Arguments Used in Public Comments to Support or Oppose the US Department of Agriculture’s Minimum Stocking Requirements: A Content Analysis

Background

In 2016, the US Department of Agriculture (USDA)’s Supplemental Nutrition Assistance Program (SNAP) Retailer Rule proposed several changes for SNAP-authorized retailers, including: requiring retailers to have at least 85% of their food sales come from items that are not cooked or heated on site before or after purchase; requiring stores to stock seven varieties of qualifying foods from four staple food groups; requiring stores to carry perishable foods in three of the four staple groups; requiring stores to carry six units of qualifying foods at all times (depth of stock); disqualifying multiple ingredient foods and accessory foods from counting toward depth of stock requirements.

A Nutritional Perspective of Ketogenic Diet in Cancer: A Narrative Review

The predominant use of glucose anaerobically by cancer cells (Warburg effect) may be the most important characteristic the majority of these cells have in common and, therefore, a potential metabolic pathway to be targeted during cancer treatment. Because this effect relates to fuel oxidation, dietary manipulation has been hypothesized as an important strategy during cancer treatment. As such, the concept of a ketogenic diet (KD) in cancer emerged as a metabolic therapy (ie, targeting cancer cell metabolism) rather than a dietary approach. The therapeutic mechanisms of action of this high-fat, moderate-to-low protein, and very-low-carbohydrate diet may potentially influence cancer treatment and prognosis. Considering the lack of a dietetics-focused narrative review on this topic, we compiled the evidence related to the use of this diet in humans with diverse cancer types and stages, also focusing on the nutrition and health perspective. The use of KD in cancer shows potentially promising, but inconsistent, results. The limited number of studies and differences in study design and characteristics contribute to overall poor quality evidence, limiting the ability to draw evidence-based conclusions. However, the potential positive influences a KD may have on cancer treatment justify the need for well-designed clinical trials to better elucidate the mechanisms by which this dietary approach affects nutritional status, cancer prognosis, and overall health. The role of registered dietitian nutritionists is demonstrated to be crucial in planning and implementing KD protocols in oncology research settings, while also ensuring patients’ adherence and optimal nutritional status.     

Dietary Supplement Use in a Large,Representative Sample of the US Armed Forces

Background

Dietary supplement (DS) use is prevalent among the US Armed Forces personnel, but representative cross-service comparisons and characteristics of personnel using DSs are limited.

How Predictable Are Human Stratum Corneum Lipid/Water Partition Coefficients? Assessment and Useful Correlations for Dermal Absorption

Partition coefficients between human stratum corneum lipids and water (K^sclip/w) are collected or deduced from a variety of sources in a manner that approximately doubles the available data compared to the current state-of-the-art model (Hansen et al., Adv Drug Deliv Rev. 2013;65(2):251-264). An additional datum for water itself in porcine SC that considerably extends the molecular size and lipophilicity range of the data set is considered. The data are analyzed in terms of an extended linear free energy relationship involving octanol/water partition coefficients, Abraham solvation parameters, and a secondary, power law molecular weight dependence. The optimum fit to log K^sclip/w for the full data set reduces the standard error of prediction from 0.50 for a Hansen-like model to 0.39; corresponding multiplicative errors in K^sclip/w are reduced from a factor of 3.1 to one of 2.5. The difference in performance is driven by the water datum, which requires a more complex dependence on molecular size than that afforded by Abraham parameters. In the absence of the water value, the Hansen-like model, which does not include a dependence on molecular size, is essentially optimum. A comparison is presented to fluid-phase phospholipid–water systems, which have a demonstrably different structure–property relationship.     

Evaluation of Hydrogen Exchange Mass Spectrometry as a Stability-Indicating Method for Formulation Excipient Screening for an IgG4 Monoclonal Antibody

Antibodies are molecules that exhibit diverse conformational changes on different timescales, and there is ongoing interest to better understand the relationship between antibody conformational dynamics and storage stability. Physical stability data for an IgG4 monoclonal antibody (mAb-D) were gathered through traditional forced degradation (temperature and stirring stresses) and accelerated stability studies, in the presence of different additives and solution conditions, as measured by differential scanning calorimetry, size exclusion chromatography, and microflow imaging. The results were correlated with hydrogen exchange mass spectrometry (HX-MS) data gathered for mAb-D in the same formulations. Certain parameters of the HX-MS data, including hydrogen exchange in specific peptide segments in the C_H2 domain, were found to correlate with stabilization and destabilization of additives on mAb-D during thermal stress. No such correlations between mAb physical stability and HX-MS readouts were observed under agitation stress. These results demonstrate that HX-MS can be set up as a streamlined methodology (using minimal material and focusing on key peptide segments at key time points) to screen excipients for their ability to physically stabilize mAbs. However, useful correlations between HX-MS and either accelerated or real-time stability studies will be dependent on a particular mAb's degradation pathway(s) and the type of stresses used.     

Development of Stabilizing Formulations of a Trivalent Inactivated Poliovirus Vaccine in a Dried State for Delivery in the Nanopatch™ Microprojection Array

The worldwide switch to inactivated polio vaccines (IPVs) is a key component of the overall strategy to achieve and maintain global polio eradication. To this end, new IPV vaccine delivery systems may enhance patient convenience and compliance. In this work, we examine Nanopatch? (a solid, polymer microprojection array) which offers potential advantages over standard needle/syringe administration including intradermal delivery and reduced antigen doses. Using trivalent IPV (tIPV) and a purpose-built evaporative dry-down system, candidate tIPV formulations were developed to stabilize tIPV during the drying process and on storage. Identifying conditions to minimize tIPV potency losses during rehydration and potency testing was a critical first step. Various classes and types of pharmaceutical excipients (～50 total) were then evaluated to mitigate potency losses (measured through D-antigen ELISAs for IPV1, IPV2, and IPV3) during drying and storage. Various concentrations and combinations of stabilizing additives were optimized in terms of tIPV potency retention, and 2 candidate tIPV formulations containing cyclodextrin and a reducing agent (e.g., glutathione), maintained ≥80% D-antigen potency during drying and subsequent storage for 4 weeks at 4°C, and ≥60% potency for 3 weeks at room temperature with the majority of losses occurring within the first day of storage.     

Coformulation of Broadly Neutralizing Antibodies 3BNC117 and PGT121: Analytical Challenges During Preformulation Characterization and Storage Stability Studies

In this study, we investigated analytical challenges associated with the formulation of 2 anti-HIV broadly neutralizing antibodies (bnAbs), 3BNC117 and PGT121, both separately at 100 mg/mL and together at 50 mg/mL each. The bnAb formulations were characterized for relative solubility and conformational stability followed by accelerated and real-time stability studies. Although the bnAbs were stable during 4°C storage, incubation at 40°C differentiated their stability profiles. Specific concentration-dependent aggregation rates at 30°C and 40°C were measured by size exclusion chromatography for the individual bnAbs with the mixture showing intermediate behavior. Interestingly, although the relative ratio of the 2 bnAbs remained constant at 4°C, the ratio of 3BNC117 to PGT121 increased in the dimer that formed during storage at 40°C. A mass spectrometry-based multiattribute method, identified and quantified differences in modifications of the Fab regions for each bnAb within the mixture including clipping, oxidation, deamidation, and isomerization sites. Each bnAb showed slight differences in the levels and sites of lysine residue glycations. Together, these data demonstrate the ability to differentiate degradation products from individual antibodies within the bnAb mixture, and that degradation rates are influenced not only by the individual bnAb concentrations but also by the mixture concentration.