Prospective assessment of patient morbidity from prone sacral positioning.
Sacrectomy positioning must balance surgical exposure, localization, associated operative procedures, and patient safety. Poor positioning may increase hemorrhage, risk of blindness, and skin breakdown. The authors prospectively identified positioning-related morbidity in 17 patients undergoing 19 prone sacral procedures from September 2008 to August 2009 following institution of a standardized positioning protocol. Key elements include skull traction/head suspension, an open radiolucent frame, and wide draping for associated closure and reconstructive procedures. Tumors included 5 chordomas, 4 high-grade sarcomas, 1 chondrosarcoma, 2 presacral extradural myxopapillary ependymomas, and 5 others. Mean patient age was 49.9 years (range 17-74 years); mean body mass index was 27.6 kg/m(2) (range 19.3-43.9 kg/m(2)). Mean preoperative Braden skin integrity score was 21.1 (range 17-23). Average operative time was 501 minutes (range 158-1136 minutes). Prone surgery was a part of staged anterior/posterior resections in 8 patients. Localization was conducted using fluoroscopy in 13 patients and intraoperative CT in 4 patients. All imaging studies were successful. One patient developed a transient ulnar nerve palsy attributed to positioning. Three patients (two of whom were morbidly obese) developed Stage I pressure injuries to the chest and another developed Stage II pressure injury following a 1136-minute procedure. Morbidity was only observed in patients with morbid obesity or with procedures lasting in excess of 10 hours. A positioning protocol using head suspension on an open radiolucent frame facilitates oncological sacral surgery with reasonable patient morbidity. Morbid obesity and procedure times in excess of 10 hours are risk factors for positioning-related complications. To the authors' knowledge, this is the first report of surgical positioning morbidity in this patient population.


The role of liver X receptor-alpha in the fatty acid regulation of hepatic gene expression.
Liver X receptors (LXR) alpha and beta play an important role in regulating the expression of genes involved in hepatic bile and fatty acid synthesis, glucose metabolism, as well as sterol efflux. Studies with human embryonic kidney 293 cells indicate that unsaturated fatty acids interfere with oxysterols binding to LXR and antagonize oxysterol-induced LXRalpha activity. In this report, we evaluated the effects of unsaturated fatty acids on LXR-regulated hepatic gene expression. The LXR agonist, T1317, induced mRNAs encoding sterol regulatory element-binding protein 1c (SREBP-1c) and two SREBP-1c-regulated lipogenic genes, e.g. fatty-acid synthase and the S14 protein in primary hepatocytes. Treatment of hepatocytes with eicosapentaenoic acid (20:5n-3) suppressed these mRNAs in the absence and presence of T1317. The cis-regulatory elements targeted by T1317 were not required for fatty-acid suppression of FAS or S14 promoter activity. In contrast to SREBP-1-regulated lipogenic genes, 20:5n-3 had no effect on the T1317 induction of ABCG5 or ABCG8 in the rat hepatoma cell line, FTO-2B. These two genes require LXR but not SREBP-1c for their expression. Feeding rats a diet supplemented with fish oil suppressed hepatic SREBP-1c-regulated genes and induced PPARalpha-regulated genes but had no effect on the LXR-regulated transcripts, CYP7A1, ABCG5, or ABCG8. Transfection studies, using either full-length hLXRalpha or a chimera containing only the LXRalpha ligand binding domain, indicate that a wide array of unsaturated fatty acids had little effect on LXRalpha activity in primary hepatocytes or FTO-2B. These studies suggest that LXRalpha is not a target for unsaturated fatty acid regulation in primary rat hepatocytes or in liver. Thus, oxysterol/LXR-mediated regulation of transcripts involved in bile acid synthesis or sterol efflux appear insensitive to dietary unsaturated fatty acids. The unsaturated fatty acid suppression of SREBP-1 and its targeted lipogenic genes is independent of LXRalpha


LADAR detection statistics in the presence of pointing errors.
The probability of detection of optically rough targets with pulsed LADAR systems that use direct detection is considered. It is assumed that the LADAR operates under conditions of both unintentional pointing offset bias (i.e., bore-sight error) andjitter. Under these conditions the probabilities of detection of targets in both the near field and the far field of the collecting aperture (i.e., for resolved, partially resolved, and unresolved targets) and for both large and small photoelectron counts are derived, and in many cases of practical interest accurate, elementary analytic approximations that are useful for parametric system studies are obtained. A number of technical references are appended, in which some of the key results are derived. In particular, an interesting new mathematical result involving the complementary incomplete gamma function and an analytic expression for the probability distribution function of a signal photoelectron count obeying BoseEinstein statistics (such as that arising from unresolved targets) immersed in Poisson noise is derived.


Platforms and Analytical Tools Used in Nucleic Acid Sequence-Based Microbial Genotyping Procedures.
In the decade and a half since the introduction of next-generation sequencing (NGS), the technical feasibility, cost, and overall utility of sequencing have changed dramatically, including applications for infectious disease epidemiology. Massively parallel sequencing technologies have decreased the cost of sequencing by more than 6 orders or magnitude over this time, with a corresponding increase in data generation and complexity. This review provides an overview of the basic principles, chemistry, and operational mechanics of current sequencing technologies, including both conventional Sanger and NGS approaches. As the generation of large amounts of sequence data becomes increasingly routine, the role of bioinformatics in data analysis and reporting becomes all the more critical, and the successful deployment of NGS in public health settings requires careful consideration of changing information technology, bioinformatics, workforce, and regulatory requirements. While there remain important challenges to the sustainable implementation of NGS in public health, in terms of both laboratory and bioinformatics capacity, the impact of these technologies on infectious disease surveillance and outbreak investigations has been nothing short of revolutionary. Understanding the important role that NGS plays in modern public health laboratory practice is critical, as is the need to ensure appropriate workforce, infrastructure, facilities, and funding consideration for routine NGS applications, future innovation, and rapidly scaling NGS-based infectious disease surveillance and outbreak response activities. *This article is part of a curated collection.


Treatment strategies for hydrocephalus related to Dandy-Walker syndrome: evaluating procedure selection and success within the Hydrocephalus Clinical Research Network.
Treating Dandy-Walker syndrome-related hydrocephalus (DWSH) involves either a CSF shunt-based or endoscopic third ventriculostomy (ETV)-based procedure. However, comparative investigations are lacking. This study aimed to compare shunt-based and ETV-based treatment strategies utilizing archival data from the Hydrocephalus Clinical Research Network (HCRN) registry. A retrospective review of prospectively collected and maintained data on children with DWSH, available from the HCRN registry (14 sites, 2008-2018), was performed. The primary outcome was revision-free survival of the initial surgical intervention. The primary exposure was either shunt-based (i.e., cystoperitoneal shunt [CPS], ventriculoperitoneal shunt [VPS], and/or dual-compartment) or ETV-based (i.e., ETV alone or with choroid plexus cauterization [CPC]) initial surgical treatment. Primary analysis included multivariable Cox proportional hazards models. Of 8400 HCRN patients, 151 (1.8%) had DWSH. Among these, the 102 patients who underwent shunt placement (79 VPSs, 16 CPSs, 3 other, and 4 multiple proximal catheter) were younger (6.6 vs 18.8 months, p < 0.001) and more frequently had 1 or more comorbidities (37.3% vs 14.3%, p = 0.005) than the 49 ETV-treated children (28 ETV-CPC). Fifty percent of the shunt-based and 51% of the ETV-based treatments failed. Notably, 100% (4/4) of the dual-compartment shunts failed. Adjusting for age, baseline ventricular size, and comorbidities, ETV-based treatment was not significantly associated with earlier failure compared with shunt-based treatment (HR for failure 1.32, 95% CI 0.77-2.26; p = 0.321). Complication rates were low: 4.9% and 6.1% (p = 0.715) for shunt- and ETV-based procedures, respectively. There was no difference in survival between ETV-CPC- and ETV-based treatment when adjusting for age (HR for failure 0.86, 95% CI 0.29-2.55, p = 0.783). In this North American, multicenter, prospective database review, shunt-based and ETV-based primary treatment strategies of DWSH appear similarly durable. Pediatric neurosurgeons can reasonably consider ETV-based initial treatment given the similar durability and the low complication rate. However, given the observational nature of this study, the treating surgeon might need to consider subgroups that were too small for a separate analysis. Very young children with comorbidities were more commonly treated with shunts, and older children with fewer comorbidities were offered ETV-based treatment. Future studies may determine preoperative characteristics associated with ETV treatment success in this population.


Cardiac transplantation in children and adolescents.
Cardiac transplantation represents an expanding therapeutic modality for end-stage heart disease in children and adolescents. During the past 5 years, 27 patients (15 boys; 12 girls) between the ages of 2 and 18 have undergone cardiac transplantation. The preoperative diagnosis was cardiomyopathy in 24 (six familial), congenital heart disease in two, and endocardial fibroelastosis in one. Immunosuppression included cyclosporine, azathioprine, and prednisone. There were 22 survivors, with four hospital deaths (three infection, one pulmonary hypertension), and one death at 4.5 years from graft atherosclerosis. The actuarial survival at 4 years was 83 +/- 7.4% and that at 5 years was 69 +/- 14.2%. Renal function was stable at 4 years, with an average creatinine clearance of 69.75 +/- 27.0 ml/min/m2. Hypertension was present in 21 of 22 patients, who require multiple drug therapy. Rehabilitation is 100% among discharged patients, with 14 in school, six employed, and two toddlers.


Outage Probability of MRC for κ-μ Shadowed Fading Channels under Co-Channel Interference.
In this paper, exact closed-form expressions are derived for the outage probability (OP) of the maximal ratio combining (MRC) scheme in the κ-μ shadowed fading channels, in which both the independent and correlated shadowing components are considered. The scenario assumes the received desired signals are corrupted by the independent Rayleigh-faded co-channel interference (CCI) and background white Gaussian noise. To this end, first, the probability density function (PDF) of the κ-μ shadowed fading distribution is obtained in the form of a power series. Then the incomplete generalized moment-generating function (IG-MGF) of the received signal-to-interference-plus-noise ratio (SINR) is derived in the closed form. By using the IG-MGF results, closed-form expressions for the OP of MRC scheme are obtained over the κ-μ shadowed fading channels. Simulation results are included to validate the correctness of the analytical derivations. These new statistical results can be applied to the modeling and analysis of several wireless communication systems, such as body centric communications.


Impact of Discharge Components on Readmission Rates for Children Hospitalized with Asthma.
To describe hospital-based asthma-specific discharge components at children's hospitals and determine the association of these discharge components with pediatric asthma readmission rates. This is a multicenter retrospective cohort study of pediatric asthma hospitalizations in 2015 at children's hospitals participating in the Pediatric Health Information System. Children ages 5 to 17 years were included. An electronic survey assessing 13 asthma-specific discharge components was sent to quality leaders at all 49 hospitals. Correlations of combinations of asthma-specific discharge components and adjusted readmission rates were calculated. The survey response rate was 92% (45 of 49 hospitals). Thirty-day and 3-month adjusted readmission rates varied across hospitals, ranging from 1.9% to 3.9% for 30-day readmissions and 5.7% to 9.1% for 3-month readmissions. No individual or combination discharge components were associated with lower 30-day adjusted readmission rates. The only single-component significantly associated with a lower rate of readmission at 3 months was having comprehensive content of education (P < .029). Increasing intensity of discharge components in bundles was associated with reduced adjusted 3-month readmission rates, but this did not reach statistical significance. This was seen in a 2-discharge component bundle including content of education and communication with the primary medical doctor, as well as a 3-discharge component bundle, which included content of education, medications in-hand, and home-based environmental mitigation. Children's hospitals demonstrate a range of asthma-specific discharge components. Although we found no significant associations for specific hospital-level discharge components and asthma readmission rates at 30 days, certain combinations of discharge components may support hospitals to reduce healthcare utilization at 3 months.


How long are patients willing to wait in the emergency department before leaving without being seen?
Our goal was to evaluate patients' threshold for waiting in an emergency department (ED) waiting room before leaving without being seen (LWBS). We analyzed whether willingness to wait was influenced by perceived illness severity, age, race, triage acuity level, or insurance status. We conducted this survey-based study from March to July 2010 at an urban academic medical center. After triage, patients were given a multiple-choice questionnaire, designed to ascertain how long they would wait for medical care. We collected data including age, gender, race, insurance status, and triage acuity level. We looked at the association between willingness to wait and these variables, using stratified analysis and logistic regression. Of the 375 patients who were approached, 340 (91%) participated. One hundred seventy-one (51%) were willing to wait up to 2 hours before leaving, 58 (17%) would wait 2 to 8 hours, and 110 (32%) would wait indefinitely. No association was found between willingness to wait and race, gender, insurance status, or perceived symptom severity. Patients willing to wait >2 hours tended to be older than 25, have higher acuity, and prefer the study site ED. Many patients have a defined, limited period that they are willing to wait for emergency care. In our study, 50% of patients were willing to wait up to 2 hours before leaving the ED without being seen. This result suggests that efforts to reduce the percentage of patients who LWBS must factor in time limits.


Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls.
The neural mechanisms underlying feelings of fatigue are poorly understood. The primary purpose of the study was to use functional magnetic resonance imaging (fMRI) to determine the association between feelings of mental fatigue and blood oxygen level dependent (BOLD) brain responses during a mentally fatiguing cognitive task. Healthy, non-fatigued controls and chronic fatigue syndrome (CFS) patients were included to determine the influence of chronic levels of fatigue on brain responses. We hypothesized that mental fatigue would be significantly related to brain activity during a fatiguing cognitive task but not during either a non-fatiguing motor (finger tapping) or cognitive (auditory monitoring) task. Patients (n=9) and controls (n=11) completed a finger tapping task, a simple auditory monitoring task and a challenging working memory task, designed to induce mental fatigue, while undergoing fMRI. Fatigue was measured prior to scanning and following each task during fMRI data collection. Results showed that mental fatigue was significantly related to brain activity during the fatiguing cognitive task but not the finger tapping or simple auditory monitoring tasks. Significant (p< or =0.005) positive relationships were found for cerebellar, temporal, cingulate and frontal regions. A significant (p=0.001) negative relationship was found for the left posterior parietal cortex. CFS participants did not differ from controls for either finger tapping or auditory monitoring tasks, but exhibited significantly greater activity in several cortical and subcortical regions during the fatiguing cognitive task. Our results suggest an association between subjective feelings of mental fatigue and brain responses during fatiguing cognition.


Sustainability science: an ecohealth perspective.
Sustainability science is emerging as a transdisciplinary effort to come to grips with the much-needed symbiosis between human activity and the environment. While there is recognition that conventional economic growth must yield to policies that foster sustainable development, this has not yet occurred on any broad scale. Rather, there is clear evidence that the Earth's ecosystems and landscapes continue to degrade as a consequence of the cumulative impact of human activities. Taking an ecohealth approach to sustainability science provides a unique perspective on both the goals and the means to achieve sustainability. The goals should be the restoration of full functionality to the Earth's ecosystems and landscapes, as measured by the key indicators of health: resilience, organization, vitality (productivity), and the absence of ecosystem distress syndrome. The means should be the coordinated (spatially and temporally) efforts to modify human behaviors to reduce cumulative stress impacts. Achieving ecosystem health should become the cornerstone of sustainability policy-for healthy ecosystems are the essential precondition for achieving sustainable livelihoods, human health, and many other societal objectives, as reflected in the Millennium Development Goals.


Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes.
Gene duplication followed by neo- or sub-functionalization deeply impacts the evolution of protein families and is regarded as the main source of adaptive functional novelty in eukaryotes. While there is ample evidence of adaptive gene duplication in prokaryotes, it is not clear whether duplication outweighs the contribution of horizontal gene transfer in the expansion of protein families. We analyzed closely related prokaryote strains or species with small genomes (Helicobacter, Neisseria, Streptococcus, Sulfolobus), average-sized genomes (Bacillus, Enterobacteriaceae), and large genomes (Pseudomonas, Bradyrhizobiaceae) to untangle the effects of duplication and horizontal transfer. After removing the effects of transposable elements and phages, we show that the vast majority of expansions of protein families are due to transfer, even among large genomes. Transferred genes--xenologs--persist longer in prokaryotic lineages possibly due to a higher/longer adaptive role. On the other hand, duplicated genes--paralogs--are expressed more, and, when persistent, they evolve slower. This suggests that gene transfer and gene duplication have very different roles in shaping the evolution of biological systems: transfer allows the acquisition of new functions and duplication leads to higher gene dosage. Accordingly, we show that paralogs share most protein-protein interactions and genetic regulators, whereas xenologs share very few of them. Prokaryotes invented most of life's biochemical diversity. Therefore, the study of the evolution of biology systems should explicitly account for the predominant role of horizontal gene transfer in the diversification of protein families.


Gender-based constraints affecting biofortified cassava production, processing and marketing among men and women adopters in Oyo and Benue States, Nigeria.
This study identified gender-based constraints affecting the production, processing and marketing of biofortified cassava in two states in Nigeria, using a mixed methods approach. The study identified major differences between the two study sites (Benue and Oyo). The scale of production of biofortified cassava is higher in Oyo state among adult men because of their active involvement and collaboration with research institutes within the state and the ease of transporting products to Lagos State for designated diverse markets. However, in Benue state more adult and young women are engaged in cultivation, processing and marketing business to meet up with the increased demand due to higher consumer acceptance in this region. Gender analysis revealed that lack of access to hired-labour restricted the scale of production among women in especially Oyo state. Low product price and high price of processing equipment, poor market infrastructure and middle men exploitation were constraints significantly more mentioned by women in general. Majorly, the men identified limited processing facilities/equipment as the most important constraint affecting the demand of biofortified cassava roots, while generally women were more constrained by the shortage of basic amenities and trainings that hindered their processing efficiency. The study proposes integration of gender-responsive strategies to further enhance the delivery of biofortified cassava products in Nigeria.


Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos.
Early development of certain mammalian embryos is protected by complex checkpoint systems to maintain the genomic integrity. Several metabolic pathways are modulated in response to genetic insults in mammalian cells. The present study investigated the relationship between the genetic integrity, embryo metabolites and developmental competence in preimplantation stage mouse embryos with the aim to identify early biomarkers which can predict embryonic genetic integrity using spent medium profiling by NMR spectroscopy. Embryos carrying induced DNA lesions (IDL) developed normally for the first 2.5 days, but began to exhibit a developmental delay at embryonic day 3.5(E3.5) though they were morphologically indistinguishable from control embryos. Analysis of metabolites in the spent medium on E3.5 revealed a significant association between pyruvate, lactate, glucose, proline, lysine, alanine, valine, isoleucine and thymine and the extent of genetic instability observed in the embryos on E4.5. Further analysis revealed an association of apoptosis and micronuclei frequency with P53 and Bax transcripts in IDL embryos on the E4.5 owing to delayed induction of chromosome instability. We conclude that estimation of metabolites on E3.5 in spent medium may serve as a biomarker to predict the genetic integrity in pre-implantation stage embryos which opens up new avenues to improve outcomes in clinical IVF programs.


Effect of smoking on reproductive hormones and semen parameters of infertile Saudi Arabians.
The purpose of this retrospective study is to look into the effect of smoking on semen and hormonal profile of Saudi Arabians attending infertility clinics. Medical record numbers of patients who attended infertility clinics and who underwent full assessment were identified rom Quadramed system and out-patient log books between January 2010 and December 2012. The standard protocol of the patients include full history, age, number of years of marriage personal habits of smoking, alcohol consumption, primary or secondary infertility. Standard laboratory tests which were performed, included, complete blood picture, random blood sugar, testosterone, follicle stimulation hormone, luteinizing hormone, prolactin level and semen analysis; volume, count, progressive motility and morphology. The data was entered in the database and analyzed. During the study period, 279 patients attended and infertility clinic and only 258 gave the sample for analysis. The average age of patients in the smoking group was 34.23 ± 7.66 and in the nonsmokers 34.07 ± 7.92 years. Primary infertility was more common in smokers versus nonsmokers P < 0.001 confidence interval (CI)< -44.0705, total serum testosterone level was lower 383.8 ± 239.5 versus 422.5 ± 139.2 ng/dL (0.009 CI< -9.9415), serum prolactin level was higher 18.68 ± 13.28 versus 12.85 ± 12.34 ng/mL (0.001 CI < 8.3794). The average volume of the semen among the smokers was 2.8 ± 1.35 mL and in nonsmokers it was 3.08 ± 0.76 mL (P < 0.008 CI< -0.123). The mean progressive motility in smokers was 31.5 ± 23.1 compared to nonsmokers 40.05 ± 25.43% (0.002 CI< -3.2962) and total sperm count was 119.52 ± 114.12 and 139.71 ± 104.82 million/mL (0.07 CI < 1.4657). This study shows that the effect of smoking is dramatic reduction in the hormonal levels and semen parameters. It is recommended that smoking men undergoing fertility treatment should stop smoking to increase their chances of having offspring.


The uptake of the pharmacy-dispensed naloxone kit program in Ontario: A population-based study.
Naloxone is a life-saving antidote for opioid overdoses. In June 2016, the Ontario government implemented the Ontario Naloxone Program for Pharmacies (ONPP) to enhance access to naloxone. We examined the initial uptake of naloxone through the ONPP and characteristics of the individuals receiving and pharmacies dispensing naloxone kits. We conducted a population-based study of all Ontario residents who received a naloxone kit between July 1, 2016 and March 31, 2018. This involved 1) a cross-sectional analysis of monthly rates of kits dispensed; and 2) a descriptive analysis of all individuals and pharmacies who accessed and dispensed naloxone, respectively. We stratified individuals according to their opioid exposure as: prescription opioid agonist therapy (OAT) recipients, prescription opioid recipients, those with past opioid exposure and those with no/unknown opioid exposure. We calculated a Lorenz curve comparing the cumulative percent of naloxone-dispensing pharmacies and cumulative percent of naloxone kits dispensed and the corresponding Gini coefficient. Naloxone dispensing through the ONPP increased considerably from 1.9 to 54.3 kits per 100,000 residents over the study period. In this time, 2,729 community pharmacies dispensed 91,069 kits to 67,910 unique individuals. Uptake was highest among prescription OAT recipients (40.7% of OAT recipients dispensed at least one kit), compared with 1.6% of prescription opioid recipients, 1.0% of those with past opioid exposure and 0.3% with no/unknown opioid exposure. Naloxone dispensing was highly clustered among pharmacies (Gini = 0.78), with 55.6% of Ontario pharmacies dispensing naloxone, and one-third (33.7%) of kits dispensed by the top 1.0% of naloxone-dispensing pharmacies. The ONPP launch led to a rapid increase in the number of naloxone kits dispensed in Ontario. Although the program successfully engaged people prescribed OAT, efforts to increase uptake among others at risk of opioid overdose appear warranted. Opportunities for expanding pharmacy participation should be identified and pursued.


Marine Dispersal Scales Are Congruent over Evolutionary and Ecological Time.
The degree to which offspring remain near their parents or disperse widely is critical for understanding population dynamics, evolution, and biogeography, and for designing conservation actions. In the ocean, most estimates suggesting short-distance dispersal are based on direct ecological observations of dispersing individuals, while indirect evolutionary estimates often suggest substantially greater homogeneity among populations. Reconciling these two approaches and their seemingly competing perspectives on dispersal has been a major challenge. Here we show for the first time that evolutionary and ecological measures of larval dispersal can closely agree by using both to estimate the distribution of dispersal distances. In orange clownfish (Amphiprion percula) populations in Kimbe Bay, Papua New Guinea, we found that evolutionary dispersal kernels were 17 km (95% confidence interval: 12-24 km) wide, while an exhaustive set of direct larval dispersal observations suggested kernel widths of 27 km (19-36 km) or 19 km (15-27 km) across two years. The similarity between these two approaches suggests that ecological and evolutionary dispersal kernels can be equivalent, and that the apparent disagreement between direct and indirect measurements can be overcome. Our results suggest that carefully applied evolutionary methods, which are often less expensive, can be broadly relevant for understanding ecological dispersal across the tree of life.


Unclear associations between small pelagic fish and jellyfish in several major marine ecosystems.
During the last 20 years, a series of studies has suggested trends of increasing jellyfish (Cnidaria and Ctenophora) biomass in several major ecosystems worldwide. Some of these systems have been heavily fished, causing a decline among their historically dominant small pelagic fish stocks, or have experienced environmental shifts favouring jellyfish proliferation. Apparent reduction in fish abundance alongside increasing jellyfish abundance has led to hypotheses suggesting that jellyfish in these areas could be replacing small planktivorous fish through resource competition and/or through predation on early life stages of fish. In this study, we test these hypotheses using extended and published data of jellyfish, small pelagic fish and crustacean zooplankton biomass from four major ecosystems within the period of 1960 to 2014: the Southeastern Bering Sea, the Black Sea, the Northern California Current and the Northern Benguela. Except for a negative association between jellyfish and crustacean zooplankton in the Black Sea, we found no evidence of jellyfish biomass being related to the biomass of small pelagic fish nor to a common crustacean zooplankton resource. Calculations of the energy requirements of small pelagic fish and jellyfish stocks in the most recent years suggest that fish predation on crustacean zooplankton is 2-30 times higher than jellyfish predation, depending on ecosystem. However, compared with available historical data in the Southeastern Bering Sea and the Black Sea, it is evident that jellyfish have increased their share of the common resource, and that jellyfish can account for up to 30% of the combined fish-jellyfish energy consumption. We conclude that the best available time-series data do not suggest that jellyfish are outcompeting, or have replaced, small pelagic fish on a regional scale in any of the four investigated ecosystems. However, further clarification of the role of jellyfish requires higher-resolution spatial, temporal and taxonomic sampling of the pelagic community.


TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice.
The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans.


Mapping the local protein interactome of the NuA3 histone acetyltransferase.
Protein-protein interactions modulate cellular functions ranging from the activity of enzymes to signal transduction cascades. A technology termed transient isotopic differentiation of interactions as random or targeted (transient I-DIRT) is described for the identification of stable and transient protein-protein interactions in vivo. The procedure combines mild in vivo chemical cross-linking and non-stringent affinity purification to isolate low abundance chromatin-associated protein complexes. Using isotopic labeling and mass spectrometric readout, purified proteins are categorized with respect to the protein 'bait' as stable, transient, or contaminant. Here we characterize the local interactome of the chromatin-associated NuA3 histone lysine-acetyltransferase protein complex. We describe transient associations with the yFACT nucleosome assembly complex, RSC chromatin remodeling complex and a nucleosome assembly protein. These novel, physical associations with yFACT, RSC, and Nap1 provide insight into the mechanism of NuA3-associated transcription and chromatin regulation.


How Subclonal Modeling Is Changing the Metastatic Paradigm.
A concerted effort to sequence matched primary and metastatic tumors is vastly improving our ability to understand metastasis in humans. Compelling evidence has emerged that supports the existence of diverse and surprising metastatic patterns. Enhancing these efforts is a new class of algorithms that facilitate high-resolution subclonal modeling of metastatic spread. Here we summarize how subclonal models of metastasis are influencing the metastatic paradigm. Clin Cancer Res; 23(3); 630-5. ©2016 AACR.


Anaesthetic and Perioperative Management of 14 Male New Zealand White Rabbits for Calvarial Bone Surgery.
Calvarial bone surgery on rabbits is frequently performed. This report aims to document a simple and practical anaesthetic and perioperative management for this procedure. Fourteen male New Zealand white rabbits were included in the study. Subcutaneous (SC) dexmedetomidine, ketamine and buprenorphine ± isoflurane vaporized in oxygen administered through a supraglottic airway device (V-gel®) provided clinically suitable anaesthesia. Supplemental oxygen was administered throughout recovery. Monitoring was clinical and instrumental (pulse-oximetry, capnography, invasive blood pressure, temperature, arterial blood gas analysis). Lidocaine was infiltrated at the surgical site and meloxicam was injected subcutaneously as perioperative analgesia. After surgery, pain was assessed five times daily (composite behavioural pain scale and grimace scale). Postoperative analgesia included SC meloxicam once daily for four days and buprenorphine every 8 h for three days (unless both pain scores were at the lowest possible levels). Rescue analgesia (buprenorphine) was administered in case of the score > 3/8 in the composite pain scale, >4/10 on the grimace scale or if determined necessary by the caregivers. Airway management with a V-gel® was possible but resulted in respiratory obstruction during the surgery in two cases. Hypoventilation was observed in all rabbits. All rabbits experienced pain after the procedure. Monitoring, pain assessments and administration of postoperative analgesia were recommended for 48 h.


The mitochondrial dynamism-mitophagy-cell death interactome: multiple roles performed by members of a mitochondrial molecular ensemble.
Mitochondrial research is experiencing a renaissance, in part, because of the recognition that these endosymbiotic descendants of primordial protobacteria seem to be pursuing their own biological agendas. Not only is mitochondrial metabolism required to produce most of the biochemical energy that supports their eukaryotic hosts (us) but mitochondria can actively (through apoptosis and programmed necrosis) or passively (through reactive oxygen species toxicity) drive cellular dysfunction or demise. The cellular mitochondrial collective autoregulates its population through biogenic renewal and mitophagic culling; mitochondrial fission and fusion, 2 components of mitochondrial dynamism, are increasingly recognized as playing central roles as orchestrators of these processes. Mitochondrial dynamism is rare in striated muscle cells, so cardiac-specific genetic manipulation of mitochondrial fission and fusion factors has proven useful for revealing noncanonical functions of mitochondrial dynamics proteins. Here, we review newly described functions of mitochondrial fusion/fission proteins in cardiac mitochondrial quality control, cell death, calcium signaling, and cardiac development. A mechanistic conceptual paradigm is proposed in which cell death and selective organelle culling are not distinct processes, but are components of a unified and integrated quality control mechanism that exerts different effects when invoked to different degrees, depending on pathophysiological context. This offers a plausible explanation for seemingly paradoxical expression of mitochondrial dynamics and death factors in cardiomyocytes wherein mitochondrial morphometric remodeling does not normally occur and the ability to recover from cell suicide is severely limited.


Effects of Cover Crops on Pratylenchus penetrans and the Nematode Community in Carrot Production.
Cover cropping is a common practice in U.S. Midwest carrot production for soil conservation, and may affect soil ecology and plant-parasitic nematodes-to which carrots are very susceptible. This study assessed the impact of cover crops-oats (Avena sativa), radish (Raphanus sativus) cv. Defender, rape (Brassica napus) cv. Dwarf Essex, and a mixture of oats and radish-on plant-parasitic nematodes and soil ecology based on the nematode community in Michigan carrot production systems. Research was conducted at two field sites where cover crops were grown in Fall 2014 preceding Summer 2015 carrot production. At Site 1, root-lesion (Pratylenchus penetrans) and stunt (Tylenchorhynchus sp.) nematodes were present at low population densities (less than 25 nematodes/100 cm3 soil), but were not significantly affected (P > 0.05) by cover crops. At Site 2, P. penetrans population densities were increased (P ≤ 0.05) by 'Defender' radish compared to other cover crops or fallow control during cover crop growth and midseason carrot production. At both sites, there were few short-term impacts of cover cropping on soil ecology based on the nematode community. At Site 1, only at carrot harvest, radish-oats mixture and 'Dwarf Essex' rape alone enriched the soil food web based on the enrichment index (P ≤ 0.05) while rape and radish increased structure index values. At Site 2, bacterivore abundance was increased by oats or radish cover crops compared to control, but only during carrot production. In general, cover crops did not affect the nematode community until nearly a year after cover crop growth suggesting that changes in the soil community following cover cropping may be gradual.


Perception of threat from emotions and its role in poor emotional expression within eating pathology.
Recent research has documented links between eating disorder (ED) symptomatology and emotional expression deficits. Relevant theoretical models have alluded to the functional role of disordered eating in alleviating affect that is felt to be otherwise unmanageable and threatening. Nevertheless, research examining ED individuals' perceptions of emotional states has been sparse, while empirical studies have predominantly focused on global conceptualizations of emotion, failing to address discrete affect states. The current study had three aims: (a) to determine the relation between ED symptomatology and emotional expression, in a sample of women with ED, in an attempt to confirm previous findings of an inverse relation; (b) to test the hypothesis that women with ED inhibit the expression of emotions perceived as threatening, by examining the relation between emotional expression and perceptions of threat from emotion, while partialling out the effects of depression; and (c) to determine whether, amongst women with ED, perceptions of threat from anger are uniquely associated with emotional inhibition, when the effects of depression and body dissatisfaction are controlled for. Results demonstrated that (a) emotional expression was negatively related with the three Eating Disorders Inventory-3 subscales (drive for thinness, bulimia and body dissatisfaction); (b) perceived threat from emotion, particularly anger, was negatively correlated with emotional expression, when depression was partialled out in the analysis; and (c) perceived threat from anger significantly and uniquely predicted emotional inhibition, over and above the effects of body dissatisfaction and depression, in a sample of women with ED symptomatology. It is suggested that anger may be perceived as particularly threatening amongst women with ED, and play a significant role in the emotional expression difficulties that this population experiences. The implications of the current findings are discussed in line with relevant theory and research, with particular reference to the new Schematic Propositional Analogical Associative Representation System for Eating Disorders (SPAARS-ED) model.


Treatment of chronic subdural hematomas with subdural evacuating port system placement in the intensive care unit: evolution of practice and comparison with bur hole evacuation in the operating room.
OBJECTIVE The aims of this study were to evaluate a multiyear experience with subdural evacuating port system (SEPS) placement for chronic subdural hematoma (cSDH) in the intensive care unit at a tertiary neurosurgical center and to compare SEPS placement with bur hole evacuation in the operating room. METHODS All cases of cSDH evacuation were captured over a 7-year period at a tertiary neurosurgical center within an integrated health care delivery system. The authors compared the performance characteristics of SEPS and bur hole placement with respect to recurrence rates, change in recurrence rates over time, complications, length of stay, discharge disposition, and mortality rates. RESULTS A total of 371 SEPS cases and 659 bur hole cases were performed (n = 1030). The use of bedside SEPS placement for cSDH treatment increased over the 7-year period, from 14% to 80% of cases. Reoperation within 6 months was higher for the SEPS (15.6%) than for bur hole drainage (9.1%) across the full 7-year period (p = 0.002). This observed overall difference was due to a higher rate of reoperation during the same hospitalization (7.0% for SEPS vs 3.2% for bur hole; p = 0.008). Over time, as the SEPS procedure became more common and modifications of the SEPS technique were introduced, the rate of in-hospital reoperation after SEPS decreased to 3.3% (p = 0.02 for trend), and the difference between SEPS and bur hole recurrence was no longer significant (p = 0.70). Complications were uncommon and were similar between the groups. CONCLUSIONS Overall performance characteristics of bedside SEPS and bur hole drainage in the operating room were similar. Modifications to the SEPS technique over time were associated with a reduced reoperation rate.


Nicastrin gene polymorphisms, cognitive ability level and cognitive ageing.
The hypothesis that polymorphisms in the gene for nicastrin (NCSTN) are associated with differences in cognitive level and ageing was tested in 462 relatively healthy surviving participants of the Scottish Mental Survey 1932. None had a history of dementia. They were tested on the Moray House Test of verbal reasoning at age 11 in 1932 and at age 79 between 1999 and 2001. At age 79 they also took tests of non-verbal reasoning, short- and long-term verbal declarative memory, Verbal Fluency, and a short screening test for dementia. Subjects who possessed at least one copy of the NCSTN B haplotype (Hap B) had higher scores on the Moray House Test (a test principally of verbal reasoning) at age 11 (p=0.036) and age 79 (p=0.027). The effect of Hap B on cognition at age 79 was non-significant after adjusting for the effect at age 11. Therefore, the effect of Hap B in this sample is on the life-long stable trait of cognitive ability, and not on age-related cognitive change. The possibility that this result might be a selection effect was not supported by the samples being in Hardy-Weinberg equilibrium with respect to the distribution of NCSTN genotypes.


Real-world outcomes in patients with metastatic castration-resistant prostate cancer receiving second-line chemotherapy versus an alternative androgen receptor-targeted agent (ARTA) following early progression on a first-line ARTA in a US community oncology setting.
This retrospective observational study assessed if second-line chemotherapy vs. androgen receptor-targeted agents (ARTAs; abiraterone/enzalutamide) is associated with improved outcomes in metastatic castration-resistant prostate cancer (mCRCaP) patients who experience early progression on first-line ARTAs in a US community setting. Patients with mCRCaP (n = 345) who progressed ≤ 12 months after first-line ARTA and received second-line chemotherapy (docetaxel/cabazitaxel; n = 147) or ARTA (n = 198) between May 2011 and October 2014 were identified. Overall survival (OS), prostate-specific antigen (PSA) response and progression, and clinical response were compared for second-line chemotherapy vs. ARTA, using one-sided tests from second-line therapy initiation. Multivariate analyses were adjusted for: year, age, metastases, opioid use, Eastern Cooperative Oncology Group performance score, PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase (LDH), and albumin levels. Patients receiving second-line chemotherapy vs. ARTA were younger (median: 74 vs. 79 years) and had a poorer prognosis in terms of PSA, LDH, alkaline phosphatase, albumin and hemoglobin levels, opioid use, and Halabi risk score (P < 0.05). Response rates were higher for chemotherapy vs. ARTA (PSA: adjusted odds ratio = 2.27, P = 0.005; clinical: adjusted odds ratio = 1.78; P = 0.020) and time to PSA progression was longer (adjusted hazard ratio [aHR] = 0.66; P = 0.010). A trend favored chemotherapy vs. ARTA for OS (aHR = 0.81, P = 0.148). Among patients with poor prognostic features, those receiving chemotherapy had significantly improved OS (Halabi intermediate-/high-risk score: aHR = 0.55, P = 0.009; hemoglobin < 11 g/dl: aHR = 0.41, P = 0.002; LDH > upper limit of normal: aHR = 0.18, P = 0.014; albumin < lower limit of normal: aHR = 0.42, P = 0.020). Following early progression on first-line ARTA, second-line chemotherapy may be more beneficial in mCRCaP compared with second-line ARTA in patients with a poor prognosis.


Synapse-specific representation of the identity of overlapping memory engrams.
Memories are integrated into interconnected networks; nevertheless, each memory has its own identity. How the brain defines specific memory identity out of intermingled memories stored in a shared cell ensemble has remained elusive. We found that after complete retrograde amnesia of auditory fear conditioning in mice, optogenetic stimulation of the auditory inputs to the lateral amygdala failed to induce memory recall, implying that the memory engram no longer existed in that circuit. Complete amnesia of a given fear memory did not affect another linked fear memory encoded in the shared ensemble. Optogenetic potentiation or depotentiation of the plasticity at synapses specific to one memory affected the recall of only that memory. Thus, the sharing of engram cells underlies the linkage between memories, whereas synapse-specific plasticity guarantees the identity and storage of individual memories.


Cosmeceuticals: the evidence behind the retinoids.
A wide range of cosmeceutical products are available on the market currently, but evidence to support their use is often lacking in the literature. Specifically, there is a substantial amount of evidence supporting the efficacy of tretinoin in photoaging, but the evidence supporting retinoid-based cosmeceuticals remains sparse. The authors review the current data in the literature related to vitamin A-derived cosmeceutical products and conclude that cosmeceuticals containing retinaldehyde have been shown in large randomized, controlled trials to have the most beneficial effect on aging skin.


Criteria for oil spill recovery: a case study of the intertidal community of Prince William Sound, Alaska, following the Exxon Valdez oil spill.
Marine intertidal organisms in Prince William Sound were exposed to crude oil following the TN Exxon Valdez oil spill in 1989. The intertidal communities were also subjected to mechanical disturbance during invasive oil spill remediation and cleanup efforts. Using monitoring data collected from 1989 to 1997, impacts and eventual recovery were assessed at oiled but uncleaned sites and oiled and cleaned study areas. A statistical model where recovery was defined as parallelism between the time profiles at control and oiled sites was evaluated. Statistical analysis and graphical presentations of the data suggest intertidal epibiota communities recovered from the oil spill by 1992 at the oiled sites and by 1994 at the oiled and remediated sites. Empirical data from the intertidal monitoring program supports the use of tests of parallelism in evaluating recovery and the need to avoid simply the comparison of sample means from control and oiled sites.


Reliability of Ashworth and Modified Ashworth scales in children with spastic cerebral palsy.
Measurement of spasticity is a difficult and unresolved problem, partly due to its complexity and the fact that there are many factors involved. In the assessment of spasticity in the pediatric disabled population, methods that are easily used in practice are ordinal scales that still lack reliability. A prospective cross-sectional observational study was planned to determine the reliability of the Ashworth Scale (AS) and the Modified Ashworth Scale (MAS) in children with spastic cerebral palsy (CP). The study included 38 children with spastic diplegic CP. The mean age for the children was 52.9 months (SD: 19.6) ranging from 18 to 108 months. The functional levels of children were classified according to the Gross Motor Function Classification System. 20 children were in Level II (52.6%), 18 were in Level III (47.4%) and 9 were in Level I (23.7%). Spasticity in hip flexors, adductors, internal rotators, hamstrings, gastrocnemius were assessed by AS and MAS. Each child was assessed by three physiotherapists in two different sessions, a week apart. The intrarater reliability was determined by paired comparison of measurements for each therapist for the two assessments. Interrater reliability was determined by paired comparisons of the three therapists' measurements on the same day. The inter and intrarater reliability of the scales were evaluated by the intraclass correlation coefficient (ICC). According to ICC scores, interrater reliability of AS and MAS varied from moderate to good. ICC scores of AS were between 0.54 and 0.78 and MAS were between 0.61-0.87. Test-retest results of AS and MAS varied from poor to good. ICC values were between 0.31 and 0.82 for AS and between 0.36 and 0.83 for MAS. The interrater and intrarater reliability of AS and MAS are related to muscle and joint characters. The repetition of measurements by the same physiotherapist, and experience may not affect reliability. These scales are not very reliable and assessments of spasticity using these scales should be therefore interpreted with great caution.


Century-old mystery of Puccinia striiformis life history solved with the identification of Berberis as an alternate host.
The life history of Puccinia striiformis remains a mystery because the alternate host has never been identified. Inoculation of grasses using aeciospores from naturally infected Berberis chinensis and B. koreana resulted in infection on Poa pratensis, producing uredinia typical of stripe rust caused by P. striiformis. Analyses using real-time polymerase chain reaction and DNA sequence confirmed the rust fungus as P. striiformis. Pycnia and aecia were produced on B. chinensis, B. holstii, B. koreana, and B. vulgaris after inoculation using germinating telia of P. striiformis f. sp. tritici. Wheat inoculated with aeciospores from B. chinensis resulted in uredinia, which demonstrated that Berberis spp. also serve as alternate hosts for the wheat stripe rust pathogen. The elucidation of the complete life history for P. striiformis f. sp. tritici will provide a powerful tool to rapidly advance our knowledge of the genetics of this rust fungus, and will lead to the development of improved strategies for a better control of stripe rust.


Individual differences in personality change across the adult life span.
A precise and comprehensive description of personality continuity and change across the life span is the bedrock upon which theories of personality development are built. Little research has quantified the degree to which individuals deviate from mean-level developmental trends. In this study, we addressed this gap by examining individual differences in personality trait change across the life span. Data came from a nationally representative sample of 9,636 Dutch participants who provided Big Five self-reports at five assessment waves across 7 years. We divided our sample into 14 age groups (ages 16-84 at initial measurement) and estimated latent growth curve models to describe individual differences in personality change across the study period for each trait and age group. Across the adult life span, individual differences in personality change were small but significant until old age. For Openness, Conscientiousness, Extraversion, and Agreeableness, individual differences in change were most pronounced in emerging adulthood and decreased throughout midlife and old age. For Emotional Stability, individual differences in change were relatively consistent across the life span. These results inform theories of life span development and provide future directions for research on the causes and conditions of personality change.


Poly-substance use and sexual risk behaviours: a cross-sectional comparison of adolescents in mainstream and alternative education settings.
Surveys of young people under-represent those in alternative education settings (AES), potentially disguising health inequalities. We present the first quantitative UK evidence of health inequalities between AES and mainstream education school (MES) pupils, assessing whether observed inequalities are attributable to socioeconomic, familial, educational and peer factors. Cross-sectional, self-reported data on individual- and poly-substance use (PSU: combined tobacco, alcohol and cannabis use) and sexual risk-taking from 219 pupils in AES (mean age 15.9 years) were compared with data from 4024 pupils in MES (mean age 15.5 years). Data were collected from 2008 to 2009 as part of the quasi-experimental evaluation of Healthy Respect 2 (HR2). AES pupils reported higher levels of substance use, including tobacco use, weekly drunkenness, using cannabis at least once a week and engaging in PSU at least once a week. AES pupils also reported higher levels of sexual health risk behaviours than their MES counterparts, including: earlier sexual activity; less protection against sexually transmitted infections (STIs); and having 3+ lifetime sexual partners. In multivariate analyses, inequalities in sexual risk-taking were fully explained after adjusting for higher deprivation, lower parental monitoring, lower parent-child connectedness, school disengagement and heightened intentions towards early parenthood among AES vs MES pupils. However, an increased risk (OR = 1.73, 95% CI 1.15, 2.60) of weekly PSU was found for AES vs MES pupils after adjusting for these factors and the influence of peer behaviours. AES pupils are more likely to engage in health risk behaviours, including PSU and sexual risk-taking, compared with MES pupils. AES pupils are a vulnerable group who may not be easily targeted by conventional population-level public health programmes. Health promotion interventions need to be tailored and contextualised for AES pupils, in particular for sexual health and PSU. These could be included within interventions designed to promote broader outcomes such as mental wellbeing, educational engagement, raise future aspirations and promote resilience.


Pulp Fibroblast Cell Apoptosis After Application of Hema Dentine Bonding Material with Ethanol and Water Solvent.
The most common main materials for dentin bonding for composite resin restoration is 2-hydroxyethyl methacrylate (HEMA). HEMA has beneficial physical and chemical properties, and stable, yet toxic. The addition of ethanol or water, may reduce the toxic effect of HEMA. Ethanol solvent has lower H-bonding capacity compared to water solvent, so it can bind less free radicals from the residual monomer. This study aimed to analyze apoptosis due to dentine bonding application with ethanol and water solvent. Fibroblast culture cells were obtained from extracted third molar, by means of tripsinasion method. The cells were divided into 4 groups as reached confluent: cell culture without treatment as control, cell culture with scaffold chitosan, cell culture with scaffold and polymerized dentin bonding with ethanol or water solvent. Apoptosis observation was conducted using immunohistochemistry method with ethidium bromide acridin orange staining, under fluorescent microscope with 40´ magnification. There was a significant difference among groups (p=0.0001), yet no differences found between different solvent. Apoptosis rate in fibroblast cells culture exposed to HEMA bonding with ethanol solvent was 67%, while the cells exposed to HEMA bonding with water solvent was 44%. The effect of dentin bonding with ethanol solvent and water solvent towards apoptosis rate of pulp fibroblast cells is not different.


The role of a modulatory neuron in feeding and satiation in Aplysia: effects of lesioning of the serotonergic metacerebral cells.
Food-induced arousal in Aplysia is characterized by a progressive increase in the speed and strength of biting responses elicited by a seaweed stimulus. Data from semi-intact and dissected preparations suggest that the identified, serotonergic, metacerebral cells (MCCs) of the cerebral ganglion contribute to food-induced arousal by enhancing the strength of buccal muscle contractions, and by modulating the output of the central pattern generator for biting movements. In order to test this hypothesis in intact, free-moving animals and to determine if the MCCs play a role in satiation of feeding, the behavior of animals that had their MCCs destroyed by intracellular injection of proteases was compared with that of B Cell-Lesion and Dye injection control animals (Experiment 1) or surgical control animals (Experiment 2). Nonfeeding behaviors such as defensive withdrawal responses, locomotion, and righting reflexes were unaffected by MCC lesioning. Also unaffected by MCC lesioning were appetitive feeding behaviors and the amount of food needed to satiate animals. Significant behavioral deficits in consummatory feeding behaviors, which remained stable for periods exceeding 10 d, were observed in the MCC-lesioned animals but not in controls. Lesioned animals exhibited a slowing of rate of repetitive biting responses by 40% of controls and had reduced magnitudes of repetitive bites, particularly at the end of a testing run of 10 consecutive bites. The deficit in bite magnitude was minimally evident in food-deprived animals (Experiment 1) but became more pronounced as animals were fed to satiation (Experiment 2). MCC-lesioned animals still exhibited a residual build-up of the rate and magnitude of biting responses at the onset of feeding behavior. This suggests that, in addition to the MCCs, there are other sources of modulation that contribute to plasticity of consummatory responses during the food-induced arousal state.


A critical review of "Internet addiction" criteria with suggestions for the future.
In the last 5 years a deluge of articles on the topic of Internet addiction (IA) has proposed many candidate symptoms as evidence of this proposed disease. We critically reviewed the current approach to the measurement and identification of this new excessive behavior syndrome. Three popular models of IA were discussed: Griffith's components model; Young's Internet Addiction Test (IAT); and the criteria by Tao et al. (2010). We selected these models because they are widely cited and propose specific criteria for IA disorder. Our approach is not meant to provide an exhaustive review, but to discuss and critique the most salient trends in the field. The models of Internet addiction share some criteria, including feeling a loss of control over Internet use; ensuing psychological, social, or professional conflict or problems; and preoccupation when not using the Internet. Other criteria inconsistently mentioned include: mood management, tolerance, withdrawal, and craving/anticipation. The models studied here share the assumption that the Internet can produce a qualitative shift to a diseased state in humans. We critically discussed the above criteria and concluded that the evidence base is currently not strong enough to provide support for an Internet addiction disorder. Future research areas are suggested: (1) Focusing on common impaired dimensions, (2) exploring neuroimaging as a model building tool, and (3) identifying shifts in the rewarding aspects of Internet use. Given the lack of consensus on the subject of Internet addiction, a focus on problem behaviors appears warranted.


Total synthesis of a functional designer eukaryotic chromosome.
Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.


Impact of structurally modifying hyaluronic acid on CD44 interaction.
CD44 is a widely-distributed type I transmembrane glycoprotein that binds hyaluronic acid (HA) in most cell types, including primary tumor cells and cancer-initiating cells and has roles in cell migration, cell-cell, and cell-matrix adhesion. HA-derived conjugates and nanoparticles that target the CD44 receptor on cells have been reported for targeted delivery of therapeutics and imaging agents. Altering crucial interactions of HA with CD44 active sites holds significant importance in modulating targeting ability of hyaluronic acid to other cancer types that do not express the CD44 receptor or minimizing the interaction with CD44+ cells that are not target cells. The approach adopted here was deacetylation of the N-acetyl group and selective sulfation on the C6-OH on the HA polymer, which form critical interactions with the CD44 active site. Major interactions identified by molecular modeling were confirmed to be hydrogen bonding of the C6-OH with Tyr109 and hydrophobic interaction of the N-acetyl group with Tyr46, 83 and Ile 92. Modified HA was synthesized and characterized and its interactions were assessed by in vitro and molecular modeling approaches. In vitro techniques included flow cytometry and fluorescence polarization, while in silico approaches included docking and binding calculations by a MM-PBSA approach. These studies indicated that while both deacetylation and sulfation of HA individually decrease CD44 interaction, both chemical modifications are required to minimize interaction with CD44+ cells. The results of this study represent the first step to effective retargeting of HA-derived NPs for imaging and drug delivery.


Effectiveness and adequacy of blinding in the moderation of pain outcomes: Systematic review and meta-analyses of dry needling trials.
Blinding is critical to clinical trials because it allows for separation of specific intervention effects from bias, by equalising all factors between groups except for the proposed mechanism of action. Absent or inadequate blinding in clinical trials has consistently been shown in large meta-analyses to result in overestimation of intervention effects. Blinding in dry needling trials, particularly blinding of participants and therapists, is a practical challenge; therefore, specific effects of dry needling have yet to be determined. Despite this, dry needling is widely used by health practitioners internationally for the treatment of pain. This review presents the first empirical account of the influence of blinding on intervention effect estimates in dry needling trials. The aim of this systematic review was to determine whether participant beliefs about group allocation relative to actual allocation (blinding effectiveness), and/or adequacy of blinding procedures, moderated pain outcomes in dry needling trials. Twelve databases (MEDLINE, EMBASE, AMED, Scopus, CINAHL, PEDro, The Cochrane Library, Trove, ProQuest, trial registries) were searched from inception to February 2016. Trials that compared active dry needling with a sham that simulated dry needling were included. Two independent reviewers performed screening, data extraction, and critical appraisal. Available blinding effectiveness data were converted to a blinding index, a quantitative measurement of blinding, and meta-regression was used to investigate the influence of the blinding index on pain. Adequacy of blinding procedures was based on critical appraisal, and subgroup meta-analyses were used to investigate the influence of blinding adequacy on pain. Meta-analytical techniques used inverse-variance random-effects models. The search identified 4,894 individual publications with 24 eligible for inclusion in the quantitative syntheses. In 19 trials risk of methodological bias was high or unclear. Five trials were adequately blinded, and blinding was assessed and sufficiently reported to compute the blinding index in 10 trials. There was no evidence of a moderating effect of blinding index on pain. For short-term and long-term pain assessments pooled effects for inadequately blinded trials were statistically significant in favour of active dry needling, whereas there was no evidence of a difference between active and sham groups for adequately blinded trials. The small number and size of included trials meant there was insufficient evidence to conclusively determine if a moderating effect of blinding effectiveness or adequacy existed. However, with the caveats of small sample size, generally unclear risk of bias, statistical heterogeneity, potential publication bias, and the limitations of subgroup analyses, the available evidence suggests that inadequate blinding procedures could lead to exaggerated intervention effects in dry needling trials.


Epitopes of Bordetella pertussis lipopolysaccharides as potential markers for typing of isolates with monoclonal antibodies.
Three hybridomas (P1P3, D7 and 60.5) producing monoclonal antibodies (mAbs) against Bordetella pertussis lipopolysaccharide (LPS) were established. All reacted with the LPS from a typical, vaccine strain of B. pertussis (1414), but not with that of a variant strain (A100). Two of these mAbs (P1P3 and 60.5) cross-reacted with a B. bronchiseptica LPS; only one (P1P3) reacted with a B. parapertussis LPS. ELISA reactivities with intact LPSs, and defined partial structures covalently linked to bovine serum albumin, were compared. mAb 60.5 bound to the terminal region of a distal trisaccharide consisting of N-acetylated amino sugars. D7 reacted with a substructure which can be modified in the B. parapertussis and B. bronchiseptica LPSs by addition of a polymeric O-chain. P1P3 bound to a nonacetylated glucosamine substituted with L-glycero-D-manno-heptose, present in the 'core' of the B. pertussis LPS. These mAbs may be useful for rapid typing of Bordetella in clinical isolates.


Use of patient flow analysis to improve patient visit efficiency by decreasing wait time in a primary care-based disease management programs for anticoagulation and chronic pain: a quality improvement study.
Patients with chronic conditions require frequent care visits. Problems can arise during several parts of the patient visit that decrease efficiency, making it difficult to effectively care for high volumes of patients. The purpose of the study is to test a method to improve patient visit efficiency. We used Patient Flow Analysis to identify inefficiencies in the patient visit, suggest areas for improvement, and test the effectiveness of clinic interventions. At baseline, the mean visit time for 93 anticoagulation clinic patient visits was 84 minutes (+/- 50 minutes) and the mean visit time for 25 chronic pain clinic patient visits was 65 minutes (+/- 21 minutes). Based on these data, we identified specific areas of inefficiency and developed interventions to decrease the mean time of the patient visit. After interventions, follow-up data found the mean visit time was reduced to 59 minutes (+/-25 minutes) for the anticoagulation clinic, a time decrease of 25 minutes (t-test 39%; p < 0.001). Mean visit time for the chronic pain clinic was reduced to 43 minutes (+/- 14 minutes) a time decrease of 22 minutes (t-test 34 %; p < 0.001). Patient Flow Analysis is an effective technique to identify inefficiencies in the patient visit and efficiently collect patient flow data. Once inefficiencies are identified they can be improved through brief interventions.


Five potential consequences of climate change for invasive species.
Scientific and societal unknowns make it difficult to predict how global environmental changes such as climate change and biological invasions will affect ecological systems. In the long term, these changes may have interacting effects and compound the uncertainty associated with each individual driver. Nonetheless, invasive species are likely to respond in ways that should be qualitatively predictable, and some of these responses will be distinct from those of native counterparts. We used the stages of invasion known as the "invasion pathway" to identify 5 nonexclusive consequences of climate change for invasive species: (1) altered transport and introduction mechanisms, (2) establishment of new invasive species, (3) altered impact of existing invasive species, (4) altered distribution of existing invasive species, and (5) altered effectiveness of control strategies. We then used these consequences to identify testable hypotheses about the responses of invasive species to climate change and provide suggestions for invasive-species management plans. The 5 consequences also emphasize the need for enhanced environmental monitoring and expanded coordination among entities involved in invasive-species management.


Anaerobic biodegradation of DDT to DDD in soil.
DDT labeled with carbon-14 was added to soil, and the mixture was incubated anaerobically for 2 weeks and 4 weeks. DDT and seven possible decomposition products were separated by thin-layer chromatography, and the radioactivity of material from individual spots was determined by liquid scintillation. The DDT was dechlorinated by soil microorganisms to DDD, and only traces of other degradation products were detected. No degradation of DDT was detected in sterile soil.


Molecular biology and biochemistry of natriuretic peptide family.
The natriuretic peptide family consists of three endogenous ligands; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and is involved in the regulation of cardiovascular homeostasis. Both ANP and BNP act mainly as cardiac hormones and are produced predominantly by the atrium and ventricle, respectively. Expression of the BNP and ANP genes is greatly augmented in patients with congestive heart failure and animal models of ventricular hypertrophy or cardiomyopathy. In the heart, the BNP gene expression is regulated differently from the ANP gene expression both at transcriptional and post-transcriptional levels. Transgenic technology has provided the direct evidence that BNP as well as ANP is involved in the chronic blood pressure control. Contrasting with ANP and BNP, CNP does not act as a cardiac hormone but as a neuropeptide or an endothelium-derived autocrine/paracrine regulator. Endothelial production of CNP is remarkably augmented by various cytokines and growth factors such as transforming growth factor-beta and tumour necrosis factor-alpha, suggesting the pathophysiological significance of CNP in the process of various vascular disorders. Chromosomal mapping of natriuretic peptides has revealed that the CNP gene is localized on mouse chromosome 1, while ANP and BNP are tightly linked on mouse chromosome 4, suggesting that CNP, a local regulator, is functionally and evolutionarily distinct from ANP and BNP, both of which are cardiac hormones. Understanding the molecular biology and biochemistry of the natriuretic peptide family will lead to the better understanding of its physiological and pathophysiological implication, and the clinical application in cardiorenal regulation.


[Visceral Leishmaniasis in HIV-Infected Patients: The Challenge of Relapse and Treatment Failure].
Visceral leishmaniasis is an endemic disseminated infection, considered to be the third most frequent opportunistic parasitic infection in Europe. It is especially prevalent in patients co-infected with human immunodeficiency virus, in whom it poses a great therapeutic challenge due to increased risk of relapse. The goal of this study is to characterize a population of co-infected patients, as well as the efficiency of the adopted treatment strategies. Retrospective study with a sample composed of all patients with visceral leishmaniasis and human immunodeficiency virus admitted in an Infectious Diseases ward over a period of 10 years. Of the 23 enrolled patients, two were female (8.7%). The mean TCD4+ cell count was 104.4 cells/uL (± 120.3cells/uL), only two patients had undetectable viral load (< 20 copies/mL) and 16 (69.6%) were not under antiretroviral therapy at the time of diagnosis. Treatment-wise, liposomal amphotericin B was used in 18 patients, meglumine antimoniate in four and miltefosine in one. Fourteen (60.9%) were adherent to secondary prophylaxis protocol. A relapse rate of 26.1% was observed (six patients). Co-infection is responsible for higher treatment failure rates and more relapses. TCD4+ cell count is the main predictive factor of relapse, and strict adherence to chemoprophylaxis protocols unequivocally results in a reduction of relapse rate. Combined treatment strategies using liposomal amphotericin B and miltefosine yield fewer therapeutic failures than the classic approach. We therefore conclude that alternative, combined therapeutic protocols seem to be a viable solution for these patients.


The relationship between agonist states of the M1 muscarinic receptor and the hydrolysis of inositol lipids in transfected murine fibroblast cells (B82) expressing different receptor densities.
We studied the relationship between the M1 muscarinic receptor density and the receptor-mediated hydrolysis of inositol lipids in cloned murine fibroblast B82 cells which were transfected with the m1 muscarinic receptor gene. Of the seven clones examined, the M1 muscarinic receptor densities in these cells characterized by (-)[3H]methyl-3-quinuclidinyl benzilate ([-)-[3H]MQNB binding ranged from 12 fmol/10(6) cells in LK3-1 cells to 260 fmol/10(6) cells in the LK3-8 cells. Carbachol/(-)[3H]MQNB competition curves for the LK3-1 cells (with low receptor density) had a Hill coefficient close to unity. The competition curves for carbachol in the clones with higher receptor densities had Hill coefficients less than 1 and were best fitted by a computerized nonlinear least-squares regression program for the two-site model. The percentage of the M1 muscarinic receptors which had high affinity for carbachol decreased as the receptor density increased, suggesting that the presence of endogenous factors in these cells may be important for the agonist affinity state of the receptor. Concentration-response curves for carbachol-stimulated [3H]inositol monophosphate [( 3H]IP1) accumulation were also obtained. A significant correlation was observed between the density of M1 muscarinic receptor with high affinity for carbachol and the maximum [3H]IP1 accumulation in these cells. There is no significant difference among the EC50 values and the dissociation constant of high-affinity state values of the carbachol/(-)[3H] MQNB competition curves. These results suggest that the high-affinity state for carbachol may be the functional state of the M1 muscarinic receptors in these transfected B82 cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Modelling the COVID-19 pandemic in context: an international participatory approach.
The SARS-CoV-2 pandemic has had an unprecedented impact on multiple levels of society. Not only has the pandemic completely overwhelmed some health systems but it has also changed how scientific evidence is shared and increased the pace at which such evidence is published and consumed, by scientists, policymakers and the wider public. More significantly, the pandemic has created tremendous challenges for decision-makers, who have had to implement highly disruptive containment measures with very little empirical scientific evidence to support their decision-making process. Given this lack of data, predictive mathematical models have played an increasingly prominent role. In high-income countries, there is a long-standing history of established research groups advising policymakers, whereas a general lack of translational capacity has meant that mathematical models frequently remain inaccessible to policymakers in low-income and middle-income countries. Here, we describe a participatory approach to modelling that aims to circumvent this gap. Our approach involved the creation of an international group of infectious disease modellers and other public health experts, which culminated in the establishment of the COVID-19 Modelling (CoMo) Consortium. Here, we describe how the consortium was formed, the way it functions, the mathematical model used and, crucially, the high degree of engagement fostered between CoMo Consortium members and their respective local policymakers and ministries of health.


IL-2-induced tumor necrosis factor (TNF)-beta expression: further analysis in the IL-2 knockout model, and comparison with TNF-alpha, lymphotoxin-beta, TNFR1 and TNFR2 modulation.
IL-2 induces the stimulation of inflammatory and immune reactions, and the apoptosis of antigen-activated cells. However, the molecular basis of these pleiotropic functions is largely unknown. We have previously reported that IL-2 induces genes involved in cytoskeleton organization, oncogene regulation and transcriptional control. In an IL-2-dependent cell line, we have also shown that IL-2 induces tumor necrosis factor (TNF)-beta mRNA through the Jak-STAT pathway. Here, we first demonstrate in vitro that IL-2 induces mature and partially spliced TNF-beta mRNA in the splenocytes and lymph node cells of both IL-2(-/-) and IL-2(+/-) mice. Under the same experimental conditions, IL-2 is seen to induce TNF-alpha mRNA. mRNA expression is followed by semiquantitative RT-PCR and this analysis is then extended in vivo by studying different lymphoid organs from IL-2(-/-)animals. Strikingly, the expression of TNF-beta mRNA is noted to be extremely low in the spleens and lymph nodes of IL-2(-/-) mice. Similarly, TNF-alpha, lymphotoxin (LT)-beta, TNFR1 and TNFR2 mRNA levels are also low in the spleens of IL-2(-/-) animals, whereas IFN-gamma and IL-4 mRNA levels remain unaffected in these animals. The experimental values are significantly different (P < or = 0.05) from those of control IL-2(+/-) animals. Western blot analysis of TNF-alpha expression confirmed and extended the results at the protein level. For the first time, we demonstrate that IL-2 directly or indirectly regulates genes of the TNF-TNFR family in secondary lymphoid organs. Furthermore, IL-2(-/-) animals in which thymopoiesis is unaffected show normal expression of these genes. Altogether, our data further define the pleiotropic effects of IL-2 at the molecular level.


Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors.
Patients with acromegaly usually harbor macroadenomas measuring between 10 and 30 mm in maximal diameter. Giant (adenoma size ≥40 mm) GH-secreting pituitary tumors are rarely encountered and the aim of this study is to analyze different methods for managing them. We have identified 34 patients (15 men and 19 females) with giant adenomas among 762 subjects (4.5%) with acromegaly in our records, and characterized their clinical characteristics and response to treatment. Mean age at diagnosis was 34.9±12.5 years (range, 16-67 years). Mean adenoma size was 49.4±9.4 mm (range, 40-80 mm); 30 adenomas showed cavernous sinus invasion and 32 had suprasellar extension. Twenty-nine (85%) patients had visual field defects. Mean baseline IGF1 was 3.4±1.8×ULN. All patients except one underwent pituitary surgery (one to three procedures), but none achieved hormonal remission following first surgery. Among the 28 subjects with visual disturbances, 14 recovered post-operatively and 13 improved. Treatment with somatostatin analogs was given to all patients after surgical failure. Six achieved remission, nine others were partially controlled (IGF1<1.5×ULN; 3/9 when combined with cabergoline), and 17 did not respond (two were lost). Nine patients were treated with pegvisomant, alone (n=4) or in combination with somatostatin analogs (n=5); five are in remission and two are partially controlled. Pasireotide-LAR achieved hormonal remission in one of the six patients. Currently, after a mean follow-up period of 8.9 years, 17 patients are in biochemical remission, eight are partially controlled, and seven are uncontrolled (two were lost to follow-up). Giant GH-secreting adenomas are invasive, uncontrolled by surgery, and respond poorly to medical treatment. Aggressive multimodal therapy is critical for their management, enhancing control rate and biochemical remission.


The nature and consequences of coinfection in humans.
Many fundamental patterns of coinfection (multi-species infections) are undescribed, including the relative frequency of coinfection by various pathogens, differences between single-species infections and coinfection, and the burden of coinfection on human health. We aimed to address the paucity of general knowledge on coinfection by systematically collating and analysing data from recent publications to understand the types of coinfection and their effects. From an electronic search to find all publications from 2009 on coinfection and its synonyms in humans we recorded data on i) coinfecting pathogens and their effect on ii) host health and iii) intensity of infection. The most commonly reported coinfections differ from infections causing highest global mortality, with a notable lack of serious childhood infections in reported coinfections. We found that coinfection is generally reported to worsen human health (76% publications) and exacerbate infections (57% publications). Reported coinfections included all kinds of pathogens, but were most likely to contain bacteria. These results suggest differences between coinfected patients and those with single infections, with coinfection having serious health effects. There is a pressing need to quantify the tendency towards negative effects and to evaluate any sampling biases in the coverage of coinfection research.


Acute respiratory distress syndrome after cardiac surgery.
Acute respiratory distress syndrome (ARDS) is a leading cause of postoperative respiratory failure, with a mortality rate approaching 40% in the general population and 80% in the subset of patients undergoing cardiac surgery. The increased risk of ARDS in these patients has traditionally been associated with the use of cardiopulmonary bypass (CPB), the need for blood product transfusions, large volume shifts, mechanical ventilation and direct surgical insult. Indeed, the impact of ARDS in the cardiac population is substantial, affecting not only survival but also in-hospital length of stay and long-term physical and psychological morbidity. No patient undergoing cardiac surgery can be considered ARDS risk-free. Early identification of those at higher risk is crucial to warrant the adoption of both surgical and non-surgical specific preventative strategies. The present review focuses on epidemiology, risk assessment, pathophysiology, prevention and management of ARDS in the specific setting of patients undergoing cardiac surgery.


New systems of work organization and workers' health.
This paper aims at identifying major changes in and around work organizations, their effects upon job characteristics and the health and well-being of today's employees, and related research challenges. Increased internationalization and competition, increased utilization of information and communication technology, the changing workforce configuration, and flexibility and new organizational practices are considered. As work has changed from physical to mental in nature, job characteristics have changed significantly. Meanwhile work and family life have blended. New systems of work organization have become more prevalent, but they do not represent a radical change across the whole economy. New practices may have an adverse impact upon job characteristics, but their effects depend on their design, implementation, and management. Research recommendations include improved monitoring of changes in work organization and studies into their health and safety consequences, intervention studies, studies into the motivating potential of modern work practices, studies of marginalized workers and workers in less developed countries, and "mechanism studies".


Sodium enoxaparin and venovenous hemofiltration in treating sudden sensorineural hearing loss and tinnitus.
Sudden sensorineural hearing loss (SSNHL) constitutes a considerable diagnostic challenge because it may be caused by many diverse conditions that may be difficult to recognize. No definitive treatment for SSNHL is universally accepted; the goal of this study was to evaluate the efficacy of sodium enoxaparin associated with venovenous hemofiltration in a therapeutic regimen. We treated 20 patients divided randomly into two numerically equal groups (A and B). Group A patients underwent this therapeutic protocol: Hemofiltration was performed at the first and last day of the protocol while, beginning on the second day of the protocol, sodium enoxaparin was administered subcutaneously at a dose of 4,000 IU once a day for 10 days. After the first hemofiltration, all the patients with complete auditory recovery were discharged without receiving the treatment with sodium enoxaparin. Group B patients received conventional therapy (cortisone, vasoactive agents, and vitamin complexes) administered in physiological solution intravenously twice daily for 10 days. In our randomized, controlled trial, treated patients in group A showed more improvement than did those in group B.


Expression, purification and crystallisation of phosphorylase kinase catalytic domain.
The catalytic subunit of phosphorylase kinase is composed of a kinase catalytic core domain (residues 1 to 298), which has a 33% identity with the kinase core of the cyclic AMP-dependent protein kinase, and a C-terminal calmodulin binding domain. The kinase domain of the catalytic subunit has been expressed in Escherichia coli, purified and crystallised in the presence of ATP and magnesium from 5% (w/v) polyethylene glycol 8000, 10% (v/v) glycerol, 50 mM Hepes/NaOH (pH 6.9). A three-fold excess of magnesium to ATP was used for crystal growth. The inclusion of glycerol in the crystallization medium produced a marked reduction in mosaic spread of the diffraction spots from greater than 1 degree to 0.3 degree. The crystals are orthorhombic, space group P2(1)2(1)2(1) with unit cell dimensions a = 47.1 A, b = 69.1 A, c = 112.9 A and one molecule per asymmetric unit. Data to 3 A resolution have been collected and structure determination is in progress.


Acute spinal subdural hematoma: MR and CT findings with pathologic correlates.
To determine the MR and CT findings that characterize acute spinal subdural hematoma (ASSH). The MR, CT, and clinical findings in three patients with surgically proved ASSH were reviewed and also correlated with the postmortem MR, CT, and cryomicrotome findings in three other patients, two with ASSH and one with an acute spinal epidural hematoma. Imaging findings in ASSH included: (a) hyperdense lesions on plain CT within the dural sac, distinct from the adjacent low-density epidural fat and silhouetted against the lower-density spinal cord and cauda equina, which it compressed; (b) lack of direct continuity with the adjacent osseous structures; (c) clumping, loculation, and streaking of blood within the dural sac on both MR and Ct; and (d) an inhomogeneous and variable signal intensity to the ASSH on all MR pulse sequences, but, nevertheless, a striking low signal intensity on T2-weighted spin-echo or T2-weighted gradient-echo to a major part of the ASSH because of deoxyhemoglobin. Plain CT was most helpful in compartmentalizing the hematoma. When MR and plain CT are obtained as complementary studies, they provide characteristic findings that allow the prompt diagnosis of ASSH.


Statins in the treatment of depression: Hype or hope?
Many patients with depression do not respond sufficiently to antidepressant treatment, necessitating other treatment approaches. HMG-CoA reductase inhibitors (i.e. statins), which are frequently used for their cardioprotective properties, have also been studied regarding potential antidepressant effects. Possible mechanisms underlying an antidepressant effect of statins may include the anti-inflammatory, antioxidant and lipid lowering properties of this class of drugs. This review provides an overview of this field by reviewing the following aspects: 1) Candidate mechanisms that could mediate putative antidepressant effects of statins; 2) The evidence for and against antidepressant effects of statins in patients with major depressive disorder and among individuals with a medical disease and depressive symptoms; and 3) The safety of statin treatment. Three small placebo-controlled trials conducted in Iran (total N=172) have found that statins as add-on to selective serotonin reuptake inhibitors (SSRIs) have antidepressant effects in patients with major depressive disorder (MDD). Statin treatment in individuals without MDD do not seem to affect mood or protect against development of depression. Treatment with statins - including the combination with SSRIs - is generally considered to be safe. While the initial evidence for the antidepressant effect of the combination of an SSRI and a statin is promising, larger clinical trials, appropriately powered, and with depression as a pre-defined primary endpoint are needed.


Rhamnolipids from non-pathogenic Burkholderia thailandensis E264: Physicochemical characterization, antimicrobial and antibiofilm efficacy against oral hygiene related pathogens.
Biosurfactants are naturally occurring surface active compounds that have mainly been exploited for environmental applications and consumer products, with their biomedical efficacy an emerging area of research. Rhamnolipids area major group of biosurfactants that have been reported for their antimicrobial and antibiofilm efficacy. One of the main limiting factors for scaled up production and downstream applications of rhamnolipids is the fact that they are predominantly produced from the opportunistic pathogen Pseudomonas aeruginosa. In this article, we have reported the production and characterisation of long chain rhamnolipids from non-pathogenic Burkholderia thailandensis E264 (ATCC 700388). We have also investigated the antibacterial and antibiofilm properties of these rhamnolipids against some oral pathogens (Streptococcus oralis, Actinomyces naeslundii, Neisseria mucosa and Streptococcus sanguinis), important for oral health and hygiene. Treating these bacteria with different concentrations of long chain rhamnolipids resulted in a reduction of 3-4 log of bacterial viability, placing these rhamnolipids close to being classified as biocidal. Investigating long chain rhamnolipid efficacy as antibiofilm agents for prospective oral-related applications revealed good potency against oral-bacteria biofilms in a co-incubation experiments, in a pre-coated surface format, in disrupting immature biofilms and has shown excellent combination effect with Lauryl Sodium Sulphate which resulted in a drastic decrease in its minimal inhibitory concentration against different bacteria. Investigating the rhamnolipid permeabilization effect along with their ability to induce the formation of reactive oxygen species has shed light on the mechanism through which inhibition/killing of bacteria may occur.


Update on the safety and efficacy of commercial ultrasound contrast agents in cardiac applications.
Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs.