The Influence of Crystal Habit on the Prediction of Dry Powder Inhalation Formulation Performance Using the Cohesive–Adhesive Force Balance Approach

The aim of this investigation was to study the influence of crystalline habit of active pharmaceutical ingredients on the cohesive–adhesive force balance within model dry powder inhaler (DPI) formulations and the corresponding affect on DPI formulation performance. The cohesive–adhesive balance (CAB) approach to colloid probe atomic force microscopy (AFM) was employed to determine the cohesive and adhesive interactions of micronized budesonide particles against the {102} and {002} faces of budesonide single crystals and crystalline substrates of different sugars (cyclodextrin, lactose, trehalose, raffinose, and xylitol), respectively. These data were used to measure the relative level of cohesion and adhesion via CAB and the possible influence on in vitro performance of a carrier-based DPI formulation. Varying the crystal habit of the drug had a significant effect on the cohesive measurement of micronized budesonide probes, with the cohesive values on the {102} faces being approximately twice that on the {002} crystal faces. However, although different CAB values were measured with the sugars with respect to the crystal faces chosen for the cohesive-based measurement, the overall influence on the rank order of the CAB values was not directly influenced. For these data sets, the CAB gradient indicated that a decrease in the dominance of the adhesive forces led to a concomitant increase in fine particle delivery, reaching a plateau as the cohesive forces became dominant. The study suggested that crystal habit of the primary drug crystals influences the cohesive interactions and the resulting force balance measurements of colloid probe CAB analysis.     

What Math Matters? Types of Mathematics Knowledge and Relationships to Methods Course Performance

This study investigated the effect of a departmental focus on enhanced mathematics knowledge for teaching on overall performance in upper elementary mathematics methods courses. The study examined the effect of performance on a new course in mathematics for teaching on performance at the methods course level. In addition, the effect of performance on a high-stakes test of general elementary-level mathematics content knowledge was explored. Mathematics knowledge for teaching was found to be a highly significant predictor of first semester methods course performance, arguably pedagogical content knowledge, whereas knowledge of the general elementary mathematics content appeared less related.     

Milk- and starter-feeding strategies to reduce cross sucking in pair-housed calves in outdoor hutches

Social housing of preweaned calves can benefit their welfare, but housing and cross sucking are potential barriers to adoption for farmers. For farms using outdoor hutches, an option is to pair adjacent hutches with a shared fence. Our objective was to investigate milk- or starter-feeding strategies to mitigate cross sucking in this system. Holstein heifers were housed in pairs (n = 32 pairs) and divided into 4 treatments (n = 8 pairs each) in a 2 × 2 factorial design: milk in an open bucket with starter in only a bucket (OB-SB), milk in an open bucket and starter in both a bucket and a specialized teat bottle (Braden bottle; OB-BB), milk in a slow-flow teat bucket with starter in only a bucket (TB-SB), or milk in a slow-flow teat bucket and starter in both a bucket and a specialized teat bottle (TB-BB). When starter was first offered (d 6 ± 1 of life, mean ± SD), calf latency to approach was recorded, averaged within pairs, and compared between starter treatments using a linear mixed model with fixed effect of treatment and random effect of pair within treatment. Calves were initially bottle fed; milk treatments began on d 14 ± 1 of life and ended when calves were completely weaned (d 53 ± 1). Calves were observed for behaviors such as drinking milk and cross sucking twice weekly for 30 min during the afternoon milk meal using continuous video, with values averaged within pairs. Linear mixed models were run separately before (wk 3–6) and after (wk 7–8) weaning, with fixed effects of milk- and starter-feeding treatments, week, and the 2- and 3-way interactions, with week as repeated measure and pair as subject. Pairs with Braden bottles and buckets approached starter sooner than those with only buckets (Braden bottles vs. no Braden bottles: 13.1 ± 6.1 vs. 33.2 ± 6.1 min, LSM ± SEM). Before weaning, pairs with open buckets for both milk and starter cross sucked for at least twice as long (OB-SB: 2.9 ± 0.3 min) as all other treatments (OB-BB: 1.5 ± 0.3 min; TB-SB: 0.4 ± 0.3 min; TB-BB: 0.5 ± 0.3 min). This pattern held during weaning, when cross sucking increased overall (OB-SB: 3.9 ± 0.4 min; OB-BB: 1.8 ± 0.4 min; TB-SB: 0.9 ± 0.4 min; TB-BB: 1.6 ± 0.4 min). Regardless of starter treatment, calves spent less time cross sucking when fed milk in teat buckets, which extended the milk meal relative to open buckets (teat bucket vs. open bucket: preweaning = 7.0 ± 0.2 vs. 1.6 ± 0.2 min; weaning = 3.0 ± 0.1 vs. 0.6 ± 0.1 min). When calves are fed milk in open buckets, a novel option for reducing cross sucking is to provide starter through a specialized bottle. Nonetheless, providing milk in slow-flow teat buckets had the greatest effect on reducing cross sucking by directing suckling to the teat instead of another calf or pen objects.     

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.