Oxytocin signaling is necessary for synaptic maturation of adult-born neurons.

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.

Signaling mechanisms underlying activity-dependent integration of adult-born neurons in the mouse olfactory bulb.

Adult neurogenesis has fascinated the field of neuroscience for decades given the prospects of harnessing mechanisms that facilitate the rewiring and/or replacement of adult brain tissue. The subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle are the two main areas in the brain that exhibit ongoing neurogenesis. Of these, adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and continued circuit integration within adult brain tissue. This review focuses on some of the recognized molecular and signaling mechanisms underlying activity-dependent adult-born neuron development. Notably, olfactory activity and behavioral states contribute to adult-born neuron plasticity through sensory and centrifugal inputs, in which calcium-dependent transcriptional programs, local translation, and neuropeptide signaling play important roles. This review also highlights areas of needed continued investigation to better understand the remarkable phenomenon of adult-born neuron integration.

Evaluation of cytotoxic effect of siphonochilone from African ginger: an in vitro analysis.

Plants provide a wide array of compounds that can be explored for potential anticancer properties. Siphonochilone, a furanoterpene that represents one of the main components of the African plant Siphonochilus aethiopicus, shows numerous health benefits. However, to date, its antiproliferative properties have not been tested. The aim of this study was to analyze the cytotoxic effects of siphonochilone on a panel of cancer cell lines and its underlying mechanism of action. Our results demonstrated that siphonochilone exhibited significant cytotoxic effects on pancreatic, breast, lung, colon, and liver cancer cell lines showing a IC50 ranging from 22 to 124 µM at 72 h of treatment and highlighting its cytotoxic effect against MCF7 and PANC1 breast and pancreas cancer cell lines (22.03 and 39.03 µM, respectively). Cell death in these tumor lines was mediated by apoptosis by the mitochondrial pathway, as evidenced by siphonochilone-induced depolarization of the mitochondrial membrane potential. In addition, siphonochilone treatment involves the generation of reactive oxygen species that may contribute to apoptosis induction. In this work, we described for the first time the cytotoxic properties of siphonochilone and provided data about the molecular processes of cell death. Although future studies will be necessary, our results support the interest in this molecule in relation to their clinical application in cancer, and especially in breast and pancreatic cancer.

Deubiquitinase USP9X loss sensitizes renal cancer cells to mTOR inhibition.

Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase gene USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients' primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients' sensitivity to mTOR inhibitors. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.

An integrated microfluidic-based biosensor using a magnetically controlled MNPs-enzyme microreactor to determine cholesterol in serum with fluorometric detection.

This work provides a microfluidic-based biosensor to determine total cholesterol in serum based on integrating the reaction/detection zone of a microfluidic chip of a magnetically retained enzyme microreactor (MREµR) coupled with the remote fluorometric detection through a bifurcated fiber-optic bundle (BFOB) connected with a conventional spectrofluorometer. The method is based on developing the enzymatic hydrolysis and oxidation of cholesterol at microscale size using both enzymes (cholesterol esterase (ChE) and cholesterol oxidase (ChOx)) immobilized on magnetic nanoparticles (MNPs). The biocatalyst reactions were followed by monitoring the fluorescence decreasing by the naphtofluorescein (NF) oxidation in the presence of the previous H2O2 formed. This microfluidic biosensor supposes the physical integration of a minimal MREµR as a bioactive enzyme area and the focused BFOB connected with the spectrofluorometer detector. The MREµR was formed by a 1 mm length of magnetic retained 2:1 ChE-MNP/ChOx-MNP mixture. The dynamic range of the calibration graph was 0.005-10 mmol L-1, expressed as total cholesterol concentration with a detection limit of 1.1 µmol L-1 (r2 = 0.9999, sy/x = 0.03, n = 10, r = 3). The precision expressed as the relative standard deviation (RSD%) was between 1.3 and 2.1%. The microfluidic-based biosensors showed a sampling frequency estimated at 30 h-1. The method was applied to determine cholesterol in serum samples with recovery values between 94.8 and 102%. The results of the cholesterol determination in serum were also tested by correlation with those obtained using the other two previous methods.

Antibody-Drug Conjugates Containing Payloads from Marine Origin.

Antibody-drug conjugates (ADCs) are an important class of therapeutics for the treatment of cancer. Structurally, an ADC comprises an antibody, which serves as the delivery system, a payload drug that is a potent cytotoxin that kills cancer cells, and a chemical linker that connects the payload with the antibody. Unlike conventional chemotherapy methods, an ADC couples the selective targeting and pharmacokinetic characteristics related to the antibody with the potent cytotoxicity of the payload. This results in high specificity and potency by reducing off-target toxicities in patients by limiting the exposure of healthy tissues to the cytotoxic drug. As a consequence of these outstanding features, significant research efforts have been devoted to the design, synthesis, and development of ADCs, and several ADCs have been approved for clinical use. The ADC field not only relies upon biology and biochemistry (antibody) but also upon organic chemistry (linker and payload). In the latter, total synthesis of natural and designed cytotoxic compounds, together with the development of novel synthetic strategies, have been key aspects of the consecution of clinical ADCs. In the case of payloads from marine origin, impressive structural architectures and biological properties are observed, thus making them prime targets for chemical synthesis and the development of ADCs. In this review, we explore the molecular and biological diversity of ADCs, with particular emphasis on those containing marine cytotoxic drugs as the payload.

Mapping the distribution of stem/progenitor cells across the mouse middle ear during homeostasis and inflammation.

The middle ear epithelium is derived from neural crest and endoderm, which line distinct regions of the middle ear cavity. Here, we investigate the distribution of putative stem cell markers in the middle ear, combined with an analysis of the location of label-retaining cells (LRCs) to create a map of the middle ear mucosa. We show that proliferating cells and LRCs were associated with specific regions of the ear epithelium, concentrated in the hypotympanum at the base of the auditory bulla and around the ear drum. Sox2 was widely expressed in the endodermally derived ciliated pseudostratified epithelium of the hypotympanum. This part of the middle ear showed high levels of Wnt activity, as indicated by the expression of Axin2, a readout of Wnt signalling. Keratin 5 showed a more restricted expression within the basal cells of this region, with very little overlap between the Sox2- and keratin 5-positive epithelium, indicating that these genes mark distinct populations. Little expression of Sox2 or keratin 5 was observed in the neural crest-derived middle ear epithelium that lined the promontory, except in cases of otitis media when this epithelium underwent hyperplasia. This study lays the foundation for furthering our understanding of homeostasis and repair in the middle ear.

PTEN expression and mutations in TSC1, TSC2 and MTOR are associated with response to rapalogs in patients with renal cell carcinoma.

The mammalian target of rapamycin (mTOR) pathway inhibitors are key drugs for the treatment of many tumor types, however, there are no predictive biomarkers in clinical use. Here, we performed a molecular and immunohistochemical characterization of key mTOR pathway components in a series of 105 renal cell carcinoma patients treated with rapalogs, aimed at identifying markers of treatment response. Mutational analysis in MTOR, TSC1 and TSC2 was performed through targeted next-generation sequencing (NGS), and immunohistochemistry (IHC) was performed for PTEN, pAKT, pS6K1, pS6 and p21. Among patients with NGS data, 11 of 87 (13%) had mTOR pathway mutations (8 in MTOR, 1 in TSC1 and 2 in TSC2). When comparing the molecular data to the response of the patients, we found that partial response was more frequent in cases with mTOR pathway mutations than in those without mutations (odds ratio [OR] = 0.08, 95% confidence interval [CI] = 0.008-0.79, p = 0.030 univariate; p = 0.038 multivariable). Regarding IHC, negative PTEN staining was detected in 58% of the tumors, and it was more frequent in rapalog responder patients (OR = 0.24, 95% CI = 0.065-0.86, p = 0.029 univariate; p = 0.029 multivariable). Mutations and PTEN IHC were not mutually exclusive events and its combination improved response prediction (OR = 0.16, 95% CI = 0.04-0.62, p = 0.008 univariate; p = 0.013 multivariable). The staining of other proteins did not show and association with response and no association with PFS was observed in unselected patients. In conclusion, our findings suggest that mTOR pathway mutations, negative PTEN IHC and their combination are potential markers of rapalog response.

Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa-miR-139-5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease-free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa-miR-139-5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa-miR-139-5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa-miR-139-5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa-miR-139-5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.

Regular dental attendance and periodontal health knowledge: A cross-sectional survey.

OBJECTIVES: To explore dental clinics' performance on periodontal education by comparing knowledge about periodontal health of regular and inconsistent dental attenders. SUBJECTS AND METHODS: A population-based study with a cross-sectional design was performed in Galicia (Northwestern Spain). Participants were randomly selected from 16 different areas and a questionnaire applied face-to-face. The survey included items on socio-demographic features, habits and routines, periodontal status and periodontal health knowledge. Participants were grouped according to the median of overall knowledge, and a logistic regression analysis was performed to explore the relationship between good periodontal knowledge and frequency of dental visits. RESULTS: A total of 8,206 individuals were invited to enter the study, and 3,553 of them accepted the invitation (43.3%). Most participants (59.3%; n = 1,945) fit within the regular dental attenders' group. Younger women holding a university degree and visiting their dentist regularly elicited higher knowledge about periodontal health. Regular use of dental services increased the chances of being in the higher knowledge group (OR: 1.67; 95% CI: 1.40-2.00). CONCLUSIONS: Reported regular dental attendance is related to periodontal health knowledge. Specific interventions for promoting tailored patient education on periodontal topics during routine dental visits may have a positive effect on laypersons' knowledge about periodontal health.

Concomitant Medications and Risk of Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: Peripheral neuropathy is the dose-limiting toxicity of many oncology drugs, including paclitaxel. There is large interindividual variability in the neuropathy, and several risk factors have been proposed; however, many have not been replicated. Here we present a comprehensive study aimed at identifying treatment and physiopathology-related paclitaxel-induced neuropathy risk factors in a large cohort of well-characterized patients. PATIENTS AND METHODS: Analyses included 503 patients with breast or ovarian cancer who received paclitaxel treatment. Paclitaxel dose modifications caused by the neuropathy were extracted from medical records and patients self-reported neuropathy symptoms were collected. Multivariate logistic regression analyses were performed to identify concomitant medications and comorbidities associated with paclitaxel-induced neuropathy. RESULTS: Older patients had higher neuropathy: for each increase of 1 year of age, the risk of dose modifications and grade 3 neuropathy increased 4% and 5%, respectively. Cardiovascular drugs increased the risk of paclitaxel dose reductions (odds ratio [OR], 2.51; p = .006), with a stronger association for beta-adrenergic antagonists. The total number of concomitant medications also showed an association with dose modifications (OR, 1.25; p = .012 for each concomitant drug increase). A dose modification predictive model that included the new identified factors gave an area under the curve of 0.74 (p = 1.07 × 10-10). Preexisting nerve compression syndromes seemed to increase neuropathy risk. CONCLUSION: Baseline characteristics of the patients, including age and concomitant medications, could be used to identify individuals at high risk of neuropathy, personalizing chemotherapy treatment and reducing the risk of severe neuropathy. IMPLICATIONS FOR PRACTICE: Peripheral neuropathy is a common adverse effect of many cancer drugs, including chemotherapeutics, targeted therapies, and immune checkpoint inhibitors. About 40% of survivors of cancer have functional deficits caused by this toxicity, some of them irreversible. Currently, there are no effective treatments to prevent or treat this neuropathy. This study, performed in a large cohort of well-characterized patients homogenously treated with paclitaxel, identified concomitant medications, comorbidities, and demographic factors associated with peripheral neuropathy. These factors could serve to identify patients at high risk of severe neuropathy for whom alternative non-neurotoxic alternatives may be considered.

Comparing the efficacy, exposure, and cost of clinical trial analysis methods.

This study aimed to compare three commonly used analysis methods for clinical trials in epilepsy in terms of statistical efficiency, nonefficacious exposure, and cost. A realistic seizure diary simulator was employed to produce 102 000 trials, which were analyzed by the 50%-responder rate method (RR50), median percentage change (MPC), and time to prerandomization (TTP). Half the trials compared a placebo to a drug that was 20% better, and the other half compared two placebos. The former were used to calculate statistical power; the latter were used for type 1 error rates. Based on the number of patients needed to achieve 90% power, expected number of patient-days of nonefficacious exposures and expected cost were calculated for each method. MPC demonstrated the highest efficacy, lowest exposure, and lowest cost. RR50 demonstrated the lowest efficacy, highest exposure, and highest cost. Costs were: MPC $1 295 000, TTP $1 315 720, and RR50 $2 331 000. Selecting an optimal analysis method for a primary outcome in an epilepsy trial can have consequences in terms of nonefficacious exposure and cost. This study provides evidence supporting the use of MPC (preferred) or TTP, and evidence suggesting that RR50 would incur high costs and excess exposures.

Periodontal awareness and what it actually means: A cross-sectional study.

OBJECTIVES: To assess periodontal awareness among laypersons, to characterize the very aware of periodontitis and to disclose whether high awareness implies sufficient periodontal knowledge. SUBJECTS AND METHODS: Cross-sectional study on laypersons randomly selected by quota sampling from March 2015 to June 2016. The questionnaire of periodontal awareness included aspects of aetiology, risk factors, signs and symptoms, related risks, prevention, treatment and related attitudes. It was applied by 12 interviewers in the community in each four province capitals, in a sort of pathfinder survey method. RESULTS: A 43.3% response rate was obtained, and 3,553 people entered the study. "Very aware": 19.4%. "Aware": 42.7%. "Not aware": 37.9%. Age, oral self-care and educational achievements characterized those "very aware." Any additional degree beyond compulsory education halves the chances for being "not periodontally aware." Very aware people likely to have periodontitis were elder, less educated, with a smoking history and less knowledge of the disease. Gaps of knowledge among the "very aware" were identified in all aspects except for "prevention" and "treatment.". CONCLUSIONS: Very periodontally aware people were in their late 40-60 s, followed sound oral care routines and held a degree but elicited insufficient knowledge about aetiology, signs-symptoms, related risks or periodontal risk factors.

Gain-of-function mutations in DNMT3A in patients with paraganglioma.

PURPOSE: The high percentage of patients carrying germline mutations makes pheochromocytomas/paragangliomas the most heritable of all tumors. However, there are still cases unexplained by mutations in the known genes. We aimed to identify the genetic cause of disease in patients strongly suspected of having hereditary tumors. METHODS: Whole-exome sequencing was applied to the germlines of a parent-proband trio. Genome-wide methylome analysis, RNA-seq, CRISPR/Cas9 gene editing, and targeted sequencing were also performed. RESULTS: We identified a novel de novo germline mutation in DNMT3A, affecting a highly conserved residue located close to the aromatic cage that binds to trimethylated histone H3. DNMT3A-mutated tumors exhibited significant hypermethylation of homeobox-containing genes, suggesting an activating role of the mutation. CRISPR/Cas9-mediated knock-in in HeLa cells led to global changes in methylation, providing evidence of the DNMT3A-altered function. Targeted sequencing revealed subclonal somatic mutations in six additional paragangliomas. Finally, a second germline DNMT3A mutation, also causing global tumor DNA hypermethylation, was found in a patient with a family history of pheochromocytoma. CONCLUSION: Our findings suggest that DNMT3A may be a susceptibility gene for paragangliomas and, if confirmed in future studies, would represent the first example of gain-of-function mutations affecting a DNA methyltransferase gene involved in cancer predisposition.

Exploring the Ring-Closing Metathesis for the Construction of the Solomonamide Macrocyclic Core: Identification of Bioactive Precursors.

New synthetic strategies directed toward the novel cyclopeptides solomonamides have been explored utilizing an olefin metathesis as the key reaction. In the various strategies investigated, we worked on minimally oxidized systems, and the olefin metathesis reaction demonstrated efficiency and validity for the construction of the macrocyclic core. The described synthetic strategies toward the solomonamides are well suited for the subsequent access to the natural products and represent flexible and diversity-oriented routes that allow for the generation of a variety of analogues via oxidative transformations. In addition, preliminary biological evaluations of the generated solomonamide precursors revealed antitumor activity against various tumor cell lines.

Impact of human galectin-1 binding to saccharide ligands on dimer dissociation kinetics and structure.

Endogenous lectins can control critical biological responses, including cell communication, signaling, angiogenesis and immunity by decoding glycan-containing information on a variety of cellular receptors and the extracellular matrix. Galectin-1 (Gal-1), a prototype member of the galectin family, displays only one carbohydrate recognition domain and occurs in a subtle homodimerization equilibrium at physiologic concentrations. Such equilibrium critically governs the function of this lectin signaling by allowing tunable interactions with a preferential set of glycosylated receptors. Here, we used a combination of experimental and computational approaches to analyze the kinetics and mechanisms connecting Gal-1 ligand unbinding and dimer dissociation processes. Kinetic constants of both processes were found to differ by an order of magnitude. By means of steered molecular dynamics simulations, the ligand unbinding process was followed monitoring water occupancy changes. By determining the water sites in a carbohydrate binding place during the unbinding process, we found that rupture of ligand-protein interactions induces an increase in energy barrier while ligand unbinding process takes place, whereas the entry of water molecules to the binding groove and further occupation of their corresponding water sites contributes to lowering of the energy barrier. Moreover, our findings suggested local asymmetries between the two subunits in the dimer structure detected at a nanosecond timescale. Thus, integration of experimental and computational data allowed a more complete understanding of lectin ligand binding and dimerization processes, suggesting new insights into the relationship between Gal-1 structure and function and renewing the discussion on the biophysics and biochemistry of lectin-ligand lattices.

Thyroid Disease and Oral Lichen Planus as Comorbidity: A Prospective Case-Control Study.

BACKGROUND: Thyroid disease has been mentioned to have a possible relation to the development of oral lichen planus (OLP). OBJECTIVE: Because goiter is considered endemic in many countries, we proposed to determine whether thyroid disease constitutes a comorbidity of OLP. METHODS: Two hundred and fifteen patients diagnosed as having OLP were evaluated concerning their serum thyroid-stimulating hormone and thyroxine (T4) levels. The results were contrasted with those obtained in control series of the same number of subjects matched for age and sex. RESULTS: Diagnosis of thyroid disease was present in 15.3% of OLP patients (33/215) and in 5.2% (12/215) of the control group. In relation to OLP patients, the odds ratio of presence of thyroid disorders was 3.06 and that of using levothyroxine medication 3.21. CONCLUSIONS: In the present study, OLP patients were associated with thyroid disease, specifically with hypothyroidism. Because most thyroid patients need T4 treatment, our findings confirmed that OLP and thyroid disease could be comorbidities.

Available web-based dental implants information for patients. How good is it?

BACKGROUND: Massive use of the Internet for health issues has raised concerns about the quality of the information available and about consumers' ability to tell "good" from "bad" information. PURPOSE: To assess the quality of patient-addressed, dental implants-related websites in terms of reliability, accessibility, usability and readability. MATERIALS AND METHODS: Two search engines (Google and Yahoo) were used in this study. The first 100 sites, as listed by each engine, were considered for the study. Each site was categorised and analysed for quality using the DISCERN and the LIDA instruments. The Flesch-Kinkaid Reading Grade Level (FKRGL) and the Flesh Reading Ease Score (FRES) were used to assess legibility. RESULTS: After applying the inclusion and exclusion criteria, 32 single websites entered the study. The median score for the DISCERN instrument (3 [2-3]) indicated serious or potentially important shortcoming in the quality of the information obtained. LIDA scores showed modest percentages for accessibility (79.36 [74.60-85.31]) and intermediate for usability (59.20 (50.46-68.51)) and reliability (55.55 [45.37-66.66]). Legibility indices reached scores within the range of difficult to read (FRES = 51.72 [38.70-55.27]); FKRGL = 12.76 [10.07-14.87]). CONCLUSIONS: Available e-health information on dental implants in English language is difficult to read for the average patient and poor in terms of quality.

Available web-based teaching resources for health care professionals on screening for oral cancer.

OBJECTIVES: To identify websites with adequate information on oral cancer screening for healthcare professionals (HCPs) and to assess both their quality and contents. STUDY DESIGN: Websites were identified using Google and HON medical professional search engines using the terms "screening for oral cancer". The first 100 sites retrieved by each engine were analysed using the DISCERN questionnaire (reliability), the V instrument (contents on oral cancer) and further by the Flesch-Kinkaid Reading Grade Level and the Flesch Reading Ease (readability). RESULTS: The overall rating showed minimal shortcomings in the quality of the information in the websites. The coverage and correctness of information on "visual examination" was rated as fair/good, whereas updating of contents resulted very variable (eg: 81% for visual examination and 18.2% for molecular biomarkers). These results permitted to rank the websites housing relevant information for oral cancer. Top ranking websites were affiliated to the Oral Cancer Foundation (USA), WHO Collaborating Centre for oral cancer (UK) whose webpage is entitled "Oral Cancer Education and Research", and the Clinical Guidelines maintained by the British Columbia Cancer Agency (Canada) and the British Dental Association (UK) respectively. CONCLUSIONS: There are web-based, HCP-addressed, resources on screening for oral cancer housing heterogeneous information both in quality and contents. The use of specific evaluation tools permits the selection of reliable websites on this topic with a potential to improve the existing educational gaps among HCPs.

Effect of Size and Location of Unruptured Intracranial Aneurysms on Self-Reported Headache.

AIM: To describe the relationship between aneurysm size and location with the prevalence of headache at diagnosis and three- and six-month follow-up in a sample of patients with UIA. MATERIAL AND METHODS: In this cohort study, patients were diagnosed with UIAs by digital subtraction angiography (DSA). Follow-up visits occurred three and six months after the diagnosis. Headache presence was registered, and headache was further classified by phenotypes. After DSA, the recorded variables were aneurysm number, morphology, location, and size (diameter [W], neck [N], and dome-neck distance [H]). The aspect ratio (H/N) and the dome/neck ratio (W/N) were calculated. The outcome of this study was the self-reported headache status at follow-up. RESULTS: Data from 42 patients and 46 aneurysms were available; 81.0% of patients were women, with a mean age of 57.4±14.3 years. Headache was reported by 61.9% of the patients. The pain phenotype was tension-type in 38.1%, migraine in 11.9%, neuralgia in 2.4%, and unclassifiable in 9.5%. The median (min-max) measurements were W=5.05 (0.89-22.9); N=3.02 (0.52-17.9); H=5.08 (0.92-23.0); aspect ratio 1.59 (0.68-17.69) and W/N ratio 1.65 (0.62-16.92). Thirty-three patients (37 aneurysms) received treatment, 47.8% by surgical clipping and 32.6% by endovascular occlusion. In the treated patients, headaches had persisted in 14.3% until the first visit and in 9.5% until the second visit. There were no differences in any registered variables between patients with and without headaches at follow-up. CONCLUSION: In this study, data was found that support that headaches in patients with UIAs improve after treatment and that such improvement is probably unrelated to the size and shape of the UIAs.