Association of Tear Cytokine Ratios with Symptoms and Signs of Dry Eye Disease: Biomarker Data from the Dry Eye Assessment and Management Study.

PURPOSE: To assess the relationship between tear inflammatory cytokine ratios (CRs) and signs and symptoms of dry eye disease (DED) to investigate the possible use of tear CRs, which may better address the complexity of cytokine interactions than absolute cytokine levels, as a DED biomarker. METHODS: Tear concentrations of IL-1b, IL-6, IL-8, IL-10, IL-17A, IFN-g, and TNF-a were measured using standardized procedures, as were DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)]. Ratios between pro-inflammatory (IL-1b, IL-8, IL-17A, IFN-g, and TNF-a) and anti-inflammatory (IL-10) cytokines were calculated. Given its opposing roles in inflammation, IL-6 was tested as both a pro- and anti-inflammatory cytokine. Correlations between CR and DED symptoms and signs were calculated using Spearman correlation coefficients (rho). RESULTS: At baseline, 131 patients, 80.2% female and mean age 54.2 years (SD 14.1, range 20-82), from 10 sites of the Dry Eye Assessment and Management study had sufficient tear volumes ≥4 µL for analysis. IL-6:IL-10, IL-8:IL-10, and TNF-a:IL-10 had some significant correlations, mostly with conjunctival or corneal staining or the composite sign severity score (IL-8:IL-10 and conjunctival staining: rho = 0.19, p = 0.03; IL-6:IL-10 and corneal staining: rho = 0.31, p < 0.001; IL-8:IL-10 and corneal staining: rho = 0.21, p = 0.01; IL-6:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; IL-8:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; TNF-a:IL-10 and corneal staining: rho = 0.29, p < 0.001; TNF-a:IL-10 and Schirmer test: rho = -0.23, p = 0.009). CRs had no significant correlation with DED symptoms. All significant correlations using IL-6 in the denominator (anti-inflammatory) produced counterintuitive results based on clinical understanding of the disease. CONCLUSIONS: Pro- to anti-inflammatory CR was weakly correlated with some DED signs and not with symptoms, as measured by OSDI. Future studies in different dry eye populations are needed and should address sampling biases and tear collection techniques.

Artificial Intelligence Improves Patient Follow-Up in a Diabetic Retinopathy Screening Program.

Purpose: We examine the rate of and reasons for follow-up in an Artificial Intelligence (AI)-based workflow for diabetic retinopathy (DR) screening relative to two human-based workflows. Patients and Methods: A DR screening program initiated September 2019 between one institution and its affiliated primary care and endocrinology clinics screened 2243 adult patients with type 1 or 2 diabetes without a diagnosis of DR in the previous year in the San Francisco Bay Area. For patients who screened positive for more-than-mild-DR (MTMDR), rates of follow-up were calculated under a store-and-forward human-based DR workflow ("Human Workflow"), an AI-based workflow involving IDx-DR ("AI Workflow"), and a two-step hybrid workflow ("AI-Human Hybrid Workflow"). The AI Workflow provided results within 48 hours, whereas the other workflows took up to 7 days. Patients were surveyed by phone about follow-up decisions. Results: Under the AI Workflow, 279 patients screened positive for MTMDR. Of these, 69.2% followed up with an ophthalmologist within 90 days. Altogether 70.5% (N=48) of patients who followed up chose their location based on primary care referral. Among the subset of patients that were seen in person at the university eye institute under the Human Workflow and AI-Human Hybrid Workflow, 12.0% (N=14/117) and 11.7% (N=12/103) of patients with a referrable screening result followed up compared to 35.5% of patients under the AI Workflow (N=99/279; χ2df=2 = 36.70, p < 0.00000001). Conclusion: Ophthalmology follow-up after a positive DR screening result is approximately three-fold higher under the AI Workflow than either the Human Workflow or AI-Human Hybrid Workflow. Improved follow-up behavior may be due to the decreased time to screening result.

Outcome of silicone sling frontalis suspension in children with simple congenital and complex ptosis.

OBJECTIVE: To compare the outcome of silicone sling frontalis suspension (FS) surgery in children with simple congenital ptosis and children with complex ptosis. DESIGN: A retrospective cohort study. PARTICIPANTS: All pediatric patients who underwent silicone sling FS surgery between 2009 and 2020 at a single centre. METHODS: Patients were divided based on etiology into simple congenital ptosis and complex congenital ptosis. Pre- and postoperative margin-to-reflex distance (MRD1) measurements were determined from clinical photographs. Main outcome measures were assessed as differences in improvement in eyelid height and reoperation rate between the groups. RESULTS: Two-hundred and eight children were included: 139 simple and 69 complex cases, with 83 females (40%). Mean (±SD) age at intervention was 1.9 ± 2.9 years. Complex cases included blepharophimosis epicanthus inversus syndrome (n = 35), Marcus Gunn jaw-winking syndrome (n = 12), oculomotor palsy (n = 8), congenital fibrosis of extraocular muscles (n = 3), chronic progressive external ophthalmoplegia (n = 3), and others. Mean MRD1 improved by an average of 1.6 mm in both groups. Repeat ptosis correction was performed in 50 of 171 patients (29%) without a history of failed ptosis procedures, and this rate was similar between simple and complex cases. Children under 3 years of age had higher rates of repeat ptosis repair than older children (n = 59 of 175 [34%] vs n = 5 of 33 [15%]; p = 0.03, χ2 test). CONCLUSIONS: Silicone sling FS has a favourable outcome in 70% of pediatric patients. Preoperative and final MRD1 and reoperation rates were similar between both groups, suggesting that despite the higher complexity in atypical cases, the outcome is similar.

Introducing Surgical Equity into Contemporary Medical Education: Results From Operation Equity, a Pilot Curriculum.

OBJECTIVE: To date, education about health equity for early-stage healthcare trainees is largely situated outside of surgical disciplines. This study aims to evaluate the effectiveness of a surgical equity curriculum offered to a voluntary group of medical and graduate students. DESIGN: Mixed-methods cohort study from January to June 2021. Pre- and post-course surveys measured domains of attitudes, self-reported confidence, and knowledge via 5-point Likert scale and multiple-choice questions. Paired t tests were used to analyze quantitative responses. Qualitative responses were studied via iterative thematic analysis. SETTING: At the University of Pennsylvania in Philadelphia, PA which provides tertiary level, institutional care, 10, interdisciplinary 1.5-hour sessions were held over 1 semester, teaching surgical equity topics that spanned the peri-operative continuum. PARTICIPANTS: Twenty-four medical and graduate students from across the University of Pennsylvania enrolled. Twenty completed both surveys. RESULTS: From pre- to post-course, students improved across all domains. Students improved in their self-rated ability to identify strategies to talk about sensitive health topics with patients (pre: 20%, post: 90%) and identify strategies to address healthcare disparities in surgery (pre: 10%, post: 90%). Qualitatively, from pre- to post-course, more students could articulate the role of bias and identify opportunities for surgeons to engage in surgical equity. The course strengthened any pre-existing interest in surgical equity, and for 1 student, created interest in a surgical career where it had not previously existed. Many also expressed greater resolve to provide patient-centric care. CONCLUSIONS: Formal curricula can improve students' ability to advocate for surgical equity. A similar framework may fill a need for medical students interested in health equity and surgical careers at other institutions.

Silicone sling frontalis suspension for congenital ptosis: Outcome of 174 consecutive cases.

BACKGROUND: Frontalis suspension (FS) is the treatment of choice in congenital ptosis with poor levator function. We report the surgical outcome of FS using a double triangle configuration of silicone slings in children. METHODS: A retrospective cohort study of all paediatric patients with simple myogenic congenital ptosis repaired with FS over a 12-year period (2009-2020). Each silicone sling was secured by simple knots. Pre- and post-operative margin reflex distance (MRD1 ) measurements were determined from clinical photographs using ImageJ Software. Main outcome measures were improvement in eyelid height, eyelid asymmetry, reoperation rate and timing. RESULTS: One hundred and thirty nine patients (174 eyes) were included, with 35 (25%) having bilateral surgery. Mean (±SD) age was 1.4 ± 1.9 years. Mean follow up time was 32 ± 20.5 months. Sixteen patients (11%) had a history of previous ptosis repair surgery. Mean MRD1 improved by an average of 1.5 mm. The final MRD1 in the group of patients who did not have a second procedure was a mean of 2.1 mm. The MRD1 difference between both eyes in all unilateral cases improved from 2.5 mm preoperatively to 1.2 mm at final visit (p < 0.001). In the 123 cases without a history of previous ptosis surgery, repeat ptosis repair was performed in 37 (30%) patients, 34.9 ± 19.9 months after the initial procedure. Overall, repeat repair was performed in 47 patients (34%). CONCLUSIONS: Double triangle silicone sling frontalis suspension has a favourable outcome in two-thirds of paediatric patients with simple myogenic congenital ptosis. Failed cases can be addressed with a second repair, using either autogenous fascia lata or a second silicone sling.

Pan-Cancer Survival Classification With Clinicopathological and Targeted Gene Expression Features.

Prognostication for patients with cancer is important for clinical planning and management, but remains challenging given the large number of factors that can influence outcomes. As such, there is a need to identify features that can robustly predict patient outcomes. We evaluated 8608 patient tumor samples across 16 cancer types from The Cancer Genome Atlas and generated distinct survival classifiers for each using clinical and histopathological data accessible to standard oncology workflows. For cancers that had poor model performance, we deployed a random-forest-embedded sequential forward selection approach that began with an initial subset of the 15 most predictive clinicopathological features before sequentially appending the next most informative gene as an additional feature. With classifiers derived from clinical and histopathological features alone, we observed cancer-type-dependent model performance and an area under the receiver operating curve (AUROC) range of 0.65 to 0.91 across all 16 cancer types for 1- and 3-year survival prediction, with some classifiers consistently outperforming those for others. As such, for cancers that had poor model performance, we posited that the addition of more complex biomolecular features could enhance our ability to prognose patients where clinicopathological features were insufficient. With the inclusion of gene expression data, model performance for 3 select cancers (glioblastoma, stomach/gastric adenocarcinoma, ovarian serous carcinoma) markedly increased from initial AUROC scores of 0.66, 0.69, and 0.67 to 0.76, 0.77, and 0.77, respectively. As a whole, this study provides a thorough examination of the relative contributions of clinical, pathological, and gene expression data in predicting overall survival and reveals cancer types for which clinical features are already strong predictors and those where additional biomolecular information is needed.

Increased Firearm Injury During the COVID-19 Pandemic: A Hidden Urban Burden.

BACKGROUND: Public health measures were instituted to reduce COVID-19 spread. A decrease in total emergency department volume followed, but the impact on injury is unknown. With lockdown and social distancing potentially increasing domicile discord, we hypothesized that intentional injury increased during COVID-19, driven primarily by an increase in penetrating trauma. STUDY DESIGN: A retrospective review of acute adult patient care in an urban Level I trauma center assessed injury patterns. Presenting patient characteristics and diagnoses from 6 weeks pre to 10 weeks post statewide stay-at-home orders (March 16, 2020) were compared, as well as with 2015-2019. Subsets were defined by intentionality (intentional vs nonintentional) and mechanism of injury (blunt vs penetrating). Fisher exact and Wilcoxon tests were used to compare proportions and means. RESULTS: There were 357 trauma patients that presented pre stay-at-home order and 480 that presented post stay-at-home order. Pre and post groups demonstrated differences in sex (35.6% vs 27.9% female; p = 0.02), age (47.4 ± 22.1 years vs 42 ± 20.3 years; p = 0.009), and race (1.4% vs 2.3% Asian; 63.3% vs 68.3% Black; 30.5% vs 22.3% White; and 4.8% vs 7.1% other; p = 0.03). Post stay-at-home order mechanism of injury revealed more intentional injury (p = 0.0008). Decreases in nonintentional trauma after adoption of social isolation paralleled declines in daily emergency department visits. Compared with earlier years, 2020 demonstrated a significantly greater proportion of intentional violent injury during the peripandemic months, especially from firearms. CONCLUSIONS: Unprecedented social isolation policies to address COVID-19 were associated with increased intentional injury, especially gun violence. Meanwhile, emergency department and nonintentional trauma visits decreased. Pandemic-related public health measures should embrace intentional injury prevention and management strategies.

Neurology consults in emergency departments: Opportunities to streamline care.

OBJECTIVE: To use the variations in neurology consultations requested by emergency department (ED) physicians to identify opportunities to implement multidisciplinary interventions in an effort to reduce ED overcrowding. METHODS: We retrospectively analyzed ED visits across 3 urban hospitals to determine the top 10 most common chief complaints leading to neurology consultation. For each complaint, we evaluated the likelihood of consultation, admission rate, admitting services, and provider-to-provider variability of consultation. RESULTS: Of 145,331 ED encounters analyzed, 3,087 (2.2%) involved a neurology consult, most commonly with chief complaints of acute-onset neurologic deficit, subacute neurologic deficit, or altered mental status. ED providers varied most in their consultation for acute-onset neurologic deficit, dizziness, and headache. Neurology consultation was associated with a 2.3-hour-longer length of stay (LOS) (95% CI: 1.6-3.1). Headache in particular has an average of 6.7-hour-longer ED LOS associated with consultation, followed by weakness or extremity weakness (4.4 hours) and numbness (4.1 hours). The largest estimated cumulative difference (number of patients with the specific consultation multiplied by estimated difference in LOS) belongs to headache, altered mental status, and seizures. CONCLUSION: A systematic approach to identify variability in neurology consultation utilization and its effect on ED LOS helps pinpoint the conditions most likely to benefit from protocolized pathways.

Race, gender, and language concordance in the care of surgical patients: A systematic review.

BACKGROUND: No consensus exists on whether patient-provider race, gender, and language concordance provides benefits to surgical patients. We report a systematic review of the association between patient-provider concordance and patient preferences and outcomes in surgery. METHODS: A systematic review of the literature was performed in Medline and PubMed using defined search terms to identify studies related to patient-provider concordance in surgical patients. We included studies with full manuscripts published in English within the United States (1998 to July 2018). RESULTS: Out of 253 titles screened, 16 studies met inclusion criteria. Five studies had level 4 evidence and 11 studies had level 3 evidence. The majority of patients preferred providers with a similar background (n = 4/6). Race, gender, and language-concordance had no effect on adherence to provider recommendations (n = 3/3). No effect of race concordance on the quality of care was seen (n = 2/3). Gender concordance was associated with improved quality of care (n = 2/3). There were mixed effects of concordance on the effectiveness of communication (n = 2). CONCLUSION: Few studies examine patient-provider concordance. Most patients prioritize culturally, technically, and clinically competent providers over concordance. Future research is needed regarding the influence of concordance on patient outcomes in surgery within specific patient populations and clinical settings.

Carbon Nanomaterials in Direct Liquid Fuel Cells.

Fuel cells have attracted more attentions due to many advantages they can provide, including high energy efficiency and low environmental burden. To form a stable, low cost and efficient catalyst, we presented here the state of the art of electrocatalyst fabrication approaches, involving carbon nanotubes and their multifunctional nanocomposites incorporated with noble metals, such as Pt, Pd, Au, their binary and ternary systems. Both fuel oxidation reactions and oxygen reduction reactions were emphasized with comprehensive examples and future prospects.

Effect of Glutathione on the Taste and Texture of Type I Sourdough Bread.

Type I sourdough fermentations with Lactobacillus sanfranciscensis as predominant organism accumulate reduced glutathione through glutathione reductase (GshR) activity of L. sanfranciscensis. Reduced glutathione acts as chain terminator for gluten polymerization but is also kokumi-active and may thus enhance bread taste. This study implemented a type I model sourdough fermentations to quantitate glutathione accumulation sourdough, bread dough, and bread and to assess the effect of L. sanfranciscensis GshR on bread volume by comparison of L. sanfranciscensis and an isogenic strain devoid of GshR. L. sanfranciscensis sourdough accumulated the highest amount of reduced glutathione during proofing. Bread produced with the wild type strain had a lower volume when compared to the gshR deficient mutant. The accumulation of γ-glutamyl-cysteine was also higher in L. sanfranciscensis sourdoughs when compared to doughs fermented with the gshR mutant strain. The accumulation of reduced glutathione in L. sanfranciscensis bread did not enhance the saltiness of bread.

Synthesis of Taste-Active γ-Glutamyl Dipeptides during Sourdough Fermentation by Lactobacillus reuteri.

This study aimed to assess whether peptides influence the taste of sourdough bread. γ-Glutamyl dipeptides with known kokumi taste threshold, namely γ-Glu-Glu, γ-Glu-Leu, γ-Glu-Ile, γ-Glu-Phe, γ-Glu-Met, and γ-Glu-Val, were identified in sourdough by liquid chromatography-tandem mass spectrometry in MRM mode. γ-Glutamyl dipeptides were found in higher concentrations in sourdough fermented with Lactobacillus reuteri when compared to the chemically acidified controls. Proteolysis was an important factor for generation of γ-glutamyl dipeptides. Sourdoughs fermented with four strains of L. reuteri had different concentrations of γ-Glu-Glu, γ-Glu-Leu, and γ-Glu-Met, indicating strain-specific differences in enzyme activity. Buffer fermentations with L. reuteri confirmed the ability of the strains to convert amino acids to γ-glutamyl dipeptides as well as the strain-specific differences. Sensory evaluation of bread revealed that sourdough bread with higher concentrations of γ-glutamyl dipeptides ranked higher with respect to the taste intensity when compared to regular bread and type I sourdough bread. Sourdough breads fermented with L. reuteri LTH5448 and L. reuteri 100-23 differed with respect to the intensity of the salty taste; this difference corresponded to a different concentration of γ-glutamyl dipeptides. These results suggest a strain-specific contribution of γ-glutamyl dipeptides to the taste of bread. The use of sourdough fermented with glutamate and kokumi peptide accumulating lactobacilli improved the taste of bread without adverse effect on other taste or quality attributes.

Formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations - A review.

Fermented foods are valued for their rich and complex odour and taste. The metabolic activity of food-fermenting microorganisms determines food quality and generates odour and taste compounds. This communication reviews the formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations. Pathways of the generation of taste compounds are presented for soy sauce, cheese, fermented meats, and bread. Proteolysis or autolysis during food fermentations generates taste-active amino acids and peptides; peptides derived from proteolysis particularly impart umami taste (e.g. α-glutamyl peptides) or bitter taste (e.g. hydrophobic peptides containing proline). Taste active peptide derivatives include pyroglutamyl peptides, γ-glutamyl peptides, and succinyl- or lactoyl amino acids. The influence of fermentation microbiota on proteolysis, and peptide hydrolysis, and the metabolism of glutamate and arginine is well understood, however, the understanding of microbial metabolic activities related to the formation of taste-active peptide derivatives is incomplete. Improved knowledge of the interactions between taste-active compounds will enable the development of novel fermentation strategies to develop tastier, less bitter, and low-salt food products, and may provide novel and "clean label" ingredients to improve the taste of other food products.

Direct method of tracing the wetting states on nanocomposite surfaces.

Identifying the two distinctive wetting states on a nanostructured surface remains an open challenge. We report here a direct method of tracing the Wenzel and Cassie states by using Ag nanoparticles as tracing agents. The method provides an answer to the long-standing question of whether there is a transition from the Wenzel to Cassie state in the sliding angle drop on superhydrophobic nanocomposite thin films containing multiwalled carbon nanotubes.