Semaphorin-3F/Neuropilin-2 Transcriptional Expression as a Predictive Biomarker of Occult Lymph Node Metastases in HNSCC

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), A Way to Build Europe; Asociación Española contra el Cáncer (LABAE18025AVIL).The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head and neck squamous cell carcinomas. We analyzed the transcriptional expression of SEMA3F and NRP2 in a cohort of 53 patients with cN0 squamous cell carcinoma treated with an elective neck dissection. Occult lymph node metastases were found in 37.7% of the patients. Patients with occult lymph node metastases (cN0/pN+) had significantly lower SEMA3F expression values than patients without lymph node involvement (cN0/pN0). Considering the expression of the SEMA3F-NRP2 genes, patients were classified into two groups according to the risk of occult nodal metastasis: Group 1 (n = 34), high SEMA3F/low NRP2 expression, with a low risk of occult nodal involvement (14.7% cN0/pN+); Group 2 (n = 19), low SEMA3F or high SEMA3F/high NRP2 expression, with a high risk of occult nodal involvement (78.9% cN0/pN+). Multivariate analysis showed that patients in Group 2 had a 26.2 higher risk of lymph node involvement than patients in Group 1. There was a significant relationship between the transcriptional expression values of the SEMA3F-NRP2 genes and the risk of occult nodal metastases

Semaphorin-3F/Neuropilin-2 Transcriptional Expression as a Predictive Biomarker of Occult Lymph Node Metastases in HNSCC.

The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head and neck squamous cell carcinomas. We analyzed the transcriptional expression of SEMA3F and NRP2 in a cohort of 53 patients with cN0 squamous cell carcinoma treated with an elective neck dissection. Occult lymph node metastases were found in 37.7% of the patients. Patients with occult lymph node metastases (cN0/pN+) had significantly lower SEMA3F expression values than patients without lymph node involvement (cN0/pN0). Considering the expression of the SEMA3F-NRP2 genes, patients were classified into two groups according to the risk of occult nodal metastasis: Group 1 (n = 34), high SEMA3F/low NRP2 expression, with a low risk of occult nodal involvement (14.7% cN0/pN+); Group 2 (n = 19), low SEMA3F or high SEMA3F/high NRP2 expression, with a high risk of occult nodal involvement (78.9% cN0/pN+). Multivariate analysis showed that patients in Group 2 had a 26.2 higher risk of lymph node involvement than patients in Group 1. There was a significant relationship between the transcriptional expression values of the SEMA3F-NRP2 genes and the risk of occult nodal metastases

Brain functional abnormality in drug naïve adolescents with borderline personality disorder during self- and other-reflection

A disturbed sense of identity is one of the major features of borderline personality disorder (BPD), which manifests early in the course of the disorder, and is potentially examinable using functional imaging during tasks involving self-reflection. Twenty-seven medication-naïve adolescent female patients with BPD, who had no psychiatric comorbidities, and 28 matched healthy female controls underwent fMRI while answering questions either about themselves or acquaintances. Control conditions consisted of answering questions involving factual knowledge and a low-level baseline (cross fixation). When self-reflection was compared to fact processing, BPD patients exhibited reduced activation in the right dorsolateral prefrontal cortex (DLPFC), as well as in the left parietal and calcarine cortex and the right precuneus. In contrast, other-reflection was associated with relatively lower activation in the medial frontal cortex in BPD patients, with further analysis revealing that this change reflected a failure of de-activation during the fact processing condition. There were no differences between the BPD patients and controls when self- and other-processing was examined against low-level baseline. This study provides evidence of reduced DLPFC activation during self-reflection in adolescent females with BPD, which may reflect diminished top-down cognitive control of this process, but not other-reflection in the disorder

A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection

Background: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. Methods: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiretroviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and a plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. Results: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (388 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (65 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.57 episodes per 100 person-years). Conclusions: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months

Structured Treatment Interruptions and Low Doses of IL-2 in Patients with Primary HIV Infection. Inflammatory, Virological and Immunological Outcomes

BACKGROUND: Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of interleukin-2 (IL-2) in treated PHI patients is unknown. METHODS: Twelve PHI patients with viral load (VL) 500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL 500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19). CONCLUSIONS: STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials

Practice patterns and clinical outcomes in acute appendicitis differ in the elderly patient

Background: Appendicitis is the most frequent global abdominal surgical emergency. An ageing population, who often exhibit atypical symptoms and delayed presentations, challenge conventional diagnostic and treatment paradigms. Objectives: This study aims to delineate disparities in presentation, management, and outcomes between elderly patients and younger adults suffering from acute appendicitis. Methods: This subgroup analysis forms part of ESTES SnapAppy, a time-bound multi-center prospective, observational cohort study. It includes patients aged 15 years and above who underwent laparoscopic appendectomy during a defined 90-day observational period across multiple centers. Statistical comparisons were performed using appropriate tests with significance set at p < 0.05. Results: The study cohort comprised 521 elderly patients (≥65 years) and 4,092 younger adults (18–64 years). Elderly patients presented later (mean duration of symptoms: 7.88 vs. 3.56 days; p < 0.001) and frequently required computed tomography (CT) scans for diagnosis (86.1% vs. 54.0%; p < 0.001). The incidence of complicated appendicitis was higher in the elderly (46.7% vs. 20.7%; p < 0.001). Delays in surgical intervention were notable in the elderly (85.0% operated within 24 h vs. 88.7%; p = 0.018), with longer operative times (71.1 vs. 60.3 min; p < 0.001). Postoperative complications were significantly higher in the elderly (27.9% vs. 12.9%; p < 0.001), including severe complications (6.9% vs. 2.4%; p < 0.001) and prolonged hospital stays (7.9 vs. 3.6 days; p < 0.001). Conclusions: Our findings highlight significant differences in the clinical course and outcomes of acute appendicitis in the elderly compared to younger patients, suggesting a need for age-adapted diagnostic pathways and treatment strategies to improve outcomes in this vulnerable population

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large‐scale studies. In response, we used cross‐sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to infer age‐related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta‐analysis and one‐way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to examine age‐related trajectories inferred from cross‐sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter‐individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age‐related morphometric patterns

Millores aerodinàmiques en trens de mercaderies

L’objectiu d’aquest projecte és definir millores aerodinàmiques fàcilment implantables en un tren de mercaderies per tal de facilitar el transport de mercaderies a Alta Velocitat. L’estudi principal del projecte s’ha realitzat mitjançant el software de simulació CFD COMSOL Multiphysics 4.1. En aquest s’han implementat models comuns de tren de mercaderies i de tren amb perfil aerodinàmic, i s’han realitzat simulacions a diferents velocitats (baixa, mitjana i alta) en un determinat volum de control invariable per als dos models. Les simulacions s’han realitzat amb models 2D i posteriorment amb models 3D, analitzant-ne el perfil de velocitats, de pressions, i d’energia cinètica turbulenta al voltant dels cossos. El model de ferrocarril de mercaderies utilitzat es basa en el transport de contenidors intermodals de 20 peus. Els resultats observats donen fe d’una menor resistència a l’avanç en trens aerodinàmicament preparats respecte a ferrocarrils amb formes amb excessius angles vius i excessives separacions entre els seus vagons. Així mateix es comprova l’avantatge que atorga la homogeneïtat en les formes del vehicle. Amb la realització d’aquest projecte es conclou que mitjançant l’implementació de les millores aerodinàmiques més bàsiques en models de ferrocarrils de mercaderies ajuda significativament a la millora en la velocitat del transport a igualtat de potència consumida. Aquest factor pot ser important per a l’increment d’usuaris del transport de mercaderies per ferrocarril, suposant això una millora pel que fa a emissions d’agents contaminants a l’atmosfera en comparació amb el transport mitjançant camions

Millores aerodinàmiques en trens de mercaderies

L’objectiu d’aquest projecte és definir millores aerodinàmiques fàcilment implantables en un tren de mercaderies per tal de facilitar el transport de mercaderies a Alta Velocitat. L’estudi principal del projecte s’ha realitzat mitjançant el software de simulació CFD COMSOL Multiphysics 4.1. En aquest s’han implementat models comuns de tren de mercaderies i de tren amb perfil aerodinàmic, i s’han realitzat simulacions a diferents velocitats (baixa, mitjana i alta) en un determinat volum de control invariable per als dos models. Les simulacions s’han realitzat amb models 2D i posteriorment amb models 3D, analitzant-ne el perfil de velocitats, de pressions, i d’energia cinètica turbulenta al voltant dels cossos. El model de ferrocarril de mercaderies utilitzat es basa en el transport de contenidors intermodals de 20 peus. Els resultats observats donen fe d’una menor resistència a l’avanç en trens aerodinàmicament preparats respecte a ferrocarrils amb formes amb excessius angles vius i excessives separacions entre els seus vagons. Així mateix es comprova l’avantatge que atorga la homogeneïtat en les formes del vehicle. Amb la realització d’aquest projecte es conclou que mitjançant l’implementació de les millores aerodinàmiques més bàsiques en models de ferrocarrils de mercaderies ajuda significativament a la millora en la velocitat del transport a igualtat de potència consumida. Aquest factor pot ser important per a l’increment d’usuaris del transport de mercaderies per ferrocarril, suposant això una millora pel que fa a emissions d’agents contaminants a l’atmosfera en comparació amb el transport mitjançant camions