A further step towards the characterisation of Terebellides (Annelida, Trichobranchidae) diversity in the Northeast Atlantic, with the description of a new species.

Several new species of genus Terebellides Sars, 1835 (Annelida, Trichobranchidae) have been recently described from the Northeast Atlantic Ocean after the detection of a large complex of species based on DNA sequence data from previous research. Some of those species (belonging to the so-called Group A) have already been described elsewhere. In this paper, we revise several Terebellides clades belonging to Groups B, C and D resulting in the identification of five nominal species: Terebellidesgracilis Malm, 1874, Terebellidesatlantis Williams, 1984, Terebellideswilliamsae Jirkov, 1989, Terebellidesirinae Gagaev, 2009, and Terebellidesshetlandica Parapar, Moreira & O'Reilly, 2016, plus one new species described here as Terebellideslavesquei sp. nov. All these species are characterised by a combination of morphological features complemented with a nucleotide diagnostic approach (specific COI nucleotides in the alignment position). Morphological characters used to discriminate between taxa refer to the branchial shape, presence/absence of ciliated papillae dorsal to thoracic notopodia and the morphology of thoracic and abdominal uncinal teeth. An updated identification key to all described species of this genus in NE Atlantic waters is also included.

Revision of the Laonice bahusiensis complex (Annelida: Spionidae) with a description of three new species.

The morphological reexamination of specimens previously identified as Laonice bahusiensis Sderstrm, 1920 from North European and Mediterranean collections, supported by the molecular analysis of freshly collected material, enabled the recognition of four different species in the region: the genuine L. bahusiensis, L. irinae n. sp. from North European waters, and L. grimaldii n. sp. and L. mediterranea n. sp. from the Mediterranean Sea. The morphology of these species is described and illustrated, and their distributions are clarified based on old and new materials. A key for their identification is also provided. The Bayesian analysis of the COI sequences (483 bp) showed that these four species form a clade, namely the L. bahusiensis species complex, morphologically characterized by the continuous dorsal crests on postbranchiate chaetigers in the adults. The genetic p-distances between the species of the complex ranged from 13.27% to 17.99%, while the intraspecific variability ranged from 0.6% to 1.57%. Together with the sister species Laonice cirrata (Sars, 1851), the L. bahusiensis complex formed the Laonice (Laonice) clade, which is morphologically characterized by the prostomium fused with the anterior peristomial margin. However, the monophyly of the L. bahusiensis complex, as well as that of the clade Laonice (Laonice), needs to be further supported through the analysis of a greater set of genes from a larger number of species.

To name but a few: descriptions of five new species of Terebellides (Annelida, Trichobranchidae) from the North East Atlantic.

The number of described species of the genus Terebellides Sars, 1835 (Annelida, Trichobranchidae) has greatly increased in the last years, particularly in the North East Atlantic. In this context, this paper deals with several putative species recently delineated by molecular means within a well delimited clade of Terebellides. Species are characterised here by a combination of morphological characters, and a complementary nucleotide diagnostic approach. Three species were identified as the nominal species T. stroemii Sars, 1835, T. bigeniculatus Parapar, Moreira & Helgason, 2011 and T. europaeaLavesque et al., 2019. Five species are described as new: T. bakkeni sp. nov., T. kongsrudi sp. nov., T. norvegica sp. nov., T. ronningae sp. nov. and T. scotica sp. nov. The distinctive morphological characters refer to the branchial shape, absence or presence of papillae on lamellae of anterior margin of branchial dorsal lobes, absence or presence of ciliated papillae dorsal to thoracic notopodia, geniculate chaetae in one or two chaetigers, and the morphology of thoracic and abdominal uncini teeth. Furthermore, the description of T. bigeniculatus is revised and complemented after examination of type specimens. An updated identification key to all species of the genus in NE Atlantic and a proposal of a classification of different types of abdominal uncini to be used in taxonomy are also included.

Species delimitation analyses of NE Atlantic Chaetozone (Annelida, Cirratulidae) reveals hidden diversity among a common and abundant marine annelid.

The polychaetes of the family Cirratulidae (Annelida) are common inhabitants in continental shelf benthic environments and considered an important group of organisms in environmental monitoring surveys. The family represents a taxonomic and systematic challenge, as monophyly of genera and evolutionary relationships within the family remain to be explored in a proper phylogenetic framework. Bitentaculate cirratulids, especially the genus Chaetozone, form one of the most species-diverse group of polychaetes worldwide. In this study, we aimed at evaluating the species diversity of the genus Chaetozonein benthic environments in the North East Atlantic by molecular means. We tested whether traditional morphological diagnostic characters are able to discriminate between the species hypothesis after species delimitation analyses, and assessed monophyly of the genera involved. Two DNA markers were sequenced from about 200 specimens belonging to Chaetozone, Aphelochaeta, Dodecaceria, Cirriformia and Cirratulus - the universal mitochondrial barcoding region COI, and the D1-D2 regions of the nuclear 28S rRNA - and analyzed with Bayesian inference, Maximum Likelihood and the species delimitation methods mPTP and GMYC. The first phylogeny of the family Cirratulidae is inferred and the genera Chaetozone, Dodecaceria and Cirratulus are recovered monophyletic. A total of 14 clusters of sequences - corresponding to species of Chaetozone - were found in the study area, and only one of them is here referred to a nominal species, Chaetozone setosa. Our results reveal several species complexes in the genus Chaetozone, that some of these independent lineages are unnamed and undescribed, and that morphological diagnostic features are in most cases unable to discriminate between the most similar species.

A revision of the French Trichobranchidae (Polychaeta), with descriptions of nine new species.

Trichobranchidae from French waters are revised based on material available in French marine stations and newly collected specimens. This research is the first part of the "Spaghetti Project" aiming to revise French species of terebellids and trichobranchids. It confirms the absence of the so-called cosmopolitan species Terebellides stroemii from French waters, and describes eight new species of Terebellides: T. bonifi n. sp., T. ceneresi n. sp., T. europaea n. sp., T. gentili n. sp., T. gralli n. sp., T. lilasae n. sp., T. parapari n. sp. and T. resomari n. sp. and one species of Trichobranchus: T. demontaudouini n. sp. using both morphological and molecular tools. An identification key for all European species of Trichobranchidae is provided.

Systematic re-structure and new species of Sphaerodoridae (Annelida) after morphological revision and molecular phylogenetic analyses of the North East Atlantic fauna.

Detailed morphological study of more than 2600 North East Atlantic (NEA) sphaerodorids (SphaerodoridaeAnnelida) and phylogenetic analyses of DNA sequences of representatives of several identified morphospecies enforced changing the current systematic classification within the family allowed the discovery of new species provided new information about the morphological and genetic characterisation of members of this group and increased the species occurrence data to better infer their geographic and bathymetric distribution ranges. Phylogenetic analyses of nuclear (18S rRNA and 28S rRNA) and mitochondrial sequences (COI and 16S rRNA) of NEA short-bodied sphaerodorids revealed outstanding results including paraphyly of the genera Sphaerodoropsis Sphaerodoridium, and Sphaerephesia. The number of longitudinal and transverse rows of dorsal macrotubercles is proposed as potential synapomorphies for the main clades and are consequently herein used for the genera delimitation. The new classification proposed here implies nomenclatural changes and the erection of a new genus Geminofilum gen. n. to accommodate the species previously considered as Sphaerodoropsis with two transverse rows of dorsal macrotubercles per segment. Four species are being described herein: Euritmianordica Capa & Bakken sp. n. Sphaerephesiamultichaeta Capa Moreira & Parapar sp. n. Sphaerephesiaponsi Capa Parapar & Moreira sp. n. and Sphaerodoridiumceliae Moreira Capa & Parapar sp. n. Characterisation of the other 21 species including updated iconography and an identification key to all NEA short-bodied sphaerodorids are provided.

Species delimitation in Amblyosyllis (Annelida, Syllidae).

Amblyosyllis is a worldwide distributed group of annelids mainly found in coastal environments. It is well known among the polychaete specialists mostly because of its notable beauty, showing bright colourful patterns and outstanding long and coiled appendices. Amblyosyllis is a monophyletic genus easy to identify due to its distinct diagnostic features; however, the species and their boundaries are, in most cases, not well defined. Herein, we provide an extensive sample of Amblyosyllis material (115 specimens) from several world geographic areas. We have studied the morphological features of each specimen and photographed them alive. Two mitochondrial DNA markers (COI and 16S) and one nuclear gene fragment (28S, D1 region) were sequenced. We performed phylogenetic analyses based on each DNA partition, as well as the combined data sets, obtaining congruent results. Species delimitation methods such as distance analyses, statistical parsimony networks and multi-rate Poisson tree processes were also applied. The combined results obtained from different methodologies and data sets are used to differentiate between, at least, 19 lineages compatible with the separately evolving meta-populations species concept. Four of these lineages are identified as nominal species, including the type species of Amblyosyllis, A. rhombeata. For three other lineages previously synonymized names are recovered, and seven lineages are described as new species. All of these species are described and supported by appropriate iconography. We recognize several morphological characters useful to identify species of Amblyosyllis, which in some cases should also be combined with molecular methods for species delineation. The genetic divergence in the genus is high, contrary to the morphological homogeneity observed. Two species show a wide geographical distribution, while the rest have a more restricted distribution. There are several examples of species with overlapping distribution patterns.

Three, two, one! Revision of the long-bodied sphaerodorids (Sphaerodoridae, Annelida) and synonymization of Ephesiella, Ephesiopsis and Sphaerodorum.

BACKGROUND: Long-bodied sphaerodorids (Annelida, Sphaerodoridae) is the common name for members of the three closely and morphologically homogenous currently accepted genera of benthic marine bristle worms: Ephesiella, Ephesiopsis and Sphaerodorum. Members of this group share the presence of two dorsal and longitudinal rows of macrotubercles with terminal papillae, and two longitudinal rows of microtubercles, features that are unique among sphaerodorids. Genera are distinguished by the chaetae morphology. Members of Ephesiella are characterised by having compound chaetae (except, sometimes, simple chaetae in the first chaetigers), Sphaerodorum bear only simple chaetae, and Ephesiopsis have both compound and simple chaetae in all parapodia. METHODS: Mitochondrial (partial COI and 16S rDNA) and nuclear (partial 18S rDNA and 28S rDNA) sequence data of long-bodied sphaerodorids with compound and simple chaetae, and an outgroup of additional seven sphaerodorid species were analysed separately and in combination using Bayesian inference (BA), and Maximum Likelihood (ML) methods. Long-bodied sphaerodorids from around the world (including type specimens) were examined under a range of optical equipment in order to evaluate putative generic and specific diagnostic features, in addition to intraspecific variability. RESULTS: Phylogenetic analyses of mitochondrial and nuclear DNA sequences of specimens identified as Ephesiella and Sphaerodorum, based on chaeta morphology, were performed. Sphaerodorum and Ephesiella were recovered as paraphyletic and nested within each other. Revision of current nominal species diagnostic features are performed and discussed. DISCUSSION: Results contradict current generic definitions. Recovery of paraphyletic compound and simple chaetae clades urge the synonymization of these two genera of long-bodied sphaerodorids. Morphological data also suggest the synonymization of Ephesiopsis.

Correction: Proceraea exoryxae sp. nov. (Annelida, Syllidae, Autolytinae), the first known polychaete miner tunneling into the tunic of an ascidian.

[This corrects the article DOI: 10.7717/peerj.3374.].

A mega-cryptic species complex hidden among one of the most common annelids in the North East Atlantic.

We investigate mitochondrial (COI, 16S rDNA) and nuclear (ITS2, 28S rDNA) genetic structure of North East Atlantic lineages of Terebellides, a genus of sedentary annelids mainly inhabiting continental shelf and slope sediments. We demonstrate the presence of more than 25 species of which only seven are formally described. Species boundaries are determined with molecular data using a broad range of analytical methods. Many of the new species are common and wide spread, and the majority of the species are found in sympatry with several other species in the complex. Being one of the most regularly encountered annelid taxa in the North East Atlantic, it is more likely to find an undescribed species of Terebellides than a described one.

Proceraea exoryxae sp. nov. (Annelida, Syllidae, Autolytinae), the first known polychaete miner tunneling into the tunic of an ascidian.

While studying organisms living in association with the solitary tunicate Phallusia nigra (Ascidiacea, Ascidiidae) from a shallow fringing reef at Zeytouna Beach (Egyptian Red Sea), one of the collected ascidians showed peculiar perforations on its tunic. Once dissected, the perforations revealed to be the openings of a network of galleries excavated in the inner tunic (atrium) by at least six individuals of a polychaetous annelid. The worms belonged to the Autolytinae (Syllidae), a subfamily that is well known to include specialized predators and/or symbionts, mostly associated with cnidarians. The Red Sea worms are here described as Proceraea exoryxae sp. nov., which are anatomically distinguished by the combination of simple chaetae only in anterior chaetigers, and a unique trepan with 33 teeth in one outer ring where one large tooth alternates with one medium-sized tricuspid tooth, and one inner ring with small teeth located just behind the large teeth. Male and female epitokes were found together with atokous individuals within galleries. Proceraea exoryxae sp. nov. constitutes the first known miner in the Autolytinae and the second species in this taxon known to live symbiotically with ascidians. The implications of finding this specialized parasite are discussed considering that Phallusia nigra has been introduced worldwide, in tropical and sub-tropical ecosystems, where it has the potential of becoming invasive.

Antonbruunia sociabilis sp. nov. (Annelida: Antonbruunidae) associated with the chemosynthetic deep-sea bivalve Thyasira scotiae Oliver & Drewery, 2014, and a re-examination of the systematic affinities of Antonbruunidae.

Antonbruunia sociabilis sp. nov., an abundant endosymbiont of Thyasira scotiae from a putative sulphidic 'seep' in the Hatton-Rockall Basin (1187-1200 m), North-East Atlantic Ocean, is described. The new species is compared with A. viridis and A. gerdesi from the West Indian Ocean and South-East Pacific Ocean respectively. The three species can be distinguished using a suite of morphological characters, and are associated with geographically separated chemosynthetic bivalve molluscs from different families (Thyasiridae, Lucinidae, Vesicomyidae) living in sediments at different depths. New morphological features are recognized for Antonbruunia and a re-assessment of its systematic affinities indicates a close relationship with the Pilargidae. Previous suggestions of an affiliation with the Nautiliniellidae, recently incorporated into the Calamyzinae (Chrysopetalidae), were not supported. The apparent morphological similarities between the two groups are indicative of convergence related to their shared relationships with chemosynthetic bivalves. The first molecular analyses of Antonbruunia (16S and 18S rDNA) clearly indicate that a close relationship to Pilargidae (represented by Ancistrosyllis sp. and Sigambra sp.) is more likely than an affinity to Calamyzinae (represented by Calamyzas amphictenicola, Natushima sp., and Vigtorniella sp.).

Phylogeny of scale-worms (Aphroditiformia, Annelida), assessed from 18SrRNA, 28SrRNA, 16SrRNA, mitochondrial cytochrome c oxidase subunit I (COI), and morphology.

The phylogeny of scale-worms, benthic polychaetes carrying dorsal scales (elytra), including taxa from Acoetidae, Aphroditidae, Eulepethidae, Pholoidae, Pholoididae, Polynoidae and Sigalionidae (Aphroditiformia), is assessed from the nuclear markers 18SrRNA and 28SrRNA, and mitochondrial 16SrRNA and cytochrome c oxidase subunit I (COI), and 24 morphological characters. The data sets are analyzed both separately and combined, with Bayesian analyses, maximum likelihood and parsimony. In total, 56 terminal taxa are examined, including 48 taxa from all scale-worm families, and eight out-group species. The results indicate that Aphroditidae and Eulepethidae are the most basally placed families among the scale-worms. The Pholoididae and Pisionidae are positioned within and synonymized with the Sigalionidae, and Pholoidae may be part of the same group. The subfamily Iphioninae falls out as sister group to a clade consisting of Polynoidae and Acoetidae and is elevated to Iphionidae. The families now included in the Aphroditiformia are Acoetidae, Aphroditidae, Eulepethidae, Pholoidae, Polynoidae, Iphionidae and Sigalionidae, and the subfamily name Harmothoinae and Acholoinae are treated as a junior synonyms of Polynoinae.

From one to ten in a single stroke--resolving the European Eumidasanguinea (Phyllodocidae, Annelida) species complex.

We investigate the genetic structure of European lineages of the polychaete Eumida sanguinea with mitochondrial COI and nuclear ITS, and demonstrate the presence of ten cryptic species. Within the E. sanguinea species complex there are six different white pigmentation patterns but only three of these are unique for a single species. No other consistent morphological differences were observed. We give new species names to seven of the lineages from our study, providing examples of combined morphological and molecular diagnoses, apply the available name E. sanguinea to one species, and leave two lineages with single representatives unnamed. We also include new data and a diagnosis for the poorly known E. notata, which also belongs to the E. sanguinea species complex.

Phylogeny of Syllidae (Polychaeta) based on combined molecular analysis of nuclear and mitochondrial genes.

The phylogeny of Syllidae is assessed in a combined analysis of molecular data from nuclear 18S rDNA and mitochondrial 16S rDNA and cytochrome c oxidase subunit I. In total, 103 terminal taxa are examined: 88 syllids in the four classical subfamilies Eusyllinae, Exogoninae, Syllinae and Autolytinae, as well as 15 outgroup taxa from Phyllodocida and Eunicida. Maximum parsimony analysis of the combined data set indicates that Syllidae, as currently delineated, is monophyletic, though not with very high support values. Astreptosyllis Kudenov & Dorsey, 1982, Streptosyllis Webster & Benedict, 1884 and SyllidesÖrsted, 1845 comprise a monophyletic group well differentiated from the rest of the Syllidae. The subfamilies Autolytinae and Syllinae are monophyletic. Exogoninae is monophyletic, although not well supported, and Eusyllinae is clearly paraphyletic. Results corroborate previous studies about the evolution of reproductive modes in that epigamy is the plesiomorphic condition and schizogamy appeared independently in Autolytinae and Syllinae.

Increased levels of tumour necrosis factor-alpha (TNF-alpha) in patients with Type II diabetes mellitus after myocardial infarction are related to endothelial dysfunction.

The pathophysiology of insulin resistance and atherosclerosis may share a common inflammatory basis, maintaining endothelial dysfunction, suggesting why patients with T2DM (Type II diabetes mellitus) have an impaired prognosis after an MI (myocardial infarction), but it remains unclear how these parameters are inter-related. Forty patients with an MI (20 patients with and 20 patients without T2DM) took part in this cross-sectional study. Endothelium-dependent [FMD (flow-mediated dilation)] and -independent [NTG (nitroglycerine)] vasodilatation (determined by ultrasound), S(I) (insulin sensitivity index; determined by isoglycaemic-hyperinsulinaemic clamp) and serum levels of CRP (C-reactive protein), TNF-alpha (tumour necrosis factor-alpha), IL-6 (interleukin 6), resistin and adiponectin (determined by ELISA) were measured. Associations between FMD/NTG and S(I), and CRP, TNF-alpha, IL-6, adiponectin, resistin, lipids, blood pressure, BMI (body mass index) and brachial artery diameter were then assessed. FMD (2.1 compared with 4.7%; P<0.05), NTG (14.9 compared with 21.2%; P<0.05) and S(I) [4.3 compared with 6.6 10(-4) dl.kg(-1) of body weight.min(-1).(mu-units/ml)(-1); P<0.05], and adiponectin levels (3.1 compared with 6.4 microg/ml; P<0.01) were all lower in patients with T2DM. TNF-alpha (6.9 compared with 1.8 pg/ml; P<0.01) and IL-6 (2.3 compared with 1.2 pg/ml; P<0.01) levels were higher in patients with T2DM, whereas differences in CRP and resistin levels did not attain statistical significance between the two groups. TNF-alpha concentrations and brachial artery diameter were negatively, whereas S(I) was positively, correlated with FMD. Adjustment for age weakened the association for S(I), whereas TNF-alpha and brachial artery diameter remained significantly associated with FMD after adjustment for group, age and BMI. Endothelial dysfunction and low-grade inflammation co-exist in T2DM after MI. These results suggest that the endothelium is negatively impacted in multiple ways by the diabetic state after an MI.

Phylogeny of Aphroditiformia (Polychaeta) based on molecular and morphological data.

The phylogeny of Aphroditiformia, benthic polychaetes carrying dorsal elytra, is assessed from nuclear 18S rDNA, mitochondrial cytochrome c oxidase subunit I (COI), and 31 morphological characters. Two non-elytrabearing taxa, Palmyra and Pisione, are included to assess their relationship to the elytrabearers. The data are analysed both separately and combined, with parsimony, maximum likelihood and Bayesian analyses. In total, 19 terminal taxa are examined, including 12 elytrabearing taxa from all scale-worm groups, Palmyra, Pisione, and five outgroup taxa. The results show that Palmyra and Pisione are nested within Aphroditiformia. Palmyra is sister to Aphrodita, and both Pisione and Pholoe are positioned within Sigalionidae, suggesting that both family names Pisionidae and Pholoidae should be treated as junior synonyms of Sigalionidae.

Persistent endothelial dysfunction is related to elevated C-reactive protein (CRP) levels in Type II diabetic patients after acute myocardial infarction.

The atherosclerotic process is an ongoing dynamic and progressive state arising from endothelial dysfunction and inflammation. Although suffering from an acute coronary artery disease, patients with Type II diabetes have a poor outcome compared with non-diabetic patients, which may only partly be explained by traditional risk factors. Our purpose was to compare non-traditional risk factors, such as endothelial function, C-reactive protein (CRP) and adiponectin, in Type II diabetic and non-diabetic patients following AMI (acute myocardial infarction). Twenty Type II diabetic patients were compared with 25 non-diabetic patients at baseline (1-3 days from the onset of chest pain) and at 60 days follow-up after an AMI. Using high-resolution ultrasound, brachial artery responses to FMD (flow-mediated vasodilatation; endothelium-dependent vasodilatation) and NTG (nitroglycerine-induced vasodilatation; endothelium-independent vasodilatation) were measured. Plasma levels of CRP and adiponectin were measured by ELISA. At baseline, FMD (1.9 compared with 3.2%; P=0.22) and CRP levels (6.95 compared with. 5.51 mg/l; P=0.40) did not differ between Type II diabetic and non-diabetic patients, whereas adiponectin levels were lower in Type II diabetic patients (2.8 compared with 5.0 ng/ml; P<0.05). At 60 days follow-up, there were significant differences in FMD (1.5 compared with 4.1%; P<0.02), CRP (4.23 compared with 1.46 mg/ml; P<0.01) and adiponectin (3.3 compared with 5.3 ng/ml; P<0.05) levels between Type II diabetic and non-diabetic patients. In contrast, NTG responses improved in both groups between baseline and follow-up (Type II diabetic patients, 9.7 compared with 13.2% respectively, P<0.05; non-diabetic patients, 7.9 compared with 12.4% respectively, P<0.01). These results show a persistent endothelium-dependent dysfunction and inflammatory activity in patients with Type II diabetes, but not in non-diabetic patients, after AMI. These findings may, in part explain, the poor outcome in coronary artery disease seen in Type II diabetes.

Tetrahydrobiopterin increases insulin sensitivity in patients with type 2 diabetes and coronary heart disease.

Tetrahydrobiopterin (BH(4)) is an essential cofactor of nitric oxide synthase that improves endothelial function in diabetics, smokers, and patients with hypercholesterolemia. Insulin resistance has been suggested as a contributing factor in the development of endothelial dysfunction via an abnormal pteridine metabolism. We hypothesized that BH(4) would restore flow-mediated vasodilation (FMD, endothelial-dependent vasodilation), which may affect insulin resistance in type 2 diabetic patients. Thirty-two subjects (12 type 2 diabetic subjects, 10 matched nondiabetic subjects, and 10 healthy unmatched subjects) underwent infusion of BH(4) or saline in a random crossover study. Insulin sensitivity index (S(I)) was measured by hyperinsulinemic isoglycemic clamp. FMD was measured using ultrasonography. BH(4) significantly increased S(I) in the type 2 diabetics [3.6 +/- 0.6 vs. 4.9 +/- 0.7 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P < 0.05], while having no effects in nondiabetics [8.9 +/- 1.1 vs. 9.0 +/- 0.9 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.92] or in healthy subjects [17.5 +/- 1.6 vs. 18 +/- 1.8 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.87]. BH(4) did not affect the relative changes in brachial artery diameter from baseline FMD (%) in type 2 diabetic subjects (2.3 +/- 0.8 vs. 1.8 +/- 1.0%, P = 0.42), nondiabetic subjects (5.3 +/- 1.1 vs. 6.6 +/- 0.9%, P = 0.32), or healthy subjects (11.9 +/- 0.6 vs. 11.0 +/- 1.0%, P = 0.48). In conclusion, BH(4) significantly increases insulin sensitivity in type 2 diabetic patients without any discernible improvement in endothelial function.