A modest proposal to investigate chronic uterine pain

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135600/1/bjo14393_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135600/2/bjo14393.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135600/3/bjo14393-sup-0002-s02.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135600/4/bjo14393-sup-0001-s01.pd

Fyn Kinase regulates GluN2B subunit-dominant NMDA receptors in human induced pluripotent stem cell-derived neurons

NMDA receptor (NMDAR)-mediated fast excitatory neurotransmission is implicated in a broad range of physiological and pathological processes in the mammalian central nervous system. The function and regulation of NMDARs have been extensively studied in neurons from rodents and other non-human species, and in recombinant expression systems. Here, we investigated human NMDARs in situ by using neurons produced by directed differentiation of human induced pluripotent stem cells (iPSCs). The resultant cells showed electrophysiological characteristics demonstrating that they are bona fide neurons. In particular, human iPSC-derived neurons expressed functional ligand-gated ion channels, including NMDARs, AMPA receptors, GABAA receptors, as well as glycine receptors. Pharmacological and electrophysiological properties of NMDAR-mediated currents indicated that these were dominated by receptors containing GluN2B subunits. The NMDAR currents were suppressed by genistein, a broad-spectrum tyrosine kinase inhibitor. The NMDAR currents were also inhibited by a Fyn-interfering peptide, Fyn(39-57), but not a Src-interfering peptide, Src(40-58). Together, these findings are the first evidence that tyrosine phosphorylation regulates the function of NMDARs in human iPSC-derived neurons. Our findings provide a basis for utilizing human iPSC-derived neurons in screening for drugs targeting NMDARs in neurological disorders

Priming of adult incision response by early life injury: neonatal microglial inhibition has persistent but sexually dimorphic effects in adult rats

Neonatal hindpaw incision primes developing spinal nociceptive circuitry, resulting in enhanced hyperalgesia following re-injury in adulthood. Spinal microglia contribute to this persistent effect and microglial inhibition at the time of adult re-incision blocks the enhanced hyperalgesia. Here, we pharmacologically inhibited microglial function with systemic minocycline or intrathecal SB203580 at the time of neonatal incision and evaluated sex-dependent differences following adult re-incision. Incision in adult male and female rats induced equivalent hyperalgesia and spinal dorsal horn expression of genes associated with microglial proliferation (Emr1) and transformation to a reactive phenotype (Irf8). In control adults with prior neonatal incision, the enhanced degree and duration of incision-induced hyperalgesia and spinal microglial responses to re-incision were equivalent in males and females. However, microglial inhibition at the time of the neonatal incision revealed sex-dependent effects: the persistent mechanical and thermal hyperalgesia following re-incision in adulthood was prevented in males but unaffected in females. Similarly, re-incision induced Emr1 and Irf8 gene expression was downregulated in males, but not in females following neonatal incision with minocycline. To evaluate the distribution of re-incision hyperalgesia, prior neonatal incision was performed at different body sites. Hyperalgesia was maximal when the same paw was re-incised, and was increased following prior incision at ipsilateral, but not contralateral sites; supporting a segmentally restricted spinal mechanism. These data highlight the contribution of spinal microglial mechanisms to persistent effects of early-life injury in males, and sex-dependent differences in the ability of microglial inhibition to prevent the transition to a persistent pain state spans developmental stages.Significant Statement: Following the same surgery, some patients develop persistent pain. Contributory mechanisms are not fully understood, but early-life experience and sex/gender may influence the transition to chronic pain. Surgery and painful procedural interventions in vulnerable preterm neonates are associated with long-term alterations in somatosensory function and pain that differ in males and females. Surgical injury in neonatal rodents primes the developing nociceptive system and enhances re-injury response in adulthood. Neuroimmune interactions are critical mediators of persistent pain, but sex-dependent differences in spinal neuroglial signaling influence the efficacy of microglial inhibitors following adult injury. Neonatal microglial inhibition has beneficial long-term effects on re-injury response in adult males only, emphasizing the importance of evaluating sex-dependent differences at all ages in pre-clinical studies

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Health-related quality of life as measured with EQ-5D among populations with and without specific chronic conditions: A population-based survey in Shaanxi province, China

© 2013 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. Methods: A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. Results: The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. Conclusion: The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs. © 2013 Tan et al.National Nature Science Foundation (No. 8107239

Particle swarm optimization with sequential niche technique for dynamic finite element model updating

Peer reviewedPostprin

Chemical Biology is.....

Chemical Biology is a relatively new field, and as such is not yet simply or succinctly defined. It includes such a wide range of fundamental problems that this commentary could only include just a few snapshots of potential areas of interest. Overarching themes and selected recent successes and ideas in chemical biology are described to illustrate broadly the scope of the field, but should not be taken as exhaustive. The Chemical Biology Section of Chemistry Central Journal is pleased to receive manuscripts describing research into all and any aspects of the subject

Somatization and psychological distress among women with vulvar vestibulitis syndrome

ObjectiveTo investigate the distribution of psychological characteristics and pain reporting among women with vulvar vestibulitis syndrome (VVS).MethodsIn this exploratory study, 109 women with VVS completed a battery of questionnaires to assess pain with intercourse and psychological characteristics (e.g. somatization, anxiety, distress). The distribution of these characteristics was compared, first with a conventional binary classification schema (primary and secondary) and subsequently with a 3â category schema (primary, latent primary, secondary).ResultsSeverity of pain with intercourse did not differ among the subgroups using either classification schema. Women with primary VVS consistently showed higher levels of somatization, anxiety, and distress compared with those with secondary VVS. Using a 3â tiered classification system, we found no difference between latent primary diagnosis and the other 2 groups (primary and secondary).ConclusionThis study highlights the critical need for research on subtype definition and the role of psychological factors in VVS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135448/1/ijgo38.pd