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With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP-2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3-4 months) and old (22-24 months), male and female, C57BL/6J mice. Cell proliferation, vessel-like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel-like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex-based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT-1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel-like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP-2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP-2.

Angiogenesis is a vital process during the regeneration of bone tissue. The aim of this study was to investigate angiogenesis at the fracture site as well as at distal locations from obesity-induced type 2 diabetic mice that were treated with bone morphogenetic protein-2 (BMP-2, local administration at the time of surgery) to heal a femoral critical sized defect (CSD) or saline as a control. Mice were fed a high fat diet (HFD) to induce a type 2 diabetic-like phenotype while low fat diet (LFD) animals served as controls. Endothelial cells (ECs) were isolated from the lungs (LECs) and bone marrow (BMECs) 3 weeks post-surgery, and the fractured femurs were also examined. Our studies demonstrate that local administration of BMP-2 at the fracture site in a CSD model results in complete bone healing within 3 weeks for all HFD mice and 66.7% of LFD mice, whereas those treated with saline remain unhealed. At the fracture site, vessel parameters and adipocyte numbers were significantly increased in BMP-2 treated femurs, irrespective of diet. At distal sites, LEC and BMEC proliferation was not altered by diet or BMP-2 treatment. HFD increased the tube formation ability of both LECs and BMECs. Interestingly, BMP-2 treatment at the time of surgery reduced tube formation in LECs and humeri BMECs. However, migration of BMECs from HFD mice treated with BMP-2 was increased compared to BMECs from HFD mice treated with saline. BMP-2 treatment significantly increased the expression of CD31, FLT-1, and ANGPT2 in LECs and BMECs in LFD mice, but reduced the expression of these same genes in HFD mice. To date, this is the first study that depicts the systemic influence of fracture surgery and local BMP-2 treatment on the proliferation and angiogenic potential of ECs derived from the bone marrow and lungs.

Background Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test. Methods In May 2013, we implemented exome sequencing in routine diagnostics for patients suffering from PIDs. This study reports the clinical utility and diagnostic yield for a heterogeneous group of 254 consecutively referred PID patients from 249 families. For the majority of patients, the clinical diagnosis was based on clinical criteria including rare and/or unusual severe bacterial, viral, or fungal infections, sometimes accompanied by autoimmune manifestations. Functional immune defects were interpreted in the context of aberrant immune cell populations, aberrant antibody levels, or combinations of these factors. Results For 62 patients (24%), exome sequencing identified pathogenic variants in well-established PID genes. An exome-wide analysis diagnosed 10 additional patients (4%), providing diagnoses for 72 patients (28%) from 68 families altogether. The genetic diagnosis directly indicated novel treatment options for 25 patients that received a diagnosis (34%). Conclusion Exome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients. Importantly, molecularly defined diagnoses indicated altered therapeutic options in 34% of cases. In addition, exome sequencing harbors advantages over gene panels as a truly generic test for all genetic diseases, including in silico extension of existing gene lists and re-analysis of existing data. Electronic supplementary material The online version of this article (10.1186/s13073-019-0649-3) contains supplementary material, which is available to authorized users.

The purpose of this study to examine the role of Radio Cairo as propaganda and political persuasion tools for Egypt’s foreign policy in the era of President Sadat.The study used content analysis as a research tool to examine how the Egyptian media used propaganda techniques in communicating messages to the Arab audiences in the Middle East in issue regarding Egypt’s leadership in the peace process; the right of the Palestinian people for a national homeland; and Israel’s right to exist. The Arabic materials and the scripts of Radio Cairo programming during three- weeks used for analysis.Egyptian media concentrated mainly on six major techniques in communicating their messages to the Arab people regarding the Camp David agreements and the separate peace treaty with Israel, which included the following: Focusing Attention or Spotlighting; Testimonial, Division and Name calling; Self-Interest or Ad Hominem; Omission of Material; and Bandwagon.The study concluded that, Radio Cairo had notable success in affecting the audiences and public opinion therein. The majority of Egyptian people greeted Sadat’s decision to visit Israel and the Camp David Agreements with relief and approval. They hailed Sadat as the “Peace Hero” and the “Savior of the Masses”. Radio Cairo also played a highly important role in bringing the people of the Middle East, including the Israel’s, closer to peace by stimulating positive thinking. Finally, Radio Cairo helped to make Israel for the first time, acceptable to the Arabs, particularly the moderate Arab states and to the Egyptian people themselves.

Background & Aims Cultural, religious, and financial barriers can hinder uptake of colorectal cancer (CRC) screening in Arab communities. We aim to understand attitudes and barriers that contribute to the low rate of CRC screening among Palestinians in the West Bank. Methods We performed a national, cross-sectional study of Palestinian adults older than 50 years. A self-administered questionnaire was developed and validated. Data were randomly collected in all major districts of the West Bank. The primary outcome was the willingness to undergo CRC screening. Multivariable logistic regression models were used to assess the strength of association between the primary outcome and its predictors while controlling for possible confounders. Results Of 1601 people approached for an interview, 1352 agreed to participate (response rate, 84%). Only 193 had undergone CRC screening (14%); 1069 (79%) agreed to take a fecal occult blood test, 906 (67%) agreed to a colonoscopy examination, and 1098 (81%) were willing to undergo CRC screening if recommended by a physician. Only 194 (14%) said they had been informed about CRC screening by a physician. Urban residents were more likely to be screened for CRC than nonurban residents (odds ratio, 0.73; 95% confidence interval, 0.56–0.93; P = .011). Multivariable analysis showed that lack of education beyond elementary school or familiarity with CRC screening, distrust of Western medicine, religious objection, and finding the test to be embarrassing were all associated with decreased odds of accepting CRC screening. Conclusions Based on a national, cross-sectional study of Palestinian adults, there are many cultural and religious barriers to CRC screening. Improving our understanding of these could increase screening among Arab populations in the Middle East and in Western countries.