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Accurate assessment of biomechanical risk associated with pushing/pulling tasks represents a challenging issue, especially in the health system where personnel are often required to maneuver beds and carts. Most studies in this field have been carried out in the laboratory, while few data have been collected under actual working conditions. This study aims to characterize the forces exerted during non-powered hospital bed maneuvering. Twenty participants were required to move a bed (equipped with a customized handlebar to measure exerted forces) along an actual hospital path including straight, turn and maneuver phases. The results show that higher forces are associated with the initial phase (peak and mean values 222 and 68 N) while the straight, turn and maneuvering phases required similar (lower) efforts. The combined effect of left, right and transversal forces suggests that the trunk of the operator might experience axial rotation, thus calling for further investigations of this aspect.

La detección de vasos anómalos a nivel intracraneal no es un hallazgo infrecuente y no siempre está asociada a la presencia de malformaciones arteriovenosas. Otras entidades como las conexiones arterioarteriales o un patrón flebítico también pueden presentarse como unos vasos en localización intracraneal anómala. El diagnóstico mediante pruebas no invasivas es importante para determinar la necesidad de realizar pruebas más cruentas como una angiografía cerebral por sustracción digital o para estimar el riesgo de sangrado en malformaciones arteriovenosas y, por tanto, evaluar la necesidad de tratamiento endovascular/quirúrgico. En este manuscrito presentamos un algoritmo de diagnóstico diferencial de la presencia de vasos anómalos intracraneales de acuerdo con su localización (intra/extraaxiales) y su funcionalidad (arterialización o no de dichos vasos). Asimismo, analizaremos los puntos importantes de la angioarquitectura de las principales malformaciones arteriovenosas con riesgo de sangrado intracraneal, como son las malformaciones arteriovenosas piales y las fístulas durales.

Background: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. Aim: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. Methods: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. Results: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1β, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. Conclusion: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk. Graphic abstract:

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p< 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

La terapia hormonal de afirmación de género con testosterona (GAHT, por sus siglas en inglés) permite, a las personas transgénero del espectro masculino, modificar las características sexuales secundarias del sexo asignado al nacer, aliviando así los síntomas de la disforia de género durante el proceso denominado transición. Sin embargo, se debe tener presente que se desconoce, en la actualidad, el efecto de la GAHT sobre la fertilidad a largo plazo, y el potencial efecto gonadotóxico de la misma. La demanda de un correcto asesoramiento reproductivo y la opción de realizar técnicas de preservación de la fertilidad (PF) han aumentado de forma exponencial en los últimos años, comportando cambios profundos en el manejo clínico de estas personas.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged ⩽55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes.

Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA1c. We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions.

To investigate depression, anxiety and cognitive impairment and their associations with clinical and socio-demographic variables in type 2 diabetes. The Zung Self-Rating Depression–Anxiety Scale and Mini-Mental State Examination (MMSE) were administered at baseline and after 4 years to 498 consecutive patients, 249 non-insulin treated (NIT) and 249 insulin treated (IT), aged 40–80 years. At baseline, IT patients were older, had longer disease duration, higher HbA1c and did more glucose monitoring (p< 0.001, all) but their depression scores were lower than among NIT (p= 0.006), with no differences for anxiety or MMSE. After 4 years, 72 patients were lost to the follow-up, of whom 18 had died. 41 NIT had switched to insulin and increased BMI (p= 0.004), blood pressure (p< 0.001), retinopathy severity (p= 0.03) and microalbuminuria (p= 0.0045), but did not change their scores for depression, anxiety or MMSE. The remaining 171 NIT improved fasting glucose (p= 0.006), total cholesterol (p< 0.0001), triglyceride (p= 0.0026) and HbA1c (p= 0.0006). Despite increased prevalence of microalbuminuria and retinopathy (p< 0.0001, both), depression (p= 0.04) and MMSE (p= 0.0007) improved. Foot ulcers (p= 0.03), retinopathy (p< 0001), microalbuminuria (p= 0.0047) and hypertension (p< 0.0001) increased in the remaining 214 IT patients, in whom depression (p= 0.0005) and anxiety (p< 0.0001) worsened while MMSE improved slightly (p= 0.0002). On multivariate analysis, depression was associated with being a woman and anxiety with diabetes duration and lower schooling, which also affected MMSE scores. Depression was associated with female gender and worsening complications but not modified by diabetes duration or switching to insulin therapy. Diabetes duration and lower schooling may affect anxiety and cognitive impairment.

Background and aims: To assess, in patients with Type 1 diabetes (T1 DM), the effects of adding a carbohydrate counting programme (CCP) to continuing education by Group Care on coping ability, quality of life (QoL), knowledge of diabetes, and metabolic control. Materials and methods: Out of 56 patients with T1 DM followed by Group Care, 27 were randomized to receive an 8-session CCP and 29 controls continued Group Care without a CCP. QoL, knowledge, and coping ability were assessed at baseline and after 30 months. Glycated hemoglobin (HbA1c), body weight, blood glucose, hypoglycemic episodes, and insulin dosages were checked every 3 months. Results: QoL improved (p<0.0001) in both CCP (88.7±9.2 vs78.0±9.9) and control patients (88.7±12.5 vs80.4±11.7). At the end of study, patients on CCP had better scores in knowledge [difference 0.72 (95% CI 0.44; 0.99), p<0.0001] and the 3 coping areas [problem solving: 1.75 (1.2; 2.3), p<0.0001; social support seeking: −1.4 (−2.3; −0.48) p<0.005; avoidance: −1.59 (−2.6; −0.56), p<0.005] than controls. All variables showed a greater, although not statistically significant, improvement in patients with poor schooling. At 30 months, HbA1cwas lower in the CCP patients than controls (7.2±0.9 vs7.9±1.4), p<0.05. There were no changes in insulin dosage, hypoglycemic episodes or blood lipids. Conclusions: This study confirms that Group Care improves QoL in people with T1 DM, but suggests that specific educational and psychological supports are needed to modify adaptation to the disease. The CCP we developed appears effective in promoting change, also in patients with poor schooling.

Aim: Central serotoninergic activity may modulate glucose metabolism vianeuroendocrine effectors. Group Care is a clinico-pedagogic intervention that improves metabolic control and quality of life in Type 2 diabetes through lifestyle modification and, possibly, central mechanisms. The hypothesis that central serotoninergic activity is modified in patients followed by Group Care was tested by measuring their hypothalamic-pituitary-adrenal response to citalopram, a selective serotonin reuptake inhibitor. Methods and subjects: Ten healthy controls and 17 non-obese, non-insulin-treated patients with Type 2 diabetes received, in random order, iv infusions of either 20 mg citalopram or saline. Nine patients had been long-term on Group Care and 8 had always been on traditional one-to-one care. Circulating glucose, insulin, ACTH, cortisol, DHEA, GH and PRL were measured every 15 min for 240 min. Differences between areas under the curves after citalopram and saline (Δ-AUC) were calculated. Results: Citalopram stimulated ACTH and cortisol secretion in healthy subjects (p=0.026 and p=0.011, respectively) and patients on Group Care (p=0.056 and p=0.038) but not in patients on traditional care. In healthy subjects, basal glucose correlated with growth hormone Δ- AUC (r=0.820; p=0.004) and inversely with insulin Δ-AUC (r=−0.822; p=0.003). The former correlation was preserved in the patients (r=0.637; p=0.026). Conclusions: Diabetes may blunt the response of the hypothalamic-pituitary-adrenal axis to citalopram, but this is preserved in patients followed by a long-term intervention model that improves clinical as well as cognitive and emotional variables.

Eighteen patients with severe and refractory Tourette syndrome (TS) underwent bilateral thalamic deep brain stimulation (DBS).

Background: Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid neoplasia that have lost radioiodine (131I) uptake with heterogeneous results. Aim: Retrospective analysis of the recovery rate of 1311 uptake after RA treatment in patients from 11 Spanish hospitals. Methods: Twenty-seven patients (14 men, 13 women) with papillary [21], follicular [4], and oncocytic [2] thyroid cancer initially treated with total thyroidectomy plus 131I, and with 131I negative metastatic disease, were given 13-cis RA (0.66–1.5 mg/kg for 5–12 weeks) followed by a therapeutic 131I dose (3700–7400 MBq); 3 months later thyroglobulin levels and computed tomography imaging were performed. Results: In 9 out 27 cases (33%) (8 papillary, 1 follicular) optimal positive 131I scan was observed after RA treatment; in the remaining 18, 10 had a suboptimal uptake (7 papillary, 2 follicular, 1 oncocytic) and in the rest there was no 131I uptake recovery (6 papillary, 1 follicular, 1 oncocytic). In 17 positive responses to RA (either optimal or suboptimal) in which image follow-up was available, decrease or stabilization of metastatic growth was observed in 7, while tumor mass increased at short term in the remaining 10. No major side effects were detected. Conclusion: Quite a high rate of 131I uptake recovery after RA treatment may be obtained in advanced differentiated thyroid cancer, but the potential modification of the natural course of the disease is uncertain. A better biological characterization of these tumors allowing the identification of potential responders to RA may improve the outcome of RA coadjuvant therapy.

Aim: To verify if Group Care, a model to manage Type 2 diabetes (T2DM) by systemic continuing group education, can be administered by nurses and dieticians under pedagogic guidance, and improve metabolic control, quality of life, Locus of Control, and insulin resistance. Material and subjects: Twenty-five patients with non-insulin-treated T2DM were randomized to Group Care and 24 to continued habitual individual care and education delivered by a diabetes specialist and pedagogist, respectively. Six nurses and 1 dietician received training by an accredited programme, a detailed operating manual and pedagogical supervision throughout the study. Follow-up was for 2 yr and included measurements of fasting blood glucose, glycated hemoglobin (HbA1c), body mass index, waist circumference, lipids, creatinine, blood pressure, serum insulin, homeostasis model assessment (HOMA) index of insulin resistance, health behaviors, quality of life, state and trait anxiety, and Locus of Control. Results: One patient on Group Care and 3 controls dropped out. At the end of study, the patients on Group Care had lower HbA1c (7.6± 0.8 vs 8.4± 1.3, p<0.05), insulin (18.0± 9.6 vs 24.3± 13.7, p<0.001), HOMA index (6.9± 5.4 vs 9.2± 6.6, p<0.05), and fatalistic attitude (17.2± 5.9 vs 24.9± 4.2, p<0.001) and better quality of life (65.0± 11.0 vs 78.4± 19.6, p<0.001) than controls. Conclusions: Group Care delivered by trained nurses and dietitan is associated with better outcomes than those obtained by a medically and pedagogically qualified team. It may offer a model for health operators to re-organize clinical practice and for patients to improve lifestyle and strengthen the therapeutic alliance with their carers.

Clinical and epidemiological studies on cancer etiology seldom treat coffee drinking as a potential effect modifier. Yet caffeine exerts significant effects upon a large variety of physiologic, cellular and molecular systems. Caffeine, ‘the world's most popular drug’, is also a fundamental research tool, widely used in clinical studies on drug metabolism, and in experimental studies on cell cycle checkpoints, DNA repair, and apoptosis, among many other. Caffeine can profoundly alter cell cycle checkpoint function and several mechanisms of DNA repair, as well as carcinogen metabolism. The impact of caffeine on cell cycle checkpoint function occurs in spite of it being nonmutagenic in traditional mutagenesis assays. A complex body of biologic evidence suggests that caffeine-containing beverages can both enhance and antagonise potentially carcinogenic exposures. However, most pathways leading to the ultimate effects in human beings remain unknown. It is unclear whether any of the hundreds of compounds contained in coffee and tea exert a direct and significant carcinogenic effect per sein any human tissue at usual conditions of use. Reasons exist to consider that coffee may sometimes be an indirect, positive confounder. The study of interactions between caffeine-containing beverages and environmental agents in well defined groups of healthy and diseased people could yield new insights into checkpoint signal transduction and other mechanisms of carcinogenesis. Information on the use of caffeine-containing beverages should more often be integrated in studies on the role of gene–environment interactions in the pathogenesis of cancer.

BACKGROUND: Hereditary factors have been reported in 5-10% of cases with exocrine pancreatic cancer and recent data support a role for BRCA2. AIMS: We have studied the prevalence of germline BRCA2 mutations in two groups of patients with exocrine pancreatic cancer from an unselected series in Spain: group A included 24 cases showing familial aggregation of cancer and group B included 54 age, sex, and hospital matched cases without such evidence. METHODS: Information was obtained by interview of patients and was validated by a telephone interview with a structured questionnaire. In patients from group A, >80% of the coding sequence of BRCA2 was analysed; in patients from group B, the regions in which germline BRCA2 mutations have been described to be associated with pancreatic cancer were screened. RESULTS: Telephone interviews led to reclassification of 7/54 cases (13%). Familial aggregation of cancer was found in 24/165 cases (14.5%); six patients had a first degree relative with pancreatic cancer (3.6%) and nine patients had relatives with breast cancer. Germline BRCA2 mutations were not identified in any patient from group A (0/23). Among group B cases, one germline variant (T5868G>Asn1880Lys) was found in a 59 year old male without a family history of cancer. The 6174delT mutation was not found in any of the 71 cases analysed. CONCLUSIONS: The overall prevalence of BRCA2 mutations among patients with pancreatic cancer in Spain is low and the 6174delT mutation appears to be very infrequent. Our data do not support screening patients with cancer of the pancreas for germline BRCA2 mutations to identify relatives at high risk of developing this tumour.

Abstract: We investigated the hypothesis that benfotiamine, a lipophilic derivative of thiamine, affects replication delay and generation of advanced glycosylation endproducts (AGE) in human umbilical vein endothelial cells cultured in the presence of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM) concentrations of D-glucose, with and without 150 μM thiamine or benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase activity. AGE generation after 20 days was assessed fluorimetrically. Cell replication was impaired by high glucose (72.3% ±5.1% of that in physiological glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%±2.4%, p=0.005) or benfotiamine (87.5%±89%, p=0.006), although it was not completely normalized (p=0.001 and p=0.008, respectively) to that in physiological glucose. Increased AGE production in high glucose (159.7%±38.9% of fluorescence in physiological glucose, p0.003) was reduced by thiamine (113.2%±16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%±49.8%, p=0.03 vs. high glucose alone) to levels similar to those observed in physiological glucose. Benfotiamine, a derivative of thiamine with better bioavailability, corrects defective replication and increased AGE generation in endothelial cells cultured in high glucose, to a similar extent as thiamine. These effects may result from normalization of accelerated glycolysis and the consequent decrease in metabolites that are extremely active in generating nonenzymatic protein glycation. The potential role of thiamine administration in the prevention or treatment of vascular complications of diabetes deserves further investigation.

Occupational exposures may increase the risk of exocrine pancreatic cancer. This study aimed to identify occupations that in Spain may be associated with such risk.

Ring networks are enjoying renewed interest as Storage Area Networks (SANs), i.e., networks for interconnecting storage devices (e.g., disk, disk arrays and tape drives) and storage data clients. This paper addresses the problem of fairness in ring networks with spatial reuse operating under dynamic traffic scenarios. To this end, in the first part of the paper the Max-Min fairness definition is extended to dynamic traffic scenarios and an algorithm for computing Max-Min fair rates in a dynamic environment is introduced. In the second part of the paper the extended Max-Min fairness definition is used as a measure to compare the performance in dynamic conditions of three fairness algorithms proposed for ring-based SANs. These algorithms are characterized by different fairness cycle sizes (number of links involved in each instance of the fairness algorithm), i.e., different complexity. The results show that the performance increases as the fairness cycle size decreases. In particular, the Global-cycle algorithm (implemented in the Serial Storage Architecture - SSA), whose cycle size is equal to the number N of links in the ring, exhibits the lowest performance, while the One-cycle algorithm, so called because of its cycle size equal to 1, has the best performance. The Variable-cycle algorithm, whose cycle size changes between 1 and N links, performs in between and provides the best tradeoff between performance and complexity.

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Diabetic eye disease remains a major cause of blindness in the world. Laser treatment for proliferative diabetic retinopathy and diabetic macular edema became available more than two decades ago. The outcome of treatment depends on the timing of laser treatment. The laser treatment is optimally delivered when high-risk characteristics have developed in proliferative retinopathy or diabetic macular edema and before this has significantly affected vision. Laser treatment is usually successful if applied during this optimal period whereas the treatment benefit falls sharply if the treatment is applied too late.

In order to optimize the timing of laser treatment in diabetic eye disease screening programs have been established. The oldest screening program is 20 years old and several programs have been established during the last decade. In this paper the organisation and methods of screening programs are described including direct and photographic screening. The incidence and prevalence of blindness is much lower in populations where screening for diabetic eye disease has been established compared to diabetic populations without screening. Technical advantages may allow increased efficiency and telescreening.

From a public health standpoint screening for diabetic eye disease is one of the most cost effective health procedures available. Diabetic eye disease can be prevented using existing technology and the cost involved is many times less than the cost of diabetic blindness.

Background: The aim was to analyse the magnitude, direction and predictors of change in the main hospital discharge diagnosis (HDD) after a clinical expert review, among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases. Methods: A total of 602 patients with a suspicion diagnosis of pancreas cancer (PC), cancer of the extrahepatic biliary system (CEBS) or benign biliopancreatic pathologies (BPP) were prospectively recruited at five general hospitals. A structured form was used to collect information from medical records. A panel of experts revised all diagnostic information and established the main clinico-pathological diagnosis (CPD) by consensus. Results: Of the 204 cases with a HDD of PC, 176 (86%) were deemed to have a CPD of PC, eight of CEBS, twelve a neoplasm of different origin, four BPP and four syndromic diagnoses. Thus, 28 cases (14%) were false positives. Of the 129 patients with a HDD of CEBS, 15 (12%) were false positives. Nine of the 396 cases with a HDD of non-PC (2%) had a CPD of PC (false negatives), whilst 14 of 471 patients with a HDD of non-CEBS (3%) were deemed to have CEBS. Overall, sensitivity and specificity of HDD for PC were, respectively, 95 and 93%, and for CEBS, 89 and 97%. Cytohistological confirmation and laparotomy were independent predictors of diagnostic change. Conclusions: Validity of the HDD was high, but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results, and highlights the need to review all HDDs. Alternatively, only patients at high risk of misdiagnosis could be reviewed: primarily, those lacking a cytohistological diagnosis or a laparotomy. No exclusions appear warranted solely on the basis of age, gender or tumour spread.