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.

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.

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.

[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.

Cycles triggered with GnRH agonist: exploring low-dose HCG for luteal support.

The aim of this study in patients at risk of ovarian hyperstimulation syndrome (OHSS) was to determine the efficacy and safety of luteal support using human chorionic gonadotrophin (HCG) after triggering ovulation with gonadotrophin-releasing hormone (GnRH) agonist in IVF/intracytoplasmic sperm injection antagonist cycles. A total of 192 OHSS-risk patients, following a GnRH antagonist protocol (0.25mg/day cetrorelix) during recombinant FSH stimulation, were triggered with 1.5mg s.c. leuproreline for ovulation. A total of three boluses of HCG were used for luteal support, 1000IU (group A, n=44), 500IU (group B, n=115) or 250IU (group C, n=33) every third day, starting the day after oocyte retrieval. For the reproductive outcome, main variables were biochemical and clinical pregnancy rates, and for OHSS, the variables were the numbers of moderate and severe OHSS cases. Overall pregnancy rate was 51.8% and clinical pregnancy rate was 43.4%. This study observed eight cases of moderate (4.2%) and seven of severe OHSS (3.6%). Six out of the seven (85.7%) severe cases were late-onset OHSS, related to pregnancy. In conclusion, GnRH agonist single dose for triggering ovulation and low doses of HCG used as luteal-phase support seem to secure a normal pregnancy outcome without increasing the OHSS risk.

[The advantages of neuropsychological examination batteries in attention deficit hyperactivity disorder]. / Ventajas de las baterías de exploración neuropsicológica en el trastorno por déficit de atención/hiperactividad.

INTRODUCTION: The neuropsychological assessment of the functions of attention and the executive functions in patients with clinical features compatible with a diagnosis of attention deficit hyperactivity disorder (ADHD) is considered a priority study to be able to offer a basic study. It is also necessary to be able to carry out a short- and long-term developmental follow-up of patients. DEVELOPMENT: An algorithm for diagnosing ADHD is proposed that includes both traditional and computerised tests for assessing the functions of attention and the executive functions. The development of new neuropsychological batteries for this purpose involves the use of several tests in computerised form that offer technical and methodological advantages as regards their use and the later treatment of the data obtained. CONCLUSIONS: The advantages of computerised assessment include management of answer times, minimum expression of the effect exerted by the researcher, savings in time, accurate and fast scoring, statistical management of new scores, and greater proximity to research programmes.

Effect of atorvastatin on bone mineral density in patients with acute coronary syndrome.

OBJECTIVE: The aim of this paper is to evaluate the effect of atorvastatin on bone mineral density in patients with acute ischemic heart disease. MATERIAL AND METHODS: Eighty-three patients (52 male and 31 female) with acute coronary syndrome were studied. They received treatment with atorvastatin using low doses (20 mg) and high doses (40 mg-80 mg). Initial and final cholesterol, triglyceride, calcium, phosphorus, 25-hydroxyvitamin D were obtained from every patient. Spine and hip bone mineral density were performed at the beginning and one year later. RESULTS: Atorvastatin treatment increases vitamin D (33%, p = 0.007) and decreases the individuals with vitamin D insufficiency. Bone mineral density increased in the spine (1.31%, p = 0.02), but it was significant only in male and patients presenting vitamin D levels higher than 30 nmol/l. CONCLUSION: Atorvastatin has a beneficial effect on bone metabolism in patients with acute ischemic heart disease (mainly males) by incrementing bone mineral density in which vitamin D levels are required to be higher than 30 nmol/l for the drug to be effective.

Carcinoma urotelial micropapilar de vejiga: reporte de un caso y revisión de la literatura / Micropapillary urothelial carcinoma of the bladder: a case report and literature review

El carcinoma urotelial micropapilar (CMP) de vejiga es una variante anatomopatológica infrecuente, de comportamiento agresivo. Se presenta habitualmente como carcinoma de alto grado, en estadios avanzados, sin signos clínicos distintos al del carcinoma vesical convencional. El tratamiento debe ser precoz y agresivo, fundamentalmente quirúrgico, dado que la radioterapia y la quimioterapia no han demostrado utilidad hasta el momento. Es necesario el reconocimiento de esta entidad pues su capacidad metástasica está asociada a una alta incidencia de mortalidad. Presentamos el caso de un varón de 64 años con hematuria de larga evolución diagnosticado de carcinoma micropapilar infiltrante de vejiga con compromiso de uréter.

Micropapillary urothelial carcinoma (MCP) of the urinary bladder is an rare anatomopathology variant aggressive behaviour. It is usually found as a high grade and stage carcinoma, and doesn't differ clinically from normal cell carcinoma of the bladder. Treatment should be early and aggressive, because radiotherapy and chemotherapy have shown limited results the therapy is surgically based. The diagnosis of this disease is required because its metastasic capacity is associate with a significantly increased mortality risk. In this study we report de case of a 64 years old man with a long development hematuria diagnosed of Micropapillary carcinoma infiltrating the bladder involving the ureter.

Normal and hyperspherical mode analysis of NO-doped Kr crystals upon Rydberg excitation of the impurity.

Molecular dynamics simulations and both normal mode and hyperspherical mode analyses of NO-doped Kr solid are carried out in order to get insights into the structural relaxation of the medium upon electronic excitation of the NO molecule. A combined study is reported on the time evolution of the cage radius and on the density of vibrational states, according to the hyperspherical and normal mode analyses. For the hyperspherical modes, hyper-radial and grand angular contributions are considered. For the normal modes, radial and tangential contributions are examined. Results show that the first shell radius dynamics is driven by modes with frequencies at approximately 47 and approximately 15 cm-1. The first one is related to the ultrafast regime where a large part of the energy is transmitted to the lattice and the second one to relaxation and slow redistribution of the energy. The density of vibrational states gamma(omega) is characterized by a broad distribution of bands peaking around the frequencies of approximately 13, approximately 19, approximately 25, approximately 31, approximately 37, approximately 47, and approximately 103 cm-1 (very small band). The dominant modes in the relaxation process were at 14.89, 23.49, and 53.78 cm-1; they present the largest amplitudes and the greatest energy contributions. The mode at 14.89 cm-1 is present in both the fit of the first shell radius and in the hyper-radial kinetic energy spectrum and resulted the one with the largest amplitude, although could not be revealed by the total kinetic energy power spectrum.

Tamoxifen and endometrial cancer. Is screening necessary? A review of the literature.

Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti-oestrogenic activity in the breast and oestrogenic effects in various tissues such as the endometrium, bone and cardiovascular territory. As adjuvant hormone therapy, it has a clear beneficial effect in patients with breast cancer, reducing relapses, contralateral breast cancer and mortality. Its most important secondary effect is a greater rate of occurrence of endometrial cancer. Although the risk/benefit ratio is clearly positive, the follow-up on these patients is still an issue. In women with metrorrhagia, it is clear that an endometrial sample must be obtained for histological examination and the best procedure today is hysteroscopic-directed biopsy. Nevertheless, the need to screen asymptomatic patients is not universally accepted. The vaginal ultrasound scan gives a great number of false positives. This entails more aggressive and more expensive procedures such as hysteroscopic-directed biopsy, meaning greater expense and more complications. As a result, the cost/benefit ratio is not very favourable. The rate of occurrence of endometrial cancer in 1026 tamoxifen-treated patients with breast cancer in our hospital between 1999 and 2001 was 1.25%. Two cases were diagnosed in asymptomatic patients. In this article, we analyse the literature on the need to screen patients on tamoxifen and about the most appropriate diagnostic protocol.

Liver enzymes elevation after HAART in HIV-HCV co-infection.

Hepatitis C virus (HCV) co-infection is common among human immunodeficiency virus (HIV) patients. The incidence and risk factors associated with hepatotoxicity in this population after high active antiretroviral therapy (HAART) is initiated are still not well-understood. We argued to evaluate the incidence and risk factors associated with liver enzyme elevation (LEE) and their clinical significance. A retrospective chart review of patients who started HAART and had follow up at our centre for at least 1 year was undertaken. The frequency and severity of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation after treatment initiation were investigated and searched for clinical manifestations. Between January 1996 and March 2002, 85 HIV-HCV co-infected patients began HAART and continued follow up for at least 1 year. The incidence of severe toxicity [grades 3 + 4 LEE: >5 and >10 times the upper limit of normal (ULN) of ALT or AST] was calculated at 4% per person-years. There were no clinical manifestations of liver toxicity, and patients continued their treatment with a trend towards a decrease of their enzymes. No statistical differences in opportunistic infections or mortality were evident. The variables associated with severe hepatotoxicity were a higher baseline AST, higher international normalized ratio (INR) and lower albumin. A baseline AST < 2.1 ULN had a negative predictive value of 92% of leading to severe hepatotoxicity. In HIV-HCV co-infected patients therefore, the group at a higher risk of developing higher transaminase elevations is the one with a higher baseline AST, higher INR and lower albumin.

Symmetrical fetal growth retardation after gestational cocaine exposure in the rat.

Cocaine use during pregnancy results in an increase in different maternal and perinatal complications. The fetal effects of cocaine could be mainly related to the disturbances in the brain development, microcephaly being the most common brain abnormality. The aim of this study was to analyze maternal outcome and fetal somatic effects of cocaine and to evaluate the hypothesis that maternal cocaine exposure would specifically impair fetal global brain development. Fifty-four timed-pregnant female Sprague-Dawley rats were daily injected with 15 or 40 mg/kg per day from gestational day (GD) 1 or 8 and sacrificed at gestational day 20. By analyzing different maternal and fetal outcomes, it could be suggested that the cocaine exposure in pregnant rats decreased maternal weight gain without significant maternal mortality, did not affect the mean number of fetuses by litter, although notably increased stillbirths, reduced fetal birth weight, and reduced the fetal central nervous system weight. Present results are globally in agreement with the literature and underline a possible selective effect of cocaine on the fetal CNS resulting in symmetrical intrauterine fetal growth retardation in contrast to the asymmetrical retardation of undernutrition.