Genomic Research and American Indian Tribal Communities in Oklahoma: Learning From Past Research Misconduct and Building Future Trusting Partnerships.

Research misconduct and consequential harms have been inflicted upon American Indian/Alaska Native communities for decades. To protect their people and culture and to retain oversight over research, many Native communities have established tribal health research and institutional review boards. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study showcases a successful, trusting research collaboration with tribal nations and academic investigators in Oklahoma. In 2006, the TODAY Study investigators proposed a modification of the study protocol to collect biological specimens from participants for genomic analyses and indefinite storage. Partnering American Indian tribal nations elected not to participate in the genomics collection and repository proposal. Reasons included 1) protection of cultural values, 2) concerns regarding community anonymity, 3) a potential threat to tribal services eligibility, 4) broad informed consent language, and 5) vague definitions of data access and usage. The nations believed the proposed genomics analyses presented a risk of harm to their people and nations without clear benefit. Since the 2006 proposal and the advancement of genomics research, many tribal communities in Oklahoma, appreciating the potential benefits of genomic research, are developing policies regarding oversight of/access to data and biological specimens to mitigate risks and provide members and communities with opportunities to participate in safe and meaningful genomic research.

The Cost-Effectiveness of Meniscal Repair Versus Partial Meniscectomy in the Setting of Anterior Cruciate Ligament Reconstruction.

PURPOSE: To compare the cost-effectiveness of anterior cruciate ligament (ACL) reconstruction with meniscal repair to ACL reconstruction with partial meniscectomy. METHODS: A decision-analytic Markov disease progression model with a 40-year horizon was created simulating outcomes after both meniscal repair and partial meniscectomy at the time of ACL reconstruction. Event probabilities, costs, and utilities were used for the index procedures. The development of osteoarthritis and subsequent knee replacement were either calculated or selected from published literature. Difference in cost, difference in quality-adjusted life-years (QALYs), and incremental cost-effective ratio were calculated to determine which index procedure is most cost-effective. RESULTS: There is total direct cost from ACL reconstruction with meniscus repair of $17,898 compared with that with partial meniscectomy of $24,768 (cost savings of $6,870). There was an estimated gain of 18.00 QALYs after ACL reconstruction with meniscus repair compared with 17.16 QALYs with partial meniscectomy (increase of 0.84 QALYs). In this scenario, meniscus repair is the dominant index procedure at the time of ACL reconstruction. CONCLUSIONS: Meniscal repair at the time of ACL reconstruction is more cost-effective than partial meniscectomy. LEVEL OF EVIDENCE: Level IV, economic and decision analysis.

Comparative analysis of anatomic and reverse total shoulder arthroplasty: in-hospital outcomes and costs.

BACKGROUND: The rate of shoulder arthroplasty has continued to increase at an exponential rate during the past decade in large part owing to approval by the Food and Drug Administration of reverse shoulder arthroplasty. Whereas reverse shoulder arthroplasty has resulted in expanded surgical indications, there are numerous reports of relatively high complication rates. The increased prevalence of both anatomic and reverse shoulder arthroplasty underscores the need to elucidate whether perioperative outcomes are influenced by type of total shoulder arthroplasty. The purpose of this study was to determine the impact of shoulder arthroplasty type, anatomic or reverse, with respect to perioperative adverse events, in-hospital death, prolonged hospital stay, nonroutine disposition, and hospital charges in a nationally representative sample. METHODS: By use of the Nationwide Inpatient Sample database from 2011, the first year that reverse total shoulder arthroplasty received a unique International Classification of Diseases, Ninth Revision procedure code, an estimated 51,052 patients undergoing total shoulder arthroplasty were separated into anatomic total shoulder arthroplasty (58%) and reverse total shoulder arthroplasty (43%). Comparisons of early outcome measures between anatomic and reverse total shoulder cohorts were performed by bivariate and multivariable analyses with logistic regression modeling. RESULTS: Compared with anatomic shoulder arthroplasty recipients, patients undergoing reverse shoulder replacement were at higher risk for in-hospital death, multiple perioperative complications, prolonged hospital stay, increased hospital cost, and nonroutine discharge. CONCLUSION: Despite the expanding indications for reverse shoulder arthroplasty, it is an independent risk factor for inpatient morbidity, mortality, and hospital costs and should perhaps be offered more judiciously and performed in the hands of appropriately trained shoulder specialists.

4-Isoxazolyl-1,4-dihydropyridines exhibit binding at the multidrug-resistance transporter.

The 4-isoxazolyl-dihydropyridines (IDHPs) exhibit inhibition of the multidrug-resistance transporter (MDR-1), and exhibit an SAR distinct from their activity at voltage gated calcium channels (VGCC). Among the four most active IDHPs, three were branched at C-5 of the isoxazole, including the most active analog, 1k.

Distribution of airborne influenza virus and respiratory syncytial virus in an urgent care medical clinic.

BACKGROUND: Considerable controversy exists with regard to whether influenza virus and respiratory syncytial virus (RSV) are spread by the inhalation of infectious airborne particles and about the importance of this route, compared with droplet or contact transmission. METHODS: Airborne particles were collected in an urgent care clinic with use of stationary and personal aerosol samplers. The amounts of airborne influenza A, influenza B, and RSV RNA were determined using real-time quantitative polymerase chain reaction. Health care workers and patients participating in the study were tested for influenza. RESULTS: Seventeen percent of the stationary samplers contained influenza A RNA, 1% contained influenza B RNA, and 32% contained RSV RNA. Nineteen percent of the personal samplers contained influenza A RNA, none contained influenza B RNA, and 38% contained RSV RNA. The number of samplers containing influenza RNA correlated well with the number and location of patients with influenza (r= 0.77). Forty-two percent of the influenza A RNA was in particles < or = 4.1 microm in aerodynamic diameter, and 9% of the RSV RNA was in particles < or = 4.1 microm. CONCLUSIONS: Airborne particles containing influenza and RSV RNA were detected throughout a health care facility. The particles were small enough to remain airborne for an extended time and to be inhaled deeply into the respiratory tract. These results support the possibility that influenza and RSV can be transmitted by the airborne route and suggest that further investigation of the potential of these particles to transmit infection is warranted.

The existence of hypoglossal root ganglion cells in adult humans: potential clinical implications.

INTRODUCTION: Ganglion cells of the hypoglossal nerve (HN) have been confirmed in certain animals but have been thought not to be present in man. To investigate for the presence of these structures in adult humans and if present, to verify their functionality, the present study was performed. MATERIALS AND METHODS: We harvested adult cadaveric HN and observed for ganglion cells. Histological and immunohistochemical analyses were performed on all specimens. RESULTS: Ganglion cells were found in 33% of specimens. Using immunohistochemistry, we found that these ganglia were sympathetic in nature. Based on our findings, ganglion cells do exist in the human HN although they are located sporadically and are found inconstantly. CONCLUSIONS: Such information may be valuable in elucidating other functions of the HN and may aid in the histological diagnosis of this nerve. Additionally, pathology involving HN such as paragangliomas, are supported by our findings of the presence of autonomic ganglion cells in some HN specimens.

Sialic acid capping of CD8beta core 1-O-glycans controls thymocyte-major histocompatibility complex class I interaction.

Bidentate interaction of a T-cell receptor and CD8alphabeta heterodimer with a peptide-MHCI complex is required for the generation of cytotoxic T-lymphocytes. During thymic development, the modification of CD8beta glycans influences major histocompatibility complex class I binding to T-cell precursors called thymocytes. ES mass spectrometry (MS) and tandem MS/MS analysis were used to identify the changes occurring in the CD8beta-glycopeptides during T-cell development. Several threonine residues proximal to the CD8beta Ig headpiece are glycosylated with core-type 1 O-glycans. Non-sialylated glycoforms are present in immature thymocytes but are virtually absent in mature thymocytes. These results suggest how sialylation in a discrete segment of the CD8beta stalk by ST3Gal-1 sialyltransferase creates a molecular developmental switch that affects ligand binding.