Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

OBJECTIVES: The worldwide incidence of metabolic syndrome (MetS) has increased in recent decades. In this study, we investigated the socioeconomic inequalities associated with MetS and its components in a sample of the Iranian Kurdish population. METHODS: We used data from 3,996 participants, aged 35 years to 70 years, from the baseline phase of the Dehgolan Prospective Cohort Study (February 2018 to March 2019). The concentration index and concentration curve were used to measure inequality and the Blinder-Oaxaca decomposition method was used to examine the contribution of various determinants to the observed socioeconomic inequality in MetS and its components. RESULTS: The prevalence of MetS was 34.44% (95% confidence interval [CI], 32.97 to 35.93). The prevalence of MetS was 26.18% for those in the highest socioeconomic status (SES), compared with 40.51% for participants in the lowest SES. There was a significant negative concentration index for MetS (C=-0.13; 95% CI, -0.16 to -0.09), indicating a concentration of MetS among participants with a lower SES. The most prevalent component was abdominal obesity (59.14%) with a significant negative concentration index (C=-0.21; 95% CI, -0.25 to -0.18). According to decomposition analysis, age, gender, and education were the highest contributing factors to inequality in MetS and its components. CONCLUSIONS This study showed socioeconomic inequality in MetS. People with a low SES were more likely to have MetS. Therefore, policymakers and health managers need to develop appropriate strategies to reduce these inequalities in MetS across age groups, genders, and education levels, especially among women and the elderly.

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

Objectives: The aim of this study was to compare morbidities and duration of surgery, as well as bone formation in alveolar defects reconstructed with symphysis bone combined with allograft and iliac crest bone graft in patients with cleft palate. Patients and Methods: This randomized clinical trial was performed with 22 patients with unilateral alveolar cleft with a follow-up period of 12 months. In 12 patients, alveolar defects were reconstructed with chin bone graft plus allograft (Group A), while for the other 10 patients, iliac bone crest was used as donor site (Group B). Duration of surgery as well as occurrence of morbidities and complications were recorded. In addition, conebeam computed tomographic (CBCT) scans were performed before surgery and 12 months after surgical procedures in order to compare bone formation between the two groups. Results: Postoperative CBCT demonstrated a mean bone fill percentage of 76.9% of the alveolar defect in Group A, compared with 77.0% in Group B. Paresthesia in the lower lip or chin did not occur in any patients of Group A. The mean duration of the surgical process was significantly shorter for Group A (40 minutes vs 76 minutes, P<0.001). In addition, patients in Group A regained normal gait faster than patients in Group B (1 day vs 9.5 days). Conclusion Mandibular symphysis bone graft in combination with allograft results in favorable outcomes in patients with unilateral alveolar clefts.

OBJECTIVE: To determine the effectiveness and safety of essential oil from Citrus aurantium on anxiety in patients undergoing coronary angiography. METHODS: A single-blind, randomized controlled trial was conducted in 80 patients experiencing coronary angiography in Imam Ali Hospital in Kermanshah, Iran from April to November in 2016. All patients were randomly divided into intervention and control groups by a random number table, 40 cases in each group. The patients in the intervention group inhaled Citrus aurantium essential oil for 15-20 min about 60 min before angiography. Following the same procedure, distilled water was used instead of Citrus aurantium in the control group. Spielbergers State-Trait Anxiety Inventory (STAI) was filled in and vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory and pulse rate were recorded before and 20 min after the intervention. Adverse reactions after intervention were observed. RESULTS: In the intervention group, the mean scores of STAI, SBP, DBP, respiratory and pulse rate were 53.30 ± 10.13, 134.82 ± 11.75 mm Hg, 84.49 ± 6.99 mm Hg, 17.87 ± 1.73 times/min, and 76.48 ± 12.55 beats/min at baseline and significantly decreased to 42.37 ± 10.15, 124.49 ± 10.48 mm Hg, 79.23 ± 6.62 mm Hg, 14.54 ± 1.43 times/min, and 70.03 ± 13.66 beats/min respectively 20 min after intervention (all P<0.05); however, in the control group, neither anxiety scores nor vital signs changed significantly (P>0.05). All subjects reported no adverse reactions. CONCLUSION: Inhalation of the essential oil from Citrus aurantium was effective in reducing anxiety and stress levels in patients undergoing coronary angiography. TRIAL REGISTRATION IRCT2016040816797N2 (retrospectively registered on 21 April 2016, https://en.irct.ir/trial/15600 ).

Background: Nicotine can have detrimental effects on dental implant osseointegration. This study aimed to evaluate the influence of systemic L-arginine supplement on the osseointegration of dental implants in nicotine consumer dogs. Methods: Twelve 1-year Labrador Retriever dogs had their right and left third and fourth mandibular premolars removed, and the sockets were left to heal for 6 months. Dogs were randomly divided into three groups (n = 16): group 1—0.2 mg/kg nicotine was injected twice daily; group 2—0.2 mg/kg nicotine was injected twice daily in addition to 200 mg/kg L-arginine capsules taken orally; and group 3—placebo. Forty-eight dental implants were inserted into the healed sockets of the dog’s mandible and were assessed by implant stability quotient (ISQ) using resonance frequency analysis (RFA) during 4 weeks and insertion and removal torque value analysis. Results: No implant failure occurred during the study period. The change in torque value between insertion and removal was similar in the placebo and nicotine+arginine consumer dogs (p = 0.276), which shows a positive effect of arginine supplementation in nicotine consumers. There was a significant difference in torque value change between nicotine+arginine vs. nicotine consumers (p = 0.049) and placebo vs. nicotine (p = 0.003). After 4 weeks, the placebo had the most significant improvement in torque value (47.0 ± 16.9), followed by nicotine+arginine (25.1 ± 37.8), and the worst torque value was for the nicotine group (− 5.7 ± 24.0) pound per inch. The results show that except in the first week, there are significant differences in ISQ between the groups in different periods. ISQ in all of the groups has reduced at first but then increased over time. At the time of implant placement, insertion torque was significantly higher in the nicotine consumer group than the nicotine+arginine consumer group and placebo group (p = 0.020). Conclusion Arginine supplementation promotes bone healing and implant primary stability by improving dental implant osseointegration biomechanical characteristics.

OBJECTIVES: This study aimed to explain the health-related quality of life (HRQoL) gap between the poorest and the wealthiest quintiles in the capitals of Kermanshah and Kurdistan Provinces (Kermanshah and Sanandaj), in western Iran. METHODS: This was a cross-sectional study conducted among 1772 adults. Data on socio-demographic characteristics, socioeconomic status (SES), lifestyle factors, body mass index, and HRQoL of participants were collected using a self-administered questionnaire. The slope and relative indices of inequality (SII and RII, respectively) were employed to examine socioeconomic inequality in poor HRQoL. Blinder-Oaxaca (BO) decomposition was used to quantify the contribution of explanatory variables to the gap in the prevalence of poor HRQoL between the wealthiest and the poorest groups. RESULTS: The overall crude and age-adjusted prevalence of poor HRQoL among adults was 32.0 and 41.8%, respectively. The SII and RII indicated that poor HRQoL was mainly concentrated among individuals with lower SES. The absolute difference (%) in the prevalence of poor HRQoL between the highest and lowest SES groups was 28.4. The BO results indicated that 49.9% of the difference was explained by different distributions of age, smoking behavior, physical inactivity, chronic health conditions, and obesity between the highest and lowest SES groups, while the remaining half of the gap was explained by the response effect. CONCLUSIONS: We observed a pro-rich distribution of poor HRQoL among adults in the capitals of Kermanshah and Kurdistan Provinces. Policies and strategies aimed at preventing and reducing smoking, physical inactivity, chronic health conditions, and obesity among the poor may reduce the gap in poor HRQoL between the highest and lowest SES groups in Iran.
Adult ; Body Mass Index ; Cross-Sectional Studies ; Health Status Disparities ; Humans ; Iran* ; Life Style ; Obesity ; Prevalence ; Quality of Life* ; Smoke ; Smoking ; Social Class ; Socioeconomic Factors*

No abstract available.
Breast* ; Magnetic Resonance Imaging*

PURPOSE: Adenosis lesions of the breast, including sclerosing adenosis and adenosis tumors, are a group of benign proliferative disorders that may mimic the features of malignancy on imaging. In this study, we aim to describe the features of breast adenosis lesions with suspicious or borderline findings on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: In our database, we identified 49 pathologically proven breast adenosis lesions for which the final assessment of the breast MRI report was classified as either category 4 (n=45) or category 5 (n=4), according to the Breast Imaging Reporting and Data System (BI-RADS) published by the American College of Radiology (ACR). The lesions had a final diagnosis of either pure adenosis (n=33, 67.3%) or mixed adenosis associated with other benign pathologies (n=16, 32.7%). RESULTS: Of the 49 adenosis lesions detected on DCE-MRI, 32 (65.3%) appeared as enhancing masses, 16 (32.7%) as nonmass enhancements, and one (2.1%) as a tiny enhancing focus. Analysis of the enhancing masses based on the ACR BI-RADS lexicon revealed that among the mass descriptors, the most common features were irregular shape in 12 (37.5%), noncircumscribed margin in 20 (62.5%), heterogeneous internal pattern in 16 (50.0%), rapid initial enhancement in 32 (100.0%), and wash-out delayed en-hancement pattern in 21 (65.6%). Of the 16 nonmass enhancing lesions, the most common descriptors included focal distribution in seven (43.8%), segmental distribution in six (37.5%), clumped internal pattern in nine (56.3%), rapid initial enhancement in 16 (100.0%), and wash-out delayed enhancement pattern in eight (50.0%). CONCLUSION: Adenosis lesions of the breast may appear suspicious on breast MRI. Awareness of these suspi-cious-appearing features would be helpful in obviating unnecessary breast biopsies.
Biopsy ; Breast* ; Diagnosis ; Fibrocystic Breast Disease ; Information Systems ; Magnetic Resonance Imaging* ; Pathology ; Subject Headings

OBJECTIVES: It is difficult to achieve adhesion between resin cement and zirconia ceramics using routine surface preparation methods. The aim of this study was to evaluate the effects of CO2 and Er:YAG laser treatment on the bond strength of resin cement to zirconia ceramics. MATERIALS AND METHODS: In this in-vitro study 45 zirconia disks (6 mm in diameter and 2 mm in thickness) were assigned to 3 groups (n = 15). In control group (CNT) no laser treatment was used. In groups COL and EYL, CO2 and Er:YAG lasers were used for pretreatment of zirconia surface, respectively. Composite resin disks were cemented on zirconia disk using dual-curing resin cement. Shear bond strength tests were performed at a crosshead speed of 0.5 mm/min after 24 hr distilled water storage. Data were analyzed by one-way ANOVA and post hoc Tukey's HSD tests. RESULTS: The means and standard deviations of shear bond strength values in the EYL, COL and CNT groups were 8.65 +/- 1.75, 12.12 +/- 3.02, and 5.97 +/- 1.14 MPa, respectively. Data showed that application of CO2 and Er:YAG lasers resulted in a significant higher shear bond strength of resin cement to zirconia ceramics (p < 0.0001). The highest bond strength was recorded in the COL group (p < 0.0001). In the CNT group all the failures were adhesive. However, in the laser groups, 80% of the failures were of the adhesive type. CONCLUSIONS: Pretreatment of zirconia ceramic via CO2 and Er:YAG laser improves the bond strength of resin cement to zirconia ceramic, with higher bond strength values in the CO2 laser treated samples.
Adhesives ; Ceramics* ; Lasers, Gas ; Resin Cements* ; Water