Modifications Of Joint Mobility Range Induced By Eccentric Contraction

Dynamic eccentric contraction causes muscle damage consisting of: myofibrills disorganization, Z-lines disruption and cell membrane lesions. This damage is indirectly evidenced by a massive, delayed (4th-5th day) CK release in the serum. Negative work induces also a clinical condition defined as "Delayed Onset Muscle Soreness" (DaMS), characterized by delayed onset (8-24h) muscle pain, lowering in muscle pain threshold (24-4Bh), swelling of the exerted limb (72h). Stiffness and restricted range of movement in the joints related to the exerted muscles are also described, but the phenomena are less investigasted. The aim of this study was to evaluate the range of knee joint mobility before and after a standardized eccentric effort. Twelve healthy runners, aged 24-35 years, were examined. They performed a step-test (20' duration, 15 cycles/min), to exert the quadriceps femoris muscle of one side eccentrically. The day before the test, all the subjects underwent evaluation of Pressure Pain Threshold (PPT) of the exerted muscle and Passive Joint Mobility (PJM) of the knee. These evaluations were repeated immediately after the test and on the following 6 days; on the same days, the perceived pain was also measured by means of a force-transducer equipped with a 2.5 cm diameter rounded probe and a digital analyser (unit:Kg/f), applied on 12 pre-established spots on the quadriceps muscle surface; the mean of the 12 recordings was taken as, the final threshold value. PJM was measured by means of a manual goniometer on prone subjects; the exerted lower limb was moved from the rest position to the maxmal pain-free flexion; the degree at which the subject felt the minimum discomfort was recorded. Student's "ttest" for paired data was employed for statistical analysis. PPT showed a significant decrease after 24 and 4Bh in the exerted muscle, while pain reached maximum value at the 4Bh measurement. PJM showed a significant reduction 24-72h after the effort. DaMS is a complex phenomena, whose explanation is still unclear; particularly the temporal dissociation between symptoms and signs of muscle damage. The reduction of PJM has been attributed to edema of the connective tissue, due to the eccentric contraction stress. However the maximal thickness of the eccentrically exerted limb is usually found at 72h, while the reduction of PJM starts at 24h. The results of the present study show that the temporal pattern of PJM reduction is fairly similar to that of pain and hyperalgesia. This could suggest a reflex origin of the phenomenon, due to painful symptoms, through a tonic activation of antagonist muscles

Correlation between Migraine Severity and Cholesterol Levels.

INTRODUCTION: Several studies have documented increased cardiovascular risk factors, particularly hypercholesterolemia, in the migraine population with respect to controls. However, no studies have investigated the possible relationship between headache severity parameters and lipid serum levels. METHODS: This study evaluated the lipid asset in 52 migraine patients (17 with and 36 without aura) before and after treatment with drugs for migraine prophylaxis for 3 months. RESULTS: High frequency (HF, ≥ 8/month) and intensity (HI, ≥ 5 Numeric Rating Score) vs. low frequency (LF, < 8/month) and intensity (LI, < 5) of crises were associated with significantly higher cholesterol levels, both total (TC, HF vs. LF, P < 0.0001; HI vs. LI, P < 0.0001) and LDL (LDL-c, HF vs. LF, P < 0.0001, and HI vs. LI, P < 0.0001). In treated patients, a significant decrease in number and intensity of crises was associated with a significant reduction of TC and LDL-c (P < 0.001). A direct linear correlation was also found between frequency and intensity of crises and lipid levels (TC/frequency, P < 0.0001; TC/intensity, P < 0.0001; LDL-c/frequency, P < 0.0001; LDL-c/intensity, P < 0.0001). No significant difference was found in the evaluated parameters for the subgroups of patients with and without aura. DISCUSSION: This study shows a significant positive association between migraine frequency and intensity with total and LDL cholesterol, demonstrating for the first time a significant reduction of these lipid parameters after migraine prophylaxis. However, in view of the retrospective design of the study and the small population size, these results should be considered as preliminary, to be confirmed by future prospective controlled trials

Clinical features, histopathology and differential diagnosis of sarcoidosis

Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas and manifesting with clinical pictures that vary on the basis of the organs that are mainly affected. Lungs and intrathoracic lymph nodes are the sites that are most often involved, but virtually no organ is spared from this disease. Histopathology is distinctive but not pathognomonic, since the findings can be found also in other granulomatous disorders. The knowledge of these findings is important because it could be helpful to differentiate sarcoidosis from the other granulomatous-related diseases. This review aims at illustrating the main clinical and histopathological findings that could help clinicians in their routine clinical practice

Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis: role of mast cells.

The effects of ultramicronized palmitoylethanolamide were evaluated on pain behaviours and markers of mast cell (MC) activity in 'a rat model of endometriosis plus ureteral calculosis (ENDO+STONE)-induced viscerovisceral hyperalgesia (VVH). Female Sprague-Dawley rats that underwent surgical induction of endometriosis were randomly assigned to receive active (ultramicronized palmitoylethanolamide 10 mg·kg-1 ·d-1, orally) or placebo treatment for 25 days. At day 21, they underwent ureteral stone formation and were video-recorded till day 25 to evaluate ureteral and uterine pain behaviours. At autopsy (day 25), ureteral condition and number and diameter of endometrial cysts were evaluated. The following were then measured: number and percentage of degranulating MCs, number of vessels, chymase, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and Flk-1 (VEGF receptor) in cysts, and NGF in dorsal root ganglia (DRG). Ultramicronized palmitoylethanolamide-treated vs placebo-treated rats showed significantly lower number, duration and complexity of ureteral crises, shorter duration of uterine pain, and smaller cyst diameter (0.0001 < P < 0.004); a significantly higher percentage of expelled stones (P < 0.0001); significantly lower MC number (P<0.01), vessel number (P< 0.01), chymase (P< 0.05), NGF (P<0.05), VEGF (P< 0.01), and Flk-1 (P< 0.01) expression in cysts and NGF expression in DRG (P< 0.01). In all animals, the global duration of ureteral crises correlated linearly and directly with cyst diameter, MC number and chymase in cysts, and NGF in cysts and DRG (0.02 < P < 0.0002). Ultramicronized palmitoylethanolamide significantly reduces VVH from ENDO+STONE, probably by modulating MC expression/activity in cysts, thus reducing central sensitization due to noxious signals from endometriotic lesions. The results suggest potential utility of the compound for VVH in clinics

Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines

Lymphoblastoid cell lines (LCLs) are generated by transforming primary B cells with Epstein-Barr virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell transcriptomic profiles of five LCLs and present a simple discrete-time simulation to explore the influence of stochasticity on LCL clonal evolution. Single-cell RNA sequencing (scRNA-seq) revealed substantial phenotypic heterogeneity within and across LCLs with respect to immunoglobulin isotype; virus-modulated host pathways involved in survival, activation, and differentiation; viral replication state; and oxidative stress. This heterogeneity is likely attributable to intrinsic variance in primary B cells and host-pathogen dynamics. Stochastic simulations demonstrate that initial primary cell heterogeneity, random sampling, time in culture, and even mild differences in phenotype-specific fitness can contribute substantially to dynamic diversity in populations of nominally clonal cells

Microevolution of serial clinical isolates of Cryptococcus neoformans var. grubii and C. gattii

This is the final version. Available from the publisher via the DOI in this record.The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and relapse isolates may reveal evidence of determinative, microevolutionary changes within the host. Here, we analyzed serial isolates cultured from cerebrospinal fluid specimens of 18 South African patients with recurrent cryptococcal meningitis. The time between collection of the incident isolates and collection of the relapse isolates ranged from 124 days to 290 days, and the analyses revealed that, during this period within the patients, the isolates underwent several genetic and phenotypic changes. Considering the vast genetic diversity of cryptococcal isolates in subSaharan Africa, it was not surprising to find that the relapse isolates had acquired different genetic and correlative phenotypic changes. They exhibited various mechanisms for enhancing virulence, such as growth at 39°C, adaptation to stress, and capsule production; a remarkable amplification of ERG11 at the native and unlinked locus may provide stable resistance to fluconazole. Our data provide a deeper understanding of the microevolution of Cryptococcus species under pressure from antifungal chemotherapy and host immune responses. This investigation clearly suggests a promising strategy to identify novel targets for improved diagnosis, therapy, and prognosis.Wellcome TrustNational Institute of Allergy and Infectious Disease

A classification of chronic pain for ICD-11.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450869

Development of a DNA aptamer for direct and selective homocysteine detection in human serum

l-Homocysteine has been an amino acid intermediate of interest for over 20 years due to its implication in various adverse health conditions, including cardiovascular disease. Here, we report the first in vitro selection and application of high affinity aptamers for the target l-homocysteine. Two novel aptamer sequences were selected following 8 rounds of selection that displayed high affinity binding and selectivity to homocysteine compared to other amino acids. One of the selected aptamers, Hcy 8 (KD = 600 ± 300 nM), was used to develop a gold-nanoparticle biosensor capable of sensitive and selective homocysteine detection in human serum, with a limit of detection of 0.5 μM and a linear range of 0.5-3.0 μM. This biosensor allows rapid detection of free homocysteine in human serum samples at low cost, with little preparation time and could be adapted to be part of a po

Myofascial trigger points in cluster headache patients: a case series

Active myofascial trigger points (MTrPs) have been found to contribute to chronic tension-type headache and migraine. The purpose of this case series was to examine if active trigger points (TrPs) provoking cluster-type referred pain could be found in cluster headache patients and, if so, to evaluate the effectiveness of active TrPs anaesthetic injections both in the acute and preventive headache's treatment. Twelve patients, 4 experiencing episodic and 8 chronic cluster headache, were studied. TrPs were found in all of them. Abortive infiltrations could be done in 2 episodic and 4 chronic patients, and preemptive infiltrations could be done in 2 episodic and 5 chronic patients, both kind of interventions being successful in 5 (83.3%) and in 6 (85.7%) of the cases respectively. When combined with prophylactic drug therapy, injections were associated with significant improvement in 7 of the 8 chronic cluster patients. Our data suggest that peripheral sensitization may play a role in cluster headache pathophysiology and that first neuron afferent blockade can be useful in cluster headache management