Two Cases of Cerebral Salt Wasting Syndrome Developing after Cranial Vault Remodeling in Craniosynostosis Children

Hyponatremia has been recognized as an important postoperative metabolic complication after central nervous system (CNS) operations in children. If not appropriately treated, the postoperative hyponatremia can cause several types of CNS and circulatory disorders such as cerebral edema, increased intracranial pressure. The postoperative hyponatremia after CNS surgery has been considered as one of the underlying causes of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In some cases, however, the cerebral salt wasting (CSW) syndrome has been detected. CSW syndrome is far less well-known than SIADH and also different from SIADH in diagnosis and treatment. It causes an increase in urine output and urine sodium after a trauma of CNS and dehydration symptoms. The appropriate treatment of CSW syndrome is opposite the usual treatment of hyponatremia caused by SIADH. The latter is treated with fluid restriction because of the increased level of free water and its dilutional effect causing hyponatremia, whereas the former is treated with fluid and sodium resuscitation because of the unusual loss of high urinary sodium. Early diagnosis and treatment of CSW syndrome after CNS surgery are, therefore, essential. We made a diagnosis of CSW syndrome in two craniosynostosis children manifesting postoperative hyponatremia and supplied them an appropriate amount of water and sodium via intravenous route. The hyponatremia or natricuresis of the children improved and neurologic and circulatory sequelae could be prevented

Offender Assessment, Case Planning, and Referral to Community-Based Treatment: Effects of a Structured Process Improvement Initiative

This article is part of the supplement: Abstracts from the 2014 Addiction Health Services Research (AHSR) Conferenc

TDP-43 Liquid-Liquid Phase Separation (LLPS) Deficiency Attenuates Amyloid Beta Deposition in the 5XFAD Transgenic Mouse Model of Alzheimer\u27s Disease

Background: TAR DNA-binding protein 43 (TDP-43) can be found within the cell nucleus in most tissues and is a fundamental component to protein production, as it works to slice and reconfigure mRNA molecules. Recently, TDP-43 inclusions have been identified as a prevalent proteinopathy in the brains of individuals diagnosed with Alzheimer\u27s Disease (AD). However, despite the growing body of evidence demonstrating the important role of TDP-43 in AD pathogenesis, whether and how TDP-43 proteinopathy and other AD pathological hallmarks interact remain largely unknown. Furthermore, TDP-43 has a high propensity to undergo liquid-liquid phase separation (LLPS), a biological process necessary for the condensation of proteins, nucleic acids, and other biomolecules. Purpose of Research: The correlation between TDP-43 LLPS and AD deposition is an intriguing, yet currently unexplored area of interest. The purpose of this study is to investigate whether and how TDP-43 and its phase separation are involved in amyloid deposition in APP transgenic mice for Alzheimer\u27s Disease. Methods: We crossed our recently generated mice expressing endogenous LLPS-deficient murine TDP-43 with the widely used 5XFAD transgenic mouse model. Different approaches were then performed to assess amyloid deposition and associated neuroinflammation. Results: When compared to 5XFAD mice, 5XFAD mice expressing LLPS-deficient TDP-43 showed significantly reduced amyloid deposition throughout the brain. Neuroinflammation, as evaluated by GFAP and Iba1 expression was also alleviated by LLPS-deficient TDP-43. Conclusion: For the first time, our study demonstrates the likely role TDP-43 LLPS plays in amyloid deposition. And, targeting TDP-43 LLPS may serve as a novel therapeutic approach to Alzheimer\u27s Disease treatment.https://digitalcommons.unmc.edu/surp2021/1036/thumbnail.jp

TDP-43 Phase Separation Does Not Likely Regulate LPS-Induced Neuroinflammation

Immunohistochemistry (IHC) was performed to assess whether Transactive response Deoxyribonucleic acid binding Protein 43 (TDP-43) liquid-liquid phase separation (LLPS) regulates lipopolysaccaride (LPS)-induced neuroinflammation. Quantification and intensity results of glia cells and cytokines indicate that TDP-43 LLPS does not likely regulate LPS-induced neuroinflammation.https://digitalcommons.unmc.edu/surp2021/1060/thumbnail.jp

A comprehensive estimate of recent carbon sinks in China using both top-down and bottom-up approaches

Atmospheric inversions use measurements of atmospheric CO2 gradients to constrain regional surface fluxes. Current inversions indicate a net terrestrial CO2 sink in China between 0.16 and 0.35 PgC/yr. The uncertainty of these estimates is as large as the mean because the atmospheric network historically contained only one high altitude station in China. Here, we revisit the calculation of the terrestrial CO2 flux in China, excluding emissions from fossil fuel burning and cement production, by using two inversions with three new CO2 monitoring stations in China as well as aircraft observations over Asia. We estimate a net terrestrial CO2 uptake of 0.39-0.51 PgC/yr with a mean of 0.45 PgC/yr in 2006-2009. After considering the lateral transport of carbon in air and water and international trade, the annual mean carbon sink is adjusted to 0.35 PgC/yr. To evaluate this top-down estimate, we constructed an independent bottom-up estimate based on ecosystem data, and giving a net land sink of 0.33 PgC/yr. This demonstrates closure between the top-down and bottom-up estimates. Both top-down and bottom-up estimates give a higher carbon sink than previous estimates made for the 1980s and 1990s, suggesting a trend towards increased uptake by land ecosystems in China.</p

Photoconductivity of biased graphene

Graphene is a promising candidate for optoelectronic applications such as photodetectors, terahertz imagers, and plasmonic devices. The origin of photoresponse in graphene junctions has been studied extensively and is attributed to either thermoelectric or photovoltaic effects. In addition, hot carrier transport and carrier multiplication are thought to play an important role. Here we report the intrinsic photoresponse in biased but otherwise homogeneous graphene. In this classic photoconductivity experiment, the thermoelectric effects are insignificant. Instead, the photovoltaic and a photo-induced bolometric effect dominate the photoresponse due to hot photocarrier generation and subsequent lattice heating through electron-phonon cooling channels respectively. The measured photocurrent displays polarity reversal as it alternates between these two mechanisms in a backgate voltage sweep. Our analysis yields elevated electron and phonon temperatures, with the former an order higher than the latter, confirming that hot electrons drive the photovoltaic response of homogeneous graphene near the Dirac point

Effects of a strategy to improve offender assessment practices: Staff perceptions of implementation outcomes

Background: This implementation study examined the impact of an organizational process improvement intervention (OPII) on a continuum of evidence based practices related to assessment and community reentry of drug-involved offenders: Measurement/Instrumentation, Case Plan Integration, Conveyance/Utility, and Service Activation/Delivery. Methods: To assess implementation outcomes (staff perceptions of evidence-based assessment practices), a survey was administered to correctional and treatment staff (n = 1509) at 21 sites randomly assigned to an Early- or Delayed-Start condition. Hierarchical linear models with repeated measures were used to examine changes in evidence-based assessment practices over time, and organizational characteristics were examined as covariates to control for differences across the 21 research sites. Results: Results demonstrated significant intervention and sustainability effects for three of the four assessment domains examined, although stronger effects were obtained for intra- than inter-agency outcomes. No significant effects were found for Conveyance/Utility. Conclusions: Implementation interventions such as the OPII represent an important tool to enhance the use of evidence-based assessment practices in large and diverse correctional systems. Intra-agency assessment activities that were more directly under the control of correctional agencies were implemented most effectively. Activities in domains that required cross-systems collaboration were not as successfully implemented, although longer follow-up periods might afford detection of stronger effects

Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels

Colorectal cancer (CRC) resistance to fluoropyrimidines and other inhibitors of thymidylate synthase (TS) is a serious clinical problem often associated with increased intracellular levels of TS. Since the tumour suppressor gene p53, which is mutated in 50% of CRC, regulates the expression of several genes, it may modulate TS activity, and changes in the status of p53 might be responsible for chemoresistance. Therefore, this study was aimed to investigate TS levels and sensitivity to TS inhibitors in wild-type (wt) and mutant (mt) p53 CRC cells, Lovo and WiDr, respectively, transfected with mt and wt p53. Lovo 175X2 cells (transfected with mt p53) were more resistant to 5-fluorouracil (5-FU; 2-fold), nolatrexed (3-fold), raltitrexed (3-fold) and pemetrexed (10-fold) in comparison with the wt p53 parental cells Lovo 92. Resistance was associated with an increase in TS protein expression and catalytic activity, which might be caused by the loss of the inhibitory effect on the activity of TS promoter or by the lack of TS mRNA degradation, as suggested by the reversal of TS expression to the levels of Lovo 92 cells by adding actinomycin. In contrast, Lovo li cells, characterized by functionally inactive p53, were 3-13-fold more sensitive to nolatrexed, raltitrexed and pemetrexed, and had a lower TS mRNA, protein expression and catalytic activity than Lovo 92. However, MDM-2 expression was significantly higher in Lovo li, while no significant differences were observed in Lovo 175X2 cells with respect to Lovo 92. Finally, mt p53 WiDr transfected with wt p53 were not significantly different from mt p53 WiDr cells with respect to sensitivity to TS inhibitors or TS levels. Altogether, these results indicate that changes in the status of p53, can differently alter sensitivity to TS inhibitors by affecting TS levels, depending on activity or cell line, and might explain the lack of clear correlation between mutations in p53 and clinical outcome after chemotherapy with TS inhibitors

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases