Inactivity as a key factor inducting insulin resistance and metabolic syndrome

2009/2010Introduction. The metabolic syndrome is a cluster of alterations, including insulin resistance, dyslipidaemia, hypertension, hyperglycaemia, abdominal obesity, hyperhomocysteinemia, inflammation and oxidative stress, leading to type II diabetes and cardiovascular disease. The metabolic syndrome is usually associated with sedentary lifestyle and overweight, while regular physical activity and weight loss can counteract these alterations and prevent type II diabetes and cardiovascular disease. Aim of the Thesis. In order to define the net role of inactivity as key factor inducing insulin resistance and metabolic syndrome independently from changes in body fat we have investigated the net impact of experimental bed rest on human metabolism. Experimental bed rest in healthy, young, lean subjects represents a suitable model to determine the effects of inactivity on physiology, avoiding potential interferences and confounding effects of diseases, ageing, energy unbalance and excess body fat. We have focused on inactivity-related development of insulin resistance, dyslipidaemia, hypertension as well as inflammation and oxidative stress. These aspects have been investigated during four different experimental bed rest protocols, lasting 2 months (WISE-Toulouse, France) and 5 weeks (Valdoltra, Slovenia 2006–2007–2008). Energy requirements and intakes were strictly controlled to avoid changes in fat mass. Results and discussion. Muscle atrophy. Muscle atrophy was evidenced after three weeks of bed rest and was worsened by prolonged exposure to inactivity (WISE, Valdoltra studies). However, muscle loss rate was higher in the first 5 weeks of bed rest while it decreased in the second month of inactivity (WISE). Time-course analysis of insulin resistance development. Insulin resistance, measured by an oral glucose tolerance test, rapidly developed in the first week of inactivity and was maintained after 5 weeks of bed rest, as assessed by the ISI-Belfiore index of insulin sensitivity (Valdoltra 2008). Cardiovascular regulation. In the first week of bed rest, baroreflex sensitivity decreased indicating that, in an early phase, alterations in the sympatovagal balance paralleled changes in insulin resistance development. At the end of 5 week-bed rest, heart rate and heart rate variability as well as systolic blood pressure variability, indexes of cardiovascular regulation, were also impaired (Valdoltra 2008). Plasma lipids and lipid metabolism. Five weeks of bed rest induced a decrease in high-density lipoprotein (HDL) cholesterol. During inactivity, cholesteryl ester transfer protein (CETP), a key enzyme involved in HDL metabolism, was up-regulated and changes in CETP inversely correlated with changes in HDL-to-non-HDL cholesterol ratio. Conversely, changes in CETP and HDL were not directly correlated to insulin resistance (Valdoltra studies). Cell membrane lipids. Bed rest reduced monounsaturated FAs, enhanced n-6 polyunsaturated FA total contents and affected activities of both Δ-5 and Δ-9 desaturases, enzymes involved in FA metabolism. These data further support that membrane FA composition and activities of Δ-5 and Δ-9 desaturases are predictive indicators of metabolic syndrome development. Moreover, arachidonic-to-eicosapentaenoic acid ratio, reflecting the competitive role of these FAs in the modulation of inflammatory processes, was shifted towards pro-inflammatory state (Valdoltra studies). Oxidative stress and glutathione kinetics. Bed rest induced oxidative stress as showed by enhanced muscle protein carbonylation, a marker of tissue exposure to oxidative damage, and increased muscle glutathione absolute synthesis, as assessed by a new one-sample, double-isotope tracers infusion method (Valdoltra 2007). Homocysteinemia and homocysteine kinetics. Plasma homocysteine level was increased by bed rest, due to a decrease in homocysteine clearance related to remethylation (WISE). Hyperhomocysteinemia is a further evidence of inactivity-mediated oxidative stress and increased cardiovascular risk. Conclusions. Physical inactivity in healthy young subjects is a suitable model to define the net impact of physical inactivity on the development of metabolic alterations observed in patients with the metabolic syndrome. Our results indicate that inactivity is directly involved in insulin resistance development, low-grade systemic inflammation, dyslipidaemia, hyperhomocysteinemia, oxidative stress and autonomic-cardiovascular abnormalities.XXIII Ciclo198

White Matter Imaging Correlates of Early Cognitive Impairment Detected by the Montreal Cognitive Assessment after Transient Ischemic Attack and Minor Stroke

BACKGROUND AND PURPOSE:  Among screening tools for cognitive impairment in large cohorts, the Montreal Cognitive assessment (MoCA) appears to be more sensitive to early cognitive impairment than the Mini-Mental State Examination (MMSE), particularly after transient ischemic attack (TIA) or minor stroke. We reasoned that if MoCA-detected early cognitive impairment is pathologically significant, then it should be specifically associated with the presence of white matter hyperintensities (WMH) and reduced fractional anisotropy (FA) on MRI. METHODS: Consecutive eligible patients with TIA or minor stroke (Oxford Vascular Study) underwent MRI and cognitive assessment. We correlated MoCA and MMSE scores with WMH and FA, then specifically studied patients with low MoCA and normal MMSE. RESULTS: Among 400 patients, MoCA and MMSE scores were significantly correlated (all p<0.001) with WMH volumes (rMoCA=-0.336, rMMSE=-0.297) and FA (rMoCA=0.409, rMMSE=0.369), and -on voxel-wise analyses- with WMH in frontal white matter and reduced FA in almost all white matter tracts. However, only the MoCA was independently correlated with WMH volumes (r=-0.183, p<0.001), average FA values (r=0.218, p<0.001), and voxel-wise reduced FA in anterior tracts after controlling for the MMSE. In addition, patients with low MoCA but normal MMSE (N=57) had higher WMH volumes (t=3.1,p=0.002), lower average FA (t=-4.0,p<0.001), and lower voxel-wise FA in almost all white matter tracts than those with normal MoCA and MMSE (N=238). CONCLUSIONS: In patients with TIA or minor stroke, early cognitive impairment detected with the MoCA but not with the MMSE was independently associated with white matter damage on MRI, particularly reduced FA

Prehistoric pottery and the instrumental kit for its production. Description of the archaeological record of Coro Trasito (Tella-Sin, Huesca)

Resumen: En este artículo presentamos los instrumentos de trabajo relacionados con la producción cerámica. El punto de partida es una serie de programas experimentales que nos permiten definir la aparición y el desarrollo de los rastros de uso en las superficies de los distintos instrumentos relacionados con esa producción, una vez reconocidos a nivel arqueológico. Esto incluye el uso de instrumentos manufacturados en materias primas de distinto origen: minerales (lítico tallado, cantos y/o guijarros naturales, fragmentos de cerámica?), y materias duras de origen animal (espátulas/punzones de hueso, instrumentos de conchas?). Una vez definidos estos tipos de instrumentos de trabajo, aplicamos el estudio a un yacimiento arqueológico concreto. En este caso, describimos los instrumentos recuperados en Coro Trasito (Tella-Sin, Huesca) que tienen que ver con la producción y el mantenimiento de la cerámica, especialmente en un periodo cronológico relacionado con el Neolítico antiguoAbstract: In this work, we present the working tools related to pottery production. The starting point is a series of experimental programs that allow us to define the presence and development of usewear traces on the surfaces of the different instruments related to that production ?which were recognized in archaeological contexts. This includes the use of tools manufactured in raw materials of different origin: minerals (lithic knapped blanks, natural cobbles and/or pebbles, pottery sticks?), and hard materials of animal origin (bone spatulas/awls, shell tools?). Once these types of working tools have been defined, we bring the study to specific archaeological contexts. In this case, we describe the instruments recovered in Coro Trasito (Tella-Sin, Huesca) and how these tools relate to the production and upkeep of pottery vessels, especially during a chronological period related to the ancient Neolithic period

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5–11 December, to 17.5% (25/143 samples) in the week 12–18, to 65.9% (89/135 samples) in the week 19–25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased fromone in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons

Patent foramen ovale and unexplained stroke

Comment on: N Engl J Med. 2005 Dec 1;353(22):2361-72