Niemann–Pick type C (NP-C) is a rare neurodegenerative disorder. Management is mainly supportive and symptomatic. The investigational use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a ...promising role in treating NP-C, although efficacy and safety have not been established. We conducted searches of MEDLINE, Cochrane, EMBASE, and other databases of reported cases of HP-β-CD compassionate use in NP-C disease. Sixteen reported cases were eligible, including evaluable information of 17 patients. The median onset age of HP-β-CD was 14 years (range 2–49 years). Intrathecal route was employed in 16 patients, in 3 patients simultaneously to IV infusions. Intracerebroventricular route was used in two patients. An objective improvement of clinical outcomes was measured in 14 patients, mainly by the NIH NP-C Clinical Severity Score and brainstem auditory evoked potential. Besides, an increase in metabolism and activities of the brain were observed in image tests and cholesterol biomarkers. Most patients showed some clinical benefit or a stabilization of NP-C progression. There were 17 adverse events (AEs) reported in 11 patients, 11 of them related to the drug and 6 to the route of administration. Loss of hearing was reported in four patients. The most severe AE were fever and chemical meningitis. Results suggest that efficacy may be partial and dependent on the early administration of the drug, the severity of the disease, and interpersonal variability. HP-β-CD could help stabilize NP-C with low toxicity potential, although some AEs have been reported. Moreover, controlled clinical trials would be necessary to evaluate the role of HP-β-CD in NP-C.
Abstract Super-high density olive orchards may increase profitability for table olive producers. However, water needs and fruit damage could limit their viability. Deficit irrigation scheduling would ...reduce the amount of water required, but rehydration before harvest is extremely important. The aim of this work was to compare a typical deficit farm management model with a regulated deficit irrigation one based on the plant water status. The experiment was carried out during three seasons in a three years-old (4 × 1.5 m) commercial table olive orchard. In both irrigation scheduling plots, seasonal amount of applied water was similar. Irrigation treatments were: common farm management (CFM), an almost constant rate of irrigation, and Regulated deficit (RDI) based on midday shaded water potential. Vegetative measurements suggested that RDI increased the external surface of the hedge, and this was related with greater yield in this treatment. Significant differences were found in of fruit size at harvest in some seasons, with larger fruits in RDI compared to CFM. However, fruit damage occurred during mechanical harvest in both irrigation managements, despite the higher skin firmness in RDI, and shows the need to carry out postharvest treatments to improve the quality of the final product. Accurate control of the tree water status would allow optimizing the amount of water available for table olive orchards.
This paper presents a new methodology for measurement of the instantaneous average exhaust mass flow rate in reciprocating internal combustion engines to be used to determinate real driving emissions ...on light duty vehicles, as part of a Portable Emission Measurement System (PEMS). Firstly a flow meter, named MIVECO flow meter, was designed based on a Pitot tube adapted to exhaust gases which are characterized by moisture and particle content, rapid changes in flow rate and chemical composition, pulsating and reverse flow at very low engine speed. Then, an off-line methodology was developed to calculate the instantaneous average flow, considering the “square root error” phenomenon. The paper includes the theoretical fundamentals, the developed flow meter specifications, the calibration tests, the description of the proposed off-line methodology and the results of the validation test carried out in a chassis dynamometer, where the validity of the mass flow meter and the methodology developed are demonstrated.
•The paper presents a novel Pitot average mass flow meter, named MIVECO.•MIVECO is designed to determinate real driving emissions on light duty vehicles.•MIVECO includes a method for eliminating the 'square root error' in pulsating flow.•The paper includes design, calibration, validation, error and uncertainty analysis.
Both vedolizumab and ustekinumab are approved for the management of Crohn's disease CD. Data on which one would be the most beneficial option when anti-tumour necrosis factor anti-TNF agents fail are ...limited.
To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD.
CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index HBI. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors.
A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab vs ustekinumab was associated with a higher risk of treatment discontinuation (hazard ratio HR 2.55, 95% confidence interval CI: 2.02-3.21), adjusted by corticosteroids at baseline HR 1.27; 95% CI: 1.00-1.62, moderate-severe activity in HBI HR 1.79; 95% CI: 1.20-2.48, and high levels of C-reactive protein at baseline HR 1.06; 95% CI: 1.02-1.10. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them.
In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.
Con el objetivo de determinar la influencia de las pingüineras sobre la diversidad de la vegetación en la Isla Decepción, se estudió la composición de briófitas de un transecto de aproximadamente 2 ...km entre el Lago Irízar y la pingüinera (Pygoscelis antarcticus) de Punta La Descubierta. Fueron detectados un total de 39 carpetas de vegetación formadas principalmente por briófitos, distribuidas en tres sectores principales, aledaño al Lago Irízar, en Collado Vapor y en Punta La Descubierta. Los briófitos registrados corresponden a 15 especies de musgos y sólo 2 hepáticas, con 11 familias representadas. Se detectó que dos musgos, Sanionia uncinata y Politrychastrum alpinum, con 31 y 9 registros, dominaban las carpetas, con mayor abundancia y frecuencia. Además, se encontró un nuevo registro para la isla del musgo Bryum orbiculatifolium, el cual crece directamente asociado a la pingüinera. Además, se encontró que hay 5 especies de musgos comunes a los tres sectores, aunque otras 5 especies crecen solo en el sector de la pingüinera, diferenciándose esta comunidad de las otras dos. No se detectaron plantas vasculares en todo el sitio de estudio, por lo que se discute la posibilidad de que estos sitios se encuentran en estados de colonización temprana y donde su biota está marcada por la presencia de musgos pioneros que crecen alrededor de las pingüineras, influenciadas probablemente por el aporte de nutrientes del guano depositado.
Aim
Neurogenic lower urinary tract dysfunction (NLUTD) is very common in multiple sclerosis (MS) patients. Early diagnosis and treatment are crucial to avoid irreversible damage and improve quality ...of life. Our aim was to develop recommendations to improve NLUTD identification in MS patients, along with their referral and management.
Methods
A multidisciplinary group of 14 experts in the management of patients with MS and NLUTD (nine urologists, three neurologists, and two rehabilitators) was selected. A comprehensive review of the literature was undertaken and a set of recommendations was generated and submitted to a Delphi panel of 114 experts. Recommendations were presented according to the grade of agreement (GA).
Results
Early diagnosis in asymptomatic patients with risk factors for complications is recommended (GA 94%). Postvoid residual volume should be measured if changes in urinary symptoms (GA 87%), preferably ultrasound‐guided (GA 86%). Early referral to urologist is recommended if urinary incontinence (GA 91%), significant post‐void residual volume (94%), quality of life impairment (GA 98%) and recurrent urinary infections (GA 97%). The initial evaluation should include physical examination (GA 99%) and urodynamics including cystometry (GA 89%), pressure‐flow study (90%) and electromyography (GA 70%). The panel recommends multidisciplinary collaboration (GA 100%) with a rehabilitation specialist and trained nurses in the management of NLUTD (GA 99%).
Conclusions
Multidisciplinary management for patients with NLUTD due to MS is advised, including urologists, neurologists, rehabilitation, and nurses. Panel recommends early diagnosis with post‐void residual volume in symptomatic patients before referring to urologist and urodynamics when referred.
Although the emergence of multi-parametric magnetic resonance imaging (mpMRI) has had a profound impact on the diagnosis of prostate cancers (PCa), analyzing these images remains still complex even ...for experts. This paper proposes a fully automatic system based on Deep Learning that performs localization, segmentation and Gleason grade group (GGG) estimation of PCa lesions from prostate mpMRIs. It uses 490 mpMRIs for training/validation and 75 for testing from two different datasets: ProstateX and Valencian Oncology Institute Foundation. In the test set, it achieves an excellent lesion-level AUC/sensitivity/specificity for the GGGFormula: see text2 significance criterion of 0.96/1.00/0.79 for the ProstateX dataset, and 0.95/1.00/0.80 for the IVO dataset. At a patient level, the results are 0.87/1.00/0.375 in ProstateX, and 0.91/1.00/0.762 in IVO. Furthermore, on the online ProstateX grand challenge, the model obtained an AUC of 0.85 (0.87 when trained only on the ProstateX data, tying up with the original winner of the challenge). For expert comparison, IVO radiologist's PI-RADS 4 sensitivity/specificity were 0.88/0.56 at a lesion level, and 0.85/0.58 at a patient level. The full code for the ProstateX-trained model is openly available at https://github.com/OscarPellicer/prostate_lesion_detection . We hope that this will represent a landmark for future research to use, compare and improve upon.
Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn’s disease (CD). Both diseases show an uncontrolled intestinal immune response ...that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4β7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin β7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.
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