Do habitat and elevation promote hybridization during secondary contact between three genetically distinct groups of warbling vireo (Vireo gilvus)?

Following postglacial expansion, secondary contact can occur between genetically distinct lineages. These genetic lineages may be associated with specific habitat or environmental variables and therefore, their distributions in secondary contact could reflect such conditions within these areas. Here we used mtDNA, microsatellite, and morphological data to study three genetically distinct groups of warbling vireo (Vireo gilvus) and investigate the role that elevation and habitat play in their distributions. We studied two main contact zones and within each contact zone, we examined two separate transects. Across the Great Plains contact zone, we found that hybridization between eastern and western groups occurs along a habitat and elevational gradient, whereas hybridization across the Rocky Mountain contact zone was not as closely associated with habitat or elevation. Hybrids in the Great Plains contact zone were more common in transitional areas between deciduous and mixed-wood forests, and at lower elevations (<1000 m). Hybridization patterns were similar along both Great Plains transects indicating that habitat and elevation play a role in hybridization between distinct eastern and western genetic groups. The observed patterns suggest adaptation to different habitats, perhaps originating during isolation in multiple Pleistocene refugia, is facilitating hybridization in areas where habitat types overlap.

Compatibility and stability of an admixture of multiple anaesthetic drugs for opioid-free anaesthesia.

The ability to combine and use drugs in a single infusion device may be useful in resource-limited settings. This study examined the chemical stability of an opioid-sparing mixture of ketamine, lidocaine and magnesium sulphate when combined in a single syringe. High-performance liquid chromatography and atomic absorption spectrophotometry were performed on six syringes containing the three-drug mixture. Since most opioid-sparing techniques typically rely on a 24-hour infusion regime, we tested stability at the initial admixing and 24 hours later. Stability was defined as a measured drug concentration within 10% of expected, with the absence of precipitation or pH alterations. Pharmacokinetic simulations were conducted to further show that the achieved plasma drug concentrations were well within an effective analgesic range. All mixed drug concentration measurements were within the required 10% reference limit. No obvious precipitation or interaction occurred, and pH remained stable. Drug stability was maintained for 24 hours. Pharmacokinetic simulations showed that ketamine and lidocaine were within their minimum analgesic effect concentrations. Our results show that this three-drug mixture is chemically stable for up to 24 hours after mixing, with a pharmacokinetic simulation illustrating safe, clinically useful predicted plasma concentrations when using the described admixture.

Oncolytic virus in gliomas: a review of human clinical investigations.

Gliomas remain one of the more frustrating targets for oncologic therapy. Glioma resistance to conventional therapeutics is a product of their immune-privileged milieu behind the blood-brain barrier, in addition to their suppressive effect on the immune response itself. Taking the lead from the growing success of immunotherapy for systemic cancers, such as lung cancer and melanoma, immunotherapeutics has emerged as a major player in the potential treatment of gliomas, with oncolytic viruses in particular showing significant promise as evidenced by the recent Breakthrough and Fast Tract Designations for PVSRIPO and DNX2401. This review serves as a useful and updated compendium of the completed human clinical investigations for several oncolytic viruses in the treatment of gliomas.

Effects of sodium salicylate and time postpartum on mammary tissue proliferation, gene transcript profile, and DNA methylation.

Previous studies have demonstrated nonsteroidal antiinflammatory drug treatment in early lactation had a positive impact on whole-lactation milk production in older cows. The objective of this study was to evaluate proliferative, transcriptional, and epigenetic changes in the mammary gland that could explain increased production responses due to nonsteroidal antiinflammatory drug treatment. Sodium salicylate (SAL; 125 g/d) or water (CON) were administered via oral drench to multiparous Holstein cows (n = 8/treatment) once daily for 3 d beginning approximately 24 h after parturition, and mammary tissue was collected on d 1, 4, and 45 postpartum. Day 1 tissue was collected immediately preceding the initial drench, and d 4 tissue was collected 24 h following the final drench. Blood was collected twice weekly and analyzed for plasma glucose, insulin, ß-hydroxybutyrate, free fatty acids, and prolactin. Cows were milked twice daily until d 7 of lactation, and thrice daily for the remainder of the study. Total RNA extracted from tissue was deep-sequenced and analyzed for differential gene expression using DESeq2. We detected no treatment effect on milk yield or plasma metabolites through 45 d of lactation; additionally, no change in mammary epithelial cell proliferation was detected when assessed by Ki67 labeling. Comparison of SAL versus CON revealed that only 16 of 18,286 genes were differentially expressed (false discovery rate <0.1) in mammary tissue collected on d 45, whereas no differentially expressed genes due to treatment were detected on d 1 or 4. Analysis of transcriptional differences over time showed downregulation of pathways related to immune cell recruitment and differentiation, and extensive overlap with pathways related to cholesterol synthesis and liver X receptor signaling. Global DNA methylation of mammary tissue was decreased for CON compared with SAL. Transcriptome analysis emphasized extensive involvement of immune-related signaling pathways in the switch from lactogenesis to galactopoiesis, and changes in methylation with SAL treatment merit future investigation into epigenetic effects on milk production.

Macrophage-derived Wnt signaling increases endothelial permeability during skeletal muscle injury.

OBJECTIVE: The inflammatory response and the presence of macrophages are reported to be necessary for proper muscle regeneration. However, our understanding of the molecular mechanisms governing how macrophages signal to promote muscle regeneration is incomplete. METHODS AND RESULTS: Here we conditionally deleted Wls, which is required for Wnt secretion, from macrophages and examined the impact on endothelial permeability following muscle injury. The expression of Wnt ligands and Wls was increased in the tibialis anterior (TA) of mice 2 days following BaCl2 injury. Loss of macrophage Wls inhibited the loss of endothelial barrier function, as measured by transendothelial resistance and Evans blue dye permeability assays. Interestingly, the blockade in endothelial permeability correlated with reduced VEGF levels and pretreatment of wild type endothelial cells with a VEGFR2 blocking antibody was sufficient to reduce endothelial permeability induced by stimulated macrophage supernatant. We also found that macrophage Wls-null TAs had myocytes with reduced cross-sectional area 7 day post-injury suggesting a delay in muscle regeneration. CONCLUSION: Our results indicate that macrophage-derived Wnt signaling increases endothelial permeability in a VEGF-dependent fashion following muscle injury. Our findings implicate macrophages as a primary source of Wnt ligands following muscle injury and highlight the Wnt pathway as a therapeutic target following injury.

Effects of molasses-based liquid feed supplementation to a high-straw dry cow diet on feed intake, health, and performance of dairy cows across the transition period.

The objective of this study was to determine the effects of adding molasses-based liquid feed to a high-straw dry cow diet on intake, behavior, health, and performance of dairy cows across the transition period. Holstein cows (n = 40) entering their second lactation or greater were enrolled at dry-off (∼45 d before expected calving) and assigned to 1 of 2 treatments: a high-straw dry cow total mixed ration (TMR) with either (1) no molasses [CON; n = 20; 10.7% crude protein (CP), 1.45 Mcal/kg of net energy for lactation (NEL)] or (2) supplemented with 1 kg/cow daily [dry matter (DM) basis] of molasses-based liquid feed (LF; n = 20; 11.2% CP, 1.49 Mcal/kg of NEL). At calving all cows were fed the same lactating TMR (14.9% CP, 1.68 Mcal/kg of NEL) and followed for 28 d. During the dry period, cows fed the LF diet had greater DM intake (15.3 ± 0.24 vs. 13.4 ± 0.24 kg/d) and tended to have a shorter interval between meals (192.8 ± 8.38 vs. 216.5 ± 7.97 min) and more frequent meals (6.3 ± 0.27 vs. 5.6 ± 0.27 meals/d), while consuming their feed faster (0.09 ± 0.001 vs. 0.08 ± 0.001 kg of DM/min) compared with cows fed the CON diet. Regardless of treatment, cows sorted [100% × (actual intake/predicted intake)] against the longest ration particles (>19 mm), with cows fed the CON diet sorting more against these (81.1 ± 2.6 vs. 93.9 ± 2.6%). Cows fed the CON diet did not sort for or against short particles (<8, >4 mm; 100.2 ± 0.31%), but cows fed the LF diet tended to sort against these (99.2 ± 0.31%). Post-calving, cows fed the LF diet did not sort for long particles (98.5 ± 1.1%), but cows fed the CON diet continued to sort against these (96.3 ± 1.1%). Cows fed the LF diet had higher mean reticulorumen pH in the dry period (6.4 ± 0.05 vs. 6.2 ± 0.06 pH), in the first week after calving (CON = 5.7 ± 0.06 pH, LF = 5.8 ± 0.06 pH), and tended to have higher mean reticulorumen pH in the second week after calving (CON = 5.7 ± 0.06 pH, LF = 5.9 ± 0.06 pH). The results suggest that supplementing a molasses-based liquid feed in high-straw dry cow diets may improve intake and consistency in nutrients consumed during the dry period and in early lactation, as well as possibly promoting better rumen health across the transition period.

Moisture content of high-straw dry cow diets affects intake, health, and performance of transition dairy cows.

The objective of this study was to determine the effect of adding water to a high-straw dry cow diet on feeding behavior, health, and performance of dairy cows. Holstein cows (n = 40) entering their second or greater lactation were enrolled at dry off (∼45 d before expected calving) and assigned to 1 of 2 dietary treatments, consisting of a high-straw dry cow total mixed ration [TMR; 36% wheat straw, 41% corn silage, 23% pellet, on a dry matter (DM) basis, formulated for 11.6% crude protein, 1.35 Mcal/kg net energy for lactation] with (1) no water (CON; n = 20; DM = 53.4%) or (2) water added to decrease the DM by ∼10 percentage points (wet diet, WD; n = 20; DM = 45.4%). Upon calving, all cows were fed the same lactating TMR (45.2% DM, 14.9% crude protein, 1.68 Mcal/kg net energy for lactation) and followed for 28 d. Dry matter intake, feeding behavior, and rumination activity were recorded automatically. Fresh TMR and orts samples were collected 2×/wk to determine differences in sorting. A particle separator was used to separate feed samples into 4 fractions: long (>19 mm), medium (<19, >8 mm), short (<8, >4 mm), and fine (<4 mm) particles. Feed sorting was calculated as actual intake of each particle fraction expressed as a % of predicted intake. Cows fed WD had greater DM intake during the dry period than cows fed CON (CON = 13.4 ± 0.24, WD = 14.2 ± 0.24 kg/d), but rumination did not differ (CON = 522.2 ± 8.48, WD = 518.5 ± 8.69 min/d) between treatments. Cows fed WD tended to consume their feed faster (CON = 0.08 ± 0.001, WD = 0.09 ± 0.001 kg of DM/min) compared with CON cows. Regardless of treatment, cows sorted against the longest ration particles, with cows fed CON sorting more against these (CON = 81.1 ± 2.51%, WD = 94.9 ± 2.58%). Cows fed CON tended to sort more in favor of the medium particles than those fed WD (CON = 105.0 ± 0.36%, WD = 104.2 ± 0.37%). Postcalving DM intake and feeding behavior were not affected by dry diet treatment. Cows fed WD experienced a less rapid daily decline in rumen pH during the first 7 d after calving compared with those fed the CON diet. The results suggest that increasing the moisture content of high-straw dry cow diets, by adding water, may improve intake and reduce sorting against the longest ration particles, which may help promote consistency in targeted nutrients consumed during the dry period and greater rumen health in early lactation.

Effects of wheat straw chop length in high-straw dry cow diets on intake, health, and performance of dairy cows across the transition period.

The study investigated the effect of chop length of wheat straw in a high-straw dry cow diet on the feeding behavior, health, and performance of Holstein dairy cows across the transition period. Forty cows were enrolled at dry off, approximately 45 d before expected calving, and assigned to 1 of 2 dietary treatments containing (on a dry matter basis) 36% corn silage, 35% dry cow pellet, and 29% wheat straw. Diets were formulated to target an energy consumption of 19 Mcal/d of net energy for lactation per cow. The diets differed in the chop length of wheat straw: (1) long straw chopped with a 10.16-cm screen (LDD; n = 20), or (2) short straw chopped with a 2.54-cm screen (SDD; n = 20). Dietary treatments were fed throughout the dry period. Feeding behavior, rumination time, and reticulorumen pH were monitored electronically, and feed samples were collected to determine feed sorting. Blood samples were taken weekly, and body condition scores and body weights were taken every 2 wk. Postcalving, all cows were fed the same lactating cow total mixed ration for 28 d; the same measurements were recorded with the addition of daily milk yield and twice weekly milk components. During the dry period, cows fed the SDD treatment consumed more dry matter (15.6 vs. 15.0 kg/d), had more consistent dry matter intake in the week leading up to calving, had a faster feeding rate, consumed 0.4 kg/meal more, and had 0.6 fewer meals per day. No differences were observed in rumination time or mean reticulorumen pH between treatments in both the dry and lactating period. Regardless of treatment during the dry period, cows sorted against the long particles (>19 mm) and in favor of the short particles (<8, >4 mm), but cows fed the LDD treatment sorted to a greater extent than cows fed the SDD treatment. Dietary treatment in the dry period did not influence feed sorting behavior postcalving. Cows fed the LDD treatment had a greater daily change (decline) in rumen pH in the first week postcalving and had a greater blood ß-hydroxybutyrate concentration in the third week postcalving. Overall, the results from this study indicate that feeding shorter chopped wheat straw in a high-straw dry cow diet improved intake, reduced sorting during the dry period, and resulted in greater metabolic health and rumen stability in early lactation.

Behavior, health, and productivity of early-lactation dairy cows supplemented with molasses in automated milking systems.

The objective of this study was to determine the effect of molasses-based liquid feed (LF) supplementation within automated milking systems (AMS) on the behavior, health, and production of early-lactation dairy cows. In 6 commercial AMS dairy herds, 390 dairy cows were randomly assigned before calving to 1 of 2 treatments, within farm, balanced by parity: (1) control group (CON) receiving a standard AMS pellet [mean = 3.9 kg/d on a dry matter (DM) basis, n = 188], or (2) same amount of standard AMS pellet (mean = 3.6 kg/d on a DM basis, n = 202) plus 1 kg/d DM of LF for multiparous cows (1.6 kg/d as fed) and 0.88 kg/d DM for primiparous cows (1.4 kg/d as fed). Across farms, cows were fed partial mixed rations similar in ingredient and nutrient composition. Cows on the LF treatment received supplementation for the first 60 d in milk (DIM). Blood samples were taken 2 times/wk for the first 3 wk postcalving to assess ß-hydroxybutyrate (BHB). Samples with BHB ≥1.2 mmol/L were classified as a positive case of subclinical ketosis (SCK). Cow body condition and lameness were scored every 10 d postcalving until 60 DIM. No differences were detected between treatments for milk yield (average milk yield = 37.4 ± 1.98 kg/d) and milking frequency (average milking frequency = 3.2 ± 0.01 times/d). Similarly, no difference between treatments in daily AMS visits was detected (average AMS visits = 5.3 ± 0.3 times/d). However, CON cows experienced more AMS refusals/d than LF cows (LF = 1.6 refusals/d, CON = 2.1 refusals/d). No difference between treatments in daily rumination time was detected (average rumination time = 476 ± 10.8 min/d). Treatment was associated with the number of times cows tested positive for SCK; cows on LF had fewer repeated diagnoses of SCK, such that 15% of cows on LF had ≥3 diagnoses of SCK out of 5 tests, compared with 27% of CON cows. Cows receiving molasses tended to have lower blood BHB values at ∼15 DIM. Molasses supplementation also allowed cows to maintain a more stable body condition score, as LF cows tended to lose less body condition over the first 60 DIM compared with CON cows. Overall, the results of this study demonstrate that supplementing a molasses-based LF to AMS cows may help support the energy demands of milk production in early lactation and, thus, reduce the incidence of repeat positive SCK tests during that time period.

Effects of early postpartum sodium salicylate treatment on long-term milk, intake, and blood parameters of dairy cows.

Previous research has shown that cows who receive treatment with nonsteroidal anti-inflammatory drugs after calving may have increased milk yield beginning near peak lactation, resulting in greater 305-d milk production. It has not been demonstrated whether this response is associated with greater feed intake following the first 3 wk of lactation. Dry matter intake (DMI) and milk yield were measured daily for 56 cows over the first 120 d in milk. Cows in their second parity and greater were blocked by parity and alternately enrolled 12 to 36 h after calving into 1 of 2 treatments: either 3 daily drenches of water or 3 daily drenches of a similar volume of water containing 125 g of sodium salicylate (SAL) beginning 12 to 36 h after calving. Cows were housed in individual stalls to monitor DMI. Blood samples were collected before calving and on the last day of treatment, as well as at 7, 11, 14, 18, 21, 35, 49, 63, 77, 91, 105, and 120 d in milk. The SAL treatment did not affect estimated 305-d milk, fat, or protein yields (from monthly test days), daily milk yield or components, energy-corrected milk, fat-corrected milk, or DMI; however, an interaction between parity and treatment was observed for DMI, where second-parity SAL cows had decreased intake with no differences observed in older cows. This resulted in a parity by treatment interaction for the ratio of energy-corrected milk to DMI. Similarly, no main effects of treatment were observed for plasma glucose, ß-hydroxybutyrate (BHB), or fatty acid concentrations, but we noted interactions between treatment and parity for glucose, BHB, and insulin. Older cows had greater plasma glucose and insulin concentrations and decreased plasma BHB following SAL but no differences were observed in second parity animals. Alterations in glucose and insulin resulted in a tendency for a treatment by time interaction for the revised quantitative insulin sensitivity check index. Feeding behavior was also altered following SAL administration, resulting in fewer but longer meals, as well as a tendency for greater meal weight. A tendency for a treatment by week interaction for inter-meal interval was observed, as well as a parity by treatment interaction for meal weight. Despite the lack of a milk yield response, SAL had a prolonged programming effect on feeding behavior and blood variables over the first 120 DIM, with responses largely dependent on parity.

Short communication: Sodium salicylate negatively affects rumen fermentation in vitro and in situ.

Administration of sodium salicylate (SS) to cows in early lactation has a positive effect on whole-lactation milk production but a negative effect on metabolism in some cases. The objective of this trial was to determine whether SS directly affects rumen fermentation. Experiment 1 was designed to investigate the effects of direct inclusion of SS in a 24-h batch culture, and experiment 2 was designed to test the fermentative ability of rumen fluid from heifers who had received SS. In experiment 1, we combined strained and pooled rumen fluid from 3 heifers in a 2:1 ratio with McDougall's buffer, and added 150 mL of the inoculum to each flask (n = 5/treatment) with 2.5 g of fermentation substrate similar to a lactating cow ration, ground to 1 mm. We then added premixed treatments (1-mL volume) to achieve the desired final amount of SS (CON1 = 0 mg, LOW = 125 mg, MED = 250 mg, HI = 375 mg). In experiment 2, 6 heifers (n = 3/treatment) were drenched daily for 3 d, either with 62.5 g of SS dissolved in water (SAL) or an equal volume of water (CON2). Rumen fluid was collected from each heifer and was not pooled. After the fluid was mixed 2:1 with McDougall's buffer, 150 mL of inoculum was added to the fermentation flasks (n = 4/heifer) with 2.5 g of fermentation substrate. This experiment was performed the day before SS treatment began and repeated 1, 13, and 35 d after the end of the treatment period. We also performed an in situ experiment at each of these time points. In the first experiment, inclusion of SS resulted in a decrease in dry matter disappearance (DMD) over 24 h, as well as an increase in final pH. We detected no difference between treatments for gas production asymptotic volume, rate, or lag. In the second experiment, we detected a significant treatment × day interaction for DMD: we observed no difference between groups during a 24-h batch culture on the day following treatment, but SAL resulted in lower DMD on d 13 and d 35. We detected no treatment effect on the final pH of the batch culture or on any gas-production parameters. We observed a tendency for SAL to decrease the DMD rate in situ on the day after treatment. These results indicate that SS administration has a negative effect on rumen microorganisms.

Effect of dietary sugar concentration and sunflower seed supplementation on lactation performance, ruminal fermentation, milk fatty acid profile, and blood metabolites of dairy cows.

Previous research has shown that both sunflower seed (SF) and sucrose (SC) supplementation can result in variation in milk fat concentration and composition, possibly due to altered fermentation patterns and biohydrogenation of fatty acids in the rumen. The objective of this study was to determine the effects of different sugar concentrations with or without SF supplementation on lactation performance, ruminal fermentation, and milk fatty acid profile in lactating dairy cows. Eight multiparous Holstein dairy cows (body weight=620±15kg, 60±10 d in milk, mean ± standard deviation) were randomly assigned to treatments in a replicated 4×4 Latin square design with a 2×2 factorial arrangement of treatments. Each 21-d period consisted of a 14-d diet adaptation period and 7-d collection period. Dairy cows were fed 1 of the following 4 diets: (1) no additional SC without SF supplementation (NSC-SF), (2) no additional SC with SF supplementation (NSC+SF), (3) SC without SF supplementation (SC-SF), and (4) SC with SF supplementation (SC+SF). The diets contained the same amount of forages (corn silage and alfalfa hay). Four isonitrogenous and isoenergetic diets were formulated by replacing corn grain with SC and SF and balanced using change in proportions of canola meal and sugar beet pulp. No interaction was detected between SC and SF supplementation with respect to dry matter intake, milk yield, and composition. A tendency was found for an interaction between inclusion of SC and SF on energy-corrected milk with the highest amount in the SC-SF diet. Ruminal pH and the molar proportion of acetate were affected by SC inclusion, with an increase related to the SC-SF diet. Diets containing SF decreased the concentrations of short-chain fatty acids (4:0 to 10:0) and medium-chain fatty acids (12:0 to 16:0) in milk fat. The addition of SC tended to decrease the concentration of total trans-18:1. These data provide evidence that exchanging SC for corn at 4% of dietary dry matter influenced milk fat content and rumen pH, resulting in a tendency for decreased concentration of trans-18:1 in milk fat. Sucrose alone did not alter the milk fatty acid profile when cows were fed a combination of unsaturated fat and sugar, although several significant interactions between sugar and unsaturated fat were observed.

Hot topic: Early postpartum treatment of commercial dairy cows with nonsteroidal antiinflammatory drugs increases whole-lactation milk yield.

Previous research has shown that postpartum administration of the nonsteroidal antiinflammatory drug (NSAID) sodium salicylate can increase 305-d milk yield in older dairy cattle (parity 3 and greater). However, in this prior work, sodium salicylate was delivered to cows via the drinking water, a method that does not align well with current grouping strategies on commercial dairy farms. The objective of the current study was to replicate these results on a commercial dairy farm with a simplified treatment protocol and to compare sodium salicylate with another NSAID, meloxicam. Dairy cattle in their second lactation and greater (n=51/treatment) were alternately assigned to 1 of 3 treatments at parturition, with treatments lasting for 3d. Experimental treatments began 12 to 36 h after parturition and were (1) 1 placebo bolus on the first day and 3 consecutive daily drenches of sodium salicylate (125 g/cow per day; SAL); (2) 1 bolus of meloxicam (675 mg/cow) and 3 drenches of an equal volume of water (MEL); or (3) 1 placebo bolus and 3 drenches of water (CON). Blood samples were collected on the first day of treatment, immediately following the last day of treatment, and 7d after the last day of treatment; plasma was analyzed for glucose, ß-hydroxybutyrate (BHB), free fatty acids, haptoglobin, and paraoxonase. Milk production, body condition score, reproductive status, and retention in the herd were monitored for 365 d posttreatment, and effects of treatment, parity, days in milk, and interactions were evaluated in mixed effects models. Significance was declared at P<0.05. Whole-lactation milk and protein yields were greater in NSAID-treated cows, although 305-d fat production was not affected. There was a significant interaction of treatment and parity for plasma glucose concentration; MEL increased plasma glucose concentrations compared with CON and SAL in older cows. Sodium salicylate decreased plasma BHB concentration compared with MEL at 7d posttreatment, although no difference was detected immediately following treatment. Haptoglobin concentrations were elevated in SAL cows compared with CON. There was a tendency for CON cows to be removed from the herd more quickly than MEL cows (42 vs. 26% at 365 d posttreatment). Body condition score, concentrations of plasma free fatty acids and paraoxonase, and time to pregnancy were not affected by treatment. These results indicate that NSAID administration in postpartum cows has the potential to be a viable way to improve productivity and potentially longevity in commercial dairies, although further research is necessary to optimize recommendations for producers.

Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.

This study was designed to evaluate whether subjects with amyloid beta (Aß) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aß pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aß+) or negative (Aß-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aß+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aß+ MCI subjects demonstrated greater worsening compared with Aß- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aß+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aß+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aß+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aß+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aß+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aß- subjects do.

Invited review: Inflammation during the transition to lactation: New adventures with an old flame.

For dairy cattle, the first several weeks of lactation represent the highest-risk period in their lives after their own neonatal period. Although more than 50% of cows during this period are estimated to suffer from at least one subclinical disorder, the complicated admixture of normal adaptations to lactation, infectious challenges, and metabolic disorders has made it difficult to determine which physiological processes are adaptive and which are pathological during this time. Subacute inflammation, a condition that has been well documented in obesity, has been a subject of great interest among dairy cattle physiologists in the past decade. Many studies have now clearly shown that essentially all cows experience some degree of systemic inflammation in the several days after parturition. The magnitude and likely persistence of the inflammatory state varies widely among cows, and several studies have linked the degree of postpartum inflammation to increased disease risk and decreased whole-lactation milk production. In addition to these associations, enhancing postpartum inflammation with repeated subacute administration of cytokines has impaired productivity and markers of health, whereas targeted use of nonsteroidal anti-inflammatory drugs during this window of time has enhanced whole-lactation productivity in several studies. Despite these findings, many questions remain about postpartum inflammation, including which organs are key initiators of this state and what signaling molecules are responsible for systemic and tissue-specific inflammatory states. Continued in vivo work should help clarify the degree to which mild postpartum inflammation is adaptive and whether the targeted use of anti-inflammatory drugs or nutrients can improve the health and productivity of dairy cows.

High-intensity interval training has positive effects on performance in ice hockey players.

In spite of the well-known benefits that have been shown, few studies have looked at the practical applications of high-intensity interval training (HIIT) on athletic performance. This study investigated the effects of a HIIT program compared to traditional continuous endurance exercise training. 24 hockey players were randomly assigned to either a continuous or high-intensity interval group during a 4-week training program. The interval group (IG) was involved in a periodized HIIT program. The continuous group (CG) performed moderate intensity cycling for 45-60 min at an intensity that was 65% of their calculated heart rate reserve. Body composition, muscle thickness, anaerobic power, and on-ice measures were assessed pre- and post-training. Muscle thickness was significantly greater in IG (p=0.01) when compared to CG. The IG had greater values for both ∆ peak power (p<0.003) and ∆ mean power (p<0.02). Additionally, IG demonstrated a faster ∆ sprint (p<0.02) and a trend (p=0.08) for faster ∆ endurance test time to completion for IG. These results indicate that hockey players may utilize short-term HIIT to elicit positive effects in muscle thickness, power and on-ice performance.

Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway.

Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1-6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.

Pipeline for illumination correction of images for high-throughput microscopy.

The presence of systematic noise in images in high-throughput microscopy experiments can significantly impact the accuracy of downstream results. Among the most common sources of systematic noise is non-homogeneous illumination across the image field. This often adds an unacceptable level of noise, obscures true quantitative differences and precludes biological experiments that rely on accurate fluorescence intensity measurements. In this paper, we seek to quantify the improvement in the quality of high-content screen readouts due to software-based illumination correction. We present a straightforward illumination correction pipeline that has been used by our group across many experiments. We test the pipeline on real-world high-throughput image sets and evaluate the performance of the pipeline at two levels: (a) Z'-factor to evaluate the effect of the image correction on a univariate readout, representative of a typical high-content screen, and (b) classification accuracy on phenotypic signatures derived from the images, representative of an experiment involving more complex data mining. We find that applying the proposed post-hoc correction method improves performance in both experiments, even when illumination correction has already been applied using software associated with the instrument. To facilitate the ready application and future development of illumination correction methods, we have made our complete test data sets as well as open-source image analysis pipelines publicly available. This software-based solution has the potential to improve outcomes for a wide-variety of image-based HTS experiments.

Candida tropicalis infectious endocarditis in a dog with a patent ductus arteriosus.

A 6-month-old male intact miniature Australian Shepherd presented for surgical consultation for a previously diagnosed patent ductus arteriosus. Echocardiogram revealed a patent ductus arteriosus and a hyperechoic oscillating lesion within the main pulmonary artery. Blood cultures and eventual post-mortem examination revealed Candida tropicalis endocarditis. This case report highlights a rare case of fungal endocarditis with both echocardiographic and post-mortem findings.