Galectin-3 Mediates Vascular Dysfunction in Obesity by Regulating NADPH Oxidase 1.

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease, but underlying mechanisms remain elusive. Metabolic dysfunction, especially hyperglycemia, is thought to be a major contributor, but how glucose impacts vascular function is unclear. GAL3 (galectin-3) is a sugar-binding lectin upregulated by hyperglycemia, but its role as a causative mechanism of cardiovascular disease remains poorly understood. Therefore, the objective of this study was to determine the role of GAL3 in regulating microvascular endothelial vasodilation in obesity. METHODS: GAL3 was measured and found to be markedly increased in the plasma of overweight and obese patients, as well as in the microvascular endothelium of diabetic patients. To investigate causative mechanisms in cardiovascular disease, mice deficient in GAL3 were bred with obese db/db mice to generate lean, lean GAL3 knockout, obese, and obese GAL3 knockout genotypes. Endothelial cell-specific GAL3 knockout mice with novel AAV-induced obesity recapitulated whole-body knockout studies to confirm cell specificity. RESULTS: Deletion of GAL3 did not alter body mass, adiposity, or plasma indices of glycemia and lipidemia, but levels of plasma reactive oxygen species as assessed by plasma thiobarbituric acid reactive substances were normalized in obese GAL3 knockout mice. Obese mice exhibited profound endothelial dysfunction and hypertension, both of which were rescued by GAL3 deletion. Isolated microvascular endothelial cells from obese mice had increased expression of NOX1 (nicotinamide adenine dinucleotide phosphate oxidase 1), which we have previously shown to contribute to increased oxidative stress and endothelial dysfunction, which was normalized in microvascular endothelium from mice lacking GAL3. Cell-specific deletion confirmed that endothelial GAL3 regulates obesity-induced NOX1 overexpression and subsequent microvascular function. Furthermore, improvement of metabolic syndrome by increasing muscle mass, improving insulin signaling, or treating with metformin decreased microvascular GAL3, and thereby NOX1, expression levels. CONCLUSIONS: Deletion of GAL3 normalizes microvascular endothelial function in obese db/db mice, likely through a NOX1-mediated mechanism. Pathological levels of GAL3, and in turn NOX1, are amenable to improvements in metabolic status, presenting a potential therapeutic target to ameliorate pathological cardiovascular consequences of obesity.

Purine synthesis suppression reduces the development and progression of pulmonary hypertension in rodent models.

AIMS: Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of pulmonary hypertension (PH). Proliferative cells utilize purine bases from the de novo purine synthesis (DNPS) pathways for nucleotide synthesis; however, it is unclear whether DNPS plays a critical role in VSMC proliferation during development of PH. The last two steps of DNPS are catalysed by the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC). This study investigated whether ATIC-driven DNPS affects the proliferation of pulmonary artery smooth muscle cells (PASMCs) and the development of PH. METHODS AND RESULTS: Metabolites of DNPS in proliferative PASMCs were measured by liquid chromatography-tandem mass spectrometry. ATIC expression was assessed in platelet-derived growth factor-treated PASMCs and in the lungs of PH rodents and patients with pulmonary arterial hypertension. Mice with global and VSMC-specific knockout of Atic were utilized to investigate the role of ATIC in both hypoxia- and lung interleukin-6/hypoxia-induced murine PH. ATIC-mediated DNPS at the mRNA, protein, and enzymatic activity levels were increased in platelet-derived growth factor-treated PASMCs or PASMCs from PH rodents and patients with pulmonary arterial hypertension. In cultured PASMCs, ATIC knockdown decreased DNPS and nucleic acid DNA/RNA synthesis, and reduced cell proliferation. Global or VSMC-specific knockout of Atic attenuated vascular remodelling and inhibited the development and progression of both hypoxia- and lung IL-6/hypoxia-induced PH in mice. CONCLUSION: Targeting ATIC-mediated DNPS compromises the availability of purine nucleotides for incorporation into DNA/RNA, reducing PASMC proliferation and pulmonary vascular remodelling and ameliorating the development and progression of PH.

Higher Dose Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation Increases Feeding Volumes and White Matter Microstructural Complexity in Open-Label Study of Infants Slated for Gastrostomy Tube.

OBJECTIVE: To determine whether transcutaneous auricular vagus nerve stimulation (taVNS) paired with twice daily bottle feeding increases the volume of oral feeds and white matter neuroplasticity in term-age-equivalent infants failing oral feeds and determined to need a gastrostomy tube. STUDY DESIGN: In this prospective, open-label study, 21 infants received taVNS paired with 2 bottle feeds for 2 - 3 weeks (2x). We compared 1) increase oral feeding volumes with 2x taVNS and previously reported once daily taVNS (1x) to determine a dose response, 2) number of infants who attained full oral feeding volumes, and 3) diffusional kurtosis imaging and magnetic resonance spectroscopy before and after treatment by paired t tests. RESULTS: All 2x taVNS treated infants significantly increased their feeding volumes compared with 10 days before treatment. Over 50% of 2x taVNS infants achieved full oral feeds but in a shorter time than 1x cohort (median 7 days [2x], 12.5 days [1x], P < .05). Infants attaining full oral feeds showed greater increase in radial kurtosis in the right corticospinal tract at the cerebellar peduncle and external capsule. Notably, 75% of infants of diabetic mothers failed full oral feeds, and their glutathione concentrations in the basal ganglia, a measure of central nervous system oxidative stress, were significantly associated with feeding outcome. CONCLUSIONS: In infants with feeding difficulty, increasing the number of daily taVNS-paired feeding sessions to twice-daily significantly accelerates response time but not the overall response rate of treatment. taVNS was associated with white matter motor tract plasticity in infants able to attain full oral feeds. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04643808).

Postless Hip Distraction Systems Decrease the Amount of Traction Force Needed to Obtain Adequate Hip Distraction Versus a Conventional Post Hip Distractor.

PURPOSE: To directly compare hip distraction distance and traction force data for hip arthroscopy performed using a post-basedsystem versus a postless system. METHODS: Adult patients undergoing primary hip arthroscopy for femoroacetabular impingement were prospectively enrolled. Before March 26, 2019, arthroscopy was performed using a post-based system. After this date, the senior author converted to using a postless system. Intraoperative traction force and fluoroscopic distraction distance were measured to calculate hip stiffness coefficients at holding traction (k-hold) and maximal traction (k-max). We used multivariable regression analysis to determine whether postless arthroscopy was predictive of lower stiffness coefficients when controlling for other relevant patient-specific factors. RESULTS: Hip arthroscopy was performed with a post-based system in 105 patients and with a postless system in 51. Mean holding traction force (67.5 ± 14.0 kilograms-force [kgf] vs 55.8 ± 15.3 kgf) and mean maximum traction force (96.0 ± 16.6 kgf vs 69.9 ± 14.1 kgf) were significantly lower in the postless group. On multivariable analysis, postless traction was an independent predictor of decreased k-hold (ß = -31.4; 95% confidence interval, -61.2 to -1.6) and decreased k-max (ß = -90.4; 95% confidence interval, -127.8 to -53.1). Male sex, Beighton score of 0, and poor hamstring flexibility were also predictors of increased k-hold and k-max in the multivariable model. CONCLUSIONS: Postless traction systems decrease the amount of traction force required for adequate hip distraction for both maximal and holding traction forces when compared with post-based systems. Postless traction systems may help further reduce distraction-type neurologic injuries and pain after hip arthroscopy by lowering the traction force required to safely distract the hip. LEVEL OF EVIDENCE: Level III, prospective cohort-historical control comparative study.

The Role of Atypical Chemokine Receptors in Neuroinflammation and Neurodegenerative Disorders.

Neuroinflammation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Neuroinflammation provides protection in acute situations but results in significant damage to the nervous system if chronic. Overexpression of chemokines within the brain results in the recruitment and activation of glial and peripheral immune cells which can propagate a cascading inflammatory response, resulting in neurodegeneration and the onset of neurodegenerative disorders. Recent work has identified the role of atypical chemokine receptors (ACKRs) in neurodegenerative conditions. ACKRs are seven-transmembrane domain receptors that do not follow canonical G protein signaling, but regulate inflammatory responses by modulating chemokine abundance, location, and availability. This review summarizes what is known about the four ACKRs and three putative ACKRs within the brain, highlighting their known expression and discussing the current understanding of each ACKR in the context of neurodegeneration. The ability of ACKRs to alter levels of chemokines makes them an appealing therapeutic target for neurodegenerative conditions. However, further work is necessary to understand the expression of several ACKRs within the neuroimmune system and the effectiveness of targeted drug therapies in the prevention and treatment of neurodegenerative conditions.

High fidelity fiber orientation density functions from fiber ball imaging.

The fiber orientation density function (fODF) in white matter is a primary physical quantity that can be estimated with diffusion MRI. It has often been employed for fiber tracking and microstructural modeling. Requirements for the construction of high fidelity fODFs, in the sense of having good angular resolution, adequate data to avoid sampling errors, and minimal noise artifacts, are described for fODFs calculated with fiber ball imaging. A criterion is formulated for the number of diffusion encoding directions needed to achieve a given angular resolution. The advantages of using large b-values (≥6000 s/mm2 ) are also discussed. For the direct comparison of different fODFs, a method is developed for defining a local frame of reference tied to each voxel's individual axonal structure. The Matusita anisotropy axonal is proposed as a scalar fODF measure for quantifying angular variability. Experimental results, obtained at 3 T from human volunteers, are used as illustrations.

The Prevalence of Metabolic and Endocrine Disturbances on Fracture Nonunion.

OBJECTIVE: This study aims to determine the prevalence of metabolic disturbance in all fracture nonunion cases and identify the most common endocrine abnormalities seen using a simple screening algorithm. METHODS: A retrospective review study was performed evaluating patients who underwent operative intervention for nonunion from January 2010 to December 2018 at 2 level-1 trauma centers. Preoperative laboratory values were recorded for a 9-test "nonunion panel." A metabolic or endocrine abnormality, specifically an abnormality in the thyroid or parathyroid axis, was evaluated. RESULTS: 42% of patients had an undiagnosed metabolic laboratory abnormality. When multiple tests were used, the rate of metabolic dysfunction was between 60% and 75%, depending on the definition of vitamin D insufficiency vs deficiency used. CONCLUSION: Results indicate a relatively high prevalence of metabolic disturbance in patients with nonunion and suggest metabolic screening for all nonunion patients not only those without a mechanical or infectious cause. LEVEL OF EVIDENCE: IV, retrospective case series.

A Microfluidic Platform to Monitor Real-Time Effects of Extracellular Vesicle Exchange between Co-Cultured Cells across Selectively Permeable Barriers.

Exosomes and other extracellular vesicles (EVs) play a significant yet poorly understood role in cell-cell communication during homeostasis and various pathological conditions. Conventional in vitro and in vivo approaches for studying exosome/EV function depend on time-consuming and expensive vesicle purification methods to obtain sufficient vesicle populations. Moreover, the existence of various EV subtypes with distinct functional characteristics and submicron size makes their analysis challenging. To help address these challenges, we present here a unique chip-based approach for real-time monitoring of cellular EV exchange between physically separated cell populations. The extracellular matrix (ECM)-mimicking Matrigel is used to physically separate cell populations confined within microchannels, and mimics tissue environments to enable direct study of exosome/EV function. The submicron effective pore size of the Matrigel allows for the selective diffusion of only exosomes and other smaller EVs, in addition to soluble factors, between co-cultured cell populations. Furthermore, the use of PEGDA hydrogel with a very small pore size of 1.2 nm in lieu of Matrigel allows us to block EV migration and, therefore, differentiate EV effects from effects that may be mediated by soluble factors. This versatile platform bridges purely in vitro and in vivo assays by enabling studies of EV-mediated cellular crosstalk under physiologically relevant conditions, enabling future exosome/EV investigations across multiple disciplines through real-time monitoring of vesicle exchange.

A Genetically Engineered Rotavirus NSP2 Phosphorylation Mutant Impaired in Viroplasm Formation and Replication Shows an Early Interaction between vNSP2 and Cellular Lipid Droplets.

Many RNA viruses replicate in cytoplasmic compartments (virus factories or viroplasms) composed of viral and cellular proteins, but the mechanisms required for their formation remain largely unknown. Rotavirus (RV) replication in viroplasms requires interactions between virus nonstructural proteins NSP2 and NSP5, which are associated with components of lipid droplets (LDs). We previously identified two forms of NSP2 in RV-infected cells, a cytoplasmically dispersed form (dNSP2) and a viroplasm-specific form (vNSP2), which interact with hypophosphorylated and hyperphosphorylated NSP5, respectively, indicating that a coordinated phosphorylation cascade controls viroplasm assembly. The cellular kinase CK1α phosphorylates NSP2 on serine 313, triggering the localization of vNSP2 to sites of viroplasm assembly and its association with hyperphosphorylated NSP5. Using reverse genetics, we generated a rotavirus with a phosphomimetic NSP2 (S313D) mutation to directly evaluate the role of CK1α NSP2 phosphorylation in viroplasm formation. Recombinant rotavirus NSP2 S313D (rRV NSP2 S313D) is significantly delayed in viroplasm formation and in virus replication and interferes with wild-type RV replication in coinfection. Taking advantage of the delay in viroplasm formation, the NSP2 phosphomimetic mutant was used as a tool to observe very early events in viroplasm assembly. We show that (i) viroplasm assembly correlates with NSP5 hyperphosphorylation and (ii) vNSP2 S313D colocalizes with RV-induced LDs without NSP5, suggesting that vNSP2 phospho-S313 is sufficient for interacting with LDs and may be the virus factor required for RV-induced LD formation. Further studies with the rRV NSP2 S313D virus are expected to reveal new aspects of viroplasm and LD initiation and assembly.IMPORTANCE Reverse genetics was used to generate a recombinant rotavirus with a single phosphomimetic mutation in nonstructural protein 2 (NSP2 S313D) that exhibits delayed viroplasm formation, delayed replication, and an interfering phenotype during coinfection with wild-type rotavirus, indicating the importance of this amino acid during virus replication. Exploiting the delay in viroplasm assembly, we found that viroplasm-associated NSP2 colocalizes with rotavirus-induced lipid droplets prior to the accumulation of other rotavirus proteins that are required for viroplasm formation and that NSP5 hyperphosphorylation is required for viroplasm assembly. These data suggest that NSP2 phospho-S313 is sufficient for interaction with lipid droplets and may be the virus factor that induces lipid droplet biogenesis in rotavirus-infected cells. Lipid droplets are cellular organelles critical for the replication of many viral and bacterial pathogens, and thus, understanding the mechanism of NSP2-mediated viroplasm/lipid droplet initiation and interaction will lead to new insights into this important host-pathogen interaction.

Optimized rectification of fiber orientation density function.

PURPOSE: To demonstrate an optimized rectification strategy for fiber orientation density functions (fODFs). THEORY AND METHODS: In white matter, fODFs can be estimated with diffusion MRI. However, because of signal noise, imaging artifacts and other factors, experimentally determined fODFs may take on unphysical negative values in some directions. Here, we show how to rectify such fODFs to eliminate all negative values while minimizing the mean square difference between the original and rectified fODFs. The method is demonstrated for a mathematical model and for fODFs estimated from experimental human data using both constrained spherical deconvolution and fiber ball imaging. Comparison with an alternative nonoptimized rectification approach is also provided. RESULTS: For the mathematical model, it is found that the optimized rectification procedure removes negative fODF values while at the same time reducing the mean square error. Relative to the alternative rectification approach, the optimized fODFs are substantially more accurate. For the experimental data, the optimized fODFs have a lower average fractional anisotropy axonal and often fewer small peaks than the original, unrectified fODFs. The calculation of optimized fODFs is straightforward where the main step is the finding of the root to an equation in one variable, as may be efficiently accomplished with the bisection method. CONCLUSION: Unphysical negative fODF values can be easily eliminated in a manner that minimizes the mean square difference between the original and rectified fODFs. Optimized fODF rectification may be useful in applications for which negative values are problematic.

A new diversity index.

We introduce here a new index of diversity based on consideration of reasonable propositions that such an index should have in order to represent diversity. The behaviour of the index is compared with that of the Gini-Simpson diversity index, and is found to predict more realistic values of diversity for small communities, in particular when each species is equally represented and for small communities. The index correctly provides a measure of true diversity that is equal to the species richness across all values of species and organism numbers when all species are equally represented, as well as Hill's more stringent 'doubling' criterion when they are not. In addition, a new graphical interpretation is introduced that permits a straightforward visual comparison of pairs of indices across a wide range within a parameter space based on species and organism numbers.

Decreasing Pain and Fear in Medical Procedures with a Pediatric Population (DREAM): A Pilot Randomized Within-Subject Trial.

BACKGROUND: Many children with injuries, including burns and fractures, experience moderate to severe pain during medical procedures. Recent studies claim that nonpharmacologic pain management using virtual reality (VR) could distract children from procedural pain by engaging multiple senses. AIMS: The aims of this pilot randomized clinical trial were to assess the acceptability and feasibility of VR distraction in children with burns or fractures undergoing painful medical procedures, as well as the staff nurses, and assess the preliminary efficacy of VR distraction on pain intensity, pain-related fear, and subsequent recall of both. MATERIALS AND METHOD: A within-subject study design, in which participants served as their own control, was used. A total of 20 children from 7 to 17 years old with an injury were recruited at the surgical-trauma outpatient clinics of the Centre hospitalier universitaire Sainte-Justine (CHU Sainte-Justine). Each participant received both standard and experimental treatments through randomized order. Pain (numerical rating scale) and pain-related fear (Children's Fear Scale) measures were taken before the procedure and after each sequence, followed by a measure of children's (graphic rating scale) and nurses' acceptability of the intervention through their satisfaction level. Recall of pain intensity and pain-related fear were assessed 24 hours after the procedure. Wilcoxon signed-rank tests were used, with a significance level at 0.05. RESULTS: Results showed that VR distraction was an acceptable and feasible intervention for children and nurses of these outpatient clinics. Preliminary effects showed that, compared to standard of care, children participants reported a significant decrease in pain intensity (p = .023) and pain-related fear (p = .011) during VR as well as less recalled pain-related fear (p = .012) at 24 hours after the procedure. No side effects were reported. CONCLUSION: VR is a promising intervention with children undergoing painful procedures because it is immersive and engages multiple senses. It is a low-cost intervention well accepted by children and nursing staff at this clinical site and is easy to implement in daily practice for procedural pain management.

Spanish-Speaking Therapists Increasingly Switch to Telepsychology During COVID-19: Networked Virtual Reality May Be Next.

Background: Social distancing restrictions imposed due to the Novel Coronavirus 2019 (COVID-19) pandemic resulted in a rapid shift in the delivery of psychological interventions from in-person to telehealth. Much of the research on this transition has been conducted with English-speaking mental health providers, leaving a gap in understanding related to how this shift has impacted Spanish-speaking treatment providers. Methods: Fifty non-U.S. Spanish-speaking therapists completed a survey related to their use of telecommunication modalities; client population characteristics; professional, ethical, and legal/regulatory issues; and telehealth training and practice. Participants completed the survey at one time point and retrospectively described their use of telehealth both pre-pandemic and during the pandemic. Results: Most of the 50 Spanish-speaking therapists surveyed reported using telepsychology 58% before COVID-19 versus 84% during the COVID-19 pandemic (χ2 = 5.76, p < 0.05). Compared with pre-pandemic, the number of hours therapists spent using telepsychology per week increased significantly for early adopter therapists (those who began using telehealth before the pandemic began) (Z = -3.18, p = 0.001) and also for late adopter therapists who only began using telehealth during the pandemic (Z = -3.74, p < 0.001). Many therapists reported equity issues. Most participants also reported ethical and regulatory concerns regarding security/confidentiality or Health Insurance Porability and Accountability Act. Conclusions: The rapid adoption of technology to deliver therapy during COVID-19 has spurred growing pains for Spanish-speaking therapists and their underserved clients, and more research is needed to better understand and improve the therapists' adoption of these technologies with diverse patient populations.

Triple diffusion encoding MRI predicts intra-axonal and extra-axonal diffusion tensors in white matter.

PURPOSE: To demonstrate how triple diffusion encoding (TDE) MRI can be applied to separately estimate the intra-axonal and extra-axonal diffusion tensors in white matter (WM). METHODS: Using a TDE pulse sequence with an axially symmetric b-matrix, diffusion MRI data were acquired at 3T for 3 healthy adults with an axial b-value of 4000 s/mm2 , a radial b-value of 307 s/mm2 , and 64 diffusion encoding directions. This acquisition was then repeated with the radial b-value set to 0. A previously proposed theory was applied to these data in order to estimate the intra-axonal diffusivity and axonal water fraction for each WM voxel. Conventional single diffusion encoding data were also obtained with b-values of 1000 and 2000 s/mm2 , which provided additional information sufficient for determining both the intra-axonal and extra-axonal diffusion tensors. RESULTS: From the TDE data, the average intra-axonal diffusivity in WM was found to be 2.24 ± 0.18 µm2 /ms, and the average axonal water fraction was found to be 0.60 ± 0.11. From the 2 diffusion tensors, average WM values were estimated for several compartment-specific diffusion parameters. In particular, the extra-axonal mean diffusivity was 1.09 ± 0.19 µm2 /ms, the intra-axonal fractional anisotropy was 0.50 ± 0.14, and the extra-axonal fractional anisotropy was 0.23 ± 0.13. CONCLUSION: By using a simple TDE pulse sequence with an axially symmetric b-matrix, the diffusion tensors for the intra-axonal and extra-axonal spaces can be separately estimated in adult WM. This allows one to determine compartment-specific diffusion properties for these 2 water pools.

N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats.

BACKGROUND: Neonatal abstinence syndrome (NAS) is a significant problem. Opioid withdrawal induces oxidative stress and disrupts glutamate and glutathione homeostasis. We hypothesized that N-acetylcysteine (NAC) administered during acute opioid withdrawal in neonatal rats would decrease withdrawal behaviors and normalize CNS glutathione and glutamate. METHODS: Osmotic minipumps with methadone (opioid dependent, OD) and saline (Sham) were implanted into Sprague Dawley dams 7 days prior to delivery. Pups were randomized to receive either naloxone plus saline or NAC (50-100 mg/kg), administered on postnatal day (PND) 7. We performed MR spectroscopy on PND6-7 before, 30 min, and 120 min after withdrawal. On PND7, we assessed withdrawal behaviors for 90 min after naloxone administration and summed scores during peak withdrawal period. RESULTS: Mean summed behavioral scores were significantly different between groups (χ2 (2) = 10.49, p = 0.005) but not different between NAC/NAL/OD and Sham (p = 0.14): SAL/NAL/OD = 17.2 ± 4.2 (n = 10); NAC/NAL/OD = 11.3 ± 5.6 (n = 9); Sham = 6.5 ± 0.6 (n = 4). SAL/NAL/OD pups had decreased glutathione at 120 min (p = 0.01), while NAC/NAL/OD pups maintained pre-withdrawal glutathione (p = 0.26). CONCLUSION: In antenatal OD, NAC maintains CNS glutathione and mitigates acute opioid withdrawal in neonatal rats. This is the first study to demonstrate acute opioid withdrawal neurochemical changes in vivo in neonatal OD. NAC is a potential novel treatment for NAS.

Virtual reality hand therapy: A new tool for nonopioid analgesia for acute procedural pain, hand rehabilitation, and VR embodiment therapy for phantom limb pain.

INTRODUCTION: Affordable virtual reality (VR) technology is now widely available. Billions of dollars are currently being invested into improving and mass producing VR and augmented reality products. PURPOSE OF THE STUDY: The purpose of the present study is to explore the potential of immersive VR to make physical therapy/occupational therapy less painful, more fun, and to help motivate patients to cooperate with their hand therapist. DISCUSSION: The following topics are covered: a) psychological influences on pain perception, b) the logic of how VR analgesia works, c) evidence for reduction of acute procedural pain during hand therapy, d) recent major advances in VR technology, and e) future directions-immersive VR embodiment therapy for phantom limb (chronic) pain. CONCLUSION: VR hand therapy has potential for a wide range of patient populations needing hand therapy, including acute pain and potentially chronic pain patients. Being in VR helps reduce the patients' pain, making it less painful for patients to move their hand/fingers during hand therapy, and gamified VR can help motivate the patient to perform therapeutic hand exercises, and make hand therapy more fun. In addition, VR camera-based hand tracking technology may be used to help therapists monitor how well patients are doing their hand therapy exercises, and to quantify whether adherence to treatment increases long-term functionality. Additional research and development into using VR as a tool for hand therapist is recommended for both acute pain and persistent pain patient populations.

Optimization of data acquisition and analysis for fiber ball imaging.

The inverse Funk transform of high angular resolution diffusion imaging (HARDI) data provides an estimate for the fiber orientation density function (fODF) in white matter (WM). Since the inverse Funk transform is a straightforward linear transformation, this technique, referred to as fiber ball imaging (FBI), offers a practical means of calculating the fODF that avoids the need for a response function or nonlinear numerical fitting. Nevertheless, the accuracy of FBI depends on both the choice of b-value and the number of diffusion-encoding directions used to acquire the HARDI data. To inform the design of optimal scan protocols for its implementation, FBI predictions are investigated here with in vivo data from healthy adult volunteers acquired at 3 T for b-values spanning 1000 to 10,000 s/mm2, for diffusion-encoding directions varying in number from 30 to 256 and for TE ranging from 90 to 120 ms. Our results suggest b-values above 4000 s/mm2 with at least 64 diffusion-encoding directions are adequate to achieve reasonable accuracy with FBI for calculating axon-specific diffusion measures and for performing WM fiber tractography (WMFT).

Identifying the translational complexity of magnetic resonance spectroscopy in neonates and infants.

Little attention has been paid to relating MRS outputs of vendor-supplied platforms to those from research software. This comparison is crucial to advance MRS as a clinical prognostic tool for disease or injury, recovery, and outcome. The work presented here investigates the agreement between metabolic ratios reported from vendor-provided and LCModel fitting algorithms using MRS data obtained on Siemens 3 T TIM Trio and 3 T Skyra MRI scanners in a total of 55 premature infants and term neonates with hypoxic ischemic encephalopathy (HIE). We compared peak area ratios in single voxels placed in basal ganglia (BG) and frontal white matter (WM) using standard PRESS (TE = 30 ms and 270 ms) and STEAM (TE = 20 ms) MRS sequences at multiple times after birth from 5 to 60 days. A total of 74 scans met quality standards for inclusion, reflecting a spectrum of neonatal disease and several months of early infant development. For the long TE PRESS sequence, N-acetylaspartate (NAA) and Choline (Cho) ratios to Creatine (Cr) correlated strongly between LCModel and vendor-supplied software in the BG. For shorter TEs, the ratios of NAA/Cr and Cho/Cr were more closely related using STEAM at TE = 20 ms in BG and WM, which was significantly better than using PRESS at TE = 30 ms in the BG of HIE infants. At short TEs, however, it is still unclear which MRS sequence, STEAM or PRESS, is superior and thus more work is required in this regard for translating research-generated MRS ratios to clinical diagnosis and prognostication, and unlocking the potential of MRS for in vivo metabolomics. MRS at both long and short TEs is desirable for standard metabolites such as NAA, Cho and Cr, along with important lower concentration metabolites such as myo-inositol and glutathione.

Cerebellar Modulation of Mesolimbic Dopamine Transmission Is Functionally Asymmetrical.

Cerebral and cerebellar hemispheres are known to be asymmetrical in structure and function, and previous literature supports that asymmetry extends to the neural dopamine systems. Using in vivo fixed potential amperometry with carbon fiber microelectrodes in anesthetized mice, the current study assessed hemispheric lateralization of stimulation-evoked dopamine in the nucleus accumbens (NAc) and the influence of the cerebellum in regulating this reward-associated pathway. Our results suggest that cerebellar output can modulate mesolimbic dopamine transmission, and this modulation contributes to asymmetrically lateralized dopamine release. Dopamine release did not differ between hemispheres when evoked by medial forebrain bundle (MFB) stimulation; however, dopamine release was significantly greater in the right NAc relative to the left when evoked by electrical stimulation of the cerebellar dentate nucleus (DN). Furthermore, cross-hemispheric talk between the left and right cerebellar DN does not seem to influence mesolimbic release given that lidocaine infused into the DN opposite to the stimulated DN did not alter release. These studies may provide a neurochemical mechanism for studies identifying the cerebellum as a relevant node for reward, motivational behavior, saliency, and inhibitory control. An increased understanding of the lateralization of dopaminergic systems may reveal novel targets for pharmacological interventions in neuropathology of the cerebellum and extending projections.