Penicillium citrinum CFAM 521 Isolated From the Amazon Region: A Novel Source of a Fibrinolytic Enzyme.

Fibrinolytic agents are essential in treating thrombosis, playing a critical role in improving survival rates in cardiovascular diseases. Microbial fibrinolytic proteases have emerged as promising alternatives due to their affordability, specificity, lower toxicity, and reduced side effects. Consequently, the search for microorganisms capable of producing these enzymes has gained significant economic importance in the pharmaceutical industry. This study reports and characterizes a novel fibrinolytic enzyme produced by Penicillium citrinum CFAM 521, a strain isolated from the Amazon region. The enzyme was purified using a polyethylene glycol (PEG)-phosphate salt aqueous two-phase system (ATPS). The effects of PEG molecular weight, PEG concentration, and phosphate concentration on the protease partition coefficient (K) were evaluated through a 22 full factorial design. The enzyme exhibited both fibrinolytic and fibrinogenolytic activities. After partitioning in a two-phase system with 10% (w/w) PEG and 15% (w/w) sodium phosphate, the fibrinolytic proteases were predominantly retained in the salt-rich bottom phase (K = 0.33). The enzyme has a molecular weight of 34 kDa, with optimal pH and temperature at 9°C and 37°C, respectively. Inhibitory analysis confirmed that it is a serine protease, and its activity was enhanced by the addition of Mn2+. Notably, the enzyme exhibited no hemolytic activity. Therefore, P. citrinum CFAM 521 represents a novel source of fibrinolytic enzymes, highlighting its potential as an alternative for the development of thrombolytic agents.

Surfactant-Mediated Microalgal Flocculation: Process Efficiency and Kinetic Modelling.

Microalgae are a valuable source of lipids, proteins, and pigments, but there are challenges in large-scale production, especially in harvesting. Existing methods lack proven efficacy and cost-effectiveness. However, flocculation, an energy-efficient technique, is emerging as a promising solution. Integrating surfactants enhances microalgal harvesting and disruption simultaneously, reducing processing costs. This study investigated cetyltrimethylammonium bromide (CTAB), dodecyltrimethylammonium bromide (DTAB), and sodium dodecyl sulphate (SDS) for harvesting Tetraselmis sp. strains (75LG and 46NLG). CTAB exhibits superior results, with 88% harvesting efficiency at 1500 and 2000 mg L-1 for 75LG and 46NLG, respectively, for 60 min of sedimentation-thus being able to reduce the operating time. Beyond evaluating harvesting efficiency, our study explored the kinetics of the process; the modified Gompertz model led to the best fit. Furthermore, the largest kinetic constants were observed with CTAB, thus highlighting its efficacy in optimising the microalgal harvesting process. With the incorporation of the suggested enhancements, which should be addressed in future work, CTAB could hold the potential to optimise microalgal harvesting for cost-effective and sustainable large-scale production, eventually unlocking the commercial potential of microalgae for biodiesel production.

Anadenanthera colubrina regulated LPS-induced inflammation by suppressing NF-κB and p38-MAPK signaling pathways.

We aimed to determine the chemical profile and unveil Anadenanthera colubrina (Vell.) Brenan standardized extract effects on inflammatory cytokines expression and key proteins from immunoregulating signaling pathways on LPS-induced THP-1 monocyte. Using the RT-PCR and Luminex Assays, we planned to show the gene expression and the levels of IL-8, IL-1ß, and IL-10 inflammatory cytokines. Key proteins of NF-κB and MAPK transduction signaling pathways (NF-κB, p-38, p-NF-κB, and p-p38) were detected by Simple Western. Using HPLC-ESI-MSn (High-Performance Liquid-Chromatography) and HPLC-HRESIMS, we showed the profile of the extract that includes an opus of flavonoids, including the catechins, quercetin, kaempferol, and the proanthocyanidins. Cell viability was unaffected up to 250 µg/mL of the extract (LD50 = 978.7 µg/mL). Thereafter, the extract's impact on the cytokine became clear. Upon LPS stimuli, in the presence of the extract, gene expression of IL-1ß and IL-10 were downregulated and the cytokines expression of IL-1ß and IL-10 were down an upregulated respectively. The extract is involved in TLR-4-related NF-κB/MAPK pathways; it ignited phosphorylation of p38 and NF-κB, orchestrating a reduced signal intensity. Therefore, Anadenanthera colubrina's showed low cytotoxicity and profound influence as a protector against the inflammation, modulating IL-1ß and IL-10 inflammatory cytokines gene expression and secretion by regulating intracellular NF-κB and p38-MAPK signaling pathways.

Corneal Higher Order Aberrations and Epithelial Remodeling With Femtosecond Laser-Assisted LASIK Topography-guided and Customized Asphericity Ablation in the Contralateral Eye: A Randomized, Double-Blind, Prospective Study.

PURPOSE: To evaluate refractive results, corneal higher order aberrations (HOAs), and epithelial remodeling in the preoperative and postoperative period of regular corneas that had topography-guided femtosecond laser-assisted laser in situ keratomileusis (LASIK) (Contoura WaveLight; Alcon Laboratories, Inc) and compare them with the contralateral eye that underwent ablation customized by asphericity (Custom-Q WaveLight; Alcon Laboratories, Inc) in myopic eyes with or without astigmatism. METHODS: A prospective, randomized, and double-blind study was conducted. Patients underwent preoperative and postoperative epithelial mapping and corneal tomography to assess the epithelial thickness map, HOAs of the corneal anterior surface, visual acuity, and refractive evaluation. RESULTS: This study enrolled 96 normal eyes of 48 patients. Uncorrected distance visual acuity of 20/20 or better was achieved in 97% of patients and gains in corrected distance visual acuity and effectiveness in correcting refractive astigmatism were similar in both techniques. Seventeen sectors of the corneal epithelium map were assessed by spectral-domain optical coherence tomography and no significant differences were found between techniques preoperatively and postoperatively (P > .05). HOA root mean square, coma Z3±1, trefoil Z3-3, and tissue consumption exhibited statistically significant between-technique differences (P < .05). CONCLUSIONS: The Contoura and Custom-Q techniques were similar with respect to refractive and visual outcomes after 3 months, as well as in epithelial remodeling. The Contoura provides lower postoperative HOA root mean square, coma Z3±1, and trefoil Z3-3 values, but the techniques showed no differences in the correction of the corneal astigmatic wavefront component and in the spherical aberration after 3 months. [J Refract Surg. 2023;39(11):751-758.].

Melioidosis in Timor-Leste: First Case Description and Phylogenetic Analysis.

Burkholderia pseudomallei, the causative agent of melioidosis, has not yet been reported in Timor-Leste, a sovereign state northwest of Australia. In the context of improved access to diagnostic resources and expanding clinical networks in the Australasian region, we report the first 3 cases of culture-confirmed melioidosis in Timor-Leste. These cases describe a broad range of typical presentations, including sepsis, pneumonia, multifocal abscesses, and cutaneous infection. Phylogenetic analysis revealed that the Timor-Leste isolates belong to the Australasian clade of B. pseudomallei, rather than the Asian clade, consistent with the phylogeographic separation across the Wallace Line. This study underscores an urgent need to increase awareness of this pathogen in Timor-Leste and establish diagnostic laboratories with improved culture capacity in regional hospitals. Clinical suspicion should prompt appropriate sampling and communication with laboratory staff to target diagnostic testing. Local antimicrobial guidelines have recently been revised to include recommendations for empiric treatment of severe sepsis.

O Ministério da Saúde em face da desordem da informação sobre a covid-19: uma análise do canal de informações Saúde sem Fake News / The Ministry of Health in the face of the information disorder on covid-19: an analysis of the information channel Saúde sem Fake News / El Ministerio de Salud frente al desorden informativo sobre la covid-19: un análisis del canal de información Saúde sem Fake News

A pandemia da covid-19 tem desafiado a humanidade, com implicações alarmantes. Por essa razão, também há uma forte preocupação com a circulação de informações falsas que atrapalham a luta contra a doença e comprometem o cumprimento de orientações seguras para prevenção e tratamento da infecção. Neste artigo, analisamos as ações empregadas para combater esse tipo de conteúdo através do projeto Saúde sem Fake News do Ministério da Saúde, enquanto estava ativo, e propomos a elaboração de uma nova categorização das verificações classificadas pelo canal como "Isto é fake news!", a partir do conceito e da metodologia de desordem da informação. Como resultado, identificamos que o canal adotou uma postura reativa que se limitava a atestar a veracidade ou falsidade das verificações, sem problematizar as suas especificidades, ignorando os aspectos essenciais para o efetivo combate da desinformação

The covid-19 pandemic has challenged humanity, with alarming implications. Thus, there is also a strong concern about the circulation of false information that hinders the fight against the disease and compromise the fulfillment of safe guidelines for the prevention and the treatment of infection. In this article we analyze the actions to fight against this type of content through the Saúde sem Fake News project of the Ministry of Health, while it was active, and propose the formulation of a new categorization of the checks classified by the channel as "This is fake news!", based on the concept and the methodology of information disorder. As a result, we identified that the channel adopted a reactive stance that limited itself to attesting to the veracity or the falsity of the verifications, not questioning their specificities, ignoring essential aspects for the effective fight against misinformation

La pandemia de covid-19 ha desafiado a la humanidad, con implicaciones alarmantes. Por eso, también existe una fuerte preocupación por la circulación de informaciones falsas que dificultan la lucha contra la enfermedad y compromete el cumplimiento de pautas seguras para la prevención y el tratamiento de la infección. En este artículo analizamos las acciones utilizadas para combatir este tipo de contenido a través del proyecto Saúde sem Fake News del Ministerio de Salud, mientras estuvo activo, y proponemos la elaboración de una nueva categorización de las verificaciones clasificadas por el canal como "Esta es una información falsa!" basándonos en el concepto y la metodología del desorden de la información. Como re-sultado, identificamos que el canal adoptó una postura reactiva, limitada a certificar la veracidad o falsedad de las verificaciones, sin analizar sus especificidades, ignorando aspectos esenciales para la lucha eficaz contra la desinformación

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

BACKGROUND AND OBJECTIVES: COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19. METHODS: This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS: Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION: Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis. TRIAL REGISTRATION INFORMATION: The study was registered under ClinicalTrials.gov identifier NCT04895462.

Influence of oral biofilm index, caries experience, and laboratory markers of disease progression on the oral carriage of Candida in HIV-infected and non-infected children: a cross-sectional study.

The present study aimed to compare the oral Candida rate between infected and uninfected children with the human immunodeficiency virus (HIV), as well as analyze the association between Candida spp. and predisposing factors of colonization, like oral biofilm index, caries experience, and laboratory markers of AIDS progression. A cross-sectional study was employed. Candida species were identified and quantified from saliva samples of 50 HIV-infected and 50 uninfected children. Biofilm index and decayed, missing, and filled teeth (dmft/DMFT) indices were assessed by oral clinical examinations. Additionally, CD4+ T lymphocyte count and viral load were obtained from medical records of the HIV-infected children. Candida species were cultured from 74% of the HIV-infected children and 46% of uninfected ones (p = 0.0076). Candida albicans and Candida parapsilosis were the most frequently isolated species in both studied groups. The isolation of Candida species was significantly higher in HIV-infected children with CD4 ≤ 15% (p = 0.0146); it had influence of mature oral biofilm and the caries index (dmft + DMFT ≥ 8) (p < 0.05) and was associated with the plasma viral load. The present data show that the HIV infection, oral biofilm index, caries experience, and laboratory markers of AIDS progression exert an influence on the prevalence of oral Candida in children.

Gastrointestinal Carriage of Antimicrobial Resistance in School-Aged Children in Three Municipalities of Timor-Leste.

Invasive bacterial infections are a leading cause of death in children, primarily in low- and middle-income countries (LMIC). Links between carriage of antimicrobial-resistant organisms and more resistant infections have been established; however, little has been reported regarding community carriage of antibiotic-resistant organisms such as extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales in LMIC. The aim of this study was to determine colonic carriage of ESBL-producing fluoroquinolone- and aminoglycoside-resistant Enterobacterales in healthy children in three municipalities of Timor-Leste. In November 2020, 621 stool samples were collected from school-aged children and underwent screening for the presence of Enterobacterales species and antimicrobial resistance (AMR). Ciprofloxacin-resistant Gram-negative organisms were cultured from 16.5% (95% CI 6.2−26.9), and gentamicin resistance was identified in 6.8% (95% CI 2.8−10.7). Compared to the prevalence of ciprofloxacin resistance in Dili (36.1%), there was significantly lower prevalence in the rural municipalities of Ermera (12.9%; AOR 0.38, 95% CI 0.24−0.60, p < 0.001) and Manufahi (4.5%; AOR 0.07, 95% CI 0.01−0.51, p = 0.009). The overall cluster-adjusted prevalence of ESBL-producing bacteria was 8.3%, with no significant differences between municipalities. This study demonstrates high rates of carriage of AMR among school-aged children in Timor-Leste, with higher rates observed in Dili compared to rural municipalities. Empiric antibiotic guidelines should include recommendations for treating community-acquired infections that account for the possibility of antimicrobial resistance.

Antimicrobial Activity of Aspergillus sp. from the Amazon Biome: Isolation of Kojic Acid.

The antimicrobial potential of Aspergillus sp., isolated from the Amazon biome, which is stored at the Amazon Fungi Collection-CFAM at ILMD/FIOCRUZ, was evaluated. The fungal culture was cultivated in yeast extract agar and sucrose (YES) for cold extraction of the biocompounds in ethyl acetate at 28 °C for 7 days in a BOD type incubator. The obtained extract was evaluated for its antimicrobial activity against Candida albicans and Gram-positive and negative bacteria by the "cup plate" method and the determination of the minimum inhibitory concentration (MIC) by the broth microdilution method. The extract was subjected to thin layer chromatography (TLC) and fractionated by open and semipreparative column chromatography. The fractions of interest had their chemical constituents elucidated by nuclear magnetic resonance and mass spectrometry. The elucidated molecule was evaluated for cytotoxicity against the human fibroblast strain (MRC5). The extract presented inhibitory activity against both Gram-positive and negative bacteria, with the range of inhibition halos from 5.3 to 14 mm in diameter and an MIC ranging from 500 to 15.6 µg/mL. Seventy-one fractions were collected and TLC analysis suggested the presence of substances with double bond groups: coumarins, flavonoids, phenolic, alkaloids, and terpenes. NMR and MS analyses demonstrated that the isolated molecule was kojic acid. The results of the cytotoxicity test showed that MRC5 cells presented viability at concentrations from 500 to 7.81 µg/mL. The kojic acid molecule of Aspergillus sp., with antibacterial activity and moderate toxicity at the concentrations tested, is a promising prototype of an alternative active principle of an antimicrobial drug.

Anandenanthera colubrina (Vell.) Brenan as an inhibitor of HIV-1 BaL infection.

We reported the in vitro anti-HIV-1 activity, cytotoxicity, cytokines expression and chemical profile of Anadenanthera colubrina. Cytotoxicity was evaluated on TZM-bl, HL2/3 cells and macrophages. Anti-HIV-1 activity was determined by Luciferase assay (TZM-bl cells) and by HIV-p24 quantification (macrophages) assessed by ELISA. TZM-bl and HL2/3 cells were used to determine cell-cell fusion inhibition. Cytokines expression was assessed by ELISA. Chemical composition was determined by Gas Chromatography Coupled to Mass Spectrometry. At 66.6 µg/mL, the extract maintained the cell viability above 90%. At 33.28 µg/mL, the extract reduced 82.8% of HIV-1 infection (TZM-bl cells) and HIV-p24 expression (macrophages). The extract inhibited approximately 70% of TZM-bl and HL2/3 cells fusion. Extract did't induce inflammatory response. Phytochemical analysis showed presence of flavonoid, phenolic acids, fatty acids and sugars. This is the first study presenting the anti-HIV effect of A. colubrina, showing low cytotoxicity and no inflammatory stimuli, important requirements for a microbicide development.

In vitro inhibition of a multispecies oral cavity biofilm by Syzygium aromaticum essential oil.

OBJECTIVE: To evaluate the anti-fungal activity of Syzygium aromaticum essential oil and its inhibition of a multispecies biofilm in patients with oral candidiasis. BACKGROUND: Inhibiting biofilm formation on the denture surface is an important practice for preventing denture stomatitis. MATERIALS AND METHODS: The anti-fungal activity against Candida albicans and non-albicans Candida species was evaluated through the microdilution method to define Minimal Inhibitory (MIC) and Fungicidal (MFC) Concentrations. Time-kill assay assessed growth kinetics of C. albicans based on pre-determined time points (0, 1, 2, 4, 6 and 24 hours). A multi-species biofilm was formed using human saliva from patients with oral candidiasis and anti-biofilm activity determined by Colony Forming Units per milliliter (CFU/mL) count, fluorescence microscopy with calcofluor white to observe yeast presence and structure, and metabolic activity by XTT (2,3-Bis-(2Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-carboxanilide) reduction assay. RESULTS: The essential oil showed an anti-fungal activity against all Candida species (MIC 500-1000 µg/mL, MFC 1000-2000 µg/mL), and the time-kill assay showed that 2000 µg/mL (from 2 hours onward) and 1000 µg/mL (from 4 hours onward) concentrations had substantially lower yeast growth than the negative control. In the biofilm analysis, the essential oil had a lower CFU/mL count and a biofilm metabolic activity (91.4%) than seen with its negative control, and in both analyses, the essential oil was not significantly different from the positive control (chlorhexidine). Morphological analysis showed amorphous and fragmented cellular structures after treatment with the essential oil. CONCLUSION: Syzygium aromaticum essential oil had anti-fungal activities, reduced the Candida growth kinetics substantially and inhibited the multi-species biofilm formation.

Biological properties of Schinus terebinthifolia Raddi essential oil

Abstract Schinus terebinthifolia Raddi green fruits essential oil (EO) was evaluated regarding its phytochemical profile, antimicrobial and cytotoxic activities, and toxicity. Gas chromatography with mass spectrometry was applied to identify its constituents, thereafter the minimum inhibitory concentration, minimum bactericidal and fungicidal concentrations, and its antibiofilm activity were evaluated. The EO cytotoxicity was assessed in tumor and non-tumor human cells, and in vivo toxicity was evaluated in a Galleria mellonella model. The major constituents of S. terebinthifolia EO were alpha-phellandrene and beta-phellandrene. The EO had a weak activity against all strains of Candida albicans (MIC 1000µg/mL) and had no activity against non-albicans strains, bacteria, and C. albicans biofilm. Cytostatic activity against all tumor cell lines was shown. Additionally, cell viability remained at EO concentrations up to 62.5 µg/mL. At 16 mg/mL, 50% hemolysis was observed, and it had low toxicity in vivo. Overall, the S. terebinthifolia EO was characterized by low antimicrobial and antibiofilm activities, with no evidence of toxicity to human tumor and non-tumor cells

Yeast-Host Interactions: Anadenanthera colubrina Modulates Virulence Factors of C. albicans and Inflammatory Response In Vitro.

Oral candidiasis is one of the most common fungal infections in humans. Its incidence has increased widely, as well as the antifungal resistance, demanding for the search for novel antifungal therapeutic agents. Anadenanthera colubrina (Vell.) Brenan is a plant species that has been proven to possess pharmacological effects, including antifungal and anti-inflammatory activities. This study evaluated in vitro the effects of standardized A. colubrina extract on virulence factors of Candida albicans and its regulation on immune response through C. albicans-host interaction. Antifungal activity was evaluated by Broth Microdilution Method against reference Candida strains (C. albicans, C. glabrata, C. tropicalis; C. dubliniensis). Anti-biofilm effect was performed on C. albicans mature biofilm and quantified by CFU/mL/g of biofilm dry weight. Proleotlytic enzymatic activities of proteinase and phospholipase were assessed by Azocasein and Phosphatidylcholine assays, respectively. Cytotoxicity effect was determined by Cell Titer Blue Viability Assay on Human Gingival Fibroblasts. Co-cultured model was used to analyze C. albicans coexisting with HGF by Scanning Electron Microscopy and fluorescence microscopies; gene expression was assessed by RT-PCR of C. albicans enzymes (SAP-1, PLB-1) and of host inflammatory cytokines (IL-6, IL-8, IL-1ß, IL-10). Cytokines secretion was analysed by Luminex. The extract presented antifungal effect with MIC<15.62 µg/ml against Candida strains. Biofilm and proteolytic activity were significant reduced at 312.4 µg/ml (20 × 15.62 µg/ml) extract concentration. Cell viability was maintained higher than 70% in concentrations up to 250 µg/ml (LD50 = 423.3 µg/ml). Co-culture microscopies demonstrated a substantial decreased in C. albicans growth and minimal toxicity against host cells. Gene expressions of SAP-1/PLB-1 were significantly down-regulated and host immune response was modulated by a significant decreased on IL-6 and IL-8 cytokines secretion. A. colubrina had antifungal activity on Candida strains, antibiofilm, and anti-proteolytic enzyme effects against C. albicans. Presented low cytotoxicity to the host cells and modulatory effects on the host immune response.

Tumefactive demyelinating lesions spectrum disorders and the potential role of contemporary disease modifying treatments: a case report.

Marburg disease is a fulminant variant of multiple sclerosis (MS), in which the diagnosis may be particularly difficult and with high rates of mortality. We describe the case of a women with a clinical picture, radiographic features, and neuropathological findings consistent with the classical descriptions of Marburg disease. Initially, our patient did not improved with the acute phase treatments but later showed a good response to natalizumab (NTZ) treatment. This report highlights not only the utility of brain biopsy in the accurate diagnosis of this challenging condition but also the potential role of NTZ as an effective therapeutic option.

Trends in hospital readmissions in Multiple Sclerosis patients between 2009 and 2015.

BACKGROUND: Readmission rate is an important healthcare quality metric and remains a problem in Multiple Sclerosis (MS) patients, nonetheless information about this issue is scarce. We present the first study to estimate hospital readmissions in a MS hospital-based European cohort. METHODS: Retrospective cohort study of patients with at least one hospitalization with a primary discharge of MS from August 1, 2009 and July 31, 2015. The primary outcome was hospitalization within 30 days post-discharge (30-DR). The secondary outcomes included length of stay during index and readmission, total hospital readmissions during the study period, predictors and causes of readmission. RESULTS: Forty-four (41.5%) patients had a hospital readmission during the six years of this study, 11.3% of them 30-DR, mainly due to infections (58.5%). The two most common comorbidities in these patients were neurogenic bladder (47.7%) and ischemic heart disease (18.1%). Progressive MS subtype was the main predictor of 30-DR, even after adjustment for therapy (OR: 6.29; p = 0.016), with an area under the curve of 0.73. CONCLUSION: Progressive MS subtypes and "second-line drugs" carry a higher risk of hospital readmission soon after discharge. The impact and cost-effectiveness of strategies to lower readmission rates in MS should be the focus of upcoming studies.

DR|GRADUATE: Uncertainty-aware deep learning-based diabetic retinopathy grading in eye fundus images.

Diabetic retinopathy (DR) grading is crucial in determining the adequate treatment and follow up of patient, but the screening process can be tiresome and prone to errors. Deep learning approaches have shown promising performance as computer-aided diagnosis (CAD) systems, but their black-box behaviour hinders clinical application. We propose DR|GRADUATE, a novel deep learning-based DR grading CAD system that supports its decision by providing a medically interpretable explanation and an estimation of how uncertain that prediction is, allowing the ophthalmologist to measure how much that decision should be trusted. We designed DR|GRADUATE taking into account the ordinal nature of the DR grading problem. A novel Gaussian-sampling approach built upon a Multiple Instance Learning framework allow DR|GRADUATE to infer an image grade associated with an explanation map and a prediction uncertainty while being trained only with image-wise labels. DR|GRADUATE was trained on the Kaggle DR detection training set and evaluated across multiple datasets. In DR grading, a quadratic-weighted Cohen's kappa (κ) between 0.71 and 0.84 was achieved in five different datasets. We show that high κ values occur for images with low prediction uncertainty, thus indicating that this uncertainty is a valid measure of the predictions' quality. Further, bad quality images are generally associated with higher uncertainties, showing that images not suitable for diagnosis indeed lead to less trustworthy predictions. Additionally, tests on unfamiliar medical image data types suggest that DR|GRADUATE allows outlier detection. The attention maps generally highlight regions of interest for diagnosis. These results show the great potential of DR|GRADUATE as a second-opinion system in DR severity grading.

Chemical Composition, Antibacterial and Antifungal Potential of an Extract From the Leaves of Guapira Graciliflora Mart. Against Oral Microorganisms of Dental Interest

Abstract Objective: To perform an in vitro analysis of antibacterial and antifungal potential of an alcoholic extract from the leaves of Guapira Graciliflora Mart. against oral microorganisms and determine its chemical composition. Material and Methods: A hydroalcoholic extract of the leaves form G. graciliflora was obtained through maceration, vacuum concentration and freeze-drying. Antibacterial and antifungal activities were evaluated against Streptococcus mutans, Streptococcus salivarius, Streptococcus oralis, Streptococcus parasanguinis, Streptococcus mitis and strains of Candida albicans using broth microdilution method. Phytochemical analysis determined the total phenolic compounds, protein concentration and total of sugars present in the extract. Results: G. Graciliflora demonstrated antifungal activity against the LM 11 and LM 410 clinical isolates of C. albicans (MIC 0.5 mg/mL and 2 mg/mL, respectively). The other microorganisms tested were resistant to the extract. The phytochemical analysis revealed 3% proteins, 13% total sugars and 17% phenolic compounds. Conclusion: G. Graciliflora has antifungal activity against clinical strains of C. albicans and exhibits proteins, sugars and phenolic compounds in its chemical composition.