Asociación del colesterol remanente con el grado de control glucémico y la presencia de complicaciones microvasculares en personas con diabetes mellitus tipo 1 / Association of remnant cholesterol with glycemic control and presence of microvascular complications in individuals with type 1 diabetes mellitus

Introducción Este trabajo investiga la relación entre el colesterol remanente, las métricas de glucosa y las complicaciones crónicas de la diabetes tipo 1 en individuos con sistemas flash de glucosa. Material y métodos Se recopilaron variables clínicas y métricas de glucosa de personas usuarias de sensores de glucosa. Se llevaron a cabo modelos estadísticos para estudiar la asociación del colesterol remanente con las métricas de glucosa, así como con la retinopatía y la nefropatía diabética. Resultados Se incluyeron 383 personas con una edad de 48,3±16,2 años, siendo un 54,1% mujeres, con un colesterol remanente de 16±10mg/dl. Los resultados mostraron que el colesterol remanente se asocia a un menor tiempo en rango (p=0,015) y a un mayor tiempo por encima del rango (p=0,003). La nefropatía diabética fue la única complicación que se asoció con un colesterol remanente mayor a 30mg/dl, OR: 8,93: IC 95%: 2,99-26,62; p<0,001. Conclusión El colesterol remanente se asocia de forma independiente con la hiperglucemia y la nefropatía diabética en personas con diabetes tipo 1. (AU)

Introduction This study examines the relationship between remnant cholesterol, glucose metrics, and chronic complications of type 1 diabetes in users of glucose monitoring systems. Material and methods Clinical variables and glucose metrics were collected from individuals using glucose sensors. Statistical models were employed to investigate the association of remnant cholesterol with glucose metrics, diabetic retinopathy, and diabetic nephropathy. Results A total of 383 individuals, aged 48.3±16.2 years, with 54.1% women, and a remnant cholesterol level of 16±10mg/dL, were included. The results demonstrated that remnant cholesterol was associated with less time within the target range (P=.015) and more time above the target range (P=.003). Diabetic nephropathy was the only complication associated with remnant cholesterol levels exceeding 30mg/dL; OR: 8.93; 95% CI: 2.99-26.62, P<.001. Conclusion Remnant cholesterol is independently associated with hyperglycemia and diabetic nephropathy in individuals with type 1 diabetes. (AU)

Quantitative analysis of Tr1 lymphocytes in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is usually accompanied by a low-grade inflammatory phenomenon, which participates in the pathogenesis of different complications of this condition. The inflammatory response is under the regulation of different mechanisms, including T regulatory (Treg) lymphocytes. However, the possible role of type 1 T regulatory (Tr1) cells in T2DM has not been explored so far. AIM: To carry out a quantitative analysis of Tr1 lymphocytes and other immune cell subsets in patients with T2DM and correlate these results with clinical findings and treatments. MATERIALS AND METHODS: Sixty patients with T2DM and twenty-three healthy controls were included in the study. Biochemical and anthropometric variables were evaluated, and Tr1 lymphocytes (CD4+CD49+LAG-3+IL-10+) and other cell subsets (Th17, Th22 and Foxp3 + Treg cells) were analyzed in peripheral blood samples by multiparametric flow cytometry. RESULTS: Significant increased levels of Tr1 cells were detected in patients with severe and mild disease, compared to healthy controls. In addition, CD4+IL-10+ lymphocytes were also increased in patients with T2DM. In contrast, similar levels of Foxp3+ Treg cells, Th17 and Th22 lymphocytes were observed in patients and controls. Likewise, no significant associations were detected between Tr1 cell levels and different clinical and laboratory parameters. However, those patients receiving glucagon-like peptide-1 receptor agonists (GLP-1-RA) showed similar levels of Tr1 cells than healthy controls, and significant lower numbers than untreated patients. CONCLUSION: We observed an increase in Tr1 and CD4+IL10+ lymphocyte levels in T2DM. Moreover, GLP1-RA treatment was significantly associated with normalization of the Tr1 levels. This highlights another potential immune dysfunction in patients with T2DM, which could participate in the pathogenesis of this condition.

Asociación del colesterol remanente con el grado de control glucémico y la presencia de complicaciones microvasculares en personas con diabetes mellitus tipo 1 / Association of remnant cholesterol with glycemic control and presence of microvascular complications in individuals with type 1 diabetes mellitus

Introducción Este trabajo investiga la relación entre el colesterol remanente, las métricas de glucosa y las complicaciones crónicas de la diabetes tipo 1 en individuos con sistemas flash de glucosa. Material y métodos Se recopilaron variables clínicas y métricas de glucosa de personas usuarias de sensores de glucosa. Se llevaron a cabo modelos estadísticos para estudiar la asociación del colesterol remanente con las métricas de glucosa, así como con la retinopatía y la nefropatía diabética. Resultados Se incluyeron 383 personas con una edad de 48,3±16,2 años, siendo un 54,1% mujeres, con un colesterol remanente de 16±10mg/dl. Los resultados mostraron que el colesterol remanente se asocia a un menor tiempo en rango (p=0,015) y a un mayor tiempo por encima del rango (p=0,003). La nefropatía diabética fue la única complicación que se asoció con un colesterol remanente mayor a 30mg/dl, OR: 8,93: IC 95%: 2,99-26,62; p<0,001. Conclusión El colesterol remanente se asocia de forma independiente con la hiperglucemia y la nefropatía diabética en personas con diabetes tipo 1. (AU)

Introduction This study examines the relationship between remnant cholesterol, glucose metrics, and chronic complications of type 1 diabetes in users of glucose monitoring systems. Material and methods Clinical variables and glucose metrics were collected from individuals using glucose sensors. Statistical models were employed to investigate the association of remnant cholesterol with glucose metrics, diabetic retinopathy, and diabetic nephropathy. Results A total of 383 individuals, aged 48.3±16.2 years, with 54.1% women, and a remnant cholesterol level of 16±10mg/dL, were included. The results demonstrated that remnant cholesterol was associated with less time within the target range (P=.015) and more time above the target range (P=.003). Diabetic nephropathy was the only complication associated with remnant cholesterol levels exceeding 30mg/dL; OR: 8.93; 95% CI: 2.99-26.62, P<.001. Conclusion Remnant cholesterol is independently associated with hyperglycemia and diabetic nephropathy in individuals with type 1 diabetes. (AU)

Association of remnant cholesterol with glycemic control and presence of microvascular complications in individuals with type 1 diabetes mellitus.

INTRODUCTION: This study examines the relationship between remnant cholesterol, glucose metrics, and chronic complications of type 1 diabetes in users of glucose monitoring systems. MATERIAL AND METHODS: Clinical variables and glucose metrics were collected from individuals using glucose sensors. Statistical models were employed to investigate the association of remnant cholesterol with glucose metrics, diabetic retinopathy, and diabetic nephropathy. RESULTS: A total of 383 individuals, aged 48.3 ±â€¯16.2 years, with 54.1% women, and a remnant cholesterol level of 16 ±â€¯10 mg/dL, were included. The results demonstrated that remnant cholesterol was associated with less time within the target range (p = 0.015) and more time above the target range (p = 0.003). Diabetic nephropathy was the only complication associated with remnant cholesterol levels exceeding 30 mg/dL, OR 8.93, 95% CI (2.99-26.62), p < 0.001. CONCLUSION: Remnant cholesterol is independently associated with hyperglycemia and diabetic nephropathy in individuals with type 1 diabetes.

DNA-Modulated and Mechanoresponsive Excitonic Couplings Reveal Chiroptical Correlation of Conformation, Tension, and Dynamics of DNA Self-Assembly.

Study of the conformational and mechanical behaviors of biomolecular assemblies is vital to the rational design and realization of artificial molecular architectures with biologically relevant functionality. Here, we revealed DNA-modulated and mechanoresponsive excitonic couplings between organic chromophores and verified strong correlations between the excitonic chiroptical responses and the conformational and mechanical states of DNA self-assemblies irrespective of fluorescence background interference. Besides, the excitonic chiroptical effect allowed sensitive monitoring of DNA self-assembled nanostructures due to small molecule bindings or DNA strand displacement reactions. Moreover, we developed a new chiroptical reporter, a DNA-templated dimer of an achiral cyanine5 and an intrinsically chiral BODIPY, that exhibited unique multiple-split spectral line shape of exciton-coupled circular dichroism, largely separated response wavelengths, and enhanced anisotropy dissymmetry factor (g-factor). These results shed light on a promising chiroptical spectroscopic tool for studying biomolecular recognition and binding, conformation dynamics, and soft mechanics in general.

Risk assessment of silver and microplastics release from antibacterial food containers under conventional use and microwave heating.

The evaluation of the migration of ionic silver and nanoparticulated silver (AgNPs) from antimicrobial plastic packaging to food is crucial to ensure its safety. Migration assays were performed on reusable silver-containing polypropylene (PP) food containers and a silicone baby bottle, using food simulants, under conventional or microwave heating and repeated use. The PP containers released significant amounts of silver, increasing with temperature, contact time, acidity and lower crystallinity. Silver migration in the silicone bottle was much lower. Risk assessment of released silver was done considering European authorities safety recommendations, with some containers far exceeding these levels. No significant AgNPs release was detected in the simulants by single particle-ICPMS. Silver-containing microplastics and silicone microparticles were detected by SEM in the food simulants after the migration assays. Consumers may be continuously exposed to the harmful effects of ionic silver and microplastics, which can potentially lead to health issues.

Finding answers in lipid profile in COVID-19 patients.

INTRODUCTION: A small percentage of patients will develop a severe form of COVID-19 caused by SARS-CoV-2 infection. Thus, it is important to predict the potential outcomes identifying early markers of poor prognosis. In this context, we evaluated the association of SARS-CoV-2 infection with lipid abnormalities and their role in prognosis. METHODS: Single-center, retrospective, observational study of COVID-19 patients admitted from March to October 2020. Clinical and laboratory data, comorbidities, and treatments for COVID-19 were evaluated. Main outcomes including intensive care unit (ICU) admission and mortality were analyzed with a multivariable Cox proportional hazards regression model. RESULTS: We selected 1489 from a total of 2038 consecutive patients with confirmed COVID-19, who had a complete lipid profile before ICU admission. During the follow-up performed in 1109 patients, we observed a decrease in T-c, HDL-c, and LDL-c in 28.6%, 42.9%, and 30.4% of patients, respectively, and an increase in TG in 76.8%. The decrease of both T-c and HDL- c was correlated with a decrease in albumin levels (r = 0.39 and r = 0.37, respectively). Kaplan-Meier survival curves found an increased ICU admission in patients with lower T-c (HR 0.55, CI 0.36-0.86), HDL-c (HR 0.61, CI 0.45-0.84), and LDL-c (HR 0.85, CI 0.74-0.97). Higher values of T-c (HR 0.45, CI 0.36-0.57), HDL-c (HR 0.66, CI 0.54-0.81), and LDL-c (HR 0.86, CI 0.78-0.94) showed a protective effect on mortality. CONCLUSIONS: Abnormalities in lipid profile are a frequent complication of SARS-CoV-2 infection and might be related to morbidity and mortality. FUNDING: Proyectos de Investigación en Salud (FIS) and cofinanced by FEDER.

One year of the pandemic - how European endocrinologists responded to the crisis: a statement from the European Society of Endocrinology.

Changes that COVID-19 induced in endocrine daily practice as well as the role of endocrine and metabolic comorbidities in COVID-19 outcomes were among the striking features of this last year. The aim of this statement is to illustrate the major characteristics of the response of European endocrinologists to the pandemic including the disclosure of the endocrine phenotype of COVID-19 with diabetes, obesity and hypovitaminosis D playing a key role in this clinical setting with its huge implication for the prevention and management of the disease. The role of the European Society of Endocrinology (ESE) as a reference point of the endocrine community during the pandemic will also be highlighted, including the refocusing of its educational and advocacy activities.

COVID-19 and endocrine and metabolic diseases. An updated statement from the European Society of Endocrinology.

BACKGROUND: COVID-19 has completely changed our daily clinical practice as well as our social relations. Many organs and biological systems are involved in SARS-Cov-2 infection, either due to direct virus-induced damage or to indirect effects that can have systemic consequences. Endocrine system is not only an exception but its involvement in COVID-19 is so relevant that an "endocrine phenotype" of COVID-19 has progressively acquired clinical relevance. AIM: We have been appointed by the European Society of Endocrinology (ESE) to update with the current statement ESE members and the whole endocrine community on the emerging endocrine phenotype of COVID-19 and its implication for the prevention and management of the disease. CONCLUSIONS: Diabetes has a major role in this phenotype since it is one of the most frequent comorbidities associated with severity and mortality of COVID-19. Careful management including treatment modifications may be required for protecting our patients rather with known diabetes from the most dangerous consequences of COVID-19 or hospitalized with COVID-19, but also in patients with SARS-CoV-2 induced newly onset diabetes. Obesity increases susceptibility to SARS-CoV-2 and the risk for COVID-19 adverse outcome. Adequate nutritional management needs to be granted to patients with obesity or undernourishment in order to limit their increased susceptibility and severity of COVID-19 infection. Lack of vitamin D, hypocalcemia and vertebral fractures have also emerged as frequent findings in the hospitalized COVID-19 population and may negatively impact on the outcome of such patients. Also, in patients with adrenal insufficiency prompt adaptation of glucocorticoid doses may be needed. Moreover, in this updated statement role of sex hormones as well as peculiar pituitary and thyroid aspects of COVID-19 have been included. Finally, in view of the mass vaccination, potential implications for endocrine patients should be considered.

Maximum adenoma diameter, regardless of uni- or bilaterality, is a risk factor for autonomous cortisol secretion in adrenal incidentalomas.

PURPOSE: To evaluate differences between patients with unilateral and bilateral adrenal incidentalomas (AIs) in the prevalence of autonomous cortisol secretion (ACS) and related comorbidities. METHODS: In this multicentre retrospective study, AIs ≥ 1 cm without overt hormonal excess were included in the study. ACS was defined by a post-dexamethasone suppression test (DST) serum cortisol ≥ 5.0 µg/dl, in the absence of signs of hypercortisolism. For the association of ACS with the prevalence of comorbidities, post-DST serum cortisol was also analysed as a continuous variable. RESULTS: Inclusion criteria were met by 823 patients, 66.3% had unilateral and 33.7% bilateral AIs. ACS was demonstrated in 5.7% of patients. No differences in the prevalence of ACS and related comorbidities were found between bilateral and unilateral AIs (P > 0.05). However, we found that tumour size was a good predictor of ACS (OR = 1.1 for each mm, P < 0.001), and the cut-off of 25 mm presented a good diagnostic accuracy to predict ACS (sensitivity of 69.4%, specificity of 74.1%). During a median follow-up time of 31.2 (IQR = 14.4-56.5) months, the risk of developing dyslipidaemia was increased in bilateral compared with unilateral AIs (HR = 1.8, 95% CI = 1.1-3.0 but, this association depended on the tumour size observed at the end of follow-up (HR adjusted by last visit-tumour size = 0.9, 95% CI = 0.1-16.2). CONCLUSIONS: Tumour size, not bilaterality, is associated with a higher prevalence of ACS. During follow-up, neither tumour size nor bilaterality were associated with the development of new comorbidities, yet a larger tumour size after follow-up explained the association of bilateral AIs with the risk of dyslipidaemia.

Hydrogeological constraints for the genesis of the extreme lithium enrichment in the Salar de Atacama (NE Chile): A thermohaline flow modelling approach.

The Salar de Atacama (SdA) is the largest Li reserve globally. The origin of Li, together with the rest of solutes, has been object of debate. Thus, rock weathering at low temperature, hydrothermal leaching or magmatic origin together with subsequent evaporation has been hypothesized. However, the extreme Li enrichment (>4000 mg/L) and the location of the Li-Mg-rich brines around the Salar Fault System (SFS) that crosses the nucleus of the SdA in half remain unexplained. The objective of this work is to define the thermohaline groundwater flow in the SdA basin to account for the genesis of its extreme Li enrichment. Thermohaline flow modelling has demonstrated the critical effect of the minimum hydraulic head (MHH) of the regional water table on the groundwater flow of salt flats. The MHH divides the basin into two isolated hydrodynamic systems and constitutes the endpoint towards which the most evaporated brines converge. The spatial mismatch between the locations of the Li-Mg-rich brines in the central-western zone of the nucleus (in the SFS) and the MHH in the easternmost zone of the nucleus discards recent evaporative concentration of the recharge water as the main mechanism of Li enrichment. Moreover, the persistence of a saline interface surrounding the nucleus at depth, regardless of the temperature gradient, also precludes lateral recharge (predominantly from the east) to ascend along the SFS. On the other hand, the computed thermohaline flow is compatible with the remobilization of buried layers of Li-Mg-enriched salts and/or clays by dilute recharge waters coming from the west or southwest of the basin. Here, the role of faults and density-driven flow is key to allow efficient downward and upward flow rates that favour the remobilization of Li and Mg.

Towards more sustainable brine extraction in salt flats: Learning from the Salar de Atacama.

Salt flats are hydrogeological systems with highly valuable wetland and lake ecosystems. The brine pumping carried out to extract lithium is modifying the natural evaporation discharge of salt flats. A methodology to evaluate the impacts caused on water table and evaporation discharge by brine exploitation in salt flats is proposed and applied to the Salar de Atacama. The methodology included field measurements of water table and evaporation rate, followed by its spatio-temporal analysis and the application of the results to a numerical model to improve the brine exploitation design. The spatio-temporal analysis of the water table depth and evaporation rates measured in the field concluded that the evaporation discharge decreased from 12.85 to 10.95 m3·s-1 between 1986 and 2018, that is around 15%. This reduction compensated part of the extractions and could contribute to the preservation of the mixing zone ecosystems. At present, this damping capacity is already amortized in the nucleus and the marginal zone is beginning to be affected by the brine pumping. The sensitivity of the phreatic evaporation on the water table depth justified the great uncertainty of the previous evaporation discharge estimations. Thus, an average error lower than 0.5 m was enough to modify the evaporation by >60%. Therefore, considerable effort should invested to faithfully quantify the discharge by evaporation which is critical in water balance of salt flat basins. The numerical model pointed out that the total pumping outflow should be distributed in the largest possible area. This minimizes the water table drawdown and maximizes the capacity of the evaporation decline to compensate the extractions. The results of this work serve as guidelines to improve the efficiency of future salt flat exploitations.

The effect of brine pumping on the natural hydrodynamics of the Salar de Atacama: The damping capacity of salt flats.

The Salar de Atacama is used as a case study to analyse and quantify coupled natural (evaporation and recharge) and anthropogenic processes (pumping of lithium-rich brine) to abstract their patterns to other salt flats using a three-dimensional groundwater flow model. Important changes in the dynamics of the water table between the pre-operational period (1986-1994) and operational period (1994-2015) are observed. The water table exhibited a gradual drawdown during the pre-operational period because the evaporation was greater than the recharge for most of these periods. This negative balance was counteracted by some sharp rises that were produced by direct rainfall events on the salt flat. The deep lateral recharge that arrived from the mountains did not produce abrupt changes in the water table because the rainfall events in the mountains were damped by the distance of the recharge zone and great thickness of the unsaturated zone. The natural evolution of the water table was modified by the intensive brine pumping that was performed in the south-western Salar de Atacama during the operational period. As evaporation depends on the water table depth, the pumping caused a drawdown of the water table, resulting in an evaporation rate reduction that partially compensated for the pumped brine in the water balance of the basin. This effect is defined as the damping capacity of salt flats. Thus, salt flats have a high capacity for dampening oscillations in their water table in response to both natural and anthropogenic disturbances which is of great importance for the management of lake and wetland ecosystems and brine exploitation. The limit of the dampening capacity of salt flats is defined by the evaporation extinction depth, which is in the range of 0.5-2 m.

Hydrodynamics of salt flat basins: The Salar de Atacama example.

The Salar de Atacama is one of the most well-known saline endorheic basins in the world. It accumulates the world main lithium reserves and contains very sensitive ecosystems. The objective of this work is to characterize the hydrodynamics of the Salar de Atacama, and to quantify its complex water balance prior to the intense brine extraction. The methodology and results can be extrapolated to the groundwater flow and recharge of other salt flats. A three-dimensional groundwater flow model using low computational effort was calibrated against hundreds of hydraulic head measurements. The water infiltrated from the mountains ascends as a vertical flux through the saline interface (mixing zone) produced by the density contrast between the recharged freshwater and the evaporated brine of the salt flat nucleus. This water discharges and is largely evaporated from lakes or directly from the shallow water table. On the other hand, the very low hydraulic gradients, coupled with the presence of the mixing zone that operates as barrier, leads the salt flat nucleus to act as a hydrodynamically quasi-isolated area. The computed water table shows the lowest hydraulic head in the salt flat nucleus near the discharge at the mixing zone. The groundwater balance of the Salar de Atacama in its natural regime was quantified resulting in an inflow/outflow of 14.9 m3·s-1. This balance considers the basin as an endorheic system. The very low infiltration values that are generally assumed for hyperarid basins are not consistent with the hydrogeology of the Salar de Atacama. Indeed, very high infiltration rates (up to 85% of rainfall) occur because of the high degree of fracturing of rocks and the scarce vegetation. This high infiltration is consistent with the light isotopic composition of the water from the recharge area (Altiplano). Therefore, the existence of additional inflows outside the basin is unlikely.

Diagnostic approach to subcutaneous nodules in patients with neuroendocrine tumours treated with depot somatostatin analogs: a cross-sectional study.

BACKGROUND: The presence of cutaneous nodules in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) receiving depot somatostatin analogs (SSAs) is a diagnostic challenge as differential diagnosis between injection site reactions and metastases is essential. OBJECTIVE: To characterize the clinical, radiological, cytological and histopathological features of subcutaneous nodules in patients with GEP-NETs treated with SSAs. MATERIALS AND METHODS: Retrospective, cross-sectional study of patients with GEP-NETs treated with SSAs in whom subcutaneous nodules were detected on routine abdominal computed tomography (CT) scans. High resolution and colour Doppler ultrasonography was performed. Those patients with inconclusive radiological studies went through fine-needle aspiration cytology (FNAC) and/or biopsy. RESULTS: Twelve patients (five males, seven females) were included (six midgut carcinoid NETs, six pancreatic NETs). Three patients received intramuscular depot octreotide, seven subcutaneous lanreotide, and two both treatments. CT scan findings were nonspecific. Sonography revealed a hyperechoic pattern in recent injections, and a hypoechoic pattern with a characteristic hyperechoic peripheral rim in long-term injections (more than 3 months after injection). On colour Doppler sonography, nodules showed no signs of intralesional vascularity. Fine-needle aspiration cytology (FNAC) was performed in five patients, revealing a characteristic acellular proteinaceous material. Biopsy in four patients showed different reactional infiltrates around the acellular material. CONCLUSIONS: High resolution and colour Doppler ultrasonography may be very useful for the differential diagnosis of subcutaneous nodules in patients with GEP-NETs treated with SSAs. FNAC and a biopsy are useful tests for confirmation of the diagnosis in patients with inconclusive findings. We propose a management algorithm.

Comparison of sample preparation strategies for target analysis of total thyroid hormones levels in serum by liquid chromatography-quadrupole time-of-flight-mass spectrometry.

This paper describes a novel method based on liquid chromatography quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS) for target analysis of total THs in serum. Several sample preparation strategies have been evaluated to reduce matrix effect (namely, HybridSPE cartridges, supported liquid extraction, SLE and solid phase extraction, SPE). Deproteinization and further clean-up with mixed-mode SPE was selected as the best strategy for sample preparation, since achieved the cleanest extracts and reduced ionization suppression effects (between -11 and -24%). Method validation was performed by the analysis of control human serum samples. Criteria for confirming THs identity in serum extracts were based on retention times, accurate masses, isotopic pattern and MS/MS fragmentation pattern. Moreover, the quantitation capabilities of the LC-QTOF-MS method were also evaluated in terms of linearity, precision, accuracy and sensitivity by the application of matrix-matched calibration. Additionally, the developed LC-QTOF-MS method successfully provides qualitative information on endogenous components responsible of ion suppression (e.g. lysophosphatidylcholines), via post acquisition data analysis. This demonstrates the significant advantage of using LC-QTOF-MS, as it allows retrospective querying of the acquired data without the need of re-injecting/re-processing the samples.