Picalm, a novel regulator of GLUT4-trafficking in adipose tissue.

Objective: Picalm (phosphatidylinositol-binding clathrin assembly protein), a ubiquitously expressed clathrin-adapter protein, is a well-known susceptibility gene for Alzheimer's disease, but its role in white adipose tissue (WAT) function has not yet been studied. Transcriptome analysis revealed differential expression of Picalm in WAT of diabetes-prone and diabetes-resistant mice, hence we aimed to investigate the potential link between Picalm expression and glucose homeostasis, obesity-related metabolic phenotypes, and its specific role in insulin-regulated GLUT4 trafficking in adipocytes.

Methods: Picalm expression and epigenetic regulation by microRNAs (miRNAs) and DNA methylation were analyzed in WAT of diabetes-resistant (DR) and diabetes-prone (DP) female New Zealand Obese (NZO) mice and in male NZO after time-restricted feeding (TRF) and alternate-day fasting (ADF).

Rational design and evaluation of 2-((pyrrol-2-yl)methylene)thiophen-4-ones as RNase L inhibitors.

Ribonuclease L (RNase L) plays a crucial role in an antiviral pathway of interferon-induced innate immunity by degrading RNAs to prevent viral replication. Modulating RNase L activity thus mediates the innate immune responses and inflammation. Although a few small molecule-based RNase L modulators have been reported, only limited molecules have been mechanistically investigated.

Small-molecule screening of ribonuclease L binders for RNA degradation.

Small molecules targeting the ubiquitous latent ribonuclease (RNase L), which has limited sequence specificity toward single-stranded RNA substrates, hold great potential to be developed as broad-spectrum antiviral drugs by modulating the RNase L-mediated innate immune responses. The recent development of proximity-inducing bifunctional molecules, as described in the strategy of ribonuclease targeting chimeras, demonstrated that small-molecule RNase L activators can function as the essential RNase L-recruiting component to design bifunctional molecules for targeted RNA degradation. However, only a single screening study on small-molecule RNase L activators with poor potency has been reported to date.

Synthesis and evaluation of RNase L-binding 2-aminothiophenes as anticancer agents.

Aminothiophene is a scaffold that is widely present in drugs and biologically active small molecules as chemical probes. In this study, 43 compounds sharing a 2-aminothiophenone-3-carboxylate (ATPC) scaffold, known to activate the ribonuclease L (RNase L), were synthesized and selected ATPCs showed enhancement of thermal stability of RNase L upon binding. Screening of antiproliferation activities against human cancer cell lines revealed that ATPCs represented by compounds 4l and 50 showed potent single-digit micromolar antiproliferation activity against human cancer cell lines.

Spindle cell haemangioma of the tongue.

Background: Spindle cell hemangioma (SCH) is an uncommon benign vascular tumor that rarely occurs in the mouth.

Methods And Results: We present an SCH arising in the tongue of a 52-year-old otherwise healthy woman. SCH should be considered in the differential diagnosis of vascular tumors in the oral cavity and not misinterpreted as a more aggressive vascular tumor.

Postoperative immunosuppression after open and laparoscopic liver resection: assessment of cellular immune function and monocytic HLA-DR expression.

Background And Objectives: Major abdominal procedures are strongly associated with postoperative immunosuppression and subsequent increased patient morbidity. It is believed that laparoscopic surgery causes less depletion of the systemic immune function because of the reduced tissue trauma. Various cytokines and monocytic HLA-DR expression have been successfully implemented to assess postoperative immune function.

In a porcine model of mixed acidemia HES 130/0.4 may support more stable hemodynamics during CVVH when compared to gelatine.

Purpose: Continuous veno-venous hemofiltration (CVVH) and mixed acidemia often occur simultaneously in critically ill patients. In a previous study in non-acidemic pigs we found that colloids and CVVH interact specifically with respect to hemodynamic stability, with favorable effects for 6% HES 130/0.4 versus 4% gelatine (GEL) infusion.

Pig specific vascular anatomy allows acute infrarenal aortic occlusion without hind limb ischemia and stepwise occlusion without clinical signs.

Objective: In a porcine, aortic graft model we found 5 animals to develop and survive unnoticed, complete infrarenal aortic occlusion and 2 pigs with an acute occlusion but rather unspecific clinical symptoms. We investigated the pigs' vascular system to classify the anatomic capabilities to compensate for an acute abdominal aortic occlusion.

Design Of Study: Retrospective analysis of CT scans and clinical data to specify unexpected results in a case series of infrarenal occlusion in a porcine model.

Prolonged hypoxemia and acidemia in anesthetized pigs: a model for research on extracorporeal organ support in an intensive care setting.

Purpose: Hypoxemia and acidemia (hypoxemia/acidemia) are serious complications in the critically ill and often occur in unstable patients exposed to extracorporeal organ support. Still, little is known about the biocompatibility interactions of hypoxemia/acidemia with extracorporeal circuits (ECC). Existing animal models often include the release of mediator cascades (sepsis-, lung injury models) or are based on small laboratory animals.

Audiological findings after multichannel cochlear implantation in patients with Mondini dysplasia.

Mondini dysplasia is a congenital malformation of the inner ear. To date, five individuals with this malformation have received cochlear implants at the South of England Cochlear Implant Centre. The aim of this study was to review the audiological findings of these individuals after implantation.

Comparison of two cochlear implant speech processors in better versus poorer performers.

The performance and subjective preferences for two different speech-processing strategies, the Speak strategy in the Cochlear Spectra 22 speech processor and the Multipeak (Mpeak) strategy in the Mini Speech Processor (MSP), are compared within two adult patient groups. Ten experienced cochlear implant (CI) users were selected for this study. One group of 5 CI users have significant open-set speech recognition, and the second group consisted of experienced CI users who have little or no open-set speech recognition on standardized tests (< 30% on sentence tests; < 10% on monosyllabic word tests).

A longitudinal study of symptoms, anxiety and subjective well-being in patients with vertigo.

In a prospective longitudinal study of the relationship between symptoms and anxiety in people with vertigo, 101 patients were evaluated on two occasions separated by a 7 month interval. At Time 1 the age, gender, vertigo type, duration of illness, medication, and audiovestibular test results of patients were recorded, and they completed questionnaires assessing handicap, emotional distress, predisposition to anxiety, and symptoms indicative of vertigo and of somatic anxiety. These questionnaires were re-administered at Time 2, and patients also indicated whether their vertigo was more or less severe than at Time 1.

Symptoms, anxiety and handicap in dizzy patients: development of the vertigo symptom scale.

Questionnaires assessing symptoms, anxiety and handicap were completed by 127 vertiginous patients. Factor analysis identified four distinct symptom clusters which formed the basis for the construction of scales quantifying the number and frequency of symptoms of: (a) vertigo (of long and short duration); (b) autonomic sensations and anxiety arousal; and (c) somatization. Scores on the vertigo severity scale were significantly related to clinical diagnosis and had near-zero correlations with measures of anxiety.

Somatic and psychological factors contributing to handicap in people with vertigo.

Questionnaires assessing symptoms, disability and handicap, predisposition to anxiety, and current anxiety and depression were completed by 127 people attending neuro-otology clinics with a major complaint of vertigo or dysequilibrium. Definite signs of vestibular dysfunction (spontaneous or positional nystagmus, or canal paresis) were found in 56% of the sample, but the presence or absence of abnormal vestibular test results was unrelated to diagnosis, reported symptoms, handicap and psychological status. Two-thirds of employed respondents admitted to occupational difficulties, and more than one in seven had left work because of vertigo.

A non-invasive, objective test of endolymphatic hydrops.

Our previous work has shown that auditory brainstem responses (ABRs) can be used to measure the basilar membrane travelling wave velocity (TWV). Based upon the hypothesis that increased pressure in the scala media will increase the stiffness of the basilar membrane and, hence, increase the speed of the travelling wave. ABRs have been used to provide a means of objectively testing for endolymphatic hydrops.

Verification of a new test of endolymphatic hydrops.

A new objective test of endolymphatic hydrops has been described previously. The test uses auditory brain-stem response (ABR) techniques to estimate the basilar membrane travelling wave velocity (TWV). The underlying hypothesis is that raised pressure in the scala media will lead to an increase in the stiffness of the basilar membrane and that this will give rise to a travelling wave velocity that is greater than normal.