GAIT TRAINING WITH AUDITORY RHYTHMS AND INSTRUCTIONS IN CHRONIC STROKE

During walking in healthy adults, characteristic movement patterns between the upper and lower body relate directly to walking velocity. In persons who suffer a stroke, walking velocity decreases as motor deficits appear in both the arm and leg opposite the side of the stroke. Recent findings indicate that treadmill walking to a metronome beat impacts arm motion, however, the effect is dependent on the severity of motor deficits. The changes in arm motion lead to changes that are indicative of improvements in overall walking function. The purpose of this project is to determine the efficacy of over-ground gait training using an external auditory rhythm directed at arm movement versus leg movement on improving movement coordination, walking velocity, and daily physical activity in persons who have suffered a stroke

Effect of Estradiol-17β on Placental Size

Meishan embryos transferred to recipient females on day 2.5 are larger, contain greater numbers of trophectoderm cells, and secrete greater amounts of estradiol-17β when gestated in a Yorkshire compared with Meishan uterus to day 12. Additionally, placentae of Meishan conceptuses are larger when gestated in a Yorkshire compared with Meishan uterus throughout gestation. Embryonic estradiol-17β secretion during elongation on day 12 to 13 of gestation is temporally associated with endometrial secretion of growth factors, including IGF-I, which has been shown to increase mitotic rate in the trophectoderm of pig embryos. This experiment was conducted to determine if estradiol-17β administration to Meishan females at the time of conceptus elongation would increase placental size at term. Meishan females (n=12) were checked twice daily for estrus (0700 and 1900), and each bred to a Meishan boar at 0 and 24 h after the onset of estrus (day 0). Females were randomly assigned in equal numbers to receive injections of sesame oil (VEH) starting on day 12 (CONTROL), 1 mg of estradiol-17β in VEH starting on day 12 (E212), or 1 mg of estradiol-17β in VEH starting day 13 (E213). The injections were initiated at 0700 or 1900 (corresponding to the time of day they first exhibited estrus) and continued at 6-hour intervals for 48 hours, resulting in 8 mg of estradiol-17β given in eight injections. Pregnant females were killed on day 112 of gestation and ovulation rate, litter size, implantation site length, fetal weight, crown-rump length, placental weight, and placental surface area were quantified. There were no differences among E212, E213, and CONTROL females in ovulation rate or litter size, which averaged 16.3 ± .7 and 11.8 ± .7, respectively. Fetal weight and crown-rump length were not different (P\u3e.10) among E212, E213, and CONTROL females, averaging 802 ± 26 g and 24.3 ± .3 cm. Placentae were markedly heavier (176 ± 14 and 174 ± 16 g vs. 134 ± 10 g,

Networks and the epidemiology of infectious disease

The science of networks has revolutionised research into the dynamics of interacting elements. It could be argued that epidemiology in particular has embraced the potential of network theory more than any other discipline. Here we review the growing body of research concerning the spread of infectious diseases on networks, focusing on the interplay between network theory and epidemiology. The review is split into four main sections, which examine: the types of network relevant to epidemiology; the multitude of ways these networks can be characterised; the statistical methods that can be applied to infer the epidemiological parameters on a realised network; and finally simulation and analytical methods to determine epidemic dynamics on a given network. Given the breadth of areas covered and the ever-expanding number of publications, a comprehensive review of all work is impossible. Instead, we provide a personalised overview into the areas of network epidemiology that have seen the greatest progress in recent years or have the greatest potential to provide novel insights. As such, considerable importance is placed on analytical approaches and statistical methods which are both rapidly expanding fields. Throughout this review we restrict our attention to epidemiological issues

Toward understanding ambulatory activity decline in Parkinson disease

BACKGROUND: Declining ambulatory activity represents an important facet of disablement in Parkinson disease (PD). OBJECTIVE: The primary study aim was to compare the 2-year trajectory of ambulatory activity decline with concurrently evolving facets of disability in a small cohort of people with PD. The secondary aim was to identify baseline variables associated with ambulatory activity at 1- and 2-year follow-up assessments. DESIGN: This was a prospective, longitudinal cohort study. METHODS: Seventeen people with PD (Hoehn and Yahr stages 1-3) were recruited from 2 outpatient settings. Ambulatory activity data were collected at baseline and at 1- and 2-year annual assessments. Motor, mood, balance, gait, upper extremity function, quality of life, self-efficacy, and levodopa equivalent daily dose data and data on activities of daily living also were collected. RESULTS: Participants displayed significant 1- and 2-year declines in the amount and intensity of ambulatory activity concurrently with increasing levodopa equivalent daily dose. Worsening motor symptoms and slowing of gait were apparent only after 2 years. Concurrent changes in the remaining clinical variables were not observed. Baseline ambulatory activity and physical performance variables had the strongest relationships with 1- and 2-year mean daily steps. LIMITATIONS: The sample was small and homogeneous. CONCLUSIONS: Future research that combines ambulatory activity monitoring with a broader and more balanced array of measures would further illuminate the dynamic interactions among evolving facets of disablement and help determine the extent to which sustained patterns of recommended daily physical activity might slow the rate of disablement in PD.This study was funded primarily by the Davis Phinney Foundation and the Parkinson Disease Foundation. Additional funding was provided by Boston University Building Interdisciplinary Research Careers in Women's Health (K12 HD043444), the National Institutes of Health (R01NS077959), the Utah Chapter of the American Parkinson Disease Association (APDA), the Greater St Louis Chapter of the APDA, and the APDA Center for Advanced PD Research at Washington University. (Davis Phinney Foundation; Parkinson Disease Foundation; K12 HD043444 - Boston University Building Interdisciplinary Research Careers in Women's Health; R01NS077959 - National Institutes of Health; Utah Chapter of the American Parkinson Disease Association (APDA); Greater St Louis Chapter of the APDA; APDA Center for Advanced PD Research at Washington University

The Effect of Uterine Environment on Meishan and Yorkshire Fetal Development and Placental Size and Vascularity

When Meishan (M) and Yorkshire (Y) embryos were cotransferred to Y recipients that were then allowed to farrow, it was observed that the birth weights of M and Y littermates were similar averaging 1.15 ± .06 kg. In contrast, placentae matched to M piglets were markedly smaller (.70% lighter) and more vascular (.two-fold) than Y placentae. To investigate the effect of uterine environment on conceptus development to term, M and Y embryos were cotransferred to M recipients (n=3) that were slaughtered one day before expected parturition (day 113). Fetal weight, placental weight, and placental surface area were recorded. Additionally, a section of the intact maternal placental interface was excised, fixed, embedded, sectioned, and stained to allow quantitation of the placental vascular density (PVD). As observed when M and Y fetuses were cogestated by Y recipients, littermate M and Y fetuses gestated in M uteri were similar in weight (1.04 ± .03 vs. 1.03 ± .05 kg) at term. Further, M conceptuses exhibited markedly reduced (P\u3c.03) placental weights (170 ± 19 vs. 249 ± 10 g) and surface areas (1017 ± 70 vs. 1506 ± 96 cm 2 ) compared with their Y littermates. As was the case for conceptuses gestated in Y uteri, the similarity in fetal weight between the two breeds with very different placental sizes appears to result from an increased (P\u3c.09) M PVD compared with littermate Y fetuses (2.5 ± .3 vs. 1.4 ± .4%). These data indicate that in both the M and Y uterine environment, the reduced size of the M compared with Y placenta is compensated for by an increase in PVD. Currently it is unknown whether M placentae contain a greater amount of vasculature (total volume) or a similar amount of vasculature simply squeezed into a smaller space. To investigate breed differences in total placental vasculature we have perfused placentae of M and Y conceptuses cogestated in M uteri on d 113 of gestation with vascular casting material and will compare the volumes of the corrosion casts

Use of Asynchronous Embryo Transfer to Investigate the Role of Uterine-embryo Timing on Placental Size

The ability of the uterus to accommodate a finite amount of placental tissue appears to be a major limitation to litter size. Meishan preimplantation conceptuses contain fewer cells, produce less estradiol-17β, elongate to a shorter length, and exhibit a reduced placental size throughout gestation than Yorkshire conceptuses. Uterine luminal embryonic estradiol-17β and growth factor content are positively associated at elongation. Based on these data, we have argued that growth factor quantity regulates the length an embryo attains at elongation, and ultimately limits placental size. Recently, we injected Meishan gilts every 6 hours with estradiol-17β on day 12 and 13 of gestation, resulting in a 40% increase in placental size at term compared with vehicle-injected Meishan gilts. This study was conducted to determine if transfer of embryos into the oviducts of asynchronous females (more or less advanced uterine environments) would alter fetal and/or placental size at term. Embryos (1 to 4 cells) were flushed from the oviducts of each donor gilt on day 2.5 of gestation and transferred in equal numbers to the oviducts of a recipient gilt on day 1.5, 2.5, or 3.5 of their estrous cycle. Gilts were slaughtered on day 112 of gestation and fetal and placental weight, placental surface area, and implantation site lengths were determined. Although litter sizes were similar (8.4 ± 1.1), conceptuses transferred to day 3.5 recipients had heavier fetuses (1.57 ± .09 vs. 1.23 ± .04 kg, P\u3c.001), larger placental surface area (1812 ± 106 vs. 1458 ± 43 cm 2 , P\u3c.01) and occupied longer implantation site length (34 ± 3 vs. 25 ± 1 cm, P\u3c.001) than those transferred to recipients on day 1.5 or 2.5. These data demonstrate that oviductal transfer of embryos to a reproductive tract as little as 24 hours more advanced can result in dramatic alterations in placental growth and function during gestation

Role of Vascular Endothelial Growth Factor in Placental Vascularization

The ratio of a fetus’s weight to that of its placenta has been used in our laboratory as an estimate of placental efficiency, which defines the number of grams of placenta required to support a gram of fetus. Because the pig placenta is noninvasive, nutrients from the mother must diffuse from uterine blood vessels to placental blood vessels at the placental-endometrial interface. A pig placenta can respond to increasing fetal nutrient demands by either increasing in size, and thus surface area in contact with the endometrium, or by increasing the number of blood vessels per unit area at the fetal-maternal interface. Previous studies from our laboratory have shown Meishan and Yorkshire conceptuses gestated in a Meishan uterus had markedly smaller placentae than Meishan or Yorkshire conceptuses gestated in a Yorkshire uterus whereas fetal weights across the two uterine environments were much more similar. These data suggested that conceptuses in a Meishan uterine environment have a greater vascular density at the placentalendometrial interface. Greater densities of blood vessels can be achieved by either vasodilation (increasing the diameter of existing blood vessels) or angiogenesis (growth of new vessels from preexisting ones). Hypoxia, or inadequate oxygen transport, has been shown to increase angiogenic factors, such as vascular endothelial growth factor (VEGF), which stimulate blood vessel development. It is possible that VEGF may be important in stimulating increased blood vessel density in the pig placenta, as it has been to shown to do in the ovine placenta. Our objective was to determine if VEGF mRNA expression was associated with placental and/or endometrial vascular density, placental efficiency, and litter size during late gestation. We observed a positive association of both placental vascular density (r=0.37, p\u3c0.05) and VEGF mRNA levels (r=0.35; P\u3c.05) with placental efficiency . There was also a positive correlation between VEGF mRNA levels and the number of conceptuses in a litter (r=0.42; P\u3c.05) on day 70, 90, and 110 of gestation. Although Yorkshire uteri exhibited greater endometrial vascular density than Meishan uteri on day 70 of gestation, placentae of conceptuses gestated in a Meishan uterus had greater amounts of VEGF mRNA than placentae of conceptuses gestated in a Yorkshire uterus. The greater amounts of placental VEGF mRNA of conceptuses gestated in a Meishan uterus on day 70 may have resulted in the increased placental vascular density observed on day 90. We conclude that the increased litter size of the Meishan female may stem from her having smaller, more vascular placentae than placentae of conceptuses gestated in the uterus of a Yorkshire female, to allow for efficient nutrient delivery to the fetus. The increased placental vascular density of a conceptus gestated in the uterus of a Meishan female may result from increased placental VEGF mRNA production induced from an endometrial induced hypoxia on day 70 of gestation

Balance differences in people with Parkinson disease with and without freezing of gait

Published in final edited form as: Gait Posture. 2015 September ; 42(3): 306–309. doi:10.1016/j.gaitpost.2015.06.007.BACKGROUND: Freezing of gait (FOG) is a relatively common and remarkably disabling impairment associated with Parkinson disease (PD). Laboratory-based measures indicate that individuals with FOG (PD+FOG) have greater balance deficits than those without FOG (PD-FOG). Whether such differences also can be detected using clinical balance tests has not been investigated. We sought to determine if balance and specific aspects of balance, measured using Balance Evaluation Systems Test (BESTest), differs between PD+FOG and PD-FOG. Furthermore, we aimed to determine if time-efficient clinical balance measures (i.e. Mini-BESTest, Berg Balance Scale (BBS)) could detect balance differences between PD+FOG and PD-FOG. METHODS: Balance of 78 individuals with PD, grouped as either PD+FOG (n=32) or PD-FOG (n=46), was measured using the BESTest, Mini-BESTest, and BBS. Between-groups comparisons were conducted for these measures and for the six sections of the BESTest using analysis of covariance. A PD composite score was used as a covariate. RESULTS: Controlling for motor sign severity, PD duration, and age, PD+FOG had worse balance than PD-FOG when measured using the BESTest (p=0.008, F=7.35) and Mini-BESTest (p=0.002, F=10.37), but not the BBS (p=0.27, F=1.26). BESTest section differences were noted between PD+FOG and PD-FOG for reactive postural responses (p<0.001, F=14.42) and stability in gait (p=0.003, F=9.18). CONCLUSIONS: The BESTest and Mini-BESTest, which specifically assessed reactive postural responses and stability in gait, were more likely than the BBS to detect differences in balance between PD+FOG and PD-FOG. Because it is more time efficient to administer, the Mini-BESTest may be the preferred tool for assessing balance deficits associated with FOG.This study was conducted with funding from the Davis Phinney Foundation, Parkinson's Disease Foundation, NIH R01 NS077959, NIH UL1 TR000448, Greater St. Louis American Parkinson Disease Association (APDA), APDA Center for Advanced PD Research at Washington University in St. Louis. The funding sources had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. (Davis Phinney Foundation; Parkinson's Disease Foundation; R01 NS077959 - NIH; UL1 TR000448 - NIH; Greater St. Louis American Parkinson Disease Association (APDA); APDA Center for Advanced PD Research at Washington University in St. Louis

Two-year trajectory of fall risk in people with Parkinson disease: a latent class analysis

Published in final edited form as: Arch Phys Med Rehabil. 2016 March ; 97(3): 372–379.e1. doi:10.1016/j.apmr.2015.10.105.OBJECTIVE: To examine fall risk trajectories occurring naturally in a sample of individuals with early to middle stage Parkinson disease (PD). DESIGN: Latent class analysis, specifically growth mixture modeling (GMM), of longitudinal fall risk trajectories. SETTING: Assessments were conducted at 1 of 4 universities. PARTICIPANTS: Community-dwelling participants with PD of a longitudinal cohort study who attended at least 2 of 5 assessments over a 2-year follow-up period (N=230). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fall risk trajectory (low, medium, or high risk) and stability of fall risk trajectory (stable or fluctuating). Fall risk was determined at 6 monthly intervals using a simple clinical tool based on fall history, freezing of gait, and gait speed. RESULTS: The GMM optimally grouped participants into 3 fall risk trajectories that closely mirrored baseline fall risk status (P=.001). The high fall risk trajectory was most common (42.6%) and included participants with longer and more severe disease and with higher postural instability and gait disability (PIGD) scores than the low and medium fall risk trajectories (P<.001). Fluctuating fall risk (posterior probability <0.8 of belonging to any trajectory) was found in only 22.6% of the sample, most commonly among individuals who were transitioning to PIGD predominance. CONCLUSIONS: Regardless of their baseline characteristics, most participants had clear and stable fall risk trajectories over 2 years. Further investigation is required to determine whether interventions to improve gait and balance may improve fall risk trajectories in people with PD.Supported by the Davis Phinney Foundation, the Parkinson's Disease Foundation, National Institutes of Health (NIH) (grant nos. NIH R01 NS077959 and NIH UL1 TR000448), the Massachusetts and Utah Chapters of the American Parkinson Disease Association (APDA), the Greater St Louis Chapter of the APDA, and the APDA Center for Advanced Research at Washington University. (Davis Phinney Foundation; Parkinson's Disease Foundation; NIH R01 NS077959 - National Institutes of Health (NIH); NIH UL1 TR000448 - National Institutes of Health (NIH); Utah Chapter of the American Parkinson Disease Association (APDA); Greater St Louis Chapter of the APDA; APDA Center for Advanced Research at Washington University; Massachusetts Chapter of the American Parkinson Disease Association (APDA)