Utility of the INECO frontal screening (IFS) in the detection of executive dysfunction in patients with relapsing-remitting multiple sclerosis (RRMS).

Several studies have reported that about 65 % of patients with relapsing-remitting multiple sclerosis (RRMS) suffer from cognitive impairment, with executive dysfunction being the most frequently described. Even if several executive screening tests have been designed to specifically detect executive deficits, few studies have investigated their ability to tackle such dysfunction particularly in multiple sclerosis (MS). The aim of the present study was to evaluate the sensitivity and specificity of the INECO frontal screening (IFS) in the detection of executive dysfunction in patients with relapsing-remitting MS (RRMS). 54 patients with RRMS were included in the study. 34 presented executive dysfunction while 20 did not. 32 control subjects matched for age, sex, and educational level were also included. All were evaluated with the IFS and with a battery of classical executive tests. A patient was considered to have executive dysfunction if he/she scored a one and a half standard deviation below the control mean in at least one of the classical executive tests. Sensitivity and specificity of the IFS in its ability to detect executive dysfunction in MS was analyzed. Using a cut-off of 25.5 points, sensitivity of the IFS was 73.53 %, and specificity 78.13 % in differentiating controls from MS patients with executive dysfunction. The IFS showed excellent concurrent validity with executive tasks. The IFS can be considered a brief, easy-to-administer, cost-less tool for the detection of executive dysfunction in patients with RRMS.

Natural treatment system for wastewater (NTSW) in a livestock farm, with five years of pilot plant management and monitoring.

This paper reports results of a 5-year trial study of a natural treatment system for wastewater (NTSW) on a livestock pig farm on Gran Canaria (Canary Islands, Spain). The pilot plant consist of a rotary screen, a first-generation multi-chamber digester, and two horizontal subsurface flow treatment wetlands (HSFCW) with a pond installed between them. Results show that the removal efficiency of total chemical oxygen demand (CODt), total suspended solids (TSS), volatile solids (VS) and total dissolved solids (TDS) of the treatment were 91.77%, 95.99%, 82.62%, and 55.78%, respectively. Other removal values include 93.79% for total nitrogen (TN) and 93.05% for phosphorus (P2O5). The results demonstrate the suitability of NTSW solutions applied to livestock waste in pig farms and their potential application to other farms of similar size.

Adherence to the Mediterranean diet in health personnel from the province of Las Palmas.

INTRODUCTION AND OBJECTIVES: Given the proven protective effect of the Mediterranean Diet, adherence to it by healthcare personnel and the influence of different factors on dietary compliance were evaluated. METHODS: A cross-sectional study was conducted on healthcare personnel, obtaining the data through anonymous surveys that collected demographic characteristics, professional activity, history of cardiovascular risk factors, alcohol, and tobacco consumption, physical activity, and adherence to the Mediterranean Diet, using the 14-point Mediterranean Diet Adherence Score (MEDAS). Adherence and related factors were measured. RESULTS AND CONCLUSIONS: Of a total of 922 respondents (664 women) mean aged 42.61 years (range 20-69), 61.2% showed a good adherence to the Mediterranean Diet. Adherence was significantly associated with the professional categories of physicians (OR = 1.92; 95% CI: 1.20-3.06; p = 0.01) and nurses (OR = 1.67; 95% CI: 1.08-2.57). Furthermore, it was associated with physical exercise (OR = 1.78; 95% CI: 1.29-2.47; p < 0.001) and cooking at home (OR = 1.35; 95% CI: 1.00-1.80; p = 0.05). However, adherence was not significantly associated with age or sex, comorbidities, working hours, alcohol, or tobacco consumption. Quantifying knowledge of the diet would be useful, as well as increasing educational programs, promoting physical exercise and cooking habits.

Tone and reactivity of vascular smooth muscle in germfree rat mesentery.

Microcirculatory observations and measurements were made by in vivo microscopy in 35 germfree and 26 conventional rats. The rate of vasomotor activity, "vasomotion," of precapillary arterioles was found markedly decreased in the germfree animals. All precapillary vessels in the germfree rats were markedly hyporeactive to the catecholamines, epinephrine and norepinephrine, as compared to similar vessels of conventional rats. The vessels in the germfree animals were also less responsive to vasopressin but not angiotensin. A greater lumen:wall ratio of primary arterioles, but not of secondary arterioles and metarterioles, found in germfree animals is related to change in vessel lumen alone without concomitant change in wall thickness. The germfree rat is characterized by possessing a hypotonic, catecholamine-refractory mesoappendix microvasculature.

Application of a mathematical model to predict simultaneous reactions in anaerobic plug-flow reactors as a primary treatment for constructed wetlands.

Anaerobic digestion technologies offer a set of advantages when they are implemented as a primary treatment phase prior to the use of constructed wetland systems in low cost wastewater facilities. The aim of this study is to describe a model capable of reflecting the complex functioning of anaerobic lagoons, subject to continuous flux in the feed pipe, taking into account that physicochemical properties are subject to a concentration gradient and biochemical ones to simultaneous reactions which depend on each other. Based on both Stokes and advection-diffusion-reaction equations, the proposed model includes twenty-one variables to describe hydraulic, physical, biochemical and physicochemical characteristics that take place in different points of the system and at different moments of time. Drawn up by the International Water Association, the anaerobic digestion model ADM1 is included for the purpose of incorporating the anaerobic processes in the calculation. The finite element method was used to solve the nonlinear, second order partial differential equations of the model. The calculation strategy was designed using a flowchart. Using the open-source FreeFem++ software, a simulation of the mathematical model, in bi-dimensional space, is presented to demonstrate the dynamic behaviour of the proposed model. This yields essential information about the performance of the substrate, cells, and the biochemical reaction products in each of the points within the reactor. Simulations show the potential of this methodology to carry out studies of the behaviour of each of the variables contemplated in the model, as well as comparative studies of the various possible options. In addition, this methodology can be used to help modify the behaviour of the variables based on digester geometry and the boundary values the system is subject to. From the results, it can be concluded that the proposed methodology can be a useful tool for calculating and designing the aforementioned synergistic systems of anaerobic digester plug-flow reactors and constructed wetlands.

Vascular smooth muscle: quantitation of cell thickness in the wall of arterioles in the living animal in situ.

The wall of microarterial vessels, in the living animal in situ, was examined at magnification up to x 6500 on the television screen. The optical resolution af the cell components of the wall was sufficiently clear to permit image formation and splitting for permanent recording and quantitation. Thickness of single smooth muscle cells at rest was estimated to be 2.08 microns (S.D. +/- 0.24 micron) and 2.78 microns (S.D. +/- 0.59 micron) by two different approaches. Changes in cell thickness during activity were also recorded and quantitated.

Soil net nitrogen mineralisation across global grasslands.

Soil nitrogen mineralisation (Nmin), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net Nmin) varies with soil properties and climate. However, because most global-scale assessments of net Nmin are laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net Nmin across 30 grasslands worldwide. We find that realised Nmin is largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential Nmin only weakly correlates with realised Nmin, but contributes to explain realised net Nmin when combined with soil and climatic variables. We provide novel insights of global realised soil net Nmin and show that potential soil net Nmin data available in the literature could be parameterised with soil and climate data to better predict realised Nmin.

Erythrocytes in sickle cell anemia are heterogeneous in their rheological and hemodynamic characteristics.

To understand the contribution to the pathophysiology of sickle cell anemia of the different erythrocyte density types present in the blood of these patients, we have studied the viscosimetric and hemodynamic characteristics of four major classes of hemoglobin SS erythrocytes. We have isolated reticulocytes, discocytes, dense discocytes, and irreversibly sickled cells (fractions I-IV) on Percoll-Renografin density gradients. Bulk viscosity was studied in a coneplate viscosimeter and the hemodynamic studies were performed on the isolated, artificially perfused mesoappendix vasculature of the rat (Baez preparation). Bulk viscosity measurements at shear rates of 230 S-1 demonstrate that when the cells are oxygenated, fraction I (reticulocyte rich) has a higher viscosity than expected from its low intracellular hemoglobin concentration. The rest of the fractions exhibit moderate increases in bulk viscosity pari-passu with the corresponding increases in density (mean corpuscular hemoglobin concentration). When deoxygenated, all cell fractions nearly doubled their bulk viscosity and the deoxy-oxy differences remained constant. The Baez preparation renders a different picture: oxygenated fractions behave as predicted by the viscosimetric data, but, when deoxygenated, cell fractions exhibit dramatically increased peripheral resistance and the deoxy-oxy difference are directly proportional to cell density, thus, the largest increases were observed for fractions III and IV. The differences between the rheological and the hemodynamic measurements are most probably due to the different sensitivity of the two methods to the extent of intracellular polymerization. These results also demonstrate that the hitherto unrecognized fraction III cells (very dense discocytes that change shape very little on deoxygenation) are as detrimental to the microcirculation as the irreversibly sickled cell-rich fraction IV. They may, however, induce obstruction by a different mechanism. As the extent to which these fractions are populated by erythrocytes varies considerably from patient to patient, the distribution function of cell densities in each sickle cell anemia patient might have consequences for the type of pathophysiological events occurring in their microcirculation.

Some aspects of the pathophysiology of homozygous Hb CC erythrocytes.

We have studied erythrocytes from homozygous CC patients in vitro and in perfused rat mesoappendix vasculature to answer some long-standing questions. By examination of wet whole blood preparations, and by comparing the cell distribution on isopycnic continuous density gradients of whole blood samples from a splenectomized CC patient with those from three intact CC patients, we have demonstrated the presence of a distinct crystal-containing band of cells that is present in the former, but totally absent from the latter. We conclude that Hb CC cells containing crystals circulate in Hb CC individuals, but in intact patients they are effectively removed by the spleen. By use of 31P nuclear magnetic resonance and viscosity measurements on cells, we have demonstrated that intracellular aggregation of hemoglobin C occurs on deoxygenation even when no crystal formation is detectable by morphological methods. These two observations are in apparent contradiction with the absence of clinical microcirculatory impairment found in both intact and splenectomized CC patients. The contradiction was resolved by rheological studies on isolated rat mesoappendix preparations and erythrocyte diameter measurements that lead to the conclusion that the hemorheological properties of CC cells in the microcirculation are nearly normal because their increased viscosity is offset by their smaller diameter and size.

Improvement in postoperative mortality in elective gastrectomy for gastric cancer: Analysis of predictive factors in 1066 patients from a single centre.

BACKGROUND: Gastrectomy represents the main treatment for gastric adenocarcinoma. This procedure is associated with substantial morbidity and mortality. The aim of this study was to evaluate the postoperative mortality changes across the study period and to identify predictive factors of 30-day mortality after elective gastrectomy for gastric cancer. METHODS: This was a retrospective cohort study of a prospective database from a single centre. Patients treated with an elective gastrectomy from 1996 to 2014 for gastric adenocarcinoma were included. We compared postoperative mortality between four time periods: 1996-2000, 2001-2005, 2006-2010, and 2011-2014. Univariate and multivariate analyses were applied to identify predictors of 30-day postoperative mortality. RESULTS: We included 1066 patients (median age 65 years; 67% male). The 30-day mortality rate was 4.7%. Mortality decreased across the four time periods; from 6.5% to 1.8% (P = 0.022). In the univariate analysis, age, ASA score, albumin <3.5, multivisceral resection, splenectomy, intrathoracic esophagojejunal anastomosis, R status, and T status were significantly associated with postoperative mortality. In the multivariate analysis, ASA class 3 (OR 10.06; CI 1.97-51.3; P = 0.005) and multivisceral resection (OR 1.6; CI 1.09-2.36; P = 0.016) were associated with higher postoperative 30-day mortality; surgery between 2011 and 2014 was associated with lower postoperative 30-day mortality (OR 0.55; CI 0.33-0.15; P = 0.030). CONCLUSION: There was a decrease in postoperative 30-day mortality during this 18-year period at our institution. We have identified ASA score and multivisceral resection as predictors of 30-day mortality for elective gastrectomy for cancer.

Postoperative adjuvant treatment for gastric cancer improves long-term survival after curative resection and D2 lymphadenectomy. Results from a Latin American Center.

BACKGROUND: The benefits of adjuvant treatment in the context of a D2 lymph node dissection are controversial. The aim was to investigate the effects of postoperative adjuvant treatment on the survival of patients with a curative resection for gastric cancer and a D2 lymph node dissection. METHODS: We performed a retrospective cohort study. Patients operated from 1996 to 2013 were selected. We compared long term survival of patients treated with surgery alone and those with surgery plus postoperative adjuvant treatment. A multivariate analysis for survival was applied in every stage. RESULTS: The study included 580 patients. Two-hundred and four patients received postoperative adjuvant treatment (AD) and 376 patients were treated only with surgery (SU). Patients in the AD group were younger (60 versus 68, p < 0.001), had a lower rate of multiple organ resection (21% versus 39%, p < 0.001) and had less postoperative complications (14% versus 32%, p < 0.001). In the AD group, patients had more advanced disease (stage III; 77% versus 66%, p < 0.001). No difference was found in lymph nodes resected (31 versus 30, p = ns). The median survival with adjuvant treatment was 33 months (39% 5 year survival) and 22 months (31% 5 year survival) for patients without adjuvant treatment (p = 0.003). On multivariate analysis, patients with stage IIIB and IIIC had significantly better overall and disease specific long-term survival with adjuvant treatment. CONCLUSIONS: These results suggest that there is a long-term survival benefit for patients treated with postoperative adjuvant treatment for stages IIIB and IIIC gastric cancer after D2 lymph node dissection.

The protective effect of superoxide dismutase and catalase against formation of reactive oxygen species during reduction of cyclized norepinephrine ortho-quinone by DT-diaphorase.

Norepinephrine was oxidized by the Mn(3+)-pyrophosphate complex to the corresponding o-quinone at pH 6.5. Cyclized norepinephrine ortho-quinone showed an absorption maximum at 289 and 483 nm. No oxygen consumption was observed during oxidation of norepinephrine to o-quinone by Mn3+ and subsequent cyclization. The reduction of cyclized norepinephrine ortho-quinone to the corresponding hydroquinone was catalyzed by DT-diaphorase. However, the hydroquinone formed proved to be unstable in the presence of oxygen, since reduction of cyclized norepinephrine o-quinone by DT-diaphorase was accompanied by continuous oxidation of NADH and oxygen consumption. Addition of the chelator DETAPAC or SOD to the incubation mixture during reduction of cyclized norepinephrine ortho-quinone by DT-diaphorase strongly inhibited NADPH oxidation and oxygen consumption, suggesting that manganese and superoxide radicals were involved in hydroquinone autoxidation. Elimination of the effects of superoxide radicals, manganese and H2O2 on autoxidation of hydroquinone by addition of SOD, catalase and DETAPAC to the incubation mixture resulted in a 79% inhibition of NADH oxidation, suggesting that 21% of the autoxidation is oxygen-dependent. However, the effect of these additions on oxygen consumption was even more pronounced (93% inhibition).

Microvascular reactivity of the myopathic Syrian hamster cremaster muscle.

The myopathic Syrian hamster is a genetic model of congestive heart failure that exhibits focal myocytolytic necrosis in both heart and skeletal muscle. Previous investigations of microvascular morphology in heart and skeletal muscle have shown severe arteriolar constrictions without fixed anatomical vessel lesions. This study tested the hypothesis that these constrictions indicate a hyperreactivity of the myopathic microvasculature in vivo and that the reactivity corresponds to the developmental course of myocyte pathology. The microcirculation of the cremaster muscle was studied in eight myopathic and six control hamsters in the active stage of necrosis (39-81 days of age) and five myopathic and six control hamsters in the later stage of muscle healing (150-213 days of age). The internal diameter of second order arterioles was measured during topically applied noradrenaline. The myopathic arterioles of the younger group constricted at significantly lower concentrations of noradrenaline (p less than 0.01) and constricted to 35-50% of their resting internal diameter over a narrower range of noradrenaline (p less than 0.01). This indicated both a reduced threshold to noradrenaline and an enhanced response to the agonist. Active myocytolytic necrosis was found in the contralateral cremaster muscle of each myopathic hamster. The older myopathic and control hamsters showed no significant differences in arteriolar responsiveness to applied noradrenaline and no active necrosis. These results indicate a relation between a hyperreactive microvasculature and active necrosis and a normal reacting microvasculature and diminished necrosis in the two phases of the disease. Thus a general correspondence between vascular responsiveness and myocyte pathology exists in this model of heart failure and muscular dystrophy.

Plasma neurotransmitters, blood pressure, and heart rate during supine-resting, orthostasis, and moderate exercise conditions in major depressed patients.

Major depressed patients showed greater heart rate, noradrenaline, and free-serotonin values than normal. Conversely, platelet-serotonin values in major depressed patients were significantly lower than normal. Patients registered the normal differential blood pressure reduction during orthostasis. They also revealed progressive and significantly higher heart rate rises during orthostasis and exercise periods, when compared to normals. Whereas noradrenaline showed maximal rises during the two last periods, adrenaline only showed small but significant increase during exercise. The analysis of correlations, together with the above data, suggests that major depressed patients register maximal neural sympathetic activity as well as adrenal glands sympathetic hypoactivity. In addition, these patients show hyperparasympathetic activity, as reflected by the free-serotonin profile. Finally, the fact that both the Hamilton Depression Rating Scale and the self-rating Beck Depression Inventory correlated positively with noradrenaline/adrenaline ratio and free-serotonin values strongly suggests that both neural sympathetic and cholinergic mechanisms are involved in major depression.

Plasma neurotransmitters, blood pressure, and heart rate during supine resting, orthostasis, and moderate exercise in dysthymic depressed patients.

Dysthymic depressed patients showed platelet-serotonin (pS) + plasma-free serotonin values greater than normal as well as plasma noradrenaline values lower than normal during supine resting period (0'). Conversely, no significant differences were observed in the 0' values of any other of the measured parameters: systolic, diastolic and differential blood pressure (SBP, DBP, DP), heart rate (HR), adrenaline (Ad), dopamine (DA), cortisol, and platelet aggregability between patients and controls. Although patients showed then normal DP reduction at orthostasis (1'), this was not prevented by atropine as it does in controls. Patients but not normals showed significant rises of DBP at orthostasis and exercise (5') periods, which were positively correlated with NA rises. On the contrary, the abnormally raised resting fS values registered in patients showed progressive and significant reductions throughout the test that were negatively correlated with DBP-NA values. Adrenaline did not show the normal 5'-fS peak. The above findings suggest that dysthymics show hypoactivity of the two branches of the sympathetic system (neural + adrenal) along with hyperparasympathetic activity. Furthermore, their low NA + high pS values contrast with the high NA + low pS registered in major depressed subjects.

Psychoneuroendocrinological and immunological parameters in cancer patients: involvement of stress and depression.

Plasma noradrenaline (NA), adrenaline (A), dopamine (DA), platelet serotonin (pS), free serotonin (fS), cortisol (CRT), growth hormone (GH), peripheral blood lymphocytes (lymph), lymphocyte subpopulations (LSS) and CD4/CD8 ratio were serially assessed in 50 non-medicated, advanced cancer patients (spontaneous evolution) and in age- and sex-paired controls. Clonidine tests and psychiatric evaluations were also serially performed. Patients showing long symptomless periods had all normal values except for raised pS, whereas those who remained free of symptoms for only a short time had raised NA, A and CRT, plus lowered pS values. Further increases in NA, A and CRT, plus additional increases in DA and fS, occurred during exacerbation periods, during which times reductions in lymph, LSS and NK also were observed. Patients in terminal stages showed maximal decreases of all neurotransmitters and immunological parameters; only DA and fS remained raised. Psychiatric interviews performed simultaneously with the clonidine tests revealed a low incidence of moderate depression during symptomless periods and no depression during exacerbation periods. Several significant positive and negative correlations between neurotransmitters and immunological parameters were found during exacerbation periods. Pain, although not intense, and other symptoms required occasional administration of low doses of non-opiate analgesics.

On the relationship of brain vasculature to production of neurological deficit and morphological changes following acute unilateral common carotid artery ligation in gerbils.

The known susceptibility of the Mongolian gerbil to cerebral infarction following unilateral carotid artery ligation has been attributed in the past to the demonstrated absences of an anastomotic supply between the anterior and posterior cerebral circulations. In a study of 34 adult gerbils exposed to such a procedure, 11, or 33%, developed severe neurological sequelae and succumbed to the procedure in less than 30 hr, whereas 23 animals survived with only minor or transient neurological signs. All animals displayed the expected lack of an anastomosis between the anterior and posterior circulations, but in addition the animals which survived the procedure were found to have a prominent early cross-connection between the anterior cerebral arteries, whereas the animals which succumbed had no such connection. Neuropathological changes in susceptible animals were apparent as early as 3 and one-half hr after ligation and consisted of edema, initially perivascular and then intraneuronal, slowed by acute necrosis. A variety of other vascular anomalies was encountered. We conclude that the peculiar susceptibility of Mongolian gerbils to cerebral infarction following acute unilateral common carotid artery ligation is not related primarily to lack o adequate collaterals between the anterior and the anterior cerebral arteries, but to the degree of adequate adequacy of communication between the anterior cerebral arteries. The critical difference may be more one of degree, i.e. the point at which the medial branches of the anterior cerebral artery fust to become anazygos vessel, rather than an actual difference in the pattern of distribution of the anterior cerebral arteries. The presence of other variation in vascular supply in a relatively small series suggests that results of similar studies of infarction and response to treatment be interpreted with caution.

Formation of reactive oxygen species during one-electron reduction of noradrenochrome catalyzed by NADPH-cytochrome P-450 reductase.

One-electron reduction of noradrenochrome catalyzed by NADPH-cytochrome P-450 reductase resulted primarily in the formation of o-semiquinone and, probably, also o-hydroquinone. Under aerobic conditions these reduced form(s) autoxidize, accompanied by the formation of reactive oxygen species, as revealed by continuous NADPH oxidation and oxygen consumption. The presence of manganese-pyrophosphate complex contributed to autoxidation of the o-semiquinone during the reduction of noradrenochrome catalyzed by NADPH-cytochrome P-450 reductase, since the addition of the metal chelator diethylenetriamine pentaacetic acid (DETAPAC) resulted in a 34% inhibition of NADPH oxidation. Oxygen in the ground state was found to be predominantly involved in the autoxidation of o-semiquinone during the reduction of noradrenochrome catalyzed by NADPH-cytocbrome P-450 reductase, since the addition of superoxide dismutase (SOD) to the incubation mixture only inhibited NADPH oxidation 13% and 6% in the absence and presence of DETAPAC, respectively. The addition of catalase to the incubation mixture resulted in a slight increase in NADPH oxidation, both in the absence and in the presence of diethylenetriamine pentaacetic acid. However, no effect of catalase and SOD together on NADPH oxidation was observed, either in the absence or presence of DETAPAC.

The possible role of one-electron reduction of aminochrome in the neurodegenerative process of the dopaminergic system.

We present for discussion a possible molecular mechanism explaining the formation of reactive oxygen species involved in the neurodegenerative process of dopaminergic system in Parkinson's disease. This new hypothesis involves one-electron reduction of aminochrome to o-semiquinone radical, which seems to be the reaction responsible for neurodegenerative process of dopaminergic system. Leukoaminochrome o-semiquinone is extremely reactive with oxygen, which reoxidizes by reducing oxygen to superoxide radicals. Superoxide radicals enzymatically or spontaneously dismutate to dioxygen and hydrogen peroxide which is a precursor of hydroxyl radicals. ESR-experiments have showed that aminochrome o-semiquinone is extremely reactive in the presence of oxygen compared to dopamine o-semiquinone. In addition, the antioxidant enzymes superoxide dismutase and catalase play a prooxidant role by increasing the autoxidation rate and formation of superoxide radicals. One electron reduction of aminochrome to o-semiquinone can be performed by flavoenzymes which use NADPH and NADH as electron donator. The ability of aminochrome o-semiquinone to autoxidize in the presence of oxygen gives rise to a redox cycling process which will continue until oxygen, NADH and/or NADPH are depleted. Depletion of NADPH will prevent glutathione reductase from reducing glutathione, which is one of the main antioxidants in the cell. In addition depletion of NADH will prevent the formation of ATP in the electron transport chain in the mitochondria. Two antioxidants, probably, neuroprotective reactions are also discussed.