Alterations in glucose metabolism proteins responsible for the Warburg effect in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most frequent esophageal tumor in the world. ESCC presents late diagnosis, highly aggressive behavior and poor survival. Changes in tumor cell energy metabolism appear to have a prominent role in malignant transformation. Tumor cells consume glucose avidly and produce lactic acid, even under normoxia. Among the factors that may contribute to the stimulation of glycolysis in tumor cells, there are changes in the glycolytic pathway enzymes such as: pyruvate kinase M1 and M2 (PKM2 and PKM1), hexokinase II (HKII), glucose transporter isoform 1 (GLUT-1), and transcription factor induced by hypoxia (HIF1α), responsible for the transcription of proteins cited. The objective of this study is to evaluate the alterations of these proteins and their association with clinicopathological data in ESCC. We performed immunohistochemistry to determine HIF-1α, GLUT-1, PKM1, PKM2, HK2 and Ki67-expression in ESCC patients and controls. Also, we used RT-qPCR to evaluated mRNA expression of GLUT-1 in esophageal mucosa of individuals without cancer, but are alcohol drinkers and tobacco smokers. Our results showed the exclusively expression of GLUT-1 in tumors cells and dysplastic samples. We also observed a compartmentalization of the expression of PKM1 and PKM2 in relation to tumor cells and stroma associated to tumor areas. All of the proteins evaluated, excepted GLUT-1, were frequently detected in normal mucosa. No correlations between clinicopathological features and protein expressions were observed. GLUT-1 expression appears in initial tumor lesions and is maintained through ESCC evolution. We reported for the first time PKM1 staining in normal esophagus and ESCC, being mostly present in more differentiated cells.

Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) shows a 5-year survival rate below 10%, demonstrating the urgency in improving its treatment. Alterations in epidermal growth factor receptors are closely related to malignancy transformation in a number of tumors and recent successful targeted therapies have been directed to these molecules. Therefore, in this study, we analyzed the expression of EGFR and HER2 and evaluated EGFR mutation profile as well as the presence of mutations in hotspots of KRAS and BRAF in ESCC patients. METHODS: We performed RT-qPCR, immunohistochemistry and Fluorescent in situ hybridization to determine EGFR and HER2 expression in ESCC patients, and direct sequencing and PCR-RFLP for mutations and polymorphism analysis. RESULTS: Our results showed an increased EGFR mRNA expression in tumors compared to surrounding tissue (p <0.05), with 11% of the cases presenting at least a four-fold difference between tumor and paired adjacent mucosa. EGFR protein overexpression was present only in 4% of the cases. The median expression of HER2 mRNA was not different between tumors and adjacent mucosa. Still, 7% of the tumors presented at least a 25-fold higher expression of this gene when compared to its paired counterpart. Immunohistochemical analysis revealed that 21% of the tumors were positive for HER2 (scores 2+ and 3+), although only 3+ tumors presented amplification of this gene. Mutation analysis for EGFR (exons 18-21), KRAS (codons 12 and 13) and BRAF (V600E) showed no mutations in any of the hotspots of these genes in almost 100 patients analyzed. EGFR presented synonymous polymorphisms at codon 836 (C>T) in 2.1% of the patients, and at codon 787 (G>A) in 79.2% of the cases. This last polymorphism was also evaluated in 304 healthy controls, which presented a similar frequency (73.7%) in comparison with ESCC patients. The absence of mutations of EGFR, KRAS and BRAF as well as the overexpression of EGFR and HER2 in less than 10% of the patients suggest that this signaling pathway is altered in only a small proportion of patients with ESCC. CONCLUSION: HER receptors target therapies may have the potential to be effective in only a minor fraction of patients with ESCC.

"Laying bricks to build integrated career guidance plans": Best practices in vocational education and training in Andalusia, Spain.

Vocational Education and Training (VET) policies are paying increasing attention towards the need to develop quality career guidance processes. Career guidance plays an essential role in this challenge by enabling people to develop the career management skills that allow them to become aware of their full potential and to construct life projects that facilitate the emotional management of uncertainty and complexity, participating as responsible agents in their environment. After conducting a literature review on each of these key elements, we set out to identify best practices in VET as "building blocks" for the construction of an integrated career guidance plan in VET. This study adopts an approach based on qualitative methodology, specifically a documentary type of research has been carried out. The documents analysed correspond to 88 best practices identified in Andalusia (Spain). The analysis strategy used was a content analysis. For this purpose, a system of categories has been designed, from a deductive perspective, which has contributed to a systematic analysis of them. One of the first conclusions of the study is the uneven development o best practices in the different VET professional pathways. The practices carried out in the centres begin to incorporate different elements and thus facilitate the creation of a suitable context for the development of comprehensive career guidance plans in VET. The article closes by offering implications for the development of guidance in the education system (at VET level) and discusses lines of future research.

24-month Real-World Study of Spinal Cord Stimulation in Failed Back Surgery Patients with Refractory Pain.

BACKGROUND: Failed Back Surgery Syndrome (FBSS) causes disability and lowers health-related quality of life (HRQoL) for patients. Many patients become refractory to Conventional Medical Management (CMM) and Spinal Cord Stimulation (SCS) is advised. However, comparative effectiveness research of both clinical approaches still lacks further evidence. OBJECTIVES: This study describes Comparative Effectiveness Research of CMM versus SCS to provide real world evidence regarding the appropriate means for FBSS management, in terms of Patient-Reported Outcomes Measures. STUDY DESIGN: Naturalistic, pragmatic, prospective observational multicenter SEFUDOCE-study. SETTING: FBSS patients attending clinical programmed visits in Pain Unit at Hospital Universitario de La Princesa and at Hospital General Universitario de Alicante (Spain). METHODS: Study evaluates the impact on pain, functional limitation, and HRQoL of CMM versus SCS in the management of FBSS. Patients completed Pain Detect Questionnaire, Oswestry Disability Index, EQ-5D-3L, Medical Outcomes Study Sleep Scale, and Hospital Anxiety and Depression Scale at baseline and at 3, 6, 12, 18 and 24 months. Longitudinal data were analysed with repeated-measures one-way analysis of variance adjusting by confounders. RESULTS: Eighty-five adults patients with FBSS receiving treatment according to current clinical practice were assessed. After 24 months, the PainDETECT Questionnnaire showed that CMM patients maintained similar scores, while SCS patients reduced their overall score (current pain: 6 CMM versus 4.21 SCS, P = 0.0091; intensity strongest pain: 7.77 CMM versus 6.07 SCS, P = 0.0103; average pain: 6.46 CMM versus 4.75 SCS, P = 0.0012). For the Oswestry Disability Index, the Medical Outcomes Study Sleep Scale, and the Hospital Anxiety and Depression Scale no significant inter-group differences were found. EQ-5D utility improved in SCS patients from baseline (baseline: 0.32 CMM versus 0.22 SCS; 24-month: 0.37 CMM versus 0.63 SCS, P = 0.026). Twenty-four month follow-up showed unlikely presence of neuropathic pain and moderate disability in SCS patients, whereas the CMM patients maintained baseline health state. LIMITATIONS: Given the nature of the intervention, conducting a blinded study was not considered practically feasible. A larger sample could also overcome having younger patients in the SCS arm. CONCLUSIONS: SCS may improve the HRQoL and functionality of FBSS patients with refractory pain in the long-term compared to CMM alone.

Arousing the Sound: A Field Study on the Emotional Impact on Children of Arousing Sound Design and 3D Audio Spatialization in an Audio Story.

Sound from media increases the immersion of the audience in the story, adding credibility to the narration but also generating emotions in the spectator. A study on children aged 9-13 years (N = 253), using an audio story, investigated the emotional impact of arousal vs. neutral treatment of sound and 3D vs. stereo mix spatialization. The emotional impact was measured combining three different measures: physiological (Electrodermal activity), self-report (pre-post exposition), and richness of mental images elicited by the story (using Think-aloud technique after exposition). Results showed higher emotional impact of the arousal and 3D audio conditions with different patterns according to the age of the participants and distinctive types of interaction when both variables were combined.

Associations of Vitamin D Deficiency, Parathyroid hormone, Calcium, and Phosphorus with Perinatal Adverse Outcomes. A Prospective Cohort Study.

Vitamin D deficiency during pregnancy has been linked to perinatal adverse outcomes. Studies conducted to date have recommended assessing interactions with other vitamin D-related metabolites to clarify this subject. We aimed to evaluate the association of vitamin D deficiency during early pregnancy with preterm birth. Secondary outcomes included low birth weight and small for gestational age. Additionally, we explored the role that parathyroid hormone, calcium and phosphorus could play in the associations. We conducted a prospective cohort study comprising 289 pregnant women in a hospital in Granada, Spain. Participants were followed-up from weeks 10-12 of gestation to postpartum. Serum 25-hydroxyvitamin D, parathyroid hormone, calcium, and phosphorus were measured within the first week after recruitment. Pearson's χ2 test, Mann-Whitney U test, binary and multivariable logistic regression models were used to explore associations between variables and outcomes. 36.3% of the participants were vitamin D deficient (<20 ng/mL). 25-hydroxyvitamin D concentration was inversely correlated with parathyroid hormone (ρ = -0.146, p = 0.013). Preterm birth was associated with vitamin D deficiency in the multivariable model, being this association stronger amongst women with parathyroid hormone serum levels above the 80th percentile (adjusted odds ratio (aOR) = 6.587, 95% CI (2.049, 21.176), p = 0.002). Calcium and phosphorus were not associated with any studied outcome. Combined measurement of 25-hydroxyvitamin D and parathyroid hormone could be a better estimator of preterm birth than vitamin D in isolation.

A Prototypicality Validation of the Comprehensive Assessment of Psychopathic Personality (CAPP) Model Spanish Version.

The Comprehensive Assessment of Psychopathic Personality (CAPP) is a newly developed, lexically based, conceptual model of psychopathy. The content validity of the Spanish language CAPP model was evaluated using prototypicality analysis. Prototypicality ratings were collected from 187 mental health experts and from samples of 143 health professionals and 282 community residents. Across the samples the majority of CAPP items were rated as highly prototypical of psychopathy. The Self, Dominance, and Attachment domains were evaluated as being more prototypical than the Behavioral and Cognitive domains. These findings are consistent with findings from similar studies in other languages and provide further support for the content validation of the CAPP model across languages and the lexical approach.

Quality of life during pregnancy and its influence on oral health: a systematic review / Calidad de vida durante el embarazo y su influencia en la salud bucal: una revisión sistemática

Abstract: Objective: To perform a systematic review of scientific literature on the impact of oral health on the quality of life of pregnant women. Methods: A systematic search following PRISMA guidelines was carried out and 16 specific articles/studies on the subject were selected. Results: Pregnant women's quality of life (QoL) is related to age, number of pregnancies, pain, difficulty eating and presence of dental caries. Quality of life was directly related to oral health. Conclusions: It was found that most studies associating QoL and oral health during pregnancy were cross-sectional and observational; therefore, for a better understanding of these impacts, performing longitudinal studies from the beginning of pregnancy until postpartum is necessary. The need for preventive oral health counseling and dental care assistance during pregnancy is highlighted.

Objetivo: Realizar una revisión sistemática de la literatura científica sobre el impacto de la salud oral en la calidad de vida de las embarazadas. Métodos: Se lleva a cabo una búsqueda sistemática y se seleccionaron 16 artículos específicos sobre el tema, siguiendo las directrices PRISMA. Resultados: La calidad de vida (CdV) en la embarazada está relacionado con la edad, número de embarazos, dolor, dificultad para comer y presencia de caries. La calidad de vida se relacionó directamente con la salud oral. Conclusiones: A través de esta revisión se encontró que la mayoría de los estudios que relacionaban la CdV y la salud oral durante la gestación fueron de corte observacional transversal, por ello para una mejor comprensión de estos impactos, es necesario realizar estudios longitudinales desde el comienzo del embarazo hasta el posparto. Se destaca la necesidad de asesoramiento de salud oral preventiva y una ruta de atención dental durante el embarazo.

HPV infection in Brazilian patients with esophageal squamous cell carcinoma: interpopulational differences, lack of correlation with surrogate markers and clinicopathological parameters.

The role of HPV in esophageal squamous cell carcinoma (ESCCs) is controversial. Therefore, we determined, through different methodologies, the prevalence of HPV in 264 ESCC samples from Brazil, and correlated it with the presence of surrogate markers and clinicopathological characteristics. HPV is present in 13% of ESCC, and with a 3-fold variation between high and medium incidence areas. Most HPV positive tumors were infected with HPV16, but this was not associated with p16 expression, TP53 mutation status, patient age, amount of tobacco or alcohol consumption, or overall survival. We conclude that HPV infection may not have a role in ESCC.

Evaluation of the heme oxygenase-1 expression in esophagitis and esophageal cancer induced by different reflux experimental models and diethylnitrosamine.

PURPOSE: To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis. METHODS: Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch. RESULTS: The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression. CONCLUSION: Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.

Evaluation of the heme oxygenase-1 expression in esophagitis and esophageal cancer induced by different reflux experimental models and diethylnitrosamine / Avaliação da expressão da Heme Oxigenase-1 em esofagite e câncer de esôfago induzidos por diferentes modelos experimentais de refluxo e diethilnitrosamina

PURPOSE: To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis. METHODS: Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch. RESULTS: The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression. CONCLUSION: Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.

OBJETIVO: Estudar a expressão da HO-1 (enzima induzida pelo estresse) em diferentes peças esofágicas obtidas de um estudo experimental em ratos que avaliou o papel do refluxo gastroesofágico e duodeno esofágico na carcinogênese experimental. MÉTODOS: Blocos de parafina contendo peças de esôfago provenientes de um estudo experimental com ratos foram utilizados para verificar a expressão imunohistoquímica da HO-1. Os ratos haviam sido divididos nos seguintes grupos: (1) Cardioplastia com o objetivo de promover refluxo ácido, (2) Anastomose esofagoduodenal para indução de refluxo misto (ácido e biliar), (3) sem tratamento (controles), (4) cardioplastia + dietil-nitrosamina (DEN), (5) Anastomose esofagoduodenal + DEN, (6) DEN. Amostras contendo três peças de cada grupo com as lesões histopatológicas mais graves encontradas em cada braço do estudo foram escolhidas para avaliação da expressão imunoistoquímica da HO-1. RESULTADOS: A expressão da HO-1 foi observada somente nas peças de esôfago de ratos submetidos à anastomose esofagoduodenal (Grupos 2 e 5) e analise da intensidade média da fluorescência demonstrou uma diferença significativa na expressão da HO-1 nesses grupos quando comparada com o grupo controle (4,8 e 4,6 vezes respectivamente) (p<0,05). As células inflamatórias localizadas dentro dos tumores e nas regiões adjacentes ao epitélio foram as que mais intensamente expressaram a HO-1. Ratos expostos ao refluxo ácido (gástrico) apresentaram pouca ou nenhuma atividade da HO-1. CONCLUSÃO: Esofagite de refluxo induzida pelo refluxo com conteúdo duodenal provocou considerável estresse oxidativo, que parece exercer um papel importante na carcinogênese esofágica. O refluxo puramente ácido não foi capaz de induzir estresse oxidativo nesse modelo experimental

Sporothrix schenckii isolated from domestic cats with and without sporotrichosis in Rio de Janeiro, Brazil.

A total of 148 cats with a clinical and mycologic diagnosis of sporotrichosis and 84 apparently healthy cats with domiciliary contact with the affected animals were studied. Sporothrix schenckii was isolated from 148 (n = 148; 100%) clinical samples of cutaneous lesion (biopsy, swab or aspiration of purulent secretion), 47 (n = 71; 66.2%) nasal cavities, 33 (n = 79; 41.8%) oral cavities, and 15 (n = 38; 39.5%) nails of cats with sporotrichosis. Histopathological examination revealed yeast-like structures in 50 (n = 70; 71.4%) of the biopsies studied. S. schenckii was isolated from the blood culture of one cat (n = 5, 20%) with the disseminated cutaneous form of the disease. On another occasion, the fungus was isolated from the testis of one (n = 7; 14.3%) of the animals submitted to sterilization. In the group of cats with domiciliary contacts, 3 (n = 84; 3.57%) oral swabs showed positive cultures. Isolation of S. schenckii from different clinical specimens during both the clinical and preclinical phase reinforces the zoonotic potential of feline sporotrichosis.

Sporotrichosis: an emergent zoonosis in Rio de Janeiro

During the period from 1987 to 1998, 13 cases of human sporotrichosis were recorded at the Research Center Evandro Chagas Hospital (CPqHEC) in Rio de Janeiro. Two of these patients related scratch by a sick cat. During the subsequent period from July 1998 to July 2000, 66 human, 117 cats and 7 dogs with sporotrichosis were diagnosed at the CPqHEC. Fifty-two humans (78.8 percent) reported contact with cats with sporotrichosis, and 31 (47 percent) of them reporting a history of a scratch or bite. This epidemic, unprecedented in the literature, involving cats, dogs and human beings may have started insidiously before 1998