Geometry of Middle to Late Triassic extensional deformation pattern in the Cordillera del Viento (Southern Central Andes): A combined field and geophysical study

Combined field and gravimetric-magnetic data reveal a complex pattern of extensional structures superimposed to the late Carboniferous – Early Permian Gondwanan orogen at the inner sectors of the Southern Central Andes, in the westernmost part of the Chos Malal fold and thrust belt at the cordillera del Viento area. W-NW, NW basement structures of regional significance, segmented by minor NE structures are bounding Late Triassic depocenters and structural highs corresponding to the cordillera del Viento rifting, equivalent to the Precuyo cycle. A pattern of roughly N-S trending structures recognized in the field associated with Andean thrusts do not show evidences of previ­ous structural controls, as they cut the magnetic anomalies. Field observations show that W-NW, NW and NE normal structures control changes in Late Triassic sedimentary thicknesses and are associated with synextensional geometries. Our model indicates that Late Triassic rifting in the area would have had a regional W-NW to NW trend being segmented by minor NE structures. Both sets were reactivated dur­ing Andean times, acting W-NW and NW structures as transfer zones between decoupled contractional panels and NE structures as frontal contractional structures. N-S contractional structures did not respect rifting architecture cutting through the depocenters and occasionaly exhuming synextensional geometries.La combinacion de datos de campo, junto con magnéticos y gravimétricos, revelan un patrón complejo de estructuras sobreimpuestas al orógeno gondwánico (Carbonífero superior– Pérmico) en el sector interno de la faja plegada y corrida de los Andes Centrales australes, en el área de la cordillera del Viento. Estructuras de basamento W-NW, NW de significancia regional, segmentadas por estruturas menores NE están limitando depocentros y altos estructurales correspondientes al rifting del Triásico Superior de la cordillera del Viento, equivalente de las unidades del ciclo Precuyo. En el campo se reconoce además un patrón de estructuras de rumbo N, asociadas a fallas andinas que no muestran evidencias de un control estrutural previo, ya que las anomalías magnéticas están cortadas por éstas. Las observaciones de campo demuestran que tanto las estructuras W-NW y NW como las NE controlan cambios de espesor de los sedimentos del Triásico Superior y se asocian a geometrías sinextensionales. El modelo propuesto indica que el rifting del Triásico Superior podría haber tenido una geometría elongada según el patrón de estructuras identificadas W-NW a NW, segmentado por estructuras menores NE. Ambas muestran reactivación durante tiempos andinos, las primeras actuando como zonas de transferencia entre sectores que muestran diferentes grados y mecánicas de contracción y las últimas como estructuras frontales contraccionales. Las estructuras contraccionales de orientación N-S no respetan la arquitectura del rift triásico, cortando los depocentros y eventualmente exhumando geometrías sinextensionales

Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation

BACKGROUND: Spinal cord stimulation (SCS) has been shown to be effective in the management of certain neuropathic pain conditions, however, the underlying mechanisms are incompletely understood. In this study, we investigated repetitive SCS in a rodent neuropathic pain model, revealing long-lasting and incremental attenuation of hyperalgesia and a mechanism of action involving endocannabinoids. METHOD: Animals were implanted with monopolar electrodes at the time of partial sciatic nerve injury. Dorsal columns at spinal segments T12/13 were stimulated 3 days later (early SCS), and again at day 7 (late SCS) using low-frequency parameters. Hypersensitivity to cutaneous mechanical stimuli was assessed using von Frey filaments. Pharmacological agents, selected to identify endocannabinoid and opioid involvement, were administered intraperitoneally, 10 min before SCS. RESULTS: Early SCS caused partial reversal of mechanical hypersensitivity with corresponding changes in the biomarker of central sensitization, [phospho-Tyr1472 ]-GluN2B. The partial reversal of hyperalgesia by early SCS was amplified by co-administration of LY 2183240, an inhibitor of endocannabinoid reuptake/breakdown. This amplification was inhibited by a CB1 R antagonist, AM251, but not by a CB2 R antagonist, AM630. Early SCS-induced reversal of hyperalgesia was attenuated by naloxone, indicating a role for opioids. Late SCS resulted in an incremental level of reversal of hyperalgesia, which was inhibited by AM251, but not by CB2 or opioid receptor antagonists. CONCLUSION: The endocannabinoid system, and in particular the CB1 R, plays a pivotal role in the long-lasting and incremental reversal of hyperalgesia induced by repetitive SCS in a neuropathic pain model

Landscape response to late Pleistocene climate change in NW Argentina: Sediment flux modulated by basin geometry and connectivity

Citation: Schildgen, T. F., Robinson, R. A. J., Savi, S., Phillips, W. M., Spencer, J. Q. G., Bookhagen, B., . . . Strecker, M. R. (2016). Landscape response to late Pleistocene climate change in NW Argentina: Sediment flux modulated by basin geometry and connectivity. Journal of Geophysical Research-Earth Surface, 121(2), 392-414. doi:10.1002/2015jf003607Fluvial fill terraces preserve sedimentary archives of landscape responses to climate change, typically over millennial timescales. In the Humahuaca Basin of NW Argentina (Eastern Cordillera, southern Central Andes), our 29 new optically stimulated luminescence ages of late Pleistocene fill terrace sediments demonstrate that the timing of past river aggradation occurred over different intervals on the western and eastern sides of the valley, despite their similar bedrock lithology, mean slopes, and precipitation. In the west, aggradation coincided with periods of increasing precipitation, while in the east, aggradation coincided with decreasing precipitation or more variable conditions. Erosion rates and grain size dependencies in our cosmogenic Be-10 analyses of modern and fill terrace sediments reveal an increased importance of landsliding compared to today on the west side during aggradation, but of similar importance during aggradation on the east side. Differences in the timing of aggradation and the Be-10 data likely result from differences in valley geometry, which causes sediment to be temporarily stored in perched basins on the east side. It appears as if periods of increasing precipitation triggered landslides throughout the region, which induced aggradation in the west, but blockage of the narrow bedrock gorges downstream from the perched basins in the east. As such, basin geometry and fluvial connectivity appear to strongly influence the timing of sediment movement through the system. For larger basins that integrate subbasins with differing geometries or degrees of connectivity (like Humahuaca), sedimentary responses to climate forcing are likely attenuated

Happiness and health behaviours in Chilean college students: A cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Happiness has been associated with a range of favourable health outcomes through two pathways: its relationship with favourable biological responses to stress and with healthy lifestyles and prudent health behaviours. There are a substantial number of cross-cultural studies about happiness, but none of them has studied the association of happiness with perceived stress and health behaviours in Latin American samples. Therefore, the aim of this study was to examine the association between general happiness and these variables in a Latin American sample.</p> <p>Methods</p> <p>We conducted a survey to examine the status of 3461 students aged between 17 and 24 years old (mean age = 19.89; SD = 1.73) who attended University of Santiago de Chile during 2009. The healthy behaviours indexes assessed were the frequency of daily physical exercise, fruits/vegetables intake, breakfast and lunch intake, smoking, alcohol and other drugs consumption. We also included the assessment of perceived stress and Body Mass Index. All of them were evaluated using a self-report questionnaire.</p> <p>Results</p> <p>The univariate and multivariate binary logistic regression analyses showed that being female and younger was related to a higher happiness, as well as that people self-reporting daily physical activity, having lunch and fruits and vegetables each day had a higher likelihood (OR between 1.33 and 1.40) of being classified as "very happy". Those who informed felt stressed in normal circumstances and during tests situations showed a lower likelihood (0.73 and 0.82, respectively) of being considered "very happy". Regarding drug consumption, taking tranquilizers under prescription was negative related to "subjective happiness" (OR = 0.62), whereas smoking was positive associated (OR = 1.20).</p> <p>Conclusions</p> <p>The findings of this study mainly support the relationship between happiness and health outcomes through the two pathways previously mentioned. They also underscore the importance of that some healthy behaviours and person's cognitive appraisal of stress are integrated into their lifestyle for college students. Additionally, highlight the importance of taking into account these variables in the design of strategies to promote health education in university setting.</p

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe