Small mammals reduce activity during high moon illumination under risk of predation by introduced predators.

Predation influences prey survival and drives evolution of anti-predator behaviour. Anti-predator strategies by prey are stimulated by direct encounters with predators, but also by exposure to indicators of risk such as moonlight illumination and vegetation cover. Many prey species will suffer increased risk on moonlit nights, but risk may be reduced by the presence of dense vegetation. Determining the role of vegetation in reducing perceived risk is important, especially given predictions of increased global wildfire, which consumes vegetation and increases predation. We used remote cameras in southeastern Australia to compare support for the predation risk and habitat-mediated predation risk hypotheses. We examined the influence of moonlight and understorey cover on seven 20-2500 g mammalian prey species and two introduced predators, red foxes and feral cats. Activity of all prey species reduced by 40-70% with increasing moonlight, while one species (bush rat) reduced activity in response to increasing moonlight more sharply in low compared to high understorey cover. Neither predator responded to moonlight. Our findings supported the predation risk hypothesis and provided limited support for the habitat-mediated predation risk hypothesis. For prey, perceived costs of increased predation risk on moonlit nights outweighed any benefits of a brighter foraging environment.

A Prospective Study to Examine Responsiveness and Minimally Important Differences (MIDs) for the CLEFT-Q Scales Following Three Cleft-Specific Operations.

The aim of this study was to examine internal responsiveness and estimate minimally important differences (MIDs) for CLEFT-Q scales.In this prospective cohort study, participants completed the CLEFT-Q appearance and health-related quality of life (HRQL) scales before and six months after cleft-related surgery.Seven cleft centres in Canada, USA and UK participated.Patients were ages 8-29 years with CL/P.Patients underwent rhinoplasty, orthognathic or cleft lip scar revision surgery.Internal responsiveness was examined using Cohen's d effect sizes (ESs) based on the following interpretation: 0.20-0.49 small, 0.50-0.79 moderate and ≥ 0.80 large. MIDs were estimated using two distribution-based approaches.Participants had a rhinoplasty (n = 31), orthognathic (n = 21) or cleft lip scar revision (n = 18) surgery. Most participants were males (56%) and aged 8-11 years (41%). Following rhinoplasty, ESs were larger for the nose (0.92, p = 0.001) and nostrils (0.94, p < 0.001) scales than for the face scale (0.51, p = 0.003). MIDs ranged between 6.2-10.4. For orthognathic surgery, larger ES was observed for the jaws scale (1.80, p < 0.001) compared with the teeth (1.16, p < 0.001), face (1.15, p = 0.001) and lips (0.94, p < 0.001) scales. MIDs ranged between 5.9-14.4. In the cleft lip scar revision sample, the largest ES was observed for the nose scale (0.76, p = 0.03), followed by lips (0.58, p = 0.009) and cleft lip scar (0.50, p = 0.043) scales. MIDs ranged between 6.4-12.3.CLEFT-Q detected change in key outcomes for three cleft-specific surgeries, providing evidence of its responsiveness. Estimated MIDs will aid in interpreting this PROM.

Outcome of reconstruction of cutaneous limb defects in dogs using hygroscopic "self-inflating" tissue expanders.

OBJECTIVES: To describe the placement of self-inflating tissue expanders and clinical outcomes in 12 consecutive cases of reconstruction of distal cutaneous limb defects in dogs. MATERIALS AND METHODS: Cases of distal cutaneous limb defect were divided into three groups based on the location of the placement of the self-inflating tissue expanders: Group A (n=4): on, or proximal to, the elbow and stifle; Group B (n=4): distal to the elbow or stifle and proximal to the carpus or tarsus; and Group C (n=4): distal to the carpus or tarsus. Owner satisfaction and clinical outcome were documented. RESULTS: Thirteen cases were originally included, but one was excluded because of incomplete follow-up. In one case, the self-inflating tissue expanders were removed before expansion started. A mean of five expanders were implanted per dog (range 2 to 9). Devices were removed after a mean of 24 days (range 13 to 42 days). Primary closure was achieved in eight of 11 cases, including all cases from Group A and 75% and 33% of cases from Groups B and C, respectively. All incompletely reconstructed defects or areas of wound dehiscence healed by second intention. Eight of 12 owners were satisfied. CLINICAL SIGNIFICANCE: Self-inflating tissue expanders can be used as an alternative for the reconstruction of limb defects in dogs in which direct primary closure would otherwise not be achievable. Defects below the carpus and tarsus are more challenging to treat with this method.

Adenosine triphosphate bioluminescence to validate decontamination of endoscopes.

The reports of outbreaks involving carbapenemase-resistant Enterobacteriaceae (CRE) associated with gastrointestinal endoscopy prompted a review and study of a novel method of assessing cleaning. This study assessed adenosine triphosphate (ATP) bioluminescence to demonstrate cleanliness prior to endoscopy. ATP testing was compared with microbiological monitoring for 127 endoscopes. Samples were taken after cleaning, reprocessing and storage, but immediately before the endoscopy procedure. We recommend implementing ATP testing prior to endoscopy procedures as an alternative to microbiological testing at periodic intervals. ATP testing provides a convenient assessment of endoscopy hygiene to demonstrate safety and quality assurance.

Randomized clinical trial of intraoperative endoscopic retrograde cholangiopancreatography versus laparoscopic bile duct exploration in patients with choledocholithiasis.

BACKGROUND: Various minimally invasive approaches exist for the management of choledocholithiasis at the time of laparoscopic cholecystectomy. The aim of this study was to compare endoscopic retrograde cholangiopancreatography (ERCP) with laparoscopic bile duct exploration (LBDE) and test the hypothesis that intraoperative ERCP is no different to LBDE in terms of rate of bile duct clearance or retained stones. METHODS: Eligible patients with choledocholithiasis undergoing emergency laparoscopic cholecystectomy were randomized to intraoperative ERCP or LBDE in a 1 : 1 ratio. The primary outcomes were rates of bile duct clearance and retained stones. Secondary outcomes were postprocedure complication rate, mortality rate, postoperative length of hospital stay, conversion to open surgery rate, procedural time and total duration of surgery. RESULTS: Some 104 patients were randomized, and 52 patients in each group were included in an intention-to-treat analysis. Duct clearance rates were 87 per cent for patients who had intraoperative ERCP and 69 per cent for those in the LBDE group (P = 0·057). The rate of retained stones was lower in the ERCP group than in the LBDE group: 15 versus 42 per cent respectively (P = 0·004). Median postoperative length of stay was shorter with ERCP (2 days versus 3 days for LBDE; P = 0·015). CONCLUSION: Intraoperative ERCP is more effective than LBDE in terms of minimizing the rate of retained stones in patients with choledocholithiasis undergoing emergency laparoscopic cholecystectomy. REGISTRATION NUMBER: ACTRN12613000761763 (http://www.anzctr.org.au/).

Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells.

As an alternative to the transplantation of islets, a human liver cell line has been genetically engineered to reverse type 1 diabetes (TID). The initial liver cell line (Huh7ins) commenced secretion of insulin in response to a glucose concentration of 2.5 mmol/l. After transfection of the Huh7ins cells with human islet glucokinase, the resultant Melligen cells secreted insulin in response to glucose within the physiological range; commencing at 4.25 mmol/l. Melligen cells exhibited increased glucokinase enzymatic activity in response to physiological glucose concentrations, as compared with Huh7ins cells. When transplanted into diabetic immunoincompetent mice, Melligen cells restored normoglycemia. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that both cell lines expressed a range of ß-cell transcription factors and pancreatic hormones. Exposure of Melligen and Huh7ins cells to proinflammatory cytokines (TNF-α, IL-1ß, and IFN-γ) affected neither their viability nor their ability to secrete insulin to glucose. Gene expression (microarray and qRT-PCR) analyses indicated the survival of Melligen cells in the presence of known ß-cell cytotoxins was associated with the expression of NF-κB and antiapoptotic genes (such as BIRC3). This study describes the successful generation of an artificial ß-cell line, which, if encapsulated to avoid allograft rejection, may offer a clinically applicable cure for T1D.

Effect of multilevel laboratory rat caging system on the well-being of the singly-housed Sprague Dawley rat.

Current regulations emphasize that good husbandry practices allow animals to engage in species appropriate postural adjustments without touching the enclosure walls. This study evaluated the well-being of rats housed in a commercially available multilevel rat caging system, with or without access to the upper level of the caging. The evaluation methodologies included assessment of behavioral observations in the home cage, physiological assessment of metabolism and immune function, and determination of the affective state using a spatial cognitive bias assay. The study determined that rats that were provided access to the full multilevel cage during testing after initial restriction to the lower level of the cage demonstrated behavioral changes consistent with a positive affective state, while those with no changes to their housing situation had no significant differences in their affective states. Rats that were consistently housed with access restricted to the lower level of the cage exhibited a tendency to increased neutrophil:lymphocyte ratios as compared with those provided with access to all levels of the multilevel cage. There were no differences in body weight demonstrated between the experimental groups. Overall use of the cage space, as documented through analysis of behavioral observations in the home cage, demonstrated no significant differences in preferred location in the cage during the light or dark cycles, though rats with access to both levels of the cage were significantly more active during the light cycle. The results of this study suggest that the use of a multilevel caging system may improve the well-being of rats used in research.

Long-term reversal of diabetes in non-obese diabetic mice by liver-directed gene therapy.

BACKGROUND: Type 1 diabetes (T1D) results from an autoimmune attack against the insulin-producing ß-cells of the pancreas. The present study aimed to reverse T1D by gene therapy. METHODS: We used a novel surgical technique, which involves isolating the liver from the circulation before the delivery of a lentiviral vector carrying furin-cleavable human insulin (INS-FUR) or empty vector to the livers of diabetic non-obese diabetic mice (NOD). This was compared with the direct injection of the vector into the portal circulation. Mice were monitored for body weight and blood glucose. Intravenous glucose tolerance tests were performed. Expression of insulin and pancreatic transcription factors was determined by the reverse transcriptase-polymerase chain reaction and immunohistochemistry and immunoelectron microscopy was used to localise insulin. RESULTS: Using the novel surgical technique, we achieved long-term transduction (42% efficiency) of hepatocytes, restored normoglycaemia for 150 days (experimental endpoint) and re-established normal glucose tolerance. We showed the expression of ß-cell transcription factors, murine insulin, glucagon and somatostatin, and hepatic storage of insulin in granules. The expression of hepatic markers, C/EBP-ß, G6PC, AAT and GLUI was down-regulated in INS-FUR-treated livers. Liver function tests remained normal, with no evidence of intrahepatic inflammation or autoimmune destruction of the insulin-secreting liver tissue. By comparison, direct injection of INS-FUR reduced blood glucose levels, and no pancreatic transdifferentiation or normal glucose tolerance was observed. CONCLUSIONS: This gene therapy protocol has, for the first time, permanently reversed T1D with normal glucose tolerance in NOD mice and, as such, represents a novel therapeutic strategy for the treatment of T1D.

Sentinel node status predicts survival in thick melanomas: the Oxford perspective.

AIMS: To determine the prognostic value of SLNB in patients with thick melanoma in terms of overall survival (OS) and recurrence-free survival (RFS). METHODS: 136 patients with primary tumours (Breslow thickness ≥ 4.0 mm) underwent SLNB. OS and RFS were calculated and a multivariate Cox regression model used to determine the important prognostic factors for predicting OS and RFS. RESULTS: Median Breslow thickness was 5.5 mm and 60% were ulcerated. Median follow up was 4 years (95% CI = 4-5) with 54 patients having died at the time of analysis. 5-year OS for SLNB positive patients was 32%, compared to 78% for negative patients. The significant predictors of poorer OS were increasing age (p = 0.03), increasing Breslow thickness (p = 0.03) and SLNB positivity (p < 0.0001). 5 year RFS was significantly worse in the SLNB positive population compared to the negative patients (p < 0.0001); 27% versus 66% respectively. CONCLUSIONS: Patients with a thick melanoma and a positive SLNB have a significantly worse RFS and OS compared to those with a negative SLNB. Over three-quarters of patients with a negative SLNB survived five years. These findings have implications for the subpopulations included in adjuvant therapy trials and we advocate SLNB be recommended in patients with thick melanomas.

Factors that predict bleeding following endoscopic mucosal resection of large colonic lesions.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) for large colonic laterally spreading tumors (LSTs) is a safe, efficacious, and cost-effective treatment. The most common serious complication is delayed bleeding, which reduces these advantages, but consensus guidelines for large-polyp EMR do not exist. PATIENTS AND METHODS: Data from two large prospective intention-to-treat studies of EMR for colonic LSTs 20 mm or greater in size were analyzed. Data collection was comprehensive, and included patient and lesion characteristics. EMR technique and cessation of anticoagulant and antiplatelet therapy was standardized. Clinically significant delayed bleeding was defined as that requiring hospital admission. RESULTS: EMR was performed on 302 lesions in 288 patients. There was clinically significant delayed bleeding in 21 cases (7 %). Ten underwent colonoscopy. One required angiography. One required surgery after perforation following hemostatic clip placement. There were no deaths. Risk factors for bleeding on multivariate analysis were right colon location [adjusted odds ratio (OR) 4.4, P = 0.01], use of aspirin (OR 6.3, P = 0.005), and age (OR per decade of age 1.70). All bleeds occurred before aspirin was restarted. Patient characteristics, including ASA grade and co-morbidity type, were not predictive. Despite requiring more complex EMR, larger lesion size ( P = 0.2), multiple excisions rather than en bloc resection ( P = 0.1), polyp morphology ( P = 0.2), and previous attempts ( P = 0.5), were not associated with increased risk. CONCLUSIONS: Proximal lesion location is a highly significant risk for clinically significant delayed bleeding following colonic EMR, and this knowledge could form the basis of a targeted therapeutic trial. Recent aspirin use also increases bleeding risk--specific consensus guidelines in this area are required for colonic EMR.

Randomized controlled trial of fibrin sealant to reduce postoperative drainage following elective lymph node dissection.

BACKGROUND: Excessive postoperative drainage following groin and axillary lymphadenectomy may be associated with a prolonged hospital stay and an increased complication rate. The use of fibrin sealant before wound closure may reduce postoperative wound drainage. METHODS: Consecutive patients undergoing elective groin or axillary lymphadenectomy were randomized to standard wound closure or to having fibrin sealant sprayed on to the wound bed before closure. Postoperative wound drainage, duration of drainage and complications were recorded, as were locoregional recurrence, distant metastasis and mortality. RESULTS: A total of 74 patients requiring 38 groin and 36 axillary dissections were randomized. The median postoperative wound drainage volume for the groin dissection cohort was 762 (range 25-3255) ml in the control group and 892 (265-2895) ml in the treatment group (P = 0·704). Drainage volumes in the axillary cohort were 590 (230-9605) and 565 (30-1835) ml in the control and treatment groups respectively (P = 0·217). There was no difference in the duration of drainage or postoperative complication rate between the treatment groups in both the axillary and groin cohorts. Local recurrence, distant metastasis and mortality rates did not differ between the treatment groups. CONCLUSION: There was no advantage in using fibrin sealant during elective lymphadenectomy in terms of reducing drainage output or postoperative complication rate.

Fluticasone propionate for treatment of esophageal lichen planus. A case series.

Esophageal lichen planus is a rare condition, and although the majority of cases occur in conjunction with lichen planus at other sites, the endoscopic features are often misinterpreted resulting in a delay in diagnosis. We report a series of five patients presenting to our unit between 2005 and 2009. All five patients were female and presented with dysphagia. Endoscopy demonstrated proximal esophageal stricturing in four patients. Characteristic histological findings were found in four patients. Lichen planus was diagnosed at other sites, and preceded gastrointestinal symptoms, in all patients; five had oral involvement, two had genital involvement, and one had dermal involvement. All patients received proton pump inhibitor therapy without demonstrable benefit. Administration of oral fluticasone proprionate resulted in symptomatic improvement in three patients.

Synthesis and properties of a novel anisotropic self-inflating hydrogel tissue expander.

The advent of self-inflating hydrogel tissue expanders heralded a significant advance in the reconstructive techniques available for the surgical restoration of a wide variety of soft tissue defects. However, their use in specific applications such as cleft palate surgery is limited on account of their isotropic expansion. An anisotropic self-inflating hydrogel tissue expander has been developed which markedly increases the potential indications for which this restorative tool may be employed. These include complex pediatric soft tissue reconstructions of the palate, nose, ear and digits. Anisotropic expansion in a hydrogel polymer network composed of methyl methacrylate and vinylpyrrolidone has been achieved by annealing the xerogel under a compressive load for a specified time period. By controlling the anisotropic processing conditions and composition we have been able to accurately tailor the ultimate expansion ratio up to 1500%. The expansion rate of the xerogel has also been significantly reduced by encapsulating the polymer within a semi-permeable silicone membrane. The structure and properties of the novel anisotropic hydrogel were characterized by attenuated total reflectance infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis and small-angle neutron scattering.

Autoimmune pancreatitis: an important diagnostic consideration in obstructive jaundice due to a pancreatic mass lesion.

Autoimmune or immunoglobulin G subtype (IgG4) pancreatitis is a newly recognised clinical entity and is an important differential diagnosis for patients presenting with obstructive jaundice. Knowledge of autoimmune pancreatitis (AIP) continues to evolve both for pathogenesis and management; however diagnosis is often not straightforward or even considered, therefore a high index of suspicion remains an important tool for the treating physician. The six cases presented illustrate both the difficulties in diagnosis as well as management of this condition.

Congenital absence of flexor digitorum superficialis: implications for assessment of little finger lacerations.

Absence of flexor digitorum superficialis function in the little finger is a relatively common congenital anomaly that can complicate assessment of little finger injuries. We reviewed the prevalence of unilateral and bilateral absence of superficialis function in the published literature. In appropriate studies identified (1352 people), the anomaly was unilateral in 92 individuals (6.8%) and bilateral in 81 (6.0%). If superficialis function is absent in one little finger, the probability of absence in the opposite hand is 0.64. If superficialis function is present, the probability of absence in the other little finger is 0.02 (1 in 50). Absence of little finger superficialis function in one hand is therefore not a reliable indicator of this function in the opposite hand.