Daytime course of sleepiness in de novo Parkinson's disease patients

Normal subjects show an increase of sleepiness in the morning, early afternoon and before sleep. In the advanced stages of Parkinson's disease (PD) the mean level of sleepiness is quite high, while with respect to healthy subjects it seems to be unchanged in the early stages. The aim of this study was to evaluate the time–course of the sleepiness level during the wakefulness period in untreated patients with early‐stage Parkinson's disease. Eighteen Parkinson's disease patients who had never been treated before with dopaminergic drugs (male = 9, female = 9, age: 68.39 ± 1.89, mean ± standard error) and 18 healthy subjects (male = 9, female = 9, age: 67.22 ± 1.98) were recruited for this study. All subjects underwent continuous actigraphic recording for three consecutive days, during which they also completed the Karolinska Sleepiness Scale (KSS) once an hour throughout wakefulness. Our results showed a higher level of sleepiness in the patients than the controls in the hours following awakening and in the early afternoon, specifically at 08:00 and 14:00 hours (08:00 hours, PD patients, KSS: 3 ± 0.3 versus healthy subjects, KSS: 2 ± 0.2, P < 0.05; 14:00 hours, PD patients, KSS: 4.4 ± 0.5 versus healthy subjects, KSS: 3 ± 0.3, P < 0.05). We suggest that some daytime hours are sensitive windows showing the first increase of sleepiness which will spread later to the whole daytime.     

Beyond the joints,the extra-articular manifestations in rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients.The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.     

Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8–152.0) to 63.3 (52.0–79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.     

Investigation of the mechanical properties of the human crural fascia and their possible clinical implications

The mechanical properties of deep fasciae strongly affect muscular actions, development of pathologies, such as acute and chronic compartment syndromes, and the choice of the various fascial flaps. Actually, a clear knowledge of the mechanical characterization of these tissues still lacks. This study focuses attention on experimental tests of different regions of human crural fascia taken from an adult frozen donor. Tensile tests along proximal–distal and medial–lateral direction at a strain rate of 120 %/s were performed at the purpose of evaluating elastic properties. Viscous phenomena were investigated by applying incremental relaxation tests at total strain of 7, 9 and 11 % and observing stress decay for a time interval of 240 s. The elastic response showed that the fascia in the anterior compartment is stiffer than in the posterior compartment, both along the proximal–distal and medial–lateral directions. This result can explain why the compartment syndromes are more frequent in this compartment with respect to posterior one. Furthermore, the fascia is stiffer along the proximal–distal than along medial–lateral direction. This means that the crural fascia can adapt to the muscular variation of volume in a transversal direction, while along the main axis it could be considered as a structure that contributes to transmitting the muscular forces at a distance and connecting the different segments of the limb. The stress relaxation tests showed that the crural fascia needs 120 s to decrease stress of 40 %, suggesting a similar time also in the living so that the static stretching could have an effect on the fascia.