Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders.

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne (YnMyr) chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), aged 1-50 years, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%) and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%) and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each) as well as hypertrophy of the clava (24%) were common neuroimaging findings. Acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localization and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-myristoylation was similarly affected in acbd6-deficient zebrafish and X. tropicalis models, including Fus, Marcks and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders.

Comparison of the effect of ursodeoxycholic acid and multistrain synbiotic on indirect hyperbilirubinemia among neonates treated with phototherapy: A double-blind, randomized, placebo-controlled clinical trial study.

Background: This study was aimed at evaluating the effect of ursodeoxycholic acid (UDCA) and multistrain synbiotic on indirect hyperbilirubinemia among neonates treated with phototherapy. Materials and Methods: This double-blind, randomized clinical trial was conducted on 120 subjects presenting with indirect hyperbilirubinemia in 2019. Subjects were randomly divided into three groups of synbiotic, UDCA, and control. The synbiotic group received five drops/day of synbiotic in addition to phototherapy. UDCA group received 10 mg/kg/day of Ursobil divided every 12 h in addition to phototherapy. The Control group received a placebo (water) in addition to phototherapy. Phototherapy was discontinued when the bilirubin levels reached <10 mg/dL. Total bilirubin levels were measured using the diazo method at 12, 24, and 36 h after hospitalization. This study used repeated measure analysis of variance and post hoc tests. Results: The mean total of bilirubin was substantially decreased in both synbiotic and UDCA groups as compared to the control group at 24 h after hospitalization (P < 0.001). Moreover, the Bonferroni post hoc test showed significant differences regarding the mean total of bilirubin between the three groups (P < 0.05) except for the association between UDCA and synbiotic at 24 h after hospitalization (P > 0.99). Conclusion: Findings suggest that UDCA and synbiotic administration alongside phototherapy are more effective in reducing bilirubin levels as compared to phototherapy alone.

Designing and Characterization of Tregitope-Based Multi-Epitope Vaccine Against Multiple Sclerosis: An Immunoinformatic Approach.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system(CNS). It is widely accepted that the development and progression of MS result from aberrant activation of potentially encephalitogenic reactive-T cells against CNS antigens. The pathologic roles of both CD4+ (T helper; Th) and CD8+ T cells have been demonstrated in MS lesions. OBJECTIVE: In the present work, we applied a series of bioinformatics tools to design a dendritic cell (DC)-targeting Tregitope-based multi-epitope vaccine for MS to induce tolerance in pathogenic myelin-specific T cells. METHODS: The 3D structure of anti-DEC205 scFv and the remaining part of the vaccine were modeled by ROSIE Antibody server and ITASSER software, respectively. AIDA web server (ab initio domain assembly server) was applied to assemble two parts of the vaccine and build the full construct. Following modeled structure refinement and validation, physicochemical properties, and allergenicity of the vaccine were assessed. In the final step, in silico cloning was done to ensure high-level expression in the desired host. RESULTS: This vaccine consists of three main parts; 1) Anti-DEC205 scFv antibody, 2) multiepitope vaccine part composed of multiple pathogenic CD4+, and CD8+ T cell epitopes originated from multiple known antigens in MS patients, as well as T-regulatory (Treg)-inducing epitopes (Tregitopes), and 3) vasoactive intestinal peptide (VIP). All parts of the final vaccine were joined together with the help of proper linkers. After vaccine construction, the three-D structure, as well as different physicochemical and immunological features of the vaccine were predicted. Finally, in silico gene cloning was also carried out to assure efficient production of protein vaccine in Escherichia coli K12 expression strain. CONCLUSION: Computational study revealed that this vaccination can regulate MS disease progression and even relapse by harnessing pathogenic T cells.

Melatonin as a complementary and prophylactic agent against COVID-19 in high-risk populations: A narrative review of recent findings from clinical and preclinical studies.

The coronavirus disease 2019 (COVID-19) pandemic has been going on around the world for more than a year and has cost a lot, as well as affected the quality of life of many. The psychological stress like delirium and sleep disturbances caused by the COVID-19 has affected many people in direct or indirect way by the disease. Insomnia and sleep deprivation have a negative effect on the immune system as well as disorders of the hormonal system, including the production and secretion of melatonin, known as the sleep hormone. Melatonin is a known anti-inflammatory and antioxidant agent in addition to its role in regulating circadian rhythms. In this review, we investigated the relationship between the effect of psychological stress caused by COVID-19 on patients, their families, health care workers, and occupations as well as how melatonin might act as a prophylactic agent with sedative effects and sleep enhancement potential. Search terms "melatonin" and "COVID-19" were manually searched on PubMed or other electronic database and relevant articles were included. Based on the review of scholarly articles, it can be inferred that melatonin, as an endogenous hormone controlling and regulating sleep and wakefulness in various researches, has a good potential due to its antioxidant and anti-inflammatory with minimal side effects. These beneficial effects highlight the impact of melatonin as an adjuvant and a potential alternative for the better management of SARS-CoV-2 infection in high-risk populations.

NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement.

The inflammasome as a multiprotein complex has a role in activating ASC and caspase-1 resulting in activating IL-1ß in various infections and diseases like corona virus infection in various tissues. It was shown that these tissues are affected by COVID-19 patients. According to the current evidence, melatonin is not veridical while possessing a high safety profile, however, it possesses indirect anti-viral actions owing to its anti-oxidation, anti-inflammation, and immune improving properties. This study aims to assess the impacts of melatonin as the complementary treatments on oxidative stress agents and inflammasome activation in patients with COVID-19. Melatonin supplement (9 mg daily, orally) was provided for the patients hospitalized with a COVID-19 analysis for 14 days. For measuring IL-10, IL-1ß, and TNF-α cytokines and malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) level and the expression of CASP1 and ASC genes, blood samples were gathered from the individuals at the start and termination of the therapy. Our findings indicated that melatonin is used as a complementary treatment to reduce the levels of TNF-α and IL-1ß cytokines, MDA, and NO levels in COVID-19 patients and significantly increase SOD level, however, the levels of IL-10 cytokine possesses no considerable changes. The findings revealed that genes of CASP1 and ASC were dysregulated by melatonin regulating the inflammasome complex. Based on the findings of the current study, it is found that melatonin can be effective as a medicinal supplement in decreasing the inflammasome multiprotein complex and oxidative stress along with beneficial impacts on lung cytokine storm of COVID-19 patients.

Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial.

BACKGROUND: Melatonin has been known as an anti-inflammatory agent and immune modulator that may address progressive pathophysiology of coronavirus disease 2019 (COVID-19). AIM OF THE STUDY: To evaluate the clinical efficacy of adjuvant, use of melatonin in patients with COVID-19. METHODS: This single-center, double-blind, randomized clinical trial included 74 hospitalized patients with confirmed mild to moderate COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from April 25, 2020-June 5, 2020. Patients were randomly assigned in a 1:1 ratio to receive standard of care and standard of care plus melatonin at a dose of 3 mg three times daily for 14 d. Clinical characteristics, laboratory, and radiological findings were assessed and compared between two study groups at baseline and post-intervention. Safety and clinical outcomes were followed up for four weeks. RESULTS: A total of 24 patients in the intervention group and 20 patients in the control group completed the treatment. Compared with the control group, the clinical symptoms such as cough, dyspnea, and fatigue, as well as the level of CRP and the pulmonary involvement in the intervention group had significantly improved (p <0.05). The mean time of hospital discharge of patients and return to baseline health was significantly shorter in the intervention group compared to the control group (p <0.05). No deaths and adverse events were observed in both groups. CONCLUSIONS: Adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.

A cross-linked anti-TNF-α aptamer for neutralization of TNF-α-induced cutaneous Shwartzman phenomenon: A simple and novel approach for improving aptamers' affinity and efficiency.

To increase the efficiency of aptamers to their targets, a simple and novel method has been developed based on aptamer oligomerization. To this purpose, previously anti-human TNF-α aptamer named T1-T4 was trimerized through a trimethyl aconitate core for neutralization of in vitro and in vivo of TNF-α. At first, 54 mer T1-T4 aptamers with 5'-NH2 groups were covalently coupled to three ester residues in the trimethyl aconitate. In vitro activity of novel anti-TNF-α aptamer and its dissociation constant (Kd ) was done using the L929 cell cytotoxicity assay. In vivo anti-TNF-α activity of new oligomerized aptamer was assessed in a mouse model of cutaneous Shwartzman. Anchoring of three T1-T4 aptamers to trimethyl aconitate substituent results in formation of the 162 mer fragment, which was well revealed by gel electrophoresis. In vitro study indicated that the trimerization of T1-T4 aptamer significantly improved its anti-TNF-α activity compared to non-modified aptamers (P < 0.0001) from 40% to 60%. The determination of Kd showed that trimerization could effectively enhance Kd of aptamer from 67 nM to 36 nM. In vivo study showed that trimer aptamer markedly reduced mean scar size from 15.2 ± 1.2 mm to 1.6 ± 0.1 mm (P < 0.0001), which prevent the formation of skin lesions. In vitro and in vivo studies indicate that trimerization of anti-TNF-α aptamer with a novel approach could improve the anti-TNF-α activity and therapeutic efficacy. According to our findings, a new anti-TNF-α aptamer described here could be considered an appropriate therapeutic agent in treating several inflammatory diseases.

Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment.

Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease. A number of medications have been suggested to treat or control the disease but have been discontinued due to their side effects. Melatonin, as an intrinsic molecule, possesses pharmacological anti-inflammatory and antioxidant properties that decreases in concentration with age; as a result, older people are more prone to various diseases. In this study, patients who were hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) were given a melatonin adjuvant (9 mg daily, orally) for fourteen days. In order to measure markers of Th1 and Th2 inflammatory cytokines (such as interleukin (IL)-2, IL-4, and interferon (IFN)-γ) as well as the expression of Th1 and Th2 regulatory genes (signal transducer and activator of transcription (STAT)4, STAT6, GATA binding protein 3 (GATA3), and T-box expressed in T cell (T-bet)), blood samples were taken from patients at the beginning and end of the treatment. Adjuvant therapy with melatonin controlled and reduced inflammatory cytokines in patients with COVID-19. Melatonin also controlled and modulated the dysregulated genes that regulate the humoral and cellular immune systems mediated by Th1 and Th2. In this study, it was shown for the first time that melatonin can be used as a medicinal adjuvant with anti-inflammatory mechanism to reduce and control inflammatory cytokines by regulating the expression of Th1 and Th2 regulatory genes in patients with COVID-19.

KDM5A mutations identified in autism spectrum disorder using forward genetics.

Autism spectrum disorder (ASD) is a constellation of neurodevelopmental disorders with high phenotypic and genetic heterogeneity, complicating the discovery of causative genes. Through a forward genetics approach selecting for defective vocalization in mice, we identified Kdm5a as a candidate ASD gene. To validate our discovery, we generated a Kdm5a knockout mouse model (Kdm5a-/-) and confirmed that inactivating Kdm5a disrupts vocalization. In addition, Kdm5a-/- mice displayed repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis. Loss of KDM5A also resulted in dysregulation of the hippocampal transcriptome. To determine if KDM5A mutations cause ASD in humans, we screened whole exome sequencing and microarray data from a clinical cohort. We identified pathogenic KDM5A variants in nine patients with ASD and lack of speech. Our findings illustrate the power and efficacy of forward genetics in identifying ASD genes and highlight the importance of KDM5A in normal brain development and function.

Catalytic and structural effects of flexible loop deletion in organophosphorus hydrolase enzyme: A thermostability improvement mechanism.

Thermostability improvement of enzymes used industrially or commercially would develop their capacity and commercial potential due to increased enzymatic competence and cost-effectiveness. Several stabilizing factors have been suggested to be the base of thermal stability, like proline replacements, disulfide bonds, surface loop truncation and ionic pair networks creation. This research evaluated the mechanism of increasing the rigidity of organophosphorus hydrolase enzyme by flexible loop truncation. Bioinformatics analysis revealed that the mutated protein retains its stability after loop truncation (five amino acids deleted). The thermostability of the wild-type (OPH-wt) and mutated (OPH-D5) enzymes were investigated by half-life, Delta Gi, and fluorescence and far-UV CD analysis. Results demonstrated an increase half-life and Delta Gi in OPH-D5 compared to OPH-wt. These results were confirmed by extrinsic fluorescence and circular dichroism (CD) spectrometry experiments, therefore, as rigidity increased in OPHD5 after loop truncation, half-life and Delta Gi also increased. Based on these findings, a strong case is presented for thermostability improvement of OPH enzyme by flexible loop truncation after bioinformatics analysis.

Disulfide bridge formation to increase thermostability of DFPase enzyme: A computational study.

Organophosphate compounds bioremediation by use of organophosphorus degradation enzymes such as DFPase is a developing interest in industry and medicine. The most important problem with the bio-catalytic enzymes is their instability on high temperatures. This work carried out to find suitable locations for introducing disulfide bridges in DFPase enzyme. We employed some computational approaches to design the disulfide bridges and evaluate their roles in the enzyme structural thermostability. According to the in silico results, mutant 6 (V24C, C76) increased the enzyme thermostability relative to wild-type.

Angelman Syndrome: A Case Report.

Objective Angelman syndrome (AS) is a neurodevelopmental disorder presented by jerky movement, speech delay and cognitive disability epilepsy as well as dysmorphic features. It occurs due to an expression deletion in 15q11-q13 chromosome. In this article, we present an eight yr boy referred to Pediatrics Neurologic Clinic Mashhad, Iran for speech delay. He had abnormal behavior ataxia unusual laughing facial expression intellectual disability and mandibular prognathism. Metabolic screening tests and brain MRI were normal. Genetic analysis was pathognomonic for AS.

Constructing Chimeric Antigen for Precise Screening of HTLV-I Infection.

Individual preparation of two human T-cell lymphotropic virus type I (HTLV-I) diagnostic GST fused peptides (MTA-1 and GD21) is time-consuming and expensive. The aim of this study was to design a novel single chimeric antigen (SCA) to obviate separate expression of proteins and reduce the cost of reagent preparation. Structural protein fragments, including immunodominant B cell linear epitopes, were selected and different SCAs were designed. Tertiary structure, epitope exposure, solubility and stability were calculated for each SCA and compared with each other. The synthetic DNA encoding the interested SCA was sub-cloned into pET32a expression vector, expressed as a soluble form in Escherichia coli BL21 (DE3) cells and purified under native condition using affinity chromatography. The SDS-PAGE results indicated that thioredoxin-fused SCA was successfully expressed as a soluble form in E. coli BL21 (DE3) cells. The results of ELISA confirmed that SCA reacted with anti-HTLV-I antibodies in a concentration-dependent manner. Our results indicated that the designed SCA may be a good candidate for the screening of HTLV-I carriers with antigen-antibody-based tests.

Farsi Version of the Mammography Self-efficacy Scale for Iranian Women.

BACKGROUND: Self-efficacy is a crucial factor in adopting mammography behavior. A reliable and valid instrument is necessary to measure self-efficacy among Iranian women. OBJECTIVE: The aim of this study is to translate the original version of Champion's Mammography Self-efficacy Scale into Farsi and then to estimate the Farsi version's reliability and validity. METHODS: In a cross-sectional study, 200 women 40 years or older who were referred to health centers in Iran were invited to complete the related questionnaires during an interview. Cronbach's α coefficients and item-total correlations were measured to evaluate the reliability of the scales. Content and face validities were evaluated using the opinions of a panel of experts, and construct validity was estimated through applying confirmatory factor analysis. Logistic regression and χ tests were used to estimate theoretical relationships. RESULTS: In terms of reliability, the internal consistency α was .904 and the test-retest reliability correlation over a 4-week period was 0.624. With regard to the confirmatory factor analysis, the proportion of χ to degrees of freedom was 0.394, giving a P value of .852 and a root-mean-square error of approximation less than 0.001 with confidence intervals of less than 0.001 and 0.018, with a comparative fit index of 1, normed fit index of 0.999, relative fit index of 0.993, and incremental fit index of 1. CONCLUSION: The items that form the self-efficacy measurement scale in the Farsi version are highly reliable and valid. IMPLICATIONS FOR PRACTICE: Healthcare professionals and nursing health communities may apply the instrument to determine women's self-efficacy and to plan appropriate educational interventions, aiming at promoting women's mammography behavior.

The Cytoplasmic and Periplasmic Expression Levels and Folding of Organophosphorus Hydrolase Enzyme in Escherichia coli.

BACKGROUND: Organophosphorus hydrolase (OPH) is a type of organophosphate-degrading enzyme which is widely used in the bioremediation process. OBJECTIVES: In this study, the periplasmic and cytoplasmic productions and the activity of recombinant OPH in Escherichia coli were investigated and compared using two pET systems (pET21a and pET26b). MATERIALS AND METHODS: The sequence encoding the opd gene was synthesized and expressed in the form of inclusion body using pET21a-opd and in the periplasmic space in pET26b-opd. RESULTS: Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed a band of about 37 kDa with a maximum expression level at 30°C from pET21a-opd.However, the obtained results of the periplasmic space extraction of OPH (pET26b-opd) showed a very weak band, while the cytoplasmic expression of OPH (pET21a-opd) produced a strong protein band. CONCLUSIONS: The activities studied by the production of PNP were determined by following the increase at 410 nm. The maximum PNP was produced at 30°C with an optical density of 10.62 in the presence of cytoplasmic expression of OPH (pET21a-opd). Consequently, our results suggest cytoplasmic expression system as an appropriate candidate with a high amount of OPH in spite of inclusion body formation, which needs an additional refolding step.

Antibacterial activity of ethyl acetate and aqueous extracts of Mentha longifolia L. and hydroalcoholic extract of Zataria multiflora Boiss. plants against important human pathogens.

OBJECTIVE: To determine the potential antibacterial activity of ethyl acetate and aqueous extracts from Mentha longifolia L. (M. longifolia) and hydroalcoholic extract of Zataria multiflora Boiss. (Z. multiflora) against important human pathogens. METHODS: Pseudomonas aeruginosa, Shigella dysenteriae, Klebsiella pneumoniae (K. pneumonia), Enterobacter cloacae, Salmonella typhi, Proteus mirabilis, Serratia marcescens, Bacillus cereus, Staphylococcus saprophyticus and Staphylococcus aureus were kinds of pathogenic bacteria to determine the antibacterial effect of aqueous and ethyl acetate extracts of M. longifolia and hydroalcoholic extract of Z. multiflora using broth microdiluation method. RESULTS: The lowest minimum inhibitory concentration and minimum bactericidal concentration values for K. pneumonia and Pseudomonas aeruginosa (1.25 and 2.5 mg/mL) were observed by the hydroalcoholic extract of Z. multiflora and the lowest minimum inhibitory concentration and minimum bactericidal concentration values for K. pneumonia and Serratia marcescens (2.5 and 5 mg/mL) were observed by the aqueous extracts of M. longifolia. CONCLUSIONS: In conclusion, it seems that Z. multiflora and M. longifolia extracts could inhibit the growth of all of the mentioned bacteria.

Investigation of caspase-1 activity and interleukin-1ß production in murine macrophage cell lines infected with Leishmania major.

OBJECTIVE: To investigate the caspase-1 dependent inflammatory pathway activity and interleukin-1ß (IL-1ß) secretion in murine macrophage cell lines J774G8 infected with Leishmania major (L. major) using caspase-1 activity assay and ELISA. METHODS: Novy-MacNeal-Nicolle biphasic medium was applied to produce promastigote form of L. major. Metacyclic promastigotes in the stationary phase were applied to infect macrophage. Caspase-1 activity and IL-1ß secretion were assessed by the CPP32/caspase-1 fluorometric protease assay and ELISA IL-1ß kits, respectively, with time intervals of 6, 18 and 30 h. RESULTS: Our study showed an increase in caspase-1 activity and IL-1ß secretion in infected samples compared to non-infected macrophages. The highest increase in IL-1ß production was observed after 6 h of infection. CONCLUSIONS: These results arise that the activation of inflammasome pathway could be one of the innate immunity pathways against L. major.

Farsi version of the multidimensional health locus of control and God locus of health control scales: validity and reliability study among Iranian women with a family history of breast cancer.

OBJECTIVE: To determine the Persian version's reliability and validity of the Multidimensional Health Locus of Control and God Health Locus of Control scales among women with family history of breast cancer. METHODS: The cross-sectional study was conducted in Sabzevar, Iran, in 2012. It randomly selected women with family members affected by breast cancer. Predesigned questionnaires were completed through interviews. Content and face validity was evaluated using the opinions of a panel of experts, and construct validity was confirmed by applying confirmatory factor analysis.The instruments' reliability was assessed using Cronbach's alpha and test-retest reliability. RESULTS: There were 200 women in the study with their age ranging between 18 and 69 years and revealed the following; root mean square error of approximation for Multidimensional Health Locus of Control Scale = 0.013, and God Locus of Health Control Scale = 0.077; comparative fit index = 0.999, 0.998; incremental fit index = 0.999, 0.998;Tucker-Lewis fit index = 0.998, 0.998; and normed fit index = 0.983, 0.997 respectively. Cronbach's alpha was 0.61 for Internal Health Locus of Control, 0.8 for Chance Health Locus of Control, 0.68 for Power Health Locus of Control and 0.9 for God Locus Health Control. CONCLUSION: The Persian version of the subscales supported the main version.

Introduction of a New Diagnostic Method for Breast Cancer Based on Fine Needle Aspiration (FNA) Test Data and Combining Intelligent Systems.

BACKGROUND: Accurate Diagnosis of Breast Cancer is of prime importance. Fine Needle Aspiration test or "FNA", which has been used for several years in Europe, is a simple, inexpensive, noninvasive and accurate technique for detecting breast cancer. Expending the suitable features of the Fine Needle Aspiration results is the most important diagnostic problem in early stages of breast cancer. In this study, we introduced a new algorithm that can detect breast cancer based on combining artificial intelligent system and Fine Needle Aspiration (FNA). METHODS: We studied the Features of Wisconsin Data Base Cancer which contained about 569 FNA test samples (212 patient samples (malignant) and 357 healthy samples (benign)). In this research, we combined Artificial Intelligence Approaches, such as Evolutionary Algorithm (EA) with Genetic Algorithm (GA), and also used Exact Classifier Systems (here by Fuzzy C-Means (FCM)) to separate malignant from benign samples. Furthermore, we examined artificial Neural Networks (NN) to identify the model and structure. This research proposed a new algorithm for an accurate diagnosis of breast cancer. RESULTS: According to Wisconsin Data Base Cancer (WDBC) data base, 62.75% of samples were benign, and 37.25% were malignant. After applying the proposed algorithm, we achieved high detection accuracy of about "96.579%" on 205 patients who were diagnosed as having breast cancer. It was found that the method had 93% sensitivity, 73% specialty, 65% positive predictive value, and 95% negative predictive value, respectively. If done by experts, Fine Needle Aspiration (FNA) can be a reliable replacement for open biopsy in palpable breast masses. Evaluation of FNA samples during aspiration can decrease insufficient samples. FNA can be the first line of diagnosis in women with breast masses, at least in deprived regions, and may increase health standards and clinical supervision of patients. CONCLUSION: Such a smart, economical, non-invasive, rapid and accurate system can be introduced as a useful diagnostic system for comprehensive treatment of breast cancer. Another advantage of this method is the possibility of diagnosing breast abnormalities. If done by experts, FNA can be a reliable replacement for open biopsy in palpable breast masses. Evaluation of FNA samples during aspiration can decrease insufficient samples.