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41.
Sean C. Forbes Rebecca J. Willcocks William T. Triplett William D. Rooney Donovan J. Lott Dah-Jyuu Wang Jim Pollaro Claudia R. Senesac Michael J. Daniels Richard S. Finkel Barry S. Russman Barry J. Byrne Erika L. Finanger Gihan I. Tennekoon Glenn A. Walter H. Lee Sweeney Krista Vandenborne 《PloS one》2014,9(9)
Introduction
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in functional deficits. However, these functional declines are often not able to be quantified in clinical trials for DMD until after age 7. In this study, we hypothesized that 1H2O T2 derived using 1H-MRS and MRI-T2 will be sensitive to muscle involvement at a young age (5–7 years) consistent with increased inflammation and muscle damage in a large cohort of DMD subjects compared to controls.Methods
MR data were acquired from 123 boys with DMD (ages 5–14 years; mean 8.6 SD 2.2 years) and 31 healthy controls (age 9.7 SD 2.3 years) using 3-Tesla MRI instruments at three institutions (University of Florida, Oregon Health & Science University, and Children’s Hospital of Philadelphia). T2-weighted multi-slice spin echo (SE) axial images and single voxel 1H-MRS were acquired from the lower leg and thigh to measure lipid fraction and 1H2O T2.Results
MRI-T2, 1H2O T2, and lipid fraction were greater (p<0.05) in DMD compared to controls. In the youngest age group, DMD values were different (p<0.05) than controls for the soleus MRI-T2, 1H2O T2 and lipid fraction and vastus lateralis MRI-T2 and 1H2O T2. In the boys with DMD, MRI-T2 and lipid fraction were greater (p<0.05) in the oldest age group (11–14 years) than the youngest age group (5–6.9 years), while 1H2O T2 was lower in the oldest age group compared to the young age group.Discussion
Overall, MR measures of T2 and lipid fraction revealed differences between DMD and Controls. Furthermore, MRI-T2 was greater in the older age group compared to the young age group, which was associated with higher lipid fractions. Overall, MR measures of T2 and lipid fraction show excellent sensitivity to DMD disease pathologies and potential therapeutic interventions in DMD, even in the younger boys. 相似文献42.
The effect of adding low concentrations of a sediment/microbial community suspension to speed up the development of the denitrification capacity in the restored HSSF of a hybrid CW was studied during a one-year period after the filling of the horizontal filter with new light weight aggregates (LWA). Two HSSF filters with the same LWA substrate but different wastewater flow regimes were used as donor systems for the bioaugmentation. NO3-N concentrations in the outflows of all variants of studied MCs were significantly influenced by the time factor (p < 0.001, repeated measures ANOVA). Post hoc comparison indicated that MCs bioaugmented with the sediment suspension from a similar HSSF had significantly lower NO3-N concentrations than the control MCs (p < 0.05, Fisher LSD test), whereas MCs bioaugmented with the sediment suspension from a less similar HSSF did not show significant differences compared to the control MCs. This finding emphasizes the importance of the similarity of flow regime and water parameters in choosing a donor system for bioaugmentation. High variability of the effect of bioaugmentation shows that its importance for full scale operation may be overshadowed by the effect of other factors determining denitrification intensity. 相似文献
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46.
Christina S. Polyak Krista Yuhas Benson Singa Monica Khaemba Judd Walson Barbra A. Richardson Grace John-Stewart 《PLoS medicine》2016,13(1)
Background
Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings.Methods and Findings
Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥18 mo with CD4 count > 350 cells/mm3 in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression.Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52–3.38; p < 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52–241.02; p = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82–2.27, and IRR = 1.43, 95% CI 0.54–3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.Conclusions
CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX guidelines.Trial registration
ClinicalTrials.gov NCT01425073相似文献47.
Monkeypox virus, a zoonotic member of the genus Orthopoxviridae, can cause a severe, smallpox-like illness in humans. Monkeypox virus is thought to be endemic to forested areas of western and Central Africa. Considerably more is known about human monkeypox disease occurrence than about natural sylvatic cycles of this virus in non-human animal hosts. We use human monkeypox case data from Africa for 1970-2003 in an ecological niche modeling framework to construct predictive models of the ecological requirements and geographic distribution of monkeypox virus across West and Central Africa. Tests of internal predictive ability using different subsets of input data show the model to be highly robust and suggest that the distinct phylogenetic lineages of monkeypox in West Africa and Central Africa occupy similar ecological niches. High mean annual precipitation and low elevations were shown to be highly correlated with human monkeypox disease occurrence. The synthetic picture of the potential geographic distribution of human monkeypox in Africa resulting from this study should support ongoing epidemiologic and ecological studies, as well as help to guide public health intervention strategies to areas at highest risk for human monkeypox. 相似文献
48.
Paul Micevych Clair B. Eckersell Krista Holland Akemi Smith 《Developmental neurobiology》1996,30(4):465-479
Estrogenic regulation of cholecystokinin (CCK) and its receptors is correlated with the initiation and termination of lordosis behavior. To understand the effect of circulating estrogen concentration on the temporal aspects of CCK mRNA expression in the posterodorsal medial amygdaloid nucleus (MeApd) and the central part of the medial preoptic nucleus (MPNc) of the limbic-hypothalamic circuit, ovariectomized female rats were treated with a 10 mm Silastic™ capsule filled with estradiol, a bolus injection of 50 μg estradiol benzoate or 2 μg estradiol benzoate every 4 days for five “cycles.” In situ hybridization was used to compare the relative changes of CCK mRNA levels at 0 h to levels measured at 6, 12, 24, 48, 72, or 96 h after estrogen administration. In the MPNc and the MeApd, the 10-mm capsule significantly increased and maintained CCK mRNA levels from 6 to 96 h. The range of the increase was 3.0–5.1-fold in the MPNc and 2.8–5.0 in the MeApd. The 50-μg injections significantly increased and maintained CCK mRNA levels in the MPNc from 12 to 96 h (range of the increase 2.4–4.1-fold) and in the MeApd from 24 to 96 h (range of the increase 2.2–2.8-fold). The repeated administration of 2 μg estrogen induced a significant increase of message levels in the MPNc at 12 and 24 h that were 4.2- and 4.7-fold, respectively. In the MeApd this estrogen treatment did not significantly increase CCK mRNA. These studies demonstrate that small doses (2 μg) of estrogen that mimic the pattern and circulating levels of estrogen dramatically stimulate CCK mRNA levels in the limbic-hypothalamic circuit. To further study this steroid stimulation, ovariectomized female rats were implanted with estradiol-filled cannulae into the bed nucleus of the stria terminalis or MeA. Estrogen elevated CCK mRNA levels locally in each nucleus. Implants in the bed nucleus also elevated CCK mRNA levels in the MeApd indicating that physiologic estrogen stimulation of CCK in the MeApd is the result of both local and distal transsynaptic elevation of CCK mRNA levels. The site-specific induction of CCK mRNA levels within the limbic-hypothalamic nuclei provides another important facet of estrogenic modulation of CCK induction. © 1996 John Wiley & Sons, Inc. 相似文献
49.
Alice Toso Simona Schifano Charlotte Oxborough Krista McGrath Luke Spindler Anabela Castro Lucy Evangelista Vanessa Filipe Maria José Gonçalves Antonio Marques Inês Mendes da Silva Raquel Santos Maria João Valente Iona McCleery Michelle Alexander 《American journal of physical anthropology》2021,176(2):208-222
50.
We investigated the applicability of the Gestalt principle of perceptual grouping by proximity in the haptic modality. To do so, we investigated the influence of element proximity on haptic contour detection. In the course of four sessions ten participants performed a haptic contour detection task in which they freely explored a haptic random dot display that contained a contour in 50% of the trials. A contour was defined by a higher density of elements (raised dots), relative to the background surface. Proximity of the contour elements as well as the average proximity of background elements was systematically varied. We hypothesized that if proximity of contour elements influences haptic contour detection, detection will be more likely when contour elements are in closer proximity. This should be irrespective of the ratio with the proximity of the background elements. Results showed indeed that the closer the contour elements were, the higher the detection rates. Moreover, this was the case independent of the contour/background ratio. We conclude that the Gestalt law of proximity applies to haptic contour detection. 相似文献