Associations between the perception of dental pain and pain anxiety, mental pain, and dental anxiety in Iranian sample.

OBJECTIVE: This study examined the perception of dental pain and its relationship to pain anxiety, dental anxiety, and mental pain. METHODS: This cross-sectional study was conducted on 328 patients referred to dental clinics in Kermanshah (Iran) from 2020 to 2021. The instruments used in this study included scales assessing pain anxiety, dental anxiety, mental pain, and pain perception. RESULTS: There was a significant relationship (p = .001) between pain perception with dental anxiety (r = .38), pain anxiety (r = .45), and mental pain (r = .25). CONCLUSION: Psychological factors are associated with the perception of dental pain. Given the importance of dental care to overall health, psychological interventions may help to reduce the perception of dental pain and fear of seeing dentists in Iran.

Synthesized Anti-HER2 Trastuzumab-MCC-DM1 Conjugate: An Evaluation of Efficacy and Cytotoxicity.

Background: Trastuzumab is a humanized monoclonal antibody that targets site-specifically human epidermal growth factor-2 receptor (HER2) cell surface antigen overexpressed in approximately 20% of human breast carcinomas. Despite its positive therapeutic outcomes, a large proportion of individuals are unresponsive to the treatment with the trastuzumab or develop resistance to it. Objective: To evaluate a chemically synthesized trastuzumab-based antibody-drug conjugate (ADC) to improve the trastuzumab therapeutic index. Methods: The current study explored the physiochemical characteristics of the trastuzumab conjugated to a cytotoxic chemotherapy agent DM1 via Succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker, created in our earlier study, using SDS-PAGE, UV/VIS, and RP-HPLC analyses. The antitumor effects of the ADCs were analyzed using MDA-MB-231 (HER2-negative) and SK-BR-3 (HER2-positive) cell lines utilizing in vitro cytotoxicity, viability, and binding assays. Three different formats of a HER2-targeting agent: trastuzumab, synthesized trastuzumab-MCC-DM1, and commercially available drug T-DM1 (Kadcyla®) were compared. Results: UV-VIS spectroscopic analysis showed that the trastuzumab-MCC-DM1 conjugates, on average, entailed 2.9 DM1 payloads per trastuzumab. A free drug level of 2.5% was determined by RP-HPLC. The conjugate appeared as two bands on a reducing SDS-PAGE gel. MTT viability assay showed that conjugating trastuzumab with DM1 significantly improved the antiproliferative effects of this antibody in vitro. Importantly, the evaluations using LDH release and cell apoptosis assays confirmed that trastuzumab maintains its ability to induce cell death response while conjugating with the DM1. The binding efficiency of trastuzumab-MCC-DM1 was comparable to that of the naked trastuzumab. Conclusion: Trastuzumab-MCC-DM1 was found effective against HER2+ tumors. The potency of this synthesized conjugate brings it closer to the commercially available T-DM1.

A coumarin-based fluorescent chemosensor as a Sn indicator and a fluorescent cellular imaging agent.

In the present study, fluorogenic coumarin-based probes (1-3) through condensation of 4-hydroxy coumarin with malondialdehyde bis(diethyl acetal)/triethyl orthoformate were prepared. The absorption and fluorescence emission properties of 2b and 3 in different solvents were studied, and a considerable solvatochromic effect was observed. The sensitivity of chemosensors 2b and 3 toward various cations and anions was investigated. It was revealed that compound 3 had a distinct selectivity toward Sn2+, possibly via a chelation enhanced quenching mechanism. The fluorescence signal was quenched over the concentration range of 6.6-120 µM, with an LOD value of 3.89 µM. The cytotoxicity evaluation of 3 against breast cancer cell lines demonstrated that the chemosensor was nontoxic and could be used successfully in cellular imaging. The probe responded to tin ions not only via fluorescence quenching, but also through colorimetric signal change. The change in optical properties was observed in ambient conditions and inside living cells.

Current Status and Future Trends of Acceptance and Commitment Therapy (ACT) for Smoking Cessation: A Narrative Review with Specific Attention to Technology-Based Interventions.

Background: During recent decades, it has become evident that cigarette smoking has led to an increase in cancer, risk of death, and economic problems or sanitation issues worldwide. Acceptance and commitment therapy (ACT), as a third-wave behavioral therapy, has devoted significant attention to smoking cessation. However, this treatment has been utilized in different formats and protocols. Moreover, addressing its challenges and progress needs examination and integration. Accordingly, the primary aim of this study was to present a narrative review for summarizing and integrating the current data on the effectiveness of ACT on smoking cessation. This study also aimed to investigate the challenges and the future of this field. Methods: The publications from January 1, 2010 to October 9, 2021 were identified by searching MEDLINE, Embase, Scopus, PsycINFO, and Web of Science electronic databases. The search was performed with the following keywords: "Acceptance AND Commitment Therapy" OR "Acceptance" AND "smoking" OR "tobacco" OR "cigarette" OR "smoker" OR "Nicotine". The inclusion criterion was studies with interventions aimed at reducing smoking cessation in smokers. Findings: A total of 17 articles were analyzed in this study. The results showed that this treatment has significant effectiveness in smoking cessation and psychiatric comorbidities. Moreover, the role of experiential avoidance in smoking cessation was discussed in detail. Conclusion: ACT is a suitable psychotherapy module for smoking cessation. However, it needs some upgrades regarding technology. To this end, smartphone applications and AVATAR therapy technologies were discussed with their advantages and solvable disadvantages.

Ovarian volume, not follicle count, is independently associated with androgens in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is diagnosed based on chronic anovulation, androgen excess (clinical and/or biochemical), and polycystic ovaries in ultrasound. The aim of the present study was to evaluate which parameters in the transvaginal ultrasound (TVUS) of ovaries could be better associated with concurrent hormonal imbalance in the women with PCOS. METHODS: Using a cross-sectional design, this study focused on 61 subjects (18-40 years) with PCOS. Patients were recruited at three academic hospitals during the 2017-2019 period. PCOS was defined according to the Rotterdam criteria. The association of ovarian morphology with hormonal and metabolic feature was investigated using linear regression models, adjusted for a set of possible confounding variables including age, mensuration status and body mass index (BMI). RESULTS: The mean volume of both ovaries was positively associated with the total testosterone level (ß = 0.025, P value < 0.001), free androgen index (ß = 0.041, P value < 0.001) and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (ß = 0.032, P value = 0.004), even after adjustments made for age, mensuration status and BMI (fully-adjusted model). In contrast, in the fully-adjusted model, antral follicle count (AFC), follicle number per ovary (FNPO), ovarian area, stromal area, and ratio of stromal area to ovarian area (S/A) were not associated with androgen levels and LH/FSH ratio. In addition, after full adjustments, ovarian volume, AFC, FNPO, ovarian area, stromal area and S/A were not associated with insulin resistance, which was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSION: Increased ovarian volume is, thus, highly predictive of hyperandrogenemia and high LH/FSH ratio in PCOS patients.

Effect of resveratrol administration on ovarian morphology, determined by transvaginal ultrasound for the women with polycystic ovary syndrome (PCOS).

Intake of resveratrol has been associated with improved ovarian morphology under in vitro and in the animal models; however, this finding has not been confirmed in trials. The aim of our study was, therefore, to use a placebo-controlled approach with the detailed assessment of the ovarian morphology by applying transvaginal ultrasound to examine the effectiveness of this therapeutic approach in this group of women. The mean age of all participants was 28·61 (sd 4·99) years, with the mean BMI of 28·26 (sd 5·62) kg/m2. Resveratrol therapy, as compared with placebo, was associated with a significantly higher rate of improvement in the ovarian morphology (P = 0·02). Women who received resveratrol had a more dominant follicle than those getting placebo, with a significant reduction in the ovarian volume (P < 0·05). However, the number of follicle count per ovary (FNPO), stromal area (SA), ovarian echogenicity and distribution of follicles were not significantly altered (P > 0·05). Forty-one women with polycystic ovary syndrome (PCOS) were randomly assigned (1:1) to 3 months of daily 1000 mg resveratrol or placebo. Random assignment was done by blocked randomisation. Our primary endpoints were the change in the ovarian volume, SA and antral FNPO from the baseline to 3 months. Secondary endpoints were improvement in the distribution of follicles and ovarian echogenicity. Differences between the resveratrol and control groups were evaluated by Chi-square, Fisher's exact test and repeated-measures ANOVA. Treatment with resveratrol significantly reduced the ovarian volume and polycystic ovarian morphology, thus suggesting a disease-modifying effect in PCOS.

The synergistic effect of vitamin D supplement and mindfulness training on pain severity, pain-related disability and neuropathy-specific quality of life dimensions in painful diabetic neuropathy: a randomized clinical trial with placebo-controlled.

PURPOSE: This study aimed to examine the synergistic effect of Vitamin D (VD) Supplement and mindfulness on neuropathic pain severity, Pain-Related Disability and Neuropathy-Specific Quality of Life (QOL) dimensions in painful diabetic neuropathy. METHODS: In this randomized controlled trial, 225 patients with painful diabetic neuropathy were randomly allocated to five groups: (1) mindfulness and placebo, (2) placebo, (3) mindfulness, (4) VD, and (5) mindfulness and VD. Mindfulness training includes twelve sessions, and VD patients received a daily four thousand IU oral dosage (four capsules) with 28,000 IU vitamin D weekly for 12 weeks. Laboratory analyses, Sun exposure time, Vitamin D intake, BMI and physical activity were measured in pre-test and post-test. Pain-Related Disability measured with The Pain Disability Index (PDI). For other outcome variables, Neuropathy, a Specific QOL questionnaire and Neuropathic pain severity scale were utilized. Data were analyzed using one-way repeated-measures analysis of variance (ANOVA), Scheffe Post-hoc test and paired sample t-test. RESULTS: In baseline, measures were not different among the groups. At the end-of-treatment, results showed improvement in all groups except the "placebo only" group for outcome variables. There was no difference between VD and mindfulness groups (within and not combined with placebo) in posttest. However, "VD + mindfulness" has a greater improvement rather than VD and mindfulness groups (P < 0.05). Moreover, both protocols have no significant effects on FBS, BMI and energy intakes (P > 0.05). CONCLUSION: Combining VD and mindfulness can reduce pain severity and pain-related disability, so with these changes, patients experience improve in their quality of life.

A pilot randomized controlled trial of dialectical behavior therapy (DBT) for reducing craving and achieving cessation in patients with marijuana use disorder: feasibility, acceptability, and appropriateness.

OBJECTIVE: To conduct a pilot RCT investigating the feasibility, acceptability, and preliminary efficacy of dialectical behavioral therapy (DBT) for marijuana cessation and craving reduction. METHODS: Sixty-one patients with marijuana use disorder diagnoses were randomly assigned to a DBT group or a control group (psycho-education). Patients completed measures at pre-intervention, post-intervention, and at two-month follow-up. The Marijuana Craving Questionnaire (MCQ) and marijuana urine test kits were used to assess craving and abstinence respectively. RESULTS: The feasibility of DBT was significantly higher than control group feasibility. In the DBT 29/30 participants completed all sessions (96% retention) and 24/31 control group participants completed all sessions (77% retention) (χ2 = 4.95, p = 0.02). Moreover, 29/30 (96%) participants in the DBT group completed the two-month follow-up and 20/31 (64.5%) control group members completed the two-month follow-up (χ2 = 9.97, p = 0.002). The results showed that patients in the DBT group had significantly higher intervention acceptability rates (16.57 vs. 9.6) than those in the control group. This pattern was repeated for appropriateness rates (p < 0.05). The overall results for craving showed that there was no significant difference between the groups (F = 3.52, p > 0.05), although DBT showed a significant reduction in the "emotionality" subscale compared to the control group (F = 19.94, p < 0.05). To analyze cessation rates, DBT was compared to the control group at the posttest (46% vs. 16%) and follow-up (40% vs. 9.5%) and the results confirmed higher effectiveness in the DBT group for cessation (p < 0.05). Furthermore, among those who had lapsed, participants in the DBT group had fewer consumption days than those in the control group (p < 0.05). CONCLUSIONS: DBT showed feasibility, acceptability, and promising efficacy in terms of the marijuana cessation rate. CLINICAL TRIAL REGISTRATION: Thailand Registry of Clinical Trials, TCTR20200319007.

The effect of bone marrow-derived mesenchymal stem cell co-transplantation with hematopoietic stem cells on liver fibrosis alleviation and survival in patients with class III ß-thalassemia major.

BACKGROUND: Hepatic fibrosis is a common complication in transfusion-dependent thalassemia patients. Data on the co-transplantation of mesenchymal stem cells (MSCs) with hematopoietic stem cells (HSCs) in beta-thalassemia major patients are scarce. Therefore, we aimed to evaluate the effect of co-transplantation of bone marrow-derived MSC with HSCs on the liver fibrosis alleviation and transplant outcomes in class III beta-thalassemia major. METHODS: Between April 1998 and January 2017, a total of 224 consecutive patients with class III beta-thalassemia major underwent allogeneic HSCT in the Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran. To assess liver fibrotic changes after transplantation, 47 patients participated in the MSC plus HSC group and 30 patients in the HSC only group at the end of the follow-up period. All patients underwent laboratory tests, especially serum ferritin and liver function testing, hepatic T2* MRI, liver biopsy, and FibroScan before and 2 years after transplantation. Kaplan-Meier curves were derived to determine survival and were compared using the log-rank test. Repeated-measure, mixed-effect linear regression models were used to examine the changes in liver fibrosis over time. RESULTS: The 10-year OS rate was 71.84% in the mesenchymal group and 61.89% in the non-mesenchymal group (P value = 0.294), while the 10-year TFS rate was 63.64% in the mesenchymal group and 52.78% in the non-mesenchymal group (P value = 0.285). No significant difference was observed in the 10-year NRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD between the two groups. In addition, the results of repeated-measure, mixed-effect linear regression models showed that none of the variables determining hepatic fibrosis had a significant difference between patients receiving MSCs and patients who did not receive MSCs. CONCLUSIONS: Based on the results of this study, a single infusion of MSCs at the time of HSCT to patients with class III beta-thalassemia major could not significantly improve the liver fibrosis alleviation and transplantation outcomes, including OS, TFS, TRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD.

Predicting the quality of life based on pain dimensions and psychiatric symptoms in patients with Painful diabetic neuropathy: a cross-sectional prevalence study in Iranian patients.

BACKGROUND: This study aimed to predict the quality of life (QOL) in patients with Painful Diabetic Neuropathy (PDN) based on pain severity, pain catastrophizing, pain acceptance, depression, anxiety, and sleep disturbance. Also, this study was aimed to assess the prevalence of psychiatric symptoms in Iranian patients with PDN. METHOD: 1120 patients (mean age, 53.6 ± 12.6 years) participated in the research. Data were collected by the Quality of life questionnaire (NeuroQoL); Beck Depression Inventory, Beck Anxiety Inventory, the visual analog scale for pain severity, Pain Catastrophizing Scale (PCS), Chronic Pain Acceptance Questionnaire (CPAQ) and Pittsburgh Sleep Quality Index (PSQI). Finally, the data were analyzed using SPSS-26 by multiple regression analysis. RESULTS: The results showed the regression models' significance, and the dependent variables predicted 42% of total changes in the QOL. The most significant predicting factors were depression, pain catastrophizing, pain acceptance, pain severity, sleep disturbance, and anxiety in order. In patients with PDN, the prevalence of sleep disturbances, depression, and anxiety were 85.5%, 68.2%, and 62.1%, respectively. Also, comorbid depression and anxiety were found in 47% of patients. CONCLUSION: Results demonstrated a significant relationship between pain-related and psychiatric dimensions with QOL. Thus, it is suggested to design more specific psychological-based rehabilitation interventions in which these variables are considered. They should focus on more significant variables (such as depression and pain catastrophizing) to reach better treatment outcomes. Furthermore, this research shows a high level of anxiety, depression, and sleep disturbance in Iranian patients with PDN. Thus, experts and clinicians are suggested to focus on reducing these psychiatric symptoms.

The Effectiveness of Acceptance and Commitment Therapy on Pain Acceptance and Pain Perception in Patients with Painful Diabetic Neuropathy: A Randomized Controlled Trial.

INTRODUCTION: Neuropathic pain is a complex phenomenon in patients with diabetes. These patients have many problems, such as psychological problems, high-level pain perception, and pain acceptance. This study aimed to evaluate the effectiveness of acceptance and commitment therapy on pain acceptance and pain perception in patients with painful diabetic neuropathy. METHODS: This study was performed according to the clinical trial method. The sample size was 50 participants. In this study, participants were divided into interventional and control groups. According to the diagnosis of neurologists, all participants received conventional medications to manage neuropathic pain. The intervention group received acceptance and commitment therapy for eight sessions. The results in the three phases of pre-test, post-test, and follow-up were evaluated. After completing the study, to comply with ethical standards, the control group received psycho-education. The tools used were the McGill Pain Questionnaire (MPQ) and the Chronic Pain Acceptance Questionnaire (CPAQ). Statistical analysis includes mean, standard deviation, and repeated-measures (ANOVA) conducted by SPSS software version 22. RESULTS: The results demonstrated that in the post-test and follow-up phases, acceptance and commitment therapy could improve pain acceptance and reduce pain perception in the intervention group compared to the control group (P < 0.01). CONCLUSION: The results indicated that acceptance and commitment therapy could be used as a psychological intervention besides pharmacotherapy to improve pain acceptance and reduce pain perception in patients with painful diabetic neuropathy. CLINICAL TRAIL REGISTRATION: This study was registered at the Iranian Registry of Clinical Trials (IRCT20180205038630N4).

68Ga-DOTATATE PET/CT Compared with 131I-MIBG SPECT/CT in the Evaluation of Neural Crest Tumors.

OBJECTIVES: 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) has shown promising results in imaging of neural crest tumors (NCT). Herein, we compared the performance of 68Ga-DOTATATE PET/CT and 131I-MIBG single photon emission computed tomography (SPECT)/CT in the initial diagnosis, staging and follow-up of patients with NCTs. METHODS: Twenty-five patients (males:females=8:17; age range=2-71 years) with clinically proven or suspicious neuroblastoma, pheochromocytoma (PCC) or paraganglioma (PGL) were enrolled in this prospective study and underwent both 68Ga-DOTATATE PET/CT and 131I-MIBG SPECT/CT. A composite reference standard derived from histopathological information, together with anatomical and functional imaging findings, was used to validate the results. Imaging findings were assessed on a per-patient and on a per-lesion basis. Sensitivity and accuracy were assessed using McNemar's test. RESULTS: Referring to radiological imaging and histopathological findings as reference standard, 68Ga-DOTATATE and 131I-MIBG scans showed a sensitivity and accuracy of (100%, 96%) and (86.7%, 88%), respectively, on a per-patient basis. In PCC/PGL patients, on a per-patient basis, the sensitivity of 68Ga-DOTATATE was 100% and that of 131I-MIBG was 77.8%. In neuroblastoma patients, on a per-patient basis, the sensitivities of both 68Ga-DOTATATE and 131I-MIBG were 100%. Overall, in this patient cohort, 68Ga-DOTATATE PET/CT identified 52 lesions and 131I-MIBG SPECT/CT identified only 30 lesions. On a per-lesion analysis, 68Ga-DOTATATE was found to be superior to 131I-MIBG in detecting lesions in all anatomical locations, particularly osseous lesions. According to the McNemar test results, differences were not statistically significant. CONCLUSION: This relatively small patient cohort suggests 68Ga-DOTATATE PET/CT be superior to 131I-MIBG SPECT/CT in providing particularly valuable information for both primary staging and follow-up in patients with NCT.

Selective immediate detection of Cu2+ by a pH-sensitive rhodamine-based fluorescence probe in breast cancer cell-line.

A biocompatible fluorogenic chemosensor (N-(3-carboxy acryloyl)) rhodamine B (RHA) comprising a furan-2,5-dione receptor and a rhodamine fluorophore via an iminohydrazine crosslinker has been prepared for more scrutinizing optical properties and utilization in molecular imaging of living cells. The consequences indicated that RHA not only is a good pH indicator in acidic media but also can be used as a great sensitive fluoroionophore with high selectivity. The fluorescence emission of the molecule RHA is quite stable in the presence of 15 diverse cations, 18 anions (especially H2PO4-, S2, and F-), and 5 amino acids with the different functional group as a model, except Cu2+ ions with observable emission intensity changing. The Cu2+ probe has a dual functional effect, an "on-off" mechanism in solvent media, and an "off-on" mechanism in Phosphate Buffered Saline (PBS) in acidic pH conditions. The detection limits for Cu2+ in acetone-water media was 0.69 µM and 0.18 µM in pH = 5.0. Moreover, RHA can fluorescently and colorimetrically image Cu2+ ions in acidic and neutral pH with low cytotoxicity in living cells.

Effectiveness of acceptance and commitment therapy (ACT) on depression and sleep quality in painful diabetic neuropathy: a randomized clinical trial.

BACKGROUND: Neuropathic pain is a complicated phenomenon in patients with diabetes. These patients have many problems, especially depression and Sleep disturbance. This study aimed to assess the effectiveness of Acceptance and Commitment Therapy on depression and Sleep disturbance in patients with painful diabetic neuropathy. METHODS: The current paper was conducted according to the clinical trial method with 50 participants. Participants were separated into intervention and control groups randomly. Based on the diagnosis of neurologists, all participants received standard medications to regulate neuropathic pain. The intervention group received ACT for eight sessions. The results were evaluated in the pre-test, post-test, and follow-up. The tools used were the Pittsburgh sleep quality index (PSQI) and Beck's depression inventory. Statistical analysis includes descriptive statistics, and repeated-measures (ANOVA) conducted by SPSS (version 26) software. Results: Results showed that in the intervention group, the treatment led to improved depressive symptoms (F = 6.81, P < 0.05). Besides, for sleep quality, treatment in all subscales, except for the Hypnotic medicine subscale, significantly improved the intervention group's situations. It was also observed that the overall quality of sleep in the ACT group showed a more significant improvement (P < 0.05). All the above results remained the same until the end of the follow-up period (P < 0.05). CONCLUSION: ACT, as a complementary treatment, can improve the psychiatric symptoms and problems in people with neuropathic pain. Therefore, it is necessary to include psychotherapy services along with medical treatment in outpatient and hospitalization units. TRIAL REGISTRATION NUMBER: IRCT201802050388630N4. Registered in 02/05/2018.

Diagnostic fficiency of 68Ga-DOTATATE PET/CT as ompared to 99mTc-Octreotide SPECT/CT andonventional orphologic odalities in euroendocrine umors.

OBJECTIVES: In view of somatostatin receptor (SSR) expression on cell membranes of the majority of neuroendocrine tumors (NETs), functional imaging exploiting analogs of SSR alongside the anatomical imaging is the mainstay of this diagnostic modality. In this prospective study, we assessed and directly compared the diagnostic parameters of 68Ga-DOTATATE PET/CT and 99mTc-Octreotide SPECT/CT, as well as CT/MRI. METHODS: Twenty-five NET patients, either histologically proven or highly suspicious for NET, who were referred for Octreotide Scan were enrolled in this prospective study. They all underwent 99mTc-Octreotide SPECT/CT and then 68Ga-DOTATATE PET/CT. A blind interpretation was conducted for each imaging as well as for the previously obtained conventional imaging (CT or MRI). The patient-based and lesion-based analysis were conducted and the results of the three modalities were compared. The histopathologic confirmation or follow-up data were considered as the gold standard. Also, the impact of 68Ga-DOTATATE PET/CT on the patient's management was assessed. RESULTS: Overall, 77 lesions in 14 patients, 135 in 19 and 86 in 16 were detected on 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. On patient-based analysis, the sensitivity was 65%, 90% and 71% for 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. Also, the specificity was 80%, 80% and 75% for 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. The correlation between 68Ga-DOTATATE PET/CT and 99mTc-Octreotide SPECT/CT results was significant (=0.02; kappa value=0.57), no correlation, however, was depicted with CI (=0.07; kappa value=0.35). On lesion-based analysis, 68Ga-DOTATATE PET/CT found more organs (=0.02) and lesions (=0.001) in comparison with 99mTc-Octreotide SPECT/CT and also more lesions in comparison with CT/MRI (=0.003). In addition, comparing with 99mTc-Octreotide SPECT/CT and CT/MRI, 68Ga-DOTATATE PET/CT revealed more data in 44% and 36% of the patients, resulting in management modification in 24% and 20%, respectively. CONCLUSION: Comparing with 99mTc-Octreotide SPECT/CT and CT/MRI, 68Ga-DOTATATE PET/CT provided more sensitivity and specificity in patients with NETs showing more involved organs as well as tumoral lesions. Also, 68Ga-DOTATATE PET/CT led to change of management in up to one-fourth of the patients, especially in a sub-group re-evaluated for recurrence.

Convergent effects of a functional C3 variant on brain atrophy, demyelination, and cognitive impairment in multiple sclerosis.

BACKGROUND: Complement system activation products are present in areas of neuroinflammation, demyelination, and neurodegeneration in brains of patients with multiple sclerosis (MS). C3 is a central element in the activation of complement cascades. A common coding variant in the C3 gene (rs2230199, C3R102G) affects C3 activity. OBJECTIVES: To assess the effects of rs2230199 on MS severity using clinical, cognitive, and imaging measures. METHODS: In total, 161 relapse-onset MS patients (Expanded Disability Status Scale (EDSS) ≤ 6) underwent physical assessments, cognitive tests (Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and California Verbal Learning Test (CVLT)), and magnetic resonance imaging (MRI). Lesion volumes were quantified semi-automatically. Voxel-wise analyses were performed to assess the effects of rs2230199 genotype on gray matter (GM) atrophy ( n = 155), white matter (WM) fractional anisotropy (FA; n = 105), and WM magnetization transfer ratio (MTR; n = 90). RESULTS: While rs2230199 minor-allele dosage (C3-102G) showed no significant effect on EDSS and Multiple Sclerosis Functional Composite (MSFC), it was associated with worse cognitive performance ( p = 0.02), lower brain parenchymal fraction ( p = 0.003), and higher lesion burden ( p = 0.02). Moreover, voxel-wise analyses showed lower GM volume in subcortical structures and insula, and lower FA and MTR in several WM areas with higher copies of rs2230199 minor allele. CONCLUSION: C3-rs2230199 affects white and GM damage as well as cognitive impairment in MS patients. Our findings support a causal role for complement system activity in the pathophysiology of MS.

Thirty biologically interpretable clusters of transcription factors distinguish cancer type.

BACKGROUND: Transcription factors are essential regulators of gene expression and play critical roles in development, differentiation, and in many cancers. To carry out their regulatory programs, they must cooperate in networks and bind simultaneously to sites in promoter or enhancer regions of genes. We hypothesize that the mRNA co-expression patterns of transcription factors can be used both to learn how they cooperate in networks and to distinguish between cancer types. RESULTS: We recently developed a new algorithm, Thresher, that combines principal component analysis, outlier filtering, and von Mises-Fisher mixture models to cluster genes (in this case, transcription factors) based on expression, determining the optimal number of clusters in the process. We applied Thresher to the RNA-Seq expression data of 486 transcription factors from more than 10,000 samples of 33 kinds of cancer studied in The Cancer Genome Atlas (TCGA). We found that 30 clusters of transcription factors from a 29-dimensional principal component space were able to distinguish between most cancer types, and could separate tumor samples from normal controls. Moreover, each cluster of transcription factors could be either (i) linked to a tissue-specific expression pattern or (ii) associated with a fundamental biological process such as cell cycle, angiogenesis, apoptosis, or cytoskeleton. Clusters of the second type were more likely also to be associated with embryonically lethal mouse phenotypes. CONCLUSIONS: Using our approach, we have shown that the mRNA expression patterns of transcription factors contain most of the information needed to distinguish different cancer types. The Thresher method is capable of discovering biologically interpretable clusters of genes. It can potentially be applied to other gene sets, such as signaling pathways, to decompose them into simpler, yet biologically meaningful, components.

The Prevalence and Predicting Factors of Pulmonary Thromboembolism in Patients with Exacerbated Chronic Obstructive Pulmonary Disease.

BACKGROUND AND AIMS: The risk of pulmonary thromboembolism (PTE) in patients with exacerbated chronic obstructive pulmonary disease (e-COPD) is higher than in non-COPD states. This study aimed to evaluate the prevalence and the parameters that are critical for finding the incidence of PTE in patients with e-COPD. METHODS: This cross-sectional study was performed on 68 consecutive patients with the e-COPD, referred to the Pulmonary Disease Department at the Shariati Hospital in Tehran between 2013 and 2014. In addition to collecting data on the history of disease and physical examination, arterial blood sampling, spirometry, electrocardiography and echocardiography were performed for all patients. All patients underwent the computed the tomography pulmonary angiography (CT-PA) as a method of choice for diagnosing PTE. RESULTS: Out of 68 cases (7.4%), five were had CT angiography findings suggesting PTE. These patients were all male and had a higher mean age (79 vs. 65 years), lower mean systolic blood pressure (88.36 vs. 118.33 mmHg), and a higher mean heart rate (133.12 vs 90.33 beats/min), compared to e-COPD patients without PTE. Arterial blood gas analysis in patients with PTE demonstrated a lower HC03 (2.33 vs. 9.44 mEq/l) and PC02 (44.35 vs. 51.43 mmHg) levels. The mean LVEF was lower in patients with PTE (34.14 ±4.49% vs. 46.94 ± 8.27%). CONCLUSION: The prevalence of PTE in our series of patients with e-COPD was 7.4%. According to the study results, male gender, advanced age, hypotension, tachycardia, and respiratory alkalosis are factors indicating possible PTE among patients with e-COPD.

Association between low bone mass and the serum RANKL and OPG in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a risk factor for Osteopenia and osteoporosis. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) regulate bone remodeling and osteoclastogenesis. This study aimed to evaluate the relation between serum OPG, RANKL concentration, and bone mineral density (BMD) in patients with kidney stone disease. METHODS: Forty-four nephrolithiasis patients with either low bone mass or normal BMD (considered control group) were enrolled in this study. BMD was measured at lumbar spine (L1-L4) and femoral neck by dual-energy X-ray absorptiometry (DEXA). The serum OPG and RANKL were determined using the ELISA method. RESULTS: The median levels of serum OPG were significantly higher in nephrolithiasis patients with low bone mass compared to the nephrolithiasis patients with normal BMD (3.9 pmol/l versus 3.1 pmol/l; P = 0.03), respectively. Negative correlation was detected between bone densities of femoral neck and OPG in patients with nephrolithiasis (r = -.0344, P = 0.02). CONCLUSION: The present study showed that high serum fasting OPG levels may be indicative of femoral neck BMD in patients with nephrolithiasis.