Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin

Kallikrein-related peptidases KLK5, KLK7 and KLK14 are important proteases in skin desquamation and aberrant KLK activity is associated with inflammatory skin diseases such as Netherton syndrome but also with various serious forms of cancer. Previously, we have identified KLK7 as the first protease target of vaspin (Serpin A12). Here, we report KLK14 as a second KLK protease to be inhibited by vaspin. In conclusion, vaspin represents a multispecific serpin targeting the kallikrein proteases KLK7 and KLK14, with distinct exosites regulating recognition of these target proteases and opposing effects of heparin binding on the inhibition reaction

Adjuvant Use and the Intensification of Pharmacologic Management for Pain in Nursing Home Residents with Cancer: Data from a US National Database

Objectives: Our objective was to describe the prevalence of adjuvants to opioid therapy and changes in these agents for pharmacologic management in nursing home residents with cancer. Methods: We included Medicare beneficiaries with cancer and documented opioid use at nursing home admission in 2011–2013 (N = 3268). The Minimum Data Set 3.0 provided information on sociodemographic and clinical characteristics. Part D claims provided information on opioid and adjuvant use during the 7 days after admission and 90 days later. Proportions of changes in these agents were estimated. Separate logistic models estimated associations between resident characteristics and (1) use of adjuvants at admission and (2) intensification of pharmacologic management at 90 days. Results: Nearly 20% of patients received adjuvants to opioids at admission, with gabapentin the most common adjuvant (34.4%). After 90 days, approximately 25% had maintained or intensified pharmacologic management. While advanced age (≥ 85 vs. 65–74 years, adjusted odds ratio [aOR] 0.80; 95% confidence interval [CI] 0.63–1.02) and comorbidities, including dementia (aOR 0.65; 95% CI 0.53–0.82) and depression (aOR 1.55; 95% CI 1.29–1.87), were associated with adjuvant use at admission, worse cognitive impairment (severe vs. no/mild, aOR 0.80; 95% CI 0.64–0.99) and presence of more severe pain (moderate/severe vs. no pain, aOR 1.60; 95% CI 1.26–2.03) were associated with intensification of drug regimen. Conclusion: Given aging-related changes and the presence of comorbid conditions in older adults, safety studies of these practices are warranted

An Evidence-Based Systematic Review of Elderberry and Elderflower (Sambucus nigra) by the Natural Standard Research Collaboration

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing

Quality characteristics, chemical composition, and sensory properties of butter from cows on pasture versus indoor feeding systems

peer-reviewedThis study evaluated the effects of 3 widely practiced cow feeding systems in the United States, Europe, and Southern Hemisphere regions on the characteristics, quality, and consumer perception of sweet cream butter. Fifty-four multiparous and primiparous Friesian cows were divided into 3 groups (n = 18) for an entire lactation. Group 1 was housed indoors and fed a total mixed ration diet (TMR) of grass silage, maize silage, and concentrates; group 2 was maintained outdoors on perennial ryegrass-only pasture (GRS); and group 3 was maintained outdoors on a perennial ryegrass/white clover pasture (CLV). Mid-lactation butter was manufactured in triplicate with milk from each group in June 2015 (137 ± 7 d in milk) and was analyzed over a 6-mo storage period at 5°C for textural and thermal properties, fatty acid composition, sensory properties, and volatile compounds. The nutritional value of butters was improved by pasture feeding, and butter from pasture-fed cows had significantly lower thrombogenicity index scores compared with butters from TMR-fed cows. In line with these results, pasture-derived milks (GRS and CLV) produced butter with significantly higher concentrations of conjugated linoleic acid (cis-9,trans-11) and trans-β-carotene than TMR butter. Alterations in the fatty acid composition of butter contributed to significant differences in textural and thermal properties of the butters. Total mixed ration–derived butters had significantly higher hardness scores at room temperature than those of GRS and CLV. Onset of crystallization for TMR butters also occurred at significantly higher temperatures compared with pasture butters. Volatile analysis of butter by gas chromatography-mass spectrometry identified 25 compounds present in each of the butters, 5 of which differed significantly based on feeding system, including acetone, 2-butanone, 1-pentenol, toluene, and β-pinene. Toluene was very significantly correlated with pasture-derived butter. Sensory analysis revealed significantly higher scores for GRS-derived butter in several attributes including “liking” of appearance, flavor, and color over those of TMR butter. Partial least square regression plots of fatty acid profiles showed clear separation of butter derived from grazed pasture-based perennial ryegrass or perennial rye/white clover diets from that of a TMR system, offering further insight into the ability of fatty acid profiling to verify such pasture-derived dairy products.Science Foundation Irelan

Effect of pasture versus indoor feeding systems on raw milk composition and quality over an entire lactation

peer-reviewedThe aim of this study was to investigate the effects of different feeding systems on milk quality and composition. Fifty-four multiparous and primiparous Friesian lactating cows were divided into 3 groups (n=18) to study the effects of 3 feeding systems over a full lactation. Group 1 was housed indoors and offered a total mixed ration diet (TMR), group 2 was maintained outdoors on a perennial ryegrass pasture (referred to as grass), and group 3 was also grazed outdoors on a perennial ryegrass/white clover pasture (referred to as clover). Bulk milk samples were collected from each group at morning and afternoon milkings once weekly from March 11 to October 28 in 2015. Milk from pasture-fed cows (grass and clover) had significantly higher concentrations of fat, protein, true protein, and casein. The pasture feeding systems induced significantly higher concentrations of saturated fatty acids C11:0, C13:0, C15:0, C17:0, C23:0, and unsaturated fatty acids C18:2n-6 trans, C18:3n-3, C20:1, and C20:4n-6 and a greater than 2-fold increase in the conjugated linoleic acid C18:2 cis-9,trans-11 content of milk compared with that of the TMR feeding system. The TMR feeding system resulted in milks with increased concentrations of C16:0, C18:2n-6 cis, C18:3n-6 cis, C22:0 C22:1n-9, and C18:2 cis-10,trans-12. Principal component analysis of average fatty acid profiles showed clear separation of milks from the grazed pasture-based diets to that of a TMR system throughout lactation, offering further insight into the ability to verify pasture-derived milk by fatty acid profiling