Search

Leptospira species are difficult to culture. Thus, when there is suspicion for an infectious etiology to uveitis, bacterial cultures may fail to identify Leptospira. We describe a case of leptospirosis-associated uveitis that evaded culture and molecular assays. DNA sequencing of the aqueous fluid showed the presence of Leptospira spp.Retrospective case review of clinical and laboratory features of a patient with ocular leptospirosis is presented.DNA sequencing identified the genome of Leptospirosis spp. in the aqueous humor.Metagenomic sequencing, by virtue of its unbiased nature, can be a helpful adjunctive test when a strong clinical suspicion for intraocular infection persists despite negative routine culture and molecular assays.

In this work, we study the charge transfer improvement by the combination of two semiconductors of SERS.

This study investigates the impact of informal competition on the innovation of Southeast Asian firms and the moderating role of female management in the informal competition–innovation nexus. In the Southeast Asian context, the informal sector employs around 78% of the working population, which is higher than the world average of 61% and the Asia-Pacific average of 68%. The analysis is based on firm-level data collected by the World Bank for eight Southeast Asian countries in 2015–2016. The quantitative analysis was conducted with the use of the multilevel mixed-effects logistic regression method to address the hierarchical/multilevel problem. Additionally, the potential endogeneity problem was taken into account with the use of the propensity score matching technique. The findings show that informal competition induces firms to increase their product and process innovations. Furthermore, female management is important in leveraging the positive effects of informal competition on innovation.

BACKGROUND Cost-effective automated surveillance systems could leverage social media content analysis, with the potential to serve as early indicators of conjunctivitis and other systemic infectious diseases. OBJECTIVE We investigated whether large language models, specifically GPT-3.5 and GPT-4, can provide probabilistic assessments of whether or not social media posts about conjunctivitis could indicate an outbreak. METHODS 12,194 conjunctivitis-related Tweets were obtained using a targeted Boolean search in multiple languages for 9 countries. These Tweets were provided in prompts to GPT-3.5 and GPT-4, obtaining probabilistic assessments which were validated by two human raters. We then calculated Pearson correlations of these time series with post volume and the occurrence of known outbreaks in nine selected countries, with time series bootstrap used to compute confidence intervals. RESULTS Probabilistic assessments derived from GPT-3.5 showed correlations of 0.60 (95% CI: 0.47–0.70) and 0.53 (95% CI: 0.40–0.65) with the two human raters, with higher results for GPT-4. Weekly averages of GPT-3.5 probabilities showed substantial correlations with weekly Tweet volume for some countries, with correlations ranging from 0.10 (95% CI: 0.0–0.29) to 0.53 (95% CI: 0.39–0.89), with larger correlations for GPT-4. More modest correlations were found for correlation with known epidemics, with substantial correlation only in American Samoa (0.40 (95% CI: 0.16–0.81)). CONCLUSIONS These findings suggest that GPT prompting can efficiently assess content of social media post and possible outbreaks to a degree comparable to that of humans. Further, we found that automated content analysis of Twitter content is related to Twitter volume for conjunctivitis-related posts in some locations, and to the occurrence of actual epidemics. Future work may improve the sensitivity and specificity of these methods for outbreak detection.

The first manifestation of a viral infection may be conjunctivitis. There are limited data on the etiology of viral conjunctivitis in Vanuatu, a country in the South Pacific Ocean. Patients presenting to one of two Vanuatu health centers with presumed infectious conjunctivitis were eligible if symptom onset was within 14 days of screening. Conjunctival and anterior nasal swabs were obtained and subjected to unbiased RNA deep sequencing (RNA-seq) to identify DNA and RNA viruses. For samples collected from May to November 2021, RNA-seq identified a viral etiology in 12/48 patients. Human adenovirus species were the most common viruses (58%) detected, followed by human herpes viruses (cytomegalovirus, varicella zoster virus, and human herpes 7 virus). Rhinovirus C, Epstein-Barr virus, and bocavirus were also detected. In summary, the etiology for viral conjunctivitis in Vanuatu appears broad. Unbiased testing may be useful for disease surveillance.

Background Seasonal and epidemic conjunctivitis (pink eye) infections are highly contagious and impose a significant economic burden worldwide. Long-term visual impairment can occur. Methods This study used metagenomic deep sequencing to evaluate pathogens causing acute infectious conjunctivitis in Burkina Faso. Results We found that pathogens causing conjunctivitis in Burkina Faso are diverse, with human adenoviruses responsible for a small fraction of the samples tested. Conclusions These results are unexpected and suggest the importance of regional surveillance.

Background Ocular rosacea is common and is often managed with long-term antibiotic treatment. Doxycycline is the most commonly selected antibiotic for the treatment of rosacea. As there is no established standard of care treatment dose for rosacea, prescribed doses of doxycycline vary widely. The FDA classifies 40 mg daily dose of doxycycline for ocular rosacea as sub-microbial in comparison to an antibiotic dose of 200 mg daily. However, this “sub-microbial” dose has never been evaluated in patients with ocular rosacea, and even the sub-microbial dose has potential to alter systemic mucosa flora. Here, we present a randomized controlled trial using RNA sequencing to fully characterize the impact of sub-microbial antibiotic dosing of doxycycline on antimicrobial resistance and bacterial composition of the ocular and gut flora. Methods In a triple-masked parallel randomized control trial, patients with ocular rosacea will be randomized to three arms: a 40-mg dose of doxycycline, a 200-mg antibiotic dose of doxycycline, or placebo. Collected rectal and lower eyelid samples will be compared for frequency of antimicrobial resistance genetic determinants and microbiome diversity. A subjective ocular surface disease index survey and objective tear breakup time measurement will be determined. Discussion These results will enhance our understanding of the overall systemic impact of long-term systemic sub-microbial antibiotic dosing for the treatment of chronic recurrent ocular inflammatory diseases. Trial registration This trial was registered on ClinicalTrials.org (NCT05296837) on March 22, 2022.

The relationship between Epstein-Barr virus (EBV) infection and uveitis is unclear. We conducted an observational cross-sectional study to determine the prevalence of EBV in uveitis and to describe the clinical features of EBV-positive uveitis cases. This study was carried out at the F.I. Proctor Foundation at the University of California, San Francisco. All patients with suspected infectious uveitis who underwent unbiased metagenomic deep sequencing (MDS) were included. Demographics, testing information, and clinical features were documented. Eleven out of 288 patients with suspected infectious uveitis had EBV detected by RNA-seq in intraocular fluid. The prevalence of EBV in uveitis in our study sample is 4%. Three out of 11 EBV-positive eyes (27%) were found to have biopsy-proven vitreoretinal lymphoma. Future studies are needed to determine if EBV may drive the development of vitreoretinal lymphoma and if its presence should heighten the suspicion of vitreoretinal lymphoma.

Vietnam is a significant producer of sugar among ASEAN countries. In the 2019/2020 season, 150,689 ha of sugarcane was harvested in Vietnam with an average cane and sugar yield of 53.39 tons/ha and 5.42 tons/ha, respectively. Sugarcane Research Institute, the main sugarcane breeding organization in Vietnam, located in Phu An Commune, Ben Cat Town, Binh Duong Province, maintains 1146 geographically and genetically diverse sugarcane germplasm. A total of 9 locally bred sugarcane varieties were released for commercial production so far, of which 4 are in large-scale production. The released varieties include 2 VN (locally bred) clones, which were named VN09-108 and VN08-270. Molecular genetic studies of sugarcane are very limited in Vietnam.

To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.Secondary analysis of a randomized controlled trial.Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests.Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months).Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively).Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.

Background Ocular rosacea is common and is often managed with long-term antibiotic treatment. Doxycycline is the most commonly selected antibiotic for the treatment of rosacea. As there is no established standard of care treatment dose for rosacea, prescribed doses of doxycycline vary widely. The FDA classifies 40 mg daily dose of doxycycline for ocular rosacea as sub-microbial in comparison to an antibiotic dose of 200 mg daily. However, this “sub-microbial” dose has never been evaluated in patients with ocular rosacea, and even the sub-microbial dose has potential to alter systemic mucosa flora. Here, we present a randomized controlled trial using RNA sequencing to fully characterize the impact of sub-microbial antibiotic dosing of doxycycline on antimicrobial resistance and bacterial composition of the ocular and gut flora. Methods In a triple-masked parallel randomized control trial, patients with ocular rosacea will be distributed to three arms: a 40 mg dose of doxycycline, a 200 mg antibiotic dose of doxycycline, or placebo. Collected rectal and lower eyelid samples will be compared for frequency of antimicrobial resistance genetic determinants and microbiome diversity. A subjective ocular surface disease index survey and objective tear breakup time measurement will be determined. Discussion These results will enhance our understanding of the overall systemic impact of long term systemic sub-microbial antibiotic dosing for the treatment of chronic recurrent ocular inflammatory diseases. Trial registration: This trial was registered on clinicaltrials.org (NCT05296837) on March 22, 2022.

We evaluated antibiotic resistance selection in Streptococcus pneumoniae isolates from children participating in an individually randomized trial of single-dose azithromycin versus placebo. After 14 days, the prevalence of resistance to erythromycin, oxacillin, and clindamycin was elevated in the azithromycin versus placebo group. There was no difference at 6 months.

Purpose of review Given the impact that society as a whole, and medicine specifically, has experienced as a result of the COVID-19 pandemic, an examination of clinical care changes enacted in the field of ophthalmology is of interest to the specialty. Recent findings In order to adapt to the reality of the COVID-19 pandemic, measures, such as broadening telehealth capabilities, adopting universal masking, careful sanitation procedures, applying virtual teaching in academic environments, and deferring elective surgeries were put in place. These were aimed at reducing person-to-person spread of SARS-CoV-2. Though best efforts were made at triaging ophthalmic emergencies during these times, unfortunate delays in care were observed in some circumstances. Finally, a prospective study interrogating the risk of spread at slit lamp distances for short periods of time was encouraging, suggesting low risk of transmissibility, though limited by a small case-positive sample size. Summary Significant changes have been made in the design and delivery of ophthalmic care during the COVID-19 pandemic. Some of these, such as telemedicine, may provide value in a postpandemic world.

PurposeThe purpose of this article was to evaluate the impact of sample collection order on the diagnostic yield of metagenomic deep sequencing (MDS) for determining the causative pathogen in infectious keratitis.MethodsWe performed a cross-sectional diagnostic test evaluation among subjects with infectious keratitis at Aravind Eye Hospital in Madurai, India. All subjects underwent corneal scrapings of the affected eye to obtain potassium hydroxide smear, Gram stain, bacterial culture, and fungal culture, in this order. The order of MDS specimen collection relative to smear and culture samples was randomized and served as the primary predictor. Outcomes included the normalized copy number of pathogenic RNA detected by MDS, the proportion of MDS samples that were diagnostic, and the agreement of MDS results with cultures.ResultsMDS samples from 46 subjects with corneal ulcers were evaluated. MDS was positive in 33 subjects (76%) and had 74% overall agreement with culture results. There was no association between order of MDS sample collection and normalized copy number of genetic material detected (P = 0.62) or the likelihood of MDS positivity (P = 0.46). However, the likelihood of agreement between MDS and cultures decreased when MDS corneal swabs were collected after other diagnostic corneal scrapings (P = 0.05).ConclusionsThe overall yield of MDS for detecting the cause of infectious keratitis was not affected by sample collection order. However, diagnostic agreement between MDS and cultures decreased when MDS samples were collected after other specimens. Additional investigation is warranted to determine whether this represents increased sensitivity of MDS compared with cultures or higher susceptibility to contaminants.

Seasonal outbreaks of infectious conjunctivitis remain a public health issue. Determination of outbreak etiologies in the context of a worldwide pandemic may provide useful information to guide public health strategies. The aim of this study was to identify pathogens associated with outpatient infectious conjunctivitis during the COVID-19 Delta surge.This prospective study was conducted from April 2021 to September 2021. All outpatients presenting to the Aravind Eye Center (Madurai, India) with signs and symptoms consistent with acute infectious conjunctivitis were eligible. Three swabs were obtained from each participant: one from each conjunctiva and one from the anterior nares. Samples were processed for metagenomic RNA deep sequencing (RNA-seq).Samples from 106 study participants were sequenced. The most common presenting symptoms were tearing (86%) and itching (71%). Preauricular lymphadenopathy was present in 38% of participants. 20% of participants had close contacts with similar symptoms. Systemic symptoms such as coughing, runny nose, vomiting or diarrhea were uncommonly reported. 60% of all participants used some medicated eye drops upon enrollment. 75% of study participants demonstrated infection with human adenovirus D (HAdV-D). 11% of conjunctivitis was associated with SARS-CoV-2. 15% had no definitive pathogen detected. 8% of all participants had codetection of more than one pathogen on RNA-seq.During the COVID-19 Delta surge in India, HAdV-D was the most common pathogen associated with infectious conjunctivitis. SARS-CoV-2 was the second most common associated pathogen. Seasonal surveillance may be necessary for the determination of emerging and reemerging pathogens responsible for infectious conjunctivitis.

Antibiotics are routinely used as part of the management of severe acute malnutrition and are known to reduce gut microbial diversity in non-malnourished children. We evaluated gut microbiomes in children participating in a randomized controlled trial (RCT) of azithromycin versus amoxicillin for severe acute malnutrition. Three hundred one children aged 6 to 59 months with uncomplicated severe acute malnutrition (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < −3 without clinical complications) were enrolled in a 1:1 RCT of single-dose azithromycin versus a 7-day course of amoxicillin (standard of care). Of these, 109 children were randomly selected for microbiome evaluation at baseline and 8 weeks. Rectal swabs were processed with metagenomic DNA sequencing. We compared alpha diversity (inverse Simpson’s index) at 8 weeks and evaluated relative abundance of microbial taxa using DESeq2. Of 109 children enrolled in the microbiome study, 95 were followed at 8 weeks. We found no evidence of a difference in alpha diversity between the azithromycin and amoxicillin groups at 8 weeks controlling for baseline diversity (mean difference −0.6, 95% CI −1.8 to 0.6, P = 0.30). Gut microbiomes did not diversify during the study. Differentially abundant genera at the P < 0.01 level included Salmonella spp. and Shigella spp., both of which were overabundant in the azithromycin compared with amoxicillin groups. We found no evidence to support an overall difference in gut microbiome diversity between azithromycin and amoxicillin among children with uncomplicated severe acute malnutrition, but potentially pathogenic bacteria that can cause invasive diarrhea were more common in the azithromycin group. Trial Registration: ClinicalTrials.gov NCT03568643.

INTRODUCTION: Sarcoidosis has traditionally been thought of as a compartmentalized disease – the inflammatory milieu within pulmonary granulomas harbors products of activated genes leading to the manifestation of the autoimmune process. However, recent research has shown that such a compartmentalized view of sarcoidosis may not be entirely accurate and that distinguishing biomarkers may be identified from the peripheral blood.(1) METHODS: Twenty participants were recruited from a convenience sample from the Francis I. Proctor Foundation at the University of California, San Francisco (UCSF). This study was approved by the UCSF Institutional Review Board and adhered to the tenets of the Declaration of Helsinki. Participants had peripheral whole blood drawn into PAXgene blood RNA tubes (QIAGEN, Germantown, MD) and prepared and stored at −80C according to manufacturer’s recommendations. Samples were deidentified and laboratory personnel handing samples and interpreting data were masked. Differential gene expression was performed to identify host transcriptome signatures.(2) Briefly, analysis of sequenced data was made using a rapid computational pipeline developed in-house to classify host genes. Quality filtered RNA transcripts were aligned to the ENSEMBL CRCh38 human genome using STAR2. Genes were filtered to include only protein-coding genes that were expressed in at least 25% of the patients. Gene count data were analyzed with DESeq2.(3) Differentially expressed genes with false discovery rate (FDR)

Objectives This study aimed to assess the role of chest X-ray (CXR) scoring methods and their correlations with the clinical severity categories and the Quick COVID-19 Severity Index (qCSI). Methods We conducted a retrospective study of 159 COVID-19 patients who were diagnosed and treated at the University Medical Center between July and September 2021. Chest X-ray findings were evaluated, and severity scores were calculated using the modified CXR (mCXR), Radiographic Assessment of Lung Edema (RALE), and Brixia scoring systems. The three scores were then compared to the clinical severity categories and the qCSI using Spearman's correlation coefficient. Results Overall, 159 patients (63 males and 96 females) (mean age: 58.3 ± 15.7 years) were included. The correlation coefficients between the mCXR score and the Brixia and RALE scores were 0.9438 and 0.9450, respectively. The correlation coefficient between the RALE and Brixia scores was marginally higher, at 0.9625. The correlation coefficients between the qCSI and the Brixia, RALE, and mCXR scores were 0.7298, 0.7408, and 0.7156, respectively. The significant difference in the mean values of the three CXR scores between asymptomatic, mild, moderate, severe, and critical groups was also noted. Conclusions There were strong correlations between the three CXR scores and the clinical severity classification and the qCSI.

Biannual mass azithromycin administration reduces all-cause childhood mortality in some sub-Saharan African settings, with the largest effects in children aged 1-5 months. Azithromycin has not been distributed to children1 month due to risk of infantile hypertrophic pyloric stenosis (IHPS).This 1:1 placebo-controlled trial, randomized neonates aged 8-27 days to a single oral dose of azithromycin (20 mg/kg) or equivalent volume of placebo in 5 regions of Burkina Faso during 2019 and 2020. The primary outcome was all-cause mortality at 6 months of age. Infants were evaluated at 21 days after treatment and at 3 and 6 months of age for vital status; family and provider surveillance for IHPS continued throughout.Of 21,832 enrolled neonates, 10,898 were allocated to azithromycin and 10,934 to placebo. At 6 months of age, 92 infants had died, 42 (0.44%) in the azithromycin group and 50 (0.52%) in the placebo group (hazard ratio 0.85, 95% confidence interval 0.56 to 1.28,Overall mortality was lower than anticipated when the trial was designed, thus limiting its power. The available data do not support the routine use of azithromycin for prevention of mortality in neonates in sub-Saharan African settings similar to the one in which this trial was conducted.ClinicalTrials.gov NCT03682653.

Background The chlamydial major outer membrane protein, encoded by the ompA gene, is a primary target for chlamydial vaccine research. However, human studies of ompA-specific immunity are limited, and prior studies have been limited in differentiating re-infection from persistent infection. The purpose of this study was to assess whether children living in trachoma-endemic communities with re-infections of ocular chlamydia were more likely to be infected with a different or similar genovar. Methodology and findings The study included 21 communities from a trachoma-hyperendemic area of Ethiopia that had been treated with a mass azithromycin distribution for trachoma. Conjunctival swabbing was offered to all children younger than 5 years of age at baseline (i.e., pre-treatment), and then at follow-up visits 2 and 6 months later. Swabs were subjected to polymerase chain reaction (PCR) to detect C. trachomatis. A random sample of 359 PCR-positive swabs, stratified by study visit and study community, was chosen for ompA sequencing. In addition, ompA sequencing was performed on all swabs of 24 children who experienced chlamydial re-infection (i.e., positive chlamydial test before treatment, negative test 2 months following mass distribution of azithromycin, and again a positive test 6 months post-treatment). ompA sequencing was successful for 351 of 359 swabs of the random sample and 44 of 48 swabs of the re-infection sample. In the random sample, ompA types clustered within households more than would be expected by chance. Among the 21 re-infected children with complete ompA data, 14 had the same ompA type before and after treatment. Conclusion The high frequency of ompA concordance suggests incomplete genovar-specific protective immunity and the need for multiple antigens as vaccine targets.

BackgroundMass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear.MethodsWe investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants' gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months.ResultsOver the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa.ConclusionsAmong villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.).

The sandwich-structured CdS/Au/TiO2 nanofibers (NFs) act as a photoanode in the photoelectrochemical cell (PEC) for hydrogen generation by splitting water. The gold nanoparticles sandwiched between the TiO2 nanofibers and the CdS quantum dots (QDs) layers play an important role in enhancing the solar-to-chemical-energy conversion efficiency. The structure and morphology of the materials were characterized by using field-emission scanning electron microscopy (FE–SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). The surface plasmon resonance (SPR) of the Au nanoparticles was investigated by using ultraviolet-visible (UV–Vis) diffuse reflectance spectroscopy. The PEC properties of the photoanode were measured on a three-electrode electrochemical analyzer. The obtained photoconversion efficiency of the CdS/Au/TiO2 NFs is 4.1% under simulated-sunlight illumination with a 150 W xenon lamp. Working photoelectrode stability was tested, and the mechanism of the enhanced PEC performance was discussed.

Background: Depression is a common psychiatric disorder worldwide as well as Vietnam, greatly affecting the quality of life and threatening patient lives due to the high risk of suicide. Early treatment and appropriate use of drugs will help improve the effectiveness of treatment and reduce the burden on public health. Objectives: To analyze antidepressant use and level of drug interactions encountered in depression outpatient. Materials and methods: 252 depression outpatients at Da Nang Psychiatric Hospital, cross-sectional description method. Results: The multivalent treatment regimen was initiated on admission in 92.1% of cases, SSRI group accounted for the highest proportion (45.6%), followed by TeCA, TCA and SNRI, at 37.9%; 16.2% and 0.3% respectively. In the SSRI group, Fluoxetin was administered for 110/166 cases (66.3%); followed by Sertralin 31.9%; Fluvoxamin and Escitalopram accounted for only 1.2% and 0.6%, respectively. Out of 480 times using supportive medicine group, the highest percentage of patients using antipsychotic drugs (51.0%), including: Olanzapine, Sulpiride,... The number of patients being administered rational drug was 223/252 cases (88.5%). The results of drug interactions are largely severe. Conclusions: Antidepressants indicated in accordance with the recommendation accounnted for a high proportion and drug interactions appear in prescriptions at a high rate (50.8%) and are mostly severe. Key words: Depression, antidepressants, antidepressants use, drug interaction

The young real estate market in Vietnam, an emerging country in Asia, has been growing remarkably. This is an attractive channel for investors, but it seems to be an unstable market and have high potential source of earnings management while investing in real estate companies listed in Vietnamese stock market. The research has been conducted to investigate the impact of the ownership structure on the earnings management of Vietnamese listed real estate companies. The research methodology includes four statistical approaches OLS, FEM, REM and REM (robust) that are employed to address econometric issues and to improve the accuracy of the regression coefficients. The research sample consists of 180 firm-year observations for 36 real estate companies listed on Vietnamese stock market over a period of five years, i.e. from 2014 to 2018. The results show that, while state ownership showed a positive influence, managerial ownership played negative significant roles in relation to earnings management. This research has implications for designing a better ownership structure in the Vietnamese real estate sector and enhancing information quality to protect investors.

In this study, a multifunctional drug delivery nanosystem Fe3O4–CdTe–alginate (FAQ) was prepared by coating Fe3O4 nanoparticles and CdTe quantum dots (QDs) simultaneously with alginate. High luminescent CdTe QDs can help label the cells for diagnostics while the superparamagnetic Fe3O4 component endows the abilities of hyperthermia and magnetic targeting to the system for cancer treatment. Besides, polymeric alginate provides biocompatibility and high stability (Zeta potential of −49.1 mV) and makes it possible to encapsulate cancer drug Doxorubicin (Dox) in the system. The fluorescence spectra of blank FAQ and FAQ loading Dox (FAQD) were analysed and compared to those of pure CdTe or Dox to confirm the formation of the nanosystems. Next, the samples were applied to in vitro treatment with several human cell lines (Hep-G2, LU-1, RD and Vero cell lines) and showed positive results with low IC50 values for these cells and exhibited higher impact of apoptosis induction and MCF7 spheroid growth delay compared to pure Dox. In particular, FAQ and FAQD have high values of r2 and show contrast increment in the MRI images. The results indicate that FAQ and FAQD can serve as excellent candidates for both cancer therapy and diagnostics.

The emergence of clinical metagenomics as an unbiased, hypothesis-free approach to diagnostic testing is set to fundamentally alter the way infectious diseases are detected. Long envisioned as the solution to the limitations of culture-based conventional microbiology, next generation sequencing methods will soon mature, and our attention will inevitably turn to how they can be applied to areas of medicine which need it most urgently. In ophthalmology, the demand for this technology is particularly pressing for the care of infectious corneal ulcers, where current diagnostic tests may fail to identify a causative organism in over half of cases. However, the optimism found in the budding discourse surrounding clinical metagenomics belies the reality that clinicians and scientists will soon be inundated by oppressive volumes of sequencing data, much of which will be foreign and unfamiliar. Therefore, our success in translating clinical metagenomics is likely to hinge on how we make sense of these data, and understanding its implications for the interpretation and implementation of sequencing into routine clinical care. In this consortium-led review, we provide an outline of these data-related issues and how they may be used to inform technical workflows, with the hope that we may edge closer to realizing the potential of clinical metagenomics for this important unmet need.

Purpose To report a case of bilateral anterior intermediate uveitis after recovery from SARS-CoV-2 associated multisystem inflammatory syndrome in children (MIS-C). Case Report A 9-year-old male presented with bilateral anterior intermediate uveitis with fluorescein angiography (FA) leakage of the disc and peripheral vasculature 1 month after recovery from MIS-C. He was treated with difluprednate 0.05% in both eyes with resolution of FA leakage, but our patient has required an extended treatment of topical therapy and the need long term immunosuppression. Conclusions This is a case of uveitis presenting after recent MIS-C related to SARS-CoV-2. Ongoing follow up and monitoring is required, and it is important for the ophthalmologist and rheumatologist to be aware of this rare complication during the current COVID-19 pandemic.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1–59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

A broad-spectrum antibiotic, typically amoxicillin, is included in many country guidelines as part of the management of uncomplicated severe acute malnutrition (SAM) in children without overt clinical symptoms of infection. Alternative antibiotics may be beneficial for children with SAM without increasing selection for beta-lactam resistance. We conducted a 1:1 randomized controlled trial of single dose azithromycin versus a 7-day course of amoxicillin for SAM. Children 6–59 months of age with uncomplicated SAM (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < −3) were enrolled in Boromo District, Burkina Faso, from June through October 2020. Rectal swabs were collected at baseline and 8 weeks after treatment and processed using DNA-Seq. We compared the resistome at the class level in children randomized to azithromycin compared with amoxicillin. We found no evidence of a difference in the distribution of genetic antibiotic resistance determinants to any antibiotic class 8 weeks after treatment. There was no difference in genetic macrolide resistance determinants (65% azithromycin, 65% placebo, odds ratio, OR, 1.00, 95% confidence interval, CI, 0.43–2.34) or beta-lactam resistance determinants (82% azithromycin, 83% amoxicillin, OR 0.94, 95% CI, 0.33–2.68) at 8 weeks. Although presence of genetic antibiotic resistance determinants to macrolides and beta-lactams was common, we found no evidence of a difference in the gut resistome 8 weeks after treatment. If there are earlier effects of antibiotics on selection for genetic antibiotic resistance determinants, the resistome may normalize by 8 weeks.

PurposeSub-analysis of the FAST Trial comparing change in CD4 (∆CD4) from baseline through 12months in uveitis patients treated with mycophenolate mofetil (MMF) and methotrexate (MTX).MethodsPatients were randomly allocated to 1.5g twice daily MMF or 25 mg weekly MTX. Individuals with CD4 counts at baseline, 6 months (or treatment failure prior), and 12 months (or treatment failure between 6 and 12months) were included. The association between treatment and ∆CD4 (cells/μL) was analyzed using multivariable linear regression.ResultsThere was no significant difference in ∆CD4 between MMF and MTX at 6months (-31.7 cells/μL for MMF compared to MTX; 95% CI: -358.2 to 294.8, P =.85) and 12months (-78.3 cells/μL for MMF compared to MTX; 95% CI: -468.0 to 311.3; P =.69).ConclusionThere was no significant difference in ∆CD4 between MMF and MTX from baseline to 12months, suggesting that MMF does not confer additional risk of CD4 lymphopenia in uveitic patients.ClinicalTrials.gov Identifier: NCT01829295.

To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil.Subanalysis of a block-randomized, observer-masked, multicenter clinical trial.Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017.Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, patients who achieved treatment success continued the same treatment for a subsequent 6 months, and treatment failures switched to the other treatment group.Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity.Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 μm and 342 μm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 μm (interquartile range [IQR], -132.3 to 4.0) and 54 μm (IQR, -95.5 to -4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 μm (IQR, -32.3 to -0.5) and 50 μm (IQR, -181.0 to -10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution of macular edema (P = 0.92).Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema.

Given the increasing importance of green bond as the main funding source for the Sustainable Development Goals, the green bond is an emerging concept in the region of Southeast Asia. In addition, the concurrent Covid-19 pandemic has caused disruption to the development of green bond around the world. This research explores the current development status of the green bond in Southeast Asian countries. A total of thirty-two semi-structured interviews were held with capital market participants in Southeast Asian countries. The results highlight barriers, opportunities, and regulation difficulties, and expected growth for the development of the green bond market. This research is concluded by indicating several propositions that can be tested in the future to generalize the findings from this work. We thus extend the knowledge of green bond in the financial markets of Southeast Asian countries, which also delivers implications for practitioners and policy-makers regarding the development of green bond in Southeast Asian countries.Compte tenu de l'importance croissante de l’obligation verte en tant que principal attribut financier des objectifs de développement durable (ODD), l'obligation verte est un concept émergent dans la région de l'Asie du Sud-Est. En outre, la pandémie concomitante de Covid-19 a perturbé le développement des obligations vertes dans le monde. Cette étude explore l'état actuel du développement de l'obligation verte dans les pays d'Asie du Sud-Est. Au total, trente-deux entretiens semi-directifs ont été menés avec des acteurs du marché des capitaux dans les pays d'Asie du Sud-Est. Les résultats mettent en évidence les obstacles, les opportunités et les difficultés de réglementation, ainsi que la croissance attendue pour le développement du marché des obligations vertes. Dans sa conclusion, cette étude émet plusieurs propositions qui peuvent être testées à l’avenir pour généraliser les résultats de ce travail. Nous étoffons ainsi la connaissance concernant les obligations vertes sur les marchés financiers des pays d'Asie du Sud-Est, ce qui comporte également des implications pour les praticien·ne·s et les décisionnaires en ce qui concerne le développement des obligations vertes dans les pays d'Asie du Sud-Est.

Viral conjunctivitis (pink eye) can be highly contagious and is of public health importance. There remains significant debate whether SARS-CoV-2 can present as a primary conjunctivitis. The aim of this study was to identify pathogens associated with outpatient infectious conjunctivitis during the COVID-19 Delta surge.This prospective study was conducted in the spring and summer months of 2021. 106 patients with acute conjunctivitis who presented to the Aravind Eye Center in Madurai, India were included. One anterior nasal swab and one conjunctival swab of each eye were obtained for each enrolled patient. Samples were subsequently processed for unbiased metagenomic RNA deep sequencing (RNA-seq). Outcomes included clinical findings and codetection of other pathogens with SARS-CoV-2 in patients with conjunctivitis.Among the 13 patients identified with human coronavirus RNA fragments in their swabs, 6 patients had SARS-CoV-2 infection, 5 patients had coinfections of SARS-CoV-2 and human adenovirus (HAdV), 1 patient had a coinfection with human coronavirus OC43 and HAdV, and 1 patient had a coinfection of Vittaforma corneae and SARS-CoV-2. 30% had bilateral disease and symptoms on presentation. Petechial hemorrhage was noted in 33% of patients with SARS-CoV-2 infection. No patients with SARS-CoV-2 or SARS-CoV-2 and HAdV infections had subepithelial infiltrates on presentation. All patients denied systemic symptoms.Among the patients presented with conjunctivitis associated with human coronavirus infection, over 50% of the patients had co-infections with other circulating pathogens, suggesting the public-health importance of broad pathogen testing and surveillance in the outpatient conjunctivitis population.

Aouidat F, Boumati S, Khan M, Tielens F, Doan BT, Spadavecchia J. Int J Nanomedicine. 2019;14:9309–9324. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. The authors raised concerns regarding errors that had been made during the calculation of the size of the nanostructures shown in Figure 2. The sizes reported in the histograms of Figure 2; a1, a2 and a3 were incorrect due to miscalculations that occurred during analysis of the gold core and polymer shells of the spherical nanostructures represented in TEM images of Figure 2A. The authors provided the editor with data from the original study and requested to remove the incorrect histograms and replace them. However, the Editor determined that this part of the article was integral to the study and the admission of these errors, because of the miscalculation, meant the data was unreliable and would not accept the correction proposed by the authors. The Editor requested for the article to be retracted and the authors were notified but do not agree with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Author(s): Arzika, Ahmed M; Maliki, Ramatou; Abdou, Amza; Mankara, Alio K; Harouna, Abdoul N; Cook, Catherine; Hinterwirth, Armin; Worden, Lee; Zhong, Lina; Chen, Cindi; Ruder, Kevin; Zhou, Zhaoxia; Lebas, Elodie; O'Brien, Kieran S; Oldenburg, Catherine E; Le, Victoria; Arnold, Benjamin F; Porco, Travis C; Keenan, Jeremy D; Lietman, Thomas M; Doan, Thuy | Abstract: We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. Although the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs.Clinical trials registrationNCT02047981.

Importance Azithromycin has been hypothesized to have activity against SARS-CoV-2. Objective To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14. Design, setting, and participants Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization. Interventions Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92). Main outcomes and measures The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21. Results Among 263 participants who were randomized (median age, 43 years; 174 [66%] women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16). Conclusions and relevance Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection. Trial registration ClinicalTrials.gov Identifier: NCT04332107.

Glaucoma is a heterogeneous group of progressive optic neurodegenerative. Although most patients with primary open angle glaucoma (POAG) are stable for many years, certain subgroups of POAG patients could progress over time even with treatment. This study is to identify aqueous humor (AH) biomarkers that may be associated with disease progression in POAG patients. Gene differential expression study of prospectively collected AH from patients with stable or progressive POAG. Metagenomic deep sequencing (MDS) was performed on the aqueous fluid of 20 patients with stable POAG and 20 patients with progressive POAG. Differential gene expression analysis was performed to identify host transcriptome signatures. A total of 21 transcripts were differentially expressed between groups. Differential transcripts identified by MDS. Twenty transcripts were up-regulated and 1 transcript was down-regulated in progressive POAG patients compared to stable patients. Of those, 11 transcripts were eye-related, and 5 transcripts were related to glaucomatous phenotypes (Fibronectin type III domain containing 3B (FNDC3B), Clusterin (CLU), Proprotein convertase subtilisin/kexin type 6 (PCSK6), Cadherin EGF LAG seven-pass G-type receptor 1 (Celsr1), and Rho guanine nucleotide exchange factor 4 (ARHGEF4)). Biomarkers associated with POAG progression can be identified from aqueous fluid. Identification of the biomarkers may improve glaucoma surveillance for progressive POAG.

PURPOSE The aim of this study was to evaluate the effect of the 4 times per year mass azithromycin distributions on the ocular surface microbiome of children in a trachoma endemic area. METHODS In this cluster-randomized controlled trial, children aged 1 to 10 years in rural communities in the Goncha Seso Enesie district of Ethiopia were randomized to either no treatment or treatment with a single dose of oral azithromycin (height-based dosing to approximate 20 mg/kg) every 3 months for 1 year. Post hoc analysis of ocular surface Chlamydia trachomatis load, microbial community diversity, and macrolide resistance determinants was performed to evaluate differences between treatment arms. RESULTS One thousand two hundred fifty-five children from 24 communities were included in the study. The mean azithromycin coverage in the treated communities was 80% (95% CI: 73%-86%). The average age was 5 years (95% CI: 4-5). Ocular surface C. trachomatis load was reduced in children treated with the 4 times per year azithromycin (P = 0.0003). Neisseria gonorrhoeae, Neisseria lactamica, and Neisseria meningitidis were more abundant in the no-treatment arm compared with the treated arm. The macrolide resistance gene ermB was not different between arms (P = 0.63), but mefA/E was increased (P = 0.04) in the azithromycin-treated arm. CONCLUSIONS We found a reduction in the load of C. trachomatis and 3 Neisseria species in communities treated with azithromycin. These benefits came at the cost of selection for macrolide resistance.

We evaluated the potential antiviral effects of azithromycin on the nasopharyngeal virome of Nigerien children who had received multiple rounds of mass drug administration. We found that the respiratory burden of non–severe acute respiratory syndrome coronaviruses was decreased with azithromycin distributions. Clinical Trials Registration. NCT02047981.

Within the past several years, immune checkpoint inhibitors (ICIs) have become more widespread in the treatment of malignancies. Concurrently, ICIs have been found to promote the development of imm...