A Panel Analysis of Institutional Finances of Medical Residencies at Non-University-Based Independent M.D. Granting Medical Schools in the United States

Traditionally, medical residency positions have been primarily funded by the federal government. However, due to declining governmental funding support over time, medical schools have resorted to fund these programs through other means such as clinical fees and payments for services. This change has affected the number and types of residencies available to medical school graduates. The purpose of this study was to measure how the availability of fiscal resources shape mission-related outputs, particularly medical residency positions at medical schools. Using academic capitalism as the theoretical framework provided a lens through which to examine how federal policies have shaped the availability and funding of medical residencies today at the institutional level. This concept has been studied in traditional colleges and universities and how they balance mission and money, but less so in the context of medical schools. This study used a fixed effect panel analysis to study the impact of selected variables over a 10-year period on financing of medical residencies. Findings included that tuition revenues, paid for by undergraduate medical students, are increasingly funding medical residency positions. There was little to no effect from hospital revenues and federal research monies on increasing the number of medical residency positions. The funding of university based medical education is particularly timely and of national importance to understand the consequences of federal policies for medical schools and how medical residency funding caps and limits have affected one of the missions of medical schools which is to train physicians

Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations

AbstractAutosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for μ- and m-calpains, which are calcium-dependent cysteine proteases. Overexpression of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration

Experimental Study on the Acellular Demal Matrix Graft for the Root Coverage in Dog

Mucogingival surgery is a plastic surgical procedure designed to correct defects in the morphology, position, and dimensions of the gingiva surrounding the teeth. Many surgical techniques have been reported in mucogingival surgery. Since these procedures also include the soft tissue esthetic approach, the term periodontal plastic surgery has been proposed to be more appropriate.1 Root coverage is a procedure that falls with this definition, and it has attracted more interest than others

Effects of Copy Number Variations on Developmental Aspects of Children With Delayed Development

Objective To determine effects of copy number variations (CNV) on developmental aspects of children suspected of having delayed development. Methods A retrospective chart review was done for 65 children who underwent array-comparative genomic hybridization after visiting physical medicine & rehabilitation department of outpatient clinic with delayed development as chief complaints. Children were evaluated with Denver Developmental Screening Test II (DDST-II), Sequenced Language Scale for Infants (SELSI), or Preschool Receptive-Expressive Language Scale (PRES). A Mann-Whitney U test was conducted to determine statistical differences of developmental quotient (DQ), receptive language quotient (RLQ), and expressive language quotient (ELQ) between children with CNV (CNV(+) group, n=16) and children without CNV (CNV(–) group, n=37). Results Of these subjects, the average age was 35.1 months (mean age, 35.1±24.2 months). Sixteen (30.2%) patients had copy number variations. In the CNV(+) group, 14 children underwent DDST-II. In the CNV(–) group, 29 children underwent DDST-II. Among variables, gross motor scale was significantly (p=0.038) lower in the CNV(+) group compared with the CNV(–) group. In the CNV(+) group, 5 children underwent either SELSI or PRES. In the CNV(–) group, 27 children underwent above language assessment examination. Both RLQ and ELQ were similar between the two groups. Conclusion The gross motor domain in DQ was significantly lower in children with CNV compared to that in children without CNV. This result suggests that additional genetic factors contribute to this variability. Active detection of genomic imbalance could play a vital role when prominent gross motor delay is presented in children with delayed development

Automatic Speech Recognition (ASR) for the Diagnosis of pronunciation of Speech Sound Disorders in Korean children

This study presents a model of automatic speech recognition (ASR) designed to diagnose pronunciation issues in children with speech sound disorders (SSDs) to replace manual transcriptions in clinical procedures. Since ASR models trained for general purposes primarily predict input speech into real words, employing a well-known high-performance ASR model for evaluating pronunciation in children with SSDs is impractical. We fine-tuned the wav2vec 2.0 XLS-R model to recognize speech as pronounced rather than as existing words. The model was fine-tuned with a speech dataset from 137 children with inadequate speech production pronouncing 73 Korean words selected for actual clinical diagnosis. The model's predictions of the pronunciations of the words matched the human annotations with about 90% accuracy. While the model still requires improvement in recognizing unclear pronunciation, this study demonstrates that ASR models can streamline complex pronunciation error diagnostic procedures in clinical fields.Comment: 12 pages, 2 figure

A study of the relationship between clinical phenotypes and plasma iduronate-2-sulfatase enzyme activities in Hunter syndrome patients

PurposeMucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II.MethodsWe hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl-α-iduronate 2-sulphate.ResultsPlasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type (P=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 nmol·4 hr-1·mL-1. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; P=0.003).ConclusionThese results show that the mild phenotype may be related to residual lysosomal enzyme activity

Ultrafast Light and Electrons: Imaging the Invisible

In this chapter, the evolutionary and revolutionary developments of microscopic imaging are overviewed with focus on ultrashort light and electrons pulses; for simplicity, we shall use the term “ultrafast” for both. From Alhazen’s camera obscura, to Hooke and van Leeuwenhoek’s optical micrography, and on to three- and four-dimensional (4D) electron microscopy, the developments over a millennium have transformed humans’ scope of visualization. The changes in the length and time scales involved are unimaginable, beginning with the visible shadows of candles at the centimeter and second scales, and ending with invisible atoms with space and time dimensions of sub-nanometer and femtosecond, respectively. With these advances it has become possible to determine the structures of matter and to observe their elementary dynamics as they fold and unfold in real time, providing the means for visualizing materials behavior and biological function, with the aim of understanding emergent phenomena in complex systems. Both light and light-generated electrons are now at the forefront of femtosecond and attosecond science and technology, and the scope of applications has reached beyond the nuclear motion as electron dynamics become accessible

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

Cytolytic DNA vaccine encoding lytic perforin augments the maturation of- and antigen presentation by- dendritic cells in a time-dependent manner

The use of cost-effective vaccines capable of inducing robust CD8+ T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8+ T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8+ T cell immunity. In vitro data showed that transfection of HEK293T cells with the cytolytic DNA resulted in the release of lactate dehydrogenase, indicative of necrotic/lytic cell death. In vitro exposure of this lytic cell debris to purified DCs from naïve C57BL/6 mice resulted in maturation of DCs as determined by up-regulation of CD80/CD86. Using activation/proliferation of adoptively transferred OT-I CD8+ T cells to measure antigen presentation by DCs in vivo, it was determined that cytolytic DNA immunisation resulted in a time-dependent increase in the proliferation of OT-I CD8+ T cells compared to canonical DNA immunisation. Overall, the data suggest that the cytolytic DNA vaccine increases the activity of DCs which has important implications for the design of DNA vaccines to improve their translational prospects.Danushka K. Wijesundara, Wenbo Yu, Ben J. C. Quah, Preethi Eldi, John D. Hayball, Kerrilyn R. Diener, Ilia Voskoboinik, Eric J. Gowans, and Branka Grubor-Bau

A novel form of constitutively active farnesylated Akt1 prevents mammary epithelial cells from anoikis and suppresses chemotherapy-induced apoptosis

Protein kinase B/Akt has been described as a central mediator of anti-apoptotic signals transduced by the PI3 kinase. Although the role of Akt in the suppression of apoptosis is well elucidated, a potential function of Akt in tumorigenesis and chemoresistance is less intensively documented. In this study, we describe the construction of a novel form of constitutively active Akt1, which relies on the deletion of its pleckstrin homology domain and the insertion of a C-terminal farnesylation sequence. Stable cell lines were generated with MCF10A mammary epithelial cells and A549 human NSCLC cells expressing constitutively active Akt1. Enigneered MCF10A cells were rendered resistant towards apoptosis resulting from loss of cellular substrate attachment (anoikis). We investigated the chemosensitivity of A549 cells expressing farnesylated Akt vs control cells. A profoundly decreased sensitivity towards Mitoxantrone and cisplatin was observed in cells expressing farnesylated Akt. No significant difference in sensitivity however was observed upon treatment with cell cycle specific chemotherapeutic agents like paclitaxel. Our data suggest, that Akt is a central mediator in the suppression of anoikis and modulation of chemotherapy-induced apoptosis. Therefore it represents a promising target for small molecule inhibitors to shift the apoptotic threshold in cancer cells after treatment with standard chemotherapy