Assessing the impact of sea level rise on port operability using LiDAR-derived digital elevation models

One of the main consequences of climate change is the sea level rise (SLR), which impacts coastal areas affecting many infrastructures, particularly seaports, whose operations may be jeopardized. In this paper, a methodological framework is developed to assess the impact of SLR on port operability by using digital elevation models derived from LiDAR data. The methodology is applied to four ports along the Catalan Coast (NW Mediterranean). The study is made for the RCP8.5 scenario from IPCC, analysing port operability every 10¿years throughout the 21st century. The approach provided here allows a port authority to determine which berthing areas will be affected at each port and at each time interval. Results show that, if no adaptation measures are taken, ports will have significant reductions of present operability for most of their activities, in particular after year 2070. This work shows that the developed methodological framework is a very useful tool for port authorities to detect operability tipping points and to design well in advance the necessary adaptation pathways to overcome the expected impacts.Peer ReviewedPostprint (author's final draft

Type 2 diabetes-associated carotid plaque burden is increased in patients with retinopathy compared to those without retinopathy

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality among subjects with type 2 diabetes (T2D), and diabetic retinopathy (DR) has been associated with an increased risk for CVD. The present study was designed to test the concept that T2D patients with DR, but without previous cardiovascular (CV) events and with normal renal function, have an increased atherosclerotic burden compared with patients without DR. METHODS: A cross-sectional study was performed using patients with normal renal function (estimated glomerular filtration rate (eGFR) >60 ml/min) and without previous CV events. A total of 312 patients (men, 51%; mean age, 57 yrs; age range 40-75 yrs) were included in the study; 153 (49%) of the patients had DR. B-mode carotid ultrasound imaging was performed for all of the study subjects to measure the carotid intima-media thickness (cIMT) and carotid plaques in the common carotid artery (CCA), bifurcation and internal carotid artery (ICA). RESULTS: The percentage of carotid plaques in T2D patients with DR was higher than in T2D patients without DR (68% vs. 52.2%, p = 0.0045), and patients with DR had a higher prevalence of ≥2 carotid plaques (44.4% vs. 21.4%; p < 0.0001). No differences were observed in the cIMT measured at different carotid regions between the patients with or without DR. Using multivariate logistic regression (adjustment for major risk factors for atherosclerosis), DR was independently associated with mean-internal cIMT (p = 0.0176), with the presence of carotid plaques (p = 0.0366) and with carotid plaque burden (≥2 plaques; p < 0.0001). CONCLUSIONS: The present study shows that DR in T2D patients without CVD and with normal renal function is associated with a higher atherosclerotic burden (presence and number of plaques) in the carotid arteries. These patients may be at a higher risk for future CV events; therefore, an ultrasound examination of the carotid arteries should be considered in patients with DR for more careful and individualised CV assessment and follow-up

Circulating soluble CD36 is similar in type 1 and type 2 diabetes mellitus versus non-diabetic subjects

The aim of this study was to determine whether plasma concentrations of sCD36 (soluble CD36) are associated with the presence of type 1 or type 2 diabetes. Plasma levels of sCD36 were analysed in 1023 subjects (225 type 1 diabetes (T1D) patients, 276 type 2 diabetes (T2D) patients, and 522 non-diabetic control subjects) using an enzyme-linked immunosorbent assay (ELISA). Multinomial and logistic regression models were performed to evaluate associations with sCD36 and its association with diabetes types. There were no significant differences in sCD36 (p = 0.144) among study groups, neither in head-to-head comparisons: non-diabetic versus T1D subjects (p = 0.180), non-diabetic versus T2D subjects (p = 0.583), and T1D versus T2D patients (p = 0.151). In the multinomial model, lower sCD36 concentrations were associated with older age (p < 0.001), tobacco exposure (p = 0.006), T2D (p = 0.020), and a higher-platelets count (p = 0.004). However, in logistic regression models of diabetes, sCD36 showed only a weak association with T2D. The current findings show a weak association of circulating sCD36 with type 2 diabetes and no association with T1D

Effects of Switching from Stavudine to Raltegravir on Subcutaneous Adipose Tissue in HIV-Infected Patients with HIV/HAART-Associated Lipodystrophy Syndrome (HALS). A Clinical and Molecular Study

HIV-1/HAART-associated lipodystrophy syndrome (HALS) has been associated with exposure to stavudine (d4T) through mitochondrial dysfunction. We performed a 48-week study to assess the effects of switching from d4T to raltegravir (RAL) on metabolic and fat molecular parameters of patients with HALS. Forty-two patients with HALS and a median exposure to d4T > 7 years were switched to RAL and followed for 48 weeks. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by DEXA were obtained at baseline and week 48. mtDNA and gene transcripts for PPAR gamma, adiponectin, cytochrome b, Cox IV, TNF alpha, MCP-1 and CD68 were assessed in paired subcutaneous fat tissue biopsies. Lipid parameters, fasting glucose, insulin, and HOMA-IR did not change significantly. Whole body fat (P = 0.0027) and limb fat mass (P<0.0001) increased from baseline. Trunk/limb fat ratio (P = 0.0022), fat mass ratio (P = 0.0020), fat mass index (P = 0.0011) and percent leg fat normalized to BMI (P<0.0001) improved after 48 weeks. Relative abundance of mtDNA, expression of PPAR gamma, adiponectin, Cyt b, and MCP-1 genes increased, whereas Cox IV, TNF alpha, and CD68 did not change significantly from baseline. Switching from d4T to RAL in patients with HALS is associated with an increase in limb fat mass and an improvement in markers of adipocyte differentiation and mitochondrial function in SAT

Advanced lipoprotein profle disturbances in type 1 diabetes mellitus: a focus on LDL particles

Background: Lipoprotein disturbances have been associated with increased cardiovascular disease (CVD) risk in type 1 diabetes mellitus (T1DM). We assessed the advanced lipoprotein profle in T1DM individuals, and analysed diferences with non-diabetic counterparts. Methods: This cross-sectional study involved 508 adults with T1DM and 347 controls, recruited from institutions in a Mediterranean region of Spain. Conventional and advanced (assessed by nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profles were analysed. Crude and adjusted (by age, sex, statin use, body mass index and leukocyte count) comparisons were performed. Results: The median (interquartile range) age of the study participants was 45 (38–53) years, 48.2% were men. In the T1DM group, the median diabetes duration was 23 (16–31) years, and 8.1% and 40.2% of individuals had nephropathy and retinopathy, respectively. The proportion of participants with hypertension (29.5 vs. 9.2%), and statin use (45.7% vs. 8.1%) was higher in the T1DM vs. controls (p<0.001). The T1DM group had a better conventional (all parameters, p<0.001) and NMR-lipid profle than the control group. Thus, T1DM individuals showed lower concentrations of atherogenic lipoproteins (VLDL-particles and LDL-particles) and higher concentrations of anti-atherogenic lipoproteins (HDL-particles) vs. controls, even after adjusting for several confounders (p<0.001 for all). While non-diabetic women had a more favourable lipid profle than non-diabetic men, women with T1DM had a similar concentration of LDL-par‑ ticles compared to men with T1DM (1231 [1125–1383] vs. 1257 [1128–1383] nmol/L, p=0.849), and a similar concentration of small-LDL-particles to non-diabetic women (672.8 [614.2–733.9] vs. 671.2 [593.5–761.4] nmol/L, respectively; p=0.790). Finally, T1DM individuals showed higher discrepancies between NMR-LDL-particles and conventional LDLcholesterol than non-diabetic subjects (prevalence of LDL-cholesterol1000 nmol/L: 38 vs. 21.2%; p<0.001). All these diferences were largely unchanged in participants without lipid-lowering drugs (T1DM, n=275; controls, n=317).This research was supported by grants from the Carlos III National Institute of Health (PI12/0183 and PI15/0625). CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM) and CIBER on Pathophysiology of Obesity and Nutrition (CIBEROBN) are initiatives of ISCIII, Spain. AJA received a research grant from the Associació Catalana de Diabetis (ACD), “Ajut per a la recerca en diabetis modalitat clínica 2018”

Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes.

Aims: To assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on human adipose cells. Main methods: Drugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (CC motif) ligand-2 using Multiplex assays. Key findings: Overall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-Ɣ and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir. Significance: The INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH

FGF21 serum levels are related to insulin resistance, metabolic changes and obesity in Mexican people living with HIV (PLWH).

Antiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH)

Association of α-klotho with subclinical carotid atherosclerosis in subjects with type 1 diabetes mellitus

Background Compelling evidence suggests that the fbroblast growth factor 23 (FGF23) / α-klotho axis is impaired in subjects with diabetes mellitus. We examined the relationship between parameters related to calcium/phosphate homeostasis, including FGF23 and α-klotho, and subclinical carotid atherosclerosis burden in type 1 diabetes mellitus (T1D) subjects. Methods This cross-sectional study involved 226 subjects with T1D and 147 age-, sex- and plaque matched, nondiabetic (non-T1D) subjects, both with normal renal function. Carotid ultrasound was performed to determine thepresence and burden of atheromatous plaques. Concentrations of the intact form of FGF23 and α-klotho were assessed by ELISA. Calcium, phosphate, parathyroid hormone, and vitamin D levels were also determined. Negative binomial regression models were used to examine relationship between parameters studied and subclinical carotid atherosclerosis. Results Only FGF23 was increased in T1D compared with non-diabetic subjects (> 2-fold; p<0.05). α-klotho was higher in subjects with subclinical carotid atherosclerosis (1.4-fold, p<0.05). Regression analysis revealed that the log α-klotho concentration was positively associated with the presence of subclinical carotid atherosclerosis both in T1D subjects (incidence rate ratio [IRR]: 1.41; 95% confdence interval [CI], 1.06–1.89; p<0.05) and in non-T1D subjects (IRR: 1.65; 95% CI, 1.02–2.75; p<0.05). The models also showed that age, smoking and albuminuria-to-creatinine ratio were positively associated with subclinical carotid atherosclerosis in T1D subjects. Interestingly, sex-related protection against plaque was also revealed in T1D women. Conclusion Higher α-klotho was associated with subclinical carotid atherosclerotic in the absence of kidney dysfunction. This fnding also points to a new pathophysiological pathway involved in the development and progression of this complication.This work was funded by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Madrid, Spain) grant PI15/0625 (to DM and EC), FEDER “Una manera de hacer Europa”, and by CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM, CB15/00071, PI. Dr. Didac Mauricio) an initiative from ISCIII, Spain, with co-funding from the European Regional Development Fund (ERDF). Miguel Servet Type 2 contract (JJ, CPII18/00004; ISCIII). Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau is accredited by the Generalitat de Catalunya as Centre de Recerca de Catalunya (CERCA)