Treatment with pancreatic enzymes fails to completely correct malabsorption and gastrointestinal symptoms in patients with cystic fibrosis (CF). The aim of the present study was to examine the small ...intestine of patients with CF without overt evidence of gastrointestinal disease using capsule endoscopy (CE).
Patients with CF received the agile patency capsule and, depending on the result of that procedure, then underwent standard CE using the PillCam SB capsule (Given Imaging, Yokneam, Israel). A stool specimen was taken on the same day as the CE for determination of the calprotectin level.
Forty-two patients with CF ages 10 to 36 years were included; 29 had pancreatic insufficiency. One patient failed to excrete the patency capsule after 36 hours and was withdrawn from the study. Pulmonary function was mild to moderate with FEV1 68.5% +/- 16% predicted. Review of the CE videos showed that most of the patients had varying degrees of diffuse areas of inflammatory findings in the small bowel including edema, erythema, mucosal breaks, and frank ulcerations. There were no adverse events. Fecal calprotectin levels were markedly high in patients with pancreatic insufficiency, 258 microg/g (normal <50).
Small bowel mucosal pathology may be detected using CE in most of the patients with CF. The high fecal calprotectin levels found are suggestive of mucosal inflammation, which may correlate with the CE findings. Additional study is required to examine the possible relation of these mucosal lesions, which may be part of a newly identified enteropathy associated with CF, with persistent intestinal malabsorption in many of these patients.
Organoids, combined with genetic editing strategies, have the potential to offer rapid and efficient investigation of gene function in many models of human disease. However, to date, the editing ...efficiency of organoids with the use of non-viral electroporation methods has only been up to 30%, with implications for the subsequent need for selection, including turnaround time and exhaustion or adaptation of the organoid population. Here, we describe an efficient method for intestinal organoid editing using a ribonucleoprotein-based CRISPR approach. Editing efficiencies of up to 98% in target genes were robustly achieved across different gut anatomical locations and developmental timepoints from multiple patient samples with no observed off-target editing. The method allowed us to study the effect of loss of the tumour suppressor gene PTEN in normal human intestinal cells. Analysis of PTEN-deficient organoids defined phenotypes that likely relate to its tumour suppressive function in vivo, such as a proliferative advantage and increased organoid budding. Transcriptional profiling revealed differential expression of genes in pathways commonly known to be associated with PTEN loss, including mTORC1 activation.
Despite decades of significant effort in research, policy, and prevention, suicide rates have continued to rise to the current peak of 14.6 per 100,000 deaths. This has resulted in a concerted effort ...to identify biomarkers associated with suicidal behavior in the brain, to provide predictions that are better than the chance of discerning who will die by suicide. We propose that the lateral habenula (LHb), and its dysfunction during a suicidal crisis, is a critical component of the transition from suicidal ideations to self-harm. Moreover, the LHb-a key functional node in brain reward circuitry-has not been ascribed a contributory role in suicidal behavior. We argue that the LHb anchors a "suicide circuit" and call for suicide researchers to directly examine the role of the LHb, and its long-term modulation, in response to the negative affect in suicidal behavior. Discerning the neural mechanisms of this contribution will require the collaboration of neuroscientists and psychologists. Consequently, we highlight and discuss research on LHb as it relates to suicidal ideation, suicidal behavior, or death by suicide. In so doing we hope to address the bench-to-bedside translational issues currently involved in suicide research and suggest a developmental framework that focuses on specific structures motivated by theoretical anchors as a way to incorporate neurobiological findings within the context of clinical theory.
Joe Manchin's Senate career began in 2010 with a bang. His race should have been a cakewalk. A popular governor and the son of a respected political family with deep roots in the Mountain State, he'd ...won endorsements from the Chamber of Commerce, the NRA, the mine workers, and their bosses. And his opponent, John Raese, was a perennial GOP also-ran, a steel and limestone magnate whom Manchin had credibly accused of trying to "buy" the election with $500,000 of his own money. By September, Raese had pulled ahead. Manchin was still popular, but Barack Obama was not. Smelling blood, Republicans cut an attack ad featuring West Virginians in plaid and frayed baseball caps sitting at a diner counter, grousing that "Washington Joe" had supported every-thingthe president had put before Congress, from the economic stimulus to the Affordable Care Act. The hit landed. But when a copy of the casting call for the ad which was, as it turned out, filmed in Philadelphia with professional actors leaked to Politico, Manchin was able to turn it against Raese.
Volked Up Adler-Bell, Sam
The New republic,
10/2019, Letnik:
250, Številka:
10
Magazine Article
Adler-Bell examines the ugly modern roots of eco-fascism. Fascists have long shared farmers' preoccupation with green living. The past few years have seen a resurgence of eco-fascist and ...eco-nationalist themes in the rhetoric of Europe's far-right parties and in the writings of online radicals. Some, inspired by Netflix's recent thriller about Ted Kaczynski, have embraced the Unabomber's nihilist primitivism. Others have adopted Norse aesthetics and a radically anti-humanist version of "deep ecology." Both the Christchurch and El Paso mass shooters included environmentalist themes in their white-nationalist manifestos. When writing about eco-fascists, the media often speaks of green politics "masking" a darker racial vision. But most eco-fascists are sincere in their environmentalism.
Choreographing the Whirlwind Adler-Bell, Sam
The New republic,
03/2019, Letnik:
250, Številka:
3
Magazine Article
Adler-Bell focuses on the proliferation of the social movements and the political upheavals in the U.S. Topics discussed include an overview of the political system in the country, and the leadership ...skills of the politicians.
A patient with chronic schizophrenia treated with fluphenazine developed neuroleptic malignant syndrome, characterized by fever, obtundation, rigidity, and tremulousness. Hyperthermia and elevated ...serum creatine kinase were successfully corrected by parenteral treatment with dantrolene. Obtundation, rigidity, and tremulousness responded to high doses of bromocriptine.
