Inflammation and tissue remodeling mediator expression during gingivitis: A comparison between experimental, naturally occurring gingivitis, and periodontal health.

BACKGROUND: The aim of this study is to evaluate the immune regulation and tissue remodeling responses during experimental gingivitis (EG) and naturally occurring gingivitis (NG) to provide a comprehensive analysis of host responses. Gingival crevicular fluid (GCF) was obtained from 2 human studies conducted in university settings. METHODS: The EG study enrolling 26 volunteers provided controls for the baseline (Day 0) from healthy disease-free participants, while Day 21 (the end of EG induction of the same group) was used to represent EG. Twenty-six NG participants age-matched with those of the EG group were recruited. GCF samples were analyzed for 39 mediators of inflammatory/immune responses and tissue remodeling using commercially available bead-based multiplex immunoassays. The differences in GI and mediator expression among groups were determined at a 95% confidence level (p ≤ 0.05) by a 2-way analysis of variance (ANOVA) with a post-hoc Tukey's test. RESULTS: Our findings showed that EG had a greater gingival index than NG and was healthy (p < 0.01 of all comparisons). Furthermore, EG showed significantly higher levels of MPO (p < 0.001), CCL3 (p < 0.05), and IL-1B (p < 0.001) than NG. In contrast, NG had increased levels of MIF (p < 0.05), Fractalkine (p < 0.001), angiogenin (p < 0.05), C3a (p < 0.001), BMP-2 (p < 0.001), OPN (p < 0.05), RANKL (p < 0.001), and MMP-13 (p < 0.001) than EG. CONCLUSIONS: Consistent with the findings from chronic (NG) versus acute (EG) inflammatory lesions, these data reveal that NG displays greater immune regulation, angiogenesis, and bone remodeling compared to EG.

A Pilot Study Exploring Caregivers' Experiences Related to the Use of a Smart Toothbrush by Children with Autism Spectrum Disorder.

BACKGROUND: Research on caregivers for children with intellectual disabilities, particularly those with autism spectrum disorder (ASD), has highlighted several obstacles to achieving better oral health. These include challenges with tolerating oral care, sensory processing differences, uncooperative behaviors, and communication impairments. There is limited understanding of what caregivers would consider "successful assistance" in improving oral health for these children. OBJECTIVES: This pilot study aimed to examine caregivers' and user's experiences with a Kids Smart Electric Toothbrush used by children with ASD. METHODS: It involved open-ended interviews and questionnaires with caregivers prior to utilization of the toothbrush and after 4 weeks of product use by the child. RESULTS: Seventeen children with ASD, aged 5-12, participated. A total of 58.8% of caregivers said their child brushed more often, and all reported brushing at least twice a day by week 4. Caregivers reported that children became more independent while brushing their teeth and achieved better quality brushing. Caregivers' frustration with the brushing process, satisfaction with the device, and need to assist the child with brushing were improved. Caregivers did encounter some technical difficulties with the app. CONCLUSION: This study will assist in exploring "smart" toothbrush technologies for oral hygiene in children with ASD.

A Brain Ischemia-Reperfusion Model for the Study of Tau Phosphorylation and O-GlcNAcylation.

Cerebral ischemia produces a decrease, loss, or instability of the assembly processes in the neuronal cytoskeleton, related to the alteration in the normal processes of phosphorylation of the Tau protein, triggering its hyperphosphorylation and altering the normal processes of formation of neuronal microtubules. Here we describe the methods used to study the impact of middle cerebral artery occlusion (MCAo) on neurological functions and Tau phosphorylation in Wistar rat brain.

ADAMTS7 Promotes Smooth Muscle Cell Foam Cell Expansion in Atherosclerosis.

Human genetic studies have repeatedly associated SNPs near the gene ADAMTS7 with atherosclerotic cardiovascular disease. Subsequent investigations in mice demonstrated that ADAMTS7 is proatherogenic, induced in response to vascular injury, and alters smooth muscle cell function. However, the mechanisms governing this function and its relationship to atherosclerosis remain unclear. Here, we report the first conditional Adamts7 transgenic mouse in which the gene can be conditionally overexpressed in smooth muscle cells, mimicking its induction in atherosclerosis. We observed that smooth muscle cell Adamts7 overexpression results in a 3.5-fold increase in peripheral atherosclerosis, coinciding with an expansion of smooth muscle foam cells. RNA sequencing of Adamts7 overexpressed primary smooth muscle cells revealed an upregulation in the expression of lipid uptake genes. Subsequent experiments in primary smooth muscle cells demonstrated that increased Spi1 and Cd36 expression leads to increased smooth muscle cell oxLDL uptake. To uncover ADAMTS7 expression in human disease, we have interrogated the largest scRNA-seq dataset of human carotid atherosclerosis. This analysis discovered that endothelial cells had the highest expression level of ADAMTS7 with lesser expression in smooth muscle cells, fibroblasts, and mast cells. Subsequent conditional knockout studies in smooth muscle cells surprisingly showed no change in atherosclerosis, suggesting redundant expression of this secreted factor in the vessel wall. Finally, mice overexpressing Adamts7 in endothelial cells also exhibit increased atherosclerosis, suggesting that multiple vascular cell types can contribute to ADAMTS7-mediated foam cell expansion. In summary, Adamts7 is expressed by multiple vascular cell types in atherosclerosis, and ADAMTS7 promotes oxLDL uptake in smooth muscle cells, increasing smooth muscle foam cell formation and peripheral atherosclerosis in mice.

Effects of a stabilized stannous fluoride dentifrice on clinical, immunomodulatory, and microbial outcomes in a human experimental gingivitis model.

BACKGROUND: Stannous fluoride dentifrice is well established for its beneficial clinical effects. In this study, we evaluated the effects of stannous fluoride on inflammation and oral microbiome. METHODS: In this randomized, parallel-arm, double-blind, controlled clinical trial, we compared clinical resolution of experimental gingivitis by evaluating bleeding on probing, gingival index, and plaque index between stannous fluoride stabilized with zinc phosphate (test) and sodium fluoride (control) dentifrices. Further, these groups were compared for oral neutrophil counts, systemic priming of neutrophils, gingival crevicular fluid (GCF) expression of inflammatory markers, and the oral microbiome. RESULTS: We found significant reduction in bleeding on probing in the test group compared to the control group in experimental gingivitis when participants used the test dentifrice prior to induction of experimental gingivitis. The test group also showed significant reductions in GCF levels of inflammatory markers (matrix metalloproteinase 8 [MMP8], receptor activator of nuclear factor kappa-Β ligand [RANKL]), oral polymorphonuclear neutrophil (PMN) counts, and systemic neutrophil priming (CD11b expression) during experimental gingivitis. Further, significant reductions in the gram-negative genera Porphyromonas, Tannerella, and Treponema were noted in the test group. CONCLUSION: The stannous fluoride stabilized with zinc phosphate dentifrice formulation demonstrated clinical reduction in gingival inflammation and a beneficial effect on microbiome and immune markers. This intervention should be explored as a preventive aid in the progression of plaque-induced gingivitis to periodontitis.

Evaluation of a digital oral health intervention (Know Your OQ™) to enhance knowledge, attitudes and practices related to oral health.

OBJECTIVE/AIM: Optimal oral health behaviours are crucial to avoid preventable dental diseases and maintain good oral health. This research aimed to evaluate the impact of a digital oral health intervention (Know Your OQ™) in changing knowledge, attitudes and practices related to oral health. MATERIALS & METHODS: Two studies were conducted with a total of 296 healthy adults. Demographic data as well as knowledge, attitudes, and practices (KAPs) related to oral health were collected before and after completion of the Know Your OQ™ intervention. The KAPs questionnaire included 19 multiple choice questions. Comprehension and feedback were also collected. RESULTS: In total, 134 (45%) male and 162 (55%) female participants completed the two studies. Across both studies, 5 out of 7 knowledge questions and 2 out of 5 attitude questions showed significant changes pre/post-intervention with participants increasing their knowledge and improving their attitudes towards oral health. Only 1 practice changed in the first study, however, in the second study, 4 out of 7 practice questions showed significant changes pre/post-intervention. Comprehensibility was high across both studies with overall, positive feedback on the intervention. CONCLUSION: A digital oral health intervention was successful in increasing knowledge, changing attitudes and self-reported practices with regards to oral health in a diverse sample of the US population.

The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis.

Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma survival, proliferation and invasion when cells are starved of glucose. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients. Glioblastoma cell lines over-expressing IL-11Rα displayed greater survival, proliferation, migration and invasion in glucose-free conditions compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα reversed these pro-tumorigenic characteristics. In addition, these IL-11Rα-over-expressing cells displayed enhanced glutamine oxidation and glutamate production compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα or the pharmacological inhibition of several members of the glutaminolysis pathway resulted in reduced survival (enhanced apoptosis) and reduced migration and invasion. Furthermore, IL-11Rα expression in glioblastoma patient samples correlated with enhanced gene expression of the glutaminolysis pathway genes GLUD1, GSS and c-Myc. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell survival and enhances cell migration and invasion in environments of glucose starvation via glutaminolysis.

Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes.

Precise control of activating H3K4me3 and repressive H3K27me3 histone modifications at bivalent promoters is essential for normal development and frequently corrupted in cancer. By coupling a cell surface readout of bivalent MHC class I gene expression with whole-genome CRISPR-Cas9 screens, we identify specific roles for MTF2-PRC2.1, PCGF1-PRC1.1 and Menin-KMT2A/B complexes in maintaining bivalency. Genetic loss or pharmacological inhibition of Menin unexpectedly phenocopies the effects of polycomb disruption, resulting in derepression of bivalent genes in both cancer cells and pluripotent stem cells. While Menin and KMT2A/B contribute to H3K4me3 at active genes, a separate Menin-independent function of KMT2A/B maintains H3K4me3 and opposes polycomb-mediated repression at bivalent genes. Release of KMT2A from active genes following Menin targeting alters the balance of polycomb and KMT2A at bivalent genes, facilitating gene activation. This functional partitioning of Menin-KMT2A/B complex components reveals therapeutic opportunities that can be leveraged through inhibition of Menin.

Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses.

There is increasing recognition of the prognostic significance of tumor cell major histocompatibility complex (MHC) class II expression in anti-cancer immunity. Relapse of acute myeloid leukemia (AML) following allogeneic stem cell transplantation (alloSCT) has recently been linked to MHC class II silencing in leukemic blasts; however, the regulation of MHC class II expression remains incompletely understood. Utilizing unbiased CRISPR-Cas9 screens, we identify that the C-terminal binding protein (CtBP) complex transcriptionally represses MHC class II pathway genes, while the E3 ubiquitin ligase complex component FBXO11 mediates degradation of CIITA, the principal transcription factor regulating MHC class II expression. Targeting these repressive mechanisms selectively induces MHC class II upregulation across a range of AML cell lines. Functionally, MHC class II+ leukemic blasts stimulate antigen-dependent CD4+ T cell activation and potent anti-tumor immune responses, providing fundamental insights into the graft-versus-leukemia effect. These findings establish the rationale for therapeutic strategies aimed at restoring tumor-specific MHC class II expression to salvage AML relapse post-alloSCT and also potentially to enhance immunotherapy outcomes in non-myeloid malignancies.

Dispositivo de medición de fuerza de los dedos y su rol en el seguimiento de las funciones de la mano / Device for measuring fingers strength and its role in monitoring hand functions

Introducción y objetivo: El amplio rango de movimiento y fuerza de la mano ha sido clave en el desarrollo de la especie humana dada su capacidad de adaptación según las demandas funcionales. El conocimiento de la anatomía y biomecánica de las estructuras que influyen en la generación de la fuerza de los dedos es crucial para el entendimiento de las alteraciones que pueden producir un deterioro de la misma. Son múltiples los estudios para valorar la fuerza de cada dedo y su rol en la funcionalidad del complejo sistema músculo-esquelético de la mano. En este trabajo descriptivo revisamos conceptos básicos y presentamos las etapas de diseño y construcción de un dispositivo tridimensional capaz de cuantificar de manera individual la fuerza de los dedos para la evaluación en pacientes sanos. Material y método: Realzamos múltiples mediciones en 20 pacientes sanos con un dispositivo que discrimina la fuerza de cada dedo y comparamos los resultados con estudios previamente publicados. Resultados: Los hallazgos numéricos de las diferentes mediciones son equiparables entre si y con los resultados en estudios previos. Conclusiones: Este nuevo dispositivo brinda la posibilidad de medir la fuerza de los dedos de manera individual, como valiosa herramienta en la evaluación del paciente sano y de pacientes con patologías traumáticas y no traumáticas, para cuantificar su grado de discapacidad, evolución postoperatoria o de su enfermedad de manera especifica al dedo comprometido y el impacto en la fuerza global de agarre. (AU)

Background and objective: The wide range of movement and strength of the hand have been key in the development of the human species given its ability to adapt according to functional demands. Knowledge of the anatomy and biomechanics of the structures that influence the generation of fingers force is crucial to understand the alterations that can cause its deterioration. Multiple studies have been conducted to assess the strength of each finger and its role in the functionality of the complex musculoskeletal system of the hand. In this descriptive paper, basic concepts are reviewed and stages of design and construction of a three-dimensional device capable of individually quantify the strength of each finger for healthy patients evaluation is presented. Methods: Multiple measurements were performed in 20 healthy patients with a device that discriminates the strength of each finger, comparing the results with previously published studies. Results: The results of the different measures are comparable with each other and with the results in previous studies. Conclusions:The use of this new device offers the possibility of measuring the strength of the fingers individually, which constitutes a valuable and novel tool in the evaluation of healthy patients and patients with traumatic and non-traumatic pathologies, to quantify their degree of disability, postoperative evolution or its disease specifically to the involved finger and its impact on the global grip strength. (AU)

Biofire FilmArray Meningitis/Encephalitis panel for the aetiological diagnosis of central nervous system infections: A systematic review and diagnostic test accuracy meta-analysis.

BACKGROUND: The FilmArray Meningitis/Encephalitis(FA/ME) panel brings benefits in clinical practice, but its diagnostic test accuracy (DTA) remains unclear. We aimed to determine the DTA of FA/ME for the aetiological diagnostic in patients with suspected central nervous system(CNS) infection. METHODS: We performed a systematic review with DTA meta-analysis (PROSPERO: CRD42020139285). We searched Embase, Medline (Ovid), and Web of Science from inception until September 1st, 2021. We assessed the study-level risk of bias with the QUADAS-2 tool and applied the GRADE approach to assess the certainty of the synthesised evidence. We included studies that simultaneously measured the reference test (CSF/blood culture for bacteria, and specific polymerase chain reaction for viruses) and the FA/ME in patients with suspected CNS infection. We performed random-effects bivariate meta-analysis models of combined sensitivity and specificity using CSF/blood cultures(reference test 1) and a final diagnosis adjudication based on clinical/laboratory criteria (reference test 2). FINDINGS: We included 19 studies (11,351 participants). For all bacteria with reference test 1 (16 studies/6183 patients) sensitivity was estimated at 89·5% (95%CI 81·1-94·4), and specificity at 97·4% (95%CI 94-98·9). With reference test 2 (15 studies/5,524 patients), sensitivity was estimated at 92·1%(95%CI 86·8-95·3) and specificity at 99.2(95%CI 98·3-99·6) For herpes simplex virus-2(HSV-2), enteroviruses, and Varicella-Zoster virus (VZV), we obtained sensitivities between 75·5 and 93·8%, and specificities above 99% (reference test 1). Certainty of the evidence was low. INTERPRETATION: FA/ME may have acceptable-to-high sensitivities and high specificities for identifying bacteria, especially for S.pneumoniae, and viruses, especially for HSV-2, and enteroviruses. Sensitivities for L.monocytogenes, H.influenzae, E.coli, and HSV-1 were suboptimal. FUNDING: None.

Tumor de colon como hallazgo incidental en un paciente con endocarditis por Streptococcus gallolyticus: experiencia desde la práctica clínica / Colon tumor as an incidental finding in a patient with endocarditis due to Streptococcus gallolyticus: experience from clinical practice

El Streptococcus gallolyticus del colon. La fisiopatología que explica este fenómeno implica el aumento local de niveles de lactato puede presentarse como el germen causal de la endocarditis infecciosa en pacientes con lesiones premalignas y malignas, colágeno, fibrinógeno y fibronectina secundario a la hiperactividad metabólica tumoral que genera un ambiente adecuado para el crecimiento y adhesión bacteriana a la pared intestinal y posterior translocación al torrente sanguíneo. Simultáneamente, se establece la presencia de infecciones secundarias por la formación de biofilms, tanto a nivel colorrectal como en válvulas cardíacas. El objetivo del manuscrito es un mapeo en la literatura médica disponible sobre la correlación entre la endocarditis por Streptococcus gallolyticus y las lesiones premalignas y malignas de colon. Simultáneamente, exponer la experiencia clínica de un hombre de 82 años con diagnóstico de endocarditis por Streptococcus gallolyticus y el hallazgo incidental de pólipos adenomatosos del colon(AU)

Streptococcus gallolyticus can present as the causative germ of infective endocarditis in patients with premalignant and malignant lesions of the colon. The pathophysiology that explains this phenomenon involves the local increase in lactate that can be presented as the causal germ of infective endocarditis in patients with premalignant and malignant lesions, collagen, fibrinogen, and fibronectin levels secondary to tumor metabolic hyperactivity, which generates a suitable environment for bacterial growth and adhesion to the intestinal wall and subsequent translocation to the bloodstream. Simultaneously, the presence of secondary infections is established due to the formation of biofilms, both at the colorectal level and in the heart valves. The objective of the manuscript is a mapping in the available medical literature on the correlation between Streptococcus gallolyticus endocarditis and premalignant and malignant colonic lesions. Simultaneously, to present the clinical experience of an 82-year-old man diagnosed with Streptococcus gallolyticus endocarditis and the incidental finding of adenomatous polyps of the colon(AU)

Natural Coinfection between Novel Species of Baculoviruses in Spodoptera ornithogalli Larvae.

Spodoptera ornithogalli (Guenée) (Lepidoptera: Noctuidae) is an important pest in different crops of economic relevance in America. For its control, strategies that include chemicals are usually used; so, the description of entomopathogens would be very useful for the formulation of biopesticides. In this regard, two different baculoviruses affecting S. ornithogalli were isolated in Colombia, with one of them being an NPV and the other a GV. Ultrastructural, molecular, and biological characterization showed that both isolates possess the 38 core genes and are novel species in Baculoviridae, named as Spodoptera ornithogalli nucleopolyhedrovirus (SporNPV) and Spodoptera ornithogalli granulovirus (SporGV). The bioassays carried out in larvae of S. ornithogalli and S. frugiperda showed infectivity in both hosts but being higher in the first. In addition, it was observed that SporGV potentiates the insecticidal action of SporNPV (maximum value in ratio 2.5:97.5). Both viruses are individually infective but coexist in nature, producing mixed infections with a synergistic effect that improves the performance of the NPV and enables the transmission of the GV, which presents a slowly killing phenotype.

Microtomographic reconstruction of mandibular defects treated with xenografts and collagen-based membranes: A pre-clinical minipig model / Reconstrucción microtomográfica de defectos mandibulares tratados con Xenoinjertos y membranas a base de colágeno: un modelo preclínico de minicerdo

Background: The goal of this study was to evaluate hard tissue response following guided bone regeneration us-ing commercially available bovine bone grafts and collagen membranes; bilayer collagen membrane and porcinepericardium-based membrane, by means of a non-destructive three-dimensional (3D) computerized volumetricanalysis following microtomography reconstruction.Material and Methods: Bone regenerative properties of various bovine bone graft materials were evaluated in theGöttingen minipig model. Two standardized intraosseous defects (15mm x 8mm x 8mm) were created bilaterallyof the mandible of eighteen animals (n=72 defects). Groups were nested within the same subject and randomlydistributed among the sites: (i) negative control (no graft and membrane), (ii) bovine bone graft/bilayer collagenmembrane (BOB) (iii) Bio-Oss® bone graft/porcine pericardium-based membrane (BOJ) and (iv) cerabone® bonegraft/porcine pericardium-based membrane (CJ). Samples were harvested at 4, 8, and 12-week time points (n=6animal/time point). Segments were scanned using computerized microtomography (μCT) and three dimensionallyreconstructed utilizing volumetric reconstruction software. Statistical analyses were performed using IBM SPSSwith a significance level of 5% Results: From a temporal perspective, tridimensional evaluation revealed gradual bone ingrowth with the presenceof particulate bone grafts bridging the defect walls, and mandibular architecture preservation over time. Volumetricanalysis demonstrated no significant difference between all groups at 4 weeks (p>0.127). At 8 and 12 weeks therewas a higher percentage of new bone formation for control and CJ groups when compared to BOB and BOJ groups(p<0.039). The natural bovine bone graft group showed more potential for graft resorption over time relative to bo-vine bone graft, significantly different between 4 and 8 weeks (p<0.003)...(AU)

Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer.

Cetuximab is a common treatment option for patients with wild-type K-Ras colorectal carcinoma. However, patients often display intrinsic resistance or acquire resistance to cetuximab following treatment. Here we generate two human CRC cells with acquired resistance to cetuximab that are derived from cetuximab-sensitive parental cell lines. These cetuximab-resistant cells display greater in vitro proliferation, colony formation and migration, and in vivo tumour growth compared with their parental counterparts. To evaluate potential alternative therapeutics to cetuximab-acquired-resistant cells, we tested the efficacy of 38 current FDA-approved agents against our cetuximab-acquired-resistant clones. We identified carfilzomib, a selective proteosome inhibitor to be most effective against our cell lines. Carfilzomib displayed potent antiproliferative effects, induced the unfolded protein response as determined by enhanced CHOP expression and ATF6 activity, and enhanced apoptosis as determined by enhanced caspase-3/7 activity. Overall, our results indicate a potentially novel indication for carfilzomib: that of a potential alternative agent to treat cetuximab-resistant colorectal cancer.

Dental caries prevalence, prospects, and challenges for Latin America and Caribbean countries: a summary and final recommendations from a Regional Consensus.

Dental caries can be effectively managed and prevented from developing into cavitated lesions while preserving tooth structure at all levels. However, the strong correlation between caries and socioeconomic factors may compromise the efficacy of preventive strategies. The high prevalence of persistent inequalities in dental caries in Latin American and Caribbean countries (LACC) is a matter of concern. The estimates of the burden of disease in some countries in this region are outdated or absent. This paper aims to summarize and present the final recommendations of a regional Consensus for Dental Caries Prevalence, Prospects, and Challenges for LACC. This consensus is based on four articles that were written by a team of Latin American experts, reviewed by dental associations, and presented and discussed in two consensus events. The following domains were explored: epidemiology, risk factors, prevention strategies, and management of dental caries with a focus on restorative procedures. Dental caries can manifest throughout the lifespan of an individual, making it a matter of concern for infants, children, adults, and older people alike. The prevalence rates of untreated caries in deciduous and permanent teeth are high in many parts of the world, including LACCs. Previous evidence suggests that the prevalence of dental caries in 12-year-olds is moderate to high in most Latin American countries. Moreover, the prevalence of treatment needs and dental caries in the adult and elderly population can also be regarded as high in this region. The risk/protective factors (e.g., sugar consumption, exposure to fluoride, and oral hygiene) probably operate similarly in all LACCs, although variations in the interplay of these factors in some countries and within the same country cannot be ruled out. Although salt and water fluoridation programs are implemented in many countries, there is a need for implementation of a surveillance policy. There is also room for improvement with regard to the introduction of minimal intervention techniques in practice and public health programs. Dental caries is a marker of social disadvantage, and oral health promotion programs and interventions aimed at reducing the burden of dental caries in LACCs must consider the complexity of the socioeconomic dynamics in this region. There is an urgent need to promote engagement of stakeholders, policymakers, medical personnel, universities, dental associations, community members, and industries to develop regional plans that enhance the oral health agenda for LACCs. A list of recommendations has been presented to underpin strategies aimed at reducing the prevalence and severity of dental caries and improving the quality of life of the impacted LACC population in the near future.

EGFRvIII Promotes Cell Survival during Endoplasmic Reticulum Stress through a Reticulocalbin 1-Dependent Mechanism.

Reticulocalbin 1 (RCN1) is an endoplasmic reticulum (ER)-residing protein, involved in promoting cell survival during pathophysiological conditions that lead to ER stress. However, the key upstream receptor tyrosine kinase that regulates RCN1 expression and its potential role in cell survival in the glioblastoma setting have not been determined. Here, we demonstrate that RCN1 expression significantly correlates with poor glioblastoma patient survival. We also demonstrate that glioblastoma cells with expression of EGFRvIII receptor also have high RCN1 expression. Over-expression of wildtype EGFR also correlated with high RCN1 expression, suggesting that EGFR and EGFRvIII regulate RCN1 expression. Importantly, cells that expressed EGFRvIII and subsequently showed high RCN1 expression displayed greater cell viability under ER stress compared to EGFRvIII negative glioblastoma cells. Consistently, we also demonstrated that RCN1 knockdown reduced cell viability and exogenous introduction of RCN1 enhanced cell viability following induction of ER stress. Mechanistically, we demonstrate that the EGFRvIII-RCN1-driven increase in cell survival is due to the inactivation of the ER stress markers ATF4 and ATF6, maintained expression of the anti-apoptotic protein Bcl-2 and reduced activity of caspase 3/7. Our current findings identify that EGFRvIII regulates RCN1 expression and that this novel association promotes cell survival in glioblastoma cells during ER stress.

Serial Perioperative Assessment of Free Flap Perfusion With Laser Angiography.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Reconstruction with microvascular free flaps is quite predictable but excessive fluids intraoperatively and excessive use of vasopressors have been implicated in postoperative complications. However, vasopressors assist in limiting fluid administration and counteract vasodilatory effects of general anesthetics, while maintaining proper intravascular volume. This is of paramount importance during surgery to ensure adequate tissue and organ perfusion. The purpose of this study is to quantify perfusion changes in free flaps at specific time points during peri- and postoperative periods, incorporating SPY technology. METHODS: A prospective study of patients who underwent free flap reconstruction was conducted (n = 9), using SPY laser angiography with indocyanine green to assess effects of general anesthetics and vasopressors on flap perfusion. Free flaps were evaluated prior to pedicle division, after inset and anastomosis, and in the immediate postoperative setting. Mean perfusion, mean arterial pressure, total operative time, fluid shifts, and vasopressor use were recorded. Data were analyzed with univariate and multivariable analyses. RESULTS: Those with major complications in this cohort, on average received less vasopressors, had shorter operation times and less blood loss, however, they received more fluids intraoperatively. CONCLUSION: Changes in mean perfusion to the free flap during the intraoperative and immediate postoperative period are nominal.

Chemical Characterization and Antiradical Properties of Pyroligneous Acid from a Preserved Bamboo, Guadua angustifolia Kunth

Abstract Pyroligneous acid (PA) was obtained by condensation of the vapors produced in the thermal decomposition of culms residues from Guadua angustifolia Kunth (G. angustifolia) cultivated in Colombia, with and without previous preservation treatment with borax salts. Chemical characterization by GC-MS showed that PA extracts has high content of phenolic compounds. Mequinol, isocreosol, 4-ethylphenol, 4-ethyl-2-methoxyphenol, 3,5-dimethoxy-4-hydroxytoluene and 2,6-dimethoxyphenol were the most abundant substances, identified. The total phenolic content (TPC) and DPPH free radical scavenging activity, were investigated. TPC showed a concentration of 1.959 mg GA g-1±0.010 and 3.844 mg GA g-1±0.027 to PAC and PAS samples. These samples also exhibited high DPPH activity of 70.975%±0.921 and, 16.667%±0.298, respectively. The chemical composition, TPC and DPPH results indicate that the PA extracts obtained from G. angustifolia may be used as a raw material in the food industry as natural preservative, in medicine as alternative to antibiotics and in agriculture as insect repellent and foliar fertilizer.

Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma.

Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue.