Moral injury and chronic pain among military veterans in an integrated behavioral health clinic.

Objective: Military service may place veterans at increased risk for perpetrating, witnessing, or failing to prevent events that violate deeply held moral values. In some cases, veterans may develop moral injury (MI) symptoms that transcend and/or overlap with mental health conditions such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Further, PTSD and MDD are 2 established risk factors for chronic pain.

Serial Sonographic Assessment of Pulmonary Edema in Patients With Hypertensive Acute Heart Failure.

Objectives: Objective measures of clinical improvement in patients with acute heart failure (AHF) are lacking. The aim of this study was to determine whether repeated lung sonography could semiquantitatively capture changes in pulmonary edema (B-lines) in patients with hypertensive AHF early in the course of treatment.

Methods: We conducted a feasibility study in a cohort of adults with acute onset of dyspnea, severe hypertension in the field or at triage (systolic blood pressure ≥ 180 mm Hg), and a presumptive diagnosis of AHF.

Phase 2 and pharmacodynamic study of oral forodesine in patients with advanced, fludarabine-treated chronic lymphocytic leukemia.

Forodesine is a new and potent purine nucleoside phosphorylase (PNP) inhibitor. Patients with chronic lymphocytic leukemia (CLL) with primary resistance to fludarabine-based therapy or with progressive disease were eligible for oral forodesine (200 mg/d) for up to 24 weeks. Eight patients with median lymphocyte count of 35.

Injectable peramivir mitigates disease and promotes survival in ferrets and mice infected with the highly virulent influenza virus, A/Vietnam/1203/04 (H5N1).

The post-exposure therapeutic efficacy of injectable peramivir against highly pathogenic avian influenza type A H5N1 was evaluated in mice and in ferrets. Seventy to eighty percent of the H5N1-infected peramivir-treated mice, and 70% in the oseltamivir treated mice survived the 15-day study period, as compared to 36% in control (vehicle) group. Ferrets were infected intranasally with H5N1 followed by treatment with multiple doses of peramivir.

No abnormal prion protein detected in the milk of cattle infected with the bovine spongiform encephalopathy agent.

Milk specimens were collected from lactating cows that had previously been challenged with bovine spongiform encephalopathy (BSE)-infected brain at 4-6 months of age. One group of 10 animals received a single oral dose of 100 g, a second group received 1 g and the third was made up of unexposed controls. The cows were inseminated artificially, and calved at approximately 2 years of age and annually thereafter.

A proof-of-principle pharmacokinetic, pharmacodynamic, and clinical study with purine nucleoside phosphorylase inhibitor immucillin-H (BCX-1777, forodesine).

The discovery of purine nucleoside phosphorylase (PNP) deficiency and T lymphocytopenia suggested that inhibition of this enzyme could serve as a therapeutic target. Inhibitors of PNP failed until structure-based synthesis of immucillin-H (BCX-1777, forodesine), a transition-state analog of PNP. The picomolar potency for PNP, T cell-selective cytotoxicity, and animal studies provided the rationale for use of forodesine in T-cell malignancies.

Purine nucleoside phosphorylase inhibitors in T-cell malignancies.

Purine nucleoside phosphorylase (PNP)-deficient children exhibit profound impairment in the T-cell component of their immune systems, but have normal B-cell function. This rare condition provides a model for the development of specific inhibitors of PNP, which should enable selective suppression of T-cell function that may be useful in the treatment of T-cell-mediated diseases. BCX-1777 (BioCryst Pharmaceuticals Inc) is a rationally designed, potent transition-state analog inhibitor of PNP.

A novel series of potent and selective small molecule inhibitors of the complement component C1s.

Activation of the classical pathway of complement has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury and acute transplant rejection. The trypsin-like serine protease C1s represents a pivotal upstream point of control in the classical pathway of complement activation and is therefore likely to be a useful target in the therapeutic intervention of these disease states. A series of thiopheneamidine-based inhibitors of C1s has been optimized to give a 70 nM inhibitor that inhibits the classical pathway of complement activation in vitro.