Search

Ricardo Machado Soares,&ast; Catarina Cunha Ferreira,&ast; Joana da Silva Fernandes, Carolina Madeira, Luís MA Silva, Eduardo Saraiva, Lígia Ribeiro, Sofia Fonseca Department of Ophthalmology - Centro Hospitalar Vila Nova de Gaia e Espinho, Porto, Portugal&ast;These authors contributed equally to this workCorrespondence: Ricardo Machado Soares, Department of Ophthalmology, Centro Hospitalar Vila Nova de Gaia e Espinho, EPE, Rua Conceição Fernandes, S/N, 4434-502, Vila Nova de Gaia, Porto, Portugal, Tel +351 915045174, Email ricardo.machado.soares@chvng.min-saude.ptPurpose: To report the long-term functional, anatomical and safety outcomes of 0.2 μg/day fluocinolone acetonide 0.19mg in patients with persistent or recurrent diabetic macular edema (DME).Methods: Retrospective, observational, single-center study of patients with recurrent or persistent DME. All patients received 0.2 μg/day of fluocinolone acetonide 0.19mg, and data were collected at baseline and months 1, 3, 6, 12, 24 and 36 after implantation. Outcomes measured included best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), and safety outcomes.Results: A total of 28 eyes from 28 patients were included. The mean age was 66.5 years (95% CI 62.8– 70.2) with a mean duration of DME of 8.8 years (95% CI 7.7– 10.0). Only two eyes were phakic. Mean follow-up was 25.4 months (95% CI 21.2– 29.6). Mean BCVA at baseline was 48.6 ETDRS letters (95% CI 41.3– 55.8) and improved as early as month 1 of follow-up with a mean gain in BCVA of 7.8 (95% CI 4.3– 11.3) ETDRS letters (p< 0.001). Statistically significant improvements in BCVA were also observed at months 6, 12 and 24. At baseline, patients had a mean CMT of 530.5μm (95% CI 463.0– 598.0), and a decrease in CMT was observed, starting at the first month of follow-up (mean CMT reduction of − 170.5μm, 95% CI − 223.8– − 117.1; p< 0.001). Statistically significant decreases in CMT were also observed at months 6, 12, 24, and 36, with the maximum decrease observed at month 12 (p< 0.001). Mean IOP at baseline was 16.4mmHg (95% CI 15.3– 17.5) and nine eyes (32.1%) had an IOP ≥ 21mmHg during follow-up.Conclusion: Our results support the effectiveness and safety profile of fluocinolone acetonide. Although additional long-term real-world evidence is required, fluocinolone acetonide may represent a safe strategy for daily, low-dose, sustained and localized release to the posterior segment of the eye, providing both functional and anatomical benefits in DME.Keywords: diabetic macular edema, intravitreal implant, best corrected visual acuity, intravitreal corticosteroid, sub-optimal response

Margarida Vale,1 Francisca Leite,2,3 Catarina Madeira1,2,4 1NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal; 2Associação CoLAB TRIALS, Évora, Portugal; 3Hospital da Luz Learning Health, Lisboa, Portugal; 4CHRC, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, PortugalCorrespondence: Catarina Madeira, CoLAB TRIALS, Largo do Senhor da Pobreza, Escola Superior de Enfermagem São João de, Deus, Évora, 7000-811, Portugal, Tel +351 91 4006726, Email catarina.madeira@colabtrials.ptPurpose: Over the last years, in response to the increasing complexity and demand of clinical trials, there has been a growing concern with the application of efficient risk management methodologies. The main objective of this work is to assess the current level of implementation of risk management activities by clinical trials sites’ teams and identify points of improvement.Methods: A cross-sectional study was conducted through an original, non-validated questionnaire created to assess the risk management practices at Portuguese clinical trial sites. The web-based survey was sent by e-mail to the clinical trial sites identified, and it was available for one month. Descriptive statistics were used to summarize the findings.Results: In total, 46 clinical trial sites accepted to participate in this study. The surveys’ answers showed that although 57.0% of sites reported the use of a systematic risk management tool, only nine sites (19.6%) described a standard tool or document that captured systematically the analysis of risks at the site level. Most of the sites (87.0%) showed willing to use a risk management tool specifically tailored for their operational needs, with the lack of knowledge about risk management being the main reason against its implementation.Conclusion: This work indicates that the surveyed clinical trial sites generally recognize the importance of risk management methodologies as an opportunity to anticipate difficulties in the trial conduct and optimize the use of sites’ resources. However, mainly due to lack of experience with risk management methodologies, sites are not currently implementing these strategies in the management of their trial-related operations. The development of a risk management tool for sites can be useful in this context.Keywords: clinical research, operational risks, planning, trial feasibility, healthcare, risk assessment tool

Ana Filipa Moleiro,1,2 Gonçalo Godinho,3 Carolina Madeira,4 Ana Faria Pereira,1 Elisete Brandão,1 Fernando Falcão-Reis,1,2 João Nuno Beato,1,2 Susana Penas1,2 1Department of Ophthalmology, Centro Hospitalar e Universitário de São João, Porto, Portugal; 2Department of Surgery and Physiology, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 3Department of Ophthalmology, Centro Hospitalar de Leiria, Leiria, Portugal; 4Department of Ophthalmology, Centro Hospitalar Gaia-Espinho, Gaia, PortugalCorrespondence: Ana Filipa Moleiro, Department of Ophthalmology, Centro Hospitalar e Universitário de São João, Alameda Hernani Monteiro, Porto, 4200-426, Portugal, Tel +351 915689259, Email anafomoleiro@gmail.comPurpose: This work aimed to longitudinally assess the peripapillary (PPCT) and subfoveal (SFCT) choroidal thickness (CT), in patients diagnosed with central (CRVO) or branch retinal vein occlusions (BRVO), correlating SFCT with central macular thickness (CMT) and PPCT with peripapillary retinal nerve fiber layer thickness (pRNFL).Patients and Methods: This was a retrospective longitudinal study of 71 eyes from 71 patients with treatment-naïve retinal vein occlusion (24 CRVO and 40 BRVO). Spectral-domain optical coherence tomography (SD-OCT, Spectralis HRA-OCT, Heidelberg) was used to measure PPCT, SFCT, pRNFL and CMT of the affected and fellow eyes at baseline (acute phase) and at 3 and 9 months post anti-VEGF treatment. IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. A p-value ≤ 0.05 was considered statistically significant.Results: Affected eyes presented a thicker baseline PPCT and SFCT compared to their fellow eyes both in CRVO and BRVO (p < 0.05). Both groups presented a significant decrease of PPCT in the affected eyes at 3 months compared to baseline (p < 0.05). At 9 months, compared to 3 months, PPCT remained stable (p > 0.05). Similarly, affected eyes’ SFCT significantly decreased at 3 months (p < 0.05) in both groups. At 9 months, compared to 3 months, SFCT decreased in the CRVO patients (p = 0.047) but remained stable in the BRVO patients (p = 0.850). No correIations between SFCT and CMT were seen at any timepoint in both groups (p > 0.05). PPCT correlates with pRNFL in CRVO at 3 months, although no other correlations were found during the follow-up. In BRVO, PPCT did not show any significant correlation with pRNFL.Conclusion: Both in CRVO and BRVO eyes, PPCT and SFCT at diagnosis are significantly thicker compared to the fellow eye, suggesting a possible increase in CT immediately after the occlusion, which is followed by a decrease at an early follow-up stage.Keywords: biomarkers, vascular retinal diseases, retinal vein occlusions, choroidal thickness, optical coherence tomography

Mário Lima-Fontes,1 Gonçalo Godinho,2 Ana Maria Cunha,1 Carolina Madeira,3 Manuel Falcão,1,4 Fernando Falcão-Reis,1,4 Ângela Carneiro1,4 1Department of Ophthalmology, Centro Hospitalar Universitário São João, Porto, Portugal; 2Department of Ophthalmology, Centro Hospitalar de Leiria, Leiria, Portugal; 3Department of Ophthalmology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal; 4Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, PortugalCorrespondence: Mário Lima-Fontes, Department of Ophthalmology, Centro Hospitalar Universitário São João, Alameda Professor Hernâni Monteiro, Porto, 4200-319, Portugal, Tel +351 918420563, Fax +351 225513669, Email marioruifontes@gmail.comPurpose: To describe a case of hypotony maculopathy following anti-VEGF intravitreal injection (IVI) in a patient with pseudoxanthoma elasticum (PE).Methods: Clinical case report.Results: A 52-year-old male complained of right eye (OD) vision loss 2 days after an uncomplicated anti-VEGF IVI for the treatment of choroidal neovascularization secondary to angioid streaks. Relevant medical history included PE, pathologic myopia, and a previous pars plana vitrectomy (PPV) due to a retinal detachment. OD best-corrected visual acuity (BCVA) dropped from 6/12 to 6/18 after the IVI. Intraocular pressure (IOP) was 3 mmHg and chorioretinal folds were evident in the posterior pole. Topical dexamethasone and atropine were prescribed, and full recovery was noticed after 3 days. Four months later, the patient developed a new episode of vision loss after another IVI. His BCVA was counting fingers, IOP was 2mmHg, and more noticeable chorioretinal folds were found. This time, an open scleral wound at the injection site was evident and a scleral suture was necessary. Once again, the patient recovered well.Conclusion: Hypotony maculopathy following intravitreal injection is a rare condition. However, the described patient presented several conditions which could be related with poor scleral wound closure: intrinsic scleral fragility due to myopia and pseudoxanthoma elasticum; repeated IVI procedures; and absence of vitreous in the posterior segment due to prior vitrectomy. Despite the good outcome, hypotony maculopathy may be a sight-threatening condition, and special attention is necessary for specific patients with risk factors.Keywords: hypotony maculopathy, intravitreal injection, anti-VEGF, pseudoxanthoma elasticum, angioid streaks

Ana Filipa Moleiro,1,2 Gonçalo Godinho,3 Carolina Madeira,4 Ana Faria Pereira,1 Elisete Brandão,1 Fernando Falcão-Reis,1,2 João Nuno Beato,1,2 Susana Penas1,2 1Department of Ophthalmology, Centro Hospitalar e Universitário de São João, Porto, Portugal; 2Department of Surgery and Physiology, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 3Department of Ophthalmology, Centro Hospitalar de Leiria, Leiria, Portugal; 4Department of Ophthalmology, Centro Hospitalar Gaia-Espinho, Gaia, PortugalCorrespondence: Ana Filipa Moleiro, Department of Ophthalmology, Centro Hospitalar e Universitário de São João, Alameda Hernani Monteiro, Porto, 4200-426, Portugal, Tel +351 915689259, Email anafomoleiro@gmail.com

Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search of effective methods of diagnosis. Altered levels of the NMDA receptor co-agonist, d-serine, have been associated with neurological disorders, including schizophrenia and epilepsy. However, whether d-serine levels are deregulated in AD remains elusive. Here, we first measured D-serine levels in post-mortem hippocampal and cortical samples from nondemented subjects (n=8) and AD patients (n=14). We next determined d-serine levels in experimental models of AD, including wild-type rats and mice that received intracerebroventricular injections of amyloid-β oligomers, and APP/PS1 transgenic mice. Finally, we assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a diagnosis of probable AD, as compared with patients with normal pressure hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and results were contrasted with CSF amyloid-β/tau AD biomarkers. d-serine levels were higher in the hippocampus and parietal cortex of AD patients than in control subjects. Levels of both d-serine and serine racemase, the enzyme responsible for d-serine production, were elevated in experimental models of AD. Significantly, d-serine levels were higher in the CSF of probable AD patients than in non-cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau index remarkably increased the sensitivity and specificity of diagnosis of probable AD in our cohort. Our results show that increased brain and CSF d-serine levels are associated with AD. CSF d-serine levels discriminated between nondemented and AD patients in our cohort and might constitute a novel candidate biomarker for early AD diagnosis.

Carolina Madeira,1 Ana Vasques,2 João Beato,1 Gonçalo Godinho,1 Luís Torrão,1 Manuel Falcão,1,3 Fernando Falcão-Reis,1,3 João Pinheiro-Costa1,4 1Department of Ophthalmology, Centro Hospitalar de São João, Porto, Portugal; 2Faculty of Medicine, University of Porto, Porto, Portugal; 3Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal; 4Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal Purpose: To systematically compare the efficacy of transepithelial accelerated corneal collagen crosslinking (TE-ACXL) with conventional corneal collagen crosslinking (C-CXL) in patients with progressive keratoconus. Methods: Eyes of patients with progressive keratoconus who were treated with C-CXL (3 mW/cm2 for 30 minutes) were compared with those who underwent TE-ACXL (6 mW/cm2 for 15 minutes). Best-corrected visual acuity (BCVA), keratometry values, corneal thickness, and topometric indexes were compared before CXL, and at 2 months, 6 months, and 12 months postoperatively. Results: The study enrolled 26 eyes of which 16 had TE-ACXL and 10 had C-CXL. Both groups were comparable at baseline and 12 months in terms of BCVA (P=0.16 and P=0.57), Kmax (maximum keratometry) (P=0.31 and P=0.73), pachymetry (P=0.75 and P=0.37), index of surface variance (ISV) (P=0.45 and P=0.86), index of vertical asymmetry (IVA) (P=0.26 and P=0.61), and index of height decentration (IHD) (P=0.27 and P=0.86, respectively). We did not observe significant differences between preoperative and 12-month postoperative readings in within-group analysis: ΔKmax (TE-ACXL, -2.13±5.41, P=0.25 vs C-CXL, 0.78±1.65, P=0.17), Δpachymetry (TE-ACXL, 4.10±14.83, P=0.41 vs C-CXL, -8.90±22.09, P=0.24), ΔISV (TE-ACXL, -8.50±21.26, P=0.24 vs C-CXL, 3.80±12.43, P=0.36), ΔIVA (TE-ACXL, -0.12±0.31, P=0.26 vs C-CXL, 0.03±0.18, P=0.61), and ΔIHD (TE-ACXL, -0.03±0.07, P=0.18 vs C-CXL, -0.01±0.03, P=0.88). Conclusion: Both TE-ACXL and C-CXL were similarly effective. Further follow-up is required to determine whether these techniques are comparable in the long-term. Keywords: cornea, keratoconus, crosslinking, transepithelial, riboflavin, ultraviolet radiation, keratometry

Background: The long-term effect of recombinant human erythropoietin (rhEPO) on the blood-lipid profile has not been well documented. The aim of this study was to evaluate whether rhEPO therapy affects the lipid pattern. [ABSTRACT FROM PUBLISHER]

The recent pandemic ushered in a marked surge in the adoption of digital health technologies (DHTs), necessitating remote approaches aiming to safeguard both patient and healthcare provider well-being. These technologies encompass an array of terms, including e-health, m-health, telemedicine, wearables, sensors, smartphone apps, digital therapeutics, virtual and augmented reality, and artificial intelligence (AI). Notably, some DHTs employed in critical healthcare decisions may transition into the realm of medical devices, subjecting them to more stringent regulatory scrutiny. Consequently, it is imperative to understand the validation processes of these technologies within clinical studies. Our study summarizes an extensive examination of clinical trials focusing on cardiovascular (CV) diseases and digital health (DH) interventions, with particular attention to those incorporating elements of AI. A dataset comprising 107 eligible trials, registered on clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) databases until 19 June 2023, forms the basis of our investigation. We focused on clinical trials employing DHTs in the European context, revealing a diverse landscape of interventions. Devices constitute the predominant category (45.8%), followed by behavioral interventions (17.8%). Within the CV domain, trials predominantly span pivotal or confirmatory phases, with a notable presence of smaller feasibility and exploratory studies. Notably, a majority of trials exhibit randomized, parallel assignment designs. When analyzing the multifaceted landscape of trial outcomes, we identified various categories such as physiological and functional measures, diagnostic accuracy, CV events and mortality, patient outcomes, quality of life, treatment adherence and effectiveness, quality of hospital processes, and usability/feasibility measures. Furthermore, we delve into a subset of 15 studies employing AI and machine learning, describing various study design features, intended purposes and the validation strategies employed. In summary, we aimed to elucidate the diverse applications, study design features, and objectives of the evolving CV-related DHT clinical trials field., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

For the first time, the pharmacokinetic (PK) profile of tryptophanol-derived isoindolinones, previously reported as p53 activators, was investigated. From the metabolites' identification, performed by liquid chromatography coupled to high resolution tandem mass spectrometry (LC-HRMS/MS), followed by their preparation and structural elucidation, it was possible to identify that the indole C2 and C3 are the main target of the cytochrome P450 (CYP)-promoted oxidative metabolism in the tryptophanol-derived isoindolinone scaffold. Based on these findings, to search for novel p53 activators a series of 16 enantiopure tryptophanol-derived isoindolinones substituted with a bromine in indole C2 was prepared, in yields of 62-89%, and their antiproliferative activity evaluated in human colon adenocarcinoma HCT116 cell lines with and without p53. Structural optimization led to the identification of two ( S )-tryptophanol-derived isoindolinones 3.9-fold and 1.9-fold more active than hit SLMP53-1, respectively. Compounds' metabolic stability evaluation revealed that this substitution led to a metabolic switch, with the impact of Phase I oxidative metabolism being minimized. Through differential scanning fluorimetry (DSF) experiments, the most active compound of the series in cell assays led to an increase in the protein melting temperature ( T ) of 10.39 °C, suggesting an effective binding to wild-type p53 core domain.m ) of 10.39 °C, suggesting an effective binding to wild-type p53 core domain.

Background: Single mutations in COL4A3/COL4A4 genes have been described in patients with autosomal dominant Alport syndrome and thin basement membrane nephropathy, without a shared definition of these patients within the medical community. We aimed to better categorize this clinical entity by examining clinical manifestations, family history, pathological features and genetics., Methods: We retrospectively analyzed patients with causative heterozygous COL4A3/COL4A4 mutations referred to us between 1990 and 2019. Index cases were defined as children who were the first to be diagnosed in their families., Results: The study included 24 index cases and 29 affected relatives, belonging to 25 families with a heterozygous mutation in the COL4A3/COL4A4 genes. During the follow-up, nine patients developed proteinuria [median age 15.7 years (range 5.6-33)], six at clinical diagnosis and four with progression toward chronic kidney disease (CKD) (three required kidney replacement therapy at 25, 45 and 53 years and one had CKD Stage 2 at 46 years). Extrarenal involvement was observed in 24.5% of patients. Hematuria was transmitted in consecutive generations, while CKD was reported in nonconsecutive generations of 11 families [median age 53 years (range 16-80)]. Seventeen patients (32%) underwent kidney biopsy: findings were consistent with Alport syndrome in 12 cases and with thin basement membrane nephropathy in 5 cases., Conclusions: Despite the benign course for these patients described in the literature, a significant percentage is at risk for disease progression. Consequently, we suggest that the assessment of these patients must take into account family history, genetic analysis and pathologic findings. After comparison with the literature, our data suggest that a different definition for Alport syndrome must be considered., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: The order and orientation of genes encoded by animal mitogenomes are typically conserved, although there is increasing evidence of multiple rearrangements among mollusks. The mitogenome from a Brazilian brown mussel (hereafter named B1) classified as Perna perna Linnaeus, 1758 and assembled from Illumina short-length reads revealed an unusual gene order very different from other congeneric species. Previous mitogenomic analyses based on the Brazilian specimen and other Mytilidae suggested the polyphyly of the genus Perna ., Methods: To confirm the proposed gene rearrangements, we sequenced a second Brazilian P. perna specimen using the "primer-walking" method and performed the assembly using as reference Perna canaliculus . This time-consuming sequencing method is highly effective when assessing gene order because it relies on sequentially-determined, overlapping fragments. We also sequenced the mitogenomes of eastern and southwestern South African P. perna lineages to analyze the existence of putative intraspecific gene order changes as the two lineages show overlapping distributions but do not exhibit a sister relationship., Results: The three P. perna mitogenomes sequenced in this study exhibit the same gene order as the reference. CREx, a software that heuristically determines rearrangement scenarios, identified numerous gene order changes between B1 and our P. perna mitogenomes, rejecting the previously proposed gene order for the species. Our results validate the monophyly of the genus Perna and indicate a misidentification of B1., Competing Interests: Rita Castilho is an Academic Editor for PeerJ., (© 2022 Cunha et al.)

This article provides five panel datasets for the projections of the mean replacement ratios of pension income relative to the worker's income. The time dimension is from year 2022 until 2055. The panel groups consider the gender, income and education of the workers. Furthermore, the variables consider different scenarios for the social security system: (1) a baseline with the current policies, (2) an increase of retirement age to 67 years, (3) an increase of the retirement age to 67 years and a 6% increase of the contribution rate, with a rate of 0-3% going to solidarity funds., Competing Interests: The author declares that he has no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article. I received no funding from any institution besides my employer which is the Central Bank of Chile. Furthermore, there are no patents or impediments to publication, including the timing of publication, with respect to the intellectual property of the article or the associated dataset., (© 2022 The Author(s). Published by Elsevier Inc.)

The present study about falls among the older adult population essentially explores bio-physiological factors. In light of the complexity of the factors that cause these accidents, it is important to identify the safety and self-care practices of institutionalized older adults and their relationship with falls in order to introduce prevention measures and personalized cognitive-behavioral strategies. The objective of this study was to: (a) determine the frequency of falls and their recurrence among institutionalized older adults, and (b) to associate the occurrence of falls among institutionalized adults with or without cognitive impairment to communication and safety practices. This was a quantitative, correlational, and longitudinal study with 204 institutionalized older adults living in two long-term care facilities in Portugal. The Scale of Practices and Behaviors for Institutionalized Elderly to Prevent Falls was administered to the sample. The prevalence of falls at a 12-month follow-up was 41.6%, of which 38.3% were recurring episodes. Older adults with cognitive decline showed lower mean scores for safety practices. Further research with larger samples should explore the relationships between communication and safety practices and falls, their recurrence, and fear of new falls.

This article provides a pooled cross-sectional sample of Chilean households from 4 survey waves (1997, 2007, 2012, 2017). The data has information on the demographics of the household, labor participation and occupation, savings rates, plus wealth of different sources. The data is available in both Excel and Stata formats. It is an important data for the study of savings, wages, pensions and wealth inequality., Competing Interests: The author declares that he has no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article. I received no funding from any institution besides my employer which is the Central Bank of Chile. Furthermore, there are no patents or impediments to publication, including the timing of publication, with respect to the intellectual property of the article or the associated dataset., (© 2022 The Author(s).)

Using region-industry panel data for Chile over the period 1985 to 2017, we find no effect of precipitation changes on GDP and a negative impact of higher summer temperatures on Agriculture-Silviculture and Fishing. An increase of one Celsius degree in the month of January implies a 3% and 12% GDP reduction in Agriculture and Fishing, respectively. There is also a negative effect of higher temperatures in January on Construction and Electricity, Gas, and Water. Our analysis suggests that climate change did not have a big impact on the Chilean economy during this period. Stress test exercises that select only the negative and statistically significant coefficients imply that the Chilean GDP would fall between -14.8% and -9% in 2050 and between -29.6% and -16.8% in 2100, according to our model., Competing Interests: The authors have declared that no competing interests exist.

Background: Inhibition of human topoisomerase I (TOP1) by camptothecin and topotecan has been shown to reduce excessive transcription of PAMP (Pathogen-Associated Molecular Pattern)-induced genes in prior studies, preventing death from sepsis in animal models of bacterial and SARS-CoV-2 infections. The TOP1 catalytic activity likely resolves the topological constraints on DNA that encodes these genes to facilitate the transcription induction that leads to excess inflammation. The increased accumulation of TOP1-DNA covalent complex (TOP1cc) following DNA cleavage is the basis for the anticancer efficacy of the TOP1 poisons developed for anticancer treatment. The potential cytotoxicity and mutagenicity of TOP1 targeting cancer drugs pose serious concerns for employing them as therapies in sepsis prevention., Methods: In this study we set up a novel yeast-based screening system that employs yeast strains expressing wild-type or a dominant lethal mutant recombinant human TOP1. The effect of test compounds on growth is monitored with and without overexpression of the recombinant human TOP1., Results: This yeast-based screening system can identify human TOP1 poisons for anticancer efficacy as well as TOP1 suppressors that can inhibit TOP1 DNA binding or cleavage activity in steps prior to the formation of the TOP1cc., Conclusions: This yeast-based screening system can distinguish between TOP1 suppressors and TOP1 poisons. The assay can also identify compounds that are likely to be cytotoxic based on their effect on yeast cell growth that is independent of recombinant human TOP1 overexpression., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Ocean warming has been a major driver of coral reef bleaching and mass mortality. Coupled to other biotic pressures, corals' ability for acclimatization and adaptation may become compromised. Here, we tested the combined effects of warming scenarios (26, 30, and 32°C) and predation (wound vs. no wound) in coral health condition (paleness, bleaching, and mortality), cellular stress responses (heat shock protein 70 kDa Hsp70, total ubiquitin Ub, and total antioxidant capacity TAC), and physiological state (integrated biomarker response index, IBR) of seven Scleractinian coral species, after being exposed for 60 days. Results show that although temperature was the main factor driving coral health condition, thermotolerant species ( Galaxea fascicularis , Psammocora contigua , and Turbinaria reniformis ) displayed increased paleness, bleaching, and mortality in predation treatments at high temperature, whereas thermosensitive species ( Acropora tenuis , Echinopora lamellosa , and Montipora capricornis brown and green morphotypes) all died at 32°C, regardless of predation condition. At the molecular level, results show that there were significant main and interactive effects of species, temperature, and predation in the biomarkers assessed. Temperature affected Hsp70, Ub, and TAC, evidencing the role of protein folding and turnover, as well as reactive oxygen species scavenging in heat stress management. Predation increased Hsp70 and Ub, suggesting the activation of the pro-phenoloxidase system and cytokine activity, whereas the combination of both stressors mainly affected TAC during moderate stress and Ub under severe stress, suggesting that redox balance and defense of homeostasis are crucial in tissue repair at high temperature. IBR levels showed an increasing trend at 32°C in predated coral fragments (although non-significant). We conclude that coral responses to the combination of high temperature and predation pressure display high inter-species variability, but these stressors may pose a higher risk of endosymbiont loss, depending on species physiology and stress intensity., 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., (Copyright © 2022 Madeira, Dias, Ferreira, Gouveia, Cabral, Diniz and Vinagre.)

Background: Neurofibromatosis Type 1 (NF-1) is a genetic disease affecting the eye, and ocular findings such as Lisch nodules (LN) or optic pathway gliomas (OPGs) are a part of its diagnostic criteria. Recent imaging technologies such as infrared (IR) imaging and optical coherence tomography (OCT) have highlighted the visualization of choroidal focal abnormalities in these patients, even in the absence of other ocular lesions. This study aimed to establish a morphological multimodal evaluation of choroidal findings in patients with NF-1, correlating them with central nervous system (CNS) findings., Methods: This retrospective study included 44 eyes from 22 patients with NF-1. Central 30° IR imaging was obtained, and the number and total area of detectable lesions were calculated. Both macular and optic disc scanning with OCT were performed, with and without the enhanced depth imaging technique, to assess the presence of choroidal focal hyperreflective lesions. Central macular thickness, ganglion cell layer, and outer nuclear layer thickness were assessed, as well as subfoveal choroidal thickness. The peripapillary retinal nerve fiber layer (RNFL) thickness was also assessed. Patients' magnetic resonance images (MRI) were reviewed and categorized by a neuroradiology specialist, determining the presence of OPGs and CNS hamartomas. Correlations between the ophthalmological and neuroradiological findings were established., Results: Patients' mean age was 16.4 ± 7.3 years and 59.1% were women. On the MRI, 86.4% of the patients had CNS hamartomas, and 34.1% of the eyes had OPGs. LN were described in 29.5% of the eyes, whereas a total of 63.4% of the eyes presented the characteristic hyperreflective lesions in IR imaging, all of them matching the underlying choroidal lesions. A mean of 2.9 ± 3.3 lesions per eye and a median total lesion area of 1.52 mm2 were found. The presence of OPGs was correlated with a greater number (P = 0.004) and a larger area (P = 0.006) of IR lesions. For a cut-off of 3.5 lesions per eye, the sensitivity and specificity for the presence of OPGs were 75% and 80%, respectively. For a total lesion area of 2.77 mm2, the sensitivity and specificity for the presence of OPGs were 69.2% and 93.1%, respectively. Eyes with OPGs presented a significant reduction in the temporal RNFL (P = 0.018) thickness, as well as a reduction in subfoveal choroid thickness (P = 0.04). No relations were found between CNS hamartomas and ophthalmological findings., Conclusions: This study suggests that focal choroidal abnormalities are correlated with the presence of CNS lesions as OPGs in patients with NF-1, and it might be a surrogate for the need for CNS imaging in these patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

This work studies the impact of the Social Explosion and COVID-19 crisis on the household sector in Chile. The Social Explosion in October 2019 represented a mass protest, much larger than similar events in other nations such as the yellow jackets. Using delinquency models calibrated with survey data, I show that household debt risk increased substantially after the Social Explosion across all income backgrounds but fell slightly with the COVID-19 pandemic due to the public policies implemented. The expansion of the public support policies in August 2020 decreased the debt risk to levels similar to before the two crises., (© 2022 The Author. Canadian Journal of Economics/Revue canadienne d'économique published by Wiley Periodicals LLC on behalf of Canadian Economics Association.)

Purpose: "In-the-bag" placement of an IOL is the Holy Grail for any cataract surgeon. However, in the absence of capsular integrity, alternative surgical options to place the IOL must be sought. We aim to report the clinical outcomes and safety profile of scleral-fixated Akreos AO60 intraocular lens implantation using Gore-Tex suture, combined with pars plana vitrectomy., Methods: This is a single-center, retrospective case series descriptive study. Electronic clinical records of all patients subjected to scleral fixation of a Bausch and Lomb Akreos AO60 IOL combined with pars plana vitrectomy, between April 1, 2017, and August 1, 2021, were reviewed. Data concerning age, sex, laterality, past ophthalmological history, pre- and postoperative best-available visual acuity, surgical indication, and intra- and postoperative complications were collected. Measured outcomes were the differences in best-available visual acuity and frequency of postoperative complications., Results: A total of 37 eyes (20 right eyes and 17 left eyes) from 36 patients (16 females and 20 males) were included in the statistical analysis. The mean age at time of surgery was 72.0 ± 12.4 years. The mean follow-up period was 548.9 days (range 39-1564 days). Globally, the mean best-available logMAR visual acuity improved from 1.61 preoperatively (0.025 decimal equivalent) to 0.57 postoperatively (0.3 decimal equivalent), this difference being statistically significant ( P < 0.001). Indications for surgery included aphakia due to complicated cataract surgery (24.3%; n  = 9); subluxated IOL due to closed trauma (21.6%; n  = 8); PEX-related subluxated IOL (16.2%; n  = 6); non-traumatic, non-PEX-related subluxated IOL (18.9%; n  = 7); subluxated crystalline lens due to closed trauma (8.1%; n  = 3); aphakia due to open-globe injury (5.4%; n  = 2); silicone-induced IOL opacification (2.7%; n  = 1); and aphakia post-endophthalmitis (2.7%; n  = 1). Postoperative complications included transient ocular hypertension (27.0%; n  = 10), transient corneal edema (18.9%; n  = 7), cystoid macular edema (18.9%, n  = 7), self-limited hypotension (5.4%, n  = 2), self-limited vitreous hemorrhage (2.7%, n  = 1), central retinal vein occlusion (2.7%, n  = 1), late retinal detachment (2.7%, n  = 1), and Akreos IOL opacification (2.7%, n  = 1). No suture-related complications were observed., Conclusion: There was a statistically significant improvement in visual acuity after scleral fixation of Akreos AO60 intraocular lens using Gore-Tex suture, with no suture-related problems recorded. This procedure seems to be a valuable alternative for posterior chamber IOL placement when secondary IOL implantation is required., Competing Interests: The authors declare that they have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 Mariana Leuzinger-Dias et al.)

Purpose: The aim of this study was to evaluate whether the coronavirus disease 19 (COVID-19) pandemic resulted in undertreatment and subsequent loss of visual acuity (VA) in patients with macular neovascularization (MNV) or retinal vein occlusion (RVO) regularly treated with intravitreal antivascular endothelial growth factor injections., Methods: Single-center, retrospective study of patients scheduled for treatment between March 19 and June 1, 2020, the national mandatory quarantine period. Patients' demographics, VA, and scheduled treatment during this period were reviewed via medical records. All patients were analyzed regarding treatment attendance rates. The visual impact of COVID-19 was assessed in patients who had been treated and presented a stable VA for >6 months before the beginning of the quarantine., Results: This study included 927 eyes from 769 patients. The attendance rate increased throughout the study timeframe ( p < 0.001) and correlated negatively with higher patient's age ( r = -0.142; p = 0.005). Patients with age-related macular degeneration (67.6%) had lower attendance rates ( p = 0.007) and were older ( p < 0.001). The visual impact analysis included 400 eyes from 325 patients. The average VA variation throughout this period was -1.7 ± 8.4 ETDRS letters and was similar in different retinal pathologies ( p = 0.334). VA variation did not correlate with the number of missed treatments per patient ( r = 0.100; p = 0.150). The prevalence of subretinal fluid and intraretinal fluid, as well as central retinal thickness decreased significantly throughout the study period ( p values of <0.001, <0.001, and 0.032, respectively)., Conclusion: The COVID-19 pandemic had a significant impact on the attendance rate of patients with MNV or RVO to their scheduled treatments, which was higher in the first week of mandatory quarantine. Nevertheless, VA did not decrease significantly during this period, with a limited VA variation regardless of primary retinal disorder and morphological parameters even improved in the eyes included in the visual impact analysis., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by The Author(s) Published by S. Karger AG, Basel.)

In recent years, nurses have developed projects in the area of hospital to community transition. The objective of the present study was to analyze the transitional care offered to elderly people after they used emergency services and were discharged to return to the community. The action research method was chosen. The participants were nurses, elderly people 70 years old or older, and their caregivers. The study was carried out from October 2018 to August 2019. The data were collected by means of semi-structured interviews with the nurses, analysis of medical records, participatory observation, phone calls to the elderly people and caregivers, and team meetings. The qualitative data were submitted to Bardin's content analysis. Statistical treatment was carried out by applying SPSS version 23.0. The institution's research ethics committee approved the research. Only 31.4% of the sample experienced care continuity after discharge, and the rate of readmission to emergency services during the first 30 days after discharge was 33.4%. The referral letters lacked data on information provided to patients or caregivers, and nurses mentioned difficulties in communication between care levels, as well as obstacles to teamwork; they also mentioned that the lack of health policies and clinical rules to formalize transitional care between the hospital and the community perpetuated non-coordination of care between the two contexts. The low level of literacy of patients and their relatives are mentioned as a cause for not understanding the information regarding seeking primary health care services and handing the discharge letter. It was concluded that there is an urgent need to mobilize health teams toward action in the patients' process of returning home, and this factor must be taken into account in care planning.