The Impact of Superior Labral Anterior to Posterior Lesions on Functional Status in Shoulder Instability: A Multicenter Cohort Study

BACKGROUND: Type IV superior labral anterior to posterior (SLAP) lesions, which are superior labral detachments associated with Bankart tears, are reported to occur in up to 25% of recurrent shoulder instability patients. However, the clinical implications of this finding are debatable. PURPOSE: To determine whether there are any functional differences between anterior instability patients with and without type IV SLAP lesions at the time of presentation and at short-term follow-up after surgical intervention. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A prospective, multicenter database was established to follow the clinical evolution of patients with shoulder instability. Patients were diagnosed as having a type IV SLAP lesion at the time of arthroscopic Bankart surgery (SLAP+). These patients were compared with a group of patients who simply had a Bankart lesion (SLAP-). The 2 groups had their functional outcomes (Western Ontario Shoulder Instability Index [WOSI]; Disability of the Arm, Shoulder, and Hand [QuickDASH]; and Walch-Duplay) compared prior to surgery and 1 year postoperatively. RESULTS: A total of 103 subjects were included in the study; of these, 56 (43 men, 13 women) completed 1-year follow-up. Twenty-three subjects had a type IV SLAP tear, and most had this repaired along with their Bankart lesion. At baseline, SLAP+ subjects had inferior QuickDASH scores compared with SLAP- subjects (37.8 vs 29.0) as well as poorer pain subscores on both the WOSI and QuickDASH. At 1-year follow-up, however, there were no significant differences in any of the outcome measures. CONCLUSION: A type IV SLAP lesion can be expected in 22% of patients with recurrent shoulder instability. This finding implies that at baseline, the patient will have slightly worse functional scores related to pain. However, following surgical management of the labral pathology, these patients will have equivalent functional outcomes at short-term follow-up. CLINICAL RELEVANCE: With surgical management of the superior and anteroinferior labrum, patients with type IV SLAP lesions will do as well as those with only Bankart tears. Thus, the presence of SLAP lesions should not alter the decision to provide surgical management and should not change the prognosis for a specific patient

Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles

Intracellular protein delivery has potential biotechnological and therapeutic application, but remains technically challenging. In contrast, a plethora of nucleic acid carriers have been developed, with lipid-based nanoparticles (LNPs) among the most clinically advanced reagents for oligonucleotide delivery. Here, we validate the hypothesis that oligonucleotides can serve as packaging materials to facilitate protein entrapment within and intracellular delivery by LNPs. Using two distinct model proteins, horseradish peroxidase and NeutrAvidin, we demonstrate that LNPs can yield efficient intracellular protein delivery in vitro when one or more oligonucleotides have been conjugated to the protein cargo. Moreover, in experiments with NeutrAvidin in vivo, we show that oligonucleotide conjugation significantly enhances LNP-mediated protein uptake within various spleen cell populations, suggesting that this approach may be particularly suitable for improved delivery of protein-based vaccines to antigen-presenting cells.National Heart, Lung, and Blood Institute (Contract HHSN268201000045C)National Institutes of Health (U.S.) (Grant R01-EB000244-27)National Institutes of Health (U.S.) (Grant 5-R01-CA132091-04)National Science Foundation (U.S.)Juvenile Diabetes Research Foundation International (Grant 17–2007-1063)United States. Dept. of Defense. Congressionally Directed Medical Research Programs (Grant W81XWH-13-1-0215

Lipid-Modified Aminoglycoside Derivatives for In Vivo siRNA Delivery

Rationally designed siRNA delivery materials that are enabled by lipid-modified aminoglycosides are demonstrated. Leading materials identified are able to self-assemble with siRNA into well-defined nanoparticles and induce efficient gene knockdown both in vitro and in vivo. Histology studies and liver function tests reveal that no apparent toxicity is caused by these nanoparticles at doses over two orders of magnitude.Damon Runyon Cancer Research Foundation (DFS-#2050-10)Alnylam Pharmaceuticals (Firm)National Institutes of Health (U.S.) (grant EB000244)National Institutes of Health (U.S.) (grant 1-RO1-CA132091-03

Winery website loyalty: the role of sales promotion and service attributes

Purpose: toward buying wine on mobile phones and m-commerce website loyalty by examining a) the mediating role of sales promotion and b) the moderating role of service attributes of the m-commerce websites in influencing the mediation. Design/methodology/approach: A total of 3,318 completed surveys were collected. Drawing on a large non-probability criterion based purposive sample across six countries (France, Germany, Greece, South Africa, United States and Canada) mediation analysis was performed to examine hypothesized relationships. Findings: Results show that sales promotion mediates the relationship between feelings towards buying wine on mobile phones and m-commerce website loyalty. Moderated mediation reveals that the indirect pathways (sales promotion) through which feelings towards buying wine over mobile exert its effect on m-commerce website loyalty is dependent on the value of service (wine delivery) attributes of the website. The results demonstrate that sales promotion and service are of paramount importance to wineries and wine marketers. Research implications/limitations: Wine producers and retailers should consider the use of sales promotion to enhance sales and loyalty to m-commerce websites. Practical implications: Wine producers and retailers should consider use sales promotion (such as SMS or push notifications) to enhance sales and influence consumer feelings and hence their loyalty. Originality/value: Wine m-commerce studies are limited, especially with an international perspective comparing 6 different countries: 3 from the old world (such as France, Germany and Greece) and 3 from the New World (North America with USA and Canada; and South Africa). Altogether those 6 countries represent around 40% of the world consumption

Difficulties associated with outpatient management of drug abusers by general practitioners. A cross-sectional survey of general practitioners with and without methadone patients in Switzerland

BACKGROUND: In Switzerland, general practitioners (GPs) manage most of the patients receiving methadone maintenance treatment (MMT). METHODS: Using a cross-sectional postal survey of GPs who treat MMT patients and GPs who do not, we studied the difficulties encountered in the out-patient management of drug-addicted patients. We sent a questionnaire to every GP with MMT patients (556) in the French-speaking part of Switzerland (1,757,000 inhabitants). We sent another shorter questionnaire to primary care physicians without MMT patients living in the Swiss Canton of Vaud. RESULTS: The response rate was 63.3%. The highest methadone dose given by GPs to MMT patients averaged 120.4 mg/day. When asked about help they would like to be given, GPs with MMT patients primarily mentioned the importance of receiving adequate fees for the care they provide. Secondly, they mentioned the importance of better training, better knowledge of psychiatric pathologies, and discussion groups on practical cases. GPs without MMT patients refuse to treat these patients mostly for emotional and relational reasons. CONCLUSION: GPs encounter financial, relational and emotional difficulties with MMT patients. They desire better fees for services and better training

Hirschsprung disease, associated syndromes and genetics: A review

Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.published_or_final_versio

Modular ‘Click-in-Emulsion’ Bone-Targeted Nanogels

A new class of nanogel demonstrates modular biodistribution and affinity for bone. Nanogels, ~70 nm in diameter and synthesized via an astoichiometric click-chemistry in-emulsion method, controllably display residual, free clickable functional groups. Functionalization with a bisphosphonate ligand results in significant binding to bone on the inner walls of marrow cavities, liver avoidance, and anti-osteoporotic effects.National Institutes of Health (U.S.) (RO1 DE016516)National Institutes of Health (U.S.) (R01 EB000244)Damon Runyon Cancer Research Foundation (DFS-#2050-10

ALADIN is Required for the Production of Fertile Mouse Oocytes

Asymmetric cell divisions depend on the precise placement of the spindle apparatus. In mammalian oocytes, spindles assemble close to the cell's center, but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygously null for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages, including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is compromised due to problems in spindle orientation and anchoring at the first meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in vitro are unable to support embryonic development beyond the two-cell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions