Comparison of CDE data in phacoemulsification between an open hospital-based ambulatory surgical center and a free-standing ambulatory surgical center

Mean CDE (cumulative dissipated energy) values were compared for an open hospital- based surgical center and a free-standing surgical center. The same model of phacoemulsifier (Alcon Infiniti Ozil) was used. Mean CDE values showed that surgeons (individual private practice) at the free-standing surgical center were more efficient than surgeons (individual private practice) at the open hospital-based surgical center (mean CDE at the hospital-based surgical center 18.96 seconds [SD = 12.51]; mean CDE at the free-standing surgical center 13.2 seconds [SD = 9.5]). CDE can be used to monitor the efficiency of a cataract surgeon and surgical center in phacoemulsification. The CDE value may be used by institutions as one of the indicators for quality control and audit in phacoemulsification

A Pilot Study of the Short Term Effectiveness and Safety of Amniotic Fluid in Severe Dry Eye Disease

The aim of this study was to evaluate if amniotic fluid (AF) mixed with artificial tears or soaked with a soft contact lens (SCL) as a treatment for severe dry eye disease (DED) would improve its signs or symptoms. In this retrospective pilot study 22 consecutive eyes of 11 patients with level 3 DED classified by DEWS 1 (Dry Eye WorkShop 1 2007), were included in the study between June 1 and September 30 in 2017. The study was conducted before DEWS II (Dry Eye WorkShop II 2017), which was published in October 2017. Therefore, DEWS II was not adopted for this study. Soft Contact Lens Acuvue Oasys of Plano with 8.8 base curve and 14 mm diameters by Johnson and Johnson were used to soak in FloGraft, which is an AF, for 30 minutes before placing in 12 eyes in Group 1. The contact lenses were placed in the left eye for 1 week. In Group 2, 10 eyes used 6 mL of artificial tears mixed with 0.25 mL of AF, which were applied to the eye four times a day for 1 week. No other eye medications were used. The eyes that were included had diffuse punctate staining and fast tear breaking times of <5 seconds with severe ocular symptoms (DEWS 1 level 3-4). Photos of fluorescein stain corneas before the treatment and 1 week after the treatment were used to compare the distribution of punctate staining as the objective outcomes for signs. Several questions adopted from the Ocular Surface disease Index (OSDI) about subjective symptoms before and after the treatment were asked, and documented on the chart. Improvement either in symptoms or signs or both of DED after 1 week at follow-up examination was recorded. Group 1, with SCL 46% had improvement after 1 week and Group 2, with artificial tears 50% had improvement after 1 week. Improvement means either symptom relief or comparatively decreased distribution of punctate staining on the cornea or both. No cases had inflammation, infection, irritation or blurred vision. We concluded that FloGraft as an AF can safely improve the symptoms or the signs of severe DED either as a mix with artificial tears or soaked with SCL by about 50% in this case series without evidence of irritation, inflammation or blurred vision in the short term

A retrospective randomized study to compare the energy delivered using CDE with different techniques and OZil® settings by different surgeons in phacoemulsification

Cumulative dissipated energy (CDE) was used with Infiniti® Vision System (Alcon Labs) as an energy delivery guide to compare four different phaco techniques and phaco settings. The supracapsular phaco technique and burst mode is known for efficiency and surgery is faster compared with the old phaco unit. In this study, we found that supracapsular phaco with burst mode had the least CDE in both cataract and nuclear sclerosis cataract with the new Infiniti® unit. We suggest that CDE can be used as one of the references to modify technique and setting to improve outcome for surgeons, especially for new surgeons

Chiral cationic polyamines for chiral microcapsules and siRNA delivery

Reported herein is the use of chiral cationic polyamines for two intriguing applications: fabrication of chiral covalently-linked microcapsules, and enantiospecific delivery of siRNA to Huh 7 cells. The microcapsules are easily fabricated from homochiral polymers, and the resulting architectures can be used for supramolecular chiral catalysis and many other potential applications. Enantiospecific delivery of siRNA to Huh 7 cells is seen by one ‘enantiomer’ of the polymers delivering siRNA with significantly improved transfection efficiency and reduced toxicity compared to the ‘enantiomeric’ polymer and commercially available transfection reagents. Taken together, the use of these easily accessible polyamine structures for diverse applications is highlighted in this Letter herein and can lead to numerous future research efforts. [Refer to PDF for graphical abstract

33354 Efficacy of apremilast in patients with mild to moderate psoriasis assessed by the physician global assessment and body surface area composite tool: Post hoc analysis from ADVANCE

Background: In ADVANCE (NCT03721172), apremilast 30 mg BID (APR) demonstrated significantly greater sPGA response vs. PBO at Week 16 (22% vs. 4%; P \u3c.0001) in patients with mild-to-moderate psoriasis. The Physician Global Assessment and Body Surface Area Composite Tool (PGA × BSA) is a simple, sensitive measure of psoriasis severity for patients with BSA\u3c10%. We performed a post hoc analysis of the efficacy results from ADVANCE using the PGA×BSA. Methods: This current post hoc analysis included all randomized patients. Missing data were imputed by multiple imputation. PGAxBSA-50/75/90 was 50%, 75% and 90% improvement in PGAxBSA from baseline. Results: Of 595 randomized patients (APR: 297; PBO: 298), baseline characteristics were similar for mean BSA (APR: 6.4; PBO: 6.3), sPGA score 2 (APR 31%; PBO: 31%), sPGA score 3 (APR: 69%; PBO: 70%), and mean PGA×BSA (APR: 17.6; PBO: 17.5). At Week 16, significantly more patients achieved PGAxBSA-50/75/90 response with APR vs. PBO: PGA×BSA-50, 67% vs. 26% (P \u3c.0001), difference 41%, 95%CI (32.7,48.5) PGA×BSA-75, 46% vs. 13% (P \u3c.0001), difference 33%, 95%CI (25.8,40.2) PGA×BSA-90, 27% vs. 3% (P \u3c.0001), difference 24%, 95%CI (18.3,29.6) A significant improvement from baseline at Week 16 in PGA×BSA was observed with APR vs PBO: Mean % change (SE) in PGA×BSA, -51.8 (4.2) vs. 1.97 (4.3); difference (95%CI): -53.8 (-65.4, -42.2), P \u3c.0001. Conclusions: The PGA×BSA Composite Tool appeared to be a sensitive and a relevant measure for mild-to-moderate psoriasis that showed significantly greater treatment differences at 50%, 75%, and 90% response thresholds at Week 16 with APR compared with PBO in ADVANCE

26085 Key efficacy and safety of apremilast in patients with mild to moderate plaque psoriasis in the phase 3 ADVANCE trial

Background: In ADVANCE, apremilast 30 mg BID (APR) demonstrated efficacy in mild-to-moderate psoriasis vs placebo (PBO). We report subgroup analyses by baseline psoriasis-involved BSA (≤5%, \u3e5%). Methods: Biologic-naive adults with mild-to-moderate psoriasis (sPGA 2-3, BSA 2%-15%, PASI 2-15) inadequately controlled with or intolerant to ≥1 topical were randomized to APR or PBO for 16 weeks. At Week 16, endpoints were compared between treatment groups and by baseline BSA. Results: At baseline, 284 patients had BSA ≤5% (APR: 143; PBO: 141); 311 had BSA \u3e5% (APR: 154; PBO: 157). Overall, a greater proportion of APR patients achieved the primary endpoint, sPGA response (score 0/1 [clear/almost clear] with ≥2-point reduction at Week 16) vs PBO (21.6% vs 4.1%, P 5%: 54.6% vs 14.9%, P 5%: 45.4% vs 17.6%, P 5%: 50.6% vs 19.2%, P 5%: 11.0 vs 10.0 DLQI 5-point improvement (baseline DLQI \u3e5): - BSA≤5%: 56.6% vs 31.2%, P =.0002 - BSA\u3e5%: 64.4% vs 36.4%, P ˂.0001. Conclusions: Greater proportions of patients achieved efficacy outcomes and greater improvements in QOL with APR vs PBO. Comparable improvements were observed between mild and moderate subgroups

Glycan profiles of gp120 protein vaccines from four major HIV-1 subtypes produced from different host cell lines under non-GMP or GMP conditions

Envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is an important target for the development of an HIV vaccine. Extensive glycosylation of Env is an important feature that both protects the virus from antibody responses and serves as a target for some highly potent broadly neutralizing antibodies. Therefore, analysis of glycans on recombinant Env proteins is highly significant. Here we present glycosylation profiles of recombinant gp120 proteins from four major clades of HIV-1 (A, B, C, and AE) produced either as research-grade material in 293 and CHO cells or as two independent lots of clinical material under GMP conditions. Almost all potential N-linked glycosylation sites were at least partially occupied in all proteins. The occupancy rates were largely consistent among proteins produced under different conditions, although a few sites showed substantial variability even between two GMP lots. Our data confirmed previous studies in the field showing high abundance of oligomannose on Env protein, with 40-50% of glycans having Man5-Man9 on all four proteins under all production conditions. Overall the differences in occupancy and glycan forms among Env from different subtypes produced under different conditions were less dramatic than anticipated and antigenicity analysis with a panel of six monoclonal antibodies showed that all four gp120s maintained their antibody-binding profiles, including antibodies that recognize glycan forms. Such findings have major implications to the final production of a clinical HIV vaccine including Env glycoprotein components. IMPORTANCE HIV-1 Env protein is a major target for the development of an HIV-1 vaccine. Env is covered with a large number of sugar-based glycan forms - about 50% of the Env molecular weight is composed of glycans. Glycan analysis of recombinant Env proteins is important to understand its roles in vial pathogenesis and immune responses. The current report presents the first extensive comparison of glycosylation patterns of recombinant gp120 proteins from four major clades of HIV-1 produced in two different cell lines, grown at either laboratory condition or at 50L GMP scale across different lots. Information learned in this study is valuable for the further design and production of HIV-1 Env proteins as the critical components of HIV-1 vaccine formulations

Correlating PMC-MMC Bonded Joint 3D FEA with Test

A viewgraph presentation on the correlation of Polymer Matrix Composites (PMC) and Metal Matrix Composites (MMC) bonded joints using three dimensional finite element analyses with materials tests is shown

Prevalence and Characteristics of Self-Reported Hypothyroidism and Its Association with Nonorgan-Specific Manifestations in US Sarcoidosis Patients: A Nationwide Registry Study

Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in patients with sarcoidosis. We aimed to determine the prevalence and clinical features of hypothyroidism and its relation to organ involvement and other clinical manifestations in patients with sarcoidosis. We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire between June 2014 and August 2019. This registry is based on a self-reported, web-based questionnaire that provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without self-reported hypothyroidism. We used multivariable logistic regression and adjusted for potential confounders to determine the association of hypothyroidism with nonorgan-specific manifestations. 14% of the sarcoidosis patients self-reported hypothyroidism and were generally middle-aged white women. Hypothyroid patients had more comorbid conditions and were more likely to have multiorgan sarcoidosis involvement, especially with cutaneous, ocular, joints, liver and lacrimal gland involvement. Self-reported hypothyroidism was associated with depression (adjusted odds ratio (aOR) 1.3, 95% CI 1.01–1.6), antidepressant use (aOR 1.3, 95% CI 1.1–1.7), obesity (aOR 1.7, 95% CI 1.4–2.1), sleep apnoea (aOR 1.7, 95% CI 1.3–2.2), chronic fatigue syndrome (aOR 1.5, 95% CI 1.2–2) and was borderline associated with fibromyalgia (aOR 1.3, 95% CI 1–1.8). Physical impairment was more common in patients with hypothyroidism. Hypothyroidism is a frequent comorbidity in sarcoidosis patients that might be a potentially reversible contributor to fatigue, depression and physical impairment in this population. We recommend considering routine screening for hypothyroidism in sarcoidosis patients especially in those with multiorgan sarcoidosis, fatigue and depression

DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks

Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations