Tick saliva inhibits the chemotactic function of MIP-1 alpha and selectively impairs chemotaxis of immature dendritic cells by down-regulating cell-surface CCR5

Ticks are blood-feeding arthropods that secrete immunomodulatory molecules through their saliva to antagonize host inflammatory and immune responses. As dendritic cells (DCs) play a major role in host immune responses, we studied the effects of Rhipicephalus sanguineus tick saliva on DC migration and function. Bone marrow-derived immature DCs pre-exposed to tick saliva showed reduced migration towards macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and regulated upon activation, normal T cell expressed and secreted (RANTES) chemokines in a Boyden microchamber assay. This inhibition was mediated by saliva which significantly reduced the percentage and the average cell-surface expression of CC chemokine receptor CCR5. In contrast, saliva did not alter migration of DCs towards MIP-3 beta, not even if the cells were induced for maturation. Next, we evaluated the effect of tick saliva on the activity of chemokines related to DC migration and showed that tick saliva per se inhibits the chemotactic function of MIP-1 alpha, while it did not affect RANTES, MIP-1 beta and MIP-3 beta. These data suggest that saliva possibly reduces immature DC migration, while mature DC chemotaxis remains unaffected. In support of this, we have analyzed the percentage of DCs on mice 48 h after intradermal inoculation with saliva and found that the DC turnover in the skin was reduced compared with controls. Finally, to test the biological activity of the saliva-exposed DCs, we transferred DCs pre-cultured with saliva and loaded with the keyhole limpet haemocyanin (KLH) antigen to mice and measured their capacity to induce specific T cell cytokines. Data showed that saliva reduced the synthesis of both T helper (Th)1 and Th2 cytokines, suggesting the induction of a non-polarised T cell response. These findings propose that the inhibition of DCs migratory ability and function may be a relevant mechanism used by ticks to subvert the immune response of the host. (c) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

The effect of additional strengthening of hip abductor and lateral rotator muscles in patellofemoral pain syndrome: a randomized controlled pilot study

Objectives: To study the effect of additional strengthening of hip abductor and lateral rotator muscles in a strengthening quadriceps exercise rehabilitation programme for patients with the patellofemoral pain syndrome. Design: Randomized controlled pilot trial. Setting: Clinical setting with home programme. Participants: Fourteen patients with patellofemoral pain syndrome. Intervention: The subjects were randomly assigned to the intervention group (strengthening of quadriceps plus strengthening of hip abductor and lateral rotator muscles) or to the control group (strengthening of quadriceps). Both groups participated in a six-week home exercise protocol. Main outcome measures: The perceived pain symptoms, isokinetic eccentric knee extensor, hip abductor and lateral rotator torques and the gluteus medius electromyographic activity were assessed before and after treatment. Parametric and non-parametric tests were used to compare the groups before and after treatment with alpha = 0.05. Results: Only the intervention group improved perceived pain symptoms during functional activities (P=0.02-0.04) and also increased their gluteus medius electromyographic activity during isometric voluntary contraction (P=0.03), Eccentric knee extensors torque increased in both groups (P=0.04 and P=0.02). There was no statistically significant difference in the hip muscles torque in either group. Conclusion: Supplementation of strengthening of hip abductor and lateral rotator muscles in a strengthening quadriceps exercise programme provided additional benefits with respect to the perceived pain symptoms during functional activities in patients with patellofemoral pain syndrome after six weeks of treatment.

One-time signature scheme from syndrome decoding over generic error-correcting codes

We describe a one-time signature scheme based on the hardness of the syndrome decoding problem, and prove it secure in the random oracle model. Our proposal can be instantiated on general linear error correcting codes, rather than restricted families like alternant codes for which a decoding trapdoor is known to exist. (C) 2010 Elsevier Inc. All rights reserved,

Molecular Identification and Phylogenetic Analysis of a Group 16SrI-B Phytoplasma Associated with Sugarcane Yellow Leaf Syndrome in Brazil

Yellow leaf syndrome was a serious problem in the beginning of the 1990s in Brazil, when yield losses were estimated to be around 50%. The disease is currently endemic, but it is considered potentially important. Previous studies have revealed only the presence of a luteovirus associated with the disease in Brazil. We report that a phytoplasma of 16SrI-B is also associated with this disease. This is the first demonstration of the presence of a group 16SrI-B phytoplasma in association with sugarcane yellow leaf in Brazil.

Occurrence of phytoplasma associated with sugarcane yellow leaf syndrome in three regions of Sao Paulo State, Brazil

Sugarcane yellow leaf syndrome caused serious damage to crops in the Sao Paulo State, Brazil, in the 1990`s. The syndrome was also reported in other countries and investigations into the etiology revealed an association between the disease and virus and/or phytoplasma. The disease is potentially important and occurs endemically in that State, and for this reason the present study was conducted in order to demonstrate the occurrence of phytoplasma in three traditional sugarcane-producing areas, in Sao Paulo State, through molecular detection From naturally infected plants. Symptomatic plants belonging to varieties SP71-6163, SP71-6180 and SP89-1115 were sampled from Piracicaba, Jau and Ribeirao Preto, and total DNA was extracted from foliar tissues. Nested PCR was conducted with primer pairs P1/ Tint-16F2n/R2, and the amplified products were analyzed by electrophoresis on agarose gels. Amplified DNA fragments of 1.2 kb evidenced the presence of phytoplasma in 36% of symptomatic plants and revealed its Occurrence in all sampled regions. The results demonstrated that phytoplasma is associated with the disease and that it is important to keep a safe inspection of nurseries and monitoring plants in the field, as well as to Select Sugarcane genotypes with a good level of resistance in breeding programs.

Biomarkers of metabolic syndrome and its relationship with the zinc nutritional status in obese women

Introduction: Obesity is a chronic disease that induces risk factors for metabolic syndrome and, is associated with disturbances in the metabolism of the zinc. Therefore, the aim of this study was to investigate the existence of relationship between the biomarkers of metabolic syndrome and the zinc nutricional status in obese women. Method: Seventy-three premenopausal women, aged between 20 and 50 years, were divided into two groups: case group, composed of obese (n = 37) and control group, composed of no obese (n = 36). The assessment of the body mass index and waist circumference were carried out using anthropometric measurements. The plasmatic and erythrocytary zinc were analyzed by method atomic absorption spectrophotometry (lambda=213.9 nm). Results: In the study, body mass index and waist circumference were higher in obese women than control group (p < 0.05). The mean plasmatic zinc was 72.2 +/- 9.0 mu g/dl in obese women and 73.4 +/- 8.5 mu g/dl in control group (p > 0.05). The mean erythrocytary zinc was 36.4 +/- 15.0 mu g/gHb and 45.4 +/- 14.3 mu g/gHb in the obese and controls, respectively (p < 0.05). Regression analysis showed that the body mass index (t=-2.85) and waist circumference (t=-2.37) have a negative relationship only with the erythrocytary zinc (R(2)=0.32, p < 0.05). Conclusions: The study shows that there are alterations in biochemical parameters of zinc in obese women, with low zinc concentrations in erythrocytes. Regression analysis demonstrates that the erythrocytary zinc is influenced by biomarkers of the metabolic syndrome, presenting an inverse relationship with the waist circumference and body mass index.

Time course proteomic profiling of human myocardial infarction plasma samples: An approach to new biomarker discovery

Background: The aim of this study was to identify novel candidate biomarker proteins differentially expressed in the plasma of patients with early stage acute myocardial infarction (AMI) using SELDI-TOF-MS as a high throughput screening technology. Methods: Ten individuals with recent acute ischemic-type chest pain (< 12 h duration) and ST-segment elevation AMI (1STEMI) and after a second AMI (2STEMI) were selected. Blood samples were drawn at six times after STEMI diagnosis. The first stage (T(0)) was in Emergency Unit before receiving any medication, the second was just after primary angioplasty (T(2)), and the next four stages occurred at 12 h intervals after T(0). Individuals (n = 7) with similar risk factors for cardiovascular disease and normal ergometric test were selected as a control group (CG). Plasma proteomic profiling analysis was performed using the top-down (i.e. intact proteins) SELDI-TOF-MS, after processing in a Multiple Affinity Removal Spin Cartridge System (Agilent). Results: Compared with the CG, the 1STEMI group exhibited 510 differentially expressed protein peaks in the first 48 h after the AMI (p < 0.05). The 2STEMI group, had similar to 85% fewer differently expressed protein peaks than those without previous history of AMI (76, p < 0.05). Among the 16 differentially-regulated protein peaks common to both STEMI cohorts (compared with the CG at T(0)), 6 peaks were persistently down-regulated at more than one time-stage, and also were inversed correlated with serum protein markers (cTnI, CK and CKMB) during 48 h-period after IAM. Conclusions: Proteomic analysis by SELDI-TOF-MS technology combined with bioinformatics tools demonstrated differential expression during a 48 h time course suggests a potential role of some of these proteins as biomarkers for the very early stages of AMI, as well as for monitoring early cardiac ischemic recovery. (C) 2011 Elsevier B.V. All rights reserved.

Effects of margarines and butter consumption on lipid profiles, inflammation markers and lipid transfer to HDL particles in free-living subjects with the metabolic syndrome

Objective: Our purpose was to examine the effects of daily servings of butter, no-trans-fat margarine and plant sterol margarine, within recommended amounts, on plasma lipids, apolipoproteins (Apos), biomarkers of inflammation and endothelial dysfunction, and on the transfer of lipids to HDL particles in free-living subjects with the metabolic syndrome. Methods: This was a randomized, single-blind study where 53 metabolic syndrome subjects (62% women, mean age 54 years) received isocaloric servings of butter, no-trans-fat margarine or plant sterol margarine in addition to their usual diets for 5 weeks. The main outcome measures were plasma lipids, Apo, inflammatory and endothelial dysfunction markers (CRP, IL-6, CD40L or E-selectin), small dense LDL cholesterol concentrations and in vitro radioactive lipid transfer from cholesterol-rich emulsions to HDL. Difference among groups was evaluated by analysis of variance. Results: There was a significant reduction in Apo-B (-10.4 %, P = 0.043) and in the Apo-B/Apo-A-1 ratio (-11.1%, P = 0.034) with plant sterol margarine. No changes in plasma lipids were noticed with butter and no-trans-fat margarine. Transfer rates of lipids to HDL were reduced in the no-trans-fat margarine group: triglycerides -42.0%, (P<0.001 vs butter and sterol margarine) and free cholesterol -16.2% (P = 0.006 vs sterol margarine). No significant effects were noted on the concentrations of inflammatory and endothelial dysfunction markers among the groups. Conclusions: In free-living subjects with the metabolic syndrome consumption of plant sterol and no-trans-fat margarines within recommended amounts reduced, respectively, Apo-B concentrations and the ability of HDL to accept lipids. European Journal of Clinical Nutrition (2010) 64, 1141-1149; doi:10.1038/ejcn.2010.122; published online 21 July 2010

Auditory processing disorder in perisylvian syndrome

We hypothesized that the processing of auditory information by the perisylvian polymicrogyric cortex may be different from the normal cortex. To characterize the auditory processing in bilateral perisylvian syndrome, we examined ten patients with perisylvian polymicrogyria (Group 1) and seven control children (Group 11). Group I was composed by four children with bilateral perisylvian polymicrogyria and six children with bilateral posterior perisylvian polymicrogyria. The evaluation included neurological and neuroimaging investigation, intellectual quotient and audiological assessment (audiometry and behavior auditory tests). The results revealed a statistically significant difference between the groups in the behavioral auditory tests, Such as, digits dichotic test, nonverbal dichotic test (specifically in right attention), and random gap detection/random gap detection expanded tests. Our data showed abnormalities in the auditory processing of children with perisylvian polymicrogyria, suggesting that perisylvian polymicrogyric cortex is functionally abnormal. We also found a correlation between the severity of our auditory findings and the extent of the cortical abnormality. (C) 2009 Elsevier B.V. All rights reserved.

Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome

The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. Metformin pharmacokinetic parameters were: t(A1/2), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.

von Wright`s Therapy to Jorgensen`s Syndrome

In his last papers about deontic logic, von Wright sustained that there is no genuine logic of norms. We argue in this paper that this striking statement by the father of deontic logic should not be understood as a death sentence to the subject. Rather, it indicates a profound change in von Wright`s understanding about the epistemic and ontological role of logic in the field of norms. Instead of a logical constructivism of deontic systems revealing a necessary structure of prescriptive discourse, which marked his earlier efforts, he adopted the view that such systems should be seem as mere objects of comparison, i.e. as providing practical standards of rationality for norm-giving activity. Within such view he proposed an interpretation of standard deontic logic in such a way to free deontic logicians from the philosophical difficulties related to the so-called Jorgensen`s dilemma and deontic paradoxes. This effort, as we claim in the present paper, is an application of Wittgenstein`s therapeutic method to dissolve philosophical difficulties caused by the use of logical tools to model relations between norms.

Longitudinal excursion and strain in the median nerve during novel nerve gliding exercises for carpal tunnel syndrome

Nerve and tendon gliding exercises are advocated in the conservative and postoperative management of carpal tunnel syndrome (CTS). However, traditionally advocated exercises elongate the nerve bedding substantially, which may induce a potentially deleterious strain in the median nerve with the risk of symptom exacerbation in some patients and reduced benefits from nerve gliding. This study aimed to evaluate various nerve gliding exercises, including novel techniques that aim to slide the nerve through the carpal tunnel while minimizing strain (sliding techniques). With these sliding techniques, it is assumed that an increase in nerve strain due to nerve bed elongation at one joint (e.g., wrist extension) is simultaneously counterbalanced by a decrease in nerve bed length at an adjacent joint (e.g., elbow flexion). Excursion and strain in the median nerve at the wrist were measured with a digital calliper and miniature strain gauge in six human cadavers during six mobilization techniques. The sliding technique resulted in an excursion of 12.4 mm, which was 30% larger than any other technique (p 0.0002). Strain also differed between techniques (p 0.00001), with minimal peak values for the sliding technique. Nerve gliding associated with wrist movements can be considerably increased and nerve strain substantially reduced by simultaneously moving neighboring joints. These novel nerve sliding techniques are biologically plausible exercises for CTS that deserve further clinical evaluation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:972-980, 2007

Familial partial epilepsy with variable foci: A new partial epilepsy syndrome with suggestion of linkage to chromosome 2

Familial partial epilepsy with variable foci (FPEVF) joins the recently recognized group of inherited partial epilepsies. We describe an Australian family with 10 individuals with partial seizures over four generations. Detailed electroclinical studies were performed on all affected and 17 clinically unaffected family members. The striking finding was that the clinical features of the seizures and interictal electroencephalographic foci differed among family members and included frontal, temporal, occipital, and centroparietal seizures. Mean age of seizure onset was 13 years (range, 0.75-43 years). Two individuals without seizures had epileptiform abnormalities on electroencephalographic studies. Penetrance of seizures was 62%. A genome-wide search failed to demonstrate definitive linkage, but a suggestion of linkage was found on chromosome 2q with a LOD score of 2.74 at recombination fraction of zero with the marker D2S133. FPEVF differs from the other inherited partial epilepsies where partial seizures in different family members are clinically similar. The inherited nature of this new syndrome may be overlooked because of relatively low penetrance and because of the variability in age at onset and electroclinical features between affected family members.

STD syndrome packets: Improving syndromic management of sexually transmitted diseases in developing countries

Objective: To design, introduce, and evaluate STD syndrome packets containing recommended drugs for each syndrome, four condoms, a partner treatment card, and a patient information leaflet, with the goal of improving sexually transmitted disease (STD) case management. Methods: Packet design evolved around available packaging technology, informed by pilot testing with nurses working in primary care clinics, doctors in private medical practices, and patients with an STD, in Hlabisa, South Africa. Evaluation 1 year later included analysis of distribution records and interviews with 16 nurses and 61 patients. Results: A cheap packet (2 U, S, cents each, excluding contents) compatible with current legislation was designed and introduced to six public sector clinics and as a short pilot to five private medical practices, Four thousand eighty-five packets were distributed to the clinics, equivalent to approximately 115% of the STDs reported over that period. All 16 nurses reported using the packets, but only 63% did so all the time because of occasional supply problems, All believed the packets improved treatment by saving time (75%), improving supply of condoms and partner cards (44%), and making treatment easier (56%), Patients also responded positively, and most said they would buy a packet (up to $5) at a pharmacy (84%) or store (63%) if available. Conclusions: The STD syndrome packets have the potential to improve STD syndromic management by standardizing therapy and improving the supply of condoms, partner cards, and information leaflets. Packets are popular with practitioners and patients, but consistent supply is essential for maximal impact, There may be scope for social marketing of the packets, which could further increase use.