Efficient Implementation of Equation-of-Motion Coupled-Cluster Singles and Doubles Method with the Density-Fitting Approximation: An Enhanced Algorithm for the Particle-Particle Ladder Term.

An efficient implementation of the density-fitted equation-of-motion coupled-cluster singles and doubles (DF-EOM-CCSD) method is presented with an enhanced algorithm for the particle-particle ladder (PPL) term, which is the most expensive part of EOM-CCSD computations. To further improve the evaluation of the PPL term, a hybrid density-fitting/Cholesky decomposition (DF/CD) algorithm is also introduced. In the hybrid DF/CD approach, four virtual index integrals are constructed on-the-fly from the DF factors; then, their partial Cholesky decomposition is simultaneously performed. The computational cost of the DF-EOM-CCSD method for excitation energies is compared with that of the resolution of the identity EOM-CCSD (RI-EOM-CCSD) (from the Q-chem 5.3 package). Our results demonstrate that DF-EOM-CCSD excitation energies are significantly accelerated compared to RI-EOM-CCSD. There is more than a 2-fold reduction for the C8H18 molecule in the cc-pVTZ basis set with the restricted Hartree-Fock (RHF) reference. This cost savings results from the efficient evaluation of the PPL term. In the RHF based DF-EOM-CCSD method, the number of flops (NOF) is 1/4O2V4, while that of RI-EOM-CCSD was reported (Epifanovsky et al. J. Chem. Phys. 2013, 139, 134105) to be 5/8O2V4 for the PPL contraction term. Further, the NOF of VVVV-type integral transformation is 1/2V4Naux in our case, while it appears to be V4Naux for RI-EOM-CCSD. Hence, our implementation is 2.5 and 2.0 times more efficient compared to RI-EOM-CCSD for these expensive terms. For the unrestricted Hartree-Fock (UHF) reference, our implementation maintains its enhanced performance and provides a 1.8-fold reduction in the computational time compared to RI-EOM-CCSD for the C7H16 molecule. Our results indicate that our DF-EOM-CCSD implementation is 1.7 and 1.4 times more efficient compared with RI-EOM-CCSD for average computational cost per EOM-CCSD iteration. Moreover, our results show that the new hybrid DF/CD approach improves upon the DF algorithm, especially for large molecular systems. Overall, we conclude that the new hybrid DF/CD PPL algorithm is very promising for large-sized chemical systems.

MacroQC 1.0: An electronic structure theory software for large-scale applications.

MacroQC is a quantum chemistry software for high-accuracy computations and large-scale chemical applications. MacroQC package features energy and analytic gradients for a broad range of many-body perturbation theory and coupled-cluster (CC) methods. Even when compared to commercial quantum chemistry software, analytical gradients of second-order perturbation theory, CC singles and doubles (CCSD), and CCSD with perturbative triples approaches are particularly efficient. MacroQC has a number of peculiar features, such as analytic gradients with the density-fitting approach, orbital-optimized methods, extended Koopman's theorem, and molecular fragmentation approaches. MacroQC provides a limited level of interoperability with some other software. The plugin system of MacroQC allows external interfaces in a developer-friendly way. The linear-scaling systematic molecular fragmentation (LSSMF) method is another distinctive feature of the MacroQC software. The LSSMF method enables one to apply high-level post-Hartree-Fock methods to large-sized molecular systems. Overall, we feel that the MacroQC program will be a valuable tool for wide scientific applications.

Efficient implementations of the symmetric and asymmetric triple excitation corrections for the orbital-optimized coupled-cluster doubles method with the density-fitting approximation.

Efficient implementations of the symmetric and asymmetric triple excitation corrections for the orbital-optimized coupled-cluster doubles (OCCD) method with the density-fitting approach, denoted by DF-OCCD(T) and DF-OCCD(T)Λ, are presented. The computational cost of the DF-OCCD(T) method is compared with that of the conventional OCCD(T). In the conventional OCCD(T) and OCCD(T)Λ methods, one needs to perform four-index integral transformations at each coupled-cluster doubles iterations, which limits its applications to large chemical systems. Our results demonstrate that DF-OCCD(T) provides dramatically lower computational costs compared to OCCD(T), and there are more than 68-fold reductions in the computational time for the C5H12 molecule with the cc-pVTZ basis set. Our results show that the DF-OCCD(T) and DF-OCCD(T)Λ methods are very helpful for the study of single bond-breaking problems. Performances of the DF-OCCD(T) and DF-OCCD(T)Λ methods are noticeably better than that of the coupled-cluster singles and doubles with perturbative triples [CCSD(T)] method for the potential energy surfaces of the molecules considered. Specifically, the DF-OCCD(T)Λ method provides dramatic improvements upon CCSD(T), and there are 8-14-fold reductions in nonparallelity errors. Overall, we conclude that the DF-OCCD(T)Λ method is very promising for the study of challenging chemical systems, where the CCSD(T) fails.

Energy and analytic gradients for the orbital-optimized coupled-cluster doubles method with the density-fitting approximation: An efficient implementation.

Efficient implementations of the orbital-optimized coupled-cluster doubles (or simply "optimized CCD," OCCD, for short) method and its analytic energy gradients with the density-fitting (DF) approach, denoted by DF-OCCD, are presented. In addition to the DF approach, the Cholesky-decomposed variant (CD-OCCD) is also implemented for energy computations. The computational cost of the DF-OCCD method (available in a plugin version of the DFOCC module of PSI4) is compared with that of the conventional OCCD (from the Q-CHEM package). The OCCD computations were performed with the Q-CHEM package in which OCCD are denoted by OD. In the conventional OCCD method, one needs to perform four-index integral transformations at each of the CCD iterations, which limits its applications to large chemical systems. Our results demonstrate that DF-OCCD provides dramatically lower computational costs compared to OCCD, and there are almost eightfold reductions in the computational time for the C6H14 molecule with the cc-pVTZ basis set. For open-shell geometries, interaction energies, and hydrogen transfer reactions, DF-OCCD provides significant improvements upon DF-CCD. Furthermore, the performance of the DF-OCCD method is substantially better for harmonic vibrational frequencies in the case of symmetry-breaking problems. Moreover, several factors make DF-OCCD more attractive compared to CCSD: (1) for DF-OCCD, there is no need for orbital relaxation contributions in analytic gradient computations; (2) active spaces can readily be incorporated into DF-OCCD; (3) DF-OCCD provides accurate vibrational frequencies when symmetry-breaking problems are observed; (4) in its response function, DF-OCCD avoids artificial poles; hence, excited-state molecular properties can be computed via linear response theory; and (5) symmetric and asymmetric triples corrections based on DF-OCCD [DF-OCCD(T)] have a significantly better performance in near degeneracy regions.

Synthetic ECM: Bioactive Synthetic Hydrogels for 3D Tissue Engineering.

The specific microenvironment that cells reside in fundamentally impacts their broader function in tissues and organs. At its core, this microenvironment is composed of precise arrangements of cells that encourage homotypic and heterotypic cell-cell interactions, biochemical signaling through soluble factors like cytokines, hormones, and autocrine, endocrine, or paracrine secretions, and the local extracellular matrix (ECM) that provides physical support and mechanobiological stimuli, and further regulates biochemical signaling through cell-ECM interactions like adhesions and growth factor sequestering. Each cue provided in the microenvironment dictates cellular behavior and, thus, overall potential to perform tissue and organ specific function. It follows that in order to recapitulate physiological cell responses and develop constructs capable of replacing damaged tissue, we must engineer the cellular microenvironment very carefully. Many great strides have been made toward this goal using various three-dimensional (3D) tissue culture scaffolds and specific media conditions. Among the various 3D biomimetic scaffolds, synthetic hydrogels have emerged as a highly tunable and tissue-like biomaterial well-suited for implantable tissue-engineered constructs. Because many synthetic hydrogel materials are inherently bioinert, they minimize unintentional cell responses and thus are good candidates for long-term implantable grafts, patches, and organs. This review will provide an overview of commonly used biomaterials for forming synthetic hydrogels for tissue engineering applications and techniques for modifying them to with bioactive properties to elicit the desired cell responses.

Assessment of the Density-Fitted Second-Order Quasidegenerate Perturbation Theory for Transition Energies: Accurate Computations of Singlet-Triplet Gaps for Charge-Transfer Compounds.

Organic light-emitting diodes (OLEDs) have been of significant interest because of their superior performance and low cost of production. Thermally activated delayed fluorescence (TADF) has attracted significant interest in the OLED technology because it improves the efficiency of OLEDs by harvesting triplet excitons. Therefore, the accurate computation of singlet-triplet transition energies (ΔES1-T1) of charge-transfer molecules is very important. However, the accurate computation of the ΔES1-T1 values is a challenging problem for single-reference methods because of the multireference character of excited states. In this research, an assessment of density-fitted second-order quasidegenerate perturbation theory (DF-QDPT2) [Bozkaya, U.; J. Chem. Theory Comput. 2019, 15, 4415-4429] for singlet-triplet transition energies (ΔES1-T1) of charge-transfer compounds is presented. The performance of the DF-QDPT2 method has been compared with those of several density-functional theory functionals, such as B3LYP, PBE0, M06-2X, ωB97X-D, and MN15; density-fitted state-averaged CASSCF (DF-SA-CASSCF); and single-state single-reference second-order perturbation theory (SS-SR-CASPT2) methods. For the TADF molecules considered, the DF-QDPT2 method provides a mean absolute error (MAE) of 0.13 eV, while the MAE values of DF-SA-CASSCF and SS-SR-CASPT2 are 0.65 and 0.74 eV, respectively. The performances of B3LYP and PBE0 are slightly better than that of DF-QDPT2, while M06-2X and ωB97X-D provide noticeably higher errors compared with DF-QDPT2. Furthermore, the standard CASSCF without state-averaging yields dramatic errors with an MAE value of 3.0 eV. Our results demonstrate that eigenvalues of the DF-QDPT2-effective Hamiltonian can be reliably used for the prediction of singlet-triplet transition energies, while eigenvalues of DF-CASSCF/DF-SA-CASSCF fail to provide accurate predictions. Overall, we conclude that the DF-QDPT2 method emerges as a very useful tool for the computation of excited-state properties.

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride.

In this study, we developed a new addition reaction of chlorosulfonyl isocyanate (CSI), starting from 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione. The addition reaction of CSI with 2-ethyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione resulted in the formation of ylidenesulfamoyl chloride, whose exact configuration was determined by X-ray crystal analysis. We explain the mechanism of product formation supported by theoretical calculations.

Anionic water pentamer and hexamer clusters: An extensive study of structures and energetics.

An extensive study of structures and energetics for anionic pentamer and hexamer clusters is performed employing high level ab initio quantum chemical methods, such as the density-fitted orbital-optimized linearized coupled-cluster doubles (DF-OLCCD), coupled-cluster singles and doubles (CCSD), and coupled-cluster singles and doubles with perturbative triples [CCSD(T)] methods. In this study, sixteen anionic pentamer clusters and eighteen anionic hexamer clusters are reported. Relative, binding, and vertical detachment energies (VDE) are presented at the complete basis set limit (CBS), extrapolating energies of aug4-cc-pVTZ and aug4-cc-pVQZ custom basis sets. The largest VDE values obtained at the CCSD(T)/CBS level are 9.9 and 11.2 kcal mol-1 for pentamers and hexamers, respectively, which are in very good agreement with the experimental values of 9.5 and 11.1 kcal mol-1. Our binding energy results, at the CCSD(T)/CBS level, indicate strong bindings in anionic clusters due to hydrogen bond interactions. The average binding energy per water molecules is -5.0 and -5.3 kcal mol-1 for pentamers and hexamers, respectively. Furthermore, our results demonstrate that the DF-OLCCD method approaches to the CCSD(T) quality for anionic clusters. The inexpensive analytic gradients of DF-OLCCD compared to CCSD or CCSD(T) make it very attractive for high-accuracy studies.

State-of-the-Art Computations of Vertical Ionization Potentials with the Extended Koopmans' Theorem Integrated with the CCSD(T) Method.

The accurate computation of ionization potentials (IPs), within 0.10 eV, is one of the most challenging problems in modern computational chemistry. The extended Koopmans' theorem (EKT) provides a systematic direct approach to compute IPs from any level of theory. In this study, the EKT approach is integrated with the coupled-cluster singles and doubles with perturbative triples [CCSD(T)] method for the first time. For efficiency, the density-fitting (DF) approximation is employed for electron repulsion integrals. Further, the EKT-CCSD(T) method is applied to a set of 23 molecules, denoted as IP23, for comparison with the experimental ionization potentials. For the IP23 set, the EKT-CCSD(T) method, along with the aug-cc-pV5Z basis set, provides a mean absolute error of 0.05 eV. Hence, our results demonstrate that direct computations of IPs at high-accuracy levels can be achieved with the EKT-CCSD(T) method. We believe that the present study may open new avenues in IP computations.

Cystatin-C and TGF-β levels in patients with diabetic nephropathy / Concentración de cistatina C y TGF-β en pacientes con nefropatía diabética

Objetivo: Evaluar la insuficiencia renal en pacientes con diabetes tipo 2 con normoalbuminuria o microalbuminuria mediante la detección de la concentración de cistatina C en suero y de TGF-β en suero y orina. Métodos: Estudio transversal realizado en el Departamento de Endocrinología de la Facultad de Medicina de la Universidad de Baskent. En el estudio, se incluyó a pacientes con diabetes mellitus tipo 2 sin nefropatía diabética manifiesta conocida. Los pacientes seleccionados se estratificaron en 4 grupos, agrupados en términos de edad, sexo, grado de microalbuminuria y filtración glomerular estimada (FGe) calculada mediante la fórmula MDRD. Resultados: Se incluyó a 78 pacientes. Se clasificaron en 4 grupos dependiendo de la excreción urinaria de albúmina y de la FGe. Se observó que la complicación macrovascular era mayor en los pacientes con microalbuminuria que en otros (p<0,01), pero no hubo diferencias con relación a otras complicaciones diabéticas. La concentración sérica de cistatina C fue significativamente mayor en los pacientes del grupo 1 con normoalbuminuria, mientras que las concentraciones de TGF-β1 en suero y orina fueron mayores en los pacientes del grupo 2 con microalbuminuria. Se observó una correlación negativa entre la concentración sérica de cistatina C y la FGe en los pacientes del grupo 2 (r=−0,892, p<0,001). Por último, se observó una correlación negativa entre la FGe y la cistatina C en todos los grupos de pacientes (r=−0,726, p=0,001). Conclusiones: Aunque se recomienda la excreción urinaria de albúmina para la detección de la nefropatía diabética tipo 2, hay un grupo de pacientes con disminución de la FGe, pero sin aumento de la excreción urinaria de albúmina, en los que estaba indicado usar la concentración de cistatina C en suero como un biomarcador temprano de nefropatía diabética (AU)

Objective: To evaluate renal impairment in type 2 diabetic patients with normoalbuminuria or microalbuminuria by detection of serum cystatin C and serum and urinary TGF-β levels. Methods: Cross-sectional study conducted at the Department of Endocrinology in Baskent University School of Medicine. Patients with type 2 diabetes mellitus without known overt diabetic nephropathy were included in the study. Recruited patients were stratified into four groups, matched in terms of age, gender, microalbuminuria level and estimated GFR calculated with MDRD. Results: 78 patients were enrolled. They were categorized into four groups depending on their urinary albumin excretion and estimated glomerular filtration rate. Macrovascular complication was found to be higher in patients with microalbuminuria than in other patients (p<0.01), but there were no differences in terms of other diabetic complications. Serum cystatin C level was significantly higher in normoalbuminuric group one patients, while serum and urinary TGF-β1 levels were higher in microalbuminuric group two patients. The serum level of cystatin C was found to negatively correlate with eGFR in group two patients (r=−0.892, p<0.001). Finally, there was a negative correlation between eGFR and cystatin C in all the patient groups (r=−0.726, p=0.001). Conclusions: Although urinary albumin excretion is recommended for the detection of type two diabetic nephropathy, there is a group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy (AU)

Cystatin-C and TGF-ß levels in patients with diabetic nephropathy.

OBJECTIVE: To evaluate renal impairment in type 2 diabetic patients with normoalbuminuria or microalbuminuria by detection of serum cystatin C and serum and urinary TGF-ß levels. METHODS: Cross-sectional study conducted at the Department of Endocrinology in Baskent University School of Medicine. Patients with type 2 diabetes mellitus without known overt diabetic nephropathy were included in the study. Recruited patients were stratified into four groups, matched in terms of age, gender, microalbuminuria level and estimated GFR calculated with MDRD. RESULTS: 78 patients were enrolled. They were categorized into four groups depending on their urinary albumin excretion and estimated glomerular filtration rate. Macrovascular complication was found to be higher in patients with microalbuminuria than in other patients (p<0.01), but there were no differences in terms of other diabetic complications. Serum cystatin C level was significantly higher in normoalbuminuric group one patients, while serum and urinary TGF-ß1 levels were higher in microalbuminuric group two patients. The serum level of cystatin C was found to negatively correlate with eGFR in group two patients (r=-0.892, p<0.001). Finally, there was a negative correlation between eGFR and cystatin C in all the patient groups (r=-0.726, p=0.001). CONCLUSIONS: Although urinary albumin excretion is recommended for the detection of type two diabetic nephropathy, there is a group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy.

Serum Adiponectin Level as a Predictor of Subclinical Cushing's Syndrome in Patients with Adrenal Incidentaloma.

Subclinical Cushing's syndrome (SCS) is a condition of slight but chronic cortisol excess in patients with adrenal incidentaloma (AI) without typical signs and symptoms of Cushing's syndrome. Adiponectin has potent roles in modulating energy balance and metabolic homeostasis and acts in opposition to glucocorticoids. This study aimed to evaluate adiponectin level in SCS and nonfunctional AI (NAI) patients and its relation with metabolic parameters. Patients with AI (n = 40) and metabolically healthy controls (n = 30) were included. In AI patients and controls, detailed medical history assessment, physical examinations, anthropometric measurements, and laboratory measurements were performed. Age, body mass index, waist circumference, and lipid profiles were significantly higher and waist-to-hip ratio and adiponectin level were significantly lower in the AI patients than in the controls. The midnight cortisol and urinary free cortisol levels were significantly higher in the SCS patients (n = 8) than in the NAI patients (n = 32). Adiponectin level of the SCS group was significantly lower than those of the NAI and control groups. The sensitivity and specificity for an adiponectin level of ≤13.00 ng/mL in predicting the presence of SCS were 87.5% and 77.4%, respectively. In conclusion, adiponectin is valuable in predicting the presence of SCS in AI patients.

Amyloid goiter due to familial mediterranean Fever in a patient with byler syndrome: a case report.

BACKGROUND: Familial Mediterranean Fever (FMF), also inherited with autosomal recessive trait, is characterized by recurrent episodes of fever, arthritis, and serositis. Congenital Byler Syndrome (Progressive Familial Intrahepatic Cholestasis) inherited with autosomal recessive trait and characterized by defective secretion of bile acids. FMF associated Amyloid A deposition occurs in many tissues and organs, but amyloid goiter is a rare entity that leads to enlargement and dysfunction of the thyroid. CASE REPORT: We present a rare case of 24 year old male patient who had liver and kidney transplantation due to Byler Syndrome and secondary amyloidosis related to FMF, diagnosed as rapidly growing large amyloid goiter. Deposits of extracellular amyloid and dense adipose metaplasia diagnostic for amyloid goiter are determined upon histopathological examination of thyroidectomy material. CONCLUSION: When goiter was detected in cases with history of systemic amyloidosis and rapidly growing goitre, amyloid goiter should be remembered at first. This case is unique since two autosomal genetic disorders are together in the same patient and important as it emphasizes the consequences of consanguineous marriage, early diagnosis and treatment compliance of FMF and the awareness of amyloid goiter in patients followed by primary care physicians and healthcare professionals.

Is the incidence of temporomandibular disorder increased in polycystic ovary syndrome?

The prevalence of temporomandibular disorders is higher among women than men (ratio 3:1 -9:1). Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in women, which is characterised by chronic low-grade inflammation and excess of androgenic hormones that lead to metabolic aberrations and ovarian dysfunction. Increased activities of various matrix metalloproteinases (particularly MMP-2 and 9) in the serum of these patients has been reported, and it has been hypothesised that high activities of MMP may contribute to loss of matrix and chronic inflammation of the fibrocartilage in temporomandibular disorders. Our aim was to evaluate the incidence of temopormandibular dysfunction in women with PCOS compared with an age-matched, disease-free, control group. We studied 50 patients with previously diagnosed PCOS and 50 volunteers who had normal menstrual cycles. We made a comprehensive clinical examination of the temporomandibular joint (TMJ) and muscles of mastication in both groups and recorded the Visual Analogue Scores (VAS) for pain. There were significant differences (p<0.001) in the incidence of temporomandibular disorders (n=43 (86%) in the PCOS group compared with n=12 24% in the control group), muscle tenderness(n=32 (64%) in the PCOS group compared with n=14 (28%) in the control group) and pain in the TMJ (mean (SD) VAS 2.9 (2.61) compared with 0.3 (1.56). We confirm the higher incidence and severity of disorders of the TMJ in patients with PCOS and suspect that chronic low-grade inflammation may play a part in the aetiology of the disease.

Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis.

INTRODUCTION: It has been known that vitamin D has some immunomodulatory effects and in autoimmune thyroid diseases, vitamin D deficiency was more prevalent. In this study, our aim was to investigate the relationship between thyroid autoantibodies and vitamin D. MATERIAL AND METHODS: Group 1 and 2 consisted of 254 and 27 newly diagnosed Hashimoto's thyroiditis (HT) and Graves' disease (GD) cases, respectively; age-matched 124 healthy subjects were enrolled as controls (group 3). All subjects (n = 405) were evaluated for 25OHD and thyroid autoantibody [anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-tg)] levels. RESULTS: Group 2 and group 1 patients had lower 25OHD levels than group 3 subjects 14.9 ±8.6 ng/ml, 19.4 ±10.1 ng/ml and 22.5 ±15.4 ng/ml, respectively (p < 0.001). Serum 25OHD levels inversely correlated with anti-tg (r = -0.136, p = 0.025), anti-TPO (r = -0.176, p = 0.003) and parathormone (PTH) (r = -0.240, p < 0.001). Group 2 patients had higher anti-tg and anti-TPO levels than group 1 and 3 (p < 0.001). CONCLUSIONS: In this study, we found that patients with autoimmune thyroid disease (AITD) present with lower vitamin D levels and GD patients have higher prevalence. Since we found an inverse correlation between vitamin D levels and thyroid antibody levels, we may suggest that vitamin D deficiency is one of the potential factors in pathogenesis of autoimmune thyroid disorders.

Frequency of Vitamin D deficiency in pregnant diabetics at Baskent University Hospital, Istanbul.

OBJECTIVE: To find out the frequency of vitamin D deficiency and its relation with glucose parameters and the incidence of gestational diabetes (GDM). METHODOLOGY: Gestational diabetes was diagnosed with 75 gram oral glucose tolerance test. Forty-four pregnant women diagnosed with GDM and 78 non-GDM pregnant women were enrolled as case and control group, respectively in this descriptive study. Vitamin D status was classified as deficiency at ≤20 ng/ml for serum 25(OH)D concentrations. RESULTS: The mean ages were 33.4±5.2 (18-44) years and 29.7±4.1 (21-39) years, mean BMI was 30.6±5.9 kg/m² (19.5-46.1) and 25.9±4.4 kg/m2 (16.5-38) in case and control groups, respectively. The frequency of GDM was found 9.38%. The mean serum vitamin D levels in GDM group were significantly lower than in non-GDM subjects (p=0.07). A total of 56.8% of GDM patients were compared with 35.8% of control group which had Vitamin D deficiency and the difference was significant (p= 0.02). There was no significant association between vitamin D levels and fasting glucose, insulin and HbA1c. Vitamin D levels were inversely correlated with clothing style, parathyroid hormone levels, dental problems and muscle cramps. CONCLUSIONS: The association of maternal Vitamin D status with the markers of glucose metabolism in pregnancy needs prospective studies.

Carotid Artery Intima Media Thickness and HsCRP; Predictors for Atherosclerosis in Prediabetic Patients?

OBJECTIVE: We aimed to assess carotid intima media thickness (CIMT) and serum high-sensitivity C-reactive protein (hs-CRP) levels as estimated markers of subclinical atherosclerosis and inflammation in prediabetic patients. METHODOLOGY: One hundred and ten patients were defined as prediabetic and seventy-six subjects (age and sex matched) were assigned as control group in our cross sectional study. Bilateral CIMT measurements and hs-CRP levels were evaluated. RESULTS: The prevalance of hypertension, hyperlipidemia, angiotensin receptor blockers and antihyperlipidemic medication use were statistically higher in the prediabetic group. Serum hs-CRP levels, left, right and maximum CIMT were statistically higher among prediabetics compared to control group. There was a positive, significant correlation between left, right, maximum CIMT and fasting blood glucose, HbA1c, hs-CRP levels and BMI. CONCLUSION: Recognising and focusing on the intervention of prediabetic state as early as possible and identifying the susceptible patients who may benefit from more aggressive preventive therapy is an important issue of primary prevention of diabetes and cardiovascular diseases.

Protein interaction analysis of senataxin and the ALS4 L389S mutant yields insights into senataxin post-translational modification and uncovers mutant-specific binding with a brain cytoplasmic RNA-encoded peptide.

Senataxin is a large 303 kDa protein linked to neuron survival, as recessive mutations cause Ataxia with Oculomotor Apraxia type 2 (AOA2), and dominant mutations cause amyotrophic lateral sclerosis type 4 (ALS4). Senataxin contains an amino-terminal protein-interaction domain and a carboxy-terminal DNA/RNA helicase domain. In this study, we focused upon the common ALS4 mutation, L389S, by performing yeast two-hybrid screens of a human brain expression library with control senataxin or L389S senataxin as bait. Interacting clones identified from the two screens were collated, and redundant hits and false positives subtracted to yield a set of 13 protein interactors. Among these hits, we discovered a highly specific and reproducible interaction of L389S senataxin with a peptide encoded by the antisense sequence of a brain-specific non-coding RNA, known as BCYRN1. We further found that L389S senataxin interacts with other proteins containing regions of conserved homology with the BCYRN1 reverse complement-encoded peptide, suggesting that such aberrant protein interactions may contribute to L389S ALS4 disease pathogenesis. As the yeast two-hybrid screen also demonstrated senataxin self-association, we confirmed senataxin dimerization via its amino-terminal binding domain and determined that the L389S mutation does not abrogate senataxin self-association. Finally, based upon detection of interactions between senataxin and ubiquitin-SUMO pathway modification enzymes, we examined senataxin for the presence of ubiquitin and SUMO monomers, and observed this post-translational modification. Our senataxin protein interaction study reveals a number of features of senataxin biology that shed light on senataxin normal function and likely on senataxin molecular pathology in ALS4.

Vitamin D deficiency is a problem for adult out-patients? A university hospital sample in Istanbul, Turkey.

OBJECTIVE: To investigate the frequency of vitamin D deficiency in relation to demographics, clinical diagnosis, season of measurement and laboratory parameters in adult out-patients. DESIGN: Descriptive, retrospective study concerning evaluation of the initial 25-hydroxyvitamin D (25(OH)D) levels determined at admission in relation to demographics, clinical diagnosis, season of measurement and laboratory parameters. 25(OH)D levels ,20 ng/ml were classified as deficiency, 20­30 ng/ml as insufficiency and .30 ng/ml as sufficiency. SETTING: Out-patient clinics at a tertiary care centre. SUBJECTS: A total of 2488 adult patients (mean age: 53?3 (SD 15?2) years; 85?2% were females) admitted to out-patient clinics at Baskent University Istanbul Hospital were included. RESULTS: Mean level of 25(OH)D in the overall population was 17?4 (SD 11?5) ng/ml while insufficiency and deficiency were evident in 24% and 66% of patients, respectively. Mean 25(OH)D levels in males .45 years old were higher than in their female counterparts (19?4 (SD 11?3) ng/ml v. 17?8 (SD 12?2) ng/ml; P,0?05). Mean 25(OH)D levels obtained in summer (18?6 (SD 11?1) ng/ml) and autumn (23?3 (SD 13?6) ng/ml) were significantly higher than levels in spring (16?1 (SD 10?3) ng/ml) and winter (14?6 (SD 10?2) ng/ml; P,0?01). Mean 25(OH)D levels were determined to be significantly lower in obese patients compared with non-obese patients (15?6 (SD 10?4) ng/ml v. 17?6 (SD 11?6) ng/ml; P,0?05). Levels of 25(OH)D were significantly negatively correlated with serum parathyroid hormone levels (r520?194; P,0?001) while significantly positively correlated with phosphorus (r50?059; P,0?01) and HDL cholesterol (r50?070; P,0?01) levels. CONCLUSIONS: Our findings indicate that vitamin D deficiency is very common among out-patients in Turkey, regardless of gender and age, especially among obese people and during winter and spring.

Clinical and epidemiological characteristics of thyroid hemiagenesis: ultrasound screening in patients with thyroid disease and normal population.

Thyroid hemiagenesis is a rare form of thyroid dysgenesis, in which one thyroid lobe fails to develop. The true prevalence of this rare abnormality is about 0.05-0.2% in normal population. We aimed to determine prevalence of thyroid hemiagenesis in patients with various thyroid disorders and a normal population in a mild to moderate iodine-deficient area. The clinical and thyroid ultrasonography records of 4,833 patients who presented with various thyroid disorders were reviewed. In addition, ultrasonographic data of two large surveys carried out for the community screening of iodine status of children (n = 4,772) and thyroid disorders of adult subjects (n = 2,935) were analyzed. In patients with thyroid disorders, we found 12 cases with thyroid hemiagenesis (0.25%). Thyroid hemiagenesis was due to the agenesis of the left lobe in all cases. The underlying thyroid diseases were Hashimoto's thyroiditis (n = 4), euthyroid multinodular goiter (n = 4), and toxic adenoma (n = 1). Three subjects have no underlying thyroid disease. In ultrasonography screening of normal population, altogether, the absence of the left lobe was detected in only two cases, indicating a true prevalence of thyroid hemiagenesis of 0.025%. None of the reviewed patients had thyroid dysfunction. Our community-based data is in accordance with previous studies in terms of prevalence and male-to-female ratio.