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31.
Aishwarya Sridharan Qingfeng Chen Kin Fai Tang Eng Eong Ooi Martin L. Hibberd Jianzhu Chen 《Journal of virology》2013,87(21):11648-11658
A characteristic clinical feature of dengue virus infection is thrombocytopenia, though its underlying mechanism is not definitively determined. By adoptive transfer of human CD34+ fetal liver cells into immunodeficient mice, we have constructed humanized mice with significant levels of human platelets, monocytes/macrophages, and hepatocytes. Infection of these mice with both lab-adapted and clinical strains of dengue virus induces characteristic human hematological changes, including transient leukopenia and thrombocytopenia. We show that the specific depletion of human platelets is not mediated by antibodies in the periphery or reduced production of human thrombopoietin in the liver but reduction of human megakaryocytes and megakaryocyte progenitors in the bone marrow of the infected mice. These findings identify inhibition of platelet production in the bone marrow as a key mechanism underlying dengue-induced thrombocytopenia and suggest the utility of the improved humanized mouse model in studying dengue virus infection and pathogenesis in a human cell context. 相似文献
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Introduction
Workplace health promotion is important in the prevention of non-communicable diseases among employees. Previous workplace health programs have shown benefits such as lowered disease prevalence, reduced medical costs and improved productivity. This study aims to evaluate the impact of a 6-year workplace health promotion program on employees’ blood pressure in a public university.Methods
In this prospective cohort study, we included 1,365 employees enrolled in the university’s workplace health promotion program, a program conducted since 2008 and using data from the 2008–2013 follow-up period. Participants were permanent employees aged 35 years and above, with at least one follow up measurements and no change in antihypertensive medication during the study period. Baseline socio-demographic information was collected using a questionnaire while anthropometry measurements and resting blood pressure were collected during annual health screening. Changes in blood pressure over time were analyzed using a linear mixed model.Results
The systolic blood pressure in the hypertension subgroup decreased 2.36 mmHg per year (p<0.0001). There was also significant improvement in systolic blood pressure among the participants who were at risk of hypertension (-0.75 mmHg, p<0.001). The diastolic blood pressure among the hypertensive and at risk subgroups improved 1.76 mmHg/year (p<0.001) and 0.56 mmHg/year (p<0.001), respectively. However, there was no change in both systolic and diastolic blood pressure among participants in the healthy subgroup over the 6-year period.Conclusion
This study shows that continuing participation in workplace health promotion program has the potential to improve blood pressure levels among employees. 相似文献33.
Laparoscopic appendectomy to remove a metallic foreign body in a wild Bornean orangutan (Pongo pygmaeus) undergoing rehabilitation 下载免费PDF全文
Karmele Llano Sanchez Ayu B. Handayani Christine L. Nelson Jaclyn W.L. Eng Wendi Prameswari Nigel Hicks Romain Pizzi 《Journal of medical primatology》2016,45(6):327-329
A laparoscopic appendectomy was performed in a wild orangutan (Pongo pygmaeus) undergoing rehabilitation, for a metal nail found on radiographs, using 3‐mm instrumentation. Post‐operative healing was rapid and uneventful, with return to the forest within 10 days. This is the first report of minimally invasive surgery in a wild orangutan. 相似文献
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We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size. 相似文献
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Li F Pincet F Perez E Eng WS Melia TJ Rothman JE Tareste D 《Nature structural & molecular biology》2007,14(10):890-896
Membrane fusion occurs when SNAREpins fold up between lipid bilayers. How much energy is generated during SNAREpin folding and how this energy is coupled to the fusion of apposing membranes is unknown. We have used a surface forces apparatus to determine the energetics and dynamics of SNAREpin formation and characterize the different intermediate structures sampled by cognate SNAREs in the course of their assembly. The interaction energy-versus-distance profiles of assembling SNAREpins reveal that SNARE motifs begin to interact when the membranes are 8 nm apart. Even after very close approach of the bilayers (approximately 2-4 nm), the SNAREpins remain partly unstructured in their membrane-proximal region. The energy stabilizing a single SNAREpin in this configuration (35 k(B)T) corresponds closely with the energy needed to fuse outer but not inner leaflets (hemifusion) of pure lipid bilayers (40-50 k(B)T). 相似文献
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Christopher W. Schmidt Ashley Remy Rebecca Van Sessen John Willman Kristin Krueger Rachel Scott Patrick Mahoney Jeremy Beach Jaqueline McKinley Ruggero D'Anastasio Laura Chiu Michele Buzon J. Rocco De Gregory Susan Sheridan Jacqueline Eng James Watson Haagen Klaus Pedro Da-Gloria Jeremy Wilson Abigail Stone Paul Sereno Jessica Droke Rose Perash Christopher Stojanowski Nicholas Herrmann 《American journal of physical anthropology》2019,169(2):207-226
40.
Wi-Sun Ryu Keun-Sik Hong Sang-Wuk Jeong Jung E. Park Beom Joon Kim Joon-Tae Kim Kyung Bok Lee Tai Hwan Park Sang-Soon Park Jong-Moo Park Kyusik Kang Yong-Jin Cho Hong-Kyun Park Byung-Chul Lee Kyung-Ho Yu Mi Sun Oh Soo Joo Lee Jae Guk Kim Jae-Kwan Cha Dae-Hyun Kim Jun Lee Moon-Ku Han Man Seok Park Kang-Ho Choi Juneyoung Lee Jeffrey L. Saver Eng H. Lo Hee-Joon Bae Dong-Eog Kim 《PLoS medicine》2022,19(2)
BackgroundPreclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke.Methods and findingsIn a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules.ConclusionsNight-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.Wi-Sun Ryu and colleagues investigate the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in ischemic stroke. 相似文献