Needle Electrode-Based Electromechanical Reshaping of Cartilage

Electromechanical reshaping (EMR) of cartilage provides an alternative to the classic surgical techniques of modifying the shape of facial cartilages. The original embodiment of EMR required surface electrodes to be in direct contact with the entire cartilage region being reshaped. This study evaluates the feasibility of using needle electrode systems for EMR of facial cartilage and evaluates the relationships between electrode configuration, voltage, and application time in effecting shape change. Flat rabbit nasal septal cartilage specimens were deformed by a jig into a 90° bend, while a constant electric voltage was applied to needle electrodes that were inserted into the cartilage. The electrode configuration, voltage (0–7.5 V), and application time (1–9 min) were varied systematically to create the most effective shape change. Electric current and temperature were measured during voltage application, and the resulting specimen shape was assessed in terms of retained bend angle. In order to demonstrate the clinical feasibility of EMR, the most effective and practical settings from the septal cartilage experimentation were used to reshape intact rabbit and pig ears ex vivo. Cell viability of the cartilage after EMR was determined using confocal microscopy in conjunction with a live/dead assay. Overall, cartilage reshaping increased with increased voltage and increased application time. For all electrode configurations and application times tested, heat generation was negligible (<1 °C) up to 6 V. At 6 V, with the most effective electrode configuration, the bend angle began to significantly increase after 2 min of application time and began to plateau above 5 min. As a function of voltage at 2 min of application time, significant reshaping occurred at and above 5 V, with no significant increase in the bend angle between 6 and 7.5 V. In conclusion, electromechanical reshaping of cartilage grafts and intact ears can be effectively performed with negligible temperature elevation and spatially limited cell injury using needle electrodes

Family coordination in families who have a child with autism spectrum disorder

Little is known about the interactions of families where there is a child with autism spectrum disorder (ASD). The present study applies the Lausanne Trilogue Play (LTP) to explore both its applicability to this population as well as to assess resources and areas of deficit in these families. The sample consisted of 68 families with a child with ASD, and 43 families with a typically developing (TD) child. With respect to the global score for family coordination there were several negative correlations: the more severe the symptoms (based on the child’s ADOS score), the more family coordination was dysfunctional. This correlation was particularly high when parents had to play together with the child. In the parts in which only one of the parents played actively with the child, while the other was simply present, some families did achieve scores in the functional range, despite the child’s symptom severity. The outcomes are discussed in terms of their clinical implications both for assessment and for interventio

Aberrant Otx2 Expression Enhances Migration and Induces Ectopic Proliferation of Hindbrain Neuronal Progenitor Cells

Dysregulation of Otx2 is a hallmark of the pediatric brain tumor medulloblastoma, yet its functional significance in the establishment of these tumors is unknown. Here we have sought to determine the functional consequences of Otx2 overexpression in the mouse hindbrain to characterize its potential role in medulloblastoma tumorigenesis and identify the cell types responsive to this lineage-specific oncogene. Expression of Otx2 broadly in the mouse hindbrain resulted in the accumulation of proliferative clusters of cells in the cerebellar white matter and dorsal brainstem of postnatal mice. We found that brainstem ectopia were derived from neuronal progenitors of the rhombic lip and that cerebellar ectopia were derived from granule neuron precursors (GNPs) that had migrated inwards from the external granule layer (EGL). These hyperplasias exhibited various characteristics of medulloblastoma precursor cells identified in animal models of Shh or Wnt group tumors, including aberrant localization and altered spatiotemporal control of proliferation. However, ectopia induced by Otx2 differentiated and dispersed as the animals reached adulthood, indicating that factors restricting proliferative lifespan were a limiting factor to full transformation of these cells. These studies implicate a role for Otx2 in altering the dynamics of neuronal progenitor cell proliferation

Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma

Napsin A is an aspartic proteinase expressed in lung and kidney. We have reported that napsin A is expressed in type II pneumocytes and in adenocarcinomas of the lung. The expression of napsin was examined in 118 lung tissues including 16 metastases by in situ hybridisation. Napsin was expressed in the tumour cell compartment in 33 of 39 adenocarcinomas (84.6%), in two of 11 large cell carcinomas and in one lung metastasis of a renal cell carcinoma. Expression of napsin was found to be associated with a high degree of differentiation in adenocarcinoma. Immunohistochemistry was performed for three proteins currently used as markers for lung adenocarcinoma : surfactant protein-A, surfactant protein-B and thyroid transcription factor-1. Thyroid transcription factor-1 showed the same sensitivity (84.6%) as napsin for adenocarcinoma, whereas surfactant protein-A and surfactant protein-B showed lower sensitivities. Among these markers, napsin showed the highest specificity (94.3%) for adenocarcinoma in nonsmall cell lung carcinoma. We conclude that napsin is a promising marker for the diagnosis of primary lung adenocarcinoma

Adherence with tobramycin inhaled solution and health care utilization

<p>Abstract</p> <p>Background</p> <p>Adherence with tobramycin inhalation solution (TIS) during routine cystic fibrosis (CF) care may differ from recommended guidelines and affect health care utilization.</p> <p>Methods</p> <p>We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year and categorized overall adherence as: low ≤ 2 cycles, medium >2 to <4 cycles, and high ≥ 4 cycles per year. Interquartile ranges (IQR) were created for health care utilization and logistic regression analysis of hospitalization risk was conducted by TIS adherence categories.</p> <p>Results</p> <p>Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54) received ≥ 4 cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving ≤ 2 cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84). High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423) and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768).</p> <p>Conclusions</p> <p>Use of TIS did not reflect recommended guidelines and may impact other health care utilization.</p

A Cellular Pathway Involved in Clara Cell to Alveolar Type II Cell Differentiation after Severe Lung Injury

Regeneration of alveolar epithelia following severe pulmonary damage is critical for lung function. We and others have previously shown that Scgb1a1-expressing cells, most likely Clara cells, can give rise to newly generated alveolar type 2 cells (AT2s) in response to severe lung damage induced by either influenza virus infection or bleomycin treatment. In this study, we have investigated cellular pathway underlying the Clara cell to AT2 differentiation. We show that the initial intermediates are bronchiolar epithelial cells that exhibit Clara cell morphology and express Clara cell marker, Scgb1a1, as well as the AT2 cell marker, pro-surfactant protein C (pro-SPC). These cells, referred to as pro-SPC[superscript +] bronchiolar epithelial cells (or SBECs), gradually lose Scgb1a1 expression and give rise to pro-SPC[superscript +] cells in the ring structures in the damaged parenchyma, which appear to differentiate into AT2s via a process sharing some features with that observed during alveolar epithelial development in the embryonic lung. These findings suggest that SBECs are intermediates of Clara cell to AT2 differentiation during the repair of alveolar epithelia following severe pulmonary injury.Singapore-MIT Alliance for Research and Technology Center. Infectious Disease Research Grou

Development and validation of an index of musculoskeletal functional limitations

BACKGROUND: While musculoskeletal problems are leading sources of disability, there has been little research on measuring the number of functionally limiting musculoskeletal problems for use as predictor of outcome in studies of chronic disease. This paper reports on the development and preliminary validation of a self administered musculoskeletal functional limitations index. METHODS: We developed a summary musculoskeletal functional limitations index based upon a six-item self administered questionnaire in which subjects indicate whether they are limited a lot, a little or not at all because of problems in six anatomic regions (knees, hips, ankles and feet, back, neck, upper extremities). Responses are summed into an index score. The index was completed by a sample of total knee replacement recipients from four US states. Our analyses examined convergent validity at the item and at the index level as well as discriminant validity and the independence of the index from other correlates of quality of life. RESULTS: 782 subjects completed all items of the musculoskeletal functional limitations index and were included in the analyses. The mean age of the sample was 75 years and 64% were female. The index demonstrated anticipated associations with self-reported quality of life, activities of daily living, WOMAC functional status score, use of walking support, frequency of usual exercise, frequency of falls and dependence upon another person for assistance with chores. The index was strongly and independently associated with self-reported overall health. CONCLUSION: The self-reported musculoskeletal functional limitations index appears to be a valid measure of musculoskeletal functional limitations, in the aspects of validity assessed in this study. It is useful for outcome studies following TKR and shows promise as a covariate in studies of chronic disease outcomes.National Institutes of Health (NIH P60 AR 47782; NIH K24 AR 02123

The spliceosome U2 snRNP factors promote genome stability through distinct mechanisms; transcription of repair factors and R-loop processing

Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress

Validation of a method for identifying nursing home admissions using administrative claims

<p>Abstract</p> <p>Background</p> <p>Currently there is no standard algorithm to identify whether a subject is residing in a nursing home from administrative claims. Our objective was to develop and validate an algorithm that identifies nursing home admissions at the resident-month level using the MarketScan Medicare Supplemental and Coordination of Benefit (COB) database.</p> <p>Methods</p> <p>The computer algorithms for identifying nursing home admissions were created by using provider type, place of service, and procedure codes from the 2000 – 2002 MarketScan Medicare COB database. After the algorithms were reviewed and refined, they were compared with a detailed claims review by an expert reviewer. A random sample of 150 subjects from the claims was selected and used for the validity analysis of the algorithms. Contingency table analysis, comparison of mean differences, correlations, and t-test analyses were performed. Percentage agreement, sensitivity, specificity, and Kappa statistics were analyzed.</p> <p>Results</p> <p>The computer algorithm showed strong agreement with the expert review (99.9%) for identification of the first month of nursing home residence, with high sensitivity (96.7%), specificity (100%) and a Kappa statistic of 0.97. Weighted Pearson correlation coefficient between the algorithm and the expert review was 0.97 (<it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>A reliable algorithm indicating evidence of nursing home admission was developed and validated from administrative claims data. Our algorithm can be a useful tool to identify patient transitions from and to nursing homes, as well as to screen and monitor for factors associated with nursing home admission and nursing home discharge.</p

Increased deep sleep in a medication-free, detoxified female offender with schizophrenia, alcoholism and a history of attempted homicide: Case report

BACKGROUND: Psychiatric sleep research has attempted to identify diagnostically sensitive and specific sleep patterns associated with particular disorders. Both schizophrenia and alcoholism are typically characterized by a severe sleep disturbance associated with decreased amounts of slow wave sleep, the physiologically significant, refreshing part of the sleep. Antisocial behaviour with severe aggression, on the contrary, has been reported to associate with increased deep sleep reflecting either specific brain pathology or a delay in the normal development of sleep patterns. The authors are not aware of previous sleep studies in patients with both schizophrenia and antisocial personality disorder. CASE PRESENTATION: The aim of the present case-study was to characterize the sleep architecture of a violent, medication-free and detoxified female offender with schizophrenia, alcoholism and features of antisocial personality disorder using polysomnography. The controls consisted of three healthy, age-matched women with no history of physical violence. The offender's sleep architecture was otherwise very typical for patients with schizophrenia and/or alcoholism, but an extremely high amount of deep sleep was observed in her sleep recording. CONCLUSIONS: The finding strengthens the view that severe aggression is related to an abnormal sleep pattern with increased deep sleep. The authors were able to observe this phenomenon in an antisocially behaving, violent female offender with schizophrenia and alcohol dependence, the latter disorders previously reported to be associated with low levels of slow wave sleep. New studies are, however, needed to confirm and explain this preliminary finding