Phytoconstituents and Ergosterol Biosynthesis-Targeting Antimicrobial Activity of Nutmeg (Myristica fragans Houtt.) against Phytopathogens.

In recent years, nutmeg (Myristica fragans Houtt.) has attracted considerable attention in the field of phytochemistry due to its diverse array of bioactive compounds. However, the potential application of nutmeg as a biorational for crop protection has been insufficiently explored. This study investigated the constituents of a nutmeg hydroethanolic extract via gas chromatography-mass spectrometry and vibrational spectroscopy. The research explored the extract's activity against phytopathogenic fungi and oomycetes, elucidating its mechanism of action. The phytochemical profile revealed fatty acids (including tetradecanoic acid, 9-octadecenoic acid, n-hexadecanoic acid, dodecanoic acid, and octadecanoic acid), methoxyeugenol, and elemicin as the main constituents. Previously unreported phytochemicals included veratone, gelsevirine, and montanine. Significant radial growth inhibition of mycelia was observed against Botrytis cinerea, Colletotrichum acutatum, Diplodia corticola, Phytophthora cinnamomi, and especially against Fusarium culmorum. Mode of action investigation, involving Saccharomyces cerevisiae labeled positively with propidium iodide, and a mutant strain affected in ERG6, encoding sterol C-24 methyltransferase, suggested that the extract induces a necrotic type of death and targets ergosterol biosynthesis. The evidence presented underscores the potential of nutmeg as a source of new antimicrobial agents, showing particular promise against F. culmorum.

Efficacy of photobiomodulation in the treatment of oral mucositis in patients undergoing antineoplastic therapy: systematic review and meta-analysis.

PURPOSE: To evaluate the effectiveness of photobiomodulation in the treatment of oral mucositis. METHODS: Systematic review and meta-analysis encompassing in the electronic databases: LILACS, MEDLINE, EMBASE, COCHRANE, SCOPUS, WEB OF SCIENCE, and CINAHL and in http://clinicaltrials.gov . Eligibility criteria were randomized, non-randomized, and observational studies that used photobiomodulation for the treatment of oral mucositis. The endpoints were reduction in the severity of oral mucositis, duration of lesions, and pain reduction. For data analysis, the Review Manager 5.4 program was used. RESULTS: A total of 316 studies were identified, 297 in the electronic databases and 19 in http://clinicaltrials.gov . After removing duplicates, 260 studies were selected for title and abstract reading, of which 223 were excluded. A total of 37 studies were chosen for full reading, of which 6 were included in the review, totaling 299 patients. The treatment used was photobiomodulation. The patients were divided into two groups: the laser group used only photobiomodulation or associated with other therapies, and the control group did not use photobiomodulation. For the endpoint reduction in the severity of oral mucositis (OM), the chance of reduction of the OM was greater in the laser group as compared to the control group. For the endpoints duration of OM lesions and pain reduction, it was not possible to carry out a meta-analysis due to the high heterogeneity between studies. In the interpretation of the meta-analysis, the reduction in the severity of oral mucositis was greater in the group that received photobiomodulation. CONCLUSION: Photobiomodulation was effective in the treatment of oral mucositis.

A Glimpse into Dendrimers Integration in Cancer Imaging and Theranostics.

Cancer is a result of abnormal cell proliferation. This pathology is a serious health problem since it is a leading cause of death worldwide. Current anti-cancer therapies rely on surgery, radiation, and chemotherapy. However, these treatments still present major associated problems, namely the absence of specificity. Thus, it is urgent to develop novel therapeutic strategies. Nanoparticles, particularly dendrimers, have been paving their way to the front line of cancer treatment, mostly for drug and gene delivery, diagnosis, and disease monitoring. This is mainly derived from their high versatility, which results from their ability to undergo distinct surface functionalization, leading to improved performance. In recent years, the anticancer and antimetastatic capacities of dendrimers have been discovered, opening new frontiers to dendrimer-based chemotherapeutics. In the present review, we summarize the intrinsic anticancer activity of different dendrimers as well as their use as nanocarriers in cancer diagnostics and treatment.

Differential Expression of Proteins in an Atypical Presentation of Autoimmune Lymphoproliferative Syndrome.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease defined as a defect in the lymphocyte apoptotic pathway. Currently, the diagnosis of ALPS is based on clinical aspects, defective lymphocyte apoptosis and mutations in Fas, FasL and Casp 10 genes. Despite this, ALPS has been misdiagnosed. The aim of this work was to go one step further in the knowledge of the disease, through a molecular and proteomic analysis of peripheral blood mononuclear cells (PBMCs) from two children, a 13-year-old girl and a 6-year-old boy, called patient 1 and patient 2, respectively, with clinical data supporting the diagnosis of ALPS. Fas, FasL and Casp10 genes from both patients were sequenced, and a sample of the total proteins from patient 1 was analyzed by label-free proteomics. Pathway analysis of deregulated proteins from PBMCs was performed on the STRING and PANTHER bioinformatics databases. A mutation resulting in an in-frame premature stop codon and protein truncation was detected in the Fas gene from patient 2. From patient 1, the proteomic analysis showed differences in the level of expression of proteins involved in, among other processes, cell cycle, regulation of cell cycle arrest and immune response. Noticeably, the most down-regulated protein is an important regulator of the cell cycle process. This could be an explanation of the disease in patient 1.

Lipid Droplets in Cancer: From Composition and Role to Imaging and Therapeutics.

Cancer is the second most common cause of death worldwide, having its origin in the abnormal growth of cells. Available chemotherapeutics still present major drawbacks, usually associated with high toxicity and poor distribution, with only a small fraction of drugs reaching the tumour sites. Thus, it is urgent to develop novel therapeutic strategies. Cancer cells can reprogram their lipid metabolism to sustain uncontrolled proliferation, and, therefore, accumulate a higher amount of lipid droplets (LDs). LDs are cytoplasmic organelles that store neutral lipids and are hypothesized to sequester anti-cancer drugs, leading to reduced efficacy. Thus, the increased biogenesis of LDs in neoplastic conditions makes them suitable targets for anticancer therapy and for the development of new dyes for cancer cells imaging. In recent years, cancer nanotherapeutics offered some exciting possibilities, including improvement tumour detection and eradication. In this review we summarize LDs biogenesis, structure and composition, and highlight their role in cancer theranostics.

Luminescent Carbon Dots from Wet Olive Pomace: Structural Insights, Photophysical Properties and Cytotoxicity.

Carbon nanomaterials endowed with significant luminescence have been synthesized for the first time from an abundant, highly localized waste, the wet pomace (WP), a semi-solid by-product of industrial olive oil production. Synthetic efforts were undertaken to outshine the photoluminescence (PL) of carbon nanoparticles through a systematic search of the best reaction conditions to convert the waste biomass, mainly consisting in holocellulose, lignin and proteins, into carbon dots (CDs) by hydrothermal carbonization processes. Blue-emitting CDs with high fluorescence quantum yields were obtained. Using a comprehensive set of spectroscopic tools (FTIR, Raman, XPS, and 1H/13C NMR) in combination with steady-state and time-resolved fluorescence spectroscopy, a rational depiction of WP-CDs structures and their PL properties was reached. WP-CDs show the up-conversion of PL capabilities and negligible cytotoxicity against two mammalian cell lines (L929 and HeLa). Both properties are excellent indicators for their prospective application in biological imaging, biosensing, and dynamic therapies driven by light.

Shrinking lung syndrome in pediatric systemic lupus erythematosus.

OBJECTIVE: To describe clinical, radiological and treatment characteristics in pediatric patients with SLS. MATERIAL AND METHODS: This is a descriptive and retrospective study in patients under 16 years old with the diagnosis of SLE complicated by SLS at the General Hospital. National Medical Center La Raza. Clinical, radiological and treatment variables were analyzed. Results are shown in frequencies and percentages. RESULTS: Data from 11 patients, 9 females and 2 males were collected. Mean age at diagnosis of SLS was 12.2 years. Age at diagnosis of SLE was 11.1 years. SLEDAI 17.3. Renal desease 72%, hematological 91%, lymphopenia 63%, mucocutaneous 72%, neurological 9%, arthritis 54%, serositis 91%, fever 81%, secondary antiphospholipid syndrome, low C3 72%, low C4 81%, positive ANA 91%, positive anti-DNA 91%. Regarding clinical manifestations of SLE: cough 81%, dyspnea 91%, hipoxemia 81%, pleuritic pain 71%, average oxygen saturation 83%. Chest X-rays findings: right hemidiaphragm affection 18%, left 63%, bilateral 18%. Elevated hemidiaphragm 91%, atelectasis 18%, pleural effusion 91%, over one third of the cardiac silhouette under the diphragm 36%, bulging diaphragm 45%, 5th. anterior rib that crosses over the diaphragm 91%. M-mode ultrasound: diaphragmatic hypomotility 100%, pleural effusion 63%. Pulmonary function tests: restrictive pattern in 45% of the cases. Treatment was with supplementary oxygen 100%, intubation 18%, antibiotics 100%, steroids 100%, intravenous immunoglobulin 54%, plasmapheresis 18%, cyclophosphamide 54% and rituximab 18%. The clinical course was favorable in 81%. CONCLUSIONS: SLS should be suspected in patients with SLE and active disease who present hipoxemia, pleuritic pain, cough, dyspnea, pleural effusion and signs of restriction on chest X-rays. Therefore, a diaphragmatic M-mode ultrasound should be performed in order to establish the diagnosis.

[Knowledge about neurodevelopmental disorders associated with the acceptance of the inclusive education model, in basic education teachers] / Conocimiento sobre trastornos del neurodesarrollo asociado con la aceptación del modelo de educación inclusiva en docentes de educación básica

OBJECTIVE: To describe the prevalence of knowledge about neurodevelopment disorders (NDDs) and the level of acceptance of models of inclusive education (IEM) in teachers. MATERIALS AND METHODS: A multicenter cross-sectional study in Mexico and Central America. A self-report instrument to teachers of basic level on knowledge in NDDs and acceptance of the IEM. RESULTS: The response of 511 teachers was obtained. The prevalence of high acceptance of the IEM was 28.6%. Of the 120 teachers who reported having extensive knowledge about intellectual disability, 3.8% were in the lowest percentile of acceptance of the IEM, 19.5% in the average percentile of acceptance and 55.5% of them were in the highest percentile acceptance (p<0.001). Among teachers, a greater knowledge about NDDs was associated with the acceptance of IEM: learning disorders RM 3.76 (95%CI 2.13-6.62); attention deficit disorders with hyperactivity RM 2.24 (95%CI 1.31-3.84) and intellectual disability RM 3.84 (95%CI 2.46-5.99). CONCLUSIONS: The teaching acceptance of IEM can be favored with greater and better training of education professionals on the different NDDs.

OBJETIVO: Describir la prevalencia del conocimiento sobre trastornos del neurodesarrollo (TdN) y el nivel de aceptación de los modelos de educación inclusiva (MEI) en docentes. MATERIAL Y MÉTODOS: Estudio transversal multicéntrico en México y Centroamérica. Aplicación de un instrumento de autorreporte a docentes de nivel básico sobre conocimiento en TdN y aceptación de los MEI. RESULTADOS: Se obtuvo la respuesta de 511 docentes. La prevalencia de alta aceptación de MEI fue de 28.6%. De los 120 docentes que refirieron tener un amplio conocimiento sobre discapacidad intelectual, 3.8% estuvieron en el percentil más bajo de aceptación de MEI, 19.5% en el percentil de aceptación promedio y 55.5% de ellos se encontraron en el percentil de mayor aceptación (p<0.001). Entre los docentes, un mayor conocimiento sobre los TdN se mostró asociado con la aceptación de MEI: trastornos del aprendizaje RM 3.76 (IC95% 2.13-6.62); trastornos por déficit de atención con hiperactividad RM 2.24 (IC95% 1.31-3.84) y discapacidad intelectual RM 3.84 (IC95% 2.46-5.99). CONCLUSIONES: La aceptación docente de MEI puede favorecerse con una mayor y mejor capacitación de los profesionales de la educación sobre los diferentes TdN.

Prevalence and incidence estimates for syphilis, chlamydia, gonorrhea, and congenital syphilis in Colombia, 1995-2016.

OBJECTIVES: To estimate adult (15-49 years old) prevalence and incidence of active syphilis, gonorrhea, and chlamydia, and incidence of congenital syphilis (CS) and adverse birth outcomes (ABOs) in Colombia, over 1995-2016. METHODS: The Spectrum-STI epidemiological model tool estimated gonorrhea and chlamydia prevalences as moving averages across prevalences observed in representative general population surveys. For adult syphilis, Spectrum-STI applied segmented polynomial regression through prevalence data from antenatal care (ANC) surveys, routine ANC-based screening, and general population surveys. CS cases and ABOs were estimated from Spectrum's maternal syphilis estimates and proportions of women screened and treated for syphilis, applying World Health Organization case definitions and risk probabilities. RESULTS: The Spectrum model estimated prevalences in 2016 of 0.70% (95% confidence interval (CI): 0.15%-1.9%) in women and 0.60% (0.1%-1.9%) in men for gonorrhea and of 9.2% (4.4%-15.4%) in women and 7.4% (3.5%-14.7%) in men for chlamydia, without evidence for trends over 1995-2016. The prevalence of active syphilis in 2016 was 1.25% (1.22-1.29%) in women and 1.25% (1.1%-1.4%) in men, decreasing from 2.6% (2.1%-3.2%) in women in 1995. Corresponding CS cases in 2016 (including cases without clinical symptoms) totaled 3 851, of which 2 245 were ABOs. Annual CS and ABO estimates decreased over 2008-2016, reflecting decreasing maternal prevalence and increasing cases averted through ANC-based screening and treatment. CONCLUSIONS: The available surveillance and monitoring data synthesized in Spectrum-STI- and the resulting first-ever national STI estimates for Colombia-highlighted Colombia's persistently high STI burden. Adult syphilis and congenital syphilis are estimated to be falling, reflecting improving screening efforts. Strengthened surveillance, including with periodic screening in low-risk populations and future refined Spectrum estimations, should support planning and implementation of STI prevention and control, including CS elimination.

Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial.

BACKGROUND: Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis. METHODS: We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedman's test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960. FINDINGS: Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35.5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0.0228). Median time to clinical remission was 41.9 months in patients assigned prednisone plus methotrexate but was not observable in the other two treatment groups (2.45 fold [95% CI 1.2-5.0] increase with prednisone plus methotrexate; p=0.012). Median time to treatment failure was 16.7 months in patients allocated prednisone, 53.3 months in those assigned prednisone plus ciclosporin, but was not observable in patients randomised to prednisone plus methotrexate (1.95 fold [95% CI 1.20-3.15] increase with prednisone; p=0.009). Median time to prednisone discontinuation was 35.8 months with prednisone alone compared with 29.4-29.7 months in the combination groups (p=0.002). A significantly greater proportion of patients assigned prednisone plus ciclosporin had adverse events, affecting the skin and subcutaneous tissues, gastrointestinal system, and general disorders. Infections and infestations were significantly increased in patients assigned prednisone plus ciclosporin and prednisone plus methotrexate. No patients died during the study. INTERPRETATION: Combined treatment with prednisone and either ciclosporin or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate. FUNDING: Italian Agency of Drug Evaluation, Istituto Giannina Gaslini (Genoa, Italy), Myositis Association (USA).

A Homology Model Reveals Novel Structural Features and an Immunodominant Surface Loop/Opsonic Target in the Treponema pallidum BamA Ortholog TP_0326.

UNLABELLED: We recently demonstrated that TP_0326 is a bona fide rare outer membrane protein (OMP) in Treponema pallidum and that it possesses characteristic BamA bipartite topology. Herein, we used immunofluorescence analysis (IFA) to show that only the ß-barrel domain of TP_0326 contains surface-exposed epitopes in intact T. pallidum. Using the solved structure of Neisseria gonorrhoeae BamA, we generated a homology model of full-length TP_0326. Although the model predicts a typical BamA fold, the ß-barrel harbors features not described in other BamAs. Structural modeling predicted that a dome comprised of three large extracellular loops, loop 4 (L4), L6, and L7, covers the barrel's extracellular opening. L4, the dome's major surface-accessible loop, contains mainly charged residues, while L7 is largely neutral and contains a polyserine tract in a two-tiered conformation. L6 projects into the ß-barrel but lacks the VRGF/Y motif that anchors L6 within other BamAs. IFA and opsonophagocytosis assay revealed that L4 is surface exposed and an opsonic target. Consistent with B cell epitope predictions, immunoblotting and enzyme-linked immunosorbent assay (ELISA) confirmed that L4 is an immunodominant loop in T. pallidum-infected rabbits and humans with secondary syphilis. Antibody capture experiments using Escherichia coli expressing OM-localized TP_0326 as a T. pallidum surrogate further established the surface accessibility of L4. Lastly, we found that a naturally occurring substitution (Leu(593) → Gln(593)) in the L4 sequences of T. pallidum strains affects antibody binding in sera from syphilitic patients. Ours is the first study to employ a "structure-to-pathogenesis" approach to map the surface topology of a T. pallidum OMP within the context of syphilitic infection. IMPORTANCE: Previously, we reported that TP_0326 is a bona fide rare outer membrane protein (OMP) in Treponema pallidum and that it possesses the bipartite topology characteristic of a BamA ortholog. Using a homology model as a guide, we found that TP_0326 displays unique features which presumably relate to its function(s) in the biogenesis of T. pallidum's unorthodox OM. The model also enabled us to identify an immunodominant epitope in a large extracellular loop that is both an opsonic target and subject to immune pressure in a human population. Ours is the first study to follow a structure-to-pathogenesis approach to map the surface topology of a T. pallidum rare OMP within the context of syphilitic infection.

α- L-iduronidase gene-based therapy using the phiC31 system to treat mucopolysaccharidose type I mice.

BACKGROUND: Mucopolysaccharidose type I (MPSI) is a lysosomal monogenic disease caused by mutations in the gene for α- L-iduronidase (IDUA). MPSI patients need a constant supply of IDUA to alleviate progression of the disease. IDUA gene transfer using integrative vectors might provide a definitive solution and support advancement to clinical trials, although studies have not yet been satisfactory. To achieve a stable IDUA gene expression in vivo, phiC31 was tested in the present study. METHODS: Several plasmid vectors were constructed and IDUA-/- mice were treated with cyclophosphamide and transfected with these vectors hydrodynamically via tail veins. IDUA expression was monitored over time. Treated and nontreated mice underwent an open-field test at age 8 months, and IDUA activity and glycosaminoglycan (GAG) content of tissues were evaluated. RESULTS: High levels of IDUA activity were detected initially (>1000 U/ml), although these levels decayed over time. The reinjection of vectors produced a similar profile of IDUA decay. Three out of six treated mice had IDUA activity in the livers, and also showed lower GAG content, reduced lysosomes and better locomotion. To investigate unsustained IDUA production, wild-type mice were submitted to the same gene therapy procedure, which generated a similar profile of IDUA decay. Anti-IDUA antibody was detected in the sera of these animals. In addition, we also found three methylated sites in the cytomegalovirus promoter region. CONCLUSIONS: phiC31-mediated gene therapy resulted in an important improvement in IDUA-/- mice, including locomotion, although the obstacles that need to be overcome to enable long-term gene therapy for MPSI are also noted.

Age estimation by volumetric analysis of teeth using cone beam computed tomography.

OBJECTIVES: To evaluate the feasibility of using the pulp volume (Pv) to total volume (Tv) ratio (Pv:Tv), obtained from cone beam computed tomography (CBCT) scans of single-rooted teeth, for age estimation in a Brazilian population sample. METHODS: After obtaining approval from the ethics committee, the study commenced by applying inclusion criteria to screen CBCT scans, resulting in a probability-based sample of participants aged 18 years and older (ranging from 18 to 82 years, with a mean age of 46.44 years). A total of 517 single-rooted teeth, including maxillary central incisors (CI), mandibular canines (C), and mandibular first premolars (FP), were chosen based on excellent agreement values (> 0.9). Pv and Tv measurements were conducted using semi-automatic segmentation with ITK-SNAP 3.8 software. Statistical analysis was performed using Jamovi software, with a significance level set at 5% (α = 0.05). RESULTS: A strong negative correlation (r > -0.7) was observed between chronological age and the Pv:Tv ratio across all examined teeth. However, when conducting regression analysis with Pv:Tv data and chronological age as the independent variable, only the mandibular FP teeth exhibited a normal distribution. The resulting linear model demonstrated moderate predictive value (approximately 64%) in explaining the variance in chronological age, but caution should be exercised when interpreting these findings. CONCLUSIONS: The method of measuring individual tooth volume using CBCT to estimate chronological age via Pv:Tv has been demonstrated as effective and reproducible within the Brazilian population sample.

Ligand-free 99mTc-polyurea dendrimer complexes: nanoradiotheranostics targeting ovarian cancer.

A folic acid-targeted polyurea (PURE) dendrimer was easily radiolabelled with Technetium-99m (99mTc-PUREG4-FA2) avoiding the use of additional ligands and bioconjugation chemistry. This straightforward strategy is enabled in PURE dendrimers due to their favourable surface terminal groups configuration, showing coordination capabilities and turning these biodendrimers into attractive platforms for nanoradiotheranostics.

Gestational and congenital syphilis epidemic in the Colombian Pacific Coast.

BACKGROUND: Congenital syphilis (CS) is a major global public health problem. Buenaventura, a socioeconomically deprived municipality in the Colombian Pacific Coast, accounts for 6.6% of all CS cases in Colombia. To begin to understand the main reasons for the high rates of the disease in Buenaventura, we conducted a retrospective electronic health record analysis of all infants admitted with CS during the first 7 months of 2011 to the Hospital Departamental de Buenaventura, the city's main birthing hospital. METHODS: The diagnosis of gestational syphilis and CS was based on a predefined Colombian public health service algorithm. Clinical, laboratory, and sociodemographic parameters for all infants studied, including maternal access to prenatal care, syphilis serologic diagnosis, and adequacy of penicillin treatment, were abstracted and analyzed. RESULTS: A total of 89 infants met the case definition for CS. Most mothers (80%) were affiliated with government-regulated or private health care insurance plans. While 64 (70%) of 92 attended at least 1 antenatal care visit and 59 of these 64 (84%) were screened for syphilis, only 5 (8%) of 59 received appropriate antibiotic therapy. Although most infants were asymptomatic at birth, prematurity (15/82) was common. Two infants died in the neonatal period, and 5 pregnancies ended in stillbirth. CONCLUSIONS: Our findings confirm that Buenaventura has a very high incidence of CS and demonstrate that existing antenatal care gestational syphilis programs are flawed. Prevention strategies should emphasize enhanced early syphilis screening in pregnancy, preferably through the implementation of point-of-care testing in the community and same-day treatment with at least 1 dose of penicillin.

Relationship between bone mineral density and trabecular bone pattern in postmenopausal osteoporotic Brazilian women.

OBJECTIVES: The aim of this study is to evaluate the relative efficacy of the mandibular trabecular bone in detecting osteoporotic-associated bone changes in Brazilian women. MATERIALS AND METHODS: Seventy-three digital panoramic radiographs of healthy and osteoporotic postmenopausal women were used. Regions of interest were selected in the mandibular angle and body of the panoramic images, which were analyzed for fractal dimension (FD) and pixel intensity (PI). Statistical analysis evaluated the distribution pattern, compared normal with osteoporotic patients and the right with the left mandible, and assessed the relationship between FD and PI. The significance level was set at 0.05. RESULTS: FD and PI values were significantly different (p < 0.05) between normal and osteoporotic patients for the right and left mandibular angle and for the left mandibular body. There was no significant difference (p > 0.05) between the right and left mandibular angle for FD and PI, but a significant difference (p < 0.05) was observed on the mandibular body for PI values. FD and PI values presented positive correlation. CONCLUSIONS: The mandibular trabecular bone was effective in detecting osteoporotic changes, with the exception of the right mandibular body. CLINICAL RELEVANCE: Mandibular trabecular bone shows a promising attempt of accurate detection of osteoporotic changes in some regions of the jaws. Fractal analysis and pixel intensity had strong positive correlation.

The role of RNA regulators, quorum sensing and c-di-GMP in bacterial biofilm formation.

Biofilms provide an ecological advantage against many environmental stressors, such as pH and temperature, making it the most common life-cycle stage for many bacteria. These protective characteristics make eradication of bacterial biofilms challenging. This is especially true in the health sector where biofilm formation on hospital or patient equipment, such as respirators, or catheters, can quickly become a source of anti-microbial resistant strains. Biofilms are complex structures encased in a self-produced polymeric matrix containing numerous components such as polysaccharides, proteins, signalling molecules, extracellular DNA and extracellular RNA. Biofilm formation is tightly controlled by several regulators, including quorum sensing (QS), cyclic diguanylate (c-di-GMP) and small non-coding RNAs (sRNAs). These three regulators in particular are fundamental in all stages of biofilm formation; in addition, their pathways overlap, and the significance of their role is strain-dependent. Currently, ribonucleases are also of interest for their potential role as biofilm regulators, and their relationships with QS, c-di-GMP and sRNAs have been investigated. This review article will focus on these four biofilm regulators (ribonucleases, QS, c-di-GMP and sRNAs) and the relationships between them.

Chemical Constituents and Antimicrobial Activity of a Ganoderma lucidum (Curtis.) P. Karst. Aqueous Ammonia Extract.

Mushroom extracts have shown potential as a source of new antimicrobial agents. This study investigates the chemical profile of an aqueous ammonia extract obtained from the carpophores of Ganoderma lucidum, which grows on Quercus ilex trees, and explores its valorization as a biorational. The major chemical constituents of the extract, identified through gas chromatography-mass spectrometry, include acetamide, oleic acid, 1,2,3,4-butanetetrol, monomethyl azelate, undecane, and palmitic acid. The anti-oomycete and antifungal activity of G. lucidum extract was evaluated against Phytophthora cinnamomi, the primary threat to Quercus spp. in the dehesa biome, as well as three Botryosphaeriaceae fungi. In vitro tests revealed minimum inhibitory concentration (MIC) values of 187.5 µg·mL-1 against P. cinnamomi and 187.5-1000 µg·mL-1 against the fungi. Furthermore, conjugation of the G. lucidum extract with chitosan oligomers (COS) synergistically enhanced its antimicrobial activity, resulting in MIC values of 78.12 and 375-500 µg·mL-1 against P. cinnamomi and the fungi, respectively. These MIC values are among the highest reported to date for natural products against these phytopathogens. Subsequent ex situ testing of the COS-G. lucidum conjugate complex on artificially inoculated Q. ilex excised stems resulted in high protection against P. cinnamomi at a dose of 782 µg·mL-1. These findings support the potential utilization of this resource from the dehesa ecosystem to protect the holm oak, aligning with sustainable and circular economy approaches.

Differences between leukemic arthritis and juvenile idiopathic arthritis.

OBJECTIVES: To determine the clinical and laboratory differences between leukemic arthritis (LA) and juvenile idiopathic arthritis (JIA) at the onset of the disease. MATERIAL AND METHODS: Patients under 16 years of age, both genders, who presented for the first time to the pediatric rheumatology service with a diagnosis of probable JIA, with arthritis and without peripheral blood blasts, in which the final diagnosis was acute lymphoblastic leukemia (ALL) or JIA. The clinical and laboratory characteristics of the patients were compared, chi-square and relative risk were used for categorical variables, and the Mann-Whitney U and T-test for the comparison of means between groups. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA. RESULTS: A total of 76 patients, 14 with LA and 62 with JIA, were analyzed. The mean age at diagnosis was lower in the leukemic arthritis group, the female gender prevailed in the JIA group, and the time to onset of symptoms was lower in the leukemic arthritis group. Patients with leukemic arthritis showed increased pain intensity, fever, weight loss, nocturnal diaphoresis, lymph node enlargement, hepatosplenomegaly, and pain that did not improve with analgesic administration. Laboratory parameters with statistical significance were the presence of anemia, leukopenia, and neutropenia. The platelet count was significant but in a low normal value, compared to the JIA. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA. The probability associated with the statistic (Chi-square) was 0.000, and the Cox and Snell R2 and Nagelkerke R2 values were 0.615 and 1, respectively. The developed model correctly classified 100% of the cases. CONCLUSIONS: The diagnosis of acute lymphoblastic leukemia should be ruled out in patients who present with arthritis and hematological alterations, mainly leukopenia and neutropenia, with joint pain disproportionate to the degree of arthritis, predominantly at night and that does not improve with the use of analgesics, fever, lymph nodes, and hepatosplenomegaly. Criteria are suggested to differentiate both diseases.

Caenorhabditis elegans as a Prediction Platform for Nanotechnology-Based Strategies: Insights on Analytical Challenges.

Nanotechnology-based strategies have played a pivotal role in innovative products in different technological fields, including medicine, agriculture, and engineering. The redesign of the nanometric scale has improved drug targeting and delivery, diagnosis, water treatment, and analytical methods. Although efficiency brings benefits, toxicity in organisms and the environment is a concern, particularly in light of global climate change and plastic disposal in the environment. Therefore, to measure such effects, alternative models enable the assessment of impacts on both functional properties and toxicity. Caenorhabditis elegans is a nematode model that poses valuable advantages such as transparency, sensibility in responding to exogenous compounds, fast response to perturbations besides the possibility to replicate human disease through transgenics. Herein, we discuss the applications of C. elegans to nanomaterial safety and efficacy evaluations from one health perspective. We also highlight the directions for developing appropriate techniques to safely adopt magnetic and organic nanoparticles, and carbon nanosystems. A description was given of the specifics of targeting and treatment, especially for health purposes. Finally, we discuss C. elegans potential for studying the impacts caused by nanopesticides and nanoplastics as emerging contaminants, pointing out gaps in environmental studies related to toxicity, analytical methods, and future directions.