Pharmacokinetics of PP353, a formulation of linezolid for intervertebral disc administration, in patients with chronic low back pain and Modic change Type 1: A first-in-human, Phase 1b, open-label, single-dose study.

Background: Bacterial infection of the intervertebral disc is difficult to treat because the tissue is usually not vascularized and systemic antibiotic therapy may not reach optimal antibacterial exposure. Here we characterize the safety, tolerability, and pharmacokinetics of PP353, a suspension of micronized linezolid, formulated for direct intervertebral disc administration.

Methods: The safety, tolerability, and pharmacokinetics of an intradiscal administration of PP353, was assessed in Part A of a Phase 1b study and consisted of a single injection of study drug (3 mL of PP353 and 150 mg linezolid).

Outcomes of X-Linked Agammaglobulinaemia Patients.

Background: X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications.

Unique and interactive effects of threat and deprivation on latent trait cortisol among emerging adults.

Though considerable work supports the Dimensional Model of Adversity and Psychopathology, prior research has not tested whether the dimensions-threat (e.g., abuse) and deprivation (e.

Individual differences in latent trait cortisol (LTC): Implications for the onset and course of future depressive symptoms.

Research suggests that various indicators of hypothalamic pituitary adrenal (HPA) axis activity prospectively predict depression, but few studies have evaluated whether trait indicators of HPA axis activity are related to depression. Further, no prior study has examined links between trait cortisol and psychopathology using a trait indicator that captures HPA axis activity over multiple time points. Here we examined whether we could construct an across-wave latent trait cortisol (LTC) factor using cortisol samples collected over 13 weeks, and whether the across-wave LTC prospectively predicted new depressive symptom onsets and symptom duration.

A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene-related peptide ligand (galcanezumab) or receptor (erenumab) antagonist.

Objective: To compare effects of an initial dose of calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) antagonists on gastrointestinal (GI) motility in patients with migraine and to explore if the mechanistic difference contributes to GI adverse events (AEs).

Background: Different frequencies of constipation have been observed between CGRP mAbs that target the ligand (galcanezumab [GMB]) or receptor (erenumab [ERE]).

Methods: Patients (n = 65) with migraine without significant GI symptoms were enrolled in a multi-center, single-blind phase IV clinical trial (NCT04294147) and randomized 1:1 to receive GMB (240 mg; n = 33) or ERE (140 mg; n = 32).

Does stress predict the development of internalizing symptoms in middle childhood? An examination of additive, mediated, and moderated effects of early family stress, daily interpersonal stress, and physiological stress.

Early life stress, daily life experiences, and the stress responsive hypothalamic-pituitary-adrenal (HPA) axis have each been examined as predictors of the development of psychopathology. Rarely have researchers attempted to understand the covariation or interaction among these stress domains using a longitudinal design in the prediction of symptoms of internalizing psychopathology, particularly during childhood. This study examined early family stress, daily interpersonal stress, indicators of diurnal cortisol, and internalizing symptoms in a racially/ethnically and socioeconomically diverse sample of twins ( = 970 children; = 9.

Changes in acute headache medication use and health care resource utilization: Results from a randomized, double-blind, placebo-controlled clinical trial evaluating galcanezumab in adults with treatment-resistant migraine (CONQUER).

Patients with migraine, particularly with multiple prior preventive treatment failures, often have high rates of acute headache medication use and are at risk for overuse (acute or symptomatic headache medication use between 10 and 15 days per month [depending on the medication] for > 3 months). Furthermore, these patients have greater health care resource utilization (HCRU). To examine acute headache medication use and HCRU with galcanezumab compared with placebo in a population with multiple prior migraine preventive treatment failures.

Participation in One Health Networks and Involvement in the COVID-19 Pandemic Response: A Global Study.

The COVID-19 pandemic exemplifies a One Health issue at the intersection of human, animal, and environmental health that requires collaboration across sectors to manage it successfully. The global One Health community includes professionals working in many different fields including human medicine, veterinary medicine, public health, ecosystem health, and, increasingly, social sciences. The aims of this cross-sectional study were to describe the involvement of the global One Health community in COVID-19 pandemic response activities.

Tolerability and safety of galcanezumab in patients with chronic cluster headache with up to 15 months of galcanezumab treatment.

Objective: The objective of the study was to assess the tolerability and safety of galcanezumab in patients with chronic cluster headache (CH) with up to 15 months of treatment.

Background: Chronic CH is a highly debilitating disease with a substantial and unmet medical need.

Methods: Patients were randomized to receive placebo or galcanezumab (300 mg) monthly for 12 weeks, followed by an optional 52-week open-label extension and 16-week posttreatment follow-up (washout).

Early adversity and depressive symptoms among early adolescent girls: the mediating role of exposure to recent interpersonal acute stress.

Early adversity confers risk for depression in part through its association with (i.e., proximal) acute stress.

Transmission risk of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to healthcare personnel following unanticipated exposure to aerosol-generating procedures: Experience from epidemiologic investigations at an academic medical center.

Healthcare personnel (HCP) with unprotected exposures to aerosol-generating procedures (AGPs) on patients with coronavirus disease 2019 (COVID-19) are at risk of infection with severe acute respiratory coronavirus virus 2 (SARS-CoV-2). A retrospective review at an academic medical center demonstrated an infection rate of <1% among HCP involved in AGPs without a respirator and/or eye protection.

Non-traumatic dental presentations at emergency departments in New Zealand.

Introduction: Many low-income New Zealanders attend emergency departments (EDs) for relief of dental pain and infection. This places a substantial burden on EDs. Better understanding of non-traumatic dental presentations (NTDPs) will aid the development of relevant health policy and clinical management strategies.

Efficacy of galcanezumab in patients with migraine and history of failure to 3-4 preventive medication categories: subgroup analysis from CONQUER study.

Background: Chronic migraine (CM) and episodic migraine (EM) are associated with substantial headache-related disability, poor quality of life and global societal burden. In this subgroup analysis from the CONQUER study, we report efficacy outcomes from a pre-specified analysis of galcanezumab versus placebo in patients with CM or EM and 3-4 prior preventive medication category failures due to inadequate efficacy (after at least 2 months at maximum tolerated dose), or safety or tolerability reasons. The patient population is of particular interest due to evidence of decreased quality of life and increased economic burden among patients with migraine that is inadequately managed and is of interest to decision-makers globally.

Galcanezumab in Patients with Multiple Previous Migraine Preventive Medication Category Failures: Results from the Open-Label Period of the CONQUER Trial.

Introduction: Results from the open-label extension of the phase 3b CONQUER trial are presented to evaluate the effectiveness and safety of galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide, for up to 6 months in patients with multiple prior migraine preventive treatment failures.

Methods: Patients were 18-75 years old with episodic or chronic migraine and 2-4 standard-of-care migraine preventive medication category failures. After 3 months of randomized treatment with galcanezumab (120 mg/month with 240 mg loading dose; n = 232) or placebo (n = 230), patients entered a 3-month open-label extension (120 mg/month galcanezumab with a blinded 240 mg loading dose for previous-placebo patients).

Propagation of Gaussian Schell-model beams in modulated graded-index media.

The evolution of partially coherent beams in longitudinally modulated graded-index media is studied. The special cases of Gaussian Schell-model beams and parametric modulation, when the modulation period is half the fiber self-imaging period, are examined in detail. We show that the widths of the intensity and coherence of Gaussian Schell-model beams undergo amplification in parametrically modulated parabolic graded-index media.

Dopaminergic Genetic Variation in Young Adolescents: Associations with Sensation-Seeking.

Deficient reward functioning, including reward-related personality, is implicated in depression's etiology. A dopaminergic genetic multilocus genetic profile score (MGPS) has previously been associated with neural reward responsivity but, despite theoretical basis, has not been studied with reward-related personality. Such research is needed to elucidate associations between genetic variation and reward-related personality in a developmentally sensitive population.

Biodiversity and Human Health Interlinkages in Higher Education Offerings: A First Global Overview.

Biodiversity is inextricably linked to human health. As an important area of research of the Convention on Biological Diversity and a key avenue for the dissemination of biodiversity and health knowledge, we investigated how well-embedded biodiversity and health interlinkages are in institutional higher education offerings. Using One Health education programs as a starting point, we collected a global list of institutions potentially carrying out education in the links between biodiversity and health through previously published research, academic partners of global conglomerates, and our own networks.