Nanostructured lipid carriers loaded with essential oils: a strategy against SARS-CoV-2.

This work aimed to investigate the effectiveness of Lippia sidoides and Syzygium aromaticum essential oils (EOs) encapsulated in nanostructured lipid carriers (NLCs) as SARS-CoV-2 inhibitors through virucidal activity assessment. We developed anionic and cationic NLCs loaded with the EOs and assessed their physicochemical properties and SARS-CoV-2 virucidal activity, focusing on the effects of EO type and the NLCs composition. The NLCs exhibited particle sizes of 141.30 to 160.53 nm for anionic and 109.30 to 138.60 nm for cationic types, with PDIs between 0.16 and 0.25. High zeta potentials (>29.0 in modulus) indicated stable formulations. The NLCs effectively encapsulated the EOs, achieving encapsulation efficiencies between 84.6 to 100% w/w of marker compound. The EOs-loaded NLCs reduced the SARS-CoV-2 virion count, exceeding 2 logs over the control. NLCs loaded with Lippia sidoides and Syzygium aromaticum EOs represent an innovative strategy for combating SARS-CoV-2.

Unraveling the functional attributes of the language connectome: crucial subnetworks, flexibility and variability.

Language processing is a highly integrative function, intertwining linguistic operations (processing the language code intentionally used for communication) and extra-linguistic processes (e.g., attention monitoring, predictive inference, long-term memory). This synergetic cognitive architecture requires a distributed and specialized neural substrate. Brain systems have mainly been examined at rest. However, task-related functional connectivity provides additional and valuable information about how information is processed when various cognitive states are involved. We gathered thirteen language fMRI tasks in a unique database of one hundred and fifty neurotypical adults (InLang [Interactive networks of Language] database), providing the opportunity to assess language features across a wide range of linguistic processes. Using this database, we applied network theory as a computational tool to model the task-related functional connectome of language (LANG atlas). The organization of this data-driven neurocognitive atlas of language was examined at multiple levels, uncovering its major components (or crucial subnetworks), and its anatomical and functional correlates. In addition, we estimated its reconfiguration as a function of linguistic demand (flexibility) or several factors such as age or gender (variability). We observed that several discrete networks could be specifically shaped to promote key functional features of language: coding-decoding (Net1), control-executive (Net2), abstract-knowledge (Net3), and sensorimotor (Net4) functions. The architecture of these systems and the functional connectivity of the pivotal brain regions varied according to the nature of the linguistic process, gender, or age. By accounting for the multifaceted nature of language and modulating factors, this study can contribute to enriching and refining existing neurocognitive models of language. The LANG atlas can also be considered a reference for comparative or clinical studies involving various patients and conditions.

Thymbra capitata essential oil has a significant antimicrobial activity against methicillin-resistant Staphylococcus aureus pre-formed biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant opportunistic pathogen with a great ability to form biofilms. Herein, the antimicrobial potential of Thymbra capitata essential oil (EO) against MRSA biofilms was investigated. The determination of the minimum inhibitory concentration (MIC) and the minimum lethal concentration (MLC) of the T. capitata EO was first investigated on a group of clinical isolates from septicaemias, diabetic foot ulcers and osteomyelitis. Biofilms were incubated with the EO at the MLC and its anti-biofilm potential was investigated. A strong antimicrobial activity was observed, with MIC and MLC values between 0·32 and 0·64 mg l-1 . However, the concentration of EO necessary for the eradication of planktonic cells was insufficient to significantly reduce the biofilm biomass of some isolates. Nevertheless, cell culturability and overall cellular metabolism was strongly reduced in all biofilms tested, only when the EO was tested. Contrary to the tested antibiotics, T. capitata EO showed a significant antimicrobial activity against MRSA biofilms, by reducing cellular metabolism and cellular culturability.

Cerebral venous sinus thrombosis as a consequence of shunt hyperdrainage: a proposal of the pathophysiological mechanism and case report.

BACKGROUND AND AIM: Shunt dysfunction is a common event, especially in children who have this intervention performed early in life. The consequences of chronic shunt overdrainage can be multiple since the cerebral hydrodynamics is altered. A thrombotic event with consequent symptoms of intracranial hypertension is discussed in this article. MATERIAL AND METHODS: We performed a detailed review of cerebral hydrodynamics and intracranial pressure compensation mechanisms and how this can alter cerebral venous circulation. Next, we report the case of a 4-year-old child with such a clinical presentation that was conducted by our team. RESULTS: A child with a history of hydrocephalus treated with a ventriculo-peritoneal (VP) shunt in his early childhood presented with symptoms of intracranial hypertension, initial computed tomography (CT) demonstrating reduced-sized ventricles. Complementary investigation showed bilateral papilledema, cranial suture closure, changes compatible with Chiari type I, and venous sinus thrombosis (transverse and sigmoid, bilaterally). The case was managed conservatively with full anticoagulation with enoxaparin. Four months after the onset of symptoms, there was an improvement in the clinical and imaging status. CONCLUSION: A condition of severe headache in a patient with an apparently functioning shunt and small ventricles on initial CT should open up a range of diagnostic possibilities, with pseudotumor cerebri syndrome and cerebral venous sinus thrombosis being suggested. The therapeutic approach in these cases must be individualized.

Effect of the intra-alveolar administration of dexamethasone on swelling, trismus, and pain after impacted lower third molar extraction: a randomized, double-blind clinical trial.

BACKGROUND: To evaluate the efficacy of intra-alveolar administration of dexamethasone 4 mg in the control of edema, trismus, and pain resulting from the extraction of impacted lower third molars and the drug permeability through the oral mucosa by in silico prediction. MATERIAL AND METHODS: The randomized, double-blind, split-mouth clinical trial included patients who had both impacted lower third molars in equivalent positions. Hemiarches were divided into control side when dexamethasone was administered orally and experimental side when dexamethasone was administered using the intra-alveolar route. Patients were evaluated considering edema, trismus, and pain. The permeability of dexamethasone through the oral mucosa was assessed by in silico prediction. Student's t-test was selected for comparative analysis of edema and trismus, and the chi-square test analyzed the distribution of postoperative pain between the sides. RESULTS: There were no significant differences between the routes of administration in measuring symptoms between the pre and postoperative times (p>0.05). In silico prediction suggested that dexamethasone molecular characteristics facilitate intra-alveolar administration. CONCLUSIONS: Intra-alveolar administration had similar efficacy to oral administration in controlling symptoms of post-surgical inflammation of impacted lower third molars.

Association of Peripheral Blood and Cutaneous Eosinophils With Bullous Pemphigoid Disease Severity and Treatment Outcomes.

BACKGROUND AND AIMS: A dermal inflammatory infiltrate rich in eosinophils is a prominent histological feature of bullous pemphigoid (BP) and peripheral blood eosinophilia has been documented in 50-60% of BP patients. Nevertheless, the impact of circulating and dermal infiltrate eosinophil levels on BP remains poorly understood. The main objective of this work was to investigate the association of peripheral blood and dermal infiltrate eosinophil levels with clinical and immunological characteristics of the disease. MATERIAL AND METHODS: Retrospective cohort study including all patients diagnosed with BP between 2011 and 2020. RESULTS: The study cohort included 233 patients with BP. The mean baseline peripheral blood eosinophil count was 956.3±408.6×106/L and the mean number of tissue eosinophils at the dermal hot spot area was 30.5±19.0. Patients with disseminated presentation (i.e. BSA>50%) had significantly higher peripheral blood eosinophil counts (P=0.028). Mucosal involvement was significantly associated with lower dermal eosinophil count (P=0.001). Requiring inpatient care and relapsing were significantly associated with high peripheral blood eosinophil count (P=0.025; P=0.020, respectively). Among the 68 patients who experienced a relapse, 31 had peripheral blood eosinophilia (i.e. >500×106/L) at relapse (44.2%). Peripheral blood eosinophil counts at baseline and at relapse were significantly correlated (r=0.82, P<0.001). CONCLUSIONS: Peripheral blood and cutaneous eosinophils levels may be useful biomarkers for disease activity and treatment outcomes in BP. Monitoring peripheral blood eosinophil counts may allow early detection of relapse.

IgG4-positive plasma cells are more often detected in chronic periapical lesions arising from permanent rather than primary teeth.

AIM: To characterize plasma cell subsets in chronic periapical lesions affecting permanent and primary teeth. METHODOLOGY: Only chronic periapical lesions without root canal treatment were selected. Twenty-one radicular cysts and 7 periapical granulomas affecting permanent teeth and 19 radicular cysts and 4 periapical granulomas affecting primary teeth were assessed for immunoglobulin (Ig) light chain (kappa and lambda), Ig heavy chain (IgG, IgG4, IgA, IgM and IgD) and plasma cell immunohistochemical markers (MUM1/IRF4, EMA and CD138). The data acquired were analysed by Student's t test, Mann-Whitney U, Friedman test followed by Dunn's multiple comparison test and Spearman's rank correlation. RESULTS: All cases were polyclonal (having similar kappa/lambda light chain ratios). IgG was most abundant compared to other Ig heavy chains (all, P < 0.001); like Ig light chains, but unlike IgA, there was greater expression of IgG in the primary compared to the permanent dentition, for both radicular cysts (P < 0.001) and periapical granulomas (P = 0.53). Notably, IgG4 expression was greater in the permanent than the primary dentition, for both radicular cyst (P < 0.05) and periapical granuloma (P = 0.65). IgM and IgD expression was scarce and variable, whereas plasma cell populations were detected efficiently through EMA, CD138 and MUM1/IRF4 markers, the latter being more sensitive in both dentitions. CONCLUSIONS: There were slight variations in the Ig light and heavy chain profiles in chronic periapical lesions when comparing the permanent and primary dentitions. The ability of IgG4+ plasma cell infiltration to modulate inflammatory responses in chronic periapical lesions arising from permanent as opposed to primary teeth should be considered in future studies.

Preferential expression of a HPV genotype in invasive cervical carcinomas infected by multiple genotypes.

Multiple infections by HPV genotypes are frequently detected in HPV+ cervical lesions but the interaction between each viral genotype during carcinogenesis is poorly understood. Here we carried out a comprehensive study to characterize the multiple HPV expression and integration by RNA-seq analyses of 19 invasive cervical carcinomas coinfected by several HPV genotypes. Analysis of tumor DNA by a hybridization assay indicated multiple infections ranging from 2 to 6 different HPV genotypes. RNA-seq analysis showed that a single HPV genotype was preferentially expressed. Finally, the search for HPV/human chimeric transcripts indicated integration from preferentially expressed genotypes. In conclusion, the present study indicated that, in invasive cervical carcinomas infected by multiple HPV genotypes, one HPV was preferentially expressed, supporting the hypothesis that a single HPV genotype was associated with cancer development.

Chronic toxicity and environmental risk assessment of antivirals in Ceriodaphnia dubia and Raphidocelis subcapitata.

Antiviral drugs are a class of medications used for treating viral infections. Due to their widespread use, especially in cases of pandemics and limited human metabolism, antivirals have been detected in multiple environmental matrices. This study aims to evaluate the chronic effects of acyclovir, efavirenz, lamivudine and zidovudine using Ceriodaphnia dubia and Raphidocelis subcapitata. The results with R. subcapitata showed the following toxicities: zidovudine (IC50 = 5.442 mg L-1) < acyclovir (IC50 = 3.612 mg L-1) < lamivudine (IC50 = 3.013 mg L-1) < efavirenz (IC50 = 0.034 mg L-1). The results of the chronic bioassay with C. dubia demonstrated that zidovudine is the least toxic (EC50 = 5.671 mg L-1), followed by acyclovir (EC50 = 3.062 mg L-1), lamivudine (EC50 = 1.345 mg L-1) and efavirenz (EC50 = 0.026 mg L-1). Both species have been shown to be sensitive to efavirenz. A risk quotient (RQ) was calculated, and efavirenz had an RQ greater than 1 for both species, and lamivudine had an RQ greater than 1 for C. dubia, representing a high ecological risk for these organisms. Antivirals pose a significant environmental risk to aquatic organisms and should be taken into consideration in future monitoring of water sources.

Leukemia cutis and eccrine squamous syringometaplasia.

Eccrine squamous syringometaplasia (ESS) is a histological term describing a mature squamous metaplasia of the eccrine ducts. Eccrine squamous syringometaplasia is not an infrequent histological finding and may be associated with chemotherapy or with a variety of non-specific conditions including infections, neoplastic conditions, and inflammatory skin diseases. We report a 75-year-old man who developed ESS within lesions of leukemia cutis (LC). The patient had an inaugural diagnosis of acute myeloid leukemia (AML) and he was not on chemotherapy when the biopsy was performed.

BRAF L597K mutation: an opportunity to treat.

The outcomes of patients with metastatic melanoma (MM) have significantly improved after the introduction of BRAF-specific inhibitors. Herein is reported a patient with MM and non-V600-BRAF mutation who responded to iBRAF/iMEK therapy. In July 2014, a 63-year-old man presented with a 4.1mm-thick V600E-BRAF wild type melanoma on the back. Metastases were identified in one sentinel node and two of 11 subsequently excised lymph nodes, with no signs of distant metastatic disease. In September 2017, lung metastasis was observed and pembrolizumab was started. Progressive disease was apparent at cycle 10 and therapy was switched to ipilimumab. After four cycles, an asymmetric response was observed. In November 2017, next generation sequencing genomic profiling disclosed a rare L597K-BRAF mutation and vemurafenib plus cobimetinib therapy was initiated in January 2018. Seven days after treatment start, a remarkable clinical improvement was observed. In April 2018, the patient achieved partial response, which was sustained until October 2018. Cases of patients with non-V600-BRAF mutations responding to iBRAF/iMEK therapy have been reported over the last years. To the best of our knowledge, this is the first case reporting response to combined iBRAF/iMEK therapy in a patient with metastatic melanoma harboring L597K mutation.

Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel.

BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements. CONCLUSIONS: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.

Cutaneous metastases from solid neoplasms in the 21st century: a retrospective study from a Portuguese tertiary care center.

INTRODUCTION: Cutaneous metastases account for 2% of all skin cancers and are usually associated with widespread disease. The main of this retrospective study was to describe and illustrate clinicopathological features of cutaneous metastases diagnosed in our centre since the beginning of this century. METHODS: All cases of cutaneous metastases from solid neoplasms diagnosed in our Dermatopathology Department from January 2000 to December 2018 were included. Statistical analysis was performed with SPSS. RESULTS: A total of 164 patients were included, with a female to male ratio of 3:2. Malignancies that most commonly metastasized to the skin were melanoma (N = 58), breast cancer (N = 54) and lung cancer (N = 13). Immunohistochemical study was performed in 99 patients (60.4%). Time diagnosis of the primary tumour and appearance of cutaneous metastases was significantly higher in breast cancer, followed by melanoma and then by lung cancer (P < 0.05). Median survival after diagnosis of cutaneous metastases was 8 months. Survival after diagnosis of cutaneous metastases was also influenced by age of the patient, both at diagnosis of the primary tumour and at diagnosis of the cutaneous metastasis. DISCUSSION: Clinical presentation of cutaneous metastases is highly variable and non-specific, being easily mistaken for other dermatological conditions. Histopathological examination is essential in this setting, and the judicious use of an immunohistochemistry panel considered the appropriate morphologic and clinical context. Survival after the diagnosis of cutaneous metastases is influenced not only by the location of the tumour but also by the age of the patient. Dermatologists should therefore be to these clinical pictures, and a high degree of suspicion is, along with a careful clinical history and physical examination. Although being limited by its retrospective nature, we describe one of the largest European series of cutaneous metastases, with findings with most of the available literature.

Cr (VI) reduction by photocatalyic process: Nb2O5 an alternative catalyst.

In this study, Nb2O5 catalyst was applied in the photocatalytic process for the Chromium reduction. Cr (VI) is a compound classified as highly toxic and often found in industrial tannery effluents. The techniques used for the photocatalytic material characterization were: X-ray diffraction, Specific surface area (B.E.T method), photo-acoustic spectroscopy, Scanning Electron Microscopy (SEM) and X-ray Dispersive Energy Spectrometry (EDS). A comparison between Nb2O5 and TiO2 (widely used in photocatalytic reactions) indicated that Nb2O5 has 20% more Cr (VI) reduction than TiO2. Tests carried out with Nb2O5 calcined at 500 °C and with non-calcined Nb2O5 showed that the heat treatment did not favor the reaction. Parameters such as pH, radiation intensity, initial concentration of Cr (VI) and amount of catalyst were studied. The results indicated that the acid (pH 2), emitted radiation intensity (250 W), initial concentration Cr (VI) at 10 mg L-1 and 1.5 g L-1 Nb2O5 non-calcined are the process optimal conditions. In addition, the reuse tests for Nb2O5 in consecutive cycles four, were realized. Photostability was maintained at approximately 90% for all cycles when Nb2O5 calcined was used. On the other hand, when using Nb2O5 non-calcined reduced by 21% during the four tests. This behavior is possibly due to the greater adsorption capacity of the non-calcined material. Making the Nb2O5 catalyst attractive for considering larger scale tests.

Bone tissue response to an MTA-based endodontic sealer, and the effect of the addition of calcium aluminate and silver particles.

AIM: To evaluate bone tissue reactions in rats to an MTA-based endodontic sealer with and without the addition of various concentrations of C3A or C3A + Ag. METHODOLOGY: Bone tissue reactions were evaluated in 45 Wistar rats after 7, 30 and 90 days (n = 5 per period). Three surgical cavities were prepared on the right femur and filled with 0.2 mL MTA Fillapex, MTA Fillapex + C3A and C3A + Ag at various concentrations: AH Plus (Dentsply DeTrey GmbH, Konstanz, Germany), EndoSequence BC (Brasseler USA, Savannah, GA, USA) or no sealer (negative control). By the end of each experimental period, animals were randomly euthanized. The samples were histologically processed and analysed using a light microscope. The presence of inflammatory cells, fibres and hard tissue barrier formation was evaluated. Data were analysed statistically using nonparametric tests to compare the differences between groups. Multiple groups were compared using the Kruskal-Wallis and Mann-Whitney U-tests with a Bonferroni correction at P = 0.05. RESULTS: The inflammatory response significantly decreased from 30 to 90 days (P < 0.05). Fibre condensation was similar amongst the groups at 07 and 30 days after intervention (P > 0.05). At 90 days, however, fibres were absent in most specimens of EndoSequence BC Sealer, AH Plus, MTA Fillapex and the control group, whilst they were still observed in samples of the modified sealers (P < 0.05). At 90 days, all specimens of AH Plus, EndoSequence BC Sealer and control group had complete formation of hard tissue barrier. In the MTA Fillapex group, as well as in the modified sealers groups, partial deposition of mineralized tissue was noticed. CONCLUSION: The hypothesis tested that the incorporation of C3A and C3A + Ag particles to MTA Fillapex would improve bone tissue repair was partially accepted, since modified MTA Fillapex did not have the same repair potential as the commercial bioceramic material.

Socio-demographic characteristics are related to the advanced clinical stage of oral cancer.

BACKGROUND: Social determinants may be associated with the onset and progression of the clinical stage of oral cancer. AIM: To evaluate the impact of socio-demographic characteristics on the prevalence of advanced clinical stage of oral cancer. MATERIAL AND METHODS: Information about 51,116 cases of oral cancer, from all Brazilian states, between 2000 and 2012, was obtained from the Cancer Registry Information System. The clinical stage of oral cancer (dependent variable) was classified as initial (stages I and II) or advanced (stages III and IV). The relationship between the clinical stage of oral cancer and the following independent variables was analyzed: sex, age, schooling, marital status, family history of cancer, and origin of referral. Analyses on frequency distribution and multivariate binary logistic regression model were performed (α<0.05). RESULTS: Compared to individuals with no schooling, those who attended elementary to high school (OR=2.461) and college education (OR = 3.050) had a higher prevalence of advanced cases of oral cancer. Individuals without a partner (OR = 14,209) demonstrated a higher prevalence compared to married individuals. Subjects aged 20-44 years (OR = 4.081) and 45-64 years (OR = 14.875) had a higher prevalence compared to those aged 15-19 years. The variables gender, family history of cancer and origin of referral integrated the binary model of logistic regression, but did not present statistical significance. CONCLUSIONS: Socioeconomic factors may be related to the advanced clinical stage of oral cancer.

Mycobacterium marinum lymphocutaneous infection.

Mycobacterium marinum is a nontuberculous mycobacteria with worldwide distribution that lives in fresh or salt water and is responsible for infections in fish, and sometimes in humans. Human disease consists mainly of cutaneous nodules, but deep structure involvement may also occur. Diagnosis of M. marinum infection remains a challenge, with a considerable time delay between onset of symptoms and diagnosis. We present a 33-year-old man with no immunosuppressive history who was seen in our department with skin nodules over his hand and forearm, distributed in a sporotrichoid pattern. His hobbies included maintaining an aquarium of tropical fish. Histological examination of the patient's skin biopsy was compatible with the diagnosis of mycobacterial infection, and the Ziehl-Neelsen staining revealed acid-fast bacilli. Molecular techniques confirmed the suspicion of M. marinum infection. A necropsy was performed on one of the patient's fish, more specifically, a Poecilia reticulata, and resulted in identification of M. marinum from its gut. The patient was treated with clarithromycin, ethambutol, and rifampicin for 9 months, with clearance of infection.

Anti-oxidants correct disturbance of redox enzymes in the hearts of rat fetuses with congenital diaphragmatic hernia.

AIM: To evaluate if the redox system is unbalanced in the hearts of nitrofen-induced congenital diaphragmatic hernia  (CDH) animals and to study the possible preventive effects of two anti-oxidant treatments, apocynin and epigallocatechin-3-gallate (EGCG). METHODS: Adult rats were divided into four groups. Group 1: rats received only vehicle on day E9.5. Group 2: rats received 100 mg nitrofen on day E9.5. Group 3: 1 month before mating rats received apocynin 1.5 mM and, when pregnant, 100 mg nitrofen on day E9.5. Group 4: same than group 3 but with EGCG 30 mg/kg. All fetuses were recovered at term and the hearts were processed. Nox activity and mRNA levels of Nox1, Nox2, Nox4, SOD1, SOD2, SOD3, catalase, and GPX1 were analyzed. Nox, SOD, and Catalase activity and H2O2 production were also evaluated. RESULTS: Nox activity, H2O2 production and Nox1, Nox2, and Nox4 mRNA levels were increased in the hearts of fetuses with CDH. There were no changes in SOD1 levels, whereas those of SOD2, SOD3, catalase, and GPX1 mRNA were decreased. Apocynin and EGCG treatments attenuated the increment of Nox and SOD activities and H2O2 production was only decreased by apocynin. CONCLUSION: These findings suggest a possible preventive effect on the abnormal redox metabolism of anti-oxidant treatments in the hearts from rat fetuses with CDH. If the same occurs in humans, it could represent a potential tool in future prenatal treatment.