Outcome of Reverse Shoulder Arthroplasty for Patients With Parkinson's Disease: A Matched Cohort Study.

Parkinson's disease (PD) is a progressive neurologic disorder that affects the musculoskeletal system. Currently, the use of reverse shoulder arthroplasty (RSA) for patients with PD has not been adequately studied. The authors sought to determine if RSA provided similar functional outcomes for patients with PD compared with a matched cohort of patients without PD.

An inter-species protein-protein interaction network across vast evolutionary distance.

In cellular systems, biophysical interactions between macromolecules underlie a complex web of functional interactions. How biophysical and functional networks are coordinated, whether all biophysical interactions correspond to functional interactions, and how such biophysical-versus-functional network coordination is shaped by evolutionary forces are all largely unanswered questions. Here, we investigate these questions using an "inter-interactome" approach.

Reverse shoulder arthroplasty for massive rotator cuff tear: risk factors for poor functional improvement.

Background: Some patients unexpectedly have poor functional improvement after reverse shoulder arthroplasty (RSA) for massive rotator cuff tear without glenohumeral arthritis. Our aim was to identify risk factors for this outcome. We also assessed the value of RSA for cases with poor functional improvement vs.

Widespread macromolecular interaction perturbations in human genetic disorders.

How disease-associated mutations impair protein activities in the context of biological networks remains mostly undetermined. Although a few renowned alleles are well characterized, functional information is missing for over 100,000 disease-associated variants. Here we functionally profile several thousand missense mutations across a spectrum of Mendelian disorders using various interaction assays.

Outcome and value of reverse shoulder arthroplasty for treatment of glenohumeral osteoarthritis: a matched cohort.

Background: Total shoulder arthroplasty (TSA) is commonly used to treat glenohumeral osteoarthritis (GHOA) with an intact rotator cuff. Recently, reverse shoulder arthroplasty (RSA) has been used for GHOA patients who are elderly or have eccentric glenoid wear. We evaluated patients with GHOA scheduled to have TSA but who were changed to RSA because of intraoperative difficulties with the glenoid component or instability and compared them with a cohort that underwent TSA to determine if the groups had similar outcomes.

Complex trauma to the shoulder girdle, including the proximal humerus, the clavicle, and the scapula: current concepts in diagnosis and treatment.

Fractures to the shoulder girdle are common injuries in an aging population. Many techniques and theories lie behind the treatment of such injuries. Knowledge and understanding of current concepts for diagnosing and treating proximal humeral, clavicular, and scapular fractures and the theory behind them will help surgeons make informed decisions with regard to patient care.

Glenosphere dissociation after reverse shoulder arthroplasty.

Background: Reverse shoulder arthroplasty (RSA) is gaining popularity for the treatment of debilitating shoulder disorders. Despite marked improvements in patient satisfaction and function, the RSA complication rate is high. Glenosphere dissociation has been reported and may result from multiple mechanisms.

The effects of glenoid wear patterns on patients with osteoarthritis in total shoulder arthroplasty: an assessment of outcomes and value.

Background: Despite the success of total shoulder arthroplasty (TSA), concerns remain about the longevity of the implant, in particular, glenoid component survivorship. The purpose of this study was to determine whether preoperative glenoid wear patterns affect clinical outcomes and value in patients undergoing TSA.

Methods: A comparative cohort study was conducted of 309 patients with a total of 344 TSA procedures, performed for primary glenohumeral osteoarthritis.

A proteome-scale map of the human interactome network.

Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ?30% larger than what is available from small-scale studies published in the literature in the last few decades.

Low incidence of tendon rerupture after distal biceps repair by cortical button and interference screw.

Background: The use of cortical suspensory fixation in conjunction with an interference screw to treat distal biceps ruptures has yielded favorable results. However, literature examining the incidence of fixation failure in a large consecutive series of patients treated with this technique is lacking.

Methods: A retrospective review of electronic medical records identified 170 distal biceps ruptures in 168 consecutive patients (164 men and 4 women) treated using a cortical button in conjunction with an interference screw.

Accuracy and reliability of the Mayo Elbow Performance Score.

Purpose: To test the reliability of the Mayo Elbow Performance Score (MEPS) and compare it with a validated outcomes instrument, the American Shoulder and Elbow Surgeons (ASES) score.

Methods: A total of 42 patients with the chief problem of elbow dysfunction formed the study cohort. Patients with an immediate surgical indication or treatment at the index visit were excluded.

Edgotype: a fundamental link between genotype and phenotype.

Classical 'one-gene/one-disease' models cannot fully reconcile with the increasingly appreciated prevalence of complicated genotype-to-phenotype associations in human disease. Genes and gene products function not in isolation but as components of intricate networks of macromolecules (DNA, RNA, or proteins) and metabolites linked through biochemical or physical interactions, represented in 'interactome' network models as 'nodes' and 'edges', respectively. Accordingly, mechanistic understanding of human disease will require understanding of how disease-causing mutations affect systems or interactome properties.

SD-OCT and autofluorescence characteristics of autoimmune retinopathy.

Aims: To report abnormal fundus hyperautofluorescence (hyper-AF) and loss of outer retinal layers by spectral domain optical coherence tomography in patients with autoimmune retinopathy (AIR).

Methods: Retrospective, observational case series of 14 eyes of 7 patients diagnosed with an AIR for whom colour fundus photographs, fundus AF images and spectral domain optical coherence tomograms (SD-OCT) were obtained at presentation.

Results: Seven patients were identified ranging in age from 24 to 73 years.

Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types.

Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations, and large numbers of somatic genomic alterations, associated with a predisposition to cancer.

Viral perturbations of host networks reflect disease etiology.

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes.

Proto-genes and de novo gene birth.

Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo. Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions.

Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses.

Background: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL), whereas HTLV-2, highly similar to HTLV-1, causes no known overt disease. HTLV gene products are engaged in a dynamic struggle of activating and antagonistic interactions with host cells.

Protein-protein interactions and networks: forward and reverse edgetics.

Phenotypic variations of an organism may arise from alterations of cellular networks, ranging from the complete loss of a gene product to the specific perturbation of a single molecular interaction. In interactome networks that are modeled as nodes (macromolecules) connected by edges (interactions), these alterations can be thought of as node removal and edge-specific or "edgetic" perturbations, respectively. Here we present two complementary strategies, forward and reverse edgetics, to investigate the phenotypic outcomes of edgetic perturbations of binary protein-protein interaction networks.

Next-generation sequencing to generate interactome datasets.

Next-generation sequencing has not been applied to protein-protein interactome network mapping so far because the association between the members of each interacting pair would not be maintained in en masse sequencing. We describe a massively parallel interactome-mapping pipeline, Stitch-seq, that combines PCR stitching with next-generation sequencing and used it to generate a new human interactome dataset. Stitch-seq is applicable to various interaction assays and should help expand interactome network mapping.

Interactome networks and human disease.

Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.

High-quality binary interactome mapping.

Physical interactions mediated by proteins are critical for most cellular functions and altogether form a complex macromolecular "interactome" network. Systematic mapping of protein-protein, protein-DNA, protein-RNA, and protein-metabolite interactions at the scale of the whole proteome can advance understanding of interactome networks with applications ranging from single protein functional characterization to discoveries on local and global systems properties. Since the early efforts at mapping protein-protein interactome networks a decade ago, the field has progressed rapidly giving rise to a growing number of interactome maps produced using high-throughput implementations of either binary protein-protein interaction assays or co-complex protein association methods.

A genome-wide gene function prediction resource for Drosophila melanogaster.

Predicting gene functions by integrating large-scale biological data remains a challenge for systems biology. Here we present a resource for Drosophila melanogaster gene function predictions. We trained function-specific classifiers to optimize the influence of different biological datasets for each functional category.

Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway identifies deformed epidermal autoregulatory factor-1 as a new glycogen synthase kinase-3 interactor.

The phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) pathway plays pivotal roles in cell survival, growth, and proliferation downstream of growth factors. Its perturbations are associated with cancer progression, type 2 diabetes, and neurological disorders. To better understand the mechanisms of action and regulation of this pathway, we initiated a large scale yeast two-hybrid screen for 33 components of the PI3K-mTOR pathway.

Edgetic perturbation models of human inherited disorders.

Cellular functions are mediated through complex systems of macromolecules and metabolites linked through biochemical and physical interactions, represented in interactome models as 'nodes' and 'edges', respectively. Better understanding of genotype-to-phenotype relationships in human disease will require modeling of how disease-causing mutations affect systems or interactome properties. Here we investigate how perturbations of interactome networks may differ between complete loss of gene products ('node removal') and interaction-specific or edge-specific ('edgetic') alterations.