Variables associated with the prevalence of self-reported work-related musculoskeletal disorders in veterinary laparoscopic surgeons.

OBJECTIVE: To investigate the relationship between physical attributes and difficulty performing laparoscopic maneuvers with the prevalence of self-reported musculoskeletal injury. STUDY DESIGN: Online survey. SAMPLE POPULATION: Surgeons (n = 140) with 3 or more years of laparoscopic experience. METHODS: Electronic survey distributed via LISTSERVEs and Facebook groups. Responses collected included surgeon attributes, presence of musculoskeletal injuries, and surgical practice data. Statistical analysis was performed using the Shapiro-Wilk test, linear regression, logistic regression, and Wilcoxon rank sum tests. RESULTS: A total of 52 of the 140 respondents reported a musculoskeletal injury with 38 specifying at least one injury (72%). Neck strain was the most prevalent reported musculoskeletal injury (18/52, 34.6%), followed by shoulder tendinopathies (16/52, 30.8%), arm/hand tendonitis (8/52, 15.4%), carpal tunnel (7/52, 13.5%), back pain (4/52, 7.7%) and arm/hand arthritis (1/52, 1.9%). Women were significantly more likely to report a musculoskeletal problem than men (p = .011) with the odds of women reporting a musculoskeletal injury 2.59 times greater than men. Women and surgeons with smaller glove sizes were significantly more likely to report shoulder tendonitis (p = .034, p = .1) and neck strain (p = .009, p = .001). Respondents with a musculoskeletal problem experienced significantly more difficulty using rotating cup biopsy forceps (p < .001) and perceived this as difficult a greater amount of time (p = .006). CONCLUSION: Female surgeons report more musculoskeletal injuries than their male counterparts. Surgeons with musculoskeletal injuries experience more difficulty performing particular laparoscopic maneuvers. CLINICAL SIGNIFICANCE: Improving ergonomics for women and surgeons with smaller glove sizes must be prioritized to improve surgeon health and laparoscopic instrument use.

Clinical presentation and short-term outcomes of dogs ≥15 kg with extrahepatic portosystemic shunts.

OBJECTIVE: To describe demographics, clinical presentation, shunt anatomy, clinical progression, and complications in large dogs ≥15 kg with single extrahepatic portosystemic shunts (EHPSS) treated with or without surgery. STUDY DESIGN: Multicenter retrospective (10 university hospitals, one private referral institution). ANIMALS: Dogs ≥15 kg (n = 63). METHODS: Medical records of dogs ≥15 kg diagnosed with EHPSS between January 01, 2005 and December 31, 2020 were reviewed. Dogs had a minimum follow-up of 90 days. Signalment, clinical signs, diagnostics, shunt anatomy, treatment interventions, and perioperative complications were assessed. RESULTS: Median age was 21.9 months (IQR: 9-36.8). The breed most represented was the Golden retriever (17/63 dogs). Portocaval (17/63) and splenocaval (15/63) shunt configurations were most common. Portal vein hypoplasia was noted in 18 imaging reports. Of the surgically treated dogs, 14/45 (35.6%) had short-term complications, and 3/45 (6.7%) had shunt-related deaths. Medical management was discontinued in 15/40 and reduced in 9/40 of surviving dogs who had surgical attenuation. All medically managed, nonattenuated dogs (18/18) were maintained on their original shunt-related medication regimens. CONCLUSIONS: Clinical presentation of dogs ≥15 kg with extrahepatic portosystemic shunts was similar to the more commonly reported small breed dogs. Surgical management of single EHPSS in large dogs ≥15 kg had similar clinical short-term outcomes as small breed dogs. CLINICAL SIGNIFICANCE: Clinicians should be aware that large breed dogs with EHPSS share similar characteristics and clinical outcomes to small breed dogs. The significance of the presence of a hypoplastic portal vein warrants further research. Surgical treatment is a viable option for large breed dogs with EHPSS.

Variables affecting surgeons' use of, and preferences for, instrumentation in veterinary laparoscopy.

OBJECTIVE: To investigate the impact of variables on use and preference of common laparoscopic instruments. STUDY DESIGN: Online survey. SAMPLE POPULATION: Surgeons (n = 140) with 3 years or more laparoscopic experience. METHODS: Electronic survey distributed via specialty group LISTSERVEs and Facebook groups. Responses collected included surgeon attributes, preferences, and surgical practice data. Statistical analysis was performed using Fishers exact, ANOVA, Tukey Kramer honestly significant difference (HSD) test, linear regression, and logistic regression. RESULTS: Ninety-eight of 140 respondents answered instrument-related questions and the completion rate of these questions was 76%: 48% of females and 49% of males responded to the survey. The median glove size of respondents was size 7 (range, 5.5 to 8.5). Closing laparoscopic Babcock forceps (p = .018), rotating cup biopsy forceps (p = .003), and manipulating endoscopic staplers (p < .001) were more difficult for surgeons with smaller glove sizes. The median difficulty score for the endoscopic stapler was 4/10 and the median percentage of time this was found difficult was 25%. Reusable instruments were preferred over disposable single-use instruments. The pistol grip was preferred for grasping and retracting (54/98, 55%) and fine dissection (46/96, 48%), while the axial grip was preferred for suturing and knot tying (61/98, 62%). CONCLUSION: Surgeons with smaller glove sizes (<6.5) experience more difficulty when using common laparoscopic instruments. The endoscopic stapler was the most difficult to use. CLINICAL SIGNIFICANCE: When purchasing laparoscopic instrumentation, surgeons should review all available options in handle size and design to improve ergonomics during minimally invasive procedures.

Healthy Aging Interventions Reduce Repetitive Element Transcripts.

Transcripts from noncoding repetitive elements (REs) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. Here, we analyze REs in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-α-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to a high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. We find that (a) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and high-fat diet (an age-accelerating treatment) increase RE expression; and (b) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. Our results suggest that RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.

Self-selected fluid volume and flavor strength does not alter fluid intake, body mass loss, or physiological strain during moderate-intensity exercise in the heat.

INTRODUCTION: The purpose of this study was to determine the effects of ad libitum flavor and fluid intake on changes in body mass (BM) and physiological strain during moderate intensity exercise in the heat. METHODS: Ten subjects (24±3yrs, 7M/3F) performed 60 min of treadmill walking at 1.3 m/s and 7% grade in an environmental chamber set to 33 °C and 10% relative humidity while carrying a 22.7 kg pack on two different occasions. Subjects consumed either plain water or water plus flavor (Infuze), ad libitum, at each visit. Pre and post exercise, fluid consumption (change in fluid reservoir weight) and BM (nude) were measured. During exercise, heart rate (HR), systolic blood pressure (SBP), rate of perceived exertion (RPE), oxygen consumption (VO2), respiratory exchange ratio (RER), core temperature (TC), and physiological strain index (PSI) were recorded every 15 min during exercise. RESULTS: No significant differences were observed for fluid consumption between fluid conditions (512 ± 97.2 mL water vs. 414.3 ± 62.5 mL Infuze). Despite a significant decrease from baseline, there were no significant differences in overall change of BM (Δ -1.18 vs. -0.64 Kg) or percent body weight loss for water and Infuze conditions, respectively (1.58 ± 0.6 and 0.79 ± 0.2%). Furthermore, there were no significant differences in HR (144 ± 6 vs. 143 ± 8 bpm), SBP (157 ± 5 vs. 155 ± 5 mmHg), RPE, VO2 (27.4 ± 0.9 vs. 28.1 ± 1.2 ml/Kg/min), RER, TC (38.1 ± 0.1 vs. 37.0 ± 0.1 °C), and peak PSI (5.4 ± 0.4 vs. 5.7 ± 0.8) between conditions. CONCLUSIONS: Offering individuals the choice to actively manipulate flavor strength did not significantly influence ad libitum fluid consumption, fluid loss, or physiological strain during 60 min of moderate intensity exercise in the heat.

Progestin therapy for obese women with complex atypical hyperplasia: levonorgestrel-releasing intrauterine device vs systemic therapy.

BACKGROUND: Though hysterectomy remains the standard treatment for complex atypical hyperplasia, patients who desire fertility or who are poor surgical candidates may opt for progestin therapy. However, the effectiveness of the levonorgestrel-releasing intrauterine device compared to systemic therapy in the treatment of complex atypical hyperplasia has not been well studied. OBJECTIVE: We sought to examine differences in treatment response between local progestin therapy with the levonorgestrel-releasing intrauterine device and systemic progestin therapy in women with complex atypical hyperplasia. METHODS: This single-institution retrospective study examined women with complex atypical hyperplasia who received progestin therapy between 2003 and 2018. Treatment response was assessed by histopathology on subsequent biopsies. Time-dependent analyses of complete response and progression to cancer were performed comparing the levonorgestrel-releasing intrauterine device and systemic therapy. A propensity score inverse probability of treatment weighting model was used to create a weighted cohort that differed based on treatment type but was similar with respect to other characteristics. An interaction-term analysis was performed to examine the impact of body habitus on treatment response, and an interrupted time-series analysis was employed to assess if changes in treatment patterns correlated with outcomes over time. RESULTS: A total of 245 women with complex atypical hyperplasia received progestin therapy (levonorgestrel-releasing intrauterine device n = 69 and systemic therapy n = 176). The mean age and body mass index were 36.9 years and 40.0 kg/m2, respectively. In the patient-level analysis, women who received the levonorgestrel-releasing intrauterine device had higher rates of complete response (78.7% vs 46.7%; adjusted hazard ratio, 3.32; 95% confidence interval, 2.39-4.62) and a lower likelihood of progression to cancer (4.5% vs 15.7%; adjusted hazard ratio, 0.28; 95% confidence interval, 0.11-0.73) compared to those who received systemic therapy. In particular, women with class III obesity derived a higher relative benefit from levonorgestrel-releasing intrauterine device therapy in achieving complete response compared to systemic therapy: class III obesity, adjusted hazard ratio 4.72, 95% confidence interval 2.83-7.89; class I-II obesity, adjusted hazard ratio 1.83, 95% confidence interval 1.09-3.09; and nonobese, adjusted hazard ratio 1.26, 95% confidence interval 0.40-3.95. In the cohort-level analysis, the obesity rate increased during the study period (77.8% to 88.2%, 13.4% relative increase, P = .033) and levonorgestrel-releasing intrauterine device use significantly increased after 2007 (6.3% to 82.7%, 13.2-fold increase, P < .001), both concomitant with a higher proportion of women achieving complete response (32.9% to 81.4%, 2.5-fold increase, P = .005). CONCLUSION: Our study suggests that local therapy with the levonorgestrel-releasing intrauterine device may be more effective than systemic therapy for women with complex atypical hyperplasia who opt for nonsurgical treatment, particularly in morbidly obese women. Shifts in treatment paradigm during the study period toward increased levonorgestrel-releasing intrauterine device use also led to improved complete response rates despite increasing rates of obesity.

Controlling a burn: outer-sphere gating of hydroxylamine oxidation by a distal base in cytochrome P460.

Ammonia oxidizing bacteria (AOB) use the cytotoxic, energetic molecule hydroxylamine (NH2OH) as a source of reducing equivalents for cellular respiration. Despite disproportionation or violent decomposition being typical outcomes of reactions of NH2OH with iron, AOB and anammox heme P460 proteins including cytochrome (cyt) P460 and hydroxylamine oxidoreductase (HAO) effect controlled, stepwise oxidation of NH2OH to nitric oxide (NO). Curiously, a recently characterized cyt P460 variant from the AOB Nitrosomonas sp. AL212 is able to form all intermediates of cyt P460 catalysis, but is nevertheless incompetent for NH2OH oxidation. We now show via site-directed mutagenesis, activity assays, spectroscopy, and structural biology that this lack of activity is attributable to the absence of a critical basic glutamate residue in the distal pocket above the heme P460 cofactor. This substitution is the only distinguishing characteristic of a protein that is otherwise effectively structurally and spectroscopically identical to an active variant. This highlights and reinforces a fundamental principal of metalloenzymology: metallocofactor inner-sphere geometric and electronic structures are in many cases insufficient for imbuing reactivity; a precisely defined outer coordination sphere contributed by the polypeptide matrix can be the key differentiator between a metalloenzyme and an unreactive metalloprotein.

Endometrial preparation for third-party parenting and cryopreserved embryo transfer.

The advent of third party parenting ushered in the era of artificial stimulation of the endometrium. Initially intended only for patients with ovarian failure, exogenous induction of endometrial receptivity was quickly shown to be as good as natural endometrial preparation, with the advantage that the timing of embryo transfer could be controlled. It is perhaps surprising that even though the ovary produces a variety of steroids, that estradiol (E2) and progesterone (P) alone would be needed to achieve optimal receptivity; no other substance has ever been shown to improve on the basic regimen of E2 and P. A variety of routes of administration are available for both E2 and P and physiologic (or supraphysiologic) serum or endometrial tissue levels of both can be achieved. The optimal duration of E2 stimulation and the timing of the onset of P administration continue to be debated, but it appears that imitating the sequence that normally occurs in nature leads to optimal results. The poorly responsive endometrium and cases of recurrent implantation failure remain a challenge, but the clear majority of patients can successfully achieve pregnancy as long as embryos of adequate quality are transferred.

The Eponymous Cofactors in Cytochrome P460s from Ammonia-Oxidizing Bacteria Are Iron Porphyrinoids Whose Macrocycles Are Dibasic.

The enzymes hydroxylamine oxidoreductase and cytochrome (cyt) P460 contain related unconventional "heme P460" cofactors. These cofactors are unusual in their inclusion of nonstandard cross-links between amino acid side chains and the heme macrocycle. Mutagenesis studies performed on the Nitrosomonas europaea cyt P460 that remove its lysine-heme cross-link show that the cross-link is key to defining the spectroscopic properties and kinetic competence of the enzyme. However, exactly how this cross-link confers these features remains unclear. Here we report the 1.45 Å crystal structure of cyt P460 from Nitrosomonas sp. AL212 and conclude that the cross-link does not lead to a change in hybridization of the heme carbon participating in the cross-link but rather enforces structural distortions to the macrocycle away from planarity. Time-dependent density functional theory coupled to experimental structural and spectroscopic analysis suggest that this geometric distortion is sufficient to define the spectroscopic properties of the heme P460 cofactor and provide clues toward establishing a relationship between heme P460 electronic structure and function.

Effects of mandatory screening labs in directing the disposition of the apparently healthy psychiatric patient in the emergency department.

OBJECTIVE: To determine whether mandatory psychiatric admission laboratory tests yield results that change the disposition of a patient with primary psychiatric complaint from admission to a psychiatric service to admission to a medical service. METHODS: This was a single center retrospective cohort chart review study approved by the facility Institutional Review Board in which we used a records database maintained by the emergency department's social workers to access the records of every patient that presented to our emergency department with a psychiatric chief complaint between the dates of December 1, 2011, and December 1, 2013. We focused on those that were admitted to either a psychiatric service or a medical service after a thorough evaluation by the department of social work and an emergency provider. We applied our inclusion and exclusion criteria and reviewed the results of the mandatory psychiatric laboratory tests (complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, acetaminophen, aspirin, blood alcohol level, urinalysis, urine pregnancy test, urine drug screen) required for admission. Our independent variables were the compulsory psychiatric admission laboratory tests and our dependent variable was the admission to a medical service. RESULTS: Of 5,606 laboratory tests that were ordered and produced results for the 682 patients enrolled in our study, 51 results were considered clinically significant abnormal results, or results requiring treatment prior to psychiatric service admission, by the 2 reviewing emergency physicians. Only one of 682 psychiatric patients received a final disposition to a medical service based upon abnormal laboratory studies. That patient presented without any medical complaints but a chief complaint of "suicidal ideation," and was found to have diabetic ketoacidosis. Based on our data, the probability that an abnormal laboratory test will result in a change in disposition is 1/682=0.1% (95% CI: 0.0% to 0.9%). CONCLUSION: Patients presenting to the emergency department with a psychiatric chief complaint and no physical complaints, abnormal vital signs, or abnormal physical exam findings have less than 1% probability that an abnormal laboratory study will change their disposition from a psychiatric admission to a medical admission.

A Sequentially Priming Phosphorylation Cascade Activates the Gliomagenic Transcription Factor Olig2.

During development of the vertebrate CNS, the basic helix-loop-helix (bHLH) transcription factor Olig2 sustains replication competence of progenitor cells that give rise to neurons and oligodendrocytes. A pathological counterpart of this developmental function is seen in human glioma, wherein Olig2 is required for maintenance of stem-like cells that drive tumor growth. The mitogenic/gliomagenic functions of Olig2 are regulated by phosphorylation of a triple serine motif (S10, S13, and S14) in the amino terminus. Here, we identify a set of three serine/threonine protein kinases (glycogen synthase kinase 3α/ß [GSK3α/ß], casein kinase 2 [CK2], and cyclin-dependent kinases 1/2 [CDK1/2]) that are, collectively, both necessary and sufficient to phosphorylate the triple serine motif. We show that phosphorylation of the motif itself serves as a template to prime phosphorylation of additional serines and creates a highly charged "acid blob" in the amino terminus of Olig2. Finally, we show that small molecule inhibitors of this forward-feeding phosphorylation cascade have potential as glioma therapeutics.

Efficiency improvement in the operating room.

BACKGROUND: In the changing health care environment, health systems, hospitals, and health care providers must focus on improving efficiency to meet an increasing demand for high-quality, low-cost health care. Much has been written about strategies and efforts to improve efficiency in the perioperative periods, yet the time when the patient is in the operating room-the intraoperative period-has received less attention. Yet, this is the period in which surgeons may have the most influence. METHODS: Systematically review published efforts to improve intraoperative efficiency; assess the outcomes of these efforts, and propose standardized reporting of future studies. RESULTS: A total of 39 studies were identified that met inclusion criteria. These divided naturally into small (single operative team), medium (multi-operative team), and large (institutional) interventions. Most studies used time or money as their metric for efficiency, though others were used as well. CONCLUSIONS: There is substantial opportunity to enhance operating room efficiency during the intraoperative period. Surgeons may have a particular role in procedural efficiency, which has been relatively unstudied. Common themes were standardizing tasks, collecting and using actionable data, and maintaining effective team communication.

Deliveries from trophectoderm biopsied, fresh and vitrified blastocysts derived from polar body biopsied, vitrified oocytes.

This longitudinal study reports preliminary findings of six patients who underwent first polar body biopsy followed by oocyte vitrification. All oocytes were warmed, inseminated by intracytoplasmic sperm injection and cultured to blastocyst. All suitable blastocysts underwent trophectoderm biopsy for aneuploidy screening, and supernumerary blastocysts were vitrified. Euploid blastocysts were transferred either fresh or in a subsequent programmed cycle. Of the 91 metaphase II oocytes, 30 had euploid first polar bodies. Development to blastocyst was more likely in oocytes with a euploid first polar body (66.7% versus 24.6%; P < 0.001). Nineteen euploid blastocysts were produced: 10 from oocytes with a euploid first polar body and nine from oocytes with an aneuploid first polar body. Five out of six patients (83%) had a live birth or ongoing pregnancy at the time of analysis. Eleven euploid blastocysts have been transferred and seven implanted (64%). Although the chromosomal status of the first polar body was poorly predictive of embryonic ploidy, an association was found between chromosomal status of the first polar body and development to blastocyst. Further study is required to characterize these relationships, but proof of concept is provided that twice biopsied, twice cryopreserved oocytes and embryos can lead to viable pregnancies.

GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.

GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3ß in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/ß-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins.DOI: http://dx.doi.org/10.7554/eLife.02663.001.

Experiences in fertility preservation: lessons learned to ensure that fertility and reproductive autonomy remain options for cancer survivors.

PURPOSE: Assess fertility preservation (FP) measures chosen by patients newly diagnosed with malignancy and their outcomes. METHODS: Reproductive-age patients referred for FP underwent counseling and elected cryopreservation vs. no treatment. Outcome measures included ovarian stimulation, FP choice, oocytes/zygotes retrieved/cryopreserved and pregnancy outcome. RESULTS: From 2005 to 2012, 136 patients were counseled with 124 electing treatment: 83 oocyte-only, 21 oocyte + zygote and 20 zygote-only cryopreservation. Age, partnership and financial status factored into FP choice. Treatment was completed in 12 ± 2 days with 14 ± 11 metaphase-II oocytes harvested and cryopreserved/cycle. Eight patients returned to attempt pregnancy; three succeeded. CONCLUSIONS: Our data demonstrate that oocyte and/or zygote banking are feasible FP options for women with malignancy; given the choice, the majority elected oocyte cryopreservation, highlighting desire for reproductive autonomy. Continued growth and research, combined with interdisciplinary communication, will ensure that appropriate candidates are offered FP and the potential for future parenthood, an important quality-of-life marker for survivors.

Mouse retinal progenitor cell dynamics on electrospun poly (ϵ-caprolactone).

Age-related macular degeneration, retinitis pigmentosa and glaucoma are among the many retinal degenerative diseases where retinal cell death leads to irreversible vision loss and blindness. Working toward a cell-replacement-based therapy for such diseases, a number of research groups have recently evaluated the feasibility of using retinal progenitor cells (RPCs) cultured and transplanted on biodegradable polymer substrates to replace damaged retinal tissue. Appropriate polymer substrate design is essential to providing a three-dimensional environment that can facilitate cell adhesion, proliferation and post-transplantation migration into the host environment. In this study, we have designed and fabricated a novel, ultra-thin electrospun poly(ϵ-caprolactone) (PCL) scaffold with microscale fiber diameters, appropriate porosity for infiltration by RPCs, and biologically compatible mechanical characteristics. We have verified that our electrospun PCL scaffold supports robust mouse RPC proliferation, adhesion, and differentiation in vitro, as well as migration into mouse retinal explants. These promising results make PCL a strong candidate for further development as a cell transplantation substrate in retinal regenerative research.

The use of progenitor cell/biodegradable MMP2-PLGA polymer constructs to enhance cellular integration and retinal repopulation.

The inability of the adult mammalian retina to regenerate can be partly attributed to the expression of injury-induced inhibitory extracellular matrix (ECM) and cell adhesion molecules. In particular, photoreceptor degeneration stimulates deposition of the inhibitory ECM proteins neurocan and CD44 at the outer limits of the dystrophic retina, where they act as a barrier against cellular migration and axonal extension. We have previously shown that degradation of these molecules, via induction of MMP2, promotes host-donor integration and retinal repopulation following transplantation. Here we present a biodegradable/biocompatible polymer scaffold that has the ability to deliver MMP2, in conjunction with retinal progenitor cells, directly to the site of retinal injury in an attempt to enhance cellular integration and promote retinal repopulation. Pre-activated MMP2, loaded into a PLGA polymer, maintained its activity throughout polymer fabrication and hydrolysis. Following delivery, significant degradation of CD44 and neurocan from the outer limits of the dystrophic retina, without further disruption of retinal architecture, was observed. As a result, the number of retinal progenitor cells that migrated beyond the glial barrier into the degenerating host increased significantly. These cells took up residence in the retinal outer nuclear layer, adopted appropriate photoreceptor morphology and expressed the mature photoreceptor markers recoverin and rhodopsin. Thus, we have created a cell delivery platform that upon transplantation provides controlled release of active-MMP2 directly to the site of retinal injury, stimulating inhibitory ECM barrier removal and enhancement of stem cell integration and retinal repopulation.

Multiplex bead array assays for detection of soluble cytokines: comparisons of sensitivity and quantitative values among kits from multiple manufacturers.

BACKGROUND: Multiplex bead array assays permit simultaneous cytometric quantitation of multiple cytokines in solution by capturing these to spectrally distinct beads. Because several manufacturers offer reagents to quantitate the same cytokines on a single instrument, a comparison should be made to determine whether these kits yield similar data and whether these data are comparable to enzyme-linked immunosorbent assay (ELISA). METHODS: This study compared cytokine detection kits by using Luminex 100. Twenty-six serum samples from seven subjects were analyzed for interferon-gamma, interleukins 1beta, 6, and 8, and tumor necrosis factor-alpha by using multiplex kits from LINCO Research, Bio-Rad Laboratories, R&D Systems, and BioSource International. Each assay was performed according to the manufacturers' specifications. Standard curves were generated by using reference concentrations supplied by each manufacturer. ELISAs for interleukin-8 were performed by using kits from R&D and BioSource. RESULTS: Cytokine levels followed similar patterns, although absolute concentrations differed among kits. ELISA and Luminex values for interleukin-8 were similar in kits from the same manufacturer. CONCLUSIONS: Because relative cytokine measurements are often valuable when performed serially, it may be possible to make interlaboratory comparisons by using different kits. When comparison of absolute values is crucial, kits from the same supplier should be used. Within-vendor, bead array, and ELISA values appear comparable.

A patient with an epignathus: management of a large oropharyngeal teratoma in a newborn.

An epignathus is an oropharyngeal teratoma composed of cells from ectodermal, mesodermal, and endodermal layers. Epignathi that arise from the palate or pharynx and protrude from the mouth result in life-threatening airway obstruction and usually cause asphyxiation shortly after birth. In our reported case, an antenatal ultrasound diagnosis allowed for preparation of an ex utero intrapartum treatment (EXIT) procedure. A tracheostomy was performed at birth with maternal-fetal blood flow still intact through the umbilical cord. Debulking of the large extraoral portion of the tumor, followed by complete intraoral resection, was performed. Masseteric function and swallowing slowly improved over several weeks. Cleft palate repair is planned at 10 months of age. In the following report, the histology, classification, and pathogenesis of these "parasitic" tumors are reviewed.

Correction of upper airway obstruction in the newborn with internal mandibular distraction osteogenesis.

Tracheostomy for management of neonatal airway obstruction may be life saving but is associated with complications and developmental problems. As an alternative, the effectiveness of internal mandibular distraction osteogenesis was investigated in select neonatal patients with micrognathia and upper airway obstruction. Preoperative tests (sleep study, direct laryngobronchoscopy, and "milk scan" for GI reflux) were used to select appropriate candidates for the procedure. Excluded were patients with 1) central apnea, 2) severe reflux, 3) other airway lesions, and 4) mild to moderate obstruction controlled by positioning. Of 44 newborns (aged <3 weeks) with upper airway obstruction and micrognathia seen in the neonatal intensive care unit, 19 underwent tracheostomy, 10 were discharged with home monitoring and positional instructions, and 15 underwent bilateral mandibular lengthening with microdistractors. Of those who underwent mandibular distraction, a tracheostomy was avoided in 14 of 15 patients. Relative improvement in the posterior airway space was seen on 3D CT scans, cephalograms, and laryngobronchoscopies obtained preoperatively, postoperatively, and during follow-up evaluation. One of these 15 patients required a tracheostomy for postoperative central apnea. In an average of just 4.5 days following completion of distraction, patients were discharged home with improved oral feeding and no feeding tube. This study suggests that for selected newborns, the use of internal microdistractors allows for avoidance of a tracheostomy and improved oral feeding.