Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

Towards Diastereomeric Pure Salts with Antisolvent Methods

Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO₂, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts.     

Non-deterministic exponential time has two-prover interactive protocols

We determine the exact power of two-prover interactive proof systems introduced by Ben-Or, Goldwasser, Kilian, and Wigderson (1988). In this system, two all-powerful noncommunicating provers convince a randomizing polynomial time verifier in polynomial time that the inputx belongs to the languageL. We show that the class of languages having tow-prover interactive proof systems is nondeterministic exponential time.We also show that to prove membership in languages inEXP, the honest provers need the power ofEXP only.The first part of the proof of the main result extends recent techniques of polynomial extrapolation used in the single prover case by Lund, Fortnow, Karloff, Nisan, and Shamir.The second part is averification scheme for multilinearity of a function in several variables held by an oracle and can be viewed as an independent result onprogram verification. Its proof rests on combinatorial techniques employing a simple isoperimetric inequality for certain graphs:     

HLA-DR mismatching correlates with early cardiac allograft rejection, incidence, and graft survival when high-confidence-level serological DR typing is used

To determine if cardiac allograft outcome is improved among patients with fewer HLA-DR mismatches with their donors, we studied 132 recipients of a primary cardiac allograft who were transplanted between December 1985 and December 1991. These recipients and their donors all had high-confidence-level serological HLA-DR typing, previously shown to correlate highly with DNA DR typing. Patients were divided in two groups based on the HLA-DR mismatch with their donors. Group I consisted of 78 patients with 1 or zero DR mismatch and group II of 54 patients with 2 DR mismatches. Allograft outcome measurements included incidence of moderate rejection, incidence of allograft vasculopathy at 12 months, cardiac function measured as left ventricular ejection fraction (LVEF) and cardiac index (CI), and actuarial graft survival up to 7 years. Groups I and group II were not different with regard to recipient age, donor age, ischemia time, pulmonary vascular resistance, sex, or PRA greater than 0%. Group II had a higher incidence of moderate rejection on the first-week biopsy (47% vs. 25%, P = 0.019), and during the first month (84% vs. 58%, P = 0.006), but no difference was found in frequency of rejection from months 2 to 12. LVEF was not different in the groups at any point. CI was better in group I at 12 months (2.76 vs. 2.5, P = 0.03). No statistically significant difference was found in incidence of allograft vasculopathy (17% vs. 26%, P = 0.204). Actual graft survival at 1 year was better for group I (91% vs. 74%, P = 0.008), and actuarial graft survival at 6 years also favored group I (76% vs. 56%, P = 0.04). Using high-confidence-level serological HLA-DR typing assignments we demonstrated that HLA-DR mismatching correlates highly with cardiac allograft outcome. Implications are that heart transplant survival could be improved if prospective matching were feasible and prioritized or if immunosuppression were tailored to the HLA-DR match.     

Palatopharyngeal surgery. A study of its effectiveness in the treatment of obstructive apnea syndrome during sleep

Palatopharyngeal surgery is a therapeutic option for obstructive Sleep Apnea Syndrome (OSAS). This operation is based on the assumption that the soft palate is the principal apneogenic area of the upper airways. The effectiveness of palatopharyngeal surgery and of correcting nasal obstruction (co-adjuvant factor of SAOS), when present, was evaluated. Thirty patients were selected by cephalometry for surgery (3 women, 27 men; age 45.3 +/- 7.5 years). The success rate was 60%, which justifies the inclusion of surgery as a useful option for treating SAOS.     

Recent advances in raisingT c and establishing the gap-symmetry of high-T c cuprate superconductors

The most recent attempts in raising T_c of cuprate superconductors were successful by synthesizing new Hg-based cuprate materials. We discuss some properties of materials from this series with varying numbers of Cu-O planes per unit cell, including the considerable rise of the critical temperature under the influence of external pressure.In the second part of this contribution, various attempts to directly determine the symmetry of the superconducting order parameter of high-T_c cuprates are mentioned and set into perspective. The experimental approaches are all based on probing the phase of the order parameter in suitably connected closed superconducting loops. The evidence for unconventional order-parameter symmetry in these materials is growing.