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.     

46,XX/69,XXX diploid-triploid mixoploidy with hypothyroidism and precocious puberty

We report a 20 month old female patient with diploid-triploid mixoploidy (46,XX/69,XXX) syndrome with hypothyroidism and precocious puberty. The triploid cell line was only expressed in the fibroblast culture and comprised the majority (95%) of the cells. Chromosome analysis of the fetal blood sample and peripheral blood sample were normal. The patient shows typical features of full triploidy (growth and severe mental retardation, cranial and facial dysmorphism, complete syndactyly of fingers 3/4, partial syndactyly of toes 2/3) and facial but no body asymmetry. At the age of 5 months central hypothyroidism and precocious puberty were diagnosed. Thin pigmented streaks were visible on the wrists and legs of the patient at the age of 16 months. This is the first patient reported so far with 46,XX/69,XXX mixoploidy suffering from hypothyroidism and precocious puberty.     

The murine immune response to the male-specific antigen mouse testicular cytochrome c

Male and female A/J mice were examined for their ability to elicit T lymphocyte and antibody (Ab) responses to the male-specific Ag, mouse testicular cytochrome c (Mt cyt). T lymphocytes from both male and female mice primed in vivo responded to the Ag in in vitro proliferation assays, and the dose-response curves were statistically indistinguishable. In addition, similar levels of Ab to Mt cyt were observed in immunized male and female mice. The B cells producing the Ab had switched isotypes to IgG1 and IgG2a, indicating that the self-reactive T helper (Th) cells in male mice were functional. Thus, male mice do not appear to be immunologically tolerant to Mt cyt, at least at the Th and B lymphocyte levels. No evidence for disease was found in male mice primed with Mt cyt. Major histocompatibility complex (MHC) class II-positive antigen-presenting cells are present in the testes and these were shown in vitro to process and present Mt cyt to a T cell hybridoma specific for the synthetic peptide Mt cyt 93-104. However, the hybridoma was not activated in the absence of exogenous Mt cyt 93-104 or Mt cyt, indicating that endogenous Mt cyt is not normally processed in sufficient quantity to effectively load MHC class II molecules with this particular Mt cyt-derived peptide. Notwithstanding any immunologic privilege of the testes, the lack of tolerance to Mt cyt and its failure to elicit an autoimmune disease could extend from the low levels of processed Mt cyt Ag available for T cell recognition. The T cell response elicited by Mt cyt contrasts the lack of response to mouse somatic cytochrome c which differs from Mt cyt at 13 amino acid residues and is expressed in most tissues and at higher levels.     

Polymorphonuclear neutrophil granulocyte chemotactic hyperresponsiveness in a case of canine acromegaly

Growth hormone (GH) has recently been shown to affect polymorphonuclear neutrophil granulocyte (PMN) function and to be secreted by mononuclear cells, indicating that the hormone may be active in an immunophysiologic network, acting as an endo- or paracrine priming agent. The purpose of the present study was to evaluate the chemotactic responsiveness of canine peripheral PMN in a dog with acromegaly, caused by spontaneous, progesterone-induced hypersecretion of GH and, secondary to this, a seven-fold increase in insulin-like growth factor I (IGF-I). The chemotactic responsiveness towards zymosan-activated serum (ZAS) and leukotriene B4 (LTB4) was evaluated at a time when the dog suffered from acromegaly and again 57 days after corrective surgery (ovariohysterectomy). The experiments showed that PMN from the patient exhibited enhanced chemotactic migration that appeared to be associated with the hypersomatotropic condition as judged from the reversibility of the phenomenon. The glucose intolerance and elevated serum alkaline phosphatase that were observed in the acromegalic dog were also shown to be reversible following surgery.     

Cardiorespiratory effects of conventional and high frequency ventilation in rabbits with bilateral pneumothoraces and surfactant depleted lungs

We compared high frequency ventilation (HFV) to conventional mechanical ventilation (CMV) under normoxic and normocapnic condition in surfactant depleted rabbits with bilateral pneumothoraces. We hypothesized that lower airway pressures would be required with HFV under these conditions. We applied CMV and HFV in 8 anaesthetized rabbits with a prototype ventilator at frequencies of 30, 100, 200, and 300 cycles/min. A positive end-expiratory pressure (PEEP) just below the pressure sufficient to open the air leak from the pneumothoraces was applied at all frequencies. Airway pressures, gas exchange, heart rate, and mean arterial pressure were recorded. Peak airway pressure decreased significantly from 2.50 to 2.10 kPa when the frequency of ventilation was increased from 30 to 300 cycles/min. There were no significant changes in mean airway pressure, PaO2, arterial pH, heart rate, and mean arterial pressure when HFV was compared to CMV. In conclusion, during HFV peak airway pressures measured at the mouth were decreased. Our ability to maintain adequate gas exchange in the face of ongoing pulmonary air leaks may reflect lower alveolar pressures.     

Social support and depression among older adults living alone: the importance of friends within and outside of a retirement community

Using socioemotional selectivity theory as a framework, the study described in this article examined the extent to which social support from friends both within and outside of a retirement community was associated with depression. Although levels of social support from friends within the retirement community were quantitatively high, they failed to have a significant effect on depression. In contrast, social support from friends living elsewhere consistently predicted low levels of depression. Practice implications include the importance of maintaining friendship ties with people living elsewhere and of strengthening friendship ties within the retirement community.     

Perceptual learning of spatial localization: specificity for orientation, position, and context

Discrimination of simple visual attributes can improve significantly with practice. We have trained human observers to perform peripherally presented tasks involving the localization of short line segments and examined the specificity of the learning for the visual location, orientation, and geometric arrangement of the trained stimulus. Several weeks of training resulted in dramatic threshold reductions. The learning was specific for the orientation and location of the trained stimulus, indicating the involvement of the earliest cortical stages in the visual pathway where the orientation and location of stimuli are mapped with highest resolution. Furthermore, improvement was also specific for both the configuration of the trained stimulus and the attribute of the stimulus that was under scrutiny during training. This degree of specificity suggests that the learning cannot be achieved by cortical recruitment alone, as proposed in current models, but is likely to involve a refinement of lateral interactions within the cortex and possibly a gating of lower level changes by attentional mechanisms.