Crystal-induced joint inflammation

L'infiammazione articolare indotta dai microcristalli e tra le piu acute ed intense che e dato conoscere. A supporto di questa affermazione si possono citare le numerose ed autorevoli testimonianze ricevute nei secoli dai personaggi affetti da gotta (1, 2), la piu nota e celebrata artropatia da microcristalli. Proprio sulla particolare capacita di questa malattia di indurre un'infiammazione particolarmente intensa ed essere poi in grado di autolimitarla, almeno durante i primi attacchi, si sono riversate molte attenzioni degli studiosi moderni, i quali hanno cercato di interpretare questo fenomeno con l'ambizione principale di poterlo trasferire ad altri tipi di infiammazione articolare. In effetti, i modelli d'infiammazione indotta dai cristalli di urato monosodico (UMS), di pirofosfato di calcio diidrato (PFCD) e da altri microcristalli di natura calcica, costituiscono un ottimo terreno di applicazione per lo studio della fisiopatologia dell'infiammazione articolare, soprattutto per cio che concerne gli eventi acuti..

Regional nanoindentation properties in different locations on the mouse tibia from C57BL/6 and Balb/C female mice

The local spatial heterogeneity of the material properties of the cortical and trabecular bone extracted from the mouse tibia is not well-known. Nevertheless, its characterization is fundamental to be able to study comprehensively the effect of interventions and to generate computational models to predict the bone strength preclinically. The goal of this study was to evaluate the nanoindentation properties of bone tissue extracted from two different mouse strains across the tibia length and in different sectors. Left tibiae were collected from four female mice, two C57BL/6, and two Balb/C mice. Nanoindentations with maximum 6 mN load were performed on different microstructures, regions along the axis of the tibiae, and sectors (379 in total). Reduced modulus (Er) and hardness (H) were computed for each indentation. Trabecular bone of Balb/C mice was 21% stiffer than that of C57BL/6 mice (20.8 ± 4.1 GPa vs. 16.5 ± 7.1 GPa). Moreover, the proximal regions of the bones were 13–36% less stiff than the mid-shaft and distal regions of the same bones. No significant differences were found for the different sectors for Er and H for Balb/C mice. The bone in the medial sector was found to be 8–14% harder and stiffer than the bone in the anterior or posterior sectors for C57BL/6 mice. In conclusion, this study showed that the nanoindentation properties of the mouse tibia are heterogeneous across the tibia length and the trabecular bone properties are different between Balb/C and C57BL/6 mice. These results will help the research community to identify regions where to characterize the mechanical properties of the bone during preclinical optimisation of treatments for skeletal diseases

Influence of intra-articular injections of sodium hyaluronate on clinical features and synovial fluid nitric oxide levels of temporomandibular osteoarthritis

Objective: This study was designed to assess the effect of intra-articular injection of sodium hyaluronate (SH) on clinical findings of temporomandibular osteoarthritis (OA) and on synovial fluid (SF) levels of nitric oxide (NO). Methods: Twenty seven patients (7 men, 20 women, mean (SD) age 53.9 (11.8) years) with OA of the temporomandibular joint were randomly allocated to receive an injection of either SH (2ml, Hyalgan®, Fidia SpA, Abano T., P.M. 500-700.000, 20mg/2ml; once a week for 5 weeks) or a Ringer's lactate solution (once a week for 3 weeks). Clinical evaluation was done before each procedure, and at 1 week, 1, 3 and 6 months post-injection. Intensity of temporomandibular joint pain, jaw function, maximal mouth opening and lateral jaw movements were recorded at each visit. NO was measured on SF collected by rinsing the joint with saline 1 ml before the treatment. Results: Injection of SH caused significant improvement in the main clinical symptoms until the last follow-up which was carried out 6 months after last injection. Among patients who received SH injection, those who reached a good outcome showed the lowest basal levels of NO. Conclusions: The results of this study showed that intra-articular injections of SH lead to a lasting improvement in the clinical symptoms of temporomandibular OA. Furthermore, our findings suggest that low NO levels in SF are related to a better outcome of temporomandibular OA among patients treated with SH intra-articular injection

RNA framework: An all-in-one toolkit for the analysis of RNA structures and post-transcriptional modifications

RNA is emerging as a key regulator of a plethora of biological processes. While its study has remained elusive for decades, the recent advent of high-throughput sequencing technologies provided the unique opportunity to develop novel techniques for the study of RNA structure and post-transcriptional modifications. Nonetheless, most of the required downstream bioinformatics analyses steps are not easily reproducible, thus making the application of these techniques a prerogative of few laboratories. Here we introduce RNA Framework, an all-in-one toolkit for the analysis of most NGS-based RNA structure probing and post-transcriptional modification mapping experiments. To prove the extreme versatility of RNA Framework, we applied it to both an in-house generated DMS-MaPseq dataset, and to a series of literature available experiments. Notably, when starting from publicly available datasets, our software easily allows replicating authors' findings. Collectively, RNA Framework provides the most complete and versatile toolkit to date for a rapid and streamlined analysis of the RNA epistructurome. RNA Framework is available for download at: http://www.rnaframework.com

Analysis of short-term blood pressure variability in pheochromocytoma/paraganglioma patients

Data on short-term blood pressure variability (BPV), which is a well-established cardiovascular prognostic tool, in pheochromocytoma and paraganglioma (PPGL) patients is still lack and conflicting. We retrospectively evaluated 23 PPGL patients referred to our unit from 2010 to 2019 to analyze 24 h ambulatory blood pressure monitoring (24-h ABPM)-derived markers of short-term BPV, before and after surgical treatment. PPGL diagnosis was assessed according to guidelines and confirmed by histologic examination. The 24-h ABPM-derived markers of short-term BPV included: circadian pressure rhythm; standard deviation (SD) and weighted SD (wSD) of 24-h, daytime, and night-time systolic and diastolic blood pressure (BP); average real variability (ARV) of 24-h, daytime, and night-time systolic and diastolic BP. 7 males and 16 females of 53 ± 18 years old were evaluated. After surgical resection of PPGL we found a significant decrease in 24-h systolic BP ARV (8.8 ± 1.6 vs. 7.6 ± 1.3 mmHg, p < 0.001), in 24-h diastolic BP ARV (7.5 ± 1.6 vs. 6.9 ± 1.4 mmHg, p = 0.031), and in wSD of 24-h diastolic BP (9.7 ± 2.0 vs 8.8 ± 2.1 mmHg, p = 0.050) comparing to baseline measurements. Moreover, baseline 24-h urinary metanephrines significantly correlated with wSD of both 24-h systolic and diastolic BP. Our study highlights as PPGL patients, after proper treatment, show a significant decrease in some short-term BPV markers, which might represent a further cardiovascular risk factor

how the mediterranean diet and some of its components modulate inflammatory pathways in arthritis

Arthritis encompasses a heterogeneous group of diseases characterised by inflammation that leads not only to joint damage, bone erosion, severe pain and disability, but also affects other organs of the body, resulting in increased morbidity and mortality. Although the mechanisms underlying the pathogenesis of joint diseases are for the most part unknown, a number of nutrient and non-nutrient components of food have been shown to affect the inflammatory process and, in particular, to influence clinical disease progression. The Mediterranean diet model has already been linked to a number of beneficial health effects: both fat and non-fat components of the Mediterranean dietary pattern have been shown to exert important anti-inflammatory activities by affecting the arachidonic acid cascade, the expression of some proinflammatory genes, and the activity of immune cells. N-3 polyunsaturated fatty acids, in particular, have been shown to affect lymphocyte and monocyte functions, crucially involved in adaptive and innate immunity. Although some aspects concerning the mechanisms of action through which the Mediterranean diet pattern exerts its beneficial effects remain to be elucidated, arthritis patients may potentially benefit from it in view of their increased cardiovascular risk and the treatment they require which may have side effects

The enthesopathy of vitamin D-resistant osteomalacia in adults

A case of an adult patient with vitamin D-resistant osteomalacia or X-linked hypophosphatemic osteomalacia (XLH) with diffuse calcification of entheses was reported. XLH is the most frequent cause of rickets in developed countries. It is characterized by an impaired renal transport of the phosphate and mutation of PFEX (phosphate regulating gene, with homologies to endopeptidase on the X-chromosome). In childhood, the classic clinical presentation includes short stature and bow leg. While at this age the main radiographic features are characterised by rickets, in adult life they are dominated by a generalised calcific enthesopathy. Concerning the pathogenesis of the enthesopathic lesions of XLH, no convincing hypothesis has yet been made. As in our patient, the extension and the severity of enthesopathy seems not related to the severity of the biochemical changes nor to the treatment with calcitriol. The calcified enthesopathy is an integral part of XLH and it is possible that it is found in adult because many years are necessary to produce it

Evolution of EEG motor rhythms after spinal cord injury: A longitudinal study

Spinal cord injury (SCI) does not only produce a lack of sensory and motor function caudal to the level of injury, but it also leads to a progressive brain reorganization. Chronic SCI patients attempting to move their affected limbs present a significant reduction of brain activation in the motor cortex, which has been linked to the deafferentation. The aim of this work is to study the evolution of the motor-related brain activity during the first months after SCI. Eighteen subacute SCI patients were recruited to participate in bi-weekly experimental sessions during at least two months. Their EEG was recorded to analyze the temporal evolution of the event-related desynchronization (ERD) over the motor cortex, both during motor attempt and motor imagery of their paralyzed hands. The results show that the a and ß ERD evolution after SCI is negatively correlated with the clinical progression of the patients during the first months after the injury. This work provides the first longitudinal study of the event-related desynchronization during the subacute phase of spinal cord injury. Furthermore, our findings reveal a strong association between the ERD changes and the clinical evolution of the patients. These results help to better understand the brain transformation after SCI, which is important to characterize the neuroplasticity mechanisms involved after this lesion and may lead to new strategies for rehabilitation and motor restoration of these patients

New approaches to the study of periodic leg movements during sleep in restless legs syndrome

Study Objectives: To describe a new approach for the analysis of quantity, type, and periodicity of the leg motor activity during sleep in patients with restless legs syndrome (RLS) and periodic leg movements (PLM). Methods: The following parameters were taken into account for LM: duration, amplitude, area under the curve, sleep stage, side, interval, and bilaterality. The analysis of inter-LM intervals was carried out by drawing their distribution graphs. A new index evaluated their periodicity and was validated by means of a Markovian analysis. The differences in inter-LM intervals, LM duration, and area under the curve between normal controls and patients and between the 3 patient subgroups identified on the basis of their periodicity were statistically analyzed. Setting: N/A Participants: Sixty-five patients with RLS and periodic LM and 22 young healthy controls. Measurements and Results: The RLS patients' inter-LM interval distribution graph showed a wide peak with a maximum located at around 15 to 30 seconds and extending from 10 to 90 seconds, not present in controls, and another peak for intervals less than 8 seconds, higher than that of controls. Three patient subgroups were identified with different proportions of these 2 peaks, periodicity, and Markovian parameters. Periodicity was not dependent on the periodic leg movement index. Patients showing the peak mainly at around 15 to 30 seconds tended to show slightly longer and higher area under the curve LM than did the other 2 subgroups. Conclusions: Our new approach seems to be useful in a new qualitative differentiation among patients with PLM, which is not possible by using the simple PLM index