[Estimation of molecular clock of Mycobacterium tuberculosis based on whole genome sequencing data].

Objective: To analyze the genomic mutation of Mycobacterium tuberculosis (M. tuberculosis) isolated in endogenous activation period and estimate the molecular clock based on the whole genome sequencing data. Methods: Literatures of the whole genome research of endogenous reactivated tuberculosis were retrieved, and the corresponding whole genome sequencing data were downloaded. We extracted the single nucleotide polymorphisms (SNPs) and strain isolation time of initial treatment and relapse of tuberculosis cases, explored the relationship between the different SNPs and interval between initial treatment and relapse by Poisson regression model, calculated the M. tuberculosis molecular clock, and estimated the mutation rate. Results: When the generation time of M. tuberculosis was 18 hours, the mutation rate in 0-2 years, i.e. short-term endogenous activation, was 6.47×10-10 (95%CI: 5.59×10-10-7.44×10-10), which was significantly higher than that in 2-14 years in long term endogenous activation (3.27×10-10, 95%CI: 2.88×10-10-3.69×10-10). The mutation rates of 0-, 1-, 2-, 3-, 5- and 7-14 years were 7.10×10-10, 6.06×10-10, 4.24×10-10, 5.34×10-10, 2.59×10-10 and 1.26×10-10 respectively. Conclusions: In the period of endogenous reactivation, the mutation rate of M. tuberculosis decreases with the interval time between initial treatment and relapse, which verifies the clinically observed phenomenon that the relapse often occurs within two years after the initial treatment of tuberculosis.

[Biocompatibility of extracellular matrix hydrogel with human iPSCs differentiated cardiomyocytes].

Objective: To observe the biocompatibility of porcine omental derived extracellular matrix (ECM) hydrogel with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the feasibility of ECM hydrogel as a delivery vector of cell transplantation. Methods: A series of chemical, physical and enzymatic methods were applied to acellularize the porcine omentum. Subsequently, the extracted ECM was prepared into thermosensitive hydrogel. The biochemical composition of the hydrogel was identified by histological staining. The microstructure was observed by scanning electron microscopy. The hydrogel was then injected into the myocardium of mice to observe its in situ gelation ability. Differentiation of human induced pluripotent stem cells into cardiomyocytes was achieved by small molecule induction, and then the obtained hiPSC-CMs were cultured. hiPSC-CMs cultured onto the prepared hydrogel were defined as the hydrogel group, while conventionally cultured hiPSC-CMs were defined as the control group. Cardiomyocyte viability and growth patterns were detected using live/dead staining, CCK-8 and phalloidin staining. Immunofluorescence staining and Western blot of cardiomyocytes were used to determine the survival and phenotypic maintenance markers of cardiomyocytes in materials. Results: The results of HE staining, oil red O staining and DAPI fluorescence staining showed that there was no significant cell debris, nucleus and lipid residue in the prepared ECM hydrogel. The Sirius red staining and Alcian blue staining showed that the hydrogel retained collagen and glycolaminoglycan, which were the main components of ECM. The prepared hydrogel behaves as a viscous liquid at 4 ℃ and as a gel state at 37 ℃. Scanning electron microscope results showed that the microstructure of the hydrogel was composed of irregular fibers and pores of different sizes. Under the guidance of ultrasound, the prepared ECM hydrogel could be successfully injected into the myocardium of mice. Immediately after the injection, the hyperechoic signal could be observed under ultrasound, suggesting that the hydrogel remained in the myocardium. HE staining of myocardial tissue evidenced that there was lump of gel in the injection area. The differentiated hiPSC-CMs were co-cultured with the prepared ECM hydrogel, and the results of live/dead staining showed that most of the hiPSC-CMs in the hydrogel group and the control group were alive, dead cells were scanty. The results of CCK-8 test showed that the absorbance values of the two groups were similar (P>0.05). The results of phalloidin staining showed that hiPSC-CMs could extend normally when co-cultured with ECM hydrogel. The cell morphology of the hydrogel group was similar with that of the control group, and there was no statistically significant difference in the F-actin coverage area per cell between the two groups (P>0.05). Immunofluorescence staining of cardiomyocyte markers showed that there was no significant difference in the coverage area of α-actinin and connexin-43 (Cx-43) per field between the hydrogel group and the control group (both P>0.05), the quantitative results of DAPI staining showed that there was no statistically significant difference in the number of cells between the two groups (P>0.05). Meanwhile, the results of Western blot showed that the expression levels of α-actinin and Cx-43 in cardiomyocytes in the hydrogel group were similar as those in the control group (both P>0.05). Conclusions: These results show that preparation of the ECM hydrogel from porcine omentum is successful. The hydrogel has good biocompatibility and no obvious cytotoxicity. Besides, the hydrogel can support the survival of hiPSC-CMs in vitro and maintain its phenotype. These properties make it a promising injectable cardiac tissue engineering material.

[Accuracy and clinical outcome of a real-time surgical navigation system for the placement of quad zygomatic implants].

Objective: To evalute the accuracy and clinical outcome of a real-time navigation system for the placement of quad zygomatic implants. Methods: Twenty-four patients [9 males and 15 females, mean age was (50.8±14.7) years old], from January 2015 to December 2019, with 96 zygomatic implants placed under a real-time navigation system in Department of Second Dental Center and Department of Oral Implantology of Ninth People's Hospital, Shanghai Jiaotong University School of Medicine were included in the study. The preoperative and the postoperative multislice CT or cone-beam CT were fused to measure and record the entry, exit and angle deviation between the planned and placed implants. The implants were divided into groups according to implant insertion approach (real-time navigation and free-hand), implant length (<47.5 mm and ≥47.5 mm) and implant position (proximal and distal implant). And the differences of implant accuracy were analyzed. The intraoperative and postoperative complications were also recorded. The implant survival rate was evaluated after 6 months follow-up. A P value<0.05 indicates statistical significance. Results: The mean entry, exit and angle deviation of zygomatic implants were (1.49±0.64) mm, [2.03(1.58, 2.40)] mm and (2.49°±1.12°), respectively. The average entry, exit and angle deviation of the navigation guided implant insertion group were (1.45±0.60) mm, (1.96±0.44) mm and (2.66±1.13°) respectively, while those of the free-hand group were (1.50±0.64) mm, (2.04±0.79) mm and (2.50°±1.13°) respectively. There was no significant difference between the two groups (P>0.05). The average entry, exit and angle deviation of the group with length<47.5 mm were (1.42±0.60) mm, (2.13±0.60) mm and (2.61°±1.08°) respectively and those of the group with length ≥ 47.5 mm were (1.52±0.65) mm, (1.98±0.82) mm and (2.43°±1.14°) respectively. No significant difference was found between the two groups (P>0.05). In proximal implant group, the average entry, exit and angle deviation were (1.55±0.69) mm, (2.05±0.92) mm and (2.48°±1.16 °) respectively while those of distal implant group were (1.43±0.57) mm, (2.01±0.57) mm and (2.49°±1.10°), respectively. No significant difference was detected between the two groups (P>0.05). All zygomatic implants were placed uneventfully. There were no intra-operative complications, and post-operative reversible complications developed in 3 patients. Two zygomatic implants were lost and the overall zygomatic implant survival rate was 97.9% (94/96) within a follow-up of 6 months. Conclusions: Quad zygomatic implant placement can be achieved with high accuracy and predictable clinical outcome under guidance of a real-time navigation system.

There's plenty of room at the Top: What will drive computer performance after Moore's law?

The miniaturization of semiconductor transistors has driven the growth in computer performance for more than 50 years. As miniaturization approaches its limits, bringing an end to Moore's law, performance gains will need to come from software, algorithms, and hardware. We refer to these technologies as the "Top" of the computing stack to distinguish them from the traditional technologies at the "Bottom": semiconductor physics and silicon-fabrication technology. In the post-Moore era, the Top will provide substantial performance gains, but these gains will be opportunistic, uneven, and sporadic, and they will suffer from the law of diminishing returns. Big system components offer a promising context for tackling the challenges of working at the Top.

Spin-orbit torque switching in a T-type magnetic configuration with current orthogonal to easy axes.

Different symmetry breaking ways determine various magnetization switching modes driven by spin-orbit torques (SOT). For instance, an applied or effective field parallel to applied current is indispensable to switch magnetization with perpendicular anisotropy by SOT. Besides of this mode, here we experimentally demonstrate a distinct field-free switching mode in a T-type magnetic system with structure of MgO/CoFeB/Ta/CoFeB/MgO where a perpendicular layer with tilted easy axis was coupled to an in-plane layer with a uniaxial easy axis. Current was applied orthogonal to both easy axes and thus also normal to an in-plane effective field experienced by the perpendicular layer. Dynamic calculation shows perpendicular layer could be switched at the same time as the in-plane layer is switched. These field-free switching modes realized in the same T-type magnetic system might expedite the birth of multi-state spin memories or spin logic devices which could be operated by all electric manners.

[Risk of bias assessment: (7) Assessing Bias in Studies of Prognostic Factors].

This paper introduces the tools related to Quality In Prognosis Studies (QUIPS) to assess the risk of bias in studies of prognostic factors and the relevant points of assessment and to illustrate the application of QUIPS in published prognostic research. The QUIPS tool identified 6 important areas to consider when evaluating validity and bias in studies of prognostic factors including participation, attrition, measurement on prognostic factors, outcomes, confounding factors, statistical analysis and reporting. It also provided a new method for evaluation on bias in the areas of prognostic research.

Study on the effect of Integrin αVß6 on proliferation and apoptosis of cervical cancer cells.

OBJECTIVE: To analyze the influence of Integrin αVß6 on proliferation and apoptosis of cervical cancer cells. PATIENTS AND METHODS: Fifty-two patients with benign cervical lesions, 55 cervical cancer patients, and 20 healthy controls were selected as research subjects. The positive expression rate of Integrin αVß6 was detected in cervical tissue samples by immunohistochemistry. The relative expressions of the proliferation-related proteins, p53, PCNA, Ki-67, and TIPE2, and the apoptosis-related proteins, Cyto-C, AIF, caspase-3, Bag-1, Bcl-2, and p-Akt were measured by Western blot. RESULTS: The positive rate of Integrin αVß6 expression was higher in tissue from cervical cancer patients than in the other two groups (p < 0.05). The levels of expression of p53, PCNA, and Ki-67 in the cervical cancer group were higher, while the levels of TIPE2 were lower compared with the other two groups (p < 0.05). The levels of expression of Bag-1 and Bcl-2 were higher in the cervical cancer group, but Cyto-C, AIF, caspase-3, and p-Akt were lower compared with the other two groups (p < 0.05). Compared with cervical cancer patients with negative Integrin αVß6 expression, patients with positive Integrin αVß6 expression had different expression levels of the proliferation- and apoptosis-related proteins, and the differences were statistically significant (p < 0.05). CONCLUSIONS: High expression of Integrin αVß6 is an important cause of active proliferation and impaired apoptosis in cervical cancer. Integrin αVß6 is a promising target for the treatment of cervical cancer.

[Copy number variants analysis in whole-genome of patients with lipoma tethered cord syndrome].

Objective: To explore the abnormality of chromosomes of patients with lipoma tethered cord syndrome and the probable association between Copy Number Variations (CNV) and lipoma tethered cord syndrome. Methods: By using the Agilent SurePrint G3 Human CGH 8×60K Microarray Kit, we performed genome-wide screening for CNV on 11 patients with lipoma tethered cord syndrome adopted by the Neurosurgery Department of Chinese PLA General Hospital and their healthy parents from March 2015 to May 2015. We analyze CNVs got by the kit against the gene databases. Unrelated confirmed polymorphisms contained in Database of Genomic Variants (DGV) were discarded. Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER) helps us with similarity inquiry, and UCSC Genome Browser helps in identification of non-polymorphic CNV. Biological process, cellular component and molecular function enrichment of these genes were conducted to confirm the association between the CNV and lipoma tethered cord syndrome. Results: 17 CNV were discovered by aCGH in 11 patients. Chr8: 39258894-39386158 and Chr15: 20481702-22509254 showed a high frequency of 5/11. Angelman syndrome and Prader-Wolli syndrome were found to be associated with the CNV of Chr15. Gene function enrichment analysis revealed that ADAM5P and ADAM3A contained in CNV obtained from patients with lipoma tethered cord syndrome was also associated with orofacial clefts. Conclusions: CNV in Chr8 and Chr15 of patients with lipoma tethered cord syndrome had a higher frequency than that of common human. It revealed that there is probable association between these two pieces of CNV and lipoma tethered cord syndrome. To explorer related genes or CNV, focusing on certain type of NTDs may increase the research efficiency and get more accurate results.

The effect of leflunomide on the transplanted endometriosis lesions in SD rats.

OBJECTIVE: To investigate the effects of the leflunomide (LEF) on the size of the transplanted endometriosis (EMS) lesions and trans- forming growth factor (TGF) -ß1gray level in SD rats. MATERIALS AND METHODS: EMS was surgically induced in rats by autologous trans- plantation and the focal volume was also measured. The rats were divided into three groups: group A: normal SD rats, group B: rats irrigated by one ml-kg⁻¹d⁻¹ saline for three weeks, and group C: rats irrigated by 35 mg-kg⁻¹d⁻¹ LEF for three weeks. The rats were then sacrificed and measured their focal volume and TGF-ß1 gray value with immunohistochemical method. RESULTS: The sizes of the focal volume in group C were significantly reduced compared to the rats before feeding, and the volume in group C was smaller than group B after feeding and so was the TGF-ß1. CONCLUSION: LEF could be a new therapeutic drug for EMS.

Common pattern of gray-matter abnormalities in drug-naive and medicated first-episode schizophrenia: a multimodal meta-analysis.

Studies of schizophrenia at drug-naive state and on antipsychotic medication have reported a number of regions of gray-matter (GM) abnormalities but the reports have been inconsistent. The aim of this study was to conduct multimodal meta-analysis to compare the cross-sectional voxel-based morphometry studies of brain GM in antipsychotic-naive first-episode schizophrenia (AN-FES) and those with antipsychotic treatment within 1 year (AT-FES) to determine the similarities and differences in these groups. We conducted two separate meta-analyses containing 24 studies with a sample size of 801 patients and 957 healthy controls. A multimodal meta-analysis method was used to compare the findings between AN-FES and AT-FES. Meta-regression analyses were done to determine the influence of different variables including age, duration of illness, and positive and negative symptom scores. Finally, jack-knife analyses were done to test the robustness of the results. AN-FES and AT-FES showed common patterns of GM abnormalities in frontal (gyrus rectus), superior temporal, left hippocampal and insular cortex. GM in the left supramarginal gyrus and left middle temporal gyrus were found to be increased in AN-FES but decreased in AT-FES, whereas left median cingulate/paracingulate gyri and right hippocampus GM was decreased in AN-FES but increased in AT-FES. Findings suggest that both AN-FES and AT-FES share frontal, temporal and insular regions as common anatomical regions to be affected indicating these to be the primary regions of GM abnormalities in both groups.

Extended boiling of peanut progressively reduces IgE allergenicity while retaining T cell reactivity.

BACKGROUND: Current peanut oral immunotherapy is hampered by frequent adverse events. It has been shown that boiling can reduce peanut allergenicity. Hypoallergenic peanut products have the potential to reduce treatment-related reactions during desensitization. OBJECTIVE: To show that extended boiling (for up to 12 h) can progressively reduce peanut allergenicity while retaining T cell reactivity. METHODS: Raw peanuts were boiled for half, 1, 2, 4 and 12 h in deionized water. After dehydration, boiled and raw peanuts were ground, defatted and soluble proteins extracted in PBS and cooking water (leachate) retained. SDS-PAGE, Western blot, inhibition ELISA, mass spectrometry and skin prick test were used to characterize changes to peanut allergens and human IgE reactivity. T cell responses to raw and boiled peanut extracts were determined by proliferation of CD4+/CD25+/CD134+ T cells in peanut-allergic and non-allergic individuals. RESULTS: Extended boiling progressively reduced peanut allergenicity through a combination of leaching of allergens into cooking water, fragmentation of allergens and denaturation of conformational epitopes. Two-hour boiling led to an eightfold reduction in IgE binding capacity of boiled peanuts as determined by inhibition ELISA, while 12-h boiling led to a 19-fold reduction. Mass spectrometry revealed an increasing number of unique allergen peptides with longer boiling times. Raw, 2- and 12-h boiled peanut extracts were equivalent in their ability to stimulate T cell activation and proliferation. CONCLUSION AND CLINICAL RELEVANCE: Progressive reduction in peanut allergenicity with extended boiling does not affect T cell reactivity. Boiled peanuts may be a candidate for oral immunotherapy.

Protective effect and mechanism of hydrogen treatment on lung epithelial barrier dysfunction in rats with sepsis.

This study aimed to explore the protective effect of hydrogen and to investigate the underlying mechanism of its preliminary effect on the alveolar epithelial barrier function in septic rats. Forty-five male Sprague-Dawley rats were divided randomly into three groups (N = 15): control [saline injection (intraperitoneal, ip), air drawing; SA], acute lung injury group [lipopolysaccharide (LPS) injection (ip, 15 mg/kg), air drawing; LA], and acute lung injury combined with hydrogen drawing group [LPS injection (ip, 15 mg/kg), 2% hydrogen drawing; LH]. The rats were euthanized after 6 h of treatment, and the extravascular lung water (EVLW), pulmonary alveolar-arterial oxygen pressure (A-aDO2), and respiratory index (RI) of each group were measured. The aquaporin-1 (AQP-1) protein expression in the lung tissues was detected using immunohistochemistry and western blotting, and the correlation between the EVLW and AQP-1 was analyzed. The lung morphology was observed with light and electron microscopy. In the LA group, EVLW (0.87 ± 0.17), A-aDO2 (113.21 ± 13.92), RI (0.65 ± 0.26), and AQP-1 expression increased. Additionally, thickened alveolar walls, significant invasion of inflammatory cells around the vessels, capillary ectasia, hyperemia/hemorrhage in the alveolar space, significantly swollen mitochondria, and increased vacuolar degeneration were observed. A significant negative correlation between AQP-1 expression and EVLW was observed (R2 = 0.8806). Compared with the LA group, EVLW (0.71 ± 0.19), A-aDO2 (132.42 ± 17.39), RI (0.75 ± 0.24), and inflammatory reaction decreased and AQP-1 expression increased in the LH group. The damage to pulmonary epithelial cells improved after hydrogen treatment in rats with sepsis; hydrogen could protect the pulmonary epithelial barrier function by acting on AQP-1.

Publisher's Note: Long-Range Phase Coherence in Double-Barrier Magnetic Tunnel Junctions with a Large Thick Metallic Quantum Well [Phys. Rev. Lett. 115, 157204 (2015)].

This corrects the article DOI: 10.1103/PhysRevLett.115.157204.

Long-Range Phase Coherence in Double-Barrier Magnetic Tunnel Junctions with a Large Thick Metallic Quantum Well.

Double-barrier heterostructures are model systems for the study of electron tunneling and discrete energy levels in a quantum well (QW). Until now resonant tunneling phenomena in metallic QWs have been observed for limited thicknesses (1-2 nm) under which electron phase coherence is conserved. In the present study we show evidence of QW resonance states in Fe QWs up to 12 nm thick and at room temperature in fully epitaxial double MgAlO_{x} barrier magnetic tunnel junctions. The electron phase coherence displayed in this QW is of unprecedented quality because of a homogenous interface phase shift due to the small lattice mismatch at the Fe-MgAlO_{x} interface. The physical understanding of the critical role of interface strain on QW phase coherence will greatly promote the development of spin-dependent quantum resonant tunneling applications.

Association between osteocalcin and glucose metabolism: a meta-analysis.

UNLABELLED: This meta-analysis aimed to investigate the associations between osteocalcin (Ocn) and fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c). It was revealed that both total Ocn and undercarboxylated Ocn (unOcn) were negatively related with FPG and HbA1c, and the association of unOcn with FPG was more pronounced in men. INTRODUCTION: The aim of this study was to investigate the strength of associations between Ocn and FPG and HbA1c using a meta-analysis approach. METHODS: A search was carried out using the databases of PubMed, ISI Web of Science, and the Cochrane library from 2007 to 2014 to identify related studies. A pooled effect size with 95 % confidence intervals (CI) was derived. RESULTS: The meta-analysis included 39 studies involving 23,381 participants. The overall correlation was -0.16 (95 % CI, -0.19 to -0.14) between total Ocn (tOcn) and FPG and -0.15 (95 % CI, -0.20 to -0.11) between undercarboxylated Ocn (unOcn) and FPG. In the analysis of the association between Ocn and HbA1c, the pooled correlation was -0.16 (95 % CI, -0.18 to -0.14) for tOcn and -0.16 (95 % CI, -0.23 to -0.08) for unOcn. The magnitude of the correlation between unOcn and FPG is significantly higher in men than in women (r = -0.18, 95 % CI, -0.21 to -0.14; r = -0.09, 95 % CI, -0. 13 to -0.05, respectively; P for interaction < 0.05). Similar trend was also found between unOcn and HbA1c but without significance (for men, r = -0.19, 95 % CI, -0.24 to -0.14; for women, r = -0.09, 95 % CI, -0.22 to 0.04, respectively; P for interaction > 0.05). No indication of significant publication bias was found in any method. CONCLUSIONS: This meta-analysis demonstrated that both unOcn and tOcn were similarly and negatively correlated with FPG and HbA1c in humans. The negative correlations between unOcn and glucose metabolism appear to be more pronounced in men than in women.

Efficacy and safety of colesevelam in combination with pioglitazone in patients with type 2 diabetes mellitus.

Colesevelam improves glycemic control in patients with type 2 diabetes when added to existing metformin-, sulfonylurea-, or insulin-based regimens. We evaluated colesevelam's effects in subjects on stable pioglitazone-based therapy. This 24-week multicenter, double-blind, randomized, placebo-controlled study enrolled adults with type 2 diabetes who had suboptimal glycemic control [HbA1c ≥ 58 mmol/mol (7.5%) and ≤ 80 mmol/mol (9.5%)] on pioglitazone (30 or 45 mg) with or without 1-2 other oral antidiabetes medications. Subjects were randomized to colesevelam 3.8 g/day (n = 280) or placebo (n = 282) added to existing pioglitazone-based therapy. Primary efficacy variable was mean change in HbA1c from baseline to Week 24. Secondary variables included safety and tolerability, fasting plasma glucose changes, glycemic responses, and lipid profile. Tertiary variables included lipid particle profile changes by nuclear magnetic resonance. Colesevelam decreased HbA1c [least-squares mean treatment difference, - 3.5 mmol/mol (- 0.32%); p < 0.001] and fasting plasma glucose (- 14.7 mg/dl; p<0.001) vs. placebo at Week 24. More subjects receiving colesevelam vs. placebo achieved HbA1c reduction ≥ 7.7 mmol/mol (0.7%) (40% vs. 25%; p<0.001) or HbA1c < 53 mmol/mol (7.0%) (21% vs. 13%; p = 0.012). Colesevelam also decreased total cholesterol (mean treatment difference, - 6.5%), LDL-cholesterol (- 16.4%), non-HDL-cholesterol (- 9.8%), apolipoprotein B (- 8.8%), and total LDL particle concentration, and increased apolipoprotein A1 (+3.4%) and triglycerides (median treatment difference, + 11.3%) vs. placebo (all p < 0.001). There were no serious drug-related adverse events, and the majority of adverse events were mild or moderate. In subjects with type 2 diabetes inadequately controlled with pioglitazone-based therapy, add-on colesevelam therapy improved glycemic control and lipid parameters and was well tolerated. ClinicalTrials.gov identifier: NCT00789750.

The glucose and lipid effects of colesevelam as monotherapy in drug-naïve type 2 diabetes.

Colesevelam has shown efficacy in adults with type 2 diabetes mellitus (T2DM) in combination with metformin-, sulfonylurea-, or insulin-based therapy, lowering hemoglobin A1c (HbA1c) and low-density lipoprotein cholesterol levels. A study was conducted to evaluate colesevelam as monotherapy in drug-naïve patients with T2DM. In this randomized, double-blind, placebo-controlled, parallel-group study, adults with T2DM who had inadequate glycemic control (HbA1c ≥7.5% and ≤9.5%) with diet and exercise alone were randomized to receive colesevelam 3.75 g/day (n=176) or placebo (n=181) for 24 weeks. The primary efficacy variable was HbA1c at week 24. Colesevelam as compared to placebo showed significant reductions from baseline in HbA1c (-2.92 mmol/mol [0.3%]; p=0.01) and fasting plasma glucose (-10.3 mg/dl; p=0.04) at week 24 with last observation carried forward. Colesevelam also significantly reduced low-density lipoprotein cholesterol (-11.2%; p<0.0001), total cholesterol (-5.1%; p=0.0005), non-high-density lipoprotein cholesterol (-7.4%; p=0.0001), and apolipoprotein B (-6.5%; p=0.0001) and increased apolipoprotein A-I (+ 2.4%; p=0.04), and triglycerides (+ 9.7%; p=0.03). Colesevelam monotherapy resulted in statistically significant improvements in glycemic and most lipid parameters in subjects with type 2 diabetes, with no new or unexpected safety and tolerability issues. Modest reductions in HbA1c and low-density lipoprotein cholesterol levels with colesevelam further support its use in combination with other antidiabetes agents when treatment targets for these parameters are close but are not quite achieved.ClinicalTrials.gov identifier: NCT00789737.