Journals
2012 EN
Alaine C. Keebaugh · Meera E. Modi · Catherine Barrett
+2 more
Background The prairie vole ( Microtus ochrogaster ) is an emerging animal model for biomedical research because of its rich sociobehavioral repertoire. Recently, lentiviral transgenic technology has been used to introduce the gene encoding the green fluorescent protein (GFP) into the prairie vole germline. However, the efficiency of transgenesis in this species is limited by the inability to reliably produce large numbers of fertilized embryos. Here we examined several factors that may contribute to variability in superovulation success including, age and parentage of the female, and latency to mating after being placed with the male. Methods Females produced from 5 genetically distinct breeder lines were treated with 100 IU of pregnant mare serum gonadotrophin (PMSG) and immediately housed with a male separated by a perforated Plexiglas divider. Ovulation was induced 72 hr later with 30 IU of human chorionic gonadotropin (hCG) and 2 hrs later mating was allowed. Results Superovulation was most efficient in young females. For example, females aged 6-11 weeks produced more embryos (14 +/- 1.4 embryos) as compared to females aged 12-20 weeks (4 +/- 1.6 embryos). Females aged 4-5 weeks did not produce embryos. Further, females that mated within 15 min of male exposure produced significantly more embryos than those that did not. Interestingly, there was a significant effect of parentage. For example, 12 out of 12 females from one breeder pair superovulated (defined as producing 5 or more embryos), while only 2 out of 10 females for other lines superovulated. Conclusions The results of this work suggest that age and genetic background of the female are the most important factors contributing to superovulation success and that latency to mating is a good predictor of the number of embryos to be recovered. Surprisingly we found that cohabitation with the male prior to mating is not necessary for the recovery of embryos but is necessary to recover oocytes. This information will dramatically reduce the number of females required to generate embryos for transgenesis in this species.
Journals
2012 EN
Catherine A. VandeVoort · Theodore L. Tollner
Background The use of therapeutic ultrasound as a contraceptive approach has involved nonhuman primates as well as rats and dogs. The current study was undertaken to determine whether this treatment could be a method for reversible contraception, using a model with testes size similar to adult humans. Methods Two methods of ultrasound exposure were used, either the transducer probe at the bottom of a cup filled with saline (Cup) or direct application to the surface of the scrotum (Direct). Four adult rhesus (Macaca mulatta) males with normal semen parameters were treated with therapeutic ultrasound at 2.5 W/cm(2) for 30 min. Treatment was given 3 times, one every other day on a Monday-Wednesday-Friday schedule. For each male, semen quality was evaluated a minimum of three times over several months prior to ultrasound exposure and weekly for two months following ultrasound treatment. Results Semen samples from all males, regardless of exposure method, exhibited a decrease in the percentage of motile sperm following ultrasound treatment. There was an average reduction in motility of 40% the week following treatment. Similarly, curvilinear velocity and the percentage of sperm with a normally shaped flagellum were also reduced in all males following ultrasound treatment. A significant reduction in the total number of sperm in an ejaculate (total sperm count) was only observed in males that received ultrasound via the cup method. Following treatment via the cup method, males exhibited up to a 91.7% decrease in average total sperm count (n = 2). Sperm count did not approach pre-treatment levels until 8 weeks following ultrasound exposure. Conclusions The sustained reduction in sperm count, percent motility, normal morphology, and sperm vigor with the cup exposure method provides proof of principle that testicular treatment with ultrasound can be an effective contraceptive approach in humans.
Journals
2012 EN
S. E. O. Meredith · Catherine Cross · Uche Amazigo
The control of onchocerciasis is not only a major success story in global health, but also one of the best examples of the power of public-private partnership at the international level as well as at the national level. The onchocerciasis story is also a leading example of the contribution of a group of called Non-Governmental Development Organizations (NGDO) to operational research which resulted in important changes in treatment strategies and policies. The four case studies presented here illustrate some key contributions the NGDOs made to the development of “community directed treatment with ivermectin” –CDTI, in Africa, which became the approved methodology within the African Programme for Onchocerciasis Control (APOC). The partnership between the international, multilateral, government institutions and the NGDO Coordination Group was the backbone of the APOC programme’s structure and facilitated progress and scale-up of treatment programmes. Contributions included piloting community–based methodology in Mali and Nigeria; research, collaboration and coordination on treatment strategies and policies, coalition building, capacity building of national health workforce and advocacy at the national and international level. While the Onchocerciasis Control Programme (OCP) and APOC provided leadership, the NGDOs working with the national health authorities played a major role in advocacy evolving the community methodology which led to achieving and maintaining- treatments with ivermectin for at least 20 years and strengthening community health systems.
Journals
2012 EN
Andrew J. Tatem · Susana B. Adamo · Nita Bharti
+13 more
The use of Global Positioning Systems (GPS) and Geographical Information Systems (GIS) in disease surveys and reporting is becoming increasingly routine, enabling a better understanding of spatial epidemiology and the improvement of surveillance and control strategies. In turn, the greater availability of spatially referenced epidemiological data is driving the rapid expansion of disease mapping and spatial modeling methods, which are becoming increasingly detailed and sophisticated, with rigorous handling of uncertainties. This expansion has, however, not been matched by advancements in the development of spatial datasets of human population distribution that accompany disease maps or spatial models. Where risks are heterogeneous across population groups or space or dependent on transmission between individuals, spatial data on human population distributions and demographic structures are required to estimate infectious disease risks, burdens, and dynamics. The disease impact in terms of morbidity, mortality, and speed of spread varies substantially with demographic profiles, so that identifying the most exposed or affected populations becomes a key aspect of planning and targeting interventions. Subnational breakdowns of population counts by age and sex are routinely collected during national censuses and maintained in finer detail within microcensus data. Moreover, demographic and health surveys continue to collect representative and contemporary samples from clusters of communities in low-income countries where census data may be less detailed and not collected regularly. Together, these freely available datasets form a rich resource for quantifying and understanding the spatial variations in the sizes and distributions of those most at risk of disease in low income regions, yet at present, they remain unconnected data scattered across national statistical offices and websites. In this paper we discuss the deficiencies of existing spatial population datasets and their limitations on epidemiological analyses. We review sources of detailed, contemporary, freely available and relevant spatial demographic data focusing on low income regions where such data are often sparse and highlight the value of incorporating these through a set of examples of their application in disease studies. Moreover, the importance of acknowledging, measuring, and accounting for uncertainty in spatial demographic datasets is outlined. Finally, a strategy for building an open-access database of spatial demographic data that is tailored to epidemiological applications is put forward.
Journals
2012 EN
John P. Greenwood · Ananth Kidambi · Arshad Zaman
+8 more
Summary We compared detection rate sf or cardiovascular magnetic resonance (CMR) perfusion and single photon emission tomography (SPECT) in the subset of patients from the CE-MARC study with significant left main stem (LMS) disease. Detection rates for LMS disease by CMR perfusion were higher than for SPECT, and CMR identified a classical LMS pattern with higher frequency. Visual perfusion defects occurred with similar frequency in patients with ≥50% and ≥70% LMS stenosis. Background Left main stem (LMS) disease is found in approximately 5% of patients with stable angina. Three-year survival in patients with >50% left main stenosis may be as low as 50%. Single photon emission tomography (SPECT) fails to detect ischemia in up to 15% of LMS stenoses, and identification of the ‘classical’ pattern of both left anterior descending (LAD) and circumflex (LCx) coronary territory ischaemia is lower still. To date, the utility of cardiovascular magnetic resonance (CMR) perfusion in LMS disease is poorly established. The CE-MARC study was a prospective study of 752 patients with suspected coronary artery disease, enrolled to undergo CMR, SPECT and X-ray coronary angiography. We assessed the diagnostic performance of SPECT and CMR to detect LMS disease in the group of CE-MARC patients with ≥50% LMS disease on quantitative X-ray angiography. We also compared subsets of patients with ≥50% and ≥70% LMS stenosis. Methods All patients with LMS disease ≥50% on quantitative angiography were identified from the CE-MARC study. All patients had undergone adenosine stress perfusion by CMR and SPECT and also invasive X-ray angiography [1]. By visual analysis we compared detection rates for LMS disease from the CMR and SPECT perfusion studies. Results Of 23 patients in the CE-MARC cohort with LMS stenosis ≥50%, one patient could not be analysed. CMR identified evidence of inducible perfusion defects in 18/ 22 (82%) of the LMS group; SPECT identified 13/22 (59%). For CMR and SPECT respectively, inducible perfusion defects were found in both LAD and LCx territories for 6/18 (33%) and 2/13 (15%). Only one patient had normal perfusion analyses (false negative) for both CMR and SPECT. Of 11 patients with ≥70% LMS stenosis, 10 (91%) had inducible perfusion defects with CMR vs. 5 (45%) with SPECT. Six (55%) vs. 2 (18%) had a LAD and LCx disease pattern. Perfusion abnormalities were detected with similar frequency in ≥50% and ≥70% groups by both CMR (p=0.64) and SPECT (p=0.49). Figure 1 summarises the detection rate of CMR and SPECT in LMS disease.
Journals
2012 EN
John P. Greenwood · Manish Motwani · Neil Maredia
+10 more
The CE-MARC study is the largest, prospective evaluation of cardiovascular magnetic resonance (CMR) in patients with suspected coronary artery disease (CAD). This predefined CE-MARC substudy compared the diagnostic performance of CMR and single-photon emission computed tomography (SPECT) in the female cohort.
Journals
2012 EN
Lisabeth V. Scalzi · Greg Hychko · Barbara E. Ostrov
+3 more
Methods A retrospective chart review was completed on all patients less than age 18, between 1990 and 2009 at Pennsylvania State University Children’s Hospital, with a diagnosis of either sJIA or NB. The following variables were identified at the time of presentation; gender, age, race, time to diagnosis, presenting signs and symptoms, neuroblastoma stage, LDH, uric acid, sedimentation rate, CRP, platelet count, hemoglobin, peripheral white blood cell count, percentage of neutrophils and lymphocytes, ferritin, and d-dimer. Other categorical information included whether or not the patients had gait disturbance or extremity pain, fever, rash, abdominal mass, arthritis, fatigue, or weight loss. Individual logistic regression models were evaluated for each variable, with sJIA or NB as the outcome. Given that patients with NB and extremity pain may be referred to orthopedics or rheumatology first, instead of a timely referral to hematology/oncology, a subgroup analysis was completed for those patients.
Journals
2012 EN
Jean-David Cohen · Dominique Fournet · Catherine M. Ludwig
+3 more
Methods Among patients with JIA treated with ETA from 2000 (n = 46), we identified patients in remission defined by a sustained good clinical response according to physicians of our departments for at least 1,5 years and discontinued ETA. The disease course was evaluated using physician and parent/patients VAS for disease activity, active joints, joints with LOM, CHAQ, ESR, CRP. A bivariate analysis of the relationship between JIA subtype, sex, age at onset JIA, disease duration at start of ETA, MTX association, time on ETA (before tapering and total), clinical remission on ETA (defined by Wallace) and disease course was undertaken using the Chi-square or Fisher’s exact test and the Wilcoxon test. Results Among the 25 patients in clinical remission on medication, 16 have discontinued ETA at the moment of the analysis. Main characteristics were: 12 (75 %) female, mean age at onset JIA was 5,5 years (1,4-13,2), JIA subtype were oligoarthritis 7 (44%), polyarthritis 1 (6%), systemic arthritis 5 (31%), enthesitis related arthritis 2 (12,5%), mean disease duration at start of ETA was 3,3 years (0,2-13), MTX was associated to ETA in 11 (69%) cases, median total time on ETA was 2,15 years (1,7-3,2). Discontinuation of ETA was progressive for all patients except 3. After discontinuation, 13 patients are in clinical remission with a median period of 1,8 years (0,5-2,2). Follow-up mean period (after ETA withdrawal) for these patients was 2,45 years (0,5-5,4). Only 3 patients experience flare with a good response after reintroduction of ETA. Median time to flare was 1,7 years (0,4-1,8). The bivariate analysis didn’t reveal baseline values able to predict successful discontinuation of ETA without flare. Conclusion Our retrospective study confirms the possibility of ETA discontinuation in JIA in case of long term of remission. We did not identify predictive factors probably because of the small cohort and, moreover, low number of patients experiencing flare. Disclosure
Journals
2012 EN
Thelma Polyviou · Yannis Pitsiladis · Wu Chean Lee
+4 more
Background It has been shown that supplementation with creatine (Cr) and glycerol (Gly), when combined with glucose (Glu) necessary for the enhancement of Cr uptake by skeletal muscle, induces significant improvements in thermoregulatory and cardiovascular responses during exercise in the heat. Purpose To determine whether Cr/Gly-induced thermoregulatory and cardiovascular responses are maintained when the majority (~75%) of the Glu in the Cr/Gly supplement is replaced with the insulintropic agent alpha lipoic acid (Ala). Methods 22 healthy endurance trained cyclists were randomly assigned to receive either 20 g/day (4 × 5 g/day) of Cr, 2 g . kg -1 BM per day (4 × 0.5 g . kg -1 BM per day) of Gly and 150 g/day (4 × 37.5 g/day) of Glu or 20 g/day (4 × 5 g/day) of Cr monohydrate, 2 g . kg -1 BM per day (4 × 0.5 g . kg -1 BM per day) of Gly (100 g/day (4 × 25 g/day) of Glu and 1000 mg/day (4 × 250 mg/day) of Ala for 7 days for 7 days. Exercise trials were conducted pre- and post-supplementation and involved 40 min of constant-load cycling exercise at 70% O 2 max by a self-paced 16.1 km time trial at 30°C and 70% relative humidity. Results Median and range values of TBW increased significantly by 2.1 (1.3-3.3) L and 1.8 (0.2-4.6) L in Cr/Gly/Glu and Cr/Gly/Glu/Ala groups respectively ( P = 0.03) and of BM not significantly by 1.8 (0.2-3.0) kg and 1.2 (0.5-2.1) kg in Cr/Gly/Glu and in Cr/Gly/Glu/Ala, respectively ( P = 0.75). During constant load exercise, heart rate (HR) and core temperature (Tcore) were significantly lower post-supplementation: HR was reduced on average by 3.3 ± 2.1 beats/min and by 4.8 ± 3.3 beats/min (mean ± SD) and Tcore by 0.2 ± 0.1 (mean ± SD) in the Cr/Gly/Glu and Cr/Gly/Glu/Ala, respectively The reduction in HR and Tcore was not significantly different between the supplementation groups. Conclusions In comparison to the established hyper hydrating Cr/Gly/Glu supplement, supplement containing Cr/Gly/Ala and decreased amount of Glu provides equal improvements in thermoregulatory and cardiovascular responses during exercise in the heat.
Springer Science+Business Media
Journals
2012 EN
ChiShuo Chen · Sushant Soni · Catherine Le
+4 more
Human embryonic stem cells [hESCs] are able to differentiate into specific lineages corresponding to regulated spatial and temporal signals. This unique attribute holds great promise for regenerative medicine and cell-based therapy for many human diseases such as spinal cord injury [SCI] and multiple sclerosis [MS]. Carbon nanotubes [CNTs] have been successfully used to promote neuronal differentiation, and silk has been widely applied in tissue engineering. This study aims to build silk-CNT composite scaffolds for improved neuron differentiation efficiency from hESCs. Two neuronal markers (β-III tubulin and nestin) were utilized to determine the hESC neuronal lineage differentiation. In addition, axonal lengths were measured to evaluate the progress of neuronal development. The results demonstrated that cells on silk-CNT scaffolds have a higher β-III tubulin and nestin expression, suggesting augmented neuronal differentiation. In addition, longer axons with higher density were found to associate with silk-CNT scaffolds. Our silk-CNT-based composite scaffolds can promote neuronal differentiation of hESCs. The silk-CNT composite scaffolds developed here can serve as efficient supporting matrices for stem cell-derived neuronal transplants, offering a promising opportunity for nerve repair treatments for SCI and MS patients.
Springer Science+Business Media