Breast cancer radioresistance may be overcome by osteopontin gene knocking out with CRISPR/Cas9 technique.

PURPOSE: Osteopontin (OPN) is a phosphoglycoprotein, with a wide range of physiological and pathological roles. High expression of OPN promotes aggressive behavior, causes poor prognosis in tumor cells, and reduces the survival of patients. Since overexpression of OPN gives rise to radioresistance, the effects of the gene knock out using the CRISPR/Cas9 system in combination with radiation are emphasized. MATERIAL AND METHODS: We used the CRISPR/Cas9 technique to knock out the OPN gene in the MDA-MB-231 cell line. After transfection, the cells were irradiated. The changes of the OPN mRNA levels, the apoptosis, and the differences in cell viability were assessed. RESULTS: A significant reduction in the OPN expression was observed alone or along with irradiation. The knocked out gene alone increased apoptosis rate. The cell viability decreased to after knocking out of the OPN gene. The gene knocking-out combined with irradiation led to more decline of cell viability. CONCLUSION: Our results demonstrated that after knocking out the OPN gene, the MDA-MB-231 cells showed a significant radiosensitivity. Therefore, the OPN knock out in combination with conventional radiotherapy, may become an efficient therapeutic target in the future.

Coarse-graining in micromagnetic simulations of dynamic hysteresis loops.

We use micromagnetic simulations based on the stochastic Landau-Lifshitz-Gilbert equation to calculate dynamic magnetic hysteresis loops at finite temperature that are invariant with simulation cell size. As a test case, we simulate a magnetite nanorod, the building block of magnetic nanoparticles that have been employed in preclinical studies of hyperthermia. With the goal to effectively simulate loops for large iron-oxide-based systems at relatively slow sweep rates on the order of 1 Oe ns-1 or less, we modify and employ a previously derived renormalization group approach for coarse-graining (Grinstein and Koch 2003 Phys. Rev. Lett. 20 207201). The scaling algorithm is shown to produce nearly identical loops over several decades in the model cell volume. We also demonstrate sweep-rate scaling involving the Gilbert damping parameter that allows orders of magnitude speed-up of the loop calculations.

Increasing prevalence and incidence rates of multiple sclerosis in Kuwait.

BACKGROUND: Kuwait was considered as low to intermediate risk area for MS. OBJECTIVES: To determine the prevalence and incidence rates of MS among Kuwaiti nationals based on 2011 population census. METHODS: This cross-sectional study was conducted between October 2010 and April 2013 using the newly developed national MS registry in Kuwait. Patients with a diagnosis of MS according to 2010 revised McDonald criteria were identified. The crude, age- and sex-specific prevalence and incidence rates among Kuwaiti patients were calculated. RESULTS: 1176 MS patients were identified of which 927 (78.8%) were Kuwaitis and 249 (21.2%) were expatriates. Among Kuwaiti patients, female to male ratio was 1.8:1 with a mean age of 35.40 ± 10.99 years. The prevalence rate of MS was 85.05 per 100,000 persons (95% CI: 82.80 - 87.04). There was a peak in prevalence among patients aged 30-39 years. The incidence of MS was 6.88 per 100,000 persons (95% CI 5.52-8.55). Between 2003 and 2011, the incidence increased 3.22 and 2.54 times in women and men respectively. CONCLUSION: Kuwait is considered a high-risk area for MS. The significant increase in prevalence and incidence rates may represent a true increase despite the improvement in case ascertainment and case definition.

[To a margin reduction in the dermatofibrosarcoma protuberans? Retrospective study of 34 cases]. / Vers une réduction des marges latérales dans les dermatofibrosarcomes de Darier et Ferrand ? Etude rétrospective de 34 cas.

INTRODUCTION: The dermatofibrosarcoma protuberans (DFSP) is a rare but not exceptional tumour. Surgical treatment should contain a wide excision to avoid local recurrence. MATERIAL AND METHOD: We report a retrospective study of 34 cases treated by the same team from 1994 to 1999. In this series, only 4 cases (12%) presented recurrences after previous treatment by the other teams. In all cases, surgical resection was performed with 3 cm lateral margin and a disease free anatomic layer removed with the tumour. RESULTS: The mean of follow up was 60 months. There was no recurrence case in our 34 patients during this period. We compare our results with those, from others teams described in international literature since 1951. Margins and results are similar with some teams who practice the Mohs surgery. CONCLUSION: These data are in favour of a reduction of the lateral margins in classical surgical procedure of DFSP. They should be consolidated by a follow-up in longer term with a prospective study.

Chlamydia pneumoniae and anti-infective therapy: their role in the pathogenesis and treatment of coronary artery disease.

Cardiovascular disease remains the most common cause of death in the United States; however, conventional cardiovascular risk factors fail to explain completely the pathogenesis of atherosclerosis and coronary artery disease. There has been recent interest in the association between Chlamydia pneumoniae and the risk of development or progression of atherosclerotic disease. This association has become evident through serologic, pathologic, and animal-based models and, more recently, through limited trials of antichlamydial antibiotics in humans. Whether C. pneumoniae is a causative agent or "innocent bystander" or whether antibiotic therapy has any role in the treatment of cardiovascular disease remains to be determined.

Therapeutic approaches for AIDS-related toxoplasmosis.

OBJECTIVE: To summarize current knowledge of prophylaxis and treatment of AIDS-related toxoplasmosis. DATA SOURCES: A MEDLINE search (1985-1994) was used to identify pertinent literature, including reviews. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: Trimethoprim/sulfamethoxazole (TMP/SMX) appears to be useful for prophylaxis against toxoplasmosis in patients with AIDS. The most effective TMP/SMX dose for prevention of toxoplasmosis needs to be determined. Dapsone in combination with pyrimethamine therapy may be an effective alternative for toxoplasmosis prophylaxis. The most effective regimen for the treatment of AIDS-related toxoplasmosis is the combination therapy of pyrimethamine/sulfadiazine. In patients who cannot tolerate sulfadiazine therapy because of adverse effects or allergy, pyrimethamine with clindamycin therapy may be considered as a second-line alternative. Lifelong suppressive therapy is required after either treatment regimen to prevent relapse. Other newer agents such as azithromycin, clarithromycin, atovaquone, or timetrexate-leucovorin need further studies to confirm their true effectiveness in the treatment of toxoplasmosis. CONCLUSIONS: TMP/SMX remains a useful agent in prophylaxis against toxoplasmosis. Pyrimethamine/sulfadiazine is the most effective combination in the treatment of acute toxoplasmosis.