Increased sympathetic activity is a well-known pathophysiological mechanism in insulin resistance (IR) and hypertension (HT). The carotid bodies (CB) are peripheral chemoreceptors that classically ...respond to hypoxia by increasing chemosensory activity in the carotid sinus nerve (CSN), causing hyperventilation and activation of the sympathoadrenal system. Besides its role in the control of ventilation, the CB has been proposed as a glucose sensor implicated in the control of energy homeostasis. However, to date no studies have anticipated its role in the development of IR. Herein, we propose that CB overstimulation is involved in the etiology of IR and HT, core metabolic and hemodynamic disturbances of highly prevalent diseases like the metabolic syndrome, type 2 diabetes, and obstructive sleep apnoea. We demonstrate that CB activity is increased in IR animal models and that CSN resection prevents CB overactivation and diet-induced IR and HT. Moreover, we show that insulin triggers CB, highlighting a new role for hyperinsulinemia as a stimulus for CB overactivation. We propose that CB is implicated in the pathogenesis of metabolic and hemodynamic disturbances through sympathoadrenal overactivation and may represent a novel therapeutic target in these diseases.
The oral glucose tolerance test (OGTT) is recommended for assessing abnormalities in glucose homeostasis. Recognised as the gold standard test for diagnosing diabetes, the OGTT provides useful ...information about glucose tolerance. However, it does not replicate the process of absorption and digestion of complex foods, such as that which occurs with a mixed meal tolerance test (MMTT), an alternative that is still not well explored in the diagnosis of metabolic alterations. The MMTT could be an asset in detecting glucose homeostasis disorders, including diabetes since it has more similarities to the common dietary pattern, allowing early detection of subtle changes in metabolic homeostasis in response to combined nutrients. This alternative has the advantage of being more tolerable and pleasant to patients since it induces a more gradual increase in blood glucose, thus reducing the risk of rebound hypoglycemia and other related complications. The present article reviewed the clinical data available regarding the possibility of screening or diagnosing altered glucose homeostasis, including type 2 diabetes mellitus, with the MMTT.
Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE type I) or dysfunction (C1-INH-HAE type II) is a rare disease characterized by recurrent episodes of edema with an estimated frequency ...of 1:50,000 in the global population without racial or gender differences. In this study we present the results of a nationwide survey of C1-INH-HAE patients referring to 17 Italian centers, the Italian network for C1-INH-HAE, ITACA.
Italian patients diagnosed with C1-INH-HAE from 1973 to 2013 were included in the study. Diagnosis of C1-INH-HAE was based on family and/or personal history of recurrent angioedema without urticaria and on antigenic and/or functional C1-INH deficiency.
983 patients (53% female) from 376 unrelated families were included in this survey. Since 1973, 63 (6%) patients diagnosed with C1-INH-HAE died and data from 3 patients were missing when analysis was performed. Accordingly, the minimum prevalence of HAE in Italy in 2013 is 920:59,394,000 inhabitants, equivalent to 1:64,935. Compared to the general population, patients are less represented in the early and late decades of life: men start reducing after the 5(th) decade and women after the 6(th). Median age of patients is 45 (IQ 28-57), median age at diagnosis is 26 years (IQ 13-41). C1-INH-HAE type 1 are 87%, with median age at diagnosis of 25 (13-40); type 2 are 13% with median age at diagnosis of 31 (IQ 16-49). Functional C1INH is ≤50% in 99% of patients. Antigen C1INH is ≤50% in 99% of type 1. C4 is ≤50% in 96% of patients. The chance of having C1-INH-HAE with C4 plasma levels >50% is < 0.05.
This nationwide survey of C1-INH-HAE provides for Italy a prevalence of 1:64,935. C1-INH-HAE patients listed in our database have a shorter life expectancy than the general population. An increased awareness of the disease is needed to reduce this discrepancy. Measurement of C4 antigen can exclude diagnosis of C1-INH-HAE with an accuracy > 95%. This parameter should be therefore considered for initial screening in differential diagnosis of angioedema.
We investigate hydrology during a past climate slightly warmer than the present: the last interglacial (LIG). With daily output of preindustrial and LIG simulations from eight new climate models we ...force hydrological model PCR‐GLOBWB and in turn hydrodynamic model CaMa‐Flood. Compared to preindustrial, annual mean LIG runoff, discharge, and 100‐yr flood volume are considerably larger in the Northern Hemisphere, by 14%, 25%, and 82%, respectively. Anomalies are negative in the Southern Hemisphere. In some boreal regions, LIG runoff and discharge are lower despite higher precipitation, due to the higher temperatures and evaporation. LIG discharge is much higher for the Niger, Congo, Nile, Ganges, Irrawaddy, and Pearl and lower for the Mississippi, Saint Lawrence, Amazon, Paraná, Orange, Zambesi, Danube, and Ob. Discharge is seasonally postponed in tropical rivers affected by monsoon changes. Results agree with published proxies on the sign of discharge anomaly in 15 of 23 sites where comparison is possible.
Plain Language Summary
It is still uncertain how the water cycle will respond to a warmer climate in the coming decades. To increase our understanding of the relationships between climate and hydrology, we study the past climate of the last interglacial, which was slightly warmer than the present. We present the results of a modeling approach, showing that while Northern Hemisphere precipitation was higher during the last interglacial, discharge of rivers was even higher, and floods were even larger. On the contrary, in the Southern Hemisphere precipitation, discharge and floods were lower. We show that, for some regions, precipitation, discharge, and floods do not have the same direction of change. The seasonal timing of discharge also changes for some large basins of the Northern Hemisphere. Finally, for 23 sites, we compare our results to geological evidence. These results form a useful term of comparison to both projections of the future and geological studies of past hydrology.
Key Points
We present the first modeling of hydrology and floods for the last interglacial
Boreal precipitation and runoff are higher than preindustrial, and boreal river discharge and flood volume are (in %) even higher
Most of the discharge occurs later in the year in large river basins of the Northern Hemisphere
The gravity wave drag parametrization of the Whole Atmosphere Community Climate Model (WACCM) has been modified to include the wave‐driven atmospheric vertical mixing caused by propagating, ...non‐breaking, gravity waves. The strength of this atmospheric mixing is represented in the model via the “effective wave diffusivity” coefficient (Kwave). Using Kwave, a new total dynamical diffusivity (KDyn) is defined. KDyn represents the vertical mixing of the atmosphere by both breaking (dissipating) and vertically propagating (non‐dissipating) gravity waves. Here we show that, when the new diffusivity is used, the downward fluxes of Fe and Na between 80 and 100 km largely increase. Larger meteoric ablation injection rates of these metals (within a factor 2 of measurements) can now be used in WACCM, which produce Na and Fe layers in good agreement with lidar observations. Mesospheric CO2 is also significantly impacted, with the largest CO2 concentration increase occurring between 80 and 90 km, where model‐observations agreement improves. However, in regions where the model overestimates CO2 concentration, the new parametrization exacerbates the model bias. The mesospheric cooling simulated by the new parametrization, while needed, is currently too strong almost everywhere. The summer mesopause in both hemispheres becomes too cold by about 30 K compared to observations, but it shifts upward, partially correcting the WACCM low summer mesopause. Our results highlight the far‐reaching implications and the necessity of representing vertically propagating non‐breaking gravity waves in climate models. This novel method of modeling gravity waves contributes to growing evidence that it is time to move away from dissipative‐only gravity wave parametrizations.
Plain Language Summary
Atmospheric gravity waves are generated in the lowest layers (∼bottom 10 km) of the atmosphere by processes such as weather systems and air masses interacting with the topography, and can propagate upward to ∼120 km. In this work, the representation of atmospheric gravity waves in a state‐of‐the‐art chemistry climate model, the Whole Atmosphere Community Climate Model (WACCM), has been updated. In the new model version, the mixing of the atmosphere caused by gravity waves that propagate upwards above 80 km and do not break is part of the total mixing of the atmosphere, which hitherto was considered to be caused by the turbulence created by gravity wave breaking. We show here that when this additional source of atmospheric mixing is taken into account, the WACCM model is better able to simulate the sodium and iron atom densities in the upper layers of the atmosphere (between ∼80 and 100 km), created by the ablation of cosmic dust. Additionally, gravity waves significantly affect the representation of CO2 mixing ratios and air temperature within the model. Our work is important because it shows that propagating gravity waves have non‐negligible impacts on basic properties of the Earth's atmosphere such as temperature, winds, and chemical species like CO2, and that the lack of their representation in current climate models needs to be addressed.
Key Points
A parametrization representing vertical mixing by non‐breaking gravity waves has been implemented in a chemistry‐climate model
Mesospheric CO2 and temperature are significantly impacted by the additional source of vertical mixing
Wave‐induced constituent transport largely reconciles the modeled mesospheric Na and Fe layers with the estimated meteoric injection rates
The carotid bodies (CBs) are peripheral chemoreceptor organs classically described as being O2 sensors, which are increasingly emerging as core players in metabolic control. Herein we evaluated CB ...activity in prediabetes patients and determined its correlation with dysmetabolism clinical features.
Prediabetes patients were recruited at the Cardiology Service, Hospital Santa Marta, Centro Hospitalar Lisboa Central, EPE (CHLC-EPE). The study was approved by CHLC-EPE and NOVA Medical School Ethics Committee. Thirty-three prediabetic and 14 age-matched, non-prediabetic, volunteers had their peripheral chemosensitivity evaluated by the Dejours test. Serum biomarkers of metabolic disease, insulin sensitivity (HOMA-IR), blood pressure, carotid intima-media thickness (cIMT) and glucose tolerance were assessed.
CB chemosensitivity was significantly increased in prediabetic group (P < 0.01). Fasting blood, glucose intolerance, fasting insulin and HOMA-IR were significantly higher in prediabetes patients. Insulin resistance correlated both with peripheral chemosensitivity, assessed by the Dejours test (P < 0.05) and with abdominal circumference (P < 0.01). HbA1c correlated with HOMA-IR (P < 0.05) and left cIMT (P < 0.05) in prediabetes patients.
We conclude that CB is overactive in prediabetes subjects and that peripheral chemosensitivity correlates with fasting insulin and insulin resistance representing a novel non-invasive functional biomarker to forecast early metabolic disease.
Cancer immunotherapy represents a novel anticancer strategy that acts directly on the immune system, promoting its activation toward cancer cells to enhance its natural ability to fight cancer. Among ...various treatments currently used or investigated, chimeric antigen receptors (CAR) T-cell therapy and immune checkpoint inhibitors (ICIs) have consistently proven their efficacy. These innovations are progressively improving the standard of care in cancer treatment, yet they are hampered by novel neurological adverse events, attributing to neurologists a key role in the multidisciplinary oncological team. Indeed, neurotoxicity may develop in up to 77% of patients who received CAR T-cell therapy and usually presents with encephalopathy characterized by a predominant frontal lobe dysfunction. This neurotoxicity is related to cytokine release syndrome, a systemic hyperinflammatory condition triggered by CAR T-cells. On the other hand, following treatment with ICIs, unrestrained T-cells may lead to central and peripheral neurological disorders by antigen-directed autoimmunity. Notably, biological and clinical similarities have been underlined between neurotoxicity related to CAR T-cell therapy and neurological manifestations of cytokine storms (e.g. COVID-19-related encephalopathy), as well as between a subgroup of ICI-related neurological adverse events and paraneoplastic neurological syndromes. Therefore, these cancer immunotherapy-related neurological syndromes may provide an unprecedented, perhaps transitory, opportunity to shed light on the underlying pathogenic mechanisms of a wide spectrum of neurological syndromes and to push forward our knowledge in neuroimmunology.
To test the efficacy of three nutrition education strategies on the intake of different vegetables in preschool children.
This is an experimental study conducted in four Portuguese preschools. The ...intervention consisted of 20-min educational sessions, once a week, for 5 weeks, with one of the following randomised educational strategies: Portuguese Food Wheel Guide (control), digital game, storybook, storybook and reward (stickers). All groups had repeated exposure to vegetables in all sessions. A pre- and post-test were conducted to determine vegetable intake, and a 6-month follow-up was realised.
Preschools of Leiria district, Portugal.
A sample of 162 children aged 3 to 6 years. All eligible children attending the preschools were invited to participate.
All interventions tested were effective in increasing vegetable consumption both in the short and medium term, without statistically significant differences, compared to the control group. Stickers were more effective in the short term than in the medium term.
The nutritional education strategies associated with repeated exposure tested in this study were effective in promoting vegetable consumption in preschool children. The use of stickers may be a valid strategy to promote the consumption of vegetables less recognised by children.
The carotid bodies (CB) are peripheral chemoreceptors that sense changes in arterial blood O2, CO2, and pH levels. Hypoxia, hypercapnia, and acidosis activate the CB, which respond by increasing the ...action potential frequency in their sensory nerve, the carotid sinus nerve (CSN). CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS) activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnea (OSA) is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH) and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future.
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