UW Neurological Surgery Recent PubMed Publications

CONCLUSIONS: Repeated annual interventions would give a three- to seven-fold increase in long-term impact compared with a one-off intervention. Other interventions will be needed to more effectively reduce the HIV burden in this population.

CONCLUSION: Our study identifies hallmarks of glioma tumorigenesis that are sensitive to MTAs and reports ST-401 as a promising chemical scaffold to develop brain-penetrant MTAs.

Legume grains are traditional crops that have been modernized as processed foods and animal protein alternatives in recent years. This modernization has largely been fueled by new technological developments driven by increased consumer demands for plant protein and gluten-free options. However, consumers must be mindful that legumes have other nutritional attributes besides protein that help achieve healthier diets, and recent evidence suggests that consuming 100 g of legume grains per day would...

A computerized measure of Referential Activity (RA), the High WRAD Proportion (HWP), which assesses the proportion of high RA language in a text, was compared to a widely used measure of episodic memory, the proportion of internal details (IP), those pertaining directly to the main event being described. Both measures, along with several additional computerized measures, were applied to narratives of past and future events, produced by two groups of speakers varying in age. The HWP and IP showed...

Narrativity has been proposed as an indicator of episodic memory strength when people discuss their past (Nelson and Horowitz in Discourse Processes 31:307-324, 2001. https://doi.org/10.1207/S15326950dp31-3_5 ). Referential Activity, the extent to which words convey a speaker's experience of being present in the event being described, has been independently hypothesized to indicate episodic memory strength (Maskit in J Psycholinguist Res, 2021. https://doi.org/10.1007/s10936-021-09761-8 ). These...

A major driver of the U.S. opioid crisis is limited access to effective medications for opioid use disorder (MOUD) that reduce overdose risks. Traditionally, jails and prisons in the U.S. have not initiated or maintained MOUD for incarcerated individuals with OUD prior to their return to the community, which places them at high risk for fatal overdose. A 2018 law (Chapter 208) made Massachusetts (MA) the first state to mandate that five county jails deliver all FDA-approved MOUDs (naltrexone...

Central nervous system (CNS) hyperexcitability is a clinically significant feature of acute ethanol withdrawal. There is evidence for a genetic contribution to withdrawal severity, but specific genetic risk factors have not been identified. The gene glyoxalase 1 (Glo1) has been previously implicated in ethanol consumption in mice, and GLO1 inhibition can attenuate drinking in mice and rats. Here, we investigated whether genetic and pharmacological manipulations of GLO1 activity can also mediate...

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CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

Conducting collaborative and comprehensive epidemiological research on neonatal sepsis in low- and middle-income countries (LMICs) is challenging due to a lack of diagnostic tests. This prospective study protocol aims to obtain epidemiological data on bacterial sepsis in newborns and young infants at Kamuzu Central Hospital in Lilongwe, Malawi. The main goal is to determine if the use of whole blood transcriptome host immune response signatures can help in the identification of infants who have...

Voltage-gated Ca(v)1 and Ca(v)2 Ca^(2+) channels are comprised of a pore-forming α(1) subunit (Ca(v)1.1-1.4, Ca(v)2.1-2.3) and auxiliary β (β(1-4)) and α(2)δ (α(2)δ-1-4) subunits. The properties of these channels vary with distinct combinations of Ca(v) subunits and alternative splicing of the encoding transcripts. Therefore, the impact of disease-causing mutations affecting these channels may depend on the identities of Ca(v) subunits and splice variants. Here, we analyzed the effects of a...

CONCLUSIONS: In patients undergoing CA/PCI, significant differences were detected between BtB BP and both invasively measured and cuff BP. The non-invasive BtB BP measurement device tested is not suitable for clinical or research use.

CONCLUSION: Although radial loops are associated with high transradial failure rates, our results suggest that the presence of a loop is not an absolute contraindication to TRA. Therefore, we recommend attempting loop navigation using our protocol. Patient age, vascular tortuosity, and recurrent radial artery size should help dictate when to convert to an alternative access site.

Related Articles

YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance.

Dev Biol. 2021 Jan 08;:

Authors: Szulzewsky F, Holland EC, Vasioukhin V

Abstract
YAP1 is a transcriptional co-activator whose activity is controlled by the Hippo signaling pathway. In addition to important functions in normal tissue homeostasis and regeneration, YAP1 has also prominent functions in cancer initiation, aggressiveness, metastasis, and therapy resistance. In this review we are discussing the molecular functions of YAP1 and its roles in cancer, with a focus on the different mechanisms of de-regulation of YAP1 activity in human cancers, including inactivation of upstream Hippo pathway tumor suppressors, regulation by intersecting pathways, miRNAs, and viral oncogenes. We are also discussing new findings on the function and biology of the recently identified family of YAP1 gene fusions, that constitute a new type of activating mutation of YAP1 and that are the likely oncogenic drivers in several subtypes of human cancers. Lastly, we also discuss different strategies of therapeutic inhibition of YAP1 functions.

PMID: 33428889 [PubMed - as supplied by publisher]

Related Articles

Identification of synergistic and antagonistic actions of environmental pollutants: Bisphenols A, S and F in the presence of DEP, DBP, BADGE and BADGE·2HCl in three component mixtures.

Sci Total Environ. 2021 Jan 04;767:144286

Authors: Jatkowska N, Kudłak B, Lewandowska P, Liu W, Williams MJ, Schiöth HB

Abstract
Ecosystems are facing increased pressure due to the emission of many classes of emerging contaminants. However, very little is known about the interactions of these pollutants, such as bisphenols (BPs), plasticizers or pharmaceuticals. By employing bioluminescent bacteria (Microtox assay), we were able to define interactions between selected emerging pollutants (namely BPA, BPS, BPF, BADGE, BADGE·2HCl, DEP, DBP) in ternary mixtures, at environmentally relevant concentration levels (down to as low as 1.89, 1.42, 3.08, and 0.326 μM for, respectively, BPA, BPF, BPS and BADGE·2HCl). We provide the first systematic analysis of bisphenols and phthalates in three component mixtures. Using this system, we performed toxicity modelling with concentration addition (CA) and independent action (IA) approaches, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. Interestingly, we mathematically and experimentally confirmed a novel synergy between BPA, BADGE and BADGE·2HCl. The synergy of BPA, BADGE and BADGE·2HCl is distinct, with both models suggesting these analytes have a similar mode of action (MOA). Moreover, we unexpectedly found a strong antagonistic impact with DEP, in mixtures containing BPA and BADGE analogues, which is confirmed with both mathematical models. Our study also shows that the impact of BPS and BPF in many mixtures is highly concentration dependent, justifying the necessity to perform mixture studies using wide concentration ranges. Overall, this study demonstrates that bioluminescent bacteria are a relevant model for detecting the synergistic and antagonist actions of environmental pollutants in mixtures, and highlights the importance of analyzing combinations of pollutants in higher order mixtures.

PMID: 33429266 [PubMed - as supplied by publisher]

The clinical impact of rare loss-of-function variants has yet to be determined for most genes. Integration of DNA sequencing data with electronic health records (EHRs) could enhance our understanding of the contribution of rare genetic variation to human disease¹. By leveraging 10,900 whole-exome sequences linked to EHR data in the Penn Medicine Biobank, we addressed the association of the cumulative effects of rare predicted loss-of-function variants for each individual gene on human disease on...

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Related Articles

Health economic analyses of the justice community opioid innovation network (JCOIN).

J Subst Abuse Treat. 2021 Jan 05;:108262

Authors: Murphy SM, Laiteerapong N, Pho MT, Ryan D, Montoya I, Shireman TI, Huang E, McCollister KE

Abstract
The Justice Community Opioid Innovation Network (JCOIN) will generate real-world evidence to address the unique needs of people with opioid use disorder (OUD) in justice settings. Evidence regarding the economic value of OUD interventions in justice populations is limited. Moreover, the variation in economic study designs is a barrier to defining specific interventions as broadly cost-effective. The JCOIN Health Economics Analytic Team (HEAT) has worked closely with the Measures Committee to incorporate common economic measures and instruments across JCOIN studies, which will: a) ensure rigorous economic evaluations within each trial; b) enhance comparability of findings across studies; and c) allow for cross-study analyses of trials with similar designs/settings (e.g., pre-reentry MOUD), to assess questions beyond the scope of a single study, while controlling for and evaluating the effect of intervention-, organizational-, and population-level characteristics. We describe shared trial characteristics relevant to the economic evaluations, and discuss potential cross-study economic analyses.

PMID: 33419602 [PubMed - as supplied by publisher]

Related Articles

Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study.

J Neurotrauma. 2021 Jan 07;:

Authors: Nolan AL, Petersen C, Iacono D, Mac Donald CL, Mukherjee P, van der Kouwe A, Jain S, Stevens A, Diamond B, Wang R, Markowitz AJ, Fischl B, Perl D, Manley GT, Keene CD, Diaz-Arrastia R, Edlow BL

Abstract
Diffusion tractography MRI can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well-defined due to a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750 μm isotropic resolution, followed by histopathologic evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein and loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of amyloid precursor protein (APP)-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.

PMID: 33412995 [PubMed - as supplied by publisher]