An Integrative Review of Micro-Credentials and Digital Badges for Pharmacy Educators.

Micro-credentials (MCs) and digital badges (DBs) have gained popularity in recent years as a means to supplement traditional degrees and certifications. MCs and DBs can play a significant role in supporting student-centered learning by offering personalized and flexible learning pathways, emphasizing real-world relevance and practical skills, and fostering a culture of continuous learning and growth. However, barriers currently exist within health professions education, including pharmacy education, that could limit the full adoption and implementation of MCs and DBs. Research on the use of MCs and DBs in Doctor of Pharmacy degree programs is sparse. In this integrative review, literature on the use of MCs and DBs in health professions education is reviewed, and perspectives on the benefits, issues, and potential future uses within Doctor of Pharmacy degree programs are presented.

Incidence and impact of malnutrition in patients with Fontan physiology.

BACKGROUND: Single-ventricle patients require a series of surgeries, with the final stage being the Fontan. This form of circulation results in several long-term complications, but the impact and consequences of nutrition status remain unclear. We sought to evaluate the incidence of malnutrition in Fontan patients and the impact on outcomes. METHODS: This study was a retrospective cohort study of children who underwent Fontan surgery between 1997 and 2018. Clinical, demographic, and nutrition data were collected, including weight, height, body mass index (BMI), and their respective z scores (z score for weight-for-age [WAZ], z score for height-for-age [HAZ], and z score for BMI-for-age [BMIZ]) pre-Fontan, at discharge, 6 months, and 1, 5, and 10 years post-Fontan. Malnutrition status was categorized using the American Society for Parenteral and Enteral Nutrition guidelines and the Michigan MTool. Fontan failure was defined as listing for heart transplant or death. RESULTS: Of the 69 patients, moderate-severe malnutrition occurred at any time point in 11% (n = 8) by WAZ, 16% (n = 11) by HAZ, and 6% (n = 4) by BMIZ. Moderate-severe malnutrition persisted in 6.5%-12.9% at 10 years post-Fontan. Compared with the pre-Fontan period, there was no change in these parameters over time. There was no statistically significant difference in Fontan failure between degrees of pre-Fontan malnutrition. CONCLUSION: There is a 6%-16% incidence of moderate-severe malnutrition in Fontan patients. Malnutrition is a condition that remains present in follow-up. There was no association with anthropometric parameters and transplant-free survival. A prospective multi-institutional study is needed to understand the impact of malnutrition on long-term outcomes.

Nematodes and trematodes associated with terrestrial gastropods in Nottingham, England.

A parasitological survey of terrestrial slugs and snails was conducted at popular dog walking locations across the city of Nottingham, with the intensions of finding gastropods infected with parasites of medical (or veterinary) importance such as lungworm (metastrongyloid nematodes) and trematodes. A total of 800 gastropods were collected from 16 sites over a 225 km2 area. The extracted nematodes and trematodes were identified by molecular barcoding. Of the 800 gastropods collected, 227 were infected (172 had nematode infections, 37 had trematode infections and 18 had both nematode and trematode infections). Of the nematode infected gastropods genotyped, seven species were identified, Agfa flexilis, Angiostoma gandavense, Angiostoma margaretae, Cosmocerca longicauda, Phasmarhabditis hermaphrodita, Phasmarhabditis neopapillosa and an unknown Cosmocercidae species. Of the trematode infected gastropods genotyped, four species were identified, Brachylaima arcuate, Brachylaima fuscata, Brachylaima mesostoma and an unknown Plagiorchioidea species. No lungworm species were found within the city of Nottingham. To our knowledge, this study represents the first survey of gastropod-associated nematodes and trematodes in the East midlands of the United Kingdom.

Addressing the Long-Term Care Crisis: Identifying Opportunities for Improvement Using Rapid Reviews.

Background: Long-term care (LTC) facilities require urgent, evidence-based care renewal. During 2020 three medical student-driven research projects aiming to study care satisfaction, patient care team dynamics, and advance care directive effectiveness in a local LTC facility required a marked shift in approach due to COVID-19 regulations. Methods: All three projects were re-invented as rapid reviews from their initial designs intended to provide a baseline for quality improvement projects. English-limited PubMed searches for publications within the past 10 years were undertaken. Review articles were prioritized and supplemented by individual studies. Students reviewed the initial abstracts, reviewed them with a supervisor/mentor, assessed the articles for quality, and synthesized major themes. Results: A total of 52 publications were evaluated for the final synthesis of all three projects. Relevant information was retrieved for all three areas, suitable for local evaluation/intervention at micro, meso, and macro policy levels. Conclusions: Rapid reviews of issue-specific, long-term care literature are low resource avenues towards coordinated care improvement. They may also serve as rapid means for regular policy updates while providing next-generation care providers with improved LTC perspectives.

Assessment of Cultural Competence in Pharmacy Students Prior to Advanced Pharmacy Practice Experiences.

Objective. To assess various aspects of cultural competence in second year Doctor of Pharmacy students' and investigate the relationship between cultural competence and students' demographics, work experience, and prior education.Methods. A 63-item survey modified from the Clinical Cultural Competency Questionnaire (CCCQ) and comprising four domains (knowledge, skills, encounters or situations, and attitudes towards cultural competency) was administered to second year pharmacy students before they started their advanced pharmacy practice experiences (APPEs). Additional questions regarding their ability to identify and recognize elements of cultural competence were asked. The effects of demographics, work experience, and education on cultural competence also were assessed.Results. Ninety-seven students (86.6%) participated in the study. The majority of participants were Asian, female, and in their late 20s. Most students agreed or strongly agreed that they could identify and recognize elements of cultural competence. However, participants indicated they were only a little or somewhat comfortable when asked questions about knowledge, skills, and comfort. Students indicated they had "quite a bit" of competence regarding attitudes towards other cultures. Previous cultural diversity training in undergraduate studies and pharmacy school were associated with higher scores on the modified CCCQ.Conclusion. The findings emphasize the importance of schools providing training in the didactic and experiential portion of the pharmacy curriculum to increase pharmacy students' knowledge, skills, comfort, and attitudes towards other cultures.

Natural variation in host-finding behaviour of gastropod parasitic nematodes (Phasmarhabditis spp.) exposed to host-associated cues.

The gastropod parasitic nematode Phasmarhabditis hermaphrodita has been formulated into a successful biological control agent (Nemaslug®, strain DMG0001) used to kill slugs on farms and gardens. When applied to soil, P. hermaphrodita uses slug mucus and faeces to find potential hosts. However, there is little information on what cues other species of Phasmarhabditis (P. neopapillosa and P. californica) use to find hosts and whether there is natural variation in their ability to chemotax to host cues. Therefore, using chemotaxis assays, we exposed nine wild isolates of P. hermaphrodita, five isolates of P. neopapillosa and three isolates of P. californica to mucus from the pestiferous slug host Deroceras invadens, as well as 1% and 5% hyaluronic acid - a component of slug mucus that is highly attractive to these nematodes. We found P. hermaphrodita (DMG0010) and P. californica (DMG0018) responded significantly more to D. invadens mucus and 1% hyaluronic acid than other strains. Also, P. hermaphrodita (DMG0007), P. neopapillosa (DMG0015) and P. californica (DMG0017) were superior at locating 5% hyaluronic acid compared to other isolates of the same genera. Ultimately, there is natural variation in chemoattraction in Phasmarhabditis nematodes, with some strains responding significantly better to host cues than others.

3D morphology of nematode encapsulation in snail shells, revealed by micro-CT imaging.

Many parasites and hosts are embroiled in an on-going arms race that affects the evolution of each participant. One such battle is between parasitic nematodes and terrestrial gastropods which have co-evolved for 90-130 MY. Recently, snails have been shown to encase and kill invading nematodes using their shell as a defence mechanism. However, there is remarkably little known about this process in terms of understanding where, when and how nematodes are fixed within the shell. Also there has never been any attempt to observe this process using methods other than light microscopy. Therefore, we used micro CT scanning of a Cepaea nemoralis shell (a common host for nematodes) to 3D visualise encased nematode parasites and quantify morphological parameters. By taking this approach future studies could use micro CT scanning of fossil shells in conchology collections to understand nematode/snail co-evolution.

Discovery of a Highly Selective Sigma-2 Receptor Ligand, 1-(4-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (CM398), with Drug-Like Properties and Antinociceptive Effects In Vivo.

The sigma-2 receptor has been cloned and identified as Tmem97, which is a transmembrane protein involved in intracellular Ca2+ regulation and cholesterol homeostasis. Since its discovery, the sigma-2 receptor has been an extremely controversial target, and many efforts have been made to elucidate the functional role of this receptor during physiological and pathological conditions. Recently, this receptor has been proposed as a potential target to treat neuropathic pain due to the ability of sigma-2 receptor agonists to relieve mechanical hyperalgesia in mice model of chronic pain. In the present work, we developed a highly selective sigma-2 receptor ligand (sigma-1/sigma-2 selectivity ratio > 1000), 1-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-3-methyl-1H- benzo[d]imidazol-2(3H)-one (CM398), with an encouraging in vitro and in vivo pharmacological profile in rodents. In particular, radioligand binding studies demonstrated that CM398 had preferential affinity for sigma-2 receptor compared with sigma-1 receptor and at least four other neurotransmitter receptors sites, including the norepinephrine transporter. Following oral administration, CM398 showed rapid absorption and peak plasma concentration (Cmax) occurred within 10 min of dosing. Moreover, the compound showed adequate, absolute oral bioavailability of 29.0%. Finally, CM398 showed promising anti-inflammatory analgesic effects in the formalin model of inflammatory pain in mice. The results collected in this study provide more evidence that selective sigma-2 receptor ligands can be useful tools in the development of novel pain therapeutics and altogether, these data suggest that CM398 is a suitable lead candidate for further evaluation.

The psychopharmacology of pseudobulbar affect.

Pseudobulbar affect (PBA) is characterized by uncontrollable emotional episodes disconnected or disproportionate with mood, in association with an array of neurologic conditions. PBA is associated with disruption of descending control of brainstem motor circuitry and dysregulation of serotonergic and glutamatergic function. PBA has been historically under recognized, though advances resulting in more specific diagnostic criteria, validated rating scales, and an approved pharmacotherapy offer opportunities for improved treatment outcomes.

Household composition and maltreatment allegations in the US: Deconstructing the at-risk single mother family.

BACKGROUND: Previous research has demonstrated the association between child maltreatment and household composition, with increased maltreatment risk generally present in single mother households. However, existing research does not fully examine the complexity and configuration of single mother households. In particular, less is known about important variants of single parent family structures, such as grandparents residing in the home, and the extent to which household compositions change across time. OBJECTIVE: The present study examines rates of maltreatment allegations across various household compositions in a sample of single biological mother households. PARTICIPANTS AND SETTING: Youth participants (N = 417) were part of the larger multi-site Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) study. METHODS: Participants completed longitudinal assessments of household composition and maltreatment allegations from ages 4 to 10. RESULTS: The present study illustrates substantial variability in the rate of maltreatment allegations across different types of single mother household compositions. In particular, the presence of non-relatives, especially unrelated males, demonstrated an increased risk for maltreatment allegations in the home. Conversely, single mother homes with two or more adult relatives, especially grandmothers, were at reduced risk for child maltreatment allegations. CONCLUSIONS: This study highlights variability in maltreatment allegations among single mother homes, including how maltreatment allegations vary across different household configurations, across child age periods and across different risk levels.

An Individual Development Plan for Pharmacy Students for Career Planning and Tracking Accreditation Standards.

Objective. To create and implement individual development plans (IDPs) to assist pharmacy students in career planning and tracking their achievement of ACPE Standards 2016, Standard 4, for Personal and Professional Development. Methods. First-year Doctor of Pharmacy students completed IDPs, which were subsequently reviewed to ensure they addressed components of the ACPE Standard 4 key elements: self-awareness, leadership, innovation and entrepreneurship, and professionalism. Faculty advisors were surveyed regarding the utility of IDPs. Descriptive statistics were used to evaluate the results. Results. Self-awareness (100%) and professionalism (100%) were the key elements most commonly documented by pharmacy students, followed by leadership (51%), and innovation and entrepreneurship (22%). Faculty advisors reported IDPs as beneficial for stimulating individualized career planning and tracking achievement of ACPE Standard 4. Conclusion. Most students enter pharmacy school recognizing the importance of self-awareness and professionalism, but require additional training to instill leadership and innovation/entrepreneurship skills. Individual development plans can be implemented in pharmacy education as a cornerstone of personal and professional development planning, as well as a means of tracking a school's progress toward meeting accreditation standards.

The effect of sertraline, haloperidol and apomorphine on the behavioural manipulation of slugs (Deroceras invadens) by the nematode Phasmarhabditis hermaphrodita.

The nematode Phasmarhabditis hermaphrodita can infect and kill many species of slugs and has been formulated into a biological control agent for farmers and gardeners. P. hermaphrodita can manipulate the behaviour of slugs, making those infected move to areas where the nematode is present. Research suggests P. hermaphrodita uses manipulation of biogenic amines to achieve this, however the exact role of serotonin and dopamine needs further elucidation. Here we fed slugs Deroceras invadens (uninfected and infected with P. hermaphrodita) apomorphine, sertraline and haloperidol and observed their behaviour when given a choice between a P. hermaphrodita infested habitat, or a parasite free area of soil. In contrast to their usual P. hermaphrodita avoidance behaviour, uninfected D. invadens fed sertraline were attracted to the nematodes and conversely those fed haloperidol avoided the nematodes. D. invadens fed apomorphine were recorded equally on the control and nematode side. D. invadens pre-infected with P. hermaphrodita fed sertraline and apomorphine were found significantly more on the side with the nematodes. However, suppressing dopaminergic signalling through feeding with haloperidol abrogated this attraction and slugs were found on both sides. These results demonstrate that serotonin and dopamine are potential regulators of behavioural manipulation by P. hermaphrodita.

Gedunin Inhibits Oligomeric Aß1-42-Induced Microglia Activation Via Modulation of Nrf2-NF-κB Signaling.

Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia in aged populations worldwide. The deposition of toxic protein aggregates such as amyloid beta (Aß) is a hallmark of AD, and there is growing awareness that a key driver of AD pathogenesis is the neuroinflammatory cascade triggered and sustained by these proteins. Consequently, interventions that suppress prolonged neuroinflammation represent viable therapeutic approaches for AD. In this context, we tested the natural product gedunin which is an anti-inflammatory molecule, found in the seeds of the neem tree (Azadirachta indica), whose mechanism of action remains to be fully elucidated. Using a mouse microglia cell line (IMG), we show that gedunin suppresses neuroinflammation arising from Aß1-42 oligomer exposure. Our results demonstrate that gedunin suppresses Aß1-42-induced NF-κB activation and its targets, including nitric oxide (NO) and IL-1ß, known proinflammatory molecules. Further, we show that gedunin inhibits neuroinflammation by activating nuclear factor 2 erythroid-related factor 2 (Nrf2) and its downstream targets γ-glutamylcysteine synthetase, heme oxygenase 1, and NADPH quinone dehydrogenase 1, which are involved in quenching reactive oxygen and nitrogen species (NO) generated by NF-κB activation. Nrf2 activation appears essential for the anti-inflammatory effect because when silenced, the proinflammatory effects of Aß1-42 are enhanced and the protective effect of gedunin against NO production is reduced. Additionally, using human neuronal cells (SH-SY5Y), we show that gedunin prevents neurotoxicity secondary to Aß-induced microglial activation. In conclusion, our findings highlight a potential therapeutic role of gedunin in neurodegenerative diseases.

Benzimidazolone-based selective σ2 receptor ligands: Synthesis and pharmacological evaluation.

Sigma receptors (σRs) are considered to be a significant and valid target for developing new medications to address several diseases. Their potential involvement in numerous central nervous system disorders, neuropathic pain, addiction, and cancer has been extensively reported. In particular, the σ2R has been identified as potential target for the development of pharmaceutical agents intended to treat the negative effects associated with drugs of abuse. As a continuation of our previous efforts to develop new selective σ2R ligands, a series of benzimidazolone derivatives were designed, synthesized, and characterized. The newly synthesized ligands were evaluated through in vitro radioligand binding assays to determine their affinity and selectivity towards both σ1 and σ2 receptors. Several derivatives displayed high affinity for the σ2R (Ki = 0.66-68.5 nM) and varied from preferring to selective, compared to σ1R (σ1/σ2 = 5.8-1139). Among them, compound 1-{4-[4-(4-fluorophenyl)piperazin-1-yl]butyl}-3-propyl-1,3-dihydrobenzimidazol-2-one dihydrochloride (14) displayed the ability to produce a dose-dependent reduction in the convulsive effects of cocaine in a rodent model after injecting 10 mg/kg (i.p.). These preliminary results support the use of selective σ2R ligands in the development of useful pharmacological tools or potential pharmacotherapies for cocaine toxicity.

Development of Phasmarhabditis hermaphrodita (and members of the Phasmarhabditis genus) as new genetic model nematodes to study the genetic basis of parasitism.

The genetic mechanisms of how free-living nematodes evolved into parasites are unknown. Current genetic model nematodes (e.g. Caenorhabditis elegans) are not well suited to provide the answer, and mammalian parasites are expensive and logistically difficult to maintain. Here we propose the terrestrial gastropod parasite Phasmarhabditis hermaphrodita as a new alternative to study the evolution of parasitism, and outline the methodology of how to keep P. hermaphrodita in the lab for genetic experiments. We show that P. hermaphrodita (and several other Phasmarhabditis species) are easy to isolate and identify from slugs and snails from around the UK. We outline how to make isogenic lines using 'semi-natural' conditions to reduce in-lab evolution, and how to optimize growth using nematode growth media (NGM) agar and naturally isolated bacteria. We show that P. hermaphrodita is amenable to forward genetics and that unc and sma mutants can be generated using formaldehyde mutagenesis. We also detail the procedures needed to carry out genetic crosses. Furthermore, we show natural variation within our Phasmarhabditis collection, with isolates displaying differences in survival when exposed to high temperatures and pH, which facilitates micro and macro evolutionary studies. In summary, we believe that this genetically amenable parasite that shares many attributes with C. elegans as well as being in Clade 5, which contains many animal, plant and arthropod parasites, could be an excellent model to understand the genetic basis of parasitism in the Nematoda.

Gastropod parasitic nematodes (Phasmarhabditis sp.) are attracted to hyaluronic acid in snail mucus by cGMP signalling.

Phasmarhabditis hermaphrodita is a parasitic nematode of terrestrial gastropods that has been formulated into a biological control agent for farmers and gardeners to kill slugs and snails. In order to locate slugs it is attracted to mucus, faeces and volatile cues; however, there is no information about whether these nematodes are attracted to snail cues. It is also unknown how wild isolates of P. hermaphrodita or different Phasmarhabditis species behave when exposed to gastropod cues. Therefore, we investigated whether P. hermaphrodita (commercial and wild isolated strains), P. neopapillosa and P. californica were attracted to mucus from several common snail species (Cepaea nemoralis, Cepaea hortensis, Arianta arbustorum and Cornu aspersum). We also examined whether snails (C. aspersum) collected from different locations around the UK differed in their attractiveness to wild isolates of P. hermaphrodita. Furthermore, we also investigated what properties of snail mucus the nematodes were attracted to, including hyaluronic acid and metal salts (FeSO4, ZnSO4, CuSO4 and MgSO4). We found that the commercial strain of P. hermaphrodita responded poorly to snail mucus compared to wild isolated strains, and C. aspersum collected from different parts of the UK differed in their attractiveness to the nematodes. We found that Phasmarhabditis nematodes were weakly attracted to all metals tested but were strongly attracted to hyaluronic acid. In a final experiment we also showed that pharmacological manipulation of cyclic guanosine monophosphate (cGMP) increased chemoattraction to snail mucus, suggesting that the protein kinase EGL-4 may be responsible for Phasmarhabditis sp. chemoattraction.

Synthesis and Structural Elucidation of a Pyranomorphinan Opioid and in Vitro Studies.

During optimization of the synthesis of the mixed µ opioid agonist/δ opioid antagonist 5-(hydroxymethyl)oxymorphone (UMB425) for scale-up, it was unexpectedly discovered that the 4,5-epoxy bridge underwent rearrangement on treatment with boron tribromide (BBr3) to yield a novel opioid with a little-studied pyranomorphinan skeleton. This finding opens the pyranomorphinans for further investigations of their pharmacological profiles and represents a novel drug class with the dual profile (µ vs δ) predicted to yield lower tolerance and dependence. The structure was assigned with the help of 1D, 2D NMR and the X-ray crystal structure.

Deuterated (d6)-dextromethorphan elicits antidepressant-like effects in mice.

The over-the-counter antitussive dextromethorphan (DM) may have rapid antidepressant actions based on its overlapping pharmacology with ketamine, which has shown fast antidepressant effects but whose widespread use remains limited by problematic side effects. We have previously shown that DM produces antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST) that are mediated in part through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic (AMPA) and sigma-1 receptors, two protein targets associated with a faster onset of antidepressant efficacy. To utilize DM clinically, however, a major challenge that must be addressed is its rapid first-pass metabolism. Two strategies to inhibit metabolism of DM and maintain stable therapeutic blood levels are 1) chemically modifying DM and 2) adding quinidine, an inhibitor of the primary metabolizer of DM, the cytochrome P450 (CYP) 2D6 enzyme. The purpose of this study was to determine if modified DM (deuterated (d6)-DM) elicits antidepressant-like effects and if AMPA and sigma-1 receptors are involved. Furthermore, d6-DM was tested in conjunction with quinidine to determine if further slowing the metabolism of d6-DM affects its antidepressant-like actions. In the FST and TST, d6-DM produced antidepressant-like effects. Upon further investigation in the FST, the most validated animal model for predicting antidepressant efficacy, d6-DM produced antidepressant-like effects both in the absence and presence of quinidine. However, pretreatment with neither an AMPA receptor antagonist (NBQX) nor sigma-1 receptor antagonists (BD1063, BD1047) significantly attenuated the antidepressant-like effects. The data suggest d6-DM has antidepressant-like effects, though it may be recruiting different molecular targets and/or acting through a different mix or ratio of metabolites from regular DM.

The gastropod shell has been co-opted to kill parasitic nematodes.

Exoskeletons have evolved 18 times independently over 550 MYA and are essential for the success of the Gastropoda. The gastropod shell shows a vast array of different sizes, shapes and structures, and is made of conchiolin and calcium carbonate, which provides protection from predators and extreme environmental conditions. Here, I report that the gastropod shell has another function and has been co-opted as a defense system to encase and kill parasitic nematodes. Upon infection, cells on the inner layer of the shell adhere to the nematode cuticle, swarm over its body and fuse it to the inside of the shell. Shells of wild Cepaea nemoralis, C. hortensis and Cornu aspersum from around the U.K. are heavily infected with several nematode species including Caenorhabditis elegans. By examining conchology collections I show that nematodes are permanently fixed in shells for hundreds of years and that nematode encapsulation is a pleisomorphic trait, prevalent in both the achatinoid and non-achatinoid clades of the Stylommatophora (and slugs and shelled slugs), which diverged 90-130 MYA. Taken together, these results show that the shell also evolved to kill parasitic nematodes and this is the only example of an exoskeleton that has been co-opted as an immune system.