The metabolic syndrome is not associated with homocysteinemia: The Persian Gulf Healthy Heart Study

Background: It is uncertain whether homocysteine and the metabolic syndrome or its components are related in the general population, as studies investigating the association between homocysteine levels and insulin resistance have shown conflicting results. Methods: In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of Iranian men and women aged ≥25 yr, a random sample of 1754 subjects were evaluated for the association of plasma homocysteine levels and the metabolic syndrome using National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria. Total homocysteine levels and high sensitivity C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assays. Results: Subjects with lower HDL-cholesterol and higher blood pressure showed significantly higher homocysteine levels (p=0.001 and p<0.0001; respectively). There was no significant difference in serum levels of homocysteine between subjects with and without the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome did not show a significant association with serum homocysteine levels after adjusting for sex, age, smoking, fruit and vegetable intake pattern, body mass index, and physical inactivity. Concurrent elevated CRP levels and the metabolic syndrome also did not show a significant association with serum homocysteine levels after adjusting for sex, age, and lifestyle cardiovascular risk factors. Conclusions: There was no association between the metabolic syndrome using NCEP-ATPIII criteria and homocysteinemia in this study. These data refute the hypothesis that homocysteine levels are influenced by the metabolic syndrome, at least in general healthy population

Self-organized Emergence of Navigability on Small-World Networks

This paper mainly investigates why small-world networks are navigable and how to navigate small-world networks. We find that the navigability can naturally emerge from self-organization in the absence of prior knowledge about underlying reference frames of networks. Through a process of information exchange and accumulation on networks, a hidden metric space for navigation on networks is constructed. Navigation based on distances between vertices in the hidden metric space can efficiently deliver messages on small-world networks, in which long range connections play an important role. Numerical simulations further suggest that high cluster coefficient and low diameter are both necessary for navigability. These interesting results provide profound insights into scalable routing on the Internet due to its distributed and localized requirements.Comment: 3 figure

Clinical characteristics of outpatients and inpatients with COVID-19 in Bushehr: A report from the south of Iran

Aim: To investigate clinical, laboratory and imaging features of COVID-19 patients in Bushehr, a southern province of Iran. Materials & methods: A total of 148 COVID-19 patients were enrolled. The patients were categorized into four groups including inpatients, outpatients, elderly and nonelderly. Clinical, laboratory and computed tomography characteristics were analyzed and compared. Results: Levels of erythrocyte sedimentation rate, CRP, lactate dehydrogenase and aspartate aminotransferas among inpatients were higher than outpatients. There were significant differences in the levels of creatinine and blood urine nitrogen between elderly and nonelderly patients. The incidence of ground-glass opacities in inpatients was significantly higher than in outpatients. Conclusion: COVID-19 is associated with more severe renal failure in elderly patients. Elderly patients with underlying conditions are at increased risk of severe progression of COVID-19

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m−2) and cyclophosphamide (2 g m−2) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m−2 and thiotepa 200 mg m−2. At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m−2 cyclophosphamide and 400 mg m−2 thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immuno-suppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity

CyberKnife for hilar lung tumors: report of clinical response and toxicity

<p>Abstract</p> <p>Objective</p> <p>To report clinical efficacy and toxicity of fractionated CyberKnife radiosurgery for the treatment of hilar lung tumors.</p> <p>Methods</p> <p>Patients presenting with primary and metastatic hilar lung tumors, treated using the CyberKnife system with Synchrony fiducial tracking technology, were retrospectively reviewed. Hilar location was defined as abutting or invading a mainstem bronchus. Fiducial markers were implanted by conventional bronchoscopy within or adjacent to tumors to serve as targeting references. A prescribed dose of 30 to 40 Gy to the gross tumor volume (GTV) was delivered in 5 fractions. Clinical examination and PET/CT imaging were performed at 3 to 6-month follow-up intervals.</p> <p>Results</p> <p>Twenty patients were accrued over a 4 year period. Three had primary hilar lung tumors and 17 had hilar lung metastases. The median GTV was 73 cc (range 23-324 cc). The median dose to the GTV was 35 Gy (range, 30 - 40 Gy), delivered in 5 fractions over 5 to 8 days (median, 6 days). The resulting mean maximum point doses delivered to the esophagus and mainstem bronchus were 25 Gy (range, 11 - 39 Gy) and 42 Gy (range, 30 - 49 Gy), respectively. Of the 17 evaluable patients with 3 - 6 month follow-up, 4 patients had a partial response and 13 patients had stable disease. AAT t a median follow-up of 10 months, the 1-year Kaplan-Meier local control and overall survival estimates were 63% and 54%, respectively. Toxicities included one patient experiencing grade II radiation esophagitis and one patient experiencing grade III radiation pneumonitis. One patient with gross endobronchial tumor within the mainstem bronchus developed a bronchial fistula and died after receiving a maximum bronchus dose of 49 Gy.</p> <p>Conclusion</p> <p>CyberKnife radiosurgery is an effective palliative treatment option for hilar lung tumors, but local control is poor at one year. Maximum point doses to critical structures may be used as a guide for limiting toxicities. Preliminary results suggest that dose escalation alone is unlikely to enhance the therapeutic ratio of hilar lung tumors and novel approaches, such as further defining the patient population or employing the use of radiation sensitizers, should be investigated.</p

Copper chelation suppresses epithelial-mesenchymal transition by inhibition of canonical and non-canonical TGF-β signaling pathways in cancer

Background: Metastatic cancer cells exploit Epithelial-mesenchymal-transition (EMT) to enhance their migration, invasion, and resistance to treatments. Recent studies highlight that elevated levels of copper are implicated in cancer progression and metastasis. Clinical trials using copper chelators are associated with improved patient survival; however, the molecular mechanisms by which copper depletion inhibits tumor progression and metastasis are poorly understood. This remains a major hurdle to the clinical translation of copper chelators. Here, we propose that copper chelation inhibits metastasis by reducing TGF-β levels and EMT signaling. Given that many drugs targeting TGF-β have failed in clinical trials, partly because of severe side effects arising in patients, we hypothesized that copper chelation therapy might be a less toxic alternative to target the TGF-β/EMT axis. Results: Our cytokine array and RNA-seq data suggested a link between copper homeostasis, TGF-β and EMT process. To validate this hypothesis, we performed single-cell imaging, protein assays, and in vivo studies. Here, we used the copper chelating agent TEPA to block copper trafficking. Our in vivo study showed a reduction of TGF-β levels and metastasis to the lung in the TNBC mouse model. Mechanistically, TEPA significantly downregulated canonical (TGF-β/SMAD2&amp;3) and non-canonical (TGF-β/PI3K/AKT, TGF-β/RAS/RAF/MEK/ERK, and TGF-β/WNT/β-catenin) TGF-β signaling pathways. Additionally, EMT markers of MMP-9, MMP-14, Vimentin, β-catenin, ZEB1, and p-SMAD2 were downregulated, and EMT transcription factors of SNAI1, ZEB1, and p-SMAD2 accumulated in the cytoplasm after treatment. Conclusions: Our study suggests that copper chelation therapy represents a potentially effective therapeutic approach for targeting TGF-β and inhibiting EMT in a diverse range of cancers

Novel therapies in breast cancer: what is new from ASCO 2008

<p>Abstract</p> <p>Introduction</p> <p>Breast cancer is the most common female cancer and the second most common cause of female cancer-related deaths in the United States. World-wide, more than one million women will be diagnosed with breast cancer annually. In 2007, more than 175,000 women were diagnosed with breast cancer in the United States. However, deaths due to breast cancer have decreased in the recent years in part because of improved screening techniques, surgical interventions, understanding of the pathogenesis of the disease, and utilization of traditional chemotherapies in a more efficacious manner. One of the more exciting areas of improvement in the treatment of breast cancer is the entrance of novel therapies now available to oncologists. In the field of cancer therapeutics, the area of targeted and biologic therapies has been progressing at a rapid rate, particularly in the treatment of breast cancer.</p> <p>Since the advent of imatinib for the successful treatment of chronic myelogenous leukemia in the 2001, clinicians have been searching for comparable therapies that could be as efficacious and as tolerable. In order for targeted therapies to be effective, the agent must be able to inhibit critical regulatory pathways which promote tumor cell growth and proliferation. The targets must be identifiable, quantifiable and capable of being interrupted.</p> <p>In the field of breast cancer, two advances in targeted therapy have led to great strides in the understanding and treatment of breast cancer, namely hormonal therapy for estrogen positive receptor breast cancer and antibodies directed towards the inhibition of human epidermal growth factor receptor (HER)2. These advances have revolutionized the understanding and the treatment strategies for breast cancer. Building upon these successes, a host of novel agents are currently being investigated and used in clinical trials that will hopefully prove to be as fruitful. This review will focus on novel therapies in the field of breast cancer with a focus on metastatic breast cancer (MBC) and updates from the recent annual ASCO meeting and contains a summary of the results.</p

A digital intake approach in specialized mental health care : study protocol of a cluster randomised controlled trial

Background: Enhancing patient participation is becoming increasingly important in mental health care as patients use to have a dependent, inactive role and nonadherence to treatment is a regular problem. Research shows promising results of initiatives stimulating patient participation in partnership with their clinicians. However, few initiatives targeting both patients’ and clinicians’ behaviour have been evaluated in randomised trials (RCT). Therefore, in GGz Breburg, a specialized mental health institution, a digital intake approach was developed aimed at exploring treatment needs, expectations and preferences of patients intended to prepare patients for the intake consultations. Subsequently, patients and clinicians discuss this information during intake consultations and make shared decisions about options in treatment. The aim of this trial is to test the efficacy of this new digital intake approach facilitated by Routine Outcome Monitoring (ROM), peer support and training of clinicians as compared to the intake as usual. The primary outcome is decisional conflict about choices in treatment. Secondary outcomes focus on patient participation, shared decision making, working alliance, adherence to treatment and clinical outcomes. Methods: This article presents the study protocol of a cluster-randomised controlled trial in four outpatient departments for adults with depression, anxiety and personality disorders, working in two different regions. Randomisation is done between two similar intake-teams within each department. In the four intervention teams the new intake approach is implemented. The four control teams apply the intake as usual and will implement the new approach after the completion of the study. In total 176 patients are projected to participate in the study. Data collection will be at baseline, and at two weeks and two months after the intake. Discussion: This study will potentially demonstrate the efficacy of the new digital intake approach in mental health care in terms of the primary outcome the degree of decisional conflict about choices in treatment. The findings of this study may contribute to the roll out of such eHealth initiatives fostering patient involvement in decision making about their treatment

Teologie politiche islamiche. Casi e frammenti contemporanei

Questo volume raccoglie i contributi di studiosi di ambito internazionale che prendono in esame aspetti poco noti o apparentemente marginali della teologia politica islamica contemporanea, come il dibattito filosofico in Iran, le correnti teopolitiche indonesiane (il paese al mondo con il maggior numero di musulmani), aspetti millenaristi dell\u2019islamismo militante, mutazioni del misticismo islamico di fronte alla modernit\ue0. Il panorama composito che ne risulta fa balenare la natura profonda delle idee e delle correnti che agitano, inquietano e pacificano il mondo islamico, il mondo