Total Margin Control Is Superior to Traditional Margin Assessment for Treatment of Low-Stage Penile Squamous Cell Carcinoma.

Purpose: Penile cancer is rare, with significant morbidity and limited literature assessing utility of peripheral and deep en face margin assessment (PDEMA) vs traditional margin assessment (vertical sections) on treatment outcomes.

Materials And Methods: This was a 32-year retrospective multicenter cohort study at 3 academic tertiary care centers. The cohort consisted of 189 patients with histologic diagnosis of in situ or T1a cutaneous squamous cell carcinoma of the penis at Brigham and Women's, Massachusetts General Hospital (1988-2020), and Memorial Sloan Kettering Cancer Center (1995-2020) treated with PDEMA surgical excision, excision/circumcision, or penectomy/glansectomy.

Moral distress among clinicians working in US safety net practices during the COVID-19 pandemic: a mixed methods study.

Objective: To explore the causes and levels of moral distress experienced by clinicians caring for the low-income patients of safety net practices in the USA during the COVID-19 pandemic.

Design: Cross-sectional survey in late 2020, employing quantitative and qualitative analyses.

Setting: Safety net practices in 20 US states.

IL-25 blockade augments antiviral immunity during respiratory virus infection.

IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression.

Proliferation Activity in Canine Gastrointestinal Lymphoma.

Gastrointestinal lymphomas are uncommon in dogs and little is known about their distinct subtypes or proliferation rate. The aim of this study was to stratify 33 canine gastrointestinal lymphoma samples according to the latest World Health Organization classification and to determine the Ki67 proliferation index by manual counting, digital image analysis and visual estimation. The Ki67 index was then correlated with subtype, immunophenotype, mitotic index, grade and tumour location.

Willingness to Use Cannabis for Gynecological Conditions: A National Survey.

Expanded legal access to cannabis in the United States has led to its increased use for treating medical conditions. We assessed the use of and attitudes toward cannabis for treating gynecological conditions. We utilized Amazon.

Cannabinoids for Pain Control During Medical Abortion: A Randomized Controlled Trial.

Objective: To evaluate whether prophylactic dronabinol, a synthetic tetrahydrocannabinol, reduces pain during medical abortion.

Methods: We conducted a randomized, double-blind, placebo-controlled trial of women undergoing medical abortion with mifepristone and misoprostol up through 70 days of gestation. All participants received 800 mg of ibuprofen and were randomized to either 5 mg of oral dronabinol or a placebo 30 minutes before misoprostol administration.

Surgical Transfiguration.

This drawing considers the nature and scope of clinicians' responsibilities to speak and act in ways that express great regard for the breadth and depth of their capacity to influence patients' pre- and postsurgical self-understandings.

ZEB1/NuRD complex suppresses TBC1D2b to stimulate E-cadherin internalization and promote metastasis in lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, due in part to the propensity of lung cancer to metastasize. Aberrant epithelial-to-mesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell-cell adhesion is reduced allowing cells to dissociate and invade.

Garden centre customer attitudes to pollinators and pollinator-friendly planting.

Growing nectar- and pollen-rich flowering plant varieties in domestic gardens and other greenspace is an important pro-environmental behaviour that supports pollinating insects. Wildlife gardening is popular in the UK; however, public attitudes and behaviour relating to planting for pollinators are currently not well understood. We investigated these through questionnaires and interviews with customers in five garden centres in Sussex, southeast England, a relevant and useful consumer group representing horticulturally-engaged members of the public.

Most ornamental plants on sale in garden centres are unattractive to flower-visiting insects.

Background: Gardeners and park managers seeking to support biodiversity in urban areas often plant ornamentals attractive to flower-visiting insects. There is a huge diversity of garden plant varieties, and some recommendations are available as to which are attractive to insects. However, these are largely not based on rigorous empirical data.

Defining Advanced Heart Failure: A Systematic Review of Criteria Used in Clinical Trials.

Background: Enrollment criteria used in advanced heart failure (HF) clinical trials might identify a common set of widely accepted quantitative characteristics as the basis of a consensus definition for advanced HF, which is currently lacking.

Methods: We reviewed all clinical trials investigating interventions in patients with advanced HF as of July 31, 2015. Eligible publications (N = 134) reported original data from clinical trials explicitly defining advanced HF in adults.

Same-Day Discharge After Minimally Invasive Myomectomy.

Objective: To estimate readmission rates of patients discharged home the same day after a minimally invasive myomectomy.

Methods: This is a retrospective case series of patients who underwent minimally invasive myomectomy and were discharged the same day, which examines the feasibility and safety by rates of readmission within Kaiser Permanente Northern California. Chart review was performed for outcomes of interest including readmission rates, emergency department, and urgent clinic visits within 48 hours, 7 days, and up to 3 months along with surgical and demographic characteristics.

Heart rate variability evaluation in the assessment and management of in-utero drug-exposed infants.

Aim: To determine whether heart rate variability parameters vary between in-utero drug-exposed infants and controls. To determine correlations between Finnegan score and heart rate variability parameters. To differentiate those drug-exposed infants who require treatment from those infants who do not.

Infantile hypotonia with failure to thrive.

Background: Pompe disease is a lysosomal glycogen storage disease (GSDII) characterized by deficiency of acid glucosidase, resulting in lysosomal glycogen accumulation in multiple tissues, with cardiac and skeletal muscles being the most seriously affected. It manifests itself as a spectrum in multiple age groups including infancy, childhood and adulthood.

Case Report: We present a case of infantile Pompe disease that was detected at a four month well visit in the presence of hypotonia and failure to thrive.

Intestinal lymphatic transport for drug delivery.

Intestinal lymphatic transport has been shown to be an absorptive pathway following oral administration of lipids and an increasing number of lipophilic drugs, which once absorbed, diffuse across the intestinal enterocyte and while in transit associate with secretable enterocyte lipoproteins. The chylomicron-associated drug is then secreted from the enterocyte into the lymphatic circulation, rather than the portal circulation, thus avoiding the metabolically-active liver, but still ultimately returning to the systemic circulation. Because of this parallel and potentially alternative absorptive pathway, first-pass metabolism can be reduced while increasing lymphatic drug exposure, which opens the potential for novel therapeutic modalities and allows the implementation of lipid-based drug delivery systems.

Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists.

An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea.

Characterization of human liver enzymes involved in the biotransformation of boceprevir, a hepatitis C virus protease inhibitor.

Boceprevir (SCH 503034), a protease inhibitor, is under clinical development for the treatment of human hepatitis C virus infections. In human liver microsomes, formation of oxidative metabolites after incubations with [(14)C]boceprevir was catalyzed by CYP3A4 and CYP3A5. In addition, the highest turnover was observed in recombinant CYP3A4 and CYP3A5.

Quantitation of parent drug and its unstable metabolites by in situ coulometric oxidation and liquid chromatography-tandem mass spectrometry.

Recent FDA and ICH guidances on safety testing of drug metabolites have challenged the way we traditionally think about quantitative bioanalytical methods. Such assays, in general, require a reference standard for each analyte to construct calibration curves and prepare quality control samples. However, early in the drug development process, metabolite standards may not be readily available, and if they are inherently unstable, they are difficult to synthesize or purify.

Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 530348 (Vorapaxar), a potent oral thrombin protease-activated receptor 1 antagonist.

Vorapaxar (SCH 530348), a potent oral thrombin protease-activated receptor 1 antagonist, is being developed as an antiplatelet agent for patients with established vascular disease. The objective of this study was to identify the human liver cytochrome P450 (P450) enzyme(s) responsible for the metabolism of SCH 530348. Human liver microsomes metabolized SCH 530348 to M19, an amine metabolite formed via carbamate cleavage, and M20 (monohydroxy-SCH 530348).

Identification of two novel metabolites of SCH 486757, a nociceptin/orphanin FQ peptide receptor agonist, in humans.

The study of human metabolism of endo-8[bis(2-chlorophenyl)methyl]-3-(2-pyrimidinyl)-8-azabicyclo[3.2.1]octan-3-ol (SCH 486757) after a 200-mg oral dose of the drug to healthy volunteers in the first-in-human study is presented.

Metabolism of loratadine and further characterization of its in vitro metabolites.

The present study demonstrated that in addition to CYP3A4 and CYP2D6, the metabolism of loratadine is also catalyzed by CYP1A1, CYP2C19, and to a lesser extent by CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP3A5. The biotransformation of loratadine was associated with the formation of desloratadine (DL) and further hydroxylation of both DL and the parent drug (loratadine). Based on the inhibition and correlation studies contribution of CYP2C19 in the formation of the major circulating metabolite DL seems to be minor.

An accurate-mass-based spectral-averaging isotope-pattern-filtering algorithm for extraction of drug metabolites possessing a distinct isotope pattern from LC-MS data.

Detection and identification (ID) of all drug metabolites following liquid chromatography (LC)/mass spectrometry (MS) analysis of complex biological matrixes are not trivial. To facilitate detection of drug-derived materials that possess highly diagnostic isotopic patterns (e.g.

A retention-time-shift-tolerant background subtraction and noise reduction algorithm (BgS-NoRA) for extraction of drug metabolites in liquid chromatography/mass spectrometry data from biological matrices.

A retention-time-shift-tolerant background subtraction and noise reduction algorithm (BgS-NoRA) is implemented using the statistical programming language R to remove non-drug-related ion signals from accurate mass liquid chromatography/mass spectrometry (LC/MS) data. The background-subtraction part of the algorithm is similar to a previously published procedure (Zhang H and Yang Y. J.

Neurogenic potential of isolated precursor cells from early post-gastrula somitic tissue.

Adult tissues are known to contain rare populations of stem cells with multilineage differentiation potential that are distinct from other resident tissue-specific stem cells. However, whether multilineage stem cells are involved in tissue development is uncertain, primarily because the identification and characterization of these cells in embryonic tissue primordia is not well established. We tested whether stem cells with multilineage potential are present within the early post-gastrula somite tissue.

Identification of human liver cytochrome P450 enzymes involved in biotransformation of vicriviroc, a CCR5 receptor antagonist.

Vicriviroc (SCH 417690), a CCR5 receptor antagonist, is currently under investigation for the treatment of human immunodeficiency virus infection. The objective of this study was to identify human liver cytochrome P450 enzyme(s) responsible for the metabolism of vicriviroc. Human liver microsomes metabolized vicriviroc via N-oxidation (M2/M3), O-demethylation (M15), N,N-dealkylation (M16), N-dealkylation (M41), and oxidation to a carboxylic acid metabolite (M35b/M37a).