Ascorbic Acid is an Abettor in Calcium Urolithiasis: An Experimental Study

Two sets of animal experiments using guinea pigs were planned to evaluate the effect of ascorbic acid supplementation on the lithogenic process. In the first set of experiments, 10, 40, and 60 mg doses of ascorbic acid/100g body weight/day were given for 105 days. Neither of the ascorbic acid doses given induced crystalluria, calcification or stone formation, thereby confirming our previous findings that ascorbic acid in the doses used by clinicians does not cause urolith formation. In the second set of experiments, ascorbic acid was supplemented in hypercalciuric (induced by calcium carbonate feeding) and hyperoxaluric (induced by sodium oxalate feeding) animals for 45 days. The results indicated that it exacerbated the calcification process in renal and bladder tissue

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent

Apolipoprotein E knock-out and knock-in mice: atherosclerosis, metabolic syndrome, and beyond: Fig. 1.

Given the multiple differences between mice and men, it was once thought that mice could not be used to model atherosclerosis, principally a human disease. Apolipoprotein E-deficient (apoEKO) mice have convincingly changed this view, and the ability to model human-like plaques in these mice has provided scientists a platform to study multiple facets of atherogenesis and to explore potential therapeutic interventions. In addition to its well-established role in lipoprotein metabolism, recent observations of reduced adiposity and improved glucose homeostasis in apoEKO mice suggest that apoE may also play a key role in energy metabolism in peripheral organs, including adipose tissue. Finally, along with apoEKO mice, knockin mice expressing human apoE isoforms in place of endogenous mouse apoE have provided insights into how quantitative and qualitative genetic alterations interact with the environment in the pathogenesis of complex human diseases

Apolipoprotein E4 Exaggerates Diabetic Dyslipidemia and Atherosclerosis in Mice Lacking the LDL Receptor

OBJECTIVEWe investigated the differential roles of apolipoprotein E (apoE) isoforms in modulating diabetic dyslipidemia—a potential cause of the increased cardiovascular disease risk of patients with diabetes.RESEARCH DESIGN AND METHODSDiabetes was induced using streptozotocin (STZ) in human apoE3 (E3) or human apoE4 (E4) mice deficient in the LDL receptor (LDLR−/−).RESULTSDiabetic E3LDLR−/− and E4LDLR−/− mice have indistinguishable levels of plasma glucose and insulin. Despite this, diabetes increased VLDL triglycerides and LDL cholesterol in E4LDLR−/− mice twice as much as in E3LDLR−/− mice. Diabetic E4LDLR−/− mice had similar lipoprotein fractional catabolic rates compared with diabetic E3LDLR−/− mice but had larger hepatic fat stores and increased VLDL secretion. Diabetic E4LDLR−/− mice demonstrated a decreased reliance on lipid as an energy source based on indirect calorimetry. Lower phosphorylated acetyl-CoA carboxylase content and higher gene expression of fatty acid synthase in the liver indicated reduced fatty acid oxidation and increased fatty acid synthesis. E4LDLR−/− primary hepatocytes cultured in high glucose accumulated more intracellular lipid than E3LDLR−/− hepatocytes concomitant with a 60% reduction in fatty acid oxidation. Finally, the exaggerated dyslipidemia in diabetic E4LDLR−/− mice was accompanied by a dramatic increase in atherosclerosis.CONCLUSIONSApoE4 causes severe dyslipidemia and atherosclerosis independent of its interaction with LDLR in a model of STZ-induced diabetes. ApoE4-expressing livers have reduced fatty acid oxidation, which contributes to the accumulation of tissue and plasma lipids

Colocalized Structural and Functional Changes in the Cortex of Patients with Trigeminal Neuropathic Pain

Background: Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level – BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy. Methodology/Principal Findings: Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional (DLPFC, Frontal, Anterior Insula, Cingulate) processing of pain. Both structural and functional (to brush-induced allodynia) scans were obtained and averaged from two different imaging sessions separated by 2–6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions. Conclusions: Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions

The Nineteenth-Century World of Turkic Dictionaries: An Overview

The author creates a bibliographic picture of the various Turkic-language dictionaries from the eleventh to the end of the nineteenth centuries, in various languages, and describes their structure. He then focuses specifically on printed Turkic dictionaries of the nineteenth century, discussing their historical context and a statistical survey that he conducted. A number of these dictionaries have been digitized; he examines some sites where they are accessible. In the appendix is a list of the dictionaries that he found in the course of his research

Flipped Instruction for Information Literacy: Five Instructional Cases of Academic Librarians

University of California, Berkeley librarians have incorporated the flipped instruction model into information literacy training by focusing on two primary elements: assigning pre-class assignments and increasing active learning techniques. We explore these two elements across five diverse instructional cases, which include one-shot and semester-long classes that were conducted through online or in-person delivery for both graduate and undergraduate students across a range of subject areas (sciences, social sciences, and humanities). We examine the enabling factors and the perceived outcomes of this instructional paradigm. Because students came to class with enhanced library understanding and experience from the pre-class assignment, they were better prepared to engage with the material and articulate additional learning needs. We note students' increased engagement during class and more time available for higher-order learning exercises and discussions. As a result, flipped instruction appears to enable more learning opportunities without increasing classroom time. The challenges of this model are the requisite commitment of time and effort, the need to foster class participation, and the facilitation of active communication within the class. We propose a framework of catalysts, building blocks, and instructional outcomes to help library instructors incorporate flipped instruction elements into their instructional design