Dental anxiety, Quality of Life and body image: gender differences in Italian and Spanish population.

BACKGROUND: Dental anxiety is an excessive and irrational negative emotional state experienced by population; the dental anxiety is common throughout the lifespan and is an obstacle to improving oral health behaviors and outcomes. The aim of this study was to assess gender differences in dental anxiety and to investigate if oral health impacts patients' Quality of Life and the perception of their body image. METHODS: The sample consisted of 366 subjects selected in Italy and Spain (January 2021-September 2021). For this study, data were gathered using Google Forms (Google LLC, Mountain View, CA, USA). Data were collected including the Dental Anxiety Scale (DAS), Oral Health Impact Profile (OHIP-14) questionnaires and Body Uneasiness Test. RESULTS: Women showed higher scores than men for the dental anxiety. The regression analysis showed that gender, age, and Oral Health Impact are predictors of "dental anxiety." A borderline significance emerges for the independent variable body uneasiness. CONCLUSIONS: The dental anxiety is widespread in the population, with a higher prevalence among women and increases with increasing age. It can negatively affect patients' Quality of Life, well-being, and self-esteem. These results underline the importance of addressing both individual and group strategies for preventing or treating dental anxiety.

MicroRNAs in Gingival Crevicular Fluid: An Observational Case-Control Study of Differential Expression in Periodontitis.

OBJECTIVES: microRNAs (miRNAs) present in the gingival crevicular fluid (GCF) of patients with chronic periodontitis may serve as biomarkers of periodontal disease. The aim of this study was to perform a miRNA-sequencing study of all miRNAs present in GCF, comparing miRNA expression level profiles between advanced chronic periodontitis (CP) patients and healthy subjects (HS). MATERIALS AND METHODS: GCF samples were collected from the single-rooted teeth of patients with severe CP (n = 11) and of HS (n = 12). miRNAs were isolated from GCF using an miRNeasy Serum/Plasma kit(Qiagen GmbH, Hilden, Germany). Reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the expression levels of miRNA candidates involved in periodontal pathogenesis. RESULTS: Of all the sequenced miRNAs, miR-199, miR-146a, miR-30a, and miR-338 were identified as best representing the CP patient samples. The validation study identified miR-199 as the most powerful biomarker used to define periodontitis. CONCLUSIONS: Upon sequencing all known miRNAs in GCF for the first time, we uncovered several potential biomarkers to define periodontitis. Identifying miRNAS in the GCF using high-throughput approaches will clarify the role of these molecules in periodontitis and provide biomarkers with potential applications.

MicroRNAs and periodontal disease: a qualitative systematic review of human studies.

PURPOSE: MicroRNAs (miRNAs) are epigenetic post-transcriptional regulators that modulate gene expression and have been identified as biomarkers for several diseases, including cancer. This study aimed to systematically review the relationship between miRNAs and periodontal disease in humans, and to evaluate the potential of miRNAs as diagnostic and prognostic biomarkers of disease. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (reference number CRD42020180683). The MEDLINE, Scopus, Cochrane Library, Embase, Web of Science, and SciELO databases were searched for clinical studies conducted in humans investigating periodontal diseases and miRNAs. Expression levels of miRNAs across the different groups were analysed using the collected data. RESULTS: A total of 1,299 references were identified in the initial literature search, and 23 articles were finally included in the review. The study designs were heterogeneous, which prevented a meta-analysis of the data. Most of the studies compared miRNA expression levels between patients with periodontitis and healthy controls. The most widely researched miRNA in periodontal diseases was miR-146a. Most studies reported higher expression levels of miR-146a in patients with periodontitis than in healthy controls. In addition, many studies also focused on identifying target genes of the differentially expressed miRNAs that were significantly related to periodontal inflammation. CONCLUSIONS: The results of the studies that we analysed are promising, but diagnostic tests are needed to confirm the use of miRNAs as biomarkers to monitor and aid in the early diagnosis of periodontitis in clinical practice.

Adolescence, Adulthood and Self-Perceived Halitosis: A Role of Psychological Factors.

(1) Background: Halitosis is a frequent condition that affects a large part of the population. It is considered a "social stigma", as it can determine a number of psychological and relationship consequences that affect people's lives. The purpose of this review is to examine the role of psychological factors in the condition of self-perceived halitosis in adolescent subjects and adulthood. (2) Type of studies reviewed: We conducted, by the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines, systematic research of the literature on PubMed and Scholar. The key terms used were halitosis, halitosis self-perception, psychological factors, breath odor and two terms related to socio-relational consequences ("Halitosis and Social Relationship" OR "Social Issue of Halitosis"). Initial research identified 3008 articles. As a result of the inclusion and exclusion criteria, the number of publications was reduced to 38. (3) Results: According to the literature examined, halitosis is a condition that is rarely self-perceived. In general, women have a greater ability to recognize it than men. Several factors can affect the perception of the dental condition, such as socioeconomic status, emotional state and body image. (4) Conclusion and practical implication: Self-perceived halitosis could have a significant impact on the patient's quality of life. Among the most frequent consequences are found anxiety, reduced levels of self-esteem, misinterpretation of other people's attitudes and embarrassment and relational discomfort that often result in social isolation.

Performance of the dentogingival junction with mta and biodentine on the treatment of invasive cervical resorptions. A literature review and case report.

Invasive cervical resorption (ICR) is an uncommon phenomenon (0.1%), however, it represents a challenge to the structural and functional integrity of the dentogingival junction, as well as a risk for the survival of the affected tooth. They are characterized by their location and invasive character, being able to appear in any tooth of the permanent dentition. It shows up after the damage to the cervical insertion apparatus, leaving the pulp without participation in the origin of the lesion. They may appear just below the junctional epithelium or at a more apical level. The MTA® (Dentsply, Tulsa dental, Tulsa OK) and the Biodentine® (Septodent, Saint Maur of Fossés, France) are two biomaterials that have demonstrated the ability to promote the neoformation of cement so they are considered an alternative in the treatment of the ICR. This article presents an ICR clinical cases treated with these biomaterials, in which favorable post-operative healing is observed. Key words:MTA, Biodentine, biomaterials, root resorption, invasive cervical resorption.

miR-1226 detection in GCF as potential biomarker of chronic periodontitis: A pilot study

BACKGROUND: The study and identification of new biomarkers for periodontal disease, such as microRNAs (miR-NAs), may give us more information about the location and severity of the disease and will serve as a basis for treatment planning and disease-monitoring. miRNAs are a group of small RNAs which are involved in gene regulation by binding to their messenger RNA target (mRNA). In this pilot study, the procedure for purifying miRNAs from gingival crevicular fluid (GCF) was, for the first time, described. In addition, the concentration of miRNAs in GCF was analyzed and compared between patients with moderate or severe chronic periodontitis (CP) and healthy controls. MATERIAL AND METHODS: GCF samples were collected from single-rooted teeth of patients with moderate or severe CP (n=9) and of healthy individuals (n=9). miRNAs were isolated from GCF using miRNeasy Serum/Plasma kit (Qiagen, CA. USA). Reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the expression of a series of miRNAs candidates that are related to bone metabolism. The significance of differences in miRNA levels between both groups was determined using Mann-Whitney U test. RESULTS: The results from this pilot study indicate that miRNAs can be isolated from GCF. Six different miRNAs were analyzed (miR-671, miR-122, miR-1306, miR-27a, miR-223, miR-1226), but only miR-1226 showed statically significant differences between the CP group and healthy controls (p < 0.05). This miRNA was downregulated in patients with CP. CONCLUSIONS: Within the limitations of the present study, it may be concluded that miR-1226 can be a promising biomarker for periodontal disease, adding relevant information to common clinical parameters used for diagnosis and prognosis of periodontitis

Palatal fenestration after orthodontic treatment. Intermodal approach and evolution. A case report.

A 15-year-old patient is referred to the Department of Periodontics of the University of Valencia. The patient reported dissatisfaction with the position of upper right canine after orthodontic treatment. Previously, in a private center, surgical approaches were performed for the traction of the canine included. On clinical examination at first appointment, generalized plaque-induced gingivitis was observed, with palatal fenestration of the root of upper right lateral incisor of approximately 75% of the total surface, with suppuration and very little gingiva inserted at the cervical level, which presents a buccal torque of the crown. Radiologically, a mild rhizolysis and bone loss adjacent to upper right lateral incisor was observed. An interdisciplinary treatment is decided between the departments of Orthodontics, Endodontics and Periodontics: - Canal treatment of upper right lateral incisor, performing a retrograde filling of the cavity with Biodentine ® (Septodent, Saint Maur de Fossés, France). - Orthodontic treatment, modifying the torque and improving the stability. - Periodontal treatment, performing a connective tissue graft by Langer technique adapted to the case. After the conclusion of the orthodontic treatment, an improvement in the situation is observed. The graft was performed, presenting at 3 months a line of fenestration in the mucosa. At 4 years, the patient is asymptomatic, without suppuration, with a total closure of the fenestration. Key words:Recession, orthodontics, connective tissue graft.

Socioeconomic factors and severity of periodontal disease in adults (35-44 years). A cross sectional study.

BACKGROUND: Periodontal disease or periodontitis is an inflammatory disease with a hight prevalence. According to the last oral health survey of the Spanish population, between 24% and 37% of Spaniards aged over 35 years have periodontitis and 6% to 10% of the adult population have deep periodontal pockets. The aim of this study was to determine the association between risk factors and the presence of periodontal pockets in the adult population. MATERIAL AND METHODS: A cross sectional or prevalence study of a representative sample of the adult population of the Valencia region was designed. The sample was recruited at 35 health centres, The study was conducted in November and December 2006 under standardized conditions as regards light sources, equipment and instruments and the position of the three previously calibrated dentist examiners. RESULTS: The sample examined consisted of 733 individuals (220 men and 513 women). Measured by the CPI, 13% were healthy and 5.5% presented bleeding. The prevalence of calculus was 59.3%, that of 3.5-5.5 mm pockets was 15.8% and that of pockets deeper than 5.5 mm was 4.6%. Almost half the sextants were healthy (2.89), 0.61 presented bleeding and 1.74 presented calculus. The mean number of sextants affected by 3.5-5.5 mm pockets was 0.46 and 0.07 presented deep pockets (>5.5 mm). An adjusted multiple logistic regression model with the presence of periodontal pockets as the dependent variable showed that the significant independent variables were low social class (OR=1.81), smoking (OR=1.68), primary education (OR=1.57), male gender (OR=1.56) and age (OR=1.08). The other study variables were not significant in this model. CONCLUSIONS: Socioeconomic factors such as primary education and low social class, as well as gender, age and smoking, were found to be associated to a significant degree with greater prevalence of periodontal disease in the adult population. Key words:Periodontal disease, adults, socioeconomic factors, periodontal pockets, cross sectional study.

Hereditary gingival fibromatosis: Characteristics and treatment approach.

Hereditary gingival fibromatosis (HGF) is a rare disorder characterized by a benign, non-hemorrhagic, fibrous gingival overgrowth that can appear in isolation or as part of a syndrome. Clinically, a pink gingiva with marked stippling can be seen to cover almost all the tooth, in many cases preventing eruption. HGF usually begins during the transition from primary to permanent teeth, giving rise to a condition that can have negative psychological effects at that age. As it does not resolve spontaneously, the treatment of choice is gingivectomy, which can be performed with an internal or external bevel incision, depending on each case and bearing in mind the changes that will take place at the dentogingival junction (DGJ). This paper describes clinical aspects and treatment in two eight-year-old boys with HGF, considering different facets of the surgical approach with conscious sedation in young children. Key words:Hereditary gingival fibromatosis, gingivectomy, internal bevel incision, external bevel incision, gingival overgrowth.

A controlled clinical study of periodontal health in anticoagulated patients: Assessment of bleeding on probing.

BACKGROUND: According to the Spanish Society of Cardiology, 700,000 patients receive oral anticoagulants, and in these cases bleeding on probing (BOP) could be altered. However, no studies have analyzed the periodontal status of these patients and the effects anticoagulants may have upon BOP. A study was made of the possible relationship between plaque index, probing depth, INR (International Normalized Ratio) and acenocoumarol dose versus the clinical signs of BOP in a sample of anticoagulated patients. Likewise, an analysis was made of oral hygiene habits and attitude towards bleeding in these patients. MATERIAL AND METHODS: A controlled observational clinical study was made in La Ribera Hospital (Valencia, Spain) involving 44 anticoagulated patients treated with Sintrom® (acenocoumarol) and a homogeneous control group of 44 non-anticoagulated patients. A survey on oral hygiene habits and attitude towards bleeding was carried out, and the main periodontal parameters were recorded. RESULTS: Probing depth was the parameter with the strongest correlation to BOP (p<0.001), followed by the plaque index (p<0.002). In contrast, no relationship was observed between acenocoumarol dose or INR and BOP. Mean BOP was greater in the control group than in the anticoagulated group (p<0.001). Oral hygiene habits and attitude towards bleeding differed significantly between groups. CONCLUSIONS: We have found no explanation why BOP was greater in the control group. What seems clear is that in the presence of the same plaque index and probing depth, anticoagulated patients did not bleed more than non-anticoagulated patients. A lack of knowledge of health and oral hygiene habits was observed in these subjects. Key words:Anticoagulant therapy, bleeding on probing, periodontal health.

Encefalitis antirreceptor de NMDA: dos casos pediátricos / Anti-NMDA receptor encephalitis: two paediatric cases

Introducción. La encefalitis asociada a anticuerpos antirreceptores de N-metil-D-aspartato (NMDA) es una patología neurológica autoinmune documentada en la población pediátrica de manera creciente en los últimos años. Se presentan dos casos de nuestra experiencia con clínica similar. Casos clínicos. Caso 1: niña de 5 años que inicia un cuadro de convulsiones y alteración de conciencia, asociando trastornos del movimiento y regresión de habilidades previamente adquiridas que evoluciona a autismo. Caso 2: niña de 13 años que presenta hemiparesia izquierda, movimientos anómalos, trastorno de conducta y disautonomía. En ambos casos se obtienen anticuerpos antirreceptores de NMDA positivos en el líquido cefalorraquídeo y se diagnostican de encefalitis antirreceptor de NMDA. En el primer caso se inicia el tratamiento con perfusión intravenosa de corticoides e inmunoglobulinas y es necesario asociar rituximab. En el segundo, corticoides e inmunoglobulinas. La evolución fue favorable en ambas pacientes, con una leve alteración del lenguaje como secuela en el primer caso y una recaída en el segundo caso, con resolución completa. Conclusión. La encefalitis antirreceptor de NMDA es un trastorno tratable y es importante el diagnóstico y tratamiento precoz, ya que mejora el pronóstico y disminuye las recaídas (AU)

Introduction. Encephalitis associated to anti-N-methyl D-aspartate (NMDA) receptor antibodies is an autoimmune neurological pathology that has been reported increasingly more frequently in the paediatric population in recent years. We report two cases from our own experience with similar clinical pictures. Case reports. Case 1: a 5-year-old girl who began with clinical signs and symptoms of convulsions and altered consciousness, associated to movement disorders and regression of previously acquired abilities that developed into autism. Case 2: a 13-year-old girl who presented left-side hemiparesis, abnormal movements, conduct disorder and dysautonomia. In both cases positive anti-NMDA receptor antibodies were obtained in cerebrospinal fluid and they were diagnosed with anti-NMDA receptor encephalitis. In the first case, treatment was established with intravenous perfusion of corticoids and immunoglobulins, and rituximab also had to be associated. In the second case, treatment consisted in corticoids and immunoglobulins. Progress was favourable in both cases, with a slight language disorder as a sequela in the first case and a relapse in the second case, with full resolution. Conclusions. Anti-NMDA receptor encephalitis is a treatable disorder and early diagnosis and treatment are crucial, since this improves the prognosis and diminishes the chances of relapses (AU)

[Anti-NMDA receptor encephalitis: two paediatric cases]. / Encefalitis antirreceptor de NMDA: dos casos pediátricos.

INTRODUCTION: Encephalitis associated to anti-N-methyl D-aspartate (NMDA) receptor antibodies is an autoimmune neurological pathology that has been reported increasingly more frequently in the paediatric population in recent years. We report two cases from our own experience with similar clinical pictures. CASE REPORTS: Case 1: a 5-year-old girl who began with clinical signs and symptoms of convulsions and altered consciousness, associated to movement disorders and regression of previously acquired abilities that developed into autism. Case 2: a 13-year-old girl who presented left-side hemiparesis, abnormal movements, conduct disorder and dysautonomia. In both cases positive anti-NMDA receptor antibodies were obtained in cerebrospinal fluid and they were diagnosed with anti-NMDA receptor encephalitis. In the first case, treatment was established with intravenous perfusion of corticoids and immunoglobulins, and rituximab also had to be associated. In the second case, treatment consisted in corticoids and immunoglobulins. Progress was favourable in both cases, with a slight language disorder as a sequela in the first case and a relapse in the second case, with full resolution. CONCLUSIONS: Anti-NMDA receptor encephalitis is a treatable disorder and early diagnosis and treatment are crucial, since this improves the prognosis and diminishes the chances of relapses.

TITLE: Encefalitis antirreceptor de NMDA: dos casos pediatricos.Introduccion. La encefalitis asociada a anticuerpos antirreceptores de N-metil-D-aspartato (NMDA) es una patologia neurologica autoinmune documentada en la poblacion pediatrica de manera creciente en los ultimos años. Se presentan dos casos de nuestra experiencia con clinica similar. Casos clinicos. Caso 1: niña de 5 años que inicia un cuadro de convulsiones y alteracion de conciencia, asociando trastornos del movimiento y regresion de habilidades previamente adquiridas que evoluciona a autismo. Caso 2: niña de 13 años que presenta hemiparesia izquierda, movimientos anomalos, trastorno de conducta y disautonomia. En ambos casos se obtienen anticuerpos antirreceptores de NMDA positivos en el liquido cefalorraquideo y se diagnostican de encefalitis antirreceptor de NMDA. En el primer caso se inicia el tratamiento con perfusion intravenosa de corticoides e inmunoglobulinas y es necesario asociar rituximab. En el segundo, corticoides e inmunoglobulinas. La evolucion fue favorable en ambas pacientes, con una leve alteracion del lenguaje como secuela en el primer caso y una recaida en el segundo caso, con resolucion completa. Conclusion. La encefalitis antirreceptor de NMDA es un trastorno tratable y es importante el diagnostico y tratamiento precoz, ya que mejora el pronostico y disminuye las recaidas.

Accidentes cerebrovasculares prenatales diagnosticados en la etapa de lactante: serie de 10 pacientes / Prenatal cerebrovascular accidents diagnosed in the early infant stage: a series of 10 patients

Introducción. El accidente cerebrovascular (ACV) fetal o prenatal se define como un suceso isquémico, trombótico o hemorrágico arterial o venoso que acontece entre las 14 semanas de gestación y el inicio del parto. Pacientes y métodos. Estudio retrospectivo de una serie de 10 pacientes afectos de un ictus, presumiblemente fetal, desapercibido durante el embarazo y diagnosticado en la etapa de lactante; se destacan cuáles han sido los síntomas y la edad en que se han identificado. Resultados. De los 10 pacientes estudiados, ninguno presentaba antecedentes maternos relevantes, pero se detectaron cuatro amenazas de parto pretérmino que se resolvieron con las medidas habituales y sin hallazgos de alteración fetal posterior. Entre el segundo y tercer trimestre de vida es cuando se han realizado los estudios que han llevado al diagnóstico, y se ha indicado por la familia una menor movilidad de un hemicuerpo respecto al contralateral como motivo de consulta. Dos pacientes presentaban una trombofilia. Con una media de seguimiento de seis años, todos asocian una parálisis cerebral infantil, la tercera parte una epilepsia y el 75% tiene dificultades de aprendizaje o discapacidad intelectual. Conclusión. Cuando los ACV no se detectan prenatalmente, es importante que en la atención primaria se busquen y detecten los signos de alarma del desarrollo psicomotor del lactante de forma precoz para iniciar su estudio y procurar una rehabilitación lo más pronto posible (AU)

Introduction. A foetal or prenatal cerebrovascular accident (CVA) is defined as an ischaemic, thrombotic or arterial or venous haemorrhagic event that occurs between the 14th week of gestation and the onset of labour. Patients and methods. We report a retrospective study of a series of 10 patients suffering from a, presumably foetal, stroke that went unnoticed during the pregnancy and was diagnosed in the early infant stage. The symptoms and the age at which they were identified are highlighted. Results. None of the 10 patients studied presented any relevant events in the mothers’ medical history, but there were four threats of a preterm birth that were solved using the usual means and without the occurrence of any alterations that later affected the foetus. The studies that led to the diagnosis were carried out between the sixth and ninth months of life, and the reason for visiting was reported by the family as being a lower degree of mobility on one side of the body with respect to the other. Two patients presented thrombophilia. With a mean follow-up time of six years, all the patients have an associated infantile cerebral palsy, a third of them have epilepsy and 75% have learning difficulties or intellectual disability. Conclusions. When CVA are not detected in the prenatal period, it is important in primary care to look for and detect the warning signs of the psychomotor development of the infant at an early stage in order to begin a study of the case and to undertake rehabilitation as early as possible (AU)

[Prenatal cerebrovascular accidents diagnosed in the early infant stage: a series of 10 patients]. / Accidentes cerebrovasculares prenatales diagnosticados en la etapa de lactante: serie de 10 pacientes.

INTRODUCTION. A foetal or prenatal cerebrovascular accident (CVA) is defined as an ischaemic, thrombotic or arterial or venous haemorrhagic event that occurs between the 14th week of gestation and the onset of labour. PATIENTS AND METHODS. We report a retrospective study of a series of 10 patients suffering from a, presumably foetal, stroke that went unnoticed during the pregnancy and was diagnosed in the early infant stage. The symptoms and the age at which they were identified are highlighted. RESULTS. None of the 10 patients studied presented any relevant events in the mothers' medical history, but there were four threats of a preterm birth that were solved using the usual means and without the occurrence of any alterations that later affected the foetus. The studies that led to the diagnosis were carried out between the sixth and ninth months of life, and the reason for visiting was reported by the family as being a lower degree of mobility on one side of the body with respect to the other. Two patients presented thrombophilia. With a mean follow-up time of six years, all the patients have an associated infantile cerebral palsy, a third of them have epilepsy and 75% have learning difficulties or intellectual disability. CONCLUSIONS. When CVA are not detected in the prenatal period, it is important in primary care to look for and detect the warning signs of the psychomotor development of the infant at an early stage in order to begin a study of the case and to undertake rehabilitation as early as possible.

TITLE: Accidentes cerebrovasculares prenatales diagnosticados en la etapa de lactante: serie de 10 pacientes.Introduccion. El accidente cerebrovascular (ACV) fetal o prenatal se define como un suceso isquemico, trombotico o hemorragico arterial o venoso que acontece entre las 14 semanas de gestacion y el inicio del parto. Pacientes y metodos. Estudio retrospectivo de una serie de 10 pacientes afectos de un ictus, presumiblemente fetal, desapercibido durante el embarazo y diagnosticado en la etapa de lactante; se destacan cuales han sido los sintomas y la edad en que se han identificado. Resultados. De los 10 pacientes estudiados, ninguno presentaba antecedentes maternos relevantes, pero se detectaron cuatro amenazas de parto pretermino que se resolvieron con las medidas habituales y sin hallazgos de alteracion fetal posterior. Entre el segundo y tercer trimestre de vida es cuando se han realizado los estudios que han llevado al diagnostico, y se ha indicado por la familia una menor movilidad de un hemicuerpo respecto al contralateral como motivo de consulta. Dos pacientes presentaban una trombofilia. Con una media de seguimiento de seis años, todos asocian una paralisis cerebral infantil, la tercera parte una epilepsia y el 75% tiene dificultades de aprendizaje o discapacidad intelectual. Conclusion. Cuando los ACV no se detectan prenatalmente, es importante que en la atencion primaria se busquen y detecten los signos de alarma del desarrollo psicomotor del lactante de forma precoz para iniciar su estudio y procurar una rehabilitacion lo mas pronto posible.

Cerebelitis aguda fulminante: caso excepcional y de evolución fatal / Fulminant acute cerebellitis: an exceptional case with a fatal outcome

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Regulation of markers of synaptic function in mouse models of depression: chronic mild stress and decreased expression of VGLUT1.

Depression has been linked to failure in synaptic plasticity originating from environmental and/or genetic risk factors. The chronic mild stress model regulates the expression of synaptic markers of neurotransmitter function and associated depressive-like behaviour. Moreover, mice heterozygous for the synaptic vesicle protein vesicular glutamate transporter 1 (VGLUT1), have been proposed as a genetic model of deficient glutamate function linked to depressive-like behaviour. Here, we aimed to identify, in these two experimental models, mechanisms of failure in synaptic plasticity, common to stress and impaired glutamate function. First, we show that chronic mild stress induced a transient decrease of different plasticity markers (VGLUT1, synapsin 1, sinaptophysin, rab3A and activity regulated cytoskeletal protein - Arc) but a long-lasting decrease of the brain derived neurotrophic factor as well as depressive-like behaviour. The immediate early gene Arc was also down-regulated in VGLUT1+/- heterozygous mice. In contrast, an opposite regulation of synapsin 1 was observed. Finally, both models showed a marked increase of cortical Arc response to novelty. Increased Arc response to novelty could be suggested as a molecular mechanism underlying failure to adapt to environmental changes, common to chronic stress and altered glutamate function. Further studies should investigate whether these changes are associated to depressive-like behaviour both in animal models and in depressed patients.

Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer.

PURPOSE: To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC). PATIENTS AND METHODS: Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU 1000 [corrected] mg/m2 continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2 continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CR) or partial response of greater than 80% in primary tumor received additional CRT (cisplatin 100 mg/m2 on days 1, 22, and 43 plus 70 Gy). RESULTS: A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was 14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank test, P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease (OS: 26 months in CF arm v 36 months in PCF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001). CONCLUSION: Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.