Oculomotor Response to Cumulative Subconcussive Head Impacts in US High School Football Players: A Pilot Longitudinal Study.
Repetitive subconcussive head impacts in sports have emerged as a complex public health issue. Most of these head impacts remain asymptomatic yet have the potential to cause insidious neurological deficit if sustained repetitively. Near point of convergence (NPC) values have shown to reflect subclinical neuronal damage; however, the longitudinal pattern of NPC changes in association with subconcussive head impacts remains unclear. To examine the NPC response to recurring subconcussive head impacts in a single high school football season through a series of repeated measurements. This prospective case-series study of US varsity high school football players included baseline measurements of NPC, measurements at pregame and postgame points from 6 in-season games, and postseason follow-up measurements (a total of 14 points). An accelerometer-embedded mouthguard measured head impact frequency and magnitude from all practices and games. During the 6 games, players wore chest-strap heart rate monitors to record heart rate and estimate their excess postexercise oxygen consumption, accounting for possible physical exertion effects on NPC values. Players participated in practices and games with no restriction. Near point of convergence. The 12 included players were all boys, with a mean (SD) age of 16.4 (0.5) years. A total of 8009 head impacts, 177 907 g of peak linear acceleration, and 16 123 371 rad/s2 of peak rotational acceleration were recorded from the players in a single football season. There was a significant increase in NPC over time until the middle of the season (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 3, 6.42 [1.93] cm; P = .01), which was significantly associated with subconcussive head impact frequency and magnitude (0.02 cm per 100 g of peak linear acceleration [SE, 0.0108; 95% CI, 0.0436-0.004]; P = .01; 0.023 cm per 10 000 rad/s2 of peak rotational acceleration [SE, 0.009; 95% CI, 0.041-0.0105]; P = .02). However, NPC values began to normalize toward baseline level from midseason (mean [SD] NPC: baseline, 5.25 [1.49] cm; pregame 6, 5.75 [2.23] cm; P = .32), as supported by a significant quadratic trend (β [SE], -0.002 [0.001] cm/d; P = .003), while participants continued to incur subconcussive head impacts. This longitudinal case series study suggests that NPC can be perturbed over the long term by subconcussive head impacts but may normalize over time. The oculomotor system may have an adaptational capacity to subclinical head impacts, yet the mechanism for such remains an open question and warrants further investigation.


Mitogen-induced blastogenic responses of lymphocytes from marihuana smokers.
Blastogenic responses in vitro to phytohemagglutinin and pokeweed mitogen were examined in microcultures of peripheral blood lymphocytes from a group of 12 healthy, long-term marihuana smokers and a group of matched control subjects. With either mitogen, no significant difference in cellular incorporation of (3H)thymidine was noted between the groups. These results were interpreted to indicate that the functional status of blood lymphocytes was not altered by long-term smoking of marihuana.


Osteogenic and tenogenic induction of hBMSCs by an integrated nanofibrous scaffold with chemical and structural mimicry of the bone-ligament connection.
A novel electrospinning nanofiber collecting device was designed and utilized to fabricate an integrated poly(ε-caprolactone) (PCL) nanofibrous scaffold with a "random-aligned-random" structure. The random region of the scaffold was subsequently soaked in a 5× simulated body fluid (5× SBF) to coat the surface of the scaffold with a mineral layer. The region-specific composition and structure thus mimic the bone-ligament connection. The ultimate tensile stress of the aligned region is significantly higher than that of the random region. Depending on the chemistry and structure of different regions of the scaffold, the seeded human bone marrow mesenchymal stem cells (hBMSCs) undergo lineage-specific differentiation. Significant up-regulation of tendon-specific marker tenomodulin (Tnmd) and Mohawk homeobox (Mkx) was induced in the aligned region compared to the random region with 3.5-fold for Tnmd and more than 20-fold for Mkx. On the other hand, up-regulation of bone-specific osteocalcin (Ocn) and osteopontin (Opn) was significantly induced in the mineralized region. Immunofluorescence of Tnmd and Ocn proteins further confirmed the regional induction of hBMSC differentiation by the chemistry and structure of the integrated nanofibrous scaffold. The biomimetic PCL nanofibrous scaffold stimulating tenogenesis and osteogenesis chemically and structurally is a promising candidate for functional repair of ligaments and tendons.


Combining temporal and spatial attention for seizure prediction.
Approximately 1% of the world population is currently suffering from epilepsy. Successful seizure prediction is necessary for those patients. Influenced by neurons in their own and surrounding locations, the electroencephalogram (EEG) signals collected by scalp electrodes carry information of spatiotemporal interactions. Therefore, it is a great challenge to exploit the spatiotemporal information of EEG signals fully. In this paper, a new seizure prediction model called Gatformer is proposed by fusing the graph attention network (GAT) and the Transformer. The temporal and spatial attention are combined to extract EEG information from the perspective of spatiotemporal interactions. The model aims to explore the temporal dependence of single-channel EEG signals and the spatial correlations among multi-channel EEG signals. It can automatically identify the most noteworthy interaction in brain regions and achieve accurate seizure prediction. Compared with the baseline models, the performance of our model is significantly improved. The false prediction rate (FPR) on the private dataset is 0.0064/h. The average accuracy, specificity and sensitivity are 98.25%, 99.36% and 97.65%. The proposed model is comparable to the state of the arts. Experiments on different datasets show that it has good robustness and generalization performance. The high sensitivity and low FPR prove that this model has great potential to realize clinical assistance for diagnosis and treatment.


Inference of a Geminivirus-Host Protein-Protein Interaction Network through Affinity Purification and Mass Spectrometry Analysis.
Viruses reshape the intracellular environment of their hosts, largely through protein-protein interactions, to co-opt processes necessary for viral infection and interference with antiviral defences. Due to genome size constraints and the concomitant limited coding capacity of viruses, viral proteins are generally multifunctional and have evolved to target diverse host proteins. Inference of the virus-host interaction network can be instrumental for understanding how viruses manipulate the host machinery and how re-wiring of specific pathways can contribute to disease. Here, we use affinity purification and mass spectrometry analysis (AP-MS) to define the global landscape of interactions between the geminivirus Tomato yellow leaf curl virus (TYLCV) and its host Nicotiana benthamiana. For this purpose, we expressed tagged versions of each of TYLCV-encoded proteins (C1/Rep, C2/TrAP, C3/REn, C4, V2, and CP) in planta in the presence of the virus. Using a quantitative scoring system, 728 high-confidence plant interactors were identified, and the interaction network of each viral protein was inferred; TYLCV-targeted proteins are more connected than average, and connect with other proteins through shorter paths, which would allow the virus to exert large effects with few interactions. Comparative analyses of divergence patterns between N. benthamiana and potato, a non-host Solanaceae, showed evolutionary constraints on TYLCV-targeted proteins. Our results provide a comprehensive overview of plant proteins targeted by TYLCV during the viral infection, which may contribute to uncovering the underlying molecular mechanisms of plant viral diseases and provide novel potential targets for anti-viral strategies and crop engineering. Interestingly, some of the TYLCV-interacting proteins appear to be convergently targeted by other pathogen effectors, which suggests a central role for these proteins in plant-pathogen interactions, and pinpoints them as potential targets to engineer broad-spectrum resistance to biotic stresses.


Mll2 is required for H3K4 trimethylation on bivalent promoters in embryonic stem cells, whereas Mll1 is redundant.
Trimethylation of histone H3 lysine 4 (H3K4me3) at the promoters of actively transcribed genes is a universal epigenetic mark and a key product of Trithorax group action. Here, we show that Mll2, one of the six Set1/Trithorax-type H3K4 methyltransferases in mammals, is required for trimethylation of bivalent promoters in mouse embryonic stem cells. Mll2 is bound to bivalent promoters but also to most active promoters, which do not require Mll2 for H3K4me3 or mRNA expression. By contrast, the Set1 complex (Set1C) subunit Cxxc1 is primarily bound to active but not bivalent promoters. This indicates that bivalent promoters rely on Mll2 for H3K4me3 whereas active promoters have more than one bound H3K4 methyltransferase, including Set1C. Removal of Mll1, sister to Mll2, had almost no effect on any promoter unless Mll2 was also removed, indicating functional backup between these enzymes. Except for a subset, loss of H3K4me3 on bivalent promoters did not prevent responsiveness to retinoic acid, thereby arguing against a priming model for bivalency. In contrast, we propose that Mll2 is the pioneer trimethyltransferase for promoter definition in the naïve epigenome and that Polycomb group action on bivalent promoters blocks the premature establishment of active, Set1C-bound, promoters.


Computational and experimental insights on the interaction of artemisinin, dihydroartemisinin and chloroquine with SARS-CoV-2 spike protein receptor-binding domain (RBD).
The mechanism of host cell invasion of severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 is connected with the interaction of spike protein (S) with angiotensin-converting enzyme 2 (ACE2) through receptor-binding domain (RBD). Small molecules targeting this assembly are being investigated as drug candidates to contrast SARS-CoV-2. In this context, chloroquine, an antimalarial agent proposed as a repurposed drug to treat coronavirus disease-19 (COVID-19), was hypothesized to bind RBD among its other mechanisms. Similarly, artemisinin and its derivatives are being studied as potential antiviral agents. In this work, we investigated the interaction of artemisinin, its metabolite dihydroartemisinin and chloroquine with RBD by means of computational tools and in vitro. Docking studies showed that the compounds interfere with the same region of the protein and molecular dynamics (MD) simulations demonstrated the stability of the predicted complexes. Bio-layer interferometry showed that chloroquine dose-dependently binds RBD (KD = 35.9 µM) more efficiently than artemisinins. [Formula: see text].


Gate-tunable giant nonreciprocal charge transport in noncentrosymmetric oxide interfaces.
A polar conductor, where inversion symmetry is broken, may exhibit directional propagation of itinerant electrons, i.e., the rightward and leftward currents differ from each other, when time-reversal symmetry is also broken. This potential rectification effect was shown to be very weak due to the fact that the kinetic energy is much higher than the energies associated with symmetry breaking, producing weak perturbations. Here we demonstrate the appearance of giant nonreciprocal charge transport in the conductive oxide interface, LaAlO3/SrTiO3, where the electrons are confined to two-dimensions with low Fermi energy. In addition, the Rashba spin-orbit interaction correlated with the sub-band hierarchy of this system enables a strongly tunable nonreciprocal response by applying a gate voltage. The observed behavior of directional response in LaAlO3/SrTiO3 is associated with comparable energy scales among kinetic energy, spin-orbit interaction, and magnetic field, which inspires a promising route to enhance nonreciprocal response and its functionalities in spin orbitronics.


Determination of omega-6 and omega-3 fatty acids in pork adipose tissue with nondestructive Raman and fourier transform infrared spectroscopy.
In order to predict omega-6 and omega-3 fatty acids in the diet of humans, seventy-three pork back fat adipose tissue samples were measured with Raman spectroscopy directly on adipose tissue and on melted fat. Melted fat samples were, in addition, measured with Fourier transform infrared (FT-IR) spectroscopy. Gas chromatography analyses were conducted as the reference analysis. Partial least squares regression (PLSR) was used to calibrate and validate all models predicting omega-3 and omega-6 fatty acids contents from spectra. Omega-6 fatty acids in melted fat measured with FT-IR was predicted with a correlation coefficient (R) of 0.93 and a root mean square error of cross-validation (RMSECV) of 1.61% of the total amount of fatty acids. Raman spectra measured on melted fat gave a prediction of omega-6 fatty acids with R=0.97, and RMSECV=0.99% of total amount of fatty acids. Omega-6 fatty acids were predicted with R=0.94, and RMSECV=1.50% of the total amount of fatty acids using Raman spectra recorded on adipose tissue. For omega-3 fatty acids, the highest R=0.91, and lowest RMSECV=0.23% of the total amount of fatty acids were obtained from Raman spectra acquired on melted fat. FT-IR and Raman spectroscopy may be used as rapid, nondestructive methods to determine omega-6 and omega-3 fatty acids in melted fat. Raman spectroscopy can also be used directly on adipose tissue.


Enhanced antitumor responses elicited by combinatorial protein transfer of chemotactic and costimulatory molecules.
Thus far, immunotherapies based on one or a few immunostimulatory molecules have shown limited antitumor efficacy. This highlights the need to use multiple immunostimulatory molecules, to target different immune cells, including immunosuppressive cells, simultaneously. Consequently, in this study, we delivered intratumorally via protein transfer four molecules, including the chemotactic molecules secondary lymphoid tissue chemokine and Fas ligand and the costimulatory molecules 4-1BBL and TNF-related activation-induced cytokine. Secondary lymphoid tissue chemokine and Fas ligand together can attract an array of immune cells and induce apoptosis in CD4(+)CD25(+) regulatory T cells (Treg), whereas 4-1BBL and TRANCE together can stimulate T cells and dendritic cells (DCs). We show that the transfer of all four molecules increases tumor-infiltrating neutrophils, DCs, and CD4(+) and CD8(+) T cells and decreases intratumoral Treg. We show that the treatment favors the generation of a Th1 cytokine milieu at the tumor site, which is attributed not only to an increase in IL-12-producting DCs and IFN-gamma-producing CD8(+) T cells, but also to a decrease in IL-10-producing Treg. Importantly, in the L5178Y lymphoma model, we show that compared with transfer of the chemotactic molecules alone or the costimulatory molecules alone, transfer of all four molecules demonstrates stronger antitumor responses against established tumors. Furthermore, we show that the antitumor responses elicited by transfer of all four molecules are mediated by long-term, systemic antitumor immunity. Hence, this study demonstrates for the first time that combinatorial use of chemotactic and costimulatory molecules provides a useful strategy for enhancing antitumor responses.


Chitosan nanofibrous scaffold with graded and controlled release of ciprofloxacin and BMP-2 nanoparticles for the conception of bone regeneration.
The repair of bone defects using grafts is commonly employed in clinical practice. However, the risk of infection poses a significant concern. Tissue engineering scaffolds with antibacterial functionalities offer a better approach for bone tissue repair. In this work, firstly, two kinds of nanoparticles were prepared using chitosan to complex with ciprofloxacin and BMP-2, respectively. The ciprofloxacin complex nanoparticles improved the dissolution efficiency of ciprofloxacin achieving a potent antibacterial effect and cumulative release reached 95 % in 7 h. For BMP-2 complexed nanoparticles, the release time points can be programmed at 80 h, 100 h or 180 h by regulating the number of coating chitosan layers. Secondly, a functional scaffold was prepared by combining the two nanoparticles with chitosan nanofibers. The microscopic nanofiber structure of the scaffold with 27.28 m2/g specific surface area promotes cell adhesion, high porosity provides space for cell growth, and facilitates drug loading and release. The multifunctional scaffold exhibits programmed release function, and has obvious antibacterial effect at the initial stage of implantation, and releases BMP-2 to promote osteogenic differentiation of mesenchymal stem cells after the antibacterial effect ends. The scaffold is expected to be applied in clinical bone repair and graft infection prevention.


Intra-renal Arteries in Nephrectomy from a Historical Aspect, a Quest Originated by Medical Illustrations to Reach Modern Angiography.
The aim of the present paper is to contribute to the understanding of the history of the anatomical study of the intra-renal arteries. The vasculature and especially the intra-renal arteries of the kidneys are an intriguing field which was first studied through art and then perfected by medicine. Angiography and microsurgery have resulted in partial nephrectomy techniques for surviving kidneys with adequate functional results. Graves' categorization dating from 1954 opened the way for innovative approaches that have resulted in modern topographical anatomy. CONCLUSION: Our understanding of the anatomy of intra-renal arteries has played a significant role in surgical anatomy and internal medicine.


Factors Influencing Infertility-related Quality of Life in Women Undergoing Assisted Reproductive Techniques: Focusing on Depression and Resilience.
The purpose of this study was to investigate factors affecting on infertility-related quality of life in women undergoing assisted reproductive techniques focusing on depression and resilience. With correlational survey design, 125 infertile women who were receiving inpatient and outpatient treatment in K university hospital in D city completed a structured questionnaire. There was a significant negative correlation between depression and resilience and between the depression and the quality of life. There was a significant positive correlation between resilience and the quality of life. The factors affecting on infertility-related quality of life were depression, burden of expenses, and relationship with husband which explained 48% in the quality of life. It is necessary to develop and apply nursing programs that include individual counseling and education for infertile couple. Social support including financial support and better environment for these women will be also essential.


Epidermal growth factor receptor (EGFR) abundance correlates with p53 and Bcl-2 accumulation and patient age in a small cohort of North African nasopharyngeal carcinoma patients.
In North Africa, nasopharyngeal carcinoma (NPC) is characterized by a bimodal distribution involving a juvenile (≤ 30 years old) and an elder population (> 30 years old). The Epstein Barr virus oncogene LMP1, the anti-apoptotic Bcl-2 protein and the tumor suppressor p53 have recently emerged as biomarkers of the disease. EGFR/ErbB1 expression is detected in the majority of NPC tumors with advanced disease. To obtain greater insight into the potential oncogenic mechanisms specific to these two NPC populations, we examined the correlation between EGFR expression and patient age, and determined the molecular profiles of its associations with the biomarkers of NPC. We performed an immunohistochemical analysis of the latter molecules in NPC specimens from eleven Algerian patients (six patients ≤ 30 years of age and five patients > 30 years of age) using the LSAB method. Evaluation of the biopsies, based on the intensity of staining and the percentage of positive cells, showed that LMP1 expression was higher in patients under 30 years of age. Conversely, EGFR, like Bcl-2 and p53, was significantly up-regulated in tumors from elderly patients. Analysis of all tumors showed that EGFR expression was constantly (100%) associated with high p53 nuclear accumulation and Bcl-2 expression in LMP1-positive tissues. Biopsies negative for Bcl-2 staining were found to display low amounts of p53 (100%), and to be constantly negative for EGFR (100%). Molecular classification of all NPC tissues showed that the majority of patients displaying a EGFR+/LMP1+/Bcl-2+/p53-high molecular pattern were in the older age group. On the other hand, the most of the EGFR negative results were associated with the juvenile form of the disease and were characterized by an important diversity of molecular patterns. Our preliminary results suggest that in Algerian patients, the bimodal distribution of NPC might be related to distinct expression profiles of viral and cellular biomarkers of NPC.


A new view of diabetic retinopathy: a neurodegenerative disease of the eye.
Diabetic retinopathy (DR) is a common complication of diabetes and a leading cause of legal blindness in working-age adults. The clinical hallmarks of DR include increased vascular permeability, leading to edema, and endothelial cell proliferation. Much of the research effort has been focused on vascular changes, but it is becoming apparent that other degenerative changes occur beyond the vascular cells of the retina. These include increased apoptosis, glial cell reactivity, microglial activation, and altered glutamate metabolism. When occurring together, these changes may be considered as neurodegenerative and could explain some of the functional deficits in vision that begin soon after the onset of diabetes. This review will present the current evidence that neurodegeneration of the retina is a critical component of DR. There are two basic hypotheses that account for loss of cells in the neural retina. First, the loss of blood-retinal barrier integrity, which initially manifests as an increase in vascular permeability, causes a failure to control the composition of the extracellular fluid in the retina, which in turn leads to edema and neuronal cell loss. Alternatively, diabetes has a direct effect on metabolism within the neural retina, leading to an increase in apoptosis, which in turn causes breakdown of the blood-retinal barrier. It is not clear which hypothesis will be found to be correct, and, in fact, it is likely that vascular permeability and neuronal apoptosis are closely linked components of DR. However, the gradual loss of neurons suggests that progress of the disease is ultimately irreversible, since these cells cannot usually be replaced. In light of this possibility, new treatments for DR should be preventive in nature, being implemented before overt clinical symptoms develop. While vascular permeability is the target that is primarily considered for new treatments of DR, evidence presented here suggests that apoptosis of neurons is also an essential target for pharmacological studies. The vision of people with diabetes will be protected only when we have discovered a means to prevent the gradual but constant loss of neurons within the inner retina.


Early congenital syphilis still occurs.
Seven cases of early congenital syphilis have been recorded in the past 10 years in the Mersey Regional Health Authority. Antenatal serology was initially negative in five mothers, who were either incubating or acquired the infection later, and treatment had probably failed in two women given erythromycin for syphilis during pregnancy. Serology should be repeated later in pregnancy in those at high risk. Social factors that define this group include women who book for antenatal care late in pregnancy, have a past history of sexually transmitted disease, and have multiple consorts. Clinical signs in the infant such as failure to thrive, hepatosplenomegaly, symmetrical rash, rhinitis, and osteochondritis should alert the clinician to the possibility of congenital syphilis. Adequate management of mother and baby requires close liaison between the genitourinary physician, microbiologist, obstetrician, and paediatrician. Penicillin remains the treatment of choice.


Risk Factors of Recurrent Wheezing in Children Under 5 Years of Age.
To identify risk factors which may lead to the occurrence of recurrent wheezing in children under five years of age. A cross-sectional study was conducted in children under 5 years old at the Out Patient Department at Naresuan University Hospital, from October 2013 to October 2014. Fifty-five children who had signs and symptoms of recurrent wheezing were assigned to the study group, whereas another fifty-five children matching on age and sex with the case who had no symptoms of recurrent wheezing were assigned to the control group. All of the parents completed the given questionnaires. Descriptive data analysis were statistically conducted to understand the characteristics of the study groups. The risk factors were analysed using both bivariate and multivariate statistical analyses which included all the important predictors with a statistically significant level of p<0.05. Mean age in the study group was 36.1 months and in the control group 25.0 months. The mean weights and heights showed no difference between the case and control groups. Bivariate analysis showed that upper respiratory tract infection [odds ratio (OR) 7.273; 95% confidence interval (CI) 2.277-23.232)], lower respiratory tract infection (OR 5.332; 95% CI 2.326-12.225), passive smoking (OR 2.368; 95% CI 1.094-5.129), and day care center attendance (OR 2.590; 95% CI 1.168-5.745) were the risk factors of recurrent wheezing. Multivariate logistic regression analysis indicate that lower respiratory tract infection [adjusted odds ratios (aOR) 0.241; 95% CI 0.088-0.659] was the most important risk factor leading to recurrent wheezing. Lower respiratory tract infection, upper respiratory tract infection, passive smoking and day care center attendance were found to be risk factors of recurrent wheezing in children under five years of age, with lower respiratory tract infection being the most risk. Targeted surveillance of these risk factors should reduce the incidence of recurrent wheezing. This is especially important for high risk patients such as asthma patients.


Platinum compounds and paclitaxel in advanced epithelial ovarian cancer.
Cisplatin is the most active agent currently employed in epithelial ovarian cancer. A meta-analysis of the Advanced Ovarian Cancer Trialists Group suggested that in terms of immediate survival platinum-based therapy was superior to nonplatinum regimens and that regimens including cisplatin were superior to single agent cisplatin given at the same doses. Intraperitoneal cisplatin seems to offer some clinical benefit when compared to systemic cisplatin in patients with minimal residual disease after initial surgery. An overview on the role of anthracyclines using data from the Advanced Ovarian Cancer Trialists Group and the Ovarian Cancer Meta-Analysis Project suggested that the addition of doxorubicin significantly improves survival and that the size of this benefit is of a similar magnitude to that of platinum. Carboplatin and cisplatin are equiactive, and the different spectrum of toxicities could offer an appropriate criterion for the choice of the platinum analogue to use in the individual patient. At present, there is no conclusive evidence that cisplatin dose intense regimens are beneficial, and the issue of dose intensity must still be considered experimental. The combination of cisplatin + paclitaxel is able to obtain a better progression-free survival and survival than the association cisplatin + cyclophosphamide. Phase I-II trials on regimens including platinum compounds, anthracyclines and paclitaxel are currently ongoing.


Is there a negative impact of winter on mental distress and sleeping problems in the subarctic: the Tromsø Study.
Prior studies have suggested that the darkness of winter impacts the level of mental distress and sleeping problems. Our study investigated whether people living in the sub-arctic had more sleeping problems or mental distress during winter. The cross sectional population Tromsø Study was conducted in Tromsø, North Norway, at 69.4 degrees North and above the Arctic Circle. The study included entire birth cohorts and random samples of the population aged 30 to 87 years. Data was collected continuously from 1 October 2007 to the end of December 2008 except July. 8951 persons completed questionnaires including the HSCL-10 and the MCTQ. There were no significant differences in the reporting of current mental distress depending on season. Significantly more reported current sleeping problems in winter than in the other seasons, and less sleeping problems was found in spring. In this sub-arctic population, insomnia was most prevalent in winter, but there were no significant seasonal differences in mental distress. Although some people in the sub-arctic clearly are mentally negatively affected by the darkness of winter, the negative impact of winter on mental distress for the adult population is not conclusive.


Multiple Sclerosis Risk Factors and Pathogenesis.
This article summarizes recent advances in the identification of genetic and environmental factors that affect the risk of developing multiple sclerosis (MS) and the pathogenic processes involved in acute relapses and relapse-independent disability progression. The number of single-nucleotide polymorphisms associated with increased risk of MS has increased to more than 200 variants. The evidence for the association of Epstein-Barr virus infection, vitamin D deficiency, obesity, and smoking with increased risk of MS has further accumulated, and, in cases of obesity and vitamin D deficiency, the evidence for causal association has strengthened. Interactions between genetic and environmental factors have been studied more extensively. Dietary factors and changes in the gut microbiota are emerging as possible modulators of the disease risk. Several processes important to MS pathogenesis have been newly investigated or investigated more comprehensively, including the role of B cells, innate immune cells, meningeal inflammation, cortical and gray matter demyelination, and early axonal and neuronal loss. MS is a complex disease in which the interaction between genetic and environmental factors causes a cascade of events, including activation of the adaptive and innate immune system, blood-brain barrier breakdown, central nervous system demyelination, and axonal and neuronal damage with variable degrees of repair. These events manifest as potentially reversible focal neurologic symptoms or progressive nonremitting physical and cognitive disability, or both. Advances in the understanding of the risk factors and pathogenic mechanisms of MS have resulted in improved therapeutic strategies. The results of ongoing or future studies are needed to successfully and fully translate these advances into clinical practice.


Patient Participation in Nursing Care: Views From Ghanaian Nurses, Nursing Students, and Patients.
Previous studies on patient participation reported inconclusive benefits of patient participation in health care. Consequently, the World Health Organization is actively highlighting the need for the participation of patients and their families in their care. The aim of this study was to explore the views of nurses, nursing students, and patients on patient participation in Ghanaian hospitals. Sixty-five participants made up of 15 patients, 25 registered general nurses, and 25 undergraduate nursing students were involved in the study. Data collection was done through interviews and focus group discussions. Content analysis was utilized in analyzing the data to generate four main categories. These categories were as follows: (a) meaning of patient participation in Ghana, (b) patient participation encouraged more during discharge education, (c) patient participation in nursing care higher in private and smaller hospitals, and (d) perceived facilitators and inhibitors of patient participation in nursing care. Participants in this study indicated that patient participation in nursing care meant involvement of patient in treatment decisions and nursing care procedures. Participants agreed that patient participation in nursing care was mostly encouraged during discharge education. Participation was perceived to be higher in private and smaller hospitals. Wealth and higher education were perceived as facilitators of patient participation while workload and high patient acuity were perceived as inhibitors.


Major Bleeding in Patients With Coronary or Peripheral Artery Disease Treated With Rivaroxaban Plus Aspirin.
In patients with coronary or peripheral artery disease, the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events and mortality and increased bleeding. This study sought to explore the effects of the combination of rivaroxaban and aspirin compared with aspirin on sites, timing, severity, and management of bleeding in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) study. This study reports, by treatment group, the number and proportion of patients; hazard rate ratios for bleeding according to site and severity; the timing of bleeding using landmark analyses; and the number and proportion of patients who received blood products and other hemostatic treatments. Of 27,395 patients enrolled (mean age 68 years, 22% women), 18,278 were randomized to the combination of rivaroxaban and aspirin or to aspirin alone and followed for a mean of 23 months. Compared with aspirin alone, the combination increased modified International Society on Thrombosis and Hemostasis major bleeding (288 of 9,152 [3.1%] vs. 170 of 9,126 [1.9%]), (HR: 1.70; 95% CI: 1.40 to 2.05; p < 0.001), International Society on Thrombosis and Hemostasis major bleeding (206 of 9,152 [2.3%] vs. 116 of 9,126 [1.3%]), (HR: 1.78; 95% CI: 1.41 to 2.23; p < 0.0001), and minor bleeding (838 of 9,152 [9.2%] vs. 503 of 9,126 [5.5%]), (HR: 1.70; 95% CI 1.52 to 1.90; p < 0.0001); the combination also increased the need for any red cell transfusion (87 of 9,152 [1.0%] vs. 44 of 9,126 [0.5%]), (HR: 1.97; 95% CI 1.37 to 2.83, p = 0.0002). The gastrointestinal (GI) tract was the most common site of increased major bleeding (140 of 9,152 [1.5%] vs. 65 of 9,126 [0.7%]), (HR: 2.15; 95% CI: 1.60 to 2.89; p < 0.001), and the increase in bleeding was predominantly in the first year after randomization. Approximately one-third of major GI bleeding was gastric or duodenal, one-third was colonic or rectal, and one-third was from an unknown GI site. The study investigators reported that approximately three-quarters of major bleeding episodes were of mild or moderate intensity. A similar proportion of patients in each treatment group who experienced major bleeding received platelets, clotting factors, or other hemostatic agents. The combination of rivaroxaban and aspirin compared with aspirin alone increased major bleeding, mainly from the GI tract. Most excess bleeding occurred during the first year after randomization, was of mild or moderate intensity, and was managed with conventional supportive therapy. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424).


Enslaving in a serial chain: interactions between grip force and hand force in isometric tasks.
This study was motivated by the double action of extrinsic hand muscles that produce grip force and also contribute to wrist torque. We explored interactions between grip force and wrist torque in isometric force production tasks. In particular, we tested a hypothesis that an intentional change in one of the two kinetic variables would produce an unintentional change in the other (enslaving). When young healthy subjects produced accurate changes in the grip force, only minor effects on the force produced by the hand (by wrist flexion/extension action) were observed. In contrast, a change in the hand force produced consistent changes in grip force in the same direction. The magnitude of such unintentional grip force change was stronger for intentional hand force decrease as compared to hand force increase. These effects increased with the magnitude of the initial grip force. When the subjects were asked to produce accurate total force computed as the sum of the hand and grip forces, strong negative covariation between the two forces was seen across trials interpreted as a synergy stabilizing the total force. An index of this synergy was higher in the space of "modes," hypothetical signals to the two effectors that could be changed by the controller one at a time. We interpret the complex enslaving effects (positive force covariation) as conditioned by typical everyday tasks. The presence of synergic effects (negative, task-specific force covariation) can be naturally interpreted within the referent configuration hypothesis.


[Need for systematic HIV serological study during pregnancy].
To evaluate human immunodeficiency virus (HIV) screening usefulness in pregnancy and to know the prevalence of this infection in an urban area of Spain. Routine prenatal screening for antibodies to HIV was offered to pregnant women from Fuenlabrada-Leganés Health Care Area (Madrid) from 1992 to 1995. Unlinked anonymous screening of HIV was done with the sera from women refusing the assay or if it had not been offered. HIV prevalence was 0.28% (CI: 95%; 0.19 to 0.40) in the 11.021 pregnant women group studied. 87.1% pregnant seropositive women were detected by consented screening. 55.6% of them recognized risk behavior (73.33% by intravenous drug use) and 44.4% did not do it. With a second anamnesis in this group 75% admitted risk conducts and 25% confirmed their ignorance about them. HIV seropositive screening in pregnant women selected only by risk behavior may be unsuccessful. For that reason, it is more convenient the perform a routine test for detection of HIV antibodies after informed consent in high prevalence areas of HIV infection.


Targeted delivery of ubiquitin-conjugated BH3 peptide-based Mcl-1 inhibitors into cancer cells.
BH3 peptides are key mediators of apoptosis and have served as the lead structures for the development of anticancer therapeutics. Previously, we reported the application of a simple cysteine-based side chain cross-linking chemistry to NoxaBH3 peptides that led to the generation of the cross-linked NoxaBH3 peptides with increased cell permeability and higher inhibitory activity against Mcl-1 ( Muppidi, A., Doi, K., Edwardraja, S., Drake, E. J., Gulick, A. M., Wang, H.-G., Lin, Q. ( 2012 ) J. Am. Chem. Soc. 134 , 14734 ). To deliver cross-linked NoxaBH3 peptides selectively into cancer cells for enhanced efficacy and reduced systemic toxicity, here we report the conjugation of the NoxaBH3 peptides with the extracellular ubiquitin, a recently identified endogenous ligand for CXCR4, a chemokine receptor overexpressed in cancer cells. The resulting ubiquitin-NoxaBH3 peptide conjugates showed increased inhibitory activity against Mcl-1 and selective killing of the CXCR4-expressing cancer cells. The successful delivery of the NoxaBH3 peptides by ubiquitin into cancer cells suggests that the ubiquitin/CXCR4 axis may serve as a general route for the targeted delivery of anticancer agents.


Chemical speciation of PM2.5 particles at urban background and rural sites in the UK atmosphere.
Fine particle (PM(2.5)) samples have been collected at two sites in the UK West Midlands, representing urban background (EROS) and rural (CPSS) locations. Chemical quantification has been carried out for major anions, metal species, total OC and EC, and for individual organic marker species including n-alkanes, hopanes, PAHs, organic acids and sterols. Concentration levels of each chemical group are presented and the patterns of individual species used to infer predominant sources of atmospheric fine particles from atmospheric measurements. Temporal and spatial variations are also discussed. The annual mean PM(2.5) concentrations were 11.6 and 10.5 microg m(-3), with large daily variations (2.7-37.1 microg m(-3)) at the two sites. Elevated PM(2.5) was mostly attributed to higher sulfate > OC > nitrate in summer and OC > nitrate > EC in winter. The mean levels of soil/dust related metals, Al > Si > Fe > Ca > Ti, were mostly different from other European sites due to differences in sampling site, local geology or climate, but comparable with earlier UK data. Trace metals, Zn > Cu > Pb > Mn > Ni, mostly showed lower concentrations compared with concentrations measured at the UK national metals network sites, except for Cu and Pb. The concentrations of PAHs were in a similar range to those previously measured within the UK, with an elevation at the urban site and in winter due to increased combustion activities, particularly for the two natural gas-related Oxy-PAHs. n-Alkanes showed a higher contribution in winter (low carbon preference index: 1.5-1.6) from anthropogenic emissions but in summer (high carbon preference index: 2.7-2.9) from biogenic sources, which are appreciable at our rural site (C(max) = 29). Similar levels of hopanes were observed at the urban (0.08-0.24 ng m(-3)) and the rural (0.07-0.23 ng m(-3)) site, with higher winter values at EROS as expected but opposite for CPSS. The concentrations of organic acids ranged from 0.19-10.2 ng m(-3) at EROS and 0.26-6.0 ng m(-3) at CPSS, with mixed patterns of seasonal variation (W/S: 0.54-2.0) for individual aliphatic and aromatic carboxylic acids, except the two resin acids which exhibited much higher levels in winter (W/S: 1.7-3.3) as expected due to higher wood smoke emissions. Cholesterol showed very low annual mean concentrations (0.13-0.16 ng m(-3)) confirming that meat cooking is not an important source at our sites.


A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification.
The effect of duration of cigarette smoking cessation on colorectal cancer risk by molecular subtypes remains unclear. Using duplication-method Cox proportional-hazards regression analyses, we examined associations between duration of smoking cessation and colorectal cancer risk according to status of CpG island methylator phenotype (CIMP), microsatellite instability, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, or DNA methyltransferase-3B (DNMT3B) expression. Follow-up of 134,204 individuals in 2 US nationwide prospective cohorts (Nurses' Health Study (1980-2008) and Health Professionals Follow-up Study (1986-2008)) resulted in 1,260 incident rectal and colon cancers with available molecular data. Compared with current smoking, 10-19, 20-39, and ≥40 years of smoking cessation were associated with a lower risk of CIMP-high colorectal cancer, with multivariate hazard ratios (95% confidence intervals) of 0.53 (0.29, 0.95), 0.52 (0.32, 0.85), and 0.50 (0.27, 0.94), respectively (Ptrend = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (Ptrend = 0.25) (Pheterogeneity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks). Differential associations between smoking cessation and cancer risks by microsatellite instability (Pheterogeneity = 0.02), DNMT3B expression (Pheterogeneity = 0.03), and BRAF (Pheterogeneity = 0.10) status appeared to be driven by the associations of CIMP-high cancer with microsatellite instability-high, DNMT3B-positive, and BRAF-mutated cancers. These molecular pathological epidemiology data suggest a protective effect of smoking cessation on a DNA methylation-related carcinogenesis pathway leading to CIMP-high colorectal cancer.


Evidence for Nipah virus recrudescence and serological patterns of captive Pteropus vampyrus.
This study aimed to describe the transmission dynamics, the serological and virus excretion patterns of Nipah virus (NiV) in Pteropus vampyrus bats. Bats in captivity were sampled every 7-21 days over a 1-year period. The data revealed five NiV serological patterns categorized as high and low positives, waning, decreasing and increasing, and negative in these individuals. The findings strongly suggest that NiV circulates in wild bat populations and that antibody could be maintained for long periods. The study also found that pup and juvenile bats from seropositive dams tested seropositive, indicating that maternal antibodies against NiV are transmitted passively, and in this study population may last up to 14 months. NiV was isolated from the urine of one bat, and within a few weeks, two other seronegative bats seroconverted. Based on the temporal cluster of seroconversion, we strongly believe that the NiV isolated was recrudesced and then transmitted horizontally between bats during the study period.


The patient with excessive worry.
Worry is a normal response to uncertainty. Education, empathetic support, reassurance, and passage of time usually ameliorate ordinary worries. However, these common-sense strategies for dealing with transient worries often prove ineffective for patients with excessive worry, many of whom meet the criteria for disorders in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Evidence-based treatments for such disorders can assist family physicians in management of persistent worry as a self-perpetuating habit across diagnostic categories. Antidepressants and cognitive behavioral therapy are effective treatments for various disorders characterized by excessive worry. Cognitive behavioral strategies that may be adapted to primary care contacts include education about the worry process, repeated challenge of cognitive distortions and beliefs that underpin worry, behavioral exposure assignments (e.g., scheduled worry periods, worry journals), and learning mindfulness meditation.


Vitamin D heritability and effect of pregnancy status in Vervet monkeys (Chlorocebus aethiops sabaeus) under conditions of modest and high dietary supplementation.
The two objectives of the current study were to: 1) investigate the genetic contributions to variations in serum vitamin D concentrations under two dietary conditions (a standard monkey biscuit diet vs. a diet designed to model typical American consumption); and 2) explore the interaction of vitamin D with pregnancy status using a cohort of pedigreed female vervet/African green monkeys. This study includes 185 female (≥3.5 years) vervet/African green monkeys (Chlorocebus aethiops sabaeus) from a multi-generational, pedigreed breeding colony. The 25(OH)D3 concentrations were first measured seven to eight weeks after consuming a "typical American" diet (TAD), deriving 37, 18, and 45% of calories from fat, protein sources, and carbohydrates, and supplemented with vitamin D to a human equivalent of 1,000 IU/day. Vitamin D concentrations were assessed again when animals were switched to a low-fat, standard biscuit diet (LabDiet 5038) for 8 months, which provided a human equivalent of approximately 4,000 IU/day of vitamin D. All statistical analyses were implemented in SOLAR. Pregnancy was associated with reduced 25(OH)D3 concentrations. Heritability analyses indicated a significant genetic contribution to 25(OH)D3 concentrations in the same monkeys consuming the biscuit diet (h(2) =0.66, P=0.0004) and TAD (h(2) =0.67, P=0.0078) diets, with higher 25(OH)D3 concentrations in animals consuming the biscuit diet. Additionally, there was a significant genotype-by-pregnancy status interaction on 25(OH)D3 concentrations (P<0.05) only among animals consuming the TAD diet. These results support the existence of a genetic contribution to differences in serum 25(OH)D3 concentrations by pregnancy status and emphasize the role of diet (including vitamin D supplementation) in modifying genetic signals as well as vitamin D concentrations.


Short-term assessment of left ventricular function, coronary hemodynamics, and catecholamine balance in severe congestive heart failure after a single oral dose of milrinone.
Systemic and coronary hemodynamics were measured before and every 10 min after oral milrinone (10 mg) administration for 50 min, together with the drug plasma level in 14 patients with congestive heart failure. Left ventricular pressure (tip manometry), volume (angiography), and derived indexes were simultaneously assessed before and 60 min after milrinone treatment. Peak positive dP/dt, Vmax, and peak velocity of contractile element significantly increased 30 min after milrinone administration by 15%, 37%, and 30%, respectively. An increase in cardiac output (25%) with a consistent decrease in systemic vascular resistance (20%) occurred after 40 min without major changes in heart rate and aortic pressure. Right atrial pressure and minimal and end-diastolic left ventricular pressures decreased significantly after 50 min, by 30%, 25%, and 20%, respectively. Peak -dP/dt increased despite a slight change in end-systolic pressure. The time constants of relaxation, tau 1 and tau 2, significantly decreased by 15% after 50 min and by 16%. A transient but significant increase of 40% in coronary sinus blood flow was observed after 30 min, while myocardial oxygen consumption was unchanged 50 min after milrinone treatment. No changes were observed in catecholamine balance with milrinone. Ejection fraction increased significantly (22%) after milrinone administration, as well as the net work of left ventricle (27%). The increase of inotropism in failing hearts with a parallel reduction in preload and afterload makes milrinone a drug potentially useful in the oral treatment of severe heart failure.


Deep-intronic ABCA4 variants explain missing heritability in Stargardt disease and allow correction of splice defects by antisense oligonucleotides.
Using exome sequencing, the underlying variants in many persons with autosomal recessive diseases remain undetected. We explored autosomal recessive Stargardt disease (STGD1) as a model to identify the missing heritability. Sequencing of ABCA4 was performed in 8 STGD1 cases with one variant and p.Asn1868Ile in trans, 25 cases with one variant, and 3 cases with no ABCA4 variant. The effect of intronic variants was analyzed using in vitro splice assays in HEK293T cells and patient-derived fibroblasts. Antisense oligonucleotides were used to correct splice defects. In 24 of the probands (67%), one known and five novel deep-intronic variants were found. The five novel variants resulted in messenger RNA pseudoexon inclusions, due to strengthening of cryptic splice sites or by disrupting a splicing silencer motif. Variant c.769-784C>T showed partial insertion of a pseudoexon and was found in cis with c.5603A>T (p.Asn1868Ile), so its causal role could not be fully established. Variant c.4253+43G>A resulted in partial skipping of exon 28. Remarkably, antisense oligonucleotides targeting the aberrant splice processes resulted in (partial) correction of all splicing defects. Our data demonstrate the importance of assessing noncoding variants in genetic diseases, and show the great potential of splice modulation therapy for deep-intronic variants.


[Three years of Q fever in the Netherlands: faster diagnosis].
To assess if more rapid diagnosis and treatment is possible and to assess if this could be improved, since the first outbreak of Q fever in 2007. Retrospective study of secondary data. Analysis of surveillance data regarding Q fever over the period 2007 to 2009 and additional information on some patients from 2007 and 2008 obtained from general practitioners. Diagnostic delay fell sharply between 2007 and 2009 and to a lesser extent, so did therapeutic delay from 2007 to 2008. In high incidence areas, diagnosis and treatment was faster with a lower proportion of patients admitted to hospital than in low incidence areas. It appears that familiarity with the condition leads to faster diagnosis coupled with a lower percentage of hospital admissions. In order to react quickly it is necessary that doctor and patient should be aware of Q fever, especially in areas of low incidence. Polymerase chain reaction diagnostic techniques should also be available.


Exploring the hierarchy of mobility performance in high-functioning older women.
Preventing mobility disability depends on matching interventions to individual needs. The purpose of this study is to improve targeting by determining whether mobility performance is associated with, and predicts, mobility disability hierarchically. The hypothesis is that poorer performance tested by more demanding tasks is more strongly associated with current and future mobility "limitation" (self-reported task modification or difficulty) than is that tested by less demanding tasks, in a graded manner. Data come from the Women's Health and Aging Study II (n = 436) at baseline and at 36-month follow-up. Logistic and multinomial regression models examined associations between performance on mobility tests and reported limitation in walking one-half mile, adjusting for risk factors for disability. We found that 76.6% of prevalent and 88.4% of new-onset self-reported limitation fit within the hypothesized hierarchical pattern. The estimated strength of association between a decrement in lower extremity performance and reported limitation increased with task demand for the primary outcome, reported limitation in walking one-half mile. For example, the odds ratios for prevalent report of walking limitation, versus no limitation, for 10% lower performance walking, dressing, repeating chair stands, and climbing, respectively, were 1.05 (95% confidence interval, 0.97-1.17), 1.08 (1.00-1.16), 1.15 (1.06-1.25), and 1.22 (1.12-1.33). This study partially supports the hypothesis that mobility performance tends to follow a hierarchical pattern. For studying mild mobility disability, walking speed may not be as useful as more demanding tests. Identifying declines in performance through more demanding tests such as climbing should improve the ability to target preventive interventions to individuals at risk of mild mobility decline within a high-functioning population.


Microchimerism and tolerance following intrauterine transplantation and transfusion for alpha-thalassemia-1.
A fetus homozygous for alpha-thalassemia-1 was given haploidentical paternal CD34 cells at 13, 19 and 24 weeks' gestation and supported through pregnancy by blood transfusion. The fetal hematocrit ranged between 27 and 47% and between one half and three quarters of this hemoglobin was of recipient (Bart's) type. Intrauterine growth proceeded normally and no significant fetal hydrops was detected. Tests for donor HLA antigens, and alpha-globin DNA, were negative on fetal blood samples drawn before birth. A positive signal for alpha-globin DNA was obtained from cord blood and from marrow obtained at 3 months of age, suggesting that some donor stem cells had persisted in the recipient. The infant's blood mononuclear cells showed little proliferative and no cytotoxic response to the donor while responses to a third party were present. Additional paternal CD34 cells given at 3 months age did not reduce transfusion dependency in the subsequent 6 months. Our results show that repeated transfusions can support an alpha-thalassemia-1 fetus through pregnancy, in this instance without significant birth defects or apparent hypoxic tissue injury. The donor stem cells did not have a survival advantage compared with endogenous stem cells, but appeared to survive in the recipient as judged by the persistence of an alpha-globin DNA signal. In vitro studies of alloreactivity suggest tolerization of the host to the donor's MHC disparity. Future efforts will focus on exploiting this tolerance to improve the level of donor chimerism.


Engineering resonances in infrared metamaterials.
Engineering resonances in metamaterials has been so far the main way of reaching simultaneously negative permittivity and negative permeability leading to negative index materials. In this paper, we present an experimental and numerical analysis of the infrared response of metamaterials made of continuous nanowires and split ring resonators (SRR) deposited on low-doped silicon when the geometry of the SRRs is gradually altered. The impact of the geometric transformation of the SRRs on the spectra of the composite metamaterial is measured in the 20-200 THz frequency range (i.e., in the 1.5-15 microm wavelength range) for the two field polarizations under normal to plane propagation. We show experimentally and numerically that tuning the SRRs towards elementary cut wires translates in a predictable manner the frequency response of the artificial material. We also analyze coupling effects between the SRRs and the continuous nanowires for different spacings between them. The results of our study are expected to provide useful guidelines for the design of negative index metamaterials on silicon.


Anomalously low electronic thermal conductivity in metallic vanadium dioxide.
In electrically conductive solids, the Wiedemann-Franz law requires the electronic contribution to thermal conductivity to be proportional to electrical conductivity. Violations of the Wiedemann-Franz law are typically an indication of unconventional quasiparticle dynamics, such as inelastic scattering, or hydrodynamic collective motion of charge carriers, typically pronounced only at cryogenic temperatures. We report an order-of-magnitude breakdown of the Wiedemann-Franz law at high temperatures ranging from 240 to 340 kelvin in metallic vanadium dioxide in the vicinity of its metal-insulator transition. Different from previously established mechanisms, the unusually low electronic thermal conductivity is a signature of the absence of quasiparticles in a strongly correlated electron fluid where heat and charge diffuse independently.


Relationship between increasing duodenal lipid doses, gastric perception, and plasma hormone levels in humans.
Duodenal lipid causes gastric relaxation, CCK secretion, and nausea. Vasopressin has been implicated in motion sickness-related nausea. We hypothesized that increasing doses of lipid enhance gastric relaxation and CCK-vasopressin secretion, resulting in a dose-related exacerbation of nausea. Nine healthy subjects received isotonic saline or lipid (1, 2, or 3 kcal/min, L1, L2, L3) duodenally. Changes in gastric volume, sensations, and plasma hormone levels were assessed during infusions and isobaric gastric distensions. Lipid infusions increased gastric volume, plasma CCK (but not vasopressin) levels, and gastric compliance during distensions, compared with saline. Plasma CCK levels were related to the dose of lipid administered [CCK levels at 30 min (pmol/l), saline: 1.1 +/- 0.2, L1: 1.8 +/- 0.2, L2: 3.0 +/- 0.2, L3: 4.3 +/- 0.6]. During distensions, nausea increased in intensity with increasing doses of lipid [score (where 0 is no sensation and 100 is strongest sensation), saline: 7 +/- 4, L1: 19 +/- 7, L2: 44 +/- 7, L3: 66 +/- 8]; however, no further rise in plasma CCK occurred. Because neither lipid nor distension alone induced significant nausea, we conclude that the interaction between these stimuli together with a modulation by CCK is responsible for the effects observed. Vasopressin is not involved in lipid- and distension-induced nausea.


[Immune responses of IgG, IgA and anti-CagA IgG to Helicobacter pylori in dyspeptic and peptic ulcer patients].
The anti-H. pylori IgG, IgA, and anti CagA responses in dyspeptic patients have been evaluated. Of 481 patients 76% tested positive for IgG anti-H. pylori, 57% for anti-CagA, and 52% IgA for anti H. pylori. There was a significant age-related increase in IgG anti-H. pylori and IgA anti-H. Pylori prevalence, whereas anti-CagA positives were unreliable in this respect. The IgG seropositivity was the highest (93%) in duodenal ulcers (DU), 82% in antral gastritis and/or bulbitis (AG +/- /B), and 71% in gastric ulcer (GU). GU patients compared with DU and AG +/- /B ones tended to have the highest IgA anti-H. pylori prevalence (78% vs. 66% and 61%). The anti-CagA seropositivity was the most pronounced (80%) in DU followed by GU (72%) and AG +/- /B (68%). It is suggested that the serodiagnosis including IgG, IgA anti-H. pylori and anti-CagA determinations can not replace endoscopy in revealing the exact nature of gastroduodenal lesions. IgA anti-H. pylori determination in female patients with GU can be a valuable diagnostic tool. It is stated that in Hungary the prevalence of CagA positive H. pylori strains in anti-H. pylori IgG positive dyspeptic patients is 85%.


The accelerated simian immunodeficiency virus macaque model of human immunodeficiency virus-associated neurological disease: from mechanism to treatment.
Highly active antiretroviral therapy has been effective in lowering viral loads in the peripheral blood, restoring immune function and reducing the incidence of opportunistic infections and dementia in human immunodeficiency virus (HIV)-infected individuals. However, motor and cognitive deficits and peripheral neuropathy continue, with some studies reporting an increase in prevalence of nervous system disease. The authors developed an accelerated, consistent simian model of HIV infection in which pigtailed macaques are dual inoculated with a neurovirulent simian immunodeficiency virus (SIV) clone and an immunosuppressive SIV strain. Infected animals invariably develop acquired immunodeficiency syndrome (AIDS) and over 90% develop central nervous system disease as well as peripheral nervous system disease with neurodegeneration by 3 months postinoculation. This model provides outstanding opportunities to delineate the pathogenesis of infection, to study the regulation of virus gene expression, and to identify host immune responses throughout the acute, clinically silent and late stages of infection. Using this model, the authors have demonstrated that the virus enters the brain within days after inoculation, that CCL2 (monocyte chemoattractant protein [MCP]-1) plays a major role in recruiting monocytes/macrophages to the brain, and that type I interferons are critical in suppressing early virus replication and inducing viral latency. This model provides a rigorous platform for the testing of potential antiretroviral, immune reconstituting, and/or neuroprotective agents and already has been used to confirm the neuroprotective properties of minocycline, which now is being tested in clinical trials of HIV-infected individuals.


Could EBT Machines Increase Fruit and Vegetable Purchases at New York City Green Carts?
Residents of some low-income neighborhoods have limited access to fresh fruits and vegetables. In 2008, New York City issued new mobile fruit and vegetable cart licenses for neighborhoods with inadequate availability of fresh produce. Some of these carts were equipped with electronic benefit transfer (EBT) machines, allowing them to accept Supplemental Nutrition Assistance Program (SNAP) benefits. This article examines the association between type and quantities of fruits and vegetables purchased from mobile fruit and vegetable vendors and consumer characteristics, including payment method. Customers at 4 produce carts in the Bronx, New York, were surveyed during 3 periods in 2013 and 2014. Survey data, including purchased fruit and vegetable quantities, were analyzed using multivariable negative binomial regressions, with payment method (cash only vs EBT or EBT and cash) as the primary independent variable. Covariates included availability of EBT, vendor, and customer sociodemographic characteristics. A total of 779 adults participated in this study. Shoppers who used SNAP benefits purchased an average of 5.4 more cup equivalents of fruits and vegetables than did shoppers who paid with cash. Approximately 80% of this difference was due to higher quantities of purchased fruits. Expanding access to EBT machines at mobile produce carts may increase purchases of fruits and vegetables from these vendors.


Intensity-modulated radiation therapy in head and neck squamous cell carcinoma: an adaptation of 2-dimensional concepts or a reconsideration of current clinical practice.
Intensity-modulated radiation therapy (IMRT) for head and neck (HN) tumors refers to a new approach to the whole treatment procedure from patient immobilization to beam delivery. Implementation of IMRT thus requires knowledge of setup uncertainties, adequate selection, and delineation of target volumes based on optimal imaging modalities, appropriate specification, and dose prescription regarding dose-volume constraints and ad hoc quality control of both the clinical and physical aspects of the whole procedure. A large number of issues still need to be resolved and/or further refined, such as the optimal selection and delineation of the target volume, in particular, with the introduction of functional imaging, and a better integration of improved dose distribution into the fractionation strategy. IMRT is associated with a potentially increased incidence of carcinogenesis, although in the HN area this risk is relative to the intrinsic risk of comorbidity and secondary cancer associated with the patient's lifestyle. Currently, the implementation of IMRT into routine clinical practice for HN cancers may not be a straightforward matter and should probably be restricted to selected institutions with adequate resources and experience. This review emphasizes these aspects and provides some recommendations for the future use of IMRT in patients with HN tumors.


Does the U.S. public support using gene drives in agriculture? And what do they want to know?
Gene drive development is progressing more rapidly than our understanding of public values toward these technologies. We analyze a statistically representative survey (n = 1018) of U.S. adult attitudes toward agricultural gene drives. When informed about potential risks, benefits, and two previously researched applications, respondents' support/opposition depends heavily (+22%/-19%) on whether spread of drives can be limited, non-native versus native species are targeted (+12%/-9%), or the drive replaces versus suppresses target species (±2%). The one-fifth of respondents seeking out non-GMO-labeled food are more likely to oppose drives, although their support exceeds opposition for limited applications. Over 62% trust U.S. universities and the Department of Agriculture to research gene drives, with the private sector and Department of Defense viewed as more untrustworthy. Uncertain human health and ecological effects are the public's most important concerns to resolve. These findings can inform responsible innovation in gene drive development and risk assessment.


Spectral content (colour) of noise exposure affects work efficiency.
As part of an effort to enhance the efficiency of workers, experiments relating to three types of noise exposure were conducted. Previous studies have proved that pink noise can cause a brain wave to reach a lower potential. In this study, we utilized physical methods, in cognitive experiments, to understand the impacts that three colour noises have on working efficiency. All 22 participants were exposed to a sound environment of quiet, red, pink and white noises respectively. After a laboratory experiment, details of psychomotor speed, continuous performance, executive function and working memory were recorded. Red, pink and white noises were significantly positive in comparison with the quiet environment of the psychomotor speed test. As for the continuous performance test, pink noise gave the only significantly positive result. Red, pink and white noise resulted in a better executive function test. Red and pink noise showed significantly positive improvement, while white noise was significantly positive in comparison with the quiet environment of the working memory test. In addition, the results from the comfort questionnaires showed that red and pink noise increase the possibility of better judgment, implementation, and overall environment. At present time, it is considered that noise has negative effects on hearing and health. However, experimental results show that certain noise can enhance environmental comfort. It is feasible, in the future, to use knowledge of colour noises to improve productivity in a workplace with a healthy environment.


Unusual endosteally formed bone tissue in a patagonian basal sauropodomorph dinosaur.
Mussaurus patagonicus (Dinosauria: Sauropodomorpha) is a basal sauropodomorph from the Late Triassic of southern Argentina that is known from a large number of individuals, including juveniles, subadults, and adults. Here, we report on the occurrence of an unusual bone tissue in an individual of M. patagonicus. The rather atypical bone tissue is located within the femoral medullary cavity and also occurs within several erosion cavities of the midinner part of the cortex. This tissue is well vascularized and is composed of a matrix that consists of abundant and densely packed osteocyte lacunae. Although some features of this tissue resembles avian medullary bone, the histological features are distinctive and share more features with the pathological, reactive bone produced in extant birds in response to a retrovirus-induced disease (avian osteopetrosis). Here, we also discuss and provide histological features to effectively differentiate endosteally formed medullary bone from pathological avian osteopetrosis.


Psychologists experience of cognitive behaviour therapy in a developing country: a qualitative study from Pakistan.
Psychological therapies especially Cognitive Behaviour Therapy (CBT) are used widely in the West to help patients with psychiatric problems. Cognitive Behaviour Therapy has an established evidence base for the treatment of different emotional disorders. In spite of these developments in the developed world, patients in most developing countries hardly benefit from non pharmacological interventions. Although a significant number of psychologists are trained in Pakistan each year, psychological interventions play only a minor role in treatment plans in Pakistan. We conducted interviews with psychologists in Pakistan, to explore their experiences and their views on "providing CBT in Pakistan". These interviews were conducted as part of a project whose focus was to try to develop culturally-sensitive CBT in Pakistan. In depth semi structured interviews were conducted with 5 psychologists working in psychiatry departments in Lahore, Pakistan. All the psychologists reported that psychotherapies, including CBT, need adjustments for use in Pakistan, although they were not able to elicit on these in details. Four major themes were discovered, hurdles in therapy, therapy related issues, involvement of the family and modification in therapy. The biggest hurdles in therapy were described to be service and resource issues. For CBT to be acceptable, accessible and effective in Non Western cultures numerous adjustments need to be made, taking into consideration; factors related to service structure and delivery, patient's knowledge and beliefs about health and the therapy itself. Interviews with the psychologists in these countries can give us insights which can guide development of therapy and manuals to support its delivery.


Conservation of distantly related membrane proteins: photosynthetic reaction centers share a common structural core.
Photosynthesis was established on Earth more than 3 billion years ago. All available evidences suggest that the earliest photosynthetic organisms were anoxygenic and that oxygen-evolving photosynthesis is a more recent development. The reaction center complexes that form the heart of the energy storage process are integral membrane pigment proteins that span the membrane in vectorial fashion to carry out electron transfer. The origin and extent of distribution of these proteins has been perplexing from a phylogenetic point of view mostly because of extreme sequence divergence. A series of integral membrane proteins of known structure and varying degrees of sequence identity have been compared using combinatorial extension-Monte Carlo methods. The proteins include photosynthetic reaction centers from proteobacteria and cyanobacterial photosystems I and II, as well as cytochrome oxidase, bacteriorhodopsin, and cytochrome b. The reaction center complexes show a remarkable conservation of the core structure of 5 transmembrane helices, strongly implying common ancestry, even though the residual sequence identity is less than 10%, whereas the other proteins have structures that are unrelated. A relationship of sequence with structure was derived from the reaction center structures; with characteristic decay length of 1.6 A. Phylogenetic trees derived from the structural alignments give insights into the earliest photosynthetic reaction center, strongly suggesting that it was a homodimeric complex that did not evolve oxygen.


Bisphenol A Exposure and Sperm ACHE Hydroxymethylation in Men.
Exposure to bisphenol A (BPA) has been shown to impact human sperm quality. The epigenetic mechanisms underlying the effect remain unknown. The acetylcholinesterase (ACHE) gene is a sperm-expressed gene encoding the acetylcholine hydrolyzing enzyme acetylcholinesterase and participates in the apoptosis of cells, including sperm. This study aimed to examine whether BPA exposure is associated with the hydroxymethylation level of the sperm ACHE gene. A total of 157 male factory workers were studied, among whom 74 had BPA exposure in the workplace (BPA exposure group) and 83 had no BPA exposure in the workplace (control group). Urine samples were collected for BPA measurement and semen samples were collected to assay for ACHE hydroxymethylation. Sperm ACHE hydroxymethylation level was higher in the BPA exposure group (p = 0.041) compared to the control group. When subjects were categorized according to tertiles of detected BPA level, higher ACHE hydroxymethylation levels were observed for the lowest, middle, and top tertiles compared to those with BPA below the limit of detection (LOD). In a linear regression analysis adjusted for confounders, a positive linear association between urine BPA concentration and 5-hydroxymethylcytosine (5hmC) rate of the sperm ACHE gene was observed, although the association did not reach statistical significance in all categories after being stratified by the BPA tertile. In conclusion, 5hmC of the sperm ACHE gene was positively associated with BPA exposure, which may provide supportive evidence for BPA's effects on male fertility or other health endpoints.


Glycolytic Switch Is Required for Transdifferentiation to Endothelial Lineage.
We have previously shown that activation of cell-autonomous innate immune signaling facilitates the transdifferentiation of fibroblasts into induced endothelial cells, and is required to generate induced endothelial cells with high fidelity for endothelial lineage. Recent studies indicate that a glycolytic switch plays a role in induced pluripotent stem cell generation from somatic cells. Seahorse and metabolomics flux assays were used to measure the metabolic changes during transdifferentiation in vitro, and Matrigel plug assay was used to assess the effects of glycolysis modulators on transdifferentiation in vivo. The metabolic switch begins rapidly after activation of innate immunity, before the expression of markers of endothelial lineage. Inhibiting glycolysis impaired, whereas facilitating glycolysis enhanced, the generation of induced endothelial cells. The toll-like receptor 3 agonist poly I:C increased expression of the mitochondrial citrate transporter Slc25A1, and the nuclear ATP-citrate lyase, in association with intracellular accumulation of citrate, the precursor for acetyl coenzyme A. These metabolic changes were coordinated with increased histone acetylation during transdifferentiation. Innate immune signaling promotes a glycolytic switch that is required for transdifferentiation, both processes being attenuated by ATP-citrate lyase knockdown. These data shed light on a novel link between metabolism and epigenetic modulation in transdifferentiation.


Deletion of DNA sequence in a nononcogenic variant of Herpesvirus saimiri.
The 110-kilobase-pair stretch of unique sequence DNA of Herpesvirus saimiri is flanked by highly repetitive DNA. Detailed restriction endonuclease mapping has localized the left junction of repetitive and unique DNA to a 100-base-pair region. H. saimiri 11att, a replication competent nononcogenic variant of strain 11, has a deletion of 2.3 kilobase pairs of sequence information that spans this left junction of repetitive and unique DNA.


Expression and secretion of lipocortin 1 in gut inflammation are not regulated by pituitary-adrenal axis.
Lipocortin 1 is considered a mediator of the anti-inflammatory actions of glucocorticoids. We have shown that this protein is overexpressed and secreted during an experimental colitis induced by intraluminal injection of trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo regulation of lipocortin 1 expression and secretion in this model, either by glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h) animals or by pituitary factors using hypophysectomized animals. Inflammation was evaluated by measuring myeloperoxidase activity and by histological scoring of the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was studied by incubating colonic specimens in-culture medium. In the colon of TNBS-injected animals, cumulative histological damage scores were increased in adrenalectomized and decreased in dexamethasone-treated animals compared with control and hypophysectomized animals. The colons of all TNBS-injected animals (controls, adrenalectomized, dexamethasone treated, hypophysectomized) overexpressed and secreted lipocortin 1. In conclusion, the induction of lipocortin 1 overexpression and secretion during this colitis occurs independently of glucocorticoids or pituitary factors.


Kinetic studies with cytosol and mitochondrial phosphoenolpyruvate carboxykinases.
1. Measurements of Michaelis constants for oxaloacetate in the reaction catalysed by liver phosphoenolpyruvate carboxykinase give values much lower than previously reported. With Mg(2+) as bivalent cation, the Michaelis constant was approx. 2.5x10(-5)m whether the enzyme used was the mitochondrial phosphoenolpyruvate carboxykinase purified from sheep liver or chicken liver or the cytosol enzyme purified from rat liver or sheep liver. 2. When Mn(2+) replaced Mg(2+) in the reaction a lower Michaelis constant of 9x10(-6)m was found, but only with the mitochondrial enzymes. 3. With all enzymes malate at high concentration was a competitive inhibitor with respect to oxaloacetate when Mn(2+) was the added cation. With Mg(2+) the inhibition by malate was competitive with the mitochondrial enzymes and non-competitive with the cytosol enzymes.


Results of the Tessier integral procedure for correction of Treacher Collins syndrome.
A new procedure is proposed for correction of the malformations of severe cases of Treacher Collins syndrome in the areas of the maxilla, mandible, and orbit. The operation essentially consists of a rotation of the midfacial segment around a transverse axis at the frontonasal angle. The midface is rotated forward anteriorly and downward posteriorly. It is stabilized by cranial grafts impinged into the temporal bone and the maxilla. The mandible is lengthened either by V shape osteotomy or bone grafting of the ramus. The mandible is fixed in an overjet class III dental occlusion. A posterior bite wafer is maintained for 2 months. The construction of the orbital cavity is completed with cranial bone grafts. The Tessier integral procedure for Treacher Collins syndrome has been done in one stage in six patients and in two stages in five patients. Sufficient data were available for analysis of only four patients.


Choroid plexus papilloma. Report of a case with cytologic differential diagnosis.
The cytopathologic features of choroid plexus papilloma observed in the ventricular fluid of a 9-month-old boy are reported and compared with other pediatric central nervous system neoplasms. The cytologic features of choroid plexus papilloma are similar to those of normal choroid plexus and may be difficult to distinguish from those of a well-differentiated papillary ependymoma. However, the cell clusters are distinct from those associated with choroid plexus carcinoma and primitive neuroectodermal tumors.


Factors influencing Clostridium botulinum spore germination, outgrowth, and toxin formation in acidified media.
Clostridium botulinum type A spores were inoculated at a level of 10(7) spores per ml into sterile beef media with protein concentrations of 1, 2, 3, 4, or 6% and acidified to pH values of 2.01 to 4.75 with hydrochloric acid or 4.19 to 4.60 with citric acid. All experimental manipulations, including blending, acidification, inoculation, incubation (30 degrees C), and analyses, were conducted in an anaerobic chamber-incubator in which atmospheric oxygen levels were maintained below 2 ppm (2 microliters/liter). Under these strict anaerobic conditions (oxidation-reduction values in media ranging from -370 to -391 mV), C. botulinum spores were consistently found to germinate, grow, and produce toxin below pH 4.6. The boundary between toxic and atoxic samples in HC1-acidified beef media was mediated by titratable acidity, pH, and protein concentration. A limiting acidity was not established for the citrate-acidified samples; all blends tested (1, 2, 3, and 4% protein and titratable acidities of 0.091 to 0.453%) became toxic within 5 weeks. At the same pH and protein concentration, citric acid was less effective than HC1 in preventing the germination of C. botulinum spores. Higher levels of cell proliferation in the beef protein, as well as enhanced gas production and putrefactive degradation, indicated that beef was a better substrate than soy for C. botulinum spores under these conditions. Reducing the inoculum to 10(4) delayed but did not prevent spore outgrowth and toxin release at pH levels below 4.6.


The effect of interactive analytical dashboard features on situation awareness and task performance.
In recent years, new types of interactive analytical dashboard features have emerged for operational decision support systems (DSS). Analytical components of such features solve optimization problems hidden from the human eye, whereas interactive components involve the individual in the optimization process via graphical user interfaces (GUIs). Despite their expected value for organizations, little is known about the effectiveness of interactive analytical dashboards in operational DSS or their influences on human cognitive abilities. This paper contributes to the closing of this gap by exploring and empirically testing the effects of interactive analytical dashboard features on situation awareness (SA) and task performance in operational DSS. Using the theoretical lens of SA, we develop hypotheses about the effects of a what-if analysis as an interactive analytical dashboard feature on operational decision-makers' SA and task performance. The resulting research model is studied with a laboratory experiment, including eye-tracking data of 83 participants. Our findings show that although a what-if analysis leads to higher task performance, it may also reduce SA, nourishing a potential out-of-the-loop problem. Thus, designers and users of interactive analytical dashboards have to carefully mitigate these effects in the implementation and application of operational DSS. In this article, we translate our findings into implications for designing dashboards within operational DSS to help practitioners in their efforts to address the danger of the out-of-the-loop syndrome.


Assessment of the correlations of lacosamide concentrations in saliva and serum in patients with epilepsy.
Therapeutic drug monitoring of antiepileptic drugs is based on patient serum samples. In this study, we evaluated the correlation between lacosamide (LCM) steady state concentrations in serum and saliva samples. Additionally, we investigated the relation with daily dose, and assessed the feasibility of saliva collection. This was an open-label, single center study including data from 25 patients at the Bethel Epilepsy Center treated with LCM (50-650 mg/d). Samples were collected in the morning (fasting values) and in selected cases at 50 minutes to 5 hours after the morning dose. Nonsignificant differences in the mean LCM morning (trough) concentration in serum and saliva were observed. Serum and saliva concentrations across all samples were highly correlated, (r = .874), with a slightly lower correlation when only fasting values were analyzed (r = .860). Higher correlation with daily dosages was observed in serum samples (r = .773) than in saliva samples (r = .604). Serum and saliva concentrations increased significantly after intake of the LCM morning dose (P < .001). The median absolute and percentage increase of LCM in serum were moderately lower than in saliva samples, with a few outliers in saliva samples. Consequently, saliva could offer great clinical potential to monitor drug concentrations and guide LCM treatment in epileptic patients.


Revisiting Tension Band Fixation for Difficult Patellar Fractures.
Patella fractures with comminution, osteoporotic bone, and/or previously failed fixation are exceedingly difficult to reduce and fix. Moreover, the risk of symptomatic constructs and patients who are poorly compliant with postoperative activity restrictions can make these complex fracture patterns an even more challenging scenario. Although there is an array of techniques described for comminuted patella fractures, there lacks an accepted surgical technique for these difficult cases. In this clinical series, we describe an enhancement to the traditional tension band construct that uses additional wires and multiple tension bands to gather and fix comminuted fracture patterns in nontransverse planes, bolster osteoporotic bone, and secure fractures in patients undergoing a revision and/or have potential to be poorly compliant with postoperative activity restrictions. The clinical outcomes of 27 patients demonstrate high rates of bony union, functional range of motion, and low rates of both infection and failure. In conclusion, using the basic principles of tension band wiring remains highly versatile, useful, and economical in approaching difficult patella fractures.


In vivo detection of macrophage recruitment in hind-limb ischemia using a targeted near-infrared fluorophore.
Macrophages are an essential component of the immune system and have protective and pathogenic functions in various diseases. Imaging of macrophages in vivo could furnish new tools to advance evaluation of disease and therapies. Critical limb ischemia is a disease in which macrophages have considerable pathogenic roles, and are potential targets for cell-based immunotherapy. We sought to develop a new near-infrared fluorescence (NIRF) imaging probe to target macrophages specifically in vivo in various pathological states, including hind-limb ischemia. We rapidly screened the photostable cyanine-based NIRF library against different blood cell lines. The identified monocyte/macrophage-selective hit was tested in vitro in live-cell labeling assay. Non-invasive NIRF imaging was performed with murine models of paw inflammation by lipopolysaccharide challenge and hind-limb ischemia with femoral artery ligation. in vivo macrophage targeting was further evaluated using intravital microscopy with Csf1r-EGFP transgenic mice and immunofluorescent staining with macrophage-specific markers. We discovered MF800, a Macrophage-specific near-infrared Fluorophore, which showed selective live-cell imaging performance in a panel of cell lines and primary human blood samples. MF800 outperforms the clinically-available NIRF contrast agent ICG for in vivo specificity in paw inflammation and hind-limb ischemia models. We observed a marked overlap of MF800-labeled cells and EGFP-expressing macrophages in intravital imaging of Csf1r-EGFP transgenic mice. In the histologic analysis, MF800-positive cells also expressed the macrophage markers CD68 and CD169. NIRF imaging showcased the potential of using MF800 to understand macrophage behavior in vivo, characterize macrophage-associated diseases, and may help in assessing therapeutic responses in the clinic.


Bone mineral density of opposing hips using dual energy X-Ray absorptiometry in single-beam and fan-beam design.
Bone densitometry focuses on bone mineral area density (BMD in g/cm2) of the proximal femur and spine in anterior-posterior (AP) projections. Artifacts, such as osteoarthritis and osteophytic calcifications (OC) influence spine BMD, especially in AP scans. If only two sites are measured, as is usual in clinical practice, there may be advantages to measuring both femora rather than one femur and the spine. This would not be useful, however, if there was strong symmetry between the two sides. Furthermore, fan beam (FB) techniques have become available for measuring BMD with less data acquisition time. We compared densitometry of opposing femora in 421 patients (369 women, mean age 59.0 +/- 4.8; 52 men, mean age 56.9 +/- 7.4) using dual-energy X-ray absorptiometry (DXA): both single-beam (SB) and FB modes were evaluated. The precision errors in vivo (short- and midterm) of total BMD were 0.7% for both SB and FB. The total BMD and BMC of the left hip (0.817 +/- 0.124 g/cm2, 31. 3 +/- 6.4 g) were significantly (P < 0.001) higher (2-3%) than the corresponding values of the right hip (0.801 +/- 0.125 g/cm2, 30.3 +/- 6.3 g) in both SB and FB (left BMD 0.802 +/- 0.117 g/cm2, BMC 30. 0 +/- 6.2 g versus right BMD 0.795 +/- 0.117 g/cm2, BMC 29.3 +/- 6.3 g) modes. However, BMD of the femoral neck and Ward's triangle were not significantly (P > 0.05) different between the two sides. The FB results were generally 2% lower than SB results. There were highly significant (P < 0.001) correlations (r > 0.9) between both hips using both SB and FB. For diagnostic procedures and longitudinal studies, one should consider that there are bilateral differences of femur BMD, as well as differences between FB and SB scan modes.


Chronic spinal cord electrical stimulation protects against 6-hydroxydopamine lesions.
Although L-dopa continues to be the gold standard for treating motor symptoms of Parkinson's disease (PD), it presents long-term complications. Deep brain stimulation is effective, but only a small percentage of idiopathic PD patients are eligible. Based on results in animal models and a handful of patients, dorsal column stimulation (DCS) has been proposed as a potential therapy for PD. To date, the long-term effects of DCS in animal models have not been quantified. Here, we report that DCS applied twice a week in rats treated with bilateral 6-OHDA striatal infusions led to a significant improvement in symptoms. DCS-treated rats exhibited a higher density of dopaminergic innervation in the striatum and higher neuronal cell count in the substantia nigra pars compacta compared to a control group. These results suggest that DCS has a chronic therapeutical and neuroprotective effect, increasing its potential as a new clinical option for treating PD patients.


Fast and near-optimal monitoring for healthcare acquired infection outbreaks.
According to the Centers for Disease Control and Prevention (CDC), one in twenty five hospital patients are infected with at least one healthcare acquired infection (HAI) on any given day. Early detection of possible HAI outbreaks help practitioners implement countermeasures before the infection spreads extensively. Here, we develop an efficient data and model driven method to detect outbreaks with high accuracy. We leverage mechanistic modeling of C. difficile infection, a major HAI disease, to simulate its spread in a hospital wing and design efficient near-optimal algorithms to select people and locations to monitor using an optimization formulation. Results show that our strategy detects up to 95% of "future" C. difficile outbreaks. We design our method by incorporating specific hospital practices (like swabbing for infections) as well. As a result, our method outperforms state-of-the-art algorithms for outbreak detection. Finally, a qualitative study of our result shows that the people and locations we select to monitor as sensors are intuitive and meaningful.


Total intravenous anesthesia including ketamine versus volatile gas anesthesia for combat-related operative traumatic brain injury.
Traumatic brain injury is a leading cause of death and severe neurologic disability. The effect of anesthesia techniques on neurologic outcomes in traumatic brain injury and potential benefits of total intravenous anesthesia (TIVA) compared with volatile gas anesthesia (VGA), although proposed, has not been well evaluated. The purpose of this study was to compare TIVA versus VGA in patients with combat-related traumatic brain injury. The authors retrospectively reviewed 252 patients who had traumatic brain injury and underwent operative neurosurgical intervention. Statistical analyses, including propensity score and matched analyses, were performed to assess differences between treatment groups (TIVA vs. VGA) and good neurologic outcome. Two hundred fourteen patients met inclusion criteria and were analyzed; 120 received VGA and 94 received TIVA. Good neurologic outcome (Glasgow Outcome Score 4-5) and decreased mortality were associated with TIVA compared with VGA (75% vs. 54%; P = 0.002 and 5% vs. 16%; P = 0.02, respectively). Multivariate logistic regression found admission Glasgow Coma Scale score of 8 or greater (odds ratio, 13.3; P < 0.001) and TIVA use (odds ratio, 2.3; P = 0.05) to be associated with good neurologic outcomes. After controlling for confounding factors using propensity analysis and repeated one-to-one matching of patients receiving TIVA with those receiving VGA with regard to Injury Severity Score, Glasgow Coma Scale score, base deficit, Head Abbreviated Injury Score, and craniectomy or craniotomy, the authors could not find an association between treatment and neurologic outcome. Total intravenous anesthesia often including ketamine was not associated with improved neurologic outcome compared with VGA. Multiple confounders limit conclusions that can be drawn from this retrospective study.


A cluster of central line-associated bloodstream infections due to rapidly growing nontuberculous mycobacteria in patients with hematologic disorders at a Japanese tertiary care center: an outbreak investigation and review of the literature.
BACKGROUND Rapidly growing nontuberculous mycobacteria (RGM) are considered rare pathogens, causing central line-associated bloodstream infection. We identified an outbreak of central line-associated bloodstream infection due to RGM at a hematology-oncology ward during a 5-month period. DESIGN Outbreak investigation and literature review. SETTING A Japanese tertiary care center. PATIENTS Adults who were hospitalized at the hematology-oncology ward from October 15, 2011, through February 17, 2012. RESULTS A total of 5 patients with a bloodstream infection due to RGM (4 cases of Mycobacterium mucogenicum and 1 case of Mycobacterium canariasense infection) were identified; of these, 3 patients had acute myeloid leukemia, 1 had acute lymphocytic leukemia, and 1 had aplastic anemia. Four of the 5 patients received cord blood transplantation prior to developing the bloodstream infection. All central venous catheters in patients with a bloodstream infection were removed. These patients promptly defervesced after catheter removal and their care was successfully managed without antimicrobial therapy. Surveillance cultures from the environment and water detected M. mucogenicum and M. canariasense in the water supply of the hematology-oncology ward. The isolates from the bloodstream infection and water sources were identical on the basis of 16S-rRNA gene sequencing. CONCLUSIONS The source of RGM in the outbreak of bloodstream infections likely was the ward tap water supply. Awareness of catheter-related bloodstream infections due to nontuberculous mycobacteria should be emphasized, especially where immunocompromised patients are at risk. Also, using antimicrobials after catheter removal to treat central line-associated bloodstream infection due to RGM may not be necessary. Infect Control Hosp Epidemiol 2015;36(1): 76-80.