Medical principles and practice : international journal of the Kuwait University, Health Science Centre
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In mammalian cells, DNA damage response initiates repair by error-free homologous recombination (HRR) or by error-prone non-homologous end joining (NHEJ). DNA damage is detected by PARP proteins that facilitate this repair, both in normal cells and in cancer cells. Cells containing BRCA1/2 mutations have an HRR-deficient repair mechanism which may result in unrepaired one-ended double-strand breaks and stalled replication forks, considered as the most lethal cell damage. ⋯ However, there is need for multicenter trials, preferably conducted without commercial guidance and funding. Some of the available trials reported resistance to PARP inhibitors. In this review, we also describe the various causes of resistance to PARP inhibitors and research indicating how resistance can be overcome.
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Regulatory T (Treg) cells play an important role in implantation of the embryo and maintenance of pregnancy after allogeneic mating. Implantation failure, miscarriage, and preeclampsia are associated with decreased numbers of Treg cells or with dysfunctional Treg cells. Treg cells are classified into naturally occurring Treg (nTreg) cells or thymus-derived Treg (tTreg) cells that differentiate in the thymus and induce tolerance to self-antigens, while induced Treg (iTreg) or peripheral Treg (pTreg) cells differentiate in the periphery and induce transient tolerance to foreign antigens. ⋯ In addition to the volume of paternal/fetal antigen-specific CD8+ T cells, the number of paternal/fetal antigen-specific Treg cells, which protect the fetus/placenta against maternal immune cell attack, increases after the second trimester of pregnancy. Clonal Treg cells which are surrogate markers of paternal/fetal antigen-specific Treg cells in humans may be involved in the development of preeclampsia during the mid- to late pregnancy stage, as evidenced by their downregulation in the decidua of preeclamptic cases. This review summarizes recent findings on Treg cells and discusses the roles, in the maintenance of pregnancy, of different types of Treg cells such as paternal/fetal antigen-specific Treg, pregnancy-associated memory Treg, nTreg (or tTreg), and iTreg (or pTreg cells).
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The musical composers in the Romantic Era (1800-1910) strived for compositions that expressed human life, including happiness, harmony, and despair. They lived in a period in which freedom of thought, expression of emotion, and inspiration by nature predominated. During this period, intensive trading with other parts of the world brought new microorganisms along, which made infections and epidemics very common. ⋯ This text dwells on diseases and the cause of death of ten composers, namely Mozart, Beethoven, Chopin, Schubert, Schumann, Mendelssohn, Brahms, Liszt, Mahler, and Bruckner. It is evident that from the perspective of modern medicine, symptoms and forensic facts are not complete, but witnesses' reports and recent medical research have provided passable and plausible clarity. Although many questions will remain unanswered, it appears that the diseases of these composers and their causes of death have their origins in alcohol abuses, age, epidemics (like tuberculosis), and syphilis.
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The clinical spectrum of systemic nocardiosis encompasses pulmonary and disseminated disease. Central nervous system (CNS) involvement is an important feature of disseminated disease with significant mortality and high relapse rate, especially in those with suppressed cell-mediated immunity. This systematic review aimed to evaluate the epidemiology, clinical features, diagnosis, therapeutic interventions, and outcome in patients with CNS nocardiosis. ⋯ CNS nocardiosis carries significant mortality, especially in immunodeficient patients. We advocate the use of surgery combined with antimicrobials to improve clinical outcome.
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The UK government had intended to introduce a comprehensive Electronic Health Record (EHR) system in England by 2020. These EHRs would run across primary, secondary, and social care, linking data in a single digital platform. The objectives of this systematic review were to identify studies that compare EHR in terms of direct comparison between systems and to evaluate them using System and Software Quality Requirements and Evaluation (SQuaRE) ISO/IEC 25010. ⋯ The following number of studies looked at the various aspects of the SQuaRE, respectively - 19 studies: functional suitability, performance efficiency: 18 studies, compatibility: 12 studies, usability: 25 studies, reliability: 6 studies, security: 2 studies, maintainability: 16 studies, portability: 13 studies. Epic was the most studied EHR system and one of the most implemented systems in the US market and one of the top ten in the UK. It is difficult to assess which is the most advantageous EHR system when they are assessed by SQuaRE's 8 characteristics for software evaluation.