Rehabilitation interventions for foot drop in neuromuscular disease

"Foot drop" or "Floppy foot drop" is the term commonly used to describe weakness or contracture of the muscles around the ankle joint. It may arise from many neuromuscular diseases

Properties of In silico designed 3-way junction nucleic acid motif for nanoparticles assembly

Organization of biological materials into specific two- and three-dimensional multifunctional scaffolds enabling to carry cell binding RNA aptamers, and therapeutic siRNA and miRNA for application in nanomedicine is a challenging task in the field of nucleic acid nanotechnology. In previous work, computer-assisted nucleic acid (NA) tetra-U/T three-way junction (3WJ) motif was designed to address questions related to assembly efficiency, versatility, stability, and immunotoxicity of various shape nanoparticles made of either RNA, or DNA, or 2’F-modified RNA strands and their hybrids. In this work we explore physicochemical properties of other 3WJ NA motif comprising 4T, 3T, 2T, 1T, and 0T links between helical stems and compare their utility as a building modules for triangular shape DNA nanoparticles. Assembly for these triangles have been verified using gel shift assays, the average hydrodynamic radius assessed by dynamic light scattering, the thermal stability determined by UV-melting experiments, and shape characterizations by AFM. We found that all DNA complexes assembled with high efficiency except the 0T construct. The overall dimension decreasing in the following order: 4T>3T>2T>1T from approximately 11nm to 7nm. The results from UV-melting experiment suggest that the most stable construct was the 0T structure and the least stable being the 4T-HP structure. This work is intended to demonstrate different design approaches of the triangular shaped Nucleic Acid complexes and highlight the importance of the thymidine linkages.Thesis (M.S.

Head Start Families Thoughts and Beliefs about Health, Nutrition, and Physical Activity

In-depth interviews were conducted with a subset of Head Start families participating in an intervention comparison research study in a southwestern state.  Families were asked to share thoughts and beliefs about eating and physical activity habits.  Questions were asked in relation to consumption of healthy snacks, consumption of fruits and vegetables, influences on purchasing and eating habits, eating out patterns, physical activity, and perceptions of what it means to be healthy.  Both intervention and comparison families felt it was essential to consume fresh fruits and vegetables.  Economic reasons were cited by respondents as the main reason for not consuming fruits, vegetables, and healthy snacks regularly. While families from both the intervention and the control groups noted that their preschooler influenced their food purchases (about one-fourth of parents were always influenced), children from the intervention group began requesting healthy foods.  Families stated engaging in daily physical activity was important; however, barriers such as health restrictions, work schedules, weather, and personal preferences affected levels of physical activity.   Information from this study is guiding improvements to a preschool program targeting childhood obesity

Repeated closed-head mild traumatic brain injury-induced inflammation is associated with nociceptive sensitization

Abstract Background Individuals who have experienced mild traumatic brain injuries (mTBIs) suffer from several comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation in long-term pain after mTBIs is not fully elucidated. Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes in inflammatory processes following mTBIs and their effects on TBI-related pain. Methods We utilized a recently developed transgenic caspase-1 luciferase reporter mouse model to monitor caspase-1 activation through a thinned skull window in the in vivo setting following three closed-head mTBI events. Organotypic coronal brain slice cultures and acutely dissociated dorsal root ganglion (DRG) cells provided tissue-relevant context of inflammation signal. Mechanical allodynia was assessed by mechanical withdrawal threshold to von Frey and thermal hyperalgesia withdrawal latency to radiant heat. Mouse grimace scale (MGS) was used to detect spontaneous or non-evoked pain. In some experiments, mice were prophylactically treated with MCC950, a potent small molecule inhibitor of NLRP3 inflammasome assembly to inhibit injury-induced inflammatory signaling. Bioluminescence spatiotemporal dynamics were quantified in the head and hind paws, and caspase-1 activation was confirmed by immunoblot. Immunofluorescence staining was used to monitor the progression of astrogliosis and microglial activation in ex vivo brain tissue following repetitive closed-head mTBIs. Results Mice with repetitive closed-head mTBIs exhibited significant increases of the bioluminescence signals within the brain and paws in vivo for at least one week after each injury. Consistently, immunoblotting and immunofluorescence experiments confirmed that mTBIs led to caspase-1 activation, astrogliosis, and microgliosis. Persistent changes in MGS and hind paw withdrawal thresholds, indicative of pain states, were observed post-injury in the same mTBI animals in vivo. We also observed enhanced inflammatory responses in ex vivo brain slice preparations and DRG for at least 3 days following mTBIs. In vivo treatment with MCC950 significantly reduced caspase-1 activation-associated bioluminescent signals in vivo and decreased stimulus-evoked and non-stimulus evoked nociception. Conclusions Our findings suggest that the inflammatory states in the brain and peripheral nervous system following repeated mTBIs are coincidental with the development of nociceptive sensitization, and that these events can be significantly reduced by inhibition of NLRP3 inflammasome activation

Design and Characterization of Compact, Programmable, Multistranded Nonimmunostimulatory Nucleic Acid Nanoparticles Suitable for Biomedical Applications

We report a thorough investigation of the role of single-stranded thymidine (ssT) linkers in the stability and flexibility of minimal, multistranded DNA nanostructures. We systematically explore the impact of varying the number of ssTs in three-way junction motifs (3WJs) on their formation and properties. Through various UV melting experiments and molecular dynamics simulations, we demonstrate that while the number of ssTs minimally affects thermodynamic stability, the increasing ssT regions significantly enhance the structural flexibility of 3WJs. Utilizing this knowledge, we design triangular DNA nanoparticles with varying ssTs, all showing exceptional assembly efficiency except for the 0T triangle. All triangles demonstrate enhanced stability in blood serum and are nonimmunostimulatory and nontoxic in mammalian cell lines. The 4T 3WJ is chosen as the building block for constructing other polygons due to its enhanced flexibility and favorable physicochemical characteristics, making it a versatile choice for creating cost-effective, stable, and functional DNA nanostructures that can be stored in the dehydrated forms while retaining their structures. Our study provides valuable insights into the design and application of nucleic acid nanostructures, emphasizing the importance of understanding stability and flexibility in the realm of nucleic acid nanotechnology. Our findings suggest the intricate connection between these ssTs and the structural adaptability of DNA 3WJs, paving the way for more precise design and engineering of nucleic acid nanosystems suitable for broad biomedical applications

In the Name of Hosayn's Blood: The Memory of Karbala as Ideological Stimulus to the Safavid Revolution

Over the past century, one of the most heavily debated topics within Safavid historiography has been the ideological sources of the Qezelbash zeal that carried the Safavid dynasty to the throne of Persia. By now, a near-consensus has been formed about Shah Esma.il's personality as an incarnation of the Godhead armed with a messianic mission of salvation. This article partly challenges this long-entrenched conceptualization by calling attention to a heretofore overlooked mission that the shaykhs of the revolutionary period set for themselves. This was their desire to avenge the spilling of Hosayn's blood, a mission which was nothing but a reincarnation of the topos of saheb al-khoruj or the "master of the uprising," a heroic typology cultivated via a particular corpus of Karbala-oriented epic literature. Based on the idea that the religiosity of the Turkishspeaking milieu that constituted the Safavid movement's grassroots was primarily shaped by this Karbala-oriented epic literature, this essay argues that Shaykh Jonayd, Shaykh Haydar, and especially Shah Esma.il successfully reformulated the Safavid Sufi program to address the codes of popular piety, which already existed, nurtured by Sufism and some Shi.ite elements, a particular mode of Islamic piety that I call "Shi.iteinflected popular Sufism.