Faculty Bibliography

As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international translational team at our "First Leo and Anne Albert Charitable Trust 'Think Tank' VCI workshop".

The dichotomy between vocal learners and non-learners is a fundamental distinction in the study of animal communication. Male zebra finches (Taeniopygia guttata) are vocal learners that acquire a song resembling their tutors', whereas females can only produce innate calls. The acoustic structure of short calls, produced by both males and females, is not learned. However, these calls can be precisely coordinated across individuals. To examine how birds learn to synchronize their calls, we developed a vocal robot that exchanges calls with a partner bird. Because birds answer the robot with stereotyped latencies, we could program it to disrupt each bird's responses by producing calls that are likely to coincide with the bird's. Within minutes, the birds learned to avoid this disruptive masking (jamming) by adjusting the timing of their responses. Notably, females exhibited greater adaptive timing plasticity than males. Further, when challenged with complex rhythms containing jamming elements, birds dynamically adjusted the timing of their calls in anticipation of jamming. Blocking the song system cortical output dramatically reduced the precision of birds' response timing and abolished their ability to avoid jamming. Surprisingly, we observed this effect in both males and females, indicating that the female song system is functional rather than vestigial. We suggest that descending forebrain projections, including the song-production pathway, function as a general-purpose sensorimotor communication system. In the case of calls, it enables plasticity in vocal timing to facilitate social interactions, whereas in the case of songs, plasticity extends to developmental changes in vocal structure.

Clinical microbiology automation is currently limited by the lack of an in-plate culture identification system. Using an inexpensive, printed, disposable colorimetric sensor array (CSA) responsive to the volatiles emitted into plate headspace by microorganisms during growth, we report here that not only the presence but the species of bacteria growing in plate was identified before colonies are visible. In 1894 trials, 15 pathogenic bacterial species cultured on blood agar were identified with 91.0% sensitivity and 99.4% specificity within 3 hours of detection. The results indicate CSAs integrated into Petri dish lids present a novel paradigm to speciate microorganisms, well-suited to integration into automated plate handling systems.

Two amino acids play a key role in the first total synthesis of lycopalhine A. L-glutamic acid serves as a convenient chiral starting material for the 13-step synthesis, and l-proline promotes an unusual 5-endo-trig Mannich cyclization that generates the central pyrrolidine ring of the Lycopodium alkaloid. The bicyclo[3.3.0]octanol moiety of the molecule is formed through an intramolecular aldol addition that may occur spontaneously in nature.

The precise connectivity of somatostatin and parvalbumin cortical interneurons is generated during development. An understanding of how these interneuron classes incorporate into cortical circuitry is incomplete but essential to elucidate the roles they play during maturation. Here, we report that somatostatin interneurons in infragranular layers receive dense but transient innervation from thalamocortical afferents during the first postnatal week. During this period, parvalbumin interneurons and pyramidal neurons within the same layers receive weaker thalamocortical inputs, yet are strongly innervated by somatostatin interneurons. Further, upon disruption of the early (but not late) somatostatin interneuron network, the synaptic maturation of thalamocortical inputs onto parvalbumin interneurons is perturbed. These results suggest that infragranular somatostatin interneurons exhibit a transient early synaptic connectivity that is essential for the establishment of thalamic feedforward inhibition mediated by parvalbumin interneurons.

The packing of the title compound, C12H9N7.H2O, is dominated by hydrogen bonding and pi-stacking. Layers parallel to [010] are established by hydrogen bonds involving all amine donor functions and one of the water donor functions, while the remaining water donor function enables the stacking of the layers along [10-1], which is accompanied by pi-stacking. In the molecule, the plane of the central tetra-zine ring forms angles of 5.33 (7) and 19.84 (8) degrees with the adjacent 3-amine-pyridine and pyridine rings, respectively.

Hereditary sensory and autonomic neuropathy type III features disturbed proprioception and a marked ataxic gait. We recently showed that joint-angle matching error at the knee is positively correlated with the degree of ataxia. Using intraneural microelectrodes, we also documented that these patients lack functional muscle spindle afferents but have preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying more on proprioceptive cues provided by tactile afferents. We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape could improve proprioceptive accuracy in patients with a congenital absence of functional muscle spindles. Passive joint angle matching at the knee was used to assess proprioceptive accuracy in 25 patients with HSAN III and 9 age-matched control subjects, with and without taping. Angles of the reference and indicator knees were recorded with digital inclinometers, and the absolute error, gradient and correlation coefficient between the two sides calculated. Patients with HSAN III performed poorly on the joint angle-matching test (mean matching error +/- SE 8.0 +/- 0.8 degrees , controls 3.0 +/- 0.3 degrees ). Following application of tape bilaterally to the knee in an X-shaped pattern, proprioceptive performance improved significantly in the patients (mean error 5.4 +/- 0.7 degrees ) but not in the controls (3.0 +/- 0.2 degrees ). Across patients, but not controls, significant increases in gradient and correlation coefficient were also apparent following taping. We conclude that taping improves proprioception at the knee in HSAN III, presumably via enhanced sensory feedback from the skin.

Electromagnetic field simulations are increasingly used to assure RF safety of patients during MRI exams. In practice, however, tissue property distribution of the patient being imaged is not known, but may be represented with a pre-existing model. Repeatedly, agreement in transmit magnetic (B1 +) field distributions between two geometries has been used to suggest agreement in heating distributions. Here we examine relative effects of anatomical differences on B1 + distribution, Specific Absorption Rate (SAR) and temperature change (DeltaT). Numerical simulations were performed for a single surface coil positioned adjacent a homogeneous phantom and bovine phantom, each with slight geometric variations, and adjacent two different human body models. Experimental demonstration was performed on a bovine phantom using MR thermometry and B1 + mapping. Simulations and experiments demonstrate that B1 + distributions in different samples can be well correlated, while notable difference in maximum SAR and DeltaT occur. This work illustrates challenges associated with utilizing simulations or experiments for RF safety assurance purposes. Reliance on B1 + distributions alone for validation of simulations and/or experiments with a sample or subject for assurance of safety in another should be performed with caution.

PURPOSE: To develop a novel framework for free-breathing MRI called XD-GRASP, which sorts dynamic data into extra motion-state dimensions using the self-navigation properties of radial imaging and reconstructs the multidimensional dataset using compressed sensing. METHODS: Radial k-space data are continuously acquired using the golden-angle sampling scheme and sorted into multiple motion-states based on respiratory and/or cardiac motion signals derived directly from the data. The resulting undersampled multidimensional dataset is reconstructed using a compressed sensing approach that exploits sparsity along the new dynamic dimensions. The performance of XD-GRASP is demonstrated for free-breathing three-dimensional (3D) abdominal imaging, two-dimensional (2D) cardiac cine imaging and 3D dynamic contrast-enhanced (DCE) MRI of the liver, comparing against reconstructions without motion sorting in both healthy volunteers and patients. RESULTS: XD-GRASP separates respiratory motion from cardiac motion in cardiac imaging, and respiratory motion from contrast enhancement in liver DCE-MRI, which improves image quality and reduces motion-blurring artifacts. CONCLUSION: XD-GRASP represents a new use of sparsity for motion compensation and a novel way to handle motions in the context of a continuous acquisition paradigm. Instead of removing or correcting motion, extra motion-state dimensions are reconstructed, which improves image quality and also offers new physiological information of potential clinical value. Magn Reson Med, 2015. (c) 2015 Wiley Periodicals, Inc.

Here we report the case of a patient with familial dysautonomia (a genetic form of afferent baroreflex failure), who had severe hypertension (230/149 mmHg) induced by the stress of his mother taking his blood pressure. His hypertension subsided when he learnt to measure his blood pressure without his mother's involvement. The case highlights how the reaction to maternal stress becomes amplified when catecholamine release is no longer under baroreflex control.