The concentrations of polycyclic aromatic hydrocarbons in fish: A systematic review.

This study was conducted on the concentrations of PAHs, including benzo[a]pyrene and the sum of four PAHs (benz[a]anthracene, chryseno, benzo[b]fluoranthene, and benzo[a]pyrene), in unsmoked fish tissues. The values were related to the time period, locality (country and region), living habits, eating habits, and types of environments of the fish species. The data obtained has been also compared with the limits established by the United States Environmental Protection Agency (U.S. EPA) and European Union (E.U.) legislation. The data were collected through a PRISMA systematic review (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) from 1982 to 2020. Only documents that presented the PAHs concentration values were selected. China, Nigeria, and Iran had the highest number of studies. The species Coptodon zillii, Siganus punctatus, and Liza abu were the most commonly used bioindicators. Fish inhabiting demersal and pelagic environments showed the highest concentrations of PAHs. The majority of PAH concentrations of the analyzed documents fell within permissible limits for human consumption, representing a total percentage of 79.49 % for benzo[a]pyrene and 82.86 % for the sum of the 4 PAHs. Although some studies identified concentrations of benzo[a]pyrene alone and benzo[a]pyrene, benz[a]anthracene, chryseno, benzo[b]fluoranthene above the legislation limits, in most of them, the concentrations reported in fish tissue were below the limits defined by European Legislation for human consumption.

RAF-like protein kinases mediate a deeply conserved, rapid auxin response.

The plant-signaling molecule auxin triggers fast and slow cellular responses across land plants and algae. The nuclear auxin pathway mediates gene expression and controls growth and development in land plants, but this pathway is absent from algal sister groups. Several components of rapid responses have been identified in Arabidopsis, but it is unknown if these are part of a conserved mechanism. We recently identified a fast, proteome-wide phosphorylation response to auxin. Here, we show that this response occurs across 5 land plant and algal species and converges on a core group of shared targets. We found conserved rapid physiological responses to auxin in the same species and identified rapidly accelerated fibrosarcoma (RAF)-like protein kinases as central mediators of auxin-triggered phosphorylation across species. Genetic analysis connects this kinase to both auxin-triggered protein phosphorylation and rapid cellular response, thus identifying an ancient mechanism for fast auxin responses in the green lineage.

Latin American formal consensus on the appropriate indications of extra-articular lateral procedures in primary anterior cruciate ligament reconstruction.

OBJECTIVES: To create a practice guideline for the appropriate indications of an extra-articular procedure in primary anterior cruciate ligament reconstruction (ACLR). METHODS: The formal consensus method described by the Haute Autorité de Santé was used. The Latin American Society of Arthroscopy, Articular Replacement, and Sports Injuries (SLARD) recruited three groups of experts on ACLR. Initially, the steering group, consisting of eight surgeons, performed a systematic review of the literature and elaborated on 192 scenarios for primary ACLR. The rating group, composed of 23 surgeons, rated each scenario in two rounds, with an in-between in-person meeting for discussion. Median scores and agreement levels were estimated to classify each scenario as inappropriate, uncertain or appropriate for adding anterolateral reconstruction. Finally, the lecture group, consisting of 10 surgeons, revised each stage of the method, results and interpretation. RESULTS: Of the scenarios, 11.97% were rated as appropriate for adding an extra-articular lateral procedure, 7.81% as inappropriate and 80.21% as uncertain. The key recommendations for the addition of extra-articular lateral techniques were as follows: it is appropriate when the patient is under 25 years of age, has high-grade physical examination findings, practises a pivoting sport and has hyperlaxity; meanwhile, it is inappropriate when the patient has low-grade physical examination findings, has normal laxity and does not practise a pivoting sport. CONCLUSIONS: The appropriate indications of extra-articular lateral procedures in primary ACLR were determined on the basis of the best available evidence and expert opinion following a formal consensus method. LEVEL OF EVIDENCE: V.

Epidemiological patterns related to deaths caused by visceral leishmaniasis in the southern Amazon region of Brazil.

BACKGROUND: We analysed the spatial and spatiotemporal patterns of visceral leishmaniasis (VL) mortality at the municipality level in an endemic state in the southern Amazon region of Brazil. Individual-level factors associated with death due to VL were also investigated. METHODS: All VL cases and deaths reported between 2007 and 2018 were included. The global and local bivariate Moran's index assessed the space-time autocorrelation of smoothed triennial VL mortality. Kulldorff's scan statistics investigated spatial and spatiotemporal clusters. A multivariable logistic regression explored sociodemographic, diagnostic and clinical variables associated with death due to VL. RESULTS: We observed an overall VL mortality and lethality of 0.14 cases/100 000 inhabitants and 11.2%, respectively. A total of 14% of the municipalities registered at least one VL-related death. In the southeastern mesoregion of the state, we detected high-risk spatial (relative risk [RR] 14.14; p<0.001) and spatiotemporal (RR 15.91; p<0.001) clusters for VL mortality. Bivariate Moran's analysis suggested a high space-time autocorrelation of VL mortality. Death by VL was associated with age ≥48 y (odds ratio [OR] 7.2 [95% confidence interval {CI} 3.4 to 15.3]), displacement for notification (OR 3.3 [95% CI 1.5 to 7.2]) and occurrence of oedema (OR 2.8 [95% CI 1.3 to 6.1]) and bleeding (OR 5.8 [95% CI 2.6 to 12.8]). CONCLUSIONS: VL mortality has a heterogeneous spatiotemporal distribution. The death-related factors suggest late diagnosis as an underlying cause of mortality.

Preferences and Practices of Brazilian Orthopedists for Thromboprophylaxis Techniques in Total Knee Arthroplasty: Survey Among Members of the Brazilian Society of Knee Surgery (SBCJ).

Objective The present study describes the preferences and current practices of a sample of knee surgeons in Brazil regarding thromboprophylaxis in total knee arthroplasty (TKA). Method In the present internet survey, surgeons from the Brazilian Knee Surgery Society (SBCJ, in the Portuguese acronym) voluntarily answered an anonymous questionnaire including time of personal surgical experience, perceptions about the best thromboprophylaxis options, and actual practices in their work environment. Results From December 2020 to January 2021, 243 participants answered the questionnaire. All, except for 3 (1.2%), reported using thromboprophylaxis, and most (76%) combined pharmacological and mechanical techniques. The most prescribed drug was enoxaparin (87%), which changed to rivaroxaban (65%) after discharge. The time of thromboprophylaxis initiation varied according to the length of training of the knee surgeon ( p ≤ 0.03), and their preferences and practices differed according to the Brazilian region ( p < 0.05) and the health system in which the surgeons work (public or private sector; p = 0.024). The option for mechanical thromboprophylaxis also depended on the training time of the surgeon. Conclusion Thromboprophylaxis preferences and practices in TKA are diverse across Brazilian regions and health systems (public or private sectors). Given the lack of a national clinical guideline, most orthopedists follow either their hospital guidelines or none. The mechanical prophylaxis method and the little use of aspirin are the points that most diverge from international guidelines and practices.

Preferences and Practices of Brazilian Orthopedists for Thromboprophylaxis Techniques in Total Knee Arthroplasty: Survey Among Members of the Brazilian Society of Knee Surgery (SBCJ) / Preferências e práticas de ortopedistas brasileiros por técnicas de tromboprofilaxia na artroplastia total do joelho: Levantamento entre membros da Sociedade Brasileira de Cirurgia do Joelho (SBCJ)

Abstract Objective The present study describes the preferences and current practices of a sample of knee surgeons in Brazil regarding thromboprophylaxis in total knee arthroplasty (TKA). Method In the present internet survey, surgeons from the Brazilian Knee Surgery Society (SBCJ, in the Portuguese acronym) voluntarily answered an anonymous questionnaire including time of personal surgical experience, perceptions about the best thromboprophylaxis options, and actual practices in their work environment. Results From December 2020 to January 2021, 243 participants answered the questionnaire. All, except for 3 (1.2%), reported using thromboprophylaxis, and most (76%) combined pharmacological and mechanical techniques. The most prescribed drug was enoxaparin (87%), which changed to rivaroxaban (65%) after discharge. The time of thromboprophylaxis initiation varied according to the length of training of the knee surgeon (p ≤ 0.03), and their preferences and practices differed according to the Brazilian region (p< 0.05) and the health system in which the surgeons work (public or private sector; p= 0.024). The option for mechanical thromboprophylaxis also depended on the training time of the surgeon. Conclusion Thromboprophylaxis preferences and practices in TKA are diverse across Brazilian regions and health systems (public or private sectors). Given the lack of a national clinical guideline, most orthopedists follow either their hospital guidelines or none. The mechanical prophylaxis method and the little use of aspirin are the points that most diverge from international guidelines and practices.

Resumo Objetivo Descrever as preferências e práticas atuais de uma amostra de cirurgiões de joelho do Brasil quanto à forma de tromboprofilaxia na artroplastia total do joelho (ATJ). Método presente pesquisa realizada pela internet, cirurgiões associados à Sociedade Brasileira de Cirurgia do Joelho (SBCJ) foram convidados a responder voluntariamente a um questionário anônimo incluindo o tempo de experiência cirúrgica pessoal, percepções sobre as melhores opções de tromboprofilaxia e as reais práticas no ambiente onde trabalham. Resultados Entre dezembro de 2020 e janeiro de 2021, 243 participantes responderam ao questionário completo. Exceto por 3 (1,2%) participantes, todos declararam praticar tromboprofilaxia, a maioria (76%) combinando as formas farmacológica e mecânica. A droga mais prescrita é a enoxaparina (87%), com modificação para rivaroxabana (65%) após a alta. O momento de início da tromboprofilaxia variou conforme o tempo de formação do cirurgião de joelho (p ≤ 0,03) e as preferências e práticas variaram conforme a região do país (p< 0,05) e o sistema de saúde no qual trabalham os cirurgiões (público ou privado; p= 0,024). A opção por tromboprofilaxia mecânica também dependeu do tempo de formação do cirurgião. Conclusão As preferências e práticas de tromboprofilaxia na ATJ são diversas nas regiões do Brasil e sistemas de saúde (público ou privado). Dada a inexistência de uma diretriz clínica nacional, a maior parte dos ortopedistas segue ou a diretriz de seu próprio hospital ou nenhuma. O método de profilaxia mecânica e a pouca utilização do ácido acetilsalicílico são os pontos que mais destoam das diretrizes e práticas internacionais.

ABP1-TMK auxin perception for global phosphorylation and auxin canalization.

The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1-3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.

To Retain or Resurface the Patella in Primary Total Knee Arthroplasty: A Comparative Study.

Objective To evaluate and compare clinically and functionally patients undergoing primary total knee arthroplasty (TKA) with preservation or replacement of the patella. Methods In a cross-sectional study, the functional results were evaluated and compared, using the Western Ontario and McMaster Universities (WOMAC) and Lequesne scores, of 158 patients undergoing primary TKA (162 knees); in 81 knees the patella was submitted to arthroplasty and in 81 the joint surface of the patella was preserved. Results No significant differences were identified in terms of the Lequesne score (p = 0.585), global WOMAC score (p = 0.169), nor in terms of its subdivisions regarding stiffness (p = 0.796) and functional capacity (p = 0.190). There was a significant difference only in terms of the subdivision that evaluates pain in the WOMAC score, being lower in the group undergoing patellar arthroplasty (p = 0.036). Conclusion In the present study, there was no difference in functional assessment in patients who underwent or not patellar replacement during primary knee arthroplasty surgery. However, individuals in whom the patella was preserved reported more pain.

To Retain or Resurface the Patella in Primary Total Knee Arthroplasty: A Comparative Study / Preservar ou substituir a patela durante a artroplastia total de joelho: Estudo comparativo

Abstract Objective To evaluate and compare clinically and functionally patients undergoing primary total knee arthroplasty (TKA) with preservation or replacement of the patella. Methods In a cross-sectional study, the functional results were evaluated and compared, using the Western Ontario and McMaster Universities (WOMAC) and Lequesne scores, of 158 patients undergoing primary TKA (162 knees); in 81 knees the patella was submitted to arthroplasty and in 81 the joint surface of the patella was preserved. Results No significant differences were identified in terms of the Lequesne score (p = 0.585), global WOMAC score (p = 0.169), nor in terms of its subdivisions regarding stiffness (p = 0.796) and functional capacity (p = 0.190). There was a significant difference only in terms of the subdivision that evaluates pain in the WOMAC score, being lower in the group undergoing patellar arthroplasty (p = 0.036). Conclusion In the present study, there was no difference in functional assessment in patients who underwent or not patellar replacement during primary knee arthroplasty surgery. However, individuals in whom the patella was preserved reported more pain.

Resumo Objetivo Avaliar e comparar clínica e funcionalmente pacientes submetidos a artroplastia total primária do joelho (ATJ) com preservação ou substituição da patela. Métodos Em um estudo transversal, foram avaliados e comparados os resultados funcionais, usando escores de Western Ontario and McMaster Universities (WOMAC, na sigla em inglês) e Lequesne, de 158 pacientes submetidos a artroplastia total primária o joelho (162 joelhos), sendo que em 81 joelhos a patela foi submetidaa artroplastiae em 81 a superfície articular da patela foi preservada. Resultados Não foram identificadas diferenças significativas quanto ao escore de Lequesne (p = 0,585), escore global de WOMAC (p = 0,169), nem quanto às subdivisões deste quanto a rigidez (p = 0,796) e a capacidade funcional (p= 0,190). Evidenciou-se diferença significativa apenas quanto à subdivisão que avalia a dor no escore de WOMAC, sendo menor no grupo submetido a artroplastia patelar (p = 0,036). Conclusão No presente estudo, não houve diferença na avaliação funcional em pacientes submetidos a substituição ou não da patela durante a cirurgia de artroplastia primária do joelho. Entretanto, os indivíduos nos quais a patela foi preservada relataram mais dor.

Direct ETTIN-auxin interaction controls chromatin states in gynoecium development.

Hormonal signalling in animals often involves direct transcription factor-hormone interactions that modulate gene expression. In contrast, plant hormone signalling is most commonly based on de-repression via the degradation of transcriptional repressors. Recently, we uncovered a non-canonical signalling mechanism for the plant hormone auxin whereby auxin directly affects the activity of the atypical auxin response factor (ARF), ETTIN towards target genes without the requirement for protein degradation. Here we show that ETTIN directly binds auxin, leading to dissociation from co-repressor proteins of the TOPLESS/TOPLESS-RELATED family followed by histone acetylation and induction of gene expression. This mechanism is reminiscent of animal hormone signalling as it affects the activity towards regulation of target genes and provides the first example of a DNA-bound hormone receptor in plants. Whilst auxin affects canonical ARFs indirectly by facilitating degradation of Aux/IAA repressors, direct ETTIN-auxin interactions allow switching between repressive and de-repressive chromatin states in an instantly-reversible manner.

Chromatin Immunoprecipitation (ChIP) to Assess Histone Marks in Auxin-treated Arabidopsis thaliana Inflorescence Tissue.

Chromatin Immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) or high-throughput sequencing (ChIP-seq) has become the gold standard for the identification of binding sites of DNA binding proteins and the localization of histone modification on a locus-specific or genome-wide scale, respectively. ChIP experiments can be divided into seven critical steps: (A) sample collection, (B) crosslinking of proteins to DNA, (C) nuclear extraction, (D) chromatin isolation and fragmentation by sonication, (E) immunoprecipitation of histone marks by appropriate antibodies, (F) DNA recovery, and (G) identification of precipitated protein-associated DNA by qPCR or high-throughput sequencing. Here, we describe a time-efficient protocol that can be used for ChIP-qPCR experiments to study the localization of histone modifications in young inflorescences of the model plants Arabidopsis thaliana.

Two Auxin Response Elements Fine-Tune PINOID Expression During Gynoecium Development in Arabidopsis thaliana.

The plant hormone auxin controls almost all aspects of plant development through the gene regulatory properties of auxin response factors (ARFs) which bind so-called auxin responsive elements (AuxREs) in regulatory regions of their target genes. It has been proposed that ARFs interact and cooperate with other transcription factors (TFs) to bind to complex DNA-binding sites harboring cis-elements for several TFs. Complex DNA-binding sites have not been studied systematically for ARF target genes. ETTIN (ETT; ARF3) is a key regulator of gynoecium development. Cooperatively with its interacting partner INDEHISCENT (IND), ETT regulates PINOID (PID), a gene involved in the regulation gynoecium apical development (style development). Here, we mutated two ETT-bound AuxREs within the PID promoter and observed increased style length in gynoecia of plants carrying mutated promoter variants. Furthermore, mutating the AuxREs led to ectopic repression of PID in one developmental context while leading to ectopically upregulated PID expression in another stage. Our data also show that IND associates with the PID promoter in an auxin-sensitive manner. In summary, we demonstrate that targeted mutations of cis-regulatory elements can be used to dissect the importance of single cis-regulatory elements within complex regulatory regions supporting the importance of the ETT-IND interaction for PID regulation. At the same time, our work also highlights the challenges of such studies, as gene regulation is highly robust, and mutations within gene regulatory regions may only display subtle phenotypes.

Auxin Response Factors promote organogenesis by chromatin-mediated repression of the pluripotency gene SHOOTMERISTEMLESS.

Specification of new organs from transit amplifying cells is critical for higher eukaryote development. In plants, a central stem cell pool maintained by the pluripotency factor SHOOTMERISTEMLESS (STM), is surrounded by transit amplifying cells competent to respond to auxin hormone maxima by giving rise to new organs. Auxin triggers flower initiation through Auxin Response Factor (ARF) MONOPTEROS (MP) and recruitment of chromatin remodelers to activate genes promoting floral fate. The contribution of gene repression to reproductive primordium initiation is poorly understood. Here we show that downregulation of the STM pluripotency gene promotes initiation of flowers and uncover the mechanism for STM silencing. The ARFs ETTIN (ETT) and ARF4 promote organogenesis at the reproductive shoot apex in parallel with MP via histone-deacetylation mediated transcriptional silencing of STM. ETT and ARF4 directly repress STM, while MP acts indirectly, through its target FILAMENTOUS FLOWER (FIL). Our data suggest that - as in animals- downregulation of the pluripotency program is important for organogenesis in plants.

Assessment of the alpha angle and mobility of the hip in patients with noncontact anterior cruciate ligament injury.

PURPOSE: To evaluate the alpha angle of the hip in patients with noncontact anterior cruciate ligament (ACL) injury and compare it with patients without injury. In addition, external and internal rotation of the hip was assessed and correlated with the alpha angle. METHODS: The alpha angle of the ipsilateral hip was assessed in 41 subjects with non-contact ACL tear and compared with 39 subjects with no tear. The external and internal rotation of the ipsilateral hip was also evaluated. RESULTS: The alpha angle was larger in subjects with noncontact ACL injury. The mean was 70.31° (±13.92°) compared with 58.55° (±13.95°) in the control group (p < 0.001). The groups were similar when considering the external, internal, and sum of rotation of the ipsilateral hip. There was no correlation between the alpha angle and decreased rotational range of motion of the hip in either group (p > 0.05). CONCLUSION: Patients with noncontact ACL injury presented a greater alpha angle when compared with the group without tear. There was no difference in the rotational mobility of the hip between groups, nor was there a correlation between the increase in the alpha angle and the decrease in the rotational mobility of the hip.

Regenerative potential of the cartilaginous tissue in mesenchymal stem cells: update, limitations, and challenges.

Advances in the studies with adult mesenchymal stem cells (MSCs) have turned tissue regenerative therapy into a promising tool in many areas of medicine. In orthopedics, one of the main challenges has been the regeneration of cartilage tissue, mainly in diarthroses. In the induction of the MSCs, in addition to cytodifferentiation, the microenvironmental context of the tissue to be regenerated and an appropriate spatial arrangement are extremely important factors. Furthermore, it is known that MSC differentiation is fundamentally determined by mechanisms such as cell proliferation (mitosis), biochemical-molecular interactions, movement, cell adhesion, and apoptosis. Although the use of MSCs for cartilage regeneration remains at a research level, there are important questions to be resolved in order to make this therapy efficient and safe. It is known, for instance, that the expansion of chondrocytes in cultivation, needed to increase the number of cells, could end up producing fibrocartilage instead of hyaline cartilage. However, the latest results are promising. In 2014, the first stage I/II clinical trial to evaluate the efficacy and safety of the intra-articular injection of MSCs in femorotibial cartilage regeneration was published, indicating a decrease in injured areas. One issue to be explored is how many modifications in the articulate inflammatory environment could induce differentiation of MSCs already allocated in that region. Such issue arose from studies that suggested that the suppression of the inflammation may increase the efficiency of tissue regeneration. Considering the complexity of the events related to the chondrogenesis and cartilage repair, it can be concluded that the road ahead is still long, and that further studies are needed.

Os avanços nos estudos com células-tronco mesenquimais (CTMs) adultas tornou a terapia regenerativa tecidual uma ferramenta promissora em diversas áreas da medicina. Na ortopedia, um dos principais desafios tem sido a regeneração do tecido cartilaginoso, sobretudo em diartroses. Na indução de CTMs, além da citodiferenciação, o contexto microambiental do tecido a ser regenerado, bem como uma disposição espacial adequada, são fatores de extrema importância. Além disso, sabe-se que a diferenciação das CTMs é basicamente determinada por mecanismos como proliferação celular (mitose), interações bioquímico-moleculares, movimento, adesão celular e apoptose. Apesar de o uso de CTMs para a regeneração da cartilagem estar ainda em âmbito de pesquisa, existem questões importantes a serem resolvidas para tornar essa terapêutica eficaz e segura. Sabe-se, por exemplo, que a expansão de condrócitos em cultura, necessária para aumentar o número de células, pode produzir fibrocartilagem, e não cartilagem hialina. No entanto, os últimos resultados são promissores. Em 2014, foi publicado o primeiro ensaio clínico fase I/II para avaliar a eficácia e a segurança da injeção intra-articular de CTMs na regeneração de cartilagem femorotibial e houve uma diminuição das áreas lesadas. Uma questão a ser explorada é o quanto modificações no próprio ambiente inflamatório articular poderiam induzir a diferenciação de CTMs já alocadas naquela região. Tal incógnita parte do princípio de estudos que sugerem que a supressão da inflamação articular aumentaria, potencialmente, a eficiência da regeneração tecidual. Considerando a complexidade dos eventos relacionados à condrogênese e ao reparo da cartilagem, conclui-se que o caminho ainda é longo, são necessárias pesquisas complementares.

Regenerative potential of the cartilaginous tissue in mesenchymal stem cells: update, limitations, and challenges / Potencial regenerativo do tecido cartilaginoso por células-tronco mesenquimais: atualização, limitações e desafios

ABSTRACT Advances in the studies with adult mesenchymal stem cells (MSCs) have turned tissue regenerative therapy into a promising tool in many areas of medicine. In orthopedics, one of the main challenges has been the regeneration of cartilage tissue, mainly in diarthroses. In the induction of the MSCs, in addition to cytodifferentiation, the microenvironmental context of the tissue to be regenerated and an appropriate spatial arrangement are extremely important factors. Furthermore, it is known that MSC differentiation is fundamentally determined by mechanisms such as cell proliferation (mitosis), biochemical-molecular interactions, movement, cell adhesion, and apoptosis. Although the use of MSCs for cartilage regeneration remains at a research level, there are important questions to be resolved in order to make this therapy efficient and safe. It is known, for instance, that the expansion of chondrocytes in cultivation, needed to increase the number of cells, could end up producing fibrocartilage instead of hyaline cartilage. However, the latest results are promising. In 2014, the first stage I/II clinical trial to evaluate the efficacy and safety of the intra-articular injection of MSCs in femorotibial cartilage regeneration was published, indicating a decrease in injured areas. One issue to be explored is how many modifications in the articulate inflammatory environment could induce differentiation of MSCs already allocated in that region. Such issue arose from studies that suggested that the suppression of the inflammation may increase the efficiency of tissue regeneration. Considering the complexity of the events related to the chondrogenesis and cartilage repair, it can be concluded that the road ahead is still long, and that further studies are needed.

RESUMO Os avanços nos estudos com células-tronco mesenquimais (CTMs) adultas tornou a terapia regenerativa tecidual uma ferramenta promissora em diversas áreas da medicina. Na ortopedia, um dos principais desafios tem sido a regeneração do tecido cartilaginoso, sobretudo em diartroses. Na indução de CTMs, além da citodiferenciação, o contexto microambiental do tecido a ser regenerado, bem como uma disposição espacial adequada, são fatores de extrema importância. Além disso, sabe-se que a diferenciação das CTMs é basicamente determinada por mecanismos como proliferação celular (mitose), interações bioquímico-moleculares, movimento, adesão celular e apoptose. Apesar de o uso de CTMs para a regeneração da cartilagem estar ainda em âmbito de pesquisa, existem questões importantes a serem resolvidas para tornar essa terapêutica eficaz e segura. Sabe-se, por exemplo, que a expansão de condrócitos em cultura, necessária para aumentar o número de células, pode produzir fibrocartilagem, e não cartilagem hialina. No entanto, os últimos resultados são promissores. Em 2014, foi publicado o primeiro ensaio clínico fase I/II para avaliar a eficácia e a segurança da injeção intra-articular de CTMs na regeneração de cartilagem femorotibial e houve uma diminuição das áreas lesadas. Uma questão a ser explorada é o quanto modificações no próprio ambiente inflamatório articular poderiam induzir a diferenciação de CTMs já alocadas naquela região. Tal incógnita parte do princípio de estudos que sugerem que a supressão da inflamação articular aumentaria, potencialmente, a eficiência da regeneração tecidual. Considerando a complexidade dos eventos relacionados à condrogênese e ao reparo da cartilagem, conclui-se que o caminho ainda é longo, são necessárias pesquisas complementares.

Femoral tunnel enlargement after anterior cruciate ligament reconstruction using RigidFix compared with extracortical fixation.

PURPOSE: The aim of this study was to compare femoral tunnel enlargement after anterior cruciate ligament (ACL) reconstruction surgery using hamstring autograft tendons fixed by bioabsorbable femoral trans-tunnel pins with that in patients in which the graft was fixed with extracortical fixation. METHODS: Forty-three patients were randomly selected from our database and included in the study. Femoral tunnel diameter was measured by computed tomography in 20 patients who underwent ACL reconstruction via anteromedial portal technique using autologous quadruple hamstrings, fixed with two bioabsorbable trans-tunnel pins, RigidFix, on the femoral side and compared with 23 patients in whom extracortical fixation, EndoButton CL, was used. The diameter of the femoral tunnel was measured at a distance of 5 mm from the tunnel entrance and at the largest diameter along the tunnel axis. Data were compared with the diameter of the drill used during surgery. Clinical evaluation was performed using the Lysholm score, IKDC subjective score and anterior knee laxity measurements. RESULTS: Femoral tunnel enlargement 5 mm from the entrance and at the largest diameter was greater in the RigidFix group than the EndoButton group. There were no significant differences between the two groups regarding age, gender, post-operative Lysholm score, IKDC subjective score or knee laxity measurements. CONCLUSION: The present study showed greater enlargement of the femoral bone tunnel when a bioabsorbable trans-tunnel pin system was used with the medial portal technique when compared to extracortical fixation. These findings confirm that femoral tunnel widening should be considered when RigidFix was used in ACL reconstruction by anteromedial portal technique. LEVEL OF EVIDENCE: III.

Genome-Wide Association Mapping and Genomic Prediction Elucidate the Genetic Architecture of Morphological Traits in Arabidopsis.

Quantitative traits in plants are controlled by a large number of genes and their interaction with the environment. To disentangle the genetic architecture of such traits, natural variation within species can be explored by studying genotype-phenotype relationships. Genome-wide association studies that link phenotypes to thousands of single nucleotide polymorphism markers are nowadays common practice for such analyses. In many cases, however, the identified individual loci cannot fully explain the heritability estimates, suggesting missing heritability. We analyzed 349 Arabidopsis accessions and found extensive variation and high heritabilities for different morphological traits. The number of significant genome-wide associations was, however, very low. The application of genomic prediction models that take into account the effects of all individual loci may greatly enhance the elucidation of the genetic architecture of quantitative traits in plants. Here, genomic prediction models revealed different genetic architectures for the morphological traits. Integrating genomic prediction and association mapping enabled the assignment of many plausible candidate genes explaining the observed variation. These genes were analyzed for functional and sequence diversity, and good indications that natural allelic variation in many of these genes contributes to phenotypic variation were obtained. For ACS11, an ethylene biosynthesis gene, haplotype differences explaining variation in the ratio of petiole and leaf length could be identified.