Whole-Blood Gene Expression Profiles Associated with Mortality in Community-Acquired Pneumonia.

(1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein-protein-interaction-network analysis identified FOS, CDC42, SLC26A10, EIF4G2, CCND3, ASXL1, UBE2S, and AURKA as the main gene hubs. (4) Conclusions: We found differences in gene expression profiles at hospital admission between CAP patients who died and those who survived. Our findings may help to identify novel candidate pathways and targets for potential intervention and biomarkers for risk stratification.

Epidemiología y frecuencia de enfermedades de transmisión sexual y su repercusión en la mucosa bucal: una revisión narrativa / Epidemiology and frequency of sexually transmitted diseases and their impact on oral mucosa: a narrative review

El objetivo de la presente revisión fue analizar y compa- rar las publicaciones sobre la prevalencia de manifestaciones bucales de pacientes infectados por el Virus de la Inmuno- deficiencia Humana, Virus del Papiloma Humano y sífilis. Se seleccionaron los artículos más relevantes y se abordó la incidencia según sexo, edad, distribución geográfica y locali- zaciones anatómicas frecuentes. Se encontró que las lesiones orales más prevalentes producidas por el Virus de la Inmu- nodeficiencia Humana son la candidiasis oral, la leucoplasia vellosa y enfermedades periodontales, entre otras. La sífilis presentó una frecuencia de 7,5% de manifestaciones orales en la etapa primaria, 92,5% en la secundaria y rara vez lesio- nes en la terciaria. Las formas más prevalentes fueron parches mucosos, pápulas y úlceras. Las lesiones orales benignas rela- cionadas con el Virus del Papiloma Humano halladas fueron la verruga vulgar, el papiloma plano, el condiloma acuminado y la hiperplasia epitelial focal. La prevalencia de carcinomas orofaríngeos y orales fue del 33,6% y del 22,2% respectiva- mente. Se encontraron similitudes en el comportamiento se- xual y las vías de transmisión de las enfermedades analizadas, y se observó que son más prevalentes en adultos jóvenes de sexo masculino y en países en vías de desarrollo (AU)

The aim of this review was to analyze and compare pub- lications on the prevalence of oral manifestations in patients infected with Human Immunodeficiency Virus, Human Pap- illoma Virus and syphilis. The most reliable studies were se- lected, and incidence was evaluated according to gender, age, geographic location and frequent anatomic sites. It was found that the most prevalent Human Immunodeficiency Virus oral lesions were oral candidiasis, hairy leukoplakia and perio- dontal diseases, among others. Syphilis had a 7.5% preva- lence of oral manifestations in the primary stage, 92.5% in the secondary, and rarely lesions in the tertiary. The most prevalent forms were mucous patches, papules and ulcers. The benign oral lesions related to the Human Papilloma Vi- rus were verruca vulgaris, squamous papilloma, condyloma acuminatum and multifocal epithelial hyperplasia. The preva- lence of oropharyngeal and oral carcinomas were 33.6% and 22.2%, respectively. Similarities were found in sexual behavior and transmis- sion routes of the diseases analyzed, which were more preva- lent among young adult males, and in developing countries (AU)

Gene expression of Candida albicans strains isolates from patients with denture stomatitis submitted to treatments with photodynamic therapy and nystatin.

The study evaluated the effect of antimicrobial photodynamic therapy (aPDT) and nystatin (NYS) in the expression of genes (ACT1, ALS1, CAP1, CAT1, EFG1, HWP1, LIP3, PLB1, SAP1, and SOD1) involved in the virulence of Candida albicans strains recovered from patients with denture stomatitis (DS). These strains were isolated from the patients before (initial) and after treatment (final), and 45 days after the treatments (follow-up). For gene expression analyses, RNA was isolated from the clinical strains, followed by cDNA synthesis and qPCR using specific primers for each target gene. The samples that present integrity were pooled to increase the RNA yield. In the end, four patients treated with aPDT and five patients treated with NYS had the clinical isolates of C. albicans submitted to gene expression evaluation. The data demonstrated a statistical difference in the expression of PLB1 and ACT1 for the different therapies (aPDT versus NYS). Also, there was a statistical difference in the expression of CAT1, SOD1, and LIP3 at the time intervals assessed (initial, final, and follow-up). In contrast, no statistical difference was found in the expression of ALS1, HWP1, EFG1, CAP1, CAT1, SOD1, LIP3, and SAP1 between the therapies, while no significant difference was detected at the time intervals evaluated for ALS1, HWP1, EFG1, CAP1, and SAP1. Therefore, the topical treatments for DS with aPDT or NYS did not effect the expression of most C. albicans virulence genes evaluated.

A randomized clinical trial evaluating Photodithazine-mediated Antimicrobial Photodynamic Therapy as a treatment for Denture stomatitis.

OBJECTIVE: This randomized clinical trial assessed antimicrobial Photodynamic Therapy (aPDT) mediated by Photodithazine (PDZ) to treat patients with denture stomatitis (DS). METHODOLOGIES: Patients with DS were randomly assigned to the groups: aPDT (n = 30) and nystatin (NYS, n = 35). aPDT patients received 6 aPDT sessions, three times a week for 15 days, which involved PDZ (200 mg/L) topical application (20 min) on the palate and upper denture, followed by LED illumination (660 nm, 50 J/cm²). NYS patients were instructed to rinse one dropper of this medication for one minute, four times a day, for 15 days. Microbiological collections of dentures and palates were performed and cultured on blood agar and CHROMAgar Candida. Microbial viability was determined, and photographs of the palates were taken for clinical evaluation. Data were analyzed by Repeated Measure Linear Model and Bonferroni (p ≤ 0.05). RESULTS: aPDT was more effective to reduce the total microbiota than NYS. At the end of the treatments, aPDT reduced 1.98 from the palate and 1.91 log10 from the denture, while NYS reduced 0.05 and 0.17 log10, respectively. Moreover, aPDT was as effective as NYS to reduce Candida. Reductions of 0.68 and 0.77 log10 were observed in the palate and denture of aPDT group, while reductions of 0.57 and 1.43 log10 were achieved in the NYS group, respectively. Regarding to oral lesion, 53.3 and 54.2 % of the patients from aPDT and NYS groups had clinical improvement. However, the recurrence of DS was observed in both groups. CONCLUSION: PDZ-mediated aPDT is a promising treatment for DS.

Agentes antirresortivos y antiangiogénicos y su relación con la osteonecrosis de los maxilares asociada a medicamentos / Antiresorptive and antiangiogenic agents and their relationship with osteonecrosis of the jaws related to medication

El objetivo de este trabajo es revisar los conocimientos actuales sobre el manejo clínico-odontológico de pacientes que consumen medicamentos antirresortivos y medicamentos antiangiogénicos o quimioterapéuticos, en relación con la prevención y/o el tratamiento de la osteonecrosis de los maxilares asociada a medicamentos. Se evaluaron similitudes y diferencias entre los bifosfonatos, denosumab y medicamentos antiangiogénicos, así como el manejo clínico de pacientes, vacaciones de medicamentos y el manejo de osteonecrosis de los maxilares ya instalada. Se encontraron similitudes en la presentación clínica, la prevención, el uso de antibioticoterapia antes de procedimientos invasivos y el tratamiento de la osteonecrosis ya instalada. Entre las diferencias, podemos mencionar que el tratamiento quirúrgico respondería mejor en pacientes medicados con denosumab o antiangiogénicos, y su suspensión sería más efectiva si se iniciara un proceso de osteonecrosis, al igual que su tasa de resolución. En cuanto a las vacaciones de medicamentos, no hay datos concluyentes para guiar esta decisión, al igual que no existe un protocolo clínico de atención en pacientes que consumen denosumab o antiangiogénicos (AU)

The aim of this study is to review the currents knowledge about the clinical and dental management of patients who consume antiresorptive and antiangiogenic agents or chemotherapeutic drugs, in relation to the prevention and/or treatment of osteonecrosis of the jaws related to medication. Similarities and differences between bisphosphonates, denosumab and antiangiogenic medications were evaluatted, as well as the clinical management of patients, drugs holidays and management of osteonecrosis of the jaws already setted. Similarities were found in the clinical presentation, prevention, use of antibiotic therapy before invasive procedures and the treatment of osteonecrosis already installed. Regarding the differences, we can mention that the surgical treatment would be better in patients medicated with denosumab or antiangiogenics and its suspension would be more effective if an osteonecrosis process is initiated, as well as its resolution rate. There are no conclusive data about drug holidays to guide this decision, and no clinical protocol of care in patients who consume denosumab or antiangiogenic agents (AU)

A quest to find good primers for gene expression analysis of Candida albicans from clinical samples.

Biofilm production contributes to several human diseases, including oral candidiasis. Among the Candida species, Candida albicans is the most prevalent. The expression of virulence genes is implicated in the pathogenic potential of Candida biofilms. However, the evaluation of microbial gene expression from in vivo biofilm samples is not trivial, specifically, assessment via quantitative PCR (qPCR) can be a challenge because of several species present in clinical samples. Hence, the necessity of primers specificity. The aim of this study was to evaluate through in silico and in vitro analyses the specificity of published primers and newly designed primers for C. albicans virulence genes: ALS1, CAP1, CAT1, EFG1, HWP1, LIP3, PLB1, SAP1, SAP4, SOD1, SOD5 and ACT1 (normalizing gene). In silico analysis was performed through a PubMed search of articles with primer sequences that evaluated gene expression of C. albicans. Then, the sequence similarity of twenty-eight primers was checked through BLASTn and ClustalW2. The analysis of secondary structures was performed using mfold. When the primers did not present satisfactory characteristics (absence of secondary structures, not discrepant Tm of forward and reverse sequences and specificity) following in vitro analysis (i.e., end point PCR), new primers were designed using Beacon Designer™ and sequences obtained from the "Candida Genome Database". The selected primers were tested in vitro by end point PCR using a panel of genomic DNA from five different Candida species (C. albicans, Candida glabrata, Candida dubliniensis, Candida krusei, and Candida tropicalis). The resulting PCR products were visualized on agarose gel. qPCR reactions were performed to determine primers' optimal concentration and PCR efficiency. End point PCR demonstrated that published primers for the SAP1 and HWP1 were specific for C. albicans and the one for SOD1 reacted with C. albicans and C. dubliniensis. The sequence of primers designed for ACT1, ALS1 and HWP1 genes were specific for C. albicans, while the ones for CAP1, CAT1, EFG1, LIP3, and PLB1 were detected in C. albicans and C. dubliniensis. After optimization, all primers presented a single peak on melt curves, correlation coefficient of ≅1 and qPCR reaction efficiency of 90-110%, with slope of ≅-3.3. Therefore, these primers should be suitable for future gene expression analyses from clinical samples.

Antimicrobial Photodynamic Therapy mediated by Photodithazine® in the treatment of denture stomatitis: A case report.

Antimicrobial Photodynamic Therapy (aPDT) mediated by Photodithazine® (PDZ) has shown efficacy in the inactivation of Candida spp. in in vitro and in vivo studies. This preliminary study reports five clinical cases of patients with denture stomatitis (DS) treated with PDZ-mediated aPDT. Five individuals diagnosed with DS were selected and submitted to aPDT 3 times a week for 15 days (6 sessions). In each session, 200 mg/L of PDZ gel was applied on the upper prostheses and on the palate of the patients for 20 min, then, illuminated by a light emitting diode at 660 nm (50 J/cm2). Microbiological samples from prostheses and palates were also performed and cultured on Sabouraud Dextrose Agar and Blood Agar. The values ​​of colony forming units per milliliter (CFU/mL) were determined. Standardized photographs of the palates were taken prior the treatment (initial), at the end (final) and until 45 days after the completion of treatments. The results demonstrated that the aPDT treatment reduced Candida spp. and the total microbiota viability ​​at the end of the treatment. For most patients, the CFU/mL values obtained in the last microbiological collection (day 45) were lower than those found before the treatment (initial). Three patients presented clinical resolution of DS (no DS signal) after aPDT treatment. One individual demonstrated reduction in palatal inflammation and another one did not show improvement in the oral lesion. Recurrence of DS was observed in all individuals in the follow-up period. PDZ-mediated aPDT may be a promising treatment for DS.

Osteopontin expression in co-cultures of human squamous cell carcinoma-derived cells and osteoblastic cells and its effects on the neoplastic cell phenotype and osteoclastic activation.

This study evaluated the temporal expression of osteopontin (OPN) in co-cultures of human osteoblastic cells (SAOS-2) and oral squamous cell carcinoma (OSCC)-derived cells (SCC9) and examined the effects of osteoblast-derived OPN on the neoplastic cell phenotype. Additionally, the effects of these co-cultures on subsequent osteoclastic activity were explored. SCC9 cells were plated on Transwell® membranes that were either coated or not coated with Matrigel and were then co-cultured with SAOS-2 cells during the peak of OPN expression. SCC9 cells exposed to OPN-silenced SAOS-2 cultures and SCC9 cells cultured alone served as controls. SCC9 cells were quantitatively evaluated for cell adhesion, proliferation, migration, and invasion into Matrigel. The impact of co-culturing SAOS-2 and SCC9 cells on the resorptive capacity of U-937-derived osteoclastic cells was also investigated. Furthermore, a reciprocal induction of SAOS-2 and SCC9 cells in terms of OPN expression over the co-culture interval was identified. SAOS-2-secreted OPN altered the SCC9 cell phenotype, leading to enhanced cell adhesion and proliferation and higher Matrigel invasion. This invasion was also enhanced, albeit to a lesser degree, by co-culture with OPN-silenced SAOS-2 cells. Cell migration was not affected. Co-culture with SAOS-2 cells-mainly during the period of peak OPN expression-promoted over-expression of IL-6 and IL-8 by SCC9 cells and enhanced the resorptive capacity of osteoclastic cells. Taken together, these results suggest that osteoblast-derived OPN affects the interactions among OSCC-derived epithelial cells, osteoblasts, and osteoclasts, which could contribute to the process of bone destruction during bone invasion by OSCC.