High deoxynivalenol and ergot alkaloid levels in wheat grain: effects on growth performance, carcass traits, rumen fermentation, and blood parameters of feedlot cattle.

This study was designed to assess the impacts of a mixture of deoxynivalenol (DON) and ergot alkaloids (EAs) on growth performance, rumen function, blood parameters, and carcass traits of feedlot cattle. Forty steers (450 ± 6.0 kg) were stratified by weight and randomly allocated to 1 of 4 treatments; control-low (CON-L), control-high (CON-H) which contained low or high wheat screenings that lacked mycotoxins at the same level as the mycotoxin-low (MYC-L; 5.0 mg/kg DON, 2.1 mg/kg EA), and mycotoxin-high (MYC-H: 10 mg/kg DON, 4.2 mg/kg EA) diets that included wheat screening with mycotoxins. Steers were housed in individual pens for a 112-day finishing trial. Intake was 24.8% lower (P < 0.001) for MYC steers compared to CON steers. As a result, average daily gains of MYC steers were 42.1% lower (P < 0.001) than CON steers. Gain to feed ratio was also lower (P < 0.001) for MYC steers compared to CON steers. Platelets, alanine aminotransferase, globulins, and blood urea nitrogen were lower (P ≤ 0.008), and lymphocytes, glutathione peroxidase activity (GPx), and interleukin-10 (IL-10) were elevated (P ≤ 0.002) in MYC steers compared to CON steers. Hot carcass weights and backfat thickness were reduced (P < 0.001) in MYC steers, resulting in leaner (P < 0.001) carcasses and higher (P < 0.007) meat yield compared to CON steers. Results suggest that a mixture of DON and EAs negatively impacted health, performance, and carcass traits of feedlot steers, with the majority of this response likely attributable to EAs. However, more research is needed to distinguish the relative contribution of each mycotoxin to the specific responses observed.

Enhancing metabolite coverage in MALDI-MSI using laser post-ionisation (MALDI-2).

Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) of metabolites can reveal how metabolism is altered throughout heterogeneous tissues. Here negative ion mode MALDI-MSI has been coupled with laser post-ionisation (MALDI-2) and applied to the MSI of low molecular weight (LMW) metabolites (

Not Waiting to Progress; How the COVID-19 Pandemic Nudged Neoadjuvant Therapy for Stage III Locally Advanced Melanoma Patients.

Background: Early-phase neoadjuvant trials have demonstrated promising results in the utility of upfront immunotherapy in locally advanced stage III melanoma and unresected nodal disease. Secondary to these results and the COVID-19 pandemic, this patient population, traditionally managed through surgical resection and adjuvant immunotherapy, received a novel treatment strategy of neoadjuvant therapy (NAT). Methods: Patients with node-positive disease, who faced surgical delays secondary to COVID-19, were treated with NAT, followed by surgery. Demographic, tumour, treatment and response data were collected through a retrospective chart review. Biopsy specimens were analysed prior to the initiation of NAT, and therapy response was analysed following surgical resection. NAT tolerability was recorded. Results: Six patients were included in this case series; four were treated with nivolumab alone, one with ipilimumab and nivolumab and one with dabrafenib and trametinib. Twenty-two incidents of adverse events were reported, with the majority (90.9%) being classified as grade one or two. All patients underwent surgical resection: three out of six patients following two NAT cycles, two following three cycles and one following six cycles. Surgically resected samples were histopathologically evaluated for the presence of disease. Five out of six patients (83%) had ≤1 positive lymph node. One patient showed extracapsular extension. Four patients demonstrated complete pathological response; two had persisting viable tumour cells. Conclusions: In this case series, we outlined how in response to surgical delays secondary to the COVID-19 pandemic, NAT was successfully applied to achieve promising treatment response in patients with locally advanced stage III melanoma.

Mitigating Breast-Cancer-Related Lymphedema-A Calgary Program for Immediate Lymphatic Reconstruction (ILR).

With increasing breast cancer survival rates, one of our contemporary challenges is to improve the quality of life of survivors. Lymphedema affects quality of life on physical, psychological, social and economic levels; however, prevention of lymphedema lags behind the progress seen in other areas of survivorship such as breast reconstruction and fertility preservation. Immediate lymphatic reconstruction (ILR) is a proactive approach to try to prevent lymphedema. We describe in this article essential aspects of the elaboration of an ILR program. The Calgary experience is reviewed with specific focus on team building, technique, operating room logistics and patient follow-up, all viewed through research and education lenses.

Trans-Atlantic aeromedical repatriation of multiple COVID-19 patients: a hybrid military-civilian model.

Here, we report the first known transcontinental aeromedical evacuation of a large number (55) of patients with known and suspected positive COVID-19. These patients were evacuated from Havana, Cuba, to the UK through MOD Boscombe Down as part of Operation BROADSHARE, the British military's overseas response to COVID-19. We describe the safe transfer of patients with COVID-19 using a combined military-civilian model. In our view, we have demonstrated that patients with COVID-19 can be aeromedically transferred while ensuring the safety of patients and crew using a hybrid military-civilian model; this report contains lessons for future aeromedical evacuation of patients with COVID-19.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

Higher Rate of Lymphedema with Inguinal versus Axillary Complete Lymph Node Dissection for Melanoma: A Potential Target for Immediate Lymphatic Reconstruction?

BACKGROUND: The present study was conducted to define the lymphedema rate at our institution in patients undergoing axillary (ALND) or inguinal (ILND) lymph node dissection (LND) for melanoma. It aimed to examine risk factors predisposing patients to a higher rate of lymphedema, highlighting which patients could be targeted for immediate lymphatic reconstruction (ILR). METHODS: A retrospective chart review was conducted between October 2015 and July 2020 to identify patients who had undergone ALND or ILND for melanoma. The main outcome measures were rates of transient and permanent lymphedema. Univariate and multivariate analyses were performed to assess the relationship between lymphedema rate and factors related to patient characteristics, surgical procedure, pathology findings, and adjuvant treatment. RESULTS: Between October 2015 and July 2020, 66 patients underwent LND for melanoma: 34 patients underwent ALND and 32 patients underwent ILND. At a median follow-up of 29 months, 85.3% (n = 29) of patients having had an ALND did not experience lymphedema, versus 50.0% (n = 16) of ILND (p = 0.0019). The rates of permanent lymphedema for patients having undergone ALND and ILND were 11.8% (n = 4) and 37.5% (n = 12) respectively (p = 0.016, NS). The rate of transient lymphedema was 2.9% (n = 1) for ALND and 12.5% (n = 4) for ILND (p = 0.13, NS). On univariate analysis, the location of LND and wound infection were found to be significant factors for lymphedema. On multivariate analysis, only the location of LND remained a significant predictor, with the inguinal location predisposing to lymphedema. CONCLUSION: This study highlights the high rate of lymphedema following ILND for melanoma and is a potential target for future patients to be considered for ILR.

Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma: An International Multi-institutional Collaboration.

BACKGROUND: Consideration of sentinel lymph node biopsy (SLNB) is recommended for patients with T1b melanomas and T1a melanomas with high-risk features; however, the proportion of patients with actionable results is low. We aimed to identify factors predicting SLNB positivity in T1 melanomas by examining a multi-institutional international population. METHODS: Data were extracted on patients with T1 cutaneous melanoma who underwent SLNB between 2005 and 2018 at five tertiary centers in Europe and Canada. Univariable and multivariable logistic regression analyses were performed to identify predictors of SLNB positivity. RESULTS: Overall, 676 patients were analyzed. Most patients had one or more high-risk features: Breslow thickness 0.8-1 mm in 78.1% of patients, ulceration in 8.3%, mitotic rate > 1/mm2 in 42.5%, Clark's level ≥ 4 in 34.3%, lymphovascular invasion in 1.4%, nodular histology in 2.9%, and absence of tumor-infiltrating lymphocytes in 14.4%. Fifty-three patients (7.8%) had a positive SLNB. Breslow thickness and mitotic rate independently predicted SLNB positivity. The odds of positive SLNB increased by 50% for each 0.1 mm increase in thickness past 0.7 mm (95% confidence interval [CI] 1.05-2.13) and by 22% for each mitosis per mm2 (95% CI 1.06-1.41). Patients who had one excised node (vs. two or more) were three times less likely to have a positive SLNB (3.6% vs. 9.6%; odds ratio 2.9 [1.3-7.7]). CONCLUSIONS: Our international multi-institutional data confirm that Breslow thickness and mitotic rate independently predict SLNB positivity in patients with T1 melanoma. Even within this highly selected population, the number needed to diagnose is 13:1 (7.8%), indicating that more work is required to identify additional predictors of sentinel node positivity.

Canadian Melanoma Conference Recommendations on High-Risk Melanoma Surveillance: A Report from the 14th Annual Canadian Melanoma Conference; Banff, Alberta; 20-22 February 2020.

Introduction: There are a lack of established guidelines for the surveillance of high-risk cutaneous melanoma patients following initial therapy. We describe a novel approach to the development of a national expert recommendation statement on high-risk melanoma surveillance (HRS). Methods: A consensus-based, live, online voting process was undertaken at the 13th and 14th annual Canadian Melanoma Conferences (CMC) to collect expert opinions relating to "who, what, where, and when" HRS should be conducted. Initial opinions were gathered via audience participation software and used as the basis for a second iterative questionnaire distributed online to attendees from the 13th CMC and to identified melanoma specialists from across Canada. A third questionnaire was disseminated in a similar fashion to conduct a final vote on HRS that could be implemented. Results: The majority of respondents from the first two iterative surveys agreed on stages IIB to IV as high risk. Surveillance should be conducted by an appropriate specialist, irrespective of association to a cancer centre. Frequency and modality of surveillance favoured biannual visits and Positron Emission Tomography Computed Tomography (PET/CT) with brain magnetic resonance imaging (MRI) among the systemic imaging modalities available. No consensus was initially reached regarding the frequency of systemic imaging and ultrasound of nodal basins (US). The third iterative survey resolved major areas of disagreement. A 5-year surveillance schedule was voted on with 92% of conference members in agreement. Conclusion: This final recommendation was established following 92% overall agreement among the 2020 CMC attendees.

Whole-genome analysis of extraintestinal Escherichia coli sequence type 73 from a single hospital over a 2 year period identified different circulating clonal groups.

Sequence type (ST)73 has emerged as one of the most frequently isolated extraintestinal pathogenic Escherichia coli. To examine the localized diversity of ST73 clonal groups, including their mobile genetic element profile, we sequenced the genomes of 16 multiple-drug resistant ST73 isolates from patients with urinary tract infection from a single hospital in Sydney, Australia, between 2009 and 2011. Genome sequences were used to generate a SNP-based phylogenetic tree to determine the relationship of these isolates in a global context with ST73 sequences (n=210) from public databases. There was no evidence of a dominant outbreak strain of ST73 in patients from this hospital, rather we identified at least eight separate groups, several of which reoccurred, over a 2 year period. The inferred phylogeny of all ST73 strains (n=226) including the ST73 clone D i2 reference genome shows high bootstrap support and clusters into four major groups that correlate with serotype. The Sydney ST73 strains carry a wide variety of virulence-associated genes, but the presence of iss, pic and several iron-acquisition operons was notable.

Feedlot performance and immune function analysis of implanted and non-implanted steers selected for alcohol dehydrogenase 1 C (ADH1C) genotype and fed a low vitamin A diet.

Previous studies have shown that the interaction between limiting vitamin A (VA) and an alcohol dehydrogenase 1 C (ADH1C) variant in beef cattle results in increased intramuscular fat in the longissimus thoracis muscle in one genotype when fed low dietary VA. Although quality grade is important for increased profitability and improving taste characteristics of beef products, limiting VA too drastically can impair animal welfare. The objectives of this study were to determine if this marker-assisted management strategy would be effective, and whether any impairment in immune function would occur in a feedlot setting. Mixed breed beef steers (n=2000) were sorted into 40 feedlot pens so that all combinations of ADH1C genotype (TT or CT), VA level (50% or 100% of recommended) and hormonal implant status (implanted (IMP) or non-implanted (NI)) were equally represented within the population. The VA×ADH1C interaction was not observed. An implant status × ADH1C interaction was observed with average daily gain (ADG; P=0.03). Steers that were IMP and CT had higher ADG than IMP TT (CT=1.69 and TT=1.62 kg/day), whereas both genotypes in the NI steers were lower (CT=1.29 and TT=1.32 kg/day). Implant status was shown to affect dry matter intake (DMI; IMP=8.55 and NI=7.87 kg; P<0.01), total days-on-feed (IMP=164.4 and NI 210.5 days; P<0.01), USDA yield grade (YIELD; IMP=2.40 and NI=2.77; P<0.01), marbling score (MARB; IMP=392 and NI=455; P<0.01), longissimus thoracis area (LTA; IMP=85.0 and NI=80.7 cm2; P=0.01) and backfat thickness (FAT; IMP=8.0 and NI 10.0 mm; P<0.01). Overall, IMP animals finished on fewer total days-on-feed with higher ADG, DMI, larger LTA, and lower YIELD, MARB and FAT. To investigate immune function parameters, crossbred steers (n=18) were selected from a prior feeding trial so that all combinations of ADH1C (TT, CT and CC) and VA (25% or 75%) were equally represented. Blood cell count analysis and peripheral blood mononuclear cell proliferation and stimulation assays were conducted. None of these immune parameters were affected by VA level. Treatment and mortality records were examined in the 2000 steer population, where no correlations with ADH1C, implant status or VA level were observed. Due to no VA × ADH1C interaction, this nutrigenetic marker-assisted management strategy is not effective at this time in commercial beef cattle feedlots, however, supplementing VA at a level as low as 25% of recommended in finishing rations would likely not result in signs of immune dysfunction.

Effects of alternate day supplementation at two levels of energy on intake, rumen fermentation, and digestibility of beef heifers fed cool-season perennial grass hay.

A study was conducted to evaluate the effects of supplementing energy daily vs. on alternate days at levels that were 1.5 and 2 times the daily amount on DMI, rumen fermentation parameters, and apparent total tract digestibility of beef heifers fed grass hay. Four cannulated Hereford heifers (339 ± 11 kg) were randomly assigned over 4 periods to a 4 × 4 Latin square design. Heifers were fed a cool-season perennial grass (CSPG) hay (10% CP and 42% ADF) and supplemented with a pelleted feed formulated to provide 3.2 Mcal/kg of DE. Treatments consisted of a nonsupplemented control (CON) and 3 supplemented treatments where the supplement was offered daily at 0.6% BW (DLY) or on alternate days at 0.9% BW (LA) and 1.2% BW (HA). Heifers fed DLY had lower ( ≤ 0.04) CSPG hay DMI (7.1 vs. 8.1 kg/d) and mean ruminal pH (6.65 vs. 6.75) and greater ( < 0.01) total short-chain fatty acid (SCFA; 77.1 vs. 69.2 m) and NH-N (4.6 vs. 3.4 mg/dL) concentrations in ruminal fluid than CON heifers. The concentration of ruminal NH-N for LA (5.8 mg/dL) was greater ( < 0.01) than for DLY. Total tract DM digestibility was greater for DLY (52.5%; ≤ 0.03) than for CON (44.2%) and LA (49.7%), whereas no effects were found ( ≥ 0.11) for DLY vs. HA. When data was analyzed for days when LA and HA were supplemented, hay DMI was greater ( < 0.05) for DLY (7.3 kg/d) vs. HA (6.0 kg/d) but not different ( = 0.16) vs. LA (6.4 kg/d), mean ruminal pH of DLY (6.64) was greater vs. HA (6.59; = 0.04) and tended to be greater vs. LA (6.60; < 0.09), and total SCFA concentration of DLY (77.9 m) was lower ( < 0.01) vs. HA (88.2 m) and tended ( = 0.08) to be lower vs. LA (84.0 m). On days when LA and HA were not supplemented, hay DMI was not different ( ≥ 0.48) for DLY vs. LA and HA, mean ruminal pH was greater ( ≤ 0.03) for LA (6.79) and HA (6.85) compared with DLY (6.67), and total SCFA concentration of DLY (76.2 m) was not different ( = 0.15) vs. LA (67.5 m) but greater ( = 0.03) vs. HA (62.0 m). These results show that reducing the amount of supplement fed on alternate supplementation programs from 2 to 1.5 times the amount of daily programs can minimize the negative effects on rumen fermentation and forage DMI.

Defining risk for low reticuloruminal pH during the diet transition period in a commercial feedlot in western Canada.

The objective of the current study was to measure reticuloruminal pH in cattle in a commercial feedlot setting to determine the incidence and extent of low reticuloruminal pH for steers and heifers as they transition to a high-concentrate finishing diet. Reticuloruminal pH was measured in 16 "mixed breed" steers (4 steers/pen with 4 pens) and 16 "mixed breed" heifers (4 heifers/pen with 4 pens) housed in commercial feedlot pens, with 227 ± 13 and 249 ± 6 cattle/pen cohort steers and heifers, respectively, for the diet transition period. Cattle were transitioned from a diet of 53.5% forage and 46.5% concentrate to a diet of 9.5% forage and 90.5% concentrate on a DM basis using a 40-d transition with 5 dietary steps with the diets containing 41.4, 44.8, 49.8, 52.5, 55.1, and 64.0% nonfibrous carbohydrate. In addition, wheat replaced barley as the grain source during the dietary transition. Reticuloruminal pH was measured using orally administered pH measurement devices that were retrieved at slaughter. Data were analyzed using a mixed model including the fixed effects of sex, diet, and the 2-way interaction to evaluate the effect of diet and sex and with the fixed effects of sex, diet, and day relative to each dietary change along with the 2- and 3-way interactions to evaluate temporal responses as a result of diet change. A repeated measures statement was included for the effect of day. Both the mean and minimum reticuloruminal pH values decreased as the proportion of concentrate in the diet increased ( < 0.001). The area and duration that pH was <5.6 increased with greater inclusion of concentrate in the diet ( < 0.001). The number of cattle experiencing low reticuloruminal pH, defined as pH < 5.6 for >180 min, increased with increasing concentrate, and by the end of the 40-d dietary transition, 83% of the cattle had experienced at least 1 bout of low reticuloruminal pH, with most experiencing between 1 and 3 bouts/diet. These data are interpreted to suggest that cattle are at high risk for experiencing low reticuloruminal pH during the dietary transition but that the extent of low reticuloruminal pH is mild. Moreover, the data suggest that the risk for low reticuloruminal pH increases with increasing proportion of concentrate in the diet. The results also suggest that susceptibility to low reticuloruminal pH may differ between steers and heifers.

Effect of dietary energy substrate and days on feed on apparent total tract digestibility, ruminal short-chain fatty acid absorption, acetate and glucose clearance, and insulin responsiveness in finishing feedlot cattle.

The objective of this study was to determine the effect of dietary energy substrate and days on feed on apparent total tract digestibility, ruminal fermentation, short-chain fatty acid (SCFA) absorption, plasma glucose and acetate clearance rates, and insulin responsiveness. Eight ruminally cannulated, crossbred growing heifers were randomly allocated to 1 of 2 dietary treatments. The control (CON) diet consisted of 75.2% barley grain, 9.8% canola meal, 9% mineral and vitamin supplement, and 6% barley silage (DM basis). To evaluate the effect of energy source, a high-lipid, high-fiber byproduct pellet (HLHFP) was included in the diet by replacing 55% of the barley grain and 100% of canola meal. The study consisted of 4 consecutive 40-d periods (P1 to P4), with data and sample collection occurring in the last 12 d of each period. Dry matter intake tended ( = 0.10) to decrease by period and HLHFP-fed heifers tended to eat less ( = 0.09). The ADG of the CON was greater than that of the HLHFP during P1 and P4 (treatment × period, = 0.02). Heifers fed HLHFP tended to have greater mean ruminal pH (6.10 vs. 5.96; = 0.07) than heifers fed the CON, but pH was not affected by period. The CON heifers had a greater digestibility for DM, OM, CP, and NDF ( ≤ 0.03), and the digestibility for DM and OM linearly increased ( = 0.01) and for CP, NDF, and starch quadratically increased ( ≤ 0.04) with advancing period. Total SCFA concentration in the rumen was greater ( < 0.01) for the CON than for the HLHFP (141.6 vs. 128.1 m). The molar proportion of acetate and isobutyrate linearly increased and butyrate and valerate linearly decreased ( ≤ 0.05) with advancing periods. The rate of valerate absorption tended to increase (linear, = 0.06) and the ruminal liquid passage rate tended to decrease (linear, = 0.08) with advancing period. The arterial clearance rate of acetate tended to quadratically increase ( = 0.06) with period, whereas the clearance rate of glucose was not affected by treatment or period. Both fasting plasma insulin and the area under the insulin curve in response to glucose infusion linearly increased ( = 0.04) with period. These data suggest that partially replacing barley grain with HLHFP negatively affects total tract digestibility and performance. Moreover, with advancing days on feed, digestibility and insulin resistance increases without changes in ruminal pH and plasma metabolite clearance rates.

Elution profiles of tobramycin and vancomycin from high-purity calcium sulphate beads incubated in a range of simulated body fluids.

The aim of this study was to characterise the elution profiles of antibiotics in combination with pharmaceutical grade calcium sulphate beads in phosphate buffered saline and other physiological solutions which more closely mimic the in vivo environment. Synthetic recrystallised calcium sulphate was combined with vancomycin hydrochloride powder and tobramycin sulphate solution and the paste was formed into 3 mm diameter hemispherical beads. Then 2 g of beads were immersed in 2 ml of either phosphate buffered saline, Dulbecco's Modified Eagle Medium or Hartmann's solution and incubated at 37℃ for up to 21 days. At a range of time points, eluent was removed for analysis by liquid chromatography-mass spectrometry (LC-MS). Tobramycin sulphate and vancomycin hydrochloride release was successfully quantified against standard curves from solutions eluted in all three physiological media (phosphate buffered saline, Dulbecco's Modified Eagle Medium and Hartmann's solution) during incubation with calcium sulphate beads. One hour eluate concentrations were high, up to 2602 µg/ml for tobramycin in phosphate buffered saline and 7417 µg/ml for vancomycin, whereas in DMEM, the levels of tobramycin were 2458 µg/ml and 4401 µg/ml for vancomycin. The levels in HRT were 2354 µg/ml for tobramycin and 5948 µg/ml for vancomycin. The results show highest levels of antibiotic elution over the first 24 h, which gradually diminish over the following 21 days.

Effects of dietary crude protein and rumen-degradable protein concentrations on urea recycling, nitrogen balance, omasal nutrient flow, and milk production in dairy cows.

The objective of this study was to determine how interactions between dietary crude protein (CP) and rumen-degradable protein (RDP) concentrations alter urea-nitrogen recycling, nitrogen (N) balance, omasal nutrient flow, and milk production in lactating Holstein cows. Eight multiparous Holstein cows (711±21kg of body weight; 91±17d in milk at the start of the experiment) were used in a replicated 4×4 Latin square design with a 2×2 factorial arrangement of dietary treatments and 29-d experimental periods. Four cows in one Latin square were fitted with ruminal cannulas to allow ruminal and omasal sampling. The dietary treatment factors were CP (14.9 vs. 17.5%; dry matter basis) and RDP (63 vs. 69% of CP) contents. Dietary RDP concentration was manipulated by including unprocessed or micronized canola meal. Diet adaptation (d 1-20) was followed by 8d (d 21-29) of sample and data collection. Continuous intrajugular infusions of [(15)N(15)N]-urea (220mg/d) were conducted for 4d (d 25-29) with concurrent total collections of urine and feces to estimate N balance and whole-body urea kinetics. Proportions of [(15)N(15)N]- and [(14)N(15)N]-urea in urinary urea, and (15)N enrichment in feces were used to calculate urea kinetics. For the low-CP diets, cows fed the high-RDP diet had a greater DM intake compared with those fed the low-RDP diet, but the opposite trend was observed for cows fed the high-CP diets. Dietary treatment had no effect on milk yield. Milk composition and milk component yields were largely unaffected by dietary treatment; however, on the low-CP diets, milk fat yield was greater for cows fed the low-RDP diet compared with those fed the high-RDP diet, but it was unaffected by RDP concentration on the high-CP diets. On the high-CP diets, milk urea nitrogen concentration was greater in cows fed the high-RDP diet compared with those fed the low-RDP diet, but it was unaffected by RDP concentration on the low-CP diets. Ruminal NH3-N concentration tended to be greater in cows fed the high-CP diet compared with those fed the low-CP diet, and it was greater in cows fed the high-RDP diet as compared with those fed the low-RDP diet. Nitrogen intake and both total N and urea-N excretion in urine were greater for cows fed the high-CP diet compared with those fed the low-CP diet. However, N balance and urinary excretion of purine derivatives were unaffected by dietary treatment. Urea-N entry rate (UER) was greater in cows fed the high-CP diet compared with those fed the low-CP diet; however, UER was unaffected by dietary RDP concentration. The proportion of urea-N recycled to the gastrointestinal tract (as a percentage of UER) was greater in cows fed the low-CP diet compared with those fed the high-CP diet. In summary, reducing dietary CP concentration decreased urinary N excretion but had no effect on milk yield, thus resulting in an overall improvement in milk N efficiency.

Effect of maturity at harvest for whole-crop barley and oat on dry matter intake, sorting, and digestibility when fed to beef cattle.

The objectives were to evaluate the effect of harvest maturity of whole-crop oat (Study 1) and whole-crop barley (Study 2) on forage intake and sorting, ruminal fermentation, ruminal digestibility, and total tract digestibility when fed to beef heifers. In Study 1, 3 ruminally cannulated heifers (417 ± 5 kg) were used in a 3 × 3 Latin square design with 24-d periods. Whole-crop oat forage harvested at the late milk (LMILK), hard dough (HD), or ripe (RP) stages was fed for ad libitum intake and heifers were supplemented (1% of BW) with alfalfa pellets, barley grain, canola meal, and a mineral and vitamin pellet. Maturity at harvest for whole-crop oat did not affect ( ≥ 0.058) forage intake, DE intake, amount of forage refused, ruminal short-chain fatty acid concentration, or digestibility of DM, OM, NDF, and ADF. Ruminal starch digestibility decreased ( < 0.001) from 92.6% at the LMILK stage to 90.0% at the RP stage, with total tract starch digestibility decreasing ( = 0.043) from 95.8% at the LMILK stage to 94.8% at the RP stage. Ruminal CP digestibility was reduced at the HD stage compared with the LMILK and RP stages ( < 0.001). Mean ruminal pH was greatest for the LMILK stage (6.36; = 0.003) compared with the HD and RP stages (6.30 and 6.28, respectively). In Study 2, 6 ruminally cannulated heifers (273 ± 16 kg) were used in a replicated 3 × 3 Latin square design with 24-d periods. Dietary treatments included ad libitum access to whole-crop barley harvested at the LMILK, HD, or RP stage and a constant rate (0.8% BW) of supplement containing alfalfa pellets, barley grain, canola meal, and a mineral and vitamin pellet. Dry matter intake, ruminal content mass, and feeding behavior were not affected by harvest maturity ( ≥ 0.16). There was a decrease in total tract digestibility of DM, OM, and NDF observed at the HD stage compared with the LMILK and RP stages ( ≤ 0.004). Ruminal NDF digestibility decreased from 69.7% at the LMILK stage to 54.4% at the HD stage and 54.9% at the RP stage ( = 0.001), whereas ruminal ADF digestibility decreased from 70.0% at the LMILK stage to 44.4% at the HD stage and 42.5% at the RP stage ( = 0.002). Minimum and mean ruminal pH were least for the LMILK stage, intermediate at the RP stage, and greatest at the HD stage ( = 0.016 and = 0.031, respectively). These data suggest that despite reductions in ruminal digestibility of NDF and ADF with advancing maturity, harvesting whole-crop oat and barley forage at the HD and RP stages of maturity did not negatively affect DMI, fermentation characteristics, or DE relative to whole-crop cereal forage harvested at the LMILK stage.

Management of uveal melanoma: a consensus-based provincial clinical practice guideline.

INTRODUCTION: Survival in uveal melanoma has remained unchanged since the early 1970s. Because outcomes are highly related to the size of the tumour, timely and accurate diagnosis can increase the chance for cure. METHODS: A consensus-based guideline was developed to inform practitioners. PubMed was searched for publications related to this topic. Reference lists of key publications were hand-searched. The National Guidelines Clearinghouse and individual guideline organizations were searched for relevant guidelines. Consensus discussions by a group of content experts from medical, radiation, and surgical oncology were used to formulate the recommendations. RESULTS: Eighty-four publications, including five existing guidelines, formed the evidence base. SUMMARY: Key recommendations highlight that, for uveal melanoma and its indeterminate melanocytic lesions in the uveal tract, management is complex and requires experienced specialists with training in ophthalmologic oncology. Staging examinations include serum and radiologic investigations. Large lesions are still most often treated with enucleation, and yet radiotherapy is the most common treatment for tumours that qualify. Adjuvant therapy has yet to demonstrate efficacy in reducing the risk of metastasis, and no systemic therapy clearly improves outcomes in metastatic disease. Where available, enrolment in clinical trials is encouraged for patients with metastatic disease. Highly selected patients might benefit from surgical resection of liver metastases.