Vacterl syndrome: Medical and stomatological considerations for comprehensive patient management.

AIM: The VACTERL association or Syndrome consists of Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal, and Limb defects. The diagnosis relies on the presence of at least three of these structural abnormalities. This study reports a single case of a patient with VACTERL Syndrome (VS), aiming to assist dentists in recognizing the general aspects, systemic changes, and oral care related to this condition. CASE REPORT: A 14-year-old female patient medically diagnosed with VS. The study evaluated the presence of systemic alterations, medication use, behavioral deviations, cognitive development, and oral aspects. The patient exhibited cardiovascular alterations including a ventricular septal defect (C), anal atresia (A), polydactyly (considered limb alteration-L), and scoliosis (a possible indication of vertebral anomalies-V). In the intraoral examination, findings included tooth crowding, enamel hypomineralization in several teeth, a deep and atretic palate, generalized gingivitis, bleeding, gingival hyperplasia, Class III malocclusion, and a right unilateral crossbite. CONCLUSION: Patients diagnosed with VACTERL syndrome experience significant systemic impairments. The research subject presented compromised oral health, challenges in dental management, delays in neuropsychomotor development, though these are not inherent to the syndrome. It is crucial to prevent oral diseases and provide early dental care for these patients to avoid the need for complex and invasive dental treatments due to systemic impairments.

A Step Forward for the Treatment of Localized Prostate Cancer Using Gold Nanoparticles Combined with Laser Irradiation.

Prostate cancer (PCA) is the second most common cancer diagnosis in men and the fifth leading cause of death worldwide. The conventional treatments available are beneficial to only a few patients and, in those, some present adverse side effects that eventually affect the quality of life of most patients. Thus, there is an urgent need for effective, less invasive and targeted specific treatments for PCA. Photothermal therapy (PTT) is a minimally invasive therapy that provides a localized effect for tumour cell ablation by activating photothermal agents (PTA) that mediate the conversion of the light beam's energy into heat at the site. As tumours are unable to easily dissipate heat, they become more susceptible to temperature increases. In the PTT field, gold nanoparticles (AuNPs) have been attracting interest as PTA. The aim of this study was to formulate AuNPs capable of remaining retained in the tumour and subsequently generating heat at the tumour site. AuNPs were synthesized and characterized in terms of size, polydispersity index (PdI), zeta potential (ZP), morphology and the surface plasmon resonance (SPR). The safety of AuNPs and their efficacy were assessed using in vitro models. A preliminary in vivo safety assessment of AuNPs with a mean size lower than 200 nm was confirmed. The morphology was spherical-like and the SPR band showed good absorbance at the laser wavelength. Without laser, AuNPs proved to be safe both in vitro (>70% viability) and in vivo. In addition, with laser irradiation, they proved to be relatively effective in PCA cells. Overall, the formulation appears to be promising for use in PTT.

Cisplatin Toxicity Causes Neutrophil-Mediated Inflammation in Zebrafish Larvae.

Cisplatin is an antineoplastic agent used to treat various tumors. In mammals, it can cause nephrotoxicity, tissue damage, and inflammation. The release of inflammatory mediators leads to the recruitment and infiltration of immune cells, particularly neutrophils, at the site of inflammation. Cisplatin is often used as an inducer of acute kidney injury (AKI) in experimental models, including zebrafish (Danio rerio), due to its accumulation in kidney cells. Current protocols in larval zebrafish focus on studying its effect as an AKI inducer but ignore other systematic outcomes. In this study, cisplatin was added directly to the embryonic medium to assess its toxicity and impact on systemic inflammation using locomotor activity analysis, qPCR, microscopy, and flow cytometry. Our data showed that larvae exposed to cisplatin at 7 days post-fertilization (dpf) displayed dose-dependent mortality and morphological changes, leading to a decrease in locomotion speed at 9 dpf. The expression of pro-inflammatory cytokines such as interleukin (il)-12, il6, and il8 increased after 48 h of cisplatin exposure. Furthermore, while a decrease in the number of neutrophils was observed in the glomerular region of the pronephros, there was an increase in neutrophils throughout the entire animal after 48 h of cisplatin exposure. We demonstrate that cisplatin can have systemic effects in zebrafish larvae, including morphological and locomotory defects, increased inflammatory cytokines, and migration of neutrophils from the hematopoietic niche to other parts of the body. Therefore, this protocol can be used to induce systemic inflammation in zebrafish larvae for studying new therapies or mechanisms of action involving neutrophils.

Copper drives prion protein phase separation and modulates aggregation.

Prion diseases are characterized by prion protein (PrP) transmissible aggregation and neurodegeneration, which has been linked to oxidative stress. The physiological function of PrP seems related to sequestering of redox-active Cu2+, and Cu2+ dyshomeostasis is observed in prion disease brain. It is unclear whether Cu2+ contributes to PrP aggregation, recently shown to be mediated by PrP condensation. This study indicates that Cu2+ promotes PrP condensation in live cells at the cell surface and in vitro through copartitioning. Molecularly, Cu2+ inhibited PrP ß-structure and hydrophobic residues exposure. Oxidation, induced by H2O2, triggered liquid-to-solid transition of PrP:Cu2+ condensates and promoted amyloid-like PrP aggregation. In cells, overexpression of PrPC initially protected against Cu2+ cytotoxicity but led to PrPC aggregation upon extended copper exposure. Our data suggest that PrP condensates function as a buffer for copper that prevents copper toxicity but can transition into PrP aggregation at prolonged oxidative stress.

(Dys)functional insights into nucleic acids and RNA-binding proteins modulation of the prion protein and α-synuclein phase separation.

Prion diseases are prototype of infectious diseases transmitted by a protein, the prion protein (PrP), and are still not understandable at the molecular level. Heterogenous species of aggregated PrP can be generated from its monomer. α-synuclein (αSyn), related to Parkinson's disease, has also shown a prion-like pathogenic character, and likewise PrP interacts with nucleic acids (NAs), which in turn modulate their aggregation. Recently, our group and others have characterized that NAs and/or RNA-binding proteins (RBPs) modulate recombinant PrP and/or αSyn condensates formation, and uncontrolled condensation might precede pathological aggregation. Tackling abnormal phase separation of neurodegenerative disease-related proteins has been proposed as a promising therapeutic target. Therefore, understanding the mechanism by which polyanions, like NAs, modulate phase transitions intracellularly, is key to assess their role on toxicity promotion and neuronal death. Herein we discuss data on the nucleic acids binding properties and phase separation ability of PrP and αSyn with a special focus on their modulation by NAs and RBPs. Furthermore, we provide insights into condensation of PrP and/or αSyn in the light of non-trivial subcellular locations such as the nuclear and cytosolic environments.

Clinical Impact of Preoperative Biliary Drainage in Patients with Ductal Adenocarcinoma of the Pancreatic Head.

Our aim was to study the association between preoperative biliary drainage (PBD) and morbidity following cephalic pancreaticoduodenectomy (CPD) for pancreatic ductal adenocarcinoma (PDAC) and its prognostic impact, which is still controversial in the literature. A retrospective study was conducted, which included 128 patients who underwent CPD for PDAC, divided into two groups: those who underwent PBD (group 1) and those who did not undergo this procedure (group 2). Group 1 was subdivided according to the drainage route: endoscopic retrograde cholangiopancreatography (ERCP), group 1.1, and percutaneous transhepatic cholangiography (PTC), group 1.2. 34.4% of patients underwent PBD, and 47.7% developed PBD-related complications, with 37% in group 1.1 and 64.7% in group 1.2 (p = 0.074). There was a significant difference between group 1 and 2 regarding bacterial colonization of the bile (45.5% vs. 3.6%, p < 0.001), but no difference was found in the colonization by multidrug-resistant bacteria, the development of Clavien-Dindo ≥ III complications, clinically relevant pancreatic fistula and delayed gastric emptying (DGE), intra-abdominal abscess, hemorrhage, superficial surgical site infection (SSI), and readmission. Between groups 1.1 and 1.2, there was a significant difference in clinically relevant DGE (44.4% vs. 5.9%, p = 0.014) and Clavien-Dindo ≥ III complications (59.3% vs. 88.2%, p = 0.040). There were no significant differences in median overall survival and disease-free survival (DFS) between groups 1 and 2. Groups 1.1 and 1.2 had a significant difference in DFS (10 vs. 5 months, p = 0.017). In this group of patients, PBD was associated with increased bacterial colonization of the bile, without a significant increase in postoperative complications or influence in survival. ERCP seems to contribute to the development of clinically significant DGE. Patients undergoing PTC appear to have an early recurrence.

Marine Natural Products as Innovative Cosmetic Ingredients.

Over the course of the last 20 years, numerous studies have identified the benefits of an array of marine natural ingredients for cosmetic purposes, as they present unique characteristics not found in terrestrial organisms. Consequently, several marine-based ingredients and bioactive compounds are under development, used or considered for skin care and cosmetics. Despite the multitude of cosmetics based on marine sources, only a small proportion of their full potential has been exploited. Many cosmetic industries have turned their attention to the sea to obtain innovative marine-derived compounds for cosmetics, but further research is needed to determine and elucidate the benefits. This review gathers information on the main biological targets for cosmetic ingredients, different classes of marine natural products of interest for cosmetic applications, and the organisms from which such products can be sourced. Although organisms from different phyla present different and varied bioactivities, the algae phylum seems to be the most promising for cosmetic applications, presenting compounds of many classes. In fact, some of these compounds present higher bioactivities than their commercialized counterparts, demonstrating the potential presented by marine-derived compounds for cosmetic applications (i.e., Mycosporine-like amino acids and terpenoids' antioxidant activity). This review also summarizes the major challenges and opportunities faced by marine-derived cosmetic ingredients to successfully reach the market. As a future perspective, we consider that fruitful cooperation among academics and cosmetic industries could lead to a more sustainable market through responsible sourcing of ingredients, implementing ecological manufacturing processes, and experimenting with inventive recycling and reuse programs.

Pluronic® F127 Hydrogel Containing Silver Nanoparticles in Skin Burn Regeneration: An Experimental Approach from Fundamental to Translational Research.

Presently, skin burns are considered one of the main public health problems and lack therapeutic options. In recent years, silver nanoparticles (AgNPs) have been widely studied, playing an increasingly important role in wound healing due to their antibacterial activity. This work is focused on the production and characterization of AgNPs loaded in a Pluronic® F127 hydrogel, as well as assessing its antimicrobial and wound-healing potential. Pluronic® F127 has been extensively explored for therapeutic applications mainly due to its appealing properties. The developed AgNPs had an average size of 48.04 ± 14.87 nm (when prepared by method C) and a negative surface charge. Macroscopically, the AgNPs solution presented a translucent yellow coloration with a characteristic absorption peak at 407 nm. Microscopically, the AgNPs presented a multiform morphology with small sizes (~50 nm). Skin permeation studies revealed that no AgNPs permeated the skin after 24 h. AgNPs further demonstrated antimicrobial activity against different bacterial species predominant in burns. A chemical burn model was developed to perform preliminary in vivo assays and the results showed that the performance of the developed AgNPs loaded in hydrogel, with smaller silver dose, was comparable with a commercial silver cream using higher doses. In conclusion, hydrogel-loaded AgNPs is potentially an important resource in the treatment of skin burns due to their proven efficacy by topical administration.

Tumor Stroma Area and Other Prognostic Factors in Pancreatic Ductal Adenocarcinoma Patients Submitted to Surgery.

Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, responsible for up to 80% of its volume. The amount of stroma can be associated with prognosis, although there are discrepancies regarding its concrete impact. The aim of this work was to study prognostic factors for PDAC patients submitted to surgery, including the prognostic impact of the tumor stroma area (TSA). A retrospective study with PDAC patients submitted for surgical resection was conducted. The TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa are independent risk factors for mortality in PDAC patients submitted to surgery. Regarding TSA, using >1.9 × 1011 µ2 as cut-off value for all stages, patients seem to have longer overall survival (OS) (31 vs. 21 months, p = 0.495). For stage II, a TSA > 2 × 1011 µ2 was significantly associated with an R0 resection (p = 0.037). For stage III patients, a TSA > 1.9 × 1011 µ2 was significantly associated with a lower histological grade (p = 0.031), and a TSA > 2E + 11 µ2 was significantly associated with a preoperative AP ≥ 120 U/L (p = 0.009) and a lower preoperative AST (≤35 U/L) (p = 0.004). Patients with PDAC undergoing surgical resection with preoperative CA19.9 > 500 U/L and AST ≥ 100 U/L have an independent higher risk of recurrence. Tumor stroma could have a protective effect in these patients. A larger TSA is associated with an R0 resection in stage II patients and a lower histological grade in stage III patients, which may contribute to a longer OS.

Immunoparalysis in critically ill children.

Immunoparalysis is associated with poorer outcomes in the paediatric intensive care unit (PICU) setting. We aimed to determine the group of patients with higher chances of immunoparalysis and correlate this status with increased risks of nosocomial infection and adverse clinical parameters. We conducted an exploratory study with prospective data collection in a university-affiliated tertiary medical, surgical, and cardiac PICU. Fifteen patients with multiple organ dysfunction syndrome were included over a period of 6 months. Monocyte's human leucocyte antigen (HLA)-DR expression and tumour necrosis factor (TNF)-α and interleukin (IL)-6 production were measured by flow-cytometry at three time points (T1 = 1-2 days; T2 = 3-5 days; T3 = 6-8 days). Using the paediatric logistic organ dysfunction-2 score to assess initial disease severity, we established the optimal cut-off values of the evaluated parameters to identify the subset of patients with a higher probability of immunoparalysis. A comparative analysis was performed between them. Sixty per cent were males; the median age was 4.1 years. Considering the presence of two criteria in T1 (classical monocytes mean fluorescence intensity [MFI] for HLA-DR ≤ 1758.5, area under the curve (AUC) = 0.775; and frequency of monocytes producing IL-6 ≤ 68.5%, AUC = 0.905) or in T3 (classical monocytes MFI of HLA-DR ≤ 2587.5, AUC = 0.675; and frequency of monocytes producing TNF-α ≤ 93.5%, AUC = 0.833), a variable to define immunoparalysis was obtained (100% sensitivity, 81.5% specificity). Forty per cent of patients were assigned to the immunoparalysis group. In this: a higher frequency of nosocomial infection (p = 0.011), vasoactive inotropic score (p = 0.014) and length of hospital stay (p = 0.036) was observed. In the subgroup with the diagnosis of sepsis/septic shock (n = 5), patients showed higher percentages of non-classical monocytes (p = 0.004). No mortality was recorded. A reduction in classical monocytes HLA-DR expression with lower frequencies of monocytes producing TNF-α and IL-6 during the first week of critical illness, appears to be a good marker of immunoparalysis; these findings relate to an increased risk of nosocomial infection and deleterious outcomes. The increased frequency of non-classical monocytes in patients with sepsis/septic shock is suggestive of a better prognosis.

In Vitro Characterization of Protein:Nucleic Acid Liquid-Liquid Phase Separation by Microscopy Methods and Nanoparticle Tracking Analysis.

Uncontrolled assembly/disassembly of physiologically formed liquid condensates is linked to irreversible aggregation. Hence, the quest for understanding protein-misfolding disease mechanism might lie in the studies of protein:nucleic acid coacervation. Several proteins with intrinsically disordered regions as well as nucleic acids undergo phase separation in the cellular context, and this process is key to physiological signaling and is related to pathologies. Phase separation is reproducible in vitro by mixing the target recombinant protein with specific nucleic acids at various stoichiometric ratios and then examined by microscopy and nanotracking methods presented herein. We describe protocols to qualitatively assess hallmarks of protein-rich condensates, characterize their structure using intrinsic and extrinsic dyes, quantify them, and analyze their morphology over time. Analysis by nanoparticle tracking provides information on the concentration and diameter of high-order protein oligomers formed in the presence of nucleic acid. Using the model protein (globular domain of recombinant murine PrP) and DNA aptamers (high-affinity oligonucleotides with 25 nucleotides in length), we provide examples of a systematic screening of liquid-liquid phase separation in vitro.

Phase separation of the mammalian prion protein: Physiological and pathological perspectives.

Abnormal phase transitions have been implicated in the occurrence of proteinopathies. Disordered proteins with nucleic acidbinding ability drive the formation of reversible micron-sized condensates capable of controlling nucleic acid processing/transport. This mechanism, achieved via liquid-liquid phase separation (LLPS), underlies the formation of long-studied membraneless organelles (e.g., nucleolus) and various transient condensates formed by driver proteins. The prion protein (PrP) is not a classical nucleic acid-binding protein. However, it binds nucleic acids with high affinity, undergoes nucleocytoplasmic shuttling, contains a long intrinsically disordered region rich in glycines and evenly spaced aromatic residues, among other biochemical/biophysical properties of bona fide drivers of phase transitions. Because of this, our group and others have characterized LLPS of recombinant PrP. In vitro phase separation of PrP is modulated by nucleic acid aptamers, and depending on the aptamer conformation, the liquid droplets evolve to solid-like species. Herein, we discuss recent studies and previous evidence supporting PrP phase transitions. We focus on the central role of LLPS related to PrP physiology and pathology, with a special emphasis on the interaction of PrP with different ligands, such as proteins and nucleic acids, which can play a role in prion disease pathogenesis. Finally, we comment on therapeutic strategies directed at the non-functional phase separation that could potentially tackle prion diseases or other protein misfolding disorders.

Current Insights and Progress in the Clinical Management of Head and Neck Cancer.

Head and neck cancer (HNC), also known as the cancer that can affect the structures between the dura mater and the pleura, is the 6th most common type of cancer. This heterogeneous group of malignancies is usually treated with a combination of surgery and radio- and chemotherapy, depending on if the disease is localized or at an advanced stage. However, most HNC patients are diagnosed at an advanced stage, resulting in the death of half of these patients. Thus, the prognosis of advanced or recurrent/metastatic HNC, especially HNC squamous cell carcinoma (HNSCC), is notably poorer than the prognosis of patients diagnosed with localized HNC. This review explores the epidemiology and etiologic factors of HNC, the histopathology of this heterogeneous cancer, and the diagnosis methods and treatment approaches currently available. Moreover, special interest is given to the novel therapies used to treat HNC subtypes with worse prognosis, exploring immunotherapies and targeted/multi-targeted drugs undergoing clinical trials, as well as light-based therapies (i.e., photodynamic and photothermal therapies).

Symptomatic perception of patients affected by chronic chikungunya: a qualitative perspective / Percepção dos sintomas de pacientes acometidos por chikungunya crônica: um olhar qualitativo

Objective: To understand the demands caused by chikungunya in the chronic phase and their impacts on patients' mental health and quality of life. Materials and methods: This is a qualitative study, performed from November 2019 to January 2020. Focus groups and deep interviews were carried out. Then, the Discourse Analysis was performed. Results: Chronic pain was the main clinical manifestation reported by the participants, being responsible for affecting aspects related to quality of life and mental health. As for psycological view, this study showed that chronic pain was also reported as one of the main symptoms related to anxiety and depression among research subjects. Conclusion: this study demonstrated how the chronic illness caused by Chikungunya impacted the subjects' perception in the domains related to quality of life and mental health. Furthermore, we seek to focus on the management of disease in a holistic way, putting the patients' own awareness of the impacts of the disease on their lives in a relevant level of their treatment.

Objetivo: Compreender as demandas causadas pela chikungunya em sua fase crônica e seus impactos na saúde mental e na qualidade de vida dos pacientes. Métodos: Trata-se de um estudo com abordagem qualitativa, realizado entre novembro de 2019 a janeiro de 2020. Inicialmetne, foram realizados grupos focais e entrevistas em profundidade; seguidas da Análise do Discurso. Resultados: A dor crônica foi a principal manifestação clínica relatada pelos participantes, sendo responsável por afetar aspectos relacionados à qualidade de vida e saúde mental. Quanto ao aspecto psicológico, este estudo mostrou que a dor crônica também foi relatada como um dos principais sintomas relacionados à ansiedade e depressão entre os sujeitos da pesquisa. Conclusão: este estudo demonstrou como a doença crônica causada pela chikungunya impactou na percepção dos sujeitos em seus domínios relacionados à qualidade de vida e saúde mental. Além disso, procuramos centrar-nos na gestão da doença de forma holística, colocando a consciência dos próprios doentes sobre os impactos da doença nas suas vidas num nível relevante do seu tratamento.

The thermoplastic techniques or single-cone technique on the quality of root canal filling with tricalcium silicate-based sealer: An integrative review.

Background: The filling of the root canal system (RCS) is an important step in endodontic treatment and aims to obtain a three-dimensional sealing of the root canal spaces to prevent bacterial contamination. For this, the selection of an appropriate sealer must be performed synchronously with the choice of the root canal filling technique. This study aims, through an integrative review, to evaluate the quality of root canal filling by comparing thermoplastic and single-cone (SC) techniques. Material and Methods: The Medline/PubMed, Scopus, Web of Science and Virtual Health Library (VHL) databases were used to find articles published until November 2021. The eligibility criteria comprised articles that evaluating the quality of root canal filling comparing thermoplastic techniques with the SC technique using tricalcium silicate-based sealer. Studies that evaluated primary teeth, endodontic retreatment or perforations, different outcomes, and studies that considered artificial teeth or different sealer and material for obturation of different techniques were excluded. For articles that were not available for access, an additional contact with authors were considered. A total of 1699 articles were found. After duplicate removal, the title and abstract of 828 articles were screened. Sixteen articles were considered for full-text analysis, but only ten articles met the eligibility criteria. Data extracted from the studies were discussed and tabulated to allow the comparison of desired factors. Results: Concerning the formation of gaps/voids, the thermoplastic techniques showed better results than the SC technique in 3 articles. On the other hand, 2 articles reported no statistical difference between the tested techniques. In addition, about the penetration of tricalcium silicate-based sealer in the dentinal tubules, of the 5 articles selected, in 4 there was no significant difference between the tested techniques and only one study showed better penetration of the sealer when using thermoplastic techniques. Conclusions: The thermoplastic technique was better in most selected studies regarding gaps and voids, but regarding the penetration of the sealer into the tubules, both techniques were effective. Key words:Root canal filling, thermoplastic techniques, tricalcium silicate.

Different wild type strains of zebrafish show divergent susceptibility to TNBS-induced intestinal inflammation displaying distinct immune cell profiles.

Little is known about the diversity in immune profile of the different wild type strains of zebrafish (Danio rerio), despite its growing popularity as an animal model to study human diseases and drug testing. In the case of data resulting from modeling human diseases, differences in the background Danio fishes have rarely been taken into consideration when interpreting results and this is potentially problematic, as many studies not even mention the source and strain of the animals. In this study, we hypothesized that different wild type zebrafish strains could present distinct immune traits. To address the differences in immune responses between two commonly used wild type strains of zebrafish, AB and Tübingen (TU), we used an intestinal inflammation model induced by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) and characterized the susceptibility and immune profile in these two strains. Our data demonstrates significant differences in survival between AB and TU strains when exposed to TNBS, suggesting important physiological differences in how these strains respond to inflammatory challenges. We observed that the AB strain presented increased mortality, higher neutrophilic intestinal infiltration, decreased goblet cell numbers and decreased IL-10 expression when exposed to TNBS, compared to the TU strain. In summary, our study demonstrates strain-specific immunological responses in AB and TU animals. Finally, the significant variations in strain-related susceptibility to inflammation and the differences in the immune profile shown here, highlight that the background of each strain need to be considered when utilizing zebrafish to model diseases and for drug screening purposes, thus better immune characterization of the diverse wild type strains of zebrafish is imperative.

Insights into the specificity for the interaction of the promiscuous SARS-CoV-2 nucleocapsid protein N-terminal domain with deoxyribonucleic acids.

The SARS-CoV-2 nucleocapsid protein (N) is a multifunctional promiscuous nucleic acid-binding protein, which plays a major role in nucleocapsid assembly and discontinuous RNA transcription, facilitating the template switch of transcriptional regulatory sequences (TRS). Here, we dissect the structural features of the N protein N-terminal domain (N-NTD) and N-NTD plus the SR-rich motif (N-NTD-SR) upon binding to single and double-stranded TRS DNA, as well as their activities for dsTRS melting and TRS-induced liquid-liquid phase separation (LLPS). Our study gives insights on the specificity for N-NTD(-SR) interaction with TRS. We observed an approximation of the triple-thymidine (TTT) motif of the TRS to ß-sheet II, giving rise to an orientation difference of ~25° between dsTRS and non-specific sequence (dsNS). It led to a local unfavorable energetic contribution that might trigger the melting activity. The thermodynamic parameters of binding of ssTRSs and dsTRS suggested that the duplex dissociation of the dsTRS in the binding cleft is entropically favorable. We showed a preference for TRS in the formation of liquid condensates when compared to NS. Moreover, our results on DNA binding may serve as a starting point for the design of inhibitors, including aptamers, against N, a possible therapeutic target essential for the virus infectivity.

The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles.

Membraneless organelles have emerged during the evolution of eukaryotic cells as intracellular domains in which multiple proteins organize into complex structures to perform specialized functions without the need of a lipid bilayer compartment. Here we describe the perinuclear space of eukaryotic cells as a highly organized network of cytoskeletal filaments that facilitates assembly of biomolecular condensates. Using bioinformatic analyses, we show that the perinuclear proteome is enriched in intrinsic disorder with several proteins predicted to undergo liquid-liquid phase separation. We also analyze immunofluorescence and transmission electron microscopy images showing the association between the nucleus and other organelles, such as mitochondria and lysosomes, or the labeling of specific proteins within the perinuclear region of cells. Altogether our data support the existence of a perinuclear dense sub-micron region formed by a well-organized three-dimensional network of structural and signaling proteins, including several proteins containing intrinsically disordered regions with phase behavior. This network of filamentous cytoskeletal proteins extends a few micrometers from the nucleus, contributes to local crowding, and organizes the movement of molecular complexes within the perinuclear space. Our findings take a key step towards understanding how membraneless regions within eukaryotic cells can serve as hubs for biomolecular condensates assembly, in particular the perinuclear space. Finally, evaluation of the disease context of the perinuclear proteins revealed that alterations in their expression can lead to several pathological conditions, and neurological disorders and cancer are among the most frequent.

Estratégias para o treino da mastigação e deglutição em indivíduos com disfunção temporomandibular e dor orofacial: uma revisão de escopo / Strategies to train mastication and swallowing in individuals with temporomandibular disorder and orofacial pain: a scoping review

RESUMO Objetivo identificar e sintetizar evidências sobre estratégias utilizadas no treino da mastigação e deglutição em indivíduos com disfunção temporomandibular e dor orofacial. Estratégia de pesquisa revisão de escopo desenvolvida com consulta nas bases de dados MEDLINE, LILACS, BBO, IBECS, BINACIS, CUMED, SOF, DeCS, Index Psi, LIPECS e ColecionaSUS (via BVS), Scopus, CINAHL, Embase, Web of Science, Cochrane e na literatura cinzenta: Biblioteca Digital Brasileira de Teses e Dissertações (BDTD), OpenGrey e Google Acadêmico. Critérios de seleção estudos quantitativos ou qualitativos, sem limite temporal e sem restrição de idioma, que continham os seguintes descritores ou palavras-chave: Articulação Temporomandibular, Síndrome da Disfunção da Articulação Temporomandibular, Transtornos da Articulação Temporomandibular, Dor Facial, Mastigação, Deglutição, Terapêutica, Terapia Miofuncional e Fonoaudiologia. Na primeira etapa, dois revisores fizeram a triagem independente dos estudos, por meio da leitura dos títulos e resumos. Na segunda etapa, os revisores leram, independentemente, os documentos pré-selecionados na íntegra. Em caso de divergência, um terceiro pesquisador foi consultado. Resultados as 11 publicações incluídas foram publicadas entre 2000 e 2018. As estratégias mais utilizadas foram o treino da mastigação bilateral simultânea, seguido da mastigação bilateral alternada. Na deglutição, foi proposto aumento do tempo mastigatório para reduzir o alimento em partículas menores e lubrificar melhor o bolo alimentar e treinos com apoio superior de língua. Conclusão o treinamento funcional demonstrou efetividade na reabilitação dos pacientes, embora não siga uma padronização e não seja realizado de forma isolada. Os estudos encontrados apresentam baixo nível de evidência. Considera-se fundamental a realização de estudos mais abrangentes e padronizados, como ensaios clínicos randomizados.

ABSTRACT Purpose To identify and synthesize evidence on strategies used to train chewing and swallowing in individuals with temporomandibular disorder and orofacial pain. Research strategy Scoping review conducted by search in MEDLINE, LILACS, BBO, IBECS, BINACIS, CUMED, SOF, DeCS, Index Psi, LIPECS, and ColecionaSUS (via VHL), Scopus, CINAHL, Embase, Web of Science, Cochrane, and the grey literature: Brazilian Digital Theses and Dissertations Library (BDTD), OpenGrey, and Google Scholar. Selection criteria Quantitative or qualitative studies, with no restriction on time or language of publication, with the following descriptors or keywords: Temporomandibular Joint; Temporomandibular Joint Dysfunction Syndrome; Temporomandibular Joint Disorders; Facial Pain; chewing (Mastication); swallowing (Deglutition); Therapeutics; Myofunctional Therapy; Speech, Language and Hearing Sciences. In the first stage, two reviewers independently screened the studies by title and abstract reading. In the second stage, the reviewers independently read the preselected documents in full text. In case of divergences, a third researcher was consulted. Results The 11 documents included in the review were published between 2000 and 2018. The mostly used training strategies were simultaneous bilateral mastication/chewing, followed by alternating bilateral mastication. In swallowing, increased mastication time was proposed to break food into smaller bits and better lubricate the bolus; training with upper tongue support was also indicated. Conclusion Functional training proved to be effective in rehabilitation, although it was not standardized or performed alone. The studies had low levels of evidence. It is essential to conduct more encompassing and standardized studies, such as randomized clinical trials.

An update of advanced nanoplatforms for Glioblastoma Multiforme Management.

Glioblastoma multiforme (GBM) is a very aggressive and heterogeneous glioma. Currently, GBM is treated with a combination of surgery, radiotherapy, chemotherapy (e.g. temozolamide) and Tumour Treating Fields. Unfortunately, the mean survival is still around 15 months. This poor prognosis is associated with therapy resistance, tumor recurrence, and limited delivery of drugs due to the blood-brain barrier nature. Nanomedicine, the application of nanotechnology to medicine, has revolutionized many health fields, specifically cancer diagnosis and treatment. This review explores the particularities of different nanosystems (i.e., superparamagnetic, polymeric and gold nanoparticles, and liposomes) as well as how they can be applied to the treatment and diagnosis of GBM. As described, the most of the cited examples are on the preclinical phase; however, positive results were obtained and thus, the distance to achieve an effective treatment is shorter every day.