Cholesterol dysregulation in peripheral blood mononuclear cells of Alzheimer's disease.

Cholesterol and the immune system are involved in Alzheimer's Disease (AD). To investigate the relations among them, we compared the cholesterol content in peripheral blood mononuclear cells (PBMC) of cognitively healthy controls and patients with mild cognitive impairment (MCI) and AD in two independent samples. Free cholesterol content of PBMC was lower in MCI and AD patients, and was modulated by APOE genotype. A decrease of CD8+ and an increase of CD16+ was also found in AD patients. These results suggest that cholesterol levels in PBMCs may represent an early signature of the disease and support the involvement of immune system in AD.

Differences in multi-echo chemical shift encoded MRI proton density fat fraction estimation based on multifrequency fat peaks selection in non-alcoholic fatty liver disease patients.

AIM: To compare the performance of multi-echo chemical-shift-encoded (MECSE) magnetic resonance imaging (MRI) proton density fat fraction (PDFF) estimation, considering three different fat frequency peak combinations, for the quantification of steatosis in patients with non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: The present study was a prospective cross-sectional research of 121 patients with metabolic syndrome and evidence of hepatic steatosis on ultrasound, who underwent a 3 T MRI examination. All patients were studied with a multifrequency MECSE sequence. The PDFF was calculated using six peaks (MECSEp123456), three peaks (MECSEp456), and a single peak (MECSEp5) model. The two simpler fat peak models were compared to the six peaks model, which was considered the reference standard. Linearity was evaluated using linear regression while agreement was described using Bland-Altman analysis. RESULTS: The mean age was 47 (±9) years and BMI was 29.9 (±2.9) kg/m2. Steatosis distribution was 15%/31%/54% (S1/S2/S3, respectively). Compared to MECSEp123456, both models provided linear PDFF measurements (R2= 0.99 and 0.97, MECSEp456 and MECSEp5 respectively). Regression slope (0.92; p<0.001) and mean Bland-Altman bias (-1.5%; 95% limits of agreement: -3.19%, 0.22%) indicated minimal underestimation by using PDFF-MECSEp456. Nonetheless, mean differences in PDFF estimations varied from -1.5% (MECSEp456,p=0.006) to -2.2% (MECSEp5,p<0.001) when compared to full six fat frequencies model. CONCLUSION: Although simpler spectral fat MECSE analysis shows a linear relationship with the standard six peaks model, their variation in estimated PDFF values introduces a low but clinically significant bias in fat quantification and steatosis grading in NAFLD patients.

Hybrid Composite-Metal Stack Drilling with Different Minimum Quantity Lubrication Levels.

Hybrid stack drilling is a very common operation used in the assembly of high-added-value components, which combines the use of composite materials and metallic alloys. This process entails the complexity of machining very dissimilar materials, simultaneously, on account of the interactions that are produced between them, during machining. This study analyzed the influence of Minimum Quantity Lubrication (MQL) on the performance of diamond-coated carbide tools when drilling Ti/carbon fiber reinforced plastics (CFRP)/Ti stacks. The main wear mechanism observed was diamond-coating detachment, followed by fragile breaks in the main cutting-edge. The tests done with the lower lubrication levels have shown an important adhesion of titanium (mainly on the secondary cutting-edge) and a higher friction between the tool and the workpiece, producing higher temperatures on the cutting region and a thermal softening effect on the workpiece. These phenomena affect the evolution of cutting power consumption with tool wear in the titanium layer. Regarding the quality of the test specimen, no significant differences were observed between the lubrication levels tested.

Insulin resistance and NAFLD: Relationship with intrahepatic iron and serum TNF-α using 1H MR spectroscopy and MRI.

AIM: The association of non-alcoholic fatty liver disease (NAFLD) with insulin resistance (IR) is well established, yet little is known of their possible relationship with intrahepatic iron and serum tumour necrosis factor (TNF)-α concentrations in adults without diabetes. Thus, this study looked at the relationship of intrahepatic iron and serum TNF-α with intrahepatic triglycerides and IR in non-diabetic adults. METHODS: In this cross-sectional study of 104 healthy non-diabetic Caucasians, a quantitative magnetic resonance (MR) imaging T2 gradient-echo technique was used to measure hepatic iron, with 1H-MR spectroscopy used to measure hepatic triglycerides. HOMA-IR was calculated to determine IR. RESULTS: The prevalence of hepatic iron overload (HIOL) was 26.6% in individuals with NAFLD vs. 0% in those without. IR was present in 87.5% of subjects with both NAFLD and HIOL, in 45.4% of those with NAFLD but not HIOL, and in 4.5% of those with neither. HOMA-IR was positively correlated with hepatic triglycerides (r = 0.56, P < 0.001) and hepatic iron (r = 0.52, P < 0.001), whereas serum TNF-α concentrations correlated with intrahepatic triglyceride levels (r = 0.28, P < 0.04), but not with intrahepatic iron. Hepatic triglycerides, serum TNF-α and age were the only significant determinants of IR in regression analyses. CONCLUSION: IR is closely associated with intrahepatic triglycerides and, to a lesser extent, intrahepatic iron, with some interplay between them. High serum TNF-α concentrations may contribute to the association between NAFLD and IR, while increased hepatic triglycerides appear to be a determinant of the development of HIOL in non-diabetic subjects without haemochromatosis.

Réplica a "Factores de riesgo cardiovascular y grosor de la íntima media carotídea en una población colombiana con psoriasis" / Comment on "Cardiovascular Risk Factors and Carotid Intima-Media Thickness in a Colombian Population With Psoriasis"

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75SeHCAT scan in bile acid malabsorption in chronic diarrhoea. / Gammagrafía con 75SeHCAT en la diarrea crónica por malabsorción de ácidos biliares.

Chronic diarrhoea is a common entity in daily clinical practice and it leads to a loss in these patients quality of life. It may be the main symptom of multiple ethiologies including bile acid malabsorption (BAM) which has a comparable prevalence to celiac disease. The BAM results from imbalances in the homeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease or ileal dysfunction (BAM type i), it can be considered idiopathic or primary (BAM type ii) or associated with other gastrointestinal entities (BAM type iii). Among the different diagnostic methods available, 75SeHCAT study is the primary current method due to its sensitivity, specificity, safety and low cost. The main disadvantage is that it's not available in all countries, so other diagnostic methods have appeared, such as serum measurement of FGF19 and C4, however they are significantly more complex and costly. The first-line treatment of bile acid diarrhoea is bile acid sequestrant, such as cholestyramine, which can be difficult to administer due to its poor tolerability and gastrointestinal side effects. These are less prominent with newer agents such as colesevelam. In summary, the BAM is a common entity underdiagnosed and undertreated, so it is essential to establish a diagnosis algorithm of chronic diarrhoea in which the 75SeHCAT study would be first or second line in the differential diagnosis of these patients.

Impact of sleep loss before learning on cortical dynamics during memory retrieval.

Evidence shows that sleep loss before learning decreases activation of the hippocampus during encoding and promotes forgetting. But it remains to be determined which neural systems are functionally affected during memory retrieval after one night of recovery sleep. To investigate this issue, we evaluated memory for pairs of famous people's faces with the same or different profession (i.e., semantically congruent or incongruent faces) after one night of undisturbed sleep in subjects who either underwent 4hours of acute sleep restriction (ASR, N=20) or who slept 8hours the pre-training night (controls, N=20). EEG recordings were collected during the recognition memory task in both groups, and the cortical sources generating this activity localized by applying a spatial beamforming filter in the frequency domain. Even though sleep restriction did not affect accuracy of memory performance, controls showed a much larger decrease of alpha power relative to a baseline period when compared to sleep-deprived subjects. These group differences affected a widespread frontotemporoparietal network involved in retrieval of episodic/semantic memories. Regression analyses further revealed that associative memory in the ASR group was negatively correlated with alpha power in the occipital regions, whereas the benefit of congruency in the same group was positively correlated with delta power in the left lateral prefrontal cortex. Retrieval-related decreases of alpha power have been associated with the reactivation of material-specific memory representations, whereas increases of delta power have been related to inhibition of interferences that may affect the performance of the task. We can therefore draw the conclusion that a few hours of sleep loss in the pre-training night, though insufficient to change the memory performance, is sufficient to alter the processes involved in retrieving and manipulating episodic and semantic information.

Causa rara de hipertensión arterial en la juventud: paraganglioma retroperitoneal con invasión vascular / An uncommon cause of high blood pressure in young people: retroperitoneal paraganglioma with vascular invasion

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Biliary complications after liver transplantation using side-to-side choledochocholedochostomy reconstruction with or without T-tube.

BACKGROUND: Biliary complications are a frequent cause of morbidity, graft loss, and death after orthotopic liver transplantation (OLT). The choledochocholedochostomy anastomosis without a T-tube is controversial, as it has been related to more biliary complications. AIMS: The aims of this study were to determine the incidence and to identify the risk factors of post-OLT biliary complications after reconstruction with or without a T-tube. MATERIALS AND METHODS: Ninety-five consecutive adult patients with deceased donor liver transplantations (overall survival rate, 86.3%; mean follow-up, 22.2 months) were analyzed to determine the incidence and type of biliary complications in 2 groups: choledochocholedochostomy with (45 patients, Group I) or without a T-tube (50 patients, Group II). The incidence of biliary complications in Groups I and II was 40% (18/45) and 30% (15/50), respectively (P > .05). In Group I, 49% of the complications were directly related to the T-tube. Biliary anastomosis stricture was more frequent in Group II (28% vs 8.9% in Group I; P = .018). Endoscopic retrograde cholangiopancreatography (ERCP) was the most common therapeutic procedure for the resolution of biliary complications in both groups (Group I, 66.5%; Group II, 58.2%). Arterial thrombosis, high pretransplantation Model for End-Stage Liver Disease (MELD) score, and donor obesity were identified as risk factors for biliary complications after OLT. CONCLUSION: OLT biliary reconstruction without a T-tube is not related to an increased risk of biliary complications, although stricutre of the anastomosis is more frequent in this group of patients. Donor obesity, arterial thrombosis, and high pretransplantation MELD score are associated with a higher incidence of biliary complications after OLT.

Progressive reduction of sleep time and quality in rats with hepatic encephalopathy caused by portacaval shunts.

Patients with liver cirrhosis show sleep disturbances. Insight into their relationship with hepatic encephalopathy (HE) can be obtained using animal models of HE. The aims of this work were to assess (1) whether rats with portacaval shunts (PCS), a model of HE, show alterations in sleep and if they are similar to those in patients with HE; (2) Whether hyperammonemia plays a role in these sleep alterations; and (3) the time course of sleep alterations in these animal models. Rats were subjected to PCS to induce HE. Another group of rats was fed an ammonium-containing diet to induce hyperammonemia. Polysomnographic recordings were acquired for 24 h and sleep architecture was analyzed in control, PCS, and hyperammonemic rats at 4, 7, and 11 weeks after surgery or diet, respectively. PCS rats show a significant reduction in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep time and increased sleep fragmentation, whereas reduced sleep occurs at 4 weeks and worsens at 7 and 11 weeks, sleep fragmentation appears at 7 weeks and worsens at 11 weeks. Hyperammonemic rats show decreased REM sleep, starting at 7 weeks and worsening at 11 weeks, with no changes in NREM sleep or sleep fragmentation. Therefore, PCS rats are a good model to study sleep alterations in HE, their mechanisms, and potential treatment. Mild hyperammonemia mainly impacts mechanisms involved in REM generation and/or maintenance but does not seem to be involved in sleep fragmentation.

Associative memory deficits in mild cognitive impairment: the role of hippocampal formation.

Neuropathological events featuring early stages of Alzheimer's disease (AD) appear in the entorhinal cortex (EC), subiculum (SB) and cornu ammonis 1 (CA1) of hippocampus, which may account for associative memory deficits in non-demented people with mild cognitive impairment (MCI). To test this hypothesis in vivo, we investigated whether volume changes in these regions are related to failures in associative memory in MCI as compared to cognitively normal (CN) elderly subjects. Volume changes in EC and hippocampal subfields were determined by using deformation-based morphometry techniques applied to probabilistic cytoarchitectonic maps derived from post mortem human brains. CN subjects were distinguished from MCI patients by firstly identifying local volume differences in EC and hippocampus, and then evaluating the way in which these anatomical changes correlated with performance in a non-intentional face-location association task. MCI patients not only performed worse than CN elders in building new associations, but they were further unable to benefit from semantic encoding to improve episodic binding. According to our initial hypothesis, local volume reductions in both EC and hippocampal CA accounted for group differences in associative memory whereas atrophy in CA, but not in EC, accounted for semantic encoding of associations. Two main conclusions can be drawn from the present study: i) access to semantic information during encoding does not reduce the episodic deficit in MCI; and ii) EC and hippocampal CA, two regions early affected by AD neuropathology, are responsible, at least partially, for associative memory deficits observed in MCI patients.

Changes in magnesium and potassium homeostasis after conversion from a calcineurin inhibitor regimen to an mTOR inhibitor-based regimen.

BACKGROUND: Transplant recipients treated with calcineurin inhibitors (CNIs) frequently show hyperkalemia, metabolic acidosis, and hypomagnesemia which could be deleterious for some patients. Conversion to inhibitors of mammalian target of rapamycin (mTOR) could improve these electrolytic disturbances. OBJECTIVE: To evaluate the potassium and magnesium changes due to converting patients from CNIs to mTOR inhibitors. METHODS: Retrospective review of 138 renal transplant patients who were converted from CNIs to mTOR inhibitors over a 6-month observation period. The following parameters were determined: potassium, sodium, chloride, magnesium, urea, glucose, and creatinine in blood and urine. We also analyzed plasma bicarbonate and calculated plasma and urine anion gap and plasma osmolarity. RESULTS: One month after conversion, a decrease was observed in serum creatinine (1.75±0.68 vs 1.61±0.61 mg/dL; P=.01), plasma potassium (4.60±0.52 vs 4.39±0.53 mEq/L; P<.001), calculated plasma osmolarity (308.7±8.5 vs 307.4±8.4 mOsm/L; P<.036), fractional excretion of sodium (1.55±0.69 vs 1.29±0.65%; P<.003), and fractional excretion of magnesium (7.15±4.08 vs 15.84±3.64%; P<.001), with an increase in serum magnesium (1.77±0.24 vs 1.95±0.29 mg/dL; P<.001). At 3 and 6 months, these differences remained unchanged. The transtubular potassium gradient did not change. CONCLUSIONS: We observed a decrease in serum magnesium due to renal magnesium wasting before switching from CNIs to mTOR inhibitors. After conversion, an increase in serum magnesium was observed together with a drop in the fractional excretion of this cation. A decrease in plasma potassium levels, plasma osmolarity, and fractional excretion of sodium consistent with minor aldosterone resistance was also detected after changing the immunosuppressive treatment.

Functional neural networks underlying semantic encoding of associative memories.

Evidence suggests that theta oscillations recruit distributed cortical representations to improve associative encoding under semantically congruent conditions. Here we show that positive effects of semantic context on encoding and retrieval of associations are mediated by changes in the coupling pattern between EEG theta sources. During successful encoding of semantically congruent face-location associations, the right superior parietal lobe showed enhanced theta phase synchronization with other regions within the lateral posterior parietal lobe (PPL) and left medial temporal lobe (MTL). However, functional coordination involving the inferior parietal lobe was higher in the incongruent condition. These results suggest a differential engagement of top-down and bottom-up mechanisms during encoding of semantically congruent and incongruent episodic associations, respectively. Although retrieval processes operated on a similar neural network, the main difference with the study phase was the larger amount of functional links shown by the lateral prefrontal cortex with regions of the MTL and PPL. All together, these results suggest that theta oscillations mediate, at least partially, the positive effect of semantic congruence on associative memory by (i) optimizing top-down attentional mechanisms through enhanced theta phase synchronization between dorsal regions of the PPL and MTL and (ii) by adjusting the control of automatic attention to sensory and contextual information reactivated in the MTL through functional connections with the inferior parietal lobe during both encoding and retrieval processes.

Antioxidant activity of different extracts of Argentinian medicinal plants against arsenic-induced toxicity in renal cells.

Chronic toxicity of arsenic resulting from drinking water is a health problem encountered in humans, especially in South America and Asia, where a correlation between oxidative stress, tumor promotion, and arsenic exposure has been observed. Differential solvent extraction (petroleum ether (PE); dichloromethane (DCM); methanol (OL) and water (W)) was performed to compare the protective (antioxidant) activity of five Argentinian medicinal plants on arsenite-induced oxidative stress in Vero cells, assayed by hydroperoxide measurement. The results were analyzed using ANOVA followed by the LSD Fisher test. The data showed that arsenite was a pro-oxidant agent which acts in a time-dose-dependent manner. Extracts from Eupatorium buniifolium (PE), Lantana grisebachii (PE, W), Mandevilla pentlandiana (PE, W), and Sebastiania commersoniana (DCM, OL, W) prevented the formation of both aqueous and lipid hydroperoxides, but Heterothalamus alienus only impeded lipid ones. Therefore, antioxidant extracts are potentially beneficial and may have a protective activity against arsenite-induced renal injury. Among these, the aqueous extract of L. grisebachii may represent the most suitable preparation for humans since the traditional usage of this plant in popular medicine is through consumption of tea.

[Multichannel intraluminal esophageal impedance: a new frontier in motility]. / Impedancia esofágica intraluminal de canal múltiple: una nueva frontera en motilidad.

Multichannel intraluminal impedance is a new technique for evaluating esophageal function and gastroesophageal reflux disease (GERD). This technique relies on the monitoring of electric conductivity in the esophagus though electrodes, and on changes developing in this variable as a result of bolus passage. The proximal distribution and duration of non-acid reflux events can now be quantified, and combined manometry defines the effectiveness of esophageal body function, until now only indirectly evaluated with pH changes. We discuss the case of a woman with persistent cough in whom intraesophageal multichannel impedance demostrates a minor acid reflux that could not be demonstrated with other diagnostic methods previously, and how this technique excludes any association between cough and non-acid reflux.

Impedancia esofágica intraluminal de canal múltiple: una nueva frontera en motilidad / No disponible

La impedancia esofágica multicanal constituye una de las másrecientes herramientas diagnósticas aplicadas a la evaluación de laenfermedad por reflujo gastroesofágico. Esta técnica se basa en lamonitorización continua de la conductividad eléctrica en un medio,en este caso el esófago, a través de electrodos situados en lalongitud de una sonda, y en los cambios que un elemento como elbolo alimentario puede producir en dicha variable. De esta técnicase derivan nuevas perspectivas en la exploración de la funciónesofágica y de la enfermedad por reflujo gastroesofágico, hastaahora sólo cuantificable de forma indirecta por las fluctuacionesgeneradas por los cambios en el pH del reflujo ácido. Presentamosel caso de una paciente con tos persistente evaluada con esteprocedimiento, en quien se demostró la presencia de reflujo gastroesofágicodébilmente ácido que no pudo ser demostrado previamentecon otras exploraciones, y de cómo la impedancia descartóla asociación entre este síntoma y el reflujo no ácido

Multichannel intraluminal impedance is a new technique for evaluatingesophageal function and gastroesophageal reflux disease(GERD). This technique relies on the monitoring of electric conductivityin the esophagus though electrodes, and on changes developingin this variable as a result of bolus passage. The proximal distributionand duration of non-acid reflux events can now be quantified,and combined manometry defines the effectiveness of esophagealbody function, until now only indirectly evaluated with pH changes.We discuss the case of a woman with persistent cough in whom intraesophagealmultichannel impedance demostrates a minor acidreflux that could not be demonstrated with other diagnostic methodspreviously, and how this technique excludes any association betweencough and non-acid reflux

Medicinal plants from the "Sierra de Comechingones", Argentina.

Argentina is a country with both rich floral biodiversity and cultural diversity. Traditional herbal medicines are important in the health care of most people, and rely heavily on the use of indigenous plants. An ethnobotanical survey of the "Sierra de Comechingones" made over a 26-year period (1979-2005), indicated that 65 families and 149 different genuses were used in traditional medicines. The use of these medicines was observed to be widespread and prevalent over orthodox medicine. Medicinal native plants from this mountain range make up 31% of the total Argentina medicinal native flora. In addition, there are 15 endemic species that grow only in the region. The botanical name, popular uses, parts utilized, as well as the distribution of these medicinal plants from the "Sierra de Comechingones", Argentina, were summarized. Previous reports on phytochemical and biological activities in relation to cancer, antimicrobials and pesticides were also included.