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Caroline N Pham,1 Nathan M Radcliffe,1–3 Daniel M Vu2 1New York University, New York, NY, USA; 2Weill Cornell Medical College, New York, NY, USA; 3New York Eye Surgery Center, New York, NY, USA Purpose: To evaluate the safety and efficacy profile of a sutureless procedure for drainage valve implantation with combined cataract removal and/or endoscopic cyclophotocoagulation (ECP).Materials and methods: A retrospective case series study of consecutive surgeries for Ahmed glaucoma valve (AGV; New World Medical) implantation in a 1-year period was analyzed. The surgery was performed using a Tisseel fibrin sealant (Baxter Healthcare Corporation) in place of sutures. Some subsets within the case series also included a cataract extraction with intraocular lens (CEIOL) insertion and/or ECP (Endo Optiks) within the same procedure. Primary outcomes for this study including efficacy (IOP change, reduction in medications) and safety (complications and reoperations) were measured out to 3 years. Comparisons between subsets were made using ANOVA with post hoc Tukey’s pairwise tests.Results: One hundred twenty-two eyes of 99 patients underwent sutureless AGV implantation surgery. Of the 122, 18 had an AGV implantation only, 46 had an AGV + CEIOL, 35 had an AGV + ECP, and 23 had an AGV + CEIOL + ECP. In total, there was a significant decrease in IOP (P0.05); 10.7% and 14.8% of eyes required a reoperation either for a complication or for uncontrolled glaucoma, respectively.Conclusion: Sutureless valve implantation is associated with a significant reduction in IOP percentage and medication use after the procedure with a safety profile comparable with other glaucoma surgeries. Keywords: Ahmed glaucoma valve, glaucoma surgery, tube shunt surgery

Background: Group C meningococcal conjugate-vaccine effectiveness in the United Kingdom declines from ~90% in the first year to 0% between 1 and 4 years after immunization in infants immunized at 2, 3, and 4 months of age and to 61% in toddlers given a single dose. Confidence intervals are wide, and the extent of protection is uncertain.Methods: Serum samples were obtained from children 3-5 years of age who were participants in a preschool booster-vaccine trial. Serum bactericidal activity was measured with human complement. Group C anticapsular antibody concentrations were measured by a radioantigen binding assay. Passive protection was analyzed in an infant rat bacteremia model.Results: Serum samples from UK children who had been immunized 2-3 years earlier as infants or toddlers had higher levels of radioantigen binding, bactericidal activity, and passive protection than did historical control serum samples from unimmunized children (P<.05). A higher proportion of children immunized as infants had serum bactericidal activity titers > or =1 : 4 (considered to be protective) than those immunized as toddlers (61% vs. 24%; P<.01), but there were no significant differences in the proportion of serum samples conferring passive protection (50% and 41%, respectively; P=.4).Conclusions: We found no evidence of lower immunity in children immunized as infants than as toddlers. On the basis of serum bactericidal activity and/or passive protection, 40%-50% of both age groups are protected at 2-3 years after immunization, which was significantly greater than in unimmunized historical controls (<5%). [ABSTRACT FROM AUTHOR]

Background: A quadrivalent meningococcal conjugate vaccine (MCV-4) is recommended for United States teenagers. The duration of protective immunity is unknown. We investigated serum antibody persistence 3 years after vaccination of adolescents.Methods: Serum samples from participants of a randomized trial who had received MCV-4 (n=52) or polysaccharide vaccine (MPSV-4; n=48) and from unvaccinated controls (n=60) were assayed for serogroups C, W-135, and Y anticapsular antibody concentrations by use of a radioantigen binding assay and for bactericidal activity (in a human complement assay) and passive protection against serogroup C bacteremia in an infant rat model.Results: A higher proportion of participants in the vaccine groups had protective bactericidal titers (> or =1 : 4), compared with that in the control group (for MCV-4 recipients vs. controls, P<.01; for MPSV-4 recipients vs. controls, P< or =.06). More MCV-4 recipients had W-135 bactericidal titers > or =1 : 4 than did MPSV-4 recipients (P=.01). More MCV-4 recipients had passive protective activity against serogroup C bacteremia than did MPSV-4 recipients (76% vs. 49%; P<.01). The differences in protective activity were largest between participants in the vaccine groups with bactericidal titers <1 : 4 (63% protective in MCV-4 recipients vs. 31% protective in MPSV-4 recipients; P=.01).Conclusions: Compared with MPSV-4, MCV-4 elicited greater persistence of antibody activity against serogroups C and W-135 at 3 years after vaccination in adolescents. On the basis of passive protection data in an infant rat model, bactericidal titers > or =1 : 4 underestimate protective immunity. [ABSTRACT FROM AUTHOR]

Purpose: To identify which features of Sturge-Weber Syndrome (SWS) were most associated with glaucoma onset, severity, and treatment failure at a tertiary care center., Design: Retrospective cross-sectional study., Subjects: Children who had SWS with and without glaucoma., Methods: Electronic health records were reviewed for all children with SWS presenting between 2014-2020. Examination and imaging findings from dermatology, neurology, and ophthalmology were collected. Logistic regression was used to identify factors associated with glaucoma-related outcomes., Main Outcome Measures: Primary outcomes included glaucoma development, progression to surgery, and treatment failure. Failure was defined as having a final intraocular pressure >21 mmHg, devastating complication, or ≤20/200 vision., Results: Twenty-three of 44 SWS patients (52.3%) developed glaucoma, and 6 of 23 patients (26.1%) had both eyes affected. Sixteen of 29 eyes (55.2%) required surgery, and 29.6% overall met our failure criteria (mean follow-up: 5.1±4.3 years). Glaucoma diagnosis was associated with bilateral port wine birthmarks (PWB; OR 5.9; 95% CI 1.3-43.2), PWB with any lower eyelid involvement (OR 9.7, 95% CI 2.6-44.5), and choroidal hemangiomas (OR 3.8, 95% CI 1.1-13.8), but was not associated with upper eyelid or leptomeningeal angiomas, seizures, prior hemispherectomy or pulsed-dye laser. Eyes that progressed to surgery were more likely to have PWB affecting the lower eyelid (OR 33.7, 95% CI 4.5-728.0). No clinical or demographic factors were associated with treatment failure. In most cases, angle surgery failed (72.7%) but was a temporizing measure before subconjunctival filtering surgery., Conclusions: Lower eyelid and choroidal angiomas were associated with glaucoma diagnosis, suggesting a spatial relationship with SWS findings. However, leptomeningeal angiomas were not associated possibly because these are further from the eye., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To describe intraocular pressure (IOP) changes after injection of subtenon triamcinolone (STT) during examination under anesthesia (EUA) for pediatric patients., Methods: Multicenter, retrospective case series of pediatric patients STT from three tertiary care ophthalmic services between November 2018 and October 2023., Results: Of 392 patients identified, 59 eyes of 41 patients (10.5%) were included. Laser was administered in 95.1% of the cases. STT dose ranged from 4 to 20 mg. The most common diagnosis was retinopathy of prematurity (43.9%). Two eyes (3.4%) of 2 patients (4.9%) were mild steroid responders. One eye (1.7%) of 1 patient (2.4%) was a moderate responder. There were no high steroid responders, and all eyes with steroid response showed a return of IOP to normal range at next visit without needing any IOP-lowering medications. No patients were diagnosed with glaucoma or required glaucoma surgery. Only 1 eye (1.7%) developed trace posterior subcapsular cataract, while no optic disc cupping or inflammation were noted., Conclusions: Subtenon triamcinolone injection is commonly used to prevent inflammation at the time of retinal photocoagulation treatment in pediatric patients. It has a favorable safety profile in relation to IOP elevation and cataract formation. There was no requirement for IOP lowering medications or surgical interventions.

Despite the increasing burden of dengue, the regional emergence of the virus in Kenya has not been examined. This study investigates the genetic structure and regional spread of dengue virus-2 in Kenya. Viral RNA from acutely ill patients in Kenya was enriched and sequenced. Six new dengue-2 genomes were combined with 349 publicly available genomes and phylogenies used to infer gene flow between Kenya and other countries. Analyses indicate two dengue-2 Cosmopolitan genotype lineages circulating in Kenya, linked to recent outbreaks in coastal Kenya and Burkina Faso. Lineages circulating in Western, Southern, and Eastern Africa exhibiting similar evolutionary features are also reported. Phylogeography suggests importation of dengue-2 into Kenya from East and Southeast Asia and bidirectional geneflow. Additional lineages circulating in Africa are also imported from East and Southeast Asia. These findings underscore how intermittent importations from East and Southeast Asia drive dengue-2 circulation in Kenya and Africa more broadly., (© 2024. The Author(s).)

Background: MicroRNAs (miRs) are emerging targets for the diagnosis, prognosis and treatment of heart failure (HF). Accumulated evidence showed that microRNA-132 (miR-132) and microRNA-152 (miR-152) play critical roles in the development of multiple pathological processes of the heart. Although their upregulations have been detected in the failing hearts of humans and animal models, little is known about the circulating levels of miR-132 and miR-152 in patients with HF., Methods: Our study was conducted from January 2022 to August 2022 at the Cardiology Department of the University Medical Center in Ho Chi Minh City, Vietnam. During study period, 36 participants were consecutively enrolled, including 18 HF patients and 18 patients who age and sex matched the non-HF controls. Serum samples of study participants were collected on admission and the expression levels of miR-132 and miR-152 were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR). The comparative cycle threshold method (ΔCt) was applied to calculate the relative expression of miRs., Results: The miR concentration in HF group was significantly lower than that in the control group. In contrast, the serum levels of miR-132 and miR-152 were significantly higher in HF patients. Further analyses of receiver operating characteristic (ROC) curve showed that miR-132 and miR-152 individually had moderate diagnostic potential for HF (with area under curve [AUC] values of 0.713 and 0.698, respectively). A positive correlation between these miRs was also confirmed., Conclusion: Serum miR-132 and miR-152 were upregulated in Vietnamese patients with HF and may serve as candidate biomarkers for diagnostic purposes., Competing Interests: Conflict of Interest: None., (© Penerbit Universiti Sains Malaysia, 2024.)

Purpose: To compare demographic and clinical factors associated with glaucoma following cataract surgery (GFCS) and glaucoma surgery rates between infants, toddlers, and older children using a large, ophthalmic registry., Design: Retrospective cohort study., Participants: Patients in the IRIS® Registry (Intelligent Research in Sight) who underwent cataract surgery at ≤ 17 years old and between January 1, 2013 and December 31, 2020., Methods: Glaucoma diagnosis and procedural codes were extracted from the electronic health records of practices participating in the IRIS Registry. Children with glaucoma diagnosis or surgery before cataract removal were excluded. The Kaplan-Meier estimator was used to determine the cumulative probability of GFCS diagnosis and glaucoma surgery after cataract surgery. Multivariable Cox regression was used to identify factors associated with GFCS and glaucoma surgery., Main Outcome Measures: Cumulative probability of glaucoma diagnosis and surgical intervention within 5 years after cataract surgery., Results: The study included 6658 children (median age, 10.0 years; 46.2% female). The 5-year cumulative probability of GFCS was 7.1% (95% confidence interval [CI], 6.1%-8.1%) and glaucoma surgery was 2.6% (95% CI, 1.9%-3.2%). The 5-year cumulative probability of GFCS for children aged < 1 year was 22.3% (95% CI, 15.7%-28.4%). Risk factors for GFCS included aphakia (hazard ratio [HR], 2.63; 95% CI, 1.96-3.57), unilateral cataract (HR, 1.48; 95% CI, 1.12-1.96), and Black race (HR, 1.61; 95% CI, 1.12-2.32). The most common surgery was glaucoma drainage device insertion (32.6%), followed by angle surgery (23.3%), cyclophotocoagulation (15.1%), and trabeculectomy (5.8%)., Conclusions: Glaucoma following cataract surgery diagnosis in children in the IRIS Registry was associated with young age, aphakia, unilateral cataract, and Black race. Glaucoma drainage device surgery was the preferred surgical treatment, consistent with the World Glaucoma Association 2013 consensus recommendations for GFCS management., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Calcific tendinitis is classically a painful condition that most commonly affects the rotator cuff, but may infrequently involve other tendons., Case Report: We discuss a 57-year-old man who presented to the emergency department with a 4-day history of right hip pain, described as the "worst pain in (his) life." The pain was first noticed at night and had progressively worsened. History, physical examination, and initial laboratory workup indicated an inflammatory vs. infectious process. Continued investigations with imaging techniques revealed the source of pain as calcific tendinitis involving the gluteus maximus tendon. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Symptoms of musculoskeletal pain in the emergency department are ubiquitous. In the proper clinical context, the diagnosis of calcific tendinitis, although uncommon, should be considered once emergent conditions are ruled out. Proper imaging techniques will facilitate accurate diagnosis, expedited pain management, and proper outpatient follow-up., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Small extracellular vesicles from adipose-derived stem cells (ASC-sEVs) have gained remarkable attention for their regenerative and protective properties against skin aging. However, the use of ASC-sEVs to further encapsulate certain natural anti-aging compounds for synergistic effects has not been actively explored. For large-scale production in skincare industry, it is also crucial to standardize cost-effective methods to produce highly pure ASC-sEVs., Methods: Human ASCs were expanded in serum-free media with different compositions to first optimize the sEV production. ASC-sEVs from different batches were then purified using tangential flow filtration and sucrose cushion ultracentrifugation, followed by extensive characterization for identity and content profiling including proteomics, lipidomics and miRNA sequencing. ASC-sEVs were further loaded with nicotinamide riboside (NR) and resveratrol by sonication-incubation method. The therapeutic effect of ASC-sEVs and loaded ASC-sEVs was tested on human keratinocyte cell line HaCaT exposed to UVB by measuring reactive oxygen species (ROS). The loaded ASC-sEVs were later applied on the hand skin of three volunteers once a day for 8 weeks and skin analysis was performed every 2 weeks., Results: Our standardized workflow produced ASC-sEVs with high yield, high purity and with stable characteristics and consistent biocargo among different batches. The most abundant subpopulations in ASC-sEVs were CD63 + (∼30%) and CD81 + -CD63 + (∼35%). Purified ASC-sEVs could be loaded with NR and resveratrol at the optimized loading efficiency of ∼20%. In UVB-exposed HaCaT cells, loaded ASC-sEVs could reduce ROS by 38.3%, higher than the sEVs (13.3%) or compounds (18.5%) individually. In human trial, application of loaded ASC-sEVs after 8 weeks substantially improved skin texture, increased skin hydration and elasticity by 104% and reduced mean pore volume by 51%., Conclusions: This study demonstrated a robust protocol to produce ASC-sEVs and exogenously load them with natural compounds. The loaded ASC-sEVs exhibited synergistic effects of both sEVs and anti-aging compounds in photoaging protection and skin rejuvenation., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field., Objectives: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health., Methods: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles., Results: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3))., Conclusion: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database., (© 2024. The Author(s).)

Prcis: Juvenile open angle glaucoma (JOAG) patients with thick central corneas and negative family history were more likely to undergo surgery, mainly trabeculectomy with half requiring additional surgery within 10 years., Purpose: To assess the characteristics and treatment outcomes of patients with JOAG in Thailand., Patients and Methods: This retrospective, multicenter study included all patients diagnosed with JOAG over 12 years from 2 tertiary hospitals in Bangkok, Thailand., Results: A total of 200 eyes from 104 patients were included in this study. The mean age of onset was 24.0±10.1 years (range: 5-40 y), with male predominance (60.5%). Over 90% of patients had bilateral JOAG and 25% had a positive family history. Negative family history (adjusted odds ratio=4.59, P =0.02) and thick central corneal thickness were surgical predictors (every 10 µm adjusted odds ratio=1.29, P =0.01). Over 70% of cases needed glaucoma surgery. Trabeculectomy with Mitomycin-C was performed on 131 eyes (65.5%) with a cumulative probability of complete success of 71.0%, 57.8%, 39.2%, and 26.9% and qualified success of 86.3%, 73.6%, 64.8%, and 45.7% at 1, 3, 5, and 10 years, respectively. The mean follow-up after surgery was 94.9 ± 69.8 months (range: 13-153 mo). There were no serious postoperative complications. Myopia and the number of baseline glaucoma medications were significantly associated with surgical failure., Conclusions: Trabeculectomy with mitomycin C was the most common primary surgery performed in Thai patients with JOAG, and successfully reduced intraocular pressure without significant complications. Patients with thicker corneas were more likely to undergo surgery. By 10 years, half of the patients required additional surgery and risk factors for failure included myopia and the number of medications., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To review the efficacy and safety of two common postoperative regimens following Kahook Dual Blade goniotomy with phacoemulsification cataract extraction (KDB-CE)., Materials and Methods: This is a retrospective review of eyes undergoing KDB-CE from May 2016 to 2018 by a single surgeon. Almost 12-month follow-up data were assessed for two common postop regimens-treatment with (1) topical prednisolone acetate 1% with pilocarpine 1% (pred-pilo) or (2) difluprednate 0.05% postoperatively. Postoperative results were compared to each respective baseline intraocular pressure (IOP) levels., Results: There were 53 eyes in the difluprednate group and 25 eyes in the pred-pilo group. In the difluprednate group, the IOP decreased at postoperative day 1 (POD1) [16 ± 5 baseline vs 15 ± 5 POD1, mean ± standard deviation (SD) in mm Hg, and p = 0.321], but increased at postoperative week 1 (POW1) due to a 15% rate of IOP-spikes (19 ± 9, p = 0.099). The number of IOP-lowering drops decreased from baseline (2 ± 1 drops) to 1 ± 1 drops at POD1 ( p < 0.0001), and remained at 1 ± 1 drops through postoperative month 12 (POM12) ( p < 0.0001). In the pred-pilo group, there was a statistically significant decrease in mean IOP at POW1 (16 ± 4 POW1 vs 18 ± 6 baseline, p = 0.044), which persisted through POM6. The number of IOP-lowering drops was not statistically significantly lower from baseline at POM3 (2 ± 1 at POM3, p = 0.188). Spikes in IOP, corneal edema, and hyphema were the most common complications., Conclusion: Both postoperative regimens were effective following KDB-CE at reducing IOP at 12 months. The difluprednate group was likely to experience an IOP-spike at POW1 but used fewer IOP-lowering drops 12 months after KDB goniotomy. In the pred-pilo group, the number of IOP-lowering drops was equivalent to baseline levels at POM3. Aside from IOP spikes, there were similar complication rates observed between the two postoperative regimens. Due to demographic differences, it was not possible to compare relative IOP-lowering efficacy between the two postoperative regimens., Clinical Significance: It is efficacious and safe to use either postoperative regimen following KBD-CE. Postoperative trajectories may differ with respect to the postoperative regimen, but further randomized controlled trials are needed to compare various topical steroid medications for postoperative regimens following KDB-CE., How to Cite This Article: Birnbaum F, Wakil S, Vu DM, et al. Postoperative Management of Kahook Dual Blade Goniotomy with Phacoemulsification Cataract Extraction. J Curr Glaucoma Pract 2023;17(4):169-174., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Background: Glaucoma secondary to familial exudative vitreoretinopathy presents as angle closure by either neovascular or non-neovascular mechanisms. We analyze the presentation and outcomes of two types of childhood glaucoma secondary to familial exudative vitreoretinopathy (FEVR)., Methods: This retrospective cross-sectional study included all patients <18 years of age diagnosed with glaucoma after or concurrently with a diagnosis of FEVR between 2010 and 2020 from Queen Sirikit National Institute of Child Health in Bangkok, Thailand. Two groups were analyzed: neovascular or non-neovascular angle-closure status. Primary outcome measures were final visual acuity and intraocular pressure (IOP) in both groups., Results: Of 144 FEVR patients, 8 children (5.5%; 11 eyes, 3 bilateral cases) developed childhood glaucoma. Mean time between FEVR presentation and glaucoma was 42.2 ± 40.0 months. In the neovascular group, 3 of 9 eyes presented with glaucoma at FEVR diagnosis; 3 of 9 eyes (33%) required glaucoma surgery. In the non-neovascular group, 2 eyes presented with acute angle closure secondary to a phacomorphic lens. Both were treated with trabeculectomy, with resolution of pupillary block. All eyes had stage 4B FEVR or greater. Six of 8 eyes had stable or better visual acuity, and 10 eyes (91%) had IOP <21 mm Hg at final follow-up., Conclusions: Childhood glaucoma secondary to FEVR is a rare complication caused by later stages of the disease. It may present as neovascular or non-neovascular angle closure, often requiring complex care. Therefore, awareness and adequate management of FEVR can help prevent additional morbidity from childhood glaucoma., (Copyright © 2023 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Poor access to diagnostic testing in resource limited settings restricts surveillance for emerging infections, such as dengue virus (DENV), to clinician suspicion, based on history and exam observations alone. We investigated the ability of machine learning to detect DENV based solely on data available at the clinic visit. We extracted symptom and physical exam data from 6,208 pediatric febrile illness visits to Kenyan public health clinics from 2014-2019 and created a dataset with 113 clinical features. Malaria testing was available at the clinic site. DENV testing was performed afterwards. We randomly sampled 70% of the dataset to develop DENV and malaria prediction models using boosted logistic regression, decision trees and random forests, support vector machines, naïve Bayes, and neural networks with 10-fold cross validation, tuned to maximize accuracy. 30% of the dataset was reserved to validate the models. 485 subjects (7.8%) had DENV, and 3,145 subjects (50.7%) had malaria. 220 (3.5%) subjects had co-infection with both DENV and malaria. In the validation dataset, clinician accuracy for diagnosis of malaria was high (82% accuracy, 85% sensitivity, 80% specificity). Accuracy of the models for predicting malaria diagnosis ranged from 53-69% (35-94% sensitivity, 11-80% specificity). In contrast, clinicians detected only 21 of 145 cases of DENV (80% accuracy, 14% sensitivity, 85% specificity). Of the six models, only logistic regression identified any DENV case (8 cases, 91% accuracy, 5.5% sensitivity, 98% specificity). Without diagnostic testing, interpretation of clinical findings by humans or machines cannot detect DENV at 8% prevalence. Access to point-of-care diagnostic tests must be prioritized to address global inequities in emerging infections surveillance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A complex interplay exists within the tumor microenvironment and extracellular matrix, which could contribute to solid tumor progression. Collagen, a major component of the extracellular matrix, may correlate with cancer prognosis. While thermal ablation has shown promise as a minimally invasive treatment of solid tumors, its impact on collagen is still unknown. In this study, we demonstrate that thermal ablation, but not cryo-ablation, induces irreversible collagen denaturation in a neuroblastoma sphere model. Prolonged collagen denaturation resulted in a significant reduction in sphere stiffness, migration, and proliferation, and an increase in apoptosis. Mechanistic analysis revealed that collagen denaturation inhibited collagen cross-linking, reduced extracellular LOX/LOXL2 expression, and resulted in decreased phosphorylation of FAK. Downstream of FAK, we observed reduced epithelial to mesenchymal transition, attenuated CDC42 expression, and decreased migration. Collectively, these results suggest that denatured collagen presents a novel target for modulating the tumor microenvironment and treating solid cancers via the LOX1/LOXL2-FAK signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to determine the antibiotic-resistant profile and to identify molecular characterization of some virulence genes of Klebsiella spp. isolated from mastitis samples in Vietnam., Materials and Method: A total of 468 samples from clinical mastitis cases were collected and submitted to the Laboratory. All samples were cultured, and Klebsiella spp. was identified through biochemical reactions and confirmed by Polymerase chain reaction (PCR). Antimicrobial resistance was tested by disk diffusion method, and virulence and resistance genes were tested by PCR., Results: An antibiogram study showed that a high proportion of isolates are multidrug-resistant (94%). All isolates were resistant to lincomycin and sulfamethoxazole, followed by ampicillin (94%), sulphonamide (66%), amoxicillin (56%), streptomycin (52%), polymyxin B (28%), colistin sulfate (12%), tetracycline (6%), ciprofloxacin (4%), florfenicol (4%), enrofloxacin (4%), piperacillin (2%), trimethoprim (2%), nalidixic acid (2%), imipenem (2%), and sulfamethoxazole/trimethoprim (2%). In contrast, all isolates showed sensitivity to gentamicin and ceftiofur. The appearance of an efflux pump system, extended-spectrum beta-lactamase (ESBL), tetracycline, and sulphonamides-resistant genes was reconfirmed using different specific primers. Capsular serotype K1 and virulence genes mag A, fim H, and ent B, responsible for hypermucoviscosity production, adherence, and enterobactin production, were confirmed in isolates. Multidrug resistance and virulence potential in Klebsiella spp. are changing this mastitis pathogen into a superbug and making its management harder., Conclusions: Klebsiella spp. associated with bovine mastitis in Nghe An province were mostly multidrug-resistant and carried virulence genes including fim H, ent B, and antimicrobials resistant genes ( bla SHV , acr A Kp , tet A, etc.), but these isolates were not ESBL producers., Competing Interests: The authors know no conflict of interest to declare., (Copyright: © Journal of Advanced Veterinary and Animal Research.)

Background: Before the SARS-CoV-2 Delta variant arrived in Vietnam, case rates suggested seroprevalence of SARS-CoV-2 was low. Beginning in March 2021, we assessed different dosing schedules and adverse events following immunization (AEFIs) for ChAdOx1 nCoV-19 vaccine among healthcare workers (HCWs)., Methods: We performed a prospective cohort study to estimate the prevalence of IgG antibodies to SARS-CoV-2 before and after ChAdOx1 nCoV-19 vaccination. We conducted antibody testing among HCWs in February 2021 (baseline), before the second dose (June-July 2021), and 1 and 3 months after the second dose. We detected antibodies to SARS-CoV-2 using Tetracore® FlexImmArray™, and surrogate neutralizing antibodies using GenScript cPass™. Neither assay can distinguish natural from vaccine-induced antibodies. We assessed AEFIs through interview post-dose 1 and 1 month post-dose 2., Results: Before vaccination, 1/617 participants (0.16%) had antibodies to SARS-CoV-2. Of these 617, 405 were vaccinated with ChAdOx1 nCoV-19 with 4-8- (60%), 9-12- (27%), or ≥13-week (13%) intervals between the 2 doses. Three months following series completion, 99% and 97% of vaccinated participants had ≥1 sample with detectable antibodies and surrogate neutralizing antibodies against SARS-CoV-2, respectively. We observed no significant differences among those with different dosing intervals at last follow-up. All participants reported PCR testing for SARS-CoV-2 during the study; 2 (0.5%) were laboratory-confirmed. AEFIs were more frequent post-dose 1 (81%) vs post-dose 2 (21%)., Conclusions: In this population, regardless of dosing interval, ChAdOx1 nCoV-19 induced antibodies within 3 months of the second dose. These findings may offer flexibility to policymakers when balancing programmatic considerations with vaccine effectiveness., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been illustrated for their roles in immunological modulation and tissue regeneration through the secretome. Additionally, culture conditions can trigger the secretion of extracellular vesicles (EVs) into extracellular environments with significant bioactivities. This study aims to investigate the roles of three EV sub-populations released by UCMSCs primed with transforming growth factor β (TGFβ) and their capacity to alter dermal fibroblast functions for skin aging. Results show that three EV sub-populations, including apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXs), were separated from conditioned media. These three EVs carried growth factors, such as FGF-2, HGF, and VEGF-A, and did not express noticeable effects on fibroblast proliferation and migration. Only EX from TGFβ-stimulated UCMSCs exhibited a better capacity to promote fibroblasts migrating to close scratched wounds than EX from UCMSCs cultured in the normal condition from 24 h to 52 h. Additionally, mRNA levels of ECM genes (COL I, COL III, Elastin, HAS II, and HAS III) were detected with lower levels in fibroblasts treated with EVs from normal UCMSCs or TGFβ-stimulated UCMSCs compared to EV-depleted condition. On the contrary, the protein levels of total collagen and elastin released by fibroblasts were greater in the cell groups treated with EVs compared to EV-depleted conditions; particularly elastin associated with TGFβ-stimulated UCMSCs. These data indicate the potential roles of EVs from UCMSCs in protecting skin from aging by promoting ECM protein production.

A 69-year-old man with myelofibrosis presented with a two-day history of left periorbital swelling, blurred vision, and non-radiating dull orbital pain. On examination, there was restricted left-sided extraocular motility with conjunctival injection, chemosis, and periorbital edema. Magnetic resonance imaging demonstrated left-sided pre- and post-septal fat stranding concerning for orbital cellulitis. Two weeks before symptom onset, the patient began fedratinib therapy for myelofibrosis but discontinued this medication upon hospital admission. After restarting fedratinib, he presented with similar right-sided ophthalmic signs. A review of his medication history revealed a temporal relationship between symptom onset and fedratinib use. After medication discontinuation, his symptoms improved rapidly.

Background: In low-resource, malaria-endemic settings, accurate diagnosis of febrile illness in children is challenging. The World Health Organization (WHO) currently recommends laboratory-confirmed diagnosis of malaria prior to starting treatment in stable children. Factors guiding management of children with undifferentiated febrile illness outside of malaria are not well understood., Methods: This study examined clinical presentation and management of a cohort of febrile Kenyan children at 5 hospital/clinic sites from January 2014 to December 2017. Chi-squared and multivariate regression analyses were used to compare frequencies and correlate demographic, environmental, and clinical factors with patient diagnosis and prescription of antibiotics., Results: Of 5735 total participants, 68% were prescribed antibiotic treatment (n = 3902), despite only 28% given a diagnosis of bacterial illness (n = 1589). Factors associated with prescription of antibiotic therapy included: negative malaria testing, reporting head, ears, eyes, nose and throat (HEENT) symptoms (ie, cough, runny nose), HEENT findings on exam (ie, nasal discharge, red throat), and having a flush toilet in the home (likely a surrogate for higher socioeconomic status)., Conclusion: In a cohort of acutely ill Kenyan children, prescription of antimalarial therapy and malaria test results were well correlated, whereas antibiotic treatment was prescribed empirically to most of those who tested malaria negative. Clinical management of febrile children in these settings is difficult, given the lack of diagnostic testing. Providers may benefit from improved clinical education and implementation of enhanced guidelines in this era of malaria testing, as their management strategies must rely primarily on critical thinking and decision-making skills., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Human bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM-MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM-MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM-MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer-based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C-peptide levels throughout the 12-month follow-up. Our data indicated that autologous BM-MSC administration was well tolerated in 30 T2DM patients. Short-term therapeutic effects were observed in patients with T2DM duration of <10 years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM-MSC population. T2DM duration directly altered the proliferation rate of BM-MSCs, abrogated the glycolysis and mitochondria respiration of BM-MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM-MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10 years and no obesity. Prior to further confirming the effects of T2DM on BM-MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation., (© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

We present the first reported quantification of trace elements in plutonium via a portable laser-induced breakdown spectroscopy (LIBS) device and demonstrate the use of chemometric analysis to enhance the handheld device's sensitivity and precision. Quantification of trace elements such as iron and nickel in plutonium metal via LIBS is a challenging problem due to the complex nature of the plutonium optical emission spectra. While rapid analysis of plutonium alloys has been demonstrated using portable LIBS devices, such as the SciAps Z300, their detection limits for trace elements are severely constrained by their achievable pulse power and length, light collection optics, and detectors. In this paper, analytical methods are evaluated as a means to circumvent the detection constraints. Three chemometric methods often used in analytical spectroscopy are evaluated; principal component regression, partial least-squares regression, and artificial neural networks. These models are evaluated based on goodness-of-fit metrics, root mean-squared error, and their achievable limits of detection (LoDs). Partial least squares proved superior for determining content of iron and nickel in plutonium metal, yielding LoDs of 15 and 20 ppm, respectively. These results of identifying the undesirable trace elements in plutonium components are critical for applications such as fabricating radioisotope thermoelectric generators or nuclear fuel.

Targeted delivery and controlled release of drugs has been considered to be an important therapeutic approach since it could allow a better treatment efficiency and less side effects. In this research, magnetite Fe 3 O 4 nanoparticles were successfully synthesized via the coprecipitation method and then loaded in alginate beads with berberine as a drug model for drug release application. Various factors such as pH values of the suspended environment and surface modifications of the drug carrier could be exploited to adjust the amount of drug release. More importantly, the amount of drug release could be effectively controlled by an on-off switching operation of a static magnetic field., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Dung The Nguyen et al.)

Purpose: To assess the number of infants at risk of delayed primary congenital glaucoma (PCG) evaluation due to long travel times to specialists., Design: Cross-sectional geospatial service coverage analysis., Methods: All American Glaucoma Society (AGS) and American Association for Pediatric Ophthalmology and Strabismus (AAPOS) provider locations were geocoded using each organization's member directory. Sixty-minute drive time regions to providers were generated using ArcGIS Pro (Esri). The geographic intersection of AGS and AAPOS service areas was computed because patients typically require visits to both types of specialists. American Community Survey data were then overlaid to estimate the number of infants within and beyond the AGS/AAPOS service areas., Results: One thousand twenty-nine AGS and 1,040 AAPOS provider locations were geocoded. The analysis yielded 944,047 infants age 0-1 year (23.6%) who live beyond the AGS/AAPOS service areas. Therefore, approximately 14-94 new PCG cases/year may be at risk of delayed diagnosis as a result of living in a potential service desert. Compared with children living within the AGS/AAPOS service areas, children aged <6 years in these potential service deserts were more likely to live in households earning below the US federal poverty level, lack health insurance, and live in a single-parent home. These communities are disproportionately likely to experience other rural health disparities and are more prevalent across the Great Plains., Conclusion: Service coverage analysis is a useful tool for identifying underserved regions for PCG referrals and evaluation. These data may assist in targeting screening programs in low access areas for pediatric glaucoma care., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Precis: Approximately 1 in 9 Florida residents over the age of 65 years (438,642 people) live more than an hour away from a glaucoma specialist, which represents a significant barrier to care., Purpose: To describe access to glaucoma care for Florida's elderly population using travel time to American Glaucoma Society (AGS) member offices., Methods: For this cross-sectional service coverage analysis, a list of AGS member locations was extracted from the AGS website, and addresses were geocoded using ArcGIS Online. Driving time regions were created using the service area tool in ArcGIS Pro 2.4 and overlaid with 2010 United States Census and 2016 American Community Survey data for all Florida residents age 65 or older., Results: Fifty-eight AGS member providers with 65 locations were identified and geocoded. There were 3,797,625 individuals aged over 65 years in Florida, of which 1,153,320 (30.4%) lived within 15 minutes of driving time from an AGS provider's office, 2,586,825 (68.1%) within 30 minutes, 3,358,983 (88.4%) within 60 minutes, and 3,491,815 (91.9%) within 120 minutes. The areas with the lowest access include rural areas near Lake Okeechobee and the Florida Panhandle. The population living beyond a 60-minute drive was more likely to be White, non-Hispanic and older, but less likely to be living below the federal poverty level or receiving public assistance than the population living within a 60-minute drive., Conclusions: There is a significant travel burden for the elderly community of Florida to reach AGS providers. Additional studies could help identify other social barriers to accessing glaucoma providers in Florida and beyond in an effort to improve patient compliance and, ultimately, vision outcomes.

Introduction Recently, an expert consensus on optimal use of procalcitonin (PCT)-guided antibiotic stewardship was published focusing mainly on Europe and the United States. However, for Asia-Pacific countries, recommendations may need adaptation due to differences in types of infections, available resources and standard of clinical care. Methods Practical experience with PCT-guided antibiotic stewardship was discussed among experts from different countries, reflecting on the applicability of the proposed Berlin consensus algorithms for Asia-Pacific. Using a Delphi process, the group reached consensus on two PCT algorithms for the critically ill and the non-critically ill patient populations. Results The group agreed that the existing evidence for PCT-guided antibiotic stewardship in patients with acute respiratory infections and sepsis is generally valid also for Asia-Pacific countries, in regard to proposed PCT cut-offs, emphasis on diagnosis, prognosis and antibiotic stewardship, overruling criteria and inevitable adaptations to clinical settings. However, the group noted an insufficient database on patients with tropical diseases currently limiting the clinical utility in these patients. Also, due to lower resource availabilities, biomarker levels may be measured less frequently and only when changes in treatment are highly likely. Conclusions Use of PCT to guide antibiotic stewardship in conjunction with continuous education and regular feedback to all stakeholders has high potential to improve the utilization of antibiotic treatment also in Asia-Pacific countries. However, there is need for adaptations of existing algorithms due to differences in types of infections and routine clinical care. Further research is needed to understand the optimal use of PCT in patients with tropical diseases.

Little is known about the extent and serotypes of dengue viruses circulating in Africa. We evaluated the presence of dengue viremia during 4 years of surveillance (2014-2017) among children with febrile illness in Kenya. Acutely ill febrile children were recruited from 4 clinical sites in western and coastal Kenya, and 1,022 participant samples were tested by using a highly sensitive real-time reverse transcription PCR. A complete case analysis with genomic sequencing and phylogenetic analyses was conducted to characterize the presence of dengue viremia among participants during 2014-2017. Dengue viremia was detected in 41.9% (361/862) of outpatient children who had undifferentiated febrile illness in Kenya. Of children with confirmed dengue viremia, 51.5% (150/291) had malaria parasitemia. All 4 dengue virus serotypes were detected, and phylogenetic analyses showed several viruses from novel lineages. Our results suggests high levels of dengue virus infection among children with undifferentiated febrile illness in Kenya.

Purpose: To compare the 18-month efficacy and safety of Kahook Dual Blade goniotomy (KDB) in combination with cataract surgery (combined group) or as a standalone procedure (standalone group)., Setting: Single surgeon practice., Design: Retrospective review study., Methods: A total of 116 eyes of 100 patients underwent KDB by a single well-experienced surgeon from May 2016 to 2018. A total of 93 eyes and 23 eyes were in the combined and standalone groups, respectively. Main outcome measures were reduction in intraocular pressure (IOP) and IOP-lowering medication and adverse events. Data were collected and analyzed using Welch t tests in R., Results: A total of 116 eyes of 100 patients were included in the analysis. Moderate or severe glaucoma was observed in 71% of eyes in the combined group compared with 83% in the standalone group. At baseline, mean IOP was 16.5 ± 5.0 mm Hg (n = 93) and 24.3 ± 9.1 mm Hg (n = 23) in the combined and standalone groups, respectively (P < .05). The IOP decreased in both groups at 12 months (14.1 ± 3.9 vs 16.9 ± 7.6, P = .24) and 18 months (14.4 ± 3.7 vs 16.7 ± 7.6, P = .5). There was a statistically significant difference in the number of drops between the combined and standalone groups at baseline (2.4 ± 1.2 vs 2.9 ± 1.0, P < .05) persisting at 12 months (1.3 ± 1.2 vs 2.6 ± 1.2, P < .05) and at 18 months (1.3 ± 1.2 vs 3.3 ± 1.2, P < .05). Complications included transient hyphemas (20 eyes [17%]) and IOP spike (20 eyes [17%]). Seven eyes required additional glaucoma surgery, 5 of which were in the standalone group., Conclusions: KDB was an effective and safe procedure for different glaucoma disease severities, whether combined with cataract surgery or as a standalone surgery. It is an alternative to consider prior to pursuing more invasive glaucoma surgeries.

Exosomes are nano-scale and closed membrane vesicles which are promising for therapeutic applications due to exosome-enclosed therapeutic molecules such as DNA, small RNAs, proteins and lipids. Recently, it has been demonstrated that mesenchymal stem cell (MSC)-derived exosomes have capacity to regulate many biological events associated with wound healing process, such as cell proliferation, cell migration and blood vessel formation. This study investigated the regenerative potentials for cutaneous tissue, in regard to growth factors associated with wound healing and skin cell proliferation and migration, by exosomes released from primary MSCs originated from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) under serum- and xeno-free condition. We found crucial wound healing-mediated growth factors, such as vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), hepatocyte growth factor (HGF), and platelet-derived growth factor BB (PDGF-BB) in exosomes derived from all three MSC sources. However, expression levels of these growth factors in exosomes were influenced by MSC origins, especially transforming growth factor beta (TGF-β) was only detected in UCMSC-derived exosomes. All exosomes released by three MSCs sources induced keratinocyte and fibroblast proliferation and migration; and, the induction of cell migration is a dependent manner with the higher dose of exosomes was used (20 μg), the faster migration rate was observed. Additionally, the influences of exosomes on cell proliferation and migration was associated with exosome origins and also target cells of exosomes that the greatest induction of primary dermal fibroblasts belongs to BMMSC-derived exosomes and keratinocytes belongs to UCMSC-derived exosomes. Data from this study indicated that BMMSCs and UCMSCs under clinical condition secreted exosomes are promising to develop into therapeutic products for wound healing treatment., (Copyright © 2020 Hoang, Nguyen, Nguyen, Nguyen, Do, Dang, Dam, Bui, Trinh, Vu, Hoang, Thanh and Than.)

Purpose: To report an unusual case of cryptococcal choroiditis and highlight the multimodal imaging findings, particularly the choriocapillaris flow voids using optical coherence tomography angiography., Methods: Retrospective review of the clinical course of a single patient with cryptococcal choroiditis., Results: A 69-year-old man undergoing chemotherapy for T-cell prolymphocytic leukemia developed disseminated crytococcal neoformans infection. He developed bilateral cryptococcal choroiditis with multiple yellow-white choroidal lesion on fundoscopy in both eyes. Multimodal imaging of the choroidal lesions revealed flow voids at the level of the choriocapillaris on optical coherence tomography angiography that corresponded to hypocyanescent areas on indocyanine green angiography when registered and overlaid on the indocyanine green angiography images. The superficial and deep capillary plexuses were spared., Conclusion: This case illustrates that optical coherence tomography angiography was useful in demonstrating that the cryptococcal choroidal lesions impaired choriocapillaris perfusion but spared the superficial and deep retinal plexuses.

Scleral buckling procedures create a challenge for intraocular pressure (IOP) control in the glaucoma patient. The encircling band is believed to compress vortex veins, causing increased episcleral venous pressure, a proposed mechanism for secondary glaucoma. Glaucoma drainage device implantation is preferred over trabeculectomy when medical management fails, but often involves modification of the glaucoma implant and manipulation of the fibrotic capsule surrounding the scleral buckle. This case demonstrates that ab externo XEN gel stent implantation may successfully reduce IOP without interfering with the previous scleral buckle, a major limitation of previous glaucoma filtering surgeries. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:289-292.]., (Copyright 2020, SLACK Incorporated.)

Autism spectrum disorder (ASD) is a complex disorder with an unclear aetiology and an estimated global prevalence of 1%. However, studies of ASD in the Vietnamese population are limited. Here, we first conducted whole exome sequencing (WES) of 100 children with ASD and their unaffected parents. Our stringent analysis pipeline was able to detect 18 unique variants (8 de novo and 10 ×-linked, all validated), including 12 newly discovered variants. Interestingly, a notable number of X-linked variants were detected (56%), and all of them were found in affected males but not in affected females. We uncovered 17 genes from our ASD cohort in which CHD8, DYRK1A, GRIN2B, SCN2A, OFD1 and MDB5 have been previously identified as ASD risk genes, suggesting the universal aetiology of ASD for these genes. In addition, we identified six genes that have not been previously reported in any autism database: CHM, ENPP1, IGF1, LAS1L, SYP and TBX22. Gene ontology and phenotype-genotype analysis suggested that variants in IGF1, SYP and LAS1L could plausibly confer risk for ASD. Taken together, this study adds to the genetic heterogeneity of ASD and is the first report elucidating the genetic landscape of ASD in Vietnamese children.

Purpose: To identify factors associated with the successful treatment of malignant glaucoma (MG)., Design: Retrospective case series., Methods: Setting: single institution; study population: 64 eyes (55 subjects) with MG; observation procedure(s): chart review; main outcome measures: anatomy, intraocular pressure (IOP), best visual acuity (BVA)., Results: 87.5% (n=56/64) of eyes with MG required surgical intervention. Vitrectomy was more likely to be successful in eyes with a history of <3 incisional surgeries, <3 glaucoma drops, or IOP ≤30 mm Hg (P < .05). If vitrectomy was performed within 30 days, recovery of anatomy, BVA, and IOP occurred sooner (P < .05). IOP reduction was greater in subjects treated with oral carbonic anhydrase inhibitors (P = .016) or Nd:YAG laser hyaloidotomy (P = .007), and without a history of MG (P = .007). Time to maximal improvement was significantly longer for IOP and BVA than anatomy (P < .001). Treatment of MG with an oral carbonic anhydrase inhibitor hastened anatomic recovery (P = .01). Time to improvement in BVA was significantly faster in men and African Americans (P < .05). Time to maximal reduction in IOP occurred sooner in eyes that underwent anterior chamber reformation in clinic (P < .002). Trabeculectomy surgery prior to MG was associated with prolonged recovery of anatomy, BVA, and IOP (P < .05)., Conclusions: Earlier vitrectomy may shorten recovery times for MG. Nd:YAG laser hyaloidotomy and oral carbonic anhydrase inhibitors may lead to greater IOP reduction. The time to maximal improvement in IOP and BVA may be longer than the time to anatomic resolution. Although trabeculectomy may impede time to recovery from MG, oral carbonic anhydrase inhibitors may shorten the time to anatomic recovery and anterior chamber reformation may hasten IOP recovery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aggressive, high-risk neuroblastoma (NB) exhibits an immature differentiation state, profound epigenetic dysregulation and high telomerase activity. It has been suggested that aggressive NB may be treatable by inducing differentiation whereas therapeutic targeting of telomerase is under investigation for multiple cancer types. While epigenetic regulation of the telomerase reverse transcriptase (TERT) promoter has been described in high-risk NB, the exact molecular mechanisms are still not completely understood. Here we used quantitative real-time polymerase chain reaction (PCR), chromatin immunoprecipitation qPCR, quantitative telomeric repeat amplification protocol, and immunoblot techniques to investigate epigenetic regulation of TERT in wild-type and genetically modified NB cell lines. We demonstrated that TERT expression is reduced during 13-cis retinoic acid-induced NB differentiation and that this inversely correlated with increased expression of AT-rich interaction domain 1A (ARID1A), a subunit of the SWItch/sucrose nonfermentable chromatin remodeling complex. We showed that ARID1A directly caused suppression of TERT and was reliant on DNA binding and co-occupancy of the TERT promoter by the SIN3 transcription regulator family member A (SIN3A) repressor complex allowing NB differentiation to proceed. Finally, using data from NB patient cohorts, we reported a significant correlation between low ARID1A expression, elevated expression of TERT, and poorly differentiated, high-risk NB. These results provide insights into a key epigenetic pathway responsible for modulating TERT-driven NB progression, which could represent a target for therapeutic intervention., (© 2019 Wiley Periodicals, Inc.)

Congenital syphilis (CS) is a preventable infection, yet the incidence has surged to the highest rates in 20 years. Because 50% of live-born infants with CS are asymptomatic at birth, there is an increasing likelihood that pediatric providers will encounter older infants whose diagnoses were missed at birth, emphasizing the importance of timely prenatal screening and treatment. We present one such case of an infant admitted twice at 3 and 4 months of age with long bone fractures and suspected nonaccidental trauma. On her second presentation, several additional symptoms prompted evaluation for and eventual diagnosis of CS. In this case, it is demonstrated that an isolated long bone fracture can be a first presentation of CS, with other classic findings possibly appearing later. Pediatric providers should be familiar with the varied presentations of CS in older children, including the radiographic findings that we describe. The rising rates of CS reveal deficiencies in our current strategy to prevent CS and, thus, we recommend reconsideration of universal syphilis screening in the third trimester and at delivery, with timely treatment to prevent CS during pregnancy., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Purpose: To assess factors associated with receipt of subsequent medical, laser, or surgical interventions after laser peripheral iridotomy (LPI)., Design: Retrospective review., Participants: A total of 1271 eyes in 692 subjects with narrow angles (NAs) that were treated with LPI., Methods: Demographic and clinical factors associated with primary angle-closure (PAC) or PAC glaucoma (PACG) versus PAC suspect (PACS) diagnosis and use of glaucoma medications at the time of LPI, as well as factors predictive of subsequent addition of glaucoma medications, and receipt of selective laser trabeculoplasty (SLT), cataract surgery, and glaucoma surgery were assessed using logistic regression with generalized estimating equations. Kaplan-Meier curves and Cox proportional-hazards regression analysis were used to assess baseline factors affecting the time to SLT, cataract surgery, or glaucoma surgery., Main Outcome Measures: Diagnosis of PAC/PACG and medical, laser, or surgical interventions after LPI., Results: African Americans (odds ratio [OR], 2.12; P < 0.001) were significantly more likely than whites to have PAC/PACG than PACS and to already be taking glaucoma medications (OR, 2.25, P < 0.001) at the time of LPI. In multivariable logistic regression analysis, African Americans were significantly more likely to be prescribed additional glaucoma medications after LPI (OR, 1.73; P = 0.025) and receive glaucoma surgery (OR, 2.7; P = 0.007), but were less likely to receive SLT (OR, 0.37; P = 0.009). In multivariate Cox proportional-hazards regression analysis, African Americans had longer time to SLT than whites (hazard ratio [HR], 0.41; P = 0.022), but a shorter time to glaucoma surgery (HR, 2.57; P = 0.004). There was no significant association between race and the likelihood of cataract surgery or time to cataract surgery (P > 0.10)., Conclusions: African Americans were more likely than whites to carry a diagnosis of PAC or PACG at the time of LPI and were significantly more likely to be prescribed additional glaucoma medications and require glaucoma surgery after LPI. Improved screening methods that target African Americans with NAs are needed so that preventive interventions such as LPI can be performed earlier to decrease the risk of progression., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Bacteremia is a leading cause of death in sub-Saharan Africa where childhood mortality rates are the highest in the world. The early diagnosis of bacteremia and initiation of treatment saves lives, especially in high-disease burden areas. However, diagnosing bacteremia is challenging for clinicians, especially in children presenting with co-infections such as malaria and HIV. There is an urgent need for a rapid method for detecting bacteremia in pediatric patients with co-morbidities to inform treatment. In this manuscript, we have developed and clinically validated a novel method for the direct detection of amphiphilic pathogen biomarkers indicative of bacteremia, directly in aqueous blood, by mimicking innate immune recognition. Specifically, we have exploited the interaction of amphiphilic pathogen biomarkers such as lipopolysaccharides (LPS) from Gram-negative bacteria and lipoteichoic acids (LTA) from Gram-positive bacteria with host lipoprotein carriers in blood, in order to develop two tailored assays - lipoprotein capture and membrane insertion - for their direct detection. Our assays demonstrate a sensitivity of detection of 4 ng/mL for LPS and 2 ng/mL for LTA using a waveguide-based optical biosensor platform that was developed at LANL. In this manuscript, we also demonstrate the application of these methods for the detection of LPS in serum from pediatric patients with invasive Salmonella Typhimurium bacteremia (n = 7) and those with Staphylococcal bacteremia (n = 7) with 100% correlation with confirmatory culture. Taken together, these results demonstrate the significance of biochemistry in both our understanding of host-pathogen biology, and development of assay methodology, as well as demonstrate a potential new approach for the rapid, sensitive and accurate diagnosis of bacteremia at the point of need.

Mycolactone, the amphiphilic macrolide toxin secreted by Mycobacterium ulcerans , plays a significant role in the pathology and manifestations of Buruli ulcer (BU). Consequently, it follows that the toxin is a suitable target for the development of diagnostics and therapeutics for this disease. Yet, several challenges have deterred such development. For one, the lipophilic nature of the toxin makes it difficult to handle and store and contributes to variability associated with laboratory experimentation and purification yields. In this manuscript, we have attempted to incorporate our understanding of the lipophilicity of mycolactone in order to define the optimal methods for the storage, handling, and purification of this toxin. We present a systematic correlation of variability associated with measurement techniques (thin-layer chromatography (TLC), mass spectrometry (MS), and UV-Vis spectrometry), storage conditions, choice of solvents, as well as the impact of each of these on toxin function as assessed by cellular cytotoxicity. We also compared natural mycolactone extracted from bacterial culture with synthesized toxins in laboratory (solvents, buffers) and physiologically relevant (serum) matrices. Our results point to the greater stability of mycolactone in organic, as well as detergent-containing, solvents, regardless of the container material (plastic, glass, or silanized tubes). They also highlight the presence of toxin in samples that may be undetectable by any one technique, suggesting that each detection approach captures different configurations of the molecule with varying specificity and sensitivity. Most importantly, our results demonstrate for the very first time that amphiphilic mycolactone associates with host lipoproteins in serum, and that this association will likely impact our ability to study, diagnose, and treat Buruli ulcers in patients.

Background: Globally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment. This study investigated the effect of maternal parasitic infections on infant vaccination in a more recent setting of active anti-parasitic therapy., Methodology/principal Findings: From 2013-2015, 576 Kenyan women were tested in pregnancy for malaria, soil-transmitted helminths, filaria, and S. haematobium, with both acute and prophylactic antiparasitic therapies given. After birth, 567 infants received 10-valent S. pneumoniae conjugate vaccine and pentavalent vaccine for hepatitis B, pertussis, tetanus, H. influenzae type B (Hib) and C. diphtheriae toxoid (Dp-t) at 6, 10, and 14 weeks. Infant serum samples from birth, 10 and 14 weeks, and every six months until age three years, were analyzed using a multiplex bead assay to quantify IgG for Hib, Dp-t, and the ten pneumococcal serotypes. Antenatal parasitic prevalence was high; 461 women (80%) had at least one and 252 (43.6%) had two or more infections during their pregnancy, with the most common being malaria (44.6%), S. haematobium (43.9%), and hookworm (29.2%). Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. Prevalences of protective antibody concentrations after vaccination were similar among the prenatal exposure groups., Conclusions/significance: These findings are in contrast with results from our prior cohort study performed when preventive anti-parasite treatment was less frequently given. The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses., Competing Interests: The authors have declared that no competing interests exist.