High satisfaction rate and range of motion can be expected in frozen shoulder after awake manipulation with brachial plexus block.

BACKGROUND: Adhesive capsulitis (AC) is a disease of the glenohumeral joint that is characterized by pain and both passive and active global stiffness with a slow and insidious onset. The disease can occur spontaneously (primary AC) or it can be secondary to other comorbidities, surgery, or trauma, such as fracture or dislocation. Multiple treatment approaches have been suggested: intra-articular steroid injection, physical therapy, manipulation under total anesthesia, and arthroscopic or open surgery. Shoulder manipulation under anesthesia is usually proposed to patients that suffer from severe AC and have already undergone several nonoperative treatments without benefit. Different techniques have been proposed. This study presents our manipulation technique and the clinical results we achieved after shoulder mobilization under brachial plexus block in patients with phase III primary AC. MATERIALS AND METHODS: A retrospective cohort study was performed on a sample of 110 patients with phase III AC who were treated with this manipulation and followed up for 1 year. Patients underwent two assessments-before the procedure (T0) and 4 months after it (T1)-based on the Numerical Rating Scale, Simple Shoulder Test, and joint range of motion to assess shoulder pain, function, and joint articulation, respectively. Furthermore, the patients had to express their degree of satisfaction with the procedure and the results achieved. RESULTS: Positive and statistically significant results were recorded in terms of pain reduction (ΔNPRS = - 5.4; p < 0.01) and improved functionality (Simple Shoulder Test Δ = 5; p < 0.01). Passive range of motion was statistically significantly increased for each movement at T1. Large increases were observed in extrarotation range of motion (ROM): R1 (Δ = 77.5°) and R2 (Δ = 70°), whereas little improvements were observed in intrarotation ROM. Patients achieved satisfying functional and articular recovery in all cases. Complications that needed further treatment occurred in three cases: a brachial plexus injury, a glenoid flake fracture, and persistent pain and stiffness. CONCLUSIONS: In this study, we proposed a standardized method of manipulation under brachial plexus block for patients affected by phase III adhesive capsulitis. The technique was applied among a large cohort of patients, who reported a high satisfaction rate and range-of-motion recovery after 4 months. This could represent an alternative treatment to surgery that has a shorter timeline and does not require patient hospitalization. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Discovery of HIV-1 integrase inhibitors through a novel combination of ligand and structure-based drug design.

Over the past 10 years, classical computer-aided molecular design methods have not been frequently applied for the discovery of novel HIV-1 integrase (IN) inhibitors, due to the intrinsic challenges that this enzyme presents. Therefore, a novel approach that combines the chemical information of known integrase inhibitors with the enzyme's detailed 3D structure in a stepwise fashion is proposed: (I) use of a pharmacophore model (PM), which takes into account in a weighted fashion the chemical features of known ligands, in analogous manner to the to search the Maybridge and the NCI 3D databases; (II) drug-likeness optimization; (III) virtual high-throughput screening of the hits matching the PM query against 1QS4 wild-type IN structure using different Docking/Scoring combinations; (IV) visual inspection and selection of the hits in function of: binding free energies; binding mode type within the active site; retrieval among the best 20% hits in more than 6 Docking/Scoring protocols at the same time. This approach aims at a rational selection of new potential HIV-1 integrase inhibitors.

The Poisson-Boltzmann equation for biomolecular electrostatics: a tool for structural biology.

Electrostatics plays a fundamental role in virtually all processes involving biomolecules in solution. The Poisson-Boltzmann equation constitutes one of the most fundamental approaches to treat electrostatic effects in solution. The theoretical basis of the Poisson-Boltzmann equation is reviewed and a wide range of applications is presented, including the computation of the electrostatic potential at the solvent-accessible molecular surface, the computation of encounter rates between molecules in solution, the computation of the free energy of association and its salt dependence, the study of pKa shifts and the combination with classical molecular mechanics and dynamics. Theoretical results may be used for rationalizing or predicting experimental results, or for suggesting working hypotheses. An ever-increasing body of successful applications proves that the Poisson-Boltzmann equation is a useful tool for structural biology and complementary to other established experimental and theoretical methodologies.