Development of dual-functional core-shell electrospun mats with controlled release of anti-inflammatory and anti-bacterial agents for the treatment of corneal alkali burn injuries.

In this study, a novel dual-drug carrier for the co-administration of an anti-inflammatory and antibiotic agent consisting of core-shell nanofibers for the treatment of cornea alkali burns was designed. The core-shell nanofibers were prepared via coaxial electrospinning of curcumin-loaded silk fibroin as the core and vancomycin-loaded chitosan/polyvinyl alcohol (PVA) as the shell. Electron microscopy (SEM and TEM) images confirmed the preparation of smooth, bead-free, and continuous fibers that formed clear core-shell structures. For further studies, nanofiber mats were cross-linked by heat treatment to avoid rapid disintegration in water and improve both mechanical properties and drug release. The release profile of curcumin and vancomycin indicated an initial burst release, continued by the extended release of both drugs within 72 hours. Rabbit corneal cells demonstrated high rates of proliferation when evaluated using a cell metabolism assay. Finally, the therapeutic efficiency of core/shell nanofibers in healing cornea alkali burn was studied by microscopic and macroscopic observation, fluorescence staining, and hematoxylin-eosin assay on rabbit eyes. The anti-inflammatory activity of fabricated fibers was evaluated by enzyme-linked immunosorbent assay and Immunofluorescence analysis. In conclusion, using a robust array of in vitro and in vivo experiments this study demonstrated the ability of the dual-drug carriers to promote corneal re-epithelialization, minimize inflammation, and inhibit corneal neovascularization. Since these parameters are critical to the healing of corneal wounds from alkali burns, we suggest that this discovery represents a promising future therapeutic agent that warrants further study in humans.

Man With Disappearing Subconjunctival Foreign Body.

A 33-year-old man reported a "pulling and popping sensation" in his left eye and had a photograph showing an irregular, serpiginous extension that was present during the episode. Examination was unremarkable. What would you do next?

A Retrospective Analysis of Vitamin D Levels in Hospitalized COVID-19 Patients With Suspected Pulmonary Embolism.

Introduction Despite using anti-coagulation therapy in hospitalized coronavirus disease 2019 (COVID-19) patients, they have high rates of pulmonary embolism (PE) and deep vein thrombosis (DVT). The main objective of this study was to evaluate the association between vitamin D deficiency and thrombotic events (defined as the occurrence of a new PE or DVT) in hospitalized COVID-19 patients. Materials and Methods This was a retrospective, cross-sectional study of 208 hospitalized COVID-19 patients who received a computed tomographic pulmonary angiography (CTPA) based on clinical suspicion of PE between January 1, 2020, and February 5, 2021. A <20 ng/mL serum vitamin D level was used to categorize vitamin D deficiency. Nonparametric tests and multivariate binary logistic regression were used to evaluate the association between serum vitamin D levels and clinical outcomes. Results The mean vitamin D level was 26.7±13.0 ng/mL (n=208), and approximately one-third of patients were vitamin D deficient (n=68, 32.7%). No association was found between vitamin D deficiency and the occurrence of thrombotic events. The incidence of PE was 19.1% in vitamin D deficient patients compared to 11.4% in vitamin D sufficient patients (p=0.13). Vitamin D deficiency was positively associated with ICU admission (OR 3.047, 95%CI 1.57-5.91, p=0.001) and mortality (OR 3.76, 95%CI 1.29-11.01, p=0.016). Conclusions This study found no association between vitamin D deficiency and the occurrence of a new PE or DVT in hospitalized COVID-19 patients. Patients with vitamin D deficiency were more likely to be admitted to the ICU and had increased overall mortality.

An investigation of the seasonal relationships between meteorological factors, water quality, and sporadic cases of Legionnaires' disease in Washington, DC.

Since the discovery of Legionnaires' disease (LD), limited progress has been made in understanding the epidemiology of sporadic cases of LD. Outbreaks have confirmed that air conditioning and potable water systems can be sources of community-acquired LD. However, studying the association between water quality and LD incidence has been challenging due to the heterogeneity of water systems across large geographic areas. Furthermore, although seasonal trends in incidence have been linked to increased rainfall and temperatures, the large geographic units have posed similar difficulties. To address this issue, a retrospective ecological study was conducted in Washington, DC, from 2001 to 2019. The study identified aseasonal pattern of LD incidence, with the majority of cases occurring between June and December, peaking in August, October, and November. Increased temperature was found to be associated with LD incidence. In surface water, higher concentrations of manganese, iron, and strontium were positively associated with LD, while aluminum and orthophosphate showed a negative association. Intreatment plant water, higher concentrations of total organic carbon, aluminum, barium, and chlorine were positively associated with LD, while strontium, zinc, and orthophosphate showed a negative association. The results for orthophosphates and turbidity were inconclusive, indicating the need for further research.

Ocular Paraneoplastic Syndromes: A Critical Review of Diffuse Uveal Melanocytic Proliferation and Autoimmune Retinopathy.

Background: Dozens of paraneoplastic syndromes affect the visual system ranging from conjunctival pemphigoid to encephalopathy of the occipital cortex. The most profiled ocular syndromes are bilateral diffuse uveal melanocytic proliferation (BDUMP) and the autoimmune retinopathies.Purpose: To review the critical features of these 2 entities then concentrate on advancements in treatment made within the last 10 years.Study Design: Literature review with structured data abstraction.Results: Major insights into pathogenesis have been wanting. Plasmapheresis appears to improve vision in a substantial proportion of patients with BDUMP. The number of clinical variables that influence visual outcome in paraneoplastic retinopathies combined with the variety of local and systemic treatment options makes interpretation of clinical effectiveness difficult.Conclusions: The rarity of these disorders makes randomized clinical trials unlikely. It may be time for a clinical professional organization to use a modified Delphi method to establish a consensus algorithm for the diagnosis and management of retinal paraneoplastic syndromes to augment clinical communications and clinical trials.

Genetic variation of Borreliella burgdorferi in Fairfax County, Virginia, targeting the OspC gene in white-footed mice.

Outer surface protein C (OspC) is a commonly used marker in population studies of Borreliella to differentiate types and establish evolution over time. Investigating the ospC genetic types of Borreliella burgdorferi across multiple organ tissues of white-footed mice has the potential to contribute to our understanding of Lyme disease and the wide spectrum of clinical presentation associated with infection. In this study, five unique tissue types were sampled from 90 mice and screened for B. burgdorferi infections. This initial screening revealed a 63% overall B. burgdorferi infection rate in the mice collected (57/90). A total of 163 tissues (30.4%) tested positive for B. burgdorferi infections and when mapped to Borreliella types, 143,894 of the initial 322,480 reads mapped to 10 of the reference sequences in the ospC strain library constructed for this study at a 97% MOI. Two tissue types, the ear and the tongue, each accounted for 90% of the observed Borreliella sequence diversity in the tissue samples surveyed. The largest amount of variation was observed in an individual ear tissue sample with six ospC sequence types, which is equivalent to 60% of the observed variation seen across all tested specimens, with statistically significant associations observed between tissue type and detected Borreliella. There is strong evidence for genetic variability in B. burgdorferi within local white-footed mouse populations and even within individual hosts by tissue type. These findings may shed light on drivers of infection sequalae in specific tissues in humans and highlights the need for expanded surveillance on the epigenetics of B. burgdorferi across reservoirs, ticks, and infected patients.

The need for larval source management accompanying urban development projects in malaria endemic areas: a case study on Bioko Island.

BACKGROUND: In 2017, several new housing districts were constructed on Bioko Island, Equatorial Guinea. This case study assessed the impact construction projects had on mosquito larval habitats and the effectiveness of larval source management in reducing malaria vector density within the surrounding area. METHODS: Anopheline larval presence was assessed at 11 new construction sites by the proportion of larval habitats containing Anopheline pupae and late instar larval stages. Bacillus thuringiensis israelensis (Bti) larvicide was applied weekly to nine locations for 30 weeks, while two locations received no larvicide and acted as controls. Adult mosquito density was monitored via human landing collections in adjacent communities of six construction sites, including the two control sites. RESULTS: The sites that received Bti had significantly lower observation rates of both pupae (3.2% vs. 18.0%; p < 0.001) and late instar Anopheles spp. mosquitoes (14.1 vs. 43.6%; p < 0.001) compared to the two untreated sites. Anopheles spp. accounted for 67% of mosquitoes collected with human landing collections and were captured at significantly lower levels in communities adjacent to treated construction sites compared to untreated sites (p < 0.001), with an estimated 38% reduction in human biting rate (IRR: 0.62, 95% CI IRR: 0.55, 0.69). Seven months after the start of the study, untreated sites were treated due to ethical concerns given results from treatment sties, necessitating immediate Bti application. The following week, the number of habitats, the proportion of larval sites with Anopheles spp. pupae, late instars, and adult biting rates in adjacent communities to these sites all decreased to comparable levels across all sites. CONCLUSION: Findings suggest larval source management represents an effective intervention to suppress mosquito populations during infrastructure development. Incorporating larval source management into ongoing and planned construction initiatives represents an opportunity to fine tune vector control in response to anthropogenetic changes. Ideally, this should become standard practice in malaria-endemic regions in order to reduce viable mosquito habitats that are common by-products of construction.

Trends in Incidence of Conjunctival Melanoma in the US.

This cohort study assesses the incidence of conjunctival melanoma, associations between demographic factors, and trends over time in the US.

Excess mortality in Belarus during the COVID-19 pandemic as the case study of a country with limited non-pharmaceutical interventions and limited reporting.

Public health intervention to contain the ongoing COVID-19 pandemic significantly differed by country since the SARS-CoV-2 spread varied regionally in time and in scale. Since vaccinations were not available until the end of 2020 non-pharmaceutical interventions (NPIs) remained the only strategies to mitigate the pandemic spread at that time. Belarus in Europe is one of a few countries with a high Human Development Index where no lockdowns have ever been implemented and only limited NPIs have taken place for a period of time. Therefore, the Belarusian case was evaluated and compared in terms of the mortality burden. Since the COVID-19 mortality was low, the excess overall mortality was studied for Belarus. Since no overall mortality data have been reported past June 2020 the analysis was complemented by the study of Google Trends funeral-related search queries up until August 2021. Depending on the model, the Belarusian mortality for June of 2020 was 29 to 39% higher than otherwise expected with the corresponding estimated excess death was from 2953 to 3690 while the reported COVID-19 mortality for June 2020 was only 157 cases. The Belarusian excess mortality for June 2020 was higher than for all neighboring countries with an excess of 5% for Poland, 5% for Ukraine, 8% for Russia, 11% for Lithuania and 11% for Latvia. The relationship between Google Trends and mortality time series was studied using Granger's test and the results were statistically significant. The results for Google Trends searches did vary by key phrase with the largest excess of 138% for April 2020 and 148% for September 2020 was observed for a key phrase "coffin", while the largest excess of 218% for January 2021 was observed for "funeral services". In summary, there are indications of the excess overall mortality in Belarus, which is larger than the reported COVID-19-related mortality.

Lupus-Induced Myopic Shift.

While ophthalmic manifestations of lupus are common, a myopic shift is a rare manifestation of systemic lupus erythematosus (SLE). An acute myopic shift is defined as a progressive worsening of nearsighted vision within a short time frame. Here, we describe the unique presentation of a young woman with a lupus-induced acute myopic shift. The patient presented with blurry vision and bleeding gums with a previous abnormal lymph node biopsy to rule out ocular lymphoma or leukemia. Her baseline prescription prior to coming in was -4.0D in both eyes. Upon exam, she presented with vision worsening: -7.0D in the right eye and -8.2D in the left eye. After completing blood laboratory tests, it became clear that she had pancytopenia, kidney damage, and elevated inflammatory markers pointing towards lupus. A diagnosis of acute binocular myopic shift induced by systemic lupus erythematosus was made.

Investigating the first stage of the COVID-19 pandemic in Ukraine using epidemiological and genomic data.

The novel coronavirus SARS-CoV-2 was first detected in China in December 2019 and has rapidly spread around the globe. The World Health Organization declared COVID-19 a pandemic in March 2020 just three months after the introduction of the virus. Individual nations have implemented and enforced a variety of social distancing interventions to slow the virus spread, that had different degrees of success. Understanding the role of non-pharmaceutical interventions (NPIs) on COVID-19 transmission in different settings is highly important. While most such studies have focused on China, neighboring Asian counties, Western Europe, and North America, there is a scarcity of studies for Eastern Europe. The aim of this epidemiological study is to fill this gap by analyzing the characteristics of the first months of the epidemic in Ukraine using agent-based modelling and phylodynamics. Specifically, first we studied the dynamics of COVID-19 incidence and mortality and explored the impact of epidemic NPIs. Our stochastic model suggests, that even a small delay of weeks could have increased the number of cases by up to 50%, with the potential to overwhelm hospital systems. Second, the genomic data analysis suggests that there have been multiple introductions of SARS-CoV-2 into Ukraine during the early stages of the epidemic. Our findings support the conclusion that the implemented travel restrictions may have had limited impact on the epidemic spread. Third, the basic reproduction number for the epidemic that has been estimated independently from case counts data and from genomic data suggest sustained intra-country transmissions.

Investigating the first stage of the COVID-19 pandemic in Ukraine using epidemiological and genomic data.

The novel coronavirus SARS-CoV-2 was first detected in China in December 2019 and has rapidly spread around the globe. The World Health Organization declared COVID-19 a pandemic in March 2020 just three months after the introduction of the virus. Individual nations have implemented and enforced a variety of social distancing interventions to slow the virus spread, that had different degrees of success. Understanding the role of non-pharmaceutical interventions (NPIs) on COVID-19 transmission in different settings is highly important. While most such studies have focused on China, neighboring Asian counties, Western Europe, and North America, there is a scarcity of studies for Eastern Europe. The aim of this study is to contribute to filling this gap by analyzing the characteristics of the first months of the epidemic in Ukraine using agent-based modelling and phylodynamics. Specifically, first we studied the dynamics of COVID-19 incidence and mortality and explored the impact of epidemic NPIs. Our stochastic model suggests, that even a small delay of weeks could have increased the number of cases by up to 50%, with the potential to overwhelm hospital systems. Second, the genomic data analysis suggests that there have been multiple introductions of SARS-CoV-2 into Ukraine during the early stages of the epidemic. Our findings support the conclusion that the implemented travel restrictions may have had limited impact on the epidemic spread. Third, the basic reproduction number for the epidemic that has been estimated independently from case counts data and from genomic data suggest sustained intra-country transmissions.

Development of an interactive, agent-based local stochastic model of COVID-19 transmission and evaluation of mitigation strategies illustrated for the state of Massachusetts, USA.

Since its discovery in the Hubei province of China, the global spread of the novel coronavirus SARS-CoV-2 has resulted in millions of COVID-19 cases and hundreds of thousands of deaths. The spread throughout Asia, Europe, and the Americas has presented one of the greatest infectious disease threats in recent history and has tested the capacity of global health infrastructures. Since no effective vaccine is available, isolation techniques to prevent infection such as home quarantine and social distancing while in public have remained the cornerstone of public health interventions. While government and health officials were charged with implementing stay-at-home strategies, many of which had little guidance as to the consequences of how quickly to begin them. Moreover, as the local epidemic curves have been flattened, the same officials must wrestle with when to ease or cease such restrictions as to not impose economic turmoil. To evaluate the effects of quarantine strategies during the initial epidemic, an agent based modeling framework was created to take into account local spread based on geographic and population data with a corresponding interactive desktop and web-based application. Using the state of Massachusetts in the United States of America, we have illustrated the consequences of implementing quarantines at different time points after the initial seeding of the state with COVID-19 cases. Furthermore, we suggest that this application can be adapted to other states, small countries, or regions within a country to provide decision makers with critical information necessary to best protect human health.

Characterization of the Vibriocidal Activity of Chitosan Microparticles: A Potential Therapeutic Agent for Emerging Multidrug-Resistant Cholera Infections.

Due to increasing reports of multidrug-resistant (MDR) Vibrio cholerae O1, the goal of this study was to characterize the in vitro antimicrobial activity of chitosan microparticles (CMs) to evaluate their potential as a novel therapeutic agent for cholera. We examined the antimicrobial activity of CMs against toxigenic V. cholerae O1 using direct enumeration, microscopy, and fluorescence microplate assays. Bacterial viability kinetics were measured with different concentrations of CMs, solution pH, and salt content using a live/dead staining technique. Growth inhibition of CM-exposed V. cholerae strains was conducted using a redox-sensitive stain and compared between wild-type and isogenic outer membrane (OM) mutants. CM concentrations above 0.1 wt % were sufficient to kill V. cholerae O1 suspensions with approximately 108 CFU/mL within 3 h. The nonviable cells demonstrated increased OM permeability that corresponded to gross morphological changes observed through scanning electron microscopy. CMs exhibited dose-dependent bactericidal activity that increased predictably at lower pH and decreased with salt addition. V. cholerae O1 strains lacking O-antigen were twice as susceptible to growth inhibition by CMs, whereas those with glycine modification to lipid A were ten times more resistant. We propose that CMs exert vibriocidal activity via electrostatic surface interactions between their positively charged amine groups and the negatively charged Gram-negative bacterial OM, resulting in disruption, increased permeability, decreased redox metabolism, and subsequent loss of cellular viability. Further research should be conducted in vivo to evaluate the efficacy of CMs as luminal agents to treat infections caused by MDR, toxigenic V. cholerae and other diarrheal pathogens.

Correction: Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1003084.].