Referral rate, profile and degree of control of patients with familial hypercholesterolemia: data from a single lipid unit from a Mediterranean area.

BACKGROUND: The challenging rigorous management of hypercholesterolemia promotes referral to specialized units. This study explored the need, based on referral rate and cardiovascular (CV) risk factor control in patients evaluated for familial hypercholesterolemia (FH), for a lipid unit (LU). METHODS: Over a four-year period, 340 referrals to our unit were analyzed to establish the lipid disorder referral rate. Moreover, 118 patients referred for potential FH during the period 2010-2018 (52.4 ± 13.9 years, 47.5% male, Caucasian, 26.3% obese, 33.1% smokers and 51.7% with some glycaemic alteration) were investigated. The Dutch Lipid Clinic Network (DLCN) score, type and dose of lipid-lowering drugs, lipid profile including lipoprotein (a) (Lp(a)) and the presence of plaques with carotid ultrasound (CU) were recorded. RESULTS: Lipids represented 6.2% of referrals (38 patient-years) requiring a 2-3 h weekly monographic outpatient consultation. The potential FH sample displayed a DLCN score ≥ 6 in 78% and modifiable CV risk factors in 51%. Only 22% achieved tight disease control despite intensive treatment. The statin-ezetimibe combination treatment group achieved better goals (73.0% vs. 45.5%, P = 0.003), and the rosuvastatin group had a higher proportion of prediabetes (60.9% vs. 39.1%, P = 0.037). Neither CU plaque presence nor Lp(a) > 50 mg/dL was linked with established CV disease patients, but higher Lp(a) concentrations were detected between them (102.5 (26.3-145.8) vs. 25.0 (13.0-52.0) mg/dL, P = 0.012). CONCLUSIONS: The referral rate, degree of control, and proportion of modifiable CV risk factors in FH patients demonstrate the need for LU in our area as well as optimize control and treatment.

A DNA barcode-assisted annotated checklist of the spider (Arachnida, Araneae) communities associated to white oak woodlands in Spanish National Parks.

BACKGROUND: A large scale semi-quantitative biodiversity assessment was conducted in white oak woodlands in areas included in the Spanish Network of National Parks, as part of a project aimed at revealing biogeographic patterns and identify biodiversity drivers. The semi-quantitative COBRA sampling protocol was conducted in sixteen 1-ha plots across six national parks using a nested design. All adult specimens were identified to species level based on morphology. Uncertain delimitations and identifications due to either limited information of diagnostic characters or conflicting taxonomy were further investigated using DNA barcode information. NEW INFORMATION: We identified 376 species belonging to 190 genera in 39 families, from the 8,521 adults found amongst the 20,539 collected specimens. Faunistic results include the discovery of 7 new species to the Iberian Peninsula, 3 new species to Spain and 11 putative new species to science. As largely expected by environmental features, the southern parks showed a higher proportion of Iberian and Mediterranean species than the northern parks, where the Palearctic elements were largely dominant. The analysis of approximately 3,200 DNA barcodes generated in the present study, corroborated and provided finer resolution to the morphologically based delimitation and identification of specimens in some taxonomically challenging families. Specifically, molecular data confirmed putative new species with diagnosable morphology, identified overlooked lineages that may constitute new species, confirmed assignment of specimens of unknown sexes to species and identified cases of misidentifications and phenotypic polymorphisms.

The Mediterranean as a melting pot: Phylogeography of Loxosceles rufescens (Sicariidae) in the Mediterranean Basin.

The species Loxosceles rufescens is native to the Mediterranean but considered cosmopolitan because it has been dispersed worldwide. A previous study revealed 11 evolutionary lineages across the Mediterranean, grouped into two main clades, without any clear phylogeographic pattern. The high genetic diversity within this species (p-distances of up to 7.8% in some Mediterranean lineages), together with the results obtained with different species delimitation methods (GMYC, TCS) could indicate the existence of cryptic species. Here we compare the mitochondrial and microsatellite diversity to elucidate if the lineages of L. rufescens in the Mediterranean should be considered different species (cryptic species) or populations of the same species. To do so, we analyzed the cox1 diversity of 196 individuals, of which, we genotyped 148, sampled from 19 localities across the Mediterranean. STRUCTURE analyses of microsatellite data identified two genetic clusters of L. rufescens. One cluster included individuals from Western Mediterranean localities (Iberian Peninsula, Morocco, Balearic Islands) and Israel, while the second one grouped individuals from Italian and Greek localities, including Sardinia, Sicily and Tunisia. These patterns suggest that geographic proximity is the more significant factor in the clustering with microsatellite data and shows the existence of gene flow between the nearest geographic areas, even if the individuals belong to different mitochondrial lineages or clades. The lack of correspondence between both genetic markers suggests that the evolutionary lineages found within L. rufescens should not be considered different species. We conclude that these phylogenetic linages and their distribution may be the result of the maternal evolutionary history of the species and human-mediated dispersion.

Low prevalence of non-alcoholic fatty liver disease in patients with type 1 diabetes is associated with decreased subclinical cardiovascular disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been proposed as an independent cardiovascular risk factor. The present study evaluated the prevalence of NAFLD in a cohort of type 1 diabetic (T1D) patients and its potential relationship with subclinical cardiovascular disease (CVD). METHODS: One hundred T1D patients (mean [±SD] age 39.4 ± 7.8 years, disease duration 21.7 ± 8.6 years) were included in the present cross-sectional study. All subjects underwent abdominal ultrasonography for detection of NAFLD, carotid ultrasonography to measure the carotid intima-media thickness (CIMT) and atheroma plaques, and cardiac tomography for evaluation of the coronary artery calcium score (CACS). RESULTS: Of the study cohort, 12% had NAFLD and 23% had a CACS >0. The T1D subjects with NAFLD had a greater CIMT than those without NAFLD (0.65 ± 0.17 vs 0.55 ± 0.14 mm; P = 0.029), but there were no significant differences between the two groups with regard to CACS, glycemic control, or the presence of carotid plaques. Patients with high liver enzyme concentrations (>20 U/L) had a higher CIMT (0.60 ± 0.16 vs 0.54 ± 0.13; P = 0.04) and there was a higher proportion of altered CACS (17 [73.9%] vs 6 [26.1%]; P = 0.001) and detection of carotid plaques (10 [76.9%] vs 3 [23.1%]; P = 0.014) in this group. CONCLUSIONS: A low prevalence of NAFLD was found in the T1D cohort that was associated globally with a low proportion of abnormal CVD imaging markers, although these imaging parameters were worse in subjects in whom NAFLD was detected.

Relationship of YKL-40 and adiponectin and subclinical atherosclerosis in asymptomatic patients with type 1 diabetes mellitus from a European Mediterranean population.

BACKGROUND: The glycoprotein YKL-40 is a new marker of early inflammation and endothelial dysfunction. Adiponectin is a collagen-like protein with anti-atherogenic and anti-inflammatory effects. Increased concentrations of both markers have been reported in patients with type 1 diabetes (T1D). AIM: To assess the possible role of YKL-40 and adiponectin as a marker of subclinical cardiovascular disease in asymptomatic patients with type 1 diabetes with no history of ischemic or macrovascular heart disease and its relationship with other classic inflammatory biomarkers. METHODS: Concentrations of YKL-40, adiponectin, IL-6, IL-1ß, TNF-α, hsCRP and homocysteine were determined in 150 T1D patients (58% men, age: 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution, BMI: 25.1 ± 3.6 kg/m(2); HbA1c 8.1 ± 2.3%, 4% smokers; 26% retinopathy, microalbuminuria 9%) and 50 controls age, sex and smoke condition matched. Subclinical atherosclerosis was assessed by a carotid ultrasonography and a computed tomography for evaluation of calcium artery calcification score (CACS). RESULTS: 82% of T1D patients and 92% of controls had a calcium score of 0. T1D patients showed a significantly higher mean common carotid artery intima media thickness (CIMT) compared to controls (0.55 ± 0.14 vs 0.48 ± 0.14 mm, p = 0.01). Concentrations of YKL-40 and adiponectin were significantly higher in T1D [42.6 (10.4-195.0) vs ±28.7 (11.0-51.2) ng/ml, p = 0.001 and 15.8 ± 9.1 vs. 12.4 ± 5.3 mg/ml, p = 0.008], with no differences when compared to other inflammatory parameters. In T1D patients no association was found between YKL-40 and adiponectin and screening test for subclinical arterial disease (neither CACS nor CIMT). A positive correlation was found between levels of YKL-40 and age and duration of disease (r = 0.28, p = 0.003; r = 0.35, p = 0.001). There were no differences in the YKL-40 in relation to the presence or absence of retinopathy or nephropathy. Levels of adiponectin were higher in patients with nephropathy (21.84 ± 8.15 vs. 14.88 ± 8.27 mg/ml, p = 0.008). CONCLUSIONS: Type 1 diabetes patients from a Mediterranean area with a longer disease evolution, although a lower degree of subclinical disease, showed significatively higher concentrations of YKL-40 and adiponectin compared with the controls. Therefore, we conclude that YKL-40 and adiponectin are early inflammatory markers in diabetic subjects even in the presence of a low atherosclerotic background.

High prevalence of vitamin D deficiency and lack of association with subclinical atherosclerosis in asymptomatic patients with Type 1 Diabetes Mellitus from a Mediterranean area.

AIMS: Several studies linked vitamin D deficiency with coronary artery disease (CAD). The aim of this study was to evaluate the relationship between the concentrations of 25-hydroxyvitamin D (25OHD) and the presence of early atherosclerosis in asymptomatic Type 1 Diabetes (T1D) patients with no previous history of ischemic heart disease. METHODS: One hundred and forty-five patients with T1D (age 37.8 ± 8 years, 57 % male, all Caucasian, disease duration 20.6 ± 8.3 years, HbA1c 7.6 ± 1.4 % (60.2 ± 11.1 mmol/mol), body mass index (BMI) 25.2 ± 3.5 kg/m2, 52.4 % smokers, 23 % retinopathy, 10 % nephropathy) and 48 controls matched for age, sex, BMI and smoking habit were studied. 25OHD deficiency was defined for values ≤20 ng/mL. A sun exposure questionnaire, carotid ultrasonography to determine carotid intima-media thickness (CIMT) and the presence of atheroma plaques and cardiac computed tomography for evaluation of calcium artery calcification (CACS) were performed. RESULTS: T1D subjects showed a high proportion of 25OHD deficiency (43.2 % vs. 21.7 %, p = 0.032). Of all, 82 % of T1D patients and 92 % of controls had a calcium score of 0. CIMT was greater in patients with T1D (0.55 ± 0.14 mm vs 0.48 ± 0.15, p = 0.01) compared with controls. T1D subjects showed no differences in the results of CACS or CIMT according to the vitamin D concentrations. CONCLUSIONS: T1D patients have lower concentrations and twice more prevalence of 25OHD deficiency than controls. There was no association between 25OHD concentrations and subclinical CAD.

Not as docile as it looks? Loxosceles venom variation and loxoscelism in the Mediterranean Basin and the Canary Islands.

The medical importance of Loxosceles spiders has promoted extensive research on different aspects of their venoms. Most of the reported cases of loxoscelism have occurred in the Americas, and thus, much work has focused on North and South American Loxosceles species. Interestingly, loxoscelism cases are rare in the Mediterranean Basin although Loxosceles rufescens, endemic to the Mediterranean, is an abundant spider even in human-altered areas. Thus, it has been suggested that the venom of L. rufescens could be of less medical relevance than that of its congeners. In this study, we challenge this hypothesis by using multiple approaches to study venom variation in selected species and lineages from the Mediterranean Basin and the Canary Islands. We found that SMase D activity, the key bioactive component of Loxosceles venom, is comparable to American species that are confirmed to have medically relevant bites. The venom protein composition using SDS-PAGE presents some differences among regional Loxosceles taxa in banding pattern and intensity, mostly between the Canarian and L. rufescens lineages. Differences between these species also exist in the expression of different paralogs of the SicTox gene family, with the Canarian species being less diverse. In conclusion, our results do not support the challenged hypothesis, and suggest that venom of these species may indeed be as potent as other Loxosceles species. Pending confirmation of loxoscelism with direct evidence of Loxosceles bites with species identification by professionals, Loxosceles in the Mediterranean region should conservatively be considered medically relevant taxa.

Ecological niche and phylogeography elucidate complex biogeographic patterns in Loxosceles rufescens (Araneae, Sicariidae) in the Mediterranean Basin.

BACKGROUND: Understanding the evolutionary history of morphologically cryptic species complexes is difficult, and made even more challenging when geographic distributions have been modified by human-mediated dispersal. This situation is common in the Mediterranean Basin where, aside from the environmental heterogeneity of the region, protracted human presence has obscured the biogeographic processes that shaped current diversity. Loxosceles rufescens (Araneae, Sicariidae) is an ideal example: native to the Mediterranean, the species has dispersed worldwide via cohabitation with humans. A previous study revealed considerable molecular diversity, suggesting cryptic species, but relationships among lineages did not correspond to geographic location. RESULTS: Delimitation analyses on cytochrome c oxidase subunit I identified 11 different evolutionary lineages, presenting two contrasting phylogeographic patterns: (1) lineages with well-structured populations in Morocco and Iberia, and (2) lineages lacking geographic structure across the Mediterranean Basin. Dating analyses placed main diversification events in the Pleistocene, and multiple Pleistocene refugia, identified using ecological niche modeling (ENM), are compatible with allopatric differentiation of lineages. Human-mediated transportation appears to have complicated the current biogeography of this medically important and synanthropic spider. CONCLUSIONS: We integrated ecological niche models with phylogeographic analyses to elucidate the evolutionary history of L. rufescens in the Mediterranean Basin, with emphasis on the origins of mtDNA diversity. We found support for the hypothesis that northern Africa was the center of origin for L. rufescens, and that current genetic diversity originated in allopatry, likely promoted by successive glaciations during the Pleistocene. We corroborated the scenario of multiple refugia within the Mediterranean, principally in northern Africa, combining results from eight atmosphere-ocean general circulation models (AOGCMs) with two different refugium-delimitation methodologies. ENM results were useful for providing general views of putative refugia, with fine-scale details depending on the level of stringency applied for agreement among models.

Low prevalence of subclinical atherosclerosis in asymptomatic patients with type 1 diabetes in a European Mediterranean population.

OBJECTIVE: To evaluate the presence of early carotid and coronary atherosclerosis in asymptomatic patients with type 1 diabetes with no history of ischemic heart disease. RESEARCH DESIGN AND METHODS: One hundred and fifty patients with type 1 diabetes (58% males; 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution; HbA1c 8.1 ± 2.3%; 52% nonsmokers; 26% retinopathy; 9% microalbuminuria) and 50 nondiabetic control subjects age and sex matched were studied. Carotid ultrasonography to determine common carotid artery intima-media thickness (c-IMT) and the presence of atheroma plaques and cardiac computed tomography for calcium analysis and quantification (coronary artery calcium score [CACS]) were performed. RESULTS: Most patients with type 1 diabetes and control subjects displayed a CACS of 0 (82 vs. 92%). Patients with type 1 diabetes with CACS ≥1 were older and had higher HbA1c (44.5 ± 5.1 vs. 36.7 ± 8.1 years [P < 0.001] and 8.5 ± 1.1 vs. 7.8 ± 1.0% [P < 0.003], respectively) and longer evolution of diabetes (25.4 ± 9.2 vs. 19.3 ± 7.4 years, P < 0.005) and mean c-IMT (0.67 ± 0.18 vs. 0.53 ± 0.11 mm, P < 0.001) compared with patients with CACS of 0. Smoking (P < 0.02), nephropathy (P < 0.05), retinopathy (P < 0.05), and male sex (P < 0.03) were significantly and positively associated with CACS ≥1. Mean c-IMT was significantly higher in patients with type 1 diabetes (0.55 ± 0.14 vs. 0.48 ± 0.14 mm, P < 0.01), and 11% of them presented atheroma plaques (8% of control subjects). Multivariant logistic regression analysis showed that c-IMT was related to CACS (ß = 6.87, P < 0.001). CONCLUSIONS: A small percentage of patients with type 1 diabetes showed data suggestive of subclinical atherosclerosis. Universal screening of coronary disease in this population is not justified. Carotid ultrasonography may be useful for screening in the subset of patients with cardiovascular risk factors and long disease evolution.

Molecular systematics of the wolf spider genus Lycosa (Araneae: Lycosidae) in the Western Mediterranean Basin.

In this study, we present the first molecular phylogeny of the wolf spider genus Lycosa Latreille, 1804 in the Western Mediterranean Basin. With a wide geographic sampling comprising 90 localities and including more than 180 individuals, we conducted species delimitation analyses with a Maximum Likelihood approach that uses a mixed Yule-coalescent model to detect species boundaries. We estimated molecular phylogenetic relationships employing Maximum Likelihood and Bayesian Inference methods using mitochondrial and nuclear sequences. We conducted divergence time analyses using a relaxed clock model implemented in BEAST. Our results recovered 12 species that form four groups: Lycosa tarantula group comprising L. tarantula the type species of the genus, L. hispanica and L. bedeli; Lycosa oculata group composed of L.oculata, L. suboculata and three putative new species; Lycosa baulnyi group formed by the maghrebian L. baulnyi and L. vachoni and Lycosa fasciiventris group that includes two widespread species, L. fasciiventris and L. munieri. We found that each group of species shows a characteristic burrowing behavior and molecular and morphological diagnostic characters. Molecular clock analyses support the hypothesis of a relatively recent evolutionary origin of diversification of the group (4.96 Mya (3.53-6.45 Mya)). The establishment of the Mediterranean-like climate and the Pleistocenic glacial cycles seem to have been the main factors that promoted the diversification within the group. Finally, the results obtained in this study together with the revision of museum specimens, descriptions, redescriptions and illustrations, lead us to propose 18 nomenclatural changes (synonymies, generic transfers and nomina dubia) concerning the genera Lycosa, Allocosa and Hogna in the Western Mediterranean.