2,178 research outputs found
Meralgia paresthetica after âall-in-oneâ appendectomy
AbstractMinimally invasive approaches have become standard for pediatric appendectomy. The laparoscopic assisted single port approach, also known as the âall-in-oneâ appendectomy, has gained recent popularity [1]. We describe a child who suffered meralgia paresthetica (a neuropathy in the distribution of the lateral femoral cutaneous nerve) after a laparoscopic assisted single port appendectomy, perhaps secondary to mobilization of the cecum
A systematic review of head-up tilt to improve consciousness in people with a prolonged disorder of consciousness
Heme consumption reduces hepatic triglyceride and fatty acid accumulation in a rat model of NAFLD fed westernized diet
Studies have identified that serum-free hemoglobin subunits correlate positively with the severity of nonalcoholic fatty liver disease (NAFLD). However, the role of hemoglobin in the development of NAFLD remains unclear. In the present study, a rat model of NAFLD was developed, using a westernized diet high in saturated fat and refined sugar. Since a westernized diet is also high in red meat, we tested the effect of hemoglobin as a dietary source of heme in our model. Sprague-Dawley rats were fed ad libitum for 4 weeks either control diet (7% fat), westernized diet (WD, 18% fat + 1% cholesterol), hemoglobin diet (7% fat + 2.5% Hb), or westernized and hemoglobin diet (18% fat + 1% cholesterol + 2.5% Hb). Rats fed WD developed features of NAFLD, including insulin resistance and accumulation of liver fatty acids in the form of triglycerides, increased lipid peroxidation (F2-Isoprostanes), and liver fibrotic marker (hydroxyproline). Hemoglobin consumption significantly influenced several biomarkers of NAFLD and hepatic biochemistry, suggesting a possible interaction with diet and/or liver lipid pathways. The complex mechanisms of interaction between WD and hemoglobin in our rat model warrants further studies to examine the role of dietary heme on NAFLD
National and international kidney failure registries: characteristics, commonalities, and contrasts
Registries are essential for health infrastructure planning, benchmarking, continuous quality improvement, hypothesis generation, and real-world trials. To date, data from these registries have predominantly been analyzed in isolated âsilos,â hampering efforts to analyze âbig dataâ at the international level, an approach that provides wide-ranging benefits, including enhanced statistical power, an ability to conduct international comparisons, and greater capacity to study rare diseases. This review serves as a valuable resource to clinicians, researchers, and policymakers, by comprehensively describing kidney failure registries active in 2021, before proposing approaches for inter-registry research under current conditions, as well as solutions to enhance global capacity for data collaboration. We identified 79 kidney-failure registries spanning 77 countries worldwide. International Society of Nephrology exemplar initiatives, including the Global Kidney Health Atlas and Sharing Expertise to support the set-up of Renal Registries (SharE-RR), continue to raise awareness regarding international healthcare disparities and support the development of universal kidney-disease registries. Current barriers to inter-registry collaboration include underrepresentation of lower-income countries, poor syntactic and semantic interoperability, absence of clear consensus guidelines for healthcare data sharing, and limited researcher incentives. This review represents a call to action for international stakeholders to enact systemic change that will harmonize the current fragmented approaches to kidney-failure registry data collection and research
Quantitative estimates for simple zeros of <i>L-</i>functions
We generalize a method of Conrey and Ghosh (Invent. Math. 94 (1988)) to prove
quantitative estimates for simple zeros of modular form L-functions of
arbitrary conductor.Comment: 19 pages, to appear in Mathematik
State/Operator Correspondence in Higher-Spin dS/CFT
A recently conjectured microscopic realization of the dS/CFT
correspondence relating Vasiliev's higher-spin gravity on dS to a Euclidean
CFT is used to illuminate some previously inaccessible aspects of
the dS/CFT dictionary. In particular it is argued that states of the boundary
CFT on are holographically dual to bulk states on geodesically
complete, spacelike slices which terminate on an at future
infinity. The dictionary is described in detail for the case of free scalar
excitations. The ground states of the free or critical model are dual
to dS-invariant plane-wave type vacua, while the bulk Euclidean vacuum is dual
to a certain mixed state in the CFT. CFT states created by operator
insertions are found to be dual to (anti) quasinormal modes in the bulk. A norm
is defined on the bulk Hilbert space and shown for the scalar case to be
equivalent to both the Zamolodchikov and pseudounitary C-norm of the
CFT.Comment: 24 page
Quantifying single nucleotide variant detection sensitivity in exome sequencing
BACKGROUND: The targeted capture and sequencing of genomic regions has rapidly demonstrated its utility in genetic studies. Inherent in this technology is considerable heterogeneity of target coverage and this is expected to systematically impact our sensitivity to detect genuine polymorphisms. To fully interpret the polymorphisms identified in a genetic study it is often essential to both detect polymorphisms and to understand where and with what probability real polymorphisms may have been missed. RESULTS: Using down-sampling of 30 deeply sequenced exomes and a set of gold-standard single nucleotide variant (SNV) genotype calls for each sample, we developed an empirical model relating the read depth at a polymorphic site to the probability of calling the correct genotype at that site. We find that measured sensitivity in SNV detection is substantially worse than that predicted from the naive expectation of sampling from a binomial. This calibrated model allows us to produce single nucleotide resolution SNV sensitivity estimates which can be merged to give summary sensitivity measures for any arbitrary partition of the target sequences (nucleotide, exon, gene, pathway, exome). These metrics are directly comparable between platforms and can be combined between samples to give âpower estimatesâ for an entire study. We estimate a local read depth of 13X is required to detect the alleles and genotype of a heterozygous SNV 95% of the time, but only 3X for a homozygous SNV. At a mean on-target read depth of 20X, commonly used for rare disease exome sequencing studies, we predict 5â15% of heterozygous and 1â4% of homozygous SNVs in the targeted regions will be missed. CONCLUSIONS: Non-reference alleles in the heterozygote state have a high chance of being missed when commonly applied read coverage thresholds are used despite the widely held assumption that there is good polymorphism detection at these coverage levels. Such alleles are likely to be of functional importance in population based studies of rare diseases, somatic mutations in cancer and explaining the âmissing heritabilityâ of quantitative traits
Niemann-Pick C1 (NPC1)/NPC1-like1 Chimeras Define Sequences Critical for NPC1âs Function as a Filovirus Entry Receptor
We recently demonstrated that Niemann-Pick C1 (NPC1), a ubiquitous 13-pass cellular membrane protein involved in lysosomal cholesterol transport, is a critical entry receptor for filoviruses. Here we show that Niemann-Pick C1-like1 (NPC1L1), an NPC1 paralog and hepatitis C virus entry factor, lacks filovirus receptor activity. We exploited the structural similarity between NPC1 and NPC1L1 to construct and analyze a panel of chimeras in which NPC1L1 sequences were replaced with cognate sequences from NPC1. Only one chimera, NPC1L1 containing the second luminal domain (C) of NPC1 in place of its own, bound to the viral glycoprotein, GP. This engineered protein mediated authentic filovirus infection nearly as well as wild-type NPC1, and more efficiently than did a minimal NPC1 domain C-based receptor recently described by us. A reciprocal chimera, NPC1 containing NPC1L1âs domain C, was completely inactive. Remarkably, an intra-domain NPC1L1-NPC1 chimera bearing only a ~130-amino acid Nâterminal region of NPC1 domain C could confer substantial viral receptor activity on NPC1L1. Taken together, these findings account for the failure of NPC1L1 to serve as a filovirus receptor, highlight the central role of the luminal domain C of NPC1 in filovirus entry, and reveal the direct involvement of Nâterminal domain C sequences in NPC1âs function as a filovirus receptor
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