Patient perspectives on the vital primary care role of community pharmacists in Nova Scotia, Canada: qualitative findings from the PUPPY Study.

OBJECTIVES: Community pharmacists play an important role in primary care access and delivery for all patients, including patients with a family physician or nurse practitioner ("attached") and patients without a family physician or nurse practitioner ("unattached"). During the COVID-19 pandemic, community pharmacists were accessible care providers for unattached patients and patients who had difficulty accessing their usual primary care providers ("semi-attached"). Before and during the pandemic, pharmacist services expanded in several Canadian provinces. The aim of this qualitative study was to explore patient experiences receiving care from community pharmacists, and their perspectives on the scope of practice of community pharmacists. METHODS: Fifteen patients in Nova Scotia, Canada, were interviewed. Participant narratives pertaining to pharmacist care were analyzed thematically. KEY FINDINGS: Attached, "semi-attached," and unattached patients valued community pharmacists as a cornerstone of care and sought pharmacists for a variety of health services, including triaging and system navigation. Patients spoke positively about expanding the scope of practice for community pharmacists, and better optimization of pharmacists in primary care. CONCLUSIONS: System decision-makers should consider the positive role community pharmacists can play in achieving primary care across the Quintuple Aim (population health, patient and provider experiences, reducing costs, and supporting equity in health).

Robust performance of a live bacterial therapeutic chassis lacking the colibactin gene cluster.

E. coli Nissle (EcN) is a non-pathogenic probiotic bacterium of the Enterobacteriaceae family that has been used for over a century to promote general gut health. Despite the history of safe usage of EcN, concerns have been raised regarding the presence of the pks gene cluster, encoding the genotoxin colibactin, due to its association with colorectal cancer. Here, we sought to determine the effect of pks island removal on the in vitro and in vivo robustness and activity of EcN and EcN-derived strains. A deletion of the pks island (Δpks) was constructed in wild type and engineered strains of EcN using lambda red recombineering. Mass spectrometric measurement of N-myristoyl-D-asparagine, released during colibactin maturation, confirmed that the pks deletion abrogated colibactin production. Growth curves were comparable between Δpks strains and their isogenic parents, and wild type EcN displayed no competitive advantage to the Δpks strain in mixed culture. Deletion of pks also had no effect on the activity of strains engineered to degrade phenylalanine (SYNB1618 and SYNB1934) or oxalate (SYNB8802). Furthermore, 1:1 mixed dosing of wild type and Δpks EcN in preclinical mouse and nonhuman primate models demonstrated no competitive disadvantage for the Δpks strain with regards to transit time or colonization. Importantly, there was no significant difference on in vivo strain performance between the clinical-stage strain SYNB1934 and its isogenic Δpks variant with regards to recovery of the quantitative strain-specific biomarkers d5- trans-cinnamic acid, and d5-hippuric acid. Taken together, these data support that the pks island is dispensable for Synthetic Biotic fitness and activity in vivo and that its removal from engineered strains of EcN will not have a deleterious effect on strain efficacy.

An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria.

Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalate in the gut and lower urinary oxalate as a potential treatment for EH. Oral administration of SYNB8802 leads to significantly decreased urinary oxalate excretion in healthy mice and non-human primates, demonstrating the strain's ability to consume oxalate in vivo. A mathematical modeling framework was constructed that combines in vitro and in vivo preclinical data to predict the effects of SYNB8802 administration on urinary oxalate excretion in humans. Simulations of SYNB8802 administration predict a clinically meaningful lowering of urinary oxalate excretion in healthy volunteers and EH patients. Together, these findings suggest that SYNB8802 is a promising treatment for EH.

Improvement of a synthetic live bacterial therapeutic for phenylketonuria with biosensor-enabled enzyme engineering.

In phenylketonuria (PKU) patients, a genetic defect in the enzyme phenylalanine hydroxylase (PAH) leads to elevated systemic phenylalanine (Phe), which can result in severe neurological impairment. As a treatment for PKU, Escherichia coli Nissle (EcN) strain SYNB1618 was developed under Synlogic's Synthetic Biotic™ platform to degrade Phe from within the gastrointestinal (GI) tract. This clinical-stage engineered strain expresses the Phe-metabolizing enzyme phenylalanine ammonia lyase (PAL), catalyzing the deamination of Phe to the non-toxic product trans-cinnamate (TCA). In the present work, we generate a more potent EcN-based PKU strain through optimization of whole cell PAL activity, using biosensor-based high-throughput screening of mutant PAL libraries. A lead enzyme candidate from this screen is used in the construction of SYNB1934, a chromosomally integrated strain containing the additional Phe-metabolizing and biosafety features found in SYNB1618. Head-to-head, SYNB1934 demonstrates an approximate two-fold increase in in vivo PAL activity compared to SYNB1618.

Comparison of anterior maxillary and mandibular alveolar parameters in African American and Caucasian women: A retrospective pilot study.

PURPOSE: The primary objective of this study was to analyze the thickness and height of alveolar bone around the maxillary and mandibular incisors. Additionally, this study aimed to compare bone parameters between Caucasian (CC) and African American (AA) female patients. MATERIALS AND METHODS: In this retrospective pilot study, 50 female subjects (25 CC and 25 AA) were included. The inclusion criteria were AA or CC women between the ages of 18 and 50 with a normo-divergent facial pattern and Angle's class I, end-on class II, or mild class III malocclusion. The distance from the cementoenamel junction (CEJ) to the buccal and lingual alveolar crest; the alveolar ridge thickness at the mid-root and apex; and the buccal and lingual bone thickness at 3, 6, and 9 mm from the CEJ were measured. RESULTS: No significant difference was found (P>0.05) in the cortical bone thickness at 3 mm, 6 mm, or 9 mm from the alveolar crest between CC and AA populations for most measurements. A significant difference in bone thickness was found (P<0.05) for the lingual surface of the central incisor, with maxillary bone thickness found to be higher than mandibular bone thickness. The measurements of lingual thickness were larger than those of buccal thickness for both races. CONCLUSION: There were no differences in maxillomandibular anterior alveolar bone measurements between normo-divergent adult AA and CC women, except for a few parameters at varying locations. However, future studies can be planned based the current pilot study data, which may provide valuable information.

Big data on a big new market: Insights from Washington State's legal cannabis market.

INTRODUCTION: Voters in eight U.S. states have passed initiatives to legalize large-scale commercial production of cannabis for non-medical use. All plan or require some form of "seed-to-sale" tracking systems, which provide a view of cannabis market activity at a heretofore unimagined level of detail. Legal markets also create a range of new matters for policy makers to address. DATA: Publicly available data were obtained on approximately 45 million individually priced items purchased in the 35 million retail transactions that took place during the first two and a half years of Washington State's legal cannabis market. Records include product type (flower, extract, lotion, liquid edible, etc.), product name, price, and potency with respect to multiple cannabinoids, notably THC and CBD. Items sold can be traced back up the supply chain through the store to the processor and producer, to the level of identifying the specific production batch and mother plant, the firm that tested the product, and test results. METHOD: Data visualization methods are employed to describe spatial-temporal patterns of multiple correlated attributes (e.g., price and potency) broken down by product. Text-analytic methods are used to subdivide the broad category of "extracts for inhalation" into more homogeneous sub-categories. To understand the competitiveness of the legal cannabis market in Washington we calculate the Herfindahl-Hirschman index (HHI) for processors and retailers. RESULTS: Cannabis prices fell steadily and proportionally at the processor and retailer levels. Retail and wholesale price maintained a roughly 3:1 ratio for multiple product types after some initial fluctuations. Although a wide range of edibles are sold, they account for a modest share of consumer spending; extracts for inhalation are a larger and heterogeneous market segment. The HHI indicates the cannabis market is highly competitive at the processor level, but less so for retail markets at the county level. CONCLUSIONS: Washington's state-legal cannabis market is diverse and rapidly evolving in terms of pricing, products, and organization. Post-legalization, researchers and policy makers may need to think in terms of a family of cannabis products, akin to how we think of new psychoactive substances and amphetamine-type stimulants, not a single drug "cannabis."

Stereoselective formation of the varietal aroma compound rose oxide during alcoholic fermentation.

The potent aroma compound rose oxide was quantified in several white wines by a headspace solid-phase microextration stable isotope dilution assay (HS-SPME-SIDA) and the enantiomeric ratios of the cis diastereomers were determined by enantioselective capillary GC. The most odor-active stereoisomer (23)-cis-rose oxide was detectable in all investigated white wines ranging from 0.2 to 12 microg/L. However, its contribution to the overall aroma in some white wine varieties can be neglected as indicated by a low odor activity value (OAV). The highest concentrations were found in Gewürztraminer wines, confirming the importance of rose oxide as a varietal aroma compound in this variety. Surprisingly, the enantiomeric ratio of cis-rose oxide in all investigated wines was substantially lower than in nonfermented musts and in some wines almost racemic cis-rose oxide was detected. Fermentation studies with a model must that contained deuterated water revealed that yeast is capable of reducing the precursor 3,7-dimethyl octa-2,5-dien-1,7-diol (geranyl diol I) yielding 3,7-dimethyl-5-octen-1,7-diol (citronellyl diol I) that gives rise to cis- and trans-rose oxide after acid catalyzed cylization. The deuterium labeling pattern of the resulting rose oxide stereoisomers and a clearly detectable kinetic isotope effect indicate that at least two different reductive pathways in yeast exist that yield cis-rose oxide with different enantiomeric ratios altering the genuine enantiomeric ratio in grape musts. The presence of (+)-cis-rose oxides in wines can therefore be attributed to the reductive yeast metabolism during fermentation. This observation corroborates recent findings that the modification of terpene derived varietal aroma is an integral part of yeast metabolism and not only a simple hydrolytical process.