Abstract
Objective
To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD).
Methods
Multicentre study of patients with BD-associated uveitis. Patients were ...refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects.
Results
We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively.
Conclusion
TCZ could be a therapeutic option in patients with BD and refractory uveitis.
The Physics of the Accelerating Universe (PAU) Survey goal is to obtain photometric redshifts (photo-z) and spectral energy distributions (SEDs) of astronomical objects with a resolution roughly one ...order of magnitude better than current broadband (BB) photometric surveys. To accomplish this, a new large field-of-view (FoV) camera (PAUCam) has been designed, built, and commissioned and is now operated at the William Herschel Telescope (WHT). With the current WHT prime focus corrector, the camera covers an ∼1° diameter FoV, of which only the inner ∼40′ diameter is unvignetted. The focal plane consists of a mosaic of 18 2k × 4k Hamamatsu fully depleted CCDs, with high quantum efficiency up to 1 m in wavelength. To maximize the detector coverage within the FoV, filters are placed in front of the CCDs inside the camera cryostat (made out of carbon fiber) using a challenging movable tray system. The camera uses a set of 40 narrowband filters ranging from ∼4500 to ∼8500 complemented with six standard BB filters, ugrizY. The PAU Survey aims to cover roughly 100 deg2 over fields with existing deep photometry and galaxy shapes to obtain accurate photometric redshifts for galaxies down to iAB ∼ 22.5, also detecting galaxies down to iAB ∼ 24 with less precision in redshift. With this data set, we will be able to measure intrinsic alignments and galaxy clustering and perform galaxy evolution studies in a new range of densities and redshifts. Here we describe the PAU camera, its first commissioning results, and its performance.
Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms ...of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrP.sup.C) into the pathogenic isoform (PrP.sup.Sc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infrequent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the first method that consistently induces spontaneous misfolding of recombinant PrP into bona fide prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fine-tuning the Protein Misfolding Shaking Amplification method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical influence of charged surfaces in this process. Keywords: Prion, Transmissible spongiform encephalopathies, Spontaneous misfolding, Strain
We report the case of a 67-year-old male with a history of arterial hypertension and atrial fibrillation, who was admitted for acute renal failure (creatinine: 4.41 mg/dl) and hypotension. He also ...presented hyponatremia (129 mmol/L) and hypokalemia (2.7 mmol/L). The patient referred profuse diarrhea during the previous two months as a possible triggering cause. Physical examination showed signs of dehydration and palpation of a polypoid mass in the rectal ampulla.
eTRANSAFE is a research project funded within the Innovative Medicines Initiative (IMI), which aims at developing integrated databases and computational tools (the eTRANSAFE ToxHub) that support the ...translational safety assessment of new drugs by using legacy data provided by the pharmaceutical companies that participate in the project. The project objectives include the development of databases containing preclinical and clinical data, computational systems for translational analysis including tools for data query, analysis and visualization, as well as computational models to explain and predict drug safety events.
This study examined the cognitive performance of older adults aged 60 and above using the Montreal Cognitive Assessment (MoCA) test and DigiMoCA, a digital tool for cognitive screening administered ...by means of a smart speaker, to investigate whether the additional variables utilised by DigiMoCA allow for the identification of significant differences between individuals with depressive symptoms and those with mild cognitive impairment, which are not detected using the original MoCA test. A total of 73 senior adults located in Northwestern Spain, 22 male and 51 female, participated in this study. Subjects were divided into four groups based on the presence of depressive symptoms and mild cognitive impairment, with the aim of analysing the results of each dimension of the MoCA and DigiMoCA tests and assessing the additional insights provided by the digital administration tool. The results indicate significant differences among groups. Individuals with depressive symptoms exhibited poorer performance in forward number span, attention, and clock drawing compared to healthy controls. Furthermore, individuals with depressive symptoms and mild cognitive impairment exhibited significantly worse memory and orientation compared to those with cognitive impairment alone. Correlations revealed that a greater severity of depressive symptoms was associated with poorer performance across cognitive domains, including visuospatial skills, attention, language, memory, and phonemic verbal fluency. This study also illustrated how the exploitation of additional variables systematically captured by digital instruments, such as completion times or response delays to individual interactions, may facilitate the early identification of cognitive and depressive conditions, providing initial evidence about the importance of integrating advanced digital tools in cognitive assessment to inspire the development of more effective, personalised interventions.
This study investigates memory performance among 73 adults over 60 years old, utilising Memory Impairment Screening (MIS) and self-reported memory failures assessed by the Memory Failures in Everyday ...questionnaire (MFE-28). Participants were divided into four groups: individuals with depressive symptoms, healthy individuals, individuals with depressive symptoms and mild cognitive impairment, and individuals with mild cognitive impairment only. Groups were organised according to their Montreal Cognitive Assessment (MoCA) and the 15-item Geriatric Depression Scale (GDS-15) scores. The study aims to analyse MIS scores and self-reported memory failures across these groups as measured with the 28-item Memory Failures Everyday (MFE-28) scale. Correlation analyses were conducted for the complete sample, while variance analyses were carried out for the four classification groups above. Bivariate linear regression analysis was carried out to explore how the combination of cognitive and depressive symptoms status influenced memory performance. Results show that subjective memory complaints and memory performance are related to depressive symptoms, and the latter is associated with worse cognitive performance. Lastly, our study highlights that individuals with mild cognitive impairment and depressive symptoms exhibit worse performance in recall tasks and report more subjective memory complaints compared to those with mild cognitive impairment alone.
This paper examines how Spanish green start-ups develop improved attitudes towards nature. Despite the prevalence of theories based on green entrepreneurs, very little research has been conducted on ...how green attributes influence nature in the framework of the new Spanish Criminal Code in what concerns corporate compliance. One hundred and fifty-two start-ups were interviewed in 2018. Smart PLS Path Modelling has been used to build an interaction model among variables. The results obtained have a significant theoretical and practical implication since they add new findings to the current literature on how start-ups incorporate the recent Criminal Code in their environmental decisions. The model reveals a strong predictive power (R-squared = 77.9%). There are grounds to say that start-ups should implement effective monitoring systems and new organisational standards, in addition to developing surveillance measures to avoid unexpected sanctions.
Upper gastrointestinal bleeding and Rigler triad Fernández-de la Varga, Margarita; Pérez Valle, Isabel; Ordieres Díaz, Carlos ...
Revista española de enfermedades digestivas,
05/2024, Letnik:
116, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Gallstone ileus is a rare complication of cholelithiasis, characterized by mechanical bowel obstruction due to a biliary calculus originating from a bilioenteric fistula. The Rigler triad, consisting ...of aerobilia, ectopic gallstone, and intestinal obstruction, is rarely observed in its complete form. We present the case of a 92-year-old male with a history of acute lithiasic cholecystitis who presented to the Emergency department with acute epigastric pain. Initial evaluation revealed gallbladder dilatation, gallstones, and gallbladder wall thickening suggestive of acute cholecystitis. During hospitalization, the patient experienced an episode of hematemesis, leading to the diagnosis of a cholecystoduodenal fistula and a large blood clot in the duodenal bulb. Further imaging showed an ectopic gallstone causing small bowel obstruction. The patient underwent urgent surgery for stone extraction, followed by endoscopic intervention for the bleeding vessel identified at a subsequent gastroscopy. Unfortunately, the patient had a poor postoperative course and passed away seven days later. This case report highlights the exceptional occurrence of both the Rigler triad and upper gastrointestinal bleeding in a patient with gallstone ileus. Surgical intervention is crucial for the initial resolution of intestinal obstruction, followed by cholecystectomy and repair of the bilioenteric fistula. Awareness of these rare presentations is important for timely diagnosis and appropriate management of this uncommon complication of cholelithiasis.
The purpose of this research is to improve the parameters of shear strength in granular volcanic soil, by adding a percentage of Portland type I cement. The first step for this research was to ...classify the soil through a Granulometry test, according to the Unified Soil Classification System (USCS), the result was considered as a poorly graded sand with gravel also considered by The American Association of State Highway and Transportation Officials (AASHTO) as “A-1-b”. In addition, the compaction curve of the volcanic soil has a Maximum Dry Density (MDD) of 1.21 kg/cm2 and an optimum moisture content of 17.8%. Also, the friction angle of 33.5° and a cohesion of 0 kg/cm2, and the results of the Direct Shear Test indicate the Residual Stresses of 0.63, 1.34 and 2.65 kg/cm2 according to the Normal Stresses 1, 2 and 4 kg/cm2, respectively. The second step was to apply a Modified Proctor Test as following: one sample for natural soil and four samples adding 3%, 5%, 7% and 9% of cement. Finally, applied the Direct Shear Test: one sample for natural soil and three samples adding 3%, 5%, and 7% of cement after 7 days of curing, then three more samples are taken adding 3, 5% and 7% of cement at 14 days of curing. The results of the Modified Proctor Test of the volcanic soil with the addition of 5% cement has a maximum peak of a Maximum Dry Density of 1.33 kg/cm2 and with an Optimal Moisture Content of 22.7%, improved the MDD by 10% in regard to the natural soil. And the results of the Direct Shear Test shown in each sample an increase from 14.6% to 79.1% in the friction angle in comparison with the natural soil from 25.8% to 161.5% in shear strength. Likewise, the behavior of the volumetric deformation is shown, presenting a greater contraction when a normal stress of 1 kg/cm2 is applied and a greater expansion when a normal stress of 4 kg/cm2 is applied. Also, the volcanic soil at 7 days of curing with 7% cement addition increases its resistance by 67.34% and the volumetric variation decreases by 50% and the volcanic soil at 14 days of curing with 5% addition of cement increases its resistance by 103.40% and the volumetric variation decreases by 25%.
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