Psychology

by Danielle D. DeSouza, Massieh Moayedi, David Q. Chen, Karen D. Davis, Mojgan Hodaie Objective Idiopathic trigeminal neuralgia (TN) is characterized by paroxysms of severe facial pain but without the major sensory loss that commonly accompanies neuropathic pain. Since neurovascular compression of the trigeminal nerve root entry zone does not fully explain the pathogenesis of TN, we determined whether there were brain gray matter abnormalities in a cohort of idiopathic TN patients. We used structural MRI to test the hypothesis that TN is associated with altered gray matter (GM) in brain areas involved in the sensory and affective aspects of pain, pain modulation, and motor function. We further determined the contribution of long-term TN on GM plasticity. Methods Cortical thickness and subcortical GM volume were measured from high-resolution 3T T1-weighted MRI scans in 24 patients with right-sided TN and 24 healthy control participants. Results TN patients had increased GM volume in the sensory thalamus, amygdala, periaqueductal gray, and basal ganglia (putamen, caudate, nucleus accumbens) compared to healthy controls. The patients also had greater cortical thickness in the contralateral primary somatosensory cortex and frontal pole compared to controls. In contrast, patients had thinner cortex in the pregenual anterior cingulate cortex, the insula and the orbitofrontal cortex. No relationship was observed between GM abnormalities and TN pain duration. Conclusions TN is associated with GM abnormalities in areas involved in pain perception, pain modulation and motor function. These findings may reflect increased nociceptive input to the brain, an impaired descending modulation system that does not adequately inhibit pain, and increased motor output to control facial movements to limit pain attacks.

by Katharina Bottermann, Michael Reinartz, Marian Barsoum, Sebastian Kötter, Axel Gödecke AKT2 is one of the three isoforms of the protein kinase AKT being involved in the modulation of cellular metabolism. Since protein-protein interactions are one possibility to convey specificity in signal transduction, we performed AKT2-protein interaction analysis to elucidate their relevance for AKT2-dependent cellular functions. We identified heat shock protein 90 kDa (HSP90), Cdc37, heat shock protein 70 kDa (HSP70), 78 kDa glucose regulated protein (GRP78), tubulin, GAPDH, ?-enolase and elongation factor 2 (EF2) as AKT2-interacting proteins by a combination of tandem affinity purification and mass spectrometry in HEK293T cells. Quantitative MS-analysis using stable isotope labeling by amino acids in cell culture (SILAC) revealed that only HSP90 and Cdc37 interact stably with AKT2, whereas the other proteins interact with low affinity with AKT2. The interactions of AKT2 with ?-enolase and EF2 were further analyzed in order to uncover the functional relevance of these newly discovered binding partners. Despite the interaction of AKT2 and ?-enolase, which was additionally validated by proximity ligation assay (PLA), no significant impact of AKT on ?-enolase activity was detected in activity measurements. AKT stimulation via insulin and/or inhibition with the ATP-competitive inhibitor CCT128930 did not alter enzymatic activity of ?-enolase. Interestingly, the direct interaction of AKT2 and EF2 was found to be dynamically regulated in embryonic rat cardiomyocytes. Treatment with the PI3-kinase inhibitor LY294002 before stimulation with several hormones stabilized the complex, whereas stimulation alone led to complex dissociation which was analyzed in situ with PLA. Taken together, these findings point to new aspects of AKT2-mediated signal transduction in protein synthesis and glucose metabolism.

by Kristina Schee, Susanne Lorenz, Merete Molton Worren, Clara-Cecilie Günther, Marit Holden, Eivind Hovig, Øystein Fodstad, Leonardo A. Meza-Zepeda, Kjersti Flatmark Colorectal cancer (CRC) is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. MicroRNAs (miRNAs) are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p) revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGF? and PI3K, thus suggesting that these miRNAs are relevant in CRC.

by L. Charles Bailey, David E. Milov, Kelly Kelleher, Michael G. Kahn, Mark Del Beccaro, Feliciano Yu, Thomas Richards, Christopher B. Forrest Objective To evaluate the validity of multi-institutional electronic health record (EHR) data sharing for surveillance and study of childhood obesity. Methods We conducted a non-concurrent cohort study of 528,340 children with outpatient visits to six pediatric academic medical centers during 2007–08, with sufficient data in the EHR for body mass index (BMI) assessment. EHR data were compared with data from the 2007–08 National Health and Nutrition Examination Survey (NHANES). Results Among children 2–17 years, BMI was evaluable for 1,398,655 visits (56%). The EHR dataset contained over 6,000 BMI measurements per month of age up to 16 years, yielding precise estimates of BMI. In the EHR dataset, 18% of children were obese versus 18% in NHANES, while 35% were obese or overweight versus 34% in NHANES. BMI for an individual was highly reliable over time (intraclass correlation coefficient 0.90 for obese children and 0.97 for all children). Only 14% of visits with measured obesity (BMI ?95%) had a diagnosis of obesity recorded, and only 20% of children with measured obesity had the diagnosis documented during the study period. Obese children had higher primary care (4.8 versus 4.0 visits, p Conclusions Multi-institutional EHR data sharing is a promising, feasible, and valid approach for population health surveillance. It provides a valuable complement to more resource-intensive national surveys, particularly for iterative surveillance and quality improvement. Low rates of obesity diagnosis present a significant obstacle to surveillance and quality improvement for care of children with obesity.

by Clare L. Armstrong, Drew Marquardt, Hannah Dies, Norbert Ku?erka, Zahra Yamani, Thad A. Harroun, John Katsaras, An-Chang Shi, Maikel C. Rheinstädter Rafts, or functional domains, are transient nano- or mesoscopic structures in the exoplasmic leaflet of the plasma membrane, and are thought to be essential for many cellular processes. Using neutron diffraction and computer modelling, we present evidence for the existence of highly ordered lipid domains in the cholesterol-rich (32.5 mol%) liquid-ordered () phase of dipalmitoylphosphatidylcholine membranes. The liquid ordered phase in one-component lipid membranes has previously been thought to be a homogeneous phase. The presence of highly ordered lipid domains embedded in a disordered lipid matrix implies non-uniform distribution of cholesterol between the two phases. The experimental results are in excellent agreement with recent computer simulations of DPPC/cholesterol complexes [Meinhardt, Vink and Schmid (2013). Proc Natl Acad Sci USA 110(12): 4476–4481], which reported the existence of nanometer size domains in a liquid disordered lipid environment.

by Hada Wuriyanghan, Bryce W. Falk The potato/tomato psyllid, Bactericera cockerelli (B. cockerelli), is an important plant pest and the vector of the phloem-limited bacterium Candidatus Liberibacter psyllaurous (solanacearum), which is associated with the zebra chip disease of potatoes. Previously, we reported induction of RNA interference effects in B. cockerelli via in vitro-prepared dsRNA/siRNAs after intrathoracic injection, and after feeding of artificial diets containing these effector RNAs. In order to deliver RNAi effectors via plant hosts and to rapidly identify effective target sequences in plant-feeding B. cockerelli, here we developed a plant virus vector-based in planta system for evaluating candidate sequences. We show that recombinant Tobacco mosaic virus (TMV) containing B. cockerelli sequences can efficiently infect and generate small interfering RNAs in tomato (Solanum lycopersicum), tomatillo (Physalis philadelphica) and tobacco (Nicotiana tabacum) plants, and more importantly delivery of interfering sequences via TMV induces RNAi effects, as measured by actin and V-ATPase mRNA reductions, in B. cockerelli feeding on these plants. RNAi effects were primarily detected in the B. cockerelli guts. In contrast to our results with TMV, recombinant Potato virus X (PVX) and Tobacco rattle virus (TRV) did not give robust infections in all plants and did not induce detectable RNAi effects in B. cockerelli. The greatest RNA interference effects were observed when B. cockerelli nymphs were allowed to feed on leaf discs collected from inoculated or lower expanded leaves from corresponding TMV-infected plants. Tomatillo plants infected with recombinant TMV containing B. cockerelli actin or V-ATPase sequences also showed phenotypic effects resulting in decreased B. cockerelli progeny production as compared to plants infected by recombinant TMV containing GFP. These results showed that RNAi effects can be achieved in plants against the phloem feeder, B. cockerelli, and the TMV-plant system will provide a faster and more convenient method for screening of suitable RNAi target sequences in planta.

by Priyanka Dixit, Laxmi Kant Dwivedi, Faujdar Ram Numerous studies have examined the empirical evidence concerning the influence of demographic and socio-economic factors influencing child immunization, but no documentation is available which shows the actual impact of antenatal care (ANC) visits on subsequent child immunization. Therefore, this paper aims to examine the net impact of ANC visits on subsequent utilization of child immunization after removing the presence of selection bias. Nationwide data from India’s latest National Family Health Survey conducted during 2005–06 is used for the present study. The analysis has been carried out in the two separate models, in the first model 1–2 ANC visit and in the second model three or more ANC visits has been compared with no visit. We have used propensity score matching method with a counterfactual model that assesses the actual ANC visits effect on treated (ANC visits) and untreated groups (no ANC visit), and have employed Mantel-Haenszel bounds to examine whether result would be free from hidden bias or not. Using matched sample analysis result shows that child immunization among the groups of women who have completed 1–2 ANC visits and those who had more than two visits was about 13 percent and 19 percent respectively, higher than the group of women who have not made any ANC visit. Findings of nearest neighbor matching with replacement method, which completely eliminated the bias, indicate that selection bias present in data set leads to overestimates the positive effects of ANC visits on child immunization. Result based on Mantel-Haenszel bounds method suggest that if around 19 percent bias would be involved in the result then also we could observe the true positive effect of 1–2 ANC visits on child immunization. This also indicates that antenatal clinics are the conventional platforms for educating pregnant women on the benefits of child immunization.

by Andreas Vilhelmsson, Tommy Svensson, Anna Meeuwisse Background Starting in the 1960s, a broad-based patients’ rights movement began to question doctors’ paternalism and to demand disclosure of medical information, informed consent, and active participation by the individual in personal health care. According to scholars, these changes contributed to downplay the biomedical approach in favor of a more patient-oriented perspective. The Swedish non-profit organization Consumer Association for Medicines and Health (KILEN) has offered the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. Methodology In this paper, qualitative content analysis was used to analyze 181 KILEN consumer reports of adverse events from antidepressant medications in order to explore patients’ views of mental ill health symptoms and the doctor-patient interaction. Principal Findings Overall, the KILEN stories contained negative experiences of the patients’ medical encounters. Some reports indicated intense emotional outrage and strong feelings of abuse by the health care system. Many reports suggested that doctors and patients had very different accounts of the nature of the problems for which the patient was seeking help. Although patients sought help for problems like tiredness and sleeplessness (often with a personal crisis of some sort as a described cause), the treating doctor in most cases was exceptionally quick in both diagnosing depression and prescribing antidepressant treatment. When patients felt they were not being listened to, trust in the doctor was compromised. This was evident in the cases when the doctor tried to convince them to take part in medical treatment, sometimes by threatening to withdraw their sick-listing. Conclusions Overall, this study suggests that the dynamics happening in the medical encounter may still be highly affected by a medical dominance, instead of a patient-oriented perspective. This may contribute to a questionable medicalization and/or pharmaceuticalization of depression.

by Susan Cassels, Lisa Manhart, Samuel M. Jenness, Martina Morris Background Migration has long been understood as an underlying factor for HIV transmission, and sexual partner concurrency has been increasingly studied as an important component of HIV transmission dynamics. However, less work has examined the role of short-term mobility in sexual partner concurrency using a network approach. Short-term mobility may be a risk for HIV for the migrant’s partner as well either through the partner’s risk behaviors while the migrant is away, such as the partner having additional partners, or via exposure to the return migrant. Methods Using data from the 2010–11 Zimbabwe Demographic and Health Survey, weighted generalized linear regression models were used to investigate the associations between short-term mobility and partnership concurrency at the individual and partnership levels. Results At the individual level, we find strong evidence of an association between short-term mobility and concurrency. Men who traveled were more likely to have concurrent partnerships compared to men who did not travel and the relationship was non-linear: each trip was associated with a 2% higher probability of concurrency, with a diminishing risk at 60 trips (p Conclusions Short-term mobility has the ability to impact population-level transmission dynamics by facilitating partnership concurrency and thus onward HIV transmission. Short-term migrants may be an important population to target for HIV testing, treatment, or social and behavioral interventions to prevent the spread of HIV.

by Monika M. Skubisz, Jeremy K. Brown, Stephen Tong, Tu’uhevaha Kaitu’u-Lino, Andrew W. Horne Background Ectopic pregnancy (EP) occurs in 1–2% of pregnancies, but is over-represented as a leading cause of maternal death in early pregnancy. It remains a challenge to diagnose early and accurately. Women often present in early pregnancy with a ‘pregnancy of unknown location’ (PUL) and the diagnosis and exclusion of EP is difficult due to a lack of reliable biomarkers. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1) levels to differentiate between EP and other pregnancy outcomes in women with a PUL. Methods Sera were collected from 120 women with a PUL at first clinical presentation and assayed for MIC-1 by ELISA. Results were classified according to ultimate pregnancy outcome and the discriminatory ability of MIC-1 to diagnose EP was assessed. Results Serum MIC-1 levels were lower in women with histologically confirmed (definite) EP (dEP) (median 552 ng/mL; interquartile range (IQR) 414–693 ng/mL) compared to women with definite viable intra-uterine pregnancies (dVIUPs) (722 ng/mL; IQR 412–1122 ng/mL), and higher when compared to women with definite non-viable intra-uterine pregnancies (dNVIUPs) (465 ng/mL; IQR 341–675 ng/mL). MIC-1 levels were significantly higher in women with dEP compared to women whose PULs resolved without medical intervention (srPUL) (401 ng/mL; IQR 315–475 ng/mL) (p1000 ng/mL. Conclusion Serum MIC-1 levels in PUL were not able to categorically diagnose EP, however, MIC-1 could distinguish women with an EP that required medical intervention and those women whose PULs spontaneously resolved. A single serum MIC-1 measurement also excluded EP at levels above 1000 ng/mL. MIC-1 may play a role in the development of a combined assay of biomarkers for the diagnosis of EP.