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Spinocerebellar ataxias (SCA) are most frequently due to (CAG)n (coding for polyglutamine, polyQ) expansions and, less so, to expansion of other oligonucleotide repeats (non-polyQ) or other type of variants (non-repeat expansion SCA). In this study we compared polyQ and non-repeat expansion SCA, in a cohort of patients with hereditary ataxia followed at a tertiary hospital. From a prospective study, 88 patients (51 families) with SCA were selected, 74 (40 families) of whom genetically diagnosed. Thirty-eight patients (51.4%, 19 families) were confirmed as having a polyQ (no other repeat-expansions were identified) and 36 (48.6%, 21 families) a non-repeat expansion SCA. Median age-at-onset was 39.5 [30.0-45.5] for polyQ and 7.0 years [1.00-21.50] for non-repeat expansion SCA. PolyQ SCA were associated with cerebellar onset, and non-repeat expansion forms with non-cerebellar onset. Time to diagnosis was longer for non-repeat expansion SCA. The most common polyQ SCA were Machado-Joseph disease (MJD/SCA3) (73.7%) and SCA2 (15.8%); whereas in non-repeat expansion SCA ATX-CACNA1A (14.3%), ATP1A3-related ataxia, ATX-ITPR1, ATX/HSP-KCNA2, and ATX-PRKCG (9.5% each) predominated. Disease duration (up to inclusion) was significantly higher in non-repeat expansion SCA, but the difference in SARA score was not statistically significant. Cerebellar peduncles and pons atrophy were more common in polyQ ataxias, as was axonal neuropathy. SCA had a wide range of genetic etiology, age-at-onset and presentation. Proportion of polyQ and non-repeat expansion SCA was similar; the latter had a higher genetic heterogeneity. While polyQ ataxias were typically linked to cerebellar onset in adulthood, non-repeat expansion forms associated with early onset and non-cerebellar presentations.
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Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.
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The COVID-19 pandemic has brought about significant changes to the life of most individuals, worldwide. This study explores the cultural factors influencing decision-making during the pandemic, and is part of the CORNER Project, funded by the Research Council of Norway, aimed at understanding institutional response in the early phases of the Covid-19 emergency in Norway, Sweden, and Italy. Semi-structured interviews with key political-administrative leaders in Italy (N = 35) were conducted and content-analyzed, allowing the identification of the underlying cultural dynamics that played a role in these decisions. Thematic analysis was used to assess the influence of cultural factors on the crisis management and early reaction of institutions and citizens to the spread of Covid. In line with previous studies, and as expected, the individualism vs. collectivism dimension can explain differential health outcomes during the outbreak. In this paper we argue that individualism-collectivism cultural values can also play a pivotal role in public compliance with Covid-19 restrictions, and psychological responses during the pandemic.
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Simulation theories predict that the observation of other's expressions modulates neural activity in the same centers controlling their production. This hypothesis has been developed by two models, postulating that the visual input is directly projected either to the motor system for action recognition (motor resonance) or to emotional/interoceptive regions for emotional contagion and social synchronization (emotional resonance). Here we investigated the role of frontal/insular regions in the processing of observed emotional expressions by combining intracranial recording, electrical stimulation and effective connectivity. First, we intracranially recorded from prefrontal, premotor or anterior insular regions of 44 patients during the passive observation of emotional expressions, finding widespread modulations in prefrontal/insular regions (anterior cingulate cortex, anterior insula, orbitofrontal cortex and inferior frontal gyrus) and motor territories (rolandic operculum and inferior frontal junction). Subsequently, we electrically stimulated the activated sites, finding that (a) in the anterior cingulate cortex and anterior insula, the stimulation elicited emotional/interoceptive responses, as predicted by the 'emotional resonance model', (b) in the rolandic operculum it evoked face/mouth sensorimotor responses, in line with the 'motor resonance' model, and (c) all other regions were unresponsive or revealed functions unrelated to the processing of facial expressions. Finally, we traced the effective connectivity to sketch a network-level description of these regions, finding that the anterior cingulate cortex and the anterior insula are reciprocally interconnected while the rolandic operculum is part of the parieto-frontal circuits and poorly connected with the formers. These results support the hypothesis that the pathways hypothesized by the 'emotional resonance' and the 'motor resonance' models work in parallel, differing in terms of spatio-temporal fingerprints, reactivity to electrical stimulation and connectivity patterns.
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Phytotoxins produced by marine microalgae, such as paralytic shellfish toxins (PSTs), can accumulate in bivalve molluscs, representing a human health concern due to the life-threatening symptoms they cause. To avoid the commercialization of contaminated bivalves, monitoring programs were established in the EU. The purpose of this work is the implementation of a PST transforming enzyme-carbamoylase-in an impedimetric test for rapid simultaneous detection of several carbamate and N-sulfocarbamoyl PSTs. Carbamoylase hydrolyses carbamate and sulfocarbamoyl toxins, which may account for up to 90% of bivalve toxicity related to PSTs. Conformational changes of carbamoylase accompanying enzymatic reactions were probed by Fourier transform mid-infrared spectroscopy (FT-MIR) and electrochemical impedance spectroscopy (EIS). Furthermore, a combination of EIS with a metal electrode and a carbamoylase-based assay was employed to harness changes in the enzyme conformation and adsorption on the electrode surface during the enzymatic reaction as an analytical signal. After optimization of the working conditions, the developed impedimetric e-tongue could quantify N-sulfocarbamoyl toxins with a detection limit of 0.1 µM. The developed e-tongue allows the detection of these toxins at concentration levels observed in bivalves with PST toxicity close to the regulatory limit. The quantification of a sum of N-sulfocarbamoyl PSTs in naturally contaminated mussel extracts using the developed impedimetric e-tongue has been demonstrated.
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Bivalvos , Intoxicación por Mariscos , Animales , Humanos , Toxinas Marinas/química , Nariz Electrónica , Bivalvos/química , Mariscos/análisis , Carbamatos , Intoxicación por Mariscos/etiologíaRESUMEN
For decades, cells of the Gram-positive bacterial pathogen Staphylococcus aureus were thought to lack a dedicated elongation machinery. However, S. aureus cells were recently shown to elongate before division, in a process that requires a shape elongation division and sporulation (SEDS)/penicillin-binding protein (PBP) pair for peptidoglycan synthesis, consisting of the glycosyltransferase RodA and the transpeptidase PBP3. In ovococci and rod-shaped bacteria, the elongation machinery, or elongasome, is composed of various proteins besides a dedicated SEDS/PBP pair. To identify proteins required for S. aureus elongation, we screened the Nebraska Transposon Mutant Library, which contains transposon mutants in virtually all non-essential staphylococcal genes, for mutants with modified cell shape. We confirmed the roles of RodA/PBP3 in S. aureus elongation and identified GpsB, SsaA, and RodZ as additional proteins involved in this process. The gpsB mutant showed the strongest phenotype, mediated by the partial delocalization from the division septum of PBP2 and PBP4, two penicillin-binding proteins that synthesize and cross-link peptidoglycan. Increased levels of these PBPs at the cell periphery versus the septum result in higher levels of peptidoglycan insertion/crosslinking throughout the entire cell, possibly overriding the RodA/PBP3-mediated peptidoglycan synthesis at the outer edge of the septum and/or increasing stiffness of the peripheral wall, impairing elongation. Consequently, in the absence of GpsB, S. aureus cells become more spherical. We propose that GpsB has a role in the spatio-temporal regulation of PBP2 and PBP4 at the septum versus cell periphery, contributing to the maintenance of the correct cell morphology in S. aureus. IMPORTANCE: Staphylococcus aureus is a Gram-positive clinical pathogen, which is currently the second cause of death by antibiotic-resistant infections worldwide. For decades, S. aureus cells were thought to be spherical and lack the ability to undergo elongation. However, super-resolution microscopy techniques allowed us to observe the minor morphological changes that occur during the cell cycle of this pathogen, including cell elongation. S. aureus elongation is not required for normal growth in laboratory conditions. However, it seems to be essential in the context of some infections, such as osteomyelitis, during which S. aureus cells apparently elongate to invade small channels in the bones. In this work, we uncovered new determinants required for S. aureus cell elongation. In particular, we show that GpsB has an important role in the spatio-temporal regulation of PBP2 and PBP4, two proteins involved in peptidoglycan synthesis, contributing to the maintenance of the correct cell morphology in S. aureus.
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Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Staphylococcus aureus/genética , Proteínas Bacterianas/metabolismo , Peptidoglicano/metabolismo , Proteínas de Unión a las Penicilinas/metabolismo , Infecciones Estafilocócicas/microbiología , Morfogénesis , Pared Celular/metabolismoRESUMEN
Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b+CD10+CD16+CD11b+ PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.
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Células Supresoras de Origen Mieloide , Neoplasias , Humanos , Neutrófilos , Células Supresoras de Origen Mieloide/metabolismo , Células Supresoras de Origen Mieloide/patología , Subtipo EP2 de Receptores de Prostaglandina E/metabolismo , Factor Estimulante de Colonias de Granulocitos/farmacología , Factor Estimulante de Colonias de Granulocitos/metabolismo , Neoplasias/patología , Antígeno CD52/metabolismo , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/metabolismoRESUMEN
Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical responses to immunotherapy. In this study, we used next-generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed to identify biomarkers associated with immunotherapy response and assess the potential application of simple non-invasive blood biomarkers as a therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICIs. Interestingly, in both, a common lymphocytic activation signature can be identified associated with the efficient response to immunotherapy, including a blood-specific CD8+ T cell activation/proliferation signature which predicts the immunotherapy response.
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Objetivo: Aprender como foi experienciar o nascimento de um filho durante a pandemia da COVID-19. Método: estudo qualitativo cujos dados foram coletados em setembro de 2021, mediante entrevistas semi-estruturadas, audiogravadas, com 11 mães e submetidos à análise de conteúdo, modalidade temática. Resultados: emergiram duas categorias, as quais mostram que o nascimento do filho durante a pandemia foi vivenciado de forma restritiva o que suscitou sentimentos como medo, ansiedade, preocupação, frustração, mas também de alívio, felicidade e superação. A possibilidade de usar recursos das mídias sociais para contatos com amigos e familiares constituiu fonte de apoio informacional e emocional. Considerações finais: O apoio da rede social, ainda que de forma virtual, foi fundamental para o enfrentamento das adversidades do período. Entre as estratégias adotadas estão o apoio da família e as redes sociais, de modo a minimizar o isolamento.
Objective: to understand what it was like to experience the birth of a child during the COVID-19 pandemic. Method: qualitative study whose data were collected in September 2021, through semi-structured, audio-recorded interviews with 11 mothers and submitted to content analysis, thematic modality. Results: two categories emerged, which show that the birth of the child during the pandemic was experienced in a restrictive way, which aroused feelings such as fear, anxiety, worry, frustration, but also relief, happiness and overcoming. The possibility of using social media resources to contact friends and family was a source of informational and emotional support. Final considerations: The support of the social network, even if it was virtual, was fundamental to face the adversities of the period, some strategies were adopted, such as family support and social networks as a way to minimize isolation.
Objetivo: comprender cómo fue vivir el nacimiento de un niño durante la pandemia de COVID-19. Método: estudio cualitativo cuyos datos fueron recolectados en septiembre de 2021, a través de entrevistas semiestructuradas, grabadas en audio con 11 madres y sometidas a análisis de contenido, modalidad temática. Resultados: surgieron dos categorías, que muestran que el nacimiento del niño durante la pandemia fue vivido de forma restrictiva, lo que despertó sentimientos como miedo, ansiedad, preocupación, frustración, pero también alivio, felicidad y superación. La posibilidad de utilizar los recursos de las redes sociales para contactar a amigos y familiares fue una fuente de apoyo informativo y emocional. Consideraciones finales: El apoyo de la red social, aunque sea virtual, fue fundamental para enfrentar las adversidades del período, se adoptaron algunas estrategias, como el apoyo familiar y las redes sociales como forma de minimizar el aislamiento.
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The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients either do not respond to ICI monotherapy or develop resistance to it after an initial response. Therefore, the identification of biomarkers for predicting the response of patients to ICI monotherapy represents an urgent issue. Great efforts are currently dedicated toward identifying blood-based biomarkers to predict responses to ICI monotherapy. In this study, more commonly utilized blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and the lung immune prognostic index (LIPI) score, as well as the frequency/number and activation status of various types of circulating innate immune cell populations, were evaluated in NSCLC patients at baseline before therapy initiation. The data indicated that, among all the parameters tested, low plasmacytoid dendritic cell (pDC), slan+-monocyte and natural killer cell counts, as well as a high LIPI score and elevated PD-L1 expression levels on type 1 conventional DCs (cDC1s), were independently correlated with a negative response to ICI therapy in NSCLC patients. The results from this study suggest that the evaluation of innate immune cell numbers and phenotypes may provide novel and promising predictive biomarkers for ICI monotherapy in NSCLC patients.
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The guava tree (Psidium guajava) is a tropical species native to South America and is recognized as the 11th most economically important fruit tree in Brazil. However, the presence of the nematode Meloidogyne enterolobii and the fungus Fusarium solani in the roots of guava plants leads to the development of root galls, causing significant damage. In contrast, the species P. guineense and P. cattleianum have been identified as resistant and immune to the nematode, respectively. In this study, the researchers aimed to compare the metabolomic profiles of infected and uninfected roots of P. guajava, P. cattleianum, and P. guineense using mass spectrometry coupled with liquid chromatography (LC-MS). The goal was to identify secondary metabolites that could potentially be utilized as biochemical resources for nematode control. The findings of the study demonstrated that the plant metabolism of all three species undergoes alterations in response to the phytopathogen inoculation. By employing molecular networks, the researchers identified that the secondary metabolites affected by the infection, whether produced or suppressed, are primarily of a polar chemical nature. Further analysis of the database confirmed the polar nature of the regulated substances after infection, specifically hydrolysable tannins and lignans in P. guineense and P. cattleianum. Interestingly, a group of non-polar substances belonging to the terpene class was also identified in the resistant and immune species. This suggests that these terpenes may act as inhibitors of M. enterolobii, working as repellents or as molecules that can reduce oxidative stress during the infection process, thus enhancing the guava resistance to the nematode. Overall, this study provides valuable insights into the metabolic alterations occurring in different Psidium spp. in response to M. enterolobii infection. The identification of specific secondary metabolites, particularly terpenes, opens up new possibilities for developing effective strategies to control the nematode and enhance guava resistance.
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The bacterial divisome is a macromolecular machine composed of more than 30 proteins that controls cell wall constriction during division. Here, we present a model of the structure and dynamics of the core complex of the E. coli divisome, supported by a combination of structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis. We focus on the septal cell wall synthase complex formed by FtsW and FtsI, and its regulators FtsQ, FtsL, FtsB, and FtsN. The results indicate extensive interactions in four regions in the periplasmic domains of the complex. FtsQ, FtsL, and FtsB support FtsI in an extended conformation, with the FtsI transpeptidase domain lifted away from the membrane through interactions among the C-terminal domains. FtsN binds between FtsI and FtsL in a region rich in residues with superfission (activating) and dominant negative (inhibitory) mutations. Mutagenesis experiments and simulations suggest that the essential domain of FtsN links FtsI and FtsL together, potentially modulating interactions between the anchor-loop of FtsI and the putative catalytic cavity of FtsW, thus suggesting a mechanism of how FtsN activates the cell wall synthesis activities of FtsW and FtsI.
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Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , División Celular , Proteínas de Ciclo Celular/metabolismo , Proteínas de la Membrana/metabolismo , Pared Celular/metabolismo , Proteínas Bacterianas/metabolismoRESUMEN
INTRODUCTION: Valve surgery through a median sternotomy has been the standard approach, but in the past decade various minimally invasive procedures have gained increasing traction among physicians and patients. MATERIALS AND METHODS: We present a series of three patients submitted to minimally invasive combined aortic and mitral valve surgery, performed through right lateral thoracotomy. RESULTS: We report no postoperative complication or mortality. Mean length of stay was 5 days, with a self-reported pain score 2/5 (mild/annoying pain). CONCLUSIONS: We report our initial experience, describing surgical technique and postoperative results, showing this technique to be safe, reproductible and comparable to conventional surgery.
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Procedimientos Quirúrgicos Cardíacos , Válvula Mitral , Humanos , Válvula Mitral/diagnóstico por imagen , Resultado del Tratamiento , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Toracotomía/métodosRESUMEN
Executive function (EF) describes a group of cognitive processes underlying the organization and control of goal-directed behaviour. Environmental experience appears to play a crucial role in EF development, with early psychosocial deprivation often linked to EF impairment. However, many questions remain concerning the developmental trajectories of EF after exposure to deprivation, especially concerning specific mechanisms. Accordingly, using an 'A-not-B' paradigm and a macaque model of early psychosocial deprivation, we investigated how early deprivation influences EF development longitudinally from adolescence into early adulthood. The contribution of working memory and inhibitory control mechanisms were examined specifically via the fitting of a computational model of decision making to the choice behaviour of each individual. As predicted, peer-reared animals (i.e. those exposed to early psychosocial deprivation) performed worse than mother-reared animals across time, with the fitted model parameters yielding novel insights into the functional decomposition of group-level EF differences underlying task performance. Results indicated differential trajectories of inhibitory control and working memory development in the two groups. Such findings not only extend our knowledge of how early deprivation influences EF longitudinally, but also provide support for the utility of computational modelling to elucidate specific mechanisms linking early psychosocial deprivation to long-term poor outcomes.
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Función Ejecutiva , Carencia Psicosocial , Memoria a Corto Plazo , Simulación por ComputadorRESUMEN
OBJECTIVES: There have been significant surgical and technological advances in bone-anchored hearing aid (BAHA) design, function, and implantation technique, but peri-implant skin complications remain the most frequent complication. The most important aspect in dealing with cutaneous complications is to identify the type of cutaneous lesion. Although Holger's Classification has been an extremely useful clinical tool, this grading system has been shown to be unsuitable for some cases. We therefore propose a new consistent and easy assessment classification of cutaneous complications associated with BAHA. METHODS: A retrospective clinical study was carried out at a tertiary centre, between January 2008 and December 2014. All patients under 18 years old with a unilateral BAHA were included in the study. RESULTS: A total of 53 children, with a BAHA, were included in the study. Post-operative skin complications were observed in 49.1% of the patients. Of the children, 28.3% presented with soft tissue hypertrophy, the most frequently reported skin complication, and grading according to the Holger's classification was not considered feasible. To overcome the difficulties we face in clinical practice, a new classification was developed and presented. CONCLUSION: The new proposed classification - Coutinho Classification - aims to fill the gaps in the one used currently by introducing new clinical features, most importantly the presence/absence of tissue overgrowth, and by providing a better description of what each category encompasses. This is an inclusive and objective new classification system, maintaining applicability, and useful in guiding the treatment.
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Audífonos , Enfermedades de la Piel , Niño , Humanos , Adolescente , Audífonos/efectos adversos , Estudios Retrospectivos , Enfermedades de la Piel/etiología , Implantación de Prótesis/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the COVID-19 outbreak, posed a primary concern of public health worldwide. The most common changes in SARS-CoV-2 are single nucleotide substitutions, also reported insertions and deletions. This work investigates the presence of SARS-CoV-2 ORF7a deletions identified in COVID-19-positive individuals. Sequencing of SARS-CoV-2 complete genomes showed three different ORF7a size deletions (190-nt, 339-nt and 365-nt). Deletions were confirmed through Sanger sequencing. The ORF7a∆190 was detected in a group of five relatives with mild symptoms of COVID-19, and the ORF7a∆339 and ORF7a∆365 in a couple of co-workers. These deletions did not affect subgenomic RNAs (sgRNA) production downstream of ORF7a. Still, fragments associated with sgRNA of genes upstream of ORF7a showed a decrease in size when corresponding to samples with deletions. In silico analysis suggests that the deletions impair protein proper function; however, isolated viruses with partial deletion of ORF7a can replicate in culture cells similarly to wild-type viruses at 24 hpi, but with less infectious particles after 48 hpi. These findings on deleted ORF7a accessory protein gene, contribute to understanding SARS-CoV-2 phenotypes such as replication, immune evasion and evolutionary fitness as well insights into the role of SARS-CoV-2_ORF7a in the mechanism of virus-host interactions.
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COVID-19 , SARS-CoV-2 , Proteínas Virales , Humanos , Técnicas de Cultivo de Célula , SARS-CoV-2/genética , Análisis de Secuencia , Eliminación de Secuencia , Proteínas Virales/genética , ARN Subgenómico/genéticaRESUMEN
The development of high-power anode materials for Na-ion batteries is one of the primary obstacles due to the growing demands for their use in the smart grid. Despite the appealingly low cost and non-toxicity, Na2Ti3O7 suffers from low electrical conductivity and poor structural stability, which restricts its use in high-power applications. Viable approaches for overcoming these drawbacks reported to date are aliovalent doping and hydrogenation/hydrothermal treatments, both of which are closely intertwined with native defects. There is still a lack of knowledge, however, of the intrinsic defect chemistry of Na2Ti3O7, which impairs the rational design of high-power titanate anodes. Here, we report hybrid density functional theory calculations of the native defect chemistry of Na2Ti3O7. The defect calculations show that the insulating properties of Na2Ti3O7 arise from the Na and O Schottky disorder that act as major charge compensators. Under high-temperature hydrogenation treatment, these Schottky pairs of Na and O vacancies become dominant defects in Na2Ti3O7, triggering the spontaneous partial phase transition to Na2Ti6O13 and improving the electrical conductivity of the composite anode. Our findings provide an explanation on the interplay between intrinsic defects, structural phase transitions, and electrical conductivity, which can aid understanding of the properties of composite materials obtained from phase transitions.
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Although neurocognitive impairment has been considered as the main argument for the surgical treatment of craniosynostosis (CS), recent studies reported subtle deficits in neurological function even in operated patients. However, the cause of these deficits remains poorly understood. This systematic review sought to examine the impact of CS on the brain microstructure, mainly on functional connectivity, and comprehensively summarize the clinical and experimental research available on this topic. A systematic review was performed considering the publications of the last 20 years in PubMed and Web of Science, including relevant human and animal studies of the types of brain-microstructure disturbances in CS. Among the 560 papers identified, 11 were selected for analysis. Seven of those were conducted in humans and 4 in animal models. Resting-state functional magnetic resonance imaging, task-based magnetic resonance imaging, and diffusion tensor imaging were the main instruments used to investigate brain connectivity in humans. The main findings were increased connectivity of the posterior segment of cingulum gyri, reduced interconnectivity of the frontal lobes, and reduced diffusivity on diffusion tensor imaging, which were associated with hyperactivity behaviors and poorer performance on neurocognitive tests. Conversely, despite the lack of evidence of brain dysfunction in animal studies, they reported a tendency toward the development of hyperactive behaviors and impairment of neurocognitive function. Skull restriction caused by CS apparently chronically increases the intracranial pressure and produces white matter injuries. The current evidence supports the contention that an early surgical approach could minimize brain-connectivity impairment in this context.
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Craneosinostosis , Imagen de Difusión Tensora , Humanos , Imagen de Difusión Tensora/métodos , Encéfalo , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética , Craneosinostosis/diagnóstico por imagen , Craneosinostosis/cirugía , Craneosinostosis/patologíaRESUMEN
INTRODUCTION: There are several factors that seem to affect the surgical success rate of tympanoplasty, one of them being the pneumatization of the contralateral mastoid. In the current literature, several studies have been published with classification proposals for temporal bone pneumatization pattern. This study aims to evaluate the role of mastoid air cell extension in relation to the sigmoid sinus in predicting the surgical success of tympanoplasty. MATERIAL AND METHODS: This case-control study was performed on patients diagnosed with chronic otitis media (COM) who underwent type I tympanoplasty. The study group did not close the tympanic membrane, or there was a retraction or lateralization of the graft. The control group consisted of patients with surgical success. RESULTS: No statistically significant difference was found between groups regrading age, gender, perforation side/type, previous nasal surgery, and the presence of chronic otitis media in contralateral ear. A statistically significant difference was found when groups were compared in relation to the degree of pneumatization of the contralateral ear (p = 0.046), and this relationship does not seem to be influenced by age. CONCLUSION: To predict surgical success in terms of tympanic membrane closure in tympanoplasty, classification of contralateral ear pneumatization degree using the sigmoid sinus as a reference seems to be a valid and easy to apply method, and makes it possible to restrict the evaluation of pneumatization to the mastoid, a cell complex that does not seem to change with age.