Real-World Evidence of the Long-Term Effectiveness of 0.2 µg/Day Fluocinolone Acetonide Implant in Persistent and Recurrent Diabetic Macular Edema - A Single Center Study.

Purpose: 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.

Multiple Lines of Evidence Support 199 SARS-CoV-2 Positively Selected Amino Acid Sites.

SARS-CoV-2 amino acid variants that contribute to an increased transmissibility or to host immune system escape are likely to increase in frequency due to positive selection and may be identified using different methods, such as codeML, FEL, FUBAR, and MEME. Nevertheless, when using different methods, the results do not always agree. The sampling scheme used in different studies may partially explain the differences that are found, but there is also the possibility that some of the identified positively selected amino acid sites are false positives. This is especially important in the context of very large-scale projects where hundreds of analyses have been performed for the same protein-coding gene. To account for these issues, in this work, we have identified positively selected amino acid sites in SARS-CoV-2 and 15 other coronavirus species, using both codeML and FUBAR, and compared the location of such sites in the different species. Moreover, we also compared our results to those that are available in the COV2Var database and the frequency of the 10 most frequent variants and predicted protein location to identify those sites that are supported by multiple lines of evidence. Amino acid changes observed at these sites should always be of concern. The information reported for SARS-CoV-2 can also be used to identify variants of concern in other coronaviruses.

Mental suffering in family daily life: a temporal journey according to Merleau-Ponty.

OBJECTIVES: to describe the family's experience in relation to daily life with a family member experiencing mental suffering. METHODS: a qualitative, descriptive, phenomenological study grounded in Merleau-Ponty's ontology of experience was conducted in ten households in a city in the state of Bahia, Brazil, where 24 participants of the Intersubjectivity Wheels reside. The descriptions produced were subjected to the Ambiguity Analytics technique. RESULTS: the descriptions were categorized into: absence as a creative power of the sense of "being" and "not being a family"; and exclusion and acceptance as expressions of mental suffering in the family context. FINAL CONSIDERATIONS: the experience of mental suffering in the family's daily life is marked by ambiguous feelings, such as joy and sadness, disappointment and satisfaction, lack of love and love. However, experiencing these feelings can mobilize the desire to "become" a family, increase the sense of autonomy and independence, and drive the formation of new family configurations.

Assessment of fatigue damage in welded aluminum joints subjected to multiaxial stress state.

The aluminum has mechanical properties enable to a better finishing in welded region. However, it fails eventually when a dynamic load is applied. This study estimated the damage by multiaxial fatigue present in welded joints of bicycle frames, the methodologies of analysis are based on Findley's and Dang Van's Methods. Seven experiments were performed on two pipes with welded joints. These pipes were choosen according to Bike S/A data, numerical simulations in bicycle frame and previous analysis of specialized literature. Therefore, lifespan result of frame, in function the distance, is 3 × 1 0 4 km - 5.5 × 1 0 4 km.

Euterpe oleracea Mart. (Açai) seed extract improves physical performance in old rats by restoring vascular function and oxidative status and activating mitochondrial muscle biogenesis.

OBJECTIVES: Alterations in cardiovascular and skeletal muscle function are hallmarks of ageing that lead to exercise intolerance. We aimed to examine whether the treatment with Euterpe oleracea Mart. seed extract (ASE) associated with exercise training improves aerobic exercise performance by promoting healthy ageing in the elderly. METHODS: Male Wistar rats were divided into five groups: Young (3 months), Old (18 months), Old+ASE (ASE 200 mg/kg/day), Old+Training (exercise training 30 min/day; 5 days/week) and Old+Training+ASE, for 4 weeks. KEY FINDINGS: ASE treatment increased the exercise time and the running distance concerning the initial maximal treadmill stress test (MTST) in the Old+Training+ASE group. Exercise training or ASE treatment restored the aorta oxidative damage and antioxidant defence. It reduced the acetylcholine (ACh)-induced vasodilation in the aorta of old animals to the same values as the young and improved hypertension. Only the association of both strategies restored the ACh-induced vasodilation in mesentery arteries. Remarkably, exercise training associated with ASE increased the antioxidant defence, nitrite levels and expression of the mitochondrial SIRT-1, PGC1α in soleus muscle homogenates. CONCLUSIONS: ASE treatment associated with exercise training contributes to better exercise performance and tolerance in ageing by improving vascular function, oxidative stress and activating the muscle SIRT-1/PGC-1α pathway.

Self-reported visual function and psychosocial impact of visual loss in EYS-associated retinal degeneration in a Portuguese population.

PURPOSE: To evaluate self-reported visual function and the psychosocial impact of visual loss EYS-associated retinal degeneration (EYS-RD) using two patient-reported outcome (PRO) measures: Michigan Retinal Degeneration Questionnaire (MRDQ) and Michigan Vision-related Anxiety Questionnaire (MVAQ). METHODS: Cross-sectional, single-center study conducted at a tertiary care hospital in Portugal. Patients with biallelic EYS variants were invited to participate. Clinical data including demographics, ETDRS best-corrected visual acuity (BCVA) in the better-seeing eye and genetic testing results were collected. Interviews were carried out during clinic visits or by phone between November 2021 and February 2022. A blind grader used horizontal and vertical spectral domain optical coherence tomography (SD-OCT) scans to manually measure ellipsoid zone (EZ) width in the nasal, temporal, superior and inferior macular quadrants to calculate the EZ area. RESULTS: Forty-nine patients (53.1% males; mean age 53 ± 14 years) were included. A positive correlation (p < .05) was found between age and most MRDQ domain scores (central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision and mesopic peripheral vision). A negative correlation was found between both BCVA and EZ area across all MRDQ domains. In MVAQ, SD-OCT EZ area negatively correlated with both rod function and cone function-related anxiety. Neither age, BCVA or gender correlated with MVAQ domains. CONCLUSIONS: This study provides strong evidence supporting a correlation between PRO measures and both functional and structural clinician-reported outcomes. The use of MRDQ and MVAQ adds a new dimension to our understanding of EYS-RD and establishes both PRO measures as important disease outcome measures.

Eyes Shut Homolog-Associated Retinal Degeneration: Natural History, Genetic Landscape, and Phenotypic Spectrum.

PURPOSE: To describe the natural history, genetic landscape, and phenotypic spectrum of Eyes shut homolog (EYS)-associated retinal degeneration (EYS-RD). DESIGN: Retrospective, single-center cohort study complemented by a cross-sectional examination. SUBJECTS: Patients with biallelic EYS variants were recruited at an inherited RD referral center in Portugal. METHODS: Every patient underwent a cross-sectional examination comprising a comprehensive ophthalmic examination including best-corrected visual acuity (BCVA), dilated slit-lamp anterior segment, and fundus biomicroscopy; ultrawide-field color fundus photography and fundus autofluorescence imaging; and spectral domain-OCT. In the setting of a retinitis pigmentosa (RP) diagnosis, every patient was classified as typical or atypical RP according to imaging criteria. Baseline demographics, age at onset of symptoms, family history, history of consanguinity, symptoms, age at diagnosis, BCVA at baseline and throughout follow-up, and EYS variants were collected from each individual patient file. MAIN OUTCOME MEASURES: Clinical/demographic, genetic, multimodal imaging data, and BCVA variation were compared between typical and atypical RP. Additionally, BCVA variation during follow-up was used as an endpoint to describe EYS-RD natural history. RESULTS: Fifty-eight patients (59% men; mean age 52 ± 14 years) from 48 White families of Portuguese ancestry were included. Twenty distinct EYS variants were identified, 8 of which are novel. In 32.8% of patients, onset of symptoms was in early adulthood (21-30 years). A clinical diagnosis of RP was established in 57 patients and cone-rod dystrophy in 1 patient. Regarding RP, 75.0% of the patients were graded as typical and 25.0% as atypical. Atypical EYS-RP commonly presents with inferior crescent-shaped macular atrophy with superior midperipheral sparing. In EYS-RD, a negative correlation was found between age and BCVA (r = -0.50; P < 0.001), with an average loss of 1.45 letters per year. When stratifying for RP phenotype, lower average loss of letters per year (P < 0.001), higher BCVA (P < 0.001), and larger ellipsoid zone widths (P < 0.001) were found in atypical RP. CONCLUSIONS: This study expands the genetic spectrum of EYS-RD by reporting 8 novel variants. A high frequency of atypical phenotypes was identified. These patients have better BCVA and larger ellipsoidal zone widths, thus presenting an overall better prognosis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Automated macular segmentation can distinguish glaucomatous from compressive optic neuropathy.

PURPOSE: To compare macular damage in glaucomatous optic neuropathy (GON) and compressive optic neuropathy (CON) and assess its diagnostic accuracy in distinguishing between diseases. METHODS: Observational, cross-sectional, single-center study. Patients with GON, CON, and healthy controls were included according to the eligibility criteria. An automated spectral-domain optical coherence tomography (SD-OCT) algorithm was used to segment the circumpapilary retinal nerve fiber layer (cpRNFL) and macula. The layer thickness was measured in each sector according to the Early Treatment Diabetic Retinopathy Study and the 6-sector Garway-Heath-based grids. Data was compared across all study groups, and the significance level was set at 0.05. RESULTS: Seventy-five eyes of 75 participants, 25 with GON, 25 with CON, and 25 healthy controls (CG), were included. Macular thickness was diminished in the ganglion cell complex of GON and CON patients compared to CG (p<0.05). The best Garway-Heath-based grid parameters for distinguishing GON and CON were the nasal-inferior (NI) and nasal-superior sectors and the NI/temporal inferior (TI) damage ratios in the macular ganglion cell (mGCL) and inner plexiform (IPL) layers. Moreover, the combination of the NI sector and NI/TI damage ratios in both layers had higher discriminative power (AUC 0.909; 95% CI 0.830-0.988; p<0.001) than combining parameters in each layer separately. CONCLUSION: Our findings suggest that the evaluation of macular segmented layers damage by SD-OCT may be a helpful add-on tool in the differential diagnosis between GON and CON.

Mental suffering in family daily life: a temporal journey according to Merleau-Ponty / Sufrimiento mental en la vida diaria de la familia: un viaje temporal según Merleau-Ponty / Sofrimento mental no cotidiano familiar: trajetória temporal segundo Merleau-Ponty

ABSTRACT Objectives: to describe the family's experience in relation to daily life with a family member experiencing mental suffering. Methods: a qualitative, descriptive, phenomenological study grounded in Merleau-Ponty's ontology of experience was conducted in ten households in a city in the state of Bahia, Brazil, where 24 participants of the Intersubjectivity Wheels reside. The descriptions produced were subjected to the Ambiguity Analytics technique. Results: the descriptions were categorized into: absence as a creative power of the sense of "being" and "not being a family"; and exclusion and acceptance as expressions of mental suffering in the family context. Final Considerations: the experience of mental suffering in the family's daily life is marked by ambiguous feelings, such as joy and sadness, disappointment and satisfaction, lack of love and love. However, experiencing these feelings can mobilize the desire to "become" a family, increase the sense of autonomy and independence, and drive the formation of new family configurations.

RESUMEN Objetivos: describir la experiencia de la familia en relación con la vida diaria de un miembro familiar que experimenta sufrimiento mental. Métodos: se realizó un estudio cualitativo, descriptivo y fenomenológico basado en la ontología de la experiencia de Merleau-Ponty en diez hogares de una ciudad en el estado de Bahía, Brasil, donde residen 24 participantes de los Círculos de Intersubjetividad. Las descripciones producidas fueron sometidas a la técnica de Análisis de Ambigüedad. Resultados: las descripciones se clasificaron en: la ausencia como un poder creativo del sentido de "ser" y "no ser una familia"; y la exclusión y aceptación como expresiones del sufrimiento mental en el contexto familiar. Consideraciones Finales: la experiencia del sufrimiento mental en la vida diaria de la familia está marcada por sentimientos ambiguos, como alegría y tristeza, decepción y satisfacción, falta de amor y amor. Sin embargo, experimentar estos sentimientos puede movilizar el deseo de "convertirse" en una familia, aumentar el sentido de autonomía e independencia, y promover la formación de nuevas configuraciones familiares.

RESUMO Objetivos: descrever a experiência da família em relação ao cotidiano com o familiar em sofrimento mental. Métodos: estudo qualitativo, descritivo, do tipo fenomenológico, fundamentado na ontologia da experiência de Merleau-Ponty, realizado em dez domicílios de uma cidade do estado da Bahia (Brasil), onde residem os 24 participantes das Rodas de Intersubjetividade. As descrições produzidas foram submetidas à técnica Analítica da Ambiguidade. Resultados: as descrições foram categorizadas em: ausência como potência criadora do sentido de "ser" e "não ser família"; e exclusão e acolhimento como expressão do sofrimento mental no contexto da família. Considerações Finais: a experiência do sofrimento mental no cotidiano da família é marcada por sentimentos ambíguos, como alegria e tristeza, decepção e satisfação, desamor e amor. Entretanto, a vivência desses sentimentos pode mobilizar o desejo de "tornar-se" família, aumentar o senso de autonomia e independência, e impulsionar a formação de novas configurações familiares.

Modified Deep Anterior Lamellar Keratoplasty Technique to Rescue Failed Penetrating Keratoplasty.

Purpose: To describe a modified deep anterior lamellar keratoplasty (DALK) technique to rescue failed penetrating keratoplasty (PK) grafts and report its results. Patients and Methods: Retrospective, case-series analysis of patients who underwent modified DALK to rescue failed corneal grafts after PK was included. Every patient had corneal graft failure (GF) diagnosis due to anterior corneal (epithelium, Bowman's, and stroma layers) or refraction disorders uncorrectable with conservative management. The main objective of the surgery and primary outcome of the study was the improvement of corrected distance visual acuity (CDVA). The study's secondary outcome was the frequency of intra- and postoperative complications. Results: This series included four eyes from three patients with a mean age of 57.7 years (range: 51-63 years). Mean follow-up of patients was thirteen months (range: 12-15 months). During follow-up, continuous improvement of corneal transparency and CDVA was observed in every patient. The only intraoperative complication reported was a peripheric DM microperforations of previous graft-host junction in two eyes. No signs of double anterior chamber, endothelial failure, GF, glaucoma, or other side effects were reported. Conclusion: Our results suggest that modified DALK in patients with GF after PK, preserving a healthy endothelium, is surgically feasible. However, further studies are needed to compare this procedure to PK and other DALK technique variations.

An Evaluation of Peer-Rated Surgical Skill and its Relationship With Detrusor Muscle Sampling in Transurethral Resection of Bladder Tumor.

OBJECTIVE: To assess the reliability of peer-review of TURBT videos as a means to evaluate surgeon skill and its relationship to detrusor sampling. METHODS: Urologists from an academic health system submitted TURBT videos in 2019. Ten blinded peers evaluated each surgeon's performance using a 10-item scoring instrument to quantify surgeon skill. Normalized composite skill scores for each surgeon were calculated using peer ratings. For surgeons submitting videos, we retrospectively reviewed all TURBT pathology results (2018-2019) to assess surgeon-specific detrusor sampling. A hierarchical logistic regression model was fit to evaluate the association between skill and detrusor sampling, adjusting for patient and surgeon factors. RESULTS: Surgeon skill scores and detrusor sampling rates were determined for 13 surgeons performing 245 TURBTs. Skill scores varied from -6.0 to 5.1 [mean: 0; standard deviation (SD): 2.40]. Muscle was sampled in 72% of cases, varying considerably across surgeons (mean: 64.5%; SD: 30.7%). Among 8 surgeons performing >5 TURBTs during the study period, adjusted detrusor sampling rate was associated with sending separate deep specimens (odds ratio [OR]: 1.97; 95% confidence interval [CI]: 1.02-3.81, P = .045) but not skill (OR: 0.81; 95% CI: 0.57-1.17, P = .191). CONCLUSION: Surgeon skill was not associated with detrusor sampling, suggesting there may be other drivers of variability of detrusor sampling in TURBT.

Predictive Models of within- and between-Species SARS-CoV-2 Transmissibility.

Viruses from the Coronaviridae family have been reported to infect a large range of hosts, including humans. The latest human-infecting coronavirus, SARS-CoV-2, turned into a pandemic and subtypes with different transmissibility have appeared since then. The SARS-CoV-2 Spike (S) protein interacts with the angiotensin-converting enzyme 2 (ACE2) host receptor, and thus, in silico models, based on the structural features of the SARS-CoV-2 S protein-ACE2 receptor complex, as well as ACE2 amino acid patterns, may be used to predict the within- and between-species transmissibility of SARS-CoV-2 subtypes. Here, it is shown that at the beginning of the pandemic, the SARS-CoV-2 S protein was, as expected for a virus that just jumped the species barrier, ill-adapted to the human ACE2 receptor, and that the replacement of one SARS-CoV-2 variant by another is partially due to a better fitting of the S protein-human ACE2 complex. Moreover, it is shown that mutations that are predicted to lead to a better fit have increased in the population due to positive selection. It is also shown that the number of ACE2-interfacing residues is positively correlated with the transmissibility rate of SARS-CoV-2 variants. Finally, it is shown that the number of species that are susceptible to infection by SARS-CoV-2, and that could be a reservoir for this virus, is likely higher than previously thought.

Sporomusa ovata as Catalyst for Bioelectrochemical Carbon Dioxide Reduction: A Review Across Disciplines From Microbiology to Process Engineering.

Sporomusa ovata is a bacterium that can accept electrons from cathodes to drive microbial electrosynthesis (MES) of acetate from carbon dioxide. It is the biocatalyst with the highest acetate production rate described. Here we review the research on S. ovata across different disciplines, including microbiology, biochemistry, engineering, and materials science, to summarize and assess the state-of-the-art. The improvement of the biocatalytic capacity of S. ovata in the last 10 years, using different optimization strategies is described and discussed. In addition, we propose possible electron uptake routes derived from genetic and experimental data described in the literature and point out the possibilities to understand and improve the performance of S. ovata through genetic engineering. Finally, we identify current knowledge gaps guiding further research efforts to explore this promising organism for the MES field.

Panorama da implementação do Programa Mais Médicos até 2021 e comparação com o Programa Médicos pelo Brasil / Implementation of the Mais Médicos Project until 2021 and comparison with the Médicos Pelo Brasil Program: an overview / Panorama de la puesta en marcha del Programa Más Médicos hasta 2021 y comparación con el Programa Médicos Por Brasil

Este artigo faz um balanço do Programa Mais Médicos (PMM), considerando seus três eixos, no período de 2013 a 2021, analisando a influência de atores sociais coletivos na implementação e nos processos de (re)formulação no programa, bem como compara normativamente o PMM com o Programa Médicos pelo Brasil (PMPB). Trata-se de um estudo de caso, que usou recursos teóricos dos estudos de implementação de políticas, do neoinstitucionalismo histórico e da teoria da mudança institucional gradual para analisar documentos, bibliografia, dados secundários e entrevistas semiestruturadas com dirigentes das políticas nacionais de regulação, formação e provimento. Focando a análise na caracterização do processo de implementação, nas continuidades e mudanças institucionais e na distribuição de recursos, no contexto político e na posição e ação de atores coletivos relevantes, o artigo descreve e analisa a implementação do programa em cada um de seus três eixos ­ infraestrutura, formação e provimento ­ e mostra que ela pode ser dividida em quatro fases: implementação inicial acelerada, implementação sustentada, implementação parcialmente bloqueada e implementação residual. Sua maior contribuição é a compreensão do que mudou e os motivos pelos quais mudou, bem como a provocação da reflexão sobre a sustentabilidade de políticas que buscam enfrentar as insuficiências na oferta e na formação médica, mesmo contra a posição hegemônica das entidades médicas.

This paper evaluates the Mais Médicos Program (PMM) in its three axes from 2013 to 2021, analyzing how collective social actors influenced its implementation and (re)formulation processes, and normatively compares the PMM with the Médicos pelo Brasil Program (PMPB). BaseD on theoretical resources from policy implementation studies, historical neo-institutionalism and the theory of gradual institutional change, this case study analyzes documents, bibliography, secondary data, and semi-structured interviews with leaders of national regulatory, training, and provision policies. Focused on the implementation process characteristics, on institutional continuities and changes, and on the distribution of resources, the political context and the position and action of relevant collective actors, the text describes and analyzes the PMM implementation in each of its three axes ­ infrastructure, training and provision ­, demonstrating that it can be divided into four phases: initial accelerated implementation, sustained implementation, partially blocked implementation and residual implementation. It contributes to an in-depth understanding of what has changed and the reasons for such change, as well as to provoke reflection on the sustainability of policies that seek to address shortcomings in medical supply and education, even against the hegemony of medical entities.

Este artículo analiza el Programa Más Médicos (PMM) a partir de la influencia de los actores sociales colectivos en los procesos de la puesta en marcha y (re)formulación de este programa teniendo en cuenta sus tres ejes, en el periodo de 2013 a 2021, así como lo compara con el Programa Médicos para Brasil (PMPB). Se trata de un estudio de caso, que utilizó recursos teóricos de los estudios de implementación de políticas, el neoinstitucionalismo histórico y la teoría del cambio institucional gradual para analizar documentos, bibliografía, datos secundarios y entrevistas semiestructuradas a líderes de políticas nacionales de regulación, formación y provisión. A partir del análisis que se centró en la caracterización del proceso de la puesta en marcha, en las continuidades y cambios institucionales y distribución de recursos, en el contexto político y en la posición y acción de los actores colectivos relevantes, el artículo describe y analiza la puesta en marcha del programa en cada uno de sus tres ejes ­ infraestructura, capacitación y provisión­ y muestra su división en cuatro fases: implementación inicial acelerada, implementación sostenida, implementación parcialmente bloqueada e implementación residual. Su mayor aporte es la comprensión de lo que ha cambiado y las razones por las que ha cambiado, así como el hecho de incitar la reflexión sobre la sostenibilidad de las políticas que buscan atender las insuficiencias en la oferta y formación médica, incluso frente a la posición hegemónica de las entidades médicas.

A New Paradigm of Multiheme Cytochrome Evolution by Grafting and Pruning Protein Modules.

Multiheme cytochromes play key roles in diverse biogeochemical cycles, but understanding the origin and evolution of these proteins is a challenge due to their ancient origin and complex structure. Up until now, the evolution of multiheme cytochromes composed by multiple redox modules in a single polypeptide chain was proposed to occur by gene fusion events. In this context, the pentaheme nitrite reductase NrfA and the tetraheme cytochrome c554 were previously proposed to be at the origin of the extant octa- and nonaheme cytochrome c involved in metabolic pathways that contribute to the nitrogen, sulfur, and iron biogeochemical cycles by a gene fusion event. Here, we combine structural and character-based phylogenetic analysis with an unbiased root placement method to refine the evolutionary relationships between these multiheme cytochromes. The evidence show that NrfA and cytochrome c554 belong to different clades, which suggests that these two multiheme cytochromes are products of truncation of ancestral octaheme cytochromes related to extant octaheme nitrite reductase and MccA, respectively. From our phylogenetic analysis, the last common ancestor is predicted to be an octaheme cytochrome with nitrite reduction ability. Evolution from this octaheme framework led to the great diversity of extant multiheme cytochromes analyzed here by pruning and grafting of protein modules and hemes. By shedding light into the evolution of multiheme cytochromes that intervene in different biogeochemical cycles, this work contributes to our understanding about the interplay between biology and geochemistry across large time scales in the history of Earth.

Impact Assessment of an Affirmative Action to Promote Diversity, Equity, Inclusion, and Respect in Brazilian Chemistry during the COVID-19 Pandemic.

In December 2019, the institutional affirmative action "Onde elas estão?" ("Where are they?") was launched for the mitigation of gender inequality in the STEM disciplines in Brazil, coincidentally in the same period which the first reports of the COVID-19 pandemic appeared in the city of Wuhan, China. Unfortunately, when evaluating the initiative through different approaches belonging to the Diversity, Equity, Inclusion, and Respect (DEIR) theories, the presence of implicit biases and the invisibility of underrepresented minorities was observed. Approximately 77.5% of the female scientists participating in the initiative were white and belonging to the wealthiest regions (75%) and with the greatest contribution to Brazil's Gross Domestic Product (GDP). On the other hand, Black, Indigenous, and Asian female chemists were not identified, nor were female chemists belonging to the North Region (Brazilian Amazon Region). The DEIR practice "Onde elas estão?" has an important role in the dissemination of highly qualified Brazilian female chemists and provides an important source of engagement and sense of community for future generations of female students to avoid abandoning STEM subjects. However, adjustments are needed that take into account greater Diversity, Inclusion, Equity, and Respect.

The Portuguese mediterranean diet wheel: development considerations.

Scientific evidence has been reporting the health and environmental benefits of the Mediterranean diet. However, countries of the Mediterranean region, Portugal included, are gradually abandoning this traditional food pattern. The aim of the present work was to develop the Portuguese Mediterranean diet wheel. Three main steps were followed: (1) establishment of the most relevant Mediterranean diet and lifestyle principles to improve this pattern among the Portuguese population; (2) converting those principles into a captivating and easy to understand tool and (3) obtaining experts' opinion. By a matter of consistency, the preservation and transmission of the Mediterranean heritage was represented through an upgrade of the current Portuguese food wheel guide. This complementary tool highlights the Mediterranean diet enlarged character that encompasses a healthy lifestyle and reinforces sociocultural and environmental features. It was launched at the end of 2016 and was nationally disseminated with the support of the Portuguese Health Directorate. Initially it was presented in a poster format image that was subsequently spread in different communication formats. This newly developed Mediterranean food guide is a complementary educational tool that will support health and education professionals in the never ending mission of promoting healthy food choices.

Topical Insulin-Utility and Results in Refractory Neurotrophic Keratopathy in Stages 2 and 3.

PURPOSE: The purpose of this study was to evaluate the clinical outcome of patients with refractory neurotrophic keratopathy (NK) in stages 2 and 3 treated with topical insulin. METHODS: Retrospective analysis of eyes with NK in stages 2 and 3 refractory to standard medical and/or surgical treatment which were treated with topical insulin (1 unit per mL). This treatment was applied 4 times per day and was continued until the persistent epithelial defect (PED) or ulcer resolved. The primary outcome of the study was the complete reepithelialization of the PED or persistent ulcer. "Best-corrected visual acuity" pretreatment and posttreatment, "days until complete reepithelialization" data, and anterior segment photographs were obtained. Outcome measures were compared before and after treatment in both groups using paired and independent samples t tests. RESULTS: Twenty-one eyes were included in this study, and 90% achieved complete reepithelialization of the PED and/or persistent ulcer within 7 to 45 days of follow-up. The mean number of days until complete reepithelialization was significantly lower in NK stage 2 (18 ± 9 days) when compared with NK stage 3 (29 ± 11 days) ( P = 0.025). The best-corrected visual acuity improved significantly in both NK stage 2 ( P < 0.001) and NK stage 3 ( P = 0.004). No side effects were reported during the follow-up. CONCLUSIONS: Our results suggest that topical insulin drops may be an effective therapeutic in refractory NK. This therapy may prove extremely useful because of its low cost and high accessibility.

Plasma rich in growth factors (PRGF -ENDORET®) to rescue necrotized orbital dermis-fat grafts.

PURPOSE: We report on the clinical course of three patients treated with topical plasma rich in growth factors (PRGF) to rescue dermal-fat grafts (DFG) with graft ulceration (GU). MATERIALS AND METHODS: A retrospective, case-series study of three patients diagnosed with GU in DFG and treated with PRGF. Drops were applied four times per day and treatment was maintained until the GU resolved. Data were collected from medical records and anterior segment photos. RESULTS: All patients showed a favorable response to topical PRGF having accomplished full resolution of the GU within a mean of 30 days of treatment (range: 21-35 days). During the full extent of follow-up, no side-effects, signs of rejection or necrosis were reported and every patient was pleased with the final aesthetic result. CONCLUSION: Our results suggest that PRGF could be an effective treatment for dermal graft ulceration in patients who underwent DFG surgery/implantation, mainly due to its low morbidity when compared to traditional procedures.