Migraine aura discrimination using machine learning: an fMRI study during ictal and interictal periods.

Functional magnetic resonance imaging (fMRI) studies on migraine with aura are challenging due to the rarity of patients with triggered cases. This study optimized methodologies to explore differences in ictal and interictal spatiotemporal activation patterns based on visual stimuli using fMRI in two patients with unique aura triggers. Both patients underwent separate fMRI sessions during the ictal and interictal periods. The Gaussian Process Classifier (GPC) was used to differentiate these periods by employing a machine learning temporal embedding approach and spatiotemporal activation patterns based on visual stimuli. When restricted to visual and occipital regions, GPC had an improved performance, with accuracy rates for patients A and B of roughly 86-90% and 77-81%, respectively (p < 0.01). The algorithm effectively differentiated visual stimulation and rest periods and identified times when aura symptoms manifested, as evident from the varying predicted probabilities in the GPC models. These findings contribute to our understanding of the role of visual processing and brain activity patterns in migraine with aura and the significance of temporal embedding techniques in examining aura phenomena. This finding has implications for diagnostic tools and therapeutic techniques, especially for patients suffering from aura symptoms.

Gellan-Based Hydrogel as a Drug Delivery System for Caffeic Acid Phenethyl Ester in the Treatment of Oral Candida albicans Infections.

Candida albicans can cause various types of oral infections, mainly associated with denture stomatitis. Conventional therapy has been linked to high recurrence, toxicity, and fungal resistance, necessitating the search for new drugs and delivery systems. In this study, caffeic acid phenethyl ester (CAPE) and gellan gum (GG) were studied as an antifungal agent and carrier system, respectively. First, we observed that different GG formulations (0.6 to 1.0% wt/vol) were able to incorporate and release CAPE, reaching a controlled and prolonged release over 180 min at 1.0% of GG. CAPE-GG formulations exhibited antifungal activity at CAPE concentrations ranging from 128 to >512 µg/mL. Furthermore, CAPE-GG formulations significantly decreased the fungal viability of C. albicans biofilms at short times (12 h), mainly at 1.0% of GG (p < 0.001). C. albicans protease activity was also reduced after 12 h of treatment with CAPE-GG formulations (p < 0.001). Importantly, CAPE was not cytotoxic to human keratinocytes, and CAPE-GG formulations at 1.0% decreased the fungal burden (p = 0.0087) and suppressed inflammation in a rat model of denture stomatitis. Altogether, these results indicate that GG is a promising delivery system for CAPE, showing effective activity against C. albicans and potential to be used in the treatment of denture stomatitis.

New Insights into Cutaneous Asepsis: Synergism between Pfaffia and Rosemary Extracts.

(1) Background: In hospitals, medical and dental clinics, antiseptics or disinfectants play an essential role in the control of nosocomial infections. This study aimed to evaluate R. officinalis and P. paniculata glycolic extracts regarding: (I) their antimicrobial action on planktonic and biofilm (monotypic and cutaneous biofilm model-S. aureus, S. epidermidis and C. acnes); and (II) their cytotoxicity on human keratinocytes (HaCaT). (2) Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were performed (CLSI protocol M7-A6 and M11-A8). MTT analysis was used to evaluate the antibiofilm activity of the extracts on biofilms and their cytotoxicity on human keratinocytes. (3) Results: The combined glycolic extracts MIX A (75% P. paniculata + 25% R. officinalis); MIX B (50% P. paniculata + 50% R. officinalis); and MIX C (25% P. paniculata + 75% R. officinalis) promoted MBC values by 50 mg/mL on S. aureus, absent on S. epidermidis, and ranged 6.25-50 mg/mL for C. acnes. The cutaneous biofilm model was reduced more than 90%. In addition, it showed biocompatibility with human keratinocytes, resulting in percentages of viability greater than 50%. (4) Conclusions: The combination of extracts promoted antimicrobial action on planktonic cultures, and monotypic and heterotypic biofilms of skin pathogens. Additionally, these extracts are biocompatible against human keratinocytes.

Corrigendum: Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit.

[This corrects the article DOI: 10.3389/fmed.2023.1130218.].

Clinical and epidemiological features of mpox in a Brazilian reference center for HIV and sexually transmitted infections: A cross-sectional study.

Background: The 2022 mpox outbreak has affected disproportionately people living with HIV (PLWH) and pre-exposure prophylaxis (PrEP) users. Methods: We conducted a cross-sectional study to evaluate factors associated with laboratory diagnosis of mpox among suspected cases, and access differences between PrEP users and PLWH with confirmed diagnostic. Results: 394 mpox suspected cases were analyzed, 309 (78.4%) confirmed. Most patients with mpox were PLWH (54.4%) and 99 (32%) PrEP users. Mpox cases were likely to be between 25 and 39 years old (aOR=2.8; p=0.042), men who have sex with men/bisexual or transgender women (aOR=17.2; p< 0.001) and to have fever (aOR=4.7; p< 0.001), adenomegaly (aOR=7.2; p< 0.001) and multiple vesicular lesions (aOR=4.2; p< 0.001). Comparing PrEP users to PLWH with confirmed mpox, PrEP users had lesions predominantly with exclusive genital involvement (p=0.016); while PLWH had higher extragenital involvement (p=0.018). Conclusions: PrEP users and PLWHA were the main epidemiological groups in our cohort. Recognizing the differences between vulnerable populations can contribute to the development public policies to control mpox in settings with reduced access to vaccines.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Silk fibroin-derived electrospun materials for biomedical applications: A review.

Electrospinning is a versatile technique for fabricating polymeric fibers with diameters ranging from micro- to nanoscale, exhibiting multiple morphologies and arrangements. By combining silk fibroin (SF) with synthetic and/or natural polymers, electrospun materials with outstanding biological, chemical, electrical, physical, mechanical, and optical properties can be achieved, fulfilling the evolving biomedical demands. This review highlights the remarkable versatility of SF-derived electrospun materials, specifically focusing on their application in tissue regeneration (including cartilage, cornea, nerves, blood vessels, bones, and skin), disease treatment (such as cancer and diabetes), and the development of controlled drug delivery systems. Additionally, we explore the potential future trends in utilizing these nanofibrous materials for creating intelligent biomaterials, incorporating biosensors and wearable sensors for monitoring human health, and also discuss the bottlenecks for its widespread use. This comprehensive overview illuminates the significant impact and exciting prospects of SF-derived electrospun materials in advancing biomedical research and applications.

Assessment of the ABC2-SPH risk score to predict invasive mechanical ventilation in COVID-19 patients and comparison to other scores.

Background: Predicting the need for invasive mechanical ventilation (IMV) is important for the allocation of human and technological resources, improvement of surveillance, and use of effective therapeutic measures. This study aimed (i) to assess whether the ABC2-SPH score is able to predict the receipt of IMV in COVID-19 patients; (ii) to compare its performance with other existing scores; (iii) to perform score recalibration, and to assess whether recalibration improved prediction. Methods: Retrospective observational cohort, which included adult laboratory-confirmed COVID-19 patients admitted in 32 hospitals, from 14 Brazilian cities. This study was conducted in two stages: (i) for the assessment of the ABC2-SPH score and comparison with other available scores, patients hospitalized from July 31, 2020, to March 31, 2022, were included; (ii) for ABC2-SPH score recalibration and also comparison with other existing scores, patients admitted from January 1, 2021, to March 31, 2022, were enrolled. For both steps, the area under the receiving operator characteristic score (AUROC) was calculated for all scores, while a calibration plot was assessed only for the ABC2-SPH score. Comparisons between ABC2-SPH and the other scores followed the Delong Test recommendations. Logistic recalibration methods were used to improve results and adapt to the studied sample. Results: Overall, 9,350 patients were included in the study, the median age was 58.5 (IQR 47.0-69.0) years old, and 45.4% were women. Of those, 33.5% were admitted to the ICU, 25.2% received IMV, and 17.8% died. The ABC2-SPH score showed a significantly greater discriminatory capacity, than the CURB-65, STSS, and SUM scores, with potentialized results when we consider only patients younger than 80 years old (AUROC 0.714 [95% CI 0.698-0.731]). Thus, after the ABC2-SPH score recalibration, we observed improvements in calibration (slope = 1.135, intercept = 0.242) and overall performance (Brier score = 0.127). Conclusion: The ABC2-SPHr risk score demonstrated a good performance to predict the need for mechanical ventilation in COVID-19 hospitalized patients under 80 years of age.

Syndesmosis dislocation and ankle ligament stress in the posterior malleolus fracture fixated - "in vitro analysis".

PURPOSE: The objectives of this study were to compare syndesmosis dislocation and ankle ligament stress after the fixation of the posterior malleolus fracture (PMF) with four different techniques by Finite Element Analysis (FEM). METHODS: Four internal fixation techniques used for fixation of PMF were assessed by FEM: posterior one-third tubular 3.5 mm buttress plate (PP) with one screw (PP 1 screw), PP with two screws (PP 2 screws), two cannulated 3.5 mm lag screws in the anteroposterior (AP) direction (AP lag screws), and two posteroanterior (PA) cannulated 3.5 mm lag screws (PA lag screws). PMF with 30% fragment size was simulated through computational processing reconstructed from computed tomography (CT). The simulated loads of 700 N and 1200 N were applied to the proximal tibial end. The FEM evaluated the syndesmosis dislocation (mm) and stress values of the posterior tibiofibular ligament (PTFL) (in Kpa) and deltoid ligament (in Kpa) in the four mentioned subgroups. RESULTS: We found that with a load of 700 N, syndesmosis dislocation varied from 6.5 to 7.9 mm, being the lowest and greatest for PA lag screw and PP 1 screw, respectively. In all groups was observed a greater dislocation in the syndesmosis at 1200 N of load. We observed that the stress values on the PTFL were lower for AP lag screws and PP 2 screws with 700 N and 1200 N, respectively. For both loads, PP 1 screw presented the greatest stress. Regarding the stress in the deltoid ligament, the AP lag screws presented the lowest stress for 700 N and PP 1 screw for 1200 N. For all fixation techniques, the syndesmosis displacement and ligament stresses were higher when 1200 N were imposed. CONCLUSION: This study demonstrated that PMF fixed with lag screws presents greater stability in the distal tibiofibular syndesmosis and higher joint loadings promoted greater displacement and ligaments stress, regardless of the fixation technique. Besides, lower stress in the syndesmosis is accompanied by a greater load on the deltoid ligament.

Saliva culture as a predictive indicator for current blood infections and antimicrobial resistance in the ICU setting.

Antimicrobial resistance is a worldwide health problem and patients in intensive care are more vulnerable, requiring strict control measures and early identification. Currently, clinical culture materials are used to identify the bacterial agent, but saliva culture is not validated, which has great clinical relevance because it participates in several pathophysiological processes. The aim of this study was to validate saliva culture in an intensive care unit environment, determining its diagnostic value for infection. For this purpose, the results of the 39-month surveillance cultures, from the database of a private hospital were evaluated. A total of 323 cultures were paired between saliva, tracheal secretions, blood and urine from patients who were hospitalized for more than 5 days. The search for correlations between the results was performed using the Spearman correlation test. Severity and evolution data were also correlated. It was possible to correlate the presence of Klebsiella spp. between blood culture and saliva culture in 25% of the results (r = 0.01) and the correlation between saliva and tracheal secretion was 33% (r = 0.33447) with p < 0.0001. In conclusion, saliva can be an excellent discriminator of systemic infections, and can be considered a useful culture in clinical practice.

Synergistic Antibiofilm Action of Cinnamomum verum and Brazilian Green Propolis Hydroethanolic Extracts against Multidrug-Resistant Strains of Acinetobacter baumannii and Pseudomonas aeruginosa and Their Biocompatibility on Human Keratinocytes.

The accumulated dental biofilm can be a source of oral bacteria that are aspirated into the lower respiratory tract causing ventilator-associated pneumonia in hospitalized patients. The aim of this study was to evaluate the synergistic antibiofilm action of the produced and phytochemically characterized extracts of Cinnamomum verum and Brazilian green propolis (BGP) hydroethanolic extracts against multidrug-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa, in addition to their biocompatibility on human keratinocyte cell lines (HaCaT). For this, High-performance liquid chromatography analysis of the plant extracts was performed; then the minimum inhibitory and minimum bactericidal concentrations of the extracts were determined; and antibiofilm activity was evaluated with MTT assay to prevent biofilm formation and to reduce the mature biofilms. The cytotoxicity of the extracts was verified using the MTT colorimetric test, evaluating the cellular enzymatic activity. The data were analyzed with one-way ANOVA and Tukey's tests as well as Kruskal-Wallis and Dunn's tests, considering a significance level of 5%. It was possible to identify the cinnamic aldehyde in C. verum and p-coumaric, caffeic, and caffeoylquinic acids as well as flavonoids such as kaempferol and kaempferide and Artepillin-C in BGP. The combined extracts were effective in preventing biofilm formation and reducing the mature biofilms of A. baumannii and P. aeruginosa. Moreover, both extracts were biocompatible in different concentrations. Therefore, C. verum and BGP hydroethanolic extracts have bactericidal and antibiofilm action against multidrug resistant strains of A. baumannii and P. aeruginosa. In addition, the combined extracts were capable of expressively inhibiting the formation of A. baumannii and P. aeruginosa biofilms (prophylactic effect) acting similarly to 0.12% chlorhexidine gluconate.

COVID-19 outcomes in people living with HIV: Peering through the waves.

OBJECTIVE: To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. METHODS: This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. RESULTS: Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). CONCLUSIONS: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group.

Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit.

Objectives: To assess the ABC2-SPH score in predicting COVID-19 in-hospital mortality, during intensive care unit (ICU) admission, and to compare its performance with other scores (SOFA, SAPS-3, NEWS2, 4C Mortality Score, SOARS, CURB-65, modified CHA2DS2-VASc, and a novel severity score). Materials and methods: Consecutive patients (≥ 18 years) with laboratory-confirmed COVID-19 admitted to ICUs of 25 hospitals, located in 17 Brazilian cities, from October 2020 to March 2022, were included. Overall performance of the scores was evaluated using the Brier score. ABC2-SPH was used as the reference score, and comparisons between ABC2-SPH and the other scores were performed by using the Bonferroni method of correction. The primary outcome was in-hospital mortality. Results: ABC2-SPH had an area under the curve of 0.716 (95% CI 0.693-0.738), significantly higher than CURB-65, SOFA, NEWS2, SOARS, and modified CHA2DS2-VASc scores. There was no statistically significant difference between ABC2-SPH and SAPS-3, 4C Mortality Score, and the novel severity score. Conclusion: ABC2-SPH was superior to other risk scores, but it still did not demonstrate an excellent predictive ability for mortality in critically ill COVID-19 patients. Our results indicate the need to develop a new score, for this subset of patients.

Potential and limitations of machine meta-learning (ensemble) methods for predicting COVID-19 mortality in a large inhospital Brazilian dataset.

The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48-71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors.

Mechanical ventilation and death in pregnant patients admitted for COVID-19: a prognostic analysis from the Brazilian COVID-19 registry score.

BACKGROUND: The assessment of clinical prognosis of pregnant COVID-19 patients at hospital presentation is challenging, due to physiological adaptations during pregnancy. Our aim was to assess the performance of the ABC2-SPH score to predict in-hospital mortality and mechanical ventilation support in pregnant patients with COVID-19, to assess the frequency of adverse pregnancy outcomes, and characteristics of pregnant women who died. METHODS: This multicenter cohort included consecutive pregnant patients with COVID-19 admitted to the participating hospitals, from April/2020 to March/2022. Primary outcomes were in-hospital mortality and the composite outcome of mechanical ventilation support and in-hospital mortality. Secondary endpoints were pregnancy outcomes. The overall discrimination of the model was presented as the area under the receiver operating characteristic curve (AUROC). Overall performance was assessed using the Brier score. RESULTS: From 350 pregnant patients (median age 30 [interquartile range (25.2, 35.0)] years-old]), 11.1% had hypertensive disorders, 19.7% required mechanical ventilation support and 6.0% died. The AUROC for in-hospital mortality and for the composite outcome were 0.809 (95% IC: 0.641-0.944) and 0.704 (95% IC: 0.617-0.792), respectively, with good overall performance (Brier = 0.0384 and 0.1610, respectively). Calibration was good for the prediction of in-hospital mortality, but poor for the composite outcome. Women who died had a median age 4 years-old higher, higher frequency of hypertensive disorders (38.1% vs. 9.4%, p < 0.001) and obesity (28.6% vs. 10.6%, p = 0.025) than those who were discharged alive, and their newborns had lower birth weight (2000 vs. 2813, p = 0.001) and five-minute Apgar score (3.0 vs. 8.0, p < 0.001). CONCLUSIONS: The ABC2-SPH score had good overall performance for in-hospital mortality and the composite outcome mechanical ventilation and in-hospital mortality. Calibration was good for the prediction of in-hospital mortality, but it was poor for the composite outcome. Therefore, the score may be useful to predict in-hospital mortality in pregnant patients with COVID-19, in addition to clinical judgment. Newborns from women who died had lower birth weight and Apgar score than those who were discharged alive.

The impact of a violent community on mental health and the benefits of a sport program for social development.

The aim of the present study was to evaluate the impact of a violent environment on mental health and the impact of a sport for social development (SSD) program on quality of life, mental distress symptoms, and heart rate variability (HRV). HRV and psychometric data were measured from 20 men professional athletes assisted by the SSD and 20 men living in the same violent community. The comparison of groups revealed greater sympathetic parameters of HRV, positive affect, and quality of life in the SSD group. Multiple regression analysis showed that the quality of life in the SSD group was positively predicted by positive affect, while in the control group the quality of life was negatively predicted by their history of traumatic events. Both groups reported high levels of exposure to traumatic events and posttraumatic stress symptoms. However, this study demonstrates the benefits of SSD programs in mental health.

Antimicrobial action of four herbal plants over mixed-species biofilms of Candida albicans with four different microorganisms.

This study aimed to evaluate the antimicrobial effect of four herbal plants glycolic extracts over mixed-species biofilm composed of Candida albicans (C. albicans) and another pathogenic bacterium as alternative therapy to be investigated. Four plants extract of Pfaffia paniculata roots; Hamamelis virginiana leaf, Stryphnodendron barbatiman tree bark and Gymnema sylvestre stem and leaves were tested over multi-species biofilm of C. albicans (ATCC 18804) and Streptococcus mutans (ATCC 35688), Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 4083) or Pseudomonas aeruginosa (ATCC 15442) for 5 min and 24 h and colony forming units per millilitre was calculated. The data were analysed using Kruskal-Wallis with Dunn's test (p ≤ 0.05). All tested extracts showed antimicrobial action over the mixed-species biofilms after 24 h. Some extracts eliminated totally the biofilms. The glycolic extract of P. paniculata, H. virginiana, S. barbatiman and G. sylvestre are effective over mixed-species biofilms and may be indicated as endodontic irrigant or intracanal medication.