Anomalous Nernst Effect in Flexible Co-Based Amorphous Ribbons.

Fe3Co67Cr3Si15B12 ribbons with a high degree of flexibility and excellent corrosion stability were produced by rapid quenching technique. Their structural, magnetic, and thermomagnetic (Anomalous Nernst Effect) properties were studied both in an as-quenched (NR) state and after stress annealing during 1 h at the temperature of 350 °C and a specific load of 230 MPa (AR). X-ray diffraction was used to verify the structural characteristics of our ribbons. Static magnetic properties were explored by inductive technique and vibrating sample magnetometry. The thermomagnetic curves investigated through the Anomalous Nernst Effect are consistent with the obtained magnetization results, presenting a linear response in the thermomagnetic signal, an interesting feature for sensor applications. Additionally, Anomalous Nernst Effect coefficient SANE values of 2.66µV/K and 1.93µV/K were estimated for the as-quenched and annealed ribbons, respectively. The interplay of the low magnetostrictive properties, soft magnetic behavior, linearity of the thermomagnetic response, and flexibility of these ribbons place them as promising systems to probe curved surfaces and propose multifunctional devices, including magnetic field-specialized sensors.

Impact of chronic gingivitis management on the cytokine and anti-PPAD expressions in juvenile systemic lupus erythematosus: A six-month follow-up.

OBJECTIVE: To evaluate how chronic gingivitis treatment impacts the oral and circulating cytokine expressions after six-month follow-up in patients with juvenile systemic lupus erythematosus (jSLE) and also to evaluate the circulating expression of anti-Porphyromonas gingivalis peptidylarginine deiminase antibodies (anti-PPAD) before and after treatment. BACKGROUND: Juvenile systemic lupus erythematosus patients present a worse periodontal condition associated with higher gingival crevicular fluid (GCF) levels of interleukin (IL)-1ß, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein (MCP)-1. MATERIALS AND METHODS: Twenty-one adolescents with jSLE (mean age: 16.2 ± 1.5 years) were recruited. Participants were rheumatologically and periodontally examined. All individuals were clinically diagnosed with gingival inflammation. Chronic gingivitis treatment consisted of supragingival scaling, prophylaxis and oral hygiene instructions. The cytokine levels were determined by bead-based multiplex assays and the anti-PPAD levels by ELISA. Gingival crevicular fluid (GCF) and serum samples were collected at baseline and 6 months after treatment. RESULTS: We observed a reduction in attachment loss, SLE Disease Activity Index (SLEDAI), IL-1ß, IL-10 and MCP-1 GCF levels, and the IL-4 and IL-5 serum levels 6 months after periodontal treatment. On the contrary, a significant increase in GCF expression of IL-4, IL-12, IL-17, IFN-γ and serum levels of anti-PPAD antibody was observed. CONCLUSION: Juvenile systemic lupus erythematosus patients seem to positively benefit from periodontal treatment by a significantly reduced CAL, a GCF reduction of pro-inflammatory cytokines and an increasing of anti-inflammatory ones. However, an increase in the GCF expression of IL-17 and the serum expression of anti-PPAD antibody 6 months after periodontal treatment might negatively affect the treatment outcome of such patients in the long term.

Invasive Seaweeds in the Iberian Peninsula: A Contribution for Food Supply.

The introduction of exotic organisms in marine ecosystems can lead to economic and ecological losses. Globally, seaweeds represent a significant part of these non-indigenous species (NIS), with 407 introduced algal species. Furthermore, the presence of NIS seaweeds has been reported as a major concern worldwide since the patterns of their potential invasion mechanisms and vectors are not yet fully understood. Currently, in the Iberian Peninsula, around 50 NIS seaweeds have been recorded. Some of these are also considered invasive due to their overgrowth characteristic and competition with other species. However, invasive seaweeds are suitable for industrial applications due to their high feedstock. Hence, seaweeds' historical use in daily food diet, allied to research findings, showed that macroalgae are a source of nutrients and bioactive compounds with nutraceutical properties. The main goal of this review is to evaluate the records of NIS seaweeds in the Iberian Peninsula and critically analyze the potential of invasive seaweeds application in the food industry.

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD).

INTRODUCTION AND AIM: The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. MATERIAL AND METHODS: NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. RESULTS: A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78-0.97). CONCLUSION: When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.

Hypoglycaemic activity of Bauhinia holophylla through GSK3-ß inhibition and glycogenesis activation.

CONTEXT: Bauhinia L. species, including Bauhinia holophylla (Bong.) Steud. (Fabaceae), have traditionally been used to treat diabetes. Bauhinia is a complex botanical genus, and the indiscriminate use of the diverse Bauhinia species is reflected in the experimental divergence of their medicinal potential. OBJECTIVE: The hypoglycaemic and hypolipidaemic effects, molecular mechanism of action and phytochemical properties of an authentic extract of B. holophylla leaves were evaluated. MATERIALS AND METHODS: A phytochemical study of a 70% EtOH extract was performed using FIA-ESI-IT-MS/MSn and HPLC-PAD-ESI-IT-MS. The extract (200 or 400 mg/kg b.w.) was administered for 14 days to streptozotocin-induced diabetic Swiss mice. Glucose tolerance and insulin sensitivity, blood parameters, gene and protein expression, and the in vivo and in vitro inhibition of intestinal glucosidases were assessed. RESULTS: HPLC-PAD-ESI-IT-MS analysis identified flavonoid derivatives of quercetin, myricetin, luteolin and kaempferol. Treatment with 400 mg/kg of the extract reduced blood glucose (269.0 ± 32.4 mg/dL vs. 468.0 ± 32.2 mg/dL for diabetic animals), improved glucose tolerance, decreased cholesterol and triglyceride levels, and increased the mRNA expression of proteins involved in glucogenesis in the liver and muscle, such as PI3-K/Akt, GS, GSK3-ß (ser-9), AMPK and Glut4. The activity of intestinal maltase was inhibited in vitro (IC50: 43.0 µg/mL for the extract compared to 516.4 µg/mL for acarbose) and in vivo. DISCUSSION AND CONCLUSIONS: Treatment with B. holophylla was associated with a marked hypoglycaemic effect through the stimulation of glycogenesis and inhibition of gluconeogenesis and intestinal glucose absorption, without increasing basal insulinaemia.

The phenotypic spectrum of congenital Zika syndrome.

In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.

Osteoblastic differentiation of bone marrow mesenchymal stromal cells in Bruck Syndrome.

BACKGROUND: Osteogenesis Imperfecta (OI) (OMIM %259450) is a heterogeneous group of inherited disorders characterized by increased bone fragility, with clinical severity ranging from mild to lethal. The majority of OI cases are caused by mutations in COL1A1 or COL1A2. Bruck Syndrome (BS) is a further recessively-inherited OI-like phenotype in which bone fragility is associated with the unusual finding of pterygia and contractures of the large joints. Notably, several studies have failed to show any abnormalities in the biosynthesis of collagen 1 in BS patientes. Evidence was obtained for a specific defect of the procollagen telopeptide lysine hydroxylation in BS, whereas mutations in the gene PLOD2 have been identified. Recently, several studies described FKBP10 mutations in OI-like and BS patients, suggesting that FKBP10 is a bonafide BS locus. METHODS: We analyzed the coding region and intron/exon boundaries of COL1A1, COL1A2, PLOD2 and FKBP10 genes by sequence analysis using an ABI PRISM 3130 automated sequencer and Big Dye Terminator Sequencing protocol. Mononuclear cells obtained from the bone marrow of BS, OI patients and healthy donors were cultured and osteogenic differentiation was induced. The gene expression of osteoblast specific markers were also evaluated during the osteoblastic differentiation of mesenchymal stem cell (MSC) by qRT-PCR using an ABI7500 Sequence Detection System. RESULTS: No mutations in COL1A1, COL1A2 or PLOD2 were found in BS patient. We found a homozygous 1-base-pair duplication (c.831dupC) that is predicted to produce a translational frameshift mutation and a premature protein truncation 17 aminoacids downstream (p.Gly278ArgfsX95). The gene expression of osteoblast specific markers BGLAP, COL1A1, MSX2, SPARC and VDR was evaluated by Real Time RT-PCR during differentiation into osteoblasts and results showed similar patterns of osteoblast markers expression in BS and healthy controls. On the other hand, when compared with OI patients, the expression pattern of these genes was found to be different. CONCLUSIONS: Our work suggests that the gene expression profiles observed during mesenchymal stromal cell differentiation into osteoblast are distinct in BS patients as compared to OI patients. The present study shows for the first time that genes involved in osteogenesis are differentially expressed in BS and OI patients.

QSAR-Driven Discovery of Novel Chemical Scaffolds Active against Schistosoma mansoni.

Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure-activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro-1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{[(4-nitro-1,2,5-oxadiazol-3-yl)oxy]methyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents.

Intermediate fibrosis staging in hepatitis C: a problem not overcome by optimal samples or pathologists' expertise.

BACKGROUND AND AIMS: The prediction of intermediate stage of fibrosis in chronic hepatitis C represents a prognostic factor for disease progression. Studies evaluating biopsy performance in intermediate stage considering current patterns of liver samples and pathologists' variability are scarce. We aimed to evaluate the effect of optimal liver specimens (≥ 20 mm and/or ≥ 11 portal tracts) and pathologists' expertise on agreement for intermediate stage of fibrosis in chronic hepatitis C. MATERIAL AND METHODS: Guided biopsies with large TruCut needle were initially scored by four pathologists with different expertise in liver disease and posteriorly reviewed by a reference hepatopathologist to evaluate fibrosis agreement. RESULTS: Of the 255 biopsies initially selected, 240 met the criteria of an optimal fragment (mean length 24 ± 5 mm; 16 ± 6 portal tracts) and were considered for analysis. The overall agreement among all fibrosis stages was 77% (κ = 0.66); intraobserver and interobserver agreement was, respectively, 97% (k = 0.96) and 73% (κ = 0.60). Excluded samples (< 20 mm and < 11 portal tracts) presented a lower agreement (40%; κ = 0.24). Stratifying fibrosis stages, an interobserver agreement of 42% was found in intermediate stage (F2), ranging from 0 to 56% according to pathologists' expertise, compared to 97% in mild (F0-F1) and 72% in advanced fibrosis (≥ F3) (p < 0.001). Of the 23% misclassified cases, fibrosis understaging occurred in 82% of specimens, predominantly in F2, even when evaluated by a hepatopathologist. CONCLUSIONS: Liver biopsy presents intrinsic limitations to assess intermediate stage of fibrosis not overcome by optimal samples and experienced pathologists' analysis, and should not be considered the gold standard method to evaluate intermediate fibrosis in chronic hepatitis C.

Humane Education in Brazil: Organisation, Challenges and Opportunities.

Humane education and the debate on alternatives to harmful animal use for training is a relatively recent issue in Brazil. While animal use in secondary education has been illegal since the late 1970s, animal use in higher science education is widespread. However, alternatives to animal experiments in research and testing have recently received attention from the Government, especially after the first legislation on animal experiments was passed, in 2008. This article proposes that higher science education should be based on a critical and humane approach. It outlines the recent establishment of the Brazilian Network for Humane Education (RedEH), as a result of the project, Mapping Animal Use for Undergraduate Education in Brazil, which was recognised by the 2014 Lush Prize. The network aims to create a platform to promote change in science education in Brazil, starting by quantitatively and qualitatively understanding animal use, developing new approaches adapted to the current needs in Brazil and Latin America, and communicating these initiatives nationally. This paper explores the trajectory of alternatives and replacement methods to harmful animal use in training and education, as well as the status of humane education in Brazil, from the point of view of educators and researchers engaged with the network.

COL1A1 and miR-29b show lower expression levels during osteoblast differentiation of bone marrow stromal cells from Osteogenesis Imperfecta patients.

BACKGROUND: The majority of Osteogenesis Imperfecta (OI) cases are caused by mutations in one of the two genes, COL1A1 and COL1A2 encoding for the two chains that trimerize to form the procollagen 1 molecule. However, alterations in gene expression and microRNAs (miRNAs) are responsible for the regulation of cell fate determination and may be evolved in OI phenotype. METHODS: In this work, we analyzed the coding region and intron/exon boundaries of COL1A1 and COL1A2 genes by sequence analysis using an ABI PRISM 3130 automated sequencer and Big Dye Terminator Sequencing protocol. COL1A1 and miR-29b expression were also evaluated during the osteoblastic differentiation of mesenchymal stem cell (MSC) by qRT-PCR using an ABI7500 Sequence Detection System. RESULTS: We have identified eight novel mutations, where of four may be responsible for OI phenotype. COL1A1 and miR-29b showed lower expression values in OI type I and type III samples. Interestingly, one type III OI sample from a patient with Bruck Syndrome showed COL1A1 and miR-29b expressions alike those from normal samples. CONCLUSIONS: Results suggest that the miR-29b mechanism directed to regulate collagen protein accumulation during mineralization is dependent upon the amount of COL1A1 mRNA. Taken together, results indicate that the lower levels observed in OI samples were not sufficient for the induction of miR-29b.

Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance. Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.

Teeth Damage during General Anesthesia.

INTRODUCTION: Dental injuries during anesthesia, especially when advanced airway management is required, represent a legal problem. Factors such as poor dental condition and excessive pressure during intubation contribute to dental damage. The maxillary central incisors are commonly affected. OBJECTIVE: The objective of this review is to know the incidence of dental injuries in adults undergoing anesthesia that requires airway management. MATERIALS AND METHODS: The search was performed in MEDLINE (through Pubmed), ClinicalTrials.gov, Scopus, LILACS (through the Virtual Health Library Regional Portal), and SciELO for all available literature on the subject up to December 2022. Inclusion criteria involved articles that studied patients aged 18 years or older who underwent general anesthesia requiring airway management with tracheal intubation or insertion of a laryngeal mask airway. RESULTS: Of all the articles, nine report dental injury associated with the type of airway management. Only one article does not have dental injury. DISCUSSION: This study addresses dental injuries related to tracheal intubation during general anesthesia. Although techniques are used to prevent them, these injuries still occur. Laryngoscopy, especially with support on the upper central incisors, can cause damage to the teeth. CONCLUSIONS: It is important that the anesthesiologist is aware of dental trauma and that orotracheal intubation or the placement of the laryngeal mask airway is performed systematically and rigorously, always considering the patient's dentition to choose the best approach in each specific situation.

Drivers of variability in Blue Carbon stocks and burial rates across European estuarine habitats.

The implementation of climate change mitigation strategies based on the conservation and restoration of Blue Carbon ecosystems requires a deep understanding of the magnitude and variability in organic carbon (Corg) storage across and within these ecosystems. This study explored the variability in soil Corg stocks and burial rates across and within intertidal estuarine habitats of the Atlantic European coast and its relation to biotic and abiotic drivers. A total of 136 soil cores were collected across saltmarshes located at different tidal zones (high marsh, N = 45; low marsh, N = 30), seagrass meadows (N = 17) and tidal flats (N = 44), and from the inner to the outer sections of five estuaries characterized by different basin land uses. Soil Corg stocks were higher in high-marsh communities (65 ± 3 Mg ha-1) than in low-marsh communities (38 ± 3 Mg ha-1), seagrass meadows (40 ± 5 Mg ha-1) and unvegetated tidal flats (46 ± 3 Mg ha-1) whereas Corg burial rates also tended to be higher in high marshes (62 ± 13 g m-2 y-1) compared to low marshes (43 ± 15 g m-2 y-1) and tidal flats (35 ± 9 g m-2 y-1). Soil Corg stocks and burial rates decreased from inner to outer estuarine sections in most estuaries reflecting the decrease in the river influence towards the estuary mouth. Higher soil Corg stocks were related to higher content of silt and clay and higher proportion of forest and natural land within the river basin, pointing at new opportunities for protecting coastal natural carbon sinks based on the conservation and restoration of upland ecosystems. Our study contributes to the global inventory of Blue Carbon by adding data from unexplored regions and habitats in Europe, and by identifying drivers of variability across and within estuaries.

Neourethra creation using autologous vascularized intestinal graft in cats.

The objective of this study was to assess the application of a urethrostomy technique that utilizes an autologous vascularized intestinal graft as a "neourethra" and to analyze its short- and long-term feasibilities. Six cats with urethral rupture and 8 cats with urethral stricture and a history of urethrostomy were included. The inclusion criteria were the indication for urethroplasty and limited urethral length for perineal urethrostomy. A segment of intestine was prepared as a graft for urethral repair. The diameter of the aboral end was adjusted to facilitate anastomosis with the urethra or neck of the urinary bladder. An ostomy was created in the prepubic region using the oral end. The postoperative follow-up period was at least 1 y. Restoration of urinary flow was successful in all cases immediately after surgery. During postoperative follow-up, minimal complications were observed, with urinary incontinence being one of the most frequent, occurring in 28.5% (4/14) of the cases. Urine culture, carried out at different times during the follow-up period, was positive in 72.7% (8/11) of the cats. The autologous graft from the vascularized intestinal segment was an appropriate urethral substitute and this urethroplasty technique therefore proved to be feasible in cats. The postoperative complications observed were not exclusive to this technique and generally could either be corrected or tolerated. Periodic clinical follow-up examinations are recommended. This procedure allows the reestablishment of urinary flow and should be considered a favorable option, particularly when there is insufficient urethral tissue to allow repair using conventional techniques.

L'objectif de cette étude était d'évaluer l'application d'une technique d'urétrostomie qui utilise une greffe intestinale vascularisée autologue comme « néo-urètre ¼ et d'analyser ses faisabilités à court et à long terme. Six chats avec rupture urétrale et huit chats avec rétrécissement urétral et antécédents d'urétrostomie ont été inclus. Les critères d'inclusion étaient l'indication d'urétroplastie et la longueur urétrale limitée pour l'urétrostomie périnéale. Un segment d'intestin a été préparé comme greffon pour la réparation urétrale. Le diamètre de l'extrémité aborale était ajusté pour faciliter l'anastomose avec l'urètre ou le col de la vessie. Une stomie a été créée dans la région prépubienne en utilisant l'extrémité orale. La période de suivi postopératoire était d'au moins 1 an. La restauration du flux urinaire a réussi dans tous les cas immédiatement après la chirurgie. Au cours du suivi postopératoire, des complications minimes ont été observées, l'incontinence urinaire étant l'une des plus fréquentes, survenant dans 28,5 % (4/14) des cas. La culture urinaire, réalisée à différents moments de la période de suivi, était positive chez 72,7 % (8/11) des chats. La greffe autologue du segment intestinal vascularisé était un substitut urétral approprié et cette technique d'urétroplastie s'est donc avérée réalisable chez le chat. Les complications postopératoires observées n'étaient pas exclusives à cette technique et pouvaient généralement être soit corrigées soit tolérées. Des examens de suivi clinique périodiques sont recommandés. Cette procédure permet le rétablissement du flux urinaire et doit être considérée comme une option favorable, en particulier lorsque le tissu urétral est insuffisant pour permettre une réparation à l'aide de techniques conventionnelles.(Traduit par Docteur Serge Messier).

Waist circumference is independently associated with liver steatosis and fibrosis in LMNA-related and unrelated Familial Partial Lipodystrophy women.

BACKGROUND: Lipodystrophies are a heterogeneous group of diseases characterized by the selective loss of subcutaneous adipose tissue and ectopic fat deposition in different organs, including the liver. This study aimed to determine the frequencies of liver steatosis (LS) and liver fibrosis (LF) in a sample of individuals with LMNA-related and unrelated Familial Partial Lipodystrophy. METHODS: This cross-sectional study included 17 women with LMNA-related FPLD and 15 women with unrelated FPLD. LS and LF were assessed using transient elastography (TE) with FibroScan®. Anthropometric and biochemical variables were included in a multiple linear regression analysis to identify the variables that were independently related to liver disease. RESULTS: Regarding the presence of LF, 22 (68.2%) women were classified as having non-significant fibrosis, and 10 (31.8%) were classified as having significant or severe fibrosis. Regarding LS, only six women (20.7%) were classified as having an absence of steatosis, and 23 (79.3%) had mild to severe steatosis. After multiple linear regression, waist circumference (but not age, body mass index, or waist-to-hip ratio) was found to be independently related to LS and LF. Among the biochemical variables, only triglyceride levels were independently related to LS but not LF. CONCLUSIONS: In women with FPLD, visceral fat accumulation appears to be the most important determinant of liver disease, including LF, rather than fat scarcity in the lower limbs.

Clinicoepidemiological profile and risk factors associated with mortality in traumatized cats admitted to a veterinary teaching hospital in Brazil.

OBJECTIVES: The aim of this study was to evaluate possible risk factors for death in traumatized cats based on the clinicoepidemiological profile, the Animal Trauma Triage (ATT) scale score and the Modified Glasgow Coma Scale (MGCS) score at the time of presentation to the hospital. METHODS: This was a cross-sectional study involving cats admitted to the emergency sector (ES) and the surgical clinic sector (SCS) of a veterinary teaching hospital (VTH) in northeastern Brazil over a 12-month period (2018-2019). Probable risk factors associated with non-survival after trauma were analyzed by calculating the prevalence ratio. The prediction of non-survival was evaluated by analyzing the receiver operating characteristic (ROC) curve employing the ATT scale score, MGCS score and rectal temperature. RESULTS: In 1 year, 89 traumatized cats were admitted to the VTH, of which 90% (n = 80) were young, 54% (n = 48) were male, 79% (n = 70) were intact, 59% (n = 53) were indoor cats and 92% (n = 82) were considered as mixed breed. Blunt trauma was the most prevalent cause of injuries, reported in 76% (n = 68) of the cats. Accidents involving falls (30%; n = 27) that affected the pelvic limbs (50.6%) were the most commonly reported. The prevalence of death among cats admitted to the ES was 9.44 times higher than that of animals treated at the SCS. Trauma as result of being run over and chest trauma were associated with a higher probability of death. Most of the animals that died had a lower rectal temperature than those that survived. The ATT scale score, MGCS score and rectal temperature were predictive of mortality. CONCLUSIONS AND RELEVANCE: Rectal temperature, ATT scale score and MGCS score were effective predictors of an unfavorable prognosis and point to the need for emergency procedures. Hypothermia, being run over and chest trauma were associated with a higher risk of mortality. Our findings highlight the importance of prompt and effective care for these conditions.

Identifying mutant-specific multi-drug combinations using comparative network reconstruction.

Targeted inhibition of aberrant signaling is an important treatment strategy in cancer, but responses are often short-lived. Multi-drug combinations have the potential to mitigate this, but to avoid toxicity such combinations must be selective and given at low dosages. Here, we present a pipeline to identify promising multi-drug combinations. We perturbed an isogenic PI3K mutant and wild-type cell line pair with a limited set of drugs and recorded their signaling state and cell viability. We then reconstructed their signaling networks and mapped the signaling response to changes in cell viability. The resulting models, which allowed us to predict the effect of unseen combinations, indicated that no combination selectively reduces the viability of the PI3K mutant cells. However, we were able to validate 25 of the 30 combinations that we predicted to be anti-selective. Our pipeline enables efficient prioritization of multi-drug combinations from the enormous search space of possible combinations.

A systematic review on neutrophils interactions with titanium and zirconia surfaces: Evidence from in vitro studies.

OBJECTIVES: This systematic review aimed to assess in vitro studies that evaluated neutrophil interactions with different roughness levels in titanium and zirconia implant surfaces. MATERIAL AND METHODS: An electronic search for literature was conducted on PubMed, Embase, Scopus, and Web of Science and a total of 14 studies were included. Neutrophil responses were assessed based on adhesion, cell number, surface coverage, cell structure, cytokine secretion, reactive oxygen species (ROS) production, neutrophil activation, receptor expression, and neutrophil extracellular traps (NETs) release. The method of assessing the risk of bias was done using the toxicological data reliability assessment tool (TOXRTOOL). RESULTS: Ten studies have identified a significant increase in neutrophil functions, such as surface coverage, cell adhesion, ROS production, and NETs released when interacting with rough titanium surfaces. Moreover, neutrophil interaction with rough-hydrophilic surfaces seems to produce less proinflammatory cytokines and ROS when compared to naive smooth and rough titanium surfaces. Regarding membrane receptor expression, two studies have reported that the FcγIII receptor (CD16) is responsible for initial neutrophil adhesion to hydrophilic titanium surfaces. Only one study compared neutrophil interaction with titanium alloy and zirconia toughened alumina surfaces and reported no significant differences in neutrophil cell count, activation, receptor expression, and death. CONCLUSIONS: There are not enough studies to conclude neutrophil interactions with titanium and zirconia surfaces. However, different topographic modifications such as roughness and hydrophilicity might influence neutrophil interactions with titanium implant surfaces.

The use of an endoscopic endonasal approach for a secondary intraorbital meningioma: illustrative case.

BACKGROUND: Meningiomas are the most frequent primary tumors in the central nervous system (CNS), but intraorbital location is uncommon and accounts for only 0.2% to 4% of all CNS meningiomas. Lesions in this compartment could be classified as primary, secondary, or ectopic. The close relationship with the optic nerve sheath is a landmark to identify the tumor as primary, whereas secondary tumors commonly come from an extension of an intracranial meningioma, and ectopic meningioma is a concept not yet completely established. OBSERVATIONS: The authors present a rare case of a secondary intraorbital meningioma operated through an endoscopic endonasal approach. Secondary meningiomas at the medial orbit are very uncommon, given their more common superior and lateral location as an extension of sphenoid meningiomas. The endoscopic endonasal route provides direct access to the medial orbit. The authors present an illustrative case of a meningioma located at the medial orbit and resected through an endoscopic endonasal approach that provided excellent visualization and anatomical exposure. Additionally, the authors review the concept and possible similarities between secondary and ectopic intraorbital meningiomas. LESSONS: An endoscopic endonasal approach should be considered as a feasible treatment option for intraorbital meningiomas, especially if they are in the medial orbital wall.