD40 scFv for engaging with macrophages and anti-Claudin18.2 (CLDN18.2) scFv for interacting with tumor cells. These nanoengagers were further constructed by coating scFv-anchored membrane into PLGA nanoparticle core. Our developed nanoengagers significantly boosted immune responses, including increased recognition and phagocytosis of tumor cells by macrophages, enhanced activation and antigen presentation, and elevated cytotoxic T lymphocyte activity. These combined benefits resulted in enhancing antitumor efficacy against highly aggressive "cold" pancreatic cancer. Overall, this study offers a versatile nanoengager design for immunotherapy, achieved through genetically engineering to incorporate antibody-anchored membrane.

Development and validation of a novel nomogram model predicting the unfavorable outcome based on NAR and collaterals status for patients with AIS.

INTRODUCTION: Stroke is a leading cause of disability and mortality globally. This study aimed to develop a prognostic nomogram based on neutrophil-to-albumin ratio (NAR) and collateral status in acute ischemic stroke (AIS) patients with anterior large vessel occlusion (LVO). MATERIAL & METHOD: 590 AIS patients with LVO assessed for regional leptomeningeal collateral (rLMC) were retrospectively enrolled, and randomly divided into a training set (n = 414) and a testing set (n = 176). Unfavorable functional outcome was defined as a modified Rankin scale (mRS) score of 3 to 6 at 3 months. We assessed the accuracy and clinical utility of the nomogram using calibration plots, area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: Both NAR and rLMC were independently associated with unfavorable outcome at 3 months (OR=8.96, p=0.0341; OR=0.89, p=0.0002, respectively). The developed nomogram (akaike information criterion (AIC)=398.77), which included NAR, rLMC and other factors, showed good performance (the AUC for the development and validation cohorts was 0.848 and 0.840 respectively) and improved the predictive value compared to a model without NAR and rLMC, according to an overall NRI of 3.27% (p=0.2401), overall IDI of 3.27% (p=0.2414), and a higher AUC (0.848 vs 0.831). CONCLUSIONS: NAR can serve as an independent predictor in AIS patients with anterior LVO, and the nomogram incorporating NAR and rLMC is reliable in predicting unfavorable outcome. Further studies with larger sample sizes are needed to validate and extend these findings.

College students' influenza vaccine hesitation: a reasoned action investigation with quantitative and qualitative data.

This two-wave longitudinal study (performed pre-COVID), using both quantitative and qualitative data, investigated college students' influenza vaccine hesitancy and confidence using the theory of planned behavior (TPB). At Time 1, college students (n = 277) completed TPB measures and reported past influenza vaccine behavior. At Time 2 (30 days later), participants indicated whether they received the influenza vaccine since Time 1. At Time 2, participants who indicated that they had not received the influenza vaccine since Time 1 also described their most important reasons for not doing so. The TPB model fit the quantitative data well; direct paths from attitude and norms to intention, and from intention to future behavior, were strong and significant. The TPB model explained 71% of the variance in intention and 28% of the variance in future behavior. Neither perceived behavioral control nor past behavior improved the model's ability to predict intentions or future behavior. From the qualitative data, participants' reasons for not getting vaccinated focused on perceived behavioral control (e.g., time cost) and attitudes (e.g., unimportance and low susceptibility). Theoretical implications for message development are discussed.

A Randomized Controlled Trial of A Theory-Based Concussion Education Video for NCAA Division I Athletes.

A large body of research demonstrates that concussions are exceedingly common and extremely difficult to detect. Despite medical efforts to develop sophisticated tools to detect concussions, research continues to demonstrate that proper detection relies on prompt and thorough symptom reporting from the injured athlete. In the context of sports, such reporting requirements are complicated by systems that reward athletic performance. This study seeks to provide student athletes who play NCAA Division I high-contact sports with a theoretically driven intervention to improve their attitudes and behavior toward concussion reporting. Division I student athletes (N = 345) viewed one of three conditions: an NCAA handout consistent with current practices, the experimental video, or a non-treatment control video, then responded to questions regarding attitudes and behaviors toward concussion reporting. Overall, results support the video's effectiveness in changing perceptions of concussion injuries. Nuances of the findings lead to a discussion for practical implications to transform concussion-reporting attitudes and behaviors among athletes.

Prognostic prediction of idiopathic membranous nephropathy using interpretable machine learning.

BACKGROUND: Established prognostic models of idiopathic membranous nephropathy (IMN) were limited to traditional modeling methods and did not comprehensively consider clinical and pathological patient data. Based on the electronic medical record (EMR) system, machine learning (ML) was used to construct a risk prediction model for the prognosis of IMN. METHODS: Data from 418 patients with IMN were diagnosed by renal biopsy at the Fifth Clinical Medical College of Shanxi Medical University. Fifty-nine medical features of the patients could be obtained from EMR, and prediction models were established based on five ML algorithms. The area under the curve, recall rate, accuracy, and F1 were used to evaluate and compare the performances of the models. Shapley additive explanation (SHAP) was used to explain the results of the best-performing model. RESULTS: One hundred and seventeen patients (28.0%) with IMN experienced adverse events, 28 of them had compound outcomes (ESRD or double serum creatinine (SCr)), and 89 had relapsed. The gradient boosting machine (LightGBM) model had the best performance, with the highest AUC (0.892 ± 0.052, 95% CI 0.840-0.945), accuracy (0.909 ± 0.016), recall (0.741 ± 0.092), precision (0.906 ± 0.027), and F1 (0.905 ± 0.020). Recursive feature elimination with random forest and SHAP plots based on LightGBM showed that anti-phospholipase A2 receptor (anti-PLA2R), immunohistochemical immunoglobulin G4 (IHC IgG4), D-dimer (D-DIMER), triglyceride (TG), serum albumin (ALB), aspartate transaminase (AST), ß2-microglobulin (BMG), SCr, and fasting plasma glucose (FPG) were important risk factors for the prognosis of IMN. Increased risk of adverse events in IMN patients was correlated with high anti-PLA2R and low IHC IgG4. CONCLUSIONS: This study established a risk prediction model for the prognosis of IMN using ML based on clinical and pathological patient data. The LightGBM model may become a tool for personalized management of IMN patients.

The application and effect of predictive nursing in the prevention of accidental events during operations for SMI patients.

OBJECTIVE: To explore the status and influencing factors of job burnout among psychiatric nurses and provide a reference for hospital managers to carry out occupational and psychological interventions. METHODS: Between September 2021 and September 2022, the psychiatric nurses in Wuhan Wudong Hospital (Wuhan Second Psychiatric Hospital) were selected as research participants using convenience sampling. The Chinese version of the nursing burnout scale was used to investigate the psychiatric nurses in the hospital, and a multiple linear regression analysis was performed on the factors affecting job burnout. RESULTS: Among the 121 psychiatric nurses, 57.85 % had no or only mild job burnout, 36.36 % had mild to moderate job burnout and 5.79 % had severe job burnout. The one-way analysis of variance indicated that there were statistical differences in the scores in terms of marital status, educational background, working years, income, work departments and shifts (p < 0.05). The multiple linear regression analysis indicated that the main influencing factors of job burnout were working years and work department (p < 0.05). CONCLUSION: The detection rate of nurses' job burnout in the featured psychiatric hospital was 42.10 %. The main influencing factors of job burnout were working years and work department, and targeted intervention can be carried out according to these two factors.

Development and validation of a prognostic nomogram based on objective nutritional indexes in ischemic stroke patients with large vessel occlusion undergoing endovascular thrombectomy.

BACKGROUND AND AIMS: Preserved nutritional status in acute ischemic stroke patients with large vessel occlusion (LVO) undergoing endovascular thrombectomy (EVT) is important but lacks an effective evaluation method. We aimed to investigate the prognostic value of objective nutritional indexes (ONIs) in LVO patients after EVT that were validated by studies in patients with other vascular diseases receiving intervention therapy and to develop a functional prediction nomogram for better stroke management. METHODS AND RESULTS: LVO patients undergoing EVT from 2016 to 2020 were retrospectively enrolled and randomly classified into training and validation cohorts at a ratio of 7:3. The ONIs, including the Controlling Nutritional Status (CONUT) score, Nutritional Risk Index (NRI), and Prognostic Nutritional Index (PNI), were calculated. A stepwise logistic regression model for 3-month poor functional outcome based on the smallest Akaike information criterion was employed to develop the nomogram, and the nomogram's determination and clinical use were tested by area under the curve (AUC), calibration plots, and decision curve analysis and compared with three earlier prognostic models. A total of 418 patients were enrolled. The CONUT independently related and increased the risk of 3-month poor functional outcome with an OR of 1.387 (95% CI: 1.133-1.698, p = 0.002). A nomogram including CONUT and other seven factors (AIC = 274.568) was developed. The AUC of the nomogram was 0.847 (95% CI: 0.799-0.894) and 0.836 (95% CI: 0.755-0.916) in the training and validation cohort, respectively, with better predictive performance and clinical utility than previous models. CONCLUSION: The CONUT independently related to the poor functional outcome, and the newly established nomogram reliably predicted the functional outcome in LVO patients after EVT.

Prolonged viral shedding in feces of children with COVID-19: a systematic review and synthesis of data.

During the coronavirus disease 2019 (COVID-19) epidemic, many reports have indicated that children shed the virus longer than adults in stool, and that most of the children had mild or even asymptomatic infections, which increased the potential risk for feces to be a source of contamination and may play an important role in the spread of the virus. In this review, we collected relevant literature to summarize the duration of fecal viral shedding in children with COVID-19. We found that in about 60% of the cases, the fecal shedding time was between 28 and 42 days, which was much longer than that of adults. We further explored the possible reason for prolonged shedding and its the potential impact. The poor hand hygiene practices of children, their tendency to swallow sputum and/or saliva, the significant difference in expression of angiotensin-converting enzyme 2 (ACE2) in intestine between children and adults, and the variance in immune status and intestinal microbiome could be considered as potential casual agents of longer fecal viral shedding duration of children.   Conclusion: Children with COVID-19 show prolonged fecal shedding compared to adults. Several mechanisms may be involved in the longer fecal viral shedding. Viral shedding in the stool could be contributing to a possible route of transmission. Therefore, we think that further preventive measures in children should be taken to reduce the spread of the disease. What is Known: • Children with COVID-19 are more likely to have asymptomatic infections and to experience mild symptoms. • Some patients continue to shed the virus in feces, despite respiratory samples testing negative. What is New: • Children with COVID-19 carried a longer-term fecal viral shedding than adults. • The poor hand hygiene practices of children, their tendency to swallow sputum and/or saliva, the difference in expression of ACE2 in intestine between children and adults, and the variance in immune status and intestinal microbiome could be considered as potential casual agents of longer fecal viral shedding duration of children.

Discovery of Novel Non-Oxime Reactivators Showing In Vivo Antidotal Efficiency for Sarin Poisoned Mice.

A family of novel efficient non-oxime compounds exhibited promising reactivation efficacy for VX and sarin inhibited human acetylcholinesterase was discovered. It was found that aromatic groups coupled to Mannich phenols and the introduction of imidazole to the ortho position of phenols would dramatically enhance reactivation efficiency. Moreover, the in vivo experiment was conducted, and the results demonstrated that Mannich phenol L10R1 (30 mg/kg, ip) could afford 100% 48 h survival for mice of 2*LD50 sarin exposure, which is promising for the development of non-oxime reactivators with central efficiency.

In vitro assessment of the dermal penetration potential of sodium fluoroacetate using a formulated product.

This paper presents experimental data on the skin absorption of sodium fluoroacetate from a formulated product using an in vitro approach and human skin. Sodium fluoroacetate is a pesticide, typically applied in formulation (1080) for the control of unwanted vertebrate invasive species. It has been assigned a Skin Notation by the ACGIH, and other international workplace health regulatory bodies, due to its predicted ability to permeate intact and abraded human skin. However, there is a distinct lack of experimental data on the skin absorption of sodium fluoroacetate to support this assignment. This study found that sodium fluoroacetate, as a formulated product, permeated the human epidermis when in direct contact for greater than 10 hr. A steady-state flux (Jss) of 1.31 ± 0.043 µg/cm2/hr and a lag time of 6.1 hr was calculated from cumulative skin permeation data. This study provides important empirical evidence in support of the assignment of a Skin Notation.

Histone deacetylase 9 deficiency exaggerates uterine M2 macrophage polarization.

The maternal-foetal interface is an immune-privileged site where the semi-allogeneic embryo is protected from attacks by the maternal immune system. Uterine macrophages are key players in establishing and maintaining pregnancy, and the dysregulation of the M1-M2 subpopulation balance causes abortion. We separated two distinct mouse uterine macrophage subpopulations during early pregnancy, CD45+ F4/80+ CD206- M1-like (M1) and CD45+ F4/80+ CD206+ M2-like (M2) cells. The M1 preponderance was significantly exaggerated at 6 hours after lipopolysaccharide (LPS) treatment, and adoptive transfer of M2 macrophages partially rescued LPS-induced abortion. RNA sequencing analysis of mouse uterine M2 versus M1 revealed 1837 differentially expressed genes (DEGs), among which 629 was up-regulated and 1208 was down-regulated. Histone deacetylase 9 (Hdac9) was one of the DEGs and validated to be significantly up-regulated in uterine M2 as compared with M1. Remarkably, this differential expression profile between M1 and M2 was also evident in primary splenic macrophages and in vitro polarized murine peritoneal, bone marrow-derived and RAW 264.7 macrophages. In Hdac9/HDAC9 knockout RAW 264.7 and human THP-1-derived macrophages, the expression of M1 differentiation markers was unchanged or decreased whereas M2 markers were increased compared with the wild-type cells, and these effects were unrelated to compromised proliferation. Furthermore, Hdac9/HDAC9 ablation significantly enhanced the phagocytosis of fluorescent microspheres in M2 Raw 264.7 cells yet decreased the capacity of THP-1-derived M1 macrophages. The above results demonstrate that Hdac9/HDAC9 deficiency exaggerates M2 macrophage polarization in mouse and human macrophages, which may provide clues for our understanding of the epigenetic regulation on macrophage M1/M2 polarization in maternal-foetal tolerance.

The impact of COVID-19 pandemic on headache symptoms and drug withdrawal among patients with medication overuse headache: a cross-sectional study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) bring about a range of psychological distress and symptom deterioration to headache patients especially to some migraineurs. Compared to migraineurs or normal control, medication overuse headache (MOH) patients are more likely to experience a worse psychological distress and poorer outcome in non-COVID-19 time. However, in COVID-19 pandemic, whether MOH patients would have greater physical and mental symptom deterioration or worse relief of headache symptoms and medications overuse remained unclear. We aim to investigate the impact of COVID-19 on MOH patients to guide for a better management in this study. METHODS: We enrolled MOH patients who were diagnosed and treated at headache clinic of West China Hospital. Information of the pre-pandemic 3 months period and COVID-19 pandemic period was collected. Univariate and multivariate logistic regression were performed to identify independent factors associated with changes in headache symptoms and drug withdrawal. RESULTS: Seventy-eight MOH patients were enrolled into the study ultimately. In comparison to pre-pandemic period, fewer MOH patients reported decreased headache days, intensity and days with acute medications per month during the pandemic. Available access to regular prophylactic medications was significantly associated with a reduction of at least 50% in headache days and decrease in headache intensity per month with respective odds ratios of 39.19 (95% CI 3.75-409.15, P = 0.002) and 10.13 (95% CI 2.33-44.12, P = 0.002). Following abrupt withdrawal and high educational level were both significant factors in decreasing headache intensity. Male sex was significantly associated with decrease in days with acute medication per month during the pandemic (odds ratios 4.78, 95%CI 1.44-15.87, P = 0.011). CONCLUSIONS: Our findings reflect that MOH patients experienced a worse relief of headache symptoms and drug withdrawal during the pandemic. Available access to regular prophylactic medications was the significant independent factor for improvement of headache symptoms. Male sex was significantly associated with decreased days with acute medications per month.

Cytochrome P450 26A1 modulates uterine dendritic cells in mice early pregnancy.

Cytochrome P450 26A1 (CYP26A1) plays important roles in the mice peri-implantation period. Inhibiting its expression or function leads to pregnancy failure. However, little is known about the underlying mechanisms involved, especially the relationship between CYP26A1 and immune cells. In this study, using Cyp26a1-specific antisense morpholigos (Cyp26a1-MO) knockdown mice model and pCR3.1-Cyp26a1 vaccine mice model, we found that the number of uterine CD45+ CD11c+ MHCIIlo-hi F4/80- dendritic cells (DCs) was significantly decreased in the treated mice. The percentage of mature DCs (CD86hi ) was obviously lower and the percentage of immature DCs (CD86lo ) was remarkably higher in uterine DCs in the treatment group than that of the control group. Further experiments found that ID2, a transcription factor associated with DCs development, and CD86, a DC mature marker molecule, were both significantly reduced in mice uteri in the treated group. In vitro, ID2 and CD86 also decreased in bone marrow-derived DCs under Cyp26a1-MO treatment. These findings provide novel information that CYP26A1 might affect the embryo implantation via modulating the differentiation and maturation of uterine DCs.

C-Phycocyanin from Spirulina Inhibits α-Synuclein and Amyloid-ß Fibril Formation but Not Amorphous Aggregation.

Proteinopathies including cataracts and neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are characterized by a series of aberrant protein folding events, resulting in amorphous aggregate or amyloid fibril formation. In the latter case, research has heavily focused on the development of small-molecule inhibitors with limited success during clinical trials. However, very few studies have focused on utilizing exogenous proteins as potential aggregation inhibitors. C-Phycocyanin, derived from Spirulina sp., has been known to exert anti-inflammatory properties; however, the ability of C-phycocyanin to inhibit protein aggregation has yet to be investigated. We have demonstrated that C-phycocyanin is an effective inhibitor of A53Tα-synuclein at extremely low substoichiometric ratios (200-fold excess of α-synuclein) and Aß40/42 fibril formation. However, C-phycocyanin is relatively ineffective in inhibiting the reduction-induced amorphous aggregation of ADH and heat-induced aggregation of catalase. In addition, 2D NMR, ion mobility-mass spectrometry, and analytical-SEC demonstrate that the interaction between C-phycocyanin and α-synuclein is through nonstable interactions, indicating that transient interactions are likely to be responsible for preventing fibril formation. Overall, this work highlights how biomolecules from natural sources could be used to aid in the development of therapeutics to combat protein misfolding diseases.

The faster-onset antidepressant effects of hypidone hydrochloride (YL-0919).

Hypidone hydrochloride (YL-0919), is a novel structural antidepressant candidate as a triple selective serotonin re-uptake inhibitor (SSRI), 5-HT1A partial agonist and 5-HT6 agonist. Here, we investigated the rapid onset antidepressant-like effects of YL-0919 and the possible mechanism in rats exposed to a chronic unpredictable stress (CUS) paradigm. In the CUS rats, it was found that fluoxetine (FLX, 10 mg/kg) treatment exerted antidepressant actions on 20-22d, while YL-0919 or vilazodone (VLZ, a dual 5-HT1A partial agonist and SSRI) administrated once daily exerted faster antidepressant-like behaviors [4 days in the sucrose preference test (SPT) and 6 days in the novelty suppressed feeding test (NSF)]. Thereafter, the serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels were reversed by treatment with YL-0919 for 7 days. Furthermore, YL-0919 treatment for 5 days reversed the brain derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling and the key synaptic proteins, such as post-synaptic density (PSD95), GluR1 and presynaptic protein synapsin1. Meanwhile, the dendritic complexity of pyramidal neurons in prefrontal cortex (PFC) were also increased in the CUS rats. These data suggest that YL-0919 exerts a faster antidepressant-like effect on behaviors and this effect maybe at least partially mediated by the BDNF-mTOR signaling related dendritic complexity increase in the PFC.

Beyond Altruism: Framing Organ Donation in a 19-year Review of Chinese News Coverage.

Despite a significant legal transformation of the organ donation system in China, the public's willingness to become organ donors remains low. This study provides the first empirical examination of how Chinese newspaper coverage reflects the complex interplay among multifaceted factors associated with the stagnant donation rate. Using framing as the primary theoretical lens, we analyzed 923 organ donation newspaper articles from 2000 to 2018 in terms of topics, facilitators and barriers, valence, and policy development. The three most common topics emphasized were: a new official information release regarding organ donation promotion; the challenges of promoting organ donation in social, cultural, and legal contexts; and the positive emotional appeals of organ donors, coordinators, and transplant surgeons. Findings suggest that the values that facilitators of and barriers to organ donation represent can be culturally favored but in conflict with each other. Sharp increases in the presence of policy development framing are associated with the official announcements of new legislation. A better understanding of trending topics and interacting influence from facilitators and barriers is imperative for developing culturally tailored messages to raise awareness about organ donation promotion.

"Fear the Flu, Not the Flu Shot": A Test of the Extended Parallel Process Model.

This study investigates the effects of manipulated threat and efficacy on college students' attitudes, intentions, and behavior toward receiving the influenza vaccine (flu shot). Meta-analysis results indicate that during the nearly 70-year history of fear-appeal research, as few as six studies have orthogonally manipulated threat and efficacy, randomly assigned participants to conditions, and included a behavioral dependent variable. While there may be several practical reasons for this, it is problematic theoretically. The primary goal of this study is to add to this small but important body of literature. We tested the Extended Parallel Process Model, utilizing a 2 (high threat/low threat) × 2 (high efficacy/low efficacy) between-subjects design with random assignment to conditions. Dependent variables were attitudes and intentions regarding the flu shot (measured immediately after reading the message at Time 1) and flu shot behavior (measured 30 days later at Time 2). Results indicate that participants in the high threat condition reported greater perceived severity, susceptibility, and fear than participants in the low threat condition; and that that participants in the high-efficacy condition reported greater self-efficacy and response-efficacy than individuals in the low efficacy condition. Nonetheless, the predicted threat × efficacy interaction was not observed for attitude, intention, or behavior. Instead, there was a main effect for efficacy (but not threat) on attitudes and intentions, and no effect for either efficacy or threat on behavior. The theoretical and practical implications of these findings are discussed.

Design, synthesis and evaluation of new classes of nonquaternary reactivators for acetylcholinesterase inhibited by organophosphates.

A new series of nonquaternary conjugates for reactivation of both nerve agents and pesticides inhibited hAChE were described in this paper. It was found that substituted salicylaldehydes conjugated to aminobenzamide through piperidine would produce efficient reactivators for sarin, VX and tabun inhibited hAChE, such as L6M1R3, L6M1R5 to L6M1R7, L4M1R3 and L4M1R5 to L4M1R7. The in vitro reactivation experiment for pesticides inhibited hAChE of these new synthesized oximes were conducted for the first time. Despite they were less efficient than obidoxime, some of them were highlighted as equal or more efficient reactivators in comparison to 2-PAM. It was found that introduction of peripheral site ligands could increase oximes' binding affinity for inhibited hAChE in most cases, which resulted in greater reactivation ability.