Search

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.

The incidence of infective endocarditis (IE) has increased globally in the past decades, including in the United States. However, little is known about the differences in trends across states, gender, and age groups within the United States. Using the Global Burden of Disease database, we analyzed the incidence and mortality trends of IE in the United States between 1990 and 2019 using Joinpoint regression analyses, and compared between states, gender, and age groups. The age-standardized incidence rate (ASIR) of IE in the United States increased from 10.2/100,000 population in 1990 to 14.4 in 2019. The increase in ASIR was greater among men than women (45.8% vs 34.1%). The incidence increase was driven by 55+ year-olds (112.7% increase), with rapid increases in the 1990s and early 2000s, followed by a plateau around the mid-2000s. In contrast, the incidence among 5-to-19-year-olds decreased by -36.6% over the 30-year period. The incidence increased among all age groups in the last 5 years of observation (2015 to 2019), with the largest increase in 5-to-19-year-olds (3.3% yearly). The 30-year increase in ASIR was greatest in Utah (66.2%) and smallest in California (30.2%). The overall age-standardized mortality attributable to IE increased in the United States by 126% between 1990 and 2019 versus 19.6% globally. In conclusion, although the overall incidence and mortality of IE increased over the past 30 years in the United States, there are significant differences between regions, gender, and age groups. These findings indicate unevenly distributed disease burden of IE across the nation., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the antifungal properties of topical antibiotics (already being used successfully to prevent bacterial endophthalmitis) and some promising antiseptics for antifungal prophylaxis in the setting of artificial corneal implantation., Methods: Several commonly used antibiotics for antimicrobial prophylaxis after artificial corneal implantation, in addition to antiseptics [benzalkonium chloride (BAK), povidone-iodine (PI), and some ionic liquids (ILs)], were tested in vitro against Candida albicans, Fusarium solani, and Aspergillus fumigatus. The time-kill activity was determined. Toxicity was assayed in vitro on human corneal epithelial cultures using trypan blue. Adhesion and tissue invasion experiments were also carried out on porcine corneas and commonly used contact lenses, with or without gamma irradiation, and by analysis with fluorescence microscopy., Results: Polymyxin B (PMB)/trimethoprim/BAK (Polytrim), PMB alone, gatifloxacin with BAK (Zymaxid), and same-concentration BAK alone exhibited antifungal activity in vitro. Moxifloxacin (MOX) or gatifloxacin without BAK-as well as trimethoprim, vancomycin, and chloramphenicol-had no effect. 1% PI and ILs had the highest efficacy/toxicity ratios (>1), and Polytrim was species dependent. Subfungicidal concentrations of Polytrim reduced adhesion of C. albicans to Kontur contact lenses. Gamma-irradiated corneas showed enhanced resistance to fungal invasion., Conclusions: Of antibiotic preparations already in use for bacterial prophylaxis after KPro surgery, Polytrim is a commonly used antibiotic with antifungal effects mediated by both PMB and BAK and may be sufficient for prophylaxis. PI as a 1% solution seems to be promising as a long-term antifungal agent. Choline-undecanoate IL is effective and virtually nontoxic and warrants further development.

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.

The Flint Water Crisis-due to changes of water source and treatment procedures-has revealed many unsolved social, environmental, and public health problems for US drinking water, including opportunistic premise plumbing pathogens (OPPP). The true health impact of OPPP, especially in vulnerable populations such as the elderly, is largely unknown. We explored 10 8 claims in the largest US national uniformly collected data repository to determine rates and costs of OPPP-related hospitalizations. In 1991-2006, 617,291 cases of three selected OPPP infections resulted in the elderly alone of $0.6 billion USD per year of payments. Antibiotic resistance significantly increased OPPP illness costs that are likely to be underreported. More precise estimates for OPPP burdens could be obtained if better clinical, microbiological, administrative, and environmental monitoring data were cross-linked. An urgent dialog across governmental and disciplinary divides, and studies on preventing OPPP through drinking water exposure, are warranted.

Introduction: The need for human cornea tissues continues to grow as an alternative option to donor tissues. Silk protein has been successfully used as a substrate to engineer corneal epithelium and stroma in vitro. Herein, we investigated the in vivo response and the effect of silk crystalline structure (beta sheet) on degradation rate of silk films in rabbit multipocket corneal models., Methods: Three different surgical techniques (peripheral-median P-M, central-superficial C-S, central-deep C-D) were used to assess the in vivo response as well as the degradation profile of silk films with low, medium and high beta sheet (crystalline) content at 2 and 3 months after surgery., Results: Approach C-D showed signs of sample degradation without inflammation, with one single incision and a pocket created by flushing air two thirds deep in the corneal stroma. In comparison, approaches P-M and C-S with multiple incisions presented manually dissected surgical pockets resulted in inflammation and possible extrusion of the samples, respectively. Low beta sheet samples lost structural integrity at 2 months after surgery C-D, while medium and high beta sheet content films showed initial evidence of degradation., Conclusions: The in vivo response to the silk films was dependent on the location of the implant and pocket depth. Crystallinity content in silk films played a significant role in the timing of material degradation, without signs of inflammation and vascularization or changes in stromal organization.

Purpose: To describe the morphological distribution of host tissue and microbial biofilms on the intraocular surfaces of Boston type I keratoprostheses (KPros) explanted because of corneal melt., Methods: Retrospective study of scanning electron microscopy (SEM) images from 4 explanted Boston type I KPros composed of polymethylmethacrylate and titanium. SEM images of KPro-associated ocular surfaces were reviewed for the presence of inflammatory cells, microbes, and/or biofilm formation. One sterile type I KPro was also imaged to serve as a (device only) control., Results: All 4 KPros were explanted because of culture-negative, clinically "sterile" donor corneal melt with impending KPro extrusion. In all cases, the rough, irregular surfaces of the device harbored more adherent corneal epithelium and stromacytes, inflammatory cells, and bacteria than the smooth, polished surface of the KPro optic. Two KPros showed not only evidence of prior bacterial colonization but marked biofilm formation., Conclusions: SEM images of explanted KPros explanted for "sterile" corneal melt demonstrated evidence of biofilm formation despite negative donor corneal cultures and the absence of clinical suspicion for infection. These results suggest that "sterile" corneal melt may be due to inflammatory host responses to low microbial burdens as seen in biofilms and/or released antigens after antibiotic-induced lysis. There was increased adherence of host tissue cells and microbial biofilms on the nonpolished surfaces of the KPro. Polishing the intraocular polymethylmethacrylate and titanium KPro surfaces may decrease microbial adhesion and biofilm formation in human subjects with KPros, but what impact this will have on rates of postoperative endophthalmitis is unknown.

Heavy metals are extensively discharged through various anthropogenic activities, resulting in an environmental risk on a global scale. In this case, microorganisms can survive in an extreme heavy metal-contaminated environment via detoxification or resistance, playing a pivotal role in the speciation, bioavailability, and mobility of heavy metals. Therefore, studies on the mechanism for the microbial transformation of heavy metals are of great importance and can provide guidance for heavy metal bioremediation. Current research studies on the microbial transformation of heavy metals mainly focus on the single oxidation, reduction and methylation pathways. However, complex microbial transformation processes and corresponding bioremediation strategies have never been clarified, which may involve the inherent physicochemical properties of heavy metals. To uncover the underlying mechanism, we reclassified heavy metals into three categories based on their biological transformation pathways, namely, metals that can be chelated, reduced or oxidized, and methylated. Firstly, we comprehensively characterized the difference in transmembrane pathways between heavy metal cations and anions. Further, biotransformation based on chelation by low-molecular-weight organic complexes is thoroughly discussed. Moreover, the progress and knowledge gaps in the microbial redox and (de)methylation mechanisms are discussed to establish a connection linking theoretical advancements with solutions to the heavy metal contamination problem. Finally, several efficient bioremediation strategies for heavy metals and the limitations of bioremediation are proposed. This review presents a solid contribution to the design of efficient microbial remediation strategies applied in the real environment. [ABSTRACT FROM AUTHOR]

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: The aim of this study was to assess the possibility of light damage to the retina by a surgical microscope during implantation of a Boston Keratoprosthesis (B-KPro) in rabbits., Methods: The retinal irradiance from a Zeiss OPMI Lumera S7 operating microscope was measured at the working distance (16.5 cm). Light transmittance through an isolated B-KPro was measured. A B-KPro was implanted into 1 eye of 12 rabbits with the optic covered during the procedure. The operated eyes were then continuously exposed to a fixed light intensity under the microscope for 1 hour. Fluorescein angiography was carried out on days 2 and 9 postsurgery, after which the animals were euthanized. Further, we compared the potential of these retinal exposures to well-accepted light safety guidelines applicable to humans., Results: Light transmittance of B-KPro revealed a blockage of short wavelengths (<390 nm) and of long wavelengths (1660-1750 nm) of light. In addition, the surgical microscope filtered a part of the blue, ultraviolet, and infrared wavelengths. Neither fluorescein angiography nor a histological examination showed any morphological retinal changes in our rabbits. Moreover, the retinal exposures were well below the safety limits., Conclusions: Modern surgical microscopes have filters incorporated in them that block the most damaging wavelengths of light. The B-KPro is made of 100% poly(methyl methacrylate), which makes it in itself a blocker of short wavelengths of light. No damage could be demonstrated in the animal study, and the retinal exposures were well below the safety limits. Together, these results suggest that light exposures during B-KPro surgery present a low risk of photochemical damage to the retina.

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 describe a case of Enterobacter amnigenus endophthalmitis., Methods: A 33-year-old, previously healthy man presented with unilateral hypopyon uveitis. Visual acuity in the affected eye was counting fingers. Initial laboratory workup was negative. Vitreous cultures revealed the offending agent., Results: The patient was treated with intravenous and intravitreal antibiotics and responded well. Final visual acuity was 20/30., Conclusion: Enterobacter species have been rarely reported as causes of endophthalmitis. E. amnigenus is almost never pathogenic in humans and previous cases have been described in immunocompromised individuals. Our case demonstrates that appropriate treatment of E. amnigenus endophthalmitis in an immunocompetent individual can result in a good visual outcome.

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.

Purpose: To describe changes in demographics and pathogens for fungal keratitis cases diagnosed at the Massachusetts Eye and Ear Infirmary., Methods: Patient demographics, clinical and laboratory findings, treatment and outcomes of 46 cases of culture-proven fungal keratitis diagnosed from January 2004 through November 2007 were compared with 23 cases of fungal keratitis previously collected over a similar period from January 1999 through November 2002., Results: During 2004-2007, the rate of fungal keratitis was 1.0 cases per month, an increase from the baseline rate of 0.5 cases per month during 1999-2002. The proportion of cases caused by filamentous fungi increased from 30% (1999-2002) to 65% (2004-2007) (P = 0.01). Soft contact lens wear accounted for 41% of fungal keratitis cases in 2004-2007, as compared with 17% in 1999-2002. The majority of patients (70%) received oral antifungal treatment in addition to topical amphotericin B and natamycin. Seventeen patients (40%) required therapeutic keratoplasty. Patients with a history of corneal transplant had the highest rate of therapeutic keratoplasties (67%) and had the poorest visual outcome (40% counting fingers or less). In the contact lens group, 94% of patients maintained vision of at least 20/40 and only 12% required surgery to control the infection., Conclusions: There has been an increase in fungal keratitis in the Boston area and a change in the causative pathogens and risk factors for infection. Filamentous fungi now account for the majority of fungal keratitis cases, whereas yeasts were the predominant pathogen in the past. Soft contact lens wear is currently the most common risk factor for development of fungal keratitis.

Most bacterial infections involve biofilms. Biofilms are collections of microorganisms encased in a matrix that is often composed of both bacterial and host materials. They form on natural surfaces such as heart valves or abiotic surfaces such as contact lenses or intraocular lenses. The biofilm matrix promotes adherence of the microbe to smooth surfaces as well as to other cells. Biofilms thereby form large 3-dimensional microbial communities of complex architecture through cell-to-cell communication and coordinated multicellular behavior. The biofilm architecture promotes the exchange of nutrients and waste products. The ability of microorganisms to attach to abiotic surfaces and grow in highly stable communities greatly confounds the medical use of implantable devices. Much effort is now being invested to understand the molecular nature of biofilms, with a view toward designing biofilm-resistant implantable devices and more effective antimicrobials.

We report a case of post-laser in situ keratomileusis atypical mycobacteria infection unresponsive and resistant to fourth-generation fluoroquinolones, which highlights the importance of a high level of suspicion and the need for multidrug therapy for effective eradication.

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]

Oleogels is a novel semi-solid system, focusing on its composition, formulation, characterization, and diverse pharmaceutical applications. Due to their stability, smoothness, and controlled release qualities, oleogels are frequently utilized in food, cosmetics, and medicinal products. Oleogels are meticulously formulated by combining oleogelators like waxes, fatty acids, ethyl cellulose, and phytosterols with edible oils, leading to a nuanced understanding of their impact on rheological characteristics. They can be characterized by methods like visual inspection, texture analysis, rheological measurements, gelation tests, and microscopy. The applications of oleogels are explored in diverse fields such as nutraceuticals, cosmetics, food, lubricants, and pharmaceutics. Oleogels have applications in topical, transdermal, and ocular drug delivery, showcasing their potential for revolutionizing drug administration. This review aims to enhance the understanding of oleogels, contributing to the evolving landscape of pharmaceutical formulations. Oleogels emerge as a versatile and promising solution, offering substantial potential for innovation in drug delivery and formulation practices. [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.

The PhoP virulence regulon is essential to Salmonella typhimurium mouse typhoid fever pathogenesis and survival within macrophages. This virulence regulon is composed of the PhoP (transcriptional regulator) and PhoQ (environmental sensor) proteins and the genetic loci they positively (pags for PhoP activated genes) and negatively (prgs for PhoP repressed genes) regulate. Three regulated loci pagC, pagD, and prgH, when singly mutated, affect the virulence of S. typhimurium for mice. Strains with phoP locus mutations are effective as live vaccines in mice, and strains with a constitutive regulatory mutation, a point mutation in PhoQ, can protect mice against typhoid fever when only very few organisms are administered. The addition of various PhoP regulon mutations further attenuates aroA mutants of S. typhimurium, suggesting that these mutations would be useful in further attenuating vaccine strains with metabolic pathway mutations. The phoP, phoQ, pagC, and pagD genes are highly conserved between S. typhimurium and S. typhi and may be valuable as mutations in live vaccines for human typhoid fever. A plasmid suicide vector that allows deletion of the pagC gene and stable insertion of heterologous antigen genes within the deleted pagC locus has been constructed and used successfully in S. typhimurium and S. typhi.

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]

Background: The Powassan virus is a rare neurotropic, tick-borne arbovirus associated with meningoencephalitis. Despite the virus's known predilection for the basal ganglia, there are no reports detailing the spectrum of movement disorders in children with Powassan meningoencephalitis., Cases: We present 3 cases of pediatric Powassan encephalitis, highlighting the diverse and evolving movement disorders associated with this disease. We observed subcortical myoclonus and progressive generalized dystonia (patient 1), transient dyskinesias and refractory focal dystonia (patient 2), and generalized dystonia evolving into chorea and lingual dyskinesias (patient 3). One patient exhibited multifocal vasculitis on magnetic resonance imaging angiography, a novel finding., Conclusions: Movement disorders were a primary source of the morbidity experienced by pediatric Powassan encephalitis patients throughout their disease course, underscoring the importance of regular monitoring and adaptable treatment strategies in this condition. Larger, prospective studies are necessary to fully delineate the spectrum of associated movement disorders in this rare and severe disease., (© 2024 International Parkinson and Movement Disorder Society.)

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]