Effect of ferric citrate on amyloid-beta peptides behavior.

Amyloid beta (Aß) aggregation and oxidative stress are two of the central events in Alzheimer's Disease (AD). Both these phenomena can be caused by the interaction of Aß with metal ions. In the last years the interaction between ZnII , CuII , and Aß was much studied, but between iron and Aß it is still little known. In this work we determine how three Aß peptides, present in AD, interact with FeIII -citrate. The three Aß peptides are: full length Aß1-42, an isoform truncated at Glutamic acid in position three, Aß3-42, and its pyroglutamated form AßpE3-42. Conformation and morphology of the three peptides, aggregated with and without FeIII -citrate were studied. Besides, we have determined the strength of the interactions Aß/FeIII -citrate studying the effect of ethylenediaminetetraacetic acid as chelator. Results reported here demonstrate that FeIII -citrate promotes the aggregation in all the three peptides. Moreover, Aspartic acid 1, Glutamic acid 3, and Tyrosine 10 have an important role in the coordination with iron, generating a more stable complex for Aß1-42 compared to that for the truncated peptides.

Effectiveness of occupational safety and health training for migrant farmworkers: a scoping review.

OBJECTIVES: Migrant farmworkers report higher rates of work-related illnesses, injuries and fatalities compared with local workers. Language and cultural barriers represent a relevant source of risk, which can be reduced by means of targeted training interventions. However, very little evidence is available about the effectiveness of Occupational Safety and Health (OSH) training programmes addressing migrant farmworkers. STUDY DESIGN: We carried out a scoping review. METHODS: Currently available literature about the effectiveness of OSH training for migrant farmworkers-in terms of improvements in at least one of the following: safety knowledge, behaviours, attitudes and beliefs and health outcomes-was searched from four databases: PubMed, PsycINFO, Scopus and Web of Science. The screening was performed independently by two authors, and any disagreement was resolved through discussion until consensus was achieved. Once the articles eligible for inclusion were selected, the objectives, design, sample and setting, interventions and findings of each study were recorded. No quality assessment tool for publications considered by this study has been used because a scoping review does not aim for critical appraisal. RESULTS: Twenty-nine publications met the inclusion criteria. Of these, nine cross-sectional studies discussed the effectiveness of training activities in terms of whether participating in any programme had or did not have a significant effect on the dependent variables, when training was considered along with other sociodemographic factors. In the majority of these studies, training appeared to have low or no effect on the dependent variables considered. Twenty mainly within-subject experimental studies addressed the effectiveness of specific training methods, reporting significant improvements especially for interventions based on a participatory approach. CONCLUSIONS: Training could greatly contribute to an effective attainment of OSH information, but the present review shows that more evidence is needed to guide the future development of effective training activities.

Bleeding versus thrombosis: role of short DAPT in complex lesions.

Therapy with dual antiplatelet agents, defined as the combination of a platelet P2Y12 inhibitor and aspirin, is required to prevent thrombotic complications, after percutaneous coronary intervention (PCI) with stent implantation. Usually current guidelines recommend administration of dual antiplatelet therapy (DAPT) following percutaneous revascularization with drug-eluting stent (DES) for a period of at least 12 months or for 6 to 12 months in patients not at high risk. Nevertheless, the treatment of stable/unstable coronary artery disease with DES implantation increasing largely, the optimal duration of DAPT is still unclear. The duration of DAPT after coronary stenting has been evaluated in recent randomized studies with conflicting results. The administration of long period of DAPT is a strategy to reduce thrombosis events but largely increase the hemorrhagic ones. Otherwise, shorter DAPT period is protective about bleeds with consequently increased ischemic events. In addition, as new DES carry a lower risk of stent thrombosis (ST) compared with the first-generation DES and possibly even bare-metal stents, a shift toward better protection from ST may have an effect on the duration and the intensity of DAPT. Whether the duration of DAPT should be shorter or longer than the currently recommended 6 to 12 months is analyzed in this review, drawing on results from the most recent studies and meta-analysis.

Operators' perception of comfort in two tractor cabs.

Workspace characteristics affect the perceived comfort level of the operator and uncomfortable working conditions have been found to have a negative impact on productivity and safety. The comfort of the operator is increasingly recognized by manufacturers as a product's added value. Comfort can positively distinguish a product and increase its competitiveness. The concept of comfort is controversial, and a clear operational definition is missing. Nevertheless, it is widely accepted that comfort is a subjective phenomenon that can be evaluated by the final users. In this study, comfort aspects of the tractor workspace interior (i.e., the cab) were investigated. Users with various levels of expertise and two medium-power utility tractors of different brands were used in a 2 x 2 mixed-factorial experimental design. Participants were involved in a dynamic assessment of the cabs, and their opinions about the different workspaces were collected through a questionnaire. Additionally, objective measurements were taken on both tractors, and subjective data were compared with objective data. Results indicate significant differences in terms of the ease of locating and operating the controls (i.e., rear-mounted three-point linkage, hydraulic system, and power take-off), the ease of starting the tractor, the ease exiting the cab, the required level of concentration in executing the tasks, the adequacy of lateral visibility from the driving station, and the level of noise at the operator's position. This article provides guidance for improving the comfort of tractor workspace interiors. Agricultural machinery manufactures would benefit from research results, differentiating themselves from competitors.

Lower serum lipid levels are related to respiratory impairment in patients with ALS.

BACKGROUND: Recently hyperlipidemia was reported to be related to a significantly better outcome in amyotrophic lateral sclerosis (ALS). To investigate this, we evaluated the status of blood lipids in a large Italian series of patients with ALS, and assessed the effect of hyperlipidemia on patients' survival. METHODS: The study population included 658 patients with ALS consecutively observed in 2 Italian ALS centers between 2000 and 2006. They were compared to a series of 658 healthy subjects, matched by age and gender. RESULTS: The mean levels of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the LDL/HDL ratio were similar in patients with ALS and controls. Total cholesterol, HDL, triglyceride, and LDL/HDL ratio levels showed a significant decrease in patients with forced vital capacity <70% compared to those with FVC >or=90%. For each level of ALS-FRS, poorer respiratory function was related to a lower LDL/HDL ratio. Univariate survival analysis did not find any significant effect of LDL/HDL ratio on survival, either when comparing patients with ratios 2.99 or patients in the first quartile of LDL/HDL ratio (2.79). No dose-response was found for LDL/HDL ratio subdividing patients into 5 quintiles. CONCLUSION: Our findings do not support the observation that patients with amyotrophic lateral sclerosis have hyperlipidemia or that hyperlipidemia in this population is related to longer survival. However, some evidence emerged that respiratory impairment, but not a worse clinical status or a lower body mass index, is related to a decrease in blood lipids and LDL/HDL ratio.

Anxiety undermines quality of life in ALS patients and caregivers.

BACKGROUND: Although depression has been widely studied in amyotrophic lateral sclerosis (ALS), there is little information on anxiety. OBJECTIVE: To detect anxiety in patients with ALS and their caregivers, comparing the diagnostic and the follow-up phases of the disease and assessing its impact on quality of life (QoL). METHODS: Anxiety has been evaluated with the State and Trait Anxiety Inventory in a series of 75 consecutive ALS patients and their primary caregivers. Anxiety has been related to depression, QoL, and satisfaction with life. RESULTS: In patients, state anxiety was significantly higher during the diagnostic phase, whilst in caregivers it was similar in the two phases. Patients' state anxiety was related to depression, shorter disease duration and lower satisfaction with life. Caregivers' state anxiety was related to their trait anxiety. Whilst in patients QoL and satisfaction with life were similar in the two phases, in caregivers there was a significant decrease of satisfaction with life in the follow-up phase. CONCLUSIONS: Treating neurologists should recognize that the diagnostic phase and the earlier period after the diagnosis is characterized by a high level of anxiety both in ALS patients and in their caregivers, and should propose pharmacological and psychological interventions to relieve this highly distressing disturbance.

ALS patients and caregivers communication preferences and information seeking behaviour.

To evaluate information preferences and information seeking behaviour in ALS patients and caregivers. Sixty ALS patients and caregivers couples were interviewed using a structured questionnaire about the content of diagnosis communication and their information seeking behaviour. The patients (35 men and 25 women) had a mean age of 63.4 years (SD 9.5). The caregivers (21 men and 39 women) had a mean age of 53.3 years (SD 14.9). The overall satisfaction with bad news communication and the impression that the physician had understood their feelings were higher amongst patients. Both parties indicated that the most important aspects to be informed were current researches, disease-modifying therapies and ALS outcome. Approximately 55% of patients and 83.3% of caregivers searched for information from sources outside the healthcare system. The most frequently checked source was internet, although its reliability was rated low. The caring neurologist should better attune the content of communication to patients' and caregivers' preferences, trying to understand what they want to know and encouraging them to make precise questions. Health professionals should be aware that ALS patients and caregivers often use internet to obtain information and should help them to better sort-out and interpret the news they found.

A longitudinal study on quality of life and depression in ALS patient-caregiver couples.

OBJECTIVES: To evaluate the modification of quality of life (QoL) and depression in a series of amyotrophic lateral sclerosis (ALS) patient-caregiver couples during a period of 9 months and compare them to patients' ALS Functional Rating Scale (ALS-FRS). METHODS: Depression was assessed with Zung Depression Scale (ZDS) and QoL with McGill Quality of Life Questionnaire (MQoL). Caregivers' burden was assessed with Caregiver Burden Inventory (CBI), and patients' feeling to be a burden with the Self-Perceived Burden Scale (SPBS). RESULTS: Thirty-one ALS patient-caregiver couples were interviewed at baseline and after 9 months. The mean ALS-FRS score was 28.7 (SD 7) at baseline and 24.1 (6.9) at the second interview (p = 0.0001). Patients' mean MQoL score slightly increased from 6.8 (1.6) to 7 (1.1) (p = 0.07); their ZDS score slightly increased (43.2 [8.7] at baseline and 45.7 [9.3] at the second interview) but they remained in the not depressed range. Caregivers' mean MQoL score slightly decreased, and their mean ZDS increased from 38.9 (8.1) to 42.2 (8.7) (p = 0.02). The mean CBI score increased from 50.3 (17.6) to 55.8 (16.4) (p = 0.03). CONCLUSIONS: We found a substantial steadiness of quality of life and depression in patients with amyotrophic lateral sclerosis over a 9-month period, vs a significant increase of burden and depression of their caregivers.

Caregiver time use in ALS.

The authors evaluated the caregiver time for 70 patients with ALS. The mean number of caregivers per patient was 2.0 (SD 1.3). Caregiver time increased with worsening of disability (p = 0.0001). The most time-consuming duties were housekeeping, feeding, and toileting. With worsening of patients' disability, families relied increasingly on paid caregivers. Caregiver time is a hidden cost of ALS care and is a major burden for caregivers.

[The problem of the chronic recurrent pain among older in-patients]. / Il problema del dolore cronico ricorrente negli anziani in ospedale.

Epidemiological data of pain prevalence, with particular attention to hospitalised subjects, are described as well as the problems of pain detection, its evaluation and management in older patients. The authors underline that chronic pain is the most frequent type of pain in advanced age, and it is often unrecognized and undertreated. Advanced age is not a sufficient reason to exclude an analgesic treatment which could improve the quality of life of these subjects. Elderly persons are at increased risk for adverse drug reactions, on the other hand, there is evidence that an appropriate use of analgesic drugs can provide significant relief and result in functional restoration, with a low risk of serious adverse effects. In the medical literature there are strategies and guidelines ad hoc. In Italy, since 2001 there is a plan drawn up by the Department of Health containing indications to fight against pain in hospital, but the adhesion of a number of hospitals to this plan seems to be not optimal.

Adhesion molecules in gonarthrosis and knee prosthesis aseptic loosening follow-up: possible therapeutic implications.

The involvement of the synovium is common in phlogistic processes of various joint diseases. Apart from synoviocytes and the other cells in the synovial tissue, circulating cells recruited from peripheral blood also participate in the phlogistic process. The increased expression of adhesion molecules on both circulating and endothelial cell surface may further this recruitment. We studied 15 patients affected by serious gonarthrosis requiring a prosthetic implant (GPI) and 7 with knee prosthesis aseptic loosening (KPL) to evaluate adhesion molecule expression and phlogistic infiltration in the synovium using immunohistochemistry and microscopic analysis. As control we studied 10 subjects affected by degenerative meniscopathies undergoing a selective arthroscopic surgical meniscectomy. Analysis with Kruskal-Wallis test showed no statistical significant differences in the expression of CD54, CD11a, CD11b and CD18 in three groups examined. The model of variance analysis (Friedman test), showed that CD54 expression is greater in patients with GPI and KPL in comparison with the other molecules. Adhesion molecules and their functions are important in arthropathies not only because their evaluation can allow us to identify the degree of inflammation and to predict its evolution, but also because pharmacological control of their expression could have important therapeutic implications.

Reactivity to autologous serum skin test and clinical features in chronic idiopathic urticaria.

The autologous-serum skin test (ASST) can cause a wheal-and-flare response in some cases of chronic idiopathic urticaria. We subjected 102 patients affected by chronic idiopathic urticaria to this test and studied some clinical parameters to detect any significant differences between ASST-positive and ASST-negative patients. The only significant difference we noted between the two groups was the incidence of angioedema (P = 0.01). We suggest that the ASST cannot be used alone either to predict the severity of urticaria or to define it as 'autoimmune'.

Cyclosporin A in patients affected by chronic idiopathic urticaria: a therapeutic alternative.

Chronic Idiopathic Urticaria (CIU) is a cutaneous disorder for which there is no identifiable specific etiologic agent. Some recent evidences suggest that CIU might be an autoimmune disease. We analyzed immunological features occurring in CIU and evaluated effectiveness and tolerance of Cyclosporin A (CsA) treatment in patients unresponsive to antihistaminic treatment. Twenty patients with CIU were recruited after a selective diagnostic protocol and were divided into two groups. CsA was prescribed for group 1 and Prednisone for group 2 as control, for 8 weeks. Before and after the therapy we performed on all patients immunological studies. For all patients symptoms disappeared after a few days of therapy. Before therapy all patients showed activated B cells (CD19+CD23+ cells) and among B CD19+ cells, about 20% were CD5+ (cells that synthesize natural autoantibodies). After treatment with Prednisone in group 2, a significant reduction of CD4+ lymphocytes (p = 0,01) was observed. Our findings might support the CIU autoimmune pathogenetic hypothesis. The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and, at dosage used, side effects were rare, mild and reversible. Thus, CsA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments.

Resting metabolic rate, body composition and thyroid hormones. Short term effects of very low calorie diet.

27 obese women (relative body weight 191 +/- 27%), aged 35 +/- 11, underwent a 15 day very low calorie diet (VLCD: 1337 kJ/day). Mean body weight loss was 6 +/- 1.5 kg. Resting metabolic rate (RMR), measured by indirect calorimetry, showed a significant decrease both in absolute values (from 1793 +/- 225 to 1569 +/- 231 kcal/day; P less than 0.001), and in keal/kg body weight/day (from 17 +/- 2, to 16 +/- 2, P less than 0.001). Serum triiodothyronine (T3) significantly decreased from 1.1 +/- 0.2 to 1 +/- 0.2 microgram/1 (P less than 0.001). Before VLCD the differences between measured RMR and theoretical RMR (RMR-T) were not significant. After VLCD RMR values were significantly (P less than 0.001) lower than RMR-T. It was concluded that fat-free mass loss, combined with periferic thyroxin (T4) reduced monodeiodination in its more active form mainly due to low calorie intake T3 could be responsible for the important reduction observed in the resting metabolic rate.

Blood pressure, metabolic variables and adipose tissue distribution in pre- and post-menopausal women.

The study was performed on 289 female patients (aged 20-60) of a family doctor in Castel D'Azzano, a small town near Verona. The following variables were considered: body mass index (BMI), tricepital, subscapular, hypomesogastric, epimesogastric, supra-iliacal and epitrochanteric skinfolds, waist, umbilical and bitrochanteric circumferences, cholesterol, triglycerides, HDL-cholesterol, glycemia, uricemia and blood pressure. A significant worsening with age was observed in the mean values of the variables. This worsening was particularly evident in women over 50. The population was subdivided according to presence or absence of menopause; the two groups were then matched for age. None of the variables showed significant differences. Our results did not confirm any of the many effects that menopause is supposed to have regarding metabolic and blood pressure alterations.

Metformin enhances insulin binding to "in vitro" down regulated human fat cells.

Insulin binding to human adipose tissue from surgical patients was determined after three different preincubation conditions: a) 24 hrs in the presence or absence of 80 ng/ml insulin; b) 24 hrs in the presence of 80 ng/ml insulin or insulin plus 4 micrograms/ml metformin; c) 48 hrs pre-incubation as in b). We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant. We suggest that metformin can correct down regulation of the insulin receptor. This finding could explain discrepant results among studies dealing with the influence of metformin on insulin binding. Moreover, these results could be useful in understanding the mechanism of action of metformin in insulin-resistant states, e.g. type II diabetes.

Starvation-induced insulin resistance: influence on 3-O-methylglucose transport.

Starvation causes insulin resistance which is partly due to decrease of insulin action on glucose transport in target cells. Preliminary data from other authors suggest that starvation is associated with an increase of the time necessary for insulin to exert its maximum effect on glucose transport. In order to verify this finding, 3-O-methylglucose (3OMG) transport was studied in isolated rat adipocytes from starved and fed rats. The total intracellular space for 3OMG was not modified by 48h starvation. After 48h starvation, 3OMG transport into fat cells was less responsive to maximum insulin concentration than in controls: 33 +/- 2% (controls) vs 23 +/- 4% (starved) of total glucose space, p less than 0.05; the sensitivity to insulin was normal or even increased in comparison to controls: 50% of maximum effect was reached at 42 microU/ml insulin in controls and at 26 microU/ml insulin in starved animals. We could not find any effect of starvation on the time-response curves of insulin action.