Diagnostic performance of MRA in abduction and external rotation position in the detection of glenoid labral lesions: a systematic review and meta-analysis.

OBJECTIVE: To compare the diagnostic performance of direct magnetic resonance arthrography (MRA) for labral lesions during conventional, abduction and external rotation (ABER), conventional plus abduction, and external rotation (ABER) positioning by using a systematic review and meta-analysis. MATERIALS AND METHODS: A comprehensive literature search was performed on the two main concepts of magnetic resonance arthrography: extremity position and labral lesions. Inclusion criteria consisted of original studies that assessed the diagnostic accuracy of MR arthrography in ABER and conventional position alone or combined for the diagnosis of labral lesions by using surgical findings as the reference standard. Meta-analyses were performed that compared MR arthrography during conventional positioning, ABER, and conventional plus ABER positioning. RESULTS: Nine studies met the inclusion and exclusion criteria. A total of 733, 504, and 313 lesions assessed by conventional MRA, ABER MRA, and conventional plus ABER MRA, respectively, were included in our analysis. Pooled sensitivities of MRA in conventional, ABER, and conventional plus ABER position for labral tear diagnosis were 81.5%, 81.6%, and 95.7%, respectively. Pooled specificities of MRA in conventional, ABER, and conventional plus ABER position for labral tear diagnosis were 88.8%, 85.6%, and 94.5%, respectively. Summary receiver operator characteristic (ROC) curve demonstrated improved accuracy of conventional plus ABER MRA compared with conventional MRA or ABER MRA with the area under the curve (AUC) of 0.99, 0.90, and 0.88, respectively. CONCLUSION: Conventional plus ABER MRA showed increased diagnostic accuracy compared to both ABER MRA and conventional MRA alone in the diagnosis of labral lesions.

Review of human supraspinatus tendon mechanics. Part I: fatigue damage accumulation and failure.

Repetitive stress injuries to the rotator cuff, and particularly the supraspinatus tendon (SST), are highly prevalent and debilitating. These injuries typically occur through the application of cyclic load below the threshold necessary to cause acute tears, leading to accumulation of incremental damage that exceeds the body's ability to heal, resulting in decreased mechanical strength and increased risk of frank rupture at lower loads. Consistent progression of fatigue damage across multiple model systems suggests a generalized tendon response to overuse. This finding may allow for interventions before gross injury of the SST occurs. Further research into the human SST response to fatigue loading is necessary to characterize the fatigue life of the tendon, which will help determine the frequency, duration, and magnitude of load spectra the SST may experience before injury. Future studies may allow in vivo SST strain analysis during specific activities, generation of a human SST stress-cycle curve, and characterization of damage and repair related to repetitive tasks.

Review of human supraspinatus tendon mechanics. Part II: tendon healing response and characterization of tendon health.

Overuse injuries of the rotator cuff, particularly of the supraspinatus tendon (SST), are highly prevalent and debilitating in work, sport, and daily activities. Despite the clinical significance of these injuries, there remains a large degree of uncertainty regarding the pathophysiology of injury, optimal methods of nonoperative and operative repair, and how to adequately assess tendon injury and healing. The tendon response to fatigue damage resulting from overuse is different from that of acute rupture and results in either an adaptive (healing) or a maladaptive (degenerative) response. Factors associated with the degenerative response include increasing age, smoking, hypercholesterolemia, biological sex (variable by tendon), diabetes mellitus, and excessive load post fatigue damage. After injury, the average healing rate of tendon is approximately 1% per day and may be significantly influenced by biologic sex (females have lower collagen synthesis rates) and excessive load after damage. Although magnetic resonance imaging (MRI) is considered the gold standard in assessing acute tears as well as tendinopathic change in the SST, ultrasonography has proven to be a valuable tool to measure tendinopathic change in real time. Ultrasonography can determine multiple mechanical and structural parameters of the SST that are altered in fatigue loading. Thus, ultrasonography may be utilized to understand how these parameters change in response to SST overuse, and may aid in determining the activity level that places the SST at greater risk of rupture.

Analysis of 10 cases of orbital infections arising from odontogenic cervicofacial infections.

BACKGROUND: Orbital cellulitis, also called postseptal cellulitis, is an infection of contents of the orbit (periorbital fat, neurovascular bundle, and the extraocular muscles). It should be differentiated from preseptal (periorbital) cellulitis which is a lesion of the anterior portion of the eyelid. However, both preseptal and postseptal cellulitis could present in a similar way with eye pain, edema, and erythema. AIM: The aim of the study was to review patients with orbital cellulitis as a complication of odontogenic cervicofacial infections seen in a Nigerian tertiary care facility. PATIENTS AND METHODS: A retrospective analysis of cases of odontogenic cervicofacial infections complicated by orbital infections that presented at a Nigerian tertiary health facility between January 2006 and September 2019 was conducted. RESULTS: A total of 10 patients with cervicofacial infections who presented with 11 orbital infections as a complication were retrieved for this study. They were six males and four females; male to female ratio was 1.5:1. Median age was 33.5 years (mean age was 34.3 years, range was 22-47 years). Based on clinical features and results of available imaging, orbital infections using the classification by Chandler et al., (1970), were one cases of type I (9.1%), seven cases (63.6%) of type II and two cases (18.2%) of type IV and one case (9.1%) of type V. There was no case of type III. CONCLUSION: Cervicofacial infections could arise from upper posterior teeth. These infections could spread into the orbit causing cellulitis especially type II.

What Is the Survivorship After Hip Arthroscopy for Femoroacetabular Impingement? A Large-database Study.

BACKGROUND: Patients with femoroacetabular impingement (FAI) may experience lasting clinical improvement after hip arthroscopy; however, some patients will still eventually undergo early conversion to THA due to unresolved symptoms and progression of arthritis. However, the risk of this has been only incompletely characterized in prior studies. QUESTIONS/PURPOSES: Using a large healthcare claims database over a 5-year period (2011-2016), we asked: (1) What is the survivorship free from THA after arthroscopic osteoplasty performed for FAI? (2) What identifiable demographic factors and patient characteristics are associated with early conversion to THA after hip arthroscopy performed for FAI? METHODS: We included all patients who underwent hip arthroscopy for FAI, between the ages of 12 years and 63 years, with 3 months of claims data before hip arthroscopy and minimum 2-year follow-up. A total of 4730 hip arthroscopy patients from 2011 to 2014 were retrieved from a US commercial claims database. Hip arthroscopy incidence doubled over time from 1.2 to 2.1 persons per 100,000. Temporal trends, patient demographics, diagnoses at time of arthroscopy, and patient comorbidities were retrieved and logistic regression performed. Survivorship analysis on 11,323 patients (lifting the 2-year follow-up requirement) was also performed to identify independent variables associated with early risk of conversion to THA. RESULTS: In patients undergoing hip arthroscopy for FAI, the overall proportion of conversion to THA within 2 years after hip arthroscopy was 7% (338 of 4730). After controlling for confounding variables such as sex, obesity, and depression, we found the following were independently associated with increased odds of conversion to THA: older age (odds ratio 1.08 [95% CI 1.01 to 1.10]; p < 0.001), osteoarthritis (OR 2.91 [95% CI 2.27 to 3.77]; p < 0.001), joint inflammation (OR 1.89 [95% CI 1.16 to 3.09]; p = 0.01), and a history of opioid use (OR 2.17 [95% CI 1.69 to 2.79]; p < 0.001). Survivorship analysis similarly revealed that older age (hazard ratio 1.08 [95% CI 1.07 to 1.09]; p < 0.001), osteoarthritis (HR 2.53 [95% CI 2.13 to 3.01]; p < 0.001), joint inflammation (HR 1.53 [95% CI 1.10 to 2.11]; p = 0.01), a history of opioid use (HR 2.02 [95% CI 1.71 to 2.38]; p < 0.001), and smoking (HR 1.55 [95% CI 1.14 to 2.11]; p = 0.005), were independently associated with increased odds of conversion to THA within 2 years after hip arthroscopy for FAI. CONCLUSIONS: Although the findings of this study are limited and should not be taken in isolation, patients with FAI who are older, carry diagnoses of inflammatory or degenerative articular disease, or who use opioids or smoke should be counseled about a potentially increased risk of undergoing early conversion to THA after hip arthroscopy. Future studies to further examine the effect of these diagnoses in prospectively collected cohorts, incorporating radiographic and patient-reported outcome measures, are needed. LEVEL OF EVIDENCE: Level III, prognostic study.

Generation and characterization of mice with mesenchyme-specific deletion of the entire ESET histone methyltransferase protein.

ESET protein (also known as SETDB1) catalyzes methylation of histone H3 at lysine 9 (H3-K9). In addition to the full-length transcript, mouse ESET gene also gives rise to alternative spicing variants encoding truncated proteins capable of retaining interaction with other epigenetic enzymes. To completely eliminate full-length ESET and its splicing variants, we have generated a conditional ESET allele with exon 4 flanked by two loxP sites for Cre-mediated DNA deletion and downstream frame-shift mutation of the entire coding region. Mating with Prx1-Cre mice and analysis of the resultant embryos revealed that mesenchyme-specific knockout of exon 4 completely eliminates full-length ESET and its truncated protein products, leading to profound defects in both the flat bones and long bones, ectopic hypertrophy of growth plate chondrocytes and downregulation of Indian hedgehog protein. In addition, exon 4 deletion results in reduced thickness of articular cartilage in E17.5 embryos, whereas deletion of exons 15-16 fails to do so. These findings offer us a useful tool to further study epigenetic regulation in a truly ESET-null background, and demonstrate that ESET plays a critical role in the control of chondrocyte hypertrophy and skeletal development.

Is there evidence that the outcomes of primary anatomic and reverse shoulder arthroplasty are getting better?

PURPOSE: Have the results of shoulder arthroplasty got better over the last two decades? To answer this question, we sought published evidence that the patient-reported outcomes and re-operation rates have improved in reports of more recently performed anatomic (TSA) and reverse (RSA) total shoulder arthroplasties. METHODS: We analyzed the arthroplasty results among studies published from 1990 to 2015, adjusting for the fact that the different publications presented patient groups with different combinations of diagnoses, used various outcome scales, and had different lengths of follow-up. RESULTS: The adjusted clinical outcomes (p = 0.048), but not the revision rates (p = 0.3), were significantly better for articles reporting more recent TSA procedures. Neither the clinical outcomes (p = 0.9) nor the revision rates (p = 0.4) were significantly better in articles reporting more recent RSA surgeries. CONCLUSIONS: Better evidence from reports with greater detail will be necessary to show that patients are realizing progressively better outcomes from shoulder arthroplasty. LEVEL OF EVIDENCE: Level IV.

Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration.

Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 × 10(-5)). Thus, it appears that rare and common variants in a single gene--FBN2--can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.

Nanoaerosols reduce required effective dose of liposomal levofloxacin against pulmonary murine Francisella tularensis subsp. novicida infection.

BACKGROUND: The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator. This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. novicida (F. novicida) infections in BALB/c mice. RESULTS: First, the analysis of quantum dots distribution in cryosections of murine lungs demonstrated that nanoaerosols penetrate the alveoli and spread more homogenously in the lungs than upon intranasal delivery. Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida. The generator was capable of delivering a sufficient dose of nanoaerosolized liposome-encapsulated levofloxacin to rescue mice against 100LD50 of F. novicida. CONCLUSIONS: The nanoaerosol-delivered dosage of liposome-encapsulated levofloxacin required to rescue mice is approximately 94× lower than the oral required dose and approximately 8× lower than the intraperitoneal dose required for rescue. In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes. This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.

Management of intraoperative posterior decentering in shoulder arthroplasty using anteriorly eccentric humeral head components.

BACKGROUND: Posterior humeral decentering presents a challenge in glenohumeral arthroplasty. Soft tissue releases and osteophyte resection can lead to intraoperative decentering not evident preoperatively. Inferior outcomes result if decentering is not addressed as a part of the arthroplasty. When there is >50% posterior subluxation of the humeral head on passive elevation of the arm at surgery, we have used an anteriorly eccentric humeral head component to improve centering of the humeral articular surface on the glenoid. METHODS: We reviewed the 2-year outcomes for 33 shoulder arthroplasties in which anteriorly eccentric humeral heads were used to manage posterior decentering identified at surgery. Rotator interval plication was performed in 16 cases as an adjunctive stabilizing procedure. Shoulders were evaluated preoperatively and postoperatively with the Simple Shoulder Test (SST). Radiographic centering was characterized before surgery and at follow-up on standardized axillary radiographs with the arm held in a position of functional elevation. RESULTS: With the anteriorly eccentric head component, preoperative radiographic humeral decentering was reduced from 10.4% ± 7.9% to 0.9% ± 2.3% postoperatively (P < .001). SST scores improved from 4.8 ± 2.3 to 10.0 ± 2.3 (P < .001). Preoperative posterior humeral head decentering did not correlate with preoperative glenoid version. Glenoid retroversion was 19.8° ± 8.9° preoperatively and 15.5° ± 7.5° postoperatively. CONCLUSIONS: Posterior decentering identified at surgery when standard trial components are in place can be addressed by replacing the anatomic humeral head with an anteriorly eccentric humeral head component.

Impaction autografting: bone-preserving, secure fixation of a standard humeral component.

BACKGROUND: When fixed with bone ingrowth, a tight diaphyseal press fit, or cement, the humeral component of a shoulder arthroplasty may present problems of malposition, stress shielding, or periprosthetic fracture or difficulty with removal at revision arthroplasty. We have avoided the need for these fixation methods by using impaction cancellous autografting of the humeral stem, minimizing contact between the prosthetic stem and the humeral cortex. This study presents the radiographic survivorship of impaction-autografted humeral implants using component subsidence as the primary endpoint. METHODS: We reviewed 286 primary anatomic shoulder arthroplasties having an average follow-up of 4.9 ± 2.7 years. Initial postoperative radiographs and minimum 2-year follow-up radiographs were evaluated by 3 observers to assess subsidence. RESULTS: Two different implants (Humeral Replacement Prosthesis [HRP] and Global Advantage prosthesis) were used. Of 286 stems, 267 (93.4%) had not subsided. The Global Advantage prosthesis had a subsidence-free survival rate of 98.5% at 5 years. The stiffer-stemmed HRP used early during the study had a higher rate of subsidence compared with the currently used Global Advantage stem (hazard ratio, 5.6; P = .001). Radiolucent lines of 2 mm or greater were less common for the Global Advantage prosthesis than for the HRP in each of 7 zones (P < .001). Total shoulder arthroplasty was associated with a higher rate of subsidence compared with hemiarthroplasty (hazard ratio, 2.6; P = .12). CONCLUSIONS: Impaction autografting provides a secure, durable, bone-preserving means of humeral component fixation in anatomic shoulder arthroplasty.

Determination of steroid injection sites using lidocaine test in adhesive capsulitis: A prospective randomized clinical trial.

BACKGROUND: To validate the usefulness of subacromial bursa lidocaine for determination of the therapeutic steroid injection site in patients with adhesive capsulitis METHODS: Ninety-two patients with adhesive capsulitis were randomly divided into the LC (lidocaine test) group (n = 46), in which LC injection was performed at the subacromial bursa prior to therapeutic steroid injection, and GH (glenohumeral) group (n = 46), in which the steroid was injected into the GH. Patients in the LC group received steroid injection at the subacromial bursa or GH according to the result of the LC. Both groups underwent the same exercise protocol. Improvement of the shoulder pain was checked at 2 weeks and 3 months postinjection and expressed on an ordinal scale. Passive range of motion was recorded preinjection, and 2 weeks and 3 months postinjection. RESULTS: Two weeks postinjection, 37 patients expressed "much improved" and 7 patients expressed "slightly improved" pain levels in the LC group, whereas 18 patients each expressed "much improved" and "slightly improved" pain levels in the GH group, which was significantly different (p < 0.01). This difference was maintained 3 months postinjection (p < 0.01). Passive range of motion in all directions improved significantly 3 months postinjection in both the LC and GH groups (p < 0.01). However, there was no significant difference between the LC and GH groups. CONCLUSIONS: We found that subacromial lidocaine injection prior to steroid injection resulted in better improvement of pain than conventional GH injection for patients with adhesive capsulitis.

No clinically significant association between CFH and ARMS2 genotypes and response to nutritional supplements: AREDS report number 38.

OBJECTIVE: To determine whether genotypes at 2 major loci associated with late age-related macular degeneration (AMD), complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2), influence the relative benefits of Age-Related Eye Disease Study (AREDS) supplements. DESIGN: Unplanned retrospective evaluation of a prospective, randomized, placebo-controlled clinical trial of vitamins and minerals for the treatment of AMD. SUBJECTS: AREDS participants (mean age, 69 years) who were at risk of developing late AMD and who were randomized to the 4 arms of AREDS supplement treatment. METHODS: Analyses were performed using the Cox proportional hazards model to predict progression to late AMD (neovascular or central geographic atrophy). Statistical models, adjusted for age, gender, smoking status, and baseline AMD severity, were used to examine the influence of genotypes on the response to therapy with 4 randomly assigned arms of AREDS supplement components: placebo, antioxidants (vitamin C, vitamin E, ß-carotene), zinc, or a combination. MAIN OUTCOME MEASURES: The influence of the genotype on the relative treatment response to the randomized components of the AREDS supplement, measured as progression to late AMD. RESULTS: Of the 1237 genotyped AREDS participants of white ethnicity, late AMD developed in 385 (31.1%) during the mean follow-up of 6.6 years. As previously demonstrated, CFH genotype (P = 0.005), ARMS2 (P< 0.0001), and supplement were associated individually with progression to late AMD. An interaction analysis found no evidence that the relative benefits of AREDS supplementation varied by genotype. Analysis of (1) CFH rs1061170 and rs1410996 combined with ARMS2 rs10490924 with the 4 randomly assigned arms of AREDS supplement and (2) analysis of the combination of CFH rs412852 and rs3766405 with ARMS2 c.372_815del443ins54 with the AREDS components resulted in no interaction (P = 0.06 and P = 0.45, respectively, before multiplicity adjustment). CONCLUSIONS: The AREDS supplements reduced the rate of AMD progression across all genotype groups. Furthermore, the genotypes at the CFH and ARMS2 loci did not statistically significantly alter the benefits of AREDS supplements. Genetic testing remains a valuable research tool, but these analyses suggest it provides no benefits in managing nutritional supplementation for patients at risk of late AMD.

Feeding and reproductive parameters of adult female Ixodes scapularis (Acari: Ixodidae) and Amblyomma americanum parasitizing white-tailed deer (Odocoileus virginianus).

White-tailed deer Odocoileus virginianus (Zimmermann) (Artiodactyla: Cervidae) are the main host for adult Ixodes scapularis Say (Acari: Ixodidae) (blacklegged tick) and all stages of Amblyomma americanum Linnaeus (Acari: Ixodidae) (lone star tick). However, literature describing the feeding and reproductive parameters of these tick species when feeding on this host is limited. We experimentally infested white-tailed deer with adult pairs of either I. scapularis or A. americanum to improve our understanding of these tick-host relationships. Our study used tick-naïve white-tailed deer and restricted host grooming throughout the infestation. For I. scapularis, the days to repletion (mean ±â€…SE, 6.04 ±â€…0.07), engorgement weight of replete females (0.20 ±â€…0.0032 g), duration of oviposition (32 ±â€…0.45 d), egg mass weight (0.10 ±â€…0.0027 g), and number of eggs laid per tick (1,803.00 ±â€…49.00) were recorded. Data from A. americanum were also recorded, including days to repletion (11.00 ±â€…0.063), engorgement weight of replete females (0.63 ±â€…0.025 g), duration of oviposition (37.00 ±â€…1.30 d), egg mass weight (0.34 ±â€…0.017 g), and number of eggs laid per tick (5,873.00 ±â€…291.00). These biological parameter data could be used as variables in models (e.g., LYMESIM 2.0) to determine how white-tailed deer influence I. scapularis and A. americanum populations in nature, and to evaluate the protective efficacy of tick-antigen-based antitick vaccines.

In Vitro Antioxidant and In Silico Evaluation of the Anti-ß-Lactamase Potential of the Extracts of Cylindrospermum alatosporum NR125682 and Loriellopsis cavenicola NR117881.

Cyanobacteria in recent times have been touted to be a suitable source for the discovery of novel compounds, including antioxidants and antibiotics, due to their large arsenal of metabolites. This study presents the in vitro antioxidant and in silico evaluation of Cylindrospermum alatosporum NR125682 and Loriellopsis cavenicola NR117881, isolated from freshwater ponds around the campus of the University of Zululand, South Africa. The isolates were confirmed using 16S rRNA. Various crude extracts of the isolated microbes were prepared through sequential extraction using hexane, dichloromethane, and 70% ethanol. The chemical constituents of the crude extracts were elucidated by FTIR and GC-MS spectroscopy. The antioxidant potential of the extracts was determined by the free radical (DPPH, ABTS, •OH, and Fe2+) systems. Molecular docking of the major constituents of the extracts against ß-lactamase was also evaluated. GC-MS analysis indicated the dominating presence of n-alkanes. The extracts exhibited varying degrees of antioxidant activity (scavenging of free radicals; an IC50 range of 8-10 µg/mL was obtained for ABTS). A good binding affinity (-6.6, -6.3 Kcal/mol) of some the organic chemicals (diglycerol tetranitrate, and 2,2-dimethyl-5-(3-methyl-2-oxiranyl)cyclohexanone) was obtained following molecular docking. The evaluated antioxidant activities, coupled with the obtained docking score, potentiates the antimicrobial activity of the extracts.

Limited Return to Preinjury Performance in NCAA Division I American Football Players With Hamstring Injuries.

Background: Hamstring strains are common among elite athletes, but their effect on return to the same level of play in American football has been incompletely characterized. Purpose: Data on National Collegiate Athletics Association Division I college football players with acute hamstring strains were gathered to identify the effects these injuries have on both return to play and athletic performance regarding velocity, workload, and acceleration. Study Design: Case Series; Level of evidence, 4. Methods: Injury data for a single Division I football team were prospectively recorded over a 4-year period. Players wore global navigation satellite system and local positioning system (GNSS/LPS) devices to record movement data in practices and games. The practice and game data were cross-referenced to evaluate players with isolated acute hamstring strains. Comparisons were made regarding players' pre- and postinjury ability to maintain high velocity (>12 mph [19.3 kph]), maximal velocity, triaxial acceleration, and inertial movement analysis (IMA). There were 58 hamstring injuries in 44 players, of which 25 injuries from 20 players had GNSS/LPS data. Results: Players were able to return to play from all 25 injury incidences at a mean of 9.2 days. At the final mean follow-up of 425 days, only 4 players had reached preinjury function in all measurements; 12 players were able to return in 2 of the 4 metrics; and only 8 players reached their preinjury ability to maintain high velocity. For those who did not achieve this metric, there was a significant difference between pre- and postinjury values (722 vs 442 m; P = .016). A total of 14 players were able to regain their IMA. Players who returned to prior velocity or acceleration metrics did so at a mean of 163 days across all metrics. Conclusion: While players may be able to return to play after hamstring strain, many players do not reach preinjury levels of acceleration or velocity, even after 13.5 months. Further studies are needed to confirm these findings, assess clinical relevance on imaging performance, and improve hamstring injury prevention and rehabilitation.

Illuminating Neuropeptide Y Y4 Receptor Binding: Fluorescent Cyclic Peptides with Subnanomolar Binding Affinity as Novel Molecular Tools.

The neuropeptide Y (NPY) Y4 receptor (Y4R), a member of the family of NPY receptors, is physiologically activated by the linear 36-amino acid peptide pancreatic polypeptide (PP). The Y4R is involved in the regulation of various biological processes, most importantly pancreatic secretion, gastrointestinal motility, and regulation of food intake. So far, Y4R binding affinities have been mostly studied in radiochemical binding assays. Except for a few fluorescently labeled PP derivatives, fluorescence-tagged Y4R ligands with high affinity have not been reported. Here, we introduce differently fluorescence-labeled (Sulfo-Cy5, Cy3B, Py-1, Py-5) Y4R ligands derived from recently reported cyclic hexapeptides showing picomolar Y4R binding affinity. With pKi values of 9.22-9.71 (radioligand competition binding assay), all fluorescent ligands (16-19) showed excellent Y4R affinity. Y4R saturation binding, binding kinetics, and competition binding with reference ligands were studied using different fluorescence-based methods: flow cytometry (Sulfo-Cy5, Cy3B, and Py-1 label), fluorescence anisotropy (Cy3B label), and NanoBRET (Cy3B label) binding assays. These experiments confirmed the high binding affinity to Y4R (equilibrium pKd: 9.02-9.9) and proved the applicability of the probes for fluorescence-based Y4R competition binding studies and imaging techniques such as single-receptor molecule tracking.

Characterization of the R162W Kir7.1 mutation associated with snowflake vitreoretinopathy.

KCNJ13 encodes Kir7.1, an inwardly rectifying K(+) channel that is expressed in multiple ion-transporting epithelia. A mutation in KCNJ13 resulting in an arginine-to-tryptophan change at residue 162 (R162W) of Kir7.1 was associated with snowflake vitreoretinal degeneration, an inherited autosomal-dominant disease characterized by vitreous degeneration and mild retinal degeneration. We used the Xenopus laevis oocyte expression system to assess the functional properties of the R162W (mutant) Kir7.1 channel and determine how wild-type (WT) Kir7.1 is affected by the presence of the mutant subunit. Recordings obtained via the two-electrode voltage-clamp technique revealed that injection of oocytes with mutant Kir7.1 cRNA resulted in currents and cation selectivity that were indistinguishable from those in water-injected oocytes, suggesting that the mutant protein does not form functional channels in the plasma membrane. Coinjection of oocytes with equal amounts of mutant and WT Kir7.1 cRNAs resulted in inward K(+) and Rb(+) currents with amplitudes that were ∼17% of those in oocytes injected with WT Kir7.1 cRNA alone, demonstrating a dominant-negative effect of the mutant subunit. Similar to oocytes injected with WT Kir7.1 cRNA alone, coinjected oocytes exhibited inwardly rectifying Rb(+) currents that were more than seven times larger than K(+) currents, indicating that mutant subunits did not alter Kir7.1 channel selectivity. Immunostaining of Xenopus oocytes or Madin-Darby canine kidney cells expressing mutant or WT Kir7.1 demonstrated distribution of both proteins primarily in the plasma membrane. Our data suggest that the R162W mutation suppresses Kir7.1 channel activity, possibly by negatively impacting gating by membrane phosphadidylinositol 4,5-bisphosphate.

E2-2 protein and Fuchs's corneal dystrophy.

BACKGROUND: Fuchs's corneal dystrophy (FCD) is a leading cause of corneal transplantation and affects 5% of persons in the United States who are over the age of 40 years. Clinically visible deposits called guttae develop under the corneal endothelium in patients with FCD. A loss of endothelial cells and deposition of an abnormal extracellular matrix are observed microscopically. In advanced disease, the cornea swells and becomes cloudy because the remaining endothelial cells are not sufficient to keep the cornea dehydrated and clear. Although rare genetic variation that contributes to both early-onset and typical late-onset forms of FCD has been identified, to our knowledge, no common variants have been reported. METHODS: We performed a genomewide association study and replicated the most significant observations in a second, independent group of subjects. RESULTS: Alleles in the transcription factor 4 gene (TCF4), encoding a member of the E-protein family (E2-2), were associated with typical FCD (P=2.3x10(-26)). The association increased the odds of having FCD by a factor of 30 for persons with two copies of the disease variants (homozygotes) and discriminated between case subjects and control subjects with about 76% accuracy. At least two regions of the TCF4 locus were associated independently with FCD. Alleles in the gene encoding protein tyrosine phosphatase receptor type G (PTPRG) were associated with FCD (P=4.0x10(-7)), but the association did not reach genomewide significance. CONCLUSIONS: Genetic variation in TCF4 contributes to the development of FCD. (Funded by the National Eye Institute and others.)