Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

Benefits of Pair-Bond Duration on Reproduction in a Lifelong Monogamous Cooperative Passerine.

AbstractLong-term social and genetic monogamy is rare in animals except birds, but even in birds it is infrequent and poorly understood. We investigated possible advantages of monogamy in a colonial, facultative cooperatively breeding bird from an arid, unpredictable environment, the sociable weaver (Philetairus socius). We documented divorce and extrapair paternity of 703 pairs over 10 years and separated effects of pair duration from breeding experience by analyzing longitudinal and cross-sectional datasets. Parts of the colonies were protected from nest predation, thereby limiting its stochastic and thus confounding effect on fitness measures. We found that 6.4% of sociable weaver pairs divorced and 2.2% of young were extrapair. Longer pair-bonds were associated with more clutches and fledglings per season and with reproducing earlier and later in the season, when snake predation is lower, but not with increased egg or fledgling mass or with nestling survival. Finally, the number of helpers at the nest increased with pair-bond duration. Results were similar for protected and unprotected nests. We suggest that long-term monogamy is associated with a better capacity for exploiting a temporally unpredictable environment and helps to form larger groups. These results can contribute to our understanding of why long-term monogamy is frequently associated with unpredictable environments and cooperation.

Subclinical choroidal involvement in Systemic Lupus Erythematosus.

PURPOSE: To assess the choroidal status of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography (OCT) and OCT-Angiography. METHODS: SLE patients with disease duration < 10 years, no disease activity and no ocular involvement were recruited and cross-sectionally evaluated. A demographically similar cohort of healthy subjects was used for comparison. The main outcome is choroidal vascularity index (CVI). As secondary outcomes, choriocapillaris parameters and choroidal thickness (CT) were evaluated. RESULTS: Forty eyes of 40 subjects (20 SLE patients and 20 healthy subjects) were studied with a mean ± SD age of 36.7 ± 9.9 years. In the SLE group, the mean ± SD duration of disease was 7.35 ± 2.21 years. Increased CVI was found in the SLE group (p = 0.022). Considering the choriocapillaris, SLE patients presented a lower number (p = 0.037) and a smaller total area (p = 0.041) of signal voids. No differences between groups were found in CT. For SLE patients, CT at subfoveal, temporal and inferior locations presented a negative moderate correlation with disease duration. A strong correlation between choriocapillaris parameters and age was demonstrated for both groups. CONCLUSIONS: This study provides evidence of subclinical choroidal changes in adult SLE patients with inactive disease and no overt ocular manifestation. Increased CVI and fewer and smaller flow voids in choriocapillaris with normal CT suggest increased choroidal vascularity in SLE.

Minute-scale detection of SARS-CoV-2 using a low-cost biosensor composed of pencil graphite electrodes.

COVID-19 has led to over 3.47 million deaths worldwide and continues to devastate primarily middle- and low-income countries. High-frequency testing has been proposed as a potential solution to prevent outbreaks. However, current tests are not sufficiently low-cost, rapid, or scalable to enable broad COVID-19 testing. Here, we describe LEAD (Low-cost Electrochemical Advanced Diagnostic), a diagnostic test that detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 6.5 min and costs $1.50 per unit to produce using easily accessible and commercially available materials. LEAD is highly sensitive toward SARS-CoV-2 spike protein (limit of detection = 229 fg⋅mL-1) and displays an excellent performance profile using clinical saliva (100.0% sensitivity, 100.0% specificity, and 100.0% accuracy) and nasopharyngeal/oropharyngeal (88.7% sensitivity, 86.0% specificity, and 87.4% accuracy) samples. No cross-reactivity was detected with other coronavirus or influenza strains. Importantly, LEAD also successfully diagnosed the highly contagious SARS-CoV-2 B.1.1.7 UK variant. The device presents high reproducibility under all conditions tested and preserves its original sensitivity for 5 d when stored at 4 °C in phosphate-buffered saline. Our low-cost and do-it-yourself technology opens new avenues to facilitate high-frequency testing and access to much-needed diagnostic tests in resource-limited settings and low-income communities.

Insights into Predicting Tooth Extraction from Panoramic Dental Images: Artificial Intelligence vs. Dentists.

OBJECTIVES: Tooth extraction is one of the most frequently performed medical procedures. The indication is based on the combination of clinical and radiological examination and individual patient parameters and should be made with great care. However, determining whether a tooth should be extracted is not always a straightforward decision. Moreover, visual and cognitive pitfalls in the analysis of radiographs may lead to incorrect decisions. Artificial intelligence (AI) could be used as a decision support tool to provide a score of tooth extractability. MATERIAL AND METHODS: Using 26,956 single teeth images from 1,184 panoramic radiographs (PANs), we trained a ResNet50 network to classify teeth as either extraction-worthy or preservable. For this purpose, teeth were cropped with different margins from PANs and annotated. The usefulness of the AI-based classification as well that of dentists was evaluated on a test dataset. In addition, the explainability of the best AI model was visualized via a class activation mapping using CAMERAS. RESULTS: The ROC-AUC for the best AI model to discriminate teeth worthy of preservation was 0.901 with 2% margin on dental images. In contrast, the average ROC-AUC for dentists was only 0.797. With a 19.1% tooth extractions prevalence, the AI model's PR-AUC was 0.749, while the dentist evaluation only reached 0.589. CONCLUSION: AI models outperform dentists/specialists in predicting tooth extraction based solely on X-ray images, while the AI performance improves with increasing contextual information. CLINICAL RELEVANCE: AI could help monitor at-risk teeth and reduce errors in indications for extractions.

Efficacy of essential oil from ginger (Zingiber officinale) for anesthesia and transport sedation of pacu (Piaractus mesopotamicus).

This study evaluated the anesthetic and sedative effects of the essential oil of Zingiber officinale (EOZO) on juvenile pacu (Piaractus mesopotamicus). Experiment 1 evaluated concentrations of 0, 50, 100, 200 and 400 mg L-1 EOZO for times of induction and recovery from anesthesia. Furthermore, hematological responses and residual components of EOZO in plasma were determined immediately after anesthesia. Experiment 2 evaluated the effect of 0, 10, 20 and 30 mg L-1 EOZO on water quality, blood variables and residual components of EOZO in plasma and tissues (muscle and liver) immediately after 2 h of transport. Survival was 100%. The three main compounds of EOZO [zingiberene (32.27%), ß-sesquiphellandrene (18.42%) and ß-bisabolene (13.93%)] were observed in animal plasma and tissues (muscle and liver) after anesthesia and transport, demonstrating a direct linear effect among the evaluated concentrations. The concentration of 200 mg L-1 EOZO promoted surgical anesthesia of pacu and prevented an increase in monocyte and neutrophil levels, yet did not alter other hematological parameters. The use of 30 mg L-1 EOZO has a sedative effect on juvenile pacu, thereby reducing oxygen consumption during transport. Furthermore, the use of 30 mg L-1 EOZO in transport water prevented an increase in hemoglobin and hematocrit, with minimal influences on other blood variables.

Oxidative responses in small juveniles of Colossoma macropomum anesthetized and sedated with Ocimum gratissimum L. essential oil.

This study evaluated the use of essential oil of Ocimum gratissimum (EOOG) for anesthesia and in transport of Colossoma macropomum. Experiment 1, Test 1, anesthesia induction and recovery times were determined using different EOOG concentrations (0, 20, 50, 100, 200, 300 mg L-1), with two size classes: Juveniles I (0.86 g) and Juveniles II (11.46 g) (independent tests in a completely randomized design). Based on the results of Test 1, in Test 2 Juveniles II were exposed to EOOG concentrations: 0, 20, 100 mg L-1. Tissue samples were collected immediately after induction and 1 h post-recovery, to assess oxidative status variables. Experiment 2, Juveniles I (0.91 g) and Juveniles II (14.76 g) were submitted to transport in water with different concentrations of EOOG (0, 5, 10 mg L-1) (independent tests in a completely randomized design). The effects on oxidative status variables were evaluated. Concentrations between 50 and 200 mg L-1 EOOG can be indicated for Juveniles I, while concentrations between 50 and 100 mg L-1 EOOG for Juveniles II. The concentration of 100 mg L-1 EOOG was able to prevent oxidative damage in the liver. In Experiment 2, the concentrations of 5 and 10 mg L-1 EOOG added to the transport water caused sedation for both studied size classes of juveniles and did not cause oscillations in water quality variables nor any mortality. The concentration of 10 mg L-1 EOOG improved the oxidative status. It can be concluded that EOOG can be used for anesthesia and transport of C. macropomum.

Phylogenomics, evolution of trophic traits and divergence times of hemiodontid fishes (Ostariophysi: Characiformes).

The South American characiform family Hemiodontidae comprises five genera and 34 species. The family lacks comprehensive phylogenetic hypotheses resolving its species relationships. The studies that addressed these questions exhibited a narrow taxon sampling or used single-locus markers. Herein we surveyed hundreds of ultraconserved elements (UCEs) loci to provide the first molecular phylogenetic hypothesis and divergence time estimates for hemiodontids encompassing all its genera and most species (27 of the 34 valid species). We also tracked the history of the protractile upper jaw in the genera Argonectes and Bivibranchia across the recovered phylogenies through ancestral state reconstruction. Our results corroborate the monophyly of Hemiodontidae and the genera Argonectes and Bivibranchia in all phylogenetic methods with maximum clade support. The genera Anodus and Hemiodus were not monophyletic because Anodus elongatus was sister to the monotypic Micromischodus instead of A. orinocensis, and H. immaculatus did not form a clade with its other congeners, but instead was sister to the clade including Anodus and Micromischodus. All remaining species of Hemiodus were placed together into a monophyletic group, where they were arranged into four major subclades. The relationship in the family is summarised as: (Bivibranchia, (Argonectes, ((H. immaculatus, (Anodus, Micromischodus)), Hemiodus clade))), in discordance with the morphological phylogeny that placed all genera monophyletic and resolved the family as: ((Anodus, Micromischodus), (Hemiodus, (Argonectes, Bivibranchia))). The origin of Hemiodontidae was estimated from the Late Cretaceous to the Middle Paleogene, with the mean age in the Paleocene, while the origin of most hemiodontid genera except Bivibranchia occurred in the Miocene. Unordered parsimony and likelihood reconstruction indicates that Argonectes and Bivibranchia developed their protractile upper jaw independently.

Egg components and offspring survival vary with group size and laying order in a cooperative breeder.

Prenatal resource allocation to offspring can be influenced by maternal environment and offspring value, and affect offspring survival. An important pathway for flexible maternal allocation is via egg components such as nutrients and hormones. In cooperative breeders, females with helpers may increase resource allocation to eggs-'differential allocation'-or reduce it-'load-lightening'. Yet, helper effects on egg composition have been poorly studied. Moreover, it is unknown how helpers' presence modulates laying order effects on egg content and survival. Here, we investigated how maternal allocation varied with group size and laying order in the cooperatively breeding sociable weaver (Philetairus socius). We estimated interactive effects of helpers and laying order on allocation to egg mass, yolk nutrients-yolk mass, proteins, lipids, carotenoids, vitamin A and vitamin E-and hormones-testosterone, androstenedione, and corticosterone. Results concurred with the 'differential allocation' predictions. Females with more helpers produced later-laid eggs with heavier yolks and more lipids, and laid eggs overall richer in lipids. Proteins, antioxidants, and hormones were not found to vary with helper number. We then analyzed how helper number modulated laying order effects on survival. Females with more helpers did not specifically produce later-laid eggs with higher survival, but eggs laid by females with more helpers were overall more likely to fledge. These findings show that some egg components (yolk mass, lipids) can positively vary according to females' breeding group size, which may improve offspring fitness.

Application of optical coherence tomography angiography for microvascular changes in patients treated with hydroxychloroquine: a systematic review and meta-analysis.

BACKGROUND: Retinal toxicity with long-term hydroxychloroquine (HCQ) treatment is a major concern. This systematic review aims to assess the application of optical coherence tomography angiography (OCTA) to detect microvascular alterations in patients under HCQ. METHODS: PubMed, Scopus, Web of Science, and Cochrane Library databases were systematically searched until January 14, 2023. Studies using OCTA as a primary diagnostic method to evaluate the macular microvasculature of HCQ users were included. Primary outcomes were macular vessel density (VD) and foveal avascular zone (FAZ) at the superficial (SCP) and deep (DCP) capillary plexus. Meta-analysis was performed using a random-effects model. RESULTS: Of 211 screened abstracts, 13 were found eligible, enrolling 989 eyes from 778 patients. High-risk patients due to longer duration of treatment presented lower VD in the retinal microvasculature than those with low-risk in SCP (P = 0.02 in fovea; P = 0.004 in parafovea) and in DCP (P = 0.007 in fovea; P = 0.01 in parafovea). When compared with healthy controls, HCQ users had lower VD in both plexus-no quantitative synthesis was presented. CONCLUSIONS: Microvascular changes were found in autoimmune patients under HCQ treatment without any documented retinopathy. However, the evidence produced so far does not allow to draw conclusion concerning the effect of drug as studies were not controlled for disease duration.

Early analysis shows that endoscopic flexor hallucis longus transfer has a promising cost-effectiveness profile in the treatment of acute Achilles tendon ruptures.

PURPOSE: Current options for treating an Achilles tendon rupture (ATR) include conservative and surgical approaches. Endoscopic flexor hallucis longus (FHL) transfer has been recently proposed to treat acute ruptures, but its cost-effectiveness potential remains to be evaluated. Therefore, the objective of this study was to perform an early cost-effectiveness analysis of endoscopic FHL transfer for acute ATRs, comparing the costs and benefits of current treatments from a societal perspective. METHODS: A conceptual model was created, with a decision tree, to outline the main health events during the treatment of an acute ATR. The model was parameterized using secondary data. A systematic review of the literature was conducted to gather information on the outcomes of current treatments. Data related to outcomes of endoscopic FHL transfers in acute Achilles ruptures was obtained from a single prospective study. Analysis was limited to the two first years. The incremental cost-effectiveness ratio was the main outcome used to determine the preferred strategy. A willingness-to-pay threshold of $100,000 per quality-adjusted life-year was used. Sensitivity analyses were performed to determine whether changes in input parameters would cause significant deviation from the reference case results. Specifically, a probability sensitivity analysis was conducted using Monte Carlo simulations, and a one-way sensitivity analysis was conducted by sequentially varying each model parameter within a given range. RESULTS: For the reference case, incremental cost-effectiveness ratios exceeded the willingness-to-pay threshold for all the surgical approaches. Overall, primary treatment was the main cost driver. Conservative treatment showed the highest direct costs related to the treatment of complications. In the probabilistic sensitivity analysis, at a willingness-to-pay threshold of $100,000, open surgery was cost-effective in 50.9%, minimally invasive surgery in 55.8%, and endoscopic FHL transfer in 72% of the iterations. The model was most sensitive to parameters related to treatment utilities, followed by the costs of primary treatments. CONCLUSION: Surgical treatments have a moderate likelihood of being cost-effective at a willingness-to-pay threshold of $100,000, with endoscopic FHL transfer showing the highest likelihood. Following injury, interventions to improve health-related quality of life may be better suited for improved cost-effectiveness. LEVEL OF EVIDENCE: Level III.

Hospital Readmissions After Total Joint Arthroplasty: An Updated Analysis and Implications for Value-Based Care.

BACKGROUND: While risk factors have been published for readmissions following primary total joint arthroplasty, little is known about the etiology of those costly adverse events. In this study, we sought to identify the reasons for 30-day readmission following primary total joint arthroplasty in a contemporary national patient sample. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried to identify 367,199 patients who underwent primary total knee (TKA) or hip arthroplasty (THA) between 2011 and 2018. The primary outcomes were the annual rates of 30-day readmissions and the causes of those readmissions. RESULTS: The 30-day readmission rate trended downward from 4.5% in 2011 to 3.3% in 2018. Medical complications accounted for 52.6% and 38.5% of readmissions following TKA and THA, respectively. Diseases of the circulatory system, abnormal laboratory values, and diseases of the digestive system were the leading causes of medical readmissions. Surgical complications accounted for 37.7% and 50.7% of readmissions following TKA and THA, respectively. Surgical site infections/wound disruption and venous thromboembolism were the leading two causes of surgical readmissions for THA and TKA. Prosthetic complications-namely dislocations and periprosthetic fractures-were the third leading cause of surgical readmissions for THA. For TKA, musculoskeletal conditions-namely pain and hematoma-were the third leading cause of surgical readmissions. CONCLUSION: Medical complications accounted for half of all TKA readmissions and more than a third of THA readmissions. This could penalize institutions participating in value-based payment programs or dissuade others who are considering participation in such programs.

Effects of live prey concentration, salinity, and weaning age on larviculture of Piaractus brachypomus reared in a recirculating aquaculture system.

This study evaluated the effects of live prey concentration (nauplii of Artemia sp.), water salinity, and weaning age on survival, growth, and stress resistance rate (Rs) of Piaractus brachypomus under larviculture in a recirculating aquaculture system (RAS). Larvae aged 6 days post-hatching (1.64 ± 0.11 mg) were distributed in 28-L tanks (five larvae L-1), in two RASs. The experiment was carried in a 2 × 2 × 2 factorial arrangement, as follows: two feeding strategies (sudden transition from live food to commercial food after 10 (FT10) and 20 (FT20) days of larviculture with Artemia); two daily initial prey concentrations (P350 = 350 and P700 = 700 nauplii larva-1, these being increased every 5 days); and two water salinities (S0 = fresh water and S2 = 2 g of salt L-1). Weight (W), total length (TL), and daily specific growth rate (SGR) were evaluated after 10, 20, 30, and 40 days of larviculture. After 40 days of larviculture, survival was evaluated and a test of air exposure was performed to determine stress resistance rate (Rs). Noteworthy results during this period are the lowest specific daily growth rate (SGR) after weaning for FT10 and the best growth results for S2 and P700. After 40 days, weight (W) and total length (TL) showed effects of P, FT, and S with higher values for P700, FT20, and S2 (P < 0.05). The interaction P × FT × S also had effects on survival and Rs at the end of the experiment, with higher survival and Rs for P700FT20S2 (P < 0.05). Larviculture of P. brachypomus in RAS, in association with the three managements-live prey concentration P700, salinity S2, and age at feed transition FT20-promotes maximization of survival, growth, and stress resistance rate of the animals. The larviculture of P. brachypomus in RAS must be carried out with an initial concentration of live prey of 700 nauplii larva-1, at a salinity of 2 g of salt L-1 and with the feeding transition starting in 20 days of larviculture, for maximization intensive larviculture of this species.

Disentangling climatic and nest predator impact on reproductive output reveals adverse high-temperature effects regardless of helper number in an arid-region cooperative bird.

Climate exerts a major influence on reproductive processes, and an understanding of the mechanisms involved and which factors might mitigate adverse weather is fundamental under the ongoing climate change. Here, we study how weather and nest predation influence reproductive output in a social species, and examine whether larger group sizes can mitigate the adverse effects of these factors. We used a 7-year nest predator-exclusion experiment on an arid-region cooperatively breeding bird, the sociable weaver. We found that dry and, especially, hot weather were major drivers of nestling mortality through their influence on nest predation. However, when we experimentally excluded nest predators, these conditions were still strongly associated with nestling mortality. Group size was unimportant against nest predation and, although positively associated with reproductive success, it did not mitigate the effects of adverse weather. Hence, cooperative breeding might have a limited capacity to mitigate extreme weather effects.

Functional characterization of the pUceS8.3 promoter and its potential use for ectopic gene overexpression.

MAIN CONCLUSION: The pUceS8.3 is a constitutive gene promoter with potential for ectopic and strong genes overexpression or active biomolecules in plant tissues attacked by pests, including nematode-induced giant cells or galls. Soybean (Glycine max) is one of the most important agricultural commodities worldwide and a major protein and oil source. Herein, we identified the soybean ubiquitin-conjugating (E2) enzyme gene (GmUBC4; Glyma.18G216000), which is significantly upregulated in response to Anticarsia gemmatalis attack and Meloidogyne incognita-induced galls during plant parasitism by plant nematode. The GmUBC4 promoter sequence and its different modules were functionally characterized in silico and in planta using transgenic Arabidopsis thaliana and G. max lines. Its full-length transcriptional regulatory region (promoter and 5´-UTR sequences, named pUceS8.3 promoter) was able to drive higher levels of uidA (ß-glucuronidase) gene expression in different tissues of transgenic A. thaliana lines compared to its three shortened modules and the p35SdAMV promoter. Notably, higher ß-glucuronidase (GUS) enzymatic activity was shown in M. incognita-induced giant cells when the full pUceS8.3 promoter drove the expression of this reporter gene. Furthermore, nematode-specific dsRNA molecules were successfully overexpressed under the control of the pUceS8.3 promoter in transgenic soybean lines. The RNAi gene construct used here was designed to post-transcriptionally downregulate the previously characterized pre-mRNA splicing factor genes from Heterodera glycines and M. incognita. A total of six transgenic soybean lines containing RNAi gene construct were selected for molecular characterization after infection with M. incognita pre-parasitic second-stage (ppJ2) nematodes. A strong reduction in the egg number produced by M. incognita after parasitism was observed in those transgenic soybean lines, ranging from 71 to 92% compared to wild-type control plants. The present data demonstrated that pUceS8.3 is a gene promoter capable of effectively driving dsRNA overexpression in nematode-induced giant cells of transgenic soybean lines and can be successfully applied as an important biotechnological asset to generate transgenic crops with improved resistance to root-knot nematodes as well as other pests.

A Biosafety Level 2 Mouse Model for Studying Betacoronavirus-Induced Acute Lung Damage and Systemic Manifestations.

The emergence of life-threatening zoonotic diseases caused by betacoronaviruses, including the ongoing coronavirus disease 19 (COVID-19) pandemic, has highlighted the need for developing preclinical models mirroring respiratory and systemic pathophysiological manifestations seen in infected humans. Here, we showed that C57BL/6J wild-type mice intranasally inoculated with the murine betacoronavirus murine hepatitis coronavirus 3 (MHV-3) develop a robust inflammatory response leading to acute lung injuries, including alveolar edema, hemorrhage, and fibrin thrombi. Although such histopathological changes seemed to resolve as the infection advanced, they efficiently impaired respiratory function, as the infected mice displayed restricted lung distention and increased respiratory frequency and ventilation. Following respiratory manifestation, the MHV-3 infection became systemic, and a high virus burden could be detected in multiple organs along with morphological changes. The systemic manifestation of MHV-3 infection was also marked by a sharp drop in the number of circulating platelets and lymphocytes, besides the augmented concentration of the proinflammatory cytokines interleukin 1 beta (IL-1ß), IL-6, IL-12, gamma interferon (IFN-γ), and tumor necrosis factor (TNF), thereby mirroring some clinical features observed in moderate and severe cases of COVID-19. Importantly, both respiratory and systemic changes triggered by MHV-3 infection were greatly prevented by blocking TNF signaling, either via genetic or pharmacologic approaches. In line with this, TNF blockage also diminished the infection-mediated release of proinflammatory cytokines and virus replication of human epithelial lung cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Collectively, results show that MHV-3 respiratory infection leads to a large range of clinical manifestations in mice and may constitute an attractive, lower-cost, biosafety level 2 (BSL2) in vivo platform for evaluating the respiratory and multiorgan involvement of betacoronavirus infections. IMPORTANCE Mouse models have long been used as valuable in vivo platforms to investigate the pathogenesis of viral infections and effective countermeasures. The natural resistance of mice to the novel betacoronavirus SARS-CoV-2, the causative agent of COVID-19, has launched a race toward the characterization of SARS-CoV-2 infection in other animals (e.g., hamsters, cats, ferrets, bats, and monkeys), as well as adaptation of the mouse model, by modifying either the host or the virus. In the present study, we utilized a natural pathogen of mice, MHV, as a prototype to model betacoronavirus-induced acute lung injure and multiorgan involvement under biosafety level 2 conditions. We showed that C57BL/6J mice intranasally inoculated with MHV-3 develops severe disease, which includes acute lung damage and respiratory distress that precede systemic inflammation and death. Accordingly, the proposed animal model may provide a useful tool for studies regarding betacoronavirus respiratory infection and related diseases.

Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators.

Viruses are obligate intracellular parasites that make use of the host metabolic machineries to meet their biosynthetic needs. Thus, identifying the host pathways essential for the virus replication may lead to potential targets for therapeutic intervention. The mechanisms and pathways explored by SARS-CoV-2 to support its replication within host cells are not fully known. Lipid droplets (LD) are organelles with major functions in lipid metabolism, energy homeostasis and intracellular transport, and have multiple roles in infections and inflammation. Here we described that monocytes from COVID-19 patients have an increased LD accumulation compared to SARS-CoV-2 negative donors. In vitro, SARS-CoV-2 infection were seen to modulate pathways of lipid synthesis and uptake as monitored by testing for CD36, SREBP-1, PPARγ, and DGAT-1 expression in monocytes and triggered LD formation in different human cell lines. LDs were found in close apposition with SARS-CoV-2 proteins and double-stranded (ds)-RNA in infected Vero cells. Electron microscopy (EM) analysis of SARS-CoV-2 infected Vero cells show viral particles colocalizing with LDs, suggestive that LDs might serve as an assembly platform. Pharmacological modulation of LD formation by inhibition of DGAT-1 with A922500 significantly inhibited SARS-CoV-2 replication as well as reduced production of mediators pro-inflammatory response. Taken together, we demonstrate the essential role of lipid metabolic reprograming and LD formation in SARS-CoV-2 replication and pathogenesis, opening new opportunities for therapeutic strategies to COVID-19.

CHOROIDAL INVOLVEMENT IN HEREDITARY TRANSTHYRETIN AMYLOIDOSIS PATIENTS.

PURPOSE: To compare the choroidal characteristics between the eyes of patients with and without hereditary transthyretin amyloidosis. METHODS: Case-control observational study with choroidal thickness and vasculature evaluation by optical coherence tomography with enhanced depth imaging protocol of the macula. RESULTS: The study included 332 eyes: 166 eyes of hereditary transthyretin amyloidosis patients and 166 eyes of healthy patients. Mean age was similar between groups (P = 0.979). For hereditary transthyretin amyloidosis patients, on average, in all sectors analyzed (in the full 5 mm-width image [G] and also in 1-mm-width central [C], nasal [N], and temporal [T] sectors), there was a higher stromal area, a lower choroidal thickness, and a lower choroidal vascularity index, compared with the control group. The linear mixed models revealed no differences according to the systemic treatment groups. CONCLUSION: Hereditary transthyretin amyloidosis patients showed statistically significant differences in choroidal characteristics, compared with eyes without pathology. These age-related and statistically significant changes compared with the healthy eyes may help in the future to better monitor the systemic hereditary transthyretin amyloidosis disease and complement other systemic evaluations, including on clinical trials to analyze more objectively, the results of new therapies.

Globe Ruptures: Outcomes and Prognostic Analysis of Severe Ocular Trauma.

PURPOSE: Eye trauma is an important cause of monocular visual loss worldwide. This study aimed to describe the structural and functional characteristics and outcomes of 281 globe ruptures. METHODS: Medical records of all patients undergoing surgery for a ruptured globe at Centro Hospitalar Universitário do Porto in the last 17 years were retrospectively reviewed. RESULTS: 281 eyes of 277 patients were included. The majority of them were males (71%) with a mean age of 59.7 ± 20.5. In 38.8% of the cases, the cause was a fall. At the time of admission, 29.5% of the eyes had a visual acuity (VA) greater than 20/200 and 12.5% had no light perception. The median time between trauma and primary repair was less than 8 h (interquartile range 5-12 h). A primary reconstruction was always attempted. Primary evisceration was performed in 14 cases (5%). In multivariable analysis, independent predictors of vision survival were male gender, shorter wound size, and absence of vitreous hemorrhage. CONCLUSION: In this large, retrospective study on globe ruptures, we identified male gender, short wound length, and the absence of vitreous hemorrhage or retinal detachment as predictors of improved functional outcome. We found a correlation between the presenting and final VAs. The Ocular Trauma Score predicted the outcome well. Our determination to reconstruct the traumatized eyes as early and as completely as possible was justified by the functional results: despite the severity of the injuries, one out of four eyes reached a final VA greater than 20/200.

The Impact of COVID-19 Pandemic on Surgical Primary Retinal Detachments.

PURPOSE: This study aimed to describe the impact of COVID-19 pandemic on the presentation characteristics, timings, and surgical decisions for primary rhegmatogenous retinal detachment (RRD). METHODS: A historical cohort including all patients who presented to the Surgical Retina Section at Centro Hospitalar Universitário do Porto (CHUPorto), over a 2-year period, was recruited and divided into 2 groups: pre-COVID and COVID groups. The onset of the COVID-19 pandemic was recorded as starting on March 18, 2020, the same day the first pandemic-related lockdown came to effect in Portugal. RESULTS: This study enrolled 449 eyes of 443 patients: 272 in the pre-COVID group and 177 in the COVID one. Of the patients, 63.6% were male, and the mean ± SD age was 63.0 ± 13.2 years (range 13-92 years). Of the eyes, 55.5% (n = 151) presented with macular detachment in the pre-COVID group compared with 66.9% (n = 119) in the COVID group (odds ratio [OR] 1.62; 95% confidence interval [CI]: 1.09-3.86; p = 0.016). The time from symptom onset to hospital admission (p = 0.021) and from admission to surgery (p < 0.001) was longer in the COVID era. In the COVID period, silicone oil (OR 2.03, 95% CI: 1.09-3.79, p = 0.025) and C3F8 gas (OR 2.42, 95% CI: 1.57-3.71, p < 0.001) were used more often. No differences in anatomical success or final visual acuity were found. CONCLUSIONS: The lockdown due to COVID pandemic affected the epidemiology of RRD. The services must adapt to the novel reality and produce backup plans for similar events. Despite the contingencies, the final results were not different between groups.