Preferred Educational Programming Among Graduate Students and Postdoctoral Fellows at Pharmacy Schools: A Pilot Survey.

Objective: To inform program development, the American Association of Colleges of Pharmacy (AACP) Graduate Education Special Interest Group Colleagues in Training Committee (CITC) investigated the professional development needs of graduate students and postdoctoral fellows at schools/colleges of pharmacy.

Methods: A cross-sectional pilot survey examined preferred programming topics, mentoring needs, and career goals. A survey invitation was posted on AACP Connect and emailed to Graduate Program Officers and Assistant/Associate Deans for Research at US pharmacy schools/colleges for distribution to trainees.

Late Miocene transformation of Mediterranean Sea biodiversity.

Understanding deep-time marine biodiversity change under the combined effects of climate and connectivity changes is fundamental for predicting the impacts of modern climate change in semi-enclosed seas. We quantify the Late Miocene-Early Pliocene [11.63 to 3.

The paradox of predictability provides a bridge between micro- and macroevolution.

The relationship between the evolutionary dynamics observed in contemporary populations (microevolution) and evolution on timescales of millions of years (macroevolution) has been a topic of considerable debate. Historically, this debate centers on inconsistencies between microevolutionary processes and macroevolutionary patterns. Here, we characterize a striking exception: emerging evidence indicates that standing variation in contemporary populations and macroevolutionary rates of phenotypic divergence is often positively correlated.

The marine biodiversity impact of the Late Miocene Mediterranean salinity crisis.

Massive salt accumulations, or salt giants, have formed in highly restricted marine basins throughout geological history, but their impact on biodiversity has been only patchily studied. The salt giant in the Mediterranean Sea formed as a result of the restriction of its gateway to the Atlantic during the Messinian Salinity Crisis (MSC) 5.97 to 5.

Identification of the mode of evolution in incomplete carbonate successions.

Background: The fossil record provides the unique opportunity to observe evolution over millions of years, but is known to be incomplete. While incompleteness varies spatially and is hard to estimate for empirical sections, computer simulations of geological processes can be used to examine the effects of the incompleteness in silico. We combine simulations of different modes of evolution (stasis, (un)biased random walks) with deposition of carbonate platforms strata to examine how well the mode of evolution can be recovered from fossil time series, and how test results vary between different positions in the carbonate platform and multiple stratigraphic architectures generated by different sea level curves.

Dose-dependent induction of CYP3A activity by St. John's wort alone and in combination with rifampin.

The dose dependence of the effect of enzyme inducers and the effect of the combined administration of two inducers that exert their effect via the same induction pathway (pregnane X receptor) have not been well studied. Using oral midazolam microdoses (30 μg), we have investigated CYP3A4 induction by St. John's wort (SJW) in 11 healthy volunteers using low (300 mg/day containing 7.

Protocol of the IntenSify-Trial: An open-label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab-paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy.

Expression of CYP3A5 protein is a basal and acquired resistance mechanism of pancreatic ductal adenocarcinoma cells conferring protection against the CYP3A and CYP2C8 substrate paclitaxel through metabolic degradation. Inhibition of CYP3A isozymes restores the cells sensitivity to paclitaxel. The combination of gemcitabine and nab-paclitaxel is an established regimen for the treatment of metastasized or locally advanced inoperable pancreatic cancer.

Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC.

Neoadjuvant chemotherapy can improve the survival of individuals with borderline and unresectable pancreatic ductal adenocarcinoma; however, heterogeneous responses to chemotherapy remain a significant clinical challenge. Here, we performed RNA sequencing (n = 97) and multiplexed immunofluorescence (n = 122) on chemo-naive and postchemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) to define the impact of neoadjuvant chemotherapy. Transcriptome analysis combined with high-resolution mapping of whole-tissue sections identified GATA6 (classical), KRT17 (basal-like) and cytochrome P450 3A (CYP3A) coexpressing cells that were preferentially enriched in post-CTX resected samples.

Qualitative analysis of community pharmacy-based COVID-19 immunization service operations.

Background: The unprecedented coronavirus disease 2019 (COVID-19) pandemic has generated worldwide impacts while positioning community pharmacies as easily accessible immunizers to rollout the COVID-19 vaccine.

Objectives: This study describes community pharmacists' experiences, success stories, and lessons learned from providing COVID-19 immunization services.

Methods: This study was conducted in February to March 2022 using semistructured interviews with licensed pharmacists practicing full-time in Alabama community pharmacies.

Current published evidence on barriers and proposed strategies for genetic testing implementation in health care settings: A scoping review.

Background: The slow uptake of genetic testing in routine clinical practice warrants the attention of researchers and practitioners to find effective strategies to facilitate implementation.

Objectives: This study aimed to identify the barriers to and strategies for pharmacogenetic testing implementation in a health care setting from published literature.

Methods: A scoping review was conducted in August 2021 with an expanded literature search using Ovid MEDLINE, Web of Science, International Pharmaceutical Abstract, and Google Scholar to identify studies reporting implementation of pharmacogenetic testing in a health care setting, from a health care system's perspective.

Effect of Clomethiazole Vs. Clorazepate on Hepatic Fat and Serum Transaminase Activities in Alcohol-Associated Liver Disease: Results from a Randomized, Controlled Phase II Clinical Trial.

Aims: Alcohol-associated liver disease (ALD) is a global health problem caused, among other factors, by oxidative stress from the formation of reactive oxygen species (ROS). One important source of ROS is microsomal ethanol metabolism catalyzed by cytochrome P450 2E1 (CYP2E1), which is induced by chronic ethanol consumption. Inhibition of CYP2E1 by clomethiazole (CMZ) decreases oxidative stress in cell cultures and improves ALD in animal studies.

Quantification of the Time Course of CYP3A Inhibition, Activation, and Induction Using a Population Pharmacokinetic Model of Microdosed Midazolam Continuous Infusion.

Background: Cytochrome P450 (CYP) 3A contributes to the metabolism of many approved drugs. CYP3A perpetrator drugs can profoundly alter the exposure of CYP3A substrates. However, effects of such drug-drug interactions are usually reported as maximum effects rather than studied as time-dependent processes.

First-in-human, randomized, double-blind, placebo-controlled, dose escalation trial of the anti-herpes simplex virus monoclonal antibody HDIT101 in healthy volunteers.

HDIT101 is a first-in-class humanized monoclonal antibody recognizing a conserved epitope in glycoprotein B, a target present on the surface of herpes simplex virus 1 (HSV-1) and HSV-2 particles as well as on virus-infected cells. This was a first-in-human, single-center, double-blind, placebo-controlled trial in 24 healthy volunteers, randomized 3:1 (placebo:active) in each of the six dose levels with escalating doses up to 12,150 mg HDIT101. HDIT101 was administered intravenously, to study safety, pharmacokinetics (PKs), and immunogenicity.

Molecular, Viral and Clinical Features of Alcohol- and Non-Alcohol-Induced Liver Injury.

Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism.

A state-wide education program on opioid use disorder: influential community members' knowledge, beliefs, and opportunities for coalition development.

Background: Deep South states, particularly Alabama, experience disproportionately higher opioid prescribing rates versus national rates. Considering limited opioid use disorder (OUD) providers in this region, collaborative efforts between non-healthcare professionals is critical in mitigating overdose mortality. The Alabama Opioid Training Institute (OTI) was created in 2019 to empower community members to take action in combatting OUD in local regions.

Primary Care Physicians', Psychiatrists', and Oncologists' Coordination While Prescribing Medications for Patients With Multiple Chronic Conditions.

Objectives: Coordination of medication prescribing is important in the care of patients with multiple chronic conditions (MCC) given the involvement of multiple providers and multiple medications used to manage MCC. The objective of this study was to identify physician and practice factors associated with physicians' coordination of prescribing for complex patients with MCC.

Methods: Our cross-sectional study used a 33-item anonymous, online survey to assess physicians' coordination practices while prescribing for patients with MCC.

Combined inhibition of CXCL12 and PD-1 in MSS colorectal and pancreatic cancer: modulation of the microenvironment and clinical effects.

Background: Immunotherapy in microsatellite stable colorectal or pancreatic cancer has not shown promising results. It has been hypothesized that targeting immunosuppressive molecules like SDF1-alpha/CXCL12 could contribute to immunotherapy and animal models showed promising results on T cell activation and migration in combination with immune checkpoint inhibition.

Methods: Here, we describe the successful application of anti-CXCL12 (NOX-A12) in patients with advanced stage pretreated metastatic colorectal and pancreatic cancer (OPERA trial).

Individuals' preference for financial over social incentives for medication adherence.

Background: Patients with chronic conditions continue to face financial and system-related barriers to medication adherence. Pharmacy, provider, and payer-based financial and social incentive-based interventions may reduce these barriers and improve adherence. However, it is unclear how patient demographics and clinical characteristics influence the type of incentives preferred by patients.

Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma.

Purpose: To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy.

Patients And Methods: This is a noncontrolled, single-arm, open-label, dose-escalating, single-center clinical trial. Seven patients with PDAC and at least one liver metastasis were included.

Perceived appropriateness of medication adherence incentives.

50% of prescriptions dispensed in the United States are not taken as prescribed, leading to approximately 125,000 deaths and 10% of hospitalizations per year. Incentives are effective in improving medication adherence; however, information about patient perceptions regarding incentives is lacking. To (1) explore perceived appropriateness of incentives among patients prescribed at least 1 medication for chronic hypertension, hyperlipidemia, heart disease, diabetes, and/or asthma/chronic obstructive pulmonary disease and (2) examine associations between perceived appropriateness and patient characteristics.

Qualitative exploration of factors influencing the plan selection process by Medicare beneficiaries.

Because Medicare plan coverage and costs change annually and older adults, the major beneficiaries of Medicare, are faced with multiple health conditions and changing medical needs, Medicare beneficiaries should evaluate their options during open enrollment every year. However, because of the complexity of plan selection, it may be challenging for Medicare beneficiaries to make an appropriate decision from among competing options. To (a) identify factors that beneficiaries consider having influenced their plan selection decision and (b) describe the decision-making process according to the consumer decision-making model (CDM).

Patient preferences for medication adherence financial incentive structures: A discrete choice experiment.

Background: Medication adherence for chronic conditions continues to be a challenge for patients. Patient incentives for medication adherence may help. Financial incentives delivered at the point of care may act as cues for medication-taking behavior.