Phenotypic Environmental Sensitivity and Mental Health During Pregnancy and Post Partum: Protocol for the Experiences of Pregnancy Longitudinal Cohort Study.

Background: Mental health problems during pregnancy and post partum are common and associated with negative short- and long-term impacts on pregnant individuals, obstetric outcomes, and child socioemotional development. Socio-environmental factors are important predictors of perinatal mental health, but the effects of the environment on mental health are heterogeneous. The differential susceptibility theory and the environmental sensitivity framework suggest that individuals differ in their degree of sensitivity to positive and negative environments, which can be captured by individual phenotypes such as temperament and personality.

Impact of genotype on clinical course in sickle cell disease and the utility of neutrophil-lymphocyte ratio: a ten-year single-institution experience.

Background: Sickle cell disease (SCD) is a diverse group of blood disorders with significant global disease burden. Contemporary interest in the underlying inflammatory paradigm of SCD has emphasized the role of the neutrophil-lymphocyte ratio (NLR) as a prognostic inflammatory marker.

Methods: We retrospectively reviewed 268 hospitalized patients with SCDs of different genotypes (HbSS, HbSβ thalassemia, HbSβ thalassemia, and HbSC), totaling 3329 hospital admissions over a 10-year period.

Importance of carbohydrate antigen (CA 19-9) and carcinoembrionic antigen (CEA) in the prognosis of patients with duodenal adenocarcinoma: a retrospective single-institution cohort study.

Background: Duodenal adenocarcinoma (DA) is a rare malignancy without validated tumor markers. In practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) are often used in the management of DA, though their prognostic value is unknown.

Materials And Methods: A single-institution retrospective review included patients diagnosed with biopsy-confirmed adenocarcinoma of the duodenum between 2006 and 2021.

Development and Narrow Validation of Computer Vision Approach to Facilitate Assessment of Change in Pigmented Cutaneous Lesions.

The documentation of the change in the number and appearance of pigmented cutaneous lesions over time is critical to the early detection of skin cancers and may provide preliminary signals of efficacy in early-phase therapeutic prevention trials for melanoma. Despite substantial progress in computer-aided diagnosis of melanoma, automated methods to assess the evolution of lesions are relatively undeveloped. This report describes the development and narrow validation of mathematical algorithms to register nevi between sequential digital photographs of large areas of skin and to align images for improved detection and quantification of changes.

From bats to pangolins: new insights into species differences in the structure and function of the immune system.

Species differences in the structure and function of the immune system of laboratory animals are known to exist and have been reviewed extensively. However, the number and diversity of wild and exotic species, along with their associated viruses, that come into contact with humans has increased worldwide sometimes with lethal consequences. Far less is known about the immunobiology of these exotic and wild species.

The other face of illness-deception: Diagnostic criteria for factitious disorder with proposed standards for clinical practice and research.

This paper aims to develop diagnostic criteria for factitious disorder (FD) and a heuristic for research by creating standards for delineating criterion groups.: Both FD and malingering are conceptualized within a rubric of illness-deception. The history of FD research was compared to the research history on malingering.

Evaluation of Cannabinoid and Terpenoid Content: Cannabis Flower Compared to Supercritical CO2 Concentrate.

A recent cannabis use survey revealed that 60% of cannabis users rely on smelling the flower to select their cannabis. Olfactory indicators in plants include volatile compounds, principally represented by the terpenoid fraction. Currently, medicinal- and adult-use cannabis is marketed in the United States with relatively little differentiation between products other than by a common name, association with a species type, and Δ-9 tetrahydrocannabinol/cannabidiol potency.

The lymphoid system: a review of species differences.

While an understanding of the structure and function of a generically described immune system is essential in contemporary biomedicine, it is clear that a one-size-fits-all approach applied across multiple species is fraught with contradictions and inconsistencies. Nevertheless, the breakthroughs achieved in immunology following the application of observations in murine systems to that of man have been pivotal in the advancement of biology and human medicine. However, as additional species have been used to further address biologic and safety assessment questions relative to the structure and function of the immune system, it has become clear that there are differences across species, gender, age and strain that must be considered.

Evaluation of the utility of popliteal lymph node examination in a cyclophosphamide model of immunotoxicity in the rat.

The objective of this study was to characterize the variability of rat lymphoid organ weights and morphology following treatment with a known immunotoxicant, with a focus on the usefulness of evaluating popliteal lymph node weight and histology. Cyclophosphamide was administered to male Sprague-Dawley rats by oral gavage at doses of 2, 7 or 12 mg/kg/day for 10 consecutive days. Left and right popliteal lymph nodes (PLN), spleen and thymus were collected at necropsy, weighed, fixed and processed for histopathology.

An inter-species protein-protein interaction network across vast evolutionary distance.

In cellular systems, biophysical interactions between macromolecules underlie a complex web of functional interactions. How biophysical and functional networks are coordinated, whether all biophysical interactions correspond to functional interactions, and how such biophysical-versus-functional network coordination is shaped by evolutionary forces are all largely unanswered questions. Here, we investigate these questions using an "inter-interactome" approach.

Exploring the evolution of a trade-off between vigilance and foraging in group-living organisms.

Even though grouping behaviour has been actively studied for over a century, the relative importance of the numerous proposed fitness benefits of grouping remain unclear. We use a digital model of evolving prey under simulated predation to directly explore the evolution of gregarious foraging behaviour according to one such benefit, the 'many eyes' hypothesis. According to this hypothesis, collective vigilance allows prey in large groups to detect predators more efficiently by making alarm signals or behavioural cues to each other, thereby allowing individuals within the group to spend more time foraging.

Downmodulation of key inflammatory cell markers with a topical Janus kinase 1/2 inhibitor.

Background: INCB018424 is a novel, potent Janus kinase (JAK)1/JAK2 inhibitor that blocks signal transduction of multiple proinflammatory cytokines.

Objectives: To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of topical INCB018424 phosphate cream in patients with plaque psoriasis.

Methods: Topical INCB018424 phosphate 1·0% or 1·5% cream was applied once daily (QD) or twice daily (BID) for 4 weeks to 2-20% body surface area in five sequential cohorts of five patients aged 18-65 years.

Small molecule immunomodulatory drugs: challenges and approaches for balancing efficacy with toxicity.

As the molecular pathobiology of immunologically based diseases, such as rheumatoid arthritis, has become clearer, pharmaceutical researchers have responded with highly efficacious and selective biological compounds. In contrast to older, nonspecific small-molecule therapeutics, the exquisite species sensitivity of monoclonal antibodies has introduced new challenges to preclinical safety studies. Repeated exposure of animals to biopharmaceutical compounds tends to be restricted in the species in which these compounds have pharmacological action, and it tends to stimulate antidrug immune responses with acceleration of clearance, thereby limiting the duration of repeat-dose studies and potentially resulting in hypersensitivity reactions.

Efficacy of the JAK2 inhibitor INCB16562 in a murine model of MPLW515L-induced thrombocytosis and myelofibrosis.

The discovery of JAK2 and MPL mutations in patients with myeloproliferative neoplasms (MPNs) provided important insight into the genetic basis of these disorders and led to the development of JAK2 kinase inhibitors for MPN therapy. Although recent studies have shown that JAK2 kinase inhibitors demonstrate efficacy in a JAK2V617F murine bone marrow transplantation model, the effects of JAK2 inhibitors on MPLW515L-mediated myeloproliferation have not been investigated. In this report, we describe the in vitro and in vivo effects of INCB16562, a small-molecule JAK2 inhibitor.

Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms.

Constitutive JAK2 activation in hematopoietic cells by the JAK2V617F mutation recapitulates myeloproliferative neoplasm (MPN) phenotypes in mice, establishing JAK2 inhibition as a potential therapeutic strategy. Although most polycythemia vera patients carry the JAK2V617F mutation, half of those with essential thrombocythemia or primary myelofibrosis do not, suggesting alternative mechanisms for constitutive JAK-STAT signaling in MPNs. Most patients with primary myelofibrosis have elevated levels of JAK-dependent proinflammatory cytokines (eg, interleukin-6) consistent with our observation of JAK1 hyperactivation.

Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors.

Malignant tumors arise, in part, because the immune system does not adequately recognize and destroy them. Expression of indoleamine-2,3-dioxygenase (IDO; IDO1), a rate-limiting enzyme in the catabolism of tryptophan into kynurenine, contributes to this immune evasion. Here we describe the effects of systemic IDO inhibition using orally active hydroxyamidine small molecule inhibitors.

Family matters: dyadic agreement in end-of-life medical decision making.

Purpose: We examined race/ethnicity and cultural context within hypothetical end-of-life medical decision scenarios and its influence on patient-proxy agreement.

Design And Methods: Family dyads consisting of an older adult and 1 family member, typically an adult child, responded to questions regarding the older adult's preferences for cardiopulmonary resuscitation, artificial feeding and fluids, and palliative care in hypothetical illness scenarios. The responses of 34 Caucasian dyads and 30 African American dyads were compared to determine the extent to which family members could accurately predict the treatment preferences of their older relative.

Smoking cessation for hospitalized smokers: an evaluation of the "Ottawa Model".

Introduction: Interventions for hospitalized smokers can increase long-term smoking cessation rates. The Ottawa Model for Smoking Cessation (the "Ottawa Model") is an application of the "5 A's" approach to cessation, customized to the hospital setting. This study evaluated the impact of implementing the Ottawa Model in 9 hospitals in eastern Ontario.

Combined inhibition of Janus kinase 1/2 for the treatment of JAK2V617F-driven neoplasms: selective effects on mutant cells and improvements in measures of disease severity.

Purpose: Deregulation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway is a hallmark for the Philadelphia chromosome-negative myeloproliferative diseases polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We tested the efficacy of a selective JAK1/2 inhibitor in cellular and in vivo models of JAK2-driven malignancy.

Experimental Design: A novel inhibitor of JAK1/2 was characterized using kinase assays.