Redistribution of mobile surface charges of an oil droplet in water in applied electric field.
Most researches on oil droplets immersed in aqueous solutions assume that the surface charges of oil droplets are, similar to that of solid particles, immobile and distributed uniformly under external electric field. However, the surface charges at the liquid-liquid interface are mobile and will redistribute under external electric field. This paper studies the redistribution of surface charges on an oil droplet under the influence of the external electrical field. Analytical expressions of the local zeta potential on the surface of an oil droplet after the charge redistribution in a uniform electrical field were derived. The effects of the initial zeta potential, droplet radius and strength of applied electric field on the surface charge redistribution were studied. In analogy to the mobile surface charges, the redistribution of Al2O3-passivated aluminum nanoparticles on the oil droplet surface was observed under applied electrical field. Experimental results showed that these nanoparticles moved and accumulated towards one side of the oil droplet under electric field. The redistribution of the nanoparticles is in qualitative agreement with the redistribution model of the mobile surface charges developed in this work.


A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism.
Gastric cardia cancer (GCC), which occurs at the gastric-esophageal boundary, is one of the most malignant tumors. Despite its high mortality and morbidity, the molecular mechanism of initiation and progression of this disease is largely unknown. In this study, using proteomics and metabolomics approaches, we found that the level of several enzymes and their related metabolic intermediates involved in glucose metabolism were deregulated in GCC. Among these enzymes, two subunits controlling pyruvic acid efflux, lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase B (PDHB), were further analyzed in vitro. Either down-regulation of LDH subunit LDHA or overexpression of PDH subunit PDHB could force pyruvic acid into the Krebs cycle rather than the glycolysis process in AGS gastric cancer cells, which inhibited cell growth and cell migration. Our results reflect an important glucose metabolic signature, especially the dysregulation of pyruvic acid efflux in the development of GCC. Forced transition from glycolysis to the Krebs cycle had an inhibitory effect on GCC progression, providing potential therapeutic targets for this disease.


The potential of Pathfinder AVHRR data for providing surrogate climatic variables across Africa and Europe for epidemiological applications.
Surface climatic conditions are key determinants of arthropod vector distribution and abundance and consequently affect transmission rates of any diseases they may carry. Remotely sensed observations by satellite sensors are the only feasible means of obtaining regional and continental scale measurements of climate at regular intervals for real-time epidemiological applications such as disease early warning systems. The potential of Pathfinder AVHRR Land (PAL) data to provide surrogate variables for near-surface air temperature and vapour pressure deficit (VPD) over Africa and Europe were assessed in this context. For the years 1988-1990 and 1992, correlations were examined between meteorological ground measurements (monthly mean air temperature and VPD(grd)) and variables derived from Advanced Very High Resolution Radiometer (AVHRR) data (LST and VPD(sat)). The AVHRR indices were derived from both daily and composite PAL data so that their relative performance could be determined. Furthermore, the ground observations were divided into African and European subsets, so that the relative performance of the satellite data at tropical/sub-tropical and temperate latitudes could be assessed.Significant correlations were shown between air temperature and LST in all months. Temporal variability existed in the strength of correlations throughout any twelve-month period, with the pattern of variability consistent between years. The adjusted r(2) values increased when elevation and the Normalised Difference Vegetation Index (NDVI) were included, in addition to LST, as predictor variables of air temperature. Attempts to derive monthly estimates of atmospheric moisture availability resulted in an over-estimation of VPD(sat) compared to ground observations, VPD(grd). The use of daily PAL data to derive monthly mean climatic indices was shown to be more accurate than those obtained using monthly maximum values from 10-day composite data. A subset of the 1992 data was then used to build linear regression models for the direct retrieval of monthly mean air temperature from PAL data. The accuracy of retrieved estimates was greatest when NDVI was included with LST as predictor variables, with root mean square errors varying from 1.83°C to 3.18 °C with a mean of 2.38 °C over the twelve months.


Internet-based treatment of pathological gambling with a three-year follow-up.
Effective therapies for pathological gambling exist, but their use is limited to about 10% of the target population. In an attempt to lower the barriers for help, Internet-based cognitive behavioural therapy (ICBT) has been shown to be effective when delivered to a non-depressed sample with pathological gambling. This study sought to extend this finding to a larger, more representative population, and also test a model to predict responder status. Following advertisement, a total of 284 participants started an 8-week ICBT programme with minimal therapist contact via e-mail and weekly telephone calls of less than 15 min. The average time spent on each participant, including telephone conversations, e-mail, and administration, was 4 h. In addition to a mixed effects model to evaluate the effectiveness of the treatment, two logistic regression analyses were performed with the following eight pre-defined response predictor variables: work-life satisfaction, primary gambling activity, debts due to gambling, social support, personal yearly salary, alcohol consumption, stage of change, and dissociative gambling. ICBT resulted in statistically significant reductions in the scores of pathological gambling, anxiety, and depression as well as an increase in quality of life compared to pre-treatment levels. Follow-ups carried out in the treatment group at 6, 18, and 36 months indicated that treatment effects were sustained. Using the eight predictor variable model rendered an acceptable predictive ability to identify responders both at post-test (AUC = .72, p < .01) and at 36-month follow-up (AUC = .70, p < .01). We conclude that ICBT for pathological gamblers, even if depressed, can be effective and that outcome can partly be predicted by pre-treatment characteristics.


Segmental alpha-receptor-mediated vasoconstriction in the canine coronary circulation.
Recent studies from this laboratory have indicated that sympathetic alpha-receptor-mediated coronary vasoconstriction can compete with local metabolic vasodilation to reduce the oxygen supply to the myocardium. In vitro studies from other laboratories on isolated coronary vessel strips suggest that large epicardial vessels are the dominant site of adrenergic alpha-receptor activity. In this study we used anesthetized, open-chest dogs to test the hypothesis that alpha-receptor-mediated vasoconstriction occurs predominantly in epicardial vessels, which are partially removed from the metabolic milieu in the myocardium. Adrenergic beta-receptor blockade was achieved by propranolol (3 mg/kg, iv). The circumflex coronary artery was pump-perfused at constant pressure to minimize passive changes in large vessel resistance. Pressure was measured at the tip of the perfusion cannula sealed in the circumflex artery, and in an apical branch of the circumflex artery. Large vessel resistance was calculated as the pressure gradient along the vessel segment divided by the coronary flow. Intracoronary injections of nitroglycerin were used as an independent measure of the vasomotor responsiveness of the large vessel segment. Adrenergic alpha-receptor activation was produced by intracoronary bolus injections of norepinephrine and by electrical stimulation of the left stellate ganglion. Alpha-receptor stimulation caused an increase in total coronary vascular resistance; however, the relative increase in the resistance of the large vessel was only about 60% of that seen for the entire coronary bed. These data suggest that, contrary to the proposed hypothesis, adrenergic alpha-receptor-mediated vasoconstriction in the large coronary vessels is not proportionally greater than that observed in the total coronary vascular bed.


The toll-like receptor-nuclear factor kappaB pathway in rheumatoid arthritis.
The study of the role cytokines play in the pathogenesis of rheumatoid arthritis (RA) has provided a whole new range of targets for drug development. Many of them (e.g. TNF, IL-1, IL-6, IL-15 and IL-18) are already being targeted in the clinic with success using neutralizing monoclonal antibodies or soluble cytokine receptors. Targeting TNF, in particular, has shown great efficacy in controlling both the inflammation and structural damage of the joints, setting a new gold standard for the treatment of RA. However, what triggers the production of inflammatory cytokines such as TNF in RA remains to be determined. In this article, we review evidence suggesting that the transcription factor Nuclear Factor kappaB (NF-kappaB) is essential for the expression of both inflammatory cytokines and tissue destructive enzymes in RA. Also, we discuss whether Toll-like receptors (TLRs), major receptors involved in pathogen recognition and potent activators of the NF-kappaB pathway, are involved in triggering the inflammatory and joint destructive process in RA and whether they constitute sensible targets for monoclonal antibodies/soluble receptors and small molecule inhibitors. We conclude that although the TLR- NF-kappaB pathway offers ample opportunities for therapeutic intervention, future drugs to be approved will need to match or exceed the efficacy and safety of anti-TNF agents, with safety the most difficult aspect to predict.


Genetic and physiological analysis of biennialism in Hyoscyamus niger.
A genetic and physiological study of biennialism in the diploid selfer Hyoscyamus niger (black henbane), an obligate long-day plant, is described. Three annual and two biennial accessions that were homozygous for their respective growth habits were selected. The early-flowering trait of two annual accessions was dominant over the late-flowering trait of the third annual accession. The late-flowering annual accession, but not the early-flowering ones, responded to vernalization. Two biennial accessions remained vegetative after more than 1 year in soil and thus had an obligate vernalization requirement. Crosses between annual and biennial accessions showed that biennialism was conferred through a single dominant gene. However, plants containing only one copy of this dominant gene were transformed from biennials into very late-flowering winter-annual plants that responded more rapidly to vernalization than biennials. Taken together, these results indicated that there were allelic differences in photoperiod-specific flowering time genes and that biennialism was a dose-dependent trait with incomplete dominance. Models for flowering time regulation in henbane involving photoperiod-, vernalization-, and most likely gibberellin-specific pathways are discussed.


Aetiology and Potential Animal Exposure in Central Nervous System Infections in Vietnam.
An estimated 73% of emerging infections are zoonotic in origin, with animal contact and encroachment on their habitats increasing the risk of spill-over events. In Vietnam, close exposure to a wide range of animals and animal products can lead to acquisition of zoonotic pathogens, a number of which cause central nervous system (CNS) infections. However, studies show the aetiology of CNS infections remains unknown in around half of cases. We used samples and data from hospitalised patients with CNS infections, enrolled into the Vietnam Initiative on Zoonotic Infections multicentre study, to determine the association between aetiology and animal contact including those in whom the cause was unknown. Among 933 patients, a pathogen or an antibody response to it was identified in 291 (31.2%, 95% CI 28.3-34.3%). The most common pathogens were Streptococcus suis (n = 91 (9.8%, 8.0-11.9%)) and Japanese encephalitis virus (JEV) (n = 72 (7.7%, 6.1-9.7%)). Commonly reported animal contact included keeping, raising or handling (n = 364 (39.0%, 35.9-42.2%)) and handling, cooking or consuming raw meat, blood or viscera in the 2 weeks prior to symptom onset (n = 371 (39.8%, 36.6-43.0%)), with the latter most commonly from pigs (n = 343 (36.9%, 33.8-40.1%). There was no association between an unknown aetiology and exposure to animals in a multivariate logistic regression. Further testing for unknown or undetected pathogens may increase diagnostic yield, however, given the high proportion of zoonotic pathogens and the presence of risk factors, increasing public awareness about zoonoses and preventive measures can be considered.


Synaptic currents generating the inhibitory surround of ganglion cells in the mammalian retina.
The receptive field (RF) of retinal ganglion cells (RGCs) consists of an excitatory central region, the RF center, and an inhibitory peripheral region, the RF surround. It is still unknown in detail which inhibitory interneurons (horizontal or amacrine cells) and which inhibitory circuits (presynaptic or postsynaptic) generate the RF surround. To study surround inhibition, light-evoked whole-cell currents were recorded from RGCs of the isolated, intact rabbit retina. The RFs were stimulated with light or dark spots of increasing diameters and with annular light stimuli. Direct inhibitory currents could be isolated by voltage clamping ganglion cells close to the Na(+)/K(+) reversal potential. They mostly represent an input from GABAergic amacrine cells that contribute to the inhibitory surround of ganglion cells. This direct inhibitory input and its physiological function were also investigated by recording light-evoked action potentials of RGCs in the current-clamp mode and by changing the intracellular Cl(-) concentration. The excitatory input of the ganglion cells could be isolated by voltage clamping ganglion cells at the Cl(-) reversal potential. Large light spots and annular light stimuli caused a strong attenuation of the excitatory input. Both GABA(A) receptors and GABA(C) receptors contributed to this inhibition, and picrotoxinin was able to completely block it. Together, these results show that the RF surround of retinal ganglion cells is mediated by a combination of direct inhibitory synapses and presynaptic surround inhibition.


Rapid acetylcholine and adenosine triphosphate oscillations triggered by stimulation of the Torpedo electric organ.
1. When the electric organ of Torpedo is stimulated a large number of synchronized cholinergic synapses are activated. This permits the measurement of changes in the tissue level of ACh associated with the release process, usually recorded as an electric discharge. 2. At 5 Hz stimulation the output per impulse and the amount of cytoplasmic (free ACh) declines for about 30 s. The output then remains constant while ACh is synthesized for about 90 s. Finally, the output and cytoplasmic ACh are exhausted after 120 s. These 'slow wave' changes in ACh represent about 50% of the total. 3. Superimposed on the 'slow wave' are rapid oscillations of 5 s period, which represent about 30% of the total ACh. 4. The amount of ATP oscillates in phase with ACh. These oscillations might result from regulation of enzymes involved in the synthesis of transmitter. 5. The amplitude of electrical discharge does not normally oscillate. Transmitter output is therefore not directly related to ACh concentration changes. The mechanism releasing ACh is a saturable process.


Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis.
Gastric cancer (GC) is a common malignancy with a global incidence that ranks fourth among all tumor types. Epithelial-to-mesenchymal transition (EMT) is a tumor biological process with a role in GC cell metastasis. Long non-coding RNAs (lncRNAs) and microRNAs possess important regulatory functions at the cellular level and in diverse pathophysiological processes. This study was conducted to investigate whether lncRNA RP11-789C1.1 regulates EMT in GC by mediating the miR-5003/E-cadherin pathway. RP11-789C1.1 and miR-5003 expression was detected in GC specimens and cell lines by quantitative real-time PCR. Western blotting and immunohistochemistry were performed to detect EMT markers in GC. Cell Counting Kit 8 assays were carried out to explore cell proliferation. Wound healing and Transwell assays were conducted to determine the migration and invasion of GC cells. To clarify the correlation between RP11-789C1.1, miR-5003, and E-cadherin, dual-luciferase reporter assays were applied. LncRNA RP11-789C1.1 was significantly down-regulated in GC patients and cell lines, along with the concomitant up-regulation of miR-5003. Silencing RP11-789C1.1 and over-expressing miR-5003 significantly promoted the tumor behavior of GC cells. Dual-luciferase reporter assays confirmed that miR-5003 was the target of both RP11-789C1.1 and E-cadherin. Furthermore, at both the mRNA and protein level, silencing RP11-789C1.1 remarkably reduced the expression of E-cadherin and promoted EMT, which were reversed by knocking down miR-5003. LncRNA RP11-789C1.1 inhibited EMT in GC through the RP11-789C1.1/miR-5003/E-cadherin axis, which could be a promising therapeutic target for GC.


Symptoms of depression and anxiety and 11-year all-cause mortality in men and women undergoing coronary artery bypass graft (CABG) surgery.
To investigate the overall and the sex-specific association of preoperative and one-year post coronary artery bypass (CABG) surgery symptoms of depression and anxiety with 11-year all-cause mortality. A multicenter prospective study including 1125 patients who completed the Hospital Anxiety and Depression Scale (HADS) before an elective CABG surgery, of whom 850 completed the HADS again at one-year follow-up. Information on all-cause mortality was obtained through the Israeli Ministry of Internal Affairs Register. Multivariable adjusted Cox regression models quantified the association of symptoms of depression and anxiety with all-cause mortality. Females comprised 22.7% of the cohort and were 5.5years older than males (70.0±9.3 and 64.4±10.3years, respectively). Controlling for sociodemographic and lifestyle factors, illness severity and post-surgery participation in cardiac rehabilitation, there was little evidence of an association between preoperative symptoms of depression and mortality in males [adjusted hazard ratio (aHRmales)=1.03, 95% CI 0.99-1.07, p=0.21] or females (aHRfemales=1.01, 95% CI 0.95-1.08, p=0.7). One-year postoperative symptoms of depression were associated with mortality in both males (aHRmales=1.05, 95% CI 1.01-1.10, p=0.03) and females (aHRfemales=1.07, 95% CI 1.02-1.13, p=0.013). Preoperative symptoms of anxiety were unrelated to mortality overall, but among females postoperative symptoms of anxiety predicted 11-year mortality (aHRfemales=1.07, 95% CI 1.00-1.14, p=0.049). There was no HADS by sex interaction (p for interaction=0.12-0.99). Symptoms of depression one-year after surgery were positively related to mortality with little evidence for sex differences. These findings underscore the need for identification and treatment of psychiatric symptoms in patients undergoing CABG surgery. ClinicalTrials.gov: NCT00356863.


Secondary nucleation of monomers on fibril surface dominates α-synuclein aggregation and provides autocatalytic amyloid amplification.
Parkinson's disease (PD) is characterized by proteinaceous aggregates named Lewy Bodies and Lewy Neurites containing α-synuclein fibrils. The underlying aggregation mechanism of this protein is dominated by a secondary process at mildly acidic pH, as in endosomes and other organelles. This effect manifests as a strong acceleration of the aggregation in the presence of seeds and a weak dependence of the aggregation rate on monomer concentration. The molecular mechanism underlying this process could be nucleation of monomers on fibril surfaces or fibril fragmentation. Here, we aim to distinguish between these mechanisms. The nature of the secondary processes was investigated using differential sedimentation analysis, trap and seed experiments, quartz crystal microbalance experiments and super-resolution microscopy. The results identify secondary nucleation of monomers on the fibril surface as the dominant secondary process leading to rapid generation of new aggregates, while no significant contribution from fragmentation was found. The newly generated oligomeric species quickly elongate to further serve as templates for secondary nucleation and this may have important implications in the spreading of PD.


Regulation of Herbaspirillum seropedicae NifA by the GlnK PII signal transduction protein is mediated by effectors binding to allosteric sites.
Herbaspirillum seropedicae is a plant growth promoting bacterium that is able to fix nitrogen and to colonize the surface and internal tissues of important crops. Nitrogen fixation in H. seropedicae is regulated at the transcriptional level by the prokaryotic enhancer binding protein NifA. The activity of NifA is negatively affected by oxygen and positively stimulated by interaction with GlnK, a PII signaling protein that monitors intracellular levels of the key metabolite 2-oxoglutarate (2-OG) and functions as an indirect sensor of the intracellular nitrogen status. GlnK is also subjected to a cycle of reversible uridylylation in response to intracellular levels of glutamine. Previous studies have established the role of the N-terminal GAF domain of NifA in intramolecular repression of NifA activity and the role of GlnK in relieving this inhibition under nitrogen-limiting conditions. However, the mechanism of this control of NifA activity is not fully understood. Here, we constructed a series of GlnK variants to elucidate the role of uridylylation and effector binding during the process of NifA activation. Our data support a model whereby GlnK uridylylation is not necessary to activate NifA. On the other hand, binding of 2-OG and MgATP to GlnK are very important for NifA activation and constitute the most important signal of cellular nitrogen status to NifA.


A Novel Approach for the Reconstruction of Premaxilla by Archwise Distraction in Bilateral Cleft Lip and Palate.
Interdental distraction osteogenesis has been introduced as a successful treatment protocol for repairing large clefts. In this article, a new method for reconstruction of the premaxilla in 2 bilateral cleft lip and palate patients is introduced. The aim was to distract the lateral segments through the curve of the dental arch, achieve complete closure of the gaps, and use the premaxilla as a bone graft. Patient 1 (20-year-old female) had double jaw surgery before but presented residual alveolar cleft and small premaxilla. Patient 2 (21-year-old male) had anterior and posterior crossbite and caries of teeth on premaxilla. Following the preliminary fixed orthodontic treatment in both patients, archwise distraction protocol was performed. The distraction duration and the achieved amount of new bone per side were 4 weeks/22 mm and 5 weeks/25 mm in Patients 1 and 2, respectively. At the end of a 2-month retention period, docking side surgery was performed and premaxilla was used as the bone graft. The protocol was very effective for not only closure of the large cleft defects but also the reconstruction of the premaxilla. Anteroposterior relationship and the patients' profiles were considerably and positively affected.


The interaction of social and emotional processes in the brain.
Social stimuli function as emotional barometers for the immediate environment are the catalysts for many emotional reactions, and have inherent value for relationships and survival independent of their current emotional content. We, therefore, propose that the neural mechanisms underlying social and emotional information processing may be interconnected. In the current study, we examined the independent and interactive effects of social and emotional processes on brain activation. Whole-brain images were acquired while participants viewed and categorized affective pictures that varied on two dimensions: emotional content (i. e., neutral, emotional) and social content (i. e., faces/people, objects/scenes). Patterns of activation were consistent with past findings demonstrating that the amygdala and part of the visual cortex were more active to emotionally evocative pictures than to neutral pictures and that the superior temporal sulcus was more active to social than to nonsocial pictures. Furthermore, activation of the superior temporal sulcus and middle occipito-temporal cortex showed evidence of the interactive processing of emotional and social information, whereas activation of the amygdala showed evidence of additive effects. These results indicate that interactive effects occur early in the stream of processing, suggesting that social and emotional information garner greater attentional resources and that the conjunction of social and emotional cues results in synergistic early processing, whereas the amygdala appears to be primarily implicated in processing biologically or personally relevant stimuli, regardless of the nature of the relevance (i. e., social, emotional, or both).


Sex differences in hypokalaemic and electrocardiographic effects of inhaled terbutaline.
Gender differences in the chronotropic effects of infused isoprenaline have previously been described. The aim of the present study was to investigate possible gender differences in hypokalaemic, chronotropic, and electrocardiographic effects of inhaled terbutaline. Twenty healthy volunteers (10 female) were recruited (mean age 24 years for women (F) and 22 years for men (M). Subjects were given either inhaled terbutaline 5 mg or placebo in single blind, randomised crossover fashion and the following measurements were made for four hours after inhalation: (a) serum potassium concentration; (b) heart rate; (c) electrocardiographic sequelae (T wave amplitude, Q-Tc interval). The effects of terbutaline on serum potassium was chosen as the primary end point for detecting a 0.3 mmol/l difference between sexes, with a beta error of 0.2 and alpha set at 0.05. The hypokalaemic effects of terbutaline were significantly greater in women, the potassium results (means and 95% CI) being as follows: lowest potassium concentration--F 3.12 (2.96-3.28) mmol/l v M 3.65 (3.49-3.81) mmol/l; percentage change from baseline at one hour--F 15.4% (11.5-19.3%) v M 8.5% (4.6-12.3%); average potassium concentration during the four hours--F 3.39 (3.33-3.46) mmol/l v M 3.78 (3.72-3.85) mmol/l. There was no significant regression between body weight and the potassium response to terbutaline. There were also significant sex differences for T wave, Q-Tc, and heart rate response. The percentage fall in T wave amplitude 30 minutes after terbutaline was: F 44.6% (32.1-57.0%) v M 22.4% (9.9-34.8%). Women are more sensitive to the hypokalaemic, chronotropic, and electrocardiographic sequelae of inhaled terbutaline.


Determinants of apamin and d-tubocurarine block in SK potassium channels.
Small conductance calcium-activated potassium channels show a distinct pharmacology. Some, but not all, are blocked by the peptide toxin apamin, and apamin-sensitive channels are also blocked by d-tubocurarine. Cloned SK channels (small conductance calcium-activated potassium channel) recapitulate these properties. We have investigated the structural basis for these differences and found that two amino acid residues on either side of the deep pore are the primary determinants of sensitivity to apamin and differential block by d-tubocurarine. Therefore, the pharmacology of SK channels compared with other potassium channels correlates with structural differences in the outer pore region. However, introduction of a tyrosine residue in the position analogous to that which determines sensitivity to external tetraethylammonium for voltage-gated potassium channels endows SK channels with an equivalent tetraethylammonium sensitivity, indicating that the outer vestibules of the pores are similar. The pharmacology of channels formed in oocytes coinjected with SK1 and SK2 mRNAs, or with SK1-SK2 dimer mRNA, show that SK subunits may form heteromeric channels.


Significant synovial pathology in a meniscectomy model of osteoarthritis: modification by intra-articular hyaluronan therapy.
IA therapy with hyaluronan (HA) is reported to provide symptomatic relief and disease modification in OA. This study assessed the pathological changes in the synovium of an ovine model of OA and evaluated the effects of two HA preparations on this pathology. Eighteen sheep had bilateral lateral meniscectomy to induce OA. Four months post-surgery animals received IA saline or HA (Hyalgan) weekly for 5 weeks or three injections of an amide derivative of HA (HYADD 4-G) every 2 weeks (n = 6 per group). Six months after meniscectomy, sheep were killed, knee joint synovium processed, scored for pathological change and compared with synovium from non-operated animals. Sections of synovium from normal and treated joints were also immunostained for TNF-alpha, HSP-47, TGF-beta, CD44, connective tissue growth factor (CTGF) or iNOS. HA synthesis by synovial fibroblasts isolated from each OA joint was quantified. Aggregate scores of pathological change were higher in OA joint synovia compared with controls, with individual measures of subintimal fibrosis and vascularity predominantly affected. Depth of intimal fibrosis was also significantly higher in meniscectomized joints. IA treatment with Hyalgan decreased aggregate score, vascularity and depth of fibrosis. HYADD 4-G treatment decreased vascularity, intimal hyperplasia and increased high-molecular weight HA synthesis by synovial fibroblasts. CD44, CTGF or iNOS expression was increased in the synovial lining of OA joints compared with normal, but there was no significant modulation of this increase by either HA preparation. Increased fibrosis and vascularity are hallmarks of pathological change in synovium in this meniscectomy model of OA. Both the IA HA and an amide derivative of HA reduced aspects of this pathology thus providing a potential mechanism for improving joint mobility and function in OA.


Dip-coating of suspensions.
Withdrawing a plate from a suspension leads to the entrainment of a coating layer of fluid and particles on the solid surface. In this article, we study the Landau-Levich problem in the case of a suspension of non-Brownian particles at moderate volume fraction 10% < φ < 41%. We observe different regimes depending on the withdrawal velocity U, the volume fraction of the suspension φ, and the diameter of the particles 2a. Our results exhibit three coating regimes. (i) At small enough capillary number Ca, no particles are entrained, and only a liquid film coats the plate. (ii) At large capillary number, we observe that the thickness of the entrained film of suspension is captured by the Landau-Levich law using the effective viscosity of the suspension η(φ). (iii) At intermediate capillary numbers, the situation becomes more complicated with a heterogeneous coating on the substrate. We rationalize our experimental findings by providing the domain of existence of these three regimes as a function of the fluid and particles properties.


Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial.
Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti-programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab. In a cohort of this single-arm, phase 2 trial (JAVELIN Merkel 200), patients with mMCC and disease progression after prior chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent review per Response Evaluation Criteria in Solid Tumors V.1.1. Other assessments included duration of response, progression-free survival, overall survival (OS), safety and biomarker analyses. As of 14 September 2018, 88 patients had been followed up for a median of 40.8 months (range 36.4-49.7 months). The ORR was 33.0% (95% CI 23.3% to 43.8%), including a complete response in 11.4% (10 patients), and the median duration of response was 40.5 months (95% CI 18.0 months to not estimable). As of 2 May 2019 (≥44 months of follow-up), the median OS was 12.6 months (95% CI 7.5 to 17.1 months) and the 42-month OS rate was 31% (95% CI 22% to 41%). Of long-term survivors (OS >36 months) evaluable for PD-L1 expression status (n=22), 81.8% had PD-L1+ tumors. In exploratory biomarker analyses, high tumor mutational burden (≥2 non-synonymous somatic variants per megabase) and high major histocompatibility complex class I expression (30% of tumors with highest expression) were associated with trends for improved ORR and OS. In long-term safety assessments (≥36 months of follow-up), no new or unexpected adverse events were reported, and no treatment-related deaths occurred. Avelumab showed continued durable responses and meaningful long-term survival outcomes in patients with mMCC, reinforcing avelumab as a standard-of-care treatment option for this disease. NCT02155647.


Demographic factors associated with the diet quality of older US men: baseline data from the Osteoporotic Fractures in Men (MrOS) study.
Throughout the world, the proportion of the male population aged 65 years and older is increasing. Yet, we have limited information regarding diet quality and predictors of diet quality in this segment of the population. The objectives of the current analyses are to describe the diet quality of a cohort of men >65 years of age, and identify lifestyle factors associated with poor diet quality. We present a cross-sectional analysis of the diet quality of 5928 men, aged 65-100 years, who are participants in the Osteoporotic Fractures in Men (MrOS) cohort study. Dietary intake was determined using a modified Block 98 food-frequency questionnaire. Diet quality was calculated using the previously validated Diet Quality Index-Revised (DQI-R). Univariate and multivariate modelling was used to estimate the variance in diet quality predicted by a number of sociodemographic factors, including age, race/ethnicity, body mass index (BMI), marital status, education, smoking status, physical activity, self-perceived health and nutritional supplement use. Overall, we found that in this geographically diverse group of older men, diet quality was low, with a mean modified DQI-R for the entire study population of 62.5 (standard deviation 13.1) out of an ideal of 100. Further, younger age, very low total calorie intake (< or = 1187 kcal day- 1), higher BMI, residence in a North or Southeast community, being of African-American or Hispanic race, being less educated, not using dietary supplements and smoking were each significant independent predictors of a poorer diet. These data may prove useful in both understanding the dietary intake of older US men as it relates to published dietary guidelines, and for targeting future dietary intervention programmes.


Rapid induction of the growth hormone gene transcription by glucocorticoids in vitro: possible involvement of membrane glucocorticoid receptors and phosphatidylinositol 3-kinase activation.
The regulation of transcription of the growth hormone (GH) gene by glucocorticoids was studied in MtT/S cells, a cell line derived from an oestrogen-induced mammotrophic tumour in the rat, and in the primary culture of the anterior pituitary gland of adult mice. The levels of the GH heteronuclear RNA (GH hnRNA), which are mainly determined by the transcription rate, increased by 25-fold during 24 h in response to dexamethasone (DEX; 1 μM) in MtT/S cells that were cultured in the medium containing charcoal-stripped serum for 7 days. The stimulatory effect of DEX on the GH hnRNA levels was detectable as early as 30 min. This rapid effect of DEX did not require on-going protein synthesis, whereas it was considered that DEX requires the presence of unknown cellular proteins produced independently of DEX stimulation. By contrast, on-going protein synthesis was required for DEX action when incubated for 6 h, as has been observed in the previous studies. The specific inhibitor of glucocorticoid receptor, RU486, inhibited both rapid (30 min) and delayed (6 h) the effects of glucocorticoids on GH hnRNA levels. Membrane impermeable glucocorticoid, corticosterone-bovine serum albumin conjugate (CSBSA), was found to have effects similar to those of DEX and free corticosterone (CS), suggesting that glucocorticoids regulate GH gene transcription at least in part through the membrane bound receptors. From pharmacological studies, it was suggested that phosphatidylinositol 3-kinase (PI3K) activation is involved in the rapid effects but not in the delayed effects of glucocorticoids. This also suggests that the delayed effects of glucocorticoids depend on mechanisms other than the activation of PI3-kinase. Finally, both rapid and delayed effects of CS and CSBSA were observed not only in MtT/S cells, but also in the mouse pituitary cells in primary culture. Therefore, it is possible that the membrane initiated action of glucocorticoids is involved in the regulation of GH transcription in normal pituitary cells, as well as in pituitary tumour cells.


Acupoints Stimulation for Anxiety and Depression in Cancer Patients: A Quantitative Synthesis of Randomized Controlled Trials.
This study aims at concluding the current evidence on the therapeutic effects of acupoints stimulation for cancer patients with anxiety and depression. Randomized controlled trials using acupoints stimulation for relieving anxiety and/or depression in cancer patients were searched, and 11 studies were finally included, of which eight trials compared acupoints stimulation with standard methods of treatment/care, and acupoints stimulation showed significantly better effects in improving depression than using standard methods of treatment/care. Four studies compared true acupoints stimulation with sham methods, and no significant differences can be found between groups for either depression or anxiety, although the pooled effects still favored true intervention. For the five studies that evaluated sleep quality, the results were conflicting, with three supporting the superiority of acupoints stimulation in improving sleep quality and two demonstrating no differences across groups. Acupoints stimulation seems to be an effective approach in relieving depression and anxiety in cancer patients, and placebo effects may partially contribute to the benefits. However, the evidence is not conclusive due to the limited number of included studies and the clinical heterogeneity identified among trials. More rigorous designed randomized, sham-controlled studies are necessary in future research.


Ultrasonography of the rumen of dairy cows.
This study describes the ultrasonographic findings of the rumen in 45 healthy dairy cows. The cows were scanned on both sides using a 5.0 MHz transducer. The dorsal visible margin of the rumen ran parallel to the lung from cranioventral to caudodorsal. It was furthest from the dorsal midline at the 9th intercostal space (48.3 ± 9.24 cm) and closest at the 12th intercostal space (22.4 ± 3.27 cm). The longitudinal groove, which could be clearly identified at all examination sites because it appeared as a triangular notch, formed the ventral margin of the dorsal sac of the rumen. The dorsal sac of the rumen was largest at the caudal flank (40.3 ± 6.33 cm), where it was adjacent to the abdominal wall. The ventral sac of the rumen extended across the ventral midline into the right hemiabdomen and its ventral margin had a largely horizontal craniocaudal course. The height of the ventral sac of the rumen exceeded that of the dorsal sac at all examination sites; the maximum height was measured at the 12th intercostal space (62.6 ± 9.53 cm). The dorsal gas cap, characterised ultrasonographically by typical reverberation artifacts, was visible in all cows from the 12th intercostal space to the caudal flank. It was largest at the 12th intercostal space (20.5 ± 7.03 cm). The transition from the gas cap to the fibre mat was marked by the abrupt cessation of the reverberation artifacts. It was not possible to differentiate a fibre mat and a ventral fluid phase. The rumen could be imaged from the right side in 21 cows (47%). Ultrasonography is well suited for the detailed examination of the rumen of cows. The reference values obtained from this study add to the diagnostic tools that are available for the assessment of bovine patients.


Anterior cingulate and posterior parietal cortices are sensitive to dissociable forms of conflict in a task-switching paradigm.
The conflict-monitoring hypothesis posits that anterior cingulate cortex (ACC) monitors conflict in information processing and recruits dorsolateral prefrontal cortex (DLPFC) to resolve competition as needed. We used fMRI to test this prediction directly in the context of a task-switching paradigm, in which subjects responded to the color or the motion of a visual stimulus. Conflict was indexed in terms of the product of activities in areas specialized for color or motion processing on a trial-by-trial basis. Here, we report that ACC and posterior parietal cortex (PPC) were sensitive to distinct forms of conflict, at the level of the response and the stimulus representation, respectively. Activity in PPC preceded increased activity in DLPFC and predicted enhanced behavioral performance on subsequent trials. These findings suggest that ACC and PPC may act in concert to detect dissociable forms of conflict and signal to DLPFC the need for increased control.


Nuclear magnetic resonance Hahn spin-echo decay (T2) in live rats with endotoxin lung injury.
To determine the possibility of using nuclear magnetic resonance imaging to study experimentally induced lung injury, we measured in the lungs of spontaneously breathing living rats the time course of both the Hahn spin-echo decay (T2) and the proton density after endotoxin injury. In order to minimize artifacts arising from motions of the nearby chest wall and heart, we used a motion-insensitive technique (the interleaved line scan). A typical Hahn T2 measurement was obtained over a region of interest from a series of images each with a different echo time, which ranged from 16 to 110 ms. Lung water content was determined by integrating the proton density over the region of interest. The Hahn T2 and proton density were measured before and at 1, 3, 6, and 9 h after intravenous injection of endotoxin. The effects of the treatment administered before and after endotoxin injection were also evaluated. Endotoxin treatment caused lengthening of both fast (T2f) and slow (T2s) Hahn T2 components but had no significant effect on the proton density, consistent with the notion that endotoxin causes lung injury without significant lung water accumulation in rats. However, the methylprednisolone treatment prevented the lengthening of T2s but did not seem to have a significant effect on T2f. Our results suggest that NMR imaging can be used to detect and monitor experimental lung injury in intact living animals, even in the absence of variations of lung water content.


Structural basis for inverting the enantioselectivity of arylmalonate decarboxylase revealed by the structural analysis of the Gly74Cys/Cys188Ser mutant in the liganded form.
Arylmalonate decarboxylase catalyzes the enantioselective decarboxylation of alpha-aryl-alpha-methylmalonate to produce optically pure alpha-arylpropionate. The enzyme is comprised of two alpha/beta domains and contains an active site situated between the two domains. The site is formed by Tyr48, Gly74-Thr75-Ser76, Tyr126, and Cys188-Gly189-Gly190 residues. Since it has been observed that the Gly74Cys/Cys188Ser mutation inverts the enantioselectivity of the enzyme, we determined the crystal structure of the Gly74Cys/Cys188Ser mutant in the liganded form at a resolution of 1.45 A to understand the structural basis for this inversion. The overall structure of the enzyme overlapped well with that of the benzylphosphonate-associated wild-type enzyme, and the mutations had little effect on the structure of the active site. A ligand molecule bound to the active site in an unusual semiplanar conformation resembling the planar enediolate reaction intermediate could be assigned as phenyl acetate. The inversion in enantioselectivity by the paired mutation is explained by the mirror symmetry between Cys74 in the mutant and Cys188 of the wild type with respect to the carbon atom in the ligand to be protonated. Comparison of the wild-type and Gly74Cys mutant crystal structures suggested that ligand binding induces a positional shift of the Cys188-Gly189-Gly190 region toward the Gly74-Thr75 pair which provides two oxyanion holes necessary to stabilize the negatively charged enediolate reaction intermediate. The ligand binding also simultaneously induces the formation of a hydrophobic cluster over the active site cleft. Thus, AMDase is proposed to have "open" and "closed" conformations of the active site that are regulated by ligand binding. These results may provide an effective strategy for the rational design to invert the enantioselectivity of enzymes.


Viable count estimates of lag time responses for Salmonella typhimurium M48 subjected to abrupt osmotic shifts.
Generally, relative lag times (RLT; lag time divided by generation time) become extended as conditions become less favourable for growth. Mellefont et al. (2003, 2004) [Mellefont, L.A., McMeekin, T.A., Ross, T., 2003. The effect of abrupt osmotic shifts on the lag phase duration of foodborne bacteria. Int. J. Food Microbiol. 83(3), 281-293; Mellefont, L.A., McMeekin, T.A., Ross, T., 2004. The effect of abrupt osmotic shifts on the lag phase duration of physiologically distinct populations of Salmonella typhimurium. Int. J. Food Microbiol. 92, 111-120] reported that abrupt osmotic shifts of Salmonella typhimurium M48 from optimal to low aw led to unexpectedly small RLTs at low aw. In this study, RLTs resulting from similar osmotic shifts were estimated by viable count (VC) and compared to turbidimetric estimates to test the hypothesis that the 'downturn' in RLT is an artefact of the turbidimetric technique used. No 'downturn' in RLT was observed with VC data and RLTs increased with increasing magnitude of osmotic shift. Anomalous turbidimetric estimates of lag time at low aw were confirmed as the likely source of the 'downturn' in RLT. The abrupt osmotic shifts resulted in a complex pattern of microbial population behaviour. Immediately after transfer from optimal aw to low aw, inactivation of a portion of the population occurred for all the conditions tested. The degree of inactivation became progressively larger with larger shifts in aw. The initial decline in population was followed by a period during which no change in numbers occurred, followed by growth that appeared, in most cases, to be exponential. At the lowest aws tested (< or =0.954), the growth response after the initial decline was at a rate slower than that of exponential phase growth. Due to the use of non-selective media containing pyruvate (to eliminate oxygen radicals), the observed patterns of inactivation, lag and regrowth at most aw conditions are unlikely to result from a temporary loss of culturability, but may represent inactivation of a portion of the population.


Long-term outcome of localized high-grade non-Hodgkin's lymphoma treated with high dose CHOP regimen and involved field radiotherapy: results of a GOELAMS study.
Most patients with localized high-grade non-Hodgkin's lymphoma (NHL) can be cured with or without adjuvant radiotherapy. However few data are available on the long-term outcome of these patients. Here we report the results of a prospective study, started in 1984, which was conducted to evaluate the long-term outcome of patients with localized high-grade NHL. In this multicenter, prospective study by the GOELAMS group, 253 patients with localized high-grade NHL were treated with 3 cycles of vindesine, cyclophosphamide, adriamycin and prednisone (VCAP, a high-dose CHOP regimen) followed by involved field radiotherapy (40 Gy). After completion of chemotherapy, 213 patients (84%) entered complete remission (CR) and 30 (12%) obtained a partial remission. Treatment failed in 6 patients (2.5%) and there were 4 toxic deaths (1.5%). Following radiotherapy, 239 (94%) of all patients were in CR. With a median follow-up of 88 months, overall survival and disease-free survival rates were 84% and 85% respectively at five years, and 78% and 82% respectively at ten years. The response to chemotherapy was decisive to survival. We observed 43 relapses (17%) at a median time of 20 months after CR, and 9 patients relapsed after five years. Eleven patients (3%) developed another malignancy in the follow-up period. High-dose CHOP followed by locoregional radiotherapy is a feasible treatment for localized high-grade NHL. It has very few complications, a good CR rate and the OS is 78% at 10 years.


T2Bacteria magnetic resonance assay for the rapid detection of ESKAPEc pathogens directly in whole blood.
To evaluate the magnetic resonance-based T2Bacteria Panel assay for direct detection of ESKAPEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli) pathogens in blood samples of patients with suspected bloodstream infection (BSI). Adult patients admitted to the Emergency Medicine Department, Infectious Diseases Unit and ICU of a large tertiary-care hospital were included if they had a blood culture (BC) ordered concomitantly with a whole-blood sample for T2Bacteria testing. Results were compared with those of BC and other clinically relevant information. A total of 140 samples from 129 BSI patients were studied. Single bacteria were detected in 15.7% (22/140) and 12.1% (17/140), and multiple bacteria in 2.9% (4/140) and 1.4% (2/140), of samples tested by T2Bacteria and BC, respectively. With respect to the six target (ESKAPEc) species, overall sensitivity and specificity of T2Bacteria across all detection channels in comparison with BC were 83.3% and 97.6%, respectively; these values increased to 89.5% and 98.4%, respectively, when a true-infection criterion (i.e. the same microorganism detected only by T2Bacteria was cultured from another sample type reflecting the source of infection) was used as the comparator. There were 808 T2Bacteria detection results across 112 samples, with concordant negative results, yielding a negative predictive value of 99.8%. The mean time to negative result was 6.1 ± 1.5 h, whereas the mean time to detection/species identification was 5.5 ± 1.4 h. The T2Bacteria Panel assay has the potential to provide accurate and timely diagnosis of ESKAPEc bacteraemia, which might support the direct therapeutic management of BSI patients.


Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers.
Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D2 dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2 dopamine receptor Taq I A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects; Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D2 dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.


Agreement in reporting between trial publications and current clinical trial registry in high impact journals: A methodological review.
The primary objective of this systematic survey was to examine the percentage of studies in which there was agreement in the reporting of the primary outcome between the currently updated version of the clinical trial registry and the published paper. We also investigated the factors associated with agreement in reporting of the primary outcome. We searched PubMed for all randomized control trials (RCT)s published in 2012-2015 in the top five general medicine journals (based on the 2014 impact factor). Two hundred abstracts (50 from each year) were randomly selected for data extraction. Agreement in reporting of 11 key study conduct items (e.g., sample size) and study characteristics (e.g., funding, number of sites) were extracted by two independent reviewers. Descriptive analyses were conducted to determine the proportion of studies on which there was agreement in reporting of key study conduct items. Generalized estimating equations were used to explore factors associated with agreement in reporting of the primary outcome. Of the 200 included studies, 87% had agreement in reporting of the primary outcome. After adjusting for other covariates, having greater than 50 sites was associated with an increased likelihood of agreement in reporting of the primary outcome (odds ratio=7.1, 95% confidence interval=1.39, 36.27, p=0.018). We identified substantive disagreement in reporting between publications and current clinical trial registry, which were associated with several study characteristics. Further measures are needed to improve reporting given the potential threats to the quality and integrity of scientific research.


Nonadherence to antiretroviral therapy among HIV-infected patients in Zambia is concentrated among a minority of patients and is highly variable across clinics.
The distribution of adherence to antiretroviral therapy (ART) can indicates whether barriers are concentrated or more distributed. We quantified the medication possession ratio (MPR) and characterized the distribution of medication nonpossession in a network of clinics in Zambia to identify 'hotspots' and predictors of poorer adherence. We analyzed a population of adults on ART for more than 3 months who made at least one clinic visit between 1 January 2013 and 28 February 2015. Pharmacy refill and clinical information were obtained through the electronic medical record system used in routine care. We constructed a Lorenz curve to visualize the distribution of poor adherence and used a multilevel logistic regression model to examine factors associated with MPR. Among 131 767 patients in 56 clinics [64% women, median age 34 years (interquartile range (IQR) 29-41), median CD4 cell count at ART initiation 351 cells/μl (IQR 220-517)], the median MPR was 85.8% (IQR 70.8-96.8). During months 7-12 on ART, 45.6% of patients had 100% MPR and 10.5% accounted for 50% of medication nonpossession. Across clinics, median MPR ranged from 49.1 to 98.5, and clinic accounted for 12% of the variability in adherence after adjusting for individual and clinic-level characteristics. A small fraction of patients account for the majority of days of medication nonpossession. Further characterization of these subpopulations is needed to target interventions. Clinic also accounted for much variability in MPR. Health systems interventions targeting clinic 'hot spots' may represent an efficient use of resources to improve ART adherence.


XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer.
The common participation of oncogenic KRAS proteins in many of the most lethal human cancers, together with the ease of detecting somatic KRAS mutant alleles in patient samples, has spurred persistent and intensive efforts to develop drugs that inhibit KRAS activity. However, advances have been hindered by the pervasive inter- and intra-lineage diversity in the targetable mechanisms that underlie KRAS-driven cancers, limited pharmacological accessibility of many candidate synthetic-lethal interactions and the swift emergence of unanticipated resistance mechanisms to otherwise effective targeted therapies. Here we demonstrate the acute and specific cell-autonomous addiction of KRAS-mutant non-small-cell lung cancer cells to receptor-dependent nuclear export. A multi-genomic, data-driven approach, utilizing 106 human non-small-cell lung cancer cell lines, was used to interrogate 4,725 biological processes with 39,760 short interfering RNA pools for those selectively required for the survival of KRAS-mutant cells that harbour a broad spectrum of phenotypic variation. Nuclear transport machinery was the sole process-level discriminator of statistical significance. Chemical perturbation of the nuclear export receptor XPO1 (also known as CRM1), with a clinically available drug, revealed a robust synthetic-lethal interaction with native or engineered oncogenic KRAS both in vitro and in vivo. The primary mechanism underpinning XPO1 inhibitor sensitivity was intolerance to the accumulation of nuclear IκBα (also known as NFKBIA), with consequent inhibition of NFκB transcription factor activity. Intrinsic resistance associated with concurrent FSTL5 mutations was detected and determined to be a consequence of YAP1 activation via a previously unappreciated FSTL5-Hippo pathway regulatory axis. This occurs in approximately 17% of KRAS-mutant lung cancers, and can be overcome with the co-administration of a YAP1-TEAD inhibitor. These findings indicate that clinically available XPO1 inhibitors are a promising therapeutic strategy for a considerable cohort of patients with lung cancer when coupled to genomics-guided patient selection and observation.


Men Selling Sex to Men in Sweden: Balancing Safety and Risk.
The purpose of this study is to examine how men who sell sex to men perceive the risks in this activity and what experiences they have of actual denigration, threats, and violence in their relations with customers. We also discuss the self-defense strategies they have used to protect themselves. The study is based on an Internet survey on Swedish websites. Statistical analyses have been carried out, and in interpreting the results, Finkelhor and Asdigian's revised routine activities theory has been used. The results show that the vulnerability of sellers of sex is greatest during the time when the sexual act is being performed, and that this is primarily linked to the customer's antagonism and seeking gratification by overstepping agreed boundaries, particularly with regard to sexual services including BDSM. Their vulnerability was also connected to the seller's diminished capacity for self-protection due to personal and external pressures. A smaller proportion of the men described risk prevention activities. These involved refusing a customer after an initial contact, protecting themselves from infection, being on their guard during the whole process, selecting the place, and deciding not to carry out certain sexual acts. An important implication concerns the occupational health and safety that men who sell sex to men can develop for themselves, while remaining within the law. International studies have demonstrated that selling sex in collective, indoor forms provides the greatest security. For decades, Swedish prostitution policy has had the ambition of reducing prostitution through targeting those who purchase sex, and those who promote prostitution in criminal legislation. This effectively prevents more systematic and collective attempts to create safer conditions for selling sex. In conclusion, it can be stated that while it is legal to sell sex in Sweden, this is done at the seller's own risk.


Television viewing and childhood obesity.
Children spend a substantial portion of their lives watching television. Investigators have hypothesized that television viewing causes obesity by one or more of three mechanisms: (1) displacement of physical activity, (2) increased calorie consumption while watching or caused by the effects of advertising, and (3) reduced resting metabolism. The relationship between television viewing and obesity has been examined in a relatively large number of cross-sectional epidemiologic studies but few longitudinal studies. Many of these studies have found relatively weak, positive associations, but others have found no associations or mixed results; however, the weak and variable associations found in these studies may be the result of limitations in measurement. Several experimental studies of reducing television viewing recently have been completed. Most of these studies have not tested directly the effects of reducing television viewing behaviors alone, but their results support the suggestion that reducing television viewing may help to reduce the risk for obesity or help promote weight loss in obese children. Finally, one school-based, experimental study was designed specifically to test directly the causal relationship between television viewing behaviors and body fatness. The results of this randomized, controlled trial provide evidence that television viewing is a cause of increased body fatness and that reducing television viewing is a promising strategy for preventing childhood obesity.


Energy- and conformer-dependent excited-state relaxation of an E/Z photoswitchable thienyl-ethene.
Bis(bithienyl)-1,2-dicyanoethene (4TCE) is a photoswitch that operates via reversible E/Z photoisomerization following absorption of visible light. cis-to-trans photoisomerization of 4TCE requires excitation below 470 nm, is relatively inefficient (quantum yield < 5%) and occurs via the lowest-lying triplet. We present excitation-wavelength dependent (565-420 nm) transient absorption (TA) studies to probe the photophysics of cis-to-trans isomerization to identify sources of switching inefficiency. TA data reveals contributions from more than one switch conformer and relaxation cascades between multiple states. Fast (∼4 ps) and slow (∼40 ps) components of spectral dynamics observed at low excitation energies (>470 nm) are readily attributed to deactivation of two conformers; this assignment is supported by computed thermal populations and absorption strengths of two molecular geometries (PA and PB) characterized by roughly parallel dipoles for the thiophenes on opposite sides of the ethene bond. Only the PB conformer is found to contribute to triplet population and the switching of cis-4TCE: high-energy excitation (<470 nm) of PB involves direct excitation to S2, relaxation from which prepares an ISC-active S1 geometry (ISC QY 0.4-0.67, kISC∼ 1.6-2.6 × 10-9 s-1) that is the gateway to triplet population and isomerization. We ascribe low cis-to-trans isomerization yield to excitation of the nonreactive PA conformer (75-85% loss) as well as loses along the PB S2→ S1→ T1 cascade (10-20% loss). In contrast, electrocyclization is inhibited by the electronic character of the excited states, as well as a non-existent thermal population of a reactive "antiparallel" ring conformation.


Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells.
CD6 is a 130-kD glycoprotein expressed on the surface of thymocytes and peripheral blood T cells that is involved in TCR-mediated T cell activation. In thymus, CD6 mediates interactions between thymocytes and thymic epithelial (TE) cells. In indirect immunofluorescence assays, a recombinant CD6-immunoglobulin fusion protein (CD6-Rg) bound to cultured human TE cells and to thymic fibroblasts. CD6-Rg binding to TF and TE cells was trypsin sensitive, and 54 +/- 4% of binding was divalent cation dependent. By screening the blind panel of 479 monoclonal antibodies (mAbs) from the 5th International Workshop on Human Leukocyte Differentiation Antigens for expression on human TE cells and for the ability to block CD6-Rg binding to TE cells, we found one mAb (J4-81) that significantly inhibited the binding of CD6-Rg to TE cells (60 +/- 7% inhibition). A second mAb to the surface antigen identified by mAb J4-81, J3-119, enhanced the binding of CD6-Rg to TE cells by 48 +/- 5%. Using covalent cross-linking and trypsin digestion, we found that mAb J4-81 and CD6-Rg both bound to the same 100-kD glycoprotein (CD6L-100) on the surface of TE cells. These data demonstrate that a 100-kD glycoprotein on TE cells detected by mAb J4-81 is a ligand for CD6.


Sensitivity to Referential Ambiguity in Discourse: The Role of Attention, Working Memory, and Verbal Ability.
The establishment of reference is essential to language comprehension. The goal of this study was to examine listeners' sensitivity to referential ambiguity as a function of individual variation in attention, working memory capacity, and verbal ability. Participants listened to stories in which two entities were introduced that were either very similar (e.g., two oaks) or less similar (e.g., one oak and one elm). The manipulation rendered an anaphor in a subsequent sentence (e.g., oak) ambiguous or unambiguous. EEG was recorded as listeners comprehended the story, after which participants completed tasks to assess working memory, verbal ability, and the ability to use context in task performance. Power in the alpha and theta frequency bands when listeners received critical information about the discourse entities (e.g., oaks) was used to index attention and the involvement of the working memory system in processing the entities. These measures were then used to predict an ERP component that is sensitive to referential ambiguity, the Nref, which was recorded when listeners received the anaphor. Nref amplitude at the anaphor was predicted by alpha power during the earlier critical sentence: Individuals with increased alpha power in ambiguous compared with unambiguous stories were less sensitive to the anaphor's ambiguity. Verbal ability was also predictive of greater sensitivity to referential ambiguity. Finally, increased theta power in the ambiguous compared with unambiguous condition was associated with higher working-memory span. These results highlight the role of attention and working memory in referential processing during listening comprehension.


Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues.
The long arm of chromosome 10 is frequently affected by allelic loss in prostate cancer. PTEN/MMAC1, a candidate tumor suppressor gene located at 10q23.3, a region commonly deleted in prostate cancer, was recently identified and found to be deleted or mutated in cancer cell lines derived from a variety of human tissues including prostate. To examine the role of PTEN/MMAC1 in the progression of prostate cancer, we screened a unique set of 50 metastatic prostate cancer tissues from 19 cancer-death patients for alterations in the PTEN/MMAC1 gene, using single-strand conformational polymorphism analysis and direct sequencing to identify sequence changes and microsatellite analysis to examine allelic loss in the vicinity of PTEN/MMAC1. Overall, gene alterations (deletions or point mutations) were observed in at least 1 metastatic site in 12 of the 19 patients studied. Two cases had homozygous deletions that were confirmed by fluorescence in situ hybridization analysis. Four patients harbored point mutations, with one mutation being found in all four tumors (a primary lesion and three different metastases) from the same patient. The remaining three mutations were detected in only one of multiple metastases. Loss of heterozygosity was found in 10 of 18 informative cases, with 1 case showing a unique pattern of microsatellite instability in each of six different metastases examined. Loss of the same allele was found in all metastases in a given patient in 9 of 10 cases. These results indicate that PTEN/MMAC1 gene alterations occur frequently in lethal prostate cancer, although a substantial amount of mutational heterogeneity is found among different metastatic sites within the same patient. These latter findings emphasize the potentially complex genetic relationship that can exist between various clonal lineages of prostate cancer cells as they evolve during the metastatic process and suggest a molecular basis for phenotypic heterogeneity of different prostate cancer foci in patients with disseminated disease.


Corallivory and the microbial debacle in two branching scleractinians.
The grazing activity by specific marine organisms represents a growing threat to the survival of many scleractinian species. For example, the recent proliferation of the corallivorous gastropod Drupella now constitutes a critical case in all South-East Asian waters. If the damaging effects caused by this marine snail on coral polyps are relatively well known, the indirect incidence of predation on coral microbial associates is still obscure and might also potentially impair coral health. In this study, we compared the main ecological traits of coral-associated bacterial and viral communities living in the mucus layer of Acropora formosa and Acropora millepora, of healthy and predated individuals (i.e., colonized by Drupella rugosa), in the Bay of Van Phong (Vietnam). Our results show a substantial impact of the gastropod on a variety of microbiological markers. Colonized corals harbored much more abundant and active epibiotic bacteria whose community composition shifted toward more pathogenic taxa (belonging to the Vibrionales, Clostridiales, Campylobacterales, and Alteromonadales orders), together with their specific phages. Viral epibionts were also greatly influenced by Drupella corallivory with spectacular modifications in their concentrations, life strategies, genotype richness, and diversity. Novel and abundant circular Rep-encoding ssDNA viruses (CRESS-DNA viruses) were detected and characterized in grazed corals and we propose that their occurrence may serve as indicator of the coral health status. Finally, our results reveal that corallivory can cause severe dysbiosis by altering virus-bacteria interactions in the mucus layer, and ultimately favoring the development of local opportunistic infections.


Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts.
A transcription factor, Cbfa1, which belongs to the runt-domain gene family, is expressed restrictively in fetal development. To elucidate the function of Cbfa1, we generated mice with a mutated Cbfa1 locus. Mice with a homozygous mutation in Cbfa1 died just after birth without breathing. Examination of their skeletal systems showed a complete lack of ossification. Although immature osteoblasts, which expressed alkaline phophatase weakly but not Osteopontin and Osteocalcin, and a few immature osteoclasts appeared at the perichondrial region, neither vascular nor mesenchymal cell invasion was observed in the cartilage. Therefore, our data suggest that both intramembranous and endochondral ossification were completely blocked, owing to the maturational arrest of osteoblasts in the mutant mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.


Perforator aneurysms of the posterior circulation: case series and review of the literature.
Posterior circulation perforator artery aneurysms are sparsely reported in the literature. The natural history of these rare lesions remains unclear and their diagnosis and management are not well-defined. We reviewed our institution's medical records and performed a comprehensive literature search for cases of posterior circulation perforator aneurysms. Diagnostic imaging, management and clinical outcomes were the primary components of interest. Our first case was a 58-year-old patient who developed an infarct after attempted endovascular treatment of a basilar perforator artery aneurysm, the second case was a 55-year-old patient with a posterior cerebral artery perforator aneurysm who did well with conservative management and the third case was a 68-year-old patient who suffered an infarct after successful Onyx embolization of a superior cerebellar artery perforator aneurysm. From the literature we identified four case reports and four case series, all describing aneurysmal lesions of the basilar perforator arteries, giving a total of 17 cases including those from our institution. All cases presented with subarachnoid hemorrhage although 47% of initial vascular imaging studies failed to reveal the aneurysm. Cumulatively, 41% of patients were treated with microsurgery, 35% were treated with endovascular therapy and 24% were managed conservatively with subsequent spontaneous aneurysm resolution at a mean interval of 10 months after rupture. Perforator aneurysms of the posterior circulation are diagnostic and therapeutic challenges. Both microsurgical and endovascular treatment of posterior circulation perforator aneurysms are technically difficult, necessitating comprehensive management by an experienced cerebrovascular team.


Subclinical immunologic and physiologic responses in hexamethylene diisocyanate-exposed auto body shop workers.
Diisocyanates are potent sensitizing agents and currently the most commonly identified cause of occupational asthma in industrialized countries. However, diisocyanate asthma is difficult to diagnose and exposure and host risk factors are unclear. Auto body shops, one of the most common hexamethylene diisocyanate (HDI) exposure settings, are particularly difficult to study due to their small size and episodic exposures. Surveillance studies of such workers are limited. We have initiated a cross-sectional field epidemiologic study, Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), to characterize the effects of diisocyanate exposures on actively employed auto body shop workers. Methods and Results We present here questionnaire, physiologic, immunologic, and exposure data on 75 subjects enrolled in the study. No overt cases of clinically apparent diisocyanate asthma were identified based on spirometry, methacholine challenge, peak flows, and symptoms. HDI-specific lymphocyte proliferation was present in 30% of HDI-exposed workers and HDI-specific IgG in 34% of HDI-exposed workers, but they were not associated. HDI-specific IgE was detected in two workers. HDI-specific lymphocyte proliferation, increased methacholine responsiveness, and symptoms of chest tightness and shortness of breath were more common in the most heavily HDI-exposed workers, the painters. More long-term follow-up of this cohort should clarify the significance of these HDI-specific immunologic responses, physiologic changes, and symptoms. These findings demonstrate the presence of HDI-specific immune responses in a large proportion of healthy HDI-exposed workers.


What do pregnant women know about preventing preterm birth?
Approximately 75% of all perinatal mortality is attributable to preterm birth and its sequelae; therefore, the prevention of preterm birth is a major public health priority. In an effort to determine what pregnant women need to be taught about this subject, 211 pregnant women in an inner-city clinic were given a questionnaire to ascertain their basic knowledge about the subject. Among the results were that almost one-half of the women surveyed did not know how many weeks constituted a normal pregnancy and one-third did not know that neonates born preterm could have health problems. The importance of teaching these and other basic facts (which nurses might think are already known by pregnant women) is a notable finding of this research. If perinatal nurses are to effectively teach pregnant women about the prevention of preterm birth, they must target the appropriate facts and build their patients' knowledge base.


Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics. No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥ 5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288.).


Usability Assessment of the Missouri Cancer Registry's Published Interactive Mapping Reports: Round Two.
Health-related data's users have trouble understanding and interpreting combined statistical and mapping information. This is the second round of a usability study conducted after we modified and simplified our tested maps based on the first round's results. To explore if the tested maps' usability improved by modifying the maps according to the first round's results. We recruited 13 cancer professionals from National American Central Cancer registries (NACCR) 2016 conference. The study involved three phases per participant: A pretest questionnaire, the multi-task usability test, and the System Usability Scale (SUS). Software was used to record the computer screen during the trial and the users' spoken comments. We measured several qualitative and quantitative usability metrics. The study's data was analyzed using spreadsheet software. In the current study, unlike the previous round, there was no significant statistical relationship between the subjects' performance on the study test and the experience in GIS tools (P = .17 previously was .03). Three out of the four (75%) of our subjects with a bachelor's degree or less accomplished the given tasks effectively and efficiently. This study developed a comparable satisfaction results to the first round study, despite that the previous round's participants were highly educated and more experienced with GIS. By considering the round one's results and by updating our maps, we made the tested maps simpler to be used by subjects who have little experience in using GIS technology, and have little spatial and statistical knowledge.


Cell wall is required for fixation of the embryonic axis in Fucus zygotes.
Establishment of a primary developmental axis generally is thought to involve rearrangements in the plasma membrane or cytoplasm of the egg. In this report the additional requirement for cell wall in polarization of Fucus zygotes was investigated. Protoplasts of fertilized eggs were tested for their ability to establish an axis in accordance with an orienting vector of unilateral light. The results demonstrate that cell wall is not required for axis formation. However, the orientation of the axis remains labile until new cell wall is synthesized. The presence of a cell wall is an absolute requirement for axis fixation.


The difficult search for organocerium(iv) compounds.
This Tutorial Review provides an overview of the historic and current development of the organometallic chemistry of cerium in its oxidation state 4+. Among the tetravalent lanthanide ions, only Ce4+ forms stable coordination compounds (e.g. (NH4)2[Ce(NO3)6]). Important fields of applications for cerium(iv) compounds include organic synthesis, bioinorganic chemistry, materials science, and industrial catalysis. In sharp contrast, organometallic cerium(iv) compounds are still exceedingly rare. The history of organocerium(iv) compounds is an exciting story of ups and downs. The so-called cerocene (= bis(η8-cyclooctatetraenyl) cerium) has been known since 1976. Other early reports e.g. about Cp4Ce (Cp = η5-cyclopentadienyl), were later disproven. However, significant progress in this field has been made in recent years through the use of carefully designed ligands and more sophisticated synthesis protocols. Taking the case of organocerium(iv) chemistry, this Tutorial Review also tries to exemplarily show how difficult synthetic and theoretical problems can eventually be solved through newly designed synthesis strategies (e.g. as accomplished for cyclopentadienyl and carbene derivatives) and a rewarding collaboration between synthetic and theoretical chemists (cf. the cerocene problem).


Pediatric submersion events in portable above-ground pools in the United States, 2001-2009.
The goal of this study was to describe the epidemiology of pediatric submersion events occurring in portable pools in the United States. A retrospective analysis of fatal and nonfatal submersion events involving children younger than 12 years in portable pools was conducted using injury and fatality data compiled by the US Consumer Product Safety Commission from 2001 through 2009. There were 209 fatal and 35 nonfatal submersion cases reported to the commission from 2001 through 2009. The majority (94%) involved children younger than 5 years, 56% involved boys, 73% occurred in the child's own yard, and 81% occurred during the summer months. The number of submersion events increased rapidly from 2001 to 2005 and then leveled off from 2005 to 2009. The use of portable pools in residential settings poses a significant risk of submersion-related morbidity and mortality to children, especially in the <5-year-old age group. No single strategy will prevent all submersion deaths and injuries; therefore, layers of protection are recommended. Industry is advised to engage in development of protective devices that are effective and affordable for portable pools, including isolation fencing, pool alarms, and safety covers. A strong and pervasive consumer education campaign is needed to make consumers aware of the dangers of portable pools, because these small, inexpensive, consumer-installed pools may not generate the same sense of risk as an in-ground pool.


Sympathetic- and parasympathetic-linked cardiac function and prediction of externalizing behavior, emotion regulation, and prosocial behavior among preschoolers treated for ADHD.
To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). Cardiac preejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia (RSA), an index of parasympathetic-linked cardiac activity, were assessed among 99 preschool children (ages 4-6 years) with ADHD both at rest and in response to behavioral challenge, before participants and their parents completed 1 of 2 versions of the Incredible Years parent and child interventions. Main effects of PEP activity and reactivity and of RSA activity and reactivity were found. Although samplewide improvements in behavior were observed at posttreatment, those who exhibited lengthened cardiac PEP at rest and reduced PEP reactivity to incentives scored higher on measures of conduct problems and aggression both before and after treatment. In contrast, children who exhibited lower baseline RSA and greater RSA withdrawal scored lower on prosocial behavior before and after treatment. Finally, children who exhibited greater RSA withdrawal scored lower on emotion regulation before and after treatment. We discuss these findings in terms of (a) individual differences in underlying neurobiological systems subserving appetitive (i.e., approach) motivation, emotion regulation, and social affiliation and (b) the need to develop more intensive interventions targeting neurobiologically vulnerable children.


Randoms and TOF gain revisited.
Time-of-flight (TOF) positron emission tomography (PET) typically reduces the variance in the images by a factor that is proportional to the size of the object to be scanned, and inversely proportional to the time resolution of the PET scanner. Attempts to better characterize this relationship and understand its limits have been published, showing that such gain also increases with random fraction. In this paper, new experimental and simulated data are analyzed and old results are incorporated in the study. The proportionality of TOF gain with time resolution is confirmed, the proportionality constant is measured, the effect of the randoms is validated, and the limit of the model for small objects is investigated.


Shape Classification Using Wasserstein Distance for Brain Morphometry Analysis.
Brain morphometry study plays a fundamental role in medical imaging analysis and diagnosis. This work proposes a novel framework for brain cortical surface classification using Wasserstein distance, based on uniformization theory and Riemannian optimal mass transport theory. By Poincare uniformization theorem, all shapes can be conformally deformed to one of the three canonical spaces: the unit sphere, the Euclidean plane or the hyperbolic plane. The uniformization map will distort the surface area elements. The area-distortion factor gives a probability measure on the canonical uniformization space. All the probability measures on a Riemannian manifold form the Wasserstein space. Given any 2 probability measures, there is a unique optimal mass transport map between them, the transportation cost defines the Wasserstein distance between them. Wasserstein distance gives a Riemannian metric for the Wasserstein space. It intrinsically measures the dissimilarities between shapes and thus has the potential for shape classification. To the best of our knowledge, this is the first. work to introduce the optimal mass transport map to general Riemannian manifolds. The method is based on geodesic power Voronoi diagram. Comparing to the conventional methods, our approach solely depends on Riemannian metrics and is invariant under rigid motions and scalings, thus it intrinsically measures shape distance. Experimental results on classifying brain cortical surfaces with different intelligence quotients demonstrated the efficiency and efficacy of our method.


Anesthesia and analgesia-related preferences and outcomes of women who have birth plans.
This study described anesthesia and analgesia-related preferences and outcomes of women who used a birth plan for labor and birth. A prospective cohort study was conducted (N = 63). Data were abstracted from medical records, birth plans, and a follow-up survey. Descriptive statistics were used for analysis. Women who elected birth plans were primarily white, college-educated, primigravida, and under the care of a certified nurse-midwife. One-third of births were induced, 10% required instrumentation, and 29% were cesarean births. Nearly every birth was associated with at least 1 labor and birth complication, although most complications were minor. Analgesic preferences were reported to be the most important birth plan request. Greater than 50% of women requested to avoid epidural analgesia; however, 65% of women received epidural analgesia. On follow-up, greater than 90% of women who received epidural analgesia reported being pleased. The majority of women agreed that the birth plan enhanced their birth experiences, added control, clarified their thoughts, and improved communication with their health care providers. Anesthesia and analgesia-related preferences were an important component of the birth plans. The majority of women favorably viewed the use of a birth plan, whether or not preferences were fulfilled or complications occurred.


Actual evidence for neuromonitoring-guided intensive care following severe traumatic brain injury.
Therapeutic interventions following severe traumatic brain injury (TBI) are substantially influenced by complex and interwoven pathophysiological cascades involving both, local and systemic alterations. Our main duty is to prevent secondary progression of the primary damage. This, in turn, obliges us to actively search and identify secondary insults related, for example, to hypoxia, hypotension, uncontrolled hyperventilation, anaemia, and hypoglycaemia. During pharmacological coma we must rely on specific cerebral monitoring which is indispensable in unmasking otherwise occult changes. In addition, extended neuromonitoring (SjvO2, ptiO2, microdialysis, transcranial Doppler sonography, electrophysiological studies, direct brain perfusion measurement) can be used to define individual pathological ICP levels which, in turn, will support our decision making. Extended neuromonitoring expands the limited knowledge derived from ICP and CPP values, thereby allowing us to adequately adapt the type, extent and speed of different therapeutic interventions. A more individualised and flexible treatment concept depends on extended neuromonitoring. The present review addresses current evidence in favour of extended neuromonitoring used to guide treatment options aimed at improving intensive care treatment of patients with severe TBI. With increasing experience gained by the use of extended neuromonitoring in clinical routine we may expect that the evidence obtained within the individual patient will translate to convincing evidence on a larger scale for the entire study population.


HTLV-1 related knowledge, attitude and behaviour patterns among mothers who participated in the Jamaica Breastfeeding Intervention Study (1996-2000).
Human T-cell Lymphotropic Virus type-1 (HTLV-1), the first human retrovirus associated with a malignant disease, is endemic in Jamaica. Vertical transmission and sexual intercourse are the major routes of transmission. Women are at greater risk of contracting the virus as it is more efficiently transmitted from male to female than in the reverse. Prevention of transmission is best achieved by health education on safe practices. The study aims to document the knowledge, attitude and behaviour pattern (KABP) of a group of women five years after they had participated in a mother-to-child transmission of HTLV-1 risk reduction study. A cross-sectional study was conducted using a 46-point structured interviewer-administered questionnaire to capture data from 88 mothers. Overall knowledge scores were computed and four rating categories created. There were large deficiencies in the knowledge and practice of women at risk of being infected with HTLV-1. Only 58% knew that HTLV-1 is sexually transmitted. A minority was aware of HTLV-1 associated diseases: Adult T-cell lymphoma/leukaemia (ATL) -30.7%; Tropical Spastic Paraparesis (TSP) -42%; Infective dermatitis -42%). Ten (11.4%) believed that HTLV-1 infection can cause HIV/AIDS and only 33% knew that there was no cure for the virus. Most women (88.6%) continued to have unprotected sex. Controlling HTLV-1 spread must be based on interrupting transmission. In Jamaica, donated blood is screened for HTLV-1 and sharing of infected needle is an insignificant mode of transmission. However although safe practices in breastfeeding and sexual intercourse are proven ways to reduce HTLV-1 transmission, these data show that knowledge and safe practices among those at risk may not be retained and health education will need to be sustained.


The cardiac effects of hyperbaric oxygen at 243 kPa using inchamber echocardiography.
The adverse effects of hyperbaric oxygen (HBO) on cardiac physiology are considered a potential hazard during the treatment of some patients. The haemodynamic effects of HBO are poorly understood and the incompatibility of electrical equipment inside the chamber has made assessment difficult. At Fremantle Hyperbaric Unit, we have modified an ultrasound machine (Logiq™ e) for safe use within the hyperbaric environment. The aim of this study was to evaluate the cardiac changes that occur during HBO using in-chamber transthoracic echocardiography (TTE) in subjects without evidence of active cardiac disease. Eleven patients and nine members of staff underwent comprehensive TTE examinations before and during HBO administered at a pressure of 243 kPa. The TTE examinations were reported by two independent cardiologists and statistically evaluated using paired Student's t-tests. There was a significant decrease in heart rate during HBO (65 vs. 70 bpm on air at atmospheric pressure, P = 0.002) resulting in a decrease in cardiac output (5.3 vs. 5.9 L·min⁻¹, P = 0.003). Left ventricular outflow tract (LVOT) dimension was larger during HBO than baseline imaging (2.30 vs. 2.23 cm, P = 0.0003). LVOT velocity time integrals (VTI) decreased (19.9 vs. 21.5 cm, P = 0.009) and therefore a similar stroke volume was maintained (61 vs. 65 ml, P = 0.5). Ventricular and atrial volumes, intracardiac flows and minor valvular abnormalities were not significantly affected by HBO. No adverse cardiac effects were observed. TTE can be safely performed within a hyperbaric chamber. Cardiac physiology is not adversely affected by HBO in individuals without active cardiac disease.


PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites.
PGC-1alpha is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser polymorphism of PGC-1alpha has previously shown association with arterial hypertension among Austrian men. Thus, we aimed at investigating this relationship in the Danish white population. The Gly482Ser polymorphism was genotyped in a total of 2562 Danish white subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView locked nucleic acid assay (LNA), and the relationships of this variant with blood pressure levels and arterial hypertension were analyzed. Furthermore, we performed a combined analysis of the data from the present study in combination with previously published results. The Ser/Ser genotype was significantly associated with a reduced risk of hypertension and with lower systolic, diastolic, and mean arterial blood pressure levels, predominantly among women. Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56 to 0.86) for hypertension compared with Gly/X carriers (P=0.001). In conclusion, the Ser allele of PGC-1alpha Gly482Ser confers a significantly reduced risk of hypertension in whites. Further studies are needed to elucidate the differential role of this polymorphism in men and women.


Alcohol consumption in very old age and its association with survival: A matter of health and physical function.
Alcohol consumption in very old age is increasing; yet, little is known about the personal and health-related characteristics associated with different levels of alcohol consumption and the association between alcohol consumption and survival among the oldest old. Nationally representative data from the Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD, ages 76-101; n=863) collected in 2010/2011 were used. Mortality was analyzed until 2014. Alcohol consumption was measured with questions about frequency and amount. Drinks per month were calculated and categorized as abstainer, light-to-moderate drinker (0.5-30 drinks/month) and heavy drinker (>30 drinks/month). Multinomial logistic regressions and Laplace regressions were performed. Compared to light-to-moderate drinkers, abstainers had lower levels of education and more functional health problems, while heavy drinkers were more often men, had higher levels of education, and no serious health or functional problems. In models adjusted only for age and sex, abstainers died earlier than drinkers. Among light-to-moderate drinkers, each additional drink/month was associated with longer survival, while among heavy drinkers, each additional drink/month was associated with shorter survival. However, after adjusting for personal and health-related factors, estimates were lower and no longer statistically significant. The association between alcohol consumption and survival in very old age seems to have an inverse J-shape; abstention and heavy use is associated with shorter survival compared to light-to-moderate drinking. To a large extent, differences in survival are due to differences in baseline health and physical function.