Demographic, morphologic, hormonal and metabolic factors associated with the rate of improvement from equine hyperinsulinaemia-associated laminitis.

BACKGROUND: Although several studies have investigated factors associated with the onset and occurrence of hyperinsulinaemia-associated laminitis (HAL), few have examined the factors associated with the rate of improvement during recovery from an acute bout of the disease. This observational study sought to discover if a range of demographic, morphologic, hormonal and metabolic variables are associated with the improvement rate from HAL in 37 naturally-occurring cases identified by 16 clinics across Germany. Each case was evaluated for laminitis severity on the day of inclusion in the trial (d 0), then after 4, 9, 14, 25 and 42 d. The horses were managed according to best clinical practice including restricting exercise and prescribing a diet of hay-only, for a minimum of 9 d. Blood samples were also collected during each evaluation, except on d 9, and analysed for glucose, insulin, ACTH and leptin. RESULTS: Based on individual clinical laminitis scores plotted against time, most horses improved markedly within 2 weeks, with a 'fast group' (n = 27) having a median (interquartile range) score on a 12-point scale of 0 (0-2) by d 14. However, there was a clear disparity within the total cohort, as ~ 1 in 4 horses demonstrated much slower improvement, with a median score of 5 (4-7) by d 14, or a marked relapse thereafter ('slow group', n = 10). Horses in the slow improvement group were younger (12.5 (8.8-16.3) vs 17 (14-24) yr; P = 0.008), but were not more likely to be heavier, male, very fat, to have presented with a previous history of laminitis or elevated ACTH concentrations, or to be receiving pergolide treatment. Of the hormonal and metabolic parameters measured, glucose and insulin concentrations were within the normal range following transition to the hay-only diet, but were higher in the group that failed to improve quickly, with a small but significant difference being evident on d 4, 14 and 25 for glucose (11 to 16%; P < 0.05), and a larger difference for insulin on d 14 and 25 (51 to 55%; P < 0.05). There was no difference between the groups in ACTH or leptin concentrations throughout the study. The main limitations of this study were the small number of slow-improvement horses and an inability to control or measure certain variables, such as feed quality. CONCLUSIONS: Young age and a modest increase in blood glucose and insulin concentrations are associated with delayed laminitis improvement.

Optical voltage sensor based on a piezoelectric thin film for grid applications.

Continuous monitoring of voltages ranging from tens to hundreds of kV over environmental conditions, such as temperature, is of great interest in power grid applications. This is typically done via instrument transformers. These transformers, although accurate and robust to environmental conditions, are bulky and expensive, limiting their use in microgrids and distributed sensing applications. Here, we present a millimeter-sized optical voltage sensor based on piezoelectric aluminum nitride (AlN) thin film for continuous measurements of AC voltages <350kVrms (via capacitive division) that avoids the drawbacks of existing voltage-sensing transformers. This sensor operated with 110µW incident optical power from a low-cost LED achieved a resolution of 170mVrms in a 5kHz bandwidth, 0.04% second harmonic distortion, and a gain deviation of +/-0.2% over the temperature range of ~20-60°C. The sensor has a breakdown voltage of 100V, and its lifetime can meet or exceed that of instrument transformers when operated at voltages <70kVrms with capacitive division. We believe that our sensor has the potential to reduce the cost of grid monitoring, providing a path towards more distributed sensing and control of the grid.

Metabolic profile distinguishes laminitis-susceptible and -resistant ponies before and after feeding a high sugar diet.

BACKGROUND: Insulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests. The identification of other biomarkers could provide an alternative or adjunct diagnostic method, to allow early intervention before laminitis develops. The present study characterised the metabolome of ponies with varying degrees of ID using basal and postprandial plasma samples obtained during a previous study, which examined the predictive power of blood insulin levels for the development of laminitis, in ponies fed a high-sugar diet. Samples from 10 pre-laminitic (PL - subsequently developed laminitis) and 10 non-laminitic (NL - did not develop laminitis) ponies were used in a targeted metabolomic assay. Differential concentration and pathway analysis were performed using linear models and global tests. RESULTS: Significant changes in the concentration of six glycerophospholipids (adj. P ≤ 0.024) and a global enrichment of the glucose-alanine cycle (adj. P = 0.048) were found to characterise the response of PL ponies to the high-sugar diet. In contrast, the metabolites showed no significant association with the presence or absence of pituitary pars intermedia dysfunction in all ponies. CONCLUSIONS: The present results suggest that ID and laminitis risk are associated with alterations in the glycerophospholipid and glucose metabolism, which may help understand and explain some molecular processes causing or resulting from these conditions. The prognostic value of the identified biomarkers for laminitis remains to be investigated in further metabolomic trials in horses and ponies.

Dental trauma splint color preference of adults.

The prevalence of dental trauma among children and adults is high. Most luxated teeth need splinting. The Titanium Trauma Splint (TTS) is a widely used appliance with good performance properties. Esthetics is increasingly important for most patients. Splints placed on the front teeth have a clearly visible impact on patients' appearance and, thus, on their quality of life during splint therapy. Therefore, the aim of the present study was to evaluate the esthetic preferences of adult patients with regard to different splint color and surface finish characteristics. TTS appliances were fabricated in four different colors (silver, gold, green and violet) and two different surface finishes (matt or polished) to yield a total of eight variants. The finished splints were applied to the teeth of a human model, photographed by a professional photographer, and printed as posters. Adults aged between 18 and 79 years were asked to complete a written survey containing items regarding their TTS color and surface preferences based on the posters with photographs as well as questions about previous tooth bleaching treatments, the importance of having esthetic teeth in general, and the prioritization of esthetic versus function-driven dentistry. Over 80% of participants preferred the silver matt splint over the other variants. Neither gender nor age nor other parameters had a significant influence on the choice of splint color or surface. Women placed greater importance on esthetic rather than function-driven treatment.

A "modified Obel" method for the severity scoring of (endocrinopathic) equine laminitis.

BACKGROUND: Laminitis is a common equine disease characterized by foot pain, and is commonly diagnosed using a five-grade Obel system developed in 1948 using sepsis-related cases. However, endocrinopathic laminitis is now the most common form of the disease and clinical signs may be mild, or spread across two Obel grades. This paper describes a modified method which assigns scores to discreet clinical signs, providing a wider scale suitable for use in a research setting. METHODS: The "modified Obel" method was developed using an iterative process. First, a prototype method was developed during the detailed observation of 37 ponies undergoing a laminitis induction experiment. The final method was refined and validated using video footage taken during the induction study and from a clinical trial of naturally occurring endocrinopathic laminitis cases. The Obel method was deconstructed and key laminitis signs were evaluated to develop a three-stage, five criteria method that employs a severity scale of 0-12. Veterinarians (n = 28) were recruited to watch and assess 15 video recordings of cases of varying severity, using the Obel and "modified Obel" methods. The inter-observer agreement (reproducibility) was determined using Kendall's coefficient of concordance (Kendall W) and Krippendorf's alpha reliability coefficient. A total of 14 veterinarians repeated the exercise 2-4 weeks after their original assessment, to determine intra-observer agreement (repeatability), assessed using a weighted kappa statistic (kw). Agreement between methods was calculated by converting all "modified Obel" scores to Obel grades and calculating the mean and distribution of the differences. RESULTS: The "modified Obel" and Obel methods showed excellent and similar inter-observer agreement based on the Kendall W value (0.87, P < 0.001 vs. 0.85, P < 0.001) and Krippendorf's alpha (95% CI) value (0.83 [0.53-0.90] vs. 0.77 [0.55-0.85]). Based on the kw value, the "modified Obel" method also had substantial repeatability, although slightly less than the Obel method, (0.80 vs. 0.91). Excellent agreement between the methods was found, with the mean difference (95% CI), comparing the Obel grade, with the "modified Obel" score converted to an Obel grade, being -0.12 (-0.19 to -0.06) grades. The Obel and converted "modified Obel" grades were identical 62% of the time (259/420) and a difference of one grade (higher or lower) occurred in 35% of cases (148/420). CONCLUSION: Both methods show excellent agreement, reproducibility and repeatability when used to diagnose endocrinopathic laminitis. The "modified Obel" method is a three-step examination process for severity-scoring of endocrinopathic laminitis, initially proposed for use within a research setting. When using the modified method a diagnosis of laminitis also requires clinical acumen. The allocation of scores for specific clinical signs should be particularly useful in research trials monitoring laminitis recovery.

The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.

There are no registered veterinary drugs for treating insulin dysregulation and preventing insulin-associated laminitis in horses. Velagliflozin is a sodium-glucose co-transport 2 inhibitor that reduces renal glucose reabsorption, promotes glucosuria, and consequently, decreases blood glucose and insulin concentrations. This study aimed to determine if velagliflozin reduced hyperinsulinemia and prevented laminitis in insulin-dysregulated ponies fed a challenge diet high in non-structural carbohydrates (NSC). An oral glucose test (1 g dextrose/kg BW) was used to screen 75 ponies for insulin dysregulation, of which 49 ponies with the highest insulin concentrations were selected. These animals were assigned randomly to either a treated group (n = 12) that received velagliflozin (0.3 mg/kg BW, p.o., s.i.d.) throughout the study, or a control group (n = 37). All ponies were fed a maintenance diet of alfalfa hay for 3 weeks, before transferring to a challenge diet (12 g NSC/kg BW/d) for up to 18 d. Blood glucose and serum insulin concentrations were measured over 4 h after feeding, on d 2 of the diet. The maximum glucose concentration was 22% lower (P = 0.014) in treated animals, with a geometric mean (95% CI) of 9.4 (8.0-11.0) mM, versus 12.1 (10.7-13.7) mM in the controls. This was reflected by lower (45%) maximum insulin concentrations in the treated group (P = 0.017), of 149 (97-228) µIU/mL, versus 272 (207-356) µIU/mL for controls. The diet induced Obel grade 1 or 2 laminitis in 14 of the 37 controls (38%), whereas no velagliflozin-treated pony developed laminitis (P = 0.011). Velagliflozin was well-tolerated, with no hypoglycemia or any clinical signs of adverse effects. The main limitation of this study was the sample size. Velagliflozin shows promise as a safe and effective compound for treating insulin dysregulation and preventing laminitis by reducing the hyperinsulinemic response to dietary NSC.

Does particulate matter along roadsides interfere with plant reproduction? A comparison of effects of different road types on Cichorium intybus pollen deposition and germination.

The roadside habitat can be challenging for plants, which must maintain normal biological processes despite an influx of airborne pollutants. While the effects of many gases on plants have been quantified, the impacts of particulate pollutants have been relatively less studied. This is especially true of field experiments where particle dispersion may be influenced by meteorology and roadway use. We examined chicory (Cichorium intybus L.) along roadsides in the Cincinnati, Ohio metropolitan area to assess particulate influence on plant pollination through stigmatic clogging. We compared flowers collected from plants situated along interstates, U.S. highways, state highways, and county roads as these different road-types vary in motor vehicle usage and thus should have varying levels of particulate deposition on flowers. We examined floral stigmas for total particulates, total pollen, and percentage of pollen tube germination to determine whether particulates may interfere with early reproductive processes. Our results suggest that there was minimal variation of particulate matter found on chicory stigmas among road-types. Furthermore, the deposition of particulates on stigmas based on road-type did not show a strong link to variation in pollen deposition and pollen germination. There was also no significant relationship between total particulate levels and pollen germination rates across all road types. Future studies should investigate other plant species that may be more sensitive to roadside pollution, such as economically important crops. Locations in which vehicle use is increasing and where pollutants are not regulated strictly should also be examined as the effects of airborne particulates in early plant reproduction would be expected to be more substantial in these areas.

Adjuvant Therapy for Gallbladder Cancer: an Analysis of the National Cancer Data Base.

BACKGROUND: The role of adjuvant therapy in patients with resected gallbladder cancer (GBC) is unclear. METHODS: The American College of Surgeons National Cancer Data Base was used to identify patients with resected GBC (pathologic stage 1-3) from 1998 to 2006 (n = 6690). We compared three groups: surgery only (S, 78.6 %), surgery plus adjuvant chemotherapy (AC, 6.2 %), and surgery plus adjuvant chemotherapy and radiation therapy (ACR, 15.1 %). Univariate and Cox regression analyses were used to determine factors influencing overall survival and the use of adjuvant therapy. RESULTS: ACR was associated with improved survival for all patients (HR 0.77, 95 % CI 0.66-0.90), especially node-positive patients (HR 0.64, 95 % CI 0.53-0.78); AC was not associated with changes in survival. Patients were less likely to have their lymph nodes examined if they had any comorbidities, lower income, or were treated at community cancer centers (all p < 0.05). Among patients with unknown lymph node status, those with T2 or T3 disease saw improved survival with ACR (T2: HR 0.79, 95 % CI 0.63-0.99; T3: HR 0.43, 95 % CI 0.30-0.62), while AC did not affect survival. CONCLUSION: ACR is associated with improved survival for patients with node-positive GBC, as well as those with T2 or T3 GBC with unknown lymph node status.

Adjuvant Chemotherapy and Radiation Therapy is Associated with Improved Survival for Patients with Extrahepatic Cholangiocarcinoma.

BACKGROUND: This study aimed to analyze adjuvant therapy among patients with extrahepatic cholangiocarcinoma (EHC) at a national level. METHODS: The American College of Surgeons National Cancer Data Base was used to identify patients with resected EHC (pathologic stages 1-3) between 1998 and 2006 (n = 8741). Three groups were compared: surgery only (S, n = 5766), surgery plus adjuvant chemotherapy (AC, n = 450), and surgery plus adjuvant chemotherapy and radiation therapy (ACR, n = 1918). The study investigated how patient demographics, provider characteristics, and tumor-specific variables were associated with receipt of adjuvant therapy and overall survival. RESULTS: Patients who received adjuvant treatment were more likely to be younger (median age S, 70 years; AC, 65 years; ACR, 63 years), in the highest income quartile (>$46,000: S, 38.3 %; AC, 43.4 %; ACR, 44.7 %), and treated at a community cancer center (S, 43.0 %; AC, 50.7 %; ACR, 52.9 %) (all p < 0.001). These patients also were more likely to have positive lymph nodes (S, 34.7 %; AC, 69.6 %; ACR, 63.3 %), positive surgical margins (S, 5.9 %; AC, 7.1 %; ACR, 10.7 %), and stage 3 disease (S, 21.4 %; AC, 37.8 %; ACR, 37.9 %) (all p < 0.001). Multivariate analysis of the entire cohort showed improved survival with ACR (hazard ratio [HR] 0.82; 95 % confidence interval [CI] 0.75-0.91). The survival benefit was independent of margin status (R0: HR 0.88; 95 % CI 0.79-0.97; R1: HR 0.49; 95 % CI 0.38-0.62). CONCLUSIONS: This national analysis suggests that ACR are associated with improved survival for high-risk EHC patients, such as those with positive lymph nodes. Until randomized clinical trials are conducted, these may be the best available data to guide adjuvant therapy for resected EHC.

Hyperbaric biofilms on engineering surfaces formed in the deep sea.

Biofouling is a major problem for long-term deployment of sensors in the marine environment. This study showed that significant biofilm formation occurred on a variety of artificial materials (glass, copper, Delrin(™) and poly-methyl methacrylate [PMMA]) deployed for 10 days at a depth of 4700 m in the Cayman Trough. Biofilm surface coverage was used as an indicator of biomass. The lowest biofilm coverage was on copper and PMMA. Molecular analyses indicated that bacteria dominated the biofilms found on copper, Delrin(™) and PMMA with 75, 55 and 73% coverage, respectively. Archea (66%) were dominant on the glass surface simulating interior sensor conditions, whereas Eukarya comprised the highest percentage of microflora (75%) on the glass simulating the exterior of sensors. Analysis of Denaturing Gradient Gel Electrophoresis profiles indicated that copper and Delrin(™) shared the same community diversity, which was not the case for glass and PMMA, or between PMMA and copper/Delrin(™). Sequence alignment matches belonged exclusively to uncultivable microorganisms, most of which were not further classified. One extracted sequence found on glass was associated with Cowellia sp., while another extracted from the PMMA surface was associated with a bacterium in the Alterominidaceae, both γ-proteobacteria. The results demonstrate the necessity of understanding biofilm formation in the deep sea and the potential need for mitigation strategies for any kind of long-term deployment of remote sensors in the marine environment.

Hydrothermal vent fields and chemosynthetic biota on the world's deepest seafloor spreading centre.

The Mid-Cayman spreading centre is an ultraslow-spreading ridge in the Caribbean Sea. Its extreme depth and geographic isolation from other mid-ocean ridges offer insights into the effects of pressure on hydrothermal venting, and the biogeography of vent fauna. Here we report the discovery of two hydrothermal vent fields on the Mid-Cayman spreading centre. The Von Damm Vent Field is located on the upper slopes of an oceanic core complex at a depth of 2,300 m. High-temperature venting in this off-axis setting suggests that the global incidence of vent fields may be underestimated. At a depth of 4,960 m on the Mid-Cayman spreading centre axis, the Beebe Vent Field emits copper-enriched fluids and a buoyant plume that rises 1,100 m, consistent with >400 °C venting from the world's deepest known hydrothermal system. At both sites, a new morphospecies of alvinocaridid shrimp dominates faunal assemblages, which exhibit similarities to those of Mid-Atlantic vents.

Expression of prestin-homologous solute carrier (SLC26) in auditory organs of nonmammalian vertebrates and insects.

Prestin, the fifth member of the anion transporter family SLC26, is the outer hair cell molecular motor thought to be responsible for active mechanical amplification in the mammalian cochlea. Active amplification is present in a variety of other auditory systems, yet the prevailing view is that prestin is a motor molecule unique to mammalian ears. Here we identify prestin-related SLC26 proteins that are expressed in the auditory organs of nonmammalian vertebrates and insects. Sequence comparisons revealed the presence of SLC26 proteins in fish (Danio, GenBank accession no. AY278118, and Anguilla, GenBank accession no. BAC16761), mosquitoes (Anopheles, GenBank accession nos. EAA07232 and EAA07052), and flies (Drosophila, GenBank accession no. AAF49285). The fly and zebrafish homologues were cloned and, by using in situ hybridization, shown to be expressed in the auditory organs. In mosquitoes, in turn, the expression of prestin homologues was demonstrated for the auditory organ by using highly specific riboprobes against rat prestin. We conclude that prestin-related SLC26 proteins are widespread, possibly ancestral, constituents of auditory organs and are likely to serve salient roles in mammals and across taxa.