Implementing point-of-care hemoglobin A1C testing in an obstetrics outpatient clinic.

BACKGROUND: A1C ≥6.0% is associated with increased risk of adverse outcomes in pregnant diabetic patients. A1C testing is recommended by the American Diabetes Association as a secondary measure of glycemic control in pregnant patients. OBJECTIVE: To determine the utility of A1C point-of-care testing (POCT) during pregnancy to facilitate rapid counseling and diabetes care, particularly in relatively low-income transient patient populations. METHODS: We performed a single-center, retrospective analysis of patients presenting to an outpatient obstetrics office with routine, in-laboratory A1C testing, before and after the implementation of POCT for A1C (n = 70 and n = 75, respectively). Demographics, results, physician referral to a nutritionist, counseling, and outcomes were retrieved from patient electronic medical records. RESULTS: In total, 9% and 23% of the in-laboratory and POCT groups, respectively, were referred for nutrition services (P = .02). Of these, 22% of the in-laboratory group and 42% of the POCT group received immediate counseling (P < .01). An inverse correlation was observed between A1C level at study entry and gestational weeks at delivery, with a Pearson r value of -0.39 (-0.58 to -0.16) for the in-laboratory group and -0.38 (-0.57 to -0.14) for the POCT group. No statistically significant difference in pregnancy outcomes was observed. CONCLUSION: Implementation of A1C POCT was associated with immediate counseling and management of the health of pregnant patients, but was not associated with improved outcomes, in a low-resource patient population.

Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry.

The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility. Using intravital microscopy, we observed that Hla disrupts neutrophil localization and clustering early in infection. Hla forms a narrow, ion-selective pore, suggesting that Hla may dysregulate calcium or other ions to impair neutrophil function. We found that sub-lytic Hla did not permit calcium influx but caused rapid membrane depolarization. Depolarization decreases the electrogenic driving force for calcium, and concordantly, Hla suppressed calcium signaling in vitro and in vivo and calcium-dependent leukotriene B4 (LTB4) production, a key mediator of neutrophil clustering. Thus, Hla disrupts the early patterning of the neutrophil response to infection, in part through direct impairment of neutrophil calcium signaling. This early mis-localization of neutrophils may contribute to establishment of infection.

New insight into glycation levels and pelvic organ prolapse - A combination of clinical and biochemical studies.

OBJECTIVES: Pelvic Organ Prolapse (POP) is a multifactorial disease with ageing as a most notable risk factor. Advanced Glycation End products (AGEs), biochemical markers of ageing are increased in prolapsed tissues. It is however unclear if AGEs are a cause or outcome of prolapse. By combining analysis of clinically relevant parameters in women with prolapse and POP tissues biochemically, this study aims to bridge the gap between existing clinical and biochemical research on the cause of POP. METHODS: Following national and local ethical approval, a case study of 49 POP and 16 control tissues was carried out. The AGEs' marker, pentosidine, was quantified via High Performance Liquid Chromatography. Oestrogen (ER-α) and glyoxalase I (GLO-I) expression of the tissues were studied. Age, obstetric factors and co-morbidities (hypertension, smoking, diabetes mellitus) were recorded and compared with biochemical findings. RESULTS: Lower expressions of ER-α and GLO-I were observed in POP tissues in the comparison to the control, which also had significantly higher pentosidine content. Prolapsed tissue population had more notable age-dependent increase in pentosidine with significant differences between the 6th and 7th decade. Hypertension and smoking, which were more prevalent amongst women with POP, were associated with higher amounts of pentosidine in the vaginal tissues. CONCLUSION: In the light of recent research regarding the relationship between POP and glycation, the present study shows that age-related oestrogen decline is a key player in glycation accumulation in prolapsed vaginal tissues and that glycation is a cause rather than an effect of prolapse. Hypertension is a significant POP association which is linked to high glycation level.

Skin advanced glycation content reflects vaginal tissue glycation level in relation to pregnancy.

A few studies have revealed that the advanced glycation content of the vaginal wall in pelvic organ prolapse tissues is elevated. This elevation makes advanced glycation a significant association with the disease. Early detection of vaginal wall glycation could therefore be relevant in the prevention and management of pelvic organ prolapse. A vaginal wall biopsy to detect this would be ideal, but is invasive. Therefore the use of a more accessible organ to access, such as skin, would be beneficial. Our previous independent study suggests that conditions such as pregnancy, can induce a change in the vaginal tissues' glycation content. The aim of this study was to assess whether the skin glycation undergoes similar changes as observed in vaginal tissue glycation in the same subjects in order to prove the hypothesis that skin advanced glycation content can predict vaginal tissue glycation. A rat model was used. The vaginal tissues from non-pregnant and E15-E18 pregnant rats and skin tissues from the same rats were taken for the measurement of advanced glycation content. The glycation marker, pentosidine, was quantified by a high performance liquid chromatography. Our results demonstrated that glycation content in vaginal wall tissues from pregnant rats was lower than the tissues from non-pregnant ones, and a strong positive association between skin and vaginal wall pentosidine level was observed. We conclude that skin pentosidine is reflective of vaginal wall pentosidine. Skin glycation may therefore be a potential tool in the prediction and management of pelvic organ prolapse.

Advanced glycation products' levels and mechanical properties of vaginal tissue in pregnancy.

OBJECTIVES: Non-enzymatic glycation is closely associated with altered mechanical properties of connective tissue. Pregnancy, marked with high levels of female hormones, confers unique alteration to the mechanical properties of pelvic connective tissues in order to meet their physiological demands. However, there are few studies on glycation content and its influence on the mechanical properties of pelvic connective tissues during pregnancy. We hypothesise that the glycation content in pelvic tissues will change with a corresponding alteration in their mechanical properties, and that these changes are influenced by hormone levels. This study aims to investigate the correlation of vaginal tissue glycation content and mechanical property changes during pregnancy in association with the expression of a key pregnancy hormone (oestrogen) receptor, and an antioxidant enzyme, glyoxalase I. STUDY DESIGN: A rat vaginal tissue model (tissues from non-pregnant and E15-E18 (last trimester) pregnant rats) was used in this study. Mechanical characteristics of vaginal tissues were analysed by a ball-indentation technique while modulus and morphology of the collagen fibrils within the tissues were measured with atomic force microscopy. A glycation marker, pentosidine, was quantified by a high performance liquid chromatography. The expression of oestrogen receptor and glyoxalase I in the tissue was qualified by immunochemical staining. The glycosaminoglycan (GAG) concentration difference in the tissues were quantified by a biochemical assay. RESULTS: Pregnant rat vaginal tissue was characterised by significantly lower amounts of pentosidine, higher oestrogen receptor and glyoxalase I expression with larger creep, lower elastic modulus, larger fibril diameter and higher GAG content than their non-pregnant counterpart. There was a negative correlation between pentosidine and vaginal tissue creep. CONCLUSION: There was a reduction in vaginal tissue pentosidine in pregnancy with an associated increase in oestrogen receptor and glyoxalase I immunoexpression. Reduced glycation was associated with increased creeping of vaginal tissue. Oestrogen may therefore play a role in the increase of the vaginal wall's capacity to stretch through glyoxalase I up-regulation and subsequent glycation reduction. The new insight of the correlation of women's oestrogen level, glycation reaction and pelvic tissue mechanical property from this study may enhance our understanding of some pelvic organ diseases.