Schiff Base Complex of Copper Immobilized on Core-Shell Magnetic Nanoparticles Catalyzed One-Pot Syntheses of Polyhydroquinoline Derivatives under Mild Conditions Supported by a DFT Study.

We synthesized a stable and reusable Schiff base complex of copper immobilized on core-shell magnetic nanoparticles [Cu(II)-SB/GPTMS@SiO2@Fe3O4] with simple, efficient, and available materials. A variety of characterization analyses including Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), thermogravimetric analysis (TGA), X-ray diffraction (XRD), vibrating-sample magnetometry (VSM), energy-dispersive X-ray spectrometry (EDX), and inductively coupled plasma (ICP) confirm that our synthesized nanocatalyst was obtained. The particle size distribution from the TEM image was obtained in the range of 42-55 nm. The existence of cupric species (Cu2+) in the catalyst was determined with XPS analysis and clearly indicated two peaks at 933.7 and 953.7 eV for Cu 2p3/2 and Cu 2p1/2, respectively. BET results showed that our catalyst synthesized with a mesoporous structure and with a specific area of 48.82 m2 g-1. After detailed characterization, the resulting nanocatalyst exhibited excellent catalytic performance for the explored catalytic reactions in the one-pot synthesis of polyhydroquinoline derivatives by the Hantzsch reaction of dimedone, ethyl acetoacetate, ammonium acetate, and various aldehydes under sustainable and mild conditions. The corresponding products 5a-l are achieved in yields of 88-97%. Additionally, density functional theory (DFT) calculations were carried out to investigate the electrostatic potential root (ESP), natural bond orbital (NBO), and molecular orbitals (MOs), drawing the reaction mechanism using the total energy of the reactant and product and the study of structural parameters.

Gaillardin inhibits autophagy and induces apoptosis in MCF-7 breast cancer cells by regulating JAK/STAT pathway.

BACKGROUND: Gaillardin is a potent anti-cancer sesquiterpene lactone found in Inula oculus-christi. AIM: The present study examined the effects of gaillardin on apoptosis and autophagy in the MCF-7 breast cancer cell line. METHODS: The MTT assay was used to unravel the antiproliferative effects of gaillardin on MCF-7 cells. The expression of apoptosis-related genes including CASP3, BAX, BCL2, STAT3, and JAK2, and key markers of autophagy such as ATG1, ATG4, ATG5, ATG7, ATG12, BECN1, and MAP1LC3A were measured by real time-PCR method. The protein expression of Caspase 3, phosphorylated JAK2, phosphorylated STAT3, ATG1, ATG4, ATG5, ATG12, Beclin1, and LC-III was determined using western blotting. RESULTS: Gaillardin treatment significantly decreased the proliferation of MCF-7 cells with a parallel upregulation of the level of pro-apoptotic caspase-3 enzyme with no effect on Bax and Bcl2 expression. The levels of phosphorylated and active forms of JAK2 and STAT3 proteins were reduced following the treatment of MCF-7 cells with gaillardin. This sesquiterpene lactone com-pound considerably downregulated the levels of six autophagy markers, including ATG1, ATG4, ATG5, ATG12, Beclin1, and LC-III in MCF-7 cells. CONCLUSION: These data indicated the apoptosis-inducing activity of gaillardin in MCF-7 cells by a mechanism that inhibits the JAK/STAT signaling pathway. Further, autophagy inhibition was the other phenomenon caused by gaillardin in MCF-7 cells. These results can provide evidence to highlight the role of gaillardin as a novel therapeutic for the treatment of breast cancer.

Gaillardin exerts potent antileukemic effects on HL-60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment.

The use of all-trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard-risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high-risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus-christi-derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high-risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL-60 cells as a single or combined-form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL-60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL-60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL-60 cells and this study provides new insight into treating APL patients, especially in the high-risk subgroup.

High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry.

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.

Laparoscopic surgery for rectal cancer, specimen extraction: transanal or transabdominal?

BACKGROUND: Comparison of natural orifice specimen extraction (NOSE) and transabdominal specimen extraction (TASE) in colorectal surgery remains controversial. Herein, we aimed to perform a retrospective analysis on surgical outcomes of NOSE and TASE at three hospitals in east of Iran. METHOD: Consecutive locally advanced rectal adenocarcinoma patients who underwent laparoscopic surgery using either NOSE or TASE from 2011 to 2017 were recruited. These patients were followed-up till 2020. Data, including postoperative complications, long-term overall and recurrence-free survival were analyzed retrospectively. RESULTS: 239 eligible patients were included in this study. 169 (70.71%) patients underwent NOSE, and 70 (29.29%) patients underwent TASE. Although this study has achieved similar outcomes in terms of overall and recurrence-free survival, metastasis, circumferential margin involvement as well as complications of intra-operative bleeding, obstruction, anastomosis-fail, rectovaginal-fistula in women and pelvic collection/abscess in both groups, we observed higher rates of locoregional recurrence, incontinency, stenosis and the close distal margins involvement in NOSE group and also obstructed defecation syndrome in TASE cases. CONCLUSION: According to our findings, NOSE laparoscopic surgery showed significantly higher incontinency, impotency, stenosis and involvement of the close distal margins rates. Nevertheless, considering the similarity of long-term overall and recurrence-free survival, metastasis, circumferential margin involvement, NOSE procedure is still could be considered as a second choice for lower rectal adenocarcinoma patients.

Recent Advances in Dietary Sources, Health Benefits, Emerging Encapsulation Methods, Food Fortification, and New Sensor-Based Monitoring of Vitamin B12: A Critical Review.

In this overview, the latest achievements in dietary origins, absorption mechanism, bioavailability assay, health advantages, cutting-edge encapsulation techniques, fortification approaches, and innovative highly sensitive sensor-based detection methods of vitamin B12 (VB12) were addressed. The cobalt-centered vitamin B is mainly found in animal products, posing challenges for strict vegetarians and vegans. Its bioavailability is highly influenced by intrinsic factor, absorption in the ileum, and liver reabsorption. VB12 mainly contributes to blood cell synthesis, cognitive function, and cardiovascular health, and potentially reduces anemia and optic neuropathy. Microencapsulation techniques improve the stability and controlled release of VB12. Co-microencapsulation of VB12 with other vitamins and bioactive compounds enhances bioavailability and controlled release, providing versatile initiatives for improving bio-functionality. Nanotechnology, including nanovesicles, nanoemulsions, and nanoparticles can enhance the delivery, stability, and bioavailability of VB12 in diverse applications, ranging from antimicrobial agents to skincare and oral insulin delivery. Staple food fortification with encapsulated and free VB12 emerges as a prominent strategy to combat deficiency and promote nutritional value. Biosensing technologies, such as electrochemical and optical biosensors, offer rapid, portable, and sensitive VB12 assessment. Carbon dot-based fluorescent nanosensors, nanocluster-based fluorescent probes, and electrochemical sensors show promise for precise detection, especially in pharmaceutical and biomedical applications.

Britannin a Sesquiterpene Lactone from Inula aucheriana Exerted an Anti-leukemic Effect in Acute Lymphoblastic Leukemia (ALL) Cells and Enhanced the Sensitivity of the Cells to Vincristine.

Since chemotherapy drugs have dose-related side effects, there is still a need for finding new agents with suitable cytotoxic effects without any harmful effects. For this purpose, we evaluated the cytotoxic effects of Britannin that is a Sesquiterpene Lactone compound Inula aucheriana, alone or in combination with Vincristine (VCR), on Acute Lymphoblastic Leukemia (ALL)-derived MOLT-4 cells. In this study, we found that Britannin decreased the viability of MOLT-4 cells with the IC50 Values of 2 µM, but had no cytotoxic effects on normal cells or Peripheral Blood Mononuclear Cells (PBMCs). Our results also showed that Britannin decreased the proliferation of MOLT-4 cells by preventing the transition of the cells from the S phase of the cell cycle through the up-regulation of p21 and p27. Moreover, this agent induced ROS-mediated apoptosis by altering the expression of Bax, Bim, Caspase3, Bcl2, and XIAP. Britannin also produced a synergistic effect with Vincristine in MOLT-4 cells. Taken together, the results of this study showed for the first time that Britannin, as a natural Sesquiterpene Lactone, has cytotoxic effects that could be considered as an anti-leukemic agent in the treatment of ALL. However, there is still a demand for further studies that examine the efficacy and the safety of this purified compound.

Whole-exome sequencing reveals a rare missense variant in DTNA in an Iranian pedigree with early-onset atrial fibrillation.

Atrial fibrillation (AF) is a morbid and heritable irregular cardiac rhythm that affects about 2%-3% of the population. Patients with early-onset AF have a strong genetic association with the disease; nonetheless, the exact underlying mechanisms need clarification. We herein present our evaluation of a 2-generation Iranian pedigree with early-onset AF. Whole-exome sequencing was applied to elucidate the genetic predisposition. Direct DNA sequencing was utilized to confirm and screen the variants in the proband and his available family members. The pathogenicity of the identified nucleotide variations was scrutinized via either segregation analysis in the family or in silico predictive software. The comprehensive variant analysis revealed a missense variant (c.G681C, p.E227D, rs1477078144) in the human α-dystrobrevin gene (DTNA), which is rare in genetic databases. Most in silico analyses have predicted this variant as a disease-causing variant, and the variant is co-segregated with the disease phenotype in the family. Previous studies have demonstrated the association between the DTNA gene and left ventricular noncompaction cardiomyopathy. Taken together, we provide the first evidence of an association between a nucleotide variation in the DTNA gene and early-onset AF in an Iranian family. However, the genetic testing of AF in the Iranian population is still limited. This finding not only further confirms the significant role of genetics in the incidence of early-onset AF but also expands the spectrum of the gene variations that lead to AF. Additionally, it may have further implications for the treatment and prevention of AF.

Endothelial nitric oxide synthase Asp298Glu (894G/T) gene polymorphism as a possible risk factor for the coronary slow flow phenomenon among Iranians.

BACKGROUND: Mounting evidence indicates an association between endothelial dysfunction and the coronary slow flow phenomenon (CSFP). In the present study, we aimed to evaluate the possible role of endothelial nitric oxide synthase (eNOS) 894G/T and interleukin-1ß (IL-1ß) 315C/T polymorphisms as possible risk factors for CSFP. METHODS: This prospective study enrolled patients with CSFP and individuals with normal coronary arteries. Genotypes were assessed using regular polymerase chain reaction and direct Sanger-sequencing techniques. RESULTS: The study population consisted of 267 individuals: 180 patients with CSFP (49 women [27.2%]) at a median age of 55 (48-62) years and 87 controls with normal coronary arteries (56 women [64.4%]) at a median age of 47 (41-58) years. The allelic distribution of eNOS 894G/T was significantly associated with CSFP (odds ratio [OR], 1.58; 95% confidence interval (CI), 1.04-2.42; P = 0.03). This polymorphism increased the risk of CSFP under the dominant model (OR 1.73; 95% CI I.02-2.95; P = 0.04). However, the allelic frequencies (1.05; 95% CI 0.68-1.59; P = 0.83) and genotypic frequencies (0.88; 95% CI 0.52-1.49; P = 0.63) of the IL-1ß 315C/T polymorphism were not associated with the incidence of CSFP in the Iranian population. CONCLUSIONS: The CSFP and control groups were statistically different regarding the eNOS 894G/T polymorphism. Our findings also demonstrated that the IL-1ß 315C/T polymorphism was not a risk factor for CSFP.

Diagnostic accuracy of ultrasound in diagnosing acute appendicitis in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Lack of timely diagnosis of acute appendicitis (AA) can lead to perforation and peritonitis, which might be associated with complications such as miscarriage, preterm delivery, fetal loss, and even maternal mortality. The aim of the present systematic review and meta-analysis was to evaluate the accuracy of ultrasonography (US) for diagnosing AA in pregnant patients. METHODS: We performed the present systematic review and meta-analysis based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Using a pre-designed standard datasheet, the two authors summarized the data of each study independently. Pregnant women with diagnosed or suspected AA, who have undergone ultrasonography, as well as using CT scan or surgery as the standard method, were included. RESULTS: A total of 8 studies consisting of 1593 patients were included. The main analysis showed that the overall sensitivity and specificity were 77.6% and 75.3% for US in diagnosing AA in pregnancy. The sensitivity of US in the first, second, and third trimesters of pregnancy were 69%, 63%, and 51%, respectively. While the corresponding figures for specificity were 85%, 85%, and 65%. There was a significant difference in the diagnostic performance of US between the first two trimesters and the third one. The DORs in these three trimesters were 36, 26, and 1.92, respectively. CONCLUSIONS: Ultrasound evaluation showed a low diagnostic accuracy for acute appendicitis in pregnant women, especially during the third trimester. These patients should be diagnosed early and accurately to prevent both complications and unnecessary operations. It can be recommended to consider alternative imaging, mostly after negative or uncertain US.

Britannin, a sesquiterpene lactone induces ROS-dependent apoptosis in NALM-6, REH, and JURKAT cell lines and produces a synergistic effect with vincristine.

BACKGROUND: Britannin, a Sesquiterpene Lactone isolated from Inula aucheriana, has recently gained attraction in the therapeutic fields due to its anti-tumor properties. This study was designed to evaluate the effect of this agent on Acute Lymphoblastic Leukemia (ALL) cell lines, either as a monotherapy or in combination with Vincristine (VCR). METHODS AND RESULTS: To determine the anti-leukemic effects of Britannin on ALL-derived cell lines and suggest a mechanism of action for the agent, we used MTT assay, Annexin-V/PI staining, ROS assay, and real-time PCR analysis. Moreover, by using a combination index (CI), we evaluated the synergistic effect of Britannin on Vincristine. We found that unlike normal Peripheral Blood Mononuclear Cells (PBMCs) and L929 cells, Britannin reduced the viability of NALM-6, REH, and JURKAT cells. Among tested cells, NALM-6 cells had the highest sensitivity to Britannin, and this agent was able to induce p21/p27-mediated G1 cell cycle arrest and Reactive Oxygen Specious (ROS)-mediated apoptotic cell death in this cell line. When NALM-6 cells were treated with Nacetyl-L-Cysteine (NAC), a scavenger of ROS, Britannin could induce neither apoptosis nor reduce the survival of the cells suggesting that the cytotoxic effect of Britannin is induced through ROS-dependent manner. Moreover, we found that a low dose of Britannin enhanced the effect of Vincristine in NALM-6 cells by inducing apoptotic cell death via altering the expression of apoptotic-related genes. CONCLUSIONS: Overall, our results proposed a mechanism for the cytotoxic effect of Britannin, either as a single agent or in combination with Vincristine, in NALM-6 cells.

Genetically engineered fusion of allergen and viral-like particle induces a more effective allergen-specific immune response than a combination of them.

Chimeric virus-like particles (VLPs) were developed as a candidate for allergen-specific immunotherapy. In this study, hepatitis B core antigen (HBcAg) that genetically fused to Chenopodium album polcalcin (Che a 3)-derived peptide was expressed in E. coli BL21, purified, and VLP formation was evaluated using native agarose gel electrophoresis (NAGE) and transmission electron microscopy (TEM). Chimeric HBc VLPs were characterized in terms of their reactivity to IgE, the induction of blocking IgG and allergen-specific IgE, basophil-activating capacity, and Th1-type immune responses. Results from IgE reactivity and basophil activation test showed that chimeric HBc VLPs lack IgE-binding capacity and basophil degranulation activity. Although chimeric HBc VLPs induced the highest level of efficient polcalcin-specific IgG antibody in comparison to those induced by recombinant Che a 3 (rChe a 3) mixed either with HBc VLPs or alum, they triggered the lowest level of polcalcin-specific IgE in mice following immunization. Furthermore, in comparison to the other antigens, chimeric HBc VLPs produced a polcalcin-specific Th1 cell response. Taken together, genetically fusion of allergen derivatives to HBc VLPs, in comparison to a mix of them, may be a more effective way to induce appropriate immune responses in allergen-specific immunotherapy. KEY POINTS: • The insertion of allergen-derived peptide into major insertion region (MIR) of hepatitis B virus core (HBc) antigen resulted in nanoparticles displaying allergen-derived peptide upon its expression in prokaryotic host. • The resultant VLPs (chimeric HBc VLPs) did not exhibit IgE reactivity with allergic patients' sera and were not able to degranulate basophils. • Chimeric HBc VLPs dramatically improved protective IgG antibody response compared with those induced by allergen mixed either with HBc VLPs or alum. • Chimeric HBc VLPs induced Th1 responses that were counterparts of Th2 responses (allergic). • Chimeric HBc VLPs increased IgG2a/ IgG1 ratio and the level of IFN-γ compared to those induced by allergen mixed with either HBc VLPs or alum. Graphical Abstract.

Saccharomyces cerevisiae as a delivery system of Zataria multiflora Boiss. essential oil as a natural preservative for food applications: Encapsulation of Iranian Zataria multiflora Boiss. essential oil.

BACKGROUND: The following study is an evaluation of the encapsulation, stability and release profile of Iranian Zateria multiflora boiss essential oil (ZEO) in Saccharomyces cerevisiae yeast cells. Encapsulation was performed with different essential oil / yeast weight ratios at different temperatures. The encapsulation efficiency and stability of the loaded yeasts and the release profiles of carvacrol and thymol (as the main active ingredients of ZEO) were also investigated. RESULT: The encapsulation efficiencies of carvacrol and thymol at a ZEO / yeast weight ratio of 1.25 were 30.9% ± 0.01% and 44.5% ± 0.02%, respectively. Loaded yeast cells were stable during the 4-week storage period. Both carvacrol and thymol showed substantial releases of around 60% during the first hour and around 70% during the second hour at two different water temperatures, followed by steady release. CONCLUSION: Zateria multiflora boiss essential oil can be encapsulated effectively in S. cerevisiae yeast cells, refrigerated without degradation, and released efficiently. Zateria multiflora boiss essential oil encapsulated into S. cerevisiae yeast may be used as a potential preservative for the food and drug industry. © 2020 Society of Chemical Industry.

Antiproliferative Effect of Gaillardin from Inula oculus-christi in Human Leukemic Cells.

Gaillardin (GLN) is a sesquiterpene lactone isolated from the chloroform extract of Inula oculus-christi L. This natural compound has shown cytotoxicity in various cancerous cell line. However, its effect on leukemic cells is ambiguous. Due to the neurotoxicity of vincristine (VCR) in acute lymphoblastic leukemia (ALL), we aimed to examine the cytotoxic effects of GLN alone and in combination with vincristine on induction of apoptosis, and cell cycle progression in ALL cell lines (NALM-6 and MOLT-4). Our results displayed that GLN could induce cytotoxic effects in MOLT-4 and NALM-6 with IC50 values of 7.3 and 6.1 µM, respectively. In this study, we demonstrated that GLN induces cytotoxicity through G0/G1 phase arrest followed by apoptosis in a dose-dependent manner. Fortunately, this natural compound did not show significant cytotoxic effects on normal cells. This study demonstrated that GLN was capable to extend chemotherapeutic sensitivity in ALL cells by reducing VCR concentration without constraining its effectiveness. Therefore, it might act as a promising anticancer agent for the treatment of leukemia.

Gene expression profile of immunoregulatory cytokines secreted from bone marrow and adipose derived human mesenchymal stem cells in early and late passages.

Mesenchymal Stem Cells (MSCs) have therapeutic potential in a variety of diseases; however, the safety and efficacy of their use remain ambiguous. Clinical applications of MSCs are under intensive investigation due to their immunomodulatory features and lack of immune reactivity. Therefore, having a clear perspective on the exact mechanisms underlying the regulation of cytokine secretion in different microenvironments seems crucially important.In the current study, samples from human bone marrow and adipose were collected, and peripheral blood mononuclear cells (PBMCs) were isolated and cultured in conventional medium. After MSC expansion, the cells from passage 3 (P3) and passage 9 (P9) were utilized to identify MSC cell surface markers and their differentiation capacity. The P3, P5, P7, and P9 cells were used for RNA extraction to qualify the expression of the main immunomodulatory cytokines IDO, VCAM-1, TGF-ß, IL-6, IL-10, and PGE2 at mRNA levels. The results indicate that VCAM-1 expression in the subcultures was reduced in bone marrow-derived MSCs. After an increase in P5, P7, and P9, IL-6 expression was reduced. In adipose-derived MSCs, the mRNA levels of IL-10 in higher passages were decreased compared with P3; other studied cytokines had no significant changes in their expression levels in either bone marrow or adipose-derived MSCs. Based on these results, it can be concluded that a suitable source for MSCs in cell therapy with stable expression of main cytokines, even in higher subcultures, appears to be adipose-derived MSCs with the exception of IL-10 secretion.

The power of the health belief model (HBM) to predict water demand management: A case study of farmers' water conservation in Iran.

The purpose of the present study was to explore the power of the Health Belief Model (HBM) to explain water conservation behavior in Northeastern Iran. The research population consisted of farmers who were farming in Neyshabur plain in Khorasan Razavi Province in northeast of Iran. A cross-sectional study was conducted among 235 farmers recruited using a multistage random sampling design. To collect data, the questionnaire was used which its validity and reliability were confirmed. The results of a structural equation modeling (SEM) indicated that perceived susceptibility, perceived benefits, and cue to action accounted for approximately 41% of the variance in farmers' water conservation behavior. Moreover, the perceived benefit was the strongest predictor of water conservation behavior, while perceived severity, perceived barriers, self-efficacy, and general beliefs not significant on behavior. These results confirmed the practicability and effectiveness HBM for examining water conservation behavior among farmers in Iran.

Randomized, double-blind, placebo-controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy.

Clinical potential of curcumin in radiotherapy (RT) setting is outstanding and of high interest. The main purpose of this randomized controlled trial (RCT) was to assess the beneficial role of nanocurcumin to prevent and/or mitigate radiation-induced proctitis in prostate cancer patients undergoing RT. In this parallel-group study, 64 eligible patients with prostate cancer were randomized to receive either oral nanocurcumin (120 mg/day) or placebo 3 days before and during the RT course. Acute toxicities including proctitis and cystitis were assessed weekly during the treatment and once thereafter using CTCAE v.4.03 grading criteria. Baseline-adjusted hematologic nadirs were also analyzed and compared between the two groups. The patients undergoing definitive RT were followed to evaluate the tumor response. Nanocurcumin was well tolerated. Radiation-induced proctitis was noted in 18/31 (58.1%) of the placebo-treated patients versus 15/33 (45.5%) of nanocurcumin-treated patients (p = 0.313). No significant difference was also found between the two groups with regard to radiation-induced cystitis, duration of radiation toxicities, hematologic nadirs, and tumor response. In conclusion, this RCT was underpowered to indicate the efficacy of nanocurcumin in this clinical setting but could provide a considerable new translational insight to bridge the gap between the laboratory and clinical practice.

Development of a simplified multivariable model to predict neutropenic complications in cancer patients undergoing chemotherapy.

PURPOSE: Neutropenic complications remain the major dose-limiting toxicities of cancer chemotherapy. The aim of this study was to develop and internally validate a comprehensive and easily measurable scoring system for prediction of severe or febrile neutropenia in the first chemotherapy cycle of patients with solid tumors or lymphoma. METHODS: This prospective cohort study included consecutive patients at a tertiary referral hospital. Many clinical and laboratory-independent variables were measured at baseline. A multivariable logistic regression analysis was applied after unadjusted analysis, and the multivariable model was transformed into a simplified risk score based on 6 bootstrapped regression coefficients. The simplified scoring system was internally validated using cross-validation. All statistical tests were two-sided. RESULTS: A total of 305 patients were enrolled and followed during 1732 chemotherapy cycles. Of these, 259 were eligible for analysis. The multivariable model revealed 6 predictive factors for severe or febrile neutropenia (scores in parentheses): high-risk regimen without colony-stimulating factor (4 points), intermediate-risk regimen without colony-stimulating factor (3 points), age > 65 years and elevated ferritin (3 points), body mass index < 23 kg/m2 and body surface area < 2 m2 (2 points), estimated glomerular filtration rate < 60 mL/min/1.73m2 (2 points), and elevated C-reactive protein (1 point). The receiver operating characteristic curve was 0.832 (95% confidence interval [Cl], 0.767-0.897) for the simplified model and 0.816 (95% Cl, 0.771-0.860) for the cross-validation. CONCLUSIONS: We developed and internally validated a user-friendly prediction model to guide personalized decision-making using available clinical data and few cost-effective laboratory tests. External validation in other centers with different patients is required.