Faculty Bibliography

OBJECTIVE:To examine the current headache medicine fellowship application process and to propose recommendations for a more unified, systematic, and transparent process. METHODS:We identified 42 headache fellowship programs using the United Council for Neurologic Subspecialties certification database. After an initial contact via e-mail, we conducted individual telephone interviews with program directors. Qualitative data coding allowed identification of emerging themes. Quantitative data were summarized with descriptive statistics. RESULTS:Forty (95%) program directors (34 adult, 6 pediatric) responded. Emerging themes included the following. (1) There are benefits and disadvantages to having a match. (2) If the match were reinstated, programs would participate only if all programs participated. (3) There should be consequences for programs that do not participate. If the match were reinstated, 37.5% of program directors responded that their program would participate without conditions; 37.5% would participate only if every program were required to participate. Fifteen percent would not participate, and 10% were not sure if they would participate. Forty percent supported sanctions against programs that did not participate in the match. CONCLUSION/CONCLUSIONS:The fellowship match potentially makes the process more systematic for both programs and applicants; however, it does not currently appear to be a feasible option for the field of headache medicine. Until the number of applicants exceeds the number of programs, we recommend instituting a universal timeline for applications and offers.

Cerebral Palsy (CP) is one of the foremost causes of childhood motor disability and disrupts the individual's development and ability to function. Several factors contribute to the development of CP such as preterm delivery, low birth weight, infection/inflammation, and additional pregnancy complications, both in preterm and term infants. As there is no specific treatment for CP, rehabilitation is the current option for the management of patients. The serious nature of this condition creates deficits that last a lifetime.  We collected studies that were published in the past 10 years, using PubMed as our main database. We chose studies that were relevant to CP and stem cell therapy. We mainly focused on various types of stem cells that can be used in treatment, mechanism of action (MOA) of stem cells, routes, dosage, and adverse effects, their efficacy, and safety in CP patients. Of all the 38 studies we reviewed, we found that five articles discussed the utilization of human umbilical cord blood [hUCB], four articles discussed autologous bone marrow stem cells, and one discussed allogeneic umbilical cord blood usage. One article discussed neural stem-like cells (NSLCs) derived from bone marrow and the remaining 27 articles were about CP and its treatment. We reviewed detailed information about the possible stem cell therapies and their benefits in patients with CP. We found that immune modulation is the major mechanism of action of stem cells, and among all the types of stem cells. Autologous umbilical cord mesenchymal stem cells appear to be safe and most effective in treatment compared to other stem cell treatments. Among all symptoms, motor symptoms are best corrected by stem cell therapy. Still, it did not show any marked improvement in treating other symptoms like speech defects, sensory or cognitive defects, or visual impairment.

Asymmetries in visual performance at isoeccentric locations are well-documented and functionally important. At a fixed eccentricity, visual performance is best along the horizontal, intermediate along the lower vertical, and poorest along the upper vertical meridian. These performance fields are pervasive across a range of visual tasks, including those mediated by contrast sensitivity. However, contrast performance fields have not been characterized with a systematic manipulation of stimulus spatial frequency, eccentricity, and size; three parameters that constrain contrast sensitivity. Further, individual differences in performance fields measurements have not been assessed. Here, we use an orientation discrimination task to characterize the pattern of contrast sensitivity across four isoeccentric locations along the cardinal meridians, and to examine whether and how this asymmetry pattern changes with systematic manipulation of stimulus spatial frequency (4 cpd to 8 cpd), eccentricity (4.5 degrees to 9 degrees), and size (3 degrees visual angle to 6 degrees visual angle). Our data demonstrate that contrast sensitivity is highest along the horizontal, intermediate along the lower vertical, and poorest along the upper vertical meridian. This pattern is consistent across stimulus parameter manipulations, even though they cause profound shifts in contrast sensitivity. Eccentricity-dependent decreases in contrast sensitivity can be compensated for by scaling stimulus size alone. Moreover, we find that individual variability in the strength of performance field asymmetries is consistent across conditions. This study is the first to systematically and jointly manipulate, and compare, contrast performance fields across spatial frequency, eccentricity, and size, and to address individual variability in performance fields.

The first aim of this study was to explore the aetiology of phenotypic relationships between different measures of executive functions. The second objective was to examine sources of the covariation between different measures of executive functions and the measure of general cognitive ability. The study sample consisted of 468 twins (154 pairs of monozygotic twins and 80 pairs of dizygotic twins) of the same and different gender who grew up together. Executive functions were evaluated by the Wisconsin Card Sorting Test, the Trail Making Test "“ form B, and verbal fluency tests. Raven's Advanced Progressive Matrices were used as a measure of general cognitive ability. The study results suggest a primarily genetic origin of the mutual covariation of different executive measures and their covariation with the general cognitive ability construct. While the shared genetic variance primarily lies in the bases of similarity/unity of the used cognitive measures, their particularity/difference is determined by a specific unshared environment. The obtained result on the presence of a single general genetic factor, which can be singled out in the case of different executive measures, at least partially speaks in favor of the thesis about the unity of various executive measures and the existence of a common basic ability. Together with the specific unshared environment, the specific genetic influence speaks in favor of a difference between each of the individual measures.

Accumulation of phosphorylated tau is a key pathological feature of Alzheimer's disease. Phosphorylated tau accumulation causes synaptic impairment, neuronal dysfunction and formation of neurofibrillary tangles. The pathological actions of phosphorylated tau are mediated by surrounding neuronal proteins; however, a comprehensive understanding of the proteins that phosphorylated tau interacts with in Alzheimer's disease is surprisingly limited. Therefore, the aim of this study was to determine the phosphorylated tau interactome. To this end, we used two complementary proteomics approaches: (i) quantitative proteomics was performed on neurofibrillary tangles microdissected from patients with advanced Alzheimer's disease; and (ii) affinity purification-mass spectrometry was used to identify which of these proteins specifically bound to phosphorylated tau. We identified 542 proteins in neurofibrillary tangles. This included the abundant detection of many proteins known to be present in neurofibrillary tangles such as tau, ubiquitin, neurofilament proteins and apolipoprotein E. Affinity purification-mass spectrometry confirmed that 75 proteins present in neurofibrillary tangles interacted with PHF1-immunoreactive phosphorylated tau. Twenty-nine of these proteins have been previously associated with phosphorylated tau, therefore validating our proteomic approach. More importantly, 34 proteins had previously been associated with total tau, but not yet linked directly to phosphorylated tau (e.g. synaptic protein VAMP2, vacuolar-ATPase subunit ATP6V0D1); therefore, we provide new evidence that they directly interact with phosphorylated tau in Alzheimer's disease. In addition, we also identified 12 novel proteins, not previously known to be physiologically or pathologically associated with tau (e.g. RNA binding protein HNRNPA1). Network analysis showed that the phosphorylated tau interactome was enriched in proteins involved in the protein ubiquitination pathway and phagosome maturation. Importantly, we were able to pinpoint specific proteins that phosphorylated tau interacts with in these pathways for the first time, therefore providing novel potential pathogenic mechanisms that can be explored in future studies. Combined, our results reveal new potential drug targets for the treatment of tauopathies and provide insight into how phosphorylated tau mediates its toxicity in Alzheimer's disease.