Rodent and Broiler Feeding Studies with Maize Containing Genetically Modified Event DP-915635-4 Show No Adverse Effects on Health or Performance.

Several regulatory agencies continue to require animal feeding studies to approve new genetically modified crops despite such studies providing little value in the safety assessment. Feeding studies with maize grain containing event DP-915635-4 (DP915635), a new corn rootworm management trait, were conducted to fulfill that requirement. Diets fed to Crl:CD®(SD) rats for 90 days contained up to 50% ground maize grain from DP915635, non-transgenic control, or non-transgenic reference hybrids (P1197, 6158, and 6365). Ross 708 broilers received phase diets containing up to 67% maize grain from each source for 42 days. Growth performance was compared between animals fed DP915635 and control diets; rats were further evaluated for clinical and neurobehavioral measures, ophthalmology, clinical pathology, organ weights, and gross and microscopic pathology, whereas carcass parts and select organ yields were determined for broilers. Reference group inclusion assisted in determining natural variation influence on observed significant differences between DP915635 and control groups. DP915635 maize grain diet consumption did not affect any measure evaluated in either feeding study. Results demonstrated DP-915635-4 maize grain safety and nutritional equivalency when fed in nutritionally adequate diets, adding to the existing literature confirming the lack of significant effects of feeding grain from genetically modified plants.

Evaluation of an in vitro experimental platform of human polarized intestinal epithelial monolayers for the hazard assessment of insecticidal proteins.

Previous work demonstrated the utility of using human-derived intestinal epithelial cell (IEC) lines cultured as polarized monolayers on Transwell® filters to differentiate between hazardous and non-hazardous proteins. The current study seeks to further resolve appropriate concentrations for evaluating proteins of unknown hazard potential using the IEC experimental platform and leverages these parameters for evaluating the potential toxicity of insecticidal proteins characteristic of those expressed in genetically modified (GM) agricultural biotechnology crops. To establish optimal test protein concentrations, effects of several known hazardous (C. perfringens epsilon toxin, Listeriolysin O, Phaseolus vulgaris erythroagglutinin, E. coli Shiga toxin 1, C. difficile Toxin B and wheat germ agglutinin) and non-hazardous (Ara-h2, ß-lactoglobulin, fibronectin and Rubisco) proteins on IEC barrier integrity and cell viability were evaluated at concentration ranges. Two insecticidal proteins (AfIP-1A and AfIP-1B) were evaluated for effects in the IEC assay, a seven-day insecticidal bioassay, and assessed in a high-dose 14-day acute oral toxicity study in mice. The results obtained from the human in vitro IEC assay were consistent with results obtained from an in vivo acute oral toxicity study, both demonstrating that the combination of AfIP-1A and AfIP-1B do not exhibit any identifiable harmful impacts on mammalian cells.

Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation.

PURPOSE: Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation. METHODS: We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis. RESULTS: There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07). CONCLUSION: Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.

Protein familiarity is a fundamental but rarely operationalized concept in the safety assessment of genetically modified crops: example of phosphomannose isomerase (PMI).

Fundamental to the safety assessment of genetically modified (GM) crops is the concept of negligible risk for newly expressed proteins for which there is a history of safe use. Although this simple concept has been stated in international and regional guidance for assessing the risk of newly expressed proteins in GM crops, its full implementation by regulatory authorities has been lacking. As a result, safety studies are often repeated at a significant expenditure of resources by developers, study results are repeatedly reviewed by regulators, and animals are sacrificed needlessly to complete redundant animal toxicity studies. This situation is illustrated using the example of the selectable marker phosphomannose isomerase (PMI) for which familiarity has been established. Reviewed is the history of safe use for PMI and predictable results of newly conducted safety studies including bioinformatic comparisons, resistance to digestion, and acute toxicity that were repeated to gain regulatory reapproval of PMI expressed from constructs in recently developed GM maize. As expected, the results of these newly repeated hazard-identification and characterization studies for PMI indicate negligible risk. PMI expressed in recently developed GM crops provides an opportunity to use the concept of familiarity by regulatory authorities to reduce risk-disproportionate regulation of these new events and lessen the resulting waste of both developer and regulator resources, as well as eliminate unnecessary animal testing. This would also correctly imply that familiar proteins like PMI have negligible risk. Together, such modernization of regulations would benefit society through enabling broader and faster access to needed technologies.

Fecal Microbiota, Forage Nutrients, and Metabolic Responses of Horses Grazing Warm- and Cool-Season Grass Pastures.

Integrating warm-season grasses into cool-season equine grazing systems can increase pasture availability during summer months. The objective of this study was to evaluate effects of this management strategy on the fecal microbiome and relationships between fecal microbiota, forage nutrients, and metabolic responses of grazing horses. Fecal samples were collected from 8 mares after grazing cool-season pasture in spring, warm-season pasture in summer, and cool-season pasture in fall as well as after adaptation to standardized hay diets prior to spring grazing and at the end of the grazing season. Random forest classification was able to predict forage type based on microbial composition (accuracy: 0.90 ± 0.09); regression predicted forage crude protein (CP) and non-structural carbohydrate (NSC) concentrations (p < 0.0001). Akkermansia and Clostridium butyricum were enriched in horses grazing warm-season pasture and were positively correlated with CP and negatively with NSC; Clostridum butyricum was negatively correlated with peak plasma glucose concentrations following oral sugar tests (p ≤ 0.05). These results indicate that distinct shifts in the equine fecal microbiota occur in response different forages. Based on relationships identified between the microbiota, forage nutrients, and metabolic responses, further research should focus on the roles of Akkermansia spp. and Clostridium butyricum within the equine hindgut.

Redesigning Rural Acute Stroke Care: A Person-Centered Approach.

Stroke service delivery in rural areas in Australia lacks evidence-based, best practice care protocols as a result of limited resources and opportunity. Healthcare redesign is an approach to improving health services by understanding barriers and enablers to service provision and work with users to develop solutions for improvement. This research aimed to qualitatively evaluate stroke care in rural Tasmania using a person-centered approach, as part of a larger healthcare redesign initiative to improve acute stroke care. Semi-structured interviews, aimed at gaining insight into experiences of healthcare staff and users, were conducted. Thematic analysis revealed three global themes (communication, holistic care, and resourcing) that demonstrated some consistency between healthcare staff and user experience, highlighting that some needs and expectations were not being met. Results of this experiential study provide important perspectives for delivering needs-based improvements in service provision for acute stroke care. Overall, this study showed that systems of stroke care in rural areas could be improved by utilizing a redesign approach including healthcare staff and users in the development of solutions for health service improvement.

Implementation of a comprehensive prehabilitation program for patients undergoing radical cystectomy.

BACKGROUND: Coordinated preoperative optimization programs for radical cystectomy (RC) are limited and non-comprehensive. We evaluated the feasibility and acceptability of a coordinated, multi-faceted prehabilitation program for RC patients at a high-volume bladder cancer referral center. METHODS: We performed a narrative literature review for prehabilitation in bladder cancer management as of December 1, 2020, with specific emphasis on examining higher-level evidence sources. We selected domains with the highest level of evidence and recruited a multidisciplinary team of experts to design our program. We implemented a comprehensive prehabilitation program with a pre-defined order set as standard of care for all patients undergoing RC beginning February 1, 2021. Demographic and clinicopathologic data were collected prospectively. Rates of adherence to the prehabilitation program services were analyzed using Stata version 13. RESULTS: A total of 82 patients were enrolled between February - December 2021, of which 67 (81%) had undergone RC at data cutoff. Mean age was 68 years (SD 11) and 63 (76%) identified as male. Neoadjuvant chemotherapy (NAC) was utilized in 48 (59%) patients. The mean Charlson Comorbidity Index was 3.8 (SD 2.3). 100% of patients were screened for malnutrition, with 82% consuming nutritional supplements. Fifty-two percent of patients attended physical therapy pre-op. The 30-day and 30- to 90-day rates of complications were 56% and 40%, respectively. Resource length of stay (RLOS) declined after implementation of prehabilitation. CONCLUSIONS: Implementation of a comprehensive prehabilitation program at a high-volume bladder cancer referral center is feasible and has a modest effect on resource consumption and complications in our early experience.

The risks of cancer in older women with BRCA pathogenic variants: How far have we come?

BACKGROUND: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. METHODS: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow-up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow-up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan-Meier method. RESULTS: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk-reducing mastectomy and bilateral salpingo-oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. CONCLUSION: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately.

Crabgrass as an equine pasture forage: impact of establishment method on yield, nutrient composition, and horse preference.

Warm-season grasses (WSG) incorporated into traditional cool-season rotational grazing systems to increase summer yields are typically established in monoculture in separate pasture areas. Few studies have evaluated alternative interseeded establishment of WSG, despite potential benefits for improving biodiversity and land-use efficiency. The objective of this study was to determine the impact of establishment method (monoculture vs. interseeded) on crabgrass pasture forage yield, nutritive value, and preference under equine grazing. Three adult standardbred mares grazed two main plots on two consecutive days (8 hr/d) for three grazing events in 2019: Jul 28/29 (GRAZE 1), Aug 20/30 (GRAZE 2), Oct 1/2 (GRAZE 3). Each main plot contained four replicates of three treatments: mixed cool-season grass (CSG); Quick-N-Big crabgrass (CRB) [Digitaria sanguinalis (L.) Scop.] interseeded into existing cool-season grass (INT), and CRB established as a monoculture (MON). The cool-season grass mix included Inavale orchardgrass [Dactylis glomerata (L.)], Tower tall fescue [Lolium arundinaceum (Schreb.) Darbysh.], and Argyle Kentucky bluegrass [Poa pratensis (L.)]. Herbage mass (HM) and sward height (SH) were measured prior to each grazing event and samples were collected (0800-1000 h) for chemical composition analysis. Observed grazing time (GT) in each sub-plot as determined by 5-min scan sampling was utilized as marker of horse preference. Forage HM was greater in MON (8043 ± 1220 kg/ha) than CSG (5001 ± 1308 kg/ha; P = 0.003), with a trend for greater total HM in MON vs. INT (6582 ± 1220 kg/ha: P = 0.06), but HM did not differ between INT and CSG. The SH was also greatest for MON (28 ± 1.11; INT: 23.6 ± 1.11; CSG: 19.7 ± 1.37 cm; P < 0.003). Forage nutrients (digestible energy and crude protein) were largely similar across treatments and met requirements of horses at maintenance. Horse GT was lower in MON (22.6 ± 3.77 min/sub-plot) than in INT (31.9 ± 3.79 min/sub-plot; P = 0.003) and there was a trend for lower GT in MON vs. CSG (29.9 ± 4.17 min/sub-plot: P = 0.07). These results indicate interseeding CRB would not effectively increase yields of traditional cool-season grass equine rotational grazing systems and would not supply similar levels of summer forage provided by monoculture establishment. Results of this study also suggest horses may prefer cool-season grass pasture forage over warm-season crabgrass.

Fecal microbiome of horses transitioning between warm-season and cool-season grass pasture within integrated rotational grazing systems.

BACKGROUND: Diet is a key driver of equine hindgut microbial community structure and composition. The aim of this study was to characterize shifts in the fecal microbiota of grazing horses during transitions between forage types within integrated warm- (WSG) and cool-season grass (CSG) rotational grazing systems (IRS). Eight mares were randomly assigned to two IRS containing mixed cool-season grass and one of two warm-season grasses: bermudagrass [Cynodon dactylon (L.) Pers.] or crabgrass [Digitaria sanguinalis (L.) Scop.]. Fecal samples were collected during transitions from CSG to WSG pasture sections (C-W) and WSG to CSG (W-C) on days 0, 2, 4, and 6 following pasture rotation and compared using 16S rRNA gene sequencing. RESULTS: Regardless of IRS or transition (C-W vs. W-C), species richness was greater on day 4 and 6 in comparison to day 0 (P < 0.05). Evenness, however, did not differ by day. Weighted UniFrac also did not differ by day, and the most influential factor impacting ß-diversity was the individual horse (R2 ≥ 0.24; P = 0.0001). Random forest modeling was unable to accurately predict days within C-W and W-C, but could predict the individual horse based on microbial composition (accuracy: 0.92 ± 0.05). Only three differentially abundant bacterial co-abundance groups (BCG) were identified across days within all C-W and W-C for both IRS (W ≥ 126). The BCG differing by day for all transitions included amplicon sequence variants (ASV) assigned to bacterial groups with known fibrolytic and butyrate-producing functions including members of Lachnospiraceae, Clostridium sensu stricto 1, Anaerovorax the NK4A214 group of Oscillospiraceae, and Sarcina maxima. In comparison, 38 BCG were identified as differentially abundant by horse (W ≥ 704). The ASV in these groups were most commonly assigned to genera associated with degradation of structural carbohydrates included Rikenellaceae RC9 gut group, Treponema, Christensenellaceae R-7 group, and the NK4A214 group of Oscillospiraceae. Fecal pH also did not differ by day. CONCLUSIONS: Overall, these results demonstrated a strong influence of individual horse on the fecal microbial community, particularly on the specific composition of fiber-degraders. The equine fecal microbiota were largely stable across transitions between forages within IRS suggesting that the equine gut microbiota adjusted at the individual level to the subtle dietary changes imposed by these transitions. This adaptive capacity indicates that horses can be managed in IRS without inducing gastrointestinal dysfunction.

Safety assessment of the insecticidal protein IPD079Ea from the fern, Ophioglossum pendulum.

As agricultural biotechnology continues to develop solutions for addressing crop pests through newly expressed proteins from novel source organisms, with different modes or sites of action and/or different spectra of activity, the safety of these proteins will be assessed. The results of hazard-identification and characterization studies for the insecticidal protein IPD079Ea, which is derived from a fern (Ophioglossum pendulum) and active against the maize pest western corn rootworm (Diabrotica virgifera virgifera, Coleoptera: Chrysomelidae) are provided. Collectively these results indicate that IPD079Ea is unlikely to present a hazard to human or animal health and support the safety of genetically modified maize expressing IPD079Ea.

Supraclavicular brachial plexus and paravertebral blocks: novel regional anaesthetic technique for brachioaxillary fistula formation with a synthetic graft.

Vascular access formation surgery for renal replacement therapy can be performed under local, regional or general anaesthesia. Regional anaesthesia may offer several advantages, however the sensory innervation to the upper medial arm can be difficult to adequately block. We describe a novel regional anaesthetic technique using both supraclavicular brachial plexus and paravertebral blocks for a multimorbid 73-year-old woman undergoing brachioaxillary fistula formation with a synthetic graft. An ultrasound-guided supraclavicular brachial plexus block was performed, followed by an ultrasound-guided T2/3 level paravertebral block. Adequate sensory blockade for surgery was achieved. Supplemental local anaesthetic infiltration was not required, and the operation was well tolerated by the patient. We consider this to be a valuable regional anaesthetic technique for vascular access formation surgery involving the upper arm.

Longitudinal Patterns of Alcohol Use Following Traumatic Brain Injury in an Active Duty and Young Veteran Military Sample: A VA TBI Model Systems Study.

OBJECTIVE: To describe alcohol use among younger military active duty service members and veterans (SMVs) in the first 5 years after traumatic brain injury (TBI) and examine whether differential alcohol use patterns emerge as a function of brain injury severity and active duty service at time of injury. SETTING: Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRCs). PARTICIPANTS: In total, 265 SMVs enrolled in the VA Traumatic Brain Injury Model Systems (TBIMS) PRC national database. Participants sustained a TBI of any severity level; received inpatient care at a PRC within 1 year of injury; were younger than 40 years; and completed survey interviews or questionnaires regarding their pre- and postinjury alcohol use for at least 3 of 4 time points (preinjury, postinjury years 1, 2, and 5). MAIN MEASURES: Self-reported alcohol use, defined as amount of weekly consumption and endorsement of binge drinking. Participant information related to demographics, injury, TBI severity, active duty status, mental health treatment, and FIM (Functional Independence Measure) total scores was also obtained to examine impact of these as covariates in the analyses. RESULTS: Alcohol use generally increased following an initial period of reduced consumption for SVMs with moderate-to-severe TBI. Individuals with mild TBI showed an opposite trend, with an initial period of increased use, followed by a decline and return to baseline levels in the long term. However, alcohol use did not significantly differ over time within this subsample after adjusting for covariates. CONCLUSIONS: The current study identified longitudinal alcohol use among a young, military/veteran cohort with a history of TBI, an at-risk population for problematic alcohol use. Patterns of self-reported alcohol consumption suggest the time frame of 2 to 5 years postinjury may be a critical window of opportunity for further intervention to maintain lowered levels of alcohol use, particularly among SVMs with moderate-to-severe TBI.

Diurnal Variation in Forage Nutrient Composition of Mixed Cool-Season Grass, Crabgrass, and Bermudagrass Pastures.

Warm-season grasses have been suggested as alternative low non-structural carbohydrate (NSC) pasture forages. The purpose of this study was to evaluate nutrient composition and diurnal changes in soluble carbohydrates for the warm-season annual 'Quick-N-Big' crabgrass [CRB; Digitaria sanguinalis (L.) Scop.] and the warm-season perennial 'Wrangler' bermudagrass [BER; Cynodon dactylon (L.) Pers] in comparison to mixed cool-season grass [CSG; 'Inavale' orchardgrass (Dactylis glomerata [L.]), 'Tower' tall fescue (Lolium arundinaceum [Schreb.] Darbysh.), and 'Argyle' Kentucky bluegrass (Poa pratensis [L.])]. Samples were collected at 4-hour intervals over 3 d when each forage reached the boot stage of maturity. Digestible energy was greatest for CSG (2.29 ± 0.34 Mcal/kg) and lowest for BER (2.13 ± 0.34 Mcal/kg), while crude protein was lowest for CSG (16.1 ± 0.29%) and neutral detergent fiber was greatest for BER (60.0 ± 0.41; P ≤ .0008). Non-structural carbohydrates were greater for CSG (17.6% ± 0.26%) compared to BER (10.6% ± 0.26%) or CRB (10.9% ± 0.26%; P < .0001). Overall, NSC was greatest in the afternoon and evening (14.5-14.9 ± 0.60%) and lowest in the early morning (11.2-11.4 ± 0.60%; P ≤ .04), but diurnal variation was most pronounced in CSG versus either Warm-season grasses. Results of this study provide needed data on nutritional composition of CRB and BER and demonstrate that these grasses may serve as pasture forages for horses where NSC intake is of concern. Results also support recommendations for restricting grazing to early morning to limit NSC consumption, particularly in CSG pastures.

Physical Therapy for Muscle Tension Dysphonia with Cervicalgia.

OBJECTIVES: This study investigated the effectiveness of a specialized manual physical therapy (PT) program at improving voice among patients diagnosed with concomitant muscle tension dysphonia (MTD) and cervicalgia at a tertiary care voice center. MATERIALS AND METHODS: Cervicalgia was determined by palpation of the anterior neck. Both voice therapy (VT) and PT was recommended for all patients diagnosed with MTD and cervicalgia. PT included full-body manual physical therapy with myofascial release. Patients underwent: 1) VT alone, 2) concurrent PT and VT (PT with VT), 3) PT alone, 4) VT, but did not have PT ordered by treating clinician (VT without PT order) or 5) VT followed by PT (VT then PT). The pairwise difference in post-Voice Handicap Index-10 (VHI-10) controlling for baseline variables was calculated with a linear regression model. RESULTS: 178 patients met criteria. All groups showed improvement with treatment. The covariate-adjusted differences in mean post-VHI-10 improvement comparing the VT alone group as a reference were as follows: PT with VT 9.95 (95% confidence interval 7.70, 12.20); PT alone 8.31 (6.16, 10.45); VT without PT order 8.51 (5.55, 11.47); VT then PT 5.47 (2.51, 8.42). CONCLUSION: Among patients diagnosed with MTD with cervicalgia, treatment with a specialized PT program was associated with improvement in VHI-10 scores regardless of whether they had VT. While VT is the standard of care for MTD, PT may also offer benefit for MTD patients with cervicalgia.

Yield, nutrient composition, and horse condition in integrated crabgrass and cool-season grass rotational grazing pasture systems.

Integration of warm-season grasses into traditional cool-season pastures can increase summer forage for grazing cattle. The aim of this study was to determine impacts of this practice on yield and nutrient composition of equine rotational pasture systems as well as horse body condition. Two 1.5 ha rotational systems (6 to 0.25 ha sections/system) were evaluated: a control system (CON) (all sections mixed cool-season grass [CSG-CON]) and an integrated rotational grazing system (IRS) (three CSG sections [CSG-IRS] and three Quick-N-Big crabgrass [Digitaria sanguinalis (L.) Scop.; CRB-IRS]). Three horses per system grazed in three periods: EARLY (mid-May to mid-July), SLUMP (mid-July to mid-September), and LATE (mid-September to mid-November). Herbage mass (HM) was measured prior to each rotation and samples were collected (0800 to 1000 h) for nutrient analysis. Grazing days were tracked to calculate carrying capacity (CC). Horse condition measures were assessed monthly. Over the full grazing season, 9,125 kg of forage was available for grazing in IRS versus 6,335 kg in CON. The CC was 390 horse d for IRS, while only 276 horse d for CON. Total HM/section did not differ during EARLY when CRB was not available (CSG-IRS: 2,537 ± 605; CSG-CON: 3,783 ± 856 kg/ha), but CC was greater in CSG-IRS (220 ± 37 horse d/ha) than CSG-CON (92 ± 26 horse d/ha; P = 0.03). In SLUMP, both HM and CC were greater in CRB-IRS (HM: 4,758 ± 698 kg/ha; CC: 196 ± 31 horse d/ha) than CSG-IRS (HM: 1,086 ± 698 kg/ha; CC: 32 ± 31 horse d/ha) or CON (HM: 970 ± 493 kg/ha; CC: 46 ± 22 horse d/ha; P < 0.02). While HM did not differ by section type in LATE (1,284 ± 158 kg/ha), CC was greater in CSG-CON (84 ± 9 horse d/ha) versus CRB-IRS (32 ± 13 horse d/ha; P = 0.03) and CSG-IRS (40 ± 13 horse d/ha; P = 0.06). During SLUMP, water-soluble carbohydrates (WSC) were lower in CRB-IRS (4.46% ± 0.80%) than CSG-CON (7.92% ± 0.90%; P < 0.04), but not CSG-IRS (5.93% ± 1.04%); however, non-structural carbohydrates (NSC) did not differ (7.05% ± 0.62%). There were no differences in WSC (6.46% ± 0.54%) or NSC (7.65% ± 0.54%) by section type in LATE. Horses in IRS maintained a body condition score (BCS) of 5.78 ± 0.48, but BCS did not differ by system (CON: 6.11 ± 0.48). Thus, integrated grazing increased summer pasture yield and provided adequate nutrition to maintain horse condition, but further research is needed to improve late-season production. Integrated grazing may not, however, provide an advantage in limiting dietary NSC, as NSC remained low for all pasture sections.

Evaluation of the safety and nutritional equivalency of maize grain with genetically modified event DP-Ø23211-2.

Feeding studies were conducted with rats and broiler chickens to assess the safety and nutrition of maize grain containing event DP-Ø23211-2 (DP23211), a newly developed trait-pyramid product for corn rootworm management. Diets containing 50% ground maize grain from DP23211, non-transgenic control, or non-transgenic reference hybrids (P0928, P0993, and P1105) were fed to Crl:CD®(SD) rats for 90 days. Ross 708 broilers were fed phase diets containing up to 67% maize grain from each source for 42 days. Body weight, gain, and feed conversion were determined for comparisons between animals fed DP23211 and control diets in each study. Additional measures included clinical and neurobehavioral evaluations, ophthalmology, clinical pathology, organ weights, and gross and microscopic pathology for rats, and carcass parts and select organ yields for broilers. Reference groups were included to determine if any observed significant differences between DP23211 and control groups were likely due to natural variation. No diet-related effects on mortality or evaluation measures were observed between animal fed diets produced with DP23211 maize grain and animal fed diets produced with control maize grain. These studies show that maize grain containing event DP-Ø23211-2 is as safe and nutritious as non-transgenic maize grains when fed in nutritionally adequate diets. The results are consistent with previously published studies, providing further demonstration of the absence of hazards from edible-fraction consumption of genetically modified plants.

Efficacy and Nontarget Effects of a Spinosad-Based Larvicide in Minnesota Vernal Pools and Cattail Marshes.

Larvicides that contain spinosad, a bacterial metabolite, are used to control mosquitoes in diverse aquatic habitats. These same habitats are home to other invertebrates, including Crustacea-fairy shrimp, isopods, and amphipods-and mollusks-fingernail clams and freshwater snails. A double-blind study evaluated the effects of Natular® G, a granular treatment containing spinosad, on spring Aedes spp. and nontarget invertebrates in vernal wetlands. Within 14 days after application, Natular G controlled larvae of spring Aedes by 53-84%, depending on species, but had no significant effects on numbers of fairy shrimp, fingernail clams, or freshwater snails. A second double-blind study evaluated effects on Coquillettidia perturbans and nontarget isopods and amphipods in cattail marshes. Treatment reduced emergence of Cq. perturbans by 25% but did not change numbers of isopods or amphipods. The 2 experiments indicate Natular G could be effective against spring Aedes in vernal wetlands, less so against Cq. perturbans in cattail marshes, and yet pose minimal risk to crustaceans and mollusks in either vernal wetlands or cattail marshes.

Genetic variants related to successful migraine prophylaxis with verapamil.

BACKGROUND: Currently, there is no biologically based rationale for drug selection in migraine prophylactic treatment. METHODS: To investigate the genetic variation underlying treatment response to verapamil prophylaxis, we selected 225 patients from a longitudinally established, deeply phenotyped migraine database (N = 5983), and collected uninterrupted quantitated verapamil treatment response data and DNA for these 225 cases. We recorded the number of headache days in the four weeks preceding treatment with verapamil and for four weeks, following completion of a treatment period with verapamil lasting at least five weeks. Whole-exome sequencing (WES) was applied to a discovery cohort consisting of 21 definitive responders and 14 definitive non-responders, and the identified single nucleotide polymorphisms (SNPs) showing significant association were genotyped in a separate confirmation cohort (185 verapamil treated patients). Statistical analysis of the WES data from the discovery cohort identified 524 SNPs associated with verapamil responsiveness (p < 0.01); among them, 39 SNPs were validated in the confirmatory cohort (n = 185) which included the full range of response to verapamil from highly responsive to not responsive. RESULTS: Fourteen SNPs were confirmed by both percentage and arithmetic statistical approaches. Pathway and protein network analysis implicated myo-inositol biosynthetic and phospholipase-C second messenger pathways in verapamil responsiveness, emphasizing the earlier pathogenic understanding of migraine. No association was found between genetic variation in verapamil metabolic enzymes and treatment response. CONCLUSION: Our findings demonstrate that genetic analysis in well-characterized subpopulations can yield important pharmacogenetic information pertaining to the mechanism of anti-migraine prophylactic medications.

History of safe exposure and bioinformatic assessment of phosphomannose-isomerase (PMI) for allergenic risk.

Newly expressed proteins in genetically engineered crops are evaluated for potential cross reactivity to known allergens as part of their safety assessment. This assessment uses a weight-of-evidence approach. Two key components of this allergenicity assessment include any history of safe human exposure to the protein and/or the source organism from which it was originally derived, and bioinformatic analysis identifying amino acid sequence relatedness to known allergens. Phosphomannose-isomerase (PMI) has been expressed in commercialized genetically engineered (GE) crops as a selectable marker since 2010 with no known reports of allergy, which supports a history of safe exposure, and GE events expressing the PMI protein have been approved globally based on expert safety analysis. Bioinformatic analyses identified an eight-amino-acid contiguous match between PMI and a frog parvalbumin allergen (CAC83047.1). While short amino acid matches have been shown to be a poor predictor of allergen cross reactivity, most regulatory bodies require such matches be assessed in support of the allergenicity risk assessment. Here, this match is shown to be of negligible risk of conferring cross reactivity with known allergens.