Evaluations of State Medical Cannabis Programs in the USA: A Narrative Review.

Background: Medical cannabis (MC) use is increasing across the USA, with functional MC programs now operating in 38 states. While program policies and practices vary widely, little is known about whether and how states evaluate their programs. Better characterization of state MC program evaluation to date could inform states, program officials, and providers about best practices and provide a roadmap for future program evaluation.

Randomized adaptive selection trial of cryotherapy, compression therapy, and placebo to prevent taxane-induced peripheral neuropathy in patients with breast cancer.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective.

Intermittent MEK inhibition for the treatment of metastatic uveal melanoma.

Introduction: Uveal melanoma (UM) is associated with poor outcomes in the metastatic setting and harbors activating mutations resulting in upregulation of MAPK signaling in almost all cases. The efficacy of selumetinib, an oral allosteric inhibitor of MEK1/2, was limited when administered at a continual dosing schedule of 75 mg BID. Preclinical studies demonstrate that intermittent MEK inhibition reduces compensatory pathway activation and promotes T cell activation.

Patient perspectives of airway clearance techniques in bronchiectasis.

Introduction: While airway clearance techniques (ACTs) are recommended for individuals with bronchiectasis, data suggests the use of and adherence to ACTs is poor.

Objective: This study aimed to identify patient perceptions regarding ACTs, the barriers and facilitators to ACTs, and factors affecting adherence.

Methods: A multi-center qualitative study using in-depth semi-structured interviews of individuals with bronchiectasis was undertaken.

Physiotherapist perspectives of airway clearance techniques in bronchiectasis.

Introduction: Our understanding regarding the personalization of airway clearance techniques (ACTs) in bronchiectasis is limited.

Objective: This study aimed to determine physiotherapist perceptions regarding the prescription of ACTs in inpatients and outpatients with bronchiectasis.

Methods: A single-center qualitative study using semi-structured interviews of physiotherapists who treated individuals with bronchiectasis was undertaken.

Diagnosis of Leptomeningeal Metastasis in Women With Breast Cancer Through Identification of Tumor Cells in Cerebrospinal Fluid Using the CNSide™ Assay.

Introduction: Diagnosis of LM is limited by low sensitivity of cerebrospinal fluid (CSF) cytopathology. Detecting tumor cells in CSF (CSF-TCs) might be more sensitive. We evaluated if CNSide (CNSide), a novel assay for tumor cell detection in CSF, can detect CSF-TCs better than conventional CSF cytology.

The histologic and molecular correlates of COVID-19 vaccine-induced changes in the skin.

A total of 22 patients who had developed an adverse cutaneous reaction to the Moderna or Pfizer vaccine underwent biopsies. Each patient was assessed light microscopically, and, in select biopsies, spike glycoprotein and cytokine assessment were also conducted. The patients developed self-limited cutaneous reactions often described clinically as urticarial or eczematous within 1 day to 4 weeks after receiving the first or second dose of the Pfizer or Moderna vaccine.

Characterization of cannabinoid receptors expressed in Ewing sarcoma TC-71 and A-673 cells as potential targets for anti-cancer drug development.

Aims: Characterizing cannabinoid receptors (CBRs) expressed in Ewing sarcoma (EWS) cell lines as potential targets for anti-cancer drug development.

Main Methods: CBR affinity and function were examined by competitive binding and G-protein activation, respectively. Cannabinoid-mediated cytotoxicity and cell viability were evaluated by LDH, and trypan blue assays, respectively.

Misalignment between COVID-19 hotspots and clinical trial sites.

Hundreds of interventional clinical trials have been launched in the United States to identify effective treatment strategies for combating the coronavirus disease 2019 (COVID-19) pandemic. However, to date, only a small fraction of these trials have completed enrollment, delaying the scientific investigation of COVID-19 and its treatment options. This study presents novel metrics to examine the geographic alignment between COVID-19 hotspots and interventional clinical trial sites and evaluate trial access over time during the evolving pandemic.

Diffuse optical tomography breast imaging measurements are modifiable with pre-surgical targeted and endocrine therapies among women with early stage breast cancer.

Purpose: Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy.

Methods: We conducted a proof of principle study in seven postmenopausal women with stage I-III breast cancer who were enrolled in pre-surgical studies of the AKT inhibitor MK-2206 (n = 4) or the aromatase inhibitors exemestane (n = 2) and letrozole (n = 1).

Phase I/II trial of ruxolitinib in combination with trastuzumab in metastatic HER2 positive breast cancer.

Purpose: Preclinical data demonstrate STAT3 as an important regulator in HER2+ tumors, and disruption of the IL6-JAK2-STAT-S100A8/S100A9 signaling cascade reduces HER2+ cell viability. Ruxolitinib is an FDA approved inhibitor of JAK1 and JAK2. We performed a phase I/II trial investigating the safety and efficacy of the combination of trastuzumab and ruxolitinib in patients with trastuzumab-resistant metastatic HER2+ breast cancer.

Impact of Standardized Patients on First Semester Nursing Students Self-Confidence, Satisfaction, and Communication in a Simulated Clinical Case.

Background: Utilizing standardized patients (SPs) as a strategy to potentially improve beginning level nursing students' confidence, satisfaction, and communication after simulated clinical cases is an innovative approach in nursing education.

Aim: The aim of this study was to examine to what extent an SP affected first semester nursing students' self-confidence, satisfaction, and communication using a simulated clinical case.

Methods: First semester undergraduate students in a bachelors of nursing program at a large university in the South-Central region of the United States (=100), were randomly assigned to one of the two groups.

Histopathologic reaction patterns to differentially cross-linked hyaluronic acid fillers: A retrospective case series.

Background: Hyaluronic acid filler reactions have been increasingly observed in recent years. Our study investigates whether the increased number of filler reactions observed since 2014 is associated with a specific histopathologic inflammatory pattern and type of filler.

Methods: The institution's dermatopathology electronic database was retrospectively searched for histopathologic reactions to hyaluronic acid from January 2014 to December 2019.

Using Participatory Mapping to Diagnose Upstream Determinants of Health and Prescribe Downstream Policy-Based Interventions.

Participatory mapping is a powerful methodology for working with community residents to examine social and environmental determinants of public health disparities. However, this empowering methodology has only been applied sparingly in public health research and practice, with limited examples in the literature. To address this literature gap, we 1) review participatory mapping approaches that may be applied to exploring place-based factors that affect community health, and 2) present a mixed-methods participatory geographic information systems (PGIS) examination of neighborhood assets (eg, streetlights) and challenges (eg, spaces of crime and violence) related to access to public parks in South Los Angeles, California.

Measuring airway clearance outcomes in bronchiectasis: a review.

While airway clearance techniques (ACTs) are recommended for individuals with bronchiectasis, many trials have demonstrated inconsistent benefits or failed to reach their primary outcome. This review determined the most common clinical and patient-reported outcome measures used to evaluate the efficacy of ACTs in bronchiectasis. A literature search of five databases using relevant keywords and filtering for studies published in English, up until the end of August 2019, was completed.

Reducing Discrepancy Between Code Status Orders and Physician Orders for Life-Sustaining Therapies: Results of a Quality Improvement Initiative.

Background: Advanced care planning through Physician Order For Life-Sustaining Therapies (POLST) has been encouraged by professional societies. But these documents may be overlooked or ignored during hospitalization and "full-code" orders written as a default, putting patients at risk for unwanted resuscitation. After 2 instances of unwanted resuscitation in which limited support POLSTs were ignored, a series of improvements were implemented.

Reduced Tolerance and Asymmetrical Crosstolerance to Effects of the Indole Quinuclidinone Analog PNR-4-20, a G Protein-Biased Cannabinoid 1 Receptor Agonist in Mice: Comparisons with Δ-Tetrahydrocannabinol and JWH-018.

Most cannabinoid 1 receptor (CBR) agonists will signal through both G protein-dependent and -independent pathways in an unbiased manner. Recruitment of -arrestin 2 desensitizes and internalizes receptors, producing tolerance that limits therapeutic utility of cannabinoids for chronic conditions. We developed the indole quinuclidinone (IQD) analog (Z)-2-((1-(4-fluorobenzyl)-1H-indol-3-yl)methylene)quinuclidin-3-one (PNR-4-20) as a novel G protein-biased agonist at CBRs, and the present studies determine if repeated administration of PNR-4-20 produces lesser tolerance to in vivo effects compared with unbiased CBR agonists Δ-tetrahydrocannabinol (Δ-THC) and 1-pentyl-3-(1-naphthoyl)indole (JWH-018).

Comparing the Performance Characteristics of Different Positive Expiratory Pressure Devices.

Background: Positive expiratory pressure (PEP) devices are widely used in clinical settings, yet the performance characteristics of these devices remain relatively unknown. This study compared the performance characteristics of 6 airway clearance devices by varying resistance and flow.

Methods: Mean PEP, peak PEP, oscillation frequency, and amplitude PEP of the Flutter, Pari PEP S, Acapella Choice, Acapella DM, Acapella DH, and Aerobika devices were obtained across flows of 5, 10, 15, 20, 25 and 30 L/min and at low, medium, and high resistance using an experimental apparatus custom-built for this bench study.

Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ-THC.

Recreational use of marijuana is associated with few adverse effects, but abuse of synthetic cannabinoids (SCBs) can result in anxiety, psychosis, chest pain, seizures and death. To potentially explain higher toxicity associated with SCB use, we hypothesized that AB-PINACA, a common second generation SCB, exhibits atypical pharmacodynamic properties at CB1 cannabinoid receptors (CB1Rs) and/or a distinct metabolic profile when compared to Δ-tetrahydrocannabinol (Δ-THC), the principal psychoactive cannabinoid present in marijuana. Liquid chromatography tandem mass spectrometry (LC/MS) identified AB-PINACA and monohydroxy metabolite(s) as primary phase I metabolites (4OH-AB-PINACA and/or 5OH-AB-PINACA) in human urine and serum obtained from forensic samples.

The tamoxifen derivative ridaifen-B is a high affinity selective CB receptor inverse agonist exhibiting anti-inflammatory and anti-osteoclastogenic effects.

Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the "ridaifen" compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity.

Characterization of structurally novel G protein biased CB agonists: Implications for drug development.

The human cannabinoid subtype 1 receptor (hCBR) is highly expressed in the CNS and serves as a therapeutic target for endogenous ligands as well as plant-derived and synthetic cannabinoids. Unfortunately, acute use of hCBR agonists produces unwanted psychotropic effects and chronic administration results in development of tolerance and dependence, limiting the potential clinical use of these ligands. Studies in β-arrestin knockout mice suggest that interaction of certain GPCRs, including μ-, δ-, κ-opioid and hCBRs, with β-arrestins might be responsible for several adverse effects produced by agonists acting at these receptors.

Selective Estrogen Receptor Modulators: Cannabinoid Receptor Inverse Agonists with Differential CB1 and CB2 Selectivity.

Selective estrogen receptor modulators (SERMs) are used to treat estrogen receptor (ER)-positive breast cancer and osteoporosis. Interestingly, tamoxifen and newer classes of SERMs also exhibit cytotoxic effects in cancers devoid of ERs, indicating a non-estrogenic mechanism of action. Indicative of a potential ER-independent target, reports demonstrate that tamoxifen binds to cannabinoid receptors (CBRs) with affinity in the low μM range and acts as an inverse agonist.

Tamoxifen Isomers and Metabolites Exhibit Distinct Affinity and Activity at Cannabinoid Receptors: Potential Scaffold for Drug Development.

Tamoxifen (Tam) is a selective estrogen receptor (ER) modulator (SERM) that is an essential drug to treat ER-positive breast cancer. Aside from known actions at ERs, recent studies have suggested that some SERMs like Tam also exhibit novel activity at cannabinoid subtype 1 and 2 receptors (CB1R and CB2Rs). Interestingly, cis- (E-Tam) and trans- (Z-Tam) isomers of Tam exhibit over a 100-fold difference in affinity for ERs.

Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.