Because limited data currently support the clinical utility of peripherally expressed biomarkers in guiding treatment decisions for patients with rheumatoid arthritis, the search has turned to the ...disease tissue. The strategic aim of the Outcome Measures in Rheumatology (OMERACT) synovitis working group over the years has been to develop novel diagnostic and prognostic synovial biomarkers. A critical step in this process is to refine and validate minimally invasive, technically simple, robust techniques to sample synovial tissue, for use both in clinical trials and routine clinical practice. The objective of the synovitis working group (SWG) at OMERACT 12 (2014) was to examine whether recently developed ultrasound (US)-guided synovial biopsy techniques could be validated according to the OMERACT filter for future clinical use recommendation.
The SWG examined whether current data reporting US-guided synovial biopsy of both large and small joints addressed the OMERACT filters of truth, discrimination, and feasibility.
There are currently limited data examining the performance of US-guided synovial biopsy, mainly from observational studies. Thus, it remains critical to evaluate its performance, within the clinical trials context, against the current gold standard of arthroscopic biopsy, with particular reference to: (1) synovial tissue yield, (2) capacity to determine treatment response as measured by a validated synovial biomarker, and (3) tolerability of the procedure.
We summarize the discrete work packages agreed to as requirements to validate US-guided synovial biopsy and therefore lead to a global consensus on the use of synovial biopsy for research and clinical practice.
The present study assessed the transitioning process of young adults with type 1 diabetes mellitus (T1D) in Italy.
We asked Pediatric Diabetes Centers (PDC) and Adult Diabetes Centers (CAD) to fill ...in a web-based survey on the current state of services, the number of transitioning adolescents with T1D within the last year, observations on limitations, and future directions.
93 centers (46 PDCs, 47 CADs) joined the study. The total number of subjects with T1D being followed by a PDC was 16,261 (13,779 minors and 2483 young adults), while CADs had 25,500 patients. The survey showed an uneven situation. Only some services had a dedicated diabetes team (78% of PDCs, 64% of CADs). 72% of PDCs and 58% of CADs reported a protocol dedicated to transition. The median age for transition was 19 (range 16-25 years); the time required for preparing transition, indicated by both PDCs and CADs, was 5.5 months. A high percentage of CADs (80%) confirmed receiving sufficient clinical information, mainly through paper or computerized reports. The transition process is hampered by a lack of resources, logistical facilities, and communication between services. While some services have a protocol, monitoring of results is only carried out in a few cases. Most specialists expressed the need to enhance integration and continuity of treatment.
The current situation could be improved. Applying standard guidelines, taking into consideration both clinicians' and patients' necessities, would lead to a more successful transition process.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective To assess visual function in low-risk preterm infants at 3, 5, and 12 months corrected age to determine whether the maturation of visual function in the first year is similar to that ...reported in term-born infants. Study design Seventy-five low-risk infants (25.0-30.9 weeks gestation) underwent ophthalmological examinations and a battery of tests (fix and follow, visual fields, acuity, attention at distance, and fixation shift) designed to assess various aspects of visual function at 3, 5, and 12 months corrected age. Results The results were comparable with normative data from term-born infants in all tests but fixation shift, suggesting that maturation of most aspects of visual function is not significantly affected by preterm birth. In contrast, >25% of preterm infants failed the fixation shift test at 3 months, with a higher percentage of failing at 5 and 12 months. Conclusions There is a specific profile of early visual behavior in low-risk preterm infants, with a high percentage of infants failing a test that specifically assesses visual attention and provides a measure of cortical processing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In the isolated population of Sardinia, a Mediterranean island, ∼25% of ALS cases carry either a p.A382T mutation of the TARDBP gene or a GGGGCC hexanucleotide repeat expansion in the first intron of ...the C9ORF72 gene.
To describe the co-presence of two genetic mutations in two Sardinian ALS patients.
We identified two index ALS cases carrying both the p.A382T missense mutation of TARDBP gene and the hexanucleotide repeat expansion of C9ORF72 gene.
The index case of Family A had bulbar ALS and frontemporal dementia (FTD) at 43. His father, who carried the hexanucleotide repeat expansion of C9ORF72 gene, had spinal ALS and FTD at 64 and his mother, who carried the TARDBP gene p.A382T missense mutation, had spinal ALS and FTD at 69. The index case of Family B developed spinal ALS without FTD at 35 and had a rapid course to respiratory failure. His parents are healthy at 62 and 63. The two patients share the known founder risk haplotypes across both the C9ORF72 9p21 locus and the TARDBP 1p36.22 locus.
Our data show that in rare neurodegenerative causing genes can co-exist within the same individuals and are associated with a more severe disease course.
Imaging of Scar in Patients with RV Origin Arrhythmias: CMR Versus EAM. Introduction: Assessment of late gadolinium enhancement (LGE) at cardiac magnetic resonance is often used to detect scar in ...patients with arrhythmias of right ventricular (RV) origin. Recently, electroanatomic mapping (EAM) has been shown to reliably detect scars corresponding to different cardiomyopathic substrates. We compared LGE with EAM for the detection of scar in patients with arrhythmias of RV origin.
Methods and Results: Thirty‐one patients with RV arrhythmias and biopsy‐proven structural heart disease (18 ARVC and 13 myocarditis), and 5 with idiopathic RV outflow tract arrhythmias underwent LGE analysis and EAM with scar validation through EAM‐guided endomyocardial biopsy. EAM scars were present in 23 (64%) patients (all with structural heart disease), whereas LGE was present only in 12 (33%). In 2 cases, EAM provided a false‐positive diagnosis of a small scar in the basal perivalvular area. LGE correctly diagnosed EAM scar in 48% of patients, resulting in high positive (92%) but low negative (50%) predictive values. The distribution of LGE was significantly associated with the distribution of EAM scars (P < 0.001 in the free wall, P = 0.003 in the outflow tract, and P = 0.023 in the posterior/inferior wall). Presence of LGE reflected a higher extension of EAM scars (34.4 ± 16.5% vs 7.9 ± 10.1% of the RV area, P < 0.001). At receiver operating characteristic (ROC) analysis, an extension of scar ≥20% of the RV area was the best cut‐off value to detect LGE (sensitivity 83%, specificity 92%). Of note, LGE missed 10 of 11 (91%) patients with EAM scars <20% of RV area.
Conclusions: LGE is significantly less sensitive than EAM in identifying RV cardiomyopathic substrates. Absence of LGE does not rule out the presence of small scars, and EAM with biopsy should be considered to increase the diagnostic yield. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1359‐1366, December 2011)
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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The binding mode of a series of competitive PARP-1 inhibitors was investigated employing a molecular docking approach by using Autodock 3.0. A particular attention was given to the ...role played by a water molecule present in some but not all the so far available crystal structures of the catalytic domain of PARP-1. Good correlation between calculated binding energies and experimental inhibitory activities was obtained either by including (
r
2
=
0.87) or not (
r
2
=
0.84) the structural water molecule. Closer inspection of our results suggested that this water molecule should be considered part of the hydration shell of polar inhibitors and not as a structural water.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We have recently described the synthesis and antifungal activity of a series of 1,4-benzothiazine and 1,4-benzoxazine imidazole derivatives that mainly showed in vivo activity against a murine ...experimental model of candidiasis but that very often lacked in vitro activity. Here, we report a docking study of a representative set of our molecules in a 3D model of CYP51 of
Candida albicans (CA-CYP51). The model was constructed on the basis of the sequence homology relationship with the recently reported crystal structure of the CYP51 of
Mycobacterium tuberculosis (MT- CYP51).
We report a docking study of a representative set of 1,4-benzothiazine and 1,4-benzoxazine imidazole derivatives in a 3D model of CYP51 of
Candida albicans (CA-CYP51).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We describe the application of full-wave and semi-analytical numerical tools for the modeling of optical wire antennas, with the aim of providing novel guidelines for analysis and design. The concept ...of antenna impedance at optical frequencies is reviewed by means of finite-element simulations, whereas a surface-impedance integral equation is derived in order to perform an accurate and efficient calculation of the current distribution, and thereby to determine the equivalent-circuit parameters. These are introduced into simple circuits models, directly borrowed from radio frequency, which are applied in order to model the phenomena of enhanced field confinement at the feed gap and light scattering by optical antennas illuminated by plane waves.
BACKGROUND Superior mesenteric artery syndrome is caused by vascular compression of the third portion of the duodenum between the aorta and the superior mesenteric artery. It may occur with acute or ...chronic symptomatology, such as vomiting or postprandial abdominal pain, and it is usually caused by a lack of mesenteric fat pad under conditions of severe weight loss. Crohn's disease can be one of them. CASE REPORT We report 2 cases of Crohn's disease patients with clinical suspicion of jejunal stricture who underwent MR-enterography with a novel approach. In fact, the examinations were performed including prone position of the patients inside the scanner, drinking of contrast medium during the examination, and prompt acquisition of fluoroscopic sequences. Both the exams showed an abrupt termination of the duodenum on its third portion and a decreased aortomesenteric distance, allowing the diagnosis of superior mesenteric artery syndrome. CONCLUSIONS A correlation between Crohn's disease and superior mesenteric artery syndrome has never before been reported in the literature. The present study provides some practical steps that may be useful in order to improve MRE standard protocol in recognizing this condition while evaluating Crohn's disease bowel lesions.
In a program aimed at the design and synthesis of novel azole inhibitors of Candida albicans CYP51 (CA-CYP51), a series of azole 1,4-benzothiazines (BT) and 1,4-benzoxazines (BO) were recently ...synthesized. A morphological study of the enzyme active site highlighted a hydrophobic access channel, and a docking study pointed out that the C-2 position of the BT or BO nucleus was oriented toward the access channel. Here, we report the design, synthesis, and microbiological evaluation of C-2-alkyl BT and BO compounds. In both series, introduction of the alkyl chain maintained and in some cases improved the anti-Candida in vitro activity; however, there was not always a strict correlation between in vitro and in vivo activity for several compounds.
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