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Platelets are needed to prevent or arrest bleeding and aggregate at the site of injury upon vascular damage. Platelets express receptors for estrogens which might affect the function of the platelets and their hemostatic ability. The aim was to identify possible differences in platelet function related to age, gender, and phases of the menstrual cycle by use of impedance aggregometry with Multiplate. In the first part of the study, platelet function was assessed in 60 healthy individuals (30 men and 30 women) in each of three age groups (20–25, 40–45, and 60–65 years). In the second part of the study, the platelet function was analyzed on four occasions during the menstrual cycle in women without oral contraceptives (OCs) (n = 17) and compared to 19 women on OCs and 18 men of similar age (20–40 years). For the women on OCs, aggregation was analyzed once during the tablet-free week and once late during the period with OCs. The men were sampled once. Women of younger age (<45 years) had significantly higher agonist-induced aggregation response than both men and post-menopausal women (60–65 years). The agonist-induced aggregation response did not differ between phases of the menstrual cycle or OC use. The results suggest that estradiol and/or progesterone affect spontaneous aggregation since it was found to be lowest in the mid-luteal phase. Spontaneous aggregation was significantly lower in women on OCs than in both men and women without OCs. Our findings indicate that fertile age is associated with higher aggregation response capacity of the platelets, possibly to prevent excessive bleeding during menstruation, but this response capacity is not altered during the menstrual cycle or by use of OCs. 相似文献
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Robert C. Lynall J. Troy Blackburn Kevin M. Guskiewicz Stephen W. Marshall Prudence Plummer Jason P. Mihalik 《Journal of Science and Medicine in Sport》2019,22(5):503-508
Objectives
Despite evidence for increased musculoskeletal injury after concussion recovery, there is a lack of dynamic balance assessments that could inform management and research into this increased injury risk post-concussion. Our purpose was to identify tandem gait dynamic balance deficits in recreational athletes with a concussion history within the past 18-months compared to matched controls.Design
Cross-sectional, laboratory study.Methods
Fifteen participants with a concussion history (age: 19.7 ± 0.9 years; 9 females; median time since concussion 126 days, range 28–432 days), and 15 matched controls (19.7 ± 1.6 years; 9 females) with no recent concussion history participated. We measured center-of-pressure (COP) outcomes (velocity, path length, speed, dual-task cost) under 4 tandem gait conditions: (1) tandem gait, (2) tandem gait, eyes closed, (3) tandem gait, eyes open, cognitive distraction, and (4) tandem gait, eyes closed, cognitive distraction.Results
The concussion history group demonstrated slower tandem gait velocity compared to the control group (4.0 cm/s difference), thus velocity was used as a covariate when analyzing COP path length and speed. The concussion history group (23.5%) demonstrated greater COP speed dual-task cost than the control group (16.3%) during the eyes closed dual-task condition. No other comparisons were statistically significant.Conclusions
There may be subtle dynamic balance differences during tandem gait that are detectable after return-to-activity following concussion, but the clinical significance of these findings is unclear. Longitudinal investigations should identify acute movement deficits in varying visual and cognitive scenarios after concussion in comparison with recovery on traditional concussion assessment tools while also recording musculoskeletal injury outcomes. 相似文献37.
There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable. 相似文献
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Sarina A. Piha-Paul Do-Youn Oh Makoto Ueno David Malka Hyun Cheol Chung Adnan Nagrial Robin K. Kelley Willeke Ros Antoine Italiano Kazuhiko Nakagawa Hope S. Rugo Filippo de Braud Andrea Iolanda Varga Aaron Hansen Hui Wang Suba Krishnan Kevin G. Norwood Toshihiko Doi 《International journal of cancer. Journal international du cancer》2020,147(8):2190-2198
We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity. 相似文献
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Samir Gupta MD MDCS AGAF Balambal Bharti MBBS MPH PhD Dennis J. Ahnen MD Daniel D. Buchanan PhD Iona C. Cheng PhD MPH Michelle Cotterchio PhD Jane C. Figueiredo PhD Steven J. Gallinger MD MSc Robert W. Haile DrPH MPH Mark A. Jenkins PhD Noralane M. Lindor MD Finlay A. Macrae MD AGAF Loïc Le Marchand MD PhD Polly A. Newcomb PhD MPH Stephen N. Thibodeau PhD Aung Ko Win MBBS MPH PhD Maria Elena Martinez PhD 《Cancer》2020,126(13):3013-3020