Synthesis and characterization of core-shell magnetic molecularly imprinted polymer nanocomposites for the detection of interleukin-6.

Interleukin-6 (IL-6) belongs to the cytokine family and plays a vital role in regulating immune response, bone maintenance, body temperature adjustment, and cell growth. The overexpression of IL-6 can indicate various health complications, such as anastomotic leakage, cancer, and chronic diseases. Therefore, the availability of highly sensitive and specific biosensing platforms for IL-6 detection is critical.

Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients.

Background: MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).

Methods: Binding of ABBV-467 to human MCL-1 was assessed in multiple cell lines.

Iterative Structure-Based Optimization of Short Peptides Targeting the Bacterial Sliding Clamp.

The bacterial DNA sliding clamp (SC), or replication processivity factor, is a promising target for the development of novel antibiotics. We report a structure-activity relationship study of a new series of peptides interacting within the SC (SC) binding pocket. Various modifications were explored including N-alkylation of the peptide bonds, extension of the N-terminal moiety, and introduction of hydrophobic and constrained residues at the C-terminus.

Preoperative Breast MRI for Newly Diagnosed Ductal Carcinoma in Situ: Imaging Features and Performance in a Multicenter Setting (ECOG-ACRIN E4112 Trial).

Background There are limited data from clinical trials describing preoperative MRI features and performance in the evaluation of mammographically detected ductal carcinoma in situ (DCIS). Purpose To report qualitative MRI features of DCIS, MRI performance in the identification of additional disease, and associations of imaging features with pathologic, genomic, and surgical outcomes from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E4112 trial. Materials and Methods Secondary analyses of a multicenter prospective clinical trial from the ECOG-ACRIN Cancer Research Group included women with DCIS diagnosed with conventional imaging techniques (mammography and US), confirmed via core-needle biopsy (CNB), and enrolled between March 2015 and April 2016 who were candidates for wide local excision (WLE) based on conventional imaging and clinical examination results.

In vivo perfusion of free skin flaps using extracorporeal membrane oxygenation.

Background: The vessel-depleted, irradiated, and frozen neck, as well as severe atherosclerosis of recipient vessels represent challenging problems in free flap transfer. Extracorporeal free flap perfusion theoretically allows free flap reconstructions in the absence of local donor vessels, but is associated with a number of technical issues. In this study, a novel technique is presented using a commercially available system for extracorporeal membrane oxygenation (ECMO), modified for small blood volumes.

Structure-based optimization of a PDZ-binding motif within a viral peptide stimulates neurite outgrowth.

Protection of neuronal homeostasis is a major goal in the management of neurodegenerative diseases. Microtubule-associated Ser/Thr kinase 2 (MAST2) inhibits neurite outgrowth, and its inhibition therefore represents a potential therapeutic strategy. We previously reported that a viral protein (G-protein from rabies virus) capable of interfering with protein-protein interactions between the PDZ domain of MAST2 and the C-terminal moieties of its cellular partners counteracts MAST2-mediated suppression of neurite outgrowth.

Medicare Spending and the Adequacy of Support With Daily Activities in Community-Living Older Adults With Disability: An Observational Study.

Background: Identifying factors that affect variation in health care spending among older adults with disability may reveal opportunities to better address their care needs while offsetting excess spending.

Objective: To quantify differences in total Medicare spending among older adults with disability by whether they experience negative consequences due to inadequate support with household activities, mobility, or self-care.

Design: Observational study of in-person interviews and linked Medicare claims.

Development of a novel resection and cutting guide for mandibular reconstruction using free fibula flap.

Introduction: The authors developed a semi-standardised resection and cutting guide for mandibular reconstruction with free fibula flap based on data of mandible sizes and angles.

Methods: After analyzing the angles and lengths of mandibular angles and segments on computer tomography, a partly-adjustable resection guide for the mandible and cutting guide for the fibula were designed.

Results: After testing and optimizing the guides on plastic models and cadavers, the guides were successfully used for mandible resection and reconstruction with free fibula flap in 8 patients with segmental mandibulectomy.

Surgical management of severe osteoradionecrosis of the mandibular bone by using double free flap reconstruction.

Purpose: Osteoradionecrosis (ORN) of the jaws represents one of the most severe complications after primary or adjuvant radiation therapy (RT) of large head and neck tumors. In advanced ORN cases, surgical management is generally considered the therapy of choice. However, in several severe ORN patients with extensive bone and soft tissue defects, functional and aesthetic reconstruction represents a huge challenge for any surgeon, with an increased risk of post-operative wound healing disorders.

Cannabis, Tobacco, Alcohol Use, and the Risk of Early Stroke: A Population-Based Cohort Study of 45 000 Swedish Men.

Background And Purpose: Current knowledge on cannabis use in relation to stroke is based almost exclusively on clinical reports. By using a population-based cohort, we aimed to find out whether there was an association between cannabis use and early-onset stroke, when accounting for the use of tobacco and alcohol.

Methods: The cohort comprises 49 321 Swedish men, born between 1949 and 1951, who were conscripted into compulsory military service between the ages of 18 and 20.

Native ESI Mass Spectrometry Can Help to Avoid Wrong Interpretations from Isothermal Titration Calorimetry in Difficult Situations.

We studied by native ESI-MS the binding of various DNA-polymerase-derived peptides onto DNA-polymerase processivity rings from Escherichia coli, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. These homodimeric rings present two equivalent specific binding sites, which leads to successive formation during a titration experiment of singly- and doubly occupied rings. By using the ESI-MS free-ring spectrum as a ruler, we derived by robust linear regression the fractions of the different ring species at each step of a titration experiment.

Moving the mandible in orthognathic surgery - A multicenter analysis.

Orthognathic surgery has always been a classical focus of maxillofacial surgery. Since more than 100 years, various surgical techniques for mandibular repositioning have been developed and clinically tested. Since the establishment of plate and screw osteosynthesis, orthognathic surgery became more stable and safe.

Surface-optimized free flaps for complex facial defects after skin cancer.

Introduction: Advanced non-melanocytic skin cancer (NMSC) in the facial region causes extensive tissue loss, possibly coverable by local flaps. Remote free flaps are the reconstructive method of choice, despite disadvantages such as color and texture mismatch, and bulkiness with regard to facial skin.

Material And Methods: Post-ablative facial NMSC defects in four patients were reconstructed using remote free flaps, including radial forearm, scapular, parascapular, and anterolateral thigh flaps.

Cysteine-rich domain 1 of CD40 mediates receptor self-assembly.

The activation of CD40 on B cells, macrophages, and dendritic cells by its ligand CD154 (CD40L) is essential for the development of humoral and cellular immune responses. CD40L and other TNF superfamily ligands are noncovalent homotrimers, but the form under which CD40 exists in the absence of ligand remains to be elucidated. Here, we show that both cell surface-expressed and soluble CD40 self-assemble, most probably as noncovalent dimers.

The anterolateral thigh as a universal donor site for soft tissue reconstruction in maxillofacial surgery.

Objective: The experience with 191 flaps from the anterolateral thigh is described with special regard to variations of vascular anatomy and possible flap designs.

Patients: Since 1992, 191 flaps from the anterolateral thigh donor site were used in 187 patients. The size of the defects varied from 3 x 5 cm to 21 x 10 cm, being located in nearly all areas of the head and neck region including the skull base.

Hepatitis A virus proteinase 3C binding to viral RNA: correlation with substrate binding and enzyme dimerization.

Proteinase 3C of hepatitis A virus (HAV) plays a key role in the viral life cycle by generating mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, 3C binds to viral RNA, and thus influences viral genome replication. In order to investigate the interplay between proteolytic activity and RNA binding at the molecular level, we subjected HAV 3C and three variants carrying mutations of the cysteine residues [C24S (Cys-24-->Ser), C172A and C24S/C172A] to proteolysis assays with peptide substrates, and to surface plasmon resonance binding studies with peptides and viral RNA.

Structure determination and ligand interactions of the PDZ2b domain of PTP-Bas (hPTP1E): splicing-induced modulation of ligand specificity.

Two versions of the PDZ2 domain of the protein tyrosine phosphatase PTP-Bas/human PTP-BL are generated by alternative splicing. The domains differ by the insertion of five amino acid residues and their affinity to the tumour suppressor protein APC. Whereas PDZ2a is able to bind APC in the nanomolar range, PDZ2b shows no apparent interaction with APC.

[Gentamicin and amikacin nephrotoxicity: comparative study in patients with initially normal renal function].

The purpose of this study was to compare the nephrotoxic potential of amikacin (AK) and gentamicin (GM) in patients (pts) with normal renal function at the beginning of the treatment (Tx) in an open comparative and prospective trial. Nephrotoxicity (NFTX) was defined as a blood creatinine (Cr) increase of at least 50% from the basal (normal) level, or an increase to higher than normal level during, at the end or after Tx. Peak and trough blood GM and AK levels were determined at 72 h of Tx to make proper adjustments in dosing.