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21.
Parietal bone defects are rare and exhibit variable etiologies. We report on a 16-year-old girl with an isolated, giant parietal bone defect with encephalomalacia, and an asymptomatic Rathke's cleft cyst. The patient presented with epilepsy. We discuss the differential diagnosis and pertinent neurologic associations. Irrespective of cause, parietal bone defects remain a benign clinical entity. However, it is important to define the extent of the bone defect and associated intracranial abnormalities, and if needed, to take early preventive steps, medical as well as surgical, against potential brain damage. 相似文献
22.
BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infections encountered by clinicians in developing countries. Although UTI seldom leads to complications, it can cause significant morbidity and mortality. OBJECTIVE: To identify the etiologic agents of UTIs and to assess their antimicrobial susceptibility pattern. METHODS: A retrospective analysis of 1420 mid-stream urine specimens processed fobr culture and antimicrobial susceptibility testing in the bacteriology laboratory of Gondar University Teaching Hospital between September 2002 and August 2003 was conducted RESULTS: Significant bacteriuria (cultures with > 10(5) colony forming units of bacteria per ml of urine) was observed in 399 (28.1%) of the specimens. Two bacteria each were isolated from 14 specimens, making the number of bacteria isolated to be 413 with the isolation rate of 29.1%. The most commonly isolated bacteria were Escherichia coli 166 (40.2%), Staphylococcus aureus 60 (14.5%), Klebisella species 42 (10.2%) and Citrobacter species 34 (8.2%). Among Gram-positive organisms S. aureus showed high level qf drug resistance for tetracycline 48 (80%), corimoxazole 32 (53.3%), chloramphenicol 32 (53.3%), amnpicillin 26 (43.3%) and penicillin 22 (36.7%). Of the Gram-negative bacteria, extremely high resistance patterns were found in Salmonella species for ampicillin 5 (100%), erythromycin 5 (100%), penicillin 5 (100%), co-trimoxazole 3 (60%), tetracycline 3 (60%) and 3 chloramphenicol (60%). Multiple drug resistance was observed in 85.7% of the isolates. Only 5.1% of the isolates were found to be sensitive to all antibiotics tested. CONCLUSION: Resistance to the commonly used antibiotics was found to be very high among the isolates leaving clinicians with very few choices of drugs or the treatment of UTIs. It is therefore, critical that the use of antimicrobial agents with in a hospital and all other responsible institutions he reviewed 相似文献
23.
Chao Zhang Anurag Verma Yuanqing Feng Marcelo C. R. Melo Michael McQuillan Matthew Hansen Anastasia Lucas Joseph Park Alessia Ranciaro Simon Thompson Meagan A. Rubel Michael C. Campbell William Beggs Jibril Hirbo Sununguko Wata Mpoloka Gaonyadiwe George Mokone Regeneron Genetic Center Thomas Nyambo Dawit Wolde Meskel Gurja Belay Charles Fokunang Alfred K. Njamnshi Sabah A. Omar Scott M. Williams Daniel J. Rader Marylyn D. Ritchie Cesar de la Fuente-Nunez Giorgio Sirugo Sarah A. Tishkoff 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(21)
Human genomic diversity has been shaped by both ancient and ongoing challenges from viruses. The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on population health. However, genetic diversity and evolutionary forces impacting host genes related to SARS-CoV-2 infection are not well understood. We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (angiotensin converting enzyme 2 [ACE2], transmembrane protease serine 2 [TMPRSS2], dipeptidyl peptidase 4 [DPP4], and lymphocyte antigen 6 complex locus E [LY6E]). We analyzed data from 2,012 ethnically diverse Africans and 15,977 individuals of European and African ancestry with electronic health records and integrated with global data from the 1000 Genomes Project. At ACE2, we identified 41 nonsynonymous variants that were rare in most populations, several of which impact protein function. However, three nonsynonymous variants (rs138390800, rs147311723, and rs145437639) were common among central African hunter-gatherers from Cameroon (minor allele frequency 0.083 to 0.164) and are on haplotypes that exhibit signatures of positive selection. We identify signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage compared with the chimpanzee genome. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19. Our study provides insights into global variation at host genes related to SARS-CoV-2 infection, which have been shaped by natural selection in some populations, possibly due to prior viral infections.Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronaviruses are enveloped, positive-sense, and single-stranded RNA viruses, many of which are zoonotic pathogens that crossed over into humans. Seven coronavirus species, including SARS-CoV-2, have been discovered that, depending on the virus and host physiological condition, may cause mild or lethal respiratory disease. There is considerable variation in disease prevalence and severity across populations and communities. Importantly, minority populations in the United States appear to have been disproportionally affected by COVID-19 (1, 2). For example, in Chicago, more than 50% of COVID-19 cases and nearly 70% of COVID-19 deaths are in African Americans (who make up 30% of the population of Chicago) (1). While social and economic factors are largely responsible for driving COVID-19 health disparities, investigating genetic diversity at host genes related to SARS-CoV-2 infection could help identify functionally important variation, which may play a role in individual risk for severe COVID-19 infection.In this study, we focused on four key genes playing a role in SARS-CoV-2 infection (3). The ACE2 gene, encoding the angiotensin-converting enzyme-2 protein, was reported to be a main binding site for severe acute respiratory syndrome coronavirus (SARS-CoV) during an outbreak in 2003, and evidence showed stronger binding affinity to SARS-CoV-2, which enters the target cells via ACE2 receptors (3, 4). The ACE2 gene is located on the X chromosome (chrX); its expression level varies among populations (5); and it is ubiquitously expressed in the lung, blood vessels, gut, kidney, testis, and brain, all organs that appear to be affected as part of the COVID-19 clinical spectrum (6). SARS-CoV-2 infects cells through a membrane fusion mechanism, which in the case of SARS-CoV, is known to induce down-regulation of ACE2 (7). Such down-regulation has been shown to cause inefficient counteraction of angiotensin II effects, leading to enhanced pulmonary inflammation and intravascular coagulation (7). Additionally, altered expression of ACE2 has been associated with cardiovascular and cerebrovascular disease, which is highly relevant to COVID-19 as several cardiovascular conditions are associated with severe disease. TMPRSS2, located on the outer membrane of host target cells, binds to and cleaves ACE2, resulting in activation of spike proteins on the viral envelope and facilitating membrane fusion and endocytosis (8). Two additional genes, DPP4 and LY6E, have been shown to play an important role in the entry of SARS-CoV-2 virus into host cells. DPP4 is a known functional receptor for the Middle East respiratory syndrome coronavirus (MERS-CoV), causing a severe respiratory illness with high mortality (9, 10). LY6E encodes a glycosylphosphatidylinositol-anchored cell surface protein, which is a critical antiviral immune effector that controls coronavirus infection and pathogenesis (11). Mice lacking LY6E in hematopoietic cells were susceptible to murine coronavirus infection (11).Previous studies of genetic diversity at ACE2 and TMPRSS2 in global human populations did not include an extensive set of African populations (5, 12–14). No common coding variants (defined here as minor allele frequency [MAF] > 0.05) at ACE2 were identified in any prior population studies. However, few studies included diverse indigenous African populations whose genomes harbor the greatest diversity among humans. This leads to a substantial disparity in the representation of African ancestries in human genetic studies of COVID-19, impeding health equity as the transferability of findings based on non-African ancestries to African populations can be low (15). Including more African populations in studying the genetic diversity of genes involved in SARS-CoV-2 infection is extremely necessary. Additionally, the evolutionary forces underlying global patterns of genetic diversity at host genes related to SARS-CoV-2 infection are not well understood. Using methods to detect natural selection signatures at host genes related to viral infections helps identify putatively functional variants that could play a role in disease risk.We characterized genetic variation and studied natural selection signatures at ACE2, TMPRSS2, DPP4, and LY6E in ethnically diverse human populations by analyzing 2,012 genomes from ethnically diverse Africans (referred to as the “African diversity” dataset), 2,504 genomes from the 1000 Genomes Project (1KG), and whole-exome sequencing of 15,977 individuals of European ancestry (EA) and African ancestry from the Penn Medicine BioBank (PMBB) dataset (SI Appendix, Fig. S1). The African diversity dataset includes populations with diverse subsistence patterns (hunter-gatherers, pastoralists, agriculturalists) and speaking languages belonging to the four major language families in Africa (Khoesan; Niger–Congo, of which Bantu is the largest subfamily; Afroasiatic; and Nilo-Saharan). We identify functionally relevant variation, compare the patterns of variation across global populations, and provide insight into the evolutionary forces underlying these patterns of genetic variation. In addition, we perform an association study using the variants identified from whole-exome sequencing at the four genes and clinical traits derived from electronic health record (EHR) data linked to the subjects enrolled in the PMBB. The EHR data include diseases related to organ dysfunctions associated with severe COVID-19, such as respiratory, cardiovascular, liver, and renal complications. Our study of genetic variation in genes involved in SARS-CoV-2 infection provides data to investigate infection susceptibility within and between populations and indicates that variants in these genes may play a role in comorbidities relevant to COVID-19 severity. 相似文献
24.
On the basis of an analysis of such methods that have led to the establishment of the Newtonian laws some problems of the interdisciplinary agreement between mechanics and biology, especially those concerning hard tissues, were discussed. In the light of examples it is shown that comparisons with technical constructions to explain form and function of bones are not sufficient since similarity of form is no proof of identical function. Mechanical phenomena of living matter can be investigated merely by their own movements whereby the differing qualities and reactions of the material have to be taken into priority consideration. 相似文献
25.
Beta 1- and beta 2-adrenoceptor antagonist activities of ICI-215001, a putative beta 3-adrenoceptor agonist.
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1. The present study was undertaken to characterize the beta 3-adrenoceptor agonist activity of ICI-215001 and to determine whether it exhibits additional activities on beta 1- and beta 2-adrenoceptors in isolated spontaneously beating atrium, trachea and ileum of guinea-pig. 2. In guinea-pig atrium, isoprenaline, a non-selective beta-adrenoceptor agonist, caused concentration-dependent, positive chronotropic effects that were inhibited by atenolol, a selective beta 1-antagonist. ICI-215001 also competitively antagonized the increase in heart rate caused by isoprenaline. 3. ICI-215001 exhibited low intrinsic activity at increasing the beating rate of atrium and no activity on resting or induced tone of tracheal strips. 4. In strips of guinea-pig trachea, contracted submaximally with carbachol, isoprenaline, caused concentration-dependent relaxations. Both ICI-118551, a selective beta 2-adrenoceptor antagonist, and ICI-215001 competitively inhibited the relaxations caused by isoprenaline. 5. In isolated strips of guinea-pig ileum longitudinal smooth muscle contracted with histamine, isoprenaline and ICI-215001 caused relaxations which were inhibited by alprenolol, a beta-adrenoceptor antagonist with modest affinity for beta 3-adrenoceptors, but were resistant to ICI-118551 and atenolol. 6. These results indicate that ICI-215001 exhibits beta 3-adrenoceptor agonist activity as demonstrated by relaxations mediated via atypical beta-adrenoceptors in the longitudinal smooth muscle of guinea-pig ileum. Further, the studies demonstrate that ICI-215001 can act as an antagonist at beta 1- and beta 2-adrenoceptors in situations where its intrinsic agonist activity is low. 相似文献
26.
The trauma-surgical intensive care unit at Harborview Medical Center has developed a multidisciplinary case review process to allow discussion of complications and issues in an open forum among multiple services. Conducted monthly, this meeting provides a forum for clear communication between members of the patient care team with the goal of developing best practices, system changes, and policies that will minimize risk for the patients and provide education for the staff. 相似文献
27.
Despite the widespread availability of a safe and effective vaccine, tetanus continues to be a significant public health problem in the developing countries. 相似文献
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Belay Tesfamariam 《Journal of cardiovascular translational research》2016,9(2):91-101
Coronary artery intervention using device implants significantly reduce the risk of restenosis and the need for revascularization but are associated with endothelial denudation and impaired function. This may be due to incomplete endothelial recovery as a result of intimal injury, presence of polymer and/or high antiproliferative drug accumulation in the intima. The permanent presence of a metal prosthesis or polymer may impair the proliferation of resident endothelial cells to cover empty areas. Attention has focused on the robust replenishment of endothelial monolayer by recruitment of circulating endothelial progenitor cells derived from the bone marrow to areas of endothelial injury. The balance between endothelial damage and repair is critical for the maintenance of intimal integrity, function, and prevention of thrombotic complications. This review will discuss on the aftereffects of intravascular device implants on endothelial injury and the pathways involved in endothelial repair and regeneration with an emphasis on endothelial progenitor cells. 相似文献