Polyautoimmunity in patients with cutaneous lupus erythematosus: A nationwide sex- and age-matched cohort study from Denmark.

Background: Polyautoimmunity is defined as having 2 or more autoimmune diseases. Little is known about polyautoimmunity in patients with cutaneous lupus erythematosus (CLE). Objectives: To estimate prevalence and 5-year incidence of non-lupus erythematosus (LE) autoimmune diseases in patients with CLE. Methods: Patients with CLE were identified In the Danish National Patient Registry and each patient was age- and sex-matched with 10 general population controls. Outcome information on non-LE autoimmune diseases was obtained by register-linkage between Danish National Patient Registry and the National Prescription Register. The risk ratio (RR) for prevalent non-LE autoimmune disease at time of CLE diagnosis was calculated in modified Poisson regression; and hazard ratios (HRs) for incident non-LE autoimmune disease were estimated in Cox regression analyses. Results: Overall, 1674 patients with CLE had a higher prevalence of a non-LE autoimmune disease than the comparators (18.5 vs 7.9%; RR 2.4; 95% CI, 2.1 to 2.6). Correspondingly, the cumulative incidence of a non-LE autoimmune disease during 5 years of follow-up was increased for the patients with CLE: HR 3.5 (95% CI, 3.0 to 4.0). Limitations: Risk of detection and misclassification bias, mainly pertaining to the CLE group. Conclusion: Patients with CLE had higher prevalence and 5-year cumulative incidence of a non-LE autoimmune disease than the general population.

Neuromodulation of somatosensory pain thresholds of the neck musculature using a novel transcranial direct current stimulation montage: a randomized double-blind, sham controlled study.

OBJECTIVES: Anodal transcranial direct current stimulation (tDCS) of primary motor cortex (M1) and cathodal of the primary sensory cortex (S1) have previously shown to modulate the sensory thresholds when administered with the reference electrode located over the contralateral supraorbital area (SO). Combining the two stimulation paradigms into one with simultaneous stimulation of the two brain areas (M1 + S1 - tDCS) may result in a synergistic effect inducing a prominent neuromodulation, noticeable in the pain thresholds. The aim of this study is to assess the efficacy of the novel M1 + S1 - tDCS montage compared to sham-stimulation in modulating the pain thresholds in healthy adults. METHODS: Thirty-nine (20 males) subjects were randomly assigned to either receiving 20 min. active M1 + S1 - tDCS or sham tDCS in a double-blinded single session study. Thermal and mechanical pain thresholds were assessed before and after the intervention. RESULTS: There were no significant differences in the pain thresholds within either group, or between the M1 + S1 - tDCS group and the Sham-tDCS group (p>0.05), indicating that the intervention was ineffective in inducing a neuromodulation of the somatosensory system. CONCLUSIONS: Experimental investigations of novel tDCS electrode montages, that are scientifically based on existing studies or computational modelling, are essential to establish better tDCS protocols. Here simultaneous transcranial direct current stimulation of the primary motor cortex and primary sensory cortex showed no effect on the pain thresholds of the neck musculature in healthy subjects. This tDCS montage may have been ineffective due to how the electrical field reaches the targeted neurons, or may have been limited by the design of a single tDCS administration. The study adds to the existing literature of the studies investigating effects of new tDCS montages with the aim of establishing novel non-invasive brain stimulation interventions for chronic neck pain rehabilitation. North Denmark Region Committee on Health Research Ethics (VN-20180085) ClinicalTrials.gov (NCT04658485).

Metabolic engineering of Pseudomonas putida for production of vanillylamine from lignin-derived substrates.

Whole-cell bioconversion of technical lignins using Pseudomonas putida strains overexpressing amine transaminases (ATAs) has the potential to become an eco-efficient route to produce phenolic amines. Here, a novel cell growth-based screening method to evaluate the in vivo activity of recombinant ATAs towards vanillylamine in P. putida KT2440 was developed. It allowed the identification of the native enzyme Pp-SpuC-II and ATA from Chromobacterium violaceum (Cv-ATA) as highly active towards vanillylamine in vivo. Overexpression of Pp-SpuC-II and Cv-ATA in the strain GN442ΔPP_2426, previously engineered for reduced vanillin assimilation, resulted in 94- and 92-fold increased specific transaminase activity, respectively. Whole-cell bioconversion of vanillin yielded 0.70 ± 0.20 mM and 0.92 ± 0.30 mM vanillylamine, for Pp-SpuC-II and Cv-ATA, respectively. Still, amine production was limited by a substantial re-assimilation of the product and formation of the by-products vanillic acid and vanillyl alcohol. Concomitant overexpression of Cv-ATA and alanine dehydrogenase from Bacillus subtilis increased the production of vanillylamine with ammonium as the only nitrogen source and a reduction in the amount of amine product re-assimilation. Identification and deletion of additional native genes encoding oxidoreductases acting on vanillin are crucial engineering targets for further improvement.

Heart rate monitored hypothermia and drowning in a 48-year-old man. survival without sequelae: a case report.

INTRODUCTION: Victims of severe hypothermia and cardiac arrest may appear dead. They are often unresponsive to on-scene resuscitation including defibrillation while profoundly hypothermic. Several cases of extreme hypothermia and prolonged cardiac arrest with good outcome have been published. We present a case of heart rate monitored (by pulse-watch) hypothermia, prolonged cardiac arrest and survival with complete recovery of neurological functions. CASE PRESENTATION: On December 22nd 2007 a physically fit, ethnic Norwegian 48-year-old male kayaker set out to paddle alone around an island in a Norwegian fjord. 3 hours 24 min into his trip the kayak capsized in 3.5 degrees C seawater about 500m from the closest shore. The accident was not observed. He managed to call for help using his cellular phone. After a search and rescue operation he was found by our air ambulance helicopter floating, prone, head submerged, with cardiopulmonary arrest and profound hypothermia. He was wearing a personal heart rate monitor/pulse watch. Following extraction, he received cardiopulmonary resuscitation during transport by air ambulance helicopter to hospital. He was warmed on cardiopulmonary bypass from 20.6 degrees C core temperature and return of spontaneous circulation was achieved 3h 27 m after cardiac arrest occurred. After 21 days of intensive care he was discharged from hospital 32 days after his accident. Testing revealed normal cognitive functions one year after the incident. He has returned to his job as an engineer, and has also taken up kayaking again. We provide heart rate and time data leading up to his cardiac arrest. CONCLUSION: Hypothermia has well established neuro-protective effects in cardiac arrest, as our case also shows. Simple cardiopulmonary resuscitation without use of drugs or defibrillation, should be continued until the patients can be re-warmed, preferably using cardiopulmonary bypass. This approach can be highly effective even in seemingly lost cases.

Limb salvage instead of amputation in 10 cases of nonreconstructible "end-point ischemia" treated with i.v. hydroxyethylrutosides plus oral anticoagulation.

The authors report on limb salvage in 10 cases of "end-point ischemia," already scheduled for urgent amputation, selected from a group of 42 atherosclerotic cases with critical limb ischemia according to the definition of the Second European Consensus Document on Critical Limb Ischemia. Patients were treated for 3 to 4 weeks with intravenous infusions of the rheologic, antioxidant and endotheliumprotective flavonoid mixture 0-(beta-hydroxyethyl)-rutosides (HR) (Venoruton; Zyma, now Novartis) which improves microvascular blood perfusion and possesses antiedematous effects. The infusions were combined with oral anticoagulation (Waran) which was continued afterwards as long-term treatment for at least 2 years. In some cases anticoagulation was later replaced by low-dose aspirin. A statistically significant favorable effect was found for both limb salvage and survival--the 10 selected cases of limb salvage in spite of "end-point ischemia" also included 1 uremic case on hemodialysis with very severe rest pain and toe necrotization. Improved microcirculation following soon after the start of treatment was observed in all 10 cases as well as an often very rapid alleviation of rest pain and beginning healing of ischemic lesions. The follow-up showed a preservation of the threatened limb for a mean time of 7.9 years in the atherosclerotic group and, in spite of high age at start of treatment (mean age 72 years), an apparently long survival of those patients who had died, on average 7.7 years. Because side effects are rare and there is a rapid alleviation of rest pain, it may be possible to give the HR infusions safely on an ambulatory basis in the out-patient department.