Beneficial effects of childhood selective dorsal rhizotomy in adulthood

Background: Selective dorsal rhizotomy (SDR) has been used to treat children with spastic cerebral palsy (CP) for over three decades. However, little is known about the outcomes of childhood SDR in adults.  Objectives: 1) To study the effects of childhood SDR on the quality of life and ambulatory function in adult life. 2) To determine late side effects of SDR in adults.   Methods: Adults (> 17.9 years) who underwent SDR in childhood (2 - 17.9 years) between 1987 and 2013 were surveyed in 2015. Patients completed a survey, including questions on demographic information, quality of life, health, surgical outcomes, motor function, manual ability, pain, braces/orthotics, post-SDR treatment, living situation, education level, work status, and side effects of SDR.  Results: In our study population of 294 patients (18.0 - 37.4 years), patients received SDR during the ages of 2.0 - 17.9 years and were followed up 2.2 to 28.3 years after surgery. Eighty-four percent had spastic diplegia, 12% had spastic quadriplegia, and 4% had spastic triplegia. The majority (88%) of patients reported improved post-SDR quality of life and 1% considered the surgery detrimental. Most (83%) would recommend the procedure to others and 3% would not. However, patients who would not recommend SDR to others ambulated with a walker or were not ambulatory at all prior to SDR. The majority (83%) of patients improved (30%) or remained stable (53%) in ambulation. Twenty-nine percent of patients reported pain, mostly in the back and lower limbs, with a mean pain level of 4.4 ± 2.4 on the Numeric Pain Rating Scale (NPRS). Decreased sensation in small areas of the lower limbs was reported by 8% of patients, though this did not affect daily life. Scoliosis was diagnosed in 28%, with 40% of these patients pursuing treatment. Whether scoliosis was related to SDR is not clear, though scoliosis is known to occur in patients with CP and also in the general population. Only 4% of patients underwent spinal fusion.  Orthopedic surgeries were pursued by 59% of patients. The most common orthopedic surgeries were hamstring lengthenings (31%), Achilles tendon lengthenings (18%), adductor lengthenings (16%), and derotational osteotomies (16%). Twenty-four percent of all patients later underwent hip surgery and 8% had surgeries on their knees.  Conclusion: Results of this study indicate that the beneficial effects of childhood SDR extend to adulthood quality of life and ambulatory function without late side effects of surgery

An Occupational Therapy Practice Guide for Sport-Related Concussion in Student Athletes

Sport-related concussion (SRC) is a prevalent injury that affects millions of youth and young adults every year (McKeithan et al., 2019). The sequelae associated with an SRC can interfere with a student athletes’ ability to participate in school, return to play, and perform daily tasks (DeMatteo et al., 2018). Common practice in concussion management highlights the significance of getting individuals back to engaging in all areas of their lives; and this is consistent with the emphasis on participation by occupational therapy (OT) practitioners (DeMatteo et al., 2018). Despite the beneficial role that OT may offer, not only is there limited literature supporting the role of OT in concussion management, but the literature has not been organized in a way that is easily accessible for OT practitioners to utilize in practice. This paper will provide a detailed overview and guidelines for OT intervention in the management of SRC in student athletes.https://soar.usa.edu/otdcapstonessummer2021/1024/thumbnail.jp

Contributions to Causal Inference in Observational Studies

The electronic health record (EHR) is a digital version of the patient chart. All clinically relevant patient information can be accessed from the EHR by professionals involved in the patient’s care. For researchers, the EHR is a rich, convenient source for data to address a vast range of medical research questions. In observational studies with EHR data, it is common to define the treatment/exposure status as a binary indicator reflecting whether patient was documented to receive a particular medication or procedure. The outcome can be any type of information on patient status documented in the EHR after the treatment has taken place. The EHR, although not designed primarily for research, can serve as a platform for observational studies in clinical medicine. An advantage of the EHR is that it can document treatments unequivocally, provided the treatment – medication or procedure – appears in the record. For example, in a study in which treatment is the route of medication (intravenous= treated, oral=control), the EHR makes it clear which route was used. This does not, however, relieve the investigator from the responsibility of defining and measuring confounding variables, and properly adjusting for them in comparative analyses. In Chapter 1, we demonstrate the use of longitudinal EHR data in an evaluation of the effects of treatment of 12,754 children with overweight/obesity in greater Dallas. Our objective in this study is to estimate the causal effect of clinician attention to elevated body v mass index (BMI), measured at up to 10 timepoints per child, on subsequent weight change. To account for bias from confounding, we use the propensity score stratification method, applied longitudinally at each timepoint. We specify the propensity score model to include baseline covariates, current values of time-varying covariates, and treatment status at the most recent visit. An alternative method of causal inference when treatments are applied longitudinally in an observational study relies on the marginal structural model (MSM). When estimating an MSM, one eliminates confounding bias by constructing a series of propensity score models for treatment at each time, then weighting the subjects based on these scores. The MSM has the interpretation of a causal model for the effect of the series of treatments on the outcome. Although MSMs are in wide use, there has been relatively little evaluation of the properties of model estimates in small samples. One can conduct a simulation study to assess properties such as the suitability of asymptotic approximations to moderate samples, best methods for computing the standard errors, choice of the weighting method, and robustness to incorrect assumptions about the MSM or the underlying propensity score model. Several simulation methods have been proposed, each with its pros and cons. In Chapter 2, we introduce a new, simplified simulation method that addresses the limitations of the existing methods. We demonstrate the use of our method in a Monte Carlo study to assess the properties of an estimated MSM involving treatment at two timepoints. An oft-cited concern with MSMs is the sensitivity of model estimates to large weights. This issue arises in particular when there are multiple timepoints. As the number of timepoints increases, an individual’s propensity score can become very small, while the estimation weights – defined as the inverse of the propensity score – becomes correspondingly large. Having a few subjects with large weights can result in an unstable estimate. In Chapter 3, we use the novel simulation method that we introduced in Chapter 2 to conduct a Monte Carlo assessment of the impact of large weights on the validity of MSM estimates. Finally, vi we estimate a series of MSMs for the child obesity example from Chapter 1 and interpret the results in light of our simulation findings

Physiological Responses & Coping Strategies of Sensory Defensive Adults

Purpose: The purpose of this study was to learn how adults cope with their sensory defensiveness (SD) and how physiological responses differ between adults who self-report as high SD versus low SD. Methods: In this continuation study participants (age 18-64; n=23) were categorized as low SD (control group; n=9) or high SD (experimental group; n=14) via their Adolescent Adult Sensory Profile (AASP) scores and Sensory Response Questionnaire (SRQ) scores (Brown, & Dunn, 2002 & Wilbarger, 2009). The last nine participants also completed the Coping Strategies Questionnaire (CSQ). All participants partook in the sensory challenge protocol which examined their electrodermal activity (EDA) responses to auditory, tactile and olfactory stimuli. Discussion: Overall, high SD group had higher EDA responses, but not all were statistically significant. The high SD group had significantly higher EDA (p \u3c 0.1) responses when the nuk brush and lawnmower were administered. The CSQ results found mental preparation/talking through was the most frequently used coping strategy. There was a strong correlation between AASP & CSQ, but not statistically significant. Limitations: With a larger sample size, the results of higher EDA responses between the low and high SD groups could become statistically significant. Difficulty with recruiting participants who self-report as low SD could influence the overall outcome. Conclusion: Adults with high SD have higher physiological responses to sensory stimuli compared to adults with low SD and these adults utilize time consuming coping strategies frequently. Occupational therapists can facilitate a more targeted intervention for adults with SD

Fractionation of human red blood cells based on intrinsic magnetization

Red blood cell (RBC) transfusion is clinically used to treat hemodynamic instability and O2 carrying deficits in patients with acute blood loss, and patients with chronic anemia caused by bone marrow failure/suppression. Currently, cold storage of human RBCs (hRBCs) can preserve hRBCs for a maximum of six weeks (i.e. 42 days), set by the United States Food and Drug Administration (US FDA). However, as stored RBCs age, they undergo biochemical and biophysical changes that are often referred to as the storage lesion, which decreases the efficacy of transfusion while increasing the risk for transfusion-associated adverse effects. It is well known that upon transfusion of stored RBCs, there is a population of RBCs (i.e. healthy RBCs) that circulate for more than 24 hours, and another smaller population (i.e. damaged RBCs) that are cleared within 24 hours post transfusion. This population of cells destined to be cleared quickly can be higher than 25% in units stored for a mean of 30 days. The objective of our current project is to remove aged RBCs based on hemoglobin content. Under the influence of ultra-high magnetic fields and gradients, we have demonstrated that it is possible to fractionate RBCs into multiple factions based solely on difference in the intrinsic magnetization of the deoxygenated form of hemoglobin inside the RBCs (i.e. labeless separation). We hypothesize for our currently funded National Institute of Heart Lung and Blood project that healthy RBCs with higher Hb content correlate with longer half lives in transfused animal models than unhealthy RBCs which have lost some of their hemoglobin. In addition, material balances are being performed to track the hemoglobin molecules that are lost during the extended periods of storage. This work will reveal the mechanism behind the lost hemoglobin during RBC storage, deepen the knowledge about aged RBCs and RBC-associated exosomes, and facilitate bulk separation of RBCs without labeling the cells. Therefore, it could be clinically beneficial if the damaged RBCs in any unit of RBCs could be separated leaving a population of only healthy RBCs behind for transfusion. When a recipient is transfused with a dose of RBCs that overwhelms their circulatory system’s ability to compensate for the increased intravascular volume, heart failure can ensue. This condition is known as Transfusion Associated Circulatory Overload (TACO). It is the second leading cause of death related to transfusion reported to the FDA

Co-targeting RNA Polymerases IV and V Promotes Efficient De Novo DNA Methylation in Arabidopsis.

The RNA-directed DNA methylation (RdDM) pathway in plants controls gene expression via cytosine DNA methylation. The ability to manipulate RdDM would shed light on the mechanisms and applications of DNA methylation to control gene expression. Here, we identified diverse RdDM proteins that are capable of targeting methylation and silencing in Arabidopsis when tethered to an artificial zinc finger (ZF-RdDM). We studied their order of action within the RdDM pathway by testing their ability to target methylation in different mutants. We also evaluated ectopic siRNA biogenesis, RNA polymerase V (Pol V) recruitment, targeted DNA methylation, and gene-expression changes at thousands of ZF-RdDM targets. We found that co-targeting both arms of the RdDM pathway, siRNA biogenesis and Pol V recruitment, dramatically enhanced targeted methylation. This work defines how RdDM components establish DNA methylation and enables new strategies for epigenetic gene regulation via targeted DNA methylation

In vivo detection of cortical optical changes associated with seizure activity with optical coherence tomography.

The most common technology for seizure detection is with electroencephalography (EEG), which has low spatial resolution and minimal depth discrimination. Optical techniques using near-infrared (NIR) light have been used to improve upon EEG technology and previous research has suggested that optical changes, specifically changes in near-infrared optical scattering, may precede EEG seizure onset in in vivo models. Optical coherence tomography (OCT) is a high resolution, minimally invasive imaging technique, which can produce depth resolved cross-sectional images. In this study, OCT was used to detect changes in optical properties of cortical tissue in vivo in mice before and during the induction of generalized seizure activity. We demonstrated that a significant decrease (P < 0.001) in backscattered intensity during seizure progression can be detected before the onset of observable manifestations of generalized (stage-5) seizures. These results indicate the feasibility of minimally-invasive optical detection of seizures with OCT