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Introdução: A Anemia Falciforme (AF) é uma condição genética complexa que leva a estados crônicos de estresse oxidativo, inflamação sistêmica e lesão por isquemia-reperfusão, resultando em danos aos tecidos e órgãos. Durante crises de dor aguda na AF, as células danificadas liberam passivamente a proteína HMGB1 (High Mobility Group Box 1), que atua como um padrão molecular associado ao dano (DAMP), ativando receptores da imunidade inata, como o Receptor Desencadeador Expresso em Células Mieloides-1 (TREM-1). Neste contexto, TREM-1 atua como amplificador da resposta imune inata, agindo sinergicamente com receptores TLRs e NLRs, enquanto sua forma solúvel (sTREM-1) tem sido apontada como um potencial biomarcador inflamatório. Estudos mostraram que níveis circulantes de sTREM-1 estão elevados em condições inflamatórias, como obesidade, doenças reumáticas e durante isquemia-reperfusão. No entanto, poucos trabalhos avaliaram a participação de TREM- 1 na resposta imune na AF, justificando a necessidade de investigações futuras. Hipotetizamos que a ativação de TREM-1 por HMGB1 leva à ativação do fator de transcrição NF-kB, resultando na produção de mediadores inflamatórios e contribuindo para episódios vaso-oclusivos na AF. Objetivos: Analisar estudos sobre o papel do receptor TREM-1 e sua importância na modulação da resposta imune inata na anemia falciforme. Metodologia: Esta revisão narrativa utilizou as principais bases de dados eletrônicas, como “PubMed”, “Google Acadêmico” e “Lilacs”, no período de 2015 a 2023 para garantir a inclusão dos estudos mais recentes e relevantes sobre o tema. Foram utilizados termos de busca como “TREM-1”, “Anemia Falciforme”, “HMGB1” e “Inflamação Crônica” e apenas análises originais em inglês foram incluídas. Resultados: Dos 30 artigos científicos revisados, 12 destacaram a ativação de TREM-1 por HMGB1, sendo este um dos principais ligantes e ativadores da via TREM-1 em doenças inflamatórias crônicas. Esses achados ressaltam a necessidade de mais estudos sobre TREM-1 na AF para a compreensão de sua influência na doença. Discussão: Os estudos evidenciaram que HMGB1 pode atuar como um ligante de TREM-1 ativando a sinalização da via em diversos tipos celulares, resultando na ativação do NF-kB regulando genes que codificam citocinas e quimiocinas pró-inflamatórios como IL-6, TNF-α e IL-1β. Na inflamação estéril, os níveis aumentados de HMGB1 por necrose e dano celular desencadeiam respostas inflamatórias mediadas por TLR4 e amplificadas por TREM-1. Isso resulta em aumento da permeabilidade vascular, recrutamento de neutrófilos e células mononucleares, e prejuízo na vasodilatação, promovendo morte celular por apoptose. Além disso, HMGB1 contribui significativamente para a inflamação e trombose na anemia falciforme, ativando inflamassoma NLRP3 em plaquetas. Conclusão: TREM-1 desempenha um papel crucial como um possível modulador da resposta imunológica em condições de inflamação crônica, sendo ativado por HMGB1. Tanto TREM-1 quanto HMGB1 estão significativamente elevados em estados inflamatórios crônicos e podem piorar clinicamente a AF, especialmente durante crises vaso-oclusivas. Como perspectivas futuras, estudos e ensaios clínicos que visem inibir/bloquear a via TREM-1, são necessários para confirmar esses achados e desenvolver novas estratégias terapêuticas promissoras na redução da inflamação e danos teciduais na AF.

Introdução: A COVID-19 é uma doença infecciosa altamente transmissível, capaz de causar um amplo espectro de manifestações clínicas. Vacinas com tecnlogias baseadas em DNA, RNA e vetores foram criadas com o intuito de reduzir sua gravidade. No contexto imunológico, a IL-10, uma citocina imunorreguladora, modula a inflamação ao inibir macrófagos e células dendríticas. No entanto, a resposta imune pode variar conforme a alta diversidade genética, como observado na população amazonense. Nesse sentido, a variante -1082 A>G (rs1800896) do gene da IL-10 pode influenciar nas concentrações de IL-10 em profissionais de saúde vacinados com a terceira dose contra COVID-19. Objetivo: Avaliar a influência da variante genética IL-10 (rs1800896) em profissionais de saúde vacinados com a terceira dose contra a COVID-19 na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas/Brasil. Metodologia: Este estudo envolveu 176 profissionais de saúde vacinados com a terceira dose e 137 doadores saudáveis (controle). O DNA foi extraído, amplificado pela Reação em Cadeia da Polimerase (PCR) convencional, submetido à técnica de Polimorfismo de Comprimento de Fragmentos de Restrição (RFLP) e avaliado em gel de agarose a 1,25%. As amostras de soro foram usadas para dosagem de citocinas por Cytometric Bead Array (CBA). Resultados: No grupo vacinado, 121 (67,61%) eram do gênero feminino e 57 (32,39%) masculino; enquanto no grupo controle, 42 (30,66%) feminino e 95 (69,34%) masculino. A mediana de idade para o grupo vacinado foi 44 anos (33-54) e 30 anos (22- 39) para o grupo controle. O genótipo AA foi mais frequente em ambos os grupos, com 128 (72,73%) no grupo vacinado e 74 (54,01%) no controle (OR = 0,3153, p < 0,0001) enquanto o genótipo AG apresentou frequência de 30 (17,04%) no grupo vacinado e 55 (40,15%) no controle (AA vs AG, OR = 0,4405 p < 0,0008). A frequência do alelo A foi maior no grupo vacinado: 286 (81,25%) em comparação ao controle: 203 (74,08%) (OR = 0,6598, p < 0,0326). O grupo vacinado apresentou concentrações séricas de IL-10 significativamente maiores que o controle (p < 0,0001), e o genótipo AG mostrou maiores concentrações de IL-10 que o AA (p < 0,0409). No grupo controle, não houve diferença significativa entre os genótipos. No grupo vacinado, tanto AA quanto AG apresentaram maiores concentrações de IL-10 em comparação ao grupo controle (p < 0,0001 para ambos). Discussão: Um estudo de Choudhary et al. associou o genótipo AG à letalidade na influenza, enquanto Badr et al. encontraram maior frequência do alelo G na COVID-19. Abood et al. mostraram que diferentes variantes do SARS-CoV-2 associam-se a genótipos distintos: AG para a variante Alpha e AA para Delta e Ômicron. O aumento de IL-10 após a vacinação corrobora com os achados de Rosati e colaboradores que observaram efeitos sistêmicos significativos e várias citocinas detectáveis até um mês após a terceira dose da vacina contra COVID-19. Conclusão: Os resultados deste estudo mostraram que a variante -1082 A>G do gene da IL-10 pode influenciar na resposta vacinal contra COVID-19, com o genótipo AG associado a maiores concentrações de IL-10 no grupo vacinado. No entanto, mais estudos são necessários para avaliar a diversidade genética das populações, tendo em vista que as variantes do SARS-CoV-2 podem influenciar na eficácia das vacinas, assim como fatores étnicos e ambientais.

Background/Aim: Panoramic radiographs have been used widely for pre-implant evaluation and the preparation of treatment protocols. Panoramic radiography is often the first choice method for the implant placements because it gives information on the overall shape of the jaws, the position of the maxillary sinus floor and the nasal cavity floor, and vertical position of the mandibular canal and the mental foramen in relation to dental implants. The specific aim of the present study was to evaluate 10-year survival rate of dental implants by analysis of dental panoramic radiographs.

Presents a corrected reprint of the article 'A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2,' by S. Hadano, C.K. Hand et al, published in the year 2001 issue of the journal 'Nature Genet.'

The aim of this study was to evaluate the content, quality, and functionality of YouTube videos on the anatomy of skull bones and to measure their educational usefulness. In this cross-sectional study, the keywords "skull bones" and "skull anatomy" were searched in the YouTube search tab. Demographic data such as type, source, duration, upload date, and view rates of the videos were recorded. The quality and content of the videos were measured using the total content score (TCS), modified DISCERN scale, JAMA score, and Global Quality Scale (GQS). SPSS 26.0 software was used for statistical analysis. Twenty-five (34.7%) of the first 72 videos found by keyword searches were included in the study. According to the GQS criteria, six of them (24%) were considered useful and 19 (76%) not useful. There was a strong statistically significant correlation between the GQS and DISCERN scores (r = 0.813, p < 0.001). There were strong statistically significant positive correlations between TCS and GQS scores (r = 0.887, p < 0.001) and between TCS and modified DISCERN scores (r = 0.691, p < 0.001). Additionally, there was a moderately strong statistically significant positive correlation between GQS and JAMA scores (r = 0.507, p < 0.05). There were also moderately strong statistically significant correlations between JAMA score and DISCERN score (r = 0.521, p < 0.001), video length (r = 0.416, p < 0.05), number of comments (r = 0.457, p < 0.05), and number of "likes" (r = 0.608, p < 0.001). There was a moderately strong statistically significant positive correlation between TCS and JAMA scores (r = 0.431, p < 0.05). Most YouTube videos have insufficient information about skull bones to meet the expectations of medical and dental school curricula. Anatomists and institutions should be encouraged to prepare and present YouTube videos using assessment systems such as DISCERN, JAMA, GQS, and TCS, in line with current anatomy curricula., (© 2024 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Coral reef science is a fast-growing field propelled by the need to better understand coral health and resilience to devise strategies to slow reef loss resulting from environmental stresses. Key to coral resilience are the symbiotic interactions established within a complex holobiont, i.e. the multipartite assemblages comprising the coral host organism, endosymbiotic dinoflagellates, bacteria, archaea, fungi, and viruses. Tara Pacific is an ambitious project built upon the experience of previous Tara Oceans expeditions, and leveraging state-of-the-art sequencing technologies and analyses to dissect the biodiversity and biocomplexity of the coral holobiont screened across most archipelagos spread throughout the entire Pacific Ocean. Here we detail the Tara Pacific workflow for multi-omics data generation, from sample handling to nucleotide sequence data generation and deposition. This unique multidimensional framework also includes a large amount of concomitant metadata collected side-by-side that provide new assessments of coral reef biodiversity including micro-biodiversity and shape future investigations of coral reef dynamics and their fate in the Anthropocene., (© 2023. The Author(s).)

Introduction: Daily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines., Materials and Methods: Consensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations., Results: Consensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus., Conclusion: Specialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications., (© 2022. The Author(s).)

Purpose: To present the first results of intraoperative irradiation (IORT) in breast cancer with a low-energy photon system used as partial breast irradiation (PBI) or as an anticipated boost before whole breast hypo-fractionated irradiation (IORT + WBI), concerning tolerance, side effects, quality of life, and patient-reported outcomes., Materials and Methods: Eighty patients treated with an Intrabeam ® system of 50 kV X-rays received a 20 Gy dose intraoperatively were included. Moderate daily hypofractionation of 2.7 Gy in 15 fractions up to 40.5 Gy was administered if high-risk factors were present. Acute post-operative toxicity, surgery complications, chronic toxicity, patient-reported cosmesis and Breast-Q questionnaire were performed at follow-up visits., Results: Thirty-one patients were treated as PBI and the remaining 49 as IORT + WBI. Only the IORT + WBI group presented acute toxicity, mainly mild acute dermatitis (11 patients) and one subacute mastitis. A total of 20 patients presented fibrosis (18 patients grade I, 2 patients grade II), 15 (30.5%) patients in the IORT + WBI group and 3 (9.6%) patients in the group of PBI. The cosmesis evaluation in 73 patients resulted poor, fair, good or excellent in 2, 7, 38 and 26 patients, respectively. In PBI group Breast-Q scored higher, especially in terms of their psychosocial well-being (78 vs 65) and satisfaction with radiation-induced toxicity (77 vs 72, respectively) compared to IORT + WBI group., Conclusion: IORT is a well-tolerated procedure with low toxicity, good cosmesis and favorable patient-reported outcomes mainly when administered as PBI., (© 2021. The Author(s).)

Purpose: Radiation-induced toxicity (RIT) is usually assessed by inspection and palpation. Due to their subjective and unquantitative nature, objective methods are required. This study aimed to determine whether a quantitative tool is able to assess RIT and establish an underlying BED-response relationship in breast cancer., Methods: Patients following seven different breast radiation protocols were recruited to this study for RIT assessment with qualitative and quantitative examination. The biologically equivalent dose (BED) was used to directly compare different radiation regimens. RIT was subjectively evaluated by physicians using the Radiation Therapy Oncology Group (RTOG) late toxicity scores. Simultaneously an objective multiprobe device was also used to quantitatively assess late RIT in terms of erythema, hyperpigmentation, elasticity and skin hydration., Results: In 194 patients, in terms of the objective measurements, treated breasts showed higher erythema and hyperpigmentation and lower elasticity and hydration than untreated breasts (p < 0.001, p < 0.001, p < 0.001, p = 0.019, respectively). As the BED increased, Δerythema and Δpigmentation gradually increased as well (p = 0.006 and p = 0.002, respectively). Regarding the clinical assessment, the increase in BED resulted in a higher RTOG toxicity grade (p < 0.001). Quantitative assessments were consistent with RTOG scores. As the RTOG toxicity grade increased, the erythema and pigmentation values increased, and the elasticity index decreased (p < 0.001, p = 0.016, p = 0.005, respectively)., Conclusions: The multiprobe device can be a sensitive and simple tool for research purpose and quantitatively assessing RIT in patients undergoing radiotherapy for breast cancer. Physician-assessed toxicity scores and objective measurements revealed that the BED was positively associated with the severity of RIT., (© 2021. The Author(s).)

Purpose: To report long-term results of a randomized trial comparing accelerated partial breast irradiation (APBI) to whole-breast irradiation (WBI) in terms of efficacy, toxicity, and cosmesis., Methods and Materials: WBI group was treated with 3D conformal external irradiation, 2 Gy daily/fraction, 5 fractions/week, to a total dose of 50 Gy. APBI group was treated with 3D conformal external irradiation 3.75 Gy/fraction, twice a day, 5 fractions/week, to a total dose of 37.5 Gy in the APBI group. Patients were followed up every 6 months up to 5 years and yearly thereafter. During follow-up visits, the clinician evaluated chronic toxicity and scored cosmetic results with a four-scale system., Results: After a median follow-up of 10.3 years, 43 patients in each group (84%) are alive without disease. One patient died after disease progression in the APBI arm, and there was no death in the WBI arm. The rest of the patients died from another disease different than breast cancer, similarly between groups. There was greater fibrosis in the APBI group (9 patients grade 1 and one grade 2) compared to WBI (3 patients grade 1 and one grade 2); p = 0.18. Regarding cosmesis, in APBI group, 19 and 21 (43.2 and 47%) patients had excellent or good results, similar to the WBI group with 18 patients (40.9%) in each cosmesis outcome. The WBI group did not have any patient with poor cosmesis but the APBI had 3 (6.8%; p = 0.24)., Conclusion: After a follow-up of 10 years, there were no differences in efficacy between the 2 treatment arms. Despite slight greater toxicity in the APBI group, the cosmesis was similar and satisfactory in both groups., (© 2021. Federación de Sociedades Españolas de Oncología (FESEO).)

Purpose: Weekly irradiation in breast cancer in elderly patients is a treatment option, whose tolerance may be influenced by the fractionation used. The objective of this study is to compare the tolerance and long-term side effects of two different fractionations., Materials and Methods: 47 elderly patients were recruited after conservative or radical treatment that also received irradiation with a dose per fraction of 6.25 Gy or 5 Gy for one session per week, 6 sessions in total. The long-term tolerance results are compared by assessing toxicity using CTCAE version 5.0 scales for dermatitis, telangectasia, fibrosis and pain of the irradiated breast. In addition, objective parameters of skin status (erythema, hyperpigmentation, elasticity and hydration) by a multi-probe MultiSkin Test-Center system were obtained and compared between groups., Results: After an average follow-up of 5 years, all patients were free of disease and with complete local control. A total of 20 patients with 6.25 Gy fractionation and 27 patients with 5 Gy fractionation have been included. Patients treated with lower fractionation had a lower incidence of dermatitis, telangectasia, fibrosis, or local pain. The decrease in elasticity measured by the multi-probe system was smaller with the fractionation of 5 Gy. No differences were observed in the other objective parameters., Conclusion: Weekly irradiation with 5 Gy fractionation is better tolerated than with higher fractionation.

A unique collection of oceanic samples was gathered by the Tara Oceans expeditions (2009-2013), targeting plankton organisms ranging from viruses to metazoans, and providing rich environmental context measurements. Thanks to recent advances in the field of genomics, extensive sequencing has been performed for a deep genomic analysis of this huge collection of samples. A strategy based on different approaches, such as metabarcoding, metagenomics, single-cell genomics and metatranscriptomics, has been chosen for analysis of size-fractionated plankton communities. Here, we provide detailed procedures applied for genomic data generation, from nucleic acids extraction to sequence production, and we describe registries of genomics datasets available at the European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these metadata to the experimental procedures applied for their generation will help the scientific community to access these data and facilitate their analysis. This paper complements other efforts to provide a full description of experiments and open science resources generated from the Tara Oceans project, further extending their value for the study of the world's planktonic ecosystems.

Acinetobacter baumannii is the source of numerous nosocomial infections in humans and therefore deserves close attention as multidrug or even pandrug resistant strains are increasingly being identified worldwide. Here we report the comparison of two newly sequenced genomes of A. baumannii. The human isolate A. baumannii AYE is multidrug resistant whereas strain SDF, which was isolated from body lice, is antibiotic susceptible. As reference for comparison in this analysis, the genome of the soil-living bacterium A. baylyi strain ADP1 was used. The most interesting dissimilarities we observed were that i) whereas strain AYE and A. baylyi genomes harbored very few Insertion Sequence elements which could promote expression of downstream genes, strain SDF sequence contains several hundred of them that have played a crucial role in its genome reduction (gene disruptions and simple DNA loss); ii) strain SDF has low catabolic capacities compared to strain AYE. Interestingly, the latter has even higher catabolic capacities than A. baylyi which has already been reported as a very nutritionally versatile organism. This metabolic performance could explain the persistence of A. baumannii nosocomial strains in environments where nutrients are scarce; iii) several processes known to play a key role during host infection (biofilm formation, iron uptake, quorum sensing, virulence factors) were either different or absent, the best example of which is iron uptake. Indeed, strain AYE and A. baylyi use siderophore-based systems to scavenge iron from the environment whereas strain SDF uses an alternate system similar to the Haem Acquisition System (HAS). Taken together, all these observations suggest that the genome contents of the 3 Acinetobacters compared are partly shaped by life in distinct ecological niches: human (and more largely hospital environment), louse, soil.

Expressed-sequence tag (EST) maps are an adjunct to sequence-based analytical methods of gene detection and localization for those species for which such data are available, and provide anchors for high-density homology and orthology mapping in species for which large-scale sequencing has yet to be done. Species for which radiation hybrid-based transcript maps have been established include human, rat, mouse, dog, cat and zebrafish. We have established a comprehensive first-generation-placement radiation hybrid map of the mouse consisting of 5,904 mapped markers (3,993 ESTs and 1,911 sequence-tagged sites (STSs)). The mapped ESTs, which often originate from small-EST clusters, are enriched for genes expressed during early mouse embryogenesis and are probably different from those localized in humans. We have confirmed by in situ hybridization that even singleton ESTs, which are usually not retained for mapping studies, may represent bona fide transcribed sequences. Our studies on mouse chromosomes 12 and 14 orthologous to human chromosome 14 show the power of our radiation hybrid map as a predictive tool for orthology mapping in humans.