Adaptation and Feasibility Study of a Digital Health Program to Prevent Diabetes among Low-Income Patients: Results from a Partnership between a Digital Health Company and an Academic Research Team.
Background. The feasibility of digital health programs to prevent and manage diabetes in low-income patients has not been adequately explored. Methods. Researchers collaborated with a digital health company to adapt a diabetes prevention program for low-income prediabetes patients at a large safety net clinic. We conducted focus groups to assess patient perspectives, revised lessons for improved readability and cultural relevance to low-income and Hispanic patients, conducted a feasibility study of the adapted program in English and Spanish speaking cohorts, and implemented real-time adaptations to the program for commercial use and for a larger trial of in multiple safety net clinics. Results. The majority of focus group participants were receptive to the program. We modified the curriculum to a 5th-grade reading level and adapted content based on patient feedback. In the feasibility study, 54% of eligible contacted patients expressed interest in enrolling (n = 23). Although some participants' computer access and literacy made registration challenging, they were highly satisfied and engaged (80% logged in at least once/week). Conclusions. Underserved prediabetic patients displayed high engagement and satisfaction with a digital diabetes prevention program despite lower digital literacy skills. The collaboration between researchers and a digital health company enabled iterative improvements in technology implementation to address challenges in low-income populations.


Cytosolic entry of Shiga-like toxin a chain from the yeast endoplasmic reticulum requires catalytically active Hrd1p.
Escherichia coli Shiga-like toxin 1 normally traffics to the endoplasmic reticulum (ER) in sensitive mammalian cells from where the catalytic A chain (SLTxA1) dislocates to the cytosol to inactivate ribosomes. Currently, no molecular details of the dislocation process are available. To investigate the mechanism of the dislocation step we expressed SLTxA1 in the ER of Saccharomyces cerevisiae. Using a combination of growth studies and biochemical tracking in yeast knock-out strains we show that SLTxA1 follows an ER-associated degradation (ERAD) pathway to enter the cytosol in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex. ER-to-cytosol dislocation of the bulk population of SLTxA1 requires Cdc48p and its ubiquitin-handling co-factor Npl4p, and this population of toxin is terminally dispatched by proteasomal degradation. A small sub-population of SLTxA1 uncouples from this classical ERAD pathway and recovers catalytic activity in the cytosol. The pathway that leads to toxicity is also Hrd1p-dependent but, unlike that for the related ricin A chain toxin, SLTxA1 dislocation does require the catalytic cysteine of Hrd1p. However it does not depend on canonical ubiquitylation since toxin variants lacking endogenous lysyl residues also utilize this pathway, and furthermore there is no requirement for a number of Cdc48p co-factors. The fraction of SLTxA1 that disengages from the ERAD pathway thus does so upstream of Cdc48p interactions and downstream of Hrd1p interactions, in a step that possibly involves de-ubiquitylation. Mechanistically therefore, the dislocation of this toxin is quite distinct from that of conventional ERAD substrates that are normally degraded, and the toxins partially characterised to date that do not require the catalytic cysteine of the major Hrd1p component of the dislocation apparatus.


Heavy transcription of yeast genes correlates with differential loss of histone H2B relative to H4 and queued RNA polymerases.
Eukaryotic chromatin is composed of nucleosomes, which contain nearly two coils of DNA wrapped around a central histone octamer. The octamer contains an H3-H4 tetramer and two H2A-H2B dimers. Gene activation is associated with chromatin disruption: a wider nucleosome-depleted region (NDR) at the promoter and reduced nucleosome occupancy over the coding region. Here, we examine the nature of disrupted chromatin after induction, using MNase-seq to map nucleosomes and subnucleosomes, and a refined high-resolution ChIP-seq method to map H4, H2B and RNA polymerase II (Pol II) genome-wide. Over coding regions, induced genes show a differential loss of H2B relative to H4, which correlates with Pol II density and the appearance of subnucleosomes. After induction, Pol II is surprisingly low at the promoter, but accumulates on the gene and downstream of the termination site, implying that dissociation is very slow. Thus, induction-dependent chromatin disruption reflects both eviction of H2A-H2B dimers and the presence of queued Pol II elongation complexes. We propose that slow Pol II dissociation after transcription is a major factor in chromatin disruption and that it may be of critical importance in gene regulation.


Expression of osterix Is Regulated by FGF and Wnt/β-Catenin Signalling during Osteoblast Differentiation.
Osteoblast differentiation from mesenchymal cells is regulated by multiple signalling pathways. Here we have analysed the roles of Fibroblast Growth Factor (FGF) and canonical Wingless-type MMTV integration site (Wnt/β-Catenin) signalling pathways on zebrafish osteogenesis. We have used transgenic and chemical interference approaches to manipulate these pathways and have found that both pathways are required for osteoblast differentiation in vivo. Our analysis of bone markers suggests that these pathways act at the same stage of differentiation to initiate expression of the osteoblast master regulatory gene osterix (osx). We use two independent approaches that suggest that osx is a direct target of these pathways. Firstly, we manipulate signalling and show that osx gene expression responds with similar kinetics to that of known transcriptional targets of the FGF and Wnt pathways. Secondly, we have performed ChIP with transcription factors for both pathways and our data suggest that a genomic region in the first intron of osx mediates transcriptional activation. Based upon these data, we propose that FGF and Wnt/β-Catenin pathways act in part by directing transcription of osx to promote osteoblast differentiation at sites of bone formation.


The effects of parvocellular lateral geniculate lesions on the acuity and contrast sensitivity of macaque monkeys.
The effects of ablating the visual pathway that passes through the parvocellular (dorsal) LGN were tested in 2 macaque monkeys by measuring acuity and both luminance and chromatic contrast sensitivity. Thresholds were tested monocularly before and after ibotenic acid was used to lesion parvocellular layers 4 and 6 of the contralateral geniculate. The injections were centered at the representation of 6 degrees in the temporal field on the horizontal meridian, and vision was tested with localized stimuli at this location. In addition, in one of the monkeys, a lesion was made in magnocellular layer 1 of the opposite geniculate, and the same thresholds were tested. Physiological and anatomical reconstructions demonstrated complete destruction of the target layers in 1 parvocellular lesions and in the magnocellular lesion, and sparing of the nontarget layers in the tested region. Parvocellular lesions caused a 3-4-fold reduction in visual acuity within the affected part of the visual field, while the magnocellular lesion did not affect acuity. Both luminance and chromatic contrast sensitivity, tested with stationary gratings of 2 c/degree, were severely reduced by parvocellular lesions, but not affected by the magnocellular lesion. However, when luminance contrast sensitivity was tested with 1 c/degree gratings, counterphase modulated at 10 Hz, it was reduced by both parvocellular and magnocellular lesions. This study demonstrates that the parvocellular pathway dominates chromatic vision, acuity, and contrast detection at low temporal and high spatial frequencies, while the magnocellular pathway may mediate contrast detection at higher temporal and lower spatial frequencies.


Flexible miniature compound lens design for high-resolution optical coherence tomography balloon imaging catheter.
We report on a new optics design for an optical coherence tomography (OCT) balloon imaging catheter. The design involves a miniature compound gradient-index (GRIN) rod lens, which consists of a fiber optic mode-field reducer and relay rod lenses to achieve predictable high lateral resolution at a desired large working distance. The compound lens design significantly simplifies the engineering process for an OCT catheter and enables 3-D full circumferential cross sectional imaging of large luminal organs such as human esophagus. An as-designed OCT catheter is developed and demonstrated for real-time in vivo swine esophagus imaging in a 3-D spiral fashion.


Responsiveness of objective, disease-specific, and generic outcome measures in patients with chronic low back pain: an assessment for improving, stable, and deteriorating patients.
Analysis of outcome data collected prospectively from 250 patients recruited to the UK Spine Stabilization Trial. To compare the responsiveness of the Shuttle Walking Test (SWT), which is an objective outcome measure, with that of a disease-specific (the Oswestry Disability Index) and 2 generic (the EQ-5D and SF-36) instruments in patients with chronic low back pain (LBP). Studies assessing the performance of subjective disease-specific and generic measures have increased in recent years, although there is a paucity of research reporting the responsiveness of objective measures in patients with LBP. The focus of investigation has been on responsiveness to improvements in LBP symptoms. For patients with deteriorating health, it remains largely unclear how outcome instruments perform. Baseline and 12-month outcome data collected on 250 patients with chronic LBP recruited to the Spine Stabilization Trial were analyzed using traditional measures of responsiveness. Analyses were performed for 3 groups of patients: those who rated their health status as improved, deteriorated, and stable at 12 months. The SWT was shown by all measures to be responsive to health improvement, although less so than other instruments. All instruments were able to detect small-to-moderate reductions in health. Instrument floor effects may be responsible for small SF-36 change scores recorded for deteriorating patients. Although shown to be responsive, including the SWT alongside disease-specific and generic instruments is unlikely to add additional information. All instruments appear responsive to patient deterioration, however, further research for the SF-36 is required.


Influence of Socioeconomic Status, Comorbidity, and Disability on Late-stage Cancer Diagnosis.
Understanding factors affecting advanced stage at diagnosis is vital to improve cancer outcomes and overall survival. We investigated the factors affecting later-stage cancer diagnosis. Patients completed self-reported questionnaires. We collected cancer stage data from medical records review. Logistic regression analyses were performed to identify factors associated with later stage cancer at diagnosis by gender. In total, 1,870 cancer patients were included in the study; 55.8% were men, 31.1% had more than one comorbid condition, and 63.5% had disabilities. About half of the patients were smokers, and drank alcohol, and 58.0% were diagnosed at an advanced stage. By cancer type, lung and liver cancers (both genders), prostate (men), colorectal, cervical, and thyroid cancer (women) were more likely to be diagnosed at a later stage. After controlling for socioeconomic factors, comorbidity (odds ratio [OR], 1.48 in men) and disability (OR, 1.64 in men and 1.52 in women) remained significantly associated with late-stage diagnosis. In this nationwide study, using combined information from patients and medical records, we found that male patients with comorbidities or disabilities, and female patients with disabilities were more likely to have advanced stage cancer at diagnosis. Targeted approaches by cancer type and health conditions are recommended.


Dynamic tuneable G protein-coupled receptor monomer-dimer populations.
G protein-coupled receptors (GPCRs) are the largest class of membrane receptors, playing a key role in the regulation of processes as varied as neurotransmission and immune response. Evidence for GPCR oligomerisation has been accumulating that challenges the idea that GPCRs function solely as monomeric receptors; however, GPCR oligomerisation remains controversial primarily due to the difficulties in comparing evidence from very different types of structural and dynamic data. Using a combination of single-molecule and ensemble FRET, double electron-electron resonance spectroscopy, and simulations, we show that dimerisation of the GPCR neurotensin receptor 1 is regulated by receptor density and is dynamically tuneable over the physiological range. We propose a "rolling dimer" interface model in which multiple dimer conformations co-exist and interconvert. These findings unite previous seemingly conflicting observations, provide a compelling mechanism for regulating receptor signalling, and act as a guide for future physiological studies.


Genetic variations observed in arterial and venous thromboembolism--relevance for therapy, risk prevention and prognosis.
We undertook genetic and biochemical assays in patients with arterial (n = 146) and venous (n = 199) thromboembolism and survivors of pulmonary embolism (n = 58) to study causation and gene-life style interactions. In the clinical material from North Western Russia, factor V Leiden was found to be a risk factor in venous thrombosis (OR = 3.6), while the methylenetetrahydrofolate reductase (MTHFR) C677T mutation was a significant variable in both venous (p = 0.03) and arterial thrombosis (p = 0.004). Homocysteine levels were determined (n = 84) and hyperhomocysteinemia correlated with the T allele of the MTHFR gene, and with smoking and coffee consumption. Vitamin supplementation reduced homocysteine levels dependent on MTHFR genotype (36% TT, 25% CT, 22% CC). In pulmonary embolism patients, frequency of the -455G/A beta-fibrinogen dimorphism was studied. Carriers of this allele were significantly underrepresented (p < 0.02) among pulmonary embolism survivors (34.5%) compared to controls (56.7%). Additionally, -455AA homozygotes were found in 11.7% controls but only 1.7% of pulmonary embolism patients (p = 0.006). In venous and arterial thrombosis cases, MTHFR and homocysteine data led to effective dietary supplementation with a reduced risk of disease progression. Results from the pulmonary embolism study may indicate that screening tests for the -455G/A beta-fibrinogen genetic variation could be of prognostic value, and may point the way for novel anticoagulation strategies.


Use of photon fields with noncoincident isocenters to improve homogeneity of dose distribution.
To compare changes in dose distribution in irregularly shaped volumes treated using fields with noncoincident isocenters compared with fields with coincident isocenters. The hypothesis was that use of fields with noncoincident isocenters would result in improved homogeneity of dose distribution. We chose to test the hypothesis in canine nasal tumors because of the increased dorsoventral thickness of the caudal compared with the rostral nasal cavity. Computed tomography images from eight dogs with nasal tumors were selected. A tissue-contouring program was used to outline contours, including the mandible as a normal tissue structure and the planning target volume (PTV), divided into a rostral and caudal volume. A traditional computerized treatment plan consisting of two parallel-opposed fields was constructed for each dog. A second treatment plan using a third caudally located field having a different isocenter was constructed for comparison. Dose-volume histograms were generated and compared for each contoured structure in both plans. In all dogs the use of noncoincident fields resulted in increased dose to the ethmoid region through the caudal field. Minimum dose in the caudal tumor PTV increased as well. At the same time, dose delivered to the mandible, prone to develop significant side effects, was lower in all dogs with the use of noncoincident fields, as it was possible to reduce the dose delivered from the ventral field. Use of photon fields with noncoincident isocenters can improve the dose distribution in irregularly shaped volumes in comparison with fields with coincident isocenters. Improved tumor dose distribution was achieved with the addition of a smaller field having a different isocenter.


Kinetics of duplex formation for individual DNA strands within a single protein nanopore.
A single oligonucleotide was covalently attached to a genetically engineered subunit of the heptameric protein pore, alpha-hemolysin, to allow DNA duplex formation inside the pore lumen. Single-channel current recording was used to study the properties of the modified pore. On addition of an oligonucleotide 8 bases in length and with a sequence complementary to the tethered DNA strand, current blockades with durations of hundreds of milliseconds occurred, representing hybridization events of individual oligonucleotides to the tethered DNA strand. Kinetic constants for DNA duplex formation at the single molecule level were derived and found to be consistent with established literature values for macroscopic duplex formation. The resultant equilibrium constant for duplex formation in the nanopore was found to be close to the experimentally derived constant for duplex formation in solution. A good agreement between the equilibrium constants for duplex formation in the nanopore and in solution was also found for two other oligonucleotide pairs. In addition, the nanopore recordings revealed details of the kinetics difficult to obtain by conventional methods, like surface plasmon resonance, which measure ensemble properties. By investigating the temperature dependence of DNA duplex formation at the single molecule level, the standard enthalpy and entropy of the interaction could be obtained.


Predictors of dying at home for patients receiving nursing services in Japan: A retrospective study comparing cancer and non-cancer deaths.
The combined effects of the patient's and the family's preferences for death at home have in determining the actual site of death has not been fully investigated. We explored this issue on patients who had been receiving end-of-life care from Visiting Nurse Stations (VNS). In Japan, it has been the government's policy to promote end-of-life care at home by expanding the use of VNS services. A retrospective national survey of a random sample of 2,000 out of the 5,224 VNS was made in January 2005. Questionnaires were mailed to VNS asking the respondents to fill in the questionnaire for each patient who had died either at home or at the hospital from July to December of 2004. Logistic regression analysis was respectively carried out to examine the factors related to dying at home for cancer and non-cancer patients. We obtained valid responses from 1,016 VNS (50.8%). The total number of patients who had died in the selected period was 4,175 (cancer: 1,664; non-cancer: 2,511). Compared to cancer patients, non-cancer patients were older and had more impairment in activities of daily living (ADL) and cognitive performance, and a longer duration of care. The factor having the greatest impact for dying at home was that of both the patient and the family expressing such preferences [cancer: OR (95% CI) = 57.00 (38.79-83.76); non-cancer: OR (95% CI) = 12.33 (9.51-15.99)]. The Odds ratio was greater compared with cases in which only the family had expressed such a preference and in which only the patient had expressed such a preference. ADL or cognitive impairment and the fact that their physician was based at a clinic, and not at a hospital, had modest effects on dying at home. Dying at home was more likely when both the patient and the family had expressed such preferences, than when the patient alone or the family alone had done so, in both cancer and non-cancer patients. Health care professionals should try to elicit the patient's and family's preferences on where they would wish to die, following which they should then take appropriate measures to achieve this outcome.


Clutch size in a larval-pupal endoparasitoid : 1. Variation across and within host species.
Clutch size decisions by Aphaereta minuta (Nees) (Hymenoptera: Braconidae), a polyphagous, gregarious, larval-pupal endoparasitoid, were studied under laboratory conditions. This parasitoid attacks larvae of Diptera inhabiting ephemeral microhabitats such as decaying plant and animal material. Females oviposit in young larval stages, but the eventual size of the host pupa determines host food availability for competing offspring. The size of the pupa can differ greatly between host species. We questioned how A. minuta females deal with this delay between the moment of oviposition and eventual host food availability, and whether they make clutch size decisions that benefit their fitness. It was shown that females indeed vary their clutch size considerably and in an adaptive way: (1) females lay larger clutches in larvae of host species that produce larger pupae, even when the larvae are the same size at the moment of oviposition, and (2) females lay larger clutches in larger larvae than in smaller larvae of the same host species. The latter seems functional as larvae parasitized at an older stage indeed developed into larger pupae compared to larvae parasitized at a younger stage. Furthermore, mortality of parasitized young host larvae was greater than that of both unparasitized larvae and parasitized older larvae. Under field conditions the risk of mortality of young host larvae is expected to be even higher due to the limited period of microhabitat (host food) availability, strong scramble type competition between the host larvae, and the longer period of being exposed to predation.


Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy.
Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood-brain barrier (BBB) to reach targets in the central nervous system (CNS). For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion. We identified a branched derivative of the well-known ApoE (141-150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript. Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes. Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues. This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases.


Effects of 5'-terminal modifications on the biological activity of defective interfering RNAs of Sindbis virus.
We have been studying defective interfering (DI) genomes of the RNA enveloped virus Sindbis virus. Deletion mapping of a DI cDNA demonstrated that only sequences at the 3' and 5' termini of the genome are required for the DI RNA to be biologically active. We constructed a series of cDNAs that transcribe DI RNAs differing only in 5'-terminal sequences. Two of the 5' termini identical to ones found in naturally occurring DI RNAs are the 5' terminus of the virion RNA (DI-549) and the first 142 nucleotides from the 5' terminus of the subgenomic 26S mRNA attached to the 5' terminus of the virion RNA (DI-15). The latter has a 42-nucleotide deletion from nucleotides 25 to 66 in the 26S RNA sequence. These DI RNA transcripts were biologically active, but one (DI-526) which did not have the 42-nucleotide deletion of DI-15 was not replicated. The DI RNA isolated after the presumed amplification of the DI-526 transcript had deleted the first 54 nucleotides of the 26S RNA sequences. The 5' terminus of Sindbis virion RNA contains a stem and loop region that is conserved among alphaviruses. An 11-nucleotide deletion in DI-549 that disrupted this stem and loop rendered this DI RNA inactive. In contrast, this same deletion in DI-15 and one that removed an additional 100 nucleotides of the virion 5' terminus did not prevent its amplification. We did not detect by computer analysis any common secondary structures among the biologically active DI RNAs that distinguished them from those RNAs that were not amplified. Our results support the conclusion that tertiary structure or the ability of the RNA to adapt its structure upon interaction with protein is important in the recognition process.


Mirror versus parallel bimanual reaching.
In spite of their importance to everyday function, tasks that require both hands to work together such as lifting and carrying large objects have not been well studied and the full potential of how new technology might facilitate recovery remains unknown. To help identify the best modes for self-teleoperated bimanual training, we used an advanced haptic/graphic environment to compare several modes of practice. In a 2-by-2 study, we compared mirror vs. parallel reaching movements, and also compared veridical display to one that transforms the right hand's cursor to the opposite side, reducing the area that the visual system has to monitor. Twenty healthy, right-handed subjects (5 in each group) practiced 200 movements. We hypothesized that parallel reaching movements would be the best performing, and attending to one visual area would reduce the task difficulty. The two-way comparison revealed that mirror movement times took an average 1.24 s longer to complete than parallel. Surprisingly, subjects' movement times moving to one target (attending to one visual area) also took an average of 1.66 s longer than subjects moving to two targets. For both hands, there was also a significant interaction effect, revealing the lowest errors for parallel movements moving to two targets (p < 0.001). This was the only group that began and maintained low errors throughout training. Combined with other evidence, these results suggest that the most intuitive reaching performance can be observed with parallel movements with a veridical display (moving to two separate targets). These results point to the expected levels of challenge for these bimanual training modes, which could be used to advise therapy choices in self-neurorehabilitation.


Adolescent understanding of DOHaD concepts: a school-based intervention to support knowledge translation and behaviour change.
A life-course approach to reduction of risk of non-communicable diseases (NCD) suggests that early-life interventions may be more effective than lifestyle modifications in middle age. Knowledge translation to develop understanding of the Developmental Origins of Health and Disease (DOHaD) within the community offers the potential to encourage informed diet and lifestyle choices supporting reduction of NCD risk in current and future generations. Many women do not make sustained dietary change before or during pregnancy, therefore appropriate nutritional behaviours need to be established prior to adulthood. This makes adolescence an appropriate stage for interventions to establish suitable dietary and lifestyle behaviours. Therefore, we engaged adolescents in a school-based educational intervention, and assessed the value of this in development of understanding of DOHaD concepts to support behaviour change that could lead to NCD risk reduction in the next generation. Modules of course work were written for 11-14 year olds and trialled in nine schools. Matched pre- and post-intervention questionnaire responses from 238 students and 99 parents, and post-intervention interviews evaluated the intervention. Understanding of a link between maternal diet during pregnancy and the health of the foetus in adulthood increased from 46% to 76% following intervention. Post-intervention evidence suggests the programme facilitated discussion of diet, lifestyle and DOHaD concepts in most families. The intervention was effective in improving understanding of DOHaD concepts and in some cases led to appropriate behaviour change. However, the sustainability of these changes remains to be determined through on-going evaluation of attitudes and behaviour within this cohort.


Influence of post mortem changes on experimental safety belt injuries.
Belt protected car occupants involved on head-on collisions do not seem to suffer as severe injuries as unembalmed cadavers subjected to comparable simulated head-on collisions. Therefore it has been questioned if cadavers constitute adequate test specimens for study of thoracic tolerances. This investigation compares injuries in safety belt wearing living and dead pigs which have been subjected to simulated head-on collisions on an acceleration tract. Tests were performed on all 20 pigs (10 living and 10 dead). The arterial side of the circulatory system of the dead pigs was infused. The force in the safety belts, the intraaortic pressure, the impact velocity and the deceleration of the sled were recorded. The tests were high speed filmed. Post mortem examination of the pigs revealed differences in injury severity. Dead pigs more easily suffered rib fractures. Deformation of the rib cage due to stripping of the periosteum and laceration of surrounding tissue occurred mainly in the dead pigs. Laceration of intrathoracic blood vessels was seen in dead pigs while isolated heart lesions were seen only in living animals. The main cause of these differences in tolerance level seems to be post mortem changes of the mechanical properties of the different tissues. The results are valid for pigs but indicate that great care has to be exercised when results obtained from cadaver experiments are evaluated concerning thoracic tolerance.


Effect of camera resolution and bandwidth on facial affect recognition.
This preliminary study explored the effect of camera resolution and bandwidth on facial affect recognition, an important process and clinical variable in mental health service delivery. Sixty medical students and mental health-care professionals were recruited and randomized to four different combinations of commonly used teleconferencing camera resolutions and bandwidths: (1) one chip charged coupling device (CCD) camera, commonly used for VHSgrade taping and in teleconferencing systems costing less than $4,000 with a resolution of 280 lines, and 128 kilobytes per second bandwidth (kbps); (2) VHS and 768 kbps; (3) three-chip CCD camera, commonly used for Betacam (Beta) grade taping and in teleconferencing systems costing more than $4,000 with a resolution of 480 lines, and 128 kbps; and (4) Betacam and 768 kbps. The subjects were asked to identify four facial affects dynamically presented on videotape by an actor and actress presented via a video monitor at 30 frames per second. Two-way analysis of variance (ANOVA) revealed a significant interaction effect for camera resolution and bandwidth (p = 0.02) and a significant main effect for camera resolution (p = 0.006), but no main effect for bandwidth was detected. Post hoc testing of interaction means, using the Tukey Honestly Significant Difference (HSD) test and the critical difference (CD) at the 0.05 alpha level = 1.71, revealed subjects in the VHS/768 kbps (M = 7.133) and VHS/128 kbps (M = 6.533) were significantly better at recognizing the displayed facial affects than those in the Betacam/768 kbps (M = 4.733) or Betacam/128 kbps (M = 6.333) conditions. Camera resolution and bandwidth combinations differ in their capacity to influence facial affect recognition. For service providers, this study's results support the use of VHS cameras with either 768 kbps or 128 kbps bandwidths for facial affect recognition compared to Betacam cameras. The authors argue that the results of this study are a consequence of the VHS camera resolution/bandwidth combinations' ability to improve signal detection (i.e., facial affect recognition) by subjects in comparison to Betacam camera resolution/bandwidth combinations.


Bistable self-starting pulses with terahertz repetition rate in a semiconductor microring laser.
We report on the prediction of stable self-starting pulses in a GaAs bulk semiconductor microring laser with terahertz repetition rate. The pulses are obtained without active or passive mode locking. Especially interesting for practical applications is the bistability between pulses and continuous waves.


LRP-1 links post-translational modifications to efficient presentation of celiac disease-specific T cell antigens.
Celiac disease (CeD) is an autoimmune disorder in which gluten-derived antigens trigger inflammation. Antigenic peptides must undergo site-specific deamidation to be presentable to CD4+ T cells in an HLA-DQ2 or -DQ8 restricted manner. While the biochemical basis for this post-translational modification is understood, its localization in the patient's intestine remains unknown. Here, we describe a mechanism by which gluten peptides undergo deamidation and concentration in the lysosomes of antigen-presenting cells, explaining how the concentration of gluten peptides necessary to elicit an inflammatory response in CeD patients is achieved. A ternary complex forms between a gluten peptide, transglutaminase-2 (TG2), and ubiquitous plasma protein α2-macroglobulin, and is endocytosed by LRP-1. The covalent TG2-peptide adduct undergoes endolysosomal decoupling, yielding the expected deamidated epitope. Our findings invoke a pathogenic role for dendritic cells and/or macrophages in CeD and implicate TG2 in the lysosomal clearance of unwanted self and foreign extracellular proteins.


Mathematical model of growth factor driven haptotaxis and proliferation in a tissue engineering scaffold.
Motivated by experimental work (Miller et al. in Biomaterials 27(10):2213-2221, 2006, 32(11):2775-2785, 2011) we investigate the effect of growth factor driven haptotaxis and proliferation in a perfusion tissue engineering bioreactor, in which nutrient-rich culture medium is perfused through a 2D porous scaffold impregnated with growth factor and seeded with cells. We model these processes on the timescale of cell proliferation, which typically is of the order of days. While a quantitative representation of these phenomena requires more experimental data than is yet available, qualitative agreement with preliminary experimental studies (Miller et al. in Biomaterials 27(10):2213-2221, 2006) is obtained, and appears promising. The ultimate goal of such modeling is to ascertain initial conditions (growth factor distribution, initial cell seeding, etc.) that will lead to a final desired outcome.


Phagolysosomes of Coxiella burnetii-infected cell lines maintain an acidic pH during persistent infection.
Coxiella burnetii, the agent of Q fever, is an obligate intracellular bacterium that multiples within vacuoles of phagolysosomal origin. Persistently infected cell lines were maintained in continuous culture for months. We studied the pH of the phagolysosomes by using two murine cell lines during early propagation of the bacteria and after establishment of persistent infection. Three strains of C. burnetii were studied because of the purported propensity of each strain to cause acute or chronic disease and to be resistant or susceptible to antibiotics. The pHs were calculated from fluorescence experiments with fluoresceinated dextran as a lysosomal probe. Phagolysosomal vacuoles maintained an acidic pH during a 36-day infection. Minimal variation of the pH occurred over the duration of the experiment with strains that caused either acute or chronic disease. Phagolysosomal pH remained stable for as long as 153 days with the Nine Mile phase II isolate. Thus, neither the course of C. burnetti infection nor the diversity of antibiotic susceptibility of the strains is related to variations in the phagolysosomal pH.


Aurora A plays a dual role in migration and survival of human glioblastoma cells according to the CXCL12 concentration.
Primary glioblastoma is the most frequent human brain tumor in adults and is generally fatal due to tumor recurrence. We previously demonstrated that glioblastoma-initiating cells invade the subventricular zones and promote their radio-resistance in response to the local release of the CXCL12 chemokine. In this work, we show that the mitotic Aurora A kinase (AurA) is activated through the CXCL12-CXCR4 pathway in an ERK1/2-dependent manner. Moreover, the CXCL12-ERK1/2 signaling induces the expression of Ajuba, the main cofactor of AurA, which allows the auto-phosphorylation of AurA.We show that AurA contributes to glioblastoma cell survival, radio-resistance, self-renewal, and proliferation regardless of the exogenous stimulation with CXCL12. On the other hand, AurA triggers the CXCL12-mediated migration of glioblastoma cells in vitro as well as the invasion of the subventricular zone in xenograft experiments. Moreover, AurA regulates cytoskeletal proteins (i.e., Actin and Vimentin) and favors the pro-migratory activity of the Rho-GTPase CDC42 in response to CXCL12. Altogether, these results show that AurA, a well-known kinase of the mitotic machinery, may play alternative roles in human glioblastoma according to the CXCL12 concentration.


Interaction of hydraulic and buckling mechanisms in blowout fractures.
The etiology of blowout fractures is generally attributed to 2 mechanisms--increase in the pressure of the orbital contents (the hydraulic mechanism) and direct transmission of impacts on the orbital walls (the buckling mechanism). The present study aims to elucidate whether or not an interaction exists between these 2 mechanisms. We performed a simulation experiment using 10 Computer-Aided-Design skull models. We applied destructive energy to the orbits of the 10 models in 3 different ways. First, to simulate pure hydraulic mechanism, energy was applied solely on the internal walls of the orbit. Second, to simulate pure buckling mechanism, energy was applied solely on the inferior rim of the orbit. Third, to simulate the combined effect of the hydraulic and buckling mechanisms, energy was applied both on the internal wall of the orbit and inferior rim of the orbit. After applying the energy, we calculated the areas of the regions where fracture occurred in the models. Thereafter, we compared the areas among the 3 energy application patterns. When the hydraulic and buckling mechanisms work simultaneously, fracture occurs on wider areas of the orbital walls than when each of these mechanisms works separately. The hydraulic and buckling mechanisms interact, enhancing each other's effect. This information should be taken into consideration when we examine patients in whom blowout fracture is suspected.


Low angle laser light scattering-absolute calibration.
A new method for the calculation of the Rayleigh factor from low angle light scattering measurements is developed. This method does not require a uniform intensity illuminating beam, hence efficiently utilizes all the beam from a focused laser source. Scattering volume is then very small, reducing sample volume and interference from contaminant particles. All the parameters necessary for the calculation of the Rayleigh factor (including the exact dependence on sample refractive index) are measurable, hence absolute calibration is possible. Over-all error is estimated to be less than 2.3% under specified conditions. Measurements are possible at scattering angles as small as 2 degrees obviating the need for angular extrapolations in the determination of molecular weight of most dissolved samples. Rayleigh factors at 22 degrees C, 633 nm, and a scattering angle of 4 degrees for water, methanol, benzene, and toluene, were found to be, respectively, 0.907, 2.56, 12.15, and 13.45 x 10(-6) cm(-1).


Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands.
The accuracy of malaria diagnosis has received renewed interest in recent years due to changes in treatment policies in favour of relatively high-cost artemisinin-based combination therapies. The use of rapid diagnostic tests (RDTs) based on histidine-rich protein 2 (HRP2) synthesized by Plasmodium falciparum has been widely advocated to save costs and to minimize inappropriate treatment of non-malarial febrile illnesses. HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections. In this study, 78,454 clinically diagnosed malaria patients were tested using HRP2-based RDTs over a period of approximately four years in four highland sites in Kenya and Uganda representing hypoendemic to mesoendemic settings. In addition, the utility of the tests was evaluated in comparison with expert microscopy for disease management in 2,241 subjects in two sites with different endemicity levels over four months. RDT positivity rates varied by season and year, indicating temporal changes in accuracy of clinical diagnosis. Compared to expert microscopy, the sensitivity, specificity, positive predictive value and negative predictive value of the RDTs in a hypoendemic site were 90.0%, 99.9%, 90.0% and 99.9%, respectively. Corresponding measures at a mesoendemic site were 91.0%, 65.0%, 71.6% and 88.1%. Although sensitivities at the two sites were broadly comparable, levels of specificity varied considerably between the sites as well as according to month of test, age of patient, and presence or absence of fever during consultation. Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies. Patients with high parasite densities were more likely to test positive with RDTs than those with low density infections. RDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission. Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied.


Evaluation of adhesion of chairside hard relining materials to denture base polymers.
Removable denture bases are made of modified poly(methyl methacrylate) (PMMA), which has reliable bond strength with resins containing methyl methacrylate (MMA). However, some hard relining materials with different chemical compositions have been reported to have less than adequate bond strength to PMMA denture base polymers. This in vitro study evaluated the initial bonding properties of chairside hard relining materials to different removable denture base polymers, as well as the structure of the interface. The tensile strength (MPa) of adhesion of 8 chairside hard relining materials (Original Truliner, GC Reline Hard, Ufigel Hard, Triad Reline, New Truliner, Light Liner, Astron LC Hard, and Flexacryl Hard) was tested against 3 denture base polymers (Ivocap Plus, Paladon 65, and Palapress Vario). Dumbbell-shaped specimens with a 6-mm diameter of bonding surface were used for tensile testing of bond strength (n=5). An MMA containing hard relining material (Original Truliner) was used as a control. Tensile strength of the bond was calculated using the bonding area and maximum force under tension. Statistical analyses of data were conducted with 2-way analysis of variance (alpha=.05). The influence of the bonding agents and the relining materials on the PMMA denture base surface layer and its structure were investigated. The depths of the swollen layers were measured with a transmission light microscope. Fracture surfaces after testing were also visually evaluated. Chemical analyses of all materials prior to testing were performed using high-performance liquid chromatography. Significant differences were found among tensile bond strengths of chairside hard relining materials to PMMA denture base polymers forming 3 different groups (P<.001). No significant difference among different denture base polymers was found with regard to tensile strength of adhesion (P=.918), but the interaction term between hard relining material and denture base polymer was found to be significant (P<.001). The tensile bond strength of the relining materials and denture base polymers was found to range from 8% to 60% of the strength of the PMMA denture base polymers. The chemical composition of the bonding agents and the relining materials and their combinations affected the depth of the swollen layers of the denture base polymers and the tensile strength of adhesion.


Multivariate analysis of factors associated with smoking cessation in women.
Appropriate smoking cessation techniques, including counseling patients to stop smoking, could prevent multiple health-related problems. Identification of relevant factors in patients that smoke may be beneficial in targeting smoking cessation efforts. This investigation explores various factors associated with smoking cessation, specifically in women. All women (n = 675) presenting to a breast health center over a one year period were surveyed regarding their tobacco use. Any association between smoking cessation and various factors was determined by multivariate analysis. Our population consisted of 47% African American women, 43% Caucasian women, and 10% women of other ethnicities. Sixty percent of all women never smoked. Of the women who had smoked, 57% quit. Except for alcohol use and exercise, no factor, including ethnicity, was associated with never smoking. Smoking cessation was associated with being married, being Caucasian, not using alcohol, and exercising. However, only Caucasian race and marriage were independently associated with smoking cessation. In our population, African American women had a lower proportion of smoking cessation than Caucasian women. In patients with similar access to care, specifically preventive care, there are ethnic and social differences in smoking cessation.


Sample size calculations for surveys to substantiate freedom of populations from infectious agents.
We develop a Bayesian approach to sample size computations for surveys designed to provide evidence of freedom from a disease or from an infectious agent. A population is considered "disease-free" when the prevalence or probability of disease is less than some threshold value. Prior distributions are specified for diagnostic test sensitivity and specificity and we test the null hypothesis that the prevalence is below the threshold. Sample size computations are developed using hypergeometric sampling for finite populations and binomial sampling for infinite populations. A normal approximation is also developed. Our procedures are compared with the frequentist methods of Cameron and Baldock (1998a, Preventive Veterinary Medicine34, 1-17.) using an example of foot-and-mouth disease. User-friendly programs for sample size calculation and analysis of survey data are available at http://www.epi.ucdavis.edu/diagnostictests/.


Concerted changes in tropical forest structure and dynamics: evidence from 50 South American long-term plots.
Several widespread changes in the ecology of old-growth tropical forests have recently been documented for the late twentieth century, in particular an increase in stem turnover (pan-tropical), and an increase in above-ground biomass (neotropical). Whether these changes are synchronous and whether changes in growth are also occurring is not known. We analysed stand-level changes within 50 long-term monitoring plots from across South America spanning 1971-2002. We show that: (i) basal area (BA: sum of the cross-sectional areas of all trees in a plot) increased significantly over time (by 0.10 +/- 0.04 m2 ha(-1) yr(-1), mean +/- 95% CI); as did both (ii) stand-level BA growth rates (sum of the increments of BA of surviving trees and BA of new trees that recruited into a plot); and (iii) stand-level BA mortality rates (sum of the cross-sectional areas of all trees that died in a plot). Similar patterns were observed on a per-stem basis: (i) stem density (number of stems per hectare; 1 hectare is 10(4) m2) increased significantly over time (0.94 +/- 0.63 stems ha(-1) yr(-1)); as did both (ii) stem recruitment rates; and (iii) stem mortality rates. In relative terms, the pools of BA and stem density increased by 0.38 +/- 0.15% and 0.18 +/- 0.12% yr(-1), respectively. The fluxes into and out of these pools-stand-level BA growth, stand-level BA mortality, stem recruitment and stem mortality rates-increased, in relative terms, by an order of magnitude more. The gain terms (BA growth, stem recruitment) consistently exceeded the loss terms (BA loss, stem mortality) throughout the period, suggesting that whatever process is driving these changes was already acting before the plot network was established. Large long-term increases in stand-level BA growth and simultaneous increases in stand BA and stem density imply a continent-wide increase in resource availability which is increasing net primary productivity and altering forest dynamics. Continent-wide changes in incoming solar radiation, and increases in atmospheric concentrations of CO2 and air temperatures may have increased resource supply over recent decades, thus causing accelerated growth and increased dynamism across the world's largest tract of tropical forest.


Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction.
Vault particles are naturally occurring proteinaceous cages with promising application as molecular containers. The use of vaults as functional transporters requires a profound understanding of their structural stability to guarantee the protection and controlled payload delivery. Previous results performed with bulk techniques or at non-physiological conditions have suggested pH as a parameter to control vault dynamics. Here we use Atomic Force Microscopy (AFM) to monitor the structural evolution of individual vault particles while changing the pH in real time. Our experiments show that decreasing the pH of the solution destabilize the barrel region, the central part of vault particles, and leads to the aggregation of the cages. Additional analyses using Quartz-Crystal Microbalance (QCM) and Differential Scanning Fluorimetry (DSF) are consistent with our single molecule AFM experiments. The observed topographical defects suggest that low pH weakens the bonds between adjacent proteins. We hypothesize that the observed effects are related to the strong polar character of the protein-protein lateral interactions. Overall, our study unveils the mechanism for the influence of a biologically relevant range of pHs on the stability and dynamics of vault particles.


Protocol for development of the guideline for reporting evidence based practice educational interventions and teaching (GREET) statement.
There are an increasing number of studies reporting the efficacy of educational strategies to facilitate the development of knowledge and skills underpinning evidence based practice (EBP). To date there is no standardised guideline for describing the teaching, evaluation, context or content of EBP educational strategies. The heterogeneity in the reporting of EBP educational interventions makes comparisons between studies difficult. The aim of this program of research is to develop the Guideline for Reporting EBP Educational interventions and Teaching (GREET) statement and an accompanying explanation and elaboration (E&E) paper. Three stages are planned for the development process. Stage one will comprise a systematic review to identify features commonly reported in descriptions of EBP educational interventions. In stage two, corresponding authors of articles included in the systematic review and the editors of the journals in which these studies were published will be invited to participate in a Delphi process to reach consensus on items to be considered when reporting EBP educational interventions. The final stage of the project will include the development and pilot testing of the GREET statement and E&E paper. The final outcome will be the creation of a Guideline for Reporting EBP Educational interventions and Teaching (GREET) statement and E&E paper. The reporting of health research including EBP educational research interventions, have been criticised for a lack of transparency and completeness. The development of the GREET statement will enable the standardised reporting of EBP educational research. This will provide a guide for researchers, reviewers and publishers for reporting EBP educational interventions.


Improving health services to displaced persons in Aceh, Indonesia: a balanced scorecard.
After the Indian Ocean tsunami in December 2004, the International Organization for Migration constructed temporary health clinics to provide medical services to survivors living in temporary accommodation centres throughout Aceh, Indonesia. Limited resources, inadequate supervision, staff turnover and lack of a health information system made it challenging to provide quality primary health services. A balanced scorecard was developed and implemented in collaboration with local health clinic staff and district health officials. Performance targets were identified. Staff collected data from clinics and accommodation centres to develop 30 simple performance measures. These measures were monitored periodically and discussed at meetings with stakeholders to guide the development of health interventions. Two years after the tsunami, 34 000 displaced persons continued to receive services from temporary health clinics in two districts of Aceh province. From March to December 2007, the scorecard was implemented in seven temporary health clinics. Interventions stimulated and tracked by the scorecard showed measurable improvements in preventive medicine, child health, capacity building of clinic staff and availability of essential drugs. By enhancing communication, the scorecard also led to qualitative benefits. The balanced scorecard is a practical tool to focus attention and resources to facilitate improvement in disaster rehabilitation settings where health information infrastructure is poor. Introducing a mechanism for rapid improvement fostered communication between nongovernmental organizations, district health officials, clinic health workers and displaced persons.


Role of pre-operative multimedia video information in allaying anxiety related to spinal anaesthesia: A randomised controlled trial.
A high incidence of anxiety has been reported in patients in the operation theatre set up. We developed a short visual clip of 206 s duration depicting the procedure of spinal anaesthesia (SAB) and aimed to compare the effect of this video on perioperative anxiety in patients undergoing procedures under SAB. A prospective randomised study of 200 patients undergoing surgery under SAB was conducted. Patients were allotted to either the nonvideo group (Group NV - those who were not shown the video) or the video group (Group V - those who were shown the video). Anxiety was assessed using the Spielberger State-Trait Anxiety Inventory during the pre-anaesthetic check-up and before surgery. Haemodynamic parameters such as heart rate (HR) and mean arterial pressure (MAP) were also noted. Student's t-test was used for normally distributed and Mann-Whitney U-test for nonnormally distributed quantitative data. Chi-square test was used for categorical data. Both groups were comparable with respect to baseline anxiety scores and haemodynamic parameters. The nonvideo group showed a significant increase in state anxiety scores before administration of SAB (P < 0.001). Patients in the video group had significantly lower HR and MAP preoperatively (P < 0.001). The prevalence of 'high anxiety' for SAB was 81% in our study which decreased to 66% in the video group before surgery. Multimedia information in the form of a short audiovisual clip is an effective and feasible method to reduce perioperative anxiety related to SAB.


Genetic diversity and linkage disequilibrium in the Polynesian population of Niue Island.
Isolated populations that recently have been derived from small homogeneous groups of founders should have low genetic diversity and high levels of linkage disequilibrium and should be ideal for mapping ancestral polymorphisms that influence complex genetic disease susceptibility. Populations that fulfill these criteria have been difficult to identify. We have been looking for Polynesian populations with these characteristics, because Polynesians have high rates of complex genetic diseases. In Niue Islanders all ancestral female (mitochondrial HSVI sequence) and 90.4% of ancestral male (Y-chromosome haplogroup) lineages are of Southeast Asian origin. The frequency of European Y-chromosome haplogroups is 7.2%. The diversities of mitochondrial HSV1 sequences (h = 0.18 +/- 0.05) and Y-chromosome haplo-groups (h = 0.18 +/- 0.05) are lower than values published for any other population. Ten autosomal microsatellites spaced over 5.8 cM show low allele numbers in Niue Islanders relative to Europeans (55 vs. 88 total alleles, respectively) and a modest reduction in heterozygous loci (0.71 +/- 0.02 vs. 0.78 +/- 0.02, p = 0.04). The higher linkage disequilibrium (d2) between these loci in Niue Islanders relative to Europeans (p = 0.001) is negatively correlated (r = -0.47, p = 0.01) with genetic distance. In summary, Niue Islanders are genetically isolated and have a homogeneous Southeast Asian ancestry. They have reduced autosomal genetic diversity and high levels of linkage disequilibrium that are consistent with the influence of genetic drift mechanisms, such as a founder effect or bottlenecks. High-powered linkage disequilibrium studies designed to map ancestral polymorphisms that influence complex genetic disease susceptibility may be feasible in this population.


Jewish Values in Medical Decision-making for Unrepresented Patients: A Ritualized Approach.
Determining appropriate care for patients who cannot speak for themselves is one of the most challenging issues in contemporary healthcare and medical decision-making. While there has been much discussion relating to patients who left some sort of instructions, such as an advance directive, or have someone to speak on their behalf, less has been written on caring for patients who have nobody at all available to speak for them. It is thus crucial to develop clear and rigorous guidelines to properly care for these patients. The Jewish tradition offers an important perspective on caring for unrepresented patients and determining approaches to guide care providers. This article develops an understanding of fundamental Jewish principles that can provide clear guidance in navigating this challenge. It applies those values to a specific set of suggested behaviors, one of which adds a novel ritualized component to what has been recommended by bioethicists in the past.


Sequential analysis of hair mercury levels in relation to fish diet of an Amazonian population, Brazil.
Several studies in the Amazonian Basin have shown that riverine populations are exposed to methylmercury through fish consumption. It has been suggested that seasonal variations in hair mercury observed through sequential analyses may be related to the changes in fish species ingested by the local communities. The aim of the present study was to investigate the relationship between fish-eating practices and seasonal variation in mercury exposure. A group of 36 women from a village located on the banks of the Tapajós River, a major tributary of the Amazon, comprised the present study population. An interview-administered questionnaire was used to gather information on socio-demographic characteristics, fish-eating practices and other relevant information. The women also provided hair samples of at least 24 cm in length for mercury analysis. Hair total and inorganic mercury concentration was measured using a cold vapor atomic absorption analytical method. Trigonometric regression analysis was done to assess the seasonal variation of total mercury levels. Variations in inorganic mercury were examined by repeated measures analysis of variance, and analysis of contrast variable with a polynomial transformation. The results showed that hair mercury levels varied with the season. Higher levels were observed in months corresponding to the dry season, with lower levels in the rainy season. Herbivorous fish predominated the diet for 47.2% of the women during the dry season, but this rose to 72.2% during the rainy season. Those who reported eating fish daily had higher mercury levels in hair compared to those who only ate fish a few times per week. Retrospective mercury analyses, evaluated by the quantity of mercury present in each centimeter of hair, indicate that mean mercury level of the population decreased over the 2 years prior to the study. The percentage of inorganic mercury over the total mercury in hair increased towards the extremities of the hair strand. Higher percentages of inorganic mercury were found for the group who ate more fish (on a daily consumption basis). These results support the assumption that there are seasonal variations in methylmercury exposure and also a relationship between type of fish species consumed and the resulting hair mercury levels.


Genome sequence of the Leisingera aquimarina type strain (DSM 24565(T)), a member of the marine Roseobacter clade rich in extrachromosomal elements.
Leisingera aquimarina Vandecandelaere et al. 2008 is a member of the genomically well characterized Roseobacter clade within the family Rhodobacteraceae. Representatives of the marine Roseobacter clade are metabolically versatile and involved in carbon fixation and biogeochemical processes. They form a physiologically heterogeneous group, found predominantly in coastal or polar waters, especially in symbiosis with algae, in microbial mats, in sediments or associated with invertebrates. Here we describe the features of L. aquimarina DSM 24565(T) together with the permanent-draft genome sequence and annotation. The 5,344,253 bp long genome consists of one chromosome and an unusually high number of seven extrachromosomal elements and contains 5,129 protein-coding and 89 RNA genes. It was sequenced as part of the DOE Joint Genome Institute Community Sequencing Program 2010 and of the activities of the Transregional Collaborative Research Centre 51 funded by the German Research Foundation (DFG).


Pure Autonomic Failure: complex abnormalities in the neural mechanisms regulating the cardiovascular system.
The aim of this study was to evaluate the sympatho-vagal interaction modulating cardiovascular function and the possible impairment of baroreceptor sensitivity in patients affected by Pure Autonomic Failure (PAF). We studied 4 patients affected by PAF and 7 controls at rest and during different levels (45 degrees, 60 degrees, 90 degrees) of head-up tilt. On a different day all subjects underwent i.v. administration of phenylephrine at dosages adequate to enhance systolic blood pressure by about 20 mmHg both at rest and during 45 degrees head-up tilt. Finally, 1.5 mg atropine was infused intravenously only in the patients. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided markers of sympathetic (low-frequency oscillations, about 0.1 Hz, LFRR) and vagal (high-frequency oscillations, about 0.25 Hz, HFRR) modulations of heart period and of sympathetic vasomotor activity (low-frequency oscillations of SAP variability, LFSAP). Baroreceptor mechanisms were quantified by means of the index alpha (calculated from the square root of the ratio between the powers of HF components of RR interval and SAP variabilities) and of the phenylephrine RR-SAP slope. Patients affected by PAF were characterized by a drastic decrease in total power of RR variability and by the absence of LFRR and LFSAP components. Moreover, HFRR, although largely predominant in its relative value, was also markedly reduced in its absolute value. Finally, the baroreceptive mechanisms appeared to be heavily impaired. In conclusion, PAF patients seem to be characterized by a complex alteration of neural mechanisms, which in addition to the signs of a sympathetic denervation include an impairment, at least functional, of the vagal modulation of heart rate.


Empty follicle syndrome in two sisters with three cycles: case report.
Empty follicle syndrome (EFS) is characterized by a lack of retrieved oocytes in the presence of multiple follicle development, in both natural and stimulated cycles. The aim of the present case report is to point out the possibility of genetic factors that could be responsible for some occurrences of EFS. Two sisters with moderate deafness underwent controlled ovarian hyperstimulation and IVF/ICSI cycles at the same centre. During all three cycles there were normal follicular development, estradiol levels and bio-available hCG plasma levels, but no oocytes and cumulus-corona complexes were retrieved, despite second hCG injections. These cases may represent an inherited condition of EFS with hearing loss with genetic factors affecting both the aetiology of EFS and the hearing loss.


Molecular therapy for gastric cancer.
Several agents that target specific molecules have been investigated for the treatment of gastric cancer in many preclinical and clinical studies. Anti-HER2 antibody, when combined with classical cytotoxic agents, has been shown to confer a significant survival benefit in patients with HER2-positive gastric cancer. This is the only targeted drug that has been shown to be successful for the treatment of gastric cancer. We need to determine specific targets for regulating gastric cancer cells by translational research, develop precise diagnostic procedures for personalized medicine, and identify candidate drugs for gastric cancer.


Drosophila MCM protein complexes.
MCM genes encode a family of evolutionarily conserved proteins required for DNA replication. In Saccharomyces cerevisiae, where they were first identified, MCM genes interact genetically with each other. Allele specificity in these interactions suggests that MCM proteins physically associate with one another and that this association is essential for function. We describe here an analysis of physical interactions among three Drosophila MCM proteins. Using specific antibodies we detect Drosophila MCMs almost exclusively in 600-kDa protein complexes. Co-immunoprecipitation data demonstrate the existence of at least two distinct types of 600-kDa complexes, one that contains DmCDC46 and one that appears to contain both DmMCM2 and Dpa (a CDC54 homologue). These complexes are stable throughout embryonic division cycles, are resistant to treatments with salt and detergent, and are present during development in tissues undergoing mitotic DNA replication as well as endoreplication. When extracts are prepared under low salt conditions all three MCM proteins co-immunoprecipitate. Consequently, we suggest that the 600-kDa complexes interact in a higher order complex.


Is there a consensus for CBCT use in Orthodontics?
This article aims to discuss current evidence and recommendations for cone-beam computed tomography (CBCT) in Orthodontics. In comparison to conventional radiograph, CBCT has higher radiation doses and, for this reason, is not a standard method of diagnosis in Orthodontics. Routine use of CBCT in substitution to conventional radiograph is considered an unaccepted practice. CBCT should be indicated with criteria only after clinical examination has been performed and when the benefits for diagnosis and treatment planning exceed the risks of a greater radiation dose. It should be requested only when there is a potential to provide new information not demonstrated by conventional scans, when it modifies treatment plan or favors treatment execution. The most frequent indication of CBCT in Orthodontics, with some evidence on its clinical efficacy, includes retained/impacted permanent teeth; severe craniofacial anomalies; severe facial discrepancies with indication of orthodontic-surgical treatment; and bone irregularities or malformation of TMJ accompanied by signs and symptoms. In exceptional cases of adult patients when critical tooth movement are planned in regions with deficient buccolingual thickness of the alveolar ridge, CBCT can be indicated provided that there is a perspective of changes in orthodontic treatment planning.


in vitro Decellularization of Rabbit Lung Tissue.
The bioscaffold can be used in tissue engineering and regenerative medicine. The scaffolds used in tissue engineering must have high porosity to facilitate accelerated angiogenesis for feeding cells and repelling cell waste outside the scaffold. In this experimental study, we attempted to produce lung three-dimensional scaffold and assay its effect on cell penetration and migration. In an experimental study, rabbit lung tissue was decellularized and used as a scaffold for rabbit blastema cells. The scaffolds were studied on the 15(th) day after culturing. Microscopic features revealed high porosity in the lung tissue scaffold. Electron microscopic imaging also showed collagen and elastin were intact, which are important properties in scaffolds designed for tissue engineering. Migration and permeation of blastema cells into the lung tissue scaffold was also observed. Rabbit lung tissue scaffolds have high porosity. Blastema cells successfully migrated toward and permeated the scaffold inside.


Implementation of single-beam multiplexing encoding with a dually modulated spatial light modulator.
We propose a novel method for signal storage and encryption, called single-beam multiplexing encoding. The single beam is composed of an inside signal beam and an outside reference beam. The signal beam is amplitude modulated, and the reference beam is phase modulated. The dual modulation is implemented by a spatial light modulator (SLM). Multiplexing holography with different reference beams from different directions, called directional multiplexing, is analyzed in detail. With an SLM based on a twisted nematic liquid crystal display, we demonstrate a single-beam directional multiplexing method using a holographic encoding technique, and the retrieved signals are presented. This encoding system is more stable, miniaturized, and flexible. It should be of great interest for applications in signal encryption as well as for high-capacity data storage.


How prepared are young, rural women in India to address their sexual and reproductive health needs? a cross-sectional assessment of youth in Jharkhand.
Young, rural Indian women lack sexual and reproductive health (SRH) information and agency and are at risk of negative sexual and reproductive health outcomes. Youth-focused interventions have been shown to improve agency and self-efficacy of young women to make decisions regarding their sexual and reproductive health. The objectives of this study were to assess young women's sexual and reproductive health knowledge; describe their health-seeking behaviors; describe young women's experiences with sexual and reproductive health issues, including unwanted pregnancy and abortion; and identify sources of information, including media sources. A cross-sectional survey with a representative sample of 1381 married and unmarried women young women (15-24 years) from three rural community development blocks in Jharkhand, India was conducted in 2012. Participants were asked a series of questions related to their SRH knowledge and behavior, as well as questions related to their agency in several domains related to self-efficacy and decision-making. Linear regression was used to assess factors associated with greater or less individual agency and to determine differences in SRH knowledge and behavior between married and unmarried women. Despite national policies, participants married young (mean 15.7 years) and bore children early (53 % with first birth by 17 years). Women achieved low composite scores on knowledge around sex and pregnancy, contraception, and abortion knowledge. Around 3 % of married young women reported experiencing induced abortion; 92 % of these women used private or illegal providers. Married and unmarried women also had limited agency in decision-making, freedom of mobility, self-efficacy, and financial resources. Most of the women in the sample received SRH information by word of mouth. Lack of knowledge about sexual and reproductive health in this context indicates that young rural Indian women would benefit from a youth-friendly SRH intervention to improve the women's self-efficacy and decision-making capacity regarding their own health. A communication intervention using outreach workers may be a successful method for delivering this intervention.


Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model.
Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the alpha-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the alpha5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.


Emotion contagion moderates the relationship between emotionally-negative families and abnormal eating behavior.
To reconcile empirical inconsistencies in the relationship between emotionally-negative families and daughters' abnormal eating, we hypothesized a critical moderating variable: daughters' vulnerability to emotion contagion. A nonclinical sample of undergraduate females (N = 92) was recruited via an advertisement and completed self-report measures validated for assessing: families' expressive negativity, daughters' susceptibility to emotion contagion, dietary restraint, and disinhibition, eating attitudes, and several control variables (interpersonal orientation, alexithymia, and the big five personality traits: extraversion, conscientiousness, openness, neuroticism, and agreeableness). All variables and interactions were entered as predictors in a multistep multiple regression equation. Only an emotion contagion by family expressivity interaction term significantly predicted unhealthy eating attitudes (β = .29, p = .02) and dietary restraint (β = .27, p = .03). Negatively expressive families significantly induced unhealthy eating and restraint but only among young women susceptible to emotion contagion (ps < .05). Young women susceptible to emotion contagion may be at increased risk for eating disorders.


Oscillatory and Aperiodic Neural Activity Jointly Predict Language Learning.
Memory formation involves the synchronous firing of neurons in task-relevant networks, with recent models postulating that a decrease in low-frequency oscillatory activity underlies successful memory encoding and retrieval. However, to date, this relationship has been investigated primarily with face and image stimuli; considerably less is known about the oscillatory correlates of complex rule learning, as in language. Furthermore, recent work has shown that nonoscillatory (1/ƒ) activity is functionally relevant to cognition, yet its interaction with oscillatory activity during complex rule learning remains unknown. Using spectral decomposition and power-law exponent estimation of human EEG data (17 women, 18 men), we show for the first time that 1/ƒ and oscillatory activity jointly influence the learning of word order rules of a miniature artificial language system. Flexible word-order rules were associated with a steeper 1/ƒ slope, whereas fixed word-order rules were associated with a shallower slope. We also show that increased theta and alpha power predicts fixed relative to flexible word-order rule learning and behavioral performance. Together, these results suggest that 1/ƒ activity plays an important role in higher-order cognition, including language processing, and that grammar learning is modulated by different word-order permutations, which manifest in distinct oscillatory profiles.


Pharmacological inhibition of p38 potentiates antimicrobial peptide TP4-induced cell death in glioblastoma cells.
Glioblastoma is the most common and deadly type of brain cancer. The poor prognosis may be largely attributed to inadequate disease response to current chemotherapeutic agents. Activation of p38 is associated with deleterious outcomes in glioblastoma patients, as its signaling mediates chemoresistance mechanisms. Antimicrobial peptide tilapia piscidin (TP) 4 was identified from Nile tilapia (Oreochromis niloticus) and exhibits strong bactericidal effects on Gram-positive and Gram-negative bacteria. TP4 also has anticancer activity toward human triple-negative breast cancer cells and glioblastoma cells. In the present study, we tested the cytotoxic effects of combined TP4 and p38 inhibitors on glioblastoma U251 cells. We found that the combination of TP4 and p38 inhibitors (SB202190 and VX-745) enhanced cytotoxicity in U251 glioblastoma cells but not noncancerous neural cells. Cytotoxicity from the combination treatments proceeded via necrosis and not apoptosis. Mechanistically, SB202190 potentiated TP4-induced mitochondrial dysfunction, reactive oxygen species generation and unbalanced antioxidant status, which resulted in necrotic cell death. Thus, we demonstrated for the first time that combinations of TP4 and p38 inhibitors have the potential to preferentially target glioblastoma cells, while sparing noncancerous neural cells.


Engineering the acetyl-CoA transportation system of candida tropicalis enhances the production of dicarboxylic acid.
Dicarboxylic acids (DCAs) can be obtained by oxidizing alkanes by Candida tropicalis. Through alpha-monocarboxylic acids (MCAs), alpha- and omega-oxidation yield alpha- or omega-DCAs, respectively. However, both MCAs and DCAs may be degraded to acetyl-CoA by beta-oxidation, resulting in a limited DCA yield. Acetyl-CoA can be transported into the mitochondrion for the TCA cycle by carnitine acetyltransferase (CAT), by which the energy generation and beta-oxidation are connected. In this paper, we present a method to reconstruct the metabolic pathway by inhibiting the acetyl-CoA transportation system. Metabolic engineering is applied on the acetyl-CoA transportation system, but not the key enzymes in beta-oxidation. Starting with the original strain W10-1, cat heterozygote CZ-15 and cat homozygote CKC-11 were obtained by gene knockout. The CAT specific activity in CZ-15 was about 50% lower than that in W10-1, resulting in a 21.0% increase of the DCA concentration, and a 12% increase of the molar conversion of alkane, reaching 61.6%. However, no CAT activity was detected in CKC-11, and CKC-11 could not grow on alkane. These results indicate that inhibition of beta-oxidation via reconstruction of the transportation process between organelles can facilitate DCA production, but that totally blocking the & betagr;-oxidation would be harmful for energy supply. We thus provide a novel insight into regulation of the beta-oxidation system and metabolic flux. Further understanding of beta-oxidation and the acetyl-CoA transportation system in Candida tropicalis is reached through examination of fermentation data by metabolic flux analysis.


Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial.
Progressive supranuclear palsy is a rare neurodegenerative disease associated with dysfunctional tau protein. BIIB092 is a humanised monoclonal antibody that binds to N-terminal tau and is thus being assessed as a potential novel treatment for progressive supranuclear palsy. We aimed to investigate the safety and tolerability of BIIB092 in individuals with progressive supranuclear palsy. This 12-week, double-blind, randomised, placebo-controlled, multiple ascending dose, phase 1b trial was done at 13 outpatient sites in the USA. Participants aged 41-86 years with probable or possible progressive supranuclear palsy with a score of 20 or greater on the Mini-Mental State Examination (MMSE) were enrolled. Three BIIB092 dose escalation cohorts (150 mg, 700 mg, or 2100 mg; eight participants per cohort) were tested sequentially. For each dose cohort, the first two participants were randomly assigned by a computer-generated scheme to receive either BIIB092 or placebo intravenously every 4 weeks for 57 days. After 2 days, the six remaining participants in each cohort were randomly assigned (5:1) to receive BIIB092 or placebo for 57 days. An additional expansion panel of 24 patients was randomly assigned (3:1) to receive 2100 mg or placebo every 4 weeks for 57 days. All participants were followed up to day 85. The primary outcome was safety, which was analysed in the treated population (all enrolled participants who received at least one dose of the study drug). This trial is registered with ClinicalTrials.gov, NCT02460094. Between Oct 2, 2015, and Oct 19, 2016, 48 participants were enrolled and randomly assigned to the BIIB092 (n=36) and placebo (n=12) groups. No apparent demographic differences were observed between the two groups at baseline. All 48 participants completed the treatment phase of the study. Adverse events were generally mild to moderate in severity; the most common in the placebo and BIIB092 groups were falls (in two [17%] of 12 patients and in ten [28%] of 36 patients), urinary tract infections (in one [8%] of 12 and in six [17%] of 36), contusions (in one [8%] of 12 and in five [14%] of 36), and headaches (in none and in five [14%] of 36). Four serious adverse events resulting in admission to hospital were reported in three participants who received BIIB092 2100 mg: two severe adverse events of urinary tract infection, one severe adverse event of change in mental status, and one moderate adverse event of aspiration pneumonia. None was considered to be related to the study drug, all were resolved, and no deaths were reported. Repeated administration of the anti-tau monoclonal antibody BIIB092, at doses of up to 2100 mg, appears to be well tolerated in participants with progressive supranuclear palsy. Results of this phase 1b trial have informed the design of the ongoing phase 2 PASSPORT (NCT03068468) study to examine the efficacy and safety of BIIB092. Bristol-Myers Squibb, Biogen.


How critical is frame selection in quantitative coronary angiographic studies?
To analyse quantitatively a coronary arterial segment from a cineangiogram, an end-diastolic or neighbouring frame is usually selected. However, different cardiologists may select other (although usually neighbouring) frames, even when the same selection criteria are followed. It is also possible that the frames are selected from different cardiac cycles. In this study the effects of such phase shifts on the reproducibility of the quantitative measurements were studied. In a total of 38 consecutive patient films obtained at a filmspeed of 25 frames s-1, the frame phi demonstrating the severity of a lesion optimally as judged by a senior cardiologist, the three preceding frames, the three following frames and one frame exactly one cycle prior to or following frame phi were selected; frame phi was always chosen in the end-diastolic phase of the cardiac cycle. In each film one coronary arterial segment with a focal lesion was analysed quantitatively in these total of 8 frames with the Cardiovascular Angiography Analysis System (CAAS). No significant differences were found in the mean difference and the standard deviations of the differences (variabilities) in the obstruction diameter, interpolated reference diameter, percent diameter stenosis, extent of the obstruction and area of atherosclerotic plaque obtained in the various frames with respect to frame phi. Therefore, it may be concluded that the selection of a cineframe for quantitative analysis in the end-diastolic phase of the cardiac cycle is not very critical.(ABSTRACT TRUNCATED AT 250 WORDS)


Capturing B type acute lymphoblastic leukemia cells using two types of antibodies.
One way to monitor minimal residual disease (MRD) is to screen cells for multiple surface markers using flow cytometry. In order to develop an alternative microfluidic based method, isolation of B type acute lymphoblastic cells using two types of antibodies should be investigated. The immunomagnetic beads coated with various antibodies are used to capture the B type acute lymphoblastic cells. Single beads, two types of beads and surface immobilized antibody were used to measure the capture efficiency. Both micro and nanosize immunomagnetic beads can be used to capture B type acute lymphoblastic cells with a minimum efficiency of 94% and maximum efficiency of 98%. Development of a microfluidic based biochip incorporating immunomagnetic beads and surface immobilized antibodies for monitoring MRD can be an alternative to current cost and time inefficient laboratory methods. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2737, 2019.


Deep brain stimulation improves survival in severe Parkinson's disease.
Levodopa and other dopaminergic treatments have not had the expected effect on survival in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor function, motor fluctuations, health-related quality of life, and to reduce medication usage and drug-induced dyskinesia in patients with severe PD refractory to medical therapy. Little however, has been described on the impact of STN-DBS on the survival of these patients. We aim in this study to examine the impact of STN-DBS on the survival of patients with severe PD. Patients who were eligible for STN-DBS were given the choice of undergoing surgery or continuing on medical treatment. Those who exercised patient choice and preferred to continue with medical treatment formed a control population. All eligible patients seen in a 10-year period are included in this study. Our primary outcome measure is a difference in mortality between the two groups with a secondary measure of admission rates to residential (nursing home) care. 106 patients underwent STN-DBS, and 41 patients exercised patient choice and declined the procedure. The two groups were matched for age, gender, ethnicity, duration of disease, rates of pre-existing depression and Levodopa equivalent doses of anti-Parkinson's medications taken. Patients undergoing STN-DBS had significantly longer survival and were significantly less likely to be admitted to a residential care home than those managed purely medically. The statistical significance of these findings persisted after adjusting for potential confounding factors (survival: p=0.002, HR 0.29 (0.13 to 0.64) (residential care home admission: OR: 0.1 (95% CI 0.0 to 0.3; p<0.001). We show for the first time that there is a survival advantage of DBS surgery in advanced PD. The effect of potential bias factors is examined. The survival advantage may arise for several postulated reasons, ranging from improvement in axial functions, such as swallowing, to some as yet unrecognised benefit of reduction in dopaminergic medication. These findings are of great interest to both patients with PD and the health professionals considering the treatment options for patients with severe PD.


Tuning the Emission Wavelength of Lead Halide Perovskite NCs via Size and Shape Control.
The advent of lead halide perovskite nanocrystals (NCs), which are easily synthesized, ultralow-cost materials and have an impeccable luminous efficiency, has drastically changed the future perspective of semiconductor quantum dot devices. Although the band gap energy of lead perovskite NCs can be tuned by the halide composition, the instability problem prevails for mixed-halide perovskite NCs, caused by phase segregation due to ion migration when an external electric field or light is applied. To avoid this problem and obtain the stable emission of RGB primary colors, in this study, two synthesis pathways of pure-halide perovskite NCs are proposed. One approach is the modified hot injection method with "centrifugation of a frozen eutectic mixture" to separate small NCs efficiently, and the other is the "low-temperature mixing and heat-up method" for target materials including CsPbI3, CsPbBr3, and CH(NH2)2PbBr3 (FAPbBr3). The emission wavelength of FAPbBr3 is tuned ion-stoichiometrically, unlike Cs perovskites. These various synthesis pathways of pure-halide perovskite NCs enable the efficient production of high-quality perovskite NCs and allow precise tuning of the emission color to the desired wavelength. Although there are still several "gaps" remaining in the available emission wavelength, the new methodology proposed in this study could potentially be employed for manufacturing more stable perovskite NC-based optoelectronic devices.


Investigating attachment, caregiving, and mental health: a model of maternal-fetal relationships.
Maternal-fetal relationships have been associated with psychosocial outcomes for women and children, but there has been a lack of conceptual clarity about the nature of the maternal relationship with the unborn child, and inconsistent findings assessing its predictors. We proposed and tested a model whereby maternal-fetal relationship quality was predicted by factors relating to the quality of the couple relationship and psychological health. We hypothesized that the contribution of individual differences in romantic attachment shown in past research would be mediated by romantic caregiving responsiveness, as maternal-fetal relationships reflect the beginnings of the caregiving system. 258 women in pregnancy (13, 23, and 33-weeks gestation) completed online measures of attachment to partner, caregiving responsiveness to partner, mental health, and thoughts about their unborn baby. Structural equation modeling was used to test a model of maternal-fetal relationships. Maternal-fetal relationship quality was higher for women at 23-weeks than 13-weeks gestation. Women in first pregnancies had higher self-reported scores of psychological functioning and quality of maternal-fetal relationships than women in subsequent pregnancies. Structural equation models indicated that the quality of the maternal-fetal relationship was best predicted by romantic caregiving responsiveness to partner and women's own psychological health, and that the association between adult romantic attachment avoidance and maternal-fetal relationships was fully mediated by caregiving responsiveness to partner, even after controlling for other factors. These data support the hypothesis that maternal-fetal relationships better reflect the operation of the caregiving system than the care-seeking (i.e., attachment) system. Models of maternal-fetal relationships and interventions with couples should consider the role of caregiving styles of mothers to partners and the relationship between expectant parents alongside other known predictors, particularly psychological health.


A comparative study of blood endotoxin detection in haemodialysis patients.
Endotoxemia is commonly reported in patients receiving haemodialysis and implicated in the pathogenesis of systemic inflammation. The Limulus Amoebocyte Lysate (LAL) assay is the most commonly used blood endotoxin detection assay. Two kinetic variations of the assay are commercially available - the turbidimetric and chromogenic assay, it is unknown which assay is superior for endotoxin detection in uremic patients. Selection of the optimum LAL technique for endotoxin detection in haemodialysis patients is important to further understanding of the sequela of endotoxemia and development of endotoxin-lowering strategies in this population. A turbidimetric and chromogenic LAL assay from the same manufacturer were directly compared. We investigated the ability of both LAL assays to detect endotoxin in uremic plasma. Plasma samples from haemodialysis patients and healthy controls were spiked with endotoxin and percentage spike recovery for the chromogenic and turbidimetric assay was determined. Assay accuracy and precision were compared between both LAL assays. The turbidimetric assay had greater accuracy than the chromogenic assay. Spike recovery was 113.8 % vs. 53.8 % for the turbidimetric and chromogenic assay respectively. Assay bias was higher in the chromogenic assay (-0.384EU/mL vs. 0.011EU/mL). The turbidimetric assay demonstrated greater precision compared to the chromogenic assay. Coefficient of variation ranged from 4.5 to 24.1 % for the turbidimetric assay and 25.8-26.5 % for the chromogenic assay. The study findings suggest that the kinetic turbidimetric LAL assay has greater accuracy and precision than the chromogenic assay and is the optimum LAL technique for endotoxin detection in haemodialysis patients, though these findings should be verified using LAL reagents from other sources.


Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy is a genetic disease associated with a risk of ventricular tachyarrhythmias and sudden death, especially in young patients. We conducted a retrospective multicenter study of the efficacy of implantable cardioverter-defibrillators in preventing sudden death in 128 patients with hypertrophic cardiomyopathy who were judged to be at high risk for sudden death. At the time of the implantation of the defibrillator, the patients were 8 to 82 years old (mean [+/-SD], 40+/-16), and 69 patients (54 percent) were less than 41 years old. The average follow-up period was 3.1 years. Defibrillators were activated appropriately in 29 patients (23 percent), by providing defibrillation shocks or antitachycardia pacing, with the restoration of sinus rhythm; the average age at the time of the intervention was 41 years. The rate of appropriate defibrillator discharge was 7 percent per year. A total of 32 patients (25 percent) had episodes of inappropriate discharges. In the group of 43 patients who received defibrillators for secondary prevention (after cardiac arrest or sustained ventricular tachycardia), the devices were activated appropriately in 19 patients (11 percent per year). Of 85 patients who had prophylactic implants because of risk factors (i.e., for primary prevention), 10 had appropriate interventions (5 percent per year). The interval between implantation and the first appropriate discharge was highly variable but was substantially prolonged (four to nine years) in six patients. In all 21 patients with stored electrographic data and appropriate interventions, the interventions were triggered by ventricular tachycardia or fibrillation. Ventricular tachycardia or fibrillation appears to be the principal mechanism of sudden death in patients with hypertrophic cardiomyopathy. In high-risk patients with hypertrophic cardiomyopathy, implantable defibrillators are highly effective in terminating such arrhythmias, indicating that these devices have a role in the primary and secondary prevention of sudden death.