The efficacy and safety of a third anti-TNF monoclonal antibody in Crohn's disease after failure of two other anti-TNF antibodies.

BACKGROUND: Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn's disease (CD) patients previously treated with infliximab (IFX). AIM: To assess the efficacy and tolerability of a third anti-TNF in CD after failure of and/or intolerance to two different anti-TNF antibodies. METHODS: Crohn's disease patients who received ADA or CZP after loss of response and/or intolerance to two anti-TNF agent were included in this retrospective study. Data were collected using a standardized questionnaire. Clinical response, duration, safety and reasons for discontinuation were assessed. RESULTS: Sixty-seven patients treated with CZP (n = 40) or ADA (n = 27) were included. A clinical response was observed in 41 (61%) at week 6 and 34 patients (51%) at week 20. The probability of remaining under treatment at 3 months, 6 months and 9 months was 68%, 60% and 45%, respectively. At the end of follow-up, the third anti-TNF had been stopped in 36 patients for intolerance (n = 13), or failure (n = 23). Two deaths were observed. CONCLUSIONS: The treatment with a third anti-TNF (CZP or ADA) agent of CD patients, who have experienced loss of response and/or intolerance to two anti-TNF antibodies, has favourable short-term and long-term efficacy. It is an option to be considered in patients with no other therapeutic options.

bHLH class transcription factors take centre stage in phytochrome signalling.

The phytochrome family of photoreceptors (there are five phytochromes in Arabidopsis, named phyA to phyE) maximally absorbs red and far-red light and plays important functions throughout the life cycle of plants. Several recent studies have shown that multiple related bHLH (basic helix-loop-helix) class transcription factors play key roles in phytochrome signal transduction. Somewhat surprisingly these transcription factors primarily act as negative regulators of phytochrome signalling. Moreover, in some cases, the phytochromes inhibit those negative regulators.

Stream Stabilization in Western Iowa, HR-352, 1994

Stream channel erosion in the deep loess soils region of western Iowa causes severe damage along hundreds of miles of streams in twenty-two counties. The goal of this project was to develop information, systems, and procedures for use in making resource allocation decisions related to the protection of transportation facilities and farmland from damages caused by stream channel erosion. Section one of this report provides an introduction. Section two presents an assessment of stream channel conditions from aerial and field reconnaissance conducted in 1993 and 1994 and a classification of the streams based on a six stage model of stream channel evolution. A Geographic Information System is discussed that has been developed to store and analyze data on the stream conditions and affected infrastructure and assist in the planning of stabilization measures. Section three presents an evaluation of two methods for predicting the extent of channel degradation. Section four presents an estimate of costs associated with damages from stream channel erosion since the time of channelization until 1992. Damage to highway bridges represent the highest costs associated with channel erosion, followed by railroad bridges and right-of-way; loss of agricultural land represents the third highest cost. An estimate of costs associated with future channel erosion on western Iowa streams is also presented in section four. Section four also presents a procedure to estimate the benefits and costs of implementing stream stabilization measures. The final section of this report, section five, presents information on the development of the organizational structure and administrative procedures which are being used to plan, coordinate, and implement stream stabilization projects and programs in western Iowa.

Monthly Labor Force Data, December 2013

Monthly Labor Force Data report produced by the Iowa Workforce Development.

Monthly Labor Force Data, January 2014

Monthly Labor Force Data report produced by the Iowa Workforce Development.

Monthly Labor Force Data, March 2014

Monthly Labor Force Data report produced by the Iowa Workforce Development.

Neuronal calcium channel mutation in a patient with congenital ataxia and attacks of hemiplegic migraine with cerebral edema

Background: Familial Hemiplegic Migraine (FHM), characterized by a prolonged unilateral hemiparesis, mainly results from mutations in the alpha-1a subunit of the calcium channel gene CACNA1A that can also cause two other dominantly inherited neurological disorders, Episodic Ataxia type 2 (EA2, with sometimes migrainous headaches) and Spinocerebellar Ataxia type 6 (SCA6, late-onset and progressive). A same mutation can have different clinical expression in a family (hemiplegic migraine, migraine-coma, cerebellar ataxia). CACNA1A mutations in FHM are usually missense, leading to gain-of-function, while truncating mutations leading to loss-of-function are usually associated with EA2. Case report: This 9-year-old girl was seen as a baby for hypotonia and transient vertical nystagmus. Her first brain MRI was normal. She evolved as a congenital ataxia, but since the age of two, she had attacks of coma, hemiparesis (either side), partial seizures, dystonic movements and fever. Attacks were initially triggered by minor head bumps, subsequently spontaneous. Brain MRIs in the acute stage always showed transient unilateral hemisphere swelling. Follow-up images revealed atrophic lesions in the temporo-occipital regions and cerebellar atrophy. A prophylactic trial with flunarizine was ineffective. Acetazolamide was recently introduced. Methods: Since our patient shared features of both FHM and EA2, we studied the CACNA1A gene by direct sequencing in the patient's and parents' DNA. Results: We identified an unreported de novo heterozygous deletion of three base pairs (c.4503_4505delCTT) predicting the deletion of one amino acid (p.Phe1502del). The CACNA1A protein contains 4 domains, each formed by six transmembrane segments. The deletion is located in a highly conserved region in segment 6 (S6) of the third domain. Mutations in S6 segments of calcium channels change single-channel conductance and channel selectivity, most resulting in loss-of-function. Outlook: In vitro expression studies of the identified mutation are underway, aiming at understanding its functional consequences and finding an efficient treatment.

Monthly Labor Force Data, April 2014

Monthly Labor Force Data report produced by the Iowa Workforce Development.

Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial.

BACKGROUND: The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. METHODS AND RESULTS: Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. CONCLUSIONS: Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.

Quality of life following third molar removal under conscious sedation

Aim: The aim of this study was to assess quality of life (QoL) and degree of satisfaction among outpatients subjected to surgical extraction of all four third molars under conscious sedation. A second objective was to describe the evolution of self-reported pain measured in a visual analogue scale (VAS) in the 7 days after extraction. Study design: Fifty patients received a questionnaire assessing social isolation, working isolation, eating and speaking ability, diet modifications, sleep impairment, changes in physical appearance, discomfort at suture removal and overall satisfaction at days 4 and 7 after surgery. Pain was recorded by patients on a 100-mm pain visual analogue scale (VAS) every day after extraction until day 7. Results: Thirty-nine patients fulfilled correctly the questionnaire. Postoperative pain values suffered small fluctuations until day 5 (range: 23 to 33 mm in a 100-mm VAS), when dicreased significantly. A positive association was observed between difficult ranked surgeries and higher postoperative pain levels. The average number of days for which the patient stopped working was 4.9. Conclusion: The removal of all third molars in a single appointment causes an important deterioration of the patient"s QoL during the first postoperative week, especially due to local pain and eating discomfort.

Monthly Labor Force Data, May 2014

Monthly Labor Force Data report produced by the Iowa Workforce Development.

Monthly Labor Force Data, June 2014

Monthly Labor Force Data report produced by the Iowa Workforce Development.