Postoperative infection following strabismus surgery: case series and increased incidence in a single large referral center

Purpose To identify and analyze cases of postoperative infection following strabismus surgery at a large referral center and to report the incidence, risk factors, and outcomes. Methods An electronic database search identified strabismus procedures at Duke Eye Center from July 1996 to October 2017. Diagnosis codes for periocular infections were used to further identify patients with possible infections following strabismus surgery. Results Of 9,111 strabismus surgeries, 13 (0.14%) met criteria for probable infection, all occurring since October 2012 (0/6580 before vs 13/2531 [0.51%] after; P < 0.0001). Mean age of infection cases was 11.4 years; 11 patients (85%) were under 18 years of age. Associated previous diagnoses were genetic abnormalities with associated developmental delay (n = 5 [38%]), previous skin or ear infection (n = 4 [31%]), and acute or chronic rhinitis (n = 3 [23%]). Infection site cultures revealed methicillin-resistant Staphylococcus aureus (n = 3 [23%]), methicillin-sensitive S. aureus (n = 3 [23%]), and Streptococcus pyogenes/group-A Streptococcus (n = 2 [15%]). Only 1 case had bilateral infection. Infection remained extraocular in all cases, but one eye lost light perception secondary to optic atrophy. No common surgeon/procedure/preparation-related risks were identified. Conclusions A unifying explanation for the increase in post–strabismus surgery infections at Duke Eye Center was not identified. Potential risk factors include age <18 years, developmental delay, immune compromise, preceding nonocular infection, and bacterial colonization

Phosphorylation of serine residues in the N-terminus modulates the activity of ACA8, a plasma membrane Ca2+-ATPase of Arabidopsis thaliana

ACA8 is a plasma membrane-localized isoform of calmodulin (CaM)-regulated Ca2+-ATPase of Arabidopsis thaliana. Several phosphopeptides corresponding to portions of the regulatory N-terminus of ACA8 have been identified in phospho-proteomic studies. To mimic phosphorylation of the ACA8 N-terminus, each of the serines found to be phosphorylated in those studies (Ser19, Ser22, Ser27, Ser29, Ser57, and Ser99) has been mutated to aspartate. Mutants have been expressed in Saccharomyces cerevisiae and characterized: mutants S19D and S57D—and to a lesser extent also mutants S22D and S27D—are deregulated, as shown by their low activation by CaM and by tryptic cleavage of the N-terminus. The His-tagged N-termini of wild-type and mutant ACA8 (6His-1M-I116) were expressed in Escherichia coli, affinity-purified, and used to analyse the kinetics of CaM binding by surface plasmon resonance. All the analysed mutations affect the kinetics of interaction with CaM to some extent: in most cases, the altered kinetics result in marginal changes in affinity, with the exception of mutants S57D (KD ∼10-fold higher than wild-type ACA8) and S99D (KD about half that of wild-type ACA8). The ACA8 N-terminus is phosphorylated in vitro by two isoforms of A. thaliana calcium-dependent protein kinase (CPK1 and CPK16); phosphorylation of mutant 6His-1M-I116 peptides shows that CPK16 is able to phosphorylate the ACA8 N-terminus at Ser19 and at Ser22. The possible physiological implications of the subtle modulation of ACA8 activity by phosphorylation of its N-terminus are discussed

Targeting TMEM16A to reverse vasoconstriction and remodelling in idiopathic PAH

Our systematic analysis of anion channels and transporters in idiopathic pulmonary arterial hypertension (IPAH) showed marked upregulation of the Cl- channel TMEM16A gene.We hypothesised that TMEM16A overexpression might represent a novel vicious circle in the molecular pathways causing PAH.We investigated healthy donor lungs (n=40) and recipient lungs with IPAH (n=38) for the expression of anion channel and transporter genes in small pulmonary arteries and pulmonary arterial smooth muscle cells (PASMC). In IPAH, TMEM16A was strongly upregulated and patch-clamp recordings confirmed an increased Cl- current in PASMC (n=9-10). These cells were depolarised and could be repolarized by TMEM16A inhibitors or knock-down experiments (n=6-10). Inhibition/knock-down of TMEM16A reduced proliferation of IPAH-PASMC (n=6). Conversely, overexpression of TMEM16A in healthy donor PASMC produced an IPAH-like phenotype. Chronic application of benzbromarone in two independent animal models significantly decreased right ventricular pressure and reversed remodelling of established PH.Our findings suggest that increased TMEM16A expression and activity comprise an important pathologic mechanism underlying vasoconstriction and remodelling of pulmonary arteries in PAH. Inhibition of TMEM16A represents a novel therapeutic approach to achieve reverse remodelling in PAH

The flipped-classroom approach to teaching horizontal strabismus in ophthalmology residency: a pilot study

PurposeTo compare the flipped classroom (home pre-taped lectures followed by in-class group exercise) to the traditional classroom (home reading assignment followed by in-class lecture) for horizontal strabismus didactics in ophthalmology residency.MethodsAll PGY2-4 residents from four U.S. ophthalmology residencies without prior residency flipped-classroom experience were invited to esotropia and exotropia sessions sequentially, with random order and assignment to flipped and traditional classrooms. Content test scores before and after the two classrooms were compared. Surveys were administered to assess participant experience.ResultsA total of 40 residents attended each session. Likert scale evaluation of preparatory material and classroom activity did not differ between sessions; however, divided by year of training, 70% of senior residents (PGY3-4) and 39% of first-year (PGY2) residents preferred the flipped classroom over the traditional classroom. Pre- and post-test scores for the flipped classroom exceeded those of the traditional classroom for the exotropia course (P&nbsp;=&nbsp;0.01 and P&nbsp;=&nbsp;0.001, resp.) but not for the esotropia course. There was significant improvement between pre- and post-tests for both styles of learning.ConclusionsThe flipped classroom had a favorable effect on test scores for only one of the two strabismus subjects but was preferred over the traditional classroom among PGY3-4 residents

N-glycosylation-dependent control of functional expression of background potassium channels K2P3.1 and K2P9.1

Two-pore domain potassium (K2P) channels play fundamental roles in cellular processes by enabling a constitutive leak of potassium from cells in which they are expressed, thus influencing cellular membrane potential and activity. Hence, regulation of these channels is of critical importance to cellular function. A key regulatory mechanism of K2P channels is the control of their cell surface expression. Membrane protein delivery to and retrieval from the cell surface is controlled by their passage through the secretory and endocytic pathways and post-translational modifications regulate their progression through these pathways. All but one of the K2P channels possess consensus N-linked glycosylation sites and here we demonstrate that the conserved putative N-glycosylation site in K2P3.1 and K2P9.1 is a glycan acceptor site. Patch-clamp analysis revealed that disruption of channel glycosylation reduced K2P3.1 current, and flow cytometry was instrumental in attributing this to a decreased number of channels on the cell surface. Similar findings were observed when cells were cultured in reduced glucose concentrations. Disruption of N-linked glycosylation has less effect on K2P9.1, with a small reduction in number of channels on the surface observed, but no functional implications detected. As non-glycosylated channels appear to pass through the secretory pathway in a manner comparable to glycosylated channels, evidence presented here suggests that the decreased number of non-glycosylated K2P3.1 channels on the cell surface may be due to their decreased stability

Flipped classroom approach to global outreach: cross-cultural teaching of horizontal strabismus to Chinese ophthalmology residents.

AimTo evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States.MethodsResidents from an ophthalmology residency program in China were invited to participate in flipped classroom sessions taught by an experienced American ophthalmology faculty in 2018. Residents were instructed to watch a pre-class video lecture prior to the in-class-case-based activity. Content tests (5 Ophthalmic Knowledge Assessment Program style questions) and surveys were administered before and after the classroom sessions (100% response rate). These results were compared to that of an American cohort who were taught the same content.ResultsThe Chinese cohort of 12 residents preferred the flipped classroom to the traditional classroom at higher rates than the American cohort of 40 residents (92% vs 55%, P=0.04) and felt that all ophthalmology topics would be appropriate for the flipped classroom teaching style (P-values between 0.008 and &lt;0.001). In both Chinese and American cohorts, we found that the exotropia curriculum saw a small but significant improvement in performance following the flipped classroom session (P=0.025 for Chinese residents; P=0.001 for US residents), whereas scores in both groups for the esotropia course did not significantly improve.ConclusionThis is the first study to evaluate the flipped classroom model implemented by a visiting ophthalmology professor in a global outreach setting. The flipped classroom sessions are viewed favorably by the Chinese residents relative to the US cohort with a modest impact on knowledge. Decreased in-person interpreter requirement and increased student engagement make this model valuable in cross-cultural visiting professorship settings. Finally, the flipped classroom may lend itself well to a virtual format to prevent the transmission of COVID-19, although such a format requires further study

Improvement in health-related quality of life following strabismus surgery for children with intermittent exotropia

A total of 197 children with IXT aged 3-11 years (and 1 parent of each child) were enrolled in a previously reported randomized clinical trial comparing two surgical procedures. The Intermittent Exotropia Questionnaire (IXTQ) was administered before surgery (baseline), and again at 6 and 36 months following surgery. The child version of the IXTQ was only completed by children 5-11 years of age (n = 123). Outcomes were classified as "resolved" (exodeviation of <10Δ, no decreased stereoacuity, and no other nonsurgical treatment for IXT or reoperation), "suboptimal" (exotropia ≥10Δ by simultaneous prism and cover test or constant esotropia ≥6Δ or loss of ≥2 octaves of stereoacuity), or "intermediate." Mean changes in Rasch-calibrated IXTQ domain scores (Child, Proxy, Parent-psychosocial, Parent-function, and Parent-surgery; converted to a 0-100 scale) were compared.12 month embargo; published: 24 April 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Health-related quality of life in children with untreated intermittent exotropia and their parents

Purpose: To determine whether health-related quality of life (HRQOL) scores improved or worsened over 3 years of observation in childhood intermittent exotropia without treatment. Methods: A total of 111 children aged 3-11 years with intermittent exotropia were assigned to observation in a previously reported randomized trial comparing patching with observation. The intermittent exotropia questionnaire (IXTQ) was administered at baseline, 6 months, and 36 months. Rasch-calibrated IXTQ domain scores (Child, Proxy, Parent-psychosocial, Parent-function, and Parent-surgery) were compared between time points. The Child IXTQ was administered only to children ≥5 years of age (n = 78). Results: Overall, Child IXTQ and Proxy IXTQ scores showed no significant change over 36 months (mean improvement from baseline to 36 months of 3.2 points [95% CI, −1.9 to 8.2] and −2.4 points [95% CI: −7.9 to 3.1], resp.). By contrast, Parent-psychosocial, Parent-function, and Parent-surgery domain scores all improved over 36 months (mean improvements of 12.8 points [95% CI, 5.9-19.6] and 14.2 points [95% CI, 8.0-20.3] and 18.5 points [95% CI, 9.7-27.3], resp.). Conclusions: HRQOL of children with intermittent exotropia remains stable with observation over 3 years (by both child and proxy report), whereas parental HRQOL improves.12 month embargo; available online 8 March 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]