Stromal p16 and SATB2 Expression Does Not Distinguish Atypical Polypoid Adenomyoma (APA) From its Benign Mimics.

Atypical polypoid adenomyoma (APA) is a polypoid biphasic lesion of low malignant potential that arises in the lower uterine segment and uterine corpus. The diagnosis of APA is often challenging on biopsy and curettage specimens, and both benign and malignant processes need to be considered in the differential. Stromal expression of p16 and SATB2 have recently been shown to distinguish APA from myoinvasive endometrioid carcinoma. The authors hypothesized that p16 and SATB2 immunohistochemistry could also aid in the distinction of APA from benign adenomyomatous polyp and endometrioid adenomyoma. The study comprised 10 APAs, 7 adenomyomatous polyps, 11 endometrioid adenomyomas, and 10 myoinvasive endometrioid carcinomas. The majority of APAs showed moderate to strong, diffuse p16 and stromal expression. However, most adenomyomatous polyps and endometrioid adenomyomas also exhibited moderate to strong, focal to diffuse p16 stromal expression. SATB2 showed weak to moderate, focal to diffuse expression in the majority of APAs, adenomyomatous polyps and endometrioid adenomyomas. In contrast, p16 and SATB2 were negative to weak and focal in 90% of myoinvasive endometrioid carcinomas. Our findings demonstrate that p16 and SATB2 may be helpful in the differential diagnosis of myoinvasive endometrioid carcinoma and APA while not useful in separating APA from adenomyomatous polyp and endometrioid adenomyoma.

Patient Experiences of Patient-Clinician Communication Among Cancer Multidisciplinary Healthcare Professionals During "Breaking Bad News": A Qualitative Systematic Review.

PURPOSE: To explore patient experiences of patient-clinician communication during the critical moments of "breaking bad news" in cancer care. METHODS: A qualitative systematic review followed the Joanna Briggs Institute methodology and has been reported according to PRISMA guidelines. Databases, including APA PsycINFO, CINAHL, MEDLINE, and Scopus, were searched from the beginning of their date range coverage to April 2023. Data extraction and quality assessment were performed, and a meta-aggregation approach was used for data synthesis. RESULTS: Twenty-eight studies were included and represented 976 patients. Key themes included (1) sensing something is wrong (prior to diagnosis), (2) reaction to the diagnosis, (3) information (during breaking bad news), (4) communication with health care professionals, (5) specialist versus nonspecialist centers, (6) decision-making, and (7) feeling supported. The review underscores the need for health care professionals to adeptly navigate and respond to individual patient needs during confronting and distressing times. CONCLUSIONS: The complexity and individuality of patient-clinician communication suggest that further education is needed among the cancer multidisciplinary team to develop personalized, empathetic communication strategies in clinical practice, catering to diverse patient preferences. The findings call for more inclusive research across different cultures and languages, and a need to understand evolving communication needs, especially in the context of increasing digital communication modalities in health care. IMPLICATIONS FOR CANCER SURVIVORSHIP: This review provides valuable new insights into developing effective communication strategies that are responsive to the diverse needs of patients undergoing cancer treatment. Its findings emphasize the importance of empathy, flexibility, and a personalized approach in delivering bad news and supporting patients throughout survivorship.

Resilience in allied health undergraduate education: a scoping review.

PURPOSE: Students of allied health disciplines deal with daily challenges. Without methods to mitigate stress, a decline in academic and clinical performance may result. This scoping review aims to examine the current evidence for the efficacy of interventions for enhancing resilience for allied health students. MATERIALS AND METHODS: Medline, Emcare and Cochrane Library were systematically searched for literature published until October 2022. The search included Quantitative studies which employed a pre-post or controlled study design to evaluate an intervention to improve resilience for university students in medical radiation, pharmacy, optometry, physiotherapy and podiatry. Screening and data extraction was conducted independently by two reviewers. Critical appraisal was conducted using Joanna Briggs Institute (JBI) critical appraisal tools. Seven studies were included. RESULTS: A range of resilience interventions were discovered in terms of the frequency and duration, method of implementation including didactic and online learning. Statistically significant findings were found in most controlled trials and pre-post studies. Interventions to enhance resilience are effective within allied health curriculum. CONCLUSIONS: The evidence that resilience can be significantly influenced by an intervention suggests that stakeholders should spend more time on designing and piloting interventions within their context. Future research should look to assess longer term and clinical related outcomes.

Universities and healthcare organizations consider resilience to be a critical capability of graduates in many allied health professions.There are positive benefits regarding the perceptions and knowledge of allied health students who participate in resilience training.Interventions should be designed to relate closely to an articulated understanding of resilience and utilize measurement tools which possess all forms of validity.

PD-L1 Expression in HPV-associated Versus HPV-independent Invasive Vulvar Squamous Cell Carcinoma.

Two etiological pathways have been implicated in the pathogenesis of vulvar squamous cell carcinoma (VSCC): a high-risk human papillomavirus (HPV)-associated route and an HPV-independent pathway characterized by TP53 mutations. Programmed cell death ligand 1 (PD-L1) has become increasingly useful in predicting the response to checkpoint inhibitor therapy in squamous cell carcinomas at various anatomical sites. This study aimed to assess the association between PD-L1 expression and the VSCC subtype to evaluate the utility of PD-L1 in prognostication and therapeutic selection based on HPV status. PD-L1 status was assessed using 3 separate metrics for the extent of PD-L1 staining in various cell types: immune cell score, tumor proportion score (TPS), and combined positive score. The study group consisted of 25 HPV-associated and 28 HPV-independent VSCCs. PD-L1 expression was positive in the majority of VSCCs according to all 3 scoring metrics (84.9% by immune cell score, 77.3% by TPS, and 90.6% by combined positive score). PD-L1 expression was observed in the majority of cases in both groups (60%-96.4%). PD-L1 expression using the TPS method was greater in HPV-independent tumors than in HPV-associated tumors ( P = 0.004), and high PD-L1 expression was also more common in the HPV-independent subtype ( P = 0.016 using the TPS method and P = 0.013 using the combined positive score method). Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.

Evaluating the in vitro wettability and coefficient of friction of a novel and contemporary reusable silicone hydrogel contact lens materials using an in vitro blink model.

PURPOSE: To evaluate the in vitro wettability and coefficient of friction of a novel amphiphilic polymeric surfactant (APS), poly(oxyethylene)-co-poly(oxybutylene) (PEO-PBO) releasing silicone hydrogel (SiHy) contact lens material (serafilcon A), compared to other reusable SiHy lens materials. METHODS: The release of fluorescently-labelled nitrobenzoxadiazole (NBD)-PEO-PBO was evaluated from serafilcon A over 7 days in a vial. The wettability and coefficient of friction of serafilcon A and three contemporary SiHy contact lens materials (senofilcon A; samfilcon A; comfilcon A) were evaluated using an in vitro blink model over their recommended wearing period; t = 0, 1, 7, 14 days for all lens types and t = 30 days for samfilcon A and comfilcon A (n = 4). Sessile drop contact angles were determined and in vitro non-invasive keratographic break-up time (NIKBUT) measurements were assessed on a blink model via the OCULUS Keratograph 5 M. The coefficient of friction was measured using a nano tribometer. RESULTS: The relative fluorescence of NBD-PEO-PBO decreased in serafilcon A by approximately 18 % after 7 days. The amount of NBD-PEO-PBO released on day 7 was 50 % less than the amount released on day 1 (6.5±1.0 vs 3.4±0.5 µg/lens). The reduction in PEO-PBO in the lens also coincided with an increase in contact angles for serafilcon A after 7 days (p < 0.05), although there were no changes in NIKBUT or coefficient of friction (p > 0.05). The other contact lens materials had stable contact angles and NIKBUT over their recommended wearing period (p > 0.05), with the exception of samfilcon A, which had an increase in contact angle after 14 days as compared to t = 0 (p < 0.05). Senofilcon A and samfilcon A also showed an increase in coefficient of friction at 14 and 30 days, respectively, compared to their blister pack values (p < 0.05). CONCLUSION: The results indicate that serafilcon A gradually depletes its reserve of PEO-PBO over 1 week, but this decrease did not significantly change the lens performance in vitro during this time frame.

Fungal Cell Wall-Associated Effectors: Sensing, Integration, Suppression, and Protection.

The cell wall (CW) of plant-interacting fungi, as the direct interface with host plants, plays a crucial role in fungal development. A number of secreted proteins are directly associated with the fungal CW, either through covalent or non-covalent interactions, and serve a range of important functions. In the context of plant-fungal interactions many are important for fungal development in the host environment and may therefore be considered fungal CW-associated effectors (CWAEs). Key CWAE functions include integrating chemical/physical signals to direct hyphal growth, interfering with plant immunity, and providing protection against plant defenses. In recent years, a diverse range of mechanisms have been reported that underpin their roles, with some CWAEs harboring conserved motifs or functional domains, while others are reported to have novel features. As such, the current understanding regarding fungal CWAEs is systematically presented here from the perspective of their biological functions in plant-fungal interactions. An overview of the fungal CW architecture and the mechanisms by which proteins are secreted, modified, and incorporated into the CW is first presented to provide context for their biological roles. Some CWAE functions are reported across a broad range of pathosystems or symbiotic/mutualistic associations. Prominent are the chitin interacting-effectors that facilitate fungal CW modification, protection, or suppression of host immune responses. However, several alternative functions are now reported and are presented and discussed. CWAEs can play diverse roles, some possibly unique to fungal lineages and others conserved across a broad range of plant-interacting fungi. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

A review of using Traditional Chinese Medicine in the management of glaucoma and cataract.

Traditional Chinese Medicine has a long history in ophthalmology in China. Over 250 kinds of Traditional Chinese Medicine have been recorded in ancient books for the management of eye diseases, which may provide an alternative or supplement to current ocular therapies. However, the core holistic philosophy of Traditional Chinese Medicine that makes it attractive can also hinder its understanding from a scientific perspective - in particular, determining true cause and effect. This review focused on how Traditional Chinese Medicine could be applied to two prevalent ocular diseases, glaucoma, and cataract. The literature on preclinical and clinical studies in both English and Chinese on the use of Traditional Chinese Medicine to treat these two diseases was reviewed. The pharmacological effects, safety profile, and drug-herb interaction of selected herbal formulas were also investigated. Finally, key considerations for conducting future Traditional Chinese Medicine studies are discussed.

Heterologously expressed SacP23, a novel bacteriocin from Paenibacillus polymyxa #23, is active against methicillin resistant Staphylococcus aureus.

Antimicrobial peptides have the potential to be used in a range of applications, including as an alternative to conventional antibiotics for the treatment of bacterial infections of humans and animals. Therefore, there is interest in identifying novel bacteriocins which have desirable physico-chemical properties or antimicrobial activities. Paenibacillus polymyxa #23, isolated from a marine sponge, has wide spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria. To explore the basis of this antimicrobial activity, the complete genome sequence of the strain was examined. Multiple genes predicted to encode antimicrobial peptides were identified. One gene was predicted to encode a novel sactipeptide bacteriocin, named SacP23. To confirm that SacP23 does have antimicrobial activity and to explore the antimicrobial spectrum of the peptide it was heterologously expressed in Bacillus subtilis. A cluster of eight genes, encoding a full complement of accessory genes as well as the structural gene expressed from the native promoter, was cloned into B. subtilis BS54A. The recombinant strain displayed antimicrobial activity against several Gram-positive bacteria, including multi-drug resistant Staphylococcus aureus. Heterologous expression of a whole gene cluster offers a powerful way to interrogate and resolve the various antimicrobial activities expressed by native strains that encode multiple compounds of interest.

Elucidation of the Binding Orientation in α2,3- and α2,6-Linked Neu5Ac-Gal Epitopes toward a Hydrophilic Molecularly Imprinted Monolith.

N-Acetylneuraminic acid and its α2,3/α2,6-glycosidic linkages with galactose (Neu5Ac-Gal) are major carbohydrate antigen epitopes expressed in various pathological processes, such as cancer, influenza, and SARS-CoV-2. We here report a strategy for the synthesis and binding investigation of molecularly imprinted polymers (MIPs) toward α2,3 and α2,6 conformations of Neu5Ac-Gal antigens. Hydrophilic imprinted monoliths were synthesized from melamine monomer in the presence of four different templates, namely, N-acetylneuraminic acid (Neu5Ac), N-acetylneuraminic acid methyl ester (Neu5Ac-M), 3'-sialyllactose (3SL), and 6'-sialyllactose (6SL), in a tertiary solvent mixture at temperatures varying from -20 to +80 °C. The MIPs prepared at cryotemperatures showed a preferential affinity for the α2,6 linkage sequence of 6SL, with an imprinting factor of 2.21, whereas the α2,3 linkage sequence of 3SL resulted in nonspecific binding to the polymer scaffold. The preferable affinity for the α2,6 conformation of Neu5Ac-Gal was evident also when challenged by a mixture of other mono- and disaccharides in an aqueous test mixture. The use of saturation transfer difference nuclear magnetic resonance (STD-NMR) on suspensions of crushed monoliths allowed for directional interactions between the α2,3/α2,6 linkage sequences on their corresponding MIPs to be revealed. The Neu5Ac epitope, containing acetyl and polyalcohol moieties, was the major contributor to the sequence recognition for Neu5Ac(α2,6)Gal(ß1,4)Glc, whereas contributions from the Gal and Glc segments were substantially lower.

Simple quantitative planimetric measurement of nigrosome-1 for clinical settings.

INTRODUCTION: Loss of MRI hyperintense signal in nigrosome-1 (assessed with susceptibility-weighted imaging) is a biomarker for Parkinson's disease (PD). Current clinical practice involves subjectively rating the appearance of nigrosome-1 which is challenging. The study aimed to test and compare a simple method for quantifying nigrosome-1 with the current subjective rating method. METHODS: Two experienced neuroradiologists measured area of hyperintense signal in nigrosome-1 (quantitative method) and rated nigrosome-1 appearance (as normal, attenuated, or absent; subjective method) in 42 patients encompassing the full spectrum of nigrosome-1 integrity (21 patients aged 55.5 ± 20.9 years with Essential tremor (ET) and a subset of 21 patients aged 69.6 ± 8.6 years with PD). Neuroradiologists were blinded to each other's measurements, clinical notes, and patient group. RESULTS: Both methods yielded a significant difference between the groups (PD vs ET; p < 0.001). Pooled (across sides) area of nigrosome-1 hyperintense signal was significantly smaller in the PD group (median = 2.1 mm2, range = 0-15.8 mm2) than ET group (median = 8.3 mm2, range = 0-15.7 mm2; p < 0.001). Inter-rater reliability was high to very high for both methods (subjective: weighted kappa = 0.640, p < 0.001; quantitative: W = 0.733, p = 0.004). Our primary hypothesis that area of nigrosome-1 hyperintense signal exhibits higher inter-rater reliability than subjective rating of nigrosome-1 appearance was not supported. CONCLUSION: The simple quantitative method, used with subjectively rated nigrosome-1 appearance, may improve confidence in longitudinal clinical reporting, when nigrosome-1 is attenuated. However, further work on the incremental diagnostic value of planimetry and bias, repeatability and reproducibility are needed before it can be recommended in clinical practice.

A Rapid Screening Platform for Simultaneous Evaluation of Biodegradation and Therapeutic Release of an Ocular Hydrogel.

This study attempts to address the challenge of accurately measuring the degradation of biodegradable hydrogels, which are frequently employed in drug delivery for controlled and sustained release. The traditional method utilizes a mass-loss approach, which is cumbersome and time consuming. The aim of this study was to develop an innovative screening platform using a millifluidic device coupled with automated image analysis to measure the degradation of Gelatin methacrylate (GelMA) and the subsequent release of an entrapped wetting agent, polyvinyl alcohol (PVA). Gel samples were placed within circular wells on a custom millifluidic chip and stained with a red dye for enhanced visualization. A camera module captured time-lapse images of the gels throughout their degradation. An image-analysis algorithm was used to translate the image data into degradation rates. Simultaneously, the eluate from the chip was collected to quantify the amount of GelMA degraded and PVA released at various time points. The visual method was validated by comparing it with the mass-loss approach (R = 0.91), as well as the amount of GelMA eluted (R = 0.97). The degradation of the GelMA gels was also facilitated with matrix metalloproteinases 9. Notably, as the gels degraded, there was an increase in the amount of PVA released. Overall, these results support the use of the screening platform to assess hydrogel degradation and the subsequent release of entrapped therapeutic compounds.

Investigating the Association between Sociodemographic Factors and Chronic Disease Risk in Adults Aged 50 and above in the Hungarian Population.

Chronic diseases are a major cause of mortality and morbidity globally, with non-communicable diseases being responsible for most deaths. Older adults are at a higher risk of developing chronic diseases due to various sociodemographic and lifestyle factors such as age, sex, income, education, employment, place of residence, dietary supplementation, tobacco use, and alcohol consumption. Understanding the relationship between these factors and chronic diseases is crucial for identifying vulnerable populations and improving healthcare delivery. Through both an online and an interview-based survey, this cross-sectional study aimed to examine these associations, focusing on adults aged 50 and above, with the goal of identifying potential areas for intervention and prevention. The study found that gender, area of residence, education status, employment status, nutritional supplementation, body mass index (BMI), alcohol usage, and age are associated with the risk of chronic disease, cardiovascular disease, and diabetes. Female gender, higher educational level, employment, normal BMI, and younger age were found to be protective factors, while living in rural areas, alcohol consumption, and older age were identified as risk factors. The study recommends targeted interventions and improved access to healthcare to reduce risk factors and enhance healthcare delivery for better health outcomes.

Use of artificial intelligence in discerning the need for prostate biopsy and readiness for clinical practice: a systematic review protocol.

BACKGROUND: Variability and inaccuracies in the diagnosis of prostate cancer, and the risk of complications from invasive tests, have been extensively reported in the research literature. To address this, the use of artificial intelligence (AI) has been attracting increased interest in recent years to improve the diagnostic accuracy and objectivity. Although AI literature has reported promising results, further research is needed on the identification of evidence gaps that limit the potential adoption in prostate cancer screening practice. METHODS: A systematic electronic search strategy will be used to identify peer-reviewed articles published from inception to the date of searches and indexed in CINAHL, IEEE Xplore, MEDLINE, Scopus, and Web of Science Core Collection databases. Registries including Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) will be searched for unpublished studies, and experts were invited to provide suitable references. The research and reporting will be based on Cochrane recommendations and PRISMA guidelines, respectively. The screening and quality assessment of the articles will be conducted by two of the authors independently, and conflicts will be resolved by a third author. DISCUSSION: This systematic review will summarise the use of AI techniques to predict the need for prostate biopsy based on clinical and demographic indicators, including its diagnostic accuracy and readiness for adoption in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336540.

Evaluating Viscosity and Tear Breakup Time of Contemporary Commercial Ocular Lubricants on an In Vitro Eye Model.

Purpose: To evaluate the link between the viscosity of ophthalmic formulation and tear film stability using a novel in vitro eye model. Methods: The viscosities and noninvasive tear breakup time (NIKBUT) of 13 commercial ocular lubricants were measured to evaluate the correlation between viscosity and NIKBUT. The complex viscosity of each lubricant was measured three times for each angular frequency (ranging from 0.1 to 100 rad/s) using the Discovery HR-2 hybrid rheometer. The NIKBUT measurements were performed eight times for each lubricant using an advanced eye model mounted on the OCULUS Keratograph 5M. A contact lens (CL; ACUVUE OASYS [etafilcon A]) or a collagen shield (CS) was used as the simulated corneal surface. Phosphate-buffered saline was used as a simulated fluid. Results: The results showed a positive correlation between viscosity and NIKBUT at high shear rates (at 10 rad/s, r = 0.67) but not at low shear. This correlation was even better for viscosities between 0 and 100 mPa*s (r = 0.85). Most of the lubricants tested in this study also had shear-thinning properties. OPTASE INTENSE, I-DROP PUR GEL, I DROP MGD, OASIS TEARS PLUS, and I-DROP PUR had higher viscosity in comparison to other lubricants (P < 0.05). All of the formulations had a higher NIKBUT than the control (2.7 ± 1.2 seconds for CS and 5.4 ± 0.9 seconds for CL) without any lubricant (P < 0.05). I-DROP PUR GEL, OASIS TEARS PLUS, I-DROP MGD, REFRESH OPTIVE ADVANCED, and OPTASE INTENSE had the highest NIKBUT using this eye model. Conclusions: The results show that the viscosity is correlated with NIKBUT, but further work is necessary to determine the underlying mechanisms. Translational Relevance: The viscosity of ocular lubricants can affect NIKBUT and tear film stability, so it is an important property to consider when formulating ocular lubricants.

Terminally Phosphorylated Triblock Polyethers Acting Both as Templates and Pore-Forming Agents for Surface Molecular Imprinting of Monoliths Targeting Phosphopeptides.

The novel process reported here described the manufacture of monolithic molecularly imprinted polymers (MIPs) using a terminally functionalized block copolymer as the imprinting template and pore-forming agent. The MIPs were prepared through a step-growth polymerization process using a melamine-formaldehyde precondensate in a biphasic solvent system. Despite having a relatively low imprinting factor, the use of MIP monolith in liquid chromatography demonstrated the ability to selectively target desired analytes. An MIP capillary column was able to separate monophosphorylated peptides from a tryptic digest of bovine serum albumin. Multivariate data analysis and modeling of the phosphorylated and nonphosphorylated peptide retention times revealed that the number of phosphorylations was the strongest retention contributor for peptide retention on the monolithic MIP capillary column.

Review of antibiotic prescriptions as part of antimicrobial stewardship programmes: results from a pilot implementation at two provincial-level hospitals in Viet Nam.

Objectives: To investigate the feasibility of retrospective prescription-based review and to describe the antibiotic prescribing patterns to provide information for an antimicrobial stewardship programme in Viet Nam. Methods: This study was conducted in two provincial-level hospitals between February and April 2020. Reviews were done by a clinical team consisting of leaders/senior doctors of each ward to assess the optimal level (optimal/adequate/suboptimal/inadequate/not assessable) of antibiotic prescriptions. Mixed-effect logistic regression at prescription level was used to explore factors associated with optimal antibiotic use. Results: The retrospective prescription-based review was accepted by study clinical wards with varied levels of participants. One hundred and eighty-three patients (326 prescriptions) in Hospital 1 and 200 patients (344 prescriptions) in Hospital 2 were included. One hundred and nineteen of the 326 (36.5%) antibiotic prescriptions in Hospital 1 and 51/344 (14.8%) antibiotic prescriptions in Hospital 2 were determined to be optimal by the review teams. The number of adequate antibiotic prescriptions were 179/326 (54.9%) and 178 (51.7%) in Hospital 1 and Hospital 2, respectively. The optimal level was lower for surgical prophylaxis antibiotics than for empirical therapy (OR = 0.06; 95% CI 0.01-0.45), higher in prescriptions in the ICU (OR = 12.00; 95% CI 3.52-40.92), higher in definitive antibiotic therapy (OR = 48.12; 95% CI 7.17-322.57) and higher in those with an indication recorded in medical records (OR = 3.46; 95% CI 1.13-10.62). Conclusions: This study provides evidence on the feasibility of retrospective prescription-based review, with adaption to the local situation. High and varying levels of optimal antibiotic prescriptions in clinical wards in hospitals were observed in Viet Nam.

Prevalence and related factors of myopic retinopathy - a hospital-based cross-section study in Vietnam.

CLINICAL RELEVANCE: Myopia prevention and anti-myopia treatment is of great importance in South East Asia. BACKGROUND: To evaluate the prevalence and related factors of myopic retinopathy in Vietnam. METHODS: A cross-sectional study was conducted on 168 eyes of 88 patients with high myopia presenting to the Refraction Department of Vietnam National Eye Hospital. Inclusion criteria were high myopia (≤-6.00D with cycloplegic retinoscopy). Consecutive presenting patients recruited between January 2020 and August 2020 consented to participate. RESULTS: Participant age range was 12-47 years. Peripapillary atrophy was present in 70.2% of participants, most commonly atrophy of one-quarter of the disc (38.7%). Central retinal changes were present in 66.1% of participants, subclassified as tessellated fundus in 60.7%, diffuse chorioretinal atrophy in 4.2% and patchy chorioretinal atrophy in 1.2%. Peripheral retinal lesions were present in 43.5% of participants, consisting of white-without-pressure in 32.1%, lattice degeneration in 16.1%, snail track degeneration in 4.2% and microcystoid degeneration in 1.2%. Myopia ≤-8.00D and axial length ≥26.5 mm were associated with additional risk of posterior ocular complications. Furthermore, age ≥19 years increased risk of central myopic retinopathy and ≥10 years since initial myopia diagnosis increased the risk of peripapillary atrophy and central retinal changes. Other factors such as the age of onset of myopia and family myopia history did not appear to alter the risk of peripheral retina damage. CONCLUSIONS: Retinal disorders were common in Vietnamese people with high myopia. Within the current cohort with high myopia, myopia ≤-8.00D and axial length ≥26.5 mm were associated with a significant further elevation of risk.

In vitro-in vivo correlation of drug release profiles from medicated contact lenses using an in vitro eye blink model.

There is still a paucity of information on how in vitro release profiles from drug-loaded contact lenses (CLs) recorded in 3D printed eye models correlate with in vivo profiles. This work aims to evaluate the release profiles of two drug-loaded CLs in a 3D in vitro eye blink model and compare the obtained results with the release in a vial and the drug levels in tear fluid previously obtained from an animal in vivo study. In vitro release in the eye model was tested at two different flow rates (5 and 10 µL/min) and a blink speed of 1 blink/10 s. Model CLs were loaded with two different drugs, hydrophilic pravastatin and hydrophobic resveratrol. The release of both drugs was more sustained and lower in the 3D eye model compared to the in vitro release in vials. Interestingly, both drugs presented similar release patterns in the eye model and in vivo, although the total amount of drugs released in the eye model was significantly lower, especially for resveratrol. Strong correlations between percentages of pravastatin released in the eye model and in vivo were found. These findings suggest that the current 3D printed eye blink model could be a useful tool to measure the release of ophthalmic drugs from medicated CLs. Nevertheless, physiological parameters such as the composition of the tear fluid and eyeball surface, tear flow rates, and temperature should be optimized in further studies.

Diagnostic test accuracy of imaging modalities for adults with acute pulmonary embolism: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the current literature on diagnostic test accuracy (DTA) of imaging modalities for adults with acute pulmonary embolism (APE). BACKGROUND: Medical imaging plays an integral role in evaluating and managing those with APE. Guidance for imaging modality use for APE diagnosis varies due to a lack of clinical standardisation. Despite this, CTPA remains the first-line imaging modality used by clinicians. METHODS: A literature search of PubMed, EMBASE, Trove and Mednar databases (2012-2020; English language) was performed. Studies assessing the DTA of imaging modalities for APE diagnosis were included. DTA studies methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2 tool). Results of eligible studies were pooled using random or fixed effects modelling the calculate the pooled DTA of explored imaging modalities for APE. The Higgins I2 test were performed to assess between study heterogeneity. RESULTS: 10 Studies, involving 998 participants, were enrolled and pooled using the random effects model. Of the explored modalities, magnetic resonance imaging (MRI), specifically pulmonary MRI and magnetic resonance pulmonary angiography (MRPA) exhibited the highest pooled DTA. Sensitivity, specificity, negative likelihood ratio, positive likelihood ratio and diagnostic odds ratio for MRPA were 0.952 (95% CI, 0.881 to 0.987), 0.857 (95% CI, 0.637 to 0.97), 5.631 (95% CI, 2.163 to 14.659), 0.06 (95% CI, 0.007 to 0.537) and 80.310 (95% CI, 15.607 to 413.25) respectively. Based on the QUADAS-2 criteria, most studies presented low to moderate risk of bias and concern regarding applicability. CONCLUSION: The explored ultrasound and MRI protocols which exhibit a lower radiation burden when compared to the current gold standard computed tomography pulmonary angiography (CTPA), have acceptable diagnostic accuracy for APE and can be useful in certain situations.

Fabrication and Characterization of an Enzyme-Triggered, Therapeutic-Releasing Hydrogel Bandage Contact Lens Material.

PURPOSE: The purpose of this study was to develop an enzyme-triggered, therapeutic-releasing bandage contact lens material using a unique gelatin methacrylate formulation (GelMA+). METHODS: Two GelMA+ formulations, 20% w/v, and 30% w/v concentrations, were prepared through UV polymerization. The physical properties of the material, including porosity, tensile strain, and swelling ratio, were characterized. The enzymatic degradation of the material was assessed in the presence of matrix metalloproteinase-9 (MMP-9) at concentrations ranging from 0 to 300 µg/mL. Cell viability, cell growth, and cytotoxicity on the GelMA+ gels were evaluated using the AlamarBlueTM assay and the LIVE/DEADTM Viability/Cytotoxicity kit staining with immortalized human corneal epithelial cells over 5 days. For drug release analysis, the 30% w/v gels were loaded with 3 µg of bovine lactoferrin (BLF) as a model drug, and its release was examined over 5 days under various MMP-9 concentrations. RESULTS: The 30% w/v GelMA+ demonstrated higher crosslinking density, increased tensile strength, smaller pore size, and lower swelling ratio (p < 0.05). In contrast, the 20% w/v GelMA+ degraded at a significantly faster rate (p < 0.001), reaching almost complete degradation within 48 h in the presence of 300 µg/mL of MMP-9. No signs of cytotoxic effects were observed in the live/dead staining assay for either concentration after 5 days. However, the 30% w/v GelMA+ exhibited significantly higher cell viability (p < 0.05). The 30% w/v GelMA+ demonstrated sustained release of the BLF over 5 days. The release rate of BLF increased significantly with higher concentrations of MMP-9 (p < 0.001), corresponding to the degradation rate of the gels. DISCUSSION: The release of BLF from GelMA+ gels was driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. This work demonstrated that a GelMA+-based material that releases a therapeutic agent can be triggered by enzymes found in the tear fluid.