Deleterious Effect of NMDA Plus Kainate on the Inner Retinal Cells and Ganglion Cell Projection of the Mouse

Combined administration of N-Methyl-D-Aspartate (NMDA) and kainic acid (KA) on the inner retina was studied as a model of excitotoxicity. The right eye of C57BL6J mice was injected with 1 µL of PBS containing NMDA 30 mM and KA 10 mM. Only PBS was injected in the left eye. One week after intraocular injection, electroretinogram recordings and immunohistochemistry were performed on both eyes. Retinal ganglion cell (RGC) projections were studied by fluorescent-cholerotoxin anterograde labeling. A clear decrease of the retinal “b” wave amplitude, both in scotopic and photopic conditions, was observed in the eyes injected with NMDA/KA. No significant effect on the “a” wave amplitude was observed, indicating the preservation of photoreceptors. Immunocytochemical labeling showed no effects on the outer nuclear layer, but a significant thinning on the inner retinal layers, thus indicating that NMDA and KA induce a deleterious effect on bipolar, amacrine and ganglion cells. Anterograde tracing of the visual pathway after NMDA and KA injection showed the absence of RGC projections to the contralateral superior colliculus and lateral geniculate nucleus. We conclude that glutamate receptor agonists, NMDA and KA, induce a deleterious effect of the inner retina when injected together into the vitreous chamber.This research was funded by the Instituto de Salud Carlos III and co‐funded by the European Regional Development Fund (ERDF) within the “Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020” (grant numbers #RD16/0008/0016; #RD16/0008/0020; #FIS/PI 18‐00754)

Permutation entropy and irreversibility in gait kinematic time series from patients with mild cognitive decline and early alzheimer’s dementia

Gait is a basic cognitive purposeful action that has been shown to be altered in late stages of neurodegenerative dementias. Nevertheless, alterations are less clear in mild forms of dementia, and the potential use of gait analysis as a biomarker of initial cognitive decline has hitherto mostly been neglected. Herein, we report the results of a study of gait kinematic time series for two groups of patients (mild cognitive impairment and mild Alzheimer’s disease) and a group of matched control subjects. Two metrics based on permutation patterns are considered, respectively measuring the complexity and irreversibility of the time series. Results indicate that kinematic disorganisation is present in early phases of cognitive impairment; in addition, they depict a rich scenario, in which some joint movements display an increased complexity and irreversibility, while others a marked decrease. Beyond their potential use as biomarkers, complexity and irreversibility metrics can open a new door to the understanding of the role of the nervous system in gait, as well as its adaptation and compensatory mechanismsThis research was funded through the Premio del Ilustre Colegio Profesional de Fisioterapeutas de la Comunidad De Madrid, prize number ICPFM-IX-201

Clinical and Cytokine Profile in Patients with Early and Late Onset Meniere Disease

Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profiles in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early-onset MD (EOMD, <35 years old), and 39 with late-onset MD (LOMD, >50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL,1 and IL-1β were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1β were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p = 0.004) and a higher prevalence of migraine than LOMD (p = 0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3, and CXCL4 were different between patients with MD or migraine and controls.ISCIII and European Regional Funds (Grants PI17/01644 and PI20/01126)Andalusian Health Government (Grant PE-0356-2018).Andalusian Health Government (Grant PI-0027-2020)

Carcinoma de paladar blando. Descripción de una serie de casos

Introduction and objective: To describe clinical and anatomical features, and surgical treatment including several techniques of reconstructive surgery of soft palate carci-nomas. Description: We conducted a retrospective study with 5 patients. All of them were diagnosed and treated in our department during 2018 and 2019. Discussion: We present our results and make a review on soft palate tumors pointing out anatomical details and most employed reconstructive surgical techniques for soft palate carci-noma´s removal. Conclusions: The incidence of oropharyngeal carcinoma is increas-ing world-wide essentially due to increasing prevalence of human papillomavirus. Soft palate carcinomas are typically HPV negative. Initially, soft palate tumors are silent, and we should suspect them to avoid late diagnosis. Transoral surgery devel-opment has promoted surgical treatment in these tumors and allows better manage-ment and need for adjuvant therapy. Reconstruction is mandatory when resection is over 50% of the soft palate.Introducción y objetivo: Describir las características clínicas, anatómicas y el trata-miento quirúrgico, incluyendo las distintas opciones de reconstrucción de los tumo-res de paladar blando. Descripción: Estudio retrospectivo de 6 pacientes diagnosti-cados y tratados en el servicio de Otorrinolaringología del hospital San Pedro de Logroño entre los años 2018 y 2019. Discusión: Exponemos los resultados de nues-tros pacientes y realizamos una revisión de los tumores de orofaringe localizados en el paladar blando, los detalles anatómicos y técnicas quirúrgicas reconstructivas más utilizadas en el tratamiento quirúrgico de los tumores de paladar blando. Conclusio-nes: La prevalencia de los tumores de orofaringe ha aumentado en los últimos años a expensas de la infección por el virus del papiloma humano (VPH). Sin embargo, los carcinomas de paladar blando son mayoritariamente P16 negativos. Estos tumores son poco sintomáticos en fases iniciales y es necesario un alto índice de sospecha para evitar diagnósticos tardíos. El desarrollo de la cirugía transoral ha impulsado el tratamiento quirúrgico de los tumores de paladar blando y puede reducir la necesidad de tratamientos complementarios hasta en un 40% de los casos. La reconstrucción se hace necesaria en resecciones mayores del 50%

A Brucella melitensis H38¿wbkF rough mutant protects against Brucella ovis in rams

Brucella melitensis and Brucella ovis are gram-negative pathogens of sheep that cause severe economic losses and, although B. ovis is non-zoonotic, B. melitensis is the main cause of human brucellosis. B. melitensis carries a smooth (S) lipopolysaccharide (LPS) with an N-formyl-perosamine O-polysaccharide (O-PS) that is absent in the rough LPS of B. ovis. Their control and eradication require vaccination, but B. melitensis Rev 1, the only vaccine available, triggers anti-O-PS antibodies that interfere in the S-brucellae serodiagnosis. Since eradication and serological surveillance of the zoonotic species are priorities, Rev 1 is banned once B. melitensis is eradicated or where it never existed, hampering B. ovis control and eradication. To develop a B. ovis specific vaccine, we investigated three Brucella live vaccine candidates lacking N-formyl-perosamine O-PS: Bov::CAΔwadB (CO2-independent B. ovis with truncated LPS core oligosaccharide); Rev1::wbdRΔwbkC (carrying N-acetylated O-PS); and H38ΔwbkF (B. melitensis rough mutant with intact LPS core). After confirming their attenuation and protection against B. ovis in mice, were tested in rams for efficacy. H38ΔwbkF yielded similar protection to Rev 1 against B. ovis but Bov::CAΔwadB and Rev1::wbdRΔwbkC conferred no or poor protection, respectively. All H38ΔwbkF vaccinated rams developed a protracted antibody response in ELISA and immunoprecipitation B. ovis diagnostic tests. In contrast, all remained negative in Rose Bengal and complement fixation tests used routinely for B. melitensis diagnosis, though some became positive in S-LPS ELISA owing to LPS core epitope reactivity. Thus, H38ΔwbkF is an interesting candidate for the immunoprophylaxis of B. ovis in B. melitensis-free areas

Multidimensional Scale of Perceived Social Support (MSPSS) in cancer patients: psychometric properties and measurement invariance

Background: The aim of this study was to evaluate the psychometric properties, convergent validity, and factorial invariance of the Multidimensional Scale of Perceived Social Support (MSPSS) in cancer patients. Method: Confi rmatory factor analysis (CFA) was conducted to explore the scale's dimensionality and test for strong measurement invariance across sex and age in a cross-sectional, multicenter, prospective study. Patients completed the MSPSS and Satisfaction with Life Scale (SWLS). Results: A total of 925 consecutive patients were recruited in 13 hospitals between July 2015 and December 2018. The CFA indicated that the original three factor model was replicated in patients with cancer. The results of the multi-group CFA revealed a strong invariance according to sex and age. The Spanish version of the MSPSS had high estimated reliability with values exceeding .90. The simple sum of the items of each scale was a good indicator of oncology patients' perceived social support. The three MSPSS subscales correlated signifi cantly with the SWLS. Women scored higher on social support by friends than men. Conclusion: The Spanish version of the MSPSS proved to be a valid, reliable instrument to assess perceived social support in cancer patients

Psychometric Properties of the PDRQ-9 in Cancer Patients: Patient-Doctor Relationship Questionnaire

Background: The patient-doctor relationship is an important concept in health care. The aim of this study was to evaluate the psychometric properties, convergent validity, and factorial invariance of the Patient Doctor Relationship Questionnaire (PDRQ-9). Method: Confirmatory factor analysis was conducted to explore the scale's dimensionality and test for strong measurement invariance across sex, age, and tumor site in a prospective, multicenter cohort of 560 patients who completed the PDRQ-9, Health-related Quality of Life Questionnaire (EORTC-QLQC30), and Brief Symptom Inventory (BSI) scales. Results: The data supported a unidimensional structure. Thresholds and factor loadings could be constrained to be invariant across sex, age, and tumor site, indicating strong measurement invariance. Scores derived from the unidimensional structure exhibited satisfactory degrees of reliability and determinacy. Evidence of convergent validity was supported by modest positive correlations with functional (p<.001) and global quality-of-life (p<.001) and negative correlations with psychological distress (p<.001). Low satisfaction with the oncologist was associated with anxiety (p=.006), and depression (p=.004). Conclusions: The PDRQ-9 is a suitable, valid instrument for assessing the quality of patient-doctor relationships in cancer patients

A Brucella melitensis H38ΔwbkF rough mutant protects against Brucella ovis in rams

Brucella melitensis and Brucella ovis are gram-negative pathogens of sheep that cause severe economic losses and, although B. ovis is non-zoonotic, B. melitensis is the main cause of human brucellosis. B. melitensis carries a smooth (S) lipopolysaccharide (LPS) with an N-formyl-perosamine O-polysaccharide (O-PS) that is absent in the rough LPS of B. ovis. Their control and eradication require vaccination, but B. melitensis Rev 1, the only vaccine available, triggers anti-O-PS antibodies that interfere in the S-brucellae serodiagnosis. Since eradication and serological surveillance of the zoonotic species are priorities, Rev 1 is banned once B. melitensis is eradicated or where it never existed, hampering B. ovis control and eradication. To develop a B. ovis specific vaccine, we investigated three Brucella live vaccine candidates lacking N-formyl-perosamine O-PS: Bov::CAΔwadB (CO2-independent B. ovis with truncated LPS core oligosaccharide); Rev1::wbdRΔwbkC (carrying N-acetylated O-PS); and H38ΔwbkF (B. melitensis rough mutant with intact LPS core). After confirming their attenuation and protection against B. ovis in mice, were tested in rams for efficacy. H38ΔwbkF yielded similar protection to Rev 1 against B. ovis but Bov::CAΔwadB and Rev1::wbdRΔwbkC conferred no or poor protection, respectively. All H38ΔwbkF vaccinated rams developed a protracted antibody response in ELISA and immunoprecipitation B. ovis diagnostic tests. In contrast, all remained negative in Rose Bengal and complement fixation tests used routinely for B. melitensis diagnosis, though some became positive in S-LPS ELISA owing to LPS core epitope reactivity. Thus, H38ΔwbkF is an interesting candidate for the immunoprophylaxis of B. ovis in B. melitensis-free areas.Publishe

Transferrin Isoforms, Old but New Biomarkers in Hereditary Fructose Intolerance

Hereditary Fructose Intolerance (HFI) is an autosomal recessive inborn error of metabolism characterised by the deficiency of the hepatic enzyme aldolase B. Its treatment consists in adopting a fructose-, sucrose-, and sorbitol (FSS)-restrictive diet for life. Untreated HFI patients present an abnormal transferrin (Tf) glycosylation pattern due to the inhibition of mannose-6-phosphate isomerase by fructose-1-phosphate. Hence, elevated serum carbohydrate-deficient Tf (CDT) may allow the prompt detection of HFI. The CDT values improve when an FSS-restrictive diet is followed; however, previous data on CDT and fructose intake correlation are inconsistent. Therefore, we examined the complete serum sialoTf profile and correlated it with FSS dietary intake and with hepatic parameters in a cohort of paediatric and adult fructosemic patients. To do so, the profiles of serum sialoTf from genetically diagnosed HFI patients on an FSS-restricted diet (n = 37) and their age-, sex- and body mass index-paired controls (n = 32) were analysed by capillary zone electrophoresis. We found that in HFI patients, asialoTf correlated with dietary intake of sucrose (R = 0.575, p < 0.001) and FSS (R = 0.475, p = 0.008), and that pentasialoTf+hexasialoTf negatively correlated with dietary intake of fructose (R = −0.386, p = 0.024) and FSS (R = −0.400, p = 0.019). In addition, the tetrasialoTf/disialoTf ratio truthfully differentiated treated HFI patients from healthy controls, with an area under the ROC curve (AUROC) of 0.97, 92% sensitivity, 94% specificity and 93% accuracy.This work was supported by Exp. No. 2018111095, Basque Government, Health Department to J.D.H., and by FEDER; Federación Española de Enfermedades Raras (FI18053)

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p 0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.Depto. de MedicinaFac. de MedicinaTRUEInstituto de Salud Carlos IIIFundación CRIS Contra el CáncerInstituto de Investigación Hospital 12 de OctubreUnión Europeapu