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Background: Rhabdomyoma is the most common cardiac tumor in fetal life. It has frequent association with tuberous sclerosis complex and may lead to heart failure, a potentially fatal condition. The use of transplacental sirolimus, a mammalian target of rapamycin inhibitor, has emerged as a novel treatment in symptomatic fetal rhabdomyomas; however, there are only few cases described., Case Presentation: A 37-year-old woman at 29 weeks and 4 days of gestation had been diagnosed with fetal cardiac tumor, adhered adjacent to the left ventricle, associated with heart dysfunction and polyhydramnios. Therapy with oral sirolimus was started, and, once serum levels were achieved, cardiac tumor reduction was observed, with progressive resolution of cardiac dysfunction. However, maternal hypertriglyceridemia was developed as a side effect, a rarely discussed theme on previous articles, and was successfully controlled with dose reduction. The patient delivered a male infant at 38 weeks and 2 days of pregnancy with no need of any resuscitation maneuver., Conclusion: Transplacental treatment with sirolimus is a promising therapeutic option to treat symptomatic fetal rhabdomyomas, but more data are demanded to determine its efficacy and safety during pregnancy. A close maternal follow-up concerning triglyceride levels is mandatory., (© 2025 S. Karger AG, Basel.)

Background: This single-blind, noninferiority trial evaluated whether 10% carbamide peroxide (CP) applied for 2 or 4 hours daily is noninferior to 8 hours., Methods: A total of 120 healthy adults, with teeth shade A2 or darker, were randomly allocated to 3 groups (n = 40). All participants used 10% CP gel in a bleaching tray for 2, 4, and 8 hours daily for 14 days, with the option to extend treatment if they were dissatisfied. Color change was measured using a spectrophotometer and shade guides at baseline, every 5 days, and 1 month posttreatment. Risk and intensity of tooth sensitivity (TS) were assessed daily using a 0 through 10 visual analog scale. Satisfaction was recorded via a Likert scale wherein 1 corresponded to very dissatisfied and 7 corresponded to very satisfied and the Orofacial Esthetic Scale. Noninferiority was tested for color change using the 1976 formula (ΔEab) at 1 month postbleaching (primary outcome), color change using the 2000 formula (ΔE00), Whiteness Index, and shade guide units, whereas TS and satisfaction were analyzed with χ 2 , analysis of variance, Kruskal-Wallis, and Friedman tests., Results: Color change in ΔEab (2 vs 8 h: mean difference, -0.6; 90% CI, -2.1 to 1.0, 4 vs 8 h: mean difference, 0.0; 90% CI, -1.6 to 1.6) and ΔE00 values for shorter durations were noninferior to 8 hours at 1 month. Whiteness Index results were inconclusive. TS risk and intensity were similar (P > .05), and patient satisfaction improved across all groups similarly (P > .05)., Conclusions: Shorter 2- and 4-hour daily bleaching with 10% CP is noninferior to the 8-hour protocol., Practical Implications: Shorter periods of at-home bleaching (2 and 4 h) can be prescribed depending on the patient's availability or preferences without jeopardizing the bleaching efficacy. This clinical trial was registered at Registro Brasileiro de Ensaios Clínicos (RBR-10vvfpcm)., Competing Interests: Disclosures None of the authors reported any disclosures., (Copyright © 2025 American Dental Association. Published by Elsevier Inc. All rights reserved.)

The hypothesis of this study is that it is possible to determine the plant stand in the soybean ( Glycine max L. Merril) crop based on the spatial variability of management units, which are limiting factors in maximizing crop yield. Our objectives were as follows: (I) to evaluate the relationship between soil physical and chemical attributes to establish potential management units for variable-rate seeding; (II) to propose a method for varying plant stands based on the law of minimum soil nutrients; an (III) to relate the interaction between different plant stands on soybean grain yield, taking into account the interaction between the spatial variability of the mapped attributes. Field experiments were carried out on two plots over two agricultural years. The areas were seeded by randomly varying the soybean stand across strips in the first year. The most limiting soil nutrient was established and used, together with the soil CEC, to determine management units (MUs), which were also used to seed soybeans in VRT (Variable Rate Technology) in the same plots in the second year. MUs with the lowest restriction for maximizing yield were sown in the second year with the lowest plant stand. Data were processed using multivariate statistics. Our findings reveal that it is possible to establish MUs for seeding soybeans with different stands following the spatial variability of limiting soil nutrients according to the law of the minimum and thus increase the crop grain yield. Spatial variability of potassium (K) in the plot, identified as limiting, affected the spatial variability of grain yield. Decreasing plant stands in MUs with the lowest limitation level increases yield. However, increasing the stand in MUs with a higher limitation level can lead to increased intraspecific competition, affecting yield as well as increasing input costs.

The microbiological and biochemical properties of a goat cheese produced using Helianthus annuus (sunflower) seed extract as a coagulant and the potentially probiotic autochthonous culture Limosilactobacillus mucosae CNPC007 were examined in comparison to a control cheese devoid of the autochthonous culture. Throughout a 60-day storage period at 6 ± 1 °C, lactobacilli maintained a count of above 8 log CFU/g. Additionally, its viability in cheeses subjected to the in vitro gastrointestinal conditions demonstrated improvement over this period. Specifically, the recovery of lactobacilli above 6 log CFU/g was observed in 16.66% of the samples in the first day, increasing to 66.66% at both 30 and 60 days. While total coliforms were detected in both cheese trials, this sanitary parameter exhibited a decline in L. mucosae cheeses during storage, falling below the method threshold (<3 MPN/g) at 60 days. This observation suggests a potential biopreservative effect exerted by this microorganism, likely attributed to the higher acidity of L. mucosae cheeses at that point (1.80 g/100 g), which was twice that of the control trial (0.97 g/100 g). Furthermore, distinct relative proportions of >30 kDa, 30-20 kDa, and <20 kDa proteins during storage was verified for L. mucosae and control cheeses. Consequently, either the H. annuus seed extract or the L. mucosae CNPC007 autochthonous culture influenced the biochemical properties of the cheese, particularly in terms of proteolysis. Moreover, L. mucosae CNPC007 acidification property resulted in a biopreservative effect throughout the storage period, indicating the potential as a promising source of probiotics for this product.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss among the elderly in Western communities, with an estimated global prevalence of 10 - 20% in people older than 65 years. AMD leads to central vision loss due to degeneration of the photoreceptors, retinal pigment epithelium and the choriocapillaris. Beckman's classification for AMD, based upon color fundus photographs, divides the disease into early, intermediate, and late forms. The late, vision-threatening stage includes both neovascular AMD and geographic atrophy. Despite its high prevalence and impact on patients' quality of life, treatment options for AMD are limited. While neovascular AMD can be medically managed with anti-VEGF intravitreal injections, until very recently there has been no approved treatment options for atrophic AMD; however, in February 2023 the first treatment for geographic atrophy - pegcetacoplan - was approved by the US FDA. We describe the current landscape of potential gene and cell therapeutic strategies for late-stage AMD, with an emphasis on the therapeutic options that might become available in the next few years., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be consideredas potential competing interests: LNA: Consultant: Apellis, Novartis. Investigator: Gyroscope, Belite, Nacuity, Janssen. RHG consultant Apellis, Novartis Roche, Genentech, Bayer.: TLE: Consultant: Novartis. Investigator: Gyroscope, Belite, Nacuity, Janssen. DCS - Co-investigator: Gyroscope, Belite, Nacuity, Janssen., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Eucalyptus species play an important role in the global carbon cycle, especially in reducing the greenhouse effect as well as storing atmospheric CO₂. Thus, assessing the amount of CO₂ released by the soil in forest areas can generate important information for environmental monitoring. This study aims to verify the relation between soil carbon dioxide (CO₂) flux (FCO₂), spectral bands, and vegetation indices (VIs) derived from a UAV-based multispectral camera over an area of eucalyptus species. Multispectral imageries (green, red-edge, and near-infrared) from the Parrot Sequoia sensor, derived vegetation indices, and the FCO₂ data from a LI-COR 8100 analyzer, combined with soil moisture and temperature data, were collected and related. The vegetation indices ATSAVI (Adjusted Transformed Soil-Adjusted VI), GSAVI (Green Soil Adjusted Vegetation Index), and SAVI (Soil-Adjusted Vegetation Index), which use soil correction factors, exhibited a strong negative correlation with FCO₂ for the species E. camaldulensis, E. saligna, and E. urophylla species. A Multivariate Analysis of Variance showed significance (p < 0.01) for the species factor, which indicates that there are differences when considering all variables simultaneously. The results achieved in this study show a specific correlation between the data of soil CO₂ emission and the eucalypt species, providing a distinction of values between the species in the statistical data., (© 2024. The Author(s).)

Clinical Relevance: The challenges of establishing retinal screening programs in rural settings may be mitigated by the emergence of deep-learning systems for early disease detection., Background: Deep-learning systems have demonstrated promising results in retinal disease detection and may be particularly useful in rural settings where accessibility remains a barrier to equitable service provision. This study aims to evaluate the real-world performance of Thirona RetCAD for the detection of referable diabetic retinopathy and age-related macular degeneration in a rural Australian population., Methods: Colour fundus images from participants with known diabetic retinopathy or age-related macular degeneration were randomly selected from ophthalmology clinics in four rural Australian centres. Grading was confirmed retrospectively by two retinal specialists. RetCAD produced a quantitative measure (0-100) for DR and AMD severity. The area under the ROC curve (AUC) was calculated. Sensitivity, specificity, and positive and negative predictive values were calculated at a pre-defined cut-point of ≥50., Results: A total of 150 images from 82 participants were included. The mean age (SD) was 64.0 (12.8) years. Seventy-nine (52.7%) eyes had evidence of referable DR, while 54 (36.0%) had evidence of referable AMD. The AUC for referable DR detection was 0.971 (95% CI 0.950-0.936) with a sensitivity of 86.1% (76.8%-92.0%) and a specificity of 91.6% (82.8%-96.1%) at the pre-defined cut-point. Using the Youden Index method, the optimal cut-point was 41.2 (sensitivity 93.7%, specificity 90.1%). The AUC for the detection of referable AMD was 0.880 (0.824-0.936). At the pre-defined cut-point sensitivity was 88.9% (77.8%-94.8%) and specificity was 66.7% (56.8%-75.3%). The optimal cut-point was 52.6 (sensitivity 87.0%, specificity 75.0%)., Conclusion: RetCAD is comparable with but does not outperform equivalent deep-learning systems for retinal disease detection. RetCAD may be suitable as an automated screening tool in a rural Australian setting.

Flavonoids are compounds that result from the secondary metabolism of plants and play a crucial role in plant development and mitigating biotic and abiotic stresses. The highest levels of flavonoids are found in legumes such as soybean. Breeding programs aim to increase desirable traits, such as higher flavonoid contents and vigorous seeds. Soybeans are one of the richest sources of protein in the plant kingdom and the main source of flavonoid derivatives for human health. In view of this, the hypothesis of this study is based on the possibility that the concentration of isoflavones in soybean seeds contributes to the physiological quality of the seeds. The aim of this study was to analyze the content of flavonoids in soybean genotypes and their influence on the physiological quality of the seeds. Seeds from thirty-two soybean genotypes were obtained by carrying out a field experiment during the 2021/22 crop season. The experimental design was randomized blocks with four replications and thirty-two F 3 soybean populations. The seeds obtained were subjected to germination, first germination counting, electrical conductivity and tetrazolium vigor and viability tests. After drying and milling the material from each genotype, liquid chromatography analysis was carried out to obtain flavonoids, performed at UPLC level. Data were submitted to analysis of variance and, when significant, the means were compared using the Scott-Knott test at 5% probability. The results found here show the occurrence of genotypes with higher amounts of flavonoids when compared to their peers. The flavonoid FLVD&#95;G2 had the highest concentration and differed from the others. Thus, we can assume that the type and concentration of flavonoids does not influence the physiological quality of seeds from different soybean genotypes, but it does indirectly contribute to viability and vigor, since the genotypes with the highest FLVD&#95;G2 levels had better FGC values. The findings indicate that there is a difference between the content of flavonoids in soybean genotypes, with a higher content of genistein. The content of flavonoids does not influence the physiological quality of seeds, but contributes to increasing viability and vigor., (© 2024. The Author(s).)

Purpose: Female carriers of X-linked inherited retinal diseases (IRDs) can show highly variable phenotypes and disease progression. Vascular reactivity, a potential disease biomarker, has not been investigated in female IRD carriers. In this study, functional optical coherence tomography angiography (OCT-A) was used to dynamically assess the retinal microvasculature of X-linked IRD carriers., Methods: Genetically confirmed female carriers of IRDs (choroideremia or X-linked retinitis pigmentosa), and healthy women were recruited. Macular angiograms (3x3mm, Zeiss Plex Elite 9000) were obtained in 36 eyes of 15 X-linked IRD female carriers and 21 age-matched control women. Two tests were applied to test vascular reactivity: (i) mild hypoxia and (ii) handgrip test, to induce a vasodilatory or vasoconstrictive response, respectively. Changes to vessel density (VD) and vessel length density (VLD) were independently evaluated during each of the tests for both the superficial and deep capillary plexuses., Results: In the control group, the superficial and deep VD decreased during the handgrip test (p<0.001 and p=0.037, respectively). Mean superficial VLD also decreased during the handgrip test (p=0.025), while the deep plexus did not change significantly (p=0.108). During hypoxia, VD and VLD increased in the deep plexus (p=0.027 and p=0.052, respectively) but not in the superficial plexus. In carriers, the physiologic vascular responses seen in controls were not observed in either plexus during either test, with no difference in VD or VLD noted (all p>0.05)., Conclusions: Functional OCT-A is a useful tool to assess dynamic retinal microvascular changes. Subclinical impairment of the physiological vascular responses seen in carriers of X-linked IRDs may serve as a valuable clinical biomarker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Gocuk, Hadoux, Catipon, Cichello, Kumar, Jolly, van Wijngaarden, Llewelyn Edwards, Ayton and Sousa.)

Yield multi-location trials associated to geostatistical techniques with environmental covariables can provide a better understanding of G x E interactions and, consequently, adaptation limits of soybean cultivars. Thus, the main objective of this study is understanding the environmental covariables effects on soybean adaptation, as well as predicting the adaptation of soybean under environmental variations and then recommend each soybean cultivar to favorable environments aiming maximize the average yield. The trials were carried out in randomized block design (RBD) with three replicates over three years, in 28 locations. Thirty-two genotypes (commercial and pre-commercial) representing different maturity groups (7.5-8.5) were evaluated in each trial were covering the Edaphoclimatic Region (REC) 401, 402 and 403. The covariables adopted as environmental descriptors were accumulated rainfall, minimum temperature, mean temperature, maximum temperature, photoperiod, relative humidity, soil clay content, soil water avaibility and altitude. After fitting means through Mixed Linear Model, the Regression-Kriging procedure was applied to spacialize the grain yield using environmental covariables as predictors. The covariables explained 32.54% of the GxE interaction, being the soil water avaibility the most important to the adaptation of soybean cultivars, contributing with 7.80%. Yield maps of each cultivar were obtained and, hence, the yield maximization map based on cultivar recommendation was elaborated., (© 2024. The Author(s).)

Traditional monitoring of asian soybean rust severity is a time- and labor-intensive task, as it requires visual assessments by skilled professionals in the field. Thus, the use of remote sensing and machine learning (ML) techniques in data processing has emerged as an approach that can increase efficiency in disease monitoring, enabling faster, more accurate and time- and labor-saving evaluations. The aims of the study were: (i) to identify the spectral signature of different levels of Asian soybean rust severity; (ii) to identify the most accurate machine learning algorithm for classifying disease severity levels; (iii) which spectral input provides the highest classification accuracy for the algorithms; (iv) to determine a sample size of leaves that guarantees the best accuracy for the algorithms. A field experiment was carried out in the 2022/2023 harvest in a randomized block design with a 6x3 factorial scheme (ML algorithms x severity levels) and four replications. Disease severity levels assessed were: healthy leaves, 25 % severity, and 50 % severity. Leaf hyperspectral analysis was carried out over a wide range from 350 to 2500 nm. From this analysis, 28 spectral bands were extracted, seeking to distinguish the spectral signature for each severity level with the least input dataset. Data was subjected to machine learning analysis using Artificial Neural Network (ANN), REPTree (DT) and J48 decision trees, Random Forest (RF), and Support Vector Machine (SVM) algorithms, as well as a traditional classification method (Logistic Regression - LR). Two different input datasets were tested for each algorithm: the full spectrum (ALL) provided by the sensor and the 28 spectral bands (SB). Tests with different sample sizes were also conducted to investigate the algorithms' ability to detect severity levels with a reduced sample size. Our findings indicate differences between the spectral curves for the severity levels assessed, which makes it possible to differentiate between healthy plants with low and high severity using hyperspectral sensing. SVM was the most accurate algorithm for classifying severity levels by using all the spectral information as input. This algorithm also provided high classification accuracy when using smaller leaf samples. This study reveals that hyperspectral sensing and the use of ML algorithms provide an accurate classification of different levels of Asian rust severity, and can be powerful tools for a more efficient disease monitoring process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This 24-month, double-blind, split-mouth randomized clinical trial aimed to compare the retention rates of a preheated thermoviscous composite resin (PHT) compared to a non-heated composite resin (NHT) in non-carious cervical lesions (NCCLs)., Methods: A total of 120 restorations were restored on NCCLs using a preheated (VisCalor bulk, Voco GmbH) and a non-heated (Admira Fusion, Voco GmbH) composite resins with 60 restorations per group. A universal adhesive in the selective enamel conditioning was applied. In the PHT group, composite was heated at 68 °C for using a bench heater. In the NHT group, no heating was employed. Both restorative materials were dispensed into caps and inserted into the NCCLs. The restorations were evaluated at baseline, 6, 12, 18, and after 24 months of clinical service using the FDI criteria. Statistical analysis was performed with Kaplan-Meier estimation analysis for retention/fracture rate and Chi-square test for the other FDI parameters (α=0.05)., Results: After 24 months 108 restorations were assessed. Seven restorations were lost (two for PHT group and five for NHT group), and the retention rates (95 % confidence interval [CI]) were 96.7 % (81.5-99.9) for PHT group and 90.8 % (81.1-96.0) for NHT group, with no statistical differences between them (p > 0.05). The hazard ratio (95 % CI) was 0.52 (0.27 to 1.01), with no significant difference within groups. In terms of all other FDI parameters that were assessed, all restorations were deemed clinically acceptable., Conclusions: Both composites showed high rates of retention rates after 24 months., Clinical Significance: The clinical performance of the new preheated thermoviscous was found to be as good as the non-heated composite after 24-month of clinical evaluation in non-carious cervical lesions., Registration of Clinical Trials: RBR-6d6gxxz., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Employing visible and near infrared sensors in high-throughput phenotyping provides insight into the relationship between the spectral characteristics of the leaf and the content of grain properties, helping soybean breeders to direct their program towards improving grain traits according to researchers' interests. Our research hypothesis is that the leaf reflectance of soybean genotypes can be directly related to industrial grain traits such as protein and fiber contents. Thus, the objectives of the study were: (i) to classify soybean genotypes according to the grain yield and industrial traits; (ii) to identify the algorithm(s) with the highest accuracy for classifying genotypes using leaf reflectance as model input; (iii) to identify the best input data for the algorithms to improve their performance. A field experiment was carried out in randomized block design with three replications and 32 soybean genotypes. At 60 days after emergence, spectral analysis was carried out on three leaf samples from each plot. A hyperspectral sensor was used to capture reflectance between the wavelengths from 450 to 824 nm. Representative spectral bands were selected and grouped into means. After harvest, grain yield was assessed and laboratory analyses of industrial traits were carried out. Spectral, industrial traits and yield data were subjected to statistical analysis. Data were analyzed by the following machine learning algorithms: J48 (J48) and REPTree (DT) decision trees, Random Forest (RF), Artificial Neural Networks (ANN), Support Vector Machine (SVM), and conventional Logistic Regression (LR) analysis. The clusters formed were used as the output of the models, while two groups of input data were used for the input of the models: the spectral variables (WL) noise-free obtained by the sensor (450-828 nm) and the spectral means of the selected bands (SB) (450.0-720.6 nm). Soybean genotypes were grouped according to their grain yield and industrial traits, in which the SVM and J48 algorithms performed better at classifying them. Using the spectral bands selected in the study improved the classification accuracy of the algorithms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The 2020 environmental catastrophe in Pantanal has highlighted the fragility of environmental policies and practices for managing and fighting fires in this biome. Therefore, it is essential to know the causes and circumstances that potentiate these fires. This study aimed to: (I) assess the relationship between fire foci and carbon absorption (GPP), precipitation, and carbon dioxide (CO 2 ) flux; (ii) analyze vegetation recovery using the differenced normalized burn ratio (ΔNBR) in Brazilian Pantanal between 2001 and 2022; and (iii) identify priority areas, where the highest intensities of fire foci have occurred, in order to guide public policies in Brazil to maintain local conservation. To this purpose, fire foci were detected using data from the MODIS MOD14/MYD14 algorithm, annual precipitation with CHIRPS (Climate Hazards Group InfraRed Precipitation with Station data), and CO 2 flux using the MODIS/MODO9A1 product, and Gross Primary Production (GPP) with the MODIS/MOD17A2 product. The severity of the burned area was also assessed using the ΔNBR index and the risk areas were determined using the averages of these images. During the time series studied, a total of 300,127 fire foci were detected throughout the Pantanal, where 2020 had the highest number of foci and the lowest accumulated precipitation. The years with the highest precipitation were 2014 and 2018. The year 2018 was also the second year with the highest GPP value. The Pettit test showed a trend for 2008 and 2011 as the points of change in the CO 2 flux and GPP variables. Principal component analysis clustered fire foci and precipitation on opposite sides, as well as GPP and CO 2 flux, while ΔNBR clustered HS, MHS and MLS classes with the years 2020, 2019, 2002 and 2021. There was a high negative correlation between fire foci × rainfall and GPP × CO 2 flux. The years with the largest areas of High severity (HS), Moderate-high severity (MHS) and Moderate-low severity (MLS) classes were 2020 and 2019, respectively. The most vulnerable areas for severe fires were the municipalities of Cáceres, Poconé, and Corumbá. The major fire catastrophe in 2020 is correlated with the low precipitation in 2019, the high precipitation in 2018, and the increased GPP, as well government policies unfavorable to the environment., (© 2023. The Author(s).)

Purpose: To describe two surgical techniques for rescuing a retained heavy silicone oil bubble in the posterior pole: 1) light pipe method and 2) perfluorocarbon liquid method., Methods: The surgical techniques are described in detail, along with an illustrative video for each., Results: A short 25-gauge metallic cannula and active suction pump are used for standard heavy silicone oil removal. Both surgical approaches are practical and effective options to complete the removal of heavy silicone oil when a bubble sinks to the posterior pole., Conclusion: Both the light pipe and perfluorocarbon methods are suitable to remove retained heavy silicone oil and thus avoid the need for further incisions and the risks associated with the use of larger gauge instrumentation.

Obtaining soybean genotypes that combine better nutrient uptake, higher oil and protein levels in the grains, and high grain yield is one of the major challenges for current breeding programs. To avoid the development of unpromising populations, selecting parents for crossbreeding is a crucial step in the breeding pipeline. Therefore, our objective was to estimate the combining ability of soybean cultivars based on the F 2 generation, aiming to identify superior segregating parents and populations for agronomic, nutritional and industrial traits. Field experiments were carried out in two locations in the 2020/2021 crop season. Leaf contents of the following nutrients were evaluated: phosphorus, potassium, calcium, magnesium, sulfur, copper, iron, manganese, and zinc. Agronomic traits assessed were days to maturity (DM) and grain yield (GY), while the industrial traits protein, oil, fiber and ash contents were also measured in the populations studied. There was a significant genotype × environment (G × A) interaction for all nutritional traits, except for P content, DM and all industrial traits. The parent G3 and the segregating populations P20 and P27 can be used aiming to obtain higher nutritional efficiency in new soybean cultivars. The segregating populations P11 and P26 show higher potential for selecting soybean genotypes that combine earliness and higher grain yield. The parent G5 and segregant population P6 are promising for selection seeking improvement of industrial traits in soybean., (© 2023. Springer Nature Limited.)

Some strategies can optimise the use of water in crops under deficit, either by increasing yield or by reducing actual crop evapotranspiration (ET), to promote the sustainable intensification of production systems. The objective was to evaluate how the spacing, planting orientation, nitrogen fertilisation and intercropping strategies impact the dynamics of water in the soil, ET partitioning, and water use indicators for forage cactus and cactus-sorghum intercropping. Four experiments were conducted between 2018 and 2020 in the Brazilian semi-arid region. In the first two sites (I and II), the cladodes of the intercropped forage cactus and sorghum were spaced at 0.10, 0.20, 0.30, 0.40 and 0.50 m with rows-oriented east-west and north-south. In site III, the intercropped rows were spaced at 1.00, 1.25, 1.50 and 1.75 m. Site IV, which contained the forage cactus crop exclusively, was treated with four nitrogen levels (50, 150, 300 and 450 kg N ha -1 ). The management interventions improved water use more by increasing dry matter than by reducing ET in the cropping system. Intercropping promoted the greatest increase in water productivity (130 %). Increasing N doses in the forage cactus-only crop reduced ET by up to 39 % but increased deep drainage losses by up to 365 %. The most promising management practices for optimising water resources were as follows: spacing of 0.10 m between cactus plants in the intercropping trial under east-west row orientation, as it promoted greater water use efficiency (76 %); spacing of 0.30 m in the north-south orientation; and row spacing of 1.50 m, as it improved water productivity (6.89 kg m -3 ). Thus, interventions in management should be adopted to optimise water use in intercropping systems with forage cactus, aiming at sustainable intensification in dry environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To quantify the rate of idiopathic macular hole progression from presentation and identify factors that may influence stratification and urgency for surgical listing based on the initial optical coherence tomography scans., Methods: The minimal linear diameter (MLD), base diameter (BD), and hole height on nasal and temporal sides of idiopathic macular hole were measured on spectral domain optical coherence tomographies, on initial presentation and just before surgery. Mean hole height, hole height asymmetry (absolute difference between nasal and temporal height), MLD/BD, and MLD change per day (MLD/day) were calculated for each patient. Multivariable linear regression analysis with MLD/day as the dependent variable was performed to identify significant risk factors for MLD progression. Minimal linear diameter was grouped to quintiles: 1: ≤290 µ m, 2: >290 µ m and ≤385 µ m, 3: >385 µ m and ≤490 µ m, 4: >490 µ m and ≤623 µ m, and 5: >623 µ m., Results: In 161 eyes (157 patients), we report significant associations with MLD/day: 1) MLD/BD ( P = 0.039) (i.e., wide BD relative to MLD lead to faster progression of MLD), 2) hole height asymmetry ( P = 0.006) (larger absolute difference between nasal and temporal hole height lead to faster progression), and 3) days between scans ( P < 0.001) (longer duration between scans had reduced MLD/day, indicating more rapid increase initially then plateaux), and relative to MLD Quintile 1, MLD Quintile 3 ( P = 0.002) and MLD Quintile 4 ( P = 0,008), and MLD Quintile 5 ( P < 0.001) all lead to a reduced MLD/day rate on multivariable regression., Conclusion: In addition to finding that the previously reported initial smaller MLD is a risk factor for rapid MLD progression, we report two novel findings, large hole height asymmetry and a low MLD/BD (wide base relative to MLD), that represent significant risk factors. These factors should be taken into consideration on presentation to stratify timing of surgery.

Medical thermography provides an overview of the human body with two-dimensional (2D) information that assists the identification of temperature changes, based on the analysis of surface distribution. However, this approach lacks spatial depth information, which can be enhanced by adding multiple images or three-dimensional (3D) systems. Therefore, the methodology applied for this paper generates a 3D point cloud (from thermal infrared images), a 3D geometry model (from CT images), and the segmented inner anatomical structures. Thus, the following computational processing was employed: Structure from Motion (SfM), image registration, and alignment (affine transformation) between the 3D models obtained to combine and unify them. This paper presents the 3D reconstruction and visualization of the respective geometry of the neck/bust and inner anatomical structures (thyroid, trachea, veins, and arteries). Additionally, it shows the whole 3D thermal geometry in different anatomical sections (i.e., coronal, sagittal, and axial), allowing it to be further examined by a medical team, improving pathological assessments. The generation of 3D thermal anatomy models allows for a combined visualization, i.e., functional and anatomical images of the neck region, achieving encouraging results. These 3D models bring correlation of the inner and outer regions, which could improve biomedical applications and future diagnosis with such a methodology., Competing Interests: The authors declare no conflicts of interest.

The regular practice of physical activity helps in the prevention and control of several non-communicable diseases. However, evidence on the role of physical activity in mitigating worsening clinical outcomes in people with COVID-19 is still unclear. The aim of this study was to verify whether different levels of physical activity provide protection for clinical outcomes caused by SARS-CoV-2 infection. A cross-sectional study was conducted with 509 adults (43.8 ± 15.71 years; 61.1% female) with a positive diagnosis of COVID-19 residing in Ribeirão Preto, São Paulo, Brazil. Participants were interviewed by telephone to determine the severity of the infection and the physical activity performed. Binary logistic regression was used to indicate the odds ratio (OR) of active people reporting less harmful clinical outcomes from COVID-19. Active people had a lower chance of hospitalization, fewer hospitalization days, less respiratory difficulty and needed less oxygen support. The results suggest that active people, compared to sedentary people, have a lower frequency of hospitalization, length of stay, breathing difficulty and need for oxygen support. These results corroborate the importance of public policies to promote the practice of physical activity, in order to mitigate the severity of the clinical outcomes of COVID-19.

Purpose: To compare outcomes of primary trabeculectomy using either mitomycin C (MMC) alone versus MMC augmented with intracamerular bevacizumab in patients with open-angle glaucoma., Methods: Retrospective, cohort, two-centre, comparative study. Patients' data were screened between October 2015 and March 2019, with inclusion requiring a minimum follow-up of 24 months. Primary outcome was intraocular pressure (IOP) lowering at 24 months, with surgical success defined with different maximum IOP targets (≤18, ≤16 and ≤14 mm Hg) and at least 30% reduction and higher than 5 mm Hg. Absolute success was achieved if no IOP-lowering medication was needed and a qualified success if otherwise. Safety outcomes were analysed., Results: A total of 110 eyes underwent trabeculectomy with MMC, 51 of these combined with intracamerular bevacizumab. Both strategies were effective in terms of IOP lowering (baseline vs 2 years postoperatively: 24.4 (8.0) mm Hg vs 12.1 (5.3) mm Hg in the MMC group; 25.1 (8.7) vs 10.8 (3.8) mm Hg in the MMC+bevacizumab group; p<0.001 in both comparisons). The MMC+bevacizumab group had a significant difference towards higher efficacy on absolute success rates at all targets (IOP≤14 or ≤16 or ≤18 mm Hg; p=0.010, p=0.039 and p=0.007, respectively). The large majority (93%) of the MMC+bevacizumab group was drop-free at 24 months, and 41% had IOP below 10 mm Hg. Complication rates were low and similar between groups, with no systemic adverse events., Conclusions: Intracamerular bevacizumab in MMC-augmented primary trabeculectomy increases the chances of obtaining low IOP outcomes. This strategy may be useful when planning for surgeries aiming at target pressures in the low teens., Trial Registration Number: ISRCTN93098069., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Medical overuse-defined as the provision of health services for which potential harms exceed potential benefits-constitutes a paradigm of low-value care and is seen as a threat to the quality of care. Value in healthcare implies a precise definition of disease. However, defining a disease may not be straightforward since clinical data do not show discrete boundaries, calling for some clinical judgment. And, if in time a redefinition of disease is needed, it is important to recognize that it can induce overdiagnosis, the identification of medical conditions that would, otherwise, never cause any significant symptoms or lead to clinical harm. A classic example is the impact of recommendations from professional societies in the late 1990s, lowering the threshold for abnormal total cholesterol from 240 mg/dl to 200 mg/dl. Due to these changes in risk factor definition, literally overnight there were 42 million new cases eligible for treatment in the United States. The same happened with hypertension-using either the 2019 NICE guidelines or the 2018 ESC/ECC guidelines criteria for arterial hypertension, the proportion of people overdiagnosed with hypertension was calculated to be between 14% and 33%. In this review, we will start by discussing resource overuse. We then present the basis for disease definition and its conceptual problems. Finally, we will discuss the impact of changing risk factor/disease definitions in the prevalence of disease and its consequences in overdiagnosis and overtreatment (a problem particularly relevant when definitions are widened to include earlier or milder disease)., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Precision agriculture techniques are widely used to optimize fertilizer and soil applications. Furthermore, these techniques could also be combined with new statistical tools to assist in phenotyping in breeding programs. In this study, the research hypothesis was that soybean cultivars show phenotypic differences concerning wavelength and vegetation index measurements., Results: In this research, we associate variables obtained via high-throughput phenotyping with the grain yield and cycle of soybean genotypes. The experiment was carried out during the 2018/2019 and 2019/2020 crop seasons, under a randomized block design with four replications. The evaluated soybean genotypes included 7067, 7110, 7739, 8372, Bonus, Desafio, Maracai, Foco, Pop, and Soyouro. The phenotypic traits evaluated were: first pod height (FPH), plant height (PH), number of branches (NB), stem diameter (SD), days to maturity (DM), and grain yield (YIE). The spectral variables evaluated were wavelengths and vegetation indices (NDVI, SAVI, GNDVI, NDRE, SCCCI, EVI, and MSAVI). The genotypes Maracai and Foco showed the highest grain yields throughout the crop seasons, in addition to belonging to the groups with the highest means for all VIs. YIE was positively correlated with the NDVI and certain wavelengths (735 and 790 nm), indicating that genotypes with higher values for these spectral variables are more productive. By path analyses, GNDVI and NDRE had the highest direct effects on the dependent variable DM, while NDVI had a higher direct effect on YIE., Conclusions: Our findings revealed that early and productive genotypes can be selected based on vegetation indices and wavelengths. Soybean genotypes with a high grain yield have higher means for NDVI and certain wavelengths (735 and 790 nm). Early genotypes have higher means for NDRE and GNDVI. These results reinforce the importance of high-throughput phenotyping as an essential tool in soybean breeding programs., (© 2022. The Author(s).)

Background and Objective: Current literature lacks good-quality evidence regarding the outcomes of early pars plana vitrectomy (PPV) for acute exogenous endophthalmitis. The aim for this study was to analyze and discuss the outcomes of PPV for endophthalmitis in a UK tertiary hospital., Patients and Methods: This study was a retrospective case series. The clinical records of consecutive patients who had PPV for acute exogenous endophthalmitis were reviewed. Demographic data, etiology, timing of onset, timing of PPV, intraand postoperative complications, baseline and final best-corrected visual acuity (BCVA), therapeutic regimens, and microbiology details were collected. Primary efficacy and safety outcome measures were BCVA improvement of two or more logMAR lines and intra- or postoperative complications, respectively., Results: Forty-one patients with a median age of 76 (interquartile range, 64 to 82) years were studied. The most common etiology was intravitreal injection (41%), followed by phacoemulsification (34%). Median interval to PPV was 1.0 (interquartile range, 1.0 to 3.0) days. In a multivariate model controlling for age, baseline BCVA, microbiology positivity, and etiology (post-intravitreal injection), PPV after 24 hours was seven times more likely to achieve significant BCVA improvement (odds ratio, 7.47; 95% confidence interval, 1.12 to 49.66; P = .038). PPV within 24 hours of presentation was associated with more intraoperative complications., Conclusions: Favorable outcomes may be achieved with current antibiotic regimens and PPV for endophthalmitis. The series suggests that an early surgical intervention may be associated with poorer functional outcomes. Tap and inject at presentation, followed by a semi-urgent PPV as required, seems to be a sensible approach. [ Ophthalmic Surg Lasers Imaging Retina. 2022;53:96-102.] .

Background: The purpose of this prospective study was to evaluate the efficacy and safety of the Ultrasound Cyclo Plasty (UCP) procedure using high-intensity focused ultrasound in surgery-naïve open-angle glaucoma patients., Methods: prospective, non-randomized, single-arm, multicenter clinical trial. Sixty-six eyes with primary open-angle glaucoma, intraocular pressure (IOP) ≥21 mmHg and with no history of filtering surgery were enrolled. Patients were treated by UCP with a therapy probe comprising six piezoelectric transducers, consecutively activated for 8 s each. Complete ophthalmic examination was performed before the procedure, 1 day after the procedure, and 1, 3, 6, 12, 18 and 24 months after the procedure. Primary outcomes were complete success (defined as IOP lowering from baseline ≥20% without additional glaucoma medications) and vision-threatening complications. Secondary outcomes were the presence of complications and the reduction of the number of medications used., Results: IOP was significantly reduced after one procedure ( p < 0.05), from a mean pre-operative value of 24.3 ± 2.9 mmHg (n = 2.3 hypotensive medications) to a mean value of 15.9 ± 3.6 mmHg (n = 2.2 hypotensive medications) at 2 years (mean IOP lowering of 33%). Surgical success was achieved in 74% of eyes. Notwithstanding side effects such as transient anterior chamber inflammation, refractive error changes, transient hypotony and macular edema, no major intra or post-operative complications such as phthisis, induced cataract, neovascularization or significant vision loss were observed., Conclusions: Ultrasound Cyclo Plasty is a valuable, effective and well-tolerated procedure to lower IOP in patients with open-angle glaucoma without previous filtering surgery.

Purpose: There are currently limited data addressing the surgical outcomes of pars plana vitrectomy (PPV) in toxoplasmosis-related macular hole (tMH). We aim to report and discuss safety and efficacy of PPV for tMH., Methods: Surgical case series (n = 11), with minimum postoperative follow-up time of 6 months. Consecutive patients who underwent PPV for tMH from 2013 to 2016 were included. Indications for surgery were: visual acuity ≥ 0.6 logarithm of the minimum angle of resolution (Snellen 20/80 or less), no intraocular inflammation for more than 6 months, extrafoveal toxoplasmosis scar, elevated tMH borders on optical coherence tomography, and patient agreement with surgery. Surgery was performed-PPV with epiretinal (if present) and internal limiting membrane peeling. Safety and efficacy of PPV for tMH were addressed by evaluating: 1) surgery-related complications and 2) visual acuity improvement., Results: A total of 11 patients (6 male), with a mean age of 33.2 ± 11.0 years were studied. Mean preoperative best-corrected visual acuity significantly improved from 1.10 ± 0.24 (Snellen 20/252) to 0.43 ± 0.18 logarithm of the minimum angle of resolution (Snellen 20/54) at last follow-up visit (P < 0.01). The rate of visual acuity improvement (i.e., a gain of at least three lines) and tMH closure was 100% for both. The only reported surgery-related complication was cataract in one case., Conclusion: Our results suggest that PPV is a safe and effective option in tMH cases. A controlled, longitudinal study would contribute to confirm these findings.

Purpose: Ultrasound cycloplasty (UCP) acts through the selective coagulation of the ciliary body using high-intensity focused ultrasound (HIFU) technology. The aim of this study was to investigate whether the application of ultrasound beams targeting the ciliary body using an external probe influences astigmatism., Methods: Multicentre, prospective, single-arm, open-label study in adult patients with primary open-angle glaucoma and moderately uncontrolled intraocular pressure (IOP) under glaucoma medication. The primary outcome was induced corneal astigmatism, calculated from topography, and assessed statistically through vector analysis. Secondary outcomes included induced total astigmatism and mean changes from baseline in best-corrected visual acuity (logMAR) and IOP. Subgroup analysis was performed to assess the impact of device centring on corneal and total induced astigmatism., Results: Fifty eyes were enrolled. Mean age was 69.6 ± 11.3 years. At 1, 3 and 6 months postprocedure, HIFU-induced corneal astigmatism was 0.88 D × 93°, 0.87 D × 106° and 1.16 D × 97°, respectively, while induced total astigmatism was 0.62 D × 103°, 0.42 × 106° and 0.39 × 107°. By the last follow-up, the percentage of patients with <0.50, <1.00, <1.50 and <2.00 D of induced corneal versus total astigmatism was 8.3% versus 46%, 29% versus 66%, 62.5% versus 88% and 79% versus 94%. Visual acuity was statistically significantly impaired at 1 month, but no difference remained by 3 and 6 months postprocedure., Conclusion: Ultrasound cycloplasty procedure is associated with increased corneal astigmatism. However, its impact on total refractive astigmatism is less pronounced., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Triple-negative breast cancer (TNBC) is a subtype of cancer, which tests negative for estrogen receptors, progesterone receptors, and lacks overexpression of the human epidermal growth factor 2 (C-erbB2, HER2/neu) gene. The expression of chemokines and their receptors, including CCR7, has been described in several types of cancer, contributing to tumor progression., Aim of the Study: This study investigated the association between the membrane and cytoplasmic CCR7 expression and the prognosis of TNBC., Materials and Methods: Surgical paraffin histopathology blocks and clinico-pathological data were assessed from 133 patients. Samples were analyzed by immunohistochemistry and immunofluorescence using the Tissue Microarray technique for scoring the intensity of CCR7 expression., Results: TNBC patients in which the CCR7 labeling was predominantly in the cytoplasm of tumor cells presented increased local tumor recurrence (P = 0.033). Conversely, there was no statistical difference in five-year overall survival between the patients with low (77%) versus high (80%) cytoplasmic CCR7 expression (P = 0.7104). Additionally, the risk of death between these groups was 1.19 (95% CI = 0.48-2.91)., Conclusion: The cytoplasmic CCR7 expression associates with an increased incidence of tumor relapse in TNBC, not affecting patients survival. Consequently, the cell compartment in which the CCR7 localizes could serve as a prognostic marker in this cancer subtype., (Copyright © 2020. Published by Elsevier GmbH.)

Purpose: The Baerveldt-XEN technique is intended to reduce the risk of early hypotony after Baerveldt implant, while keeping a good long-term intra-ocular pressure (IOP) control. The aim of this study is to discuss the surgical success rate of the Baerveldt-XEN and compare it with the commercially available flow-restrictor device (Ahmed glaucoma valve - AGV)., Methods: Single-centre, cohort study. Consecutive glaucoma patients with uncontrolled IOP > 21 mmHg on maximum tolerated medical therapy, and who had an aqueous shunt as the planned surgical procedure. Patients underwent implantation of Baerveldt-XEN. An age-, gender- and glaucoma aetiology-matched database of AGV patients was used for comparison. Complete surgical success was defined as a final IOP between 6 and 21 mmHg, and 20% reduction from baseline with no need for IOP-lowering medication. Qualified success was the same criteria but resorting to medications., Results: Twenty-four eyes from 24 subjects with glaucoma were included in this study, 12 patients underwent Baerveldt-XEN implantation and 12 AGV. Twelve months after the Baerveldt-XEN implant, the IOP reduced from 33 ± 9 mmHg to 14 ± 3 mmHg (p < 0.001). The qualified and complete success rate was 50% and 25%, respectively. With the AGV, the IOP reduced from 29 ± 7 mmHg to 16 ± 7 mmHg (p = 0.001). The matched AGV group compared to the Baerveldt-XEN, presented a higher complete success rate (58.3%) and a qualified success rate of 33.3% (p = 0.72). No sight-threatening complications were recorded in both groups., Conclusions: The Baerveldt-XEN disclosed a low complete success rate at 1 year of follow-up, although with no major safety concerns. While studies with a longer follow-up are needed to demonstrate the potential advantages and disadvantages of the Baerveldt-XEN, this technique may be less likely to achieve drop-free efficacy when compared to other flow-restrictor strategies., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To examine the influence of the inverted flap (IF) internal limiting membrane (ILM) technique in macular hole (MH) closure on outer retinal layers after MH surgery., Methods: Retrospective study. Postoperative position of ILM, recovery rate of external limiting membrane and ellipsoid zone, and best-corrected visual acuity were evaluated. The Inserted group, where the IF is placed inside the hole, was compared with the Cover group, where the IF completely covers the hole., Results: Sixty-two eyes of 58 patients who underwent vitrectomy and ILM peeling with the IF technique for large MHs (>400 µm) with successful MH closure and a follow-up of 12 months were evaluated. In the 24 eyes of the Inserted group, there was no regeneration of external limiting membrane or ellipsoid zone after 12 months. In the 38 eyes of Cover group, external limiting membrane recovered in 55.3% of patients 1 month after surgery, and in 86.1% after 12 months. The elipsoid zone layer was present in 58% of the patients., Conclusion: Poorer anatomical and visual results were associated with the IF technique where ILM insertion occurs compared with ILM placed over the hole. These findings suggest that insertion of the ILM in the hole might prevent outer retinal layers realignment and visual recovery in MH surgery.

Purpose: We hypothesize that patients with type 1 diabetes (T1D) may have abnormal retinal vascular responses before diabetic retinopathy (DR) is clinically evident. Optical coherence tomography angiography (OCTA) was used to dynamically assess the retinal microvasculature of diabetic patients with no clinically visible retinopathy., Methods: Controlled nonrandomized interventional study. The studied population included 48 eyes of 24 T1D patients and 24 demographically similar healthy volunteers. A commercial OCTA device (AngioVue) was used, and two tests were applied: (1) the hypoxia challenge test (HCT) and (2) the handgrip test to induce a vasodilatory or vasoconstrictive response, respectively. The HCT is a standardized test that creates a mild hypoxic environment equivalent to a flight cabin. The handgrip test (i.e., isometric exercise) induces a sympathetic autonomic response. Changes in the parafoveal superficial and deep capillary plexuses in both tests were compared in each group. Systemic cardiovascular responses were also comparatively evaluated., Results: In the control cohort, the vessel density of the median parafoveal superficial and deep plexuses increased during hypoxia (F1,23 = 15.69, P < 0.001 and F1,23 = 16.26, P < 0.001, respectively). In the T1D group, this physiological response was not observed in either the superficial or the deep retinal plexuses. Isometric exercise elicited a significant decrease in vessel density in both superficial and deep plexuses in the control group (F1,23 = 27.37, P < 0.0001 and F1,23 = 27.90, P < 0.0001, respectively). In the T1D group, this response was noted only in the deep plexus (F1,23 = 11.04, P < 0.01)., Conclusions: Our work suggests there is an early impairment of the physiological retinal vascular response in patients with T1D without clinical diabetic retinopathy.

Background and Objective: To compare complete internal limiting membrane (ILM) peeling with the inverted flap technique for macular hole (MH) surgery., Patients and Methods: An electronic database search on PubMed, CENTRAL, and ClinicalTrials.gov was performed. Inclusion criteria were comparative prospective/retrospective studies including patients with MH of any size with at least 6 months of follow-up. The primary outcome was MH closure rate. Secondary outcomes were best-corrected visual acuity improvement and surgery-related adverse events., Results: Sixteen papers enrolling 1,403 eyes were included (733 ILM peeling, 670 inverted flap). MH mean minimum diameter and time of symptomatic evolution were higher in the inverted flap group (531.1 μm ± 188.8 μm vs. 602.8 μm ± 223.8 μm; 10.4 ± 20.2 months vs. 12.0 ± 18.4 months; P < .01). Overall, MH closure rate was superior with the inverted flap technique (risk-ratio [RR]: 1.25; 95% confidence interval [CI], 1.14-1.38; P < .0001), as well as in all subgroups: idiopathic large MH (n = 362; RR: 1.12; 95% CI, 1.05-1.20; P < .001), myopic MH without retinal detachment (n = 133; RR: 1.35; 95% CI, 1.14-1.59; P < .001), and MH retinal detachment (n = 198; RR: 1.89; 95% CI, 1.31-2.73; P < .001)., Conclusion: This meta-analysis suggests the inverted flap technique is more effective in achieving MH closure. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:187-195.]., (Copyright 2020, SLACK Incorporated.)

Aim: Previous data suggest the existence of retinal vascular changes and impaired autoregulation in the very early stages of diabetic retinopathy (DR). We compared the retinal plexuses between patients with type 1 diabetes (T1D) without DR and a demographically similar healthy cohort, using optical coherence tomography angiography (OCT-A)., Methods: Patients with T1D and no signs of DR were prospectively recruited from an outpatient clinic. Using OCT-A (AngioVue ® ), the parafoveal superficial (SCP) and deep (DPC) capillary plexus as well as the foveal avascular zone (FAZ) and perimeter were gathered. Mean comparison tests and linear regression analysis were used as statistical tests (STATA v14)., Results: Studied population included 48 subjects (24 T1D). The analysis of SCP revealed an attenuation of the capillary network compared with the control group in both parafoveal (51.8 ± 4.5 vs. 55.8 ± 3.2, p < 0.001) and perifoveal (51.9 ± 3.3 vs. 53.9 ± 1.9, p = 0.01) regions. A similar finding was observed in the DCP for both parafoveal (56.4 ± 4.3 vs. 60.4 ± 2.2, p < 0.001) and perifoveal (54.7 ± 3.9 vs. 60.8 ± 3.4, p = 0.001) sectors. Also, a longer time since T1D diagnosis was associated with a larger FAZ area (p = 0.055) and perimeter (p = 0.03)., Conclusions: Significant differences in the retinal microvasculature were observed between healthy subjects and T1D patients using OCT-A, even before clinically detectable disease on fundus biomicroscopy.

Objective: Paraganglioma (PGL) and pheochromocytoma (PCC) are rare neuroendocrine tumors that were considered to be predominantly sporadic. However, with the identification of novel susceptibility genes over the last decade, it is currently estimated that up to 40% of cases can occur in the context of a hereditary syndrome. We aimed to characterize PGL/PCC families to exemplify the different scenarios in which hereditary syndromes can be suspected and to emphasize the importance for patients and their families of making an opportune genetic diagnosis., Materials and Methods: Retrospective analysis of patients diagnosed with PGL/PCC. Germline mutations were studied using next-generation sequencing panels including SDHA, SDHB, SDHC and SDHD. Clinical data were collected from clinical records, and all patients received genetic counseling., Results: We describe 4 families with PGL/PCC and germline mutations in SDH complex genes. 2 families have SDHB mutations and 2 SDHD mutations. The clinical presentation of the patients and their families was heterogeneous, with some being atypical according to the literature., Conclusions: PGL/PCC are more commonly associated with a germline mutation than any other cancer type, therefore, all individuals with these types of tumors should undergo genetic risk evaluation. NGS multigene panel testing is a cost-effective approach given the overlapping phenotypes. Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical and imaging surveillance and their families should undergo genetic counseling. For all these reasons, it is critical that all medical staff can suspect and diagnose these inherited cancer predisposition syndromes.

Introduction: Optical coherence tomography angiography (OCT-A) is a novel diagnostic tool with increasing applications in ophthalmology clinics that provides non-invasive high-resolution imaging of the retinal microvasculature. Our aim is to report in detail an experimental protocol for analyzing both vasodilatory and vasoconstriction retinal vascular responses with the available OCT-A technology., Methods: A commercial OCT-A device was used (AngioVue ® , Optovue, CA, United States), and all examinations were performed by an experienced technician using the standard protocol for macular examination. Two standardized tests were applied: (i) the hypoxia challenge test (HCT) and (ii) the handgrip test, in order to induce a vasodilatory and vasoconstriction response, respectively. OCT-A was performed at baseline conditions and during the stress test. Macular parafoveal vessel density of the superficial and deep plexuses was assessed from the en face angiograms. Statistical analysis was performed using STATA v14.1 and p < 0.05 was considered for statistical significance., Results: Twenty-four eyes of 24 healthy subjects (10 male) were studied. Mean age was 31.8 ± 8.2 years (range, 18-57 years). Mean parafoveal vessel density in the superficial plexus increased from 54.7 ± 2.6 in baseline conditions to 56.0 ± 2.0 in hypoxia ( p < 0.01). Mean parafoveal vessel density in the deep plexuses also increased, from 60.4 ± 2.2 at baseline to 61.5 ± 2.1 during hypoxia ( p < 0.01). The OCT-A during the handgrip test revealed a decrease in vessel density in both superficial (55.5 ± 2.6 to 53.7 ± 2.9, p < 0.001) and deep (60.2 ± 1.8 to 56.7 ± 2.8, p < 0.001) parafoveal plexuses., Discussion: In this work, we detail a simple, non-invasive, safe, and non-costly protocol to assess a central nervous system vascular response (i.e., the retinal circulation) using OCT-A technology. A vasodilatory response and a vasoconstriction response were observed in two physiologic conditions-mild hypoxia and isometric exercise, respectively. This protocol constitutes a new way of studying retinal vascular changes that may be applied in health and disease of multiple medical fields.

Background: We aimed to assess efficacy and safety of anti-tumor necrosis factor (TNF) drugs for adult chronic non-infectious uveitis (NIU). Methods: CENTRAL, MEDLINE, and EMBASE, were searched from inception to January 2019. Double-masked randomized placebo-controlled trials, assessing any anti-TNF vs. best medical intervention/standard of care in adults with chronic NIU were considered. The PRISMA and SAMPL guidelines were followed. The risk of bias was assessed using the Cochrane risk of bias tool. Overall quality of the evidence was assessed according to GRADE. PROSPERO registration: #CRD42016039068. The primary efficacy and safety outcomes were preservation of visual acuity (VA) and withdrawals due to adverse events, respectively. Meta-analysis of efficacy analysis was not performed due to significant clinical heterogeneity between studies' population and interventions. Results: A total of 1,157 references were considered and 3 studies were included. The overall risk of bias was moderate. In active NIU, adalimumab group showed an increased likelihood of VA preservation (risk ratio (RR) 1.75, 95%CI 1.32 to 2.32, n = 217), whereas the etanercept group did not (RR 0.81, 95%CI 0.57 to 1.14, n = 20). In inactive NIU, adalimumab was associated with increased likelihood of VA preservation (RR 1.31, 95%CI 1.12 to 1.53, n = 226). The rate of adverse events did not differ between anti-TNF and control arms (RR 1.03, 95%CI 0.94 to 1.13, n = 410). Conclusions: There is high quality evidence that adalimumab decreases the risk of worsening VA in active and inactive NIU and very low quality evidence that the risk of etanercept worsening VA in inactive NIU is not different from placebo. Moderate quality evidence suggests that anti-TNF agents are not different from placebo on the risk of study withdrawal.

There is limited published data currently available on scleral cysts in the posterior pole. Here, we detail the case of a patient who was suspected to have a peripapillary scleral cyst imprinting the optic nerve head (ONH) profile. The 52-year-old asymptomatic and otherwise healthy woman presented with unilateral ONH blurred margins of the left eye for 1 year. Her best-corrected visual acuity in the right and left eye was 20/20 and 20/25, respectively. Fundus observation of the right eye revealed no significant abnormalities; on the left eye a tilted disc with blurred margins in the superior quadrants and gliosis-associated changes in the lower quadrants were identified. Structural optical coherence tomography (OCT) showed a posterior hyporeflective cystic space at the level of the ONH, and OCT-angiography revealed flow void. The differential diagnosis of ONH edema was considered and the case discussed with the neuro-ophthalmology unit. Given the clinical history, the absence of symptoms and the multimodal imaging findings, a peripapillary scleral cyst was considered to be the most likely explanation for the edematous appearance and the anomalous tilted configuration of the ONH. This case suggests that although rare, even more so in the absence of an ONH coloboma, a postequatorial scleral cyst should be considered in the differential diagnosis of ONH lesions.

Background: BRCA1/2 pathogenic (P) and likely pathogenic (LP) germline variants are frequent among patients with ovarian carcinoma. However, these variants have not been extensively characterized in patients with ovarian cancer in Brazil., Methods: In this retrospective study we evaluated clinical characteristics and BRCA1/2 genetic test results from patients with ovarian carcinoma who underwent genetic counseling at A.C.Camargo Cancer Center (Brazil) between 2015 and 2017 and had performed germline genetic testing of BRCA1/2 genes., Results: Among 158 patients, 33 P and LP variants and were found (20.8%), 27 in BRCA1 and six in BRCA2, and six variants of unknown clinical significance (VUS). Thirteen percent of the patients did not have Multiplex Ligation-dependent Probe Amplification (MLPA) results. Three P variants in BRCA1 were found in more than one patient: c.5266dupC (p.Gln1756Profs*74), c.3331&#95;3334delCAAG (p.Gln1111Asnfs5*), and c.211A > G (p.Arg71Gly). One LP variant in BRCA1 had not been previously described, c.4153&#95;4154delCT (p.Leu1385Ilefs*5). Patients with previous diagnosis of breast cancer were carriers of P or LP variant in 8 of 12 cases (66.7%), and patients with a family history of ovarian or breast cancer in first- or second-degree relatives were carriers of P or LP variant in 26.7% of cases compared to 16.9% for patients without family history (p = 0.166)., Conclusion: Prevalence of BRCA1/2 germline P and LP variants is slightly higher than previously described by the largest occidental studies, with a high prevalence of variant c.5266dupC (p.Gln1756Profs*74) in BRCA1 observed. Moreover, we identified a new LP variant.