The Risk of Sympathetic Ophthalmia Associated with Open-Globe Injury Management Strategies: A Meta-analysis.

TOPIC: Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary repair, as a risk management strategy after open-globe injury (OGI) remains controversial. CLINICAL RELEVANCE: This systematic review was conducted to report the incidence of SO after primary repair compared with that of after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat. METHODS: Five journal databases were searched. This review was registered with International Prospective Register of Systematic Reviews (identifier, CRD42021262616). Searches were carried out on June 29, 2021, and were updated on December 10, 2022. Prospective or retrospective studies that reported outcomes (including SO or lack of SO) in a patient population who underwent either primary repair and primary enucleation or primary evisceration were included. A systematic review and meta-analysis were carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR). RESULTS: Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total, 7620 OGIs met the criteria for inclusion in this analysis; SO developed in 21 patients with OGI. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval [CI], 0.00%-0.25%) after OGI. Of 779 patients who underwent primary enucleation or primary evisceration, no SO cases were reported, resulting in a pooled SO estimate of 0.05% (95% CI, 0.00%-0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI, 0.00%-0.33%). The ARR using a random effects model was -0.0010 (in favour of eye removal; 95% CI, -0.0031 [in favor of eye removal] to 0.0011 [in favor of primary repair]). Grading of Recommendations, Assessment, Development, and Evaluations analysis highlighted a low certainty of evidence because the included studies were observational, and a risk of bias resulted from missing data. DISCUSSION: Based on the available data, no evidence exists that primary enucleation or primary evisceration reduce the risk of secondary SO. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Specialized Ribosomes in Health and Disease.

Ribosomal heterogeneity exists within cells and between different cell types, at specific developmental stages, and occurs in response to environmental stimuli. Mounting evidence supports the existence of specialized ribosomes, or specific changes to the ribosome that regulate the translation of a specific group of transcripts. These alterations have been shown to affect the affinity of ribosomes for certain mRNAs or change the cotranslational folding of nascent polypeptides at the exit tunnel. The identification of specialized ribosomes requires evidence of the incorporation of different ribosomal proteins or of modifications to rRNA and/or protein that lead(s) to physiologically relevant changes in translation. In this review, we summarize ribosomal heterogeneity and specialization in mammals and discuss their relevance to several human diseases.

SRPassing Co-translational Targeting: The Role of the Signal Recognition Particle in Protein Targeting and mRNA Protection.

Signal recognition particle (SRP) is an RNA and protein complex that exists in all domains of life. It consists of one protein and one noncoding RNA in some bacteria. It is more complex in eukaryotes and consists of six proteins and one noncoding RNA in mammals. In the eukaryotic cytoplasm, SRP co-translationally targets proteins to the endoplasmic reticulum and prevents misfolding and aggregation of the secretory proteins in the cytoplasm. It was demonstrated recently that SRP also possesses an earlier unknown function, the protection of mRNAs of secretory proteins from degradation. In this review, we analyze the progress in studies of SRPs from different organisms, SRP biogenesis, its structure, and function in protein targeting and mRNA protection.

Loss of Preproinsulin Interaction with Signal Recognition Particle Activates Protein Quality Control, Decreasing mRNA Stability.

Many insulin gene variants alter the protein sequence and result in monogenic diabetes due to insulin insufficiency. However, the molecular mechanisms of various disease-causing mutations are unknown. Insulin is synthesized as preproinsulin containing a signal peptide (SP). SPs of secreted proteins are recognized by the signal recognition particle (SRP) or by another factor in a SRP-independent pathway. If preproinsulin uses SRP-dependent or independent pathways is still debatable. We demonstrate by the use of site-specific photocrosslinking that the SRP subunit, SRP54, interacts with the preproinsulin SP. Moreover, SRP54 depletion leads to the decrease of insulin mRNA and protein expression, supporting the involvement of the RAPP protein quality control in insulin biogenesis. RAPP regulates the quality of secretory proteins through degradation of their mRNA. We tested five disease-causing mutations in the preproinsulin SP on recognition by SRP and on their effects on mRNA and protein levels. We demonstrate that the effects of mutations are associated with their position in the SP and their severity. The data support diverse molecular mechanisms involved in the pathogenesis of these mutations. We show for the first time the involvement of the RAPP protein quality control pathway in insulin biogenesis that is implicated in the development of neonatal diabetes caused by the Leu13Arg mutation.

A multi-center analysis of visual outcomes following open globe injury.

The purpose of this study was to examine how demographics, etiology, and clinical examination findings are related to visual outcomes in subjects with open globe injury (OGI) across a large and generalizable sample. A retrospective cohort analysis was performed using data collected from the electronic medical records of four tertiary university centers for subjects with OGI presenting from 2018 to 2021. Demographic information, injury mechanisms, clinical exam findings, visual acuity (VA) at presentation and most recent follow-up were recorded. In subjects with bilateral OGIs, only right eyes were included. A modified ocular trauma score (OTS) using presenting VA, the presence of perforating injury, OGI, and afferent pupillary defect was calculated. The risk of subjects' demographic characteristics, ocular trauma etiology, clinical findings and modified OTS on the presence of monocular blindness at follow-up were assessed using univariable and multivariable regression models. 1426 eyes were identified. The mean age was 48.3 years (SD: ± 22.4 years) and the majority of subjects were men (N = 1069, 75.0%). Univariable analysis demonstrated that subjects of Black race were 66% (OR: 1.66 [1.25-2.20]; P < 0.001) more likely to have monocular blindness relative to White race at follow-up. OTS Class 1 was the strongest predictor of blindness (OR: 38.35 [21.33-68.93]; P < 0.001). Based on multivariable analysis, lower OTS category (OTS Class 1 OR: 23.88 [16.44-45.85]; P < 0.001) moderately predicted visual outcomes (R2 = 0.275, P < 0.001). OGI has many risks of poor visual outcome across patient groups that vary by demographic category, mechanism of injury, and clinical presentation. Our findings validate that a modified OTS remains a strong predictor of visual prognosis following OGI in a large and generalizable sample.

Pathogenic signal peptide variants in the human genome.

Secreted and membrane proteins represent a third of all cellular proteins and contain N-terminal signal peptides that are required for protein targeting to endoplasmic reticulum (ER). Mutations in signal peptides affect protein targeting, translocation, processing, and stability, and are associated with human diseases. However, only a few of them have been identified or characterized. In this report, we identified pathogenic signal peptide variants across the human genome using bioinformatic analyses and predicted the molecular mechanisms of their pathology. We recovered more than 65 thousand signal peptide mutations, over 11 thousand we classified as pathogenic, and proposed framework for distinction of their molecular mechanisms. The pathogenic mutations affect over 3.3 thousand genes coding for secreted and membrane proteins. Most pathogenic mutations alter the signal peptide hydrophobic core, a critical recognition region for the signal recognition particle, potentially activating the Regulation of Aberrant Protein Production (RAPP) quality control and specific mRNA degradation. The remaining pathogenic variants (about 25%) alter either the N-terminal region or signal peptidase processing site that can result in translocation deficiencies at the ER membrane or inhibit protein processing. This work provides a conceptual framework for the identification of mutations across the genome and their connection with human disease.

Perspectives of Resident and Attending Ophthalmologists on Common Ethical Dilemmas in Research.

Purpose To assess how resident and attending ophthalmologists perceive and evaluate ethically controversial scenarios regarding mentorship, authorship, and ethics compliance that may occur during research involving residents. Methods An online survey was developed and contained 14 controversial vignettes based on common research scenarios that can occur when conducting research with trainees. The scenarios were designed to capture issues regarding three themes: mentorship, authorship, and compliance with ethical guidelines. Resident and attending ophthalmologists at eight military and civilian academic residency programs in the United States were invited to participate. Respondents used a Likert scale to assess the ethicality of the situations in addition to self-reported demographic characteristics. Results The response rate was 35.6% (77/216), consisting of 37.7% ( n = 29) residents and 62.3% ( n = 48) attendings. More attending ophthalmologists responded than residents ( p = 0.004). Many respondents identified controversies around compliance (67.3%) and authorship (57.1%) as unethical, whereas situations regarding mentorship were largely viewed as neutral to ethical (68.0%). Responses to two scenarios, one regarding mentorship and one regarding authorship, significantly differed between residents and attendings ( p = 0.001 and p = 0.022, respectively). Conclusion Academic ophthalmologists' perceptions of the ethicality of common research scenarios varied. There is a need for more prescriptive guidelines for authorship and mentorship ethics at all training levels to ensure consistency, fairness, and integrity of research.

The Use of Preoperative Prophylactic Systemic Antibiotics for the Prevention of Endopthalmitis in Open Globe Injuries: A Meta-Analysis.

TOPIC: This study reports the effect of systemic prophylactic antibiotics (and their route) on the risk of endophthalmitis after open globe injury (OGI). CLINICAL RELEVANCE: Endophthalmitis is a major complication of OGI; it can lead to rapid sight loss in the affected eye. The administration of systemic antibiotic prophylaxis is common practice in some health care systems, although there is no consensus on their use. METHODS: PubMed, CENTRAL, Web of Science, CINAHL, and Embase were searched. This was completed July 6, 2021 and updated December 10, 2022. We included randomized and nonrandomized prospective studies which reported the rate of post-OGI endophthalmitis when systemic preoperative antibiotic prophylaxis (via the oral or IV route) was given. The Cochrane Risk of Bias tool and ROBINS-I tool were used for assessing the risk of bias. Where meta-analysis was performed, results were reported as an odds ratio. PROSPERO registration: CRD42021271271. RESULTS: Three studies were included. One prospective observational study compared outcomes of patients who had received systemic or no systemic preoperative antibiotics. The endophthalmitis rates reported were 3.75% and 4.91% in the systemic and no systemic preoperative antibiotics groups, a nonsignificant difference (P = 0.68). Two randomized controlled trials were included (1555 patients). The rates of endophthalmitis were 17 events in 751 patients (2.26%) and 17 events in 804 patients (2.11%) in the oral antibiotics and IV (± oral) antibiotics groups, respectively. Meta-analysis demonstrated no significant differences between groups (odds ratio, 1.07; 95% confidence interval, 0.54-2.12). CONCLUSIONS: The incidences of endophthalmitis after OGI were low with and without systemic antibiotic prophylaxis, although high-risk cases were excluded in the included studies. When antibiotic prophylaxis is considered, there is moderate evidence that oral antibiotic administration is noninferior to IV. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

New-Onset Headache and Abnormal Eye Movements in a Four-Year-Old Child: Indicators of Increased Intracranial Pressure.

A four-year-old previously healthy child presented with new-onset, diffuse, severe headache, and left sixth nerve palsy. The child was evaluated at several acute care facilities, at which the symptom of "crossing eyes" was not addressed specifically. At our emergency department, on day 6 of symptoms, a left cranial nerve 6 palsy was diagnosed; on brain MRI scan, there was evidence of increased intracranial pressure (distended optic nerve sheaths, flattened posterior sclerae), which was confirmed by lumbar puncture, which showed an opening pressure of >36 cm H2O. Idiopathic intracranial hypertension (IIH) was diagnosed, and all symptoms abated with two months of treatment with acetazolamide. IIH should be considered in a child with headache and abnormal eye movements.

Hsp40/JDP Requirements for the Propagation of Synthetic Yeast Prions.

Yeast prions are protein-based transmissible elements, most of which are amyloids. The chaperone protein network in yeast is inexorably linked to the spreading of prions during cell division by fragmentation of amyloid prion aggregates. Specifically, the core "prion fragmentation machinery" includes the proteins Hsp104, Hsp70 and the Hsp40/J-domain protein (JDP) Sis1. Numerous novel amyloid-forming proteins have been created and examined in the yeast system and occasionally these amyloids are also capable of continuous Hsp104-dependent propagation in cell populations, forming synthetic prions. However, additional chaperone requirements, if any, have not been determined. Here, we report the first instances of a JDP-Hsp70 system requirement for the propagation of synthetic prions. We utilized constructs from a system of engineered prions with prion-forming domains (PrDs) consisting of a polyQ stretch interrupted by a single heterologous amino acid interspersed every fifth residue. These "polyQX" PrDs are fused to the MC domains of Sup35, creating chimeric proteins of which a subset forms synthetic prions in yeast. For four of these prions, we show that SIS1 repression causes prion loss in a manner consistent with Sis1's known role in prion fragmentation. PolyQX prions were sensitive to Sis1 expression levels to differing degrees, congruent with the variability observed among native prions. Our results expand the scope known Sis1 functionality, demonstrating that Sis1 acts on amyloids broadly, rather than through specific protein-protein interactions with individual yeast prion-forming proteins.

Ghost and Honorary Authorship in Ophthalmology: A Cross-Sectional Survey.

PURPOSE: To evaluate the rates of ghost and honorary authorship in ophthalmology and to determine risk factors associated with ghost and honorary authorship. DESIGN: Cross-sectional survey. METHODS: Corresponding authors of articles published in Ophthalmology, JAMA Ophthalmology, and the American Journal of Ophthalmology from June 2019 to December 2020 were emailed an electronic survey. The rates of ghost and honorary authorship, demographic characteristics of the corresponding authors with and without ghost and honorary authorship, and risk factors for ghost and honorary authorship were evaluated. RESULTS: Corresponding authors (n = 830) were emailed a survey and 278 total responses (34.1%) were received; 227 responses (27.9%) were complete and included for analysis. Most respondents (n = 206, 90.7%) believed that the International Committee of Medical Journal Editors (ICMJE) guidelines for authorship adequately address criteria for authorship. Twenty-seven corresponding authors (11.9%) reported characteristics of their articles that indicated the presence of both ghost and honorary authorship (95% CI, 7.7%-16.1%). One hundred fifteen (50.7%) reported honorary authorship (44.2%-57.2%), and 37 (16.3%) indicated ghost authorship (11.5%-21.1%). Being a resident or fellow corresponding author increased the risk of honorary authorship (OR 11.75; 1.91-231.57; P = .03). There were no factors that predicted articles having ghost authors. CONCLUSIONS: While many authors believe the ICMJE guidelines for authorship comprehensively delineate fair authorship practices, listing authors on scientific publications honorarily and excluding authors who qualify for authorship are relatively common practices in ophthalmological research. Further investigation into the drivers of honorary and ghost authorship practices in ophthalmology, and the effectiveness of preventive measures are needed to ensure fair authorship attributions.

Global Current Practice Patterns for the Management of Open Globe Injuries.

PURPOSE: To determine global current practice patterns for the management of open globe injuries and identify areas of variation. DESIGN: Cross-sectional survey. METHODS: An online survey assessed global management paradigms for open globe injuries from August 2020 to January 2021. Responses were collected from experts at eye trauma centers and emergency departments worldwide who manage ≥1 open globe injury per month. The survey assessed the use/selection of antibiotics and steroids, procedural and imaging decisions, and admission practices for open globe injuries. RESULTS: Responses were received from representatives of 36 of 42 institutions (85.7%), of which 33 (78.6%) had sufficient trauma volume to be included. Included responses were distributed across North America (n=12, 36.4%), Asia (n=12, 36.4%), South America (n=4, 12.1%), Africa (n=3, 9.1%), Europe (n=1, 3.0%), and Australia (n=1, 3.0%). Preoperative systemic antibiotics for open globe injuries were administered by 75.8% (n = 25/33) of institutions, while 30.3% (n = 10/33) administered preoperative topical antibiotics. Intraoperative ophthalmic antibiotics for open globe injuries were used by 54.5% (n = 18/33) of experts. Most institutions also administered postoperative systemic antibiotics (n = 23 [69.7%]) and topical steroids (n = 29 [87.9%]), although specific medication choices diverged. At 19 responding centers (61.3% of the 31 that had trainees), residents participated in surgical repairs. Many institutions discharged patients after repair, but 54.5% (n = 18/33) of locations routinely admitted them for observation. CONCLUSIONS: Preferred management practices for open globe injuries vary widely. To ensure the highest standard of care for all patients, evidence-based international guidelines for the treatment of these injuries are needed.

Global Current Practice Patterns for the Management of Exogenous Endophthalmitis: A Survey by the American Society of Ophthalmic Trauma.

OBJECTIVE: To investigate the global practice patterns for the management of exogenous endophthalmitis. METHODS: This cross-sectional study was conducted to assess global practice patterns for the management of exogenous endophthalmitis. An online survey comprised of questions regarding the management of exogenous endophthalmitis was distributed to institutions who are members of International Globe and Adnexal Trauma Epidemiology Study Group (IGATES) or invited affiliates of the American Society of Ophthalmic Trauma and the Asia Pacific Ophthalmic Trauma Society. Responses were gathered from August 2020 to January 2021. RESULTS: Of 42 institutions, 36 responses were received (86% response rate), of which 33 (79%) were included in the analysis. Included centers were from Asia (36%), North America (36%), South America (12%), Africa (9%), Europe (3%), and Australia (3%). Oral antibiotics were administered in 19 (58%) institutions, with moxifloxacin as the preferred agent (n = 9, 27%). The preferred method for obtaining cultures was vitreous tap (n = 25, 76%). Most institutions (n = 26, 79%) routinely administered intravitreal vancomycin and ceftazidime, while intravitreal steroids were routinely administered at 11 centers (33%). Indications for performing vitrectomy included; decreased visual acuity (n = 14, 39%); all cases of exogenous endophthalmitis (n = 4, 12%); non-response to medical therapy (n = 4, 12%); or no view of the fundus (n = 4, 12%), indicating significant variation in surgical indications. More than half (n = 17, 52%) of responding institutions routinely admitted patients with exogenous endophthalmitis to the hospital. Institutions in the United States were less likely to administer oral antibiotics (27% vs. 73%, P = .024) and to admit patients (9% vs. 73%, P < .001) compared to other countries. CONCLUSIONS: This study highlights the global variations in the management of exogenous endophthalmitis, especially as it pertains to surgical indications. Further establishment of evidence-based guidelines may be beneficial to provide more uniform guidance to optimize outcomes.

Development of a composite diffusion tensor imaging score correlating with short-term neurological status in neonatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal acquired brain injury. Although conventional MRI may predict neurodevelopmental outcomes, accurate prognostication remains difficult. As diffusion tensor imaging (DTI) may provide an additional diagnostic and prognostic value over conventional MRI, we aimed to develop a composite DTI (cDTI) score to relate to short-term neurological function. Sixty prospective neonates treated with therapeutic hypothermia (TH) for HIE were evaluated with DTI, with a voxel size of 1 × 1 × 2 mm. Fractional anisotropy (FA) and mean diffusivity (MD) from 100 neuroanatomical regions (FA/MD *100 = 200 DTI parameters in total) were quantified using an atlas-based image parcellation technique. A least absolute shrinkage and selection operator (LASSO) regression was applied to the DTI parameters to generate the cDTI score. Time to full oral nutrition [short-term oral feeding (STO) score] was used as a measure of short-term neurological function and was correlated with extracted DTI features. Seventeen DTI parameters were selected with LASSO and built into the final unbiased regression model. The selected factors included FA or MD values of the limbic structures, the corticospinal tract, and the frontotemporal cortices. While the cDTI score strongly correlated with the STO score (rho = 0.83, p = 2.8 × 10-16), it only weakly correlated with the Sarnat score (rho = 0.27, p = 0.035) and moderately with the NICHD-NRN neuroimaging score (rho = 0.43, p = 6.6 × 10-04). In contrast to the cDTI score, the NICHD-NRN score only moderately correlated with the STO score (rho = 0.37, p = 0.0037). Using a mixed-model analysis, interleukin-10 at admission to the NICU (p = 1.5 × 10-13) and tau protein at the end of TH/rewarming (p = 0.036) and after rewarming (p = 0.0015) were significantly associated with higher cDTI scores, suggesting that high cDTI scores were related to the intensity of the early inflammatory response and the severity of neuronal impairment after TH. In conclusion, a data-driven unbiased approach was applied to identify anatomical structures associated with some aspects of neurological function of HIE neonates after cooling and to build a cDTI score, which was correlated with the severity of short-term neurological functions.

Global Current Practice Patterns for the Management of Hyphema.

Purpose: Hyphema is a sequela of ocular trauma and can be associated with significant morbidity. Management of this condition is variable and can depend on individual institutional guidelines. We aimed to summarize current practices in hyphema management across ophthalmological institutions worldwide. Methods: A cross-sectional online survey was conducted across North America, Asia, South America, Africa, Europe, and Australia from August 2020 to January 2021. The survey assessed the existing practices in the management of hyphema at each institution. Results: For layered hyphema, topical steroids were routinely administered by 34 (of 36 respondents, 94.4%) institutions, of which prednisolone was the preferred choice (n = 32, 88.9%). Topical cycloplegics were used at 34 (94.4%) institutions. No institution reported routine use of antifibrinolytics. Head elevation was the most deployed procedure to promote hyphema reabsorption (n = 31, 86.3%), followed by partial bed rest (n = 21, 58.3%). The majority of institutions (n = 25, 69.4%) did not routinely pursue admission for hyphema patients, although 75.0% of institutions (n = 27) scheduled follow-up visits within 48 hours of presentation. Additionally, few institutions performed routine sickle cell trait testing for patients presenting with hyphema (n = 6, 16.7%). The decision to perform anterior chamber washout varied and was often based on intraocular pressure and the speed of hyphema resolution. Conclusion: Unanimity of international institutions on hyphema management is lacking. As it stands, many current interventions have unconvincing evidence supporting their use. Evidence-based guidelines would be beneficial in guiding decision-making on hyphema management. Additionally, areas of consensus can be used as foundations for future standard of care investigations.

Impact of Amyloid Polymorphism on Prion-Chaperone Interactions in Yeast.

Yeast prions are protein-based genetic elements found in the baker's yeast Saccharomyces cerevisiae, most of which are amyloid aggregates that propagate by fragmentation and spreading of small, self-templating pieces called propagons. Fragmentation is carried out by molecular chaperones, specifically Hsp104, Hsp70, and Hsp40. Like other amyloid-forming proteins, amyloid-based yeast prions exhibit structural polymorphisms, termed "strains" in mammalian systems and "variants" in yeast, which demonstrate diverse phenotypes and chaperone requirements for propagation. Here, the known differential interactions between chaperone proteins and yeast prion variants are reviewed, specifically those of the yeast prions [PSI+], [RNQ+]/[PIN+], and [URE3]. For these prions, differences in variant-chaperone interactions (where known) with Hsp104, Hsp70s, Hsp40s, Sse1, and Hsp90 are summarized, as well as some interactions with chaperones of other species expressed in yeast. As amyloid structural differences greatly impact chaperone interactions, understanding and accounting for these variations may be crucial to the study of chaperones and both prion and non-prion amyloids.

Multimodal Long Noncoding RNA Interaction Networks: Control Panels for Cell Fate Specification.

Lineage specification in early development is the basis for the exquisitely precise body plan of multicellular organisms. It is therefore critical to understand cell fate decisions in early development. Moreover, for regenerative medicine, the accurate specification of cell types to replace damaged/diseased tissue is strongly dependent on identifying determinants of cell identity. Long noncoding RNAs (lncRNAs) have been shown to regulate cellular plasticity, including pluripotency establishment and maintenance, differentiation and development, yet broad phenotypic analysis and the mechanistic basis of their function remains lacking. As components of molecular condensates, lncRNAs interact with almost all classes of cellular biomolecules, including proteins, DNA, mRNAs, and microRNAs. With functions ranging from controlling alternative splicing of mRNAs, to providing scaffolding upon which chromatin modifiers are assembled, it is clear that at least a subset of lncRNAs are far from the transcriptional noise they were once deemed. This review highlights the diversity of lncRNA interactions in the context of cell fate specification, and provides examples of each type of interaction in relevant developmental contexts. Also highlighted are experimental and computational approaches to study lncRNAs.

Long Noncoding RNA Moderates MicroRNA Activity to Maintain Self-Renewal in Embryonic Stem Cells.

Of the thousands of long noncoding RNAs expressed in embryonic stem cells (ESCs), few have known roles and fewer have been functionally implicated in the regulation of self-renewal and pluripotency, or the reprogramming of somatic cells to the pluripotent state. In ESCs, Cyrano is a stably expressed long intergenic noncoding RNA with no previously assigned role. We demonstrate that Cyrano contributes to ESC maintenance, as its depletion results in the loss of hallmarks of self-renewal. Delineation of Cyrano's network through transcriptomics revealed widespread effects on signaling pathways and gene expression networks that contribute to ESC maintenance. Cyrano shares unique sequence complementarity with the differentiation-associated microRNA, mir-7, and mir-7 overexpression reduces expression of a key self-renewal factor to a similar extent as Cyrano knockdown. This suggests that Cyrano functions to restrain the action of mir-7. Altogether, we provide a view into the multifaceted function of Cyrano in ESC maintenance.

Development and testing of a self-report instrument to measure actions: outpatient physical therapy improvement in movement assessment log (OPTIMAL).

BACKGROUND AND PURPOSE: Physical therapy is faced with the challenge of producing evidence that physical therapy interventions are effective. The fundamental question confronting physical therapy is whether or not physical therapy interventions make a contribution to function, health, and well-being. The individual's ability to perform actions can serve as a theoretical construct related to movement and health around which physical therapy interventions can be assessed. To this end, the aims of this study were: (1) to develop a self-report instrument to assess ability to perform mobility actions in an adult outpatient population and (2) to assess the psychometric properties of such an instrument in the appropriate population. SUBJECTS AND METHODS: An instrument was developed to assess difficulty and confidence related to 24 actions. Descriptive statistics and measures of reliability, validity, and responsiveness were computed. A total of 391 patients participated in the study. RESULTS: The coefficient for reliability was in the required range, and measures of validity and responsiveness were established as well. Three factors were identified. DISCUSSION AND CONCLUSION: The instrument provides the beginning of documentation of outcomes in movement to identify the unique contributions of physical therapist practice.