Changes in thermal nociceptive responses in dairy cows following experimentally induced Escherichia coli mastitis

<p>Abstract</p> <p>Background</p> <p>Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS) in dairy cows with experimentally induced <it>Escherichia coli </it>mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables.</p> <p>Methods</p> <p>Seven Danish Holstein-Friesian cows were kept in tie-stalls, where the <it>E. coli </it>associated mastitis was induced and laser stimulations were conducted. Measurements of rectal temperature, somatic cell counts, white blood cell counts and <it>E. coli </it>counts were conducted. Furthermore, scores were given for anorexia, local udder inflammation and milk appearance to quantify the local and systemic disease response. In order to quantify the nociceptive threshold, behavioral responses toward cutaneous NLS applied to six skin areas at the tarsus/metatarsus and udder hind quarters were registered at evening milking on day 0 (control) and days 1, 2, 3, 6 and 10 after experimental induction of mastitis.</p> <p>Results</p> <p>All clinical and paraclinical variables were affected by the induced mastitis. All cows were clinically ill on days 1 and 2. The cows responded behaviorally toward the NLS. For hind leg stimulation, the proportion of cows responding by stepping was higher on day 0 than days 3 and 6, and the frequency of leg movements after laser stimulation tended to decrease on day 1 compared to the other days. After udder stimulation, the proportion of cows responding by stepping was higher on day 1 than on all other days of testing. Significant correlations between the clinical and paraclinical variables of disease and the behavioral responses toward nociceptive stimulation were found.</p> <p>Conclusions</p> <p>Changes in behavioral responses coincide with peaks in local and systemic signs of E. coli mastitis. During the acute stage of E. coli mastitis nociceptive thermal stimulation on hind leg and mammary glands results in decreased behavioral responses toward nociceptive stimulation, which might be interpreted as hypoalgesia.</p

Twenty weeks of home-based interactive training of children with cerebral palsy improves functional abilities

BACKGROUND: Home-based training is becoming ever more important with increasing demands on the public health systems. We investigated whether individualized and supervised interactive home-based training delivered through the internet improves functional abilities in children with cerebral palsy (CP). METHODS: Thirty four children with CP (aged 9–16; mean age 10.9 ± 2.4 years) (GMFCS I-II; MACS I-II) were included in this non-randomized controlled clinical training study. 12 children (aged 7–16; mean age: 11.3+/−0.9 years) were allocated to a control group in which measurements were performed with 20 weeks interval without any intervening training. Daily activities, functional abilities of upper- and lower limbs, and balance were evaluated before, immediately after training and 12 weeks after training. The training consisted of 30 min daily home-based training for 20 weeks delivered through the internet. RESULTS: The training group on average completed 17 min daily training for the 20 week period (total of 40 h of training). The training group showed significant improvements of daily activities (AMPS), upper limb function (AHA) and functional tests of lower limbs (sit to stand, lateral step up, half knee to standing) after 20 weeks of training. No difference was found between the test after 20 weeks of training and the test 12 weeks after training. No significance was reached for balance after training. No difference was found for any parameter for the control group. CONCLUSIONS: Interactive home training of children with CP is an efficient way to deliver training, which can enable functional motor improvements and increased activity to perform daily activities. TRIAL REGISTRATION: ISRCTN13188513. Date of registration: 04/12/201

Intraoperative Ultrasound: A Tool to Support Tissue-Sparing Curative Pancreatic Resection in Focal Congenital Hyperinsulinism

Background: Focal congenital hyperinsulinism (CHI) may be cured by resection of the focal, but often non-palpable, pancreatic lesion. The surgical challenge is to minimize removal of normal pancreatic tissue.Aim: To evaluate the results of intraoperative ultrasound-guided, tissue-sparing pancreatic resection in CHI patients at an international expert center.Methods: Retrospective study of CHI patients treated at Odense University Hospital, Denmark, between January 2010 and March 2017.Results: Of 62 consecutive patients with persistent CHI, 24 (39%) had focal CHI by histology after surgery. All patients had a paternal ABCC8 or KCNJ11 mutation and a focal lesion by 18F-DOPA-PET/CT. Intraoperative ultrasound localized the focal lesion in 16/20 patients (sensitivity 0.80), including one ectopic lesion in the duodenal wall. Intraoperative ultrasound showed no focal lesion in 11/11 patients with diffuse CH (specificity 1.0). The positive predictive value for focal histology was 1.0, negative predictive value 0.73.Tissue-sparing pancreatic resection (focal lesion enucleation, local resection of tail or uncinate process) was performed in 67% (n = 16). In 11/12 having tissue-sparing resection and intraoperative ultrasound, the location of the focal lesion was exactly identified. Eight patients had resection of the pancreatic head or head/body, four with Roux-en-Y, three with pancreatico-gastrostomy and one without reconstruction. None had severe complications to surgery. Cure of hypoglycaemia was seen in all patients after one (n = 21) or two (n = 3) pancreatic resections.Conclusion: In focal CHI, tissue-sparing pancreatic resection was possible in 67%. Intraoperative ultrasound was a helpful supplement to the mandatory use of genetics, preoperative 18F-DOPA-PET/CT and intraoperative frozen sections

Stepwise bending of DNA by a single TATA-box Binding Protein

The TATA-box Binding Protein (TBP) is required by all three eukaryotic RNA polymerases for the initiation of transcription from most promoters. TBP recognizes, binds to, and bends promoter sequences called ``TATA-boxes'' in the DNA. We present results from the study of individual Saccharomyces cerevisia TBPs interacting with single DNA molecules containing a TATA-box. Using video microscopy, we observed the Brownian motion of beads tethered by short surface-bound DNA. When TBP binds to and bends the DNA, the conformation of the DNA changes and the amplitude of Brownian motion of the tethered bead is reduced compared to that of unbent DNA. We detected individual binding and dissociation events and derived kinetic parameters for the process. Dissociation was induced by increasing the salt concentration or by directly pulling on the tethered bead using optical tweezers. In addition to the well-defined free and bound classes of Brownian motion, we observed another two classes of motion. These extra classes were identified with intermediate states on a three-step, linear binding pathway. Biological implications of the intermediate states are discussed.Comment: Accepted for publication in: Biophysical Journa