The ability of an animal to detect, discriminate, and respond to odors depends on the function of its olfactory receptor neurons (ORNs), which in turn depends ultimately on odorant receptors. To understand the diverse mechanisms used by an animal in olfactory coding and computation, it is essential to understand the functional diversity of its odor receptors. The larval olfactory system of Drosophila melanogaster contains 21 ORNs and a comparable number of odorant receptors whose properties have been examined in only a limited way. We systematically screened them with a panel of ∼500 odorants, yielding >10,000 receptor-odorant combinations. We identify for each of 19 receptors an odorant that excites it strongly. The responses elicited by each of these odorants are analyzed in detail. The odorants elicited little cross-activation of other receptors at the test concentration; thus, low concentrations of many of these odorants in nature may be signaled by a single ORN. The receptors differed dramatically in sensitivity to their cognate odorants. The responses showed diverse temporal dynamics, with some odorants eliciting supersustained responses. An intriguing question in the field concerns the roles of different ORNs and receptors in driving behavior. We found that the cognate odorants elicited behavioral responses that varied across a broad range. Some odorants elicited strong physiological responses but weak behavioral responses or weak physiological responses but strong behavioral responses.T he olfactory system of the Drosophila larva achieves remarkable function with minimal structure. It detects and responds to spatial and temporal gradients of odorants, transforming chemical information into navigation via an elegant repertoire of head sweeps, runs, and turns (1-3). Its sophisticated function is based on the activities of 21 olfactory receptor neurons (ORNs), which innervate the dorsal organ of the head and send axons to the antennal lobe of the brain (4). The activities of the ORNs are in turn based on the responses of odor receptors (Ors). Thus, to understand the molecular basis of larval olfactory navigation, it is necessary to understand the function of the receptors.ORNs together express 25 members of the Or family of odor receptors and the Orco coreceptor (5-8). In each ORN, an Or and Orco together form a ligand-gated ion channel (9-11). Most ORNs express a single Or, although one ORN coexpresses Or94a and Or94b and another ORN coexpresses Or33b and Or47a (7). The significance of this coexpression remains speculative, but the response profiles of some coexpressed adult Ors are additive (12).The responses of the larval Or repertoire to a limited odorant panel was previously examined in an in vivo expression system known as the empty neuron system (8, 13). With the use of this system, 21 of the larval Ors were found to be functional. However, studies of the larval Or repertoire have been limited not only in the number of odorants examined, but also in their consideration of receptor sensitivity, tempor...

OBJECTIVE: The goal of this study was to compare the effectiveness of a youth-friendly HIV video with in-person counseling in conveying HIV knowledge and obtaining consent for HIV testing among adolescent patients of an urban emergency department. METHODS: A 2-armed, randomized controlled trial was conducted on a convenience sample of 200 stable, sexually active people aged 15 to 21 years in an urban emergency department. Participants in both the in-person counseling group and the video intervention group completed preintervention and postintervention HIV knowledge measures. HIV knowledge was the primary outcome measure, and consent for HIV testing was the secondary outcome. Characteristics associated with voluntary HIV testing were identified. RESULTS: Of 333 eligible people, 200 agreed to participate. There was no difference in preintervention HIV knowledge scores between groups. Mean postintervention knowledge scores differed significantly between the video (78.5% correct) and the counselor (66.3% correct) (P < 0.01) groups. Overall, 51% of the video group accepted HIV testing compared with 22% in the control group (P < .01). Watching the video (OR: 3.6 [95% CI: 1.8–7.2]), being female (OR: 2.1 [95% CI: 1.0–4.2]), engaging in oral sex (OR: 2.8 [95% CI: 1.4–5.9]), and being older than 18 years (OR: 3.8 [95% CI: 1.8–7.8]) were all positively associated with testing. CONCLUSIONS: A youth-friendly HIV educational video improved adolescents' HIV knowledge and increased their participation in HIV testing more than in-person counseling. video-based HIV counseling can perform as well or better than in-person counseling for adolescents in the ED.

Background Neuregulin (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials employing daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel (HG) to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery. Methods and Results NRG was encapsulated in HG and release over 14 days confirmed by ELISA in vitro. Sprague-Dawly rats were utilized for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, HG, or NRG-HG and evaluated for proliferation. Cardiomyocytes demonstrated EdU and phosphorylated histone-H3 (PH3) positivity in the NRG-HG group only. For in vivo studies, 2 month old mice (n=60) underwent LAD ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG treated mice demonstrated PH3 and Ki67 positivity along with decreased caspase-3 activity compared to all controls. NRG was detected in myocardium 6 days following injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced LVEF, decreased LV area, and augmented borderzone thickness. Conclusions Targeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances LV function in a model of ICM. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics.

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background:Advances in anterior cruciate ligament (ACL) reconstruction procedures in pediatric and adolescent patients have resulted in an increase in recent clinical studies on this topic. However, the consistency with which outcome measures are reported in this demographic is unknown.Purpose:To document outcome reporting patterns of youth ACL reconstruction studies in high-impact journals.Study Design:Systematic review; Level of evidence, 4.Methods:All articles published in 5 high-impact orthopaedic journals from 2010 to 2016 were reviewed to identify those reporting clinical outcomes of young patients who underwent ACL reconstruction. Studies that were nonclinical, reported on patients older than 18 years, or included fewer than 10 patients were excluded. Outcome measures used in all included studies were recorded.Results:Seventeen studies encompassing 772 subjects (mean age, 14.3 years; range, 6.3-18.0 years) were analyzed. Eight studies (47%) reported on Tanner stage of subjects, while 1 study reported skeletal age. Ten studies (59%) clearly documented the presence or absence of surgical complications. Range of motion was reported in 65% of studies. Leg-length discrepancy and angular deformity were each reported in 76% of studies, with 12% quantifying results through radiographic measurements. Ligament testing was variably defined by inclusion of instrumented testing (65%), Lachman test (53%), and pivot-shift test (53%). Fourteen studies (82%) explicitly reported on the rate of ACL rerupture, while 71% reported on the rate of revision surgery. Rate of return to preinjury activity was reported in 8 studies (47%), of which 2 defined criteria for return to sport and 3 defined the level of competitive sport. Patient-reported outcome measures (PROMs) were used variably. For the 3 most commonly reported PROMs (Lysholm, International Knee Documentation Committee, and Tegner), 24% of studies reported all 3 PROMs, 35% of studies reported 2 PROMs, and 6% of studies reported 1 PROM in isolation. A pediatric-specific PROM was reported in 1 of the 17 studies.Conclusion:Studies on pediatric ACL reconstruction published in high-impact journals unreliably defined subjects’ skeletal maturity, inconsistently reported on objective outcome measures, and used disparate adult-validated PROMs to assess subjective outcomes. These findings highlight the need for standardized, pediatric-specific outcome measures to be applied in future studies evaluating ACL reconstruction in children and adolescents.

Background Bernese periacetabular osteotomy (PAO) is a technically challenging procedure with potential risk for major complications and a previously reported steep learning curve. However, the impact of contemporary hip preservation fellowships on the learning curve of PAO has not been established. Questions/purposes (1) What was the frequency of major complications during the PAO learning curve of two surgeons who recently graduated from hip preservation fellowships? (2) Is increasing level of experience associated with the risk of a complication and with operative time, a possible surrogate measure of surgical performance? Methods We retrospectively studied 81 PAOs performed by one of two surgeons who recently graduated from a hip preservation fellowship during their first 4 years of practice in two institutions. One of the surgeons participated as a fellow in 78 PAOs with an increasing level of responsibility during the course of 1 full year. The other surgeon performed 41 PAOs as a fellow during 6 months, also with an increasing level of responsibility during that time. There were 68 (84%) female and 13 (16%) male patients (mean age, 18 years; range, 10-36 years). The frequency of complications was recorded early and at 1 year after surgery and graded according to a validated classification system describing five grades of complications. Complications that required surgical intervention (Grade III) and life-threatening complications (Grade IV) were considered major complications. Persistent pain after surgery, although considered a failure of PAO, was not considered a surgical complication as a result of the multifactorial etiology of pain after hip-preserving surgery. However, early reoperation and revision surgery were counted as complications. To evaluate the association between increasing level of experience and the occurrence of complications, we divided each surgeon's experience into his first 20 procedures (initial interval) and his second 20 (experienced interval) to test whether the incidence of complications or operative time was different between the two intervals. Because the association between experience and the likelihood of a complication was estimated to be consistent between the two surgeons, the analysis was performed with data pooled from the two surgeons. To test whether there was a difference in the likelihood of a complication in the Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical princ...

PurposeThis study aimed to determine the incidence of acetabular dysplasia at six months of age in patients with breech presentation and previously normal hip ultrasounds, reporting primary radiographic measurements to allow for comparison with other patient cohorts.MethodsA retrospective analysis of breech infants with initially normal clinical examinations and hip ultrasounds was performed to determine the rate of subsequent acetabular dysplasia and to characterise the distribution of acetabular index (AI). At approximately six months of age, AI was measured bilaterally on anteroposterior (AP) pelvic radiographs and reported using descriptive statistics.ResultsA total of 94 hips in 47 breech infants were eligible for analysis. All infants demonstrated normal ultrasound findings at a mean age of 6.9 ± 1.7 weeks and returned for follow-up at a mean age of 6.4 ± 0.5 months. On AP pelvic radiographs, mean right hip AI was 25.0°, with an interquartile range (IQR) (25th -75th percentile) of 23° to 27° and mean left hip AI was 25.5°, with an IQR of 22° to 28°. If one applies a single commonly used threshold value for defining dysplasia (AI ≥ 30°), 10/94 hips (10.6%) meet diagnostic criteria. Alternatively, strict adherence to previously established normative AI values stratified by gender and laterality results in 4/94 hips (4.3%) qualifying as significantly dysplastic.ConclusionsThe proportion of breech infants who, despite normal initial ultrasound findings, were diagnosed with dysplasia at six months supports observation of breech-born patients beyond six weeks. Reliance on different threshold values for diagnosing acetabular dysplasia can lead to discrepancies in incidence rates.

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