Variaciones de las células de cuadrícula y de posicionamiento de la corteza entorrinal y del giro dentado de 6 humanos de 56 a 87 años / Variations of the grid and place cells in the entorhinal cortex and dentate gyrus of 6 individuals aged 56 to 87 years

Introducción: La relación entre la corteza entorrinal y el hipocampo ha sido estudiada por diferentes autores, que han destacado la importancia de las células de cuadrícula, las células de posicionamiento y la conexión trisináptica en los procesos que regulan: la persistencia de la memoria espacial, explícita y reciente, y su posible afección con el envejecimiento. Objetivo: Observar si existen diferencias en el tamaño y número de células de cuadrícula contenidas en la lámina iii de la corteza entorrinal y en la capa granular del giro dentado del hipocampo de pacientes mayores. Métodos: Realizamos estudios posmortem del cerebro de 6 sujetos de edades comprendidas entre los 56 y 87 años. Los cortes de cerebros que contenían el giro dentado del hipocampo y la corteza entorrinal adyacente se tiñeron con el método de Klüver-Barrera, después se midió, mediante el programa Image J, el área neuronal individual, el área neuronal total, así como el número de neuronas, contenidas en cuadrículas rectangulares a nivel de la lámina iii de la corteza entorrinal y la lámina ii del giro dentado y se llevó a cabo un análisis estadístico. Resultados: Se ha observado una reducción de la población celular de la capa piramidal externa de la corteza entorrinal, así como de las neuronas de la capa granular del giro dentado relacionada con el envejecimiento. Conclusión: Nuestros resultados indican que el envejecimiento produce una disminución en el tamaño y la densidad neuronal en las células de cuadrícula de la corteza entorrinal y de posicionamiento del giro dentado.(AU)

Introduction: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. Objective: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. Methods: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. Results: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. Conclusion: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus.(AU)

Capi-score: a quantitative algorithm for identifying disease patterns in nailfold videocapillaroscopy.

OBJECTIVES: The European Alliance of Associations for Rheumatology (EULAR) supports the use of nailfold videocapillaroscopy (NVC) to identify disease patterns (DPs) associated with systemic sclerosis (SSc) and Raynaud's phenomenon (RP). Recently, EULAR proposed an easy-to-manage procedure, a so-called Fast Track algorithm, to differentiate SSc from non-SSc patterns in NVC specimens. However, subjectivity among capillaroscopists remains a limitation. Our aim was to perform a software-based analysis of NVC peculiarities in a cohort of samples from SSc and RP patients and, subsequently, build a Fast Track-inspired algorithm to identify DPs without the constraint of interobserver variability. METHODS: NVCs were examined by 9 capillaroscopists. Those NVCs whose DPs were consensually agreed (≥2 out of 3 interobservers) were subsequently analysed with an in-house developed software. Each variable's results were grouped according to the consensually agreed DPs in order to identify useful hallmarks to categorise them. RESULTS: Eight-hundred and fifty-one NVCs (21 957 images) whose DPs had been consensually agreed were software-analysed. Appropriate cut-offs set in capillary density and percentage of abnormal and giant capillaries, tortuosities and hemorrhages allowed DP categorization and the development of the CAPI-Score algorithm. This consisted of 4 rules: Rule 1, SSc vs non-SSc, accuracy 0.88; Rules 2 and 3, SSc-early vs SSc-active vs SSc-late, accuracy 0.82; Rule 4, non-SSc normal vs non-SSc non-specific, accuracy 0.73. Accuracy improved when the analysis was limited to NVCs whose DPs had achieved full consensus among interobservers. CONCLUSIONS: The CAPI-Score algorithm may become a useful tool to assign DPs by overcoming the limitations of subjectivity.

Variations of the grid and place cells in the entorhinal cortex and dentate gyrus of 6 individuals aged 56 to 87 years.

INTRODUCTION: The relationship between the entorhinal cortex (EC) and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. OBJECTIVE: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the EC and in the granular layer of the dentate gyrus (DG) of the hippocampus. METHODS: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the DG and the adjacent EC were stained according to the Klüver-Barrera method, then the ImageJ software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the EC and layer II of the DG. Statistical analysis was subsequently performed. RESULTS: We observed an age-related reduction in the cell population of the external pyramidal layer of the EC, and in the number of neurons in the granular layer of the DG. CONCLUSION: Our results indicate that ageing causes a decrease in the size and density of grid cells of the EC and place cells of the DG.

Linfoma difuso de célulasB grandes primario de cérvix. A propósito de un caso / Primary diffuse large Bcell lymphoma of the cervix: Clinical case

Introducción: La afectación primaria del tracto genital femenino por linfoma no Hodgkin es muy poco frecuente, por lo que no existe un consenso sobre el tratamiento, y por ello presentamos este caso clínico y el tratamiento realizado, así como el pronóstico de nuestra paciente. Hallazgos clínicos: La paciente presentada es una mujer de 72años que consulta por hemorragia vaginal. Diagnóstico Se diagnostica de linfoma no Hodgkin extranodal primario de cérvix de inmunofenotipoB de alto grado citológico y elevado índice proliferativo. Intervenciones terapéuticas y resultados: El tratamiento de elección fue únicamente quimioterápico. Esta paciente ha presentado una supervivencia libre de enfermedad de 5años. Actualmente se encuentra en seguimiento mediante la realización de controles analíticos anuales. Conclusión: Los síntomas de este tipo de tumor son altamente inespecíficos y la citología es frecuentemente negativa, por lo que es necesario recurrir a la biopsia. La inmunohistoquímica resulta fundamental tanto para el diagnóstico como para el pronóstico. Existen múltiples técnicas de imagen empleadas tanto para estudio de extensión como para seguimiento, destacando el papel del FDG-PET. Actualmente parece que el tratamiento más recomendable es la pauta quimioterápica R-CHOP seguida de radioterapia. El pronóstico en general es bueno, con hasta un 80% de supervivencia a los 5años.(AU)

Introduction: Primary involvement of the female genital tract by non-Hodgkin lymphoma is very rare, so there is no consensus on treatment, and for this reason we present this clinical case and the treatment performed, as well as the prognosis of our patient. Clinical findings: The patient presented is a 72-year-old woman who consulted for vaginal bleeding. Diagnosis: Primary extranodal non-Hodgkin lymphoma of the cervix with immunophenotypeB of high cytological grade and high proliferative index was diagnosed. Therapeutic interventions and results: The treatment of choice was chemotherapy only. This patient has presented a disease-free survival of 5years. It is currently being monitored by carrying out annual analytical controls. Conclusion: The symptoms of this type of tumor are highly non-specific, as well as cytology is frequently negative, which is why it is necessary to resort to biopsy. Immunohistochemistry is essential for both diagnosis and prognosis. There are multiple imaging techniques used for both extension study and follow-up, highlighting the role of FDG-PET. It currently seems that the most recommendable treatment is the R-CHOP chemotherapy regimen followed by radiotherapy.The prognosis is generally good, with up to 80% survival at 5years.(AU)

Changes in the choroid plexuses and brain barriers associated with high blood pressure and ageing.

INTRODUCTION: The choroid plexuses, blood vessels, and brain barriers are closely related both in terms of morphology and function. Hypertension causes changes in cerebral blood flow and in small vessels and capillaries of the brain. This review studies the effects of high blood pressure (HBP) on the choroid plexuses and brain barriers. DEVELOPMENT: The choroid plexuses (ChP) are structures located in the cerebral ventricles, and are highly conserved both phylogenetically and ontogenetically. The ChPs develop during embryogenesis, forming a functional barrier during the first weeks of gestation. They are composed of highly vascularised epithelial tissue covered by microvilli, and their main function is cerebrospinal fluid (CSF) production. The central nervous system (CNS) is protected by the blood-brain barrier (BBB) and the blood-CSF barrier (BCSFB). While the BBB is formed by endothelial cells of the microvasculature of the CNS, the BCSFB is formed by epithelial cells of the choroid plexuses. Chronic hypertension induces vascular remodelling. This prevents hyperperfusion at HBPs, but increases the risk of ischaemia at low blood pressures. In normotensive individuals, in contrast, cerebral circulation is self-regulated, blood flow remains constant, and the integrity of the BBB is preserved. CONCLUSIONS: HBP induces changes in the choroid plexuses that affect the stroma, blood vessels, and CSF production. HBP also exacerbates age-related ChP dysfunction and causes alterations in the brain barriers, which are more marked in the BCSFB than in the BBB. Brain barrier damage may be determined by quantifying blood S-100ß and TTRm levels.

Variaciones de los plexos coroideos y las barreras cerebrales en la hipertensión arterial y el envejecimiento / Changes in the choroid plexuses and brain barriers associated with high blood pressure and ageing

Introducción: Los plexos coroideos, los vasos sanguíneos y las barreras cerebrales están íntimamente relacionados tanto morfológica como funcionalmente. Por otro lado, la hipertensión produce cambios en el flujo sanguíneo y en los pequeños vasos y capilares cerebrales. El propósito de la presente revisión es estudiar los efectos de la hipertensión arterial sobre los plexos coroideos y las barreras cerebrales. Desarrollo: Los plexos coroideos (PC) son una estructura del cerebro situada en los ventrículos cerebrales, altamente conservada filogenética y ontogénicamente. Los PC se desarrollan temprano durante la embriogénesis y constituyen una barrera funcional en las primeras semanas de gestación. Están compuestos por tejido epitelial altamente vascularizado, cubiertos por microvellosidades y su función principal es la producción del líquido cefalorraquídeo (LCR). El sistema nervioso central se encuentra aislado y protegido por la barrera hematoencefálica (BHE) y por la barrera sangre-LCR (BSLCR). Mientras que la BHE se localiza al nivel de las células endoteliales en la microvasculatura del encéfalo, la BSLCR está formada por las células epiteliales de los plexos coroideos. La hipertensión arterial crónica induce una remodelación vascular para adaptarse a los valores elevados de presión arterial, con lo que se evita el riesgo de hiperperfusión ante presiones elevadas, pero se incrementa el riesgo de isquemia a presiones bajas; en cambio, en las personas normotensas la circulación cerebral se autorregula y el flujo sanguíneo permanece constante y se mantiene la integridad de la BHE. [...] (AU)

Introduction: The choroid plexuses, blood vessels, and brain barriers are closely related both in terms of morphology and function. Hypertension causes changes in cerebral blood flow and in small vessels and capillaries of the brain. This review studies the effects of high blood pressure (HBP) on the choroid plexuses and brain barriers. Development: The choroid plexuses (ChP) are structures located in the cerebral ventricles, and are highly conserved both phylogenetically and ontogenetically. The ChPs develop during embryogenesis, forming a functional barrier during the first weeks of gestation. They are composed of highly vascularised epithelial tissue covered by microvilli, and their main function is cerebrospinal fluid (CSF) production. The central nervous system (CNS) is protected by the blood-brain barrier (BBB) and the blood–CSF barrier (BCSFB). While the BBB is formed by endothelial cells of the microvasculature of the CNS, the BCSFB is formed by epithelial cells of the choroid plexuses. Chronic hypertension induces vascular remodelling. This prevents hyperperfusion at HBPs, but increases the risk of ischaemia at low blood pressures. In normotensive individuals, in contrast, cerebral circulation is self-regulated, blood flow remains constant, and the integrity of the BBB is preserved. Conclusions: HBP induces changes in the choroid plexuses that affect the stroma, blood vessels, and CSF production. HBP also exacerbates age-related ChP dysfunction and causes alterations in the brain barriers, which are more marked in the BCSFB than in the BBB. Brain barrier damage may be determined by quantifying blood S-100β and TTRm levels. (AU)

Variations of the grid and place cells in the entorhinal cortex and dentate gyrus of 6 individuals aged 56 to 87 years. / Variaciones de las células de cuadrícula y de posicionamiento de la corteza entorrinal y del giro dentado de 6 humanos de 56 a 87 años.

INTRODUCTION: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. OBJECTIVE: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. METHODS: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. RESULTS: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. CONCLUSION: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus.

Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process.

Staphylococcus aureus is the most frequent aetiology of bone and joint infections (BJI) and can cause relapsing and chronic infections. One of the main factors involved in the chronicization of staphylococcal BJIs is the internalization of S. aureus into osteoblasts, the bone-forming cells. Previous studies have shown that S. aureus triggers an impairment of osteoblasts function that could contribute to bone loss. However, these studies focused mainly on the extracellular effects of S. aureus. Our study aimed at understanding the intracellular effects of S. aureus on the early osteoblast differentiation process. In our in vitro model of osteoblast lineage infection, we first observed that internalized S. aureus 8325-4 (a reference lab strain) significantly impacted RUNX2 and COL1A1 expression compared to its non-internalized counterpart 8325-4∆fnbAB (with deletion of fnbA and fnbB). Then, in a murine model of osteomyelitis, we reported no significant effect for S. aureus 8325-4 and 8325-4∆fnbAB on bone parameters at 7 days post-infection whereas S. aureus 8325-4 significantly decreased trabecular bone thickness at 14 days post-infection compared to 8325-4∆fnbAB. When challenged with two clinical isogenic strains isolated from initial and relapse phase of the same BJI, significant impairments of bone parameters were observed for both initial and relapse strain, without differences between the two strains. Finally, in our in vitro osteoblast infection model, both clinical strains impacted alkaline phosphatase activity whereas the expression of bone differentiation genes was significantly decreased only after infection with the relapse strain. Globally, we highlighted that S. aureus internalization into osteoblasts is responsible for an impairment of the early differentiation in vitro and that S. aureus impaired bone parameters in vivo in a strain-dependent manner.

Urinary tract infection as the main cause of admission in cystectomized patients. / La infección del tracto urinario como causa principal de ingreso en pacientes cistectomizados.

INTRODUCTION AND OBJECTIVES: Radical cystectomy with urinary diversion associated with extended pelvic lymphadenectomy continues to be the treatment of choice in muscle invasive bladder cancer. Sixty-four percent of patients submitted to this procedure present postoperative complications, with urinary infection being responsible in 20-40% of cases. The aim of this project is to assess the rate of urinary infection as a cause of re-admission after cystectomy, and to identify protective and predisposing factors for urinary infection in our environment. Finally, we will evaluate the outcomes after the establishment of a prophylactic antibiotic protocol after removal of ureteral catheters. MATERIAL AND METHODS: Retrospective descriptive study of cystectomized patients in the Urology Service of the Hospital Clínico Universitario of Zaragoza, from January 2012 to December 2018. A urinary tract infection (UTI) prevention protocol after catheter removal is established for all patients since October 2017. RESULTS: UTI is responsible for 54.7% of readmissions, with 55.1% of these being due to UTI after removal of ureteral catheters. Of the patients who received with prophylaxis, 9.5% presented UTIs after withdrawal, compared to 10.6% in the group of patients without prophylaxis. The patient who is re-admitted for UTI after withdrawal has a mean catheter time of 24.3±7.2 days, compared to 24.5±7.4 days for patients in the group without UTI (P=.847). CONCLUSIONS: The type of urinary diversion performed is not related to the rate of urinary infection. The regression model does not identify antibiotic prophylaxis, nor catheter time, as independent factors of UTI after catheter removal.

Changes in the choroid plexuses and brain barriers associated with high blood pressure and ageing. / Variaciones de los plexos coroideos y las barreras cerebrales en la hipertensión arterial y el envejecimiento.

INTRODUCTION: The choroid plexuses, blood vessels, and brain barriers are closely related both in terms of morphology and function. Hypertension causes changes in cerebral blood flow and in small vessels and capillaries of the brain. This review studies the effects of high blood pressure (HBP) on the choroid plexuses and brain barriers. DEVELOPMENT: The choroid plexuses (ChP) are structures located in the cerebral ventricles, and are highly conserved both phylogenetically and ontogenetically. The ChPs develop during embryogenesis, forming a functional barrier during the first weeks of gestation. They are composed of highly vascularised epithelial tissue covered by microvilli, and their main function is cerebrospinal fluid (CSF) production. The central nervous system (CNS) is protected by the blood-brain barrier (BBB) and the blood-CSF barrier (BCSFB). While the BBB is formed by endothelial cells of the microvasculature of the CNS, the BCSFB is formed by epithelial cells of the choroid plexuses. Chronic hypertension induces vascular remodelling. This prevents hyperperfusion at HBPs, but increases the risk of ischaemia at low blood pressures. In normotensive individuals, in contrast, cerebral circulation is self-regulated, blood flow remains constant, and the integrity of the BBB is preserved. CONCLUSIONS: HBP induces changes in the choroid plexuses that affect the stroma, blood vessels, and CSF production. HBP also exacerbates age-related ChP dysfunction and causes alterations in the brain barriers, which are more marked in the BCSFB than in the BBB. Brain barrier damage may be determined by quantifying blood S-100ß and TTRm levels.

Prognostic factors and outcomes for pediatric patients receiving an haploidentical relative allogeneic transplant using CD3/CD19-depleted grafts.

Haploidentical hematopoietic stem cell transplantation using T-cell-depleted grafts is a valid option for pediatric patients with hematological malignancies in need of an allogeneic transplantation and lacking an HLA-identical donor. Seventy-five transplantations were performed in 70 patients. Thirty-eight patients had ALL, 32 had AML, 3 had advanced myelodysplastic syndromes and 2 juvenile myelomonocytic leukemia; 19 were in first CR, 30 in second CR, 12 in greater than second CR and 14 were considered to be in refractory disease at time of transplantation. Four patients developed graft failure. Among engrafted patients, the median time to neutrophil and platelet recovery was 13 (range 8-20) and 10 days (range 8-70), respectively. In 64 (85%) cases, ⩾1 infections were diagnosed after transplant. The probability of nonrelapse mortality by day +100 after transplantation was 10±4%. With a median follow-up of 22 months, the probability of relapse was 32±6% and disease-free survival was 52±6%. Haploidentical transplantation using CD3/CD19 depletion is associated with encouraging results especially in patients in early phase of disease. Killer-cell Ig-like receptor B haplotype donors confer a rapid natural killer cells expansion early after transplantation, resulting in lower probability of relapse and suggesting a GvL effect apart from graft-versus-host reactions. Donor infusion of high numbers of CD34+ cells is recommended in order to improve T-cell reconstitution.

Global Consensus Recommendations on Prevention and Management of Nutritional Rickets

"BACKGROUND: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. EVIDENCE: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. PROCESS: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. RESULTS: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. CONCLUSION: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required."

Nefroangioesclerosis hipertensiva, a propósito de un caso con proteinuria en rango nefrótico, sin hipoalbuminemia ni edemas / Hypertensive nephroangiosclerosis, presentation of a case with nephrotic range proteinuria, with no hypoalbuminemia or edema

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Frinoderma asociado a derivación biliopancreática / Phrynoderma After Biliopancreatic Diversion

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Takayasu's arteritis associated with Crohn's disease

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[Models of intervention in children with autism]. / Modelos de intervención en niños con autismo.

INTRODUCTION: Autism spectrum disorders make up a group of neurodevelopmental disorders that globally affect different higher brain functions in the individual, such as intelligence, the capacity to use language and social interaction. Today, although there is still no curative treatment for autism, there are a number of non pharmacological interventions that can modify the poor prognosis that is generally associated to this type of disorders. AIM: To briefly review the different approaches to the neuro rehabilitation of patients suffering from autism spectrum disorders, which are usually known as methods of intervention. DEVELOPMENT: From the categorical point of view, three types of methods of intervention can be distinguished, depending on whether the orientation is psychodynamic, biomedical or psycho educational. It is difficult to compare the results of the different methods of intervention, but researchers have identified several common elements that they should have if they are to be effective. At present, the psycho educational methods are preferred, since they are the only ones that, to date, have proved to be effective in research studies. CONCLUSIONS: Early intervention by diagnostic and early care centres, with the use of mixed models of psycho educational intervention that nevertheless also include an important percentage of behavioural elements, has proved to be capable of modifying the course of patients with autism spectrum disorders and is currently the most suitable approach.