Radical Reactions with Chiral Acylammonium Salts: Synthesis of Functionalized δ-Lactams through Giese-Initiated Organocascades.

Enantioselective Giese reactions employing chiral α,β-unsaturated acylammonium salts and subsequent diastereoselective trapping followed by lactamization deliver optically active δ-lactams. Alkyl iodides bearing tosylamides undergo radical initiation using triethylborane at low temperatures to provide carbon-centered radicals to initiate the described organocascade. Subsequent diastereoselective inter- or intramolecular trapping of the incipient α-radical leads to highly functionalized, enantioenriched mono- and bicyclic δ-lactams (up to 99:1 er, > 19:1 dr) bearing up to three stereogenic centers.

Zinc-mediated carboxylations of allylic and propargylic halides in flow: synthesis of β-lactones subsequent bromolactonization.

Zinc-mediated carboxylation of allylic halides under flow conditions delivered β,γ-unsaturated carboxylic acids and subsequent bromolactonization provides a streamlined process for the synthesis of γ-bromo-β-lactones. The described process further demonstrates the utility of organozinc reagents prepared by passage of allylic halides through a metallic zinc column integrated into a flow process. Use of a tube-in-tube reactor for efficient CO introduction led to improvements in conversion compared to a batch process and improved overall yields of β-lactones.

Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence -associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia.

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide β-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth.

Targeting AML-associated FLT3 mutations with a type I kinase inhibitor.

Tyrosine kinase domain (TKD) mutations contribute to acquired resistance to FMS-like tyrosine kinase 3 (FLT3) inhibitors used to treat FLT3-mutant acute myeloid leukemia (AML). We report a cocrystal structure of FLT3 with a type I inhibitor, NCGC1481, that retained potent binding and activity against FLT3 TKD and gatekeeper mutations. Relative to the current generation of advanced FLT3 inhibitors, NCGC1481 exhibited superior antileukemic activity against the common, clinically relevant FLT3-mutant AML cells in vitro and in vivo.

Overcoming adaptive therapy resistance in AML by targeting immune response pathways.

Targeted inhibitors to oncogenic kinases demonstrate encouraging clinical responses early in the treatment course; however, most patients will relapse because of target-dependent mechanisms that mitigate enzyme-inhibitor binding or through target-independent mechanisms, such as alternate activation of survival and proliferation pathways, known as adaptive resistance. Here, we describe mechanisms of adaptive resistance in FMS-like receptor tyrosine kinase (FLT3)-mutant acute myeloid leukemia (AML) by examining integrative in-cell kinase and gene regulatory network responses after oncogenic signaling blockade by FLT3 inhibitors (FLT3i). We identified activation of innate immune stress response pathways after treatment of FLT3-mutant AML cells with FLT3i and showed that innate immune pathway activation via the interleukin-1 receptor-associated kinase 1 and 4 (IRAK1/4) complex contributes to adaptive resistance in FLT3-mutant AML cells.

Sacroiliac joint syndrome 10 years after lumbar arthroplasty: the importance of spinopelvic alignment.

Introduction: Sagittal balance is an independent predictor of outcomes in spinal care and several authors focused their attention on the lumbar lordosis restoration as the key point to prevent secondary sacroiliac joint dysfunction (SIJD) after fusion. On the other hand, lumbar disc arthroplasty allows preservation of motion avoiding increased stress on the spinopelvic junction and preventing iatrogenic sagittal imbalance.

Methods: We analyze the incidence of a secondary SIJD and the spinopelvic alignment on a series of 31 consecutive lumbar disc prosthesis with a 10-year follow-up.

A prospective study of percutaneous balloon kyphoplasty with calcium phosphate cement in traumatic vertebral fractures: 10-year results.

Study Design: This is a prospective study to investigate the clinical and radiological results 10 years after percutaneous balloon kyphoplasty and cement augmentation with calcium phosphate cement (CPC) in traumatic vertebral fractures type A.

Objectives: Evaluation of a 10-year follow-up with radiological and computed tomography results, calculated by 2 independent radiologists, VAS, Roland Morris score, Oswestry Disability Index (ODI) score and Denis work scale and clinical examination in patients with traumatic compression fractures type A, who were treated with a balloon kyphoplasty with CPC (Calcibon™ from Biomed).

Methods: In this study, we evaluated 21 patients (8 female and 13 male) clinically and radiologically 10 years postoperative and compared them with the same group of 28 patients we operated between August 2002 and August 2003 for traumatic vertebral fractures type A with balloon kyphoplasty and CPC.