309 research outputs found

    Independence and a New Partnership in Catholic Higher Education, by Alice Gallin, OSU

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    Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities

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    OBJECTIVES: Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. METHODS: We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. RESULTS: Mean PCS and MCS scores were 36.7+/-11.7 and 42.4+/-12.2, respectively. Significant (P \u3c 0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P \u3c 0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. CONCLUSIONS: Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses

    Label-free segmentation of co-cultured cells on a nanotopographical gradient

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    The function and fate of cells is influenced by many different factors, one of which is surface topography of the support culture substrate. Systematic studies of nanotopography and cell response have typically been limited to single cell types and a small set of topographical variations. Here, we show a radical expansion of experimental throughput using automated detection, measurement, and classification of co-cultured cells on a nanopillar array where feature height changes continuously from planar to 250 nm over 9 mm. Individual cells are identified and characterized by more than 200 descriptors, which are used to construct a set of rules for label-free segmentation into individual cell types. Using this approach we can achieve label-free segmentation with 84% confidence across large image data sets and suggest optimized surface parameters for nanostructuring of implant devices such as vascular stents

    As Omicron Takes Hold and Other New Variants Arise, COVID-19 Testing Remains the Universally Agreed Tool to Effect Transition From Pandemic to Endemic State

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    The COVID-19 pandemic has caused more than 448 million cases and 6 million deaths worldwide to date. Omicron is now the dominant SARS-CoV-2 variant, making up more than 90% of cases in countries reporting sequencing data. As the pandemic continues into its third year, continued testing is a strategic and necessary tool for transitioning to an endemic state of COVID-19. Here, we address three critical topics pertaining to the transition from pandemic to endemic: defining the endemic state for COVID-19, highlighting the role of SARS-CoV-2 testing as endemicity is approached, and recommending parameters for SARS-CoV-2 testing once endemicity is reached. We argue for an approach that capitalizes on the current public health momentum to increase capacity for PCR-based testing and whole genome sequencing to monitor emerging infectious diseases. Strategic development and utilization of testing, including viral panels in addition to vaccination, can keep SARS-CoV-2 in a manageable endemic state and build a framework of preparedness for the next pandemic

    Improved Immunodetection of Endogenous α-Synuclein

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    α-Synuclein is a key molecule in understanding the pathogenesis of neurodegenerative α-synucleinopathies such as Parkinson's disease. Despite extensive research, however, its precise function remains unclear partly because of a difficulty in immunoblotting detection of endogenous α-synuclein. This difficulty has largely restricted the progress for α-synucleinopathy research. Here, we report that α-synuclein monomers tend to easily detach from blotted membranes, resulting in no or very poor detection. To prevent this detachment, a mild fixation of blotted membranes with paraformaldehyde was applied to the immunoblotting method. Amazingly, this fixation led to clear and strong detection of endogenous α-synuclein, which has been undetectable by a conventional immunoblotting method. Specifically, we were able to detect endogenous α-synuclein in various human cell lines, including SH-SY5Y, HEK293, HL60, HeLa, K562, A375, and Daoy, and a mouse cell line B16 as well as in several mouse tissues such as the spleen and kidney. Moreover, it should be noted that we could clearly detect endogenous α-synuclein phosphorylated at Ser-129 in several human cell lines. Thus, in some tissues and cultured cells, endogenous α-synuclein becomes easily detectable by simply fixing the blotted membranes. This improved immunoblotting method will allow us to detect previously undetectable endogenous α-synuclein, thereby facilitating α-synuclein research

    Mechanism, assessment and management of pain in chronic pancreatitis: Recommendations of a multidisciplinary study group

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    AbstractDescriptionPain in patients with chronic pancreatitis (CP) remains the primary clinical complaint and source of poor quality of life. However, clear guidance on evaluation and treatment is lacking.MethodsPancreatic Pain working groups reviewed information on pain mechanisms, clinical pain assessment and pain treatment in CP. Levels of evidence were assigned using the Oxford system, and consensus was based on GRADE. A consensus meeting was held during PancreasFest 2012 with substantial post-meeting discussion, debate, and manuscript refinement.ResultsTwelve discussion questions and proposed guidance statements were presented. Conference participates concluded: Disease Mechanism: Pain etiology is multifactorial, but data are lacking to effectively link symptoms with pathologic feature and molecular subtypes. Assessment of Pain: Pain should be assessed at each clinical visit, but evidence to support an optimal approach to assessing pain character, frequency and severity is lacking. Management: There was general agreement on the roles for endoscopic and surgical therapies, but less agreement on optimal patient selection for medical, psychological, endoscopic, surgical and other therapies.ConclusionsProgress is occurring in pain biology and treatment options, but pain in patients with CP remains a major problem that is inadequately understood, measured and managed. The growing body of information needs to be translated into more effective clinical care

    Modeling timing and size of juvenile Chinook salmon out-migrants at three Elwha River rotary screw traps: a window into early life history post dam removal

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    Chinook salmon (Oncorhynchus tshawytscha) populations express diverse early life history pathways that increase habitat utilization and demographic resiliency. Extensive anthropogenic alterations to freshwater habitats along with hatchery and harvest impacts have led to marked reductions in early life history diversity across much of the species’ range. The recent removal of two Elwha River dams between 2011 and 2014 restored access to over 90% of the available habitat that had been inaccessible to Chinook salmon since the early 1900s. This provided an opportunity to investigate how renewed access to this habitat might affect life history diversity. As exotherms, egg-to-fry development, juvenile growth, and movement are influenced by water temperatures. We used spatially and temporally explicit Elwha River water temperature and Chinook salmon spawning location data, in conjunction with spawn timing, emergence, growth, and movement models, to predict observed timing and sizes of juvenile Chinook salmon captured in three rotary screw traps in the mainstem and two tributaries during four trap years. This effort allowed us to test hypotheses regarding Elwha River Chinook salmon early life history, identify potential problems with the data, and predict how emergence and growth would change with increased spawning in the upper watershed. Predicted Chinook salmon emergence timing and predicted dates that juveniles reached 65 mm differed by as much as 2 months for different river locations due to large differences in thermal regimes longitudinally in the mainstem and between tributaries. For 10 out of the 12 trap–year combinations, the model was able to replicate important characteristics of the out-migrant timing and length data collected at the three traps. However, in most cases, there were many plausible parameter combinations that performed well, and in some cases, the model predictions and observations differed. Potential problems with the data and model assumptions were identified as partial explanations for differences and provide avenues for future work. We show that juvenile out-migrant data combined with mechanistic models can improve our understanding of how differences in temperature, spawning extent, and spawn timing affect the emergence, growth, and movement of juvenile fish across diverse riverine habitats

    Comparative Analysis of Acid Sphingomyelinase Distribution in the CNS of Rats and Mice Following Intracerebroventricular Delivery

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    Niemann-Pick A (NPA) disease is a lysosomal storage disorder (LSD) caused by a deficiency in acid sphingomyelinase (ASM) activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO) mice could be partially alleviated by intracerebroventricular (ICV) infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat
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