What Role Do Chronic Workloads Play in the Acute to Chronic Workload Ratio? Time to Dismiss ACWR and Its Underlying Theory.

AIM: The aim of this study was to examine the associations between the injury risk and the acute (AL) to chronic (CL) workload ratio (ACWR) by substituting the original CL with contrived values to assess the role of CL (i.e., the presence and implications of statistical artefacts). METHODS: Using previously published data, we generated a contrived ACWR by dividing the AL by fixed and randomly generated CLs, and we compared these results to real data. We also reproduced previously reported subgroup analyses, including dichotomising players' data above and below the median CL. Our analyses follow the same, previously published modelling approach. RESULTS: The analyses with original data showed effects compatible with higher injury risk for ACWR only (odd ratios, OR: 2.45, 95% CI 1.28-4.71). However, we observed similar effects by dividing AL by the "contrived" fixed and randomly generated CLs: OR 1.95 (1.18-3.52) dividing by 1510 (average CL); and OR ranging from 1.16 to 2.07, using random CL 1.53 (mean). Random ACWRs reduced the variance relative to the original AL and further inflated the ORs (mean OR 1.89, from 1.42 to 2.70). ACWR causes artificial reclassification of players compared to AL alone. Finally, neither ACWR nor AL alone confer a meaningful predictive advantage to an intercept-only model, even within the training sample (c-statistic 0.574/0.544 vs. 0.5 in both ACWR/AL and intercept-only models, respectively). DISCUSSION: ACWR is a rescaling of the explanatory variable (AL, numerator), in turn magnifying its effect estimates and decreasing its variance despite conferring no predictive advantage. Other ratio-related transformations (e.g., reducing the variance of the explanatory variable and unjustified reclassifications) further inflate the OR of AL alone with injury risk. These results also disprove the etiological theory behind this ratio and its components. We suggest ACWR be dismissed as a framework and model, and in line with this, injury frameworks, recommendations, and consensus be updated to reflect the lack of predictive value of and statistical artefacts inherent in ACWR models.

Mobile epibenthic fauna consume organic waste from coastal fin-fish aquaculture.

Organic waste released from fin-fish aquaculture is being dispersed further as industry growth has led to the expansion of open net cages in dynamic coastal locations. Here we investigate the response of three mobile epibenthic invertebrates (brittle stars, urchins and brown crabs), whose natural habitats overlap with large scale coastal salmon farming. Using fatty acids and stable isotopes, we found these organisms displayed decreases in δ13C and δ15N and elevated levels of C18 fatty acids reflective of terrestrial components of fin-fish feeds. Furthermore, we found these three species consume aquaculture organic waste not only directly adjacent to the farm vicinity (0-20 m from cage edge) but up to 1 km away in the case of brittle stars and brown crabs. As aquaculture feeds shift to contain more terrestrial ingredients, the biochemistry of fauna feeding on organic waste is also being shifted, the result of these changes is currently unclear.

Calorie restriction and not glucagon-like peptide-1 explains the acute improvement in glucose control after gastric bypass in Type 2 diabetes.

AIMS: To compare directly the impact of glucagon-like peptide-1 secretion on glucose metabolism in individuals with Type 2 diabetes listed for Roux-en-Y gastric bypass surgery, randomized to be studied before and 7 days after undergoing Roux-en-Y gastric bypass or after following a very-low-calorie diet. METHODS: A semi-solid meal test was used to investigate glucose, insulin and glucagon-like peptide-1 response. Insulin secretion in response to intravenous glucose and arginine stimulus was measured. Hepatic and pancreatic fat content was quantified using magnetic resonance imaging. RESULTS: The decrease in fat mass was almost identical in the Roux-en-Y gastric bypass and the very-low-calorie diet groups (3.0±0.3 and 3.0±0.7kg). The early rise in plasma glucose level and in acute insulin secretion were greater after Roux-en-Y gastric bypass than after a very-low-calorie diet; however, the early rise in glucagon-like peptide-1 was disproportionately greater (sevenfold) after Roux-en-Y gastric bypass than after a very-low-calorie diet. This did not translate into a greater improvement in fasting glucose level or area under the curve for glucose. The reduction in liver fat was greater after Roux-en-Y gastric bypass (29.8±3.7 vs 18.6±4.0%) and the relationships between weight loss and reduction in liver fat differed between the Roux-en-Y gastric bypass group and the very-low-calorie diet group. CONCLUSIONS: This study shows that gastroenterostomy increases the rate of nutrient absorption, bringing about a commensurately rapid rise in insulin level; however, there was no association with the large post-meal rise in glucagon-like peptide-1, and post-meal glucose homeostasis was similar in the Roux-en-Y gastric bypass and very-low-calorie diet groups. (Clinical trials registry number: ISRCTN11969319.).

Contribution of water chemistry and fish condition to otolith chemistry: comparisons across salinity environments.

This study quantified the per cent contribution of water chemistry to otolith chemistry using enriched stable isotopes of strontium ((86) Sr) and barium ((137) Ba). Euryhaline barramundi Lates calcarifer, were reared in marine (salinity 40), estuarine (salinity 20) and freshwater (salinity 0) under different temperature treatments. To calculate the contribution of water to Sr and Ba in otoliths, enriched isotopes in the tank water and otoliths were quantified and fitted to isotope mixing models. Fulton's K and RNA:DNA were also measured to explore the influence of fish condition on sources of element uptake. Water was the predominant source of otolith Sr (between 65 and 99%) and Ba (between 64 and 89%) in all treatments, but contributions varied with temperature (for Ba), or interactively with temperature and salinity (for Sr). Fish condition indices were affected independently by the experimental rearing conditions, as RNA:DNA differed significantly among salinity treatments and Fulton's K was significantly different between temperature treatments. Regression analyses did not detect relations between fish condition and per cent contribution values. General linear models indicated that contributions from water chemistry to otolith chemistry were primarily influenced by temperature and secondly by fish condition, with a relatively minor influence of salinity. These results further the understanding of factors that affect otolith element uptake, highlighting the necessity to consider the influence of environment and fish condition when interpreting otolith element data to reconstruct the environmental histories of fish.

Nitro-oleic acid targets transient receptor potential (TRP) channels in capsaicin sensitive afferent nerves of rat urinary bladder.

Nitro-oleic acid (9- and 10-nitro-octadeca-9-enoic acid, OA-NO(2)) is an electrophilic fatty acid nitroalkene derivative that modulates gene transcription and protein function via post-translational protein modification. Nitro-fatty acids are generated from unsaturated fatty acids by oxidative inflammatory reactions and acidic conditions in the presence of nitric oxide or nitrite. Nitroalkenes react with nucleophiles such as cysteine and histidine in a variety of susceptible proteins including transient receptor potential (TRP) channels in sensory neurons of the dorsal root and nodose ganglia. The present study revealed that OA-NO(2) activates TRP channels on afferent nerve terminals in the urinary bladder and thereby increases bladder activity. The TRPV1 agonist capsaicin (CAPS, 1 µM) and the TRPA1 agonist allyl isothiocyanate (AITC, 30 µM), elicited excitatory effects in bladder strips, increasing basal tone and amplitude of phasic bladder contractions (PBC). OA-NO(2) mimicked these effects in a concentration-dependent manner (1 µM-33 µM). The TRPA1 antagonist HC3-030031 (HC3, 30 µM) and the TRPV1 antagonist diaryl piperazine analog (DPA, 1 µM), reduced the effect of OA-NO(2) on phasic contraction amplitude and baseline tone. However, the non-selective TRP channel blocker, ruthenium red (30 µM) was a more effective inhibitor, reducing the effects of OA-NO(2) on basal tone by 75% and the effects on phasic amplitude by 85%. In bladder strips from CAPS-treated rats, the effect of OA-NO(2) on phasic contraction amplitude was reduced by 65% and the effect on basal tone was reduced by 60%. Pretreatment of bladder strips with a combination of neurokinin receptor antagonists (NK1 selective antagonist, CP 96345; NK2 selective antagonist, MEN 10,376; NK3 selective antagonist, SB 234,375, 1 µM each) reduced the effect of OA-NO(2) on basal tone, but not phasic contraction amplitude. These results indicate that nitroalkene fatty acid derivatives can activate TRP channels on CAPS-sensitive afferent nerve terminals, leading to increased bladder contractile activity. Nitrated fatty acids produced endogenously by the combination of fatty acids and oxides of nitrogen released from the urothelium and/or afferent nerves may play a role in modulating bladder activity.

Does bariatric surgery prior to lower limb joint replacement reduce complications?

Obesity is an increasing health concern in developed world. Bariatric surgery is considered in super-obese patients. Many of these patients will also require lower limb arthroplasty. This study was performed to investigate the complications of hip and knee replacement in patients who had bariatric surgery either before or after their joint replacement. Hospital episode statistics data for English NHS patients undergoing lower limb arthroplasty and bariatric surgery between 2005 and 2009 were analysed. The joint replacement-specific and general medical complications were compared between those undergoing joint replacement prior to bariatric surgery and vice versa, and also with the general English arthroplasty patient. One hundred and forty-three patients underwent bariatric surgery and joint replacement. Bariatric surgery was performed first in 53 and arthroplasty first in 90 patients. The mean age of obese patients was 9 years younger than the general arthroplasty population. Mean in-hospital stay was similar but general medical complications in obese patients appear to be less, possibly because of the lower age at the time of the procedure. Hip dislocation rate at 18 months was higher. Within the two obese groups wound infection rate was 3.5 times lower and readmission to hospital at 30 days appeared to be 7-times lower in patients who had bariatric surgery prior to joint replacement (p = 0.06). In this patient group, the risk of complications following joint replacement appears to be lower if bariatric surgery is performed first.

Type 2 diabetes, bariatric surgery and the risk of subsequent gestational diabetes.

Women with pre-existing abnormal glucose regulation are certain to develop gestational diabetes in pregnancy and pre-gestational type 2 diabetes will become more difficult to control. However, an increasing number of women with type 2 diabetes have had bariatric surgery. In this group, the effect of pregnancy on glucose metabolism is unknown. We report two women with type 2 diabetes who underwent laparoscopic gastric bypass surgery with normalization of plasma glucose levels. During subsequent pregnancy, maternal blood glucose levels remained completely normal throughout. This is remarkable given the predisposition to abnormal glucose tolerance and the ongoing obesity, in the face of the insulin resistance of pregnancy. Women with prior type 2 diabetes reversed by gastric bypass surgery are not at high risk for gestational diabetes.

Outcome of patients in laparoscopic training courses compared to standard patients.

BACKGROUND & AIM: Current Laparoscopic simulators have limited usefulness and patients have been used for training since the dawn of surgery. NUGITS (Northumbrian Upper Gastro Intestinal Team of Surgeons) Laparoscopic Skills courses utilise hands-on experience with simulators moving to live operating on volunteer patients. It is vital to know that the volunteer patient is not disadvantaged by greater surgical risk. METHODS: This was a case-controlled prospective comparison of patients undergoing both Laparoscopic Cholecystectomy (LC) [n=51] and Laparoscopic Inguinal Hernia (LIH) [n=62] during NUGITS training courses. They are compared with a matched (age, sex and ASA grade) control group LC (n=51) and LIH (n=62) operated on by consultants. The outcome measures were surgical peri-and post-operative complications, post-operative hospital stay, readmission and early recurrence of inguinal hernia (<6 months). RESULTS: In the LC cohort, there was no significant difference in the length of hospital stay (p=0.07) or readmission (p=0.16) in both the groups. The mean operating time was higher in the trainee compared to the control group (p=0.001). There was no difference in the post-operative morbidity or mortality in either group. In LIH cohort, the mean operating time was higher in the trainee compared with the control group. There was no significant difference in post-operative complications (p>0.05) and early post-operative recurrence of hernia (p>0.05). CONCLUSION: The post-operative outcomes of patients undergoing laparoscopic surgery during laparoscopic training courses are similar to consultant-operated patients. Thus, it is acceptable and safe to encourage patients to volunteer for laparoscopic training courses.

Nitro-oleic acid inhibits firing and activates TRPV1- and TRPA1-mediated inward currents in dorsal root ganglion neurons from adult male rats.

Nitro-oleic acid (OA-NO(2)), an electrophilic fatty acid by-product of nitric oxide and nitrite reactions, is present in normal and inflamed mammalian tissues at up to micromolar concentrations and exhibits anti-inflammatory signaling actions. The effects of OA-NO(2) on cultured dorsal root ganglion (DRG) neurons were examined using fura-2 Ca(2+) imaging and patch clamping. OA-NO(2) (3.5-35 microM) elicited Ca(2+) transients in 20 to 40% of DRG neurons, the majority (60-80%) of which also responded to allyl isothiocyanate (AITC; 1-50 microM), a TRPA1 agonist, and to capsaicin (CAPS; 0.5 microM), a TRPV1 agonist. The OA-NO(2)-evoked Ca(2+) transients were reduced by the TRPA1 antagonist 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl) acetamide (HC-030031; 5-50 microM) and the TRPV1 antagonist capsazepine (10 microM). Patch-clamp recording revealed that OA-NO(2) depolarized and induced inward currents in 62% of neurons. The effects of OA-NO(2) were elicited by concentrations >or=5 nM and were blocked by 10 mM dithiothreitol. Concentrations of OA-NO(2) >or=5 nM reduced action potential (AP) overshoot, increased AP duration, inhibited firing induced by depolarizing current pulses, and inhibited Na(+) currents. The effects of OA-NO(2) were not prevented or reversed by the NO-scavenger carboxy-2-phenyl-4,4,5,5-tetramethylimidazolineoxyl-1-oxyl-3-oxide. A large percentage (46-57%) of OA-NO(2)-responsive neurons also responded to CAPS (0.5 microM) or AITC (0.5 microM). OA-NO(2) currents were reduced by TRPV1 (diarylpiperazine; 5 microM) or TRPA1 (HC-030031; 5 microM) antagonists. These data reveal that endogenous OA-NO(2) generated at sites of inflammation may initially activate transient receptor potential channels on nociceptive afferent nerves, contributing to the initiation of afferent nerve activity, and later suppresses afferent firing.

Port-site pyoderma gangrenosum - a rare complication of surgical trauma.

We report a case of pyoderma gangrenosum occurring at the site of a laparoscopic port insertion following laparoscopic inguinal hernia repair.

Should all patients with unexplained anaemia be screened for chronic lead poisoning?

The global prevalence of lead poisoning is declining. However, the prevalence of lead poisoning in patients with either microcytic or normocytic anaemia is unknown. Blood samples from anaemic patients residing in south-east London without an obvious cause for anaemia had their blood lead concentration (BLC) analysed. A batch of 988 samples was analysed for BLC using atomic absorption spectroscopy. Median haemoglobin was 10.3 g/dL (range: 4.2-10.9) in females, 10.6 g/dL (range: 5.2-11.4) in males and 10.7 g/dL (range: 6.7-10.9) in children. Median BLC was 2.63 microg/dL (0.21-24.0 microg/dL; 95th centile 7.54 microg/dL). Fifteen samples (1.5%) had a BLC > 10.0 microg/dL, five samples (1%) > 15.0 microg/dL and one sample (0.1%) > 20.0 micrg/L. In the 106 children, median BLC was 2.34 microg/dL (0.5-14.5 microg/dL; 95th centile 6.12 microg/ dL). Only one child (14.5 microg/L) had a BLC > 10.0 pg/dL. There was a poor correlation between haemoglobin and BLC (r2 = 0.08). Routine screening for lead poisoning cannot be justified in all patients with unexplained anaemia, unless there is a history or clinical features to suggest lead toxicity. Additionally, we have shown that in this former high-risk area for lead exposure, there is a low point prevalence of significant lead poisoning, even in an anaemic population.

Severe sepsis following wound infection by an unusual organism--Clostridium novyi.

We present a case of post-operative wound infection with Clostridium novyi in a non-intravenous drug user. Clinical features included progressive cellulitis despite being on antibiotics, accompanied by hypotension, marked leucocytosis and oedema but minimal fever. While established infection with this organism is associated with high mortality, our patient survived. The administration of clindamycin and intravenous immunoglobulin in addition to early surgical assessment and aggressive debridement of affected tissue may have contributed to this successful outcome. To our knowledge, this is the only reported post-operative wound infection due to this pathogen.

Hypopharyngeal perforation: an uncommon cause of pneumoperitoneum.

Endotracheal intubation is common practice being performed both electively and as an emergency. Complications of this procedure are uncommon. A case is described of hypopharyngeal rupture after emergency intubation that presented with a pneumoperitoneum. The clinical signs, relevant investigations and management options are discussed for this injury and the need is emphasised for a high index of suspicion in order to make an early diagnosis.

Soluble P-selectin moderates complement dependent injury.

P-selectin is an adhesion molecule expressed on activated endothelial and platelet membranes containing 9 short consensus repeats (SCRs) similar to the composition of complement regulatory proteins. In our murine model of intestinal ischemia and reperfusion where local injury is mediated by the classical complement pathway we hypothesized the SCRs would moderate the complement response. Confirmatory data were sought following hindlimb ischemia and reperfusion where injury is both complement- and neutrophil-mediated. Mice deficient in P-selectin (P-/-) were found to have similar intestinal and hindlimb permeability compared to normal wild types mice (P+/+). When reconstituted with P+/+ platelets, but not P-/- platelets, P-/- mice subjected to intestinal ischemia had a significant 29% decrease in permeability (P < 0.05) and after hindlimb ischemia the decrease was 33% (P<0.05). Reperfusion after intestinal ischemia led to a 76% fall in CH50 in P-/- compared to sham animals (P < 0.05) indicating complement activation and consumption, but only a 36% fall in animals reconstituted with P+/+ platelets (P < 0.05). Full-length, soluble P-selectin (sPsel) derived from processed platelets, but not the truncated version of sPsel has been shown to adhere to a heat labile fraction of serum and sensitized red blood cells thereby reducing Clq adherence to the sensitized red cell. From these data we conclude that sPsel moderates complement activation by competing with C1q binding to antibody, thereby limiting activation of the classical pathway that mediates murine reperfusion injury.

Soluble P-selectin moderates complement-dependent reperfusion injury of ischemic skeletal muscle.

P-selectin is an adhesion molecule expressed on activated endothelial and platelet surfaces. The function of the short consensus repeats (SCRs) of P-selectin, homologous with the SCRs of complement regulatory proteins is largely unknown. In a model of murine hindlimb ischemia where local reperfusion injury is partly mediated by IgM natural antibody and classical complement pathway activation, we hypothesized that human soluble P-selectin (sP-sel) would moderate the complement component of the inflammatory response. Infusion of sP-sel supernatant or purified (p) sP-sel prepared from activated human platelets, reduced ischemic muscle vascular permeability by 48% and 43%, respectively, following reperfusion. Hindlimb immunohistochemistry demonstrated negligible C3 staining colocalized with IgM in these groups compared with intense staining in the untreated injured mice. In vitro studies of mouse serum complement hemolytic activity showed that psP-sel inhibited the classical but not alternative complement pathway. Flow cytometry demonstrated that psP-sel inhibited C1q adherence to sensitized red blood cells. From these data we conclude that sP-sel moderates skeletal muscle reperfusion injury by inhibition of the classical complement pathway.