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91.
Schwarzenbacher R von Delft F Jaroszewski L Abdubek P Ambing E Biorac T Brinen LS Canaves JM Cambell J Chiu HJ Dai X Deacon AM DiDonato M Elsliger MA Eshagi S Floyd R Godzik A Grittini C Grzechnik SK Hampton E Karlak C Klock HE Koesema E Kovarik JS Kreusch A Kuhn P Lesley SA Levin I McMullan D McPhillips TM Miller MD Morse A Moy K Ouyang J Page R Quijano K Robb A Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J Wang X West B Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2004,56(2):392-395
92.
Mary Henry Noêmi GalAn Katherine Teasdale Renata Prado Harpreet Amar Marina S. Rays Lesley Roberts Pedro Siqueira Gilles de Wildt Marcos Virmond Pranab K. Das 《PLoS neglected tropical diseases》2016,10(3)
BackgroundLeprosy is a leading cause of preventable disability worldwide. Delay in diagnosis of patients augments the transmission of infection, and allows progression of disease and more severe disability. Delays in diagnosis greater than ten years have been reported in Brazil. To reduce this delay, it is important to identify factors that hinder patients from presenting to doctors, and those that delay doctors from diagnosing patients once they have presented. This study aimed to explore factors associated with the delayed diagnosis of leprosy in Brazil.
Methodology/ Principal Findings
This is an exploratory study using a self-constructed questionnaire delivered to patients attending three leprosy referral clinics across three states in Brazil. Data were analysed to determine associations between variables and the time taken for participants to present to the health-service, and between variables and the time taken for doctors to diagnose participants once they had presented. Participants who suspected they had leprosy but feared community isolation were 10 times more likely to wait longer before consulting a doctor for their symptoms (OR 10.37, 95% CI 2.18–49.45, p = 0.003). Participants who thought their symptoms were not serious had a threefold greater chance of waiting longer before consulting than those who did (OR 3.114, 95% CI 1.235–7.856, p = 0.016). Forty-two point six per cent of participants reported initially receiving a diagnosis besides leprosy. These had a three times greater chance of receiving a later diagnosis of leprosy compared to those not misdiagnosed or not given a diagnosis (OR 2.867, 95% CI 1.288–6.384, p = 0.010).Conclusions/ Significance
This study implies a need for patient education regarding leprosy symptoms and the reduction of stigma to encourage patients to present. The high rate of misdiagnosis reported suggests a need to increase clinician suspicion of leprosy. Further education regarding disease symptoms in medical school curriculums may be advisable. 相似文献93.
Gene silencing with RNA interference in the human pathogenic fungus Aspergillus fumigatus 总被引:13,自引:0,他引:13
Aspergillus fumigatus is an opportunistic pathogenic fungus which causes fatal invasive aspergillosis among immunocompromised patients. To obtain a better understanding of the key elements involved in A. fumigatus virulence and to identify possible drug targets, it is necessary to be able to generate gene-deletion strains. Unfortunately, the molecular techniques available do not include a rapid method to disrupt and identify essential genes. RNA interference, a process in which the presence of double-stranded RNA homologous to a gene of interest results in specific degradation of the corresponding message, has been successfully tested on A. fumigatus. We have shown that expression of double stranded RNA corresponding to portions of the ALB1/PKSP and FKS1 genes results in reduced mRNA levels for those genes, with phenotypic consequences similar to that of gene disruption. The two genes could also be subjected to simultaneous interference through expression of chimeric double-stranded RNA. Use of RNA interference in Aspergillus will allow easier examination of the phenotypic consequences of reducing expression of a gene of interest, especially for essential genes. 相似文献
94.
95.
In the direct-developing sea urchin Heliocidaris erythrogramma the first cleavage division bisects the dorsoventral axis of the developing embryo along a frontal plane. In the two-celled embryo one of the blastomeres, the ventral cell (V), gives rise to all pigmented mesenchyme, as well as to the vestibule of the echinus rudiment. Upon isolation, however, the dorsal blastomere (D) displays some regulation, and is able to form a small number of pigmented mesenchyme cells and even a vestibule. We have examined the spatial and temporal determination of cell fates along the dorsoventral axis during subsequent development. We demonstrate that the dorsoventral axis is resident within both cells of the two-celled embryo, but only the ventral pole of this axis has a rigidly fixed identity this early in development. The polarity of this axis remains the same in half-embryos developing from isolated ventral (V) blastomeres, but it can flip 180° in half-embryos developing from isolated dorsal (D) blastomeres. We find that cell fates are progressively determined along the dorsoventral axis up to the time of gastrulation. The ability of dorsal half-embryos to differentiate ventral cell fates diminishes as they are isolated at progressively later stages of development. These results suggest that the determination of cell fates along the dorsoventral axis in H. erythrogramma is regulated via inductive interactions organized by cells within the ventral half of the embryo. 相似文献
96.
ABSTRACT: BACKGROUND: Urinary tract infection (UTI) represents one of the most common diseases encountered in community medical practice. In resource poor settings, treatment is usually empiric due to the high cost and long duration required for reporting diagnosis by culture and antibiotic susceptibility testing. With the growing problem of drug resistance knowledge of antibiotic susceptibility pattern is pertinent for successful eradication of invading pathogens. Our study, the first of its kind in Cameroon, analyzed the distribution and antibiotic susceptibility of bacteria causing community-acquired urinary tract infection (CAUTI) in two towns (Bamenda and Buea) with a large number of young and middle aged persons, to provide data that could guide empiric treatment. FINDINGS: We cultured 235 urine specimens and analyzed the antibiotic susceptibility of isolates by the disc diffusion technique. Uropathogens were recovered from 137 (58.3%), with prevalence rates in Buea and Bamenda being 65.9% and 54% respectively. Predominant pathogens were Escherichia coli (31.4%), Klebsiella oxytoca (25.5%) and Staphylococcus spp (24.1%). Geographic variation in uropathogen distribution and antibiotic susceptibility was observed, and a significant difference in pathogen distribution with respect to gender. The 20-39 years age group had the highest prevalence of infection. All pathogens isolated were detected in this group. Isolates exhibited low susceptibility to antibiotics tested. Bamenda isolates generally exhibited lower susceptibility compared to those from Buea. CONCLUSION: Regional variation in etiology of CAUTI and antibiotic susceptibility observed in our study emphasizes the need to establish local and national antimicrobial resistance monitoring systems in Cameroon to provide information for the development of CAUTI treatment guidelines. 相似文献
97.
Aberrant threat perception has been linked to paranoia, anxiety and other mental health problems, and is widely considered to be a core, transdiagnostic feature of psychopathology. However, to date there has been only limited investigation of whether mental health problems are associated with a biased interpretation of stimuli that have explicit (as opposed to ambiguous) connotations of threat. In the present study, 41 adolescents diagnosed with a mental illness and 45 demographically matched controls were asked to provide danger ratings of stimuli normatively rated as being either low or high in potential threat. All participants were also asked to complete background measures of cognitive function, mental health and wellbeing. The results indicated that the two groups did not differ in their capacity to discriminate between low and high threat stimuli, nor did they differ in the absolute level of threat that they attributed to these stimuli. However, for the control group, the overall level of threat perceived in facial stimuli was correlated with two important indices of mental health (depression and anxiety). No associations emerged in the clinical group. These data are discussed in relation to their potential implications for the role of aberrant threat perception in transdiagnostic models of mental health. 相似文献
98.
Ion S. Jovin Li Lei Yan Huang Zhengrong Hao Jeptha P. Curtis Joseph J. Brennan Michael S. Remetz John F. Setaro Steven E. Pfau Christopher J. Howes Jude F. Clancy Henry S. Cabin Michael W. Cleman Frank J. Giordano 《Journal of cellular and molecular medicine》2012,16(12):3022-3027
Acute coronary syndromes and acute myocardial infarctions are often related to plaque rupture and the formation of thrombi at the site of the rupture. We examined fresh coronary thrombectomy specimens from patients with acute coronary syndromes and assessed their structure and cellularity. The thrombectomy specimens consisted of platelets, erythrocytes and inflammatory cells. Several specimens contained multiple cholesterol crystals. Culture of thrombectomy specimens yielded cells growing in various patterns depending on the culture medium used. Culture in serum‐free stem cell enrichment medium yielded cells with features of endothelial progenitor cells which survived in culture for a year. Immunohistochemical analysis of the thrombi revealed cells positive for CD34, cells positive for CD15 and cells positive for desmin in situ, whereas cultured cell from thrombi was desmin positive but pancytokeratin negative. Cells cultured in endothelial cell medium were von Willebrand factor positive. The content of coronary thrombectomy specimens is heterogeneous and consists of blood cells but also possibly cells from the vascular wall and cholesterol crystals. The culture of cells contained in the specimens yielded multiplying cells, some of which demonstrated features of haematopoietic progenitor cells and which differentiated into various cell‐types. 相似文献
99.
Jamie A. G. Hamilton Miyoung Y. Lee Rae Hunter Raira S. Ank Jamie Y. Story Ganesh Talekar Talia Sisroe Dov B. Ballak Andrew Fedanov Christopher C. Porter Elan Z. Eisenmesser Charles A. Dinarello Sunil S. Raikar James DeGregori Curtis J. Henry 《Aging cell》2021,20(2)
Aging‐associated declines in innate and adaptive immune responses are well documented and pose a risk for the growing aging population, which is predicted to comprise greater than 40 percent of the world''s population by 2050. Efforts have been made to improve immunity in aged populations; however, safe and effective protocols to accomplish this goal have not been universally established. Aging‐associated chronic inflammation is postulated to compromise immunity in aged mice and humans. Interleukin‐37 (IL‐37) is a potent anti‐inflammatory cytokine, and we present data demonstrating that IL‐37 gene expression levels in human monocytes significantly decline with age. Furthermore, we demonstrate that transgenic expression of interleukin‐37 (IL‐37) in aged mice reduces or prevents aging‐associated chronic inflammation, splenomegaly, and accumulation of myeloid cells (macrophages and dendritic cells) in the bone marrow and spleen. Additionally, we show that IL‐37 expression decreases the surface expression of programmed cell death protein 1 (PD‐1) and augments cytokine production from aged T‐cells. Improved T‐cell function coincided with a youthful restoration of Pdcd1, Lat, and Stat4 gene expression levels in CD4+ T‐cells and Lat in CD8+ T‐cells when aged mice were treated with recombinant IL‐37 (rIL‐37) but not control immunoglobin (Control Ig). Importantly, IL‐37‐mediated rejuvenation of aged endogenous T‐cells was also observed in aged chimeric antigen receptor (CAR) T‐cells, where improved function significantly extended the survival of mice transplanted with leukemia cells. Collectively, these data demonstrate the potency of IL‐37 in boosting the function of aged T‐cells and highlight its therapeutic potential to overcome aging‐associated immunosenescence. 相似文献
100.
Christophe Morell André Grand Alejandro Toro-Labbé Henry Chermette 《Journal of molecular modeling》2013,19(7):2893-2900
In this work, the third derivative of the energy with respect to the number of electrons, the so-called hyper-hardness, is investigated to assess whether this quantity has a chemical meaning. To achieve this goal a new working expression for hyper-hardness is developed and analyzed. It transpired from this analysis that hyper-hardness, just like hardness, can measure the reactivity or the stability of electron systems. Interestingly, positive values of hyper-hardness point to quite stable species such as noble gases and molecules. On the other hand, radicals almost always display large negative values of hyper-hardness. 相似文献