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In 2017, Europe implemented a ban on amalgam restorations for children aged <15 years and for pregnant/breastfeeding women, highlighting the need for alternative filling materials exhibiting less surface roughness and enhanced longevity. This in vitro study aimed to examine the surface roughness variations of five amalgam-replacement materials across three time points and using six finishing methods: (1) no finishing (control), (2) Arkansas burs, (3) diamond burs, (4) tungsten carbide burs, (5) SofLex discs in descending grit size, and (6) coarse SofLex discs combined with silicone polishing. We prepared 960 samples. Each material group, i.e., Cention Forte (CNF), DeltaFil (DLF), Ketac Universal (KTU), IonoStar Molar (ISM), and Equia Forte HT (EQF), comprised 60 samples (n = 10 per finishing method) created using standardized 3D-printed metal molds. Surface roughness (Sa) was measured immediately after finishing, after 30 days of storage in distilled water, and after thermocycling (5000 cycles) using a non-contact profilometer. The results indicate that conventional and hybrid glass-ionomer cements have smoother surfaces than high-viscosity GICs. The DLF and CNF groups exhibited stable outcomes. These findings underscore the importance of selecting appropriate finishing methods based on the restorative material to minimize surface roughness.

Background: Powassan virus is an emerging neurotropic arbovirus transmitted by the tick Ixodes scapularis. This systematic review was conducted to aggregate data on its clinical manifestations, diagnostic findings, and complications., Methods: PubMed was searched until August 2023 using the term "Powassan", to identify all published cases of Powassan virus infections, as per PRISMA guidelines., Results: Among the 380 abstracts identified, 45 studies describing 84 cases (70 adult, 14 pediatric) were included. Cases were reported from the USA and Canada. Complications included paralysis in 44.1% of adult and 42.6% of pediatric cases, cognitive deficits in 33.3% of adult and 25% of pediatric cases, while the mortality rate was 19.1% and 7.1% in the adult and pediatric populations, respectively. Correlation analysis revealed an association between mortality and age (r = 0.264, p = 0.029), development of paralysis (r = 0.252, p = 0.041), or respiratory distress or failure (r = 0.328, p = 0.006). Factors associated with persistent neurological deficits were development of ataxia (r = 0.383, p = 0.006), paralysis (r = 0.278, p = 0.048), speech disorder (r = 0.319, p = 0.022), and cranial nerve involvement (r = 0.322, p = 0.017). Other significant correlations included those between speech disorders and ataxia (r = 0.526, p < 0.001), and between paralysis and respiratory distress or failure (r = 0.349, p = 0.003)., Conclusion: Powassan virus infections have significant morbidity and mortality and should be suspected in cases of encephalitis and possible tick exposure. PROSPERO registration number: CRD42023395991.

Background: The Guillain-Barre Syndrome (GBS), also known as acute idiopathic polyneuritis, is a critical acquired condition associated with preceding nonspecific infection or triggering factors like trauma, surgery, or vaccination. GBS is currently the most frequent cause of acute flaccid paralysis in India. This study evaluates the short-term and in-hospital outcomes in different subtypes of GBS., Methods: A prospective observational study was conducted at V.S. Hospital, Ahmedabad, from September 2015 to December 2017. Patients above the age of 12 were included. Patients having other underlying neurological conditions, as well as immunodeficiency disorders, were excluded. The patients were classified into different subtypes of GBS, and functional outcomes were recorded on admission and discharge according to Hughes Scoring System. All statistical analyses were performed by using SPSS software., Results: Out of 50 patients, 35 (70%) were males. The mean age was of 37.18 +/- 18.35 years. 25 (50%) patients had a preceding infection. 88% of patients presented with cranial nerve (CN) involvement had a Hughes Score of >/= 3 (p = 0.0087). They had less improvement of Hughes Score on discharge (0.13 +/- 0.04) as compared to the patients without cranial nerve involvement (0.38 +/- 0.08) (p = 0.008). Respiratory involvement was associated with a higher Hughes Score (p = 0.005) on admission. 85% of patients diagnosed with an axonal subtype of GBS had a Hughes Score of >/= 3 (p = 0.06) compared to 74% patients with demyelinating subtype. Axonal subtype required double period (11 +/- 2.34) to show improvement as compared to demyelinating subtype (6 +/- 1.2) (p = 0.020). Irrespective of the subtypes, in two different treatment cohorts (PLEX vs IVIG), there was no difference in short term functional outcomes measured by improvement in the Hughes scores (p = 0.89)., Conclusions: Early cranial nerve and respiratory involvement in patients presenting with GBS are associated with poor outcomes warranting immediate critical care involvement. In our study, amongst all the subtypes, axonal had poor clinical outcomes. Further clinical trials on the Indian subpopulation will help us evaluate the impact of different treatment modalities on this disease., (© 2022. The Author(s).)

Purpose: To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis., Methods: We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety., Results: Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea., Conclusions: Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.

Purpose: To determine the cumulative worldwide incidence of infectious endophthalmitis and associated vision loss after Boston keratoprosthesis (B-KPro) Type I/II implantation and to propose both safe and inexpensive prophylactic antibiotic regimens., Methods: Two retrospective methods were used to determine the incidence, visual outcomes and aetiologies of infectious endophthalmitis associated with the B-KPro divided per decade: (i) systematic review of the literature from 1990 through January 2013 and (ii) a surveillance survey sent to all surgeons who implanted B-KPros through 2010 with 1-year minimum follow-up. In addition, a single-Boston surgeon 20-year experience was examined., Results: From 1990 through 2010, there were 4729 B-KPros implanted worldwide by 209 U.S. surgeons and 159 international surgeons. The endophthalmitis cumulative mean incidence declined from 12% during its first decade of use to about 3% during its second decade in the Unites States and about 5% internationally during the second decade. There remains a large incidence range both in the United States (1-12.5%) and internationally (up to 17%). Poor compliance with daily topical antibiotics is an important risk factor. While Gram-positive organisms remained dominant, fungal infections emerged during the second decade., Conclusions: Daily prophylactic topical antibiotics have dramatically reduced the endophthalmitis incidence. Although Gram-positive organisms are the most common aetiology, antimicrobials must be inclusive of Gram-negative organisms. Selection of prophylactic regimens should be tailored to local antibiotic susceptibility patterns, be cost-effective, and should not promote the emergence of antimicrobial resistance. An example of a broad-spectrum, low-cost prophylactic option for non-autoimmune patients includes trimethoprim/polymyxinB once daily., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Recent use of a titanium (Ti) backplate has improved the design and biocompatibility of the Boston Keratoprosthesis (BKpro). Titanium's shiny metallic appearance, however, makes the cosmetic outcome less favorable. The purpose of this study was to develop and test a coloring surface modification of Ti., Methods: Ti coloring was achieved using electrochemical anodization. Color assessment included scanning electron microscopy, atomic force microscopy (AFM), x-ray diffraction crystallography (XRD), and Fourier transform infrared spectroscopy (FTIR). Biocompatibility assessment of Ti disks included in vitro proliferation and cytotoxicity in coculture with human corneal limbal epithelial (HCLE) cells, primary human corneal fibroblasts, and immortalized human corneal endothelial cells (HCEnCs), and in vivo intralamellar implantation in rabbit corneas. Histologic appearance (hematoxylin-eosin and trichrome staining) and presence of cell inflammation (CD45), apoptosis (TUNEL), and corneal neovascularization (CD31) were evaluated 27 and 53 days post implantation., Results: Blue and brown coloration of Ti was achieved. Analysis showed the presence of a nanoporous oxide surface with no chemical change of the modified Ti surface. In vitro assessment showed no significant differences in cell proliferation and cytotoxicity between anodized and nonanodized Ti (P > 0.05; ANOVA for all cell types). Analysis of corneal tissues harboring the Ti disks showed normal cellular appearance, and lack of CD45, TUNEL, and CD31-positive cells., Conclusions: A biocompatible Ti backplate coloring was achieved by electrochemical anodization. In vitro and in vivo results suggest that the anodized Ti is equally biocompatible and as safe as the standard nonanodized Ti. The color modification of the BKpro may improve the cosmesis and acceptance of the BKpro by patients.

Purpose: To determine the biocompatibility of a new wireless intraocular pressure (IOP) transducer (WIT) in rabbit eyes and to correlate its measurements with other pressure-measuring devices., Methods: The WIT is a ring-shaped intraocular device that allows wireless IOP measurements through radiofrequency. It was implanted into six eyes of New Zealand White rabbits after extracapsular lens extraction. A sham rabbit eye with no transducer implanted was used as a control. The animals were observed and examined by microscopy at various intervals up to 25 months after surgery. IOP was measured at various intervals by pneumotonometry, tonometry, WIT, and manometry. The data from the various devices were compared and analyzed for reproducibility. Two eyes were enucleated at 5.5 and 20 months after implantation and analyzed by histology., Results: The WIT appears to be well tolerated in the rabbit eye, with no evidence of significant inflammation or scar formation by microscopic in vivo examination. Histology did not reveal intraocular inflammation or membrane formation. Repeated IOP measurements with pneumotonometry, tonometry, and the WIT resulted in SDs of 2.70 mm Hg, 3.35 mm Hg, and 0.81 mm Hg, respectively. The concordance between the WIT and direct manometry measurements was high. A downward drift in IOP measured by the WIT was noted in three rabbits, necessitating recalibration., Conclusions: The WIT is well tolerated by the rabbit eye. Its measurements are reproducible and in close concordance with manometry. A downward IOP drift warrants further investigation.

The biocompatibility and antibacterial properties of N,N-hexyl,methyl-polyethylenimine (HMPEI) covalently attached to the Boston Keratoprosthesis (B-KPro) materials was evaluated. By means of confocal and electron microscopies, we observed that HMPEI-derivatized materials exert an inhibitory effect on biofilm formation by Staphylococcus aureus clinical isolates, as compared to the parent poly(methyl methacrylate) (PMMA) and titanium. There was no additional corneal epithelial cell cytotoxicity of HMPEI-coated PMMA compared to that of control PMMA in tissue cultures in vitro. Likewise, no toxicity or adverse reactivity was detected with HMPEI-derivatized PMMA or titanium compared to those of the control materials after intrastromal or anterior chamber implantation in rabbits in vivo., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: Integration of keratoprosthesis with the surrounding cornea is very important in preventing bacterial invasion, which may cause ocular injury. Here the authors investigated whether hydroxyapatite (HAp) coating can improve keratoprosthesis (KPro) biointegration, using polymethyl methacrylate (PMMA)--the principal component of the Boston KPro--as a model polymer., Methods: HAp coatings were induced on PMMA discs after treatment with concentrated NaOH and coating with poly-dopamine (PDA) or polydopamine and then with 11-mercaptoundecanoic acid (11-MUA). Coatings were characterized chemically (Fourier transform infrared spectroscopy [FTIR], energy dispersive X-ray spectroscopy [EDX]) and morphologically (SEM) and were used as substrates for keratocyte growth in vitro. Cylinders of coated PMMA were implanted in porcine corneas ex vivo for 2 weeks, and the force required to pull them out was measured. The inflammatory reaction to coated discs was assessed in the rabbit cornea in vivo., Results: FTIR of the coatings showed absorption bands characteristic of phosphate groups, and EDX showed that the Ca/P ratios were close to those of HAp. By SEM, each method resulted in morphologically distinct HAp films; the 11-MUA group had the most uniform coating. The hydroxyapatite coatings caused comparable enhancement of keratocyte proliferation compared with unmodified PMMA surfaces. HAp coating significantly increased the force and work required to pull PMMA cylinders out of porcine corneas ex vivo. HAp coating of implants reduced the inflammatory response around the PMMA implants in vivo., Conclusions: These results are encouraging for the potential of HAp-coated surfaces for use in keratoprostheses.

Purpose: To formulate and characterize a drug-eluting contact lens designed to provide extended, controlled release of a drug., Methods: Prototype contact lenses were created by coating PLGA (poly[lactic-co-glycolic acid]) films containing test compounds with pHEMA (poly[hydroxyethyl methacrylate]) by ultraviolet light polymerization. The films, containing encapsulated fluorescein or ciprofloxacin, were characterized by scanning electron microscopy. Release studies were conducted in phosphate-buffered saline at 37 degrees C with continuous shaking. Ciprofloxacin eluted from the contact lens was studied in an antimicrobial assay to verify antimicrobial effectiveness., Results: After a brief and minimal initial burst, the prototype contact lenses demonstrated controlled release of the molecules studied, with zero-order release kinetics under infinite sink conditions for over 4 weeks. The rate of drug release was controlled by changing either the ratio of drug to PLGA or the molecular mass of the PLGA used. Both the PLGA and the pHEMA affected release kinetics. Ciprofloxacin released from the contact lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested., Conclusions: A prototype contact lens for sustained drug release consisting of a thin drug-PLGA film coated with pHEMA could be used as a platform for ocular drug delivery with widespread therapeutic applications.

Poly(lactic-co-glycolic acid) (PLGA) hydrogels are highly utilized in biomedical research due to their biocompatibility, biodegradability, and other versatile properties. This review comprehensively explores their synthesis, properties, sustained release mechanisms, and applications in drug delivery. The introduction underscores the significance of PLGA hydrogels in addressing challenges like short half-lives and systemic toxicity in conventional drug formulations. Synthesis methods, including emulsion solvent evaporation, solvent casting, electrospinning, thermal gelation, and photopolymerization, are described in detail and their role in tailoring hydrogel properties for specific applications is highlighted. Sustained release mechanisms—such as diffusion-controlled, degradation-controlled, swelling-controlled, and combined systems—are analyzed alongside key kinetic models (zero-order, first-order, Higuchi, and Peppas models) for designing controlled drug delivery systems. Applications of PLGA hydrogels in drug delivery are discussed, highlighting their effectiveness in localized and sustained chemotherapy for cancer, as well as in the delivery of antibiotics and antimicrobials to combat infections. Challenges and future prospects in PLGA hydrogel research are discussed, with a focus on improving drug loading efficiency, improving release control mechanisms, and promoting clinical translation. In summary, PLGA hydrogels provide a promising platform for the sustained delivery of therapeutic agents and meet diverse biomedical requirements. Future advancements in materials science and biomedical engineering are anticipated to further optimize their efficacy and applicability in clinical settings. This review consolidates the current understanding and outlines future research directions for PLGA hydrogels, emphasizing their potential to revolutionize therapeutic delivery and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Previously, the PhoP-repressed locus prgH was identified as important for signalling epithelial cells to endocytose Salmonella typhimurium. Characterization of prgH revealed that it is an operon of four genes encoding polypeptides of 392 (prgH), 80 (prgI), 101 (prgJ) and 252 amino acid residues (prgK). Synthesis of the 2.6 kb prgHIJK transcript was repressed in bacteria that activate PhoP/PhoQ, indicating that PhoP/PhoQ regulates prgHIJK by transcriptional repression. The prgI, prgJ and prgK predicted gene products were similar to Shigella flexneri and Yersinia enterocolitica proteins required for secretion of Ipa and Yop virulence factors. Analysis of the culture supernatants from wild-type S. typhimurium demonstrated that at least 25 polypeptides larger than 14 kDa could be detected. In contrast, prgH1::TnphoA, phoP-constitutive and hil-deletion mutants had significant defects in their supernatant protein profiles. The invasion and supernatant protein profile defects of the prgH1::TnphoA mutant were both complemented by a 5.1 kb plasmid that included prgHIJK. These results suggest that PhoP/PhoQ regulates extracellular transport of proteins by transcriptional repression of secretion determinants and that secreted proteins may be involved in signalling epithelial cells to endocytose bacteria.

Background: Powassan virus, a North American tick-borne flavivirus, can cause severe neuroinvasive disease in humans. While Ixodes scapularis are the primary vectors of Powassan virus lineage II (POWV II), also known as deer tick virus, recent laboratory vector competence studies showed that other genera of ticks can horizontally and vertically transmit POWV II. One such tick is the Haemaphysalis longicornis, an invasive species from East Asia that recently established populations in the eastern USA and already shares overlapping geographic range with native vector species such as I. scapularis. Reports of invasive H. longicornis feeding concurrently with native I. scapularis on multiple sampled hosts highlight the potential for interspecies co-feeding transmission of POWV II. Given the absence of a clearly defined vertebrate reservoir host for POWV II, it is possible that this virus is sustained in transmission foci via nonviremic transmission between ticks co-feeding on the same vertebrate host. The objective of this study was to evaluate whether uninfected H. longicornis co-feeding in close proximity to POWV II-infected I. scapularis can acquire POWV independent of host viremia. Methods: Using an in vivo tick transmission model, I. scapularis females infected with POWV II ("donors") were co-fed on mice with uninfected H. longicornis larvae and nymphs ("recipients"). The donor and recipient ticks were infested on mice in various sequences, and mouse infection status was monitored by temporal screening of blood for POWV II RNA via quantitative reverse transcription polymerase chain reaction (q-RT-PCR). Results: The prevalence of POWV II RNA was highest in recipient H. longicornis that fed on viremic mice. However, nonviremic mice were also able to support co-feeding transmission of POWV, as demonstrated by the detection of viral RNA in multiple H. longicornis dispersed across different mice. Detection of viral RNA at the skin site of tick feeding but not at distal skin sites indicates that a localized skin infection facilitates transmission of POWV between donor and recipient ticks co-feeding in close proximity. Conclusions: This is the first report examining transmission of POWV between co-feeding ticks. Against the backdrop of multiple unknowns related to POWV ecology, findings from this study provide insight on possible mechanisms by which POWV could be maintained in nature. [ABSTRACT FROM AUTHOR]

The gram-negative facultative intracellular pathogen Salmonella enterica serotype Choleraesuis, also known as S. Choleraesuis, is a major financial loss for the pig business. C500 is a vaccine strain that has been used for preventing S. Choleraesuis infection in pigs for many years in China. Although it possessed good immunogenicity and protection efficacy, it still showed severe side effects. The truncation of the key gene rpoS in C500 was believed to take the major responsibility for its attenuation. To achieve a good balance between attenuation and immunogenicity, rpoS was restored to an active state, and other essential virulent genes of crp, fur, phoP, and aroA were evaluated for their effects of deletion on safety and immunogenicity. Animal experiments demonstrated that C5001 (C500 rpoS+ Δcrp10) and C5002 (C500 rpoS+ Δfur9) showed an excellent ability to induce an immune response. To further decrease the endotoxic activity, the combination mutations of ΔpagL7 ΔpagP81::Plpp lpxE ΔlpxR9 were introduced into the mutant strains to generate 1′-dephosphorylated lipid A. Animal experiments showed that SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: Plpp lpxE ΔlpxR9) induced higher levels of IgG and secreted IgA antibodies and provided a higher protection rate than SC1 (C500 ΔpagL7 ΔpagP81:: Plpp lpxE ΔlpxR9) and SC2 (C500 rpoS+ Δcrp10 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9). We also evaluated the ability of SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: Plpp lpxE ΔlpxR9) as a vaccine carrier to deliver heterologous protein antigens and polysaccharide antigens. The results indicated that SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: Plpp lpxE ΔlpxR9) showed an excellent ability to deliver heterologous antigens and induce the host to produce high levels of antibodies. Together, these results indicate that we constructed a safe and efficient attenuated strain of the S. Choleraesuis vaccine, which demonstrated strong resistance to infection with wild-type S. Choleraesuis and can be employed as a universal vector for the delivery of recombinant antigens. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of irreversible blindness, and early detection and treatment are crucial for preventing vision loss. This review aims to provide an overview of current diagnostic and treatment standards, recent medical and technological advances, and current challenges and future outlook for wearable glaucoma diagnostics and therapeutics. Conventional diagnostic techniques, including the rebound tonometer and Goldmann Applanation Tonometer, provide reliable intraocular pressure (IOP) measurement data at single-interval visits. The Sensimed Triggerfish and other emerging contact lenses provide continuous IOP tracking, which can improve diagnostic IOP monitoring for glaucoma. Conventional therapeutic techniques include eye drops and laser therapies, while emerging drug-eluting contact lenses can solve patient noncompliance with eye medications. Theranostic platforms combine diagnostic and therapeutic capabilities into a single device. Advantages of these platforms include real-time monitoring and personalized medication dosing. While there are many challenges to the development of wearable glaucoma diagnostics and therapeutics, wearable technologies hold great potential for enhancing glaucoma management by providing continuous monitoring, improving medication adherence, and reducing the disease burden on patients and healthcare systems. Further research and development of these technologies will be essential to optimizing patient outcomes. [ABSTRACT FROM AUTHOR]

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The recommendations for the wear and hygiene of ocular prostheses can vary among practitioners, and it is still a controversial theme in the literature. This clinical trial evaluated the microbial load, tissue health of the socket, and the participants' opinions before and after the use of two hygiene protocols. Thirty ocular prosthesis wearers used either a Daily Protocol (DPt: hygiene once a day) or Weekly Protocol (WPt: hygiene once a week) for 5 weeks with a washout of 7 days. The microbial load was quantified by the colony-forming unit count of the aerobic bacteria, Candida spp., Staphylococcus spp., and Gram-negative bacteria. The tissue health of the socket was evaluated by scores, and patients' opinion of the protocols was evaluated using the analogic visual scale (VAS). Data were analyzed by ANOVA Repeated Measures, Friedman, Cochran's Q Test, Wilcoxon, Fisher, and Pearson's chi-square tests considering p < 0.05. There was no difference in the microbial load of the microorganisms (p > 0.05). Both protocols improved socket inflammation (p = 0.005) and discharge (p < 0.001); DPt improved edema (p = 0.021) and crusting (p = 0.020). There was no difference in patients' rating responses (VAS) for all the questions of patients' opinion (Q1: p = 1.0; Q2: p = 1.0; Q3: p = 1.0; Q4: p = 1.0; Q5: p = 1.0; Q6: p = 0.317; Q7: p = 1.0; Q8: p = 0.159). There was a correlation between eye drops/edema (p = 0.030), eye drops/pain (p = 0.016), microbial load with discharge, inflammation, eyelid edema, and pain. Inflammation was correlated with edema at baseline (p < 0.001) and after DPt (p = 0.018), and with crusting at baseline (p = 0.003); edema was correlated with crusting at baseline (p < 0.001); crusting was correlated with discharge after WPt (p < 0.001). The protocols showed no effects on the microbial load of the anophthalmic socket and ocular prosthesis. However, better tissue health and patient acceptance were observed after both regimens. [ABSTRACT FROM AUTHOR]

Biofilm formation is an important microbial strategy for fungal pathogens, such as Fusarium, Aspergillus, and Candida, to establish keratitis in patients wearing soft contact lenses. Despite the well-documented 2006 outbreak of Fusarium keratitis that eventually led to the withdrawal of the Bausch & Lomb multipurpose lens care solution ReNu with MoistureLoc ("MoistureLoc") from the global market, contact lens care systems and solutions currently available on the market do not specifically target fungal biofilms. This is partially due to the lack of recognition and understanding of important roles that fungal biofilms play in contact lens associated fungal keratitis (CLAFK). This review aims to reemphasize the link between fungal biofilms and CLAFK, and deepen our comprehension of its importance in pathogenesis and persistence of this medical device-related infection. [ABSTRACT FROM AUTHOR]

Glaucoma, marked by its intricate association with intraocular pressure (IOP), stands as a predominant cause of non-reversible vision loss. In this review, the physiological relevance of IOP is detailed, alongside its potential pathological consequences. The review further delves into innovative engineering solutions for IOP monitoring, highlighting the latest advancements in wearable and implantable sensors and their potential in enhancing glaucoma management. These technological innovations are interwoven with clinical practice, underscoring their real-world applications, patient-centered strategies, and the prospects for future development in IOP control. By synthesizing theoretical concepts, technological innovations, and practical clinical insights, this review contributes a cohesive and comprehensive perspective on the IOP biosensor's role in glaucoma, serving as a reference for ophthalmological researchers, clinicians, and professionals. [ABSTRACT FROM AUTHOR]

ENGLISH SUMMARY: Dry eye disease (DED) is characterized by ocular dryness, irritation and blurred vision and has a significant impact on the patient's quality of life. This condition can be particularly severe in patients with aqueous deficient dry eye disease (ADDE) due to Sjögren's syndrome (SS), an autoimmune disease that affects the lacrimal and salivary glands. Current treatments for ADDE are often limited to symptomatic relief. A literature review was conducted to explore the current surgical interventions used or tested in humans with ADDE (I). These interventions include procedures involving the eyelids and tear ducts, transplantation of amniotic membrane or salivary glands, injections around the tear ducts and cell‐based injections into the lacrimal gland (LG). Each treatment has its advantages and disadvantages; however, treating dry eyes in patients with SS presents a particular challenge due to the systemic nature of the disease. Moreover, there is a need for new therapeutic options. Mesenchymal stem cells (MSCs) are a type of stem cell that have shown promise in regenerating damaged tissue and reducing inflammation in various diseases. Previous studies in animal models have suggested that MSCs could be effective in treating ADDE. Thus, this thesis aims to investigate the safety and efficacy of injecting MSCs into the LG as a treatment option for patients with ADDE secondary to SS. The study also aims to see this treatment in light of existing and novel investigational treatment options. The clinical studies conducted for this thesis are the first of their kind in humans. MSCs derived from healthy donors' adipose tissue (ASCs) were cultured in a laboratory, frozen and thawed ready for use. In the safety study, we performed the first human trial involving the administration of a single injection of ASCs into the LG of one eye in seven patients suffering from severe ADDE (II). The primary objective was to test the safety of this treatment, while the secondary objective was to assess improvements in subjective and objective signs of dry eye. The results of the trial showed no serious side effects within 4 months of follow‐up after treatment. On average, there was a 40% reduction in dry eye symptoms assessed with the Ocular Surface Disease Index (OSDI) questionnaire. Additionally, in the treated eye, there was a significant decrease in tear osmolarity, an increase in tear film stability and an increase in tear production. To further investigate the efficacy of this treatment, our research group performed a clinical, randomized study aiming to compare the ASC injection into the LG with the injection of a vehicle (the excipient in which the ASCs are dissolved) and observation (no intervention) (III). The study involved 20 subjects receiving ASC injection, 20 subjects receiving vehicle injection and 14 patients being observed without intervention. The subjects were examined to assess the outcomes with a 12‐month follow‐up after treatment. Both intervention groups showed a significant reduction in subjective dry eye symptoms of approximately 40%. This improvement was evident at the 1‐week follow‐up and persisted until the 12‐month follow‐up. The observation group did not experience any change in OSDI score. The ASCs group exhibited a significant mean increase in non‐invasive tear break‐up time (NIKBUT) of 6.48 s (149%) at the four‐week follow‐up, which was significantly higher than that in the vehicle group (p = 0.04). Moreover, the ASCs group showed a significant increase in NIKBUT compared to that in the observation group at the 12‐month follow‐up (p = 0.004). In both the ASCs and vehicle group, a significant increase in Schirmer test scores at the 4‐month follow‐up and the 12‐month follow‐up was observed. In conclusion, this thesis contributes valuable findings with a new treatment option for patients with dry eye disease. Injection of ASCs into the LG was shown to be safe and to improve subjective dry eye symptoms and specifically the tear film stability in patients with ADDE due to SS. Compared to other treatment modalities of ADDE, this treatment has greater potential, as ASCs could potentially be used as an anti‐inflammatory therapeutic option for managing DED of other causes as well. RESUMÉ (DANISH SUMMARY): Tørre øjne, karakteriseret ved tørhedsfornemmelse og irritation af øjnene samt sløret syn, har en betydelig indvirkning på patientens livskvalitet. Denne tilstand kan være særligt alvorlig hos patienter med nedsat tåreproduktion (ADDE) som følge af Sjögrens syndrom (SS), en autoimmun sygdom, der påvirker tårekirtlerne og spytkirtlerne. Nuværende behandlinger for ADDE er ofte begrænset til symptomlindring. Vi gennemførte en litteraturgennemgang for at undersøge, hvilke nuværende kirurgiske behandlingsmetoder, der anvendes eller testes hos patienter med ADDE (I). Disse interventioner inkluderer procedurer, der involverer øjenlåg og tårekanaler, transplantation af amnionhinde eller spytkirtler, injektioner omkring tårekanalerne samt cellebaserede injektioner i tårekirtlen. Hver behandling har sine fordele og ulemper, men behandling af tørre øjne hos patienter med SS udgør en særlig udfordring på grund af sygdommens systemiske udbredning, og der er behov for nye behandlingsmuligheder. Mesenkymale stamceller (MSCs) er en type stamcelle, der har vist lovende resultater med hensyn til at regenerere beskadiget væv og reducere inflammation i forskellige sygdomme. Tidligere undersøgelser i dyremodeller har indikeret, at MSCs kan være en effektiv behandling af ADDE. Denne afhandling har til formål at undersøge sikkerheden og effekten af injektion af MSCs i tårekirtlen som en mulig behandling til patienter med ADDE som følge af SS. Afhandlingen sigter også mod at sammenligne denne behandling med andre eksisterende, kirurgiske behandlingsmuligheder af ADDE. Som led i dette projekt udførte vi de første kliniske forsøg af sin art i mennesker. MSCs fra raske donorers fedtvæv (ASCs) blev dyrket i et laboratorium, frosset ned og er optøet klar til brug. Det første mål var at teste sikkerheden ved denne behandling og sekundært at undersøge behandlingens effekt. For at undersøge dette modtog syv forsøgspersoner med svær ADDE én injektion med ASCs i tårekirtlen på det ene øje (II). Resultaterne af forsøget viste ingen alvorlige bivirkninger inden for fire måneders opfølgning efter behandlingen. I gennemsnit fandt vi yderligere en 40% reduktion i symptomer på tørre øjne vurderet med et spørgeskema, og en markant stigning i tåreproduktionen og af tårefilmens stabilitet i det behandlede øje. For yderligere at undersøge effekten af denne behandling udførte vi et klinisk, randomiseret forsøg med det formål at sammenligne injektion af ASCs i tårekirtlen med injektion af en kontrolopløsning (væsken, hvor stamcellerne var opløst) og observation (ingen intervention) (III). Studiet omfattede 20 forsøgspersoner, der modtog ASC‐injektion, 20 forsøgspersoner, der modtog injektion af kontrolopløsningen, og 14 forsøgspersoner i observationsgruppen. Forsøgspersonerne blev undersøgt med en opfølgningstid på 12 måneder efter behandling. Begge interventionsgrupper viste en betydelig reduktion på ca. 40% i subjektive symptomer på tørre øjne. Denne forbedring var betydelig allerede ved opfølgning efter en uge og varede ved 12 måneder efter behandling. Observationsgruppen oplevede ingen betydelig ændring i symptomer. ASCs gruppen viste desuden en signifikant stigning i tårefilmsstabiliteten (NIKBUT) på 6,48 sekunder (149%) ved opfølgning efter fire uger, hvilket var markant højere end efter injektion af kontrolopløsning (p = 0,04). Desuden viste ASCs gruppen en betydelig stigning i NIKBUT sammenlignet med observationsgruppen ved opfølgning efter 12 måneder (p = 0,004). Både injektion af ASCs og kontrolopløsning medførte en betydelig stigning i tåreproduktionen ved opfølgning fire måneder og 12 måneder efter behandling. Denne afhandling bidrager med vigtige resultater inden for en ny behandlingsmulighed af tørre øjne. Injektion af ASCs i tårekirtlen viste sig at være sikker, forbedrede subjektive symptomer på tørre øjne og øgede særligt tårfilmens stabilitet hos patienter med ADDE på grund af SS. Sammenlignet med andre behandlingsmuligheder for ADDE har denne behandling vist et stort potentiale. ASCs kan muligvis også bruges som en anti‐inflammatorisk behandling af tørre øjne af andre årsager i fremtiden. [ABSTRACT FROM AUTHOR]

Lelliottia amnigena is a Gram-negative facultative anaerobic bacillus identified from water sources and later from food (onions, cream, unpasteurized milk, and Spanish pork sausages), which, under certain circumstances, can cause infections in humans, especially in immunocompromised patients. Few cases of human infections have been reported in the literature, such as endophthalmitis, urinary tract infection, pyonephrosis, and sepsis. We describe the case of a 69-year-old Caucasian male patient who lives in an urban environment and presents himself to the emergency department with chills, fever, myalgias, marked physical asthenia, dry cough, dyspnea, symptoms for which he is tested and confirmed with SARS-CoV-2 infection using real-time reverse transcriptase–polymerase chain reaction (RT-PCR) from nasal and pharyngeal swabs, after being admitted the same day (25 May 2023) to the Infectious Diseases Clinic from the County Clinical Emergency Hospital Sibiu, Romania. At the time of admission, a pulmonary computerized tomography (CT) scan was performed, which revealed a severity score of 10 out of 25. In the second week of the disease, the patient presents with hemoptysis, from which bacteriological examinations are carried out, and Pseudomonas putida and Lelliottia amnigena are identified. The evolution was slowly favorable under antiviral treatment, corticotherapy, antibiotic therapy (in the absence of the identified etiology, initially meropenem was administered in association with linezolid, and then ceftazidime-avibactam), voriconazole, anakinra, salbutamol inhaler, inhalation corticosteroids, with slow reduction in oxygen requirement, the patient continued oxygen therapy at home after discharge with a flow rate of 5 L/minute. During the third harvesting of sputum samples, P. putida was isolated along with L. amnigena, both strains of low-virulence species, and maintained susceptibility to antibiotics. In the context of an immunosuppressed patient with previous pulmonary surgery for actinomycosis, chronic obstructive pulmonary disease, and bronchiectasis, all these conditions are favorable for biofilm formation. L. amnigena remains a pathogen rarely isolated in human pathology, but we should pay more attention, especially in the immunosuppressed patient, where it can be responsible for an extremely serious clinical picture. [ABSTRACT FROM AUTHOR]

By applying dual proteome profiling to Salmonella enterica serovar Typhimurium (S. Typhimurium) encounters with its epithelial host (here, S. Typhimurium infected human HeLa cells), a detailed interdependent and holistic proteomic perspective on host-pathogen interactions over the time course of infection was obtained. Data-independent acquisition (DIA)-based proteomics was found to outperform data-dependent acquisition (DDA) workflows, especially in identifying the downregulated bacterial proteome response during infection progression by permitting quantification of low abundant bacterial proteins at early times of infection when bacterial infection load is low. S. Typhimurium invasion and replication specific proteomic signatures in epithelial cells revealed interdependent host/pathogen specific responses besides pointing to putative novel infection markers and signalling responses, including regulated host proteins associated with Salmonella-modified membranes. Author summary: As causative agents of infectious diseases, intracellular bacterial pathogens have evolved diverse immune escape and survival strategies while thriving inside their hosts. Whereas the residence of the pathogen inside the host can impact the functioning of the latter drastically, the bacterial macromolecular content is typically vastly outstripped by that of the host. This sizeable difference in macromolecular content has thus far hindered proteome profiling of bacteria and its infected host in an integrated and unbiased manner. Here, the power of dual proteome profiling–a universal mass spectrometry-based proteomic strategy for unravelling the intricate interplay between pathogen and host—is presented for the exploration of host as well as pathogen proteomic responses over the time course of the infection, thereby advancing our understanding of infectious diseases. [ABSTRACT FROM AUTHOR]

There have been multiple reports of eye infections caused by antibiotic-resistant bacteria, with increasing evidence of ineffective treatment outcomes from existing therapies. With respect to corneal infections, the most commonly used antibiotics (fluoroquinolones, aminoglycosides, and cephalosporines) are demonstrating reduced efficacy against bacterial keratitis isolates. While traditional methods are losing efficacy, several novel technologies are under investigation, including light-based anti-infective technology with or without chemical substrates, phage therapy, and probiotics. Many of these methods show non-selective antimicrobial activity with potential development as broad-spectrum antimicrobial agents. Multiple preclinical studies and a limited number of clinical case studies have confirmed the efficacy of some of these novel methods. However, given the rapid evolution of corneal infections, their treatment requires rapid institution to limit the impact on vision and prevent complications such as scarring and corneal perforation. Given their rapid effects on microbial viability, light-based technologies seem particularly promising in this regard. [ABSTRACT FROM AUTHOR]

Metal injection molding (MIM) is one of the most widely used manufacturing processes worldwide as it is a cost-effective way of producing a variety of dental and orthopedic implants, surgical instruments, and other important biomedical products. Titanium (Ti) and Ti alloys are popular modern metallic materials that have revamped the biomedical sector as they have superior biocompatibility, excellent corrosion resistance, and high static and fatigue strength. This paper systematically reviews the MIM process parameters that extant studies have used to produce Ti and Ti alloy components between 2013 and 2022 for the medical industry. Moreover, the effect of sintering temperature on the mechanical properties of the MIM-processed sintered components has been reviewed and discussed. It is concluded that by appropriately selecting and implementing the processing parameters at different stages of the MIM process, defect-free Ti and Ti alloy-based biomedical components can be produced. Therefore, this present study could greatly benefit future studies that examine using MIM to develop products for biomedical applications. [ABSTRACT FROM AUTHOR]

Microneedles (MNs) have attracted considerable interest as a means of ocular drug delivery, a challenging delivery route due to the limitations imposed by the various biological barriers associated with this organ. In this study, a novel ocular drug delivery system was developed by formulating a dissolvable MN array containing dexamethasone-loaded PLGA microparticles for scleral drug deposition. The microparticles serve as a drug reservoir for controlled transscleral delivery. The MNs displayed sufficient mechanical strength to penetrate the porcine sclera. Dexamethasone (Dex) scleral permeation was significantly higher than in topically instilled dosage forms. The MN system was able to distribute the drug through the ocular globe, with 19.2% of the administered Dex detected in the vitreous humour. Additionally, images of the sectioned sclera confirmed the diffusion of fluorescent-labelled microparticles within the scleral matrix. The system therefore represents a potential approach for minimally invasive Dex delivery to the posterior of the eye, which lends itself to self-administration and hence high patient convenience. [ABSTRACT FROM AUTHOR]

The present article reports on the management of six different and rare cases of fungal keratitides, two of which have never been documented in previous literature. This is a case series of six patients with rare fungal keratitides managed at a quaternary eye referral unit, Sydney Eye Hospital, Australia over a period of 7 months (May to December, 2022). The order of occurrence of fungi isolated was Scedosporium apiospermum, Lomenstospora prolificans, Cladosporium spp., Paecilomyces, Syncephalastrum racemosum and Quambalaria spp. A combination of medical and surgical interventions was employed, including topical and systemic anti-fungal therapy, with one requiring therapeutic penetrating keratoplasty and another eventuating in evisceration. Two patients were successfully treated with corneal debridement and two others required pars plana vitrectomy with anterior chamber washout. It is important to remain vigilant with monitoring patient symptoms and correlating with clinical signs to guide antifungal therapy even in the context of confirmed culture and sensitivity results. [ABSTRACT FROM AUTHOR]

Over the last several decades, numerous modifications and advancements have been made to design the optimal corneal biomatrix for corneal epithelial cell (CECs) or limbal epithelial stem cell (LESC) carriers. However, researchers have yet to discover the ideal optimization strategies for corneal biomatrix design and its effects on cultured CECs or LESCs. This review discusses and summarizes recent optimization strategies for developing an ideal collagen biomatrix and its interactions with CECs and LESCs. Using PRISMA guidelines, articles published from June 2012 to June 2022 were systematically searched using Web of Science (WoS), Scopus, PubMed, Wiley, and EBSCOhost databases. The literature search identified 444 potential relevant published articles, with 29 relevant articles selected based on inclusion and exclusion criteria following screening and appraising processes. Physicochemical and biocompatibility (in vitro and in vivo) characterization methods are highlighted, which are inconsistent throughout various studies. Despite the variability in the methodology approach, it is postulated that the modification of the collagen biomatrix improves its mechanical and biocompatibility properties toward CECs and LESCs. All findings are discussed in this review, which provides a general view of recent trends in this field. [ABSTRACT FROM AUTHOR]

Definitive treatment of dry eye disease (DED), one of the commonest ocular surface disorders, has remained elusive despite several recent advances in better diagnostics and the introduction of newer therapeutic molecules. The current treatment paradigms rely heavily on lubricating eye drops and anti‑inflammatory agents that may need to be used long‑term and are mainly palliative. Research is ongoing not only for a curative treatment option but also to improve the potency and efficacy of existing drug molecules through better formulations and delivery platforms. In the past two decades, significant advancement has been made in terms of preservative‑free formulations, biomaterials such as nanosystems and hydrogels, stem cell therapy, and creation of a bioengineered lacrimal gland. This review comprehensively summarizes the newer approaches to DED treatment, which are biomaterials such as nanosystems, hydrogels, and contact lenses for drug delivery, cell and tissue‑based regenerative therapy for damaged lacrimal gland and ocular surface, and tissue engineering for developing artificial lacrimal gland. Also, their potential efficacies in animal models or in vitro studies and possible limitations are discussed. The ongoing research looks promising and needs to be supported with clinical efficacy and safety studies for human use. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is prevalent in all age groups and is known to cause chronic ocular discomfort and pain, and greatly affects the quality of life. Patients with ocular surface disease (OSD) may also have reduced tear secretion due to lacrimal gland damage, thus leading to aqueous deficient DED. Even with conventional management modalities such as lubricating eyedrops, topical corticosteroids, autologous serum eyedrops, or punctal plugs, many patients continue to suffer from debilitating symptoms. Contact lenses are increasingly being used in OSD providing surface hydration, protection from environmental insults, mechanical damage from abnormal lids, and as a modality for constant drug delivery to the ocular surface. This review describes the role of soft lenses and rigid gas‑permeable scleral lenses in the management of DED associated with OSD. The efficacy of contact lenses, lens selection, and optimal lens fit are reviewed for specific indications. [ABSTRACT FROM AUTHOR]

Contact lens wear is useful in ocular conditions such as high refractive errors, irregular astigmatism, corneal ectasias, corneal dystrophies, post‑keratoplasty, post‑refractive surgeries, trauma, and ocular surface diseases. The new innovations of highly oxygen‑permeable contact lens materials have broadened the applications of contact lens suitability. Therapeutic contact lenses are medically used in the management of a wide variety of corneal conditions and ocular surface diseases. These lenses aid in pain relief, enhance corneal healing, maintain ocular homeostasis, and act as a drug delivery system. Drug delivery applications of contact lenses hold promise for improving topical therapy. The modern rigid gas permeable scleral contact lens provides symptomatic relief in painful corneal diseases such as bullous keratopathy, corneal epithelial abrasions, and erosions. It has been useful in therapeutic management as well as visual rehabilitation by enhancing the ocular surface and protecting the cornea from adverse environmental conditions. This review provides a summary of contact lenses used for the treatment of ocular surface diseases based on the current evidence available in the literature. This can help enhance the understanding and management of ocular surface diseases with respect to contact lens use in our day‑to‑day ophthalmology practice. [ABSTRACT FROM AUTHOR]

Intraocular pressure (IOP) is a key indicator to evaluate the risk and status of glaucoma, which is one of the main causes of irreversible blindness. However, the IOP value is susceptible to circadian changes and is difficult to be measured real−time. In this paper, we designed a thin−film integrated optical IOP sensor based on the interferometry principle, which could read out the IOP value by interference patterns and monitor the value changes real−time at the same time. The theoretical and experimental results indicated that our sensor exhibited a sensitivity of 0.19 μm/mmHg and an average accuracy of 0.84 mmHg over the pressure range of 0–45 mmHg, which is comparable with the other reported optical systems but with the advantage of easier fabrication process and low−cost. Our sensor device implies great potential in the application of human physiological index measurement and other chip−integrated medical sensing instruments. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) as an eye drop is an effective treatment for dry eye. However, it has potential side effects and a short ocular residence time. To overcome these obstacles, we developed a cellulose acetate phthalate-based pH-responsive contact lens (CL) loaded with CsA (CsA-CL). The CsA was continuously released from the CsA-CL at physiological conditions (37 °C, pH 7.4) without an initial burst. CsA was well-contained in the selected storage condition (4 °C, pH 5.4) for as long as 90 days. In safety assays, cytotoxicity, ocular irritation, visible light transmittance, and oxygen permeability were in a normal range. CsA concentrations in the conjunctiva, cornea, and lens increased over time until 12 h. When comparing the therapeutic efficacy between the normal control, experimental dry eye (EDE), and treatment groups (CsA eye drop, naïve CL, and CsA-CL groups), the tear volume, TBUT, corneal fluorescein staining at 7 and 14 days, conjunctival goblet cell density, and corneal apoptotic cell counts at 14 days improved in all treatment groups compared to EDE, with a significantly better result in the CsA-CL group compared with other groups (all p < 0.05). The CsA-CL could be an effective, stable, and safe option for inflammatory dry eye. [ABSTRACT FROM AUTHOR]

This study aimed to develop a miltefosine-eluting contact lens (MLF-CL) device that would allow sustained and localized miltefosine release for the treatment of Acanthamoeba keratitis. MLF-CLs were produced in three different miltefosine doses by solvent-casting a thin miltefosine-polymer film around the periphery of a methafilcon hydrogel, which was then lathed into a contact lens. During seven days of in vitro testing, all three formulations demonstrated sustained release from the lens at theoretically therapeutic levels. Based on the physicochemical characterization of MLF-CLs, MLF-CL's physical properties are not significantly different from commercial contact lenses in terms of light transmittance, water content and wettability. MLF-CLs possessed a slight reduction in compression modulus that was attributed to the inclusion of polymer-drug films but still remain within the optimal range of soft contact lenses. In cytotoxicity studies, MLF-CL indicated up to 91% viability, which decreased proportionally as miltefosine loading increased. A three-day biocompatibility test on New Zealand White rabbits revealed no impact of MLF-CLs on the corneal tissue. The MLF-CLs provided sustained in vitro release of miltefosine for a week while maintaining comparable physical features to a commercial contact lens. MLF-CL has a promising potential to be used as a successful treatment method for Acanthamoeba keratitis. [ABSTRACT FROM AUTHOR]

Purpose. This study aimed to compare predisposing factors, clinical characteristics, treatment, and prognosis of Fusarium keratitis according to the result of the initial potassium hydroxide (KOH) smear. Methods. This is a retrospective study of cases with Fusarium keratitis between January 2000 and December 2019 at two tertiary hospitals in South Korea. Patients were divided into two groups depending on the KOH smear result (KOH-positive and KOH-negative group), and its clinical factors were analyzed. Results. Among 319 fungal keratitis, seventy-nine cases were identified with Fusarium keratitis. Forty-seven cases (59.5%) were negative in the initial KOH smear prior to their diagnosis. The most common predisposing factor for Fusarium keratitis was ocular trauma (55.7%). There were no significant differences in sex, occupation, ulcer size or shape, hypopyon, and initial visual acuity between the two groups. Differences were observed between the KOH-positive group and the KOH-negative group in terms of deep corneal infiltration (50.0% vs. 78.7%, p = 0.008) and evisceration treatment (3.1% vs. 25.5%, p = 0.008). The delayed time to initiate antifungal eye drops was longer in the KOH-negative group (1.13 ± 0.49 vs. 3.93 ± 4.89, p = 0.002). Only the KOH-negative group combined bacterial infection. The significant risk factors for poor clinical outcomes were the central corneal lesion (odds ratio (OR) 3.50, p = 0.047), a large ulcer size (size ≥ 7.5 mm2) (OR 4.98, p = 0.009), and endothelial plaque (OR 7.00, p = 0.031). Conclusion. Initial KOH-negative patients often needed evisceration and had worse final visual outcomes. The delay of prompt initiation of antifungal treatment and combined bacterial infection result in a poor prognosis. This study highlights the initial KOH effect on early diagnosis and early treatment of Fusarium keratitis. [ABSTRACT FROM AUTHOR]

Powassan virus (POWV) is a tick-borne flavivirus (TBFV) that can cause severe encephalitis in humans with a case–fatality rate as high as 11%. Patients who survive severe encephalitic disease can develop long-term neurological sequelae that can be debilitating and life-long. In this study, we have sought to characterize a primary human fetal brain neural stem cell system (hNSC), which can be differentiated into neuron and astrocyte co-cultures, to serve as a translational in vitro system for infection with POWV and a comparative mosquito-borne flavivirus (MBFV), West Nile virus (WNV). We found that both viruses are able to infect both cell types in the co-culture and that WNV elicits a strong inflammatory response characterized by increased cytokines IL-4, IL-6, IL-8, TNF-α and IL-1β and activation of apoptosis pathways. POWV infection resulted in fewer cytokine responses, as well as less detectable apoptosis, while neurons infected with POWV exhibited structural aberrations forming in the dendrites. These anomalies are consistent with previous findings in which tick-borne encephalitis virus (TBEV) infected murine primary neurons formed laminal membrane structures (LMS). Furthermore, these structural aberrations are also recapitulated in brain tissue from infected mice. Our findings indicate that POWV is capable of infecting human primary neurons and astrocytes without causing apparent widespread apoptosis, while forming punctate structures reminiscent with LMS in primary human neurons and in vivo. [ABSTRACT FROM AUTHOR]