Risk of bleeding following double balloon enteroscopy in patients on continued antiplatelet and/or anticoagulation therapy.

Background and study aims Anticoagulation (AC) and antiplatelet (AP) therapy may increase the risk of gastrointestinal bleeding after double balloon enteroscopy (DBE); however, limited data are currently available regarding the incidence. The aim of this study was to assess the incidence and clinical characteristics of post-DBE bleeding in patients on AC and AP therapy. Patients and methods The medical records of patients who underwent DBE between 2009 and 2013 at Mayo Clinic, Florida, were retrospectively reviewed. Patients were divided into three groups: 1) continued AP therapy; 2) AC therapy; and 3) neither AP nor AC at the time of DBE. Follow-up data were collected at 60 days and 1 year. Results A total of 683 patients were identified; 43 on AC, 183 on AP and 457 not on AP or AC therapy. The most common indication for DBE was obscure gastrointestinal bleeding in the groups on and not on AP (85.3 % vs 70.9 %, P  < 0.0001). There was no statistical difference in post-DBE bleeding rates in patients on AP vs not on AP at 60 days (11.5 % vs 7.5 %, P  = 0.12) or 1 year (19.9 % vs 15.7 %, P  = 0.23). Rates of bleeding in patients on AC were 11.6 % within 60 days and 22.5 % within 1 year. Multivariate analysis reflected American Society of Anesthesiologist > 3 and indication for DBE of GI bleeding were independent risk factors for post-DBE bleeding within 1 year. Conclusions Continued antiplatelet use at the time of DBE was not an independent risk factor for bleeding post-DBE at 60 days or 1 year of follow up.

Development of a novel self-sanitizing mask prototype to combat the spread of infectious disease and reduce unnecessary waste.

With the spread of COVID-19, significant emphasis has been placed on mitigation techniques such as mask wearing to slow infectious disease transmission. Widespread use of face coverings has revealed challenges such as mask contamination and waste, presenting an opportunity to improve the current technologies. In response, we have developed the Auto-sanitizing Retractable Mask Optimized for Reusability (ARMOR). ARMOR is a novel, reusable face covering that can be quickly disinfected using an array of ultraviolet C lamps contained within a wearable case. A nanomembrane UVC sensor was used to quantify the intensity of germicidal radiation at 18 different locations on the face covering and determine the necessary exposure time to inactivate SARS-CoV-2 in addition to other viruses and bacteria. After experimentation, it was found that ARMOR successfully provided germicidal radiation to all areas of the mask and will inactivate SARS-CoV-2 in approximately 180 s, H1N1 Influenza in 130 s, and Mycobacterium tuberculosis in 113 s, proving that this design is effective at eliminating a variety of pathogens and can serve as an alternative to traditional waste-producing disposable face masks. The accessibility, ease of use, and speed of sanitization supports the wide application of ARMOR in both clinical and public settings.

Effect of Steric Constraint at the γ-Backbone Position on the Conformations and Hybridization Properties of PNAs.

Conformationally preorganized peptide nucleic acids (PNAs) have been synthesized through backbone modifications at the γ-position, where R = alanine, valine, isoleucine, and phenylalanine side chains. The effects of these side-chains on the conformations and hybridization properties of PNAs were determined using a combination of CD and UV-Vis spectroscopic techniques. Our results show that the γ-position can accommodate varying degrees of sterically hindered side-chains, reaffirming the bimodal function of PNAs as the true hybrids of "peptides" and "nucleic acids."

Crystal structure of chiral gammaPNA with complementary DNA strand: insights into the stability and specificity of recognition and conformational preorganization.

We have determined the structure of a PNA-DNA duplex to 1.7 A resolution by multiple-wavelength anomalous diffraction phasing method on a zinc derivative. This structure represents the first high-resolution 3D view of a hybrid duplex containing a contiguous chiral PNA strand with complete gamma-backbone modification ("gammaPNA"). Unlike the achiral counterpart, which adopts a random-fold, this particular gammaPNA is already preorganized into a right-handed helix as a single strand. The new structure illustrates the unique characteristics of this modified PNA, possessing conformational flexibility while maintaining sufficient structural integrity to ultimately adopt the preferred P-helical conformation upon hybridization with DNA. The unusual structural adaptability found in the gammaPNA strand is crucial for enabling the accommodation of backbone modifications while constraining conformational states. In conjunction with NMR analysis characterizing the structures and substructures of the individual building blocks, these results provide unprecedented insights into how this new class of chiral gammaPNA is preorganized and stabilized, before and after hybridization with a cDNA strand. Such knowledge is crucial for the future design and development of PNA for applications in biology, biotechnology, and medicine.

The structure of a gamma-modified peptide nucleic acid duplex.

This paper presents the results of an NMR spectroscopy and distance-restrained molecular dynamics (MD) study of a gamma-methylated, palindromic, 8-base pair peptide nucleic acid (gamma-PNA) duplex. The goal of this study was to examine the impact of the gamma-backbone modification on the structure of the PNA duplex. The 2D NMR information involving the backbone methyl group, especially the NOEs between the methyl protons and those of the amide and methylene groups of the backbone, led to distance restraints useful in the elucidation of the structure of the backbone of gamma-PNA. Integration of the NOE peaks resulted in 138 inter-proton distance restraints, which were used in ten independent simulated annealing followed by 2 ns restrained MD runs. These simulations led to the conclusion that the gamma-PNA duplex adopts a general P-form helical structure similar to that observed for non-modified PNA but with a smaller base pair rise, which is an A-like helical feature, and a slight helical bending towards the major groove (PDB ID ). These properties of the gamma-PNA duplex may be induced by the gamma-methyl group. A similar effect of the methyl group was revealed by a previous NMR study of single stranded gamma-PNA [A. Dragulescu-Andrasi, S. Rapireddy, B. M. Frezza, C. Gayathri, R. R. Gil and D. H. Ly, J. Am. Chem. Soc., 2006, 128, 10258-10267]. It appears that the steric constraint exerted by the gamma-methyl on the backbone orientation is relatively independent of the base pairing and stacking and thus is likely to manifest when other substituents are introduced at the gamma-position of the PNA.

Tensile strain in the anterior part of the acetabular labrum during provocative maneuvering of the normal hip.

BACKGROUND: Injury of the acetabular labrum is a well recognized cause of hip pain in the young, active patient. The exact mechanism of these injuries remains a subject of speculation, although femoroacetabular impingement and twisting maneuvers have both been proposed as critical factors. We examined the hypothesis that torsional maneuvers of the morphologically normal hip joint generate mechanical strain within the acetabular labrum, particularly in areas that are prone to injury. METHODS: Seven human cadaver specimens were loaded during five separate maneuvers with external rotation or abduction torques applied to the hip in neutral alignment and in moderate flexion or extension. Tensile strain within the acetabular labrum was measured with use of the technique of roentgen stereophotogrammetric analysis. RESULTS: Substantial tensile strains were generated within the labrum during each of the loading maneuvers, with no significant difference in strain being noted between the maneuvers. Maximum strain in the anterior part of the labrum averaged 13.6% +/- 7.8% in the axial direction and 8.4% +/- 3.0% in the circumferential direction. The highest mean and maximum strain values were found at the two o'clock position of the labrum, with the highest strain concentration at the bone-labrum interface. CONCLUSIONS: External rotation and abduction maneuvers of the morphologically normal human hip joint in moderate flexion or extension can generate substantial tensile strains in the anterior part of the acetabular labrum. This finding supports the hypothesis that injury to the anterior part of the labrum may occur from recurrent twisting or pivoting maneuvers of the hip joint in moderate flexion or extension without femoroacetabular impingement.

The 2007 Frank Stinchfield Award. The biomechanics of the hip labrum and the stability of the hip.

We explored the mechanical factors leading to the formation of labral tears and the effect of these lesions on hip kinematics at the extremes of joint motion. Using a 3D motion analysis system, the stability of six cadaveric hips was measured during loading maneuvers known to impose anterior loads on the joint margin. These measurements were repeated following venting of the capsule, and after creation of a 15-mm tear in the intact labrum. Compared to the intact hip, 43% and 60% less force was required to distract the femur by 3 mm after venting and creation of a tear. An ER torque of 177 in-lbf in 30 degrees of flexion caused the vented and torn specimens to rotate 1.5 degrees +/- 2.7 degrees and 7.1 degrees +/- 4.7 degrees more than the intact specimen, and the femoral head to displace 1.21 +/- 0.53 mm and 0.67 +/- 0.35 mm, respectively. A breach of the integrity of labral function is shown to lead to decreased femoral stability relative to the acetabulum during extreme ranges of motion.

Lyophilization does not inactivate infectious retrovirus in systemically infected bone and tendon allografts.

BACKGROUND: A review of multiple transplantations of human immunodeficiency virus-infected musculoskeletal allografts found that recipients of lyophilized (freeze-dried) bone or tendon from an infected donor all tested negative for human immunodeficiency virus. The finding that 75% of the recipients of fresh-frozen bone from the same donor contracted human immunodeficiency virus has led to speculation that freeze-drying may render retroviral-infected musculoskeletal allografts noninfectious. HYPOTHESIS: Lyophilization does not inactivate retrovirus in systemically infected bone and tendon. STUDY DESIGN: Controlled laboratory study. METHODS: Tendons and cortical bone segments from cats systemically infected with feline leukemia virus were used in this study. Feline embryonic fibroblast cells were cultured in the presence of fresh-frozen or freeze-dried cortical bone or tendon segments. At each passage, feline leukemia virus p27 antigen was measured in media by enzyme-linked immunosorbent assay, and feline leukemia virus (pro)viral nucleic acids were quantified by real-time quantitative polymerase chain reaction in the DNA extracted from cells. RESULTS: Enzyme-linked immunosorbent assay results and quantitative polymerase chain reaction results demonstrated retroviral antigen and proviral DNA in all cultured cell replicates after exposure to fresh-frozen or freeze-dried bones or tendons. CONCLUSION: Freeze-drying (lyophilization) of retroviral-infected cortical bone and tendon does not inactivate retrovirus. CLINICAL RELEVANCE: These results conclusively demonstrate that freeze-drying should not be relied on to inactivate infectious retrovirus in systemically infected musculoskeletal allografts.