Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Iron deficiency and preoperative anaemia in patients scheduled for elective hip- and knee arthroplasty - an observational study.

BACKGROUND AND OBJECTIVES: Preoperative anaemia is prevalent in elderly patients scheduled for major orthopaedic surgery and is associated with increased transfusion risk and postoperative morbidity. New guidelines recommend preoperative correction of anaemia and iron deficiency in all patients with a Hb < 13 g/dl. However, iron deficiency and other causes of preoperative anaemia in hip- (THA) and knee (TKA) arthroplasty are only sparsely studied. MATERIALS AND METHODS: Preoperative Hb and iron status were prospectively collected from 882 unselected elective fast-track THA/TKA patients and analysed according to both WHO anaemia criteria (Hb < 12 g/dl females, <13 g/dl males) and Hb < 13 g/dl for both genders. Iron deficiency (ID) and other possible anaemia causes were classified by ferritin, transferrin saturation, P-cobalamin, P-folate, C-reactive protein and creatinine. RESULTS: Ninety-five (10·8%) and 243 (27·6%) of the study population were WHO anaemic or had a Hb < 13 g/dl, respectively. Transfusion was more common in anaemic vs. non-anaemic patients 43 vs. 13%; (P < 0·001), and in patients with Hb < 13 g/dl vs. Hb > 13 g/dl 28 vs. 11% (P < 0·001). 154 (17·5%) of all patients had ID, and ID was the most common cause of anaemia with a prevalence of 41% in WHO anaemic patients and 33% in patients with Hb < 13 g/dl. A further 19 (20%) and 46 (19%) patients, respectively, had evidence of iron sequestration. CONCLUSION: Anaemia is prevalent prior to THA and TKA with iron deficiency as the most common and reversible cause.

Risk factors for post-operative periprosthetic fractures following primary total hip arthroplasty with a proximally coated double-tapered cementless femoral component.

AIMS: The aim of this study was to identify patient- and surgery-related risk factors for sustaining an early periprosthetic fracture following primary total hip arthroplasty (THA) performed using a double-tapered cementless femoral component (Bi-Metric femoral stem; Biomet Inc., Warsaw, Indiana). PATIENTS AND METHODS: A total of 1598 consecutive hips, in 1441 patients receiving primary THA between January 2010 and June 2015, were retrospectively identified. Level of pre-operative osteoarthritis, femoral Dorr type and cortical index were recorded. Varus/valgus placement of the stem and canal fill ratio were recorded post-operatively. Periprosthetic fractures were identified and classified according to the Vancouver classification. Regression analysis was performed to identify risk factors for early periprosthetic fracture. RESULTS: The mean follow-up was 713 days (1 to 2058). A total of 48 periprosthetic fractures (3.0%) were identified during the follow-up and median time until fracture was 16 days, (interquartile range 10 to 31.5). Patients with femoral Dorr type C had a 5.2 times increased risk of post-operative periprosthetic fracture compared with type B, while female patients had a near significant two times increased risk over time for post-operative fracture. CONCLUSION: Dorr type C is an independent risk factor for early periprosthetic fracture, following THA using a double tapered cementless stem such as the Bi-Metric. Surgeons should take bone morphology into consideration when planning for primary THA and consider using cemented femoral components in female patients with poor bone quality. Cite this article: Bone Joint J 2017;99-B:451-7.

Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia.

BACKGROUND: The aim of this study was to examine if gradual withdrawal of remifentanil infusion prevented opioid-induced hyperalgesia (OIH) as opposed to abrupt withdrawal. OIH duration was also evaluated. METHODS: Nineteen volunteers were enrolled in this randomized, double-blinded, placebo-controlled, crossover study. All went through three sessions: abrupt or gradual withdrawal of remifentanil infusion and placebo. Remifentanil was administered at 2.5 ng ml(-1) for 30 min before abrupt withdrawal or gradual withdrawal by 0.6 ng ml(-1) every five min. Pain was assessed at baseline, during infusion, 45-50 min and 105-110 min after end of infusions using the heat pain test (HPT) and the cold pressor test (CPT). RESULTS: The HPT 45 min after infusion indicated OIH development in the abrupt withdrawal session with higher pain scores compared with the gradual withdrawal and placebo sessions (both P<0.01. Marginal mean scores: placebo 2.90; abrupt 3.39; gradual 2.88), but no OIH after gradual withdrawal compared with placebo (P=0.93). In the CPT 50 min after end of infusion there was OIH in both remifentanil sessions compared with placebo (gradual P=0.01, abrupt P<0.01. Marginal mean scores: placebo 4.56; abrupt 5.25; gradual 5.04). There were no differences between the three sessions 105-110 min after infusion. CONCLUSIONS: We found no development of OIH after gradual withdrawal of remifentanil infusion in the HPT. After abrupt withdrawal OIH was present in the HPT. In the CPT there was OIH after both gradual and abrupt withdrawal of infusion. The duration of OIH was less than 105 min for both pain modalities. CLINICAL TRIAL REGISTRATION: NCT 01702389. EudraCT number 2011-002734-39.

Pain and pain tolerance in whiplash-associated disorders: A population-based study.

BACKGROUND: Pain is a cardinal symptom in individuals with whiplash-associated disorders (WAD). We aimed to compare pain characteristics between individuals with WAD and individuals reporting chronic pain from other causes, and to determine whether potential differences were accounted for by experimental pain tolerance. METHODS: Data from the 6th Tromsø Study (2007-2008, n = 12,981) were analysed. The number of painful locations was compared between individuals with WAD and individuals reporting chronic pain from other causes using negative binomial regression, pain frequency using multinomial logistic regression and pain intensity using multiple linear regression. Differences in experimental pain tolerance (cold pressor test) were tested using Cox regression; one model compared individuals with WAD to those with chronic pain from other causes, one compared the two groups with chronic pain to individuals without chronic pain. Subsequently, regression models investigating clinical pain characteristics were adjusted for pain tolerance. RESULTS: Of individuals with WAD, 96% also reported other causes for pain. Individuals with WAD reported a higher number of painful locations [median (inter-quartile range): 5 (3.5-7) vs. 3 (2-5), p < 0.001] and higher pain intensity (crude mean difference = 0.78, p < 0.001) than individuals with chronic pain from other causes. Pain tolerance did not differ between these two groups. Compared to individuals without chronic pain, individuals with WAD and individuals with chronic pain from other causes had reduced pain tolerance. CONCLUSIONS: Individuals with WAD report more additional causes of pain, more painful locations and higher pain intensity than individuals with chronic pain from other causes. The increased pain reporting was not accounted for by pain tolerance.

Persistent post-surgical pain and signs of nerve injury: the Tromsø Study.

BACKGROUND: The contribution of nerve lesions and neuropathic pain to persistent post-surgical pain (PPSP) is poorly established. The aim of this study was to assess the association between PPSP and symptoms and signs of possible nerve injury in an unselected surgical sample. METHODS: Eighty-one individuals with and without persistent pain after surgical procedures, were recruited from a cross-sectional study. Follow-up examination with questionnaires and quantitative sensory testing was performed 15-32 months later (21-64 months after surgery). RESULTS: The median rating of maximum pain intensity among individuals with PPSP decreased from numerical rating scale 4/10 at baseline to 2/10 at follow-up, but considerable changes occurred in both directions. Individuals with PPSP at follow-up were significantly more likely to self-report sensory abnormalities than those without PPSP; however, results from sensory testing did not differ significantly between the groups. Self-report of sensory disturbances at the site of surgery was associated with increased warm detection thresholds and tactile pain thresholds. Among individuals with PPSP, 61% had positive findings on sensory testing, suggesting probable neuropathic pain. CONCLUSION: In this study, associations between self-reported symptoms and PPSP were stronger than associations between self-reported symptoms and results of psychophysical tests. Fluctuations in pain intensity together with wide ranges for normal variability in sensory functions, hampers detection of significant group differences. Methodological aspects of quantitative sensory testing applied in a mixed clinical sample are discussed.

Twin studies of pain.

Twin studies provide a method for estimating the heritability of phenotypes and for examining genetic and environmental relationships between phenotypes. We conducted a systematic review of twin studies of pain, including both clinical and experimental pain phenotypes. Fifty-six papers were included, whereof 52 addressed clinical phenotypes. Of the most comprehensively studied phenotypes, available data indicates heritability around 50% for migraine, tension-type headache and chronic widespread pain, around 35% for back and neck pain, and around 25% for irritable bowel syndrome. However, differences in phenotype definitions make these results somewhat uncertain. All clinical studies relied on dichotomous outcomes and none used pain intensity as continuous phenotype. This is a major weakness of the reviewed studies and gives reason to question their validity with respect to pain mechanisms. Experimental pain studies indicate large differences in heritability across pain modalities. Whereas there is evidence for substantial common genetic risk across many clinical pain conditions, different experimental pain phenotypes appear to be associated with different genetic factors. Recommendations for future research include inclusion of pain intensity scaling and number of pain sites in phenotyping. Furthermore, studies examining the genetic relationships between pain phenotypes, in particular between clinical and experimental phenotypes, should be prioritized.

Age at menarche and pelvic girdle syndrome in pregnancy: a population study of 74 973 women.

OBJECTIVE: To study the association of age at menarche with presence of pelvic girdle syndrome in pregnancy. DESIGN: Population study. SETTING: Norway 1999-2007. POPULATION: A total of 74 973 pregnant women in the Norwegian Mother and Child Cohort Study. METHODS: Data were obtained by self-administered questionnaires in weeks 17 and 30 of gestation. MAIN OUTCOME MEASURE: Pelvic girdle syndrome in pregnancy at 30 weeks of gestation, defined as pain in the pubic symphysis in the anterior pelvis and in both sacroiliac joints in the posterior pelvis. RESULTS: The prevalence of pelvic girdle syndrome was 20.6% (328/1593) in women with menarche before the age of 11, it was 16.3% (3200/22 044) in women with menarche at the age of 12 and 12.7% (1252/9859) in women with menarche after the age of 14 (chi-square test for trend, P < 0.001). The inverse association of age at menarche with pelvic girdle syndrome remained after adjustment for body mass index, maternal age, parity, educational level, previous low back pain, emotional distress and physically demanding work. Women with early menarche and high body mass index had the highest prevalence of pelvic girdle syndrome, but the association of early menarche with pelvic girdle syndrome was similar in women with and without high body mass index. CONCLUSIONS: Early menarche was associated with increased prevalence of pelvic girdle syndrome in pregnancy. Factors associated with early menarche may play a role in the development of pelvic girdle pain.

Information processing deficits in head injury assessed with ERPs reflecting early and late processing stages.

ERPs provide informative measures of slowed information processing in head injury. While several studies have reported changes in long latency ERPs (N2, P3) in head injury, the data on early ERP components related to attention selection are inconclusive. The problem may be partly methodological because the standard oddball paradigm does not give an adequate basis for discriminating components contributing to the N1 and P2 waveforms. Following a suggestion by Garcia-Larrea et al. [10: Garcia-Larrea L, Lukasziewicz A-C, Maugière F. Revisiting the oddball paradigm. Non-target vs neutral stimuli and the evaluation of ERP attention effects. Neuropsychologia 1992;30:723-741] we used an extended oddball paradigm to study measures of early processing (N1-average, P250) as well as conventional cognitive ERPs (N1, P2, N2, P3) in a group of head injured patients and controls. We found evidence of deficits in early processing of neutral and non-target stimuli in the patient group, and interpret the findings as an indication that the patients are less efficient in terminating processing of irrelevant stimuli. The results further indicate that processing deviations affect both target and non-target stimuli in the oddball paradigm and thus the allocation of attention in the task as a whole.

ERP indices of resource allocation difficulties in mild head injury.

This study examined the hypothesis that distractibility is a characteristic sequela of mild closed head injury (MHI). The Minnesota Multiphasic Personality Inventory (MMPI-2) was used to study whether comorbid stress-related symptoms are associated with behavioral and electrophysiological indexes of attention. Event-related potentials (ERPs) and performance (reaction time, accuracy) were studied in patients with MHI (n = 20), patients with frontal lesions (n = 14), and healthy controls (n = 20) during a three-tone oddball task. Participants were instructed to detect rare target (2000 Hz) tones, and to withhold responding to equally rare distractor (500 Hz) tones and frequently occurring standard (1000 Hz) tones. All groups distinguished the two classes of deviants as indicated by the larger P3 amplitude to target relative to distractor tones. This indicates that the group with MHI was capable of differential allocation of attentional resources to target and non-target events. However, impaired performance and attenuated ERP amplitudes to both classes of deviants relative to patients with frontal lesions and controls, suggest limited availability, or expenditure of the resources needed for adequate task performance. In the group with MHI, both P3 amplitude and reaction time (RT) were significantly related to subjectively reported distress. The difference in RT disappeared, whereas the P3 amplitude differences between the patient groups remained when adjusting for level of distress.

Herpes simplex thymidine kinase gene transfer is required for complete regression of murine colon adenocarcinoma.

The herpes simplex thymidine kinase (HStk) gene induces regression of epithelial tumors after ganciclovir (GCV) administration. This observation has been attributed to both gene transfer and metabolic cooperation between cells (the bystander effect). This study evaluates the relative roles of the bystander effect and gene delivery of the HStk gene by the LTKOSN.2 vector. MC38 colon adenocarcinoma cells, syngeneic for C57/B16 mice, were used. Whereas in vitro proliferation assays demonstrated a bystander effect, significantly greater inhibition of proliferation occurred with HStk gene transfer. In mixtures containing 75 per cent MC38 cells with no vector (MC38 NV) and 25 per cent MC38 pretransduced with LTKOSN.2 (MC38 TK), proliferation was inhibited by 62 +/- 5 per cent. In mixtures containing 75 per cent MC38 NV with 25 per cent HStk vector-producing cells (LTKOSN.2 VPC), proliferation was inhibited by 97 +/- 1 per cent. In vivo subcutaneous mixture experiments utilized MC38 NV cells inoculated at a 1:1 ratio with various treatment cell groups followed by administration of GCV. Tumor volumes (mean +/- standard error) at 30 days were: 264 +/- 66 mm3 for MC38 TK, 0 for LTKOSN.2 VPC, 1009 +/- 335 mm3 for lacZ VPC (beta-galactosidase VPC), and 1012 +/- 212 mm3 for NIH3T3 (nontransduced cells). These data suggest that in vivo, the bystander effect alone causes tumor inhibition, but gene transfer is necessary for complete tumor elimination in immunocompetent mice.

[Spinal fractures in adults in bob-sled accidents]. / Columnafrakturer hos voksne efter styrt på plasticbobslaede.

A case study of two adults who sustained severe burst fractures of the thoracolumbar spine (T12, L1) after trivial accidents using plastic sledges. In one case a transient conus medullaris lesion was encountered. The fractures were reduced indirectly by internal fixation as well as by direct anteposition of the fragments from the spinal canal after laminectomy. The fracture mechanism is probably a result of hyperflexion combined with very little shock absorbtion from this sledgetype. Plastic sledges seem particularly hazardous for adults.

Incidental prostate adenocarcinoma in a thirty-year-old Native American.

We report a case of prostatic adenocarcinoma in a thirty-year-old Native American. The tumor was an incidental autopsy finding. We speculate on the biological and clinical significance of prostate tumors in young males.

Real time monitoring of acylations during solid phase peptide synthesis: a method based on electrochemical detection.

Monitoring of acylation reactions during solid phase peptide synthesis is important to ensure high coupling yields in all steps of the synthesis. We describe in this paper a simple and reliable method for monitoring the time course of the acylation steps as well as the washing and deprotection steps during computer-controlled solid phase peptide synthesis. The method is based on the continuous measurement of electrical conductivity in the reaction vessel. It is shown that there is a close correspondence between the degree of acylation (as determined from the amount of 9-fluorenylmethoxycarbonyl- (Fmoc) groups released during deprotection) and the conductivity profile obtained during coupling of the amino acids to the growing peptide chain. The measurements are fed back to the computer providing data for software control of the duration of the acylation, deprotection and washing steps. The method is demonstrated with pentafluorophenol esters, but is equally applicable to dihydroxybenzotriazole esters and symmetric anhydrides using the Fmoc-polyamide strategy in a continuous flow set-up with dimethylformamide (DMF) as the general solvent.

Crossed immunoelectrophoresis of bovine milk fat globule membrane protein solubilized with non-ionic detergent.

Detergent solubilized bovine milk fat globule membrane material studied by crossed immunoelectrophoresis combined with histochemical techniques revealed four major protein complexes. All four were found to bind to concanavalin A and three were identified as sialoglycoproteins. Xanthine oxidase activity was associated with the non-sialoglycoprotein precipitate. Immunoabsorption with intact milk fat globules showed an internal location of the xanthine oxidase, whereas the three other main proteins plus Mg2+-ATPase and 5'-nucleotidase were disposed on the outer membrane surface. The major proteins from milk fat globule membrane and membrane material isolated from skim milk showed immunochemical identity.