Foam formation during drainage of a surfactant solution in a microfluidic porous medium model.

Foam has been shown to have great potential to significantly improve sweep efficiency during gas injection in oil recovery, remediation of contaminated sites, gas storage, and acidification processes. The gas mobility reduction largely depends on the generation and stability of lamellae in the pore space that traps the gas phase. Most available analyses focus on foam formation during the co-injection of gas and liquid phases at different fractional flow (foam quality) or flow of foam formed before being injected in the porous media. During surfactant-alternating-gas (SAG) injection, foam is formed as the aqueous phase is displaced by the gas slug that follows. The dynamics of lamellae formation and their stability are different from that of a co-injection process, since the amount of surfactant available to stabilize the gas-liquid interfaces is fixed as fresh surfactant solution is not injected together with the gas phase. This work studies foam formation during the drainage of a surfactant solution by gas injection at a fixed flow rate. A transparent microfluidic model of a porous medium is used in order to enable the correlation of pore-scale phenomena and macroscopic flow behavior. The results show that the maximum number of lamellae increases with surfactant concentration, even much above the critical micelle concentration (CMC). The availability of surfactant molecules needed to stabilize newly formed gas-liquid interfaces rises with concentration. The higher number of lamellae formed at higher surfactant concentration leads to stronger mobility reduction of the gas phase and longer time needed for the gas to percolate through the porous medium.

Discovery of Novel miRNAs in Colorectal Cancer: Potential Biological Roles and Clinical Utility.

Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO data (discovery and validation groups). We used TCGA data from five tissues to analyze miRNA tissue specificity. miRDB was used to predict miRNA targets, and the UCSC Xena Browser was used to evaluate target expression. After successive analyses, we identified 15 novel miRNAs with the same expression patterns in CRC in both the discovery and validation groups. Four molecules (nov-miR-13844-5p, nov-miR-7154-5p, nov-miR-5035-3p, and nov-miR-590-5p) were differentially expressed in proximal and distal CRC. The nov-miR-3345-5p and nov-miR-13172-3p, which are upregulated in tumors, are only expressed in colorectal tissues. These molecules have been linked to a worse prognosis in right-sided colon and rectal carcinomas. An analysis revealed an association between eight novel miRNAs and 81 targets, mostly cancer-related genes, with varying expression based on tumor location. These findings provide new miRNAs with potential biological relevance, molecular biomarkers, and therapeutic targets for CRC treatment.

Optimization of the Green Extraction of Red Araçá (Psidium catteyanum Sabine) and Application in Alginate Membranes for Use as Dressings.

In this research, the aim was to introduce innovation to the pharmaceutical field through the exploration of an underutilized plant matrix, the red araçá, along with the utilization of sodium alginate for the development of membranes designed for active topical dressings. Within this context, optimal extraction conditions were investigated using the central composite rotational statistical design (CCRD) to obtain a red araçá epicarp extract (RAEE) rich in bioactive compounds utilizing the maceration technique. The extract acquired under the optimized conditions (temperature of 66 °C and a hydroalcoholic solvent concentration of 32%) was incorporated into a sodium alginate matrix for the production of active membranes using a casting method. Characterization of the membranes revealed that the addition of the extract did not significantly alter its morphology. Furthermore, satisfactory results were observed regarding mechanical and barrier properties, as well as the controlled release of phenolic compounds in an environment simulating wound exudate. Based on these findings, the material produced from renewable matrices demonstrates the promising potential for application as a topical dressing within the pharmaceutical industry.

TNF-α-TNFR1 Signaling Mediates Inflammation and Bone Resorption in Apical Periodontitis.

INTRODUCTION: The aim of this study was to investigate the role of the proinflammatory axis TNF-α-TNFR1 in experimentally induced periapical inflammation and bone resorption in mice. METHODS: After receiving Ethics Committee Approval (2019.1.139.58.0), experimental apical periodontitis was induced by means of inoculating oral microorganisms into the root canals of molars of mice. Genetically deficient tumor necrosis factor-α receptor-1 mice (TNFR1-/-; n = 50) response was compared with that of C57Bl6 wild-type mice (wild-type; n = 50) after 7, 14, 28, and 42 days. The analyses performed were micro-computed tomographic, histopathologic, histomicrobiological, and histometric evaluation, tartrate-resistant acid phosphatase staining, immunohistochemistry, and quantitative reverse transcriptase polymerase chain reaction. Data were analyzed by using one-way analysis of variance, followed by Tukey or Bonferroni tests (α = 5%). RESULTS: TNFR1-/- mice exhibited lower recruitment of neutrophils at 14, 28, and 42 days (P < .05), which resulted in reduced area and volume of apical periodontitis at 42 days (P < .05). The number of osteoclasts was also lower in TNFR1-/- animals at 14 and 42 days (P < .01), along with reduced synthesis of CTSK, MMP-9, and COX-2. Expression of RANKL, but not OPG, was reduced at 14 and 42 days (P < .001). The highest RANKL expression over OPG (ratio > 1) was found in wild-type animals at 7 (P < .0001) and 42 days (P < .001). CONCLUSIONS: Periapical inflammation and bone resorption were exacerbated in wild-type animals compared with TNFR1-/- mice, demonstrating that the TNF-α-TNFR1 signaling pathway mediated catabolic events in bone after root canal contamination.

Detection of Apical Dental Resorption Caused by Endodontic Infection in Mice Using Fluorescence and Bright-Field Microscopy.

The aim of this study was to evaluate the sensitivity, specificity, and predictive values of the fluorescence microscopy method in the detection of apical dental reabsorption after induction of apical periodontitis in animal models. Forty-first molars of mice, aged 6 to 8 weeks, had their root canals exposed to the oral environment or were maintained healthy as controls (n = 20). After 14 and 42 days, mice were euthanized and tissues were collected for histological evaluation by means of bright field and fluorescence microscopy. The accuracy of fluorescence microscopy in identifying apical external dental resorption was investigated using a diagnostic validation test based on the sensitivity (S) and specificity (E) properties. Bright-field microscopy revealed a higher number of specimens with scores of 1 to 3 - absence of apical dental resorption (n = 29; 52%), while fluorescence microscopy revealed a higher number of specimens with scores of 4 to 6 - presence of apical dental resorption (n = 37; 66%). Out of 56 specimens, 26 were TP, 11 were FP, and 19 were TN. No FN result was observed. Fluorescence microscopy presented a sensitivity value of 1, similar to the bright-field method, while specificity was lower (0.633). The accuracy of the fluorescent method to detect apical dental resorption was 0.804. Fluorescence microscopy revealed a higher number of false positive apical dental resorption than bright-field microscopy. The detection of apical dental resorption was not impacted by the sensitivity of the method but by its specificity.

In Vitro Transdifferentiation Potential of Equine Mesenchymal Stem Cells into Schwann-Like Cells.

Schwann cells (SCs) are essential for the regenerative processes of peripheral nerve injuries. However, their use in cell therapy is limited. In this context, several studies have demonstrated the ability of mesenchymal stem cells (MSCs) to transdifferentiate into Schwann-like cells (SLCs) using chemical protocols or co-culture with SCs. Here, we describe for the first time the in vitro transdifferentiation potential of MSCs derived from equine adipose tissue (AT) and equine bone marrow (BM) into SLCs using a practical method. In this study, the facial nerve of a horse was collected, cut into fragments, and incubated in cell culture medium for 48 h. This medium was used to transdifferentiate the MSCs into SLCs. Equine AT-MSCs and BM-MSCs were incubated with the induction medium for 5 days. After this period, the morphology, cell viability, metabolic activity, gene expression of glial markers glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), p75 and S100ß, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), and the protein expression of S100 and GFAP were evaluated in undifferentiated and differentiated cells. The MSCs from the two sources incubated with the induction medium exhibited similar morphology to the SCs and maintained cell viability and metabolic activity. There was a significant increase in the gene expression of BDNF, GDNF, GFAP, MBP, p75, and S100ß in equine AT-MSCs and GDNF, GFAP, MBP, p75, and S100ß in equine BM-MSCs post-differentiation. Immunofluorescence analysis revealed GFAP expression in undifferentiated and differentiated cells, with a significant increase in the integrated pixel density in differentiated cells and S100 was only expressed in differentiated cells from both sources. These findings indicate that equine AT-MSCs and BM-MSCs have great transdifferentiation potential into SLCs using this method, and they represent a promising strategy for cell-based therapy for peripheral nerve regeneration in horses.

Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth.

Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women-15 preterm and 16 term-were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.

New records of Amblyomma ticks parasitizing neotropical primates in Brazil.

Amblyomma is an important tick genus for animal and human health, with some species being the vectors of zoonotic pathogens, such as Rickettsia rickettsii, in the Neotropical region. Knowing their hosts may help to understand the distribution of these agents and decrease the occurrence of clinical cases. Primates are intelligent and adaptable animals that can get close to humans in the search for food. So, they may be an important epidemiological link for the spread of these ticks. Beyond that, primates also suffer from these infections, serving as sentinels for different diseases. Thus, the present study aims to report the parasitism by Amblyomma spp. on six species of Neotropical primates from different locations in Brazil. The 337 collected ticks were morphologically identified using stereomicroscopes and taxonomic keys, and six distinct species of ticks were identified. We report here the first record of nymphs of the tick species Amblyomma cajennense sensu stricto on Alouatta belzebul, a male of Amblyomma fuscum on Alouatta guariba clamitans, nymphs of Amblyomma sculptum on Leontopithecus chrysopygus and Callithrix aurita, as well as nymphs of Amblyomma geayi on Saimiri collinsi. Of the 337 tick specimens collected, 256 (75,96%) were nymphs. The importance of primates in the life cycle of these species remains to be elucidated.

Bacterial RNA virus MS2 exposure increases the expression of cancer progression genes in the LNCaP prostate cancer cell line.

Bacteriophages effectively counteract diverse bacterial infections, and their ability to treat most types of cancer has been explored using phage engineering or phage-virus hybrid platforms. In the present study, it was demonstrated that the bacteriophage MS2 can affect the expression of genes associated with the proliferation and survival of LNCaP prostate epithelial cells. LNCaP cells were exposed to bacteriophage MS2 at a concentration of 1×107 plaque forming units/ml for 24-48 h. After exposure, various cellular parameters, including cell viability, morphology, and changes in gene expression, were examined. MS2 affected cell viability adversely, reducing viability by 25% in the first 4 h of treatment; however, cell viability recovered within 24-48 h. Similarly, the AKT, androgen receptor, integrin α5, integrin ß1, MAPK1, MAPK3, STAT3, and peroxisome proliferator-activated receptor-γ coactivator 1α genes, which are involved in various normal cellular processes and tumor progression, were significantly upregulated, whereas the expression levels of HSP90, ITGB5, ITGB3, HSP27, ITGAV, and PI3K genes were unchanged. Therefore, based on viability and gene expression changes, bacteriophage MS2 severely impaired LNCaP cells by reducing anchorage-dependent survival and androgen signaling. A caveolin-mediated endocytosis mechanism for MS2-mediated signaling in prostate cancer cells was proposed based on reports involving bacteriophages T4, M13, and MS2, and their interactions with LNCaP and PC3 cell lines.

Circulating miRNAs are associated with frailty and ST-elevation myocardial infarction pathways.

BACKGROUND: Frailty and ST-Elevation Myocardial Infarction (STEMI) share similar molecular pathways. Specific biomarkers, such as microRNAs (miRNAs), may provide insights into the molecular mechanisms that cause the relationship between frailty and STEMI. OBJECTIVE: Our aim was to identify and compare circulating miRNA levels between frail and non-frail older adults following STEMI and comprehend the regulatory miRNA-gene networks and pathways involved in this condition. METHODS: This exploratory study is a subanalysis of a larger observational study. In this study, we selected patients ≥ 65 years old, following STEMI, with pre-frail/frail (n=5) and non-frail (n=4) phenotype evaluated using the Clinical Frailty Scale and serum circulating miRNA levels were analyzed. RESULTS: Pre-frail/frail patients had greater serum levels of 53 miRNAs, compared with non-frail patients. Notably, miR-103a-3p, miR-598-3p, and miR-130a-3p were the top three significantly deregulated miRNAs predicted to modulate gene expression associated with aging. Additional computational analyses showed 7,420 predicted miRNA gene targets, which were regulated by at least two of the 53 identified miRNAs. Pathway enrichment analysis showed that axon guidance and MAPK signaling were among pathways regulated by miRNA target genes. CONCLUSIONS: These novel findings suggest a correlation between the identified miRNAs, target genes, and pathways in pre-frail and frail patients with myocardial infarction.

Leukotriene B4 Loaded in Microspheres Inhibits Osteoclast Differentiation and Activation.

To investigate osteoclast formation in vivo and if leukotriene B4 (LTB4) loaded in microspheres (MS) could be used as a therapeutical strategy to promote a sustained delivery of the mediator and prevent osteoclast differentiation. Methods: In vivo, apical periodontitis was induced in mice to investigate osteoclast differentiation and signaling in absence of 5-lipoxygenase (5-LO). In vitro, LTB4-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process. Characterization and efficiency of LTB4 encapsulation were investigated. J774A.1 macrophages were cultured in the presence of monocyte colony-stimulating factor (M-CSF) and ligand for receptor activator of nuclear factor kappa B (RANKL) and then stimulated with LTB4-MS. Cytotoxicity, in vitro MS-LTB4 uptake, osteoclast formation and gene expression were measured. Results: We found that 5-LO negatively regulates osteoclastic formation in vivo during apical periodontitis development. In vitro, LTB4-MS were up-taken by macrophages and were not cytotoxic to the cells. LTB4-MS inhibited osteoclast formation and the synthesis of osteoclastogenic genes Acp5, Mmp9, Calcr and Ctsk. LTB4-MS inhibited differentiation of macrophages into an osteoclastic phenotype and cell activation under M-CSF and RANKL stimulus.

Leukotriene B4 Loaded in Microspheres Inhibits Osteoclast Differentiation and Activation

Abstract To investigate osteoclast formation in vivo and if leukotriene B4 (LTB4) loaded in microspheres (MS) could be used as a therapeutical strategy to promote a sustained delivery of the mediator and prevent osteoclast differentiation. Methods: In vivo, apical periodontitis was induced in mice to investigate osteoclast differentiation and signaling in absence of 5-lipoxygenase (5-LO). In vitro, LTB4-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process. Characterization and efficiency of LTB4 encapsulation were investigated. J774A.1 macrophages were cultured in the presence of monocyte colony-stimulating factor (M-CSF) and ligand for receptor activator of nuclear factor kappa B (RANKL) and then stimulated with LTB4-MS. Cytotoxicity, in vitro MS-LTB4 uptake, osteoclast formation and gene expression were measured. Results: We found that 5-LO negatively regulates osteoclastic formation in vivo during apical periodontitis development. In vitro, LTB4-MS were up-taken by macrophages and were not cytotoxic to the cells. LTB4-MS inhibited osteoclast formation and the synthesis of osteoclastogenic genes Acp5, Mmp9, Calcr and Ctsk. LTB4-MS inhibited differentiation of macrophages into an osteoclastic phenotype and cell activation under M-CSF and RANKL stimulus.

Resumo O objetivo deste trabalho foi Investigar a formação de osteoclastos in vivo e se o leucotrieno B4 (LTB4) incorporado em microesferas (MS) poderia ser usado como estratégia terapêutica para promover uma entrega sustentada do mediador e prevenir a diferenciação dos osteoclastos. Métodos: In vivo, a periodontite apical foi induzida em camundongos para investigar a diferenciação e sinalização de osteoclastos na ausência de 5-lipoxigenase (5-LO). In vitro, LTB4-MS foi preparado usando um processo de evaporação e extração de solvente de emulsão de óleo em água. A caracterização e a eficiência do encapsulamento do LTB4 foram investigadas. Macrófagos J774A.1 foram cultivados na presença de fator estimulador de colônia de monócitos (M-CSF) e ligante para o receptor ativador do fator nuclear kappa B (RANKL) e, então, estimulados com LTB4-MS. Citotoxicidade, captação in vitro de MS-LTB4, formação de osteoclastos e expressão gênica foram avaliadas. Resultados: A via 5-LO regula negativamente a formação de osteoclastos in vivo durante o desenvolvimento da periodontite apical. In vitro, LTB4-MS foram fagocitadas pelos macrófagos e não foram citotóxicos para as células. LTB4-MS inibiu a formação de osteoclastos e a síntese dos genes pró-osteoclastogênicos Acp5, Mmp9, Calcr e Ctsk. Conclusões: LTB4-MS inibiu a diferenciação de macrófagos em um fenótipo osteoclástico e a ativação celular sob estímulo de M-CSF e RANKL.

Use of a Geometric Parameter for Characterizing Rigid Films at Oil-Water Interfaces.

Interfacial tension and dilatational rheology are often used to characterize the mechanical response of a liquid interface using axisymmetric drop shape analysis (ADSA). It is important to note that for systems dominated by adsorption/desorption of surfactants, the contributions of extra mechanical stresses are negligible; thus, the Young-Laplace equation remains valid. However, for interfaces dominated by extra stresses, as in the case of particle monolayers or asphaltenes that clearly exhibit a skin (a rigid film), the nature of the elastic response is fundamentally different and the validity of the equation is questionable. Calculation of the interfacial tension and dilatational elasticity using drop shape analysis depends critically on the drop shape following the Young-Laplace equation. If the interface becomes more like a solid, the drop shape will deviate from being purely Laplacian. Indeed, the drop will exhibit a wrinkled surface as collapse continues. The geometric parameter RV/A, defined as the ratio (dV/V)/(dA/A) with V is the volume of the drop and A is the area of the interface), allows one to measure the deviation of the drop shape from purely Laplacian. For a simple interface (pure liquids or surfactant solutions), RV/A is quite close to the theoretical value of 1.5 of a perfect sphere. Nevertheless, if the molecules adsorbed at the interface begin to interact strongly, the ratio can vary. In the limit of long-time-scale experiments, RV/A of some drops approaches 2. We studied the evolution of the parameter RV/A for different systems, from simple to complex, as a function of oscillation frequencies and amplitudes of drop volume. The results obtained were compared to the values of the interfacial moduli and drop shape behavior to better characterize the regime change.

Absence of Tumor Necrosis Factor Receptor 1 Inhibits Osteoclast Activity in Apical Dental Resorption Caused by Endodontic Infection in Mice.

INTRODUCTION: The aim of this study was to evaluate osteoclastogenesis and dental resorption resulting from endodontic infection in wild-type (WT) and tumor necrosis factor receptor 1 genetically deficient (TNFR1 KO) mice. METHODS: After approval by the ethics committee on the use of animals, 40 mice were distributed into 2 experimental groups based on time periods: 14 days (n = 10 WT mice and n = 10 TNFR1 KO mice) and 42 days (n = 10 WT mice and n = 10 TNFR1 KO mice). After these periods, morphometric analysis was performed using bright field and fluorescence microscopy and tartrate-resistant acid phosphatase histoenzymology to identify osteoclasts. One-way analysis of variance followed by the Tukey post hoc test was used for the statistical analysis (α = 0.05). RESULTS: WT mice in the 42-day period had a greater apical dental resorption in the distal root of the first molar than TNFR1 KO mice (P < .05). On the other hand, TNFR1 KO mice showed a smaller number of osteoclasts on the dental surface than WT mice (P < .05). CONCLUSIONS: WT mice with apical periodontitis had more extensive apical dental resorptions and a larger number of osteoclasts on the tooth surface than TNFR1 KO mice.

Freeze-Dried Microfluidic Monodisperse Microbubbles as a New Generation of Ultrasound Contrast Agents.

We succeeded in freeze-drying monodisperse microbubbles without degrading their performance, that is, their monodispersity in size and echogenicity. We used microfluidic technology to generate cryoprotected highly monodisperse microbubbles (coefficient of variation [CV] <5%). By using a novel retrieval technique, we were able to freeze-dry the microbubbles and resuspend them without degradation, that is, keeping their size distribution narrow (CV <6%). Acoustic characterization performed in two geometries (a centimetric cell and a millichannel) revealed that the resuspended bubbles conserved the sharpness of the backscattered resonance peak, leading to CVs ranging between 5% and 10%, depending on the geometry. As currently observed with monodisperse bubbles, the peak amplitudes are one order of magnitude higher than those of commercial ultrasound contrast agents. Our work thus solves the question of storage and transportation of highly monodisperse bubbles. This work might open pathways toward novel clinical non-invasive measurements, such as local pressure, impossible to carry out with the existing commercial ultrasound contrast agents.

Effect of interfacial rheology on drop coalescence in water-oil emulsion.

Over the last years several studies have been conducted to understand emulsion formation and its behavior. In some applications, the aim is the phase separation of the emulsions through the coalescence of the drops, as in the oil industry. In this study, the relationship between rheological properties of oil-water interfaces and the drainage time of a thin oil film between two aqueous drops was investigated. Interfacial tension and dilatational rheology were measured using the axisymmetric drop shape analysis. We evaluated different concentrations of a nonionic surfactant (Span 80) dissolved in mineral oil (Primol 352) phase. The results indicate a direct relationship between the properties of the structure formed at the oil-water interface and the absence of droplet coalescence. For low surfactant concentrations, below the critical micelle concentration (CMC), the interface is weakly elastic (fluid-like) and the coalescence process always occurs; the draining time is not to related to the aging time of the interface. For surfactant concentrations above CMC, the elastic and viscous moduli showed significant changes with aging leading to the formation of a solid-like film at the interface preventing further coalescence. We used the characteristic times of change in interfacial rheological behavior to better explain the non-coalescence process.

Endoscopic interlaminar spine surgery guided by portable ultrasound: a new technique / Cirurgia endoscópica interlaminar da coluna vertebral guiada por ultrassom portátil: uma nova técnica / Cirugía endoscópica interlaminar de la columna vertebral guiada por ultrasonografía portátil: una nueva técnica

ABSTRACT This paper describes the technique of interlaminar endoscopic surgery guided by a portable ultrasound device. This innovation allows endoscopic surgery to be performed without the use of real-time radiography, which is associated with a higher risk of radiation damage. The portable wireless ultrasound device used for this technique, which has not been yet described in the world literature for minimally invasive surgeries, can be used as an imaging tool to delimit the interlaminar space in minimally invasive surgeries via both transverse and sagittal views. Level of evidence I; Quality of evidence A.

RESUMO Este trabalho descreve a técnica da cirurgia endoscópica interlaminar guiada por dispositivo de ultrassonografia portátil. Essa inovação permite que a cirurgia endoscópica seja realizada sem o uso de radiografias em tempo real que estão associadas ao maior risco de dano decorrentes de radiação. O dispositivo de ultrassom portátil e sem fio usado nessa técnica, que ainda não foi descrito na literatura mundial para cirurgias minimamente invasivas, pode ser usado como ferramenta de imagem para delimitar o espaço interlaminar em cirurgias minimamente invasivas através dos planos transversal e sagital. Nível de evidência I; Qualidade da evidência A.

RESUMEN Este artículo describe la técnica de la cirugía endoscópica interlaminar guiada por un dispositivo de ultrasonografía portátil. Esta innovación permite realizar la cirugía endoscópica sin utilizar radiografías en tiempo real, que se asocian a un mayor riesgo de daños por radiación. El dispositivo de ultrasonido inalámbrico portátil utilizado en esta técnica, aún no descrito en la literatura mundial para cirugías mínimamente invasivas, puede utilizarse como herramienta de imagen para delimitar el espacio interlaminar en cirugías mínimamente invasivas a través de los planos transversal y sagital. Nivel de evidencia I; Calidad de la evidencia A.

Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate Androgen Receptor Expression in LNCaP Prostate Cell Line.

Wild-type or engineered bacteriophages have been reported as therapeutic agents in the treatment of several types of diseases, including cancer. They might be used either as naked phages or as carriers of antitumor molecules. Here, we evaluate the role of bacteriophages M13 and T4 in modulating the expression of genes related to cell adhesion, growth, and survival in the androgen-responsive LNCaP prostatic adenocarcinoma-derived epithelial cell line. LNCaP cells were exposed to either bacteriophage M13 or T4 at a concentration of 1 × 105 pfu/mL, 1 × 106 pfu/mL, and 1 × 107 pfu/mL for 24, 48, and 72 h. After exposure, cells were processed for general morphology, cell viability assay, and gene expression analyses. Neither M13 nor T4 exposure altered cellular morphology, but both decreased the MTT reduction capacity of LNCaP cells at different times of treatment. In addition, genes AKT, ITGA5, ITGB1, ITGB3, ITGB5, MAPK3, and PI3K were significantly up-regulated, whilst the genes AR, HSPB1, ITGAV, and PGC1A were down-regulated. Our results show that bacteriophage M13 and T4 interact with LNCaP cells and effectively promote gene expression changes related to anchorage-dependent survival and androgen signaling. In conclusion, phage therapy may increase the response of PCa treatment with PI3K/AKT pathway inhibitors.

Notification of 6442 cases of bone tuberculosis in Brazil: epidemiological profile from 2009 to 2018 / Notificação de 6442 casos de tuberculose óssea no Brasil: perfil epidemiológico de 2009 a 2018 / Notificación de 6442 casos de tuberculosis ósea en Brasil: perfil epidemiológico de 2009 a 2018

ABSTRACT Objective: To analyze the occurrence of notified cases of bone tuberculosis in Brazil during the period from 2009 to 2018. Methods: Quantitative, descriptive and retrospective study. The data consisted of cases reported to the Notifiable Diseases Information System (SINAN) of DATASUS. To analyze the results, the non-parametric statistical Chi-squared and G tests, capable of expressing statistical associations, were used. Results: 6,442 cases of bone tuberculosis were reported in Brazil, with an average of 644.2 cases per year. The Southeast was responsible for 41.5% of the cases (n = 2676). The extrapulmonary form accounted for 87.9% (5661). There was a predominance in males (66.1%, n = 4258), Whites (41.6%, n = 2678) and in the above 35 years of age group (73.9%, n = 4757). In the data collected, the risk factor data was not correctly filled out, making reliable statistical associations impossible in this study, mainly between alcoholism, tobacco use, AIDS, diabetes, mental illness, illicit drug use and homelessness. Conclusion: There was greater notification of cases of bone tuberculosis in the Southeast and Northeast regions of Brazil, which predominantly affected young, economically productive men. Tuberculosis has a correlation with diabetes, HIV / AIDS, smoking and alcohol and drug use, according to the results of this study. Level of evidence II; Retrospective, analytical, quantitative and descriptive study.

RESUMO Objetivo: Analisar a ocorrência de casos de tuberculose óssea notificados no Brasil entre o período de 2009 a 2018. Métodos: Estudo quantitativo, descritivo e retrospectivo. Os dados consistiram em casos notificados no Sistema de Informação de Agravos de Notificação (SINAN) do DATASUS. Para análise dos resultados, foram usados testes estatísticos não paramétricos, Qui-quadrado e teste G, capazes de expressar associação estatística. Resultados: Foram notificados 6.442 casos de tuberculose óssea no Brasil, com média de 644,2 casos por ano. O Sudeste foi responsável por 41,5% dos casos (n = 2676). A forma extrapulmonar correspondeu a 87,9% (5.661). Houve predomínio no sexo masculino (66,1%, n = 4258), em brancos (41,6%, n = 2678) e maiores de 35 anos (73,9%, n = 4757). Os dados coletados não tinham preenchimento correto dos fatores de risco, o que impossibilitou a associação estatística confiável neste estudo, principalmente entre alcoolismo, tabagismo, AIDS, diabetes, doença mental, uso de drogas ilícitas e moradores de rua. Conclusões: Houve maior notificação de casos de tuberculose óssea no Sudeste e no Nordeste do Brasil, que afetou predominantemente homens jovens e em plena atividade econômica. A tuberculose tem correlação com diabetes, HIV/AIDS, tabagismo e uso de álcool e drogas ilícitas, conforme os resultados deste estudo. Nível de evidência II; Estudo retrospectivo, analítico, quantitativo e descritivo.

RESUMEN Objetivo: Analizar la ocurrencia de casos de tuberculosis ósea notificados en Brasil en el período de 2009 a 2018. Métodos: Estudio cuantitativo, descriptivo y retrospectivo. Los datos consistieron en casos notificados en el Sistema de Información de Enfermedades de Notificación (SINAN) del DATASUS. Para análisis de los resultados, fueron usados tests estadísticos no paramétricos, Chi-cuadrado y test G, capaces de expresar asociación estadística. Resultados: Fueron notificados 6.442 casos de tuberculosis ósea en Brasil, con promedio de 644,2 casos por año. El sudeste fue responsable por 41,5% de los casos (n = 2676). La forma extrapulmonar correspondió a 87,9% (5661). Hubo predominio en el sexo masculino (66,1%, n = 4258), en blancos (41,6%, n = 2678) y mayores de 35 años (73,9%, n = 4757). Los datos colectados no tenían llenado correcto de los factores de riesgo, lo que imposibilitó la asociación estadística confiable en este estudio, principalmente entre alcoholismo, tabaquismo, SIDA, diabetes, enfermedad mental, uso de drogas ilícitas y personas sin techo. Conclusiones: Hubo mayor notificación de casos de tuberculosis ósea en el sudeste y en el noreste de Brasil, que afectó predominantemente a hombres jóvenes y en plena actividad económica. La tuberculosis tiene correlación con diabetes, VIH/SIDA, tabaquismo y uso de alcohol y drogas ilícitas, conforme a los resultados de este estudio. Nivel de evidencia II; Estudio retrospectivo, analítico, cuantitativo y descriptivo.

3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats.

BACKGROUND: Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. METHODS: 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. RESULTS: The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. CONCLUSIONS: 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.