Adoption of Medicaid Expansion Is Associated with Lower Maternal Mortality.
This study explores the effect of Medicaid expansion under the Affordable Care Act on the maternal mortality ratio in the United States. A difference-in-differences research design was used to analyze the effect of Medicaid expansion on maternal mortality. Maternal mortality was defined with and without late maternal deaths, to substantiate the contribution of increased preconception and postpartum insurance coverage. To examine whether there was a racial difference in the effects of Medicaid expansion, models were stratified by the woman's race/ethnicity for non-Hispanic Black women, non-Hispanic White women, and Hispanic women. Medicaid expansion was significantly associated with lower maternal mortality by 7.01 maternal deaths per 100,000 live births (p = .002) relative to nonexpansion states. When maternal mortality definitions excluded late maternal deaths, Medicaid expansion was significantly associated with a decrease in maternal mortality per 100,000 live births by 6.65 (p = .004) relative to nonexpansion states. Medicaid expansion effects were concentrated among non-Hispanic Black mothers, suggesting that expansion could be contributing to decreasing racial disparities in maternal mortality. Although maternal mortality overall continues to increase in the United States, the maternal mortality ratio among Medicaid expansion states has increased much less compared with nonexpansion states. These results suggest that Medicaid expansion could be contributing to a relative decrease in the maternal mortality ratio in the United States. The decrease in the maternal mortality ratio is greater when maternal mortality estimates include late maternal deaths, suggesting that sustained insurance coverage after childbirth as well as improved preconception coverage could be contributing to decreasing maternal mortality.


Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.
Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.


Cyclist crash rates and risk factors in a prospective cohort in seven European cities.
Increased cycling uptake can improve population health, but barriers include real and perceived risks. Crash risk factors are important to understand in order to improve safety and increase cycling uptake. Many studies of cycling crash risk are based on combining diverse sources of crash and exposure data, such as police databases (crashes) and travel surveys (exposure), based on shared geography and time. When conflating crash and exposure data from different sources, the risk factors that can be quantified are only those variables common to both datasets, which tend to be limited to geography (e.g. countries, provinces, municipalities) and a few general road user characteristics (e.g. gender and age strata). The Physical Activity through Sustainable Transport Approaches (PASTA) project was a prospective cohort study that collected both crash and exposure data from seven European cities (Antwerp, Barcelona, London, Örebro, Rome, Vienna and Zürich). The goal of this research was to use data from the PASTA project to quantify exposure-adjusted crash rates and model adjusted crash risk factors, including detailed sociodemographic characteristics, attitudes about transportation, neighbourhood built environment features and location by city. We used negative binomial regression to model the influence of risk factors independent of exposure. Of the 4,180 cyclists, 10.2 % reported 535 crashes. We found that overall crash rates were 6.7 times higher in London, the city with the highest crash rate, relative to Örebro, the city with the lowest rate. Differences in overall crash rates between cities are driven largely by crashes that did not require medical treatment and that involved motor-vehicles. In a parsimonious crash risk model, we found higher crash risks for less frequent cyclists, men, those who perceive cycling to not be well regarded in their neighbourhood, and those who live in areas of very high building density. Longitudinal collection of crash and exposure data can provide important insights into individual differences in crash risk. Substantial differences in crash risks between cities, neighbourhoods and population groups suggest there is great potential for improvement in cycling safety.


Gene cloning and expression and characterization of a toxin-sensitive protein phosphatase from the methanogenic archaeon Methanosarcina thermophila TM-1.
With oligonucleotides modelled after conserved regions within the protein-serine/threonine phosphatases (PPs) of the PP1/2A/2B superfamily, the gene for the archaeal protein phosphatase PP1-arch2 was identified, cloned, and sequenced from the methanogenic archaeon Methanosarcina thermophila TM-1. The DNA-derived amino acid sequence of PP1-arch2 exhibited a high degree of sequence identity, 27 to 31%, with members of the PP1/2A/2B superfamily such as PP1-arch1 from Sulfolobus solfataricus, PP1alpha from rats, PP2A from Saccharomyces cerevisiae, and PP2B from humans. The activity of the recombinant PP1-arch2 was sensitive to several naturally occurring microbial toxins known to potently inhibit eucaryal PP1 and PP2A, including microcystin-LR, okadaic acid, tautomycin, and calyculin A.


Microbial desalination cell with capacitive adsorption for ion migration control.
A new microbial desalination cell with capacitive adsorption capability (cMDC) was developed to solve the ion migration problem facing current MDC systems. Traditional MDCs remove salts by transferring ions to the anode and cathode chambers, which may prohibit wastewater beneficial reuse due to increased salinity. The cMDC uses adsorptive activated carbon cloth (ACC) as the electrodes and utilizes the formed capacitive double layers for electrochemical ion adsorption. The cMDC removed an average of 69.4% of the salt from the desalination chamber through electrode adsorption during one batch cycle, and it did not add salts to the anode or cathode chamber. It was estimated that 61-82.2mg of total dissolved solids (TDS) was adsorbed to 1g of ACC electrode. The cMDC provides a new approach for salt management, organic removal, and energy production. Further studies will be conducted to optimize reactor configuration and achieve in situ electrode regeneration.


Respiratory protection for firefighters--evaluation of CBRN canisters for use during overhaul.
In the United States, there are approximately 366,600 structural fires each year. After visible flames are extinguished, firefighters begin the overhaul stage of firefighting to smother remaining hot spots and initiate investigations. Typically during overhaul significant ambient concentrations of chemical contaminants remain. However, previous research suggests that the use of air purifying respirators (APR) fitted with chemical, biological, radiological, and nuclear (CBRN) canisters may reduce occupational respiratory exposures. This pilot study used large-scale prescribed burns of representative structural materials to perform simultaneous, side-by-side, filtering and service-life evaluations of commercially available CBRN filters. Three types of CBRN canisters and one cartridge were challenged in repetitive post live-fire overhaul exposure tests using a sampling manifold apparatus. At a flow rate of 80 L/min, nine tests were conducted in the breathing zone for three different exposure durations (0-15 min, 0-30 min, and 0-60 min). Fifty different chemicals were identified for evaluation and results indicate that 21 of the 50 chemicals tested were in the air of the overhaul environment. Respirable particles and formaldehyde were consistently present above the American Conference of Governmental Industrial Hygienists (ACGIH®) recommended exposure level (REL) and threshold limit ceiling value (TLVc), respectively. Each filter effectively reduced concentrations for respirable particulates below the maximum recommended level. Formaldehyde was reduced, but not consistently filtered below the TLVc. These results were consistent across all exposure durations. This study indicates that, regardless of brand, CBRN filters provide protection from the vast majority of particle and gas-phase contaminants. However, due to formaldehyde breakthrough, CBRN filters do not provide complete protection during firefighter overhaul.


Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro.
High concentrations of lidocaine induce irreversible conduction block with little effect on resting membrane potential (Em). We assumed the mechanism of persistent neurologic deficit caused by local anesthetics may result from neural death, as represented by the loss of Em. We investigated the effects of lidocaine on Em and action potential (AP) in single crayfish giant axons in vitro. Axons were perfused with two doses of lidocaine for either 15 or 30 min, and they were continuously washed. No axons exposed to 80 mM lidocaine for 30 min showed recovery of AP and Em. Those exposed to 40 mM for 30 min and 80 mM for 15 min showed a return to baseline for Em, but no recovery of AP. Those exposed to 40 mM lidocaine for 15 min showed full recovery of Em and AP immediately after washing. The membrane depolarization was significantly greater during exposure to 80 mM lidocaine for 30 min than in other groups. We conclude that lidocaine has a direct neurotoxic effect on crayfish giant axons and that the generation of AP is more vulnerable than the maintenance of Em. The irreversibility of AP and Em is dose- and time-dependent. Highly concentrated lidocaine induced an irreversible conduction block and a complete loss of resting membrane potential in crayfish giant axons in vitro. Our results may represent a possible explanation for various grades of local anesthetic-induced neurotoxicity in clinical cases if the same toxicity occurs in mammalian nerves in vivo.


Coherent total internal reflection dark-field microscopy: label-free imaging beyond the diffraction limit.
Coherent imaging is barely applicable in life-science microscopy due to multiple interference artifacts. Here, we show how these interferences can be used to improve image resolution and contrast. We present a dark-field microscopy technique with evanescent illumination via total internal reflection that delivers high-contrast images of coherently scattering samples. By incoherent averaging of multiple coherent images illuminated from different directions we can resolve image structures that remain unresolved by conventional (incoherent) fluorescence microscopy. We provide images of 190 nm beads revealing resolution beyond the diffraction limit and slightly increased object distances. An analytical model is introduced that accounts for the observed effects and which is confirmed by numerical simulations. Our approach may be a route to fast, label-free, super-resolution imaging in live-cell microscopy.


Comparison of the prophylactic use of magnesium trisilicate mixture B.P.C., sodium citrate mixture or cimetidine in obstetrics.
The effects of magnesium trisilicate mixture B.P.C., sodium citrate mixture or cimetidine on gastric pH and aspirated gastric volumes were compared in 78 obstetric patients during elective (a), or emergency (b) surgery. Magnesium trisilicate mixture B.P.C. was associated with the most alkaline values of gastric pH (mean (a) 7.9, (b) 7.3; range 2.9-9.1). Sodium citrate 0.3 mol litre-1 mixture resulted in the narrowest range of pH values of gastric contents (mean (a) 5.4, (b) 5.9; range 3.9-7.7). The ranges of aspirated gastric volumes were wide with both antacid regimens (magnesium trisilicate 12-172 ml, sodium citrate 9-290 ml). Cimetidine increased gastric pH to greater than 2.5 in 82% of patients (mean (a) 6.2, (b) 5.0; range 1.6-7.3), and was associated with significantly smaller volumes of aspirated gastric contents (range 0.5-44 ml). When gastric pH and volume were considered together, the groups of patients who received cimetidine were found to be closest to the defined "safe limits", of pH greater than 2.5 and volume less than 25 ml.


NMR characterization and solution structure determination of the oxidized cytochrome c7 from Desulfuromonas acetoxidans.
The solution structure of the three-heme electron transfer protein cytochrome c7 from Desulfuromonas acetoxidans is reported. The determination of the structure is obtained through NMR spectroscopy on the fully oxidized, paramagnetic form. The richness of structural motifs and the presence of three prosthetic groups in a protein of 68 residues is discussed in comparison with the four-heme cytochromes c3 already characterized through x-ray crystallography. In particular, the orientation of the three hemes present in cytochrome c7 is similar to that of three out of four hemes of cytochromes c3. The reduction potentials of the individual hemes, which have been obtained through the sequence-specific assignment of the heme resonances, are discussed with respect to the properties of the protein matrix. This information is relevant for any attempt to understand the electron transfer pathway.


Reactions of nucleic acid bases with alpha-acetylenic esters. Chemical modification of poly(A) and poly(C).
The reaction of chlorotetrolic (4-chloro-2-butynoic) esters with adenine and cytosine derivatives, in which a new heterocycle bearing an alkylating chloromethyl side chain is fused to the purine or pyrimidine ring, was extended to poly(A) and poly(C) used as models of nucleic acids. The derivatization proceeds under mild conditions and its extent can be controlled by the reaction time. The additional rings can exist in two isomeric forms and the nature of the isomer formed depends on steric factors in the vicinity of the reacting base. The reaction with chlorotetrolic esters discriminates between the single-stranded (reactive) and double-stranded (unreactive) forms, between the exposed an hidden adenine and cytosine bases and even between the exposed and sterically hindered fragments of the base moiety and thus allows structural investigations of these nucleic acids. The chloromethyl group of the derivatized nucleobases can be used to bind the modified polymers to other molecules.


Nanoplankton population dynamics and dissolved oxygen change across the Bay of Izmir by neural networks.
The bay of Izmir, which is the biggest harbor on the Aegean Sea, is of upmost economical importance for Izmir, the third largest city in Turkey. Most of the studies carried out focused on the effects of intensive industrial activity and agricultural production on the bay pollution within the region. These studies, most of the time, are limited to monitoring the level of pollution. However, it is believed that these studies should be supported with models and statistical analysis techniques, as the models, especially the prediction ones, provide an important approach to assessing risk and assessment. In this study, neural network analysis was used to construct prediction models for nanoplankton population change with nutrients and other environmentally important parameters. The results indicated that, using data over a 52 week period, it is possible to predict nanoplankton population dynamics and dissolved oxygen change for the future.


The VIOXX in Prostate Cancer Prevention study: cardiovascular events observed in the rofecoxib 25 mg and placebo treatment groups.
A double-blind, randomized, placebo-controlled study was designed to determine the cumulative incidence of developing prostate cancer over 6 years of treatment with rofecoxib 25 mg/day versus placebo. Before completion, this trial was terminated following the voluntary withdrawal of rofecoxib. (On September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of rofecoxib from the market.) Here we report the cardiovascular (CV) safety data collected from this study. A total of 4741 men (44-81 years old) exhibiting prostate-specific antigen levels (PSA) between 2.5 and 10 ng/mL were enrolled. Patients were stratified by PSA level and use of low-dose aspirin (LDA), then randomized to rofecoxib 25 mg (n = 2369) or placebo (n = 2372). Safety data were analyzed in all patients receiving > or = 1 dose of study medication. All reported thrombotic CV events occurring on-treatment or within 14 days after study drug discontinuation were adjudicated by an independent panel of clinical experts blinded to treatment assignment. Rates per 100 patient-years and relative risk (RR) of thrombotic CV events, rofecoxib vs. placebo, were determined. Approximately 36% of patients had > or = 2 CV risk factors or LDA indicated. Median treatment duration was 4.14 (range: 0.03-15.90) months. Twenty-nine patients (14 rofecoxib, rate 1.27; 15 placebo, rate 1.36) experienced confirmed thrombotic CV events; RR 0.94 (95% CI: 0.45, 1.94) vs. placebo. Four patients (one rofecoxib; three placebo) died due to a confirmed thrombotic event. Significantly (p = 0.002) more patients receiving rofecoxib (n = 20; 0.8%) experienced hypertension-related adverse events versus placebo (n = 2; 0.1%). There were no cases of congestive heart failure. Rofecoxib 25 mg and placebo demonstrated similar risk of thrombotic CV events in this limited dataset.


Aging, spaced retrieval, and inflexible memory performance.
Spaced retrieval is a memory-training technique whereby information is tested at progressively longer delays. Two experiments were conducted in order to examine the effects of spaced retrieval on controlled recollection and automatic influences of memory. In Experiment 1, word pairs were read once, three times, or once and retrieved twice by young and older adults. Retrieval practice improved performance on a later test for both age groups. Experiment 2 was arranged so that recollection opposed automatic influences of retrieval practice. Retrieval practice increased intrusions on a later test only for older adults. Results suggest that because of a deficit in recollection, older adults were less able to oppose the automatic influence of spaced retrieval and thus exhibited less flexible memory performance.


Next generation sequencing of fecal DNA reveals the dietary diversity of the widespread insectivorous predator Daubenton's Bat (Myotis daubentonii) in Southwestern Finland.
Understanding predator-prey dynamics is a fundamental task in the evaluation of the adaptive capacities of species. However, direct observations or morphological identification of fecal remains do not offer an effective way to study the dietary ecology of elusive species, such as nocturnal insectivorous bats. However, recent advances in molecular techniques have opened a new method for identifying prey species from fecal samples. In this study, we amplified species-specific mitochondrial COI fragments from fecal DNA extractions from 34 individual Daubenton's bats (Myotis daubentonii) collected between 2008 and 2010 from southwestern Finland. Altogether, 128 different species of prey were identified based on a comprehensive local DNA reference library. In our study area, Daubenton's bats feed most frequently on insects of the orders Diptera (found in the diet of 94% individuals), Trichoptera (69%) and Lepidoptera (63%). The most frequent dipteran family in the diet was Chironomidae, which was found in 31 of 34 individuals. Most common prey species were chironomids Microtendipes pedellus (found in 50% of bats), Glyptotendipes cauliginellus (44%), and Procladius ferrugineus (41%). For the first time, an accurate species level list of the diet of the insectivorous Daubenton's bat (Myotis daubentonii) in Finland is presented. We report a generally applicable method for describing the arthropod diet of vertebrate predators. We compare public databases to a national database to highlight the importance of a local reference database.


A comparison of symptoms between Swedish and American post-polio individuals and assessment of lower limb strength--a four-year cohort study.
A cohort study with initial and 4-year follow-up evaluations was performed in 78 post-polio volunteers aged 34-65 years at the time of enrolment in the study, which was made to compare post-polio individuals living in Sweden and the United States, to determine whether lower limb musculature becomes weaker over time, and to determine whether individuals with complaints of post-polio syndrome, new weakness, fatigue, walking or stair climbing difficulty were weaker or lost more strength over a 4-year interval than those individuals without such complaints. Dynametrically-measured knee extensor and flexor strength and questionnaire data were obtained initially and 4 years later. The two cohorts were fairly similar, though they differed in weight gain. The Americans gained significantly (p < 0.05) more weight than the Swedish subjects. Both groups lost significant (p < 0.05) knee extensor strength (approximately 8%), but the loss was not significantly (p < 0.05) different between the groups. Knee flexor strength did not change significantly (p < 0.05) over time. Subjects acknowledging new strength loss were not significantly (p < 0.05) weaker than those denying strength loss; however, they lost significantly (p < 0.05) more isometric knee extensor strength than the other individuals. Subjects acknowledging new fatigue, walking or stair climbing difficulty were significantly (p < 0.05) weaker in both muscle groups than those without such complaints. Subjects acknowledging post-polio syndrome were significantly (p < 0.05) weaker than those denying this symptom, but the amount of loss of strength over time was not significantly (p < 0.05) different. We conclude that the two cohorts were quite similar. Knee extensor strength decreased during the study interval. Individuals acknowledging post-polio syndrome had weaker knee extensor musculature. Subjects with new fatigue, walking difficulty, or stair climbing difficulty were weaker in both the knee extensors and the knee flexors than the other subjects. Subjects reporting new muscle weakness also had a greater decline in isometric knee extensor strength during the study interval than those without such complaint.


The inhibitory effect of MEG3/miR-214/AIFM2 axis on the growth of T-cell lymphoblastic lymphoma.
T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy with poor prognosis and high recurrence rate. Long non-coding RNA (lncRNA)-MEG3 is an important tumor suppressor in various cancers. The present study investigated the potential role of maternally expressed gene 3 (MEG3) in the progression of T-LBL. Suppressed expression of MEG3 was detected in T-LBL tissues compared with adjacent histologically normal tissues. Down-regulated level of MEG3 was also found in three T-LBL cell lines (CCRF-CEM, Jurkat and SUP-T1) compared with human T-cell line H9. The proliferation of T-LBL cells was inhibited and cell apoptosis rate was largely promoted when MEG3 was upregulated by a lentiviral vector. Further research revealed that microRNA (miRNA)-214 is a direct target of MEG3. The expression of miR-214 was increased in T-LBL tissues and cell lines compared with control groups. Besides, decreased level of miR-214 was elevated adding miR-214 mimic in SUP-T1 cells transfected with LncRNA-MEG3. Similarly, upregulated level of miR-214 was downregulated adding miR-214 inhibitor in SUP-T1 cells transfected with MEG3 siRNA. Luciferase activity assay further confirmed the targeting relationship between MEG3 and miR-214. Moreover, AIFM2 protein was predicted as a target of miR-214. The expression of AIFM2 was increased by MEG3 and was downregulated by miR-214 mimic. miRNA-214 reversed the effect of MEG3 on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest in SUP-T1 cells. Moreover, relative expression of AIFM2 had a positive correlation with the expression of MEG3 and was negatively affected by miR-214. In vivo, MEG3 effectively suppressed tumor growth and the expression of proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA). Taken together, our research revealed that MEG3 worked as an anti-oncogene in T-LBL, and the MEG3-miR-214-AIFM2 pathway regulated the growth of T-LBL, providing potential prognosis markers as well as new potential targets for T-LBL treatment.


Reduced glucose metabolism enhances the glutamate-evoked release of arachidonic acid from striatal neurons.
Glucose deprivation potentiates the glutamate receptor-evoked release of arachidonic acid from cultured mouse striatal neurons. In this study we investigated whether this potentiation would be modified by the end-products of glycolysis. These enhanced responses were completely reversed by the addition of increasing concentrations of either lactate or pyruvate. This reversal was not due to increased osmolarity as substituting sucrose for lactate or pyruvate did not mimic their effects. In contrast, in the presence of glucose, neither lactate nor pyruvate was effective. Furthermore, these monocarboxylic acids rescued neuronal respiration in the absence of glucose. Inhibiting glycolysis with iodoacetate in the presence of glucose reproduced the potentiated glutamate-evoked release of arachidonic acid observed following glucose deprivation and reduced neuronal respiration to the same extent as that observed in the absence of glucose. All of these effects were overcome by the addition of either lactate or pyruvate. The reversal of the potentiated glutamate-evoked release of arachidonic acid by lactate or pyruvate was inhibited by a specific inhibitor of monocarboxylic acid transport, alpha-cyano-4-hydroxycinnamic acid, suggesting that lactate and pyruvate act intracellularly. Therefore, we propose that the enhanced release of arachidonic acid evoked by glutamate during glucose deprivation results from reduced glycolysis and hence from a depletion of lactate or pyruvate.


Activating NK cell receptor ligands are differentially expressed during progression to cervical cancer.
Human papillomavirus-induced cervical carcinomas often show impaired expression of MHC class I molecules resulting in the inability of tumor cells to directly present viral peptides to cytotoxic T lymphocytes. Loss of MHC class I expression combined with the expression of activating NK cell receptor ligands renders tumor cells potentially susceptible to NK cell attack. Thus, in this study, we analyzed the expression of activating NK cell receptor ligands, NK cell accumulation and activation status in situ in normal ectocervical tissue (NCT), cervical intraepithelial neoplasia (CIN) and squamous cervical carcinoma (CxCa). We observed that expression of the DNAM-1 ligand CD155 was frequently upregulated in CxCa, but not in CIN. The NKG2D ligand MICA was upregulated in fewer CxCa biopsies. In contrast, another NKG2D ligand ULBP2 was preferentially expressed in differentiated epithelial cells of NCT. Increased numbers of NK cells were detected in CIN as compared to NCT and CxCa. Expression of activating NK cell receptor ligands combined with loss of MHC class I was not correlated with enhanced NK cell accumulation or activation status. Furthermore, we demonstrate that cervical cancer cell lines are killed by the NK cell line, NKL, in a NKG2D- and DNAM-1-dependent manner in vitro. Since a significant number of CxCa biopsies showed low MHC class I expression combined with high expression of one or more of the tested activating NK cell receptor ligands, we conclude that CxCa might be a promising target for NK cell-based adoptive immunotherapy.


Causes and risk factors for liver injury following bone marrow transplantation.
A retrospective study of pretransplantation risk factors predisposing to liver injury following bone marrow transplantation (BMT). Liver complications are a major cause of morbidity and mortality following BMT. Determination of the pretransplantation factors that are likely to lead to liver injury may allow earlier diagnosis after BMT and may possibly improve prognosis. Medical records of BMT patients were reviewed, and results of serial liver function tests and HBV/HCV serology during the pre- and posttransplantation 1-year period were noted. Presence of liver injury was defined as alanine aminotransferase levels twice the upper limit of normal. Forty-four allogeneic and 17 autologous BMTs, performed between 1990 and 2000, were analyzed in the study. One-year survival was 77% (34 of 44 patients) for allogeneic BMT and 52% (9 of 17 patients) for autologous BMT. Seventy-two percent (32 of 44) of allogeneic transplant recipients and 47% (8 of 17) of autologous transplant recipients had liver injury during the first year of BMT. The most frequent causes of liver injury were graft-versus-host disease and drug hepatotoxicity for allogeneic BMT and drug hepatotoxicity for autologous BMT. Fulminant hepatic failure occurred in one allogeneic transplant recipient who was a pretransplantation HBV carrier and led to death. Multivariate regression analysis showed that pretransplantation HBV/HCV positivity and pretransplantation elevated liver enzyme levels of any cause were predictive risk factors for post-BMT liver injury, and close follow-up, early diagnosis, and treatment are highly recommended for BMT patients with these risk factors.


Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms.
Autologous bone marrow-derived or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials, but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is the key toward improving clinical outcomes. To determine the mechanism by which novel bone-derived stem cells support the injured heart. Cortical bone-derived stem cells (CBSCs) and cardiac-derived stem cells were isolated from enhanced green fluorescent protein (EGFP+) transgenic mice and were shown to express c-kit and Sca-1 as well as 8 paracrine factors involved in cardioprotection, angiogenesis, and stem cell function. Wild-type C57BL/6 mice underwent sham operation (n=21) or myocardial infarction with injection of CBSCs (n=67), cardiac-derived stem cells (n=36), or saline (n=60). Cardiac function was monitored using echocardiography. Only 2/8 paracrine factors were detected in EGFP+ CBSCs in vivo (basic fibroblast growth factor and vascular endothelial growth factor), and this expression was associated with increased neovascularization of the infarct border zone. CBSC therapy improved survival, cardiac function, regional strain, attenuated remodeling, and decreased infarct size relative to cardiac-derived stem cells- or saline-treated myocardial infarction controls. By 6 weeks, EGFP+ cardiomyocytes, vascular smooth muscle, and endothelial cells could be identified in CBSC-treated, but not in cardiac-derived stem cells-treated, animals. EGFP+ CBSC-derived isolated myocytes were smaller and more frequently mononucleated, but were functionally indistinguishable from EGFP- myocytes. CBSCs improve survival, cardiac function, and attenuate remodeling through the following 2 mechanisms: (1) secretion of proangiogenic factors that stimulate endogenous neovascularization, and (2) differentiation into functional adult myocytes and vascular cells.


BnpC: Bayesian non-parametric clustering of single-cell mutation profiles.
The high resolution of single-cell DNA sequencing (scDNA-seq) offers great potential to resolve intratumor heterogeneity (ITH) by distinguishing clonal populations based on their mutation profiles. However, the increasing size of scDNA-seq datasets and technical limitations, such as high error rates and a large proportion of missing values, complicate this task and limit the applicability of existing methods. Here, we introduce BnpC, a novel non-parametric method to cluster individual cells into clones and infer their genotypes based on their noisy mutation profiles. We benchmarked our method comprehensively against state-of-the-art methods on simulated data using various data sizes, and applied it to three cancer scDNA-seq datasets. On simulated data, BnpC compared favorably against current methods in terms of accuracy, runtime and scalability. Its inferred genotypes were the most accurate, especially on highly heterogeneous data, and it was the only method able to run and produce results on datasets with 5000 cells. On tumor scDNA-seq data, BnpC was able to identify clonal populations missed by the original cluster analysis but supported by Supplementary Experimental Data. With ever growing scDNA-seq datasets, scalable and accurate methods such as BnpC will become increasingly relevant, not only to resolve ITH but also as a preprocessing step to reduce data size. BnpC is freely available under MIT license at https://github.com/cbg-ethz/BnpC. Supplementary data are available at Bioinformatics online.


Evaluation of stAPP: a smartphone-based intervention to reduce prolonged sitting among Belgian adults.
Excessive uninterrupted sitting, also known as sedentary behavior, has been detrimentally associated with several health outcomes. However, the general population is often unaware of these health risks. Mobile phone technology offers great potential to increase awareness and to initiate behavior change. This study examined the short-term effects of stAPP, a smartphone-based intervention, on prolonged sitting behavior. Fifty-eight participants were randomly assigned to an intervention group (IG, n = 31) or a control group (CG, n = 27). After 1 week of baseline assessment, the IG received stAPP (i.e. smartphone, smartphone app and corresponding motion sensor) and used it during the following week. CG participants were monitored during 2 weeks without receiving stAPP. Total daily sitting time and prolonged sitting bouts (>30 min bouts of sitting) were objectively assessed using activPAL3 inclinometers. Although no significant changes emerged in the CG in any of the sitting parameters, total sitting time (on weekdays; p = 0.032), number of prolonged sitting bouts (>30 min of sitting) [both on week- (p < 0.001) and weekend days (p = 0.008)] and average duration of prolonged sitting bouts [both on week- (p = 0.004) and weekend days (p = 0.029)] decreased significantly in the IG. The stAPP smartphone-based intervention constitutes a promising intervention tool to interrupt and reduce prolonged sitting behavior. Further long-term studies on a larger scale are needed to further explore the effectiveness of a smartphone-based intervention aimed at reducing prolonged sitting behavior.


Deficiency in Calcium-Binding Protein S100A4 Impairs the Adjuvant Action of Cholera Toxin.
The calcium-binding protein S100A4 has been described to promote pathological inflammation in experimental autoimmune and inflammatory disorders and in allergy and to contribute to antigen presentation and antibody response after parenteral immunization with an alum-adjuvanted antigen. In this study, we extend these findings by demonstrating that mice lacking S100A4 have a defective humoral and cellular immune response to mucosal (sublingual) immunization with a model protein antigen [ovalbumin (OVA)] given together with the strong mucosal adjuvant cholera toxin (CT), and that this impairment is due to defective adjuvant-stimulated antigen presentation by antigen-presenting cells. In comparison to wild-type (WT) mice, mice genetically lacking S100A4 had reduced humoral and cellular immune responses after immunization with OVA plus CT, including a complete lack of detectable germinal center reaction. Further, when stimulated in vitro with OVA plus CT, S100A4-/- dendritic cells (DCs) showed impaired responses in several CT-stimulated immune regulatory molecules including the co-stimulatory molecule CD86, inflammasome-associated caspase-1 and IL-1β. Coculture of OVA-specific OT-II T cells with S100A4-/- DCs that had been pulse incubated with OVA plus CT resulted in impaired OT-II T cell proliferation and reduced production of Th1, Th2, and Th17 cytokines compared to similar cocultures with WT DCs. In accordance with these findings, transfection of WT DCs with S100A4-targeting small interfering RNA (siRNA) but not mock-siRNA resulted in significant reductions in the expression of caspase-1 and IL-1β as well as CD86 in response to CT. Importantly, also engraftment of WT DCs into S100A4-/- mice effectively restored the immune response to immunization in the recipients. In conclusion, our results demonstrate that deficiency in S100A4 has a strong impact on the development of both humoral and cellular immunity after mucosal immunization using CT as adjuvant.


True stabilization energies for the optimal planar hydrogen-bonded and stacked structures of guanine...cytosine, adenine...thymine, and their 9- and 1-methyl derivatives: complete basis set calculations at the MP2 and CCSD(T) levels and comparison with experiment.
Planar H-bonded and stacked structures of guanine...cytosine (G.C), adenine...thymine (A...T), 9-methylguanine...1-methylcytosine (mG...mC), and 9-methyladenine...1-methylthymine (mA...mT) were optimized at the RI-MP2 level using the TZVPP ([5s3p2d1f/3s2p1d]) basis set. Planar H-bonded structures of G...C, mG...mC, and A...T correspond to the Watson-Crick (WC) arrangement, in contrast to mA...mT for which the Hoogsteen (H) structure is found. Stabilization energies for all structures were determined as the sum of the complete basis set limit of MP2 energies and a (DeltaE(CCSD(T)) - DeltaE(MP2)) correction term evaluated with the cc-pVDZ(0.25,0.15) basis set. The complete basis set limit of MP2 energies was determined by two-point extrapolation using the aug-cc-pVXZ basis sets for X = D and T and X = T and Q. This procedure is required since the convergency of the MP2 interaction energy for the present complexes is rather slow, and it is thus important to include the extrapolation to the complete basis set limit. For the MP2/aug-cc-pVQZ level of theory, stabilization energies for all complexes studied are already very close to the complete basis set limit. The much cheaper D-->T extrapolation provided a complete basis set limit close (by less than 0.7 kcal/mol) to the more accurate T-->Q term, and the D-->T extrapolation can be recommended for evaluation of complete basis set limits of more extended complexes (e.g. larger motifs of DNA). The convergency of the (DeltaE(CCSD(T)) - DeltaE(MP2)) term is known to be faster than that of the MP2 or CCSD(T) correlation energy itself, and the cc-pVDZ(0.25,0.15) basis set provides reasonable values for planar H-bonded as well as stacked structures. Inclusion of the CCSD(T) correction is essential for obtaining reliable relative values for planar H-bonding and stacking interactions; neglecting the CCSD(T) correction results in very considerable errors between 2.5 and 3.4 kcal/mol. Final stabilization energies (kcal/mol) for the base pairs studied are very substantial (A...T WC, 15.4; mA...mT H, 16.3; A...T stacked, 11.6; mA...mT stacked, 13.1; G...C WC, 28.8; mG...mC WC, 28.5; G...C stacked, 16.9; mG...mC stacked, 18.0), much larger than published previously. On the basis of comparison with experimental data, we conclude that our values represent the lower boundary of the true stabilization energies. On the basis of error analysis, we expect the present H-bonding energies to be fairly close to the true values, while stacked energies are still expected to be about 10% too low. The stacking energy for the mG...mC pair is considerably lower than the respective H-bonding energy, but it is larger than the mA...mT H-bonding energy. This conclusion could significantly change the present view on the importance of specific H-bonding interactions and nonspecific stacking interactions in nature, for instance, in DNA. Present stabilization energies for H-bonding and stacking energies represent the most accurate and reliable values and can be considered as new reference data.


[Changes in intraocular pressure during prostaglandin-induced abortion (author's transl)].
Experimental animal studies have shown that local or systemic application of prostaglandin produces an acute increase in intraocular pressure. Investigations were carried out in 17 women undergoing prostaglandin-induced abortions to determine whether any changes in IOP occurred. In 16 of the patients there was no evidence of any effect; in the other one there was a transient moderate pressure elevation.


Long-term hypercoagulability, endotheliopathy and inflammation following acute SARS-CoV-2 infection.
both symptomatic and asymptomatic SARS-CoV-2 infections - coined Coronavirus disease 2019 (COVID-19) - have been linked to a higher risk of cardiovascular events after recovery. our review aims to summarize the latest evidence on the increased thrombotic and cardiovascular risk in recovered COVID-19 patients and to examine the pathophysiological mechanisms underlying the interplay among endothelial dysfunction, inflammatory response and coagulation in long-COVID. We performed a systematic search of studies on hypercoagulability, endothelial dysfunction and inflammation after SARS-CoV-2 infection. endothelial dysfunction is a major pathophysiological mechanism responsible for most clinical manifestations in COVID-19. The pathological activation of endothelial cells by a virus infection results in a pro-adhesive and chemokine-secreting phenotype, which in turn promotes the recruitment of circulating leukocytes. Cardiovascular events after COVID-19 appear to be related to persistent immune dysregulation. Patients with long-lasting symptoms display higher amounts of proinflammatory molecules such as tumor necrosis factor-α, interferon γ and interleukins 2 and 6. Immune dysregulation can trigger the activation of the coagulation pathway. The formation of extensive microclots in vivo, both during acute COVID-19 and in long-COVID-19, appears to be a relevant mechanism responsible for persistent symptoms and cardiovascular events.


Use of systemic disease signs to assess disease severity in dairy cows with acute coliform mastitis.
To evaluate the use of systemic disease signs for classifying severity of acute coliform mastitis in dairy cows. Prospective cohort study. 144 dairy cows. Cows were examined at the time of initial identification of disease (time 0) and classified as having mild, moderate, or severe disease on the basis of rectal temperature, hydration status, rumen contraction rate, and attitude. A CBC and serum biochemical analyses were performed, and milk samples were submitted for bacterial culture at time 0 and 48 hours later. 69 cows were classified as having mild disease, 44 as having moderate disease, and 31 as having severe disease. Median WBC and neutrophil counts were significantly lower in cows with moderate or severe disease at time 0 than in cows with mild disease. Band neutrophil count was significantly higher at 48 hours and serum calcium concentration was significantly lower at time 0 and at 48 hours in cows with severe or moderate disease, compared with cows with mild disease. Twenty-eight, 51, and 77% of cows with mild, moderate, and severe disease, respectively, had > 100,000 colony-forming units/ml of milk at time 0. The odds that a cow with severe disease would die or be culled were 3.6 times the odds for a cow with moderate disease and 11.2 times the odds for a cow with mild disease. Results suggest that a classification scheme based on readily observable systemic disease signs can be used to classify disease severity in cows with acute coliform mastitis.


Age differences in the impact of peers on adolescents' and adults' neural response to reward.
Prior research suggests that increased adolescent risk-taking in the presence of peers may be linked to the influence of peers on the valuation and processing of rewards during decision-making. The current study explores this idea by examining how peer observation impacts the processing of rewards when such processing is isolated from other facets of risky decision-making (e.g. risk-perception and preference, inhibitory processing, etc.). In an fMRI paradigm, a sample of adolescents (ages 14-19) and adults (ages 25-35) completed a modified High/Low Card Guessing Task that included rewarded and un-rewarded trials. Social context was manipulated by having participants complete the task both alone and while being observed by two, same-age, same-sex peers. Results indicated an interaction of age and social context on the activation of reward circuitry during the receipt of reward; when observed by peers adolescents exhibited greater ventral striatal activation than adults, but no age-related differences were evinced when the task was completed alone. These findings suggest that, during adolescence, peers influence recruitment of reward-related regions even when they are engaged outside of the context of risk-taking. Implications for engagement in prosocial, as well as risky, behaviors during adolescence are discussed.


Optical trap stiffness in the presence and absence of spherical aberrations.
Optical traps are commonly constructed with high-numerical-aperture objectives. Oil-immersion objectives suffer from spherical aberrations when used for imaging in aqueous solutions. The effect of spherical aberrations on trapping strength has been modeled by approximation, and only a few experimental results are available in the case of micrometer-sized particles. We present an experimental study of the dependence of lateral and axial optical-trap stiffness on focusing depth for polystyrene and silica beads of 2 microm diameter by using oil- and water-immersion objectives. We demonstrate a strong depth dependence of trap stiffness with the oil-immersion objective, whereas no depth dependence was observed with the water-immersion objective.


Propagation of cold atoms along a miniature magnetic guide
A cloud of laser-cooled 85Rb atoms is coupled through a magnetic funnel into a miniature waveguide formed by four current-carrying wires embedded in a silica fiber. The atom cloud has a approximately 100 &mgr;m radius within the fiber and propagates over cm distances. We study the coupling, propagation, and transverse distribution of atoms in the fiber, and find good agreement with theory. This prototype demonstrates the feasibility of miniature guides as a tool in the new field of integrated atom optics, leading to single-mode propagation of de Broglie waves and the possible preparation of 1D atom clouds.


Role of apoptosis resistance in immune evasion and metastasis of colorectal cancer.
The host immune system functions as a guardian against tumor development. It has been demonstrated that cytotoxic T lymphocyte (CTL)-mediated cytotoxic pathways function to inhibit or delay human colorectal cancer development. However, the host anti-tumor immune responses also 'edit' the tumor and select for more aggressive variants, resulting in immune evasion and tumor escape. Fas is a death receptor that mediates one of the major cytotoxic effector mechanisms of the CTLs. Fas is highly expressed in normal human colon epithelial cells but is frequently silenced in colorectal carcinoma, especially in metastatic colorectal carcinoma, suggesting that loss of Fas expression and function may be an immune evasion and tumor escape mechanism. In addition, recent studies indicated that Fas also mediates cellular proliferation signaling pathways to promote tumor development. Therefore, the death receptor Fas may not only transduce death signals to suppress tumor development but also activate cellular proliferation and the migration process to promote tumor growth and progression. Thus, understanding the mechanisms by which the Fas receptor and its associated protein complex transduces the death and survival signals may identify molecular targets for the development of therapeutic strategy to enhance the Fas-mediated death signals to increase the efficacy of cancer immunotherapy.


[The medical expert and his standards].
The expert needs clearly outlined principles which are accepted by the majority of carefully and scrupulously working physicians. These principles are world-wide known as standards. They can be changed by progress in medical science. Their value is restricted by the fact that in the particular case with its individual peculiarities they may be of no help. Presenting a few cases, some problems for the medical expert are shown. Cardiotocography, Apgar-score, ureter, problems of organisation, the lethal outcome and the difficulties of preoperative information of the patient find particular consideration. The importance of the dialogue between physician and lawery is pointed out.


Are people with autism prosopagnosic?
Difficulties in various face processing tasks have been well documented in autism spectrum disorder (ASD). Several meta-analyses and numerous case-control studies have indicated that this population experiences a moderate degree of impairment, with a small percentage of studies failing to detect any impairment. One possible account of this mixed pattern of findings is heterogeneity in face processing abilities stemming from the presence of a subpopulation of prosopagnosic individuals with ASD alongside those with normal face processing skills. Samples randomly drawn from such a population, especially relatively smaller ones, would vary in the proportion of participants with prosopagnosia, resulting in a wide range of group-level deficits from mild (or none) to severe across studies. We test this prosopagnosic subpopulation hypothesis by examining three groups of participants: adults with ASD, adults with developmental prosopagnosia (DP), and a comparison group. Our results show that the prosopagnosic subpopulation hypothesis does not account for the face impairments in the broader autism spectrum. ASD observers show a continuous and graded, rather than categorical, heterogeneity that span a range of face processing skills including many with mild to moderate deficits, inconsistent with a prosopagnosic subtype account. We suggest that pathogenic origins of face deficits for at least some with ASD differ from those of DP.


The Soleus Muscle Flap: An Overview of Its Clinical Applications for Lower Extremity Reconstruction.
Lower extremity reconstruction often poses several challenges for the reconstructive surgeon. Because of limited local tissue options, patients who sustain extensive middle to distal third tibia fractures used to be at higher risk of limb loss without adequate soft tissue coverage. The traditional principle of reconstructing middle and distal third leg wounds with free tissue transfer is being challenged by advances in understanding of local muscle flap anatomy and surgical techniques to improve the efficacy of local flaps. In this article, we examine contemporary considerations, developed by the authors, for the appropriate indications of free tissue transfer versus use of local flaps such as the soleus muscle flap. We review the versatility and reliability of the soleus muscle as a local muscle option once the technique is mastered on how to safely and effectively design and execute this flap. We highlight the importance of an algorithmic approach to soft-tissue reconstruction of the lower extremity based on the best surgical option for the patient. This includes factors such as medical history, appropriate surgical candidacy, as well as the size and mechanism of injury to decide the most viable option for lower extremity reconstruction. We show that the medial hemisoleus muscle flap is a reliable local option, both by itself or in conjunction with other local flaps, to reconstruct less extensive wounds in the middle to distal third of the leg. Ultimately, such a local muscle flap must be mastered by the reconstructive surgeon to augment his or her armamentarium to provide a well-rounded reconstructive plan in managing the soft-tissue wound, while minimizing donor-site morbidity and potentially be more cost-effective in nature.


Genetic variations in G-quadruplex forming sequences affect the transcription of human disease-related genes.
Guanine-rich DNA strands can fold into non-canonical four-stranded secondary structures named G-quadruplexes (G4s). G4s folded in proximal promoter regions (PPR) are associated either with positive or negative transcriptional regulation. Given that single nucleotide variants (SNVs) affecting G4 folding (G4-Vars) may alter gene transcription, and that SNVs are associated with the human diseases' onset, we undertook a novel comprehensive study of the G4-Vars genome-wide (G4-variome) to find disease-associated G4-Vars located into PPRs. We developed a bioinformatics strategy to find disease-related SNVs located into PPRs simultaneously overlapping with putative G4-forming sequences (PQSs). We studied five G4-Vars disturbing in vitro the folding and stability of the G4s located into PPRs, which had been formerly associated with sporadic Alzheimer's disease (GRIN2B), a severe familiar coagulopathy (F7), atopic dermatitis (CSF2), myocardial infarction (SIRT1) and deafness (LHFPL5). Results obtained in cultured cells for these five G4-Vars suggest that the changes in the G4s affect the transcription, potentially contributing to the development of the mentioned diseases. Collectively, data reinforce the general idea that G4-Vars may impact on the different susceptibilities to human genetic diseases' onset, and could be novel targets for diagnosis and drug design in precision medicine.


Social networks and health-promoting behaviors among North Korean refugees in South Korea.
Poor health behaviors among North Korean refugees (NKRs) in South Korea are serious risk factors hindering their overall well-being. Despite their significance, little is known about the roles of social networks in promoting health behaviors of NKRs. Thus, we examined how social network characteristics were associated with health-promoting behaviors among 202 NKRs. We found that social networks featuring members of religious organizations were positively associated with overall health-promoting behaviors, health responsibility, exercise, and nutrition, whereas networks with South Korean friends were negatively associated with nutrition. Findings suggest that health interventions facilitating religion-based network ties may promote health behaviors among NKRs.


Mindfulness and Executive Functions: Making the Case for Elementary School Practice.
This study explores the use of mindfulness school-based intervention program in an elementary school. Mindfulness training is an accepted and effective didactic approach to improve the executive functions (EFs) of elementary school students. This study aimed to evaluate the effects of the Mind Yeti program on the executive functions of elementary school students. A diverse sample of third, fourth, and fifth grade elementary school students (n = 177) participated in their natural classroom setting, with six sessions per week for six weeks. Students self-reported their EFs on the Executive Function Student Questionnaire (EFSQ) pre- and posttest. Paired-sample t-tests indicated that students significantly improved on the three of the six EFs examined. Additionally, students in fifth grade responded better to Mind Yeti than students in third grade. Results were consistent with the hypothesis, suggesting that Mind Yeti is an appropriate and effective intervention for improving the EFs of students.


What Is the Utility of Measuring Lactate Levels in Patients with Sepsis and Septic Shock?
Elevations in blood lactate concentrations have been studied in sepsis and other disease states for decades and are well known to be associated with increased mortality. Many studies have also demonstrated the prognostic accuracy of serial lactate levels, and some have suggested that lactate clearance may be a useful therapeutic target for resuscitation. Lactate measurements have therefore gained an increasingly prominent role in sepsis definitions, screening protocols, management guidelines, and quality measures over the past two decades. The heavy emphasis on lactate monitoring, however, has also generated controversy and concerns. Lactate is not specific to infection and its frequent use for sepsis screening and diagnosis may therefore trigger unnecessary broad-spectrum antibiotic use in some patients. Because hyperlactatemia does not always reflect fluid-responsive hypoperfusion, titrating resuscitation to lactate clearance can also lead to unnecessary fluid and volume overload. More broadly, there is a lack of high-quality evidence demonstrating that initial and serial lactate monitoring leads to better patient-centered outcomes. Indeed, a recent randomized controlled trial comparing resuscitation strategies based on lactate clearance versus normalizing capillary refill time showed no benefit and potential harm with lactate-guided therapy. In this article, we review the basic pathobiology of lactate metabolism and delineate why the traditional paradigm that hyperlactatemia reflects tissue hypoxia is overly simplistic and incomplete. We then review the evidence behind the diagnostic, prognostic, and therapeutic uses of lactate monitoring and place this in the context of evolving sepsis diagnosis and management guidelines.


Implementation of thyroid-related patient-reported outcomes in routine clinical practice.
Patient-reported outcomes (PROs) are increasingly used in clinical practice to improve clinical care. Multiple studies show that systematic use of PROs can enhance communication with patients and improve patient satisfaction, symptom management and quality of life. Further, such data can be aggregated to examine health levels for patient groups, improve quality of care, and compare patient outcomes at the institutional, regional or national level. However, there are barriers and challenges that should be handled appropriately to achieve successful implementation of PROs in routine clinical practice. This paper briefly overviews thyroid-related PROs, describes unsolved quality of life issues in benign thyroid diseases, provides examples of routine collection of PROs, and summarizes key points facilitating successful implementation of thyroid-related PROs in routine clinical practice. Finally, the paper touches upon future directions of PRO research.


Relationship between types of radiographic damage and disability in patients with rheumatoid arthritis in the EURIDISS cohort: a longitudinal study.
The aim of this study was to assess if any of the different types of radiographic damage [true joint space narrowing (JSN), (sub)luxation and erosions] are preferentially related to disability in patients with RA. Longitudinal data from 167 RA patients from the European Research on Incapacitating Diseases and Social Support study over 10 years were analysed to investigate the relationship between the three types of radiographic damage and disability [grip strength, HAQ and the dexterity scale in the Arthritis Impact Measurement Scales (AIMS)]. A longitudinal analysis including separate models per type of damage and joint group and combined models including all information was conducted. All types of damage were inversely related to grip strength in the analysis of separate models, but only true JSN independently remained statistically significant in the combined analysis [β = -0.087 (95% CI -0.151, -0.022)]. Neither JSN, (sub)luxation nor erosions were associated with HAQ score, while erosions were associated with AIMS dexterity only in the analysis of separate models. After stratifying for hand joint group, erosions at MCP joints [β = -0.288 (95% CI -0.556, -0.019)] and true JSN at the wrist [β = -0.132 (95% CI -0.234, -0.030)] were significantly related to grip strength. Erosions at the PIP [β = 0.017 (95% CI 0.005, 0.028)] and MCP joints [β = 0.114 (95% CI 0.010, 0.217)] was the only type of damage associated with HAQ and AIMS dexterity, respectively. All types of radiographically visible joint damage interfere with important aspects of physical functions. True JSN is most closely related to hand function.


Facial Nerve Schwannomas Mimicking as Vestibular Schwannomas.
Objective The objective of this study was to identify preoperative and intraoperative findings that may aid in distinguishing facial nerve schwannomas (FNS) from vestibular schwannomas (VSs), particularly in cases limited to the internal auditory canal (IAC) and cerebellopontine angle (CPA). Study Design This was a retrospective study. Setting This study was set at a Tertiary Referral Center. Patients Seventeen cases from October 2002 to July 2015 with an IAC/CPA mass presumed to be a VS who were found to have a FNS intraoperatively. Main Outcome Measures The main outcome measures included preoperative presentation, intraoperative findings, and subsequent intervention. Results Preoperative hearing loss and imbalance were seen in 70.5 and 64.7%, respectively. Suspicious intraoperative findings included: facial nerve incorporated intimately with the tumor capsule in 12 cases; spontaneous action potentials noted while drilling the bony IAC in 3 cases; and action potentials noted on stimulation of the entire tumor capsule in 10 cases. The mean long-term facial function was House-Brackmann grade II and the mean length of follow-up was 4.86 years. Conclusion FNSs are rare and may be difficult to distinguish from VS preoperatively. Surgical findings that should raise concern include spontaneous action potentials during drilling the bony IAC, absence of a plane of dissection between the facial nerve and tumor, or stimulation of the tumor capsule.


Determination of Michaelis parameters from differentials of progress curves.
First differentials of progress curves are easily obtainable in many enzyme assay systems. Such curves may be more readily applicable to kinetic analysis than are the usual progress curves. The theory for this approach is developed, and simple graphical procedures for the determination of Michaelis parameters are indicated. By using an electronic differentiator device the application of the method is demonstrated on the kinetics of three different serine proteinases with various synthetic substrates. Whenever the steady-state concentration of an intermediate of the reaction is proportional to the rate, the transition of this intermediate in substrate-depletion experiments may be analysed in similar terms. This is demonstrated with cytochrome c oxidase kinetics. A number of other possible applications are discussed.


Pediatric refractive surgery.
Refractive surgery procedures have been performed on children since the early 1980s. This article will review this history as well as current thoughts on treating children with large refractive errors. Pediatric refractive surgery has developed slowly as very few children fit the criteria for treatment. For this reason, practice patterns are varied and publications are rare. Publications in recent years have focused on intraocular procedures over laser refractive surgery. Pediatric refractive surgery is an evolving field as surgeons try to find the best long-term treatments for these young patients.


Sexual behaviour of in-school adolescents in Ibadan, South-West Nigeria.
This study was a crossectional survey conducted among 716 senior secondary school adolescents in Ibadan from March to August 2005. The result of 695 that was analyzed revealed that the mean age of 15 +/- 2.6years. 28.3% of the respondents had previous sexual exposure with higher proportions being male (p = 0.00043). Majorities' first sexual exposure was unplanned. Family settings and educational level do not have significant influence on the previous sexual exposure. The methods of sexual activity were mainly through vagina route while some had also practiced oral and anal sex. Most of those that are sexually exposed had more than one partner. About half of the respondents learn about sex from their friends while others through their parents and media. We conclude that in-school adolescents practiced unsafe sexual activity and they are therefore predisposed to STI/HIV and other reproductive health risks.


A Selective and Sensitive Gas Chromatography-Tandem Mass Spectrometry Method for Quantitation of Synthetic Musks in Human Serum.
Synthetic musk compounds are widely used as fragrances in many consumer products; however, information on human exposure and health effects is limited. Also, analytical methods for their quantification in biological matrices are limited. In this study, an integrated method was developed and validated for the analysis of selected synthetic musk compounds in human serum. The method is based on liquid-liquid extraction (LLE), sample clean-up by solid-phase extraction (SPE), and separation and detection by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The method demonstrated good recoveries (86-105%) and high sensitivity, with low method detection limits (MDLs) ranging from 0.04 to 0.17 µg/L. The method was applied to the analysis of 10 synthetic musk compounds in 40 serum samples collected from Canadian women aged 20-44 years (20 individual samples collected in 2014 and 20 pooled samples collected in 2006). The most commonly detected compound was Galaxolide (HHCB), with median concentrations of 0.59 µg/L in samples collected in 2006, and 0.34 µg/L for samples collected in 2014. Musk ketone (MK) was not detected in any of the samples collected in 2006, but was detected in 60% of the samples collected in 2014 with a median concentration of 0.29 µg/L. Tonalide (AHTN) was detected in only one sample above its MDL (0.12 µg/L). This is the first study in Canada to report levels of synthetic musks in human. The data generated from this study has been used in risk screening assessment by Environment and Climate Change Canada and Health Canada.


Efficacy of very high dose steroid treatment in a case of Landau-Kleffner syndrome.
Landau-Kleffner syndrome (LKS) is an acquired childhood aphasia associated with paroxysmal bitemporal electroencephalogram (EEG) abnormalities and, sometimes, clinical seizures. We report the case of a female aged 5 years 6 months who presented clinically with apparent hearing loss, deterioration in speech, and seizure activity over 12 days. The female had previous detailed speech/language assessments at 3 to 4 years of age due to articulation delay. LKS was diagnosed on EEG with bitemporal spike and wave activity during sleep. The patient was treated with high dose prednisolone 3mg/kg/day, intensive speech/language therapy, and followed a modified educational program. We recorded a marked regression in receptive and expressive language skills, as well as her speech, language, and cognitive profiles before and during treatment with prednisolone, during an 18-month follow-up period. The patient demonstrated an excellent clinical response highlighting the importance of a multidisciplinary approach to management of LKS.


A Generalized Sequential Bonferroni Procedure for GWAS in Admixed Populations Incorporating Admixture Mapping Information into Association Tests.
To develop effective methods for GWAS in admixed populations such as African Americans. We show that, when testing the null hypothesis that the test SNP is not in background linkage disequilibrium with the causal variants, several existing methods cannot control well the family-wise error rate (FWER) in the strong sense in GWAS. These existing methods include association tests adjusting for global ancestry and joint association tests that combine statistics from admixture mapping tests and association tests that correct for local ancestry. Furthermore, we describe a generalized sequential Bonferroni (smooth-GSB) procedure for GWAS that incorporates smoothed weights calculated from admixture mapping tests into association tests that correct for local ancestry. We have applied the smooth-GSB procedure to analyses of GWAS data on American Africans from the Atherosclerosis Risk in Communities (ARIC) Study. Our simulation studies indicate that the smooth-GSB procedure not only control the FWER, but also improves statistical power compared with association tests correcting for local ancestry. The smooth-GSB procedure can result in a better performance than several existing methods for GWAS in admixed populations.


Motor ability and inhibitory processes in children with ADHD: a neuroelectric study.
The purpose of the current study was to examine the relationship between motor ability and response inhibition using behavioral and electrophysiological indices in children with ADHD. A total of 32 participants were recruited and underwent a motor ability assessment by administering the Basic Motor Ability Test-Revised (BMAT) as well as the Go/No-Go task and event-related potential (ERP) measurements at the same time. The results indicated that the BMAT scores were positively associated with the behavioral and ERP measures. Specifically, the BMAT average score was associated with a faster reaction time and higher accuracy, whereas higher BMAT subset scores predicted a shorter P3 latency in the Go condition. Although the association between the BMAT average score and the No-Go accuracy was limited, higher BMAT average and subset scores predicted a shorter N2 and P3 latency and a larger P3 amplitude in the No-Go condition. These findings suggest that motor abilities may play roles that benefit the cognitive performance of ADHD children.


Interaction between a capacitor electrolyte and gamma-aluminum oxide studied by Fourier transform infrared spectroscopy.
The interaction between y-aluminum oxide and an ethylene glycol (EG) based capacitor electrolyte was investigated by Fourier transform infrared (FT-IR) spectroscopy. It was found that only a few ingredients of the electrolyte react with the oxide (azelaic acid, poly(1-vinyl-2-pyrrolidone) (PVP), and phosphoric acid); the others act as pH or conductivity buffers (boric acid, ammonia, and water). The adsorption of azelaic acid and PVP from the electrolyte was studied as a function of temperature, pH, and time, and the result was compared to the adsorption from model solutions of simpler composition. The influence of other components such as phosphoric acid both in the electrolyte and on the aluminum oxide was also investigated, as was the presence of water. At low pH and high temperature (T > or = 105 degrees C) the acid formed an ester with EG and this product adsorbed on the oxide surface. The PVP was attached to the adsorbed azelaic acid by hydrophobic interaction, which is pH independent. Ester formation was found to be catalyzed by other electrolyte ingredients like boric acid. At high pH, surface adsorption of azelaic acid occurs through a deprotonated species, which is mainly coordinated through outer-sphere complexation. At high temperature or after a long equilibration time, the surface of the alumina changed, resulting in less adsorption of the organic substances, independent of pH. This change is due to a selective adsorption of phosphate species from the electrolyte, which block active surface sites.


EpiGePT: a Pretrained Transformer model for epigenomics.
The transformer-based models, such as GPT-31 and DALL-E2, have achieved unprecedented breakthroughs in the field of natural language processing and computer vision. The inherent similarities between natural language and biological sequences have prompted a new wave of inferring the grammatical rules underneath the biological sequences. In genomic study, it is worth noting that DNA sequences alone cannot explain all the gene activities due to epigenetic mechanism. To investigate this problem, we propose EpiGePT, a new transformer-based language pretrained model in epigenomics, for predicting genome-wide epigenomic signals by considering the mechanistic modeling of transcriptional regulation. Specifically, EpiGePT takes the context-specific activities of transcription factors (TFs) into consideration, which could offer deeper biological insights comparing to models trained on DNA sequence only. In a series of experiments, EpiGePT demonstrates state-of-the-art performance in a diverse epigenomic signals prediction tasks as well as new prediction tasks by fine-tuning. Furthermore, EpiGePT is capable of learning the cell-type-specific long-range interactions through the self-attention mechanism and interpreting the genetic variants that associated with human diseases. We expect that the advances of EpiGePT can shed light on understanding the complex regulatory mechanisms in gene regulation. We provide free online prediction service of EpiGePT through https://health.tsinghua.edu.cn/epigept/.


Modeling the influence of body size and composition on M-mode echocardiographic dimensions.
The purpose of this study was to determine the optimal index for normalizing left ventricular (LV) echocardiographic dimensions for differences in body size. M-mode echocardiograms defined LV internal dimension at end diastole (LVIDD) and LV wall thickness (LVWT) in 107 adults (59 male, 48 female). Allometric relations were assessed between cardiac dimensions (Y) and body size variables (X) of fat-free mass (FFM), height (H), body surface area (BSA), and fat mass (FM). Further to confirmation of homogeneity of regression slopes, size exponents common to both genders were fitted by a log-linear model: ln Y = ln a + c.gender + b.ln X, where a is the proportionality coefficient, b is the size exponent, and c is the gender coefficient. For LVIDD, mean body size exponents (95% confidence interval) were FFM0.35 (0.22-0.47), H0.68 (0.32-1.03), and BSA0.44 (0.26-0.62). For LVWT, the derived exponents were FFM0.43 (0.20-0.65), H0.65 (0-1.3), and BSA0.56 (0.23-0.89). Body fatness (expressed by FM) had no influence on LV dimensions, with exponents not different from zero (P > 0.05). The root-mean-squares error from the separate regression models indicated that the FFM index was the optimal solution. Indexation of LV dimensions by H was associated with the greatest error. Because the 95% confidence interval for the FFM exponents included 0.33, we recommend that linear LV dimensions be indexed by the cube root of FFM. In the absence of FFM data, the root of BSA was found to be the best surrogate index.


Structure-Activity Relationship Studies Reveal New Astemizole Analogues Active against Plasmodium falciparum In Vitro.
In the context of drug repositioning and expanding the existing structure-activity relationship around astemizole (AST), a new series of analogues were designed, synthesized, and evaluated for their antiplasmodium activity. Among 46 analogues tested, compounds 21, 30, and 33 displayed high activities against asexual blood stage parasites (PfNF54 IC50 = 0.025-0.043 μM), whereas amide compound 46 additionally showed activity against late-stage gametocytes (stage IV/V; PfLG IC50 = 0.6 ± 0.1 μM) and 860-fold higher selectivity over hERG (46, SI = 43) compared to AST. Several analogues displaying high solubility (Sol > 100 μM) and low cytoxicity in the Chinese hamster ovary (SI > 148) cell line have also been identified.


Early life thermal stress: impacts on future temperature preference in weaned pigs (3 to 15 kg).
Thermal stress can result in productivity losses, morbidity, and mortality if proper management practices are not employed. A basic understanding of the relationship between animals and the thermal environment is crucial to assess the environment's impact on livestock performance. Therefore, the study objective was to evaluate whether different early life thermal stressors (ELTS) altered the temperature preference of pigs later in life. Twelve sows and their litters were randomly exposed to 1 of 3 ELTS treatments from 7 to 9 d of age: early life heat stress (ELHS; cycling 32 to 38 °C; n = 4), early life cold stress (ELCS; 25.4±1.1 °C without heating lamp; n = 4), or early life thermoneutral (ELTN; 25.4±1.1 °C with a heating lamp; n = 4) conditions. From 10 to 20 d, (weaning) all piglets were exposed to ELTN conditions. At weaning, pigs were randomly assigned to groups of 4 of the same sex and ELTS treatment. Temperature preference, where pigs freely choose a temperature, was assessed in 21 groups (n = 7 groups per ELTS treatment) using 1 of 3 thermal gradient apparatuses (22 to 40 °C). Testing began at 26 ± 1.3 d of age to give pigs time to acclimate to solid food after weaning and 1 group per ELTS treatment were tested simultaneously in each apparatus. Pigs were given 24 h to acclimate followed by a 24-h testing period. Behavior (active and inactive), posture (upright, sternal, and lateral lying), and location were documented every 20 min using instantaneous scan samples. Preferred feeding temperature was determined by the latency to empty a feeder in each location. Data were analyzed using PROC MIXED in SAS 9.4. A cubic regression model was used to calculate the peak temperature preference of pigs based on the temperature pigs spent most of their time. The preference range was calculated using peak temperature preference ±SE for each ELTS treatment group. Early life thermal stress altered where pigs spent most of their time within the thermal gradient (P = 0.03) with ELTN pigs preferring cooler temperatures (peak preference of 23.8 °C) compared with their ELCS exposed counterparts (peak preference of 26.0 °C; P < 0.01). However, ELHS exposed pigs (peak preference of 25.6 °C) did not differ in their temperature preference compared with ELTN or ELCS exposed counterparts (P > 0.05). In summary, ELCS exposure altered pig temperature preference later in life indicating that ELTS can alter temperature preference in pigs.


Levels of tolerance, antibiosis, and antixenosis among resistant buffalograsses and zoysiagrasses.
The western chinch bug, Blissus occiduus Barber, has been documented as one of the most serious pests of buffalograss, Buchloë dactyloides (Nuttall) Engelmann, and zoysiagrass, Zoysia japonica Steudel, grown for turf in midwestern states. Resistance to the western chinch bug has been identified in both buffalograsses and zoysiagrasses. Choice and no-choice studies were conducted to determine the categories (antibiosis, antixenosis, and tolerance) of three resistant buffalograsses (PX3-5-1', 196', and 184') and three resistant zoysiagrasses (El Toro, Emerald, and Zorro). Antibiosis studies found no significant differences in survival, nymphal development, or fecundity among the resistant and susceptible buffalograsses or zoysiagrasses, indicating that antibiosis is not an important factor in the resistance. Based on chinch bug damage ratings, 184, 196, and PX3-5-1 have comparable levels of tolerance to the known tolerant buffalograss 'Prestige', and Zorro was the most tolerant zoysiagrass. Choice studies indicated the presence of antixenosis in the buffalograss selection 196 and the zoysiagrass Emerald.


Global transcriptional profiling of a cold-tolerant rice variety under moderate cold stress reveals different cold stress response mechanisms.
Gene expression profiling under severe cold stress (4°C) has been conducted in plants including rice. However, rice seedlings are frequently exposed to milder cold stresses under natural environments. To understand the responses of rice to milder cold stress, a moderately low temperature (8°C) was used for cold treatment prior to genome-wide profiling of gene expression in a cold-tolerant japonica variety, Lijiangxintuanheigu (LTH). A total of 5557 differentially expressed genes (DEGs) were found at four time points during moderate cold stress. Both the DEGs and differentially expressed transcription factor genes were clustered into two groups based on their expression, suggesting a two-phase response to cold stress and a determinative role of transcription factors in the regulation of stress response. The induction of OsDREB2A under cold stress is reported for the first time in this study. Among the anti-oxidant enzyme genes, glutathione peroxidase (GPX) and glutathione S-transferase (GST) were upregulated, suggesting that the glutathione system may serve as the main reactive oxygen species (ROS) scavenger in LTH. Changes in expression of genes in signal transduction pathways for auxin, abscisic acid (ABA) and salicylic acid (SA) imply their involvement in cold stress responses. The induction of ABA response genes and detection of enriched cis-elements in DEGs suggest that ABA signaling pathway plays a dominant role in the cold stress response. Our results suggest that rice responses to cold stress vary with the specific temperature imposed and the rice genotype.


Increased use of recommended maternal health care as a determinant of immunization and appropriate care for fever and diarrhoea in Ghana: an analysis pooling three demographic and health surveys.
Enhancing maternal and child health are key Millennium Development Goals (MDGs). This study examined whether increased utilization of recommended maternal health care (MHC), is associated with factors that improve children's health; specifically, complete immunization and appropriate care for fever and diarrhoea in Ghana. Data from the 1998, 2003, and 2008 Ghana Demographic and Health Surveys were pooled for a nationally representative sample of 6786 women aged 15-49 years who had a child in the previous 5 years. Children aged 12-23 months were considered fully immunized if they received all eight basic immunizations. Appropriate care for children under-five was receipt of medical treatment for fever or oral rehydration therapy for diarrhoea. The effect of recommended MHC utilization (characterized as poor, intermediate or best use) on immunization and appropriate care for fever and diarrhoea was determined through logistic regression with Andersen's Behavioural Model guiding co-variate selection. Increased MHC utilization (reference: intermediate MHC use) increased the odds of immunization [poor use: odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.42-0.69; best use: OR = 1.29, 95% CI: 1.01-1.67], as well as appropriate care for fever (poor use: OR = 0.55, 95% CI: 0.35-0.88; best use: OR = 1.72, 95% CI: 1.17-2.52) and diarrhoea (poor use: OR = 0.63, 95% CI: 0.43-0.93). Survey year and region also predicted each outcome. Other determinants of immunization were maternal education, ethnicity, religion, media exposure, wealth and birth weight. Determinants of appropriate care for fever included paternal education, media exposure and wealth, and for diarrhoea, child's age and birth weight. This study proposes a linkage between MDGs; initiatives to improve maternal health through promoting increased use of recommended MHC may enhance children's health-related care. This could be useful for countries with limited resources in achieving MDGs, especially in sub-Saharan Africa where under-five mortality is the highest.


Haemagglutination-inhibition test for haemorrhagic fever with renal syndrome using virus antigen prepared from infected tissue culture fluid.
Haemagglutinating (HA) antigens of four strains of virus related to that causing haemorrhagic fever with renal syndrome (HFRS) were prepared from infected tissue culture fluids by ultracentrifugation. The titres of the precipitated antigens were increased considerably by acetone extraction and sonication. Acetone extraction completely inactivated infectious virus in the antigen preparations. The antigens were pH-dependent, with pH optima at 5.8. Good correlations were observed in human and rat sera between the titres obtained by the haemagglutination-inhibition (HI) test and an indirect fluorescent antibody test. Moreover, strong cross-reactions among these strains were demonstrated by the HI test. The HI test has not been used previously with HFRS viruses because of the danger involved in preparing HA antigen, but these results indicate that a safe method is available for serological identification of HFRS.


Zinc Finger Database (ZiFDB): a repository for information on C2H2 zinc fingers and engineered zinc-finger arrays.
Zinc fingers are the most abundant DNA-binding motifs encoded by eukaryotic genomes and one of the best understood DNA-recognition domains. Each zinc finger typically binds a 3-nt target sequence, and it is possible to engineer zinc-finger arrays (ZFAs) that recognize extended DNA sequences by linking together individual zinc fingers. Engineered zinc-finger proteins have proven to be valuable tools for gene regulation and genome modification because they target specific sites in a genome. Here we describe ZiFDB (Zinc Finger Database; http://bindr.gdcb.iastate.edu/ZiFDB), a web-accessible resource that compiles information on individual zinc fingers and engineered ZFAs. To enhance its utility, ZiFDB is linked to the output from ZiFiT--a software package that assists biologists in finding sites within target genes for engineering zinc-finger proteins. For many molecular biologists, ZiFDB will be particularly valuable for determining if a given ZFA (or portion thereof) has previously been constructed and whether or not it has the requisite DNA-binding activity for their experiments. ZiFDB will also be a valuable resource for those scientists interested in better understanding how zinc-finger proteins recognize target DNA.


A review of kidney motion under free, deep and forced-shallow breathing conditions: implications for stereotactic ablative body radiotherapy treatment.
Motion management strategies are important during stereotactic ablative body radiotherapy for abdominal targets. The kidney is a mobile retroperitoneal organ that moves with respiration. A review of the literature was performed to investigate the reported degree of kidney motion associated with various breathing conditions. A structured search was performed using Medline from January 1970 to May 2013 for all publications describing cranial-caudal kidney motion. Relevance to radiotherapy practice was reviewed based on any breathing instructions and/or immobilization equipment that could affect breathing pattern. Studies were categorized under three types of breathing conditions: Forced-shallow, breath-hold/deep and free. A total of 25 publications were identified describing cranial-caudal kidney motion with a combined total of 415 participants. Three publications described forced-shallow breathing using prone positioning or abdominal compression plates. Prone positioning, compared to supine positioning, did little to minimise kidney motion, however use of compression plates can result in kidney motion of less than 5 mm. Eight publications described deep breathing/breath hold techniques that showed average kidney motion ranging between 10 mm-40 mm. Fifteen publications investigated kidney motion under free breathing with the majority reporting mean motion of less than 10 mm. Kidney movement of up to 8.1 mm in the anterior posterior direction and 6.2 mm laterally were reported with no indications that breathing technique can influence the extent of this motion. In summary, kidney movement is complex and consideration should be made to ensure that motion management strategies provide the desired radiotherapy benefit. There are limited publications on the effectiveness of abdominal compression on reducing kidney motion which warrant further investigation in this area.


Women's empowerment and male involvement in antenatal care: analyses of Demographic and Health Surveys (DHS) in selected African countries.
Increasing women's status and male involvement are important strategies in reducing preventable maternal morbidity and mortality. While efforts to both empower women and engage men in maternal health care-seeking can work synergistically, in practice they may result in opposing processes and outcomes. This study examines whether a woman's empowerment status, in sum and across economic, socio-familial, and legal dimensions, is associated with male partner accompaniment to antenatal care (ANC). Women's empowerment was measured based on the sum of nine empowerment items in the 2010-2011 Demographic and Health Surveys in eight sub-Saharan African countries: Burkina Faso (n = 2,490), Burundi (n = 1,042), Malawi (n = 1,353), Mozambique (n = 414), Rwanda (n = 1,211), Senegal (n = 505), Uganda (n = 428) and Zimbabwe (n = 459). In cross-sectional analyses, bivariate and multivariable logistic regressions models were used to examine the odds of male partner accompaniment to ANC between women with above-average versus below-average composite and dimensional empowerment scores. In the majority of countries, male accompaniment to ANC was not uncommon. However, findings were mixed. Positive associations in women's composite empowerment and male involvement were observed in Burkina Faso (OR = 1.27, 95% CI: 1.08, 1.50) and Uganda (OR = 1.53, 95% CI: 1.00-2.35), and in the economic empowerment dimension in Burkina Faso (OR = 1.24, 95% CI: 1.05-1.47). In Malawi, significant negative associations were observed in the odds of male accompaniment to ANC and women's composite (OR = 0.77, 95% CI: 0.62-0.97) and economic empowerment scores (OR = 0.75, 95% CI: 0.59-0.94). No significant differences were observed in Burundi, Mozambique, Rwanda, Senegal, or Zimbabwe. Women's empowerment can be positively or negatively associated with male antenatal accompaniment. Male involvement efforts may benefit from empowerment initiatives that promote women's participation in social and economic spheres, provided that antenatal participation does not undermine women's preferences or autonomy. The observation of mixed and null findings suggests that additional qualitative and longitudinal research may enhance understanding of women's empowerment in sub-Saharan African settings.


A review of oral pathology in orthodontics. Part 1: Soft-tissue pathology.
Orthodontists are well placed to detect soft-tissue disease of the oral cavity and associated structures because of the frequent repeat examinations of their patients. This review describes the clinical manifestations, pathologic features, and treatment of the soft-tissue pathology most likely to be encountered by the orthodontist and uncommon soft-tissue disease with significant implications for the patient. The recognition of soft-tissue disease will allow reassurance, referral, and early intervention when required.


Comparison of TLIF with rhBMP-2 versus no TLIF and higher posterolateral rhBMP-2 dose at L5-S1 for long fusions to the sacrum with sacropelvic fixation in patients with primary adult deformity.
Comparvative case series. Data was prospectively entered and retrospectively analyzed. To evaluate the need for distal lumbar interbody fusion when sufficient recombinant human bone morphogenetic protein-2 (rhBMP-2) is used posterolaterally at L5-S1 in long spinal constructs for adult deformity via costs and radiographical and patient-reported outcome comparisons. Many authors and investigators have suggested that an interbody fusion is mandatory at L5-S1 with long fusion to the sacrum with sacropelvic fixation. Past studies have shown competitive fusion rates using rhBMP-2 versus iliac crest bone graft for long fusions. There are various advocates for anterior lumbar interbody fusion versus posterior lumbar interbody fusion versus transforaminal lumbar interbody fusion (TLIF). The optimal strategy remains elusive. Fifty-seven patients were studied at one institution. Thirty-one patients had no interbody fusion (NI group) with 20 mg of rhBMP-2 posterolaterally on 10 mL of carrier and 26 patients had TLIF at L5-S1 (TLIF group) with 6 mg of rhBMP-2 in the interbody space along with local bone graft and 6 mg of rhBMP-2 on carrier posterolaterally at L5-S1. Patients were followed for 24 to 87 months (mean follow-up, 3.92 yr). Demographics of the 2 groups were similar. There were no detected nonunions at L5-S1 in either group. By our limited cost analysis, the expense of performing a TLIF at L5-S1 is higher than that of using extra rhBMP-2 posterolaterally at that segment. Improvement in outcomes scores, namely Scoliosis Research Society-22 and Oswestry Disability Index, were the same statistically in both groups. Blood loss was greater in the TLIF group than the NI group. There were no identified rhBMP-2 adverse events in either group. Utilization of 20 mg of rhBMP-2 at L5-S1 has the potential to be less expensive than an interbody fusion in most patients having a primary long fusion for adult spinal deformity. The apparent fusion rates at L5-S1 were identical in both groups. Both strategies were successful in regard to improving patient outcomes and achieving apparent solid arthrodesis at the lumbosacral junction, which was the focus of this study. 2.


Identification and characterization of acyl-protein thioesterase 1/lysophospholipase I as a ghrelin deacylation/lysophospholipid hydrolyzing enzyme in fetal bovine serum and conditioned medium.
Ghrelin contains an octanoic acid at the third residue serine, and the presence of octanoic acid on ghrelin is critical to its physiological functions. The precise mechanism for the deacylation of ghrelin in circulation remains to be clarified, although the level of deacylated ghrelin (des-acyl ghrelin) is higher than that of acylated ghrelin in serum. In this study, rapid identification of ghrelin deacylation activity was achieved by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and a ghrelin deacylation enzyme was purified 1515-fold from fetal bovine serum. Chromatographic separation showed a 24-kDa band on SDS-PAGE corresponding to ghrelin deacylation activity, and the protein band was identified as acyl-protein thioesterase 1 (APT1)/lysophospholipase I. A ghrelin deacylation enzyme in medium from HepG2 cells was also purified and identified as APT1. Although it lacks a secretion signal sequence, APT1 may be released by cells expressing APT1, mainly from liver in vivo. APT1 was originally purified as a cytosolic lysophospholipid hydrolyzing enzyme (lysophospholipase I), and recombinant APT1 exhibited deacylation activity as well as lysophospholipase activity in vitro. APT1 is released at high levels from RAW264.7 macrophage-like cells into the culture medium after stimulation with lipopolysaccharide (LPS), and LPS suppresses APT1 mRNA and protein expressions in these cells. More potent ghrelin deacylase activities were detected in sera from LPS-treated rats than in control sera. These results suggested that the serum activity of APT1 may play an important role in determination of the concentration of des-acyl ghrelin in circulation, especially under septic inflammation.


Vasopressin augments depolarization-induced release and synthesis of serotonin in hippocampal slices.
Vasopressin may be a neurotransmitter and in vivo experiments suggest that it acts on monoamine metabolism. The rat hippocampal slice contains serotonergic nerve terminals but not cell bodies; we studied the effect of vasopressin on the synthesis and release of serotonin from these nerve terminals during depolarization. Incubation of slices in a buffer containing 60 mM K+ (high K buffer) for 10 min stimulated the release of serotonin into bathing medium and resulted in a Ca2+-dependent depletion of tissue serotonin from about 4.2 to about 2.8 ng/mg of protein. Vasopressin (10(-7) M) inhibited this depletion by about 70% so that serotonin levels fell only to 3.8 ng/mg of protein. The peptide also augmented the high K+-induced release of serotonin into the bathing medium by about 60%. The synthesis of serotonin was measured by determining its accumulation during a period when its catabolism was inhibited by pargyline. Vasopressin augmented the synthesis of serotonin in slices incubated in high K buffer by about 60%. There are serotonergic nerve endings in both the dentate gyrus and CA1 regions of the hippocampus. The effect of vasopressin on tissue serotonin was confined to the dentate gyrus regions. The data show that vasopressin acts on a specific group of hippocampal nerve endings to increase serotonin synthesis. The resulting increase in tissue serotonin may be the factor leading to the observed increase in serotonin release.