CD14 as a Mediator of the Mineralocorticoid Receptor-Dependent Anti-apolipoprotein A-1 IgG Chronotropic Effect on Cardiomyocytes.
In vitro and animal studies point to autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) as possible mediators of cardiovascular (CV) disease involving several mechanisms such as basal heart rate interference mediated by a mineralocorticoid receptor-dependent L-type calcium channel activation, and a direct pro-inflammatory effect through the engagement of the toll-like receptor (TLR) 2/CD14 complex. Nevertheless, the possible implication of these receptors in the pro-arrhythmogenic effect of anti-apoA-1 antibodies remains elusive. We aimed at determining whether CD14 and TLRs could mediate the anti-apoA-1 IgG chronotropic response in neonatal rat ventricular cardiomyocytes (NRVC). Blocking CD14 suppressed anti-apoA-1 IgG binding to NRVC and the related positive chronotropic response. Anti-apoA-1 IgG alone induced the formation of a TLR2/TLR4/CD14 complex, followed by the phosphorylation of Src, whereas aldosterone alone promoted the phosphorylation of Akt by phosphatidylinositol 3-kinase (PI3K), without affecting the chronotropic response. In the presence of both aldosterone and anti-apoA-1 IgG, the localization of TLR2/TLR4/CD14 was increased in membrane lipid rafts, followed by PI3K and Src activation, leading to an L-type calcium channel-dependent positive chronotropic response. Pharmacological inhibition of the Src pathway led to the decrease of L-type calcium channel activity and abrogated the NRVC chronotropic response. Activation of CD14 seems to be a key regulator of the mineralocorticoid receptor-dependent anti-apoA-1 IgG positive chronotropic effect on NRVCs, involving relocation of the CD14/TLR2/TLR4 complex into lipid rafts followed by PI3K and Src-dependent L-type calcium channel activation.


Better health-related quality of life (mental component summary), having a higher level of education, and being less than 75 years of age are predictors of hospital admission among cognitively intact nursing home residents: a 5-year follow-up study.
To study whether health-related quality of life (HRQOL), activities of daily living (ADL), and anxiety and depression symptoms affect the risk of hospital admission and potential interactions with having a cancer diagnosis. This study was a prospective observational study with 5-year follow-up and analyzed the follow-up data on hospital admissions until 2010 using baseline data from 227 cognitively intact nursing home (NH) residents (60 of whom had cancer) in 2004-2005. Data on HRQOL were collected by using the Short Form-36 Health Survey, divided into physical component summary (PCS) and mental component summary (MCS), and symptoms of anxiety and depression were collected by using the Hospital Anxiety and Depression Scale (HADS). ADL were obtained from registered observation and sociodemographic variables, diagnoses, and hospital admissions from the NH records. Personal identification numbers were linked to the record systems of the hospitals, thereby registering all hospital admissions. We analyzed the time elapsing between inclusion and the first hospital admission. Residents with higher HRQOL (MCS) had significantly more hospital admissions after adjustment for age, sex, marital status, education, and comorbidity. HRQOL (PCS), ADL, depression, and anxiety symptoms were not associated with hospital admissions. Cancer increased the risk after adjustment for all other risk factors but did not increase the effects of MCS, PCS, ADL, or depression or anxiety symptoms. Having a higher level of education and being less than 75 years of age were associated with hospitalization. The residents diagnosed with cancer had the most days in hospital related to diseases of the respiratory system and cancer, and diseases of the circulatory and respiratory systems were more frequent among the residents without a cancer diagnosis. Better self-reported HRQOL (MCS) was associated with hospital admissions, whereas self-reported HRQOL (PCS), ADL, and depression and anxiety symptoms were not. Cancer increased the risk but not the effects of MCS, PCS, ADL, or depression or anxiety symptoms. Having a higher level of education and being less than 75 years of age were also associated with hospitalization.


[Sodium balance and peritoneal ultrafiltration in refractory heart failure].
About 5% of patients with heart failure (HF) reach the end-stage of disease, becoming refractory to therapy. The clinical course of end-stage HF is characterized by repeated hospitalizations, severe symptoms, and poor quality of life. Peritoneal ultrafiltration (PUF), removing water and sodium (Na+), can benefit patients with end-stage HF. However, effects on fluid and electrolyte removal have not been fully characterized. In this pilot study in patients with chronic HF and moderate chronic renal failure, we evaluated the effects of water and sodium removal through PUF on ventricular remodeling, re-hospitalization, and quality of life. Patients with end-stage HF (NYHA class IV, ≥3 HF hospitalization/year despite optimal therapy), not eligible for heart transplantation underwent peritoneal catheter positioning and began a single-day exchange with icodextrin at night (n=6), or 1-2 daily exchanges with hypertonic solution (3.86%) for 2 hours with 1.5-2 L fill volume (n=3). At baseline, average ultrafiltration was 500±200 ml with icodextrin, and 700±100 ml with hypertonic solution. Peritoneal excretion of Na+ was greater with icodextrin (68±4 mEq/exchange) compared to hypertonic solution (45±19 mEq/exchange). After a median 12-month follow-up, rehospitalizations decreased, while NYHA class and quality of life (by Minnesota Living with HF questionnaire), improved. In end-stage HF patients, PUF reduced re-hospitalization and improved quality of life. It can be an additional treatment to control volume and sodium balance.


Smashing Stereotypes: Mutual Respect, Key to Embracing Diversity.
The path to a successful international career in science is daunting for most, and women in Africa are no exception. We are grossly under-represented as senior authors in high-impact publications and keynote speakers at international conferences, and rarely head major funding networks. Smashing long-held stereotypes may ease the journey.


Wearable wireless tactile display for virtual interactions with soft bodies.
We describe here a wearable, wireless, compact, and lightweight tactile display, able to mechanically stimulate the fingertip of users, so as to simulate contact with soft bodies in virtual environments. The device was based on dielectric elastomer actuators, as high-performance electromechanically active polymers. The actuator was arranged at the user's fingertip, integrated within a plastic case, which also hosted a compact high-voltage circuitry. A custom-made wireless control unit was arranged on the forearm and connected to the display via low-voltage leads. We present the structure of the device and a characterization of it, in terms of electromechanical response and stress relaxation. Furthermore, we present results of a psychophysical test aimed at assessing the ability of the system to generate different levels of force that can be perceived by users.


Expression of CD58 in normal, regenerating and leukemic bone marrow B cells: implications for the detection of minimal residual disease in acute lymphocytic leukemia.
CD58, a member of the Ig superfamily, is expressed by hematopoietic and non- hematopoietic cells. It has been demonstrated to be over-expressed in precursor-B acute lymphoblastic leukemia (ALL) blasts when compared to in their normal counterparts, suggesting its potential use in the detection of minimal residual disease (MRD) by flow cytometry (FC). To assess the reliability and accuracy of CD58 for this purpose, we studied its expression in a large series of normal and ALL bone marrow (BM) samples using quantitative FC. We studied 180 precursor-B ALL BM samples at diagnosis (8 pro-B, 164 early-B, 8 mature-B ALL) and 123 follow-up BM samples (n=54 at day +15 and n=69 at day +78), as well as 51 normal BM samples and 7 regenerating BM samples from patients with T-ALL at week 12. We used four-color quantitative FC, focusing analysis on CD58 expression. In follow-up samples from day +78, the MRD level was simultaneously evaluated by real time quantitative polymerase chain reaction (RQ-PCR) amplification of antigen receptor genes. CD58 expression was significantly higher in ALL blasts than in normal B lymphocytes, while no significant differences between regenerating and normal B lymphocytes were observed. CD58 was expressed in 99.4% of the precursor-B ALL cases and 93.5% of these showed over-expression compared to normal. No significant modulation of CD58 expression during remission induction therapy was noted. Finally, 66 (95.6%) of 69 BM samples simultaneously analyzed using both FC and RQ-PCR at day +78 showed concordant results regarding MRD. Our results confirm and further evidence the role of CD58 in the diagnosis and monitoring of precursor-B ALL. In particular, we demonstrated its stability and accuracy in MRD detection at clinically relevant time points. These findings indicate that CD58 is a powerful tool for MRD detection in precursor-B ALL.


Very early reduction in efficacy of botulinum toxin therapy for cervical dystonia in patients with subsequent secondary treatment failure: a retrospective analysis.
The objective of this study was to estimate the probability of development of partial secondary treatment failure (PSTF) in patients with cervical dystonia (CD) who had been treated over up to 9 years with repetitive intramuscular injections of botulinum neurotoxin type A (BoNT/A). The temporal course of treatment response in patients in whom PSTF was detected retrospectively was compared to patients with a normal clinical response. For this purpose, charts of all CD patients treated in our outpatient clinic between 1988 and 2001 were retrospectively analyzed. Extracted data included time of all injections, dose per visit, disease severity measured by TSUI scores, and time of determination of neutralizing antibodies. Final data analysis using a special formal definition of PSTF was based on charts of 568 patients having exclusively been treated with abobotulinumtoxinA. PSTF onset was observed in our CD cohort during the entire treatment period analyzed, with no clustering at any time point. Probability to develop PSTF was 14.5 % in 9 years. Thus, mean PSTF incidence was 1.6 % per year. The mean TSUI score of patients with retrospectively defined PSTF (n = 33) became already significantly worse after the second injection when compared with the group without PSTF (n = 535). Our data indicate that clinical response in patients developing PSTF later on differs from that of patients without PSTF already very early in the course of botulinum neurotoxin type A treatment, and that PSTF remains undetected at this early stage. Reduced response may therefore be present in a number of CD patients who think they still respond normally to continuous BoNT/A treatment.


Assessment of extracellular matrix-related biomarkers in patients with lower extremity artery disease.
The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. We tested the hypothesis that measuring blood-specific fragments generated during degradation of the extracellular matrix (ECM) could provide further insight into the pathophysiologic mechanism of arterial remodeling. The protein profile of diseased arteries from patients undergoing infrainguinal limb revascularization was assessed by a liquid chromatography and tandem mass spectrometry, nontargeted proteomic approach. The information retrieved was the basis for measurement of neoepitope fragments of ECM proteins in the blood of 195 consecutive patients with LEAD by specific enzyme-linked immunosorbent assays. Histologic and proteomic analyses confirmed the structural disorganization of affected arteries. Fourteen of 81 proteins were identified as differentially expressed in diseased arteries with respect to healthy tissues. Most of them were related to ECM components, and the difference in expression was used in multivariate analyses to establish that severe arterial lesions in LEAD patients have a specific proteome. Analysis of neoepitope fragments in blood revealed that fragments of versican and collagen type IV, alone or in combination, segregated patients with mild to moderate symptoms (intermittent claudication, Fontaine I-II) from those with severe LEAD (critical limb ischemia, Fontaine III-IV). We propose noninvasive candidate biomarkers with the ability to be clinically useful across the LEAD spectrum.


Quantitative Susceptibility Mapping for Characterization of Intraplaque Hemorrhage and Calcification in Carotid Atherosclerotic Disease.
Carotid artery intraplaque hemorrhage (IPH), an unstable component of atherosclerosis, is associated with an increased risk of stroke. To investigate quantitative susceptibility mapping (QSM) as a tool for the evaluation of IPH and calcification in vivo. Prospective. Ten healthy volunteers and 15 patients. 3.0T Susceptibility-weighted imaging (SWI), magnetization-prepared rapid acquisition with gradient echo (MP-RAGE), T1 -weighted sampling perfection with application of optimized contrasts using different flip angle evolution (T1 -SPACE), T2 -weighted turbo spin-echo (T2 WI), and time-of-flight (TOF) sequences. The vessel wall area of the carotid artery was measured with QSM and compared with T1 -SPACE on healthy volunteers. Four radiologists, blinded to clinical history and patient identity, determined the presence and area of IPH on MP-RAGE and QSM, as well as the area of calcification on T1 -SPACE and QSM. Bland-Altman analysis, Pearson correlation coefficients, linear regression analyses were performed to evaluate the concordance of area measurements. Cohen's kappa (κ) was analyzed to determine the agreement between IPH detections. The paired t-test was used to compare the group differences. In 423 matched slices, 20.1% (85/423) and 19.6% (83/423) were detected to have IPH on MP-RAGE and QSM, respectively. IPH detection by QSM and MP-RAGE showed good agreement (κ = 0.822, P < 0.001) between the two methods. There was no significant difference in IPH area measurements between QSM and MP-RAGE (7.28 mm2 ± 6.41 vs. 7.16 mm2 ± 5.99, P = 0.575). There was no significant difference in calcification area measurement between QSM and T1 -SPACE (3.51 mm2 ± 1.78 vs. 3.41 mm2 ± 2.02, P = 0.783). QSM is a novel imaging tool for the identification of IPH in patients with carotid atherosclerosis and enables differentiation of IPH and calcification. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1 J. Magn. Reson. Imaging 2020;52:534-541.


Remaining methacrylate groups in composite restorative materials.
The quantity of the remaining unreacted methacrylate groups in polymerized composite materials has been determined. Six proprietary composites were investigated by infrared multiple internal reflection spectroscopy. Infrared reflectance measurements were made before polymerization and repeated after the composites were subjected to polymerization at 37 degrees C for 24 hours. The quantities of remaining unreacted methacrylate groups were determined and the data expressed as percentages of the total amount of methacrylate groups in the unpolymerized materials. The specimens were specially prepared to ensure that the surface properties simulated the bulk properties of the polymerized composites. The quantities of remaining methacrylate groups in the six composites determined by this surface measuring technique ranged from 25 to 48%. The results demonstrate that commercially available composite materials exhibit different degrees of conversion 24 hours after the start of polymerization. These differences can be correlated to the different monomer compositions of the composite restorative resins.


Different effect of cadmium and copper on H+-ATPase activity in plasma membrane vesicles from Cucumis sativus roots.
The effect of heavy metals on plasma membrane (PM) H(+)-ATPase (EC 126.96.36.199) activity in cucumber (Cucumis sativus) roots was studied. The aim of this work was to explain the mechanism of modification of the PM H(+)-ATPase activity in plants subjected to heavy metals. Plants were treated with 10 μM Cd or Cu for 6 d. After 3 d exposure to the heavy metals, some of the plants were transferred to control conditions for a further 3 d (3/3 plants). The activity of PM H(+)-ATPase was found to be increased in plants treated with heavy metals. The highest activity measured as proton transport was observed in 3/3 plants. Estimation of transcript levels of C. sativus PM H(+)-ATPase in roots indicated that the action of Cd, but not Cu, affected the gene expression level. Transcript levels of C. sativus PM H(+)-ATPase (CsHA2, CsHA3, CsHA4, CsHA8, and CsHA9) genes increased in roots treated with Cd. Moreover, Western blot analysis with antibody against phosphothreonine and 14-3-3 protein indicated that increased activity of PM H(+)-ATPase under heavy-metal stress resulted from phosphorylation of the enzyme. It was found that Cu markedly increased the activity of catalase and ascorbate peroxidase and reduced the level of H(2)O(2) in cucumber roots. In contrast, Cd did not affect these parameters. These results indicate that Cd and Cu can, in different ways, lead to modification of PM H(+)-ATPase activity. Additionally, it was observed that treatment of plants with heavy metals led to an increased level of heat-shock proteins in the tissues. This suggests that the plants had started adaptive processes to survive adverse conditions, and increased PM H(+)-ATPase activity could further enhance the repair processes in heavy-metal-stressed plants.


The epidemiology of pregnancy outcomes in rural Burkina Faso.
To describe levels and causes of pregnancy-related mortality and selected outcomes after pregnancy (OAP) in two districts of Burkina Faso. A household census was conducted in the two study districts, recording household deaths to women aged 12-49 years from 2001 to 2006. Questions on pregnancy outcomes in the last 5 years for resident women of reproductive age were included, and an additional method - direct sisterhood - was added in part of the area. Adult female deaths were followed-up with verbal autopsies (VA) with household members. A probabilistic model for interpreting VA data (InterVA-M) was used to determine distributions of probable causes of death. An OAP survey was conducted among all women with an experience of pregnancy during the prior 12 months. It aimed to document physical and psychological disabilities, economic and social consequences and discomfort that women may suffer as a result of a pregnancy. The maternal mortality ratio (MMR) was 441 per 100 000 live births (95% CI: 397, 485), significantly higher in Diapaga [519 per 100 000 (95% CI: 454, 584)] than Ouargaye [353 per 100 000 (95% CI: 295, 411)]. MMRs were associated with wealth quintile, age and distance from a health facility. The causes of death showed higher than expected rates of sepsis (30%) and lower rates of haemorrhage (7%). A substantial proportion of all women had difficulty performing day-to-day tasks as a consequence of pregnancy. Women who had experienced stillbirths or Caesarean sections reported symptom-related indicators of poor physical health more frequently than women reporting uncomplicated deliveries, and were also more likely to be depressed. Expectations on the levels and causes of pregnancy-related mortality in Burkina Faso may need to be re-examined, and this could have programmatic implications; for example high levels of sepsis could prompt renewed efforts to reach women with skilled attendance at delivery and follow-up during the postpartum period. Further documentation of how complication-induced disabilities affect women and their families is needed. For mortality and morbidity outcomes, demonstrating variation between study districts is important to empower local decision makers with evidence of need at a subnational level.


Oral anticoagulation in a pediatric hospital: impact of a quality improvement initiative on warfarin management strategies.
There are potential risks associated with the use of warfarin in children, particularly as the dosing requirements may decrease as patients get older. Our facility is a 715-bed freestanding pediatric tertiary care center with a large cardiac surgery center. A significant number of patients receive warfarin for treatment or prophylaxis of thromboembolic events while in hospital. Initial dose of warfarin and time taken to achieve goal therapeutic international normalized ratio (INR). The intervention included: (1) revision of hospital drug formulary so that warfarin dosing was in accordance with the most recent guidelines; (2) warfarin administration restricted to one time of the day (12.00 noon); (3) target therapeutic INR level documented with each warfarin order; and (4) pharmacy computer system mandated that the pharmacist confirmed the target INR, documented the most current INR, and compared the dose with the formulary guidelines. If the warfarin dose was not in accordance with the formulary guidelines, the pharmacist contacted the physician and made dosing recommendations according to the guidelines. The number of patients with supratherapeutic INR values during the hospital admission was decreased by more than 50% and goal INR values were documented more frequently in the medical record. There was also an increase in subtherapeutic INR values. The intervention had no effect on the time taken to achieve the goal therapeutic INR. Instituting changes in a number of aspects of anticoagulation management and incorporating an intensive educational effort across a breadth of healthcare providers can improve anticoagulation management with warfarin in challenging patient populations such as children. Similar methods could possibly improve anticoagulation with other agents such as unfractionated heparin or low molecular weight heparin.


Fidgetin-Like 2 siRNA Enhances the Wound Healing Capability of a Surfactant Polymer Dressing.
Microtubules (MTs) are intracellular polymers that provide structure to the cell, serve as railways for intracellular transport, and regulate many cellular activities, including cell migration. The dynamicity and function of the MT cytoskeleton are determined in large part by its regulatory proteins, including the recently discovered MT severing enzyme Fidgetin-like 2 (FL2). Downregulation of FL2 expression with small interfering RNA (siRNA) results in a more than twofold increase in cell migration rate in vitro as well as translates into improved wound-healing outcomes in in vivo mouse models. Here we utilized a commercially available surfactant polymer dressing (SPD) as a vehicle to deliver FL2 siRNA. To this end we incorporated collagen microparticles containing FL2 siRNA into SPD (SPD-FL2-siRNA) for direct application to the injury site. Topical application of SPD-FL2 siRNA to murine models of full-thickness excision wounds and full-thickness burn wounds resulted in significant improvements in the rate and quality of wound healing, as measured clinically and histologically, compared with controls. Wound healing occurred more rapidly and with high fidelity, resulting in properly organized collagen substructure. Taken together, these findings indicate that the incorporation of FL2 siRNA into existing treatment options is a promising avenue to improve wound outcomes.


BCI Use and Its Relation to Adaptation in Cortical Networks.
Brain-computer interfaces (BCIs) carry great potential in the treatment of motor impairments. As a new motor output, BCIs interface with the native motor system, but acquisition of BCI proficiency requires a degree of learning to integrate this new function. In this review, we discuss how BCI designs often take advantage of the brain's motor system infrastructure as sources of command signals. We highlight a growing body of literature examining how this approach leads to changes in activity across cortex, including beyond motor regions, as a result of learning the new skill of BCI control. We discuss the previous research identifying patterns of neural activity associated with BCI skill acquisition and use that closely resembles those associated with learning traditional native motor tasks. We then discuss recent work in animals probing changes in connectivity of the BCI control site, which were linked to BCI skill acquisition, and use this as a foundation for our original work in humans. We present our novel work showing changes in resting state connectivity across cortex following the BCI learning process. We find substantial, heterogeneous changes in connectivity across regions and frequencies, including interactions that do not involve the BCI control site. We conclude from our review and original work that BCI skill acquisition may potentially lead to significant changes in evoked and resting state connectivity across multiple cortical regions. We recommend that future studies of BCIs look beyond motor regions to fully describe the cortical networks involved and long-term adaptations resulting from BCI skill acquisition.


The extent to which a position-based explanation accounts for binaural release from informational masking.
Detection was measured for a 500 Hz tone masked by noise (an "energetic" masker) or sets of ten randomly drawn tones (an "informational" masker). Presenting the maskers diotically and the target tone with a variety of interaural differences (interaural amplitude ratios and/or interaural time delays) resulted in reduced detection thresholds relative to when the target was presented diotically ("binaural release from masking"). Thresholds observed when time and amplitude differences applied to the target were "reinforcing" (favored the same ear, resulting in a lateralized position for the target) were not significantly different from thresholds obtained when differences were "opposing" (favored opposite ears, resulting in a centered position for the target). This irrelevance of differences in the perceived location of the target is a classic result for energetic maskers but had not previously been shown for informational maskers. However, this parallellism between the patterns of binaural release for energetic and informational maskers was not accompanied by high correlations between the patterns for individual listeners, supporting the idea that the mechanisms for binaural release from energetic and informational masking are fundamentally different.


Using in situ simulation to improve in-hospital cardiopulmonary resuscitation.
There is widespread recognition that the conduct of cardiac resuscitation is problematic. In situ simulation has been used to train and evaluate cardiac arrest teams' performance in the hospital setting, but in work at a university-affiliated, tertiary care facility, the simulated cardiac arrests were used to understand how well health care providers and their environment function during arrests, with the goal of a rapid intervention to correct problem areas. Latent conditions--innate, mostly hidden, workplace factors--can have a large detrimental impact on resuscitation efforts. Observations from a series of unannounced simulated cardiac arrests undertaken at diverse locations within a university-affiliated, tertiary care hospital were a component of an ongoing initiative to improve performance of emergency cardiovascular care. Fourteen cardiac arrest simulations revealed 24 hazardous findings, approximately two thirds of which had a high likelihood of compromising patient survival if they had occurred during an actual cardiac arrest. Categories of problems included active errors by teams and individuals and systemic or latent errors of the environment. Because the simulations were designed with the goal of discovering and documenting errors, most errors led to further actions, policies, and procedures that were rapidly adopted by the medical center to prevent their recurrence. In situ simulation of cardiac arrests elicits lifelike behaviors and allows engagement of all personnel and resources applicable to real arrests. This method allowed for remedial plans to be developed before further harm could occur. Accordingly, in situ simulation of high-risk events may be a useful, efficient technique that complements existing quality assurance processes in hospitals.


[Dependence profile in Spain: an analysis from the disability survey of 1999].
In the next future an important demographical ageing will imply a rise in the levels of co morbidity, disability and dependence of the population. The objective if this work was to estimate the dependences profile by means of assessing the levels of severity of the disability in the Spanish general population. Data come from the disease, disability and health status survey of 1999 of the Spanish Institute for Statistics, which includes 36 limitations with an score of severity (from 0= absence to 4= unable). These limitations were grouped in five kinds of disability, the mean score of severity was computed for each one, and grouped in five levels of dependence. To check the relationship between limitations and severity an analysis of correspondence was performed. To identify the pattern of dependence a multiple correspondence and a clusters analysis were computed using the variables of age, sex, kind of disability and level of dependence. There is a relationship between severity and some limitations (being the limitation on daily activities associated to the highest severity). Five groups of dependent people were identified. Those with lower dependence were middle aged, men and having sensorial disabilities and those with higher dependence were mainly women, older than 80 and with disabilities on mobility and on the activities of daily living. There are five groups of dependent population and this study allows estimating its frequency among the general population what will be very useful to evaluate the amount of resources necessary to take care of them.


The effects of indomethacin, diclofenac, and acetaminophen suppository on pain and opioids consumption after cesarean section.
Cesarean section is one of the common surgeries of women. Acute post-operative pain is one of the recognized post-operative complications. This study was planned to compare the effects of suppositories, indomethacin, diclofenac and acetaminophen, on post-operative pain and opioid usage after cesarean section. In this double-blind clinical trial study, 120 candidates of cesarean with spinal anesthesia and American Society of Anesthesiologists (ASA) I-II were randomly divided into four groups. Acetaminophen, indomethacin, diclofenac, and placebo suppositories were used in groups, respectively, after operation and the dosage was repeated every 6 h and pain score and opioid usage were compared 24 h after the surgery. The severity of pain was recorded on the basis of Visual Analog Scale (VAS) and if severe pain (VAS > 5) was observed, 0.5 mg/kg intramuscular pethidine had been used. The data were analyzed in SPSS software version 15 and analytical statistics such as ANOVA, Chi-square, and Tukey's honestly significant difference (HSD) post-hoc. Pain score was significantly higher in control group than other groups, and also pain score in acetaminophen group was higher than indomethacin and diclofenac. The three intervention groups received the first dose of pethidine far more than control group and the distance for diclofenac and indomethacin were significantly longer (P < 0.001). The use of indomethacin, diclofenac, and acetaminophen significantly reduces the amount of pethidine usage in 24 h after the surgery relation to control group. Considering the significant decreasing pain score and opioid usage especially in indomethacin and diclofenac groups rather than control group, it is suggested using of indomethacin and diclofenac suppositories for post-cesarean section analgesia.


Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure.
Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic interstitial lung diseases characterized by alveolar wall fibrosis with accumulation of extracellular matrix, interstitial remodeling, and increased numbers of activated alveolar macrophages. Animal models and in vitro studies have shown that macrophage cytokines, namely IL-1 beta and TNF-alpha, play significant roles in the development of fibrosis. We found significant increases for TNF-alpha release in both diseases (p < 0.01) and a significant increase for IL-1 beta release in asbestosis compared to normal controls (p < 0.01). Also, the mRNA expression of these cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha release in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, crocidolite, amosite asbestos, and silica stimulated IL-1 beta and TNF-alpha release and up-regulated their respective mRNA in macrophages or monocytes. To evaluate the role of IL-1 beta and TNF-alpha in the accumulation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after short term (2 h) serum-free exposure to recombinant cytokines. Both cytokines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in the lower respiratory tract in IPF and asbestosis.


Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors.
To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted. CLINICALTRIALS. NCT02072850.


Microbial Contamination of Drinking Water and Human Health from Community Water Systems.
A relatively short list of reference viral, bacterial and protozoan pathogens appears adequate to assess microbial risks and inform a system-based management of drinking waters. Nonetheless, there are data gaps, e.g. human enteric viruses resulting in endemic infection levels if poorly performing disinfection and/or distribution systems are used, and the risks from fungi. Where disinfection is the only treatment and/or filtration is poor, cryptosporidiosis is the most likely enteric disease to be identified during waterborne outbreaks, but generally non-human-infectious genotypes are present in the absence of human or calf fecal contamination. Enteric bacteria may dominate risks during major fecal contamination events that are ineffectively managed. Reliance on culture-based methods exaggerates treatment efficacy and reduces our ability to identify pathogens/indicators; however, next-generation sequencing and polymerase chain reaction approaches are on the cusp of changing that. Overall, water-based Legionella and non-tuberculous mycobacteria probably dominate health burden at exposure points following the various societal uses of drinking water.


Far-field superposition method for three-dimensional computation of light scattering from multiple cells.
A linear coherent superposition method for estimating the plane wave far-field scattering pattern from multiple biological cells computed by the finite-difference time-domain (FDTD) method is presented. The method enables the FDTD simulation results of scattering from a small number of complex scatterers, such as biological cells, to be used to estimate the far-field pattern from a large group of those same scatterers. The superposition method can be used to reduce the computational cost of FDTD simulations by enabling a single large scattering problem to be broken into smaller problems with more practical computational requirements. It is found that the method works best in cases where there is little multiple scattering interaction between adjacent cells, so the far-field pattern of multicell geometry can simply be calculated as a phase-adjusted linear superposition of the scattering from individual cells. A strategy is also presented for choosing the minimum number of cells in cases with significant multiple scattering interactions between cells.


An economic model to estimate the relative costs over 20 years of different hip prostheses.
To determine the relative costs of prostheses and factors associated with changes in these cost rankings. Economic model using published data. The main cost drivers are current costs and revision rates. Expected revision costs are a small proportion of the expected total costs. There are few competitors to the "gold standard" Charnley in terms of total expected costs over 20 years. There is no monetary advantage in using higher cost prostheses in older patients even if they were to have lower revision rates. There may be a monetary case for using prostheses with higher costs and lower revision rates in younger patients. The most cost effective prosthesis in older patients is the Stanmore. The Charnley, Exeter Polished and Muller Straight Stem are marginally more costly than the Stanmore. The study inevitably lacks good data on survival for newer prostheses. This does not affect the ability to make choices for older patients. Data are needed, however, on survival of cemented prostheses for younger patients.


A second fatty acid amide hydrolase with variable distribution among placental mammals.
Fatty acid amides constitute a large and diverse class of lipid transmitters that includes the endogenous cannabinoid anandamide and the sleep-inducing substance oleamide. The magnitude and duration of fatty acid amide signaling are controlled by enzymatic hydrolysis in vivo. Fatty acid amide hydrolase (FAAH) activity in mammals has been primarily attributed to a single integral membrane enzyme of the amidase signature (AS) family. Here, we report the functional proteomic discovery of a second membrane-associated AS enzyme in humans that displays FAAH activity. The gene that encodes this second FAAH enzyme was found in multiple primate genomes, marsupials, and more distantly related vertebrates, but, remarkably, not in a number of lower placental mammals, including mouse and rat. The two human FAAH enzymes, which share 20% sequence identity and are referred to hereafter as FAAH-1 and FAAH-2, hydrolyzed primary fatty acid amide substrates (e.g. oleamide) at equivalent rates, whereas FAAH-1 exhibited much greater activity with N-acyl ethanolamines (e.g. anandamide) and N-acyl taurines. Both enzymes were sensitive to the principal classes of FAAH inhibitors synthesized to date, including O-aryl carbamates and alpha-keto heterocycles. These data coupled with the overlapping, but distinct tissue distributions of FAAH-1 and FAAH-2 suggest that these proteins may collaborate to control fatty acid amide catabolism in primates. The apparent loss of the FAAH-2 gene in some lower mammals should be taken into consideration when extrapolating genetic or pharmacological findings on the fatty acid amide signaling system across species.


Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells.
The major problem in skin grafting is that tissue-engineered skin grafts after their transplantation are initially entirely dependent on diffusion. Since this process is slow and inefficient, nutrients, growth factors, and oxygen will insufficiently be supplied and the regenerating graft will undergo a physiological crisis, resulting in scar-like dermal structures and shrinkage. The tissue-engineering of a vascular network in human dermo-epidermal skin substitutes (DESS) is a promising approach to overcome this limitation. Here we report, for the first time, on the use of the adipose stromal vascular fraction (SVF)-derived endothelial cell population to tissue-engineer DESS containing a highly efficient capillary plexus. To develop vascular networks in vitro, we employed optimized 3D fibrin or collagen type I hydrogel systems. Upon transplantation onto immune-deficient rats, these pre-formed vascular networks anastomosed to the recipient's vasculature within only four days. As a consequence, the neo-epidermis efficiently established tissue homeostasis, the dermis underwent almost no contraction, and showed sustained epidermal coverage in vivo. Overall, the here described rapid and efficient perfusion of SVF-based skin grafts opens new perspectives for the treatment of hitherto unmet clinical needs in burn/plastic surgery and dermatology.


A family of one-dimensional lanthanide complexes bridged by two distinct carboxylate ligands with the Dy analogue displaying magnetic relaxation behaviour.
A series of isostructural lanthanide one-dimensional (1D) chain complexes, [Ln(INNO)(Bza)2(H2O)2]·(H2O) {INNO = isonicotinate N-oxide, Bza = benzoic acid; Nd(1), Eu(2), Gd(3), Tb(4), Dy(5), Er(6) and Y(7)}, have been successfully isolated by hydrothermal reactions utilizing two distinct carboxylates as co-ligands. Due to the similar steric hindrance of the two carboxylic ligands, the neighboring lanthanide ions are bridged simultaneously by their carboxyl groups from the opposite sides to form a 1D chain structure. The shape analysis of the eight-coordinated Dy analogue 5 highlights the coordination geometry of the distorted square antiprism (D4d). The solid-state luminescence of 2 and 4 was characterized. The static magnetic analysis of the Gd analogue 3 is indicative of the dominant weak intrachain antiferromagnetic interactions via the carboxylic ligands. Dynamic magnetic measurements for 5 revealed clear slow magnetic relaxation behaviour typical for single-molecule magnets (SMMs). Compound 5 represents a very rare example, reported as a mixed carboxylate bridged lanthanide SMM.


Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder.
Gender identity disorder (GID) is a conflict between a person's actual physical gender and the one they identify him or herself with. Testosterone is the key agent in the medical treatment of female to male GID patients. We conducted a dose-response analysis of testosterone replacement therapy (TRT) in 138 patients to determine the onset of the therapeutic effects. The TRT consisted of intramuscular injection of testosterone enanthate and patients were divided into three groups; 250 mg every two weeks, 250 mg every three weeks and 125 mg every two weeks. The onset of deepening of voice, increase in facial hair and cessation of menses was evaluated in each group. At one month after the start of TRT, the onset of these physical changes was more prevalent in the group receiving the higher dose of testosterone, and there were dose-dependent effects observed between the three treatment groups. On the other hand, at six months after the start of TRT, most of the patients had achieved treatment responses and there were no dose-dependent effects with regard to the percentage of patients with therapeutic effects. No significant side effects were observed in any of the treatment groups. We demonstrated that the early onset of the treatment effects of TRT is dose-dependent, but within six months of starting TRT, all three doses were highly effective. Current study provides useful information to determine the initial dose of TRT and to suggest possible changes that should be made in the continuous dosage for long term TRT.


Seventy years of continuous encroachment substantially increases 'blue carbon' capacity as mangroves replace intertidal salt marshes.
Shifts in ecosystem structure have been observed over recent decades as woody plants encroach upon grasslands and wetlands globally. The migration of mangrove forests into salt marsh ecosystems is one such shift which could have important implications for global 'blue carbon' stocks. To date, attempts to quantify changes in ecosystem function are essentially constrained to climate-mediated pulses (30 years or less) of encroachment occurring at the thermal limits of mangroves. In this study, we track the continuous, lateral encroachment of mangroves into two south-eastern Australian salt marshes over a period of 70 years and quantify corresponding changes in biomass and belowground C stores. Substantial increases in biomass and belowground C stores have resulted as mangroves replaced salt marsh at both marine and estuarine sites. After 30 years, aboveground biomass was significantly higher than salt marsh, with biomass continuing to increase with mangrove age. Biomass increased at the mesohaline river site by 130 ± 18 Mg biomass km(-2) yr(-1) (mean ± SE), a 2.5 times higher rate than the marine embayment site (52 ± 10 Mg biomass km(-2) yr(-1) ), suggesting local constraints on biomass production. At both sites, and across all vegetation categories, belowground C considerably outweighed aboveground biomass stocks, with belowground C stocks increasing at up to 230 ± 62 Mg C km(-2) yr(-1) (± SE) as mangrove forests developed. Over the past 70 years, we estimate mangrove encroachment may have already enhanced intertidal biomass by up to 283 097 Mg and belowground C stocks by over 500 000 Mg in the state of New South Wales alone. Under changing climatic conditions and rising sea levels, global blue carbon storage may be enhanced as mangrove encroachment becomes more widespread, thereby countering global warming.


Human behavioral assessments in current research of Parkinson's disease.
Parkinson's disease (PD) is traditionally classified as a movement disorder because patients mainly complain about motor symptoms. Recently, non-motor symptoms of PD have been recognized by clinicians and scientists as early signs of PD, and they are detrimental factors in the quality of life in advanced PD patients. It is crucial to comprehensively understand the essence of behavioral assessments, from the simplest measurement of certain symptoms to complex neuropsychological tasks. We have recently reviewed behavioral assessments in PD research with animal models (Asakawa et al., 2016). As a companion volume, this article will systematically review the behavioral assessments of motor and non-motor PD symptoms of human patients in current research. The major aims of this article are: (1) promoting a comparative understanding of various behavioral assessments in terms of the principle and measuring indexes; (2) addressing the major strengths and weaknesses of these behavioral assessments for a better selection of tasks/tests in order to avoid biased conclusions due to inappropriate assessments; and (3) presenting new concepts regarding the development of wearable devices and mobile internet in future assessments. In conclusion we emphasize the importance of improving the assessments for non-motor symptoms because of their complex and unique mechanisms in human PD brains.


Ab initio investigation on the second-order nonlinear optical responses in keto-enol equilibria of salicylideneanilines.
The keto-enol (K-E) tautomerization equilibrium, more precisely, the keto-amine/enol-imine equilibrium, has been investigated for a series of substituted salicylideneanilines in view of designing compounds with a contrast of second-order nonlinear optical properties. Substituting the salicylidene ring by an acceptor group or the other ring by a donor prevents the K form from being stable, whereas in the other cases, the K form can easily be converted to the E form due to the small activation barrier, figuring out in most cases that the K form is metastable. For a representative set of donor/acceptor substituents, the E and K forms present a sufficiently large contrast of beta to allow its detection by using electric-field-induced second harmonic generation or hyper-Rayleigh scattering. The largest beta values are mainly associated with species bearing a donor in the para position of the salicylidene ring and an acceptor on the other ring whereas the largest beta values are generally found for the E form.


Back muscle fatigue of younger and older adults with and without chronic low back pain using two protocols: A case-control study.
The purpose of this study was to compare back muscle fatigue of younger and older participants with and without chronic low back pain (CLBP). Twenty participants without and 20 with nonspecific CLBP participated in this study. Each group contained 10 younger (50% males; mean age: 31 ± 6 yrs) and 10 older adults (50% males; age mean: 71 ± 7 yrs). Two isometric fatigue protocols were presented randomly: (1) to maintain the unsupported trunk at the horizontal position while on a 45° Roman chair for a minute, and (2) to maintain a 10% of body weight box close to the trunk in the upright position for a minute. Surface electromyography (EMG) signals from the back (multifidus and iliocostalis) and one hip (biceps femoris) muscles were recorded bilaterally, and the median frequency fatigue estimate from linear regression slopes of the EMG time-series was computed. There were no significant (P > 0.05) age effects, and group-by-age interaction in both isometric and functional fatigue tasks. However, the CLBP groups (both younger and old) displayed more back fatigue than people without CLBP in both fatigue protocols (P < 0.01; effect size varying of d = 0.17-0.32). This study was sensitive to discriminate that individuals with CLBP did present significantly more pronounced EMG back fatigue than people without CLBP, in both younger and older adults. These results have significant clinical implications for low back pain rehabilitation programs with regard to endurance assessment in both younger and older.


Relationships between self-determination theory and theory of planned behavior applied to physical activity and exercise behavior in chronic pain.
This study examined the relationships between self-determination theory (SDT) and theory of planned behavior (TpB) applied to physical activity and exercise behavior (PA&E) in people with chronic pain. Two hundred and eleven adults with chronic musculoskeletal pain (28 males and 183 females, age range 18 to 82 years, mean age 43 years) were recruited from online support groups and clinic networks in the United States. Participants completed SDT measures relevant to PA&E on perceived autonomy support, autonomy, competence, and relatedness, as well as TpB measures relevant to PA&E on intention, attitudes, subjective norms, and perceived behavioral control. Correlational techniques and canonical correlation analysis were performed to examine the relationships and variance within and between theoretical dimensions. Overall, the SDT set accounted for 37% of the TpB variance and the TpB set accounted for 32% of the SDT set variance. The results indicate there are statistical similarities and differences between concepts in SDT and TpB models for PA&E. Using both empirical guidance and clinical expertise, researchers and practitioners should attempt to select and integrate non-redundant and complementary components from SDT, TpB, and other related health behavior theories.


Neural network computation with DNA strand displacement cascades.
The impressive capabilities of the mammalian brain--ranging from perception, pattern recognition and memory formation to decision making and motor activity control--have inspired their re-creation in a wide range of artificial intelligence systems for applications such as face recognition, anomaly detection, medical diagnosis and robotic vehicle control. Yet before neuron-based brains evolved, complex biomolecular circuits provided individual cells with the 'intelligent' behaviour required for survival. However, the study of how molecules can 'think' has not produced an equal variety of computational models and applications of artificial chemical systems. Although biomolecular systems have been hypothesized to carry out neural-network-like computations in vivo and the synthesis of artificial chemical analogues has been proposed theoretically, experimental work has so far fallen short of fully implementing even a single neuron. Here, building on the richness of DNA computing and strand displacement circuitry, we show how molecular systems can exhibit autonomous brain-like behaviours. Using a simple DNA gate architecture that allows experimental scale-up of multilayer digital circuits, we systematically transform arbitrary linear threshold circuits (an artificial neural network model) into DNA strand displacement cascades that function as small neural networks. Our approach even allows us to implement a Hopfield associative memory with four fully connected artificial neurons that, after training in silico, remembers four single-stranded DNA patterns and recalls the most similar one when presented with an incomplete pattern. Our results suggest that DNA strand displacement cascades could be used to endow autonomous chemical systems with the capability of recognizing patterns of molecular events, making decisions and responding to the environment.


Idiopathic intracranial hypertension following spinal deformity surgery in children.
Idiopathic intracranial hypertension (IIH) after pediatric spinal deformity surgery has not been previously reported. The authors conducted a retrospective analysis of more than 1500 pediatric spinal surgeries performed between 1992 and 2011. From their analysis, they report on 3 adolescent patients who underwent uncomplicated segmental spinal instrumentation for pediatric spinal deformity correction and subsequently developed features of IIH. The common variables in these 3 patients were adolescent age, spinal deformity, being overweight, symptom onset within 2 weeks postoperatively, significant estimated blood loss, and intraoperative use of ε-aminocaproic acid (antifibrinolytic) injection. The authors postulate that the development of IIH could be the result of venous outflow obstruction due to derangement of the epidural venous plexus during surgery. The use of ε-aminocaproic acid could potentially have the risk of causing IIH, probably mediated through hyperfibrinogenemia, although there have not been published cases in the neurosurgical, orthopedic, cardiac, or general surgical literature. Idiopathic intracranial hypertension after spinal deformity correction is a condition that should be recognized by neurosurgeons and orthopedic surgeons, because appropriate intervention with early medical therapy can lead to a satisfactory clinical outcome.


Role of amygdala central nucleus in aversive learning produced by shock or by unexpected omission of food.
Many psychological learning theories have noted commonalities between aversive states produced by presentation of negative reinforcers, such as electric shock, and the omission of expected positive reinforcers, such as food. Here, three groups of rats received training with one auditory cue paired with shock and another with the omission of expected food, a shock-paired cue and a food-omission control cue, or a food-omission cue and a shock control cue. Food-omission cues were established by contrast with food delivery; after extensive light-food pairings, the light was followed by the food-omission cue instead of food. Aversiveness of the food-omission cue was assessed with a conditioned punishment procedure, in which presentation of that cue was made contingent on performance of one previously trained instrumental response, whereas a second response had no consequences. We found that rats with lesions of amygdala central nucleus (CeA) showed impaired acquisition of freezing to the cue paired with shock and no evidence for acquisition of aversive properties by the cue that accompanied the omission of expected food. Furthermore, analyses of Arc and Homer1a mRNAs after rats were exposed to a two-epoch test procedure that allowed assessment of gene expression produced by two different test stimuli showed that both food-omission and shock-paired cues generated more neuronal activity in CeA than appropriate control cues. However, the number of neurons that were activated by both shock and food-omission cues was not significantly greater than expected by chance. Thus, under these test conditions, different subsets of CeA neurons represented these two aversive states.


Multiple-prism grating solid-state dye laser oscillator: optimized architecture.
A multiple-prism grating solid-state dye laser oscillator was demonstrated with its grating, deployed in a Littrow configuration, under total illumination at reduced intracavity beam expansion. This compact cavity yields laser linewidths in the 350-MHz range and smooth temporal pulses with a near-Gaussian profile.


Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.
Plasma lactate has been used as a marker of poor prognosis in clinical conditions. However, the relationship between lactate production and lung function during acellular normothermic ex vivo lung perfusion (EVLP) is unclear. We investigated the kinetics of lactate metabolism during EVLP and the correlation of this marker with outcomes after transplant. Human donor lungs in our clinical EVLP trial (CLs; n = 28) and rejected donor lungs for experimental use (Els; n = 8) were perfused ex vivo using the Toronto technique. Lactate level, lactate/pyruvate (L/P) ratio, and glucose level in the perfusate were measured. In CLs, we examined the relationship between lactate metabolism during EVLP and early post-transplant outcomes. The hypoxia-inducible factor 1 sub-unit 1α (HIF-1α) level in lung tissue was examined in ELs. We performed double-lung EVLP in CLs and single-lung EVLP in ELs. In CLs, the lactate and L/P ratios at the end of EVLP had no correlation with early post-transplant outcomes despite lactate elevation during EVLP. Although lactate elevation was also present in all ELs, we were able to identify 2 groups based on L/P ratio at the end of EVLP. The group with the high L/P ratio had higher airway pressure during EVLP and higher HIF-1α in lung tissue at the end of EVLP. Lactate increases seen in the EVLP perfusate most often represent physiologic lactate production by the lung in a setting with reduced lactate clearance. Thus, patients who underwent transplantation after EVLP had good outcomes despite lactate elevation during EVLP.


Impact of the Arthritis Foundation's Walk With Ease Program on arthritis symptoms in African Americans.
Inadequate program design and lack of access to evidence-based programs are major barriers to the management of chronic diseases such as arthritis, particularly for African Americans. This study evaluates the effectiveness of the Arthritis Foundation's Walk With Ease Program (WWE) in a subsample of African Americans who were part of a larger study that established evidence of the program's efficacy. Participants were African Americans (N = 117) with self-reported arthritis who chose to participate in either a self-directed (n = 68) or group (n = 49) 6-week WWE program. Arthritis-related symptoms (ie, pain, fatigue, stiffness; measured using visual analog scales) were assessed at baseline, 6 weeks, and 1 year. Independent samples t tests were conducted to examine group differences (ie, self-directed vs group) in arthritis-related symptoms at baseline, and paired sample t tests were conducted to examine differences over time (ie, baseline to 6 weeks and baseline to 1 year) in symptoms. Satisfaction was examined by descriptive statistics. Younger, more educated individuals chose the self-directed format (P < .001, P = .008; respectively). After the 6-week intervention, participants reported a decrease in pain (P < .001), fatigue (P = .002), and stiffness (P < .001). At 1 year, the decrease in pain (P = .04) and stiffness (P = .002) remained constant. Overall, participants were satisfied with both program formats. The individualized and group formats of the WWE program improved arthritis-related pain, fatigue, and stiffness in African Americans. Culturally appealing arthritis interventions ultimately may increase the use of existing arthritis interventions.


VEGF-induced permeability increase is mediated by caveolae.
To determine the cellular route by which vascular endothelial cell growth factor (VEGF) increases the permeability of cultured retinal endothelial cells and to test whether nitric oxide (NO) production by NO synthase (NOS) is involved in signaling VEGF's permeability enhancing effects. Cultured bovine retinal microvascular endothelial (BRE) cells were used for bioassay of permeability function and its ultrastructural correlates. The role of NOS activity in VEGF's permeability enhancing effects was tested with the use of an NOS inhibitor. Because activity of endothelial NOS (eNOS) is thought to be regulated by its interaction with the caveolar protein caveolin-1, structural relationships between eNOS, caveolin-1, and the VEGF receptor FIk-1/KDR were analyzed with double-label immunofluorescence and cell fractionation procedures. Bioassays of permeability function and structure demonstrated that VEGF increases permeability of cultured BRE cells by an NOS-dependent process of transcytotic transport in caveolae. Double-label analysis showed that Flk-1/KDR and eNOS colocalize with caveolin-1 in plasma membrane caveolae. Cell fractionation and immunoblot analysis confirmed this effect. Densitometry showed that Flk-1/KDR, eNOS, and caveolin-1 levels were highest in caveolar fractions. Similar results were obtained in studies with bovine aortic endothelial cells. These results demonstrate that VEGF increases endothelial cell permeability by an eNOS-dependent mechanism of transcytosis in caveolae. Localization of Flk-1/KDR and eNOS with caveolin-1 suggests that VEGF signaling occurs within the caveolar compartment.


Relationship between structure and fatty acid metabolism in mitochondria isolated from ischemic rat hearts.
We studied mitochondrial structure and intermediates of fatty acid metabolism in mitochondria isolated from ischemic hearts. By electron microscopy, no structural difference was detected between mitochondria isolated from control hearts and from ischemic hearts receiving glucose as the only substrate. However, major differences were observed in mitochondria obtained from control and ischemic hearts receiving both glucose and palmitate. These hearts contained a higher portion of damaged mitochondria. However, measurements of marker enzyme activities failed to show that more mitochondria were lost during the isolation procedure in ischemic than in control hearts. Many densely staining areas (or amorphous densities) were observed in the isolated mitochondria of ischemic hearts. These amorphous densities have an appearance similar to that observed in the intact ischemic heart under the same perfusion conditions. Levels of long-chain acyl-CoA in mitochondria isolated from hearts receiving glucose alone were practically the same for control and ischemic hearts and were only slightly increased in mitochondria of ischemic hearts receiving both glucose and palmitate. On the other hand, levels of long-chain acyl carnitine in mitochondria of ischemic hearts were twice those found in control hearts. The mitochondrial level of long-chain acyl carnitine was approximately four times higher in the ischemic hearts receiving palmitate compared to those receiving no palmitate. This rise in long-chain acyl carnitine levels in mitochondria isolated fom ischemic hearts receiving palmitate may be related to modifications of the mitochondrial structure and to the appearance of amorphous densities.


Test your knowledge: pharmacology.
The CRNI Certification Examination consists of 200 multiple-choice questions covering the nine core content areas of infusion nursing: Technology and Clinical Applications, Fluid and Electrolyte Balance, Pharmacology, Infection Control, Pediatrics, Transfusion Therapy, Antineoplastic Therapy, Parenteral Nutrition, and Quality Assurance. The review questions provided below are modeled on the CRNI exam and are intended to help exam candidates test their knowledge of infusion therapy practice. This special section is a regular addition to the Journal of Infusion Nursing, with each edition focusing on a single content area.


Monoclonal antibody analysis of specific antigenic similarities among pathogenic Treponema pallidum subspecies.
Murine monoclonal antibodies directed against a 47,000-dalton immunodominant surface-exposed antigen of Treponema pallidum subsp. pallidum (Nichols) were isolated. These monoclonal antibodies cross-reacted with analogous 47,000-dalton antigens of two other virulent treponemes, T. pallidum subsp. pertenue and T. pallidum subsp. endemicum (Bosnia A), as determined by radioimmunoassay and immunoblot analyses. Immunoelectron microscopy confirmed that the 47,000-dalton antigen of T. pallidum subsp. pallidum was a surface-associated cellular component. Surface binding assays and immunoelectron microscopic studies also suggested that the analogous 47,000-dalton antigenic component of T. pallidum subsp. pertenue may not have been oriented toward the bacterial surface in the same way as the T. pallidum subsp. pallidum antigen or that the relevant antigenic determinant(s) may not have been exposed to the outer surface in the same way. The significance of this antigen relative to its apparent conservation among pathogenic treponemes and its possible diagnostic and vaccinogenic potentials are discussed.


Tobacco Control and Treatment for the Pediatric Clinician: Practice, Policy, and Research Updates.
Tobacco use is the leading cause of preventable death in the United States, and exposure to tobacco smoke harms children from conception forward. There is no safe level of tobacco exposure. Although overall smoking rates have declined, the advent of new products, such as electronic cigarettes, threatens to perpetuate nicotine addiction without clear health benefits. In addition to reviewing traditional and new tobacco products, we discuss the unique role that pediatricians should play in tobacco treatment and control efforts. New policies and technologies can empower pediatric clinicians and pediatric health care systems to help parent smokers quit, and new policies outside of the health care setting might help prevent smoking initiation as well as improve cessation treatments. Future research is needed to continue to study the consequences of tobacco use exposure as well as the best ways to help patients and parents stop tobacco use.


Dynamics of the forest communities at Pasoh and Barro Colorado: comparing two 50-ha plots.
Dynamics of the Pasoh forest in Peninsular Malaysia were assessed by drawing a comparison with a forest in Panama, Central America, whose dynamics have been thoroughly described. Census plots of 50 ha were established at both sites using standard methods. Tree mortality at Pasoh over an eight-year interval was 1.46% yr(-1) for all stems > or = 10 mm diameter at breast height (dbh), and 1.48% yr(-1) for stems > or = 100 mm dbh. Comparable figures at the Barro Colorado Island site in Panama (BCI) were 2.55% and 2.03%. Growth and recruitment rates were likewise considerably higher at BCI than at Pasoh. For example, in all trees 500-700 mm in dbh, mean BCI growth over the period 1985-1995 was 6 mm yr(-1), whereas mean Pasoh growth was about 3.5 mm yr(-1). Examining growth and mortality rates for individual species showed that the difference between the forests can be attributed to a few light-demanding pioneer species at BCI, which have very high growth and mortality; Pasoh is essentially lacking this guild. The bulk of the species in the two forests are shade-tolerant and have very similar mortality, growth and recruitment. The Pasoh forest is more stable than BCI's in another way as well: few of its tree populations changed much over the eight-year census interval. In contrast, at BCI, over 10% of the species had populations increasing or decreasing at a rate of >0.05 yr(-1) compared to just 2% of the species at Pasoh). The faster species turnover at BCI can probably be attributed to severe droughts that have plagued the forest periodically over the past 30 years; Pasoh has not suffered such extreme events recently. The dearth of pioneer species at Pasoh is associated with low-nutrient soil and slow litter breakdown, but the exact mechanisms behind this association remain poorly understood.


Inhibition of growth factor effects in retinal pigment epithelial cells.
Several agents were examined for their effect on growth factor-stimulated processes in retinal pigment epithelial (RPE) cells. DNA synthesis was assessed by 3H-thymidine incorporation in density-arrested cells using previously determined maximally effective concentrations of various growth factors with and without test substances. Cell migration was assessed in Boyden chamber assays. For each test substance, trypan blue exclusion was used to determine noncytotoxic concentrations, and the effect of several concentrations were assessed on selected growth factors. The most effective, nontoxic concentration was then used for comparisons. Two cationic proteins, protamine and histone type II B, caused inhibition of RPE chemotaxis and 3H-thymidine incorporation induced by several growth factors, but a cationic polypeptide, polylysine, did not. Protamine and histone, were particularly effective inhibitors of acidic and basic fibroblast growth factors (FGF) but not if they were exposed to cells and then removed before growth factor addition. They had no effect on serum-stimulated chemotaxis or 3H-thymidine incorporation even when used in the presence of serum. Three anionic substances, heparin, pentosan polysulfate, and suramin, also inhibited RPE chemotaxis and 3H-thymidine incorporation induced by several different growth factors. They were less effective inhibitors of the FGFs than protamine and histone but were better inhibitors of serum-induced effects. Also unlike protamine and histone, the anionic substances maintained their inhibitory effect even when removed before growth factor addition. Since migration and proliferation of RPE cells are important processes in the pathogenesis of proliferative vitreoretinopathy, these agents and their mechanism of action deserve further study for potential therapeutic applications.


Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue.
Growing evidence supports the role of gut microbiota in the development of obesity, type 2 diabetes, and low-grade inflammation. The endocrine activity of adipose tissue has been found to contribute to the regulation of glucose homeostasis and low-grade inflammation. Among the key hormones produced by this tissue, apelin has been shown to regulate glucose homeostasis. Recently, it has been proposed that gut microbiota participate in adipose tissue metabolism via the endocannabinoid system (eCB) and gut microbiota-derived compounds, namely lipopolysaccharide (LPS). We have investigated gut microbiota composition in obese and diabetic leptin-resistant mice (db/db) by combining pyrosequencing and phylogenetic microarray analysis of 16S ribosomal RNA gene sequences. We observed a significant higher abundance of Firmicutes, Proteobacteria, and Fibrobacteres phyla in db/db mice compared to lean mice. The abundance of 10 genera was significantly affected by the genotype. We identified the roles of the eCB and LPS in the regulation of apelinergic system tone (apelin and APJ mRNA expression) in genetic obese and diabetic mice. By using in vivo and in vitro models, we have demonstrated that both the eCB and low-grade inflammation differentially regulate apelin and APJ mRNA expression in adipose tissue. Finally, deep-gut microbiota profiling revealed that the gut microbial community of type 2 diabetic mice is significantly different from that of their lean counterparts. This indicates specific relationships between the gut microbiota and the regulation of the apelinergic system. However, the exact roles of specific bacteria in shaping the phenotype of db/db mice remain to be determined.


Effect of age on adult stereoacuity as measured by different types of stereotest.
To examine how stereoacuity changes with age as measured by a variety of stereotests. Stereoacuity has been measured in 60 normal subjects aged 17-83 years by a single observer using TNO, Titmus, Frisby near, and Frisby-Davis distance stereotests. Motor fusion was measured at (1/3) metre and 6 metres. Overall stereoacuity measured by all tests showed a mild decline with age (p<0.001 for all tests; Spearman rank correlation). A marked reduction to screening or absent levels of stereoacuity was seen in five subjects aged over 55, but only with the TNO stereotest. All these subjects were able to achieve a stereoacuity of 200 seconds of arc or better with the Titmus test and 340 seconds of arc or better using the Frisby near stereotest. There was a small decline with age in the base out motor fusion range measured at 6 metres (p<0.05; Spearman rank correlation). No subject described difficulty in judging distances for everyday tasks. Although subjects showed some decline in stereoacuity with age by all tests, the large drop in stereoacuity seen in some older subjects using the TNO test was probably due to difficulty overcoming the dissociative effect of the test rather than a true reduction in cortical disparity detection. Results of random dot stereotests should be interpreted with caution in older patients, particularly with respect to their ability to perform everyday visual tasks.


Endothelial progenitor cells: hope beyond controversy.
The capacity to induce new blood vessel formation or to repair damaged vessels is an attractive idea that has, for a long time, captured the attention and imagination of researchers. Beside the identification of the pro-angiogenic growth factors and their counterpart inhibitors, the discovery of endothelial progenitor cells (EPC) in adults and their putative vascular-promoting and/or vascular-healing properties, has generated some of the biggest fascination and debate in the broad field of vascular biology. The simple concept of a population of undifferentiated cells being able to generate new endothelial cells and the corresponding blood vessels in adults is both intriguing and, as seen in the last 10 years, controversial. Academic rivalry or pure scientific dispute has accompanied the research on EPC for some time. The major issues put forward by opposing groups of scientists regarding the identity and the role of EPCs as well as the optimal isolation and detection techniques are discussed in this review. The clinical relevance of EPCs and their potential applications in cancer treatments are also highlighted.


Review of withdrawal catatonia: what does this reveal about clozapine?
Withdrawal symptoms are common upon discontinuation of psychiatric medications. Catatonia, a neuropsychiatric condition proposed to be associated with gamma-aminobutyric acid (GABA) hypoactivity due to its robust response to benzodiazepines, has been described as a withdrawal syndrome in case reports but is not a well-recognized phenomenon. The authors undertook a review of withdrawal catatonia with an aim to understand its presentation as well as the medications and psychoactive substances it is associated with. The review identified 55 cases of withdrawal catatonia, the majority of which occurred upon discontinuation of benzodiazepines (24 cases) and discontinuation of clozapine (20 cases). No other antipsychotic medications were identified as having been associated with the onset of a catatonic episode within 2 weeks following their discontinuation. Increasing GABA activity and resultant GABA receptor adaptations with prolonged use is postulated as a shared pharmacological mechanism between clozapine and benzodiazepines that underlie their association with withdrawal catatonia. The existing evidence for clozapine's activity on the GABA system is reviewed. The clinical presentations of benzodiazepine withdrawal catatonia and clozapine withdrawal catatonia appear to differ and reasons for this are explored. One reason is that benzodiazepines act directly on GABAA receptors as allosteric agonists, while clozapine has more complex and indirect interactions, primarily through effects on receptors located on GABA interneurons. Another possible reason for the difference in clinical presentation is that clozapine withdrawal catatonia may also involve receptor adaptations in non-GABA receptors such as dopamine and acetylcholine. The findings from our review have implications for the treatment of withdrawal catatonia, and treatment recommendations are provided. Further research understanding the uniqueness of clozapine withdrawal catatonia among antipsychotic medication may give some insight as to clozapine's differential mechanism of action.


What's the impact of quality bundles at the bedside?
Managing quality bundles can be challenging for clinical nurses. A study was undertaken to examine quality bundle volumes by patient and nursing perceptions in managing those volumes. Quantitative and qualitative data were collected from more than 400 patients and their clinical nurses in five hospitals to provide insight into bedside complexities related to quality bundles. Patients were assigned up to six bundles; critical care patients had the most bundle assignments. Nurses (N = 180) responded to a three-item survey about managing quality bundles. Although 39% of the respondents said they were always aware of the nursing interventions, only 16% responded that they could always complete them. Strategies to effectively implement quality interventions are critical to nursing workflow and, ultimately, patient care. Workflow assessments, embedded reminders, checklists, and improved data transparency at the bedside are needed to improve quality bundle compliance.


Screening for Otologic Functional Impairments in the Elderly: Whose Job is it Anyway?
Among the most prevalent of chronic conditions affecting older adults globally, hearing loss prevalence is increasing and its impact on society growing. Untreated hearing loss diminishes ones ability to communicate and its strong association with depression and cognitive decline adds further to the burden of hearing loss. Hearing health care is rarely included in the traditional medical exam for older adults, it is typically not considered a risk factor for cognitive decline or falls, and it is not a condition for which routine screening has been recommended by the U.S. Preventive Services Task Force. Yet in older adults, disability typically results from many small risks acting together with different people having a different pattern of multifactorial risk (U.S. Preventive Services Task Force, 2010). The importance of preventive hearing health care in primary care is discussed along with a screening strategy with targeted interventions designed to target older at risk adults.


Hox genes and the evolution of the arthropod body plan.
In recent years researchers have analyzed the expression patterns of the Hox genes in a multitude of arthropod species, with the hope of understanding the mechanisms at work in the evolution of the arthropod body plan. Now, with Hox expression data representing all four major groups of arthropods (chelicerates, myriapods, crustaceans, and insects), it seems appropriate to summarize the results and take stock of what has been learned. In this review we summarize the expression and functional data regarding the 10 arthropod Hox genes: labial proboscipedia, Hox3/zen, Deformed, Sex combs reduced, fushi tarazu, Antennapedia, Ultrabithorax, abdominal-A, and Abdominal-B. In addition, we discuss mechanisms of developmental evolutionary change thought to be important for the emergence of novel morphological features within the arthropods.


Activation of c-MET induces a stem-like phenotype in human prostate cancer.
Prostate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model) or represent an inducible population emerging upon appropriate stimulation of differentiated cells. Hepatocyte Growth Factor (HGF) receptor c-MET is specifically expressed in immature prostate cells. Our objective is to determine the role of immature cells in prostate cancer by analysis of the HGF/c-MET pathway.Gene-expression profiling of DU145 prostate cancer cells stimulated with HGF revealed induction of a molecular signature associated with stem cells, characterized by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 ('stem-like signature'). We confirmed the acquisition of a stem-like phenotype by quantitative PCR, FACS analysis and Western blotting. Further, HGF led to activation of the stem cell related Notch pathway by up-regulation of its ligands Jagged-1 and Delta-like 4. Small molecules SU11274 and PHA665752 targeting c-MET activity were both able to block the molecular and biologic effects of HGF. Knock-down of c-MET by shRNA infection resulted in significant reduction and delay of orthotopic tumour-formation in male NMRI mice. Immunohistochemical analysis in prostatectomies revealed significant enrichment of c-MET positive cells at the invasive front, and demonstrated co-expression of c-MET with stem-like markers CD49b and CD49f.In conclusion, activation of c-MET in prostate cancer cells induced a stem-like phenotype, indicating a dynamic relation between differentiated and stem-like cells in this malignancy. Its mediation of efficient tumour-formation in vivo and predominant receptor expression at the invasive front implicate that c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype.


Study protocol for Young & Strong: a cluster randomized design to increase attention to unique issues faced by young women with newly diagnosed breast cancer.
Each year, approximately 11% of women diagnosed with breast cancer in the United States are 45 years of age or younger. These women have concerns specific to or accentuated by their age, including fertility-related concerns, and have higher rates of psychosocial distress than women diagnosed at older ages. Current guidelines recommend that fertility risks be considered early in all treatment plans; however, the extant research indicates that attention to fertility by the healthcare team is limited. Importantly, attention to fertility may be a proxy for whether or not other important issues warranting attention in younger women with breast cancer are addressed, including genetic risks, psychosocial distress, sexual functioning, and body image concerns. The Young & Strong study tests the efficacy of an intervention designed for young women recently diagnosed with breast cancer and their oncologists with the intention to: 1) increase attention to fertility as an important surrogate for other issues facing young women, 2) educate and support young women and their providers, and 3) reduce psychosocial distress among young women with breast cancer. The study employs a cluster randomized design including 14 academic institutions and 40 community sites across the U.S. assigned to either the study intervention arm or contact-time comparison intervention arm. Academic institutions enroll up to 15 patients per site while community sites enroll up to 10 patients. Patient eligibility requirements include: an initial diagnosis of stage I-III invasive breast cancer within three months prior, without a known recurrence or metastatic breast cancer; 18-45 years of age at diagnosis; ability to read and write in English. The primary outcome is oncologists' attention to fertility concerns as determined by medical record review. Secondary outcomes include differences in patient satisfaction with care and psychosocial distress between the two study arms. Study findings will provide valuable insight into how to increase attention to fertility and other issues specific to young women with breast cancer and how to improve doctor-patient communication around these issues, which may promote better quality of care for this population. NCT01647607. Registered July 19, 2012.


Functional Foods as Modifiers of Cardiovascular Disease.
There is growing consensus that systemic inflammation is at the heart of cardiovascular disease (CVD). Inflammation is a key feature of the immune system, functioning to defend tissue integrity and function. However, chronic stimulation of inflammatory mediators leads to lasting vascular reactivity, insulin resistance, hyperlipidemia, and, subsequently, chronic disease. Dietary practices to minimize inflammatory stimuli and CVD risk include regular intakes of fatty fish rich in the eicosapentaenoic and docosahexaenoic acids that compete with the more pervasive membrane fatty acid, arachidonic acid, disrupting the metabolic cascades that stimulate inflammation. Another effective dietary strategy is to consume less arachidonic acid by reducing beef, poultry, fish, and eggs from the diet (e.g., adopting a vegetarian-like diet). Since oxidative stress plays a prominent role in immune system activation, regular ingestion of ample amounts of fruits and vegetables (8+ servings/d) rich in antioxidant compounds, the polyphenols, carotenoids, and vitamin C (e.g., citrus, tomatoes, berries, carrots, and greens), lowers inflammatory mediators and risk for chronic disease. Whole grains, legumes, and nuts have also been demonstrated in clinical trials to effectively reduce inflammatory mediators and risk for CVD. Hence, as proclaimed in antiquity, 'let food be thy medicine and medicine be thy food'.


Energy-efficient sensing in wireless sensor networks using compressed sensing.
Sensing of the application environment is the main purpose of a wireless sensor network. Most existing energy management strategies and compression techniques assume that the sensing operation consumes significantly less energy than radio transmission and reception. This assumption does not hold in a number of practical applications. Sensing energy consumption in these applications may be comparable to, or even greater than, that of the radio. In this work, we support this claim by a quantitative analysis of the main operational energy costs of popular sensors, radios and sensor motes. In light of the importance of sensing level energy costs, especially for power hungry sensors, we consider compressed sensing and distributed compressed sensing as potential approaches to provide energy efficient sensing in wireless sensor networks. Numerical experiments investigating the effectiveness of compressed sensing and distributed compressed sensing using real datasets show their potential for efficient utilization of sensing and overall energy costs in wireless sensor networks. It is shown that, for some applications, compressed sensing and distributed compressed sensing can provide greater energy efficiency than transform coding and model-based adaptive sensing in wireless sensor networks.


Measuring effects of music, noise, and healing energy using a seed germination bioassay.
To measure biologic effects of music, noise, and healing energy without human preferences or placebo effects using seed germination as an objective biomarker. A series of five experiments were performed utilizing okra and zucchini seeds germinated in acoustically shielded, thermally insulated, dark, humid growth chambers. Conditions compared were an untreated control, musical sound, pink noise, and healing energy. Healing energy was administered for 15-20 minutes every 12 hours with the intention that the treated seeds would germinate faster than the untreated seeds. The objective marker was the number of seeds sprouted out of groups of 25 seeds counted at 12-hour intervals over a 72-hour growing period. Temperature and relative humidity were monitored every 15 minutes inside the seed germination containers. A total of 14 trials were run testing a total of 4600 seeds. Musical sound had a highly statistically significant effect on the number of seeds sprouted compared to the untreated control over all five experiments for the main condition (p < 0.002) and over time (p < 0.000002). This effect was independent of temperature, seed type, position in room, specific petri dish, and person doing the scoring. Musical sound had a significant effect compared to noise and an untreated control as a function of time (p < 0.03) while there was no significant difference between seeds exposed to noise and an untreated control. Healing energy also had a significant effect compared to an untreated control (main condition, p < 0.0006) and over time (p < 0.0001) with a magnitude of effect comparable to that of musical sound. This study suggests that sound vibrations (music and noise) as well as biofields (bioelectromagnetic and healing intention) both directly affect living biologic systems, and that a seed germination bioassay has the sensitivity to enable detection of effects caused by various applied energetic conditions.


The Food Marketing Institute and the National Council of Chain Restaurants: animal welfare and the retail food industry in the United States of America.
In order to achieve real change, there must be a motivating force and all the stakeholders need to be involved. This is the premise of the animal welfare programme developed for the food retail, wholesale and chain restaurant industries in the United States of America (USA) by the Food Marketing Institute (FMI) and the National Council of Chain Restaurants (NCCR). This paper outlines a collaborative process that retailers and producers in the USA are using to enhance the care and welfare of animals in commercial food production. Although the efforts of the FMI and the NCCR are still underway, the process provides one example of how different parts of the food production system can work together to achieve positive change.


Expression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954.
Expression of the Escherichia coli enzyme nitroreductase (NTR) in mammalian cells enables them to activate the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), leading to interstrand DNA cross-linking and apoptosis in both proliferating and quiescent cells. In the work reported here, we used human hepatocellular carcinoma and squamous carcinoma cell lines constitutively expressing NTR to demonstrate that the ntr/CB1954 system results in potent, long-lasting antitumoral effects in mice. We also demonstrate that this enzyme/prodrug combination results in antitumoral effects in vivo when only a minority of tumor cells express the enzyme, using either cells constitutively expressing NTR or ntr gene delivery in situ.


Analysis of risk factors for low bone mineral density in inflammatory bowel disease.
Several risk factors have been suggested for osteoporosis which frequently occurs in inflammatory bowel disease (IBD) patients. We studied prevalence and risk factors for reduced bone mineral density (BMD) in IBD patients at the University Hospital of Zurich, Switzerland. The BMD was determined by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck in 88 IBD patients (55 with Crohn's disease, 30 with ulcerative colitis, and 3 with indeterminate colitis). Z scores were obtained by comparison with age- and sex-matched normal values, and T scores by comparison with sex-matched healthy young adults. Osteopenia and osteoporosis were defined according to the WHO guidelines. Predictive factors for BMD were analyzed by group comparison and stepwise regression analysis. Osteopenia was present in 43% of the patients at the lumbar spine and in 42% of them at the femoral neck. Osteoporosis was present in 14% of the patients at the lumbar spine and in 5% of them at the femoral neck. At the lumbar spine, stepwise regression analysis showed that body mass index, age, number of bowel resections, topic steroids, and azathioprine correlated with the Z scores. Cumulative steroid dose, topic steroids, age and bowel resection were found to be predictors for a pathological T score. At the femoral neck, regression analysis showed that body mass index, age, topic steroids, and azathioprine correlated with the Z scores. Only a low body mass index was a significant predictor for pathological femoral T scores. Osteopenia and osteoporosis are commonly found in IBD patients. Steroid treatment and bowel resection were significant risk factors for osteoporosis of the lumbar spine. However, disease-inherent factors also appear to confer a major risk, indicating that the BMD should be determined in all IBD patients, irrespective of steroid treatment.


Consensus statement for standard of care in spinal muscular atrophy.
Spinal muscular atrophy is a neurodegenerative disease that requires multidisciplinary medical care. Recent progress in the understanding of molecular pathogenesis of spinal muscular atrophy and advances in medical technology have not been matched by similar developments in the care for spinal muscular atrophy patients. Variations in medical practice coupled with differences in family resources and values have resulted in variable clinical outcomes that are likely to compromise valid measure of treatment effects during clinical trials. The International Standard of Care Committee for Spinal Muscular Atrophy was formed in 2005, with a goal of establishing practice guidelines for clinical care of these patients. The 12 core committee members worked with more than 60 spinal muscular atrophy experts in the field through conference calls, e-mail communications, a Delphi survey, and 2 in-person meetings to achieve consensus on 5 care areas: diagnostic/new interventions, pulmonary, gastrointestinal/nutrition, orthopedics/rehabilitation, and palliative care. Consensus was achieved on several topics related to common medical problems in spinal muscular atrophy, diagnostic strategies, recommendations for assessment and monitoring, and therapeutic interventions in each care area. A consensus statement was drafted to address the 5 care areas according to 3 functional levels of the patients: nonsitter, sitter, and walker. The committee also identified several medical practices lacking consensus and warranting further investigation. It is the authors' intention that this document be used as a guideline, not as a practice standard for their care. A practice standard for spinal muscular atrophy is urgently needed to help with the multidisciplinary care of these patients.


Advances in treatment of bacterial meningitis.
Bacterial meningitis kills or maims about a fifth of people with the disease. Early antibiotic treatment improves outcomes, but the effectiveness of widely available antibiotics is threatened by global emergence of multidrug-resistant bacteria. New antibiotics, such as fluoroquinolones, could have a role in these circumstances, but clinical data to support this notion are scarce. Additionally, whether or not adjunctive anti-inflammatory therapies (eg, dexamethasone) improve outcomes in patients with bacterial meningitis remains controversial; in resource-poor regions, where the disease burden is highest, dexamethasone is ineffective. Other adjunctive therapeutic strategies, such as glycerol, paracetamol, and induction of hypothermia, are being tested further. Therefore, bacterial meningitis is a substantial and evolving therapeutic challenge. We review this challenge, with a focus on strategies to optimise antibiotic efficacy in view of increasingly drug-resistant bacteria, and discuss the role of current and future adjunctive therapies.