Effect of Blood Decontamination Procedures on the Microshear Bond Strength of Resin-modified Glass Ionomer Cement to Resin Composite.

OBJECTIVE: To investigate the effect of decontamination procedures on the microshear bond strength (µSBS) of blood-contaminated resin-modified glass ionomer cement (RMGIC) bonded to resin composite (RC). METHODS: Eighty RMGIC disc specimens were allocated into 5 groups (n=16). All groups except Group 2 were contaminated with blood. Group 1 had no decontamination procedure, Group 3 was decontaminated by rinsing, Group 4 was decontaminated by 34% phosphoric acid etching, and Group 5 was decontaminated by 5% sodium hypochlorite application. RMGIC specimens were subsequently bonded with RC using a universal adhesive in self-etch mode. µSBS tests were conducted using a universal testing machine at a crosshead speed of 1 mm/min. Failure mode analysis was conducted on RMGIC fracture surfaces under a scanning electron microscope. RESULTS: µSBS results indicated that Group 4 had the highest mean µSBS value of 6.22 ± 2.14 MPa, while Group 1 had the lowest mean µSBS value of 3.53 ±1.67 MPa. Significant differences were observed in the µSBS of Group 2 with no contamination (p=0.023) and Group 4 with decontamination by phosphoric acid-etching (p=0.003) when compared to Group 1 with blood contamination. No statistically significant differences (p>0.05) were observed between all other groups' µSBS. For all groups, the predominant mode of failure was adhesive failure between the RMGIC-RC interface, with a few mixed failures in RMGIC for Groups 2-5. CONCLUSIONS: Blood contamination before adhesive application significantly reduced the µSBS between RMGIC and RC. Phosphoric acid etching was the most effective blood decontamination procedure to improve the µSBS.

Providers' and survivors' perspectives on the availability and accessibility of surgery in gastrointestinal cancer care.

BACKGROUND: Surgery is essential for gastrointestinal (GI) cancer treatment. Many patients lack access to surgical care that optimizes outcomes. Scarce availability and/or low accessibility of appropriate resources may be the reason for this, especially in economically disadvantaged areas. This study aimed to investigate providers' and survivors' perspectives on barriers and facilitators to the availability and accessibility of surgical care. METHODS: Semistructured interviews informed by surgical disparities and access-to-care conceptual frameworks with purposively selected GI cancer providers and survivors in Alabama and Mississippi were conducted. Survivors were within 3 years of diagnosis of stage I to III esophageal, pancreatic, or colorectal cancer. Transcripts were analyzed using inductive thematic and content analysis techniques. Intercoder agreement was reached at 90 %. RESULTS: The 27 providers included surgeons (n = 11), medical oncologists (n = 2), radiation oncologists (n = 2), a primary care physician (n = 1), nurses (n = 8), and patient navigators (n = 3). This study included 36 survivors with ages ranging from 44 to 87 years. Of the 36 survivors, 21 (58.3 %) were male, and 11 (30.6 %) identified as Black. Responses were grouped into 3 broad categories: (i) transportation/geographic location, (ii) specialized care/testing, and (iii) patient-/provider-related factors. The barriers included lack and cost of transportation, reluctance to travel because of uneasiness with urban centers, low availability of specialized care, overburdened referral centers, provider-related referral biases, and low health literacy. Facilitators included availability of charitable aid, centralizing multidisciplinary care, and efficient appointment scheduling. CONCLUSION: In the Deep South, barriers and facilitators to the availability and accessibility of GI surgical cancer care were identified at the health system, provider, and patient levels, especially for rural residents. Our data suggest targets for improving the use of surgery in GI cancer care.

Cortisol secretion autonomy associated with weight loss outcome after laparoscopic sleeve gastrectomy: a prospective cohort study in Asian patients.

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is a widely recognized effective bariatric surgery. However, variable weight loss outcomes post-surgery remained a clinical challenge. Currently, there is no established consensus on the factors influencing weight loss failure following LSG. This study aimed to explore the association between preoperative cortisol secretion autonomy and postoperative weight loss in obese patients undergoing LSG. PATIENTS AND METHODS: A cohort of 181 patients with simple obesity (BMI ≥ 28 kg/m2) who underwent LSG and were followed up for one year was analyzed. Weight loss was measured by the percentage of excess weight loss (%EWL), and cortisol secretion autonomy was evaluated using a 1 mg dexamethasone suppression test (DST). Regression models were used to analyze the correlation between preoperative 1 mg DST results and %EWL one year after laparoscopic sleeve gastrectomy (LSG). RESULTS: Cortisol secretion autonomy was significantly lower in the %EWL ≥ 75% group and higher in the %EWL < 75% group, showing a negative correlation with %EWL (R = -0.336, p = 0.001). Logistic regression analysis indicated that high cortisol secretion autonomy was significantly correlated with %EWL < 75% after LSG. The likelihood of %EWL being < 75% was 10.47 times greater in patients with high cortisol secretion autonomy compared to those with low cortisol secretion autonomy (odds ratio 10.472, confidence interval: 1.660-66.048, p = 0.012). CONCLUSIONS: Cortisol secretion autonomy emerges as an independent predictor of weight loss outcomes in Asian patients undergoing LSG. This finding suggests the potential for cortisol secretion autonomy to inform preoperative assessments and personalized treatment strategies in bariatric surgery.

The development and establishment of a heat inactivated preparation of Mycobacterium tuberculosis (H37Rv) as the first international standard for nucleic acid amplification techniques.

A need to develop an inactivated Mycobacterium tuberculosis (Mtb) preparation, to be used as a DNA standard, as an important and urgent requirement for Tuberculosis (TB) diagnostics standardization was identified in 2018. A candidate material was generated using a heat inactivated culture of Mtb strain H37Rv. A lyophilised preparation was evaluated for its suitability as an International Standard for molecular detection of Mtb DNA in an international collaborative study. Together with the use of quantitative PCR assays and rapid diagnostic tests, this candidate standard was demonstrated to be fit-for-purpose. Based on the results from this collaborative study, it is proposed this lyophilised heat inactivated Mtb preparation (NIBSC code: 20/152) to be established by the World Health Organization Expert Committee on Biological Standardization, as the First WHO International Standard for Mycobacterium tuberculosis (H37Rv) for nucleic acid amplification techniques with an assigned unitage of 6.3 log10 or 2 × 106 International Units per vial. The intended uses of this IS are for calibration of secondary or in-house reference preparations used in the assays for the molecular detection of Mtb DNA. It may also be used for assay validation and monitoring the performance in terms of limit of detection of rapid diagnostic tests.

The Influence of Saliva and Blood Contamination on Bonding Between Resin-modified Glass Ionomer Cements and Resin Composite.

OBJECTIVE: To investigate the influence of blood and saliva contamination on the microshear bond strength (µSBS) between resin-modified glass ionomer cement (RMGIC) and resin composite (RC). METHODS AND MATERIALS: Eighty RMGIC discs were allocated into four groups (n=20). Group 1 received universal dental adhesive application in a self-etch mode followed by a build-up with RC. Group 2 received saliva as a contaminant, Group 3 received blood as a contaminant, Group 4 received a 1:1 blood-saliva mixture as a contaminant. Specimens from Groups 2, 3, and 4 were submerged into their respective contaminants for 15 seconds and dried prior to the adhesive application, followed by the protocol for Group 1. All specimens were stored in distilled water for 24 hours. Subsequently, the bonded specimens were subjected to µSBS testing using a universal testing machine. Failure mode of the debonded RMGIC surfaces was examined using scanning electron microscopy. RESULTS: The µSBS from groups 1-4 were 10.76 ± 3.03 MPa, 9.36 ± 2.54 MPa, 6.55 ± 1.67 MPa and 8.42 ± 2.79 MPa, respectively. Contamination by blood and blood-saliva significantly decreased the µSBS (p<0.001, p=0.029). Saliva contamination alone had no statistically significant effect on the µSBS (p=0.524). A statistically significant difference in the mode of failure was detected between the experimental groups (p=0.012). CONCLUSION: Saliva contamination has no influence on µSBS between RMGIC and RC when it is dried thoroughly, while blood and blood-saliva contamination reduced µSBS between RMGIC and RC even when dried thoroughly.

Estimating excess septicaemia mortality and hospitalisation burden associated with influenza in Hong Kong, 1998 to 2019.

Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from 1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04-0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94-2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.

[Re-evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism].

Objective: The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA). Methods: This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy. Results: A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUCROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions: CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

Developing a virtual assessment protocol for the AMPLIFI Randomized Controlled Trial due to COVID-19: From assessing participants' preference to preparing the team.

Background During the COVID-19 pandemic, in-person research assessments needed to be adapted to ensure safety of participants and staff. Participants' willingness to participate in research activities, how to prepare assessors to ensure data integrity, and the feasibility of modified protocols, were unknown. Within the AMPLIFI randomized clinical trial (RCT) for cancer survivors, we elicited participants' preferences and willingness to participate in Clinic, Home, or Virtual assessments, prepared assessors for, and implemented virtual assessments. Methods 1) We conducted phone surveys of potential AMPLIFI participants; 2) Based on survey results, we modified assessments from in-person to virtual visits (VV) by videoconference. Assessors were trained and certified, i.e., assessors recorded 3 assessments that were reviewed and scored by 2 investigators. The modified protocol was proposed to 62 participants: we report numbers of those who agreed to attend VV. Results 1) Survey results: Among 74 survey respondents, 44.6% preferred, 75.7% were willing to attend Clinic Visits; 32.4% preferred, 83.8% were willing to do VV; 23% preferred, 77% were willing to do Home Visits. Survivors 70+ were less likely than 50-69 years old to be willing to do VV: no other differences were noted by gender, race, rural status or education. 2) Assessment uptake: 66.1% agreed to attend VV, and of them 75.6% completed them. Conclusion Diverse research participants adapted to protocols that prioritize their safety, although older participants may be reluctant to do virtual assessments. Virtual assessments are feasible and research teams can rigorously prepare to collect quality data through them.

Features That Middle-aged and Older Cancer Survivors Want in Web-Based Healthy Lifestyle Interventions: Qualitative Descriptive Study.

BACKGROUND: With the increasing number of older cancer survivors, it is imperative to optimize the reach of interventions that promote healthy lifestyles. Web-based delivery holds promise for increasing the reach of such interventions with the rapid increase in internet use among older adults. However, few studies have explored the views of middle-aged and older cancer survivors on this approach and potential variations in these views by gender or rural and urban residence. OBJECTIVE: The aim of this study was to explore the views of middle-aged and older cancer survivors regarding the features of web-based healthy lifestyle programs to inform the development of a web-based diet and exercise intervention. METHODS: Using a qualitative descriptive approach, we conducted 10 focus groups with 57 cancer survivors recruited from hospital cancer registries in 1 southeastern US state. Data were analyzed using inductive thematic and content analyses with NVivo (version 12.5, QSR International). RESULTS: A total of 29 male and 28 female urban and rural dwelling Black and White survivors, with a mean age of 65 (SD 8.27) years, shared their views about a web-based healthy lifestyle program for cancer survivors. Five themes emerged related to program content, design, delivery, participation, technology training, and receiving feedback. Cancer survivors felt that web-based healthy lifestyle programs for cancer survivors must deliver credible, high-quality, and individually tailored information, as recommended by health care professionals or content experts. Urban survivors were more concerned about information reliability, whereas women were more likely to trust physicians' recommendations. Male and rural survivors wanted information to be tailored to the cancer type and age group. Privacy, usability, interaction frequency, and session length were important factors for engaging cancer survivors with a web-based program. Female and rural participants liked the interactive nature and visual appeal of the e-learning sessions. Learning from experts, an attractive design, flexible schedule, and opportunity to interact with other cancer survivors in Facebook closed groups emerged as factors promoting program participation. Low computer literacy, lack of experience with web program features, and concerns about Facebook group privacy were important concerns influencing cancer survivors' potential participation. Participants noted the importance of technology training, preferring individualized help to standardized computer classes. More rural cancer survivors acknowledged the need to learn how to use computers. The receipt of regular feedback about progress was noted as encouragement toward goal achievement, whereas women were particularly interested in receiving immediate feedback to stay motivated. CONCLUSIONS: Important considerations for designing web-based healthy lifestyle interventions for middle-aged and older cancer survivors include program quality, participants' privacy, ease of use, attractive design, and the prominent role of health care providers and content experts. Cancer survivors' preferences based on gender and residence should be considered to promote program participation.

Natural Killer Anti-Tumor Activity Can Be Achieved by In Vitro Incubation With Heat-Killed BCG.

Natural Killer cell receptors allow this heterogeneous immune population to efficiently fight both tumors and infection, so their use as immunotherapy agents is an active field of research. Cytokine activation, particularly by myeloid cell-derived IL15, can induce potent NK anti-tumor responses. While studying the mechanism of action of intravesical instillations of Bacille Calmette-Guérin (BCG) as therapy for patients with high risk non-muscle invasive bladder cancer, we showed that BCG can activate a cytotoxic CD56bright NK cell population which efficiently recognized bladder cancer cells. This pioneer immunotherapy provides an invaluable model to understand the role of different immune populations in tumor elimination. However, during the propagation of BCG worldwide a large number of genetically diverse BCG substrains developed. Here, we investigated the capacity of different BCG substrains to promote NK cell activation and confirmed that they were able to activate lymphocytes. Tice, Connaught and Moreau were the substrains with a stronger NK activation effect as measured by CD56 upregulation. Surprisingly, dead mycobacteria also stimulated PBMC cultures and we further demonstrate here that subcellular fractions of BCG-Tice, in the absence of live mycobacteria, could also induce an NK cell response. Lipids from BCG-Tice, but not from Mycobacterium bovis, stimulated NK cell activation and degranulation, whereas the aqueous fraction of either bacteria did not activate lymphocytes. However, delipidated BCG-Tice bacteria were able to activate effector cells (CD3+CD56+ and NK, CD3-CD56+). These data demonstrate that different components of mycobacteria can stimulate different immune subpopulations resulting in phenotypes suitable for cancer elimination.

Confronting COVID-19 in under-resourced, African American neighborhoods: a qualitative study examining community member and stakeholders' perceptions.

OBJECTIVE: The purpose of this study was to examine perceptions of COVID-19 related to prevention, coping, and testing of African American residents in under-resourced communities in Alabama. DESIGN: Guided by the PRECEDE-PROCEED model, virtual focus groups were conducted in five urban and rural Alabama communities using secure Zoom meetings. Community residents and stakeholders (N = 36 total) participated; meetings were audio- and video-recorded, transcribed, and analyzed according to Thematic Analysis. Themes were organized by the PRECEDE portion of the model in Predisposing, Reinforcing, and Enabling barriers and facilitators in three focus areas: prevention, coping, and testing. RESULTS: Prevention barriers included apathy, difficulty with social distancing, lack of information, mixed messages from authority figures, and lack of personal protective equipment (PPE). Prevention facilitators included concerns about contracting COVID-19, clear and consistent messages from trusted sources, contact tracing, and the provision of PPE. Coping barriers included food insecurity, mental health issues, isolation, economic hardships, lack of health care access, and issues with virtual schooling and church services, which were exacerbated by the inability to connect to the internet. Facilitators to coping included religious faith, increased physical activity, and a sense of hope. Testing barriers included misunderstanding, fear, mistrust, testing restrictions, and location of testing sites. Facilitators to testing included incentives, clear information from trusted sources, convenient testing locations, and free tests. CONCLUSION: Gaining community members' perspectives can identify barriers and facilitators to prevention, coping, and testing and potentially improve outcomes. While addressing the social determinants of health (e.g. income, education, medical trust) would be an effective path by which to diminish health disparities related to COVID-19, there is an urgent need to mitigate the spread and severity of COVID-19 in vulnerable populations. Interventions should focus on downstream determinants, such as those emerging from our study.

Factors associated with abstinence after a recent smoking cessation attempt across 28 European Union member states.

INTRODUCTION: There is a lack of information regarding factors associated with successful smoking cessation on a population and European Union (EU)-wide level. Our study seeks to explore individual and country-level factors associated with abstinence after a recent smoking cessation attempt across the EU. METHODS: We obtained data from the March 2017 Special Eurobarometer 87.1 (n=27901). Regression analysis was performed on a subset of 1472 individuals who made quit attempts in the past 12 months. Sociodemographic, policy and country-level factors were assessed using logistic regression among smokers and ex-smokers who attempted to quit approximately 12 months before the survey date. We defined and examined the Cessation Ratio (ratio of number of recent quitters to those who did not succeed) across 28 EU Member States. RESULTS: In all, 14.9% (n=1018) of current smokers and 8.80% (n=454) of ex-smokers attempted to quit in approximately the last 12 months (n=1472). Cessation Ratios ranged from 0.182 (95% CI: 0.045-0.319) in Estonia to 1.060 (95% CI: 0.262-1.860) in Sweden. There is a quadratic, U-shaped relationship between odds of quitting and smoking prevalence. The lowest odds of cessation were observed at a prevalence of 26.3%, with higher odds of cessation observed above and below this point. Respondents who reported financial difficulties were less likely to quit (AOR=0.66; 95% CI: 0.52-0.83). There was no association of likelihood of success with other sociodemographic factors or the Tobacco Control Scale treatment score. CONCLUSIONS: These findings highlight a need for exploring reasons behind the variation in likelihood of abstinence following a recent quit attempt, in order to design policies targeted at population groups or countries that need greater support.

[Situation analysis of off-label drug use in China].

To introduce current literature reporting situations of the off-label drug use(OLDU) by analyzing relevant literatures published in China, this study comprehensively focused on literatures about OLDU in China in seven Chinese and English databases, then extracted and analyzed the data by different literature types. A total of 667 papers were analyzed. The number of literatures about OLDU data analyzed in hospitals was 325, and the number of clinical studies relating to OLDU was 329, in which case series and case reports were the majority(69.91%). In addition, there were 13 expert consensuses of OLDU and another 56 studies about drug use based on the real-world data characteristics and influencing factors. The number of OLDU data studies has increased year by year. Based on the existing studies, there were more western medicine reports than traditional Chinese medicines, and OLDU types were mainly for over-dosage use. The literatures from OLDU data in hospital were mostly limited to one or several tertiary hospitals in a certain area, and the OLDU types were not uniform. Clinical studies were mainly clinical control trials and case series/reports, but with contradictory reporting results. There were fewer OLDU consensus, and the recommended classification was not uniform. The characteristics and analysis of influencing factors of drug using data in real-world focused on traditional Chinese medicine injections, and the results were not the same. In the future, we shall pay more attention to and strengthen reporting and analysis of OLDU, define study objectives, and unify the content and reporting standards, so as to promote the integrated utilization of OLDU data and reflect real situations in our country.

[Prevalence and clinical characteristics of obstructive sleep apnea in patients with primary hyperaldosteronism].

Objective: To explore the proportion of obstructive sleep apnea (OSA) in primary aldosteronism (PA) in Chinese population and compare the clinical characteristics between PA patients with OSA and those without. Methods: A total of 96 patients diagnosed with PA from September 2015 to November 2018 were recruited in this study. OSA was screened by cardio-respiratory polygraphy. According to the apnea hypopnea index (AHI), the patients were divided into PA with OSA group (AHI ≥5 times) and PA without OSA group (AHI<5 times). Results: Among all patients (96), 69 (71.9%) were with OSA, among them 22 patients (22.9%) were with mild OSA, 17 patients (17.7%) were with moderate OSA and 30 patients (31.3%) were with severe OSA. Compared with the patients without OSA, the patients with OSA were elder, and had higher levels of body mass index (BMI), waist circumference (WC), hip circumference (HC), creatinine (CR) and glycosylated haemoglobin (HbA1c) (P<0.05), but lower concentrations of plasma aldosterone (PAC), supine aldosterone renin concentration ratio(ARR) and the PAC after the diagnosis test (P<0.05). Spearman correlation analyses showed that BMI, WC, HC, CR and HbA1c were positively correlated with AHI (P<0.05), while high-density lipoproteincholesterol (HDL-C), supine-PAC and saline infusion test(SIT)-post PAC were negatively correlated with AHI (P<0.05). Conclusions: The proportion of OSA in PA patients is relatively high (71.9%). Metabolic abnormalities are more common in PA patients with OSA, indicating that screening for OSA should be carried out routinely in PA patients.

Influence of Silver Diamine Fluoride Treatment on the Microtensile Bond Strength of Glass Ionomer Cement to Sound and Carious Dentin.

CLINICAL RELEVANCE: This study provides valuable information about the influence of silver diamine fluoride (SDF) treatment on the microtensile bond strength of glass ionomer cement (GIC) to dentin. SUMMARY: Objectives: To investigate the influence of silver diamine fluoride (SDF) treatment on the microtensile bond strength (mTBS) of glass ionomer cement (GIC) to sound and artificial carious dentin.Methods: Thirty dentin blocks prepared from 30 noncarious human molars were randomly allocated into either the sound (Gp1) or artificial carious dentin (Gp2) groups. A microbiological method was adopted to create artificial dentin caries lesions in Gp2 specimens. Each dentin block was sectioned into two halves perpendicularly, and each pair of block halves was randomly assigned to two subgroups to receive topical application of SDF (Gp1-SDF, Gp2-SDF) or water as control (Gp1-water, Gp2-water). An encapsulated GIC was bonded to the exposed dentin surfaces 14 days after the SDF/water application. After immersion for 7 days in artificial saliva, the GIC-dentin specimens were sectioned into beams for mTBS testing. Failure mode was examined after the mTBS test.Results: There was no significant difference in the mean mTBS values between the SDF and control subgroups (Gp1-SDF vs Gp1-water, 10.57±1.6 MPa vs 10.20±1.8 MPa; Gp2-SDF vs Gp2-water, 6.14±2.2 MPa vs 5.97±2.3 MPa; paired t-test, p>0.05). However, the mean mTBS value of the sound dentin group was significantly higher than that of the carious dentin group, irrespective of whether SDF was applied prior to GIC bonding (independent t-test, p<0.001). Proportionally more cohesive failures occurred in the sound dentin groups (Gp1-SDF, 48.4%; Gp1-water, 42.9%) compared with the carious dentin groups (Gp2-SDF, 15.6%; Gp2-water, 9.8%; p<0.05).Conclusions: SDF treatment had no significant influence on the mTBS of GIC to dentin. Compared with sound dentin, dentin with caries had lower mTBS to GIC.

[Effect of inhibiting the activity of double-stranded RNA-dependent protein kinase in sepsis mice].

Objective: To observe the effects of 2-aminopurine (2-AP), a double-stranded RNA-dependent protein kinase (PKR) inhibitor, on organ function, plasma inflammatory factor expression and 7 days mortality in sepsis mice induced by cecal ligation puncture (CLP). Methods: Forty specific specific pathogen free C57BL/6 mice were randomly divided into sham group (n=10), CLP group (n=10), CLP+2-AP group (n=10) and 2-AP group (n=10). CLP was used to establish sepsis mice models.Peripheral blood serum was collected 24 hours after operation, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Cr), blood urea nitrogen (BUN) and inflammatory factors (IL-1ß, IL-10 and TNF-α) were detected; peripheral blood and peritoneal lavage fluid were taken for bacterial clearance detection. Another 60 C57BL/6 mice were selected to observe the 7-day survival rate according to the above groups (n=15). Independent sample t test was used to compare the measurement data between groups. Results: The levels of ALT, AST, Cr and BUN in CLP Group and CLP+2-AP group were significantly higher than those in sham group (all P<0.001). The levels of ALT and AST in CLP+2-AP group were significantly lower than those in CLP Group (t=27.88, 11.33, both P<0.001); the levels of Cr and BUN in CLP+2-AP group were significantly lower than those in CLP Group (t=11.02, 7.15, bothP<0.001). Compared with sham group, the levels of pro-inflammatory (IL-1ß and TNF-α) and anti-inflammatory (IL-10) cytokines in CLP group were significantly higher (all P<0.001); the levels of IL-1ß and IL-10 in CLP+2-AP group were significantly lower (all P<0.001), but the levels of TNF-α in CLP+2-AP group were not significantly lower (P=0.33). The 7-day survival rate was 100% in sham group, 13.3% in CLP+2-AP group, 86.7% in 2-AP group and 20.0% in CLP+2-AP group. Inhibition of PKR activation slightly improved the trend of 7-days survival rate of CLP model mice (analysis by mantel Cox test, χ(2)=0.0012, P=0.97). Conclusion: In sepsis mice model, inhibition of PKR activity can reduce the expression of inflammatory factors in plasma, decrease bacterial load in blood and abdominal cavity, and protect organ function, which could suggest that inhibition of PKR activity has potential application in sepsis treatment.

BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine.

Background: Intra-vesical instillation of Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is an effective therapy for high-grade non-muscle invasive bladder cancer (NMIBC), which provokes a local immune response resulting in 70% of patients free of relapse after three years. Because non-responder patients usually have a bad prognosis, the early identification of treatment failure is crucial. We hypothesized that, if an effective immune response was taking place in the bladder, soluble factors would be released to the urine many days after BCG instillations. Methods: An extensive panel of cytokines and chemokines released into the urine seven days after every BCG instillation was screened in a cohort of NMIBC patients over three years. Results: The determinations of the urinary concentrations of cytokines, chemokines, and creatinine showed that increasing concentrations of C-X-C motif chemokine 10 (CXCL10) also known as interferon-inducible protein 10 (IP10) could be detected during the six-week induction cycle of BCG-treated patients released into the urine by CD14+ cells. In vitro, CXCL10 facilitated the recruitment of effector immune cells after the BCG-mediated upregulation of CXCR3 in both T- and natural killer (NK)-cells. Conclusions: The high concentrations of chemokine detected one week after the encounter with mycobacteria suggest that the CXCL10 axis might be related to the intensity of the immune anti-tumor response.

Contact allergy and allergic contact dermatitis caused by lavender: A retrospective study from an Australian clinic.

BACKGROUND: Lavender is commonly used in aromatherapy and in a broad range of personal and household products. It has been identified as a contact sensitizer, and has been reported to cause allergic contact dermatitis (ACD). OBJECTIVES: To report our experience with contact allergy and ACD caused by lavender, and to raise awareness of lavender as a potential contact allergen. METHOD: A retrospective database review was performed of patients attending patch testing clinics at the Skin and Cancer Foundation, Victoria, Australia, from January 1, 1993 to December 31, 2017. RESULTS: Among the 2178 patients patch tested with lavender over this period, a total of 58 positive reactions were recorded in 49 individuals, giving a positive patch test prevalence for patients tested with lavender of 2.2%. Twenty-seven patients were diagnosed with ACD. The most common sources of exposure to lavender were personal care products and essential oils. Of the patients with ACD, 74% were tested with lavender absolute, with positive results in 90% of cases. CONCLUSION: Lavender is an uncommon cause of ACD but is important to consider, given the potential for exposure through the use of personal care items and essential oils.