Variants of Triticum mosaic virus Isolated From Wheat in Colorado Show Divergent Biological Behavior.
Triticum mosaic virus (TriMV) is a recently discovered virus infecting wheat. We compared Colorado isolates C10-492 and C11-775 with the 06-123 isolate. Comparisons were made using enzyme-linked immunosorbent assay (ELISA), infectivity assay, host range, dry weight (DW), inoculation of 'Mace' wheat with temperature-sensitive resistance to Wheat streak mosaic virus, and the deduced amino acid sequence of the coat proteins (CP) and P1 proteins. Both C10-492 and C11-775 infected 'Gallatin' barley and, when compared with 06-123, had significantly reduced ELISA values and virus titers in wheat. Both Colorado isolates caused symptomless infections in Mace, whereas 06-123 caused mosaic symptoms. The amino acid sequences of the CP differed by two and one amino acids for C10-492 and C11-775, respectively, compared with 06-123. The sequence of C10-492 differed from C11-775 by one amino acid. The P1 amino acid sequence of C10-492 and C11-775 differed from 06-123 by three and one amino acids, respectively. The C10-492 and C11-775 isolates reduced DW significantly in 'Karl 92' but significantly less than 06-123. In '2317' wheat, the Colorado isolates did not consistently cause significant reduction in DW, while 06-123 did. The data collectively indicate that C10-492 and C11-775 are isolates of TriMV showing biological behavior diverse from that of 06-123.


Nonlinear optics.
Recent advances in the field of nonlinear optical phenomena are reviewed with particular emphasis placed on such topics as parametric oscillation, self-focusing and trapping of laser beams, and stimulated Raman, Rayleigh, and Brillouin scattering. The optical frequency radiation is treated classically in terms of the amplitudes and phases of the electromagnetic fields. The interactions of light waves in a material are then formulated in terms of Maxwell's equations and the electric dipole approximation. In this method, non-linear susceptibility tensors are introduced which relate the induced dipole moment to a power series expansion in field strengths. The tensor nature and the frequency dependence of the nonlinearity coefficients are considered. The various experimental observations are described and interpreted in terms of this formalism.


Active chest compression-decompression for cardiopulmonary resuscitation.
Active compression-decompression cardiopulmonary resuscitation (ACDR CPR) uses a hand-held suction device, applied mid sternum, to compress the chest then actively decompress the chest after each compression. Randomised controlled trials on use of active compression decompression cardiopulmonary resuscitation have results which are discordant. To determine clinical effects and safety of active compression-decompression cardiopulmonary resuscitation compared with standard manual cardiopulmonary resuscitation (STR). We searched the Cochrane Controlled Trials Register (May 2002), MEDLINE and EMBASE. We checked the reference list of retrieved articles and contacted enterprises manufacturing the active decompression devices. All randomised or quasi-randomised studies comparing active compression-decompression cardiopulmonary resuscitation compared with standard manual cardiopulmonary resuscitation in adults with a cardiac arrest who received cardiopulmonary resuscitation by a trained medical or paramedical team. Data were independently extracted. All data were analysed on an intention-to-treat basis. The authors of the primary studies were contacted for more information when needed. Studies were cumulated, if appropriate, and pooled relative risk (RR) estimated. Subgroup analysis according to setting (out of hospital or in hospital) and attending team composition (with physician or paramedic only) were predefined. Twelve trials were included: 10 were in out-of-hospital settings, one set in-hospital only and one had both in-hospital and out-of-hospital components. Allocation concealment was adequate in 4 trials. The two in-hospital studies were very different in quality (A and C) and size (773 and 53 patients). Both found no differences between ACDR CPR and STR in any outcome. Trials conducted in out-of-hospital settings cumulated 4162 patients. There were no differences between ACDR CPR and STR for mortality either immediately (RR 0.98 [95% CI 0.94 - 1.03]) or at hospital discharge (RR 0.99 [95% CI 0.98 - 1.01]). The pooled RR of neurological impairment, any severity, was 1.71 [95% CI 0.90 - 3.25], with a non-significant trend to more frequent severe neurological damage in survivors of ACDR CPR (RR 3.11 [95% CI 0.98 - 9.83]). However, assessment of neurological outcome was limited and there were few patients with neurological damage. There was no difference between ACDR CPR and STR with regard complications such as rib or sternal fractures, pneumothorax or hemothorax (RR 1.09 [95% CI 0.86 - 1.38]). Skin trauma and ecchymosis were more frequent with ACDR CPR. Active chest compression-decompression in patients with cardiac arrest is not associated with clear benefit.


A technique for setting analytical thresholds in massively parallel sequencing-based forensic DNA analysis.
Amplicon (targeted) sequencing by massively parallel sequencing (PCR-MPS) is a potential method for use in forensic DNA analyses. In this application, PCR-MPS may supplement or replace other instrumental analysis methods such as capillary electrophoresis and Sanger sequencing for STR and mitochondrial DNA typing, respectively. PCR-MPS also may enable the expansion of forensic DNA analysis methods to include new marker systems such as single nucleotide polymorphisms (SNPs) and insertion/deletions (indels) that currently are assayable using various instrumental analysis methods including microarray and quantitative PCR. Acceptance of PCR-MPS as a forensic method will depend in part upon developing protocols and criteria that define the limitations of a method, including a defensible analytical threshold or method detection limit. This paper describes an approach to establish objective analytical thresholds suitable for multiplexed PCR-MPS methods. A definition is proposed for PCR-MPS method background noise, and an analytical threshold based on background noise is described.


Endocrine-disrupting chemicals: economic, regulatory, and policy implications.
Endocrine-disrupting chemicals (EDCs) substantially cost society as a result of increases in disease and disability but-unlike other toxicant classes such as carcinogens-have yet to be codified into regulations as a hazard category. This Series paper examines economic, regulatory, and policy approaches to limit human EDC exposures and describes potential improvements. In the EU, general principles for EDCs call for minimisation of human exposure, identification as substances of very high concern, and ban on use in pesticides. In the USA, screening and testing programmes are focused on oestrogenic EDCs exclusively, and regulation is strictly risk-based. Minimisation of human exposure is unlikely without a clear overarching definition for EDCs and relevant pre-marketing test requirements. We call for a multifaceted international programme (eg, modelled on the International Agency for Research in Cancer) to address the effects of EDCs on human health-an approach that would proactively identify hazards for subsequent regulation.


A case of unilateral post-COVID-19 adrenal haemorrhage and follow-up during pregnancies.
The spectrum of endocrine-related complications of COVID-19 infection is expanding; one of the most concerning of which is adrenal haemorrhage due to the risk of catastrophic adrenal crisis. In this study, we present a case that highlights the challenging management of a large, indeterminate unilateral adrenal mass during pregnancy and draws attention to a rare yet probably underestimated complication of COVID-19. During hospitalization for severe COVID-19 pneumonia, a 26-year-old woman was incidentally found to have a 12.5 cm heterogeneous left adrenal mass. Soon after the discovery, she became pregnant and upon referral, she was in the seventh week of gestation, without clinical or biochemical features of hormonal excess. The uncertainty of the diagnosis and the risks of malignancy and surgical intervention were discussed with the patient, and a period of radiological surveillance was agreed upon. An MRI scan performed 3 months later showed a size reduction of the adrenal lesion to 7.9 cm, which was against malignancy. A Doppler ultrasound showed a non-vascular, well-defined round lesion consistent with an adrenal haematoma, likely a complication of the recent COVID-19 infection. The multidisciplinary team recommended further radiological follow-up. The patient then spontaneously had miscarriage at 12 weeks gestation. Subsequent radiological surveillance showed a further size reduction of the adrenal lesion to 5.5 cm. The patient conceived again during follow-up, and the repeated Doppler ultrasound showed stable appearances of the adrenal mass, and thus, it was agreed to continue radiological monitoring after delivery. The pregnancy was uneventful, and the patient delivered a healthy baby. An MRI scan performed after delivery showed a stable but persistent lesion consistent with a likely underlying adrenal lesion. Unilateral adrenal haemorrhage can occur as a complication of COVID-19 and should be considered in the differential diagnosis of heterogeneous adrenal masses if there is a history of recent infection. Management of large indeterminate adrenal masses during pregnancy poses several challenges and should be led by an experienced multidisciplinary team. Underlying adrenal tumours may trigger non-traumatic haemorrhages, especially if exacerbated by stressful illness.


Interaction between amino propeptides of type XI procollagen alpha1 chains.
Type XI collagen is a quantitatively minor yet essential constituent of the cartilage extracellular matrix. The amino propeptide of the alpha1 chain remains attached to the rest of the molecule for a longer period of time after synthesis than the other amino propeptides of type XI collagen and has been localized to the surface of thin collagen fibrils. Yeast two-hybrid system was used to demonstrate that a homodimer of alpha1(XI) amino propeptide (alpha1(XI)Npp) could form in vivo. Interaction was also confirmed using multi-angle laser light scattering, detecting an absolute weight average molar mass ranging from the size of a monomer to the size of a dimer (25,000-50,000 g/mol), respectively. Binding was shown to be saturable by ELISA. An interaction between recombinant alpha1(XI)Npp and the endogenous alpha1(XI)Npp was observed, and specificity for alpha1(XI)Npp but not alpha2(XI)Npp was demonstrated by co-precipitation. The interaction between the recombinant form of alpha1(XI)Npp and the endogenous alpha1(XI)Npp resulted in a stable association during the regeneration of cartilage extracellular matrix by fetal bovine chondrocytes maintained in pellet culture, generating a protein that migrated with an apparent molecular mass of 50-60 kDa on an SDS-polyacrylamide gel.


Fecal parasite risk in the endangered proboscis monkey is higher in an anthropogenically managed forest environment compared to a riparian rain forest in Sabah, Borneo.
Understanding determinants shaping infection risk of endangered wildlife is a major topic in conservation medicine. The proboscis monkey, Nasalis larvatus, an endemic primate flagship species for conservation in Borneo, is endangered through habitat loss, but can still be found in riparian lowland and mangrove forests, and in some protected areas. To assess socioecological and anthropogenic influence on intestinal helminth infections in N. larvatus, 724 fecal samples of harem and bachelor groups, varying in size and the number of juveniles, were collected between June and October 2012 from two study sites in Malaysian Borneo: 634 samples were obtained from groups inhabiting the Lower Kinabatangan Wildlife Sanctuary (LKWS), 90 samples were collected from groups of the Labuk Bay Proboscis Monkey Sanctuary (LBPMS), where monkeys are fed on stationary feeding platforms. Parasite risk was quantified by intestinal helminth prevalence, host parasite species richness (PSR), and eggs per gram feces (epg). Generalized linear mixed effect models were applied to explore whether study site, group type, group size, the number of juveniles per group, and sampling month predict parasite risk. At the LBPMS, prevalence and epg of Trichuris spp., strongylids, and Strongyloides spp. but not Ascaris spp., as well as host PSR were significantly elevated. Only for Strongyloides spp., prevalence showed significant changes between months; at both sites, the beginning rainy season with increased precipitation was linked to higher prevalence, suggesting the external life cycle of Strongyloides spp. to benefit from humidity. Higher prevalence, epgs, and PSR within the LBPMS suggest that anthropogenic factors shape host infection risk more than socioecological factors, most likely via higher re-infection rates and chronic stress. Noninvasive measurement of fecal parasite stages is an important tool for assessing transmission dynamics and infection risks for endangered tropical wildlife. Findings will contribute to healthcare management in nature and in anthropogenically managed environments.


Measuring the impact of public health policy.
Effective health policies and allocation of public health resources can substantially improve public health. An objective of public health practitioners and researchers is to identify key metrics that would help improve effective policies and terminate poor ones. We review articles published in 2008 surrounding measurement issues for public health policy and present a set of recommendations for future emphasis. We found that a set of consensus metrics for population health performance should be developed. However, considerable work is needed to develop appropriate metrics covering policy approaches that can affect large populations, intervention approaches within organizations, and individual-level behavioral approaches for prevention or disease management.


Cell cycle control of DNA replication.
The initiation of DNA replication in eukaryotic cells is a highly regulated process that leads to the duplication of the genetic information for the next cell generation. This requires the ordered assembly of many proteins at the origins of DNA replication to form a competent, pre-replicative chromosomal state. In addition to this competent complex, at least two cell cycle regulated protein kinase pathways are required to affect a transition to a post-replicative chromosomal state. Protein kinases required to establish mitosis prevent re-replication of the DNA. As cells exit mitosis, the cell cycle is reset, allowing the establishment of a new, competent replication state.


Urine Exosomes: An Emerging Trove of Biomarkers.
Exosomes are released by most cells and can be isolated from all biofluids including urine. Exosomes are small vesicles formed as part of the endosomal pathway that contain cellular material surrounded by a lipid bilayer that can be traced to the plasma membrane. Exosomes are potentially a more targeted source of material for biomarker discovery than unfractionated urine, and provide diagnostic and pathophysiological information without an invasive tissue biopsy. Cytoplasmic contents including protein, mRNA, miRNA, and lipids have all been studied within the exosomal fraction. Many prospective urinary exosomal biomarkers have been successfully identified for a variety of kidney or genitourinary tract conditions; detection of systemic conditions may also be possible. Isolation and analysis of exosomes can be achieved by several approaches, although many require specialized equipment or involve lengthy protocols. The need for timely analysis in the clinical setting has driven considerable innovation with several promising options recently emerging. Consensus on exosome isolation, characterization, and normalization procedures would resolve critical clinical translational bottlenecks for existing candidate exosomal biomarkers and provide a template for additional discovery studies.


Comparison of the complexation of fluoroquinolone antimicrobials with metal ions by nuclear magnetic resonance spectroscopy.
The complexation of fluoroquinolone antimicrobials with various metal ions have been studied in aqueous solution (pD 2.5, 37 degrees C) by 1H and 13C-NMR spectroscopy. The compounds examined are levofloxacin, ciprofloxacin and lomefloxacin. In each drug, new signals have appeared by the addition of Al3+, suggesting that the complexes are formed between the drug and Al3+ and that the ligand exchange is slow on the NMR time scale. Solution structure of the major species in the presence of 2.0 mol equiv of Al3+ has been proposed based on the large downfield shifts of some specific protons. Signals of both the coordinated and free drugs have shown slight broadening at 90 degrees C due to the enhanced rate in ligand dissociation process, though the coalescence phenomena are not observed even at this temperature. Thus, the complexes are supposed to be stable at the physiological condition. Titration experiments have revealed that the binding ability of levofloxacin toward Al3+ is much stronger than that of ciprofloxacin and lomefloxacin at pD 2.5. In contrast to the complexation with Al3+, the binding of these drugs with other metal ions such as Ca2+ and Mg2+ is much weaker; NMR signals have shown no appreciable downfield shift by the addition of Ca2+ and Mg2+. Based on these results, it is concluded that the fluoroquinolone antimicrobials examined in the present study at pD 2.5 exist as stable complexes in the presence of Al3+ and the absorptivity of the drugs on oral administration could be affected by Al3+.


Importance of age at infection with HIV-1 for survival and development of AIDS in UK haemophilia population. UK Haemophilia Centre Directors' Organisation.
Greater age at infection with HIV-1 is known to be associated with shorter time to development of AIDS, but the size of the differences between people infected in infancy and those infected in old age has not been examined in a single large population of patients with death as an endpoint. We, therefore, investigated the role of age at seroconversion in the entire UK population of haemophiliacs. We studied 1216 HIV-1-infected haemophilia patients in the UK who were registered with the National Haemophilia Register and were alive on Jan 1, 1985. Their estimated ages at HIV-1 seroconversion ranged from 8 months to 79 years. 10 years after seroconversion 67% (95% Cl 64-69) of the population were still alive. Survival was strongly related to age at seroconversion (86% [82-90], 72% [68-76], 45% [39-51], and 12% [5-21] at 10 years among those patients who seroconverted at ages < 15, 15-34, 35-54, and > or = 55). This steep age-gradient in survival was not explained by deaths expected in the absence of HIV infection or by confounding with other factors such as haemophilia type or severity. The age-gradient was steeper for survival (ie, time from HIV-1 infection to death) than for time to diagnosis of AIDS, partly because survival after an AIDS diagnosis was poorer in older patients, and there was also a substantial increase in mortality among HIV-infected patients who did not satisfy the formal AIDS definition and this increase was greater in older patients. Age at infection with HIV-1 is a more important determinant of survival than has previously been appreciated. Age should, therefore, be considered in future studies of disease progression, and studies that compare people infected at different ages should provide insight into the biology of the immune response to HIV-1.


Consumers' intention to use health recommendation systems to receive personalized nutrition advice.
Sophisticated recommendation systems are used more and more in the health sector to assist consumers in healthy decision making. In this study we investigate consumers' evaluation of hypothetical health recommendation systems that provide personalized nutrition advice. We examine consumers' intention to use such a health recommendation system as a function of options related to the underlying system (e.g. the type of company that generates the advice) as well as intermediaries (e.g. general practitioner) that might assist in using the system. We further explore if the effect of both the system and intermediaries on intention to use a health recommendation system are mediated by consumers' perceived effort, privacy risk, usefulness and enjoyment. 204 respondents from a consumer panel in the Netherlands participated. The data were collected by means of a questionnaire. Each respondent evaluated three hypothetical health recommendation systems on validated multi-scale measures of effort, privacy risk, usefulness, enjoyment and intention to use the system. To test the hypothesized relationships we used regression analyses. We find evidence that the options related to the underlying system as well as the intermediaries involved influence consumers' intention to use such a health recommendation system and that these effects are mediated by perceptions of effort, privacy risk, usefulness and enjoyment. Also, we find that consumers value usefulness of a system more and enjoyment less when a general practitioner advices them to use a health recommendation system than if they use it out of their own curiosity. We developed and tested a model of consumers' intention to use a health recommendation system. We found that intermediaries play an important role in how consumers evaluate such a system over and above options of the underlying system that is used to generate the recommendation. Also, health-related information services seem to rely on endorsement by the medical sector. This has considerable implications for the distribution as well as the communication channels of health recommendation systems which may be quite difficult to put into practice outside traditional health service channels.


SU-E-J-32: Evaluation of the Dosimetric Accuracy of Stereotactic Radiosurgery with Cone-Beam Computed Tomography Localization.
To evaluate the dosimetric accuracy of stereotactic radiosurgery (SRS) with cone-beam computed tomography (CBCT) guided patient localization. A Novalis TX linear accelerator with high definition multileaf collimator (HDMLC) was used for SRS treatments. 20 patients immobilized with the noninvasive BrainLab U-frame system and thermoplastic mask were selected to evaluate the dosimetric accuracy of CBCT image-guided SRS by the BrainLab iPlan Phantom Mapping module. The contours of the PTV and critical organ were transferred directly from the planning CT and MR images to the CBCT images after image registrations. The delivered dose distributions could be calculated and analyzed by copying the original treatment plans to the CBCT images and assigning the treatment isocenters on the CBCT images according to the couch shifts acquired after planning CT and CBCT image registrations. The CT electron density calibration curve used for original plans was also applied for the CBCT-based planning. The average minimum dose, mean dose, and maximum dose in PTV of the original plans and the CBCT plans were 95.45%±3.80% and 92.88%±3.25%, 110.59%±1.81% and 110.11%±2.40%, 116.55%±3.11% and 115.93%±2.78%, respectively. In the original treatment plans, the average 100% prescription dose coverage of GTV and PTV were 99.99% and 99.81%, respectively. In the CBCT plans, the average 100% prescription dose coverage of GTV and PTV were 99.90% and 98.20%, respectively. The average conformity index of the original plans and the CBCT plans were 1.846 and 1.863, respectively. Data demonstrated that the dose distributions calculated in the CBCT images were comparable to the original treatment plans. The CBCT plans only indicated a slightly higher conformity index and lower average minimum dose, mean dose, maximum dose, GTV coverage, and PTV coverage compared to the original treatment plans. Therefore, the CBCT guided localization was considered effective to assure dosimetric accuracy in SRS.


Recurrence Is Rare Following Complete Eradication of Intestinal Metaplasia in Patients With Barrett's Esophagus and Peaks at 18 Months.
There have been few studies describing the long-term durability of complete eradication of intestinal metaplasia (CE-IM) in patients with Barrett's esophagus (BE)-related neoplasia who received endoscopic eradication therapy (EET). Data are needed to guide surveillance interval protocols and identify patients at risk for recurrence. We assessed the rate of recurrence of intestinal metaplasia and dysplasia, histologic features, and outcomes after recurrence of CE-IM, and identified factors associated with recurrence. We performed a prospective study of 807 patients with BE who underwent EET, which produced CE-IM, at 4 tertiary-care referral centers, from January 2013 to October 2018. Kaplan-Meier estimates of cumulative incidence rates (IR) of recurrence were calculated for up to 5 years following CE-IM and were stratified by baseline level of histology. Density estimates of recurrence were used to determine the change in the rate of recurrence over time. We conducted logistic regression analysis to identify factors associated with recurrence. Intestinal metaplasia recurred in 121 patients (15%; IR, 5.2/100 person-years), and dysplasia recurred in 41 patients (5.1%; IR, 1.8/100 person-years), after a median follow-up time of 2317 person-years. The rate of recurrence was not constant and the time to any recurrence converged to a normal distribution; recurrences peaked at 1.6 y after patients had CE-IM. Baseline high-grade dysplasia or intramucosal cancer (adjusted odds ratio [aOR], 4.19), presence of reflux symptoms (aOR, 12.1) or hiatal hernia (aOR, 13.8), and number of sessions required to achieve CE-IM (aOR, 1.8) were associated with recurrence. In a prospective study of a large cohort of patients with BE undergoing EET, we found a low rate of recurrence after CE-IM. The rate of recurrence peaked at 1-2 y after CE-IM. These findings indicate that aggressive surveillance might not be necessary more than 1 y after CE-IM and should be considered in surveillance guidelines. Clinicaltrials.gov no: NCT02634645.


Current market rates for scholarly publishing services.
For decades, the supra-inflation increase of subscription prices for scholarly journals has concerned scholarly institutions. After years of fruitless efforts to solve this "serials crisis", open access has been proposed as the latest potential solution. However, the prices for open access publishing are also high and are rising well beyond inflation. What has been missing from the public discussion so far is a quantitative approach to determine the actual costs of efficiently publishing a scholarly article using state-of-the-art technologies, such that informed decisions can be made as to appropriate price levels. Here we provide a granular, step-by-step calculation of the costs associated with publishing primary research articles, from submission, through peer-review, to publication, indexing and archiving. We find that these costs range from less than US$200 per article in modern, large-scale publishing platforms using post-publication peer-review, to about US$1,000 per article in prestigious journals with rejection rates exceeding 90%. The publication costs for a representative scholarly article today come to lie at around US$400. We discuss the additional non-publication items that make up the difference between publication costs and final price.


Polarization of 'water-skies' above arctic open waters: how polynyas in the ice-cover can be visually detected from a distance.
The foggy sky above a white ice-cover and a dark water surface (permanent polynya or temporary lead) is white and dark gray, phenomena called the 'ice-sky' and the 'water-sky,' respectively. Captains of icebreaker ships used to search for not-directly-visible open waters remotely on the basis of the water sky. Animals depending on open waters in the Arctic region may also detect not-directly-visible waters from a distance by means of the water sky. Since the polarization of ice-skies and water-skies has not, to our knowledge, been studied before, we measured the polarization patterns of water-skies above polynyas in the arctic ice-cover during the Beringia 2005 Swedish polar research expedition to the North Pole region. We show that there are statistically significant differences in the angle of polarization between the water-sky and the ice-sky. This polarization phenomenon could help biological and man-made sensors to detect open waters not directly visible from a distance. However, the threshold of polarization-based detection would be rather low, because the degree of linear polarization of light radiated by water-skies and ice-skies is not higher than 10%.


Efficient production and purification of recombinant murine kindlin-3 from insect cells for biophysical studies.
Kindlins are essential coactivators, with talin, of the cell surface receptors integrins and also participate in integrin outside-in signalling, and the control of gene transcription in the cell nucleus. The kindlins are ~75 kDa multidomain proteins and bind to an NPxY motif and upstream T/S cluster of the integrin β-subunit cytoplasmic tail. The hematopoietically-important kindlin isoform, kindlin-3, is critical for platelet aggregation during thrombus formation, leukocyte rolling in response to infection and inflammation and osteoclast podocyte formation in bone resorption. Kindlin-3's role in these processes has resulted in extensive cellular and physiological studies. However, there is a need for an efficient method of acquiring high quality milligram quantities of the protein for further studies. We have developed a protocol, here described, for the efficient expression and purification of recombinant murine kindlin-3 by use of a baculovirus-driven expression system in Sf9 cells yielding sufficient amounts of high purity full-length protein to allow its biophysical characterization. The same approach could be taken in the study of the other mammalian kindlin isoforms.


Short-term low calorie diet intervention reduces serum advanced glycation end products in healthy overweight or obese adults.
Obesity is a metabolic and cardiovascular risk factor. A low calorie diet (LCD) is one of the treatment modalities for weight loss. Serum advanced glycation end products (AGEs) are linked to increased atherogenicity and inflammation in diseases such as diabetes and renal failure. Obesity has an inflammatory component, but interestingly there are no studies on serum AGE levels in obesity or on the effects of LCD as a therapeutic measure on these markers of glycation. We hypothesized that weight loss by caloric restriction has a beneficial effect on serum AGE levels. We investigated the prospective effects of a sole LCD intervention for weight loss on serum AGEs in a cohort of overweight and non-morbidly obese but otherwise healthy subjects. A total of 37 Japanese subjects (30 females, 7 males, mean age 48.2 +/- 9.3 years) with a mean BMI of 28.3 +/- 3.2 participated in this study. During the intervention period of 2 months, they were placed on an LCD (Diet's; 5,023 kJ/day) with meal replacement every dinner. The following data were evaluated pre- and post-intervention: AGEs, BMI, waist circumference, blood pressure, serum glucose, cholesterol, triglycerides, HDL- and LDL- cholesterol. After the intervention, BMI levels were clearly reduced by 6.3% (p < 0.001), waist circumference by 5.7% (p < 0.002) and triglycerides by 11.9 % (p < 0.002). At baseline, AGEs levels were 63 +/- 11 AU for obese subjects and 63 +/- 14 for control subjects (not significant). After intervention, AGEs were reduced by 7.21% (range 0-35%, p < 0.001). The percent change in AGEs was significantly and positively correlated with that of triglycerides (r = 0.42, p < 0.009), waist circumference (r = 0.40, p < 0.011), and BMI (r = 0.42, p < 0.007). We show for the first time that serum AGEs can be reduced by an LCD intervention on weight loss, a change that correlates with the reduction in triglycerides. This may plausibly be a reflection of a reduction in glycation/lipoxidation due to the caloric restriction and its metabolic consequences, or it may be due to the decreased intake of food containing glycotoxins, or a combination of both.


New hominin remains and revised context from the earliest Homo erectus locality in East Turkana, Kenya.
The KNM-ER 2598 occipital is among the oldest fossils attributed to Homo erectus but questions have been raised about whether it may derive from a younger horizon. Here we report on efforts to relocate the KNM-ER 2598 locality and investigate its paleontological and geological context. Although located in a different East Turkana collection area (Area 13) than initially reported, the locality is stratigraphically positioned below the KBS Tuff and the outcrops show no evidence of deflation of a younger unit, supporting an age of >1.855 Ma. Newly recovered faunal material consists primarily of C4 grazers, further confirmed by enamel isotope data. A hominin proximal 3rd metatarsal and partial ilium were discovered <50 m from the reconstructed location where KNM-ER 2598 was originally found but these cannot be associated directly with the occipital. The postcrania are consistent with fossil Homo and may represent the earliest postcrania attributable to Homo erectus.


Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors.
Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n = 7), or a diuretic, hydrochlorothiazide (n = 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P = 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)(-1) pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)(-1); P = 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)(-1)), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)(-1); P = 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P = 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r = 0.74, P = 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin-angiotensin-aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients.


The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL oncogene.
The LIM only protein Lmo2 plays an important role in hematopoiesis and leukemogenesis. Lmo2 acts as a bridging molecule between components of hematopoietic gene regulatory protein complexes. We used the yeast two-hybrid system to identify novel Lmo2 interacting proteins and found that the AF6 protein binds to Lmo2. AF6 is a recurrent fusion partner of MLL, the human homolog of Drosophila trithorax chromatin remodeling protein that is involved in childhood leukemia and mixed lineage leukemia. Our data support the notion that recurrent fusion partners of chimeric MLL proteins recruit hematopoietic gene regulatory complexes.


Assessing the health attitudes, beliefs, and behaviors of African Americans attending church: a comparison from two communities.
Public health officials and researchers continue to be increasingly concerned about the health of populations of color, especially African Americans. A survey was administered in African American churches in two communities (Wichita, KS and Tuscaloosa, AL) to gather information concerning health behaviors and beliefs and to design interventions that might improve their health status. The study examined the homogeneity of attitudes, beliefs, and behaviors across these samples and to determine the readiness to change using the Transtheoritical Model. Individuals completed a 33-item survey: 6 demographic questions, 12 health behavior questions, 8 health belief questions, 3 church attendance questions, and 4 church-based health promotion program questions. The total sample consisted of 429 respondents. The results showed that 93% of respondents have had their blood pressure checked in the past 2 years. While only 44% indicated eating a high fiber diet during the week. Thirty percent of respondents indicated that their health was dependent on fate or destiny. The findings from this study confirm that among both samples that health attitudes, beliefs, and behaviors need to be changed to lower the risk of certain diseases and disorders. The findings also indicate that both samples have similar beliefs about health that may have important implications for disseminating information to the community. Innovative and culturally sensitive programs are needed in the African American community if disparities in health are to diminish.


Preliminary Analysis From the Craniofacial Collaboration United Kingdom Developmental Outcomes in Children With Sagittal Synostosis.
The Craniofacial Collaboration United Kingdom (CC-UK) was established across the 4 Highly Specialized Craniofacial Centres (HSCCs) in the UK in 2015. This is the first wave of data to be analyzed, looking at 3-year-old children with sagittal synostosis who have had primary corrective surgery. This is a comprehensive, homogenous dataset, looking at parental measures of development and behavior. The results indicate that the majority of children are rated by their parents as falling within one standard deviation of the mean for both developmental and behavioral measures. However, there was a trend across the age groups within the sample which, although not statistically significant, indicates that more developmental difficulties may become apparent as children get older. Behavior was rated as more problematic, and the areas of greatest parental concern were Conduct (challenging or confrontational behavior) and Hyperactivity domains, where 24% of children were rated as within the clinically significant range. Although the majority of children were rated as falling within the average range, the difference in the mean between the sagittal and the normative group was significant in 5 of the 6 behavioral domains. Further research is required to examine whether these findings are stable over time and to look at the mechanism which might be driving these changes. It is anticipated that future CC-UK analysis will elucidate this more clearly.


Current treatment practice of Guillain-Barré syndrome.
To define the current treatment practice of Guillain-Barré syndrome (GBS). The study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account. We excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE. In current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations.


Controlling Fragment Competition on Pathways to Addressable Self-Assembly.
Addressable self-assembly is the formation of a target structure from a set of unique molecular or colloidal building blocks, each of which occupies a defined location in the target. The requirement that each type of building block appears exactly once in each copy of the target introduces severe restrictions on the combinations of particles and on the pathways that lead to successful self-assembly. These restrictions can limit the efficiency of self-assembly and the final yield of the product. In particular, partially formed fragments may compete with each other if their compositions overlap, since they cannot be combined. Here, we introduce a "completability" algorithm to quantify competition between self-assembling fragments and use it to deduce general principles for suppressing the effects of fragment incompatibility in the self-assembly of small addressable clusters. Competition originates from loops in the bonding network of the target structure, but loops may be needed to provide structural rigidity and thermodynamic stability. An optimal compromise can be achieved by careful choice of bonding networks and by promoting semihierarchical pathways that rule out competition between early fragments. These concepts are illustrated in simulations of self-assembly in two contrasting addressable targets of 20 unique components each.


On measurement of brain elastic response in vivo.
The elastic response behavior of brain tissue in vivo has been shown to be sensitive to the physiological environment of the brain and thus represents a useful parameter for identifying effects of controlled changes on the system. Here we describe a method for measuring brain elastic response using an epidural pressure-depth transducer and a minimum number of insertions. The method also serves to identify the nonlinear response of brain tissue.


Bacterial diversity shift determined by different diets in the gut of the spotted wing fly Drosophila suzukii is primarily reflected on acetic acid bacteria.
The pivotal role of diet in shaping gut microbiota has been evaluated in different animal models, including insects. Drosophila flies harbour an inconstant microbiota among which acetic acid bacteria (AAB) are important components. Here, we investigated the bacterial and AAB components of the invasive pest Drosophila suzukii microbiota, by studying the same insect population separately grown on fruit-based or non-fruit artificial diet. AAB were highly prevalent in the gut under both diets (90 and 92% infection rates with fruits and artificial diet respectively). Fluorescent in situ hybridization and recolonization experiments with green fluorescent protein (Gfp)-labelled strains showed AAB capability to massively colonize insect gut. High-throughput sequencing on 16S rRNA gene indicated that the bacterial microbiota of guts fed with the two diets clustered separately. By excluding AAB-related OTUs from the analysis, insect bacterial communities did not cluster separately according to the diet, suggesting that diet-based diversification of the community is primarily reflected on the AAB component of the community. Diet influenced also AAB alpha-diversity, with separate OTU distributions based on diets. High prevalence, localization and massive recolonization, together with AAB clustering behaviour in relation to diet, suggest an AAB role in the D. suzukii gut response to diet modification.


Preterm Birth and Poor Fetal Growth as Risk Factors of Attention-Deficit/ Hyperactivity Disorder.
Previous studies have shown an association between prematurity and attention- abstract deficit/hyperactivity disorder (ADHD). Results concerning late preterm infants are controversial, and studies examining fetal growth represented by weight for gestational age are scarce. Our objective was to examine the association between gestational age by each week of fetal maturity, weight for gestational age, and ADHD. In this population-based study, 10 321 patients with ADHD, diagnosed according to the International Classification of Diseases and 38 355 controls individually matched for gender, date and place of birth, were identified from Finnish nationwide registers. Perinatal data were obtained from the Finnish Medical Birth Register. Conditional logistic regression was used to examine the association between gestational age, weight for gestational age, and ADHD after controlling for confounding factors. The risk of ADHD increased by each declining week of gestation. The associations were robust after adjusting for confounders. An elevated risk also was seen among late preterm and early term infants. As for fetal growth, the odds ratio showed a U-shaped curve with an increased risk seen when the weight for gestational age was 1 SD below and 2 SD above the mean. Our findings suggest that each gestational week has significance for child's subsequent neurodevelopment and risk for ADHD. We also showed that poor fetal growth increased the risk of ADHD. This highlights the importance of taking into account both prematurity and poor fetal growth when planning the timing of birth as well as later follow-up and support policies.


Association between yogurt, milk, and cheese consumption and common carotid artery intima-media thickness and cardiovascular disease risk factors in elderly women.
Despite the contribution of dairy foods to total dietary saturated fat intake, available data indicate that dairy consumption may lower the risk of cardiovascular disease. The objective of this study was to investigate the relation between consumption of milk, cheese, and yogurt and common carotid artery intima-media thickness (CCA-IMT) in a cohort of elderly women. Dairy consumption was assessed with a validated food-frequency questionnaire in 1080 participants randomly selected from ambulant white women aged >70 y living in Perth, Western Australia. CCA-IMT was assessed by using B-mode carotid ultrasound 3 y later. Cardiovascular disease risk factors, including serum lipids and blood pressure, were assessed at baseline. Total dairy product, milk, and cheese consumption was not associated with CCA-IMT (P > 0.05), whereas yogurt consumption was negatively associated with CCA-IMT (unadjusted standardized β = -0.081, P = 0.008; baseline risk factor-adjusted standardized β = -0.075, P = 0.015). Participants who consumed >100 g yogurt/d had a significantly lower CCA-IMT than did participants with lower consumption (unadjusted = -0.024 mm, P = 0.002). This relation remained significant after adjustment for baseline, dietary, and lifestyle risk factors (multivariable analysis = -0.023 mm, P = 0.003). Increased consumption of yogurt, but not of other dairy products, is associated with a lower CCA-IMT, independent of other risk factors.


Water Fluoridation and Dental Caries in U.S. Children and Adolescents.
Fluoridation of America's drinking water was among the great public health achievements of the 20th century. Yet there is a paucity of studies from the past 3 decades investigating its dental health benefits in the U.S. This cross-sectional study sought to evaluate associations between availability of community water fluoridation (CWF) and dental caries experience in the U.S. child and adolescent population. County-level estimates of the percentage of population served by CWF (% CWF) from the Centers for Disease Control and Prevention's Water Fluoridation Reporting System were merged with dental examination data from 10 y of National Health and Nutrition Examination Surveys (1999 to 2004 and 2011 to 2014). Dental caries experience in the primary dentition (decayed and filled tooth surfaces [dfs]) was calculated for 7,000 children aged 2 to 8 y and in the permanent dentition (decayed, missing, and filled tooth surfaces [DMFS]) for 12,604 children and adolescents aged 6 to 17 y. Linear regression models estimated associations between % CWF and dental caries experience with adjustment for sociodemographic characteristics: age, sex, race/ethnicity, rural-urban location, head-of-household education, and period since last dental visit. Sensitivity analysis excluded counties fluoridated after 1998. In unadjusted analysis, caries experience in the primary dentition was lower in counties with ≥75% CWF (mean dfs = 3.3; 95% confidence limit [CL] = 2.8, 3.7) than in counties with <75% CWF (mean dfs = 4.6; 95% CL = 3.9, 5.4), a prevented fraction of 30% (95% CL = 11, 48). The difference was also statistically significant, although less pronounced, in the permanent dentition: mean DMFS (95% CL) was 2.2 (2.0, 2.4) and 1.9 (1.8, 2.1), respectively, representing a prevented fraction of 12% (95% CL = 1, 23). Statistically significant associations likewise were seen when % CWF was modeled as a continuum, and differences tended to increase in covariate-adjusted analysis and in sensitivity analysis. These findings confirm a substantial caries-preventive benefit of CWF for U.S. children and that the benefit is most pronounced in primary teeth.


Undocumented African Immigrants' Experiences of HIV Testing and Linkage to Care.
In the United States, undocumented African immigrants living with HIV enter care late, potentially leading to adverse individual and population health outcomes, yet little is known about the specific experiences of HIV diagnosis and linkage to care among this population. We conducted individual, semi-structured interviews with adults who were undocumented African immigrants living with HIV in New York City. Interviews explored perspectives regarding individual, social, institutional, and societal barriers and facilitators of HIV testing and linkage to care. Of 14 participants from 9 different African countries, 9 were women and the median age was 44 years (interquartile range: 42-50). Participants described fear of discovery by immigration authorities as a substantial barrier to HIV testing and linking to initial medical appointments. Actual and perceived structural barriers to both testing and care linkage included difficulty obtaining health insurance and a belief that undocumented immigrants are ineligible for any health services. Participants also expressed reluctance to be tested because of HIV-related stigma within the immigrant communities that they heavily relied on. After diagnosis, however, participants overwhelmingly described a positive role of health and social service providers in facilitating linkage to HIV care. Concerns about immigration status and HIV-related stigma are significant barriers to HIV testing and linkage to care among undocumented African immigrants. Multilevel efforts to reduce stigma and increase awareness of available services could enhance rates of HIV testing and care linkage in this population.


Temporal trends in hospital-based episodes of asthma care in a health maintenance organization.
Studies reporting increased asthma hospitalizations and mortality in the United States and abroad have heightened concern about the changing epidemiology of asthma. We studied 20-yr patterns of acute asthma care occurring at two large community hospitals among members of a large health maintenance organization. The presentation focuses on the conceptualization and operationalization of an "episode" of asthma care, defined as a collection of encounters (emergency room visits, urgency care visits, and hospital admissions) that cluster in time, as well as on changes in episode rates over time. We found a statistically significant increase in asthma episodes among boys younger than 5 yr of age that continued unabated from 1967 to 1987 despite a drop in asthma hospitalization rates starting in 1985. We hypothesize that this difference may reflect a change in emergency room management practices and not a true change in the underlying epidemiology of asthma. The concept of an episode of acute asthma care has not been studied in the literature and represents a potentially useful methodologic innovation. Particularly in the context of managed health care systems, studies of such episodes may be less sensitive than studies of hospital admissions to changes in the organization and delivery of acute asthma care, and thus may be better suited for studying changes in the epidemiology of asthma.


Delivering genome sequencing in clinical practice: an interview study with healthcare professionals involved in the 100 000 Genomes Project.
Genome sequencing is poised to be incorporated into clinical care for diagnoses of rare diseases and some cancers in many parts of the world. Healthcare professionals are key stakeholders in the clinical delivery of genome sequencing-based services. Our aim was to explore views of healthcare professionals with experience of offering genome sequencing via the 100 000 Genomes Project. Interview study using thematic analysis. Four National Health Service hospitals in London. Twenty-three healthcare professionals (five genetic clinicians and eight non-genetic clinicians (all consultants), and 10 'consenters' from a range of backgrounds) involved in identifying or consenting patients for the 100 000 Genomes Project. Most participants expressed positive attitudes towards genome sequencing in terms of improved ability to diagnose rare diseases, but many also expressed concerns, with some believing its superiority over exome sequencing had not yet been demonstrated, or worrying that non-genetic clinicians are inadequately prepared to discuss genome sequencing results with patients. Several emphasised additional evidence about utility of genome sequencing in terms of both main and secondary findings is needed. Most felt non-genetic clinicians could support patients during consent, as long as they have appropriate training and support from genetic teams. Many stated genetics experts will play a vital role in training and supporting non-genetic clinicians in variant interpretation and results delivery, particularly for more complex cases. Healthcare professionals responsible for delivering clinical genome sequencing have largely positive views about the potential for genome sequencing to improve diagnostic yield, but also significant concerns about practical aspects of offering these tests. Non-genetic clinicians delivering genome sequencing require guidance and support. Additional empirical evidence is needed to inform policy and practice, including how genome compares to exome sequencing; utility of secondary findings; training, in particular of non-genetic health professionals; and mechanisms whereby genetics teams can offer appropriate support to their non-genetics colleagues.


Are Doppler ultrasonography parameters symmetric between the right and left kidney?
Among numerous modalities applied for evaluation of kidney diseases, Doppler ultrasonography (DU) provides information about the hemodynamic status of the kidneys. Meanwhile, the variability in DU parameters of the right and left kidney is a matter of controversy. The aim of this study was to determine whether any difference exists between the DU indices of the right and left kidney. Retrospectively, we collected DU findings of 25 healthy potential renal transplant donors. All donors underwent renal DU and multidetector computed tomographic angiography before donor nephrectomy. DU indices, including peak systolic volume (PSV), resistive index (RI), pulsatility index (PI), end-diastolic volume (EDV), and acceleration time (AT), were recorded. The median age of the donors was 27 (range 23-39) years. The median PSV, RI, EDV, and AT for the right kidney were 29 cm/sec, 0.59, 10.9 cm/sec, and 50 msec, respectively. For the left kidney, the median PSV, RI, EDV, and AT were, respectively, 26.8 cm/sec, 0.60, 10.6 cm/sec, and 43 msec. Among the DU indices, median PI of the right kidney was significantly different from that of the left kidney (1.02 versus 0.95, P = 0.01). In conclusion, the present study revealed that right kidney DU indices, except for PI, may not differ from those of the left kidney.


Metrics for evaluation of age-related changes in erectile capacity in a rodent model.
Stimulation of the cavernous nerve elicits increases in intracavernosal pressure (ICP) and visible penile erection (VPE) in rats. The observed penile erection can be characterized by the change in ICP and the ratio of ICP over blood pressure (BP; systemic blood pressure). We evaluated correlations between ICP, BP, ICP/BP, and VPE, and the magnitude of the nerve stimulation required to elicit those responses in order to evaluate age-related changes in erectile function in a rodent model. Nine young (3 months) and 10 old (18 months) rats were used. Under anesthesia cavernous nerve stimulation was performed at stimulation strengths ranging from 0.1 to 10 mA. The ICP, BP, ICP/BP, and VPE responses to cavernous nerve stimulation were quantified and compared. Significant correlations were observed between ICP and ICP/BP in both young (r(2) = 0.886) and old (r(2) = 0.962) rats. If the ratio ICP/BP was taken as a metric of VPE and non-erection, then the threshold value for observing a VPE in the majority of animals was > or =0.5 in both young and old rats. However, higher current stimulation was required in the old than in the young animals to achieve erections. Moreover, both the maximal ICP and ICP/BP ratios achieved during erection were also lower in the old (85 +/- 2 cmH(2)O and 0.6 +/- 0.02, respectively) than young (106 +/- 3 cmH(2)O and 0.75 +/- 0.02, respectively) rats (P < 0.0001). Old rats without obvious comorbidities were capable of penile erections, but those erections were accompanied by reduced ICP responses to cavernous nerve stimulation, implying apparently reduced penile rigidity. Taken together our current observations indicate that ICP, ICP/BP, and VPE provide useful metrics/indices of erectile capacity/function, and, moreover, that improved understanding of the inter-relationships among these parameters provides a frame work for further exploration of the mechanistic basis for age-related erectile dysfunction.


Interstratified clays as fundamental particles.
Materials representing common interstratified clay minerals are shown to be composed of aggregates of fundamental particles. Transmission electron microscopy and x-ray diffraction demonstrate that the x-ray diffraction characteristics of a wide range of interstratification can be modeled experimentally by utilizing materials containing only three types of particles. The data have been incorporated into a new model that regards interstratified clay minerals as populations of fundamental particles whose x-ray diffraction patterns result from interparticle diffraction.


Application of the Health Action Process Approach to Social Distancing Behavior During COVID-19.
This study examined the social cognition determinants of social distancing behavior during the COVID-19 pandemic in samples from Australia and the US guided by the health action process approach (HAPA). Participants (Australia: N = 495, 50.1% women; US: N = 701, 48.9% women) completed HAPA social cognition constructs at an initial time-point (T1), and one week later (T2) self-reported their social distancing behavior. Single-indicator structural equation models that excluded and included past behavior exhibited adequate fit with the data. Intention and action control were significant predictors of social distancing behavior in both samples, and intention predicted action and coping planning in the US sample. Self-efficacy and action control were significant predictors of intention in both samples, with attitudes predicting intention in the Australia sample and risk perceptions predicting intention in the US sample. Significant indirect effects of social cognition constructs through intentions were observed. Inclusion of past behavior attenuated model effects. Multigroup analysis revealed no differences in model fit across samples, suggesting that observed variations in the parameter estimates were relatively trivial. Results indicate that social distancing is a function of motivational and volitional processes. This knowledge can be used to inform messaging regarding social distancing during COVID-19 and in future pandemics.


Long-term quality of life after peroral endoscopic myotomy remains compromised in patients with achalasia type III.
Background and study aims Peroral endoscopic myotomy (POEM) is an excellent endoscopic treatment for achalasia. Clinical and manometric parameters are used for evaluation and follow-up. However, clinical success does not guarantee high quality of life (QoL) scores, generating doubts about their direct relationship. We aimed to evaluate QoL scores before and after POEM at medium and long term, to evaluate differences between achalasia subtypes and find which factors related to low QoL scores. Patients and methods Achalasia-confirmed patients undergoing POEM between February 2012 and November 2016. and completing at least 1 year of follow-up, were included. Assessment before and at 1, 6, 12, 24, 36 and 48 months after POEM employed manometry, barium series, Eckardt score, and the AE-18 health-related QoL scale. Demographic, clinical, and procedure characteristics were documented, with comparisons between subgroups. Multiple logistic regression analysis was done. Results 65 of 88 patients were included (38 women, 27 men; median age 47 years, interquartile range [IQR] 20 - 81), and 50 (76.9 %) completed 4 years of follow-up. Eckardt score improved (median, preprocedure 10 vs. post-procedure 2; P = 0.002) and this persisted. There was initial improvement in median integrated relaxation pressure (IRP) (29.4 mmHg [16 - 55] vs. 10.3 mmHg [3 - 18]; P = 0.000) and median QoL scores (40 vs. 68 at 1 month; P = 0.002); however IRP increased and QoL scores decreased. Men with confirmed type III achalasia had low QoL scores. Conclusions All patients had significant clinical improvement after POEM, with medium- to long-term persistence. Though quality of life and IRP initially improved, they deteriorated in the long term. Male sex and type III achalasia seem to be associated with low QoL scores.


Size-dependent formation of membrane nanotubes: continuum modeling and molecular dynamics simulations.
Membrane nanotubes play important functional roles in numerous cell activities such as cellular transport and communication. By exerting an external pulling force over a finite region in a membrane patch, here we investigate the size dependence of the membrane nanotube formation under the continuum and atomistic modeling frameworks. It is shown that the membrane undergoes a discontinuous shape transition as the size of the pulling region and the membrane tension increase. A formula characterizing the nonlinear relationship between the maximum static pulling force and pulling size is identified. During the membrane extraction, lipids in the upper and lower leaflets exhibit different behaviors of structural rearrangements. Moreover, our computational simulations indicate that the steady state pulling force increases linearly with the pulling velocity as well as the size of the pulling region.


Mechanisms Underlying the Inhibition of Tyrosine Kinase Inhibitor-Induced Anorexia and Fatigue by Royal Jelly in Renal Cell Carcinoma Patients and the Correlation between Macrophage Colony Stimulating Factor and Inflammatory Mediators.
Inflammation is a common adverse event of anti-cancer therapy. Royal jelly (RJ) modulates inflammation by regulating the levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and interleukin (IL)-6 produced by macrophages. Macrophage colony stimulating factor (M-CSF) is a crucial regulator of macrophage activities, and we hypothesized that RJ alters M-CSF levels. In this randomized controlled trial, we investigated the association between M-CSF and adverse events in renal cell carcinoma patients treated with tyrosine kinase inhibitors (TKIs) after an oral intake of RJ (n = 16) or placebo (n = 17). The serum levels of M-CSF, TNF-α, TGF-β, and IL-6 were measured by an enzyme-linked immunosorbent assay, and their temporal changes and correlation between such changes were analyzed. The post-/pretreatment ratio of M-CSF levels was associated with anorexia after 2 weeks and fatigue after 2, 4, and 12 weeks. The M-CSF level in the RJ group was higher than that in the placebo group at the same timepoints. The TNF-α level in the RJ group was lower than that in the placebo group between 6 and 12 weeks, and the TGF-β level in the RJ group was higher than that in the placebo group; however, contrasting findings were detected after 12 weeks. Additionally, the M-CSF level was significantly correlated with the TGF-β level after 4 weeks and IL-6 level after 8 and 10 weeks. Among TNF-α, TGF-β, and IL-6, the post-/pretreatment ratio of TGF-β after 12 weeks was associated with TKI-induced anorexia, and the ratios after 10 and 12 weeks were associated with fatigue. Our results demonstrated that an oral intake of RJ suppressed anorexia and fatigue via complex mechanisms associated with inflammation-related factors, such as M-CSF and TGF-β in renal cell carcinoma patients treated with TKIs. In addition, we newly found that such RJ-related effects were dependent on the treatment duration.


Effect of respiratory acidosis on metabolism in exercise.
Five healthy males took part in two separate studies. In one study subjects breathed air (control, C) and in the other 5% CO2 in 21% O2 (respiratory acidosis, RA). Measurements were made at rest, during exercise at 30 and 60% maximal O2 uptake (VO2 max), (20 min each) and in recovery. RA was associated with higher arterial CO2 partial pressure (PCO2) and bicarbonate and lower pH than C. The increase with exercise in plasma lactate (mmol . l-1) was less in RA than C from 1.0 +/- 0.15 (SE) (C = 1.1 +/- 0.17) at rest to 5.3 +/- 1.25 (C = 6.8 +/- 0.98) at 60% VO2 max (P less than 0.10). Plasma pyruvate, alanine, and glycerol concentrations increased with exercise; free fatty acids did not change. There were no significant differences between RA and C in any of these metabolites. Norepinephrine concentrations were similar at rest but increased to a greater extent during exercise in RA than C (P less than 0.02). Epinephrine levels were also higher in RA than C at 60% VO2 max (NS); the two subjects in whom lactate was not lower with RA showed the greatest increase in epinephrine. Exercise in RA was associated with higher heart rates (P less than 0.05), blood pressures (NS), and ventilation (P less than 0.01). In hypercapnia the metabolic effects of acidosis are modified by increased levels of circulating catecholamines.


GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release.
Alternative processing of the precursor protein pro-GIP results in endogenously produced GIP(1-30)NH2, that by DPP-4 cleavage in vivo results in the metabolite GIP(3-30)NH2. We showed previously that GIP(3-30)NH2 is a high affinity antagonist of the human GIPR in vitro. Here we determine whether it is suitable for studies of GIP physiology in rats since effects of GIP agonists and antagonists are strictly species-dependent. Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation or assayed in competition binding using human 125I-GIP(1-42) as radioligand. In isolated perfused rat pancreata, insulin, glucagon, and somatostatin-releasing properties were evaluated. Competition binding demonstrated that on the rat GIP receptor (GIPR), rat GIP(3-30)NH2 bound with high affinity (Ki of 17nM), in contrast to human GIP(3-30)NH2 (Ki of 250nM). In cAMP studies, rat GIP(3-30)NH2 inhibited GIP(1-42)-induced rat GIPR activation and schild-plot analysis showed competitive antagonism with a pA2 of 13nM and a slope of 0.9±0.09. Alone, rat GIP(3-30)NH2 displayed weak, low-potent partial agonistic properties (EC50>1μM) with an efficacy of 9.4% at 0.32μM compared to GIP(1-42). In perfused rat pancreata, rat GIP(3-30)NH2 efficiently antagonized rat GIP(1-42)-induced insulin, somatostatin, and glucagon secretion. In summary, rat GIP(3-30)NH2 is a high affinity competitive GIPR antagonist and effectively antagonizes GIP-mediated G protein-signaling as well as pancreatic hormone release, while human GIP(3-30)NH2, despite a difference of only one amino acid between the two (arginine in position 18 in rat GIP(3-30)NH2; histidine in human), is unsuitable in the rat system. This underlines the importance of species differences in the GIP system, and the limitations of testing human peptides in rodent systems.


Gene expression profile predicts outcome after anthracycline-based adjuvant chemotherapy in early breast cancer.
Prognosis of early beast cancer is heterogeneous. Today, no histoclinical or biological factor predictive for clinical outcome after adjuvant anthracycline-based chemotherapy (CT) has been validated and introduced in routine use. Using DNA microarrays, we searched for a gene expression signature associated with metastatic relapse after adjuvant anthracycline-based CT without taxane. We profiled a multicentric series of 595 breast cancers including 498 treated with such adjuvant CT. The identification of the prognostic signature was done using a metagene-based supervised approach in a learning set of 323 patients. The signature was then tested on an independent validation set comprising 175 similarly treated patients, 128 of them from the PACS01 prospective clinical trial. We identified a 3-metagene predictor of metastatic relapse in the learning set, and confirmed its independent prognostic impact in the validation set. In multivariate analysis, the predictor outperformed the individual current prognostic factors, as well as the Nottingham Prognostic Index-based classifier, both in the learning and the validation sets, and added independent prognostic information. Among the patients treated with adjuvant anthracycline-based CT, with a median follow-up of 68 months, the 5-year metastasis-free survival was 82% in the "good-prognosis" group and 56% in the "poor-prognosis" group. Our predictor refines the prediction of metastasis-free survival after adjuvant anthracycline-based CT and might help tailoring adjuvant CT regimens.


Cardiovascular disease in women: insights from magnetic resonance imaging.
The presentation and identification of cardiovascular disease in women pose unique diagnostic challenges compared to men, and underrecognized conditions in this patient population may lead to clinical mismanagement.This article reviews the sex differences in cardiovascular disease, explores the diagnostic and prognostic role of cardiovascular magnetic resonance (CMR) in the spectrum of cardiovascular disorders in women, and proposes the added value of CMR compared to other imaging modalities. In addition, this article specifically reviews the role of CMR in cardiovascular diseases occurring more frequently or exclusively in female patients, including Takotsubo cardiomyopathy, connective tissue disorders, primary pulmonary arterial hypertension and peripartum cardiomyopathy. Gaps in knowledge and opportunities for further investigation of sex-specific cardiovascular differences by CMR are also highlighted.


Nanodiamonds as pH-switchable oxidation and reduction catalysts with enzyme-like activities for immunoassay and antioxidant applications.
Nanodiamonds (NDs) have recently become a focus of interest from the viewpoints of both science and technology. Their intriguing properties make them suitable as biologically active substrates, in biosensor applications as well as diagnostic and therapeutic biomedical imaging probes. Here, we demonstrate that NDs, as oxidation and reduction catalysts, possess intrinsic enzyme mimetic properties of oxidase, peroxidase and catalase, and these behaviors can be switched by modulating the pH value. NDs not only catalyze the reduction of oxygen (O2) and hydrogen peroxide (H2O2) at acidic pH, but also catalyze the dismutation decomposition of H2O2 to produce O2 at alkaline pH. It was proposed that the molecular mechanism of their peroxidase-like activity is electron-transfer acceleration, the source of which is likely derived from oxygen containing functional groups on their surface. Based on the color reaction, a nanodiamond-based enzyme linked immunosorbent assay (ELISA) was established for the detection of immunoglobulin G (IgG). Surprisingly, NDs display an excellent antioxidant activity due to the protective effect against H2O2-induced cellular oxidative damage. These findings make NDs a promising enzyme mimetic candidate and expand their applications in biocatalysis, bioassays and nano-biomedicine.


Alcoholic beverage preference and diabetes incidence across Europe: the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) project.
It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol. Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when ⩾70% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis. Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases. This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference.


Infiltration behaviour of elemental mercury DNAPL in fully and partially water saturated porous media.
Mercury is a contaminant of global concern due to its harmful effects on human health and for the detrimental consequences of its release in the environment. Sources of liquid elemental mercury are usually anthropogenic, such as chlor-alkali plants. To date insight into the infiltration behaviour of liquid elemental mercury in the subsurface is lacking, although this is critical for assessing both characterization and remediation approaches for mercury DNAPL contaminated sites. Therefore, in this study the infiltration behaviour of elemental mercury in fully and partially water saturated systems was investigated using column experiments. The properties affecting the constitutive relations governing the infiltration behaviour of liquid Hg0, and PCE for comparison, were determined using Pc(S) experiments with different granular porous media (glass beads and sands) for different two- and three-phase configurations. Results showed that, in water saturated porous media, elemental mercury, as PCE, acted as a non-wetting fluid. The required entry head for elemental mercury was higher (from about 5 to 7 times). However, due to the almost tenfold higher density of mercury, the required NAPL entry heads of 6.19cm and 12.51cm for mercury to infiltrate were 37.5% to 20.7% lower than for PCE for the same porous media. Although Leverett scaling was able to reproduce the natural tendency of Hg0 to be more prone than PCE to infiltrate in water saturated porous media, it considerably underestimated Hg0 infiltration capacity in comparison with the experimental results. In the partially water saturated system, in contrast with PCE, elemental mercury also acted as a nonwetting fluid, therefore having to overcome an entry head to infiltrate. The required Hg0 entry heads (10.45 and 15.74cm) were considerably higher (68.9% and 25.8%) than for the water saturated porous systems. Furthermore, in the partially water saturated systems, experiments showed that elemental mercury displaced both air and water, depending on the initial water distribution within the pores. This indicates that the conventional wettability hierarchy, in which the NAPL has an intermediate wetting state between the air and the water phases, is not valid for liquid elemental mercury. Therefore, for future modelling of elemental mercury DNAPL infiltration behaviour in variably water saturated porous media, a different formulation of the governing constitutive relations will be required.


Acute management of ventricular arrhythmias: role of antiarrhythmic agents.
When treating life-threatening ventricular arrhythmias such as symptomatic ventricular tachycardia and ventricular fibrillation (VT/VF), the nature of the arrhythmia must be precisely defined and the approach must be tailored to it. For hemodynamically unstable ventricular arrhythmias, DC cardioversion or high-energy defibrillation remains the approach of choice. Determining the specific role of intravenous drugs in acute conversion of VT/VF and the most appropriate long-term therapy (pharmacologic or nonpharmacologic) to prevent recurrence can be difficult. Pharmacologic conversion of stable VT/VF presents an even greater challenge, as the role of lidocaine considered the first-line agent for many decades, is now being reevaluated. Lidocaine appears to be effective in converting no more than 20% of stable VTs, compared with 70% for intravenous sotalol. The precise efficacies of parenteral procainamide, beta-blockers, and newer class III agents, including intravenous amiodarone, remain to be defined; however, intravenous amiodarone, available recently, can control unstable, recurrent VT/VF that is resistant to lidocaine or procainamide. A standard regimen of concomitant intravenous and oral amiodarone may be given for rapid and sustained control, and allows oral amiodarone to be continued in a significant number of patients.


Clustering of Sp1 sites near the promoter region of ICP34.5 in herpes simplex virus type 1.
We report that a host nuclear protein of approximately 100 kDa binds to the tandemly reiterated DR2 sequence of herpes simplex virus type 1 (HSV-1). The DR2 sequence is a repeated component in the "a" sequence, which defines the signals for cleavage and encapsidation of viral DNA; the "a" sequence also contains the promoter regulatory signals for the gene encoding the viral neurovirulence factor, ICP34.5. Characterization of the host binding protein by means of gel shifts and DNase I footprinting revealed this protein is the eukaryotic transcription factor, Sp1. Furthermore, as judged from the sequence homology, the DR2 region contains clustered matches to the consensus binding site for Sp1. Comparison of the host factor and purified Sp1 (by means of gel shifts and footprinting) confirmed these findings. Since clustered DNA recognition elements represent unusually high affinity binding sites, these repeated Sp1 motifs proximal to the ICP34.5 gene suggest that this region may be a major Sp1 binding site in the viral genome.


Postnatal ontogeny of expression of the corticosteroid receptor genes in mammalian brains: inter-species and intra-species differences.
Corticosteroids are important mediators of homeostasis and stress, and exert their effects via two transcription-factor receptors, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). Both receptors are expressed in the brain in a region-specific manner, and regulate neuroendocrine and behavioral functions. Stress during early development has been demonstrated to lead to long-term alterations in MR and GR levels and in the phenotypes that they mediate. To date, however, nearly all of this evidence has been obtained in rats, and there is actually no clear basis for extrapolation to other species. The current comparative review presents data, as available, on the following aspects of GR and MR gene expression in mouse and rat (Rodentia), tree shrew (Scandentia), common marmoset, squirrel monkey, rhesus macaque and human (Primates): (1) species-typical adult expression of MR mRNA and GR mRNA in hypothalamus, amygdala, hippocampus and neocortex; (2) species-typical neonate, infant, juvenile/adolescent and adult expression of MR mRNA and GR mRNA in hippocampus. (1) and (2) allow for identification of inter-species consistencies and differences in the relative levels of MR and GR expression across brain regions and ontogenetic stages. In addition, data are presented on (3) within-species inter-individual variation in MR and GR expression and causes thereof, including polymorphism and early life stress. Integrating the evidence in (1)-(3), it is noted that, should the expression levels of MR and GR at the time of early-life stress determine the latter's effects on the formers' long-term expression levels and functioning, then the long-term effects of early life stress on corticosteroid receptor expression and function will be species-, brain-region- and receptor-type-specific.


Natal homing in a marine fish metapopulation.
Identifying natal origins of marine fishes is challenging because of difficulties in conducting mark-recapture studies in marine systems. We used natural geochemical signatures in otoliths (ear bones) to determine natal sources in weakfish (Cynoscion regalis), an estuarine-spawning marine fish, in eastern North America. Spawning site fidelity ranged from 60 to 81%, comparable to estimates of natal homing in birds and anadromous fishes. These data were in contrast to genetic analyses of population structure in weakfish. Our findings highlight the need for consideration of spatial processes in fisheries models and have implications for the design of marine reserves in coastal regions.


Electrical Stimulation Modulates High γ Activity and Human Memory Performance.
Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62-118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with "poor" memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation.


What happens to patients following open access gastroscopy? An outcome study from general practice.
Open access gastroscopy allows general practitioners to request a gastroscopy without prior referral to a specialist. The effect of open access gastroscopy upon patient management is poorly explored. Most studies have been hospital based and have focused on diagnostic yields and on means of tightening requests to reduce inefficient use. A user evaluation can only be made by measuring outcomes in primary care. A study was undertaken to determine the impact of open access gastroscopy in general practice and in particular, the value of a normal result. All general practices in South Tees District Health Authority were asked to participate. Any of their patients who had had open access gastroscopy in the year prior to July 1990 were identified from the hospital computer and their general practitioner notes examined. Patient management during the year prior to the open access gastroscopy was compared with the year after. The main outcome measures were: detection rate and grade of lesion, change in graded score of prescribed drugs, consultation rate for dyspepsia and non-dyspepsia problems, and further hospital referral and investigations. Outcomes among those with normal and abnormal gastroscopy results were compared. The study sample comprised 715 patients, 36% of whom had a normal gastroscopy result, 34% a major abnormality and 26% a minor abnormality (4% of patients had miscellaneous diagnoses). It was found that 39% of all patients, and 60% of those with normal findings on open access gastroscopy had their drug treatment stopped or reduced in grade after the investigation. Of those with a major endoscopic abnormality 58% increased their treatment score. Consultations for dyspepsia in the year before and after gastroscopy fell by 57% overall among those with a normal gastroscopy result, by 37% among those with a minor finding and by 33% in those with a major finding. There was a 21% fall in consultations for all reasons among those with a normal gastroscopy result but those with a minor abnormality had a 23% increase in non-dyspepsia consultations. Of all patients 19% were referred to hospital subsequently. Open access gastroscopy has a major effect upon patient management in general practice, and a normal endoscopy result has an important an impact as an abnormal one. Open access gastroscopy is associated with a rationalization of drug therapy, reduced consultations and a low hospital referral rate.


Extensive CRISPR RNA modification reveals chemical compatibility and structure-activity relationships for Cas9 biochemical activity.
CRISPR (clustered regularly interspaced short palindromic repeat) endonucleases are at the forefront of biotechnology, synthetic biology and gene editing. Methods for controlling enzyme properties promise to improve existing applications and enable new technologies. CRISPR enzymes rely on RNA cofactors to guide catalysis. Therefore, chemical modification of the guide RNA can be used to characterize structure-activity relationships within CRISPR ribonucleoprotein (RNP) enzymes and identify compatible chemistries for controlling activity. Here, we introduce chemical modifications to the sugar-phosphate backbone of Streptococcus pyogenes Cas9 CRISPR RNA (crRNA) to probe chemical and structural requirements. Ribose sugars that promoted or accommodated A-form helical architecture in and around the crRNA 'seed' region were tolerated best. A wider range of modifications were acceptable outside of the seed, especially D-2'-deoxyribose, and we exploited this property to facilitate exploration of greater chemical diversity within the seed. 2'-fluoro was the most compatible modification whereas bulkier O-methyl sugar modifications were less tolerated. Activity trends could be rationalized for selected crRNAs using RNP stability and DNA target binding experiments. Cas9 activity in vitro tolerated most chemical modifications at predicted 2'-hydroxyl contact positions, whereas editing activity in cells was much less tolerant. The biochemical principles of chemical modification identified here will guide CRISPR-Cas9 engineering and enable new or improved applications.


Collodictyon--an ancient lineage in the tree of eukaryotes.
The current consensus for the eukaryote tree of life consists of several large assemblages (supergroups) that are hypothesized to describe the existing diversity. Phylogenomic analyses have shed light on the evolutionary relationships within and between supergroups as well as placed newly sequenced enigmatic species close to known lineages. Yet, a few eukaryote species remain of unknown origin and could represent key evolutionary forms for inferring ancient genomic and cellular characteristics of eukaryotes. Here, we investigate the evolutionary origin of the poorly studied protist Collodictyon (subphylum Diphyllatia) by sequencing a cDNA library as well as the 18S and 28S ribosomal DNA (rDNA) genes. Phylogenomic trees inferred from 124 genes placed Collodictyon close to the bifurcation of the "unikont" and "bikont" groups, either alone or as sister to the potentially contentious excavate Malawimonas. Phylogenies based on rDNA genes confirmed that Collodictyon is closely related to another genus, Diphylleia, and revealed a very low diversity in environmental DNA samples. The early and distinct origin of Collodictyon suggests that it constitutes a new lineage in the global eukaryote phylogeny. Collodictyon shares cellular characteristics with Excavata and Amoebozoa, such as ventral feeding groove supported by microtubular structures and the ability to form thin and broad pseudopods. These may therefore be ancient morphological features among eukaryotes. Overall, this shows that Collodictyon is a key lineage to understand early eukaryote evolution.


Use of antibiotics in upper respiratory infections on patients under 16 years old in private ambulatory medicine.
To assess antibiotic use for upper respiratory infections (URI) treatment on patients under 16 years-old who are beneficiaries of a pre-paid health care scheme. A database containing the record of all the medical prescriptions for URI treatment, from May 1997 to April 1998 was analyzed. Patients were under 16 years old and had been diagnosed with common colds, pharyngitis, bronchitis, sinusitis, otitis, and other unspecified upper respiratory tract infections. Three hundred and fifty-one physicians of seven different specialties who attended 25,300 beneficiaries wrote such prescriptions. A total of 30,889 assorted medications were prescribed to 5,533 patients with the above diagnoses. Antibiotics were prescribed for 77.5% of all diagnoses, ranging from 58% for pharyngitis to 91% for laryngitis. The most frequently used antibiotics were: penicillin, cephalosporins, and macrolides. This study presents the information of antibiotics prescription practices for URI in a pre-paid health plan in Mexico. These findings may be used to support specific campaigns for rational use of antibiotics among children attended at private ambulatory health care practices.


Core outcomes in neonatology: development of a core outcome set for neonatal research.
Neonatal research evaluates many different outcomes using multiple measures. This can prevent synthesis of trial results in meta-analyses, and selected outcomes may not be relevant to former patients, parents and health professionals. To define a core outcome set (COS) for research involving infants receiving neonatal care in a high-income setting. Outcomes reported in neonatal trials and qualitative studies were systematically reviewed. Stakeholders were recruited for a three-round international Delphi survey. A consensus meeting was held to confirm the final COS, based on the survey results. Four hundred and fourteen former patients, parents, healthcare professionals and researchers took part in the eDelphi survey; 173 completed all three rounds. Sixteen stakeholders participated in the consensus meeting. The literature reviews identified 104 outcomes; these were included in round 1. Participants proposed 10 additional outcomes; 114 outcomes were scored in rounds 2 and 3. Round 1 scores showed different stakeholder groups prioritised contrasting outcomes. Twelve outcomes were included in the final COS: survival, sepsis, necrotising enterocolitis, brain injury on imaging, general gross motor ability, general cognitive ability, quality of life, adverse events, visual impairment/blindness, hearing impairment/deafness, retinopathy of prematurity and chronic lung disease/bronchopulmonary dysplasia. A COS for clinical trials and other research studies involving infants receiving neonatal care in a high-income setting has been identified. This COS for neonatology will help standardise outcome selection in clinical trials and ensure these are relevant to those most affected by neonatal care.


The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling.
The c-Jun/AP-1 transcription factor controls key cellular behaviours, including proliferation and apoptosis, in response to JNK and Ras/MAPK signalling. While the JNK pathway has been well characterized, the mechanism of activation by Ras was elusive. Here we identify the uncharacterized ubiquitin ligase Trim7 as a critical component of AP-1 activation via Ras. We found that MSK1 directly phosphorylates Trim7 in response to direct activation by the Ras-Raf-MEK-ERK pathway, and this modification stimulates Trim7 E3 ubiquitin ligase activity. Trim7 mediates Lys63-linked ubiquitination of the AP-1 co-activator RACO-1, leading to RACO-1 protein stabilization. Consequently, Trim7 depletion reduces RACO-1 levels and AP-1-dependent gene expression. Moreover, transgenic overexpression of Trim7 increases lung tumour burden in a Ras-driven cancer model, and knockdown of Trim7 in established xenografts reduces tumour growth. Thus, phosphorylation-ubiquitination crosstalk between MSK1, Trim7 and RACO-1 completes the long sought-after mechanism linking growth factor signalling and AP-1 activation.


Penetration of Gastric Ulcer into the Splenic Artery: A Rare Complication.
Gastric ulcer and its complications are commonly encountered by physicians. Penetration is only noted in about 20% of the cases. Penetration into the splenic artery is a very rare occurrence. Making the diagnosis early on is important in order to prevent morbidity and mortality due to the brisk bleeding that can follow. In our report we describe the case, the imaging and the interventional radiological findings which helped with management. We review the literature published including radiological findings in such cases and describe the proposed pathogenesis. Definitive treatment usually involves controlling the bleeding either by means of embolization using coils or ligating the bleeding vessel.


Polymer networks with grafted cell adhesion peptides for highly biospecific cell adhesive substrates.
Polymer networks of poly(ethylene glycol) (PEG) in densely cross-linked matrices of acrylic acid (AA) and trimethylolpropane triacrylate were synthesized as biospecific cell adhesive substrates. Networks grafted with synthetic adhesion peptides produced substrates to investigate long-term, receptor-mediated cell/surface interactions, without nonspecific protein adsorption producing spurious adhesion signals. PEG rendered the networks very resistant to cell adhesion in vitro, and AA provided reactive carboxyl moieties for N-terminal grafting of peptides. Networks with higher mass fractions of AA had greater background cell adhesion, which diminished with higher mass fractions of PEG such that complete resistance to cell adhesion could be obtained. Networks grafted with inactive control peptides (GRGES or no peptide) remained completely cell nonadhesive in the presence of serum or even when preincubated with adhesion proteins, while networks grafted with bioadhesive peptides (GRGDS, GYIGSRY, or GREDVY) supported morphologically complete fibroblast adhesion. The amount of AA in the network readily controlled the amount of incorporated peptide. These networks may be suitable as analytical tools specifically to investigate long-term cell/substrate interactions in the presence of serum, yet without non-specific protein adsorption producing adhesion signals other than those immobilized for study.


Associations between maternal antioxidant intakes in pregnancy and infant allergic outcomes.
Antioxidant intakes in pregnancy may influence fetal immune programming and the risk of allergic disease. We investigated associations between maternal intakes of β-carotene, vitamin C, vitamin E, copper and zinc, and infant allergic outcomes. Antioxidant intakes of pregnant women (n = 420) assessed prospectively by a food frequency questionnaire, were examined in relation to allergic outcomes at 1 year of age (n = 300). The main relationships with allergic outcomes were seen with dietary vitamin C and copper. Specifically, higher maternal dietary vitamin C intake was associated with a reduced risk of any diagnosed infant allergic disease and wheeze. After adjustment for potential confounders the relationship with wheeze remained statistically significant. There was also an inverse linear relationship between vitamin C and food allergy. Higher dietary copper intake was associated with reduced risk of eczema, wheeze and any allergic disease. The relationship with wheeze and any allergic disease remained statistically significant in multivariate analysis, and there was also an inverse linear relationship between copper and food allergy. However, these relationships were only seen for nutrients present in food. There were no relationships between β-carotene, vitamin E or zinc and any allergic outcomes. In summary, this study suggests that maternal diet of fresh foods rich in vitamin C is associated with reduced risk of infant wheeze, and that copper intake is associated with reduced risk of several allergic outcomes.