Weibull function to describe the cumulative size distribution of clumps formed by two-dimensional grains randomly arranged on a plane.

Many manifestations of natural processes give rise to interesting morphologies; it is all too easy to cite the corrugation of the Earth's surface or of planets in general. However, limiting ourselves to 2D cases, the morphology to which crystal growth gives rise is also intriguing. In particular, it is interesting to study some characteristics of the cluster projection in 2D, namely the study of the shapes of the speckles (fractal dimension of their rims) or the distribution of their areas. Recently, for instance, it has been shown that the size cumulative distribution function (cdf) of "voids" in a corrole film on Au(111) is well described by the well known Weibull distribution. The present article focuses on the cdf of cluster areas generated by numerical simulations: the clumps (clusters) are generated by overlapping grains (disks) whose germs (disk centers) are chosen randomly in a 2000×2000 square lattice. The obtained cdf of their areas is excellently fitted to the Weibull function in a given range of surface coverage. The same type of analysis is also performed for a fixed-time clump distribution in the case of Kolmogorov-Johnson-Mehl-Avrami (KJMA) kinetics. Again, a very good agreement with the Weibull function is obtained.

Abnormal ankle-brachial index (ABI) predicts primary and secondary cardiovascular risk and cancer mortality.

BACKGROUND: An abnormal ankle-brachial pressure index (ABI) is a marker of the risk for increased total and cardiovascular (CV) mortality. However, it is not clear whether it is associated with an even worse prognosis in patients with previous CV events or with cancer mortality. MATERIALS AND METHODS: Consecutive subjects undergoing ABI assessment for suspected peripheral artery disease or for stratification of CV risk in ten centers in the Veneto Region (northeast Italy), between 2011 and 2014 were enrolled. The ABI was expressed as normal ≥0.9 to ≤1.3, and abnormal <0.9 or >1.3. All-cause mortality and CV or cancer mortality and hospitalizations for CV disease were collected from administrative databases up to December 2018. RESULTS: The study enrolled 1,177 patients. ABI was abnormal in 57.2%. Median follow-up was 61.6 months (53.4-70.1). All-cause, CV and cancer mortality were higher in patients with abnormal than normal ABI, with hazard ratios (HR) respectively 2.0 (95% CI 1.48-2.69), 1.98 (95% CI 1.24-3.17) and 1.85 (95% CI 1.09-3.15). Among subjects with abnormal ABI, the risk of overall mortality, HR 1.57 (95% CI 1.17-2.12), and CV mortality, HR 2.39 (95% CI 1.43-3.99), was higher in those with previous CV events. These latter also had a higher risk of hospitalization for myocardial infarction and stroke: HR 1.85 (95% CI 1.023.37) and 2.17 (95% CI 1.10-4.28). CONCLUSIONS: The co-existence of abnormal ABI and a history of CV events identifies subjects at higher risk, who call for a more aggressive approach. Abnormal ABI is also a predictor of cancer mortality.

The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score.

Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8+) cytotoxic T lymphocytes (CD8+-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8+-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8+-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8+ T cell recognition may provide insights for future pre-clinical studies.

Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy.

In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.

Intracellular amorphous carbonates uncover a new biomineralization process in eukaryotes.

Until now, descriptions of intracellular biomineralization of amorphous inclusions involving alkaline-earth metal (AEM) carbonates other than calcium have been confined exclusively to cyanobacteria (Couradeau et al., 2012). Here, we report the first evidence of the presence of intracellular amorphous granules of AEM carbonates (calcium, strontium, and barium) in unicellular eukaryotes. These inclusions, which we have named micropearls, show concentric and oscillatory zoning on a nanometric scale. They are widespread in certain eukaryote phytoplankters of Lake Geneva (Switzerland) and represent a previously unknown type of non-skeletal biomineralization, revealing an unexpected pathway in the geochemical cycle of AEMs. We have identified Tetraselmis cf. cordiformis (Chlorophyta, Prasinophyceae) as being responsible for the formation of one micropearl type containing strontium ([Ca,Sr]CO3 ), which we also found in a cultured strain of Tetraselmis cordiformis. A different flagellated eukaryotic cell forms barium-rich micropearls [(Ca,Ba)CO3 ]. The strontium and barium concentrations of both micropearl types are extremely high compared with the undersaturated water of Lake Geneva (the Ba/Ca ratio of the micropearls is up to 800,000 times higher than in the water). This can only be explained by a high biological pre-concentration of these elements. The particular characteristics of the micropearls, along with the presence of organic sulfur-containing compounds-associated with and surrounding the micropearls-strongly suggest the existence of a yet-unreported intracellular biomineralization pathway in eukaryotic micro-organisms.

Complexos triazenidos de platina (II): Avaliação in vitro da atividade antibacteriana e citotóxica frente a bactérias e células de medula óssea de pacientes leucêmicos de um hospital escola / Triazenidos complexes of platinum (II): In vitro evaluation of antibacterial and cytotoxic activity against bacteria and bone marrow cells from leukemic patients in a university hospital

Atualmente, apesar da ampla gama de substâncias ativas existentes, progressivamente tem se limitado o arsenal terapêutico disponível na prática clínica, isto se deve, especialmente, pelo surgimento da resistência aos agentes terapêuticos utilizados no tratamento de tumores e infecções bacterianas. Em virtude das diversas propriedades farmacológicas demonstradas pelos triazenos (TZCs), avaliaram-se compostos inéditos na busca de novos agentes biologicamente ativos, estes foram denominados C1 e C2. A atividade antibacteriana foi realizada pelo método convencional da microdiluição em caldo, através da técnica da Concentração Inibitória Mínima (CIM), frente a cepas bacterianas de referência American Type Culture Collection (ATCC) e isolados clínicos com resistência múltipla as drogas (RMD). A citotoxicidade foi analisada através do ensaio colorimétrico baseado na redução do brometo de 3-(4,5-dimetiltiazol-2-il)-2,5?difeniltetrazólio frente a células da medula óssea de dois pacientes (P1 e P2) atendidos no Hospital Universitário de Santa Maria. Os dois compostos testados apresentaram atividade antibacteriana em 26,08% (6/23) das cepas testadas, sendo ativos em 38,46% (5/13) das cepas ATCC e 10% (1/10) dos isolados clínicos RMD, apenas em espécies caracterizadas como Gram positivas. Os resultados foram satisfatórios para ambos os compostos frente à amostra P2, células mononucleares de Leucemia Mielóide Crônica, pois demonstraram indução da morte celular. Pode-se concluir que os resultados obtidos desses compostos demonstraram a existência de atividade antibacteriana, bem como, atividade antileucêmica promissora. Pesquisas complementares relacionadas a esses compostos estão em andamento.(AU)

Currently, despite the wide range of existing active substances has been progressively limited therapeutic arsenal available in clinical practice, this is, in particular, the emergence of resistance to therapeutic agents used in treating tumors and bacterial infections. Because of the diverse pharmacological properties demonstrated by triazenes (TZCs) - evaluated whether unpublished compounds in the search for new biologically active agents, they were called C1 and C2. The antibacterial activity was performed by the conventional method of broth microdilution, using the technique of Minimum Inhibitory Concentration (MIC) against the bacterial strains reference American Type Culture Collection (ATCC) and clinical isolates with multiple drug resistance (MDR). Cytotoxicity was analyzed by colorimetric assay based on the reduction of the bromide of 3 - (4,5- dimethylthiazol-2- yl) -2,5- diphenyltetrazolium against bone marrow cells from two patients (P1 and P2) seen at the Hospital university of Santa Maria. The two compounds tested showed antibacterial activity in 26.08% (6/23) of the strains, being active in 38.46 % (5/13) of the ATCC strains and 10 % (1/10) of clinical isolates MDR only characterized in species such as Gram positive. The results were satisfactory for both the sample compounds front P2, mononuclear cells from chronic myeloid leukemia, as demonstrated induction of cell death. It can be concluded that the results demonstrated the existence of these compounds to antibacterial activity, as well as promising antileukemic activity. Additional research related to these compounds are in progress.(AU)

Medical management of patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is one of the most frequent manifestations of atherosclerosis and is associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of cardiovascular events. Major risk factors of PAD are similar to those that lead to atherosclerosis in other vascular beds. However, there are differences in the power of individual risk factors in the different vascular territories. Cigarette smoking and diabetes mellitus represent the greatest risks of PAD. For prevention of the progression of PAD and accompanying cardiovascular events similar preventative measures are used as in coronary artery disease (CAD). However, recent data indicate that there are some differences in the efficacy of drugs used in the prevention of atherothrombotic events in PAD. Antiplatelet treatment is indicated in virtually all patients with PAD. In spite of the absence of hard evidence- based data on the long term efficacy of aspirin, it is still considered as a first line treatment and clopidogrel as an effective alternative. The new antiplatelet drugs ticagrelol and prasugrel also represent promising options for treatment of PAD. Statin therapy is indicated to achieve the target low density lipoprotein cholesterol level of ≤2.5 mmol/L (100 mg/dL) and there is emerging evidence that lower levels are more effective. Statins may also improve walking capacity. Antihypertensive treatment is indicated to achieve the goal blood pressure (<140/90 mmHg). All classes of antihypertensive drugs including beta-blockers are acceptable for treatment of hypertension in patients with PAD. Diabetic patients with PAD should reduce their glycosylated haemoglobin to ≤7%. As PAD patients represent the group with the highest risk of atherothrombotic events, these patients need the most intensive treatment and elimination of risk factors of atherosclerosis. These measures should be as comprehensive as those in patients with established coronary and cerebrovascular disease.

Consensus Document on Intermittent Claudication from the Central European Vascular Forum (C.E.V.F.)-3rd revision (2013) with the sharing of the Mediterranean League of Angiology and Vascular Surgery, and the North Africa and Middle East Chapter of International Union of Angiology.

This paper is the review of the Consensus Document on Intermittent Claudication of the Central European Vascular Forum (CEVF), published in 2008, and and shared with the North Africa and Middle East Chapter of International Union of Angiology and the Mediterranean League of Angiology and Vascular Surgery. The Document presents suggestions for general practitioners and vascular specialists for more precise and appropriate management of PAD, particularly of intermittent claudication, and underlines the investigations that should be required by GPs and what the GP should expect from the vascular specialist (angiologist, vascular surgeon). The idea of the Faculty is to produce a short document, which is an easy reference in daily clinical practice, both for the GPs and vascular specialists.

Avaliação do Desempenho de Culturas Convencionais na Detecção da Contaminação Bacteriana em Concentrados Plaquetários em um Hospital Universitário do Sul do Brasil / Assessment of performance of conventional culture in the detection of bacterial contamination in platelet concentrates in a University Hospital in southern Brazil

Blood transfusion is an indispensable aid to the treatmentof cancer patients. On the other hand, it involves a seriousrisk of bacterial sepsis. Platelet concentrates (PCs) arethe blood components with the highest incidence ofbacterial contamination, being responsible for mostof the septic reactions to transfusion. In this study, weassessed various conventional culture methods for thedetection of bacterial contamination in PCs. In all, 691samples of PCs (665 random donor platelets and 26apheresis platelets) from the Blood Center of the Stateof Rio Grande do Sul (HEMORGS), were analyzed. Weemployed qualitative, quantitative and daily growthculture techniques, which revealed that 2.32% of thesamples analyzed, all from random donor platelets, werecontaminated. The qualitative methodology performedbest. This result obliges us to reinforce the importanceof performing pre-transfusion bacteriological screeningon all samples of PCs, to reduce the risk of sepsis.

As transfusões sanguíneas retratam um suporte indispensável no tratamento de pacientes com câncer. Por outro lado, representam um sério risco de sepse bacteriana. Os concentrados plaquetários (CPs) são os hemocomponentes com a mais alta frequência de contaminação bacteriana, responsáveis pela maioria das reações sépticas transfusionais. Este estudo objetivou avaliar diferentes metodologias convencionais de cultura na detecção da contaminação bacteriana em CPs. Um total de 691 amostras de CPs (665 plaquetas randômicas e 26 plaquetaféreses), provenientes do Hemocentro do Estado do Rio Grande do Sul (HEMORGS), foi analisado. Foram empregadas técnicas de cultura qualitativa, quantitativa e de crescimento diário, com as quais evidenciamos 2,32% de contaminação bacteriana nas amostras analisadas, sendo todas provenientes de coleta pelo método randômico. A metodologia qualitativa apresentou o melhor desempenho. Esse fato nos permite reforçar a importância da realização de triagem bacteriológica pré-transfusional em todas as amostras de CPs para a redução dos riscos de sepse.

Comparisons between conventional, ultrasound-assisted and microwave-assisted methods for extraction of anthraquinones from Heterophyllaea pustulata Hook f. (Rubiaceae).

This work reports a comparative study about extraction methods used to obtain anthraquinones (AQs) from stems and leaves of Heterophyllae pustulata Hook (Rubiáceae). One of the conventional procedures used to extract these metabolites from a vegetable matrix is by successive Soxhlet extractions with solvents of increasing polarity: starting with hexane to eliminate chlorophylls and fatty components, following by benzene and finally ethyl acetate. However, this technique shows a low extraction yield of total AQs, and consumes large quantities of solvent and time. Ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) have been investigated as alternative methods to extract these compounds, using the same sequence of solvents. It was found that UAE increases the extraction yield of total AQs and reduces the time and amount of solvent used. Nevertheless, the combination UAE with benzene, plus MAE with ethyl acetate at a constant power of 900 W showed the best results. A higher yield of total AQs was obtained in less time and using the same amount of solvent that UAE. The optimal conditions for this latter procedure were UAE with benzene at 50 °C during 60 min, followed by MAE at 900 W during 15 min using ethyl acetate as extraction solvent.

Sand fly fauna (Diptera, pcychodidae, phlebotominae) in different leishmaniasis-endemic areas of ecuador, surveyed using a newly named mini-shannon trap.

To study the sand fly fauna, surveys were performed at four different leishmaniasis-endemic sites in Ecuador from February 2013 to April 2014. A modified and simplified version of the conventional Shannon trap was named "mini-Shannon trap" and put to multiple uses at the different study sites in limited, forested and narrow spaces. The mini-Shannon, CDC light trap and protected human landing method were employed for sand fly collection. The species identification of sand flies was performed mainly based on the morphology of spermathecae and cibarium, after dissection of fresh samples. In this study, therefore, only female samples were used for analysis. A total of 1,480 female sand flies belonging to 25 Lutzomyia species were collected. The number of female sand flies collected was 417 (28.2%) using the mini-Shannon trap, 259 (17.5%) using the CDC light trap and 804 (54.3%) by human landing. The total number of sand flies per trap collected by the different methods was markedly affected by the study site, probably because of the various composition of species at each locality. Furthermore, as an additional study, the attraction of sand flies to mini-Shannon traps powered with LED white-light and LED black-light was investigated preliminarily, together with the CDC light trap and human landing. As a result, a total of 426 sand flies of nine Lutzomyia species, including seven man-biting and two non-biting species, were collected during three capture trials in May and June 2014 in an area endemic for leishmaniasis (La Ventura). The black-light proved relatively superior to the white-light with regard to capture numbers, but no significant statistical difference was observed between the two traps.

Sand Fly Fauna (Diptera, Pcychodidae, Phlebotominae) in DifferentLeishmaniasis- Endemic Areas of Ecuador, Surveyed by Using a Newly Named Mini-Shannon Trap

To study the sand fly fauna, surveys were performed atfour different leishmaniasis-endemic areas of Ecuador, during February 2013 andApril 2014. The conventional Shannon trap was modified and simplified to anewly named mini-Shannon trap for its multiple uses at different study sites,such as limited, forested and narrow spaces. The mini-Shannon, CDC light trapsand the protected human landing method were employed for sand fly collection.The species identification of sand flies was performed mainly based on themorphology of spermathecae and cibarium, after dissection of freshsamples.  In this study, therefore, onlyfemale samples were used for analysis. A total of1,480 female sand flies belonging to 25<i> Lutzomyia</i> species were collected. Numbers of the female sand fliescollected by each trap were 417 (28.2%) by the mini-Shannon trap, 259 (17.5%)by CDC light trap and 804 (54.3%) by human landing. The total number of sand flies per trap collected bydifferent methods was markedly affected by study sites, probably because ofdifferent species compositions at each locality. Further, as an additionalstudy, the attractiveness of sand flies against the mini-Shannon traps poweredwith LED White-light and LED Black-light, waspreliminary tested, together with CDC light trap and human landing. In the test,a total of 426 sand flies of nine <i>Lutzomyia</i> species, seven man-biting and two non-man-biting species, were collected by threecapture trials during May and June 2014 in an area endemic for leishmaniasis(La Ventura). The Black-light equipped trap was relatively superior in capturenumbers to the White-light equipped one, but no significant difference wasobserved statistically between the two traps.

Sand Fly Fauna (Diptera, Pcychodidae, Phlebotominae) in Different Leishmaniasis-Endemic Areas of Ecuador, Surveyed Using a Newly Named Mini-Shannon Trap

To study the sand fly fauna, surveys were performed at four different leishmaniasis-endemic sites in Ecuador from February 2013 to April 2014. A modified and simplified version of the conventional Shannon trap was named “mini-Shannon trap” and put to multiple uses at the different study sites in limited, forested and narrow spaces. The mini-Shannon, CDC light trap and protected human landing method were employed for sand fly collection. The species identification of sand flies was performed mainly based on the morphology of spermathecae and cibarium, after dissection of fresh samples. In this study, therefore, only female samples were used for analysis. A total of 1,480 female sand flies belonging to 25 <i>Lutzomyia</i> species were collected. The number of female sand flies collected was 417 (28.2%) using the mini-Shannon trap, 259 (17.5%) using the CDC light trap and 804 (54.3%) by human landing. The total number of sand flies per trap collected by the different methods was markedly affected by the study site, probably because of the various composition of species at each locality. Furthermore, as an additional study, the attraction of sand flies to mini-Shannon traps powered with LED white-light and LED black-light was investigated preliminarily, together with the CDC light trap and human landing. As a result, a total of 426 sand flies of nine <i>Lutzomyia</i> species, including seven man-biting and two non-biting species, were collected during three capture trials in May and June 2014 in an area endemic for leishmaniasis (La Ventura). The black-light proved relatively superior to the white-light with regard to capture numbers, but no significant statistical difference was observed between the two traps.

Unbalanced risk factors, could compromise the effectiveness of physical training in patients with intermittent claudication?

AIM: The correction of atherosclerotic risk factors is the unavoidable assumption to assure the maximal effectiveness and duration of the results of any therapeutic intervention (pharmacological and surgical) for the treatment of intermittent claudication. Aim of this study has been to verify if the presence/absence of risk factors and the degree of their correction could compromise the responsiveness of claudicant patients to the supervised physical training. METHODS: Initial (IDC), absolute (ACD) claudication distance, and recovery time (RT) have been measured by maximal treadmill exercise in 74 claudicants. The measurements have been repeated after 18 days of supervised physical training consisting of a daily walk reaching either a distance goal of 1-2 km or a time goal of at least 30 min. The working load of each single training session has been tailored at 60-70% of the ACD measured by a non-maximal treadmill exercise. The patients' cohort has been stratified in 7 groups and 18 sub-groups (no smokers, smokers in the past, still smokers, no-diabetics, well balanced and unbalanced diabetes, absent, well balanced and unbalanced hypercholesterolemia, normal weight, over weight and light obesity, hypertensive and no-hypertensive, with and without previous myocardial infarction and TIAs or stroke). The mean and standard error of ICD, ACD and RT before and after 18 days of physical training have been calculated and compared with Student's t test in each group and sub-group. On the data before and after training of ICD, ACD and RT of each group of risk factors the multivariate analysis of the variance has been carried out by analysis of variance (ANOVA). All the analyses were considered significant when the P value was less than 0.05. RESULTS: ICD values increased from 55.12 to 121.86 m, ACD from 103.16 to 191.58 m, RT reduced from 204.04 to 87.46 s, confirming the relevant (P<0.0001) effectiveness of supervised physical training on the walking capacity of claudicant patients. The comparison between the deltas (value after minus value before) of each sub-group did not show any significant difference. The multivariate ANOVA of before and after ICD ACD and RT of each risk factor groups showed values relevantly lesser than 0.05, indicating that risk factors did not influence the result of physical training. CONCLUSIONS: The supervised physical training is confirmed as an effective tool for the treatment of claudicant patient. We did not find any significant difference in the response to the programme related with the presence, absence or balance degree of risk factors, and we conclude that physical training effectiveness is independent from the their presence, absence or balance degree. This statement is very important because highlights the physical training as the only therapeutic tool for peripheral arterial disease (PAD) independent from the results of the risk factors' treatment.

Effectiveness and costs of a short-course supervised training program in claudicants: proposal for a shared protocol with aerobic working load.

AIM: The purpose of this study was to assess the costs and effectiveness of a short-course physical training program, consisting of an aerobic protocol with clearly defined working loads in each single training session, in patients with intermittent claudication (IC). METHODS: Initial (ICD), absolute (ACD) claudication distance, and recovery time (RT) have been measured by maximal treadmill exercise in 74 claudicants. Ankle brachial index (ABI) has been measured too. Measurements have been repeated after 18 days of supervised physical training consisting of a daily walk reaching either a distance goal of 1-2 km or a time goal of at least 30 min. The working load of each single training session has been tailored at 60-70% of the ACD measured by a non-maximal treadmill exercise. RESULTS: ICD increased from 56.2 (+/- standard deviation/+/- standard error: 35.3/4.1) to 123.9 (66.5/7.7); ACD increased from 104.8 (49.8/5.8) to 195.1 (81.7/9.5) and RT reduced from 201.2 (98.3/11.4) to 85.8 (43.6/5.1), with P<0.0001 for all parameters. We analyzed separately patients with moderate (M-CL) and severe (S-CL) claudication, and found significant improvements in both groups. The Ds (post-training value minus pretraining value) were: ICD 89.6 (59.9/10.9) in M-CL and 50.2 (29.9/4.6) in S-CL; ACD 102.8 (66.8/11.6) in M-CL and 80.1 (41.5/6.4) in S-CL; RT -98.7 (86.9/15.1) in M-CL and -128.5 (88.1/13.7) in S-CL, with P<0.0001 for all parameters. The differences between M-CL and S-CL were significant only for ICD (P=0.0003) and ACD (P<0.05). ABI showed an increasing trend, which was statistically significant (P<0.001), but clinically irrelevant. The protocol cost was 4179 Euro (average cost 46.30 Euro to walk one additional meter). CONCLUSION: Supervised physical training is confirmed to be an effective tool for the treatment of IC, and the proposed short-course protocol gave the same improvements as the longer ones while reducing the costs. The proposed procedure for tailoring the working load of a single session identifies clearly the working load, near maximal pain but avoiding the risk of inflammatory activation.

Clonal expansions of pathogenic CD8+ effector cells in the CNS of myelin mutant mice.

Tissue damage in the CNS is critically influenced by the adaptive immune system. Primary oligodendrocyte damage (by overexpression of PLP) leads to low-grade inflammation of high pathological impact, which is mediated by CD8+ T cells. To yield further insight into pathogenesis and nature of immune responses in myelin mutated mice, we here apply a detailed immunological characterization of CD8+ T cells in PLP-transgenic and aged wild type mice. We provide evidence that T effector cells accumulate in the CNS of PLP-transgenic and wild-type mice and show a higher level of activation in mutant mice, indicated by surface markers and clonal expansions, as demonstrated by T cell receptor CDR3-spectratype analysis. Vbeta-Jbeta similarities suggest specificity against a common antigen, albeit we could not find specific responses against myelin-antigen-derived peptides. The association of primary oligodendrocyte damage with secondary expansions of pathogenic cells underlines the role of adaptive immune reactions in neurodegenerative and neuroinflammatory diseases.

Circulating levels of cytokines (IL-6 and IL-1beta) in patients with intermittent claudication, at rest, after maximal exercise treadmill test and during restore phase. Could they be progression markers of the disease?

AIM: Inflammation is considered to be one of the main mechanisms for the development and progression of peripheral arterial disease (PAD). Many studies have demonstrated that maximal exercise enhances the acute inflammatory response in claudicant patients, but no one has assessed the duration of this acute inflammatory activation. The aim of this study was to assess of the inflammatory pattern in claudicants and of the inflammatory response after maximal exercise and during the recovery from calf pain. METHODS: Eleven patients with moderate claudication (MC) (age: 60.5+/-5.8 years; body mass index [BMI]: 27.5+/-4.6; absolute claudication distance [ACD]: 165.4+/-38), 10 patients with severe claudication (SC) (age: 60.3+/-5 years; BMI: 27+/-4.5; ACD: 91+/-11.3) and 8 healthy subjects (age: 59.4+/-6.8; BMI: 28.7+/-4.16) underwent to maximal treadmill test (speed 2.5 km/h, slope 15%). At rest, just after stop of the exercise (appearance of calf pain in patients, and 6 min of treadmill in controls) the circulating levels of interleukin (IL)-1beta and IL-6 have been measured. STATISTICAL ANALYSIS: variance of mean values, Bonferroni t-test, split plot variance model, variance of d stop-before and stop-recovery have been utilized. P<0.05 has been considered the significant cut-off of the differences. RESULTS: The maximal exercise excited significant (P<0.01) inflammatory activation in all patients: MC (rest IL-1beta: 1.55, 3.3 at stop; rest IL-6: 5.97, 8.38 at the stop); SC (rest IL-1beta: 2.97, 5.72 at stop; rest IL-6: 6.98, 9.99 at the stop). During recovery, MC showed a reduction of the inflammatory activation, whilst SC showed further increase (IL-1beta: 7.55; IL-6: 11.94). CONCLUSION: The study confirms the higher inflammatory activation in claudicants and its enhancement after maximal exercise. During recovery, we found two kinds of response: type 1 (controls and MC), in which inflammation subsides, and type 2 (SC) characterized by further inflammatory increase. This trend is not univocal: 3 MC showed a type 2 response and 2 SC showed a type 1. In conclusion, inflammatory activation may depend not only on the degree of endothelial damage, but also on the individual inflammatory attitude, better assessed after maximal exercise than baseline values. This individual inflammatory responsiveness, considering the role of the rest measurement of markers of inflammation recently discussed, could be a useful marker for aggressive PAD.

Acute impairment of the endothelial function by maximal treadmill exercise in patients with intermittent claudication, and its improvement after supervised physical training.

AIM: The aim of this study was to determine the effects of maximal exercise and of physical training on endothelial function (EF) of patients with intermittent claudication (IC). METHODS: EF, assessed by ultrasonography of the brachial artery, has been measured in 22 male patients with IC before (pre-exercise EF) and after (postexercise EF) maximal treadmill test. Absolute claudication distance (ACD) and ankle brachial index (ABI) have been measured too. The measurements have been repeated after 18 days (3 times weekly, for 6 weeks) of supervised physical training. RESULTS: Before training, the pre-exercise EF was 7.6+/-2.94 and postexercise EF 5.28+/-3.3 (-33.2%) (P<0.01). After training, the pre-exercise EF was 10.3+/-4.04, whilst postexercise EF was 7.79+/-2.56 (-18.97%) (P<0.01). The differences between the pre-exercise value before and after training and between the postexercise value before and after training were significant (P<0.01). ACD and ABI after training increased respectively from 93.95 to 166.55 m and from 0.67 to 0.71 (P<0.001). CONCLUSIONS: Endothelial dysfunction takes a relevant part in the pathophysiology of IC, with 2/3 of the patients showing an EF lower than the pathological cut-off. Maximal exercise worsens the EF, according to the trend associated with the acute inflammatory response. All these features suggest that physical activity in IC should not utilize the maximal working load, in order to avoid the high inflammatory activation and the acute complications of atherosclerotic plaque. The supervised physical training, besides confirming itself as the most effective means to increase the walking ability, also proved to be able to improve the EF of these patients, as described about other diseases. It is probable that moderate hemodynamic stress reduces the levels of the inflammatory markers and increases the flow-mediated vasodilation through an ischemic preconditioning. The increased walking ability, associated with the improvement of EF could improve the heavy systemic outcome of claudicant patients, as it has been demonstrated in patients with coronary heart disease. Further prospective survival studies on cardiovascular outcomes of trained claudicant patients are needed.

Effects of elastic stocking on quality of life of patients with chronic venous insufficiency. An Italian pilot study on Triveneto Region.

AIM: Even though compression therapy is the most recommended treatment for chronic venous insufficiency (CVI) in the national and international guidelines, its application, at least in Italy, is lower than the estimated need from the prevalence of CVI in the epidemiological studies. Since we believe that the measurement of the impact of compression therapy on quality of life (QoL) could improve the compliance for this precious treatment, we carried out this study on 50 patients with CVI. METHODS: Fifty patients (23 CEAP C2 and 27 C(3-4-5), selected within a larger study on QoL in CVI), received a prescription for compression therapy. Before treatment and 4 months afterwards, the patients received the instrument for QoL assessment (MOS SF-36; CIVIQ-2; Euro-QoL 5D and a visual analogue scale). The score scales have been adjusted to poorest QoL as 0 and best QoL as 100. RESULTS: Baseline QoL of patients in class C2 did not show significant difference with the healthy Italian Population, except for the physical role item. The patients in class C(3-4-5) showed significant reduction of QoL. After 4 months all the items of the utilized instrument showed significant improvement (from P<0.01 to P<0.04 for SF-36; from P<0.099 to P<0.006 for other instruments) in all CEAP classes. CONCLUSIONS: The study unquestionably shows that the compression therapy improves the QoL of patients with CVI, and should be included in the CVI treatment covered by the Public National Health Insurance. Finally, the QoL measurement could be utilized as the scientific method to assess the effectiveness and efficacy of different therapeutic devices.