Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors

<p>Abstract</p> <p>Background</p> <p>Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease.</p> <p>Methods</p> <p>Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation.</p> <p>Results</p> <p>Mean strain was -21% ± 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% ± 3). Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR). Thirty-six patients had normal or mildly reduced RV function (strain ≤ -20%, mean -25% ± 3). There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p < 0.001). Patients with reduced RV function had higher plasma CCN2 levels than those with normal or mildly reduced RV function (p < 0.001). Plasma CCN2 ≥ 77 μg/L was an independent predictor of reduced RV function (odds ratio 15.36 [95% CI 4.15;56.86]) and had 88% sensitivity and 69% specificity for its detection (p < 0.001). Plasma CCN2 was elevated in patients with mild or greater TR/PR compared to those with no or minimal TR/PR (p = 0.008), with the highest levels seen in moderate to severe TR/PR (p = 0.03).</p> <p>Conclusions</p> <p>Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.</p

Sustainable Holocene landscape use in the Armenian highlands: insight from pollen and reveals models.

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5,000 years of environmental change and anthropogenic impact deduced from gravity sediment cores from Lake Sevan, Armenia

Lake Sevan is located in eastern Armenia close to the border to Azerbaijan. With a length of ~70 km, a width of ~50 km at an altitude of 1900 m a.s.l. it is one of the largest freshwater high-mountain lakes. The lake itself is structured in two parts: the larger southern part called Big Sevan has a maximum water depth of 34 m whereas the northern smaller part called Small Sevan has a water depth of 65 m in the centre and a maximum water depth of 83 m close to the northern shore as a result of active tectonics.Up to now, only limited information exists about more distal profundal sediments from Lake Sevan. Studies, which have been carried out so far, focused on micropaleontological investigations such as ostracods or pollen. Chemical investigations let alone multi-proxy approaches have rarely been done. In order to explore the further potential of sediments from Lake Sevan we recovered 16 gravity cores (51-141 cm length) from both parts of the lake in October 2021. All cores are clearly characterised by a more homogenous sedimentation in the lower part of the core and a more diverse succession in the upper part, which can likely be attributed to intense water level regulations since Soviet times, and anthropogenic impact in the subrecent past. In addition to that, the longest recovered sediment sequence (SEV21-6; 141 cm length) is finely laminated in the bottom part.Radiocarbon ages on two cores from the centres of each lake part indicate a rather constant sedimentation rate since 5,000 cal BP in Big (SEV21-6) and 3,000 cal BP in Small Sevan. These chronologies are currently checked using paleomagnetic secular variation stratigraphy. Subsequently, they will be used in combination with a multi-proxy approach consisting of grain sizes, CNS, XRF-scanning and visible-spectrum scanning reflectance spectroscopy (VIS-RS) analyses as well as micropaleontological parameters (pollen, diatoms) for paleoenvironmental reconstructions

The Entanglement of Landscape: Fire, Climate, and Agro-Pastoralism in the Bronze and Iron Age South Caucasus

This paper investigates how the different social and political structures in Bronze and Iron Age Armenia shaped the surrounding steppe landscape through their agro-pastoral practices. We utilized a series of sediment cores from an altitudinal transect from around Mount Aragats, Armenia in conjunction with multiple biological and geochemical proxies (pollen, non-pollen palynomorphs, XRF, brGDGTs) and the archaeological record to untangle drivers of landscape change. This novel approach integrates multiple lines of evidence in order to understand the complexity of the entanglements of climate, fire, agro-pastoralism, and vegetation in this mountain steppe landscape.In this paper we focus on the pollen and macro-charcoal results from two sediment cores. One higher in the foothills, published in Cromartie et al. (2020), and a new record located in the valley. We find the markers of human activity corresponds with Early Bronze Age Kura-Araxes expansion of cereal agriculture into this highland region. This is followed by a decline in these markers in the Middle Bronze Age when there is a shift away from permanent settlements and increases in mobile pastoralism. Human indicators of agro-pastoralism land-usage return as communities return to practice settled agriculture from the Late Bronze Age through the Iron Age. Human landscape usage is primarily isolated to the core site in the valley through most of the record, but this changes during the Iron Age when shifts in political structure may have driven communities to utilize wetlands higher in altitude. Macro-charcoal analysis across all cores records a similar fire history which appears to be driven by climate until the last 2000 years but shifts in vegetation in the previous periods suggests humans contributed to declines in the natural fire regime. Overall, our records show that even within a small geographical area, human communities unevenly utilized the landscape and the differing social-political contexts influenced these changes. We highlight that social-political and agro-pastoral change needs to be considered when reconstructing landscape usage and predicting future change

The Entanglement of Landscape: Fire, Climate, and Agro-Pastoralism in the Bronze and Iron Age South Caucasus

This paper investigates how the different social and political structures in Bronze and Iron Age Armenia shaped the surrounding steppe landscape through their agro-pastoral practices. We utilized a series of sediment cores from an altitudinal transect from around Mount Aragats, Armenia in conjunction with multiple biological and geochemical proxies (pollen, non-pollen palynomorphs, XRF, brGDGTs) and the archaeological record to untangle drivers of landscape change. This novel approach integrates multiple lines of evidence in order to understand the complexity of the entanglements of climate, fire, agro-pastoralism, and vegetation in this mountain steppe landscape.In this paper we focus on the pollen and macro-charcoal results from two sediment cores. One higher in the foothills, published in Cromartie et al. (2020), and a new record located in the valley. We find the markers of human activity corresponds with Early Bronze Age Kura-Araxes expansion of cereal agriculture into this highland region. This is followed by a decline in these markers in the Middle Bronze Age when there is a shift away from permanent settlements and increases in mobile pastoralism. Human indicators of agro-pastoralism land-usage return as communities return to practice settled agriculture from the Late Bronze Age through the Iron Age. Human landscape usage is primarily isolated to the core site in the valley through most of the record, but this changes during the Iron Age when shifts in political structure may have driven communities to utilize wetlands higher in altitude. Macro-charcoal analysis across all cores records a similar fire history which appears to be driven by climate until the last 2000 years but shifts in vegetation in the previous periods suggests humans contributed to declines in the natural fire regime. Overall, our records show that even within a small geographical area, human communities unevenly utilized the landscape and the differing social-political contexts influenced these changes. We highlight that social-political and agro-pastoral change needs to be considered when reconstructing landscape usage and predicting future change

The Entanglement of Landscape: Fire, Climate, and Agro-Pastoralism in the Bronze and Iron Age South Caucasus

This paper investigates how the different social and political structures in Bronze and Iron Age Armenia shaped the surrounding steppe landscape through their agro-pastoral practices. We utilized a series of sediment cores from an altitudinal transect from around Mount Aragats, Armenia in conjunction with multiple biological and geochemical proxies (pollen, non-pollen palynomorphs, XRF, brGDGTs) and the archaeological record to untangle drivers of landscape change. This novel approach integrates multiple lines of evidence in order to understand the complexity of the entanglements of climate, fire, agro-pastoralism, and vegetation in this mountain steppe landscape.In this paper we focus on the pollen and macro-charcoal results from two sediment cores. One higher in the foothills, published in Cromartie et al. (2020), and a new record located in the valley. We find the markers of human activity corresponds with Early Bronze Age Kura-Araxes expansion of cereal agriculture into this highland region. This is followed by a decline in these markers in the Middle Bronze Age when there is a shift away from permanent settlements and increases in mobile pastoralism. Human indicators of agro-pastoralism land-usage return as communities return to practice settled agriculture from the Late Bronze Age through the Iron Age. Human landscape usage is primarily isolated to the core site in the valley through most of the record, but this changes during the Iron Age when shifts in political structure may have driven communities to utilize wetlands higher in altitude. Macro-charcoal analysis across all cores records a similar fire history which appears to be driven by climate until the last 2000 years but shifts in vegetation in the previous periods suggests humans contributed to declines in the natural fire regime. Overall, our records show that even within a small geographical area, human communities unevenly utilized the landscape and the differing social-political contexts influenced these changes. We highlight that social-political and agro-pastoral change needs to be considered when reconstructing landscape usage and predicting future change

Impact of climate changes on vegetation and human societies during the Holocene in the South Caucasus (Vanevan, Armenia): A multiproxy approach including pollen, NPPs and brGDGTs

International audienceRelationships between steppe vegetation, human practices and climate changes in the past are crucial to disentangle human development in Eurasia. In this frame, our study investigates (1) modern pollen-vegetation relationships and (2) changes in vegetation, human activity and climate in the Holocene record of Vanevan peat (south-eastern shore of Lake Sevan, Armenia), using a multiproxy approach including sediment geochemistry (XRF), pollen, Non-Pollen Palynomorphs (NPPs), and branched Glycerol Dialkyl Glycerol Tetraethers (brGDGTs). Climate reconstructions are provided by (1) water-level changes, (2) brGDGTs, and (3) pollen transfer functions (multi-method approach: Modern Analogue Technique, Weighted Averaging Partial Least Squares regression, Random Forest, and Boosted Regression Trees). Modern pollen assemblages are selected along an altitudinal transect in Armenia. They show a dominance of Chenopodiaceae in semi-desert/steppe regions while meadows steppes, subalpine, and alpine meadows are dominated by Poaceae. Past vegetation is characterized by steppes dominated by Poaceae surrounded during the Mid-Holocene (8200-4200 a cal BP) by scarce open woodlands. Humans have influenced the local vegetation, mainly through their agricultural practices present since 5200 a cal BP with several intensification steps. Our reconstruction indicates a climate shift from a cold and arid Early Holocene toward a warmer and more humid Mid-Late Holocene. An aridification trend marks the last 5000 years causing a drop in water level, which allowed humans to live and cultivate on Lake Sevan shores. Arid events are recorded at 6.2 ka, 5.2 ka, 4.2 ka and 2.8 ka a cal BP, which are commonly related to multi-centennial-scale variations of Westerlies activity (North Atlantic Oscillation). Through our temperature reconstruction, we can assign (1) the 5.2 and 2.8 ka events as being cold and probably related to a strong Siberian High, and (2) the 4.2 ka event as being warm associated with high Arabian subtropical pressures in the South Caucasus and the Near East. Our study suggests a significant impact of these arid events on the Lake Sevan shore populations and they are consistent with cultural phases in the South Caucasus, thus showing the impact of climatic variations on cultural, land use and occupation mode development in this crossroad region between Europe, Africa and Asia

Impact of climate changes on vegetation and human societies in the South Caucasus (Vanevan, Armenia): a multiproxy approach including pollen, NPPs and brGDGTs.

International audienc