Stephen J. O'Brien

Bio: Stephen J. O'Brien is an academic researcher from Saint Petersburg State University of Information Technologies, Mechanics and Optics. The author has contributed to research in topics: Population & Gene. The author has an hindex of 153, co-authored 1062 publications receiving 93025 citations. Previous affiliations of Stephen J. O'Brien include University College Cork & QIMR Berghofer Medical Research Institute.

Effect of Genetic Variation on HIV Transmission and Progression to AIDS

Abstract: The identification of genetic factors that regulate HIV-1 infection and AIDS kinetics has clarified our view of viral pathogenesis by illuminating the importance of host-virus interactions at virtually every stage of infection. Genetic studies often point to unexpected roles for host factors, providing insights into immune regulation of HIV-1 replication and possible selective forces that may influence HIV-1 quasispecies evolution. Host genetic factors have been shown to affect susceptibility to infection, the rate of CD4 + T-cell depletion, and the rate of progression to AIDS. Thus, it is important to consider the genetic background of the host when assessing the efficacy of antiretroviral agents and vaccines in clinical trials.

“Hidden Lesions” of the Extra-articular Biceps After Subpectoral Biceps Tenodesis: Letter to the Editor:

Abstract: Dear Editor: While we commend Moon and colleagues for drawing attention to the extra-articular portion of the long head of the biceps tendon (LHBT), they inadequately define the term ‘‘hidden lesion,’’ offer a limited assessment of lesion distribution, and improperly conclude that open subpectoral biceps tenodesis is a panacea. To accurately define hidden lesions of the LHBT, one must first understand the limits of diagnostic glenohumeral arthroscopy and the anatomy and histology of what we have termed the ‘‘bicipital tunnel,’’ which confines the extra-articular segment of the LHBT. Cadaveric experiments by our group demonstrated that the fibroosseous bicipital tunnel is a closed space from the articular margin through the proximal 3 cm of the subpectoral region in all specimens. We divided the bicipital tunnel into 3 zones. Zone 1 represents the traditional bicipital groove, extending from the articular margin to the inferior margin of the subscapularis tendon. While some lesions affecting the LHBT in this zone remain hidden, it should be noted that 78% of the tendon here is actually visualized during diagnostic arthroscopy. Others have reported similar limits of diagnostic arthroscopy. Zone 2 represents a ‘‘no-man’s-land’’ between the inferior margin of the subscapularis and the proximal margin of the pectorals major tendon. This biologically active zone is particularly relevant because of its invisibility to glenohumeral arthroscopy above and to open subpectoral exposure below. Zone 3 of the bicipital tunnel represents the subpectoral region. Cross-sectional analysis of the bicipital tunnel revealed similarities between zones 1 and 2, including, most important, a dense connective tissue roof and the presence of synovial tissue. Quantitative analysis further demonstrated that zones 1 and 2 had similarly limited percentage empty tunnel, suggesting a vulnerability to a range of space-occupying lesions, such as scar, osteophytes, and loose bodies, as well as hypertrophic tenosynovium. Hidden lesions, in fact, encompass a wide array of objective findings—including loose bodies, osteophytes, cysts, osseous stenosis, soft tissue stenosis, inflamed vinculae, hypertrophic scar, and extra-articular LHBT instability—in addition to the partial tears and tenosynovitis reported by Moon et al. Acknowledgment of these lesions’ existence is critical to our comprehensive understanding of the pathogenesis and diagnosis of biceps tendinitis. In fact, we first reported the diverse nature of these lesions at the March 2013 AAOS annual meeting in a large cohort study of chronically symptomatic patients; the study was later recognized with the J. Whit Ewing Award at the AANA and was published in the journal Arthroscopy. The offending lesions of 277 patients with chronic bicepslabral complex symptoms were categorized as ‘‘inside,’’ ‘‘junctional,’’ or ‘‘bicipital tunnel’’ based strictly on direct intraoperative visualization. Inside lesions were those of the labrum and biceps anchor. Junctional lesions were those of the LHBT that could be visualized by pull test during diagnostic glenohumeral arthroscopy. We defined hidden bicipital tunnel lesions as only those visualized directly from with the subdeltoid space after complete release of the fibrous sheath in zones 1 and 2 of the bicipital tunnel. We determined that 47% of patients had true ‘‘hidden lesions’’ and that hypertrophic scar, extra-articular instability, and stenosis were actually more common than the extension of proximal partial tears reported by Moon et al. Furthermore, nearly half of patients with a normal-appearing LHBT on glenohumeral arthroscopy had 1 of the aforementioned hidden lesions, and 18% of this large clinical cohort had their essential lesion occurring within the bicipital tunnel. There are several merits to the open subpectoral biceps tenodesis technique. We would argue that the most important is its effective decompression of the bicipital tunnel, as the authors pointed out, but one should use caution in concluding that this makes it the optimal technique for all patients. A recent paper by Werner et al, for example, demonstrated equivalence of clinical outcomes for suprapectoral and subpectoral biceps tenodesis techniques. Many patients fare well with tenotomy and proximal tenodesis techniques that do not decompress the bicipital tunnel. They may be quicker, require less hardware, and reduce morbidity. Must we subject the patient with isolated proximal pathology to the infection risk associated with an axillary incision, to the risk of neurovascular injury, or to the risk of fracture? The real question is, how can we determine the location of offending lesions and use that information to select the most appropriate tenodesis technique for a particular patient? For example, age may be a risk factor for bicipital tunnel pathology. We found that patients with tunnel lesions were statistically 6 years older than those without (P = .003). Furthermore, in a large prospective study investigating the comprehensive physical examination of the biceps-labral complex, we showed that tenderness to palpation of the bicipital tunnel and the active compression test (O’Brien sign) had negative predictive values of 96% and 93%, respectively, for the aforementioned hidden lesions. The Speed test and Yergason test were quite specific for presence of these lesions, at 87% and 98%, respectively. Biceps surgery is not a one-size-fits-all strategy; rather, it is our charge as clinicians to select the optimal treatment strategy for an individual patient. In summary, it is imperative that health care providers understand the existence of the bicipital tunnel and full array of ‘‘hidden lesions’’ that are present in chronically symptomatic patients. We must not limit our The American Journal of Sports Medicine, Vol. 43, No. 3 2015 The Author(s)

Anatomy of the Biceps Tendon: From Origin to Insertion

Abstract: A detailed appreciation of biceps tendon anatomy is important to diagnosis and treatment of pathologic processes. The anatomy of the proximal biceps tendon is complex, and the biceps labral complex contains three distinct regions, which are important to clinical pathology. The distal biceps tendon is a common site of injury and open surgical repair, and recent research efforts have helped to better elucidate the structure and function of the distal biceps tendon. An in-depth understanding of the various areas of the biceps tendon, its known anatomic variants, and the specific areas of concern for pathology is crucial for the orthopedic surgeon. This chapter will outline the normal anatomy and anatomical variants of both the proximal biceps and distal biceps tendon.

A decade of GigaScience: A perspective on conservation genetics

Abstract: Abstract Wide interest in species conservation is young. To many it began early in 1903 when Teddy Roosevelt and John Muir set up a camp under the Grizzly Giant in the Mariposa Grove of California's Yosemite Valley. Over three days they decided to broaden the US National Park footprint across the USA. Conservationists were inspired in the coming decades by the writings of wildlife conservation pioneers—Osa Johnson (I Married Adventure), Karen Blixen (Out of Africa) and Rachel Carson (The Silent Spring). Countless crusaders developed a passion for preserving dwindling species in those early days, yet none of these conservation advocates mentioned the word genetics, let alone genomics. The genome sequencing projects that have followed on from these have brought in an enormous amount of data, including whole genome sequences for thousands of non-human species, both individual and population wide. This huge resource has revolutionized conservation genetics, bringing in ways to assess the health of at-risk populations, devise genetic-driven breeding strategies, and other means to attempt to preserve the over 1 million species (and growing) under threat today.

The complete mitochondrial genome of the parthenogenetic Caucasian rock lizard Darevskia unisexualis (Squamata: lacertidae) contains long tandem repeat formed by 59 bp monomer.

Abstract: The first complete mitochondrial genome sequence of parthenogenetic Caucasian rock lizard Darevskia unisexualis (Lacertidae family) is determined by hybrid assembly with Illumina HiSeq and PacBio RS II platforms. The circular 21.4 kbp mitogenome contains 13 protein-coding genes, 12S and 16S rRNA genes, 20 tRNAs, two pseudogenized tRNAs, and one long tandem repeats with 4.1 kbp length formed by 59 bp monomer repeated x70.6 times located before control region. This finding represents a new example of mitogenome variation in lizards of hybrid origin, providing fundamental data for following study of a unique hybridization system formed by parthenogenetic and bisexual species in the mountain steppe of central Armenia.

Initial sequencing and analysis of the human genome.

Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Abstract: There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.