Iron Deficiency Impairs Developing Hippocampal Neuron Gene Expression, Energy Metabolism, and Dendrite Complexity.
Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of the iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a degree of neuronal ID similar to that seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e. BdnfVI,Camk2a,Vamp1,Psd95,Cfl1, Pfn1,Pfn2, and Gda) and mitochondrial function (i.e. Ucp2,Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons were reduced. By 18DIV, partial recovery of the dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and the length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism, is responsible for the effects of fetal/neonatal ID and IDA on hippocampal neuron dendritic and synaptic maturation. Impairments in these neurodevelopmental processes likely underlie the negative impact of early life ID and IDA on hippocampus-mediated learning and memory.


Advancing the use of local ecological knowledge for assessing data-poor species in coastal ecosystems.
Many of the world's most vulnerable and rapidly changing ecosystems are also among the most data-poor, leading to an increased interest in use of local ecological knowledge (LEK) to document long-term environmental change. The integration of multiple knowledge sources for assessing species abundance and distribution has gained traction over the past decade as a growing number of case studies show concordance between LEK and scientific data. This study advances the use of quantitative approaches for synthesizing LEK by presenting a novel application of bootstrapping and statistical modeling to evaluate variance in ecological observations of fisheries practitioners. We developed an historical record of abundance for 22 marine species in Puget Sound, Washington (USA), using LEK, and we quantified variation in perceptions of abundance trends among fishers, divers, and researchers. These individuals differed in aspects of their information environments, which are characterized by how, when, and where an individual has acquired ecological information. Abundance trends derived from interviews suggest that populations of long-lived rockfishes (Sebastes spp.) have been in decline since at least the 1960s and that three rockfishes protected under the Endangered Species Act were perceived as relatively less abundant than other species. Differences in perception of rockfish abundance trends among age groups were consistent with our hypothesis that the reported magnitude of decline in abundance would increase with age, with younger respondents more likely to report high abundance than older individuals across all periods. Temporal patterns in the mean and variance of reported rockfish abundance indices were qualitatively similar between fishers and researchers; however, fishers reported higher indices of abundance than researchers for all but one rockfish species. The two respondent groups reported similar changes in rockfish abundance from the 1940s to 2000s, except for two recreationally valuable species that fishers perceived as having undergone greater declines than perceived by researchers. When aggregated at appropriate spatial-temporal scales and in a culturally appropriate manner, observations of resource users are a valuable source of ecological information. Continued development of creative analytical tools for synthesizing multiple knowledge sources will be essential for advancing the formal use of LEK in assessments of marine species.


A new method for the radiological assessment of vertebral squaring in ankylosing spondylitis.
A method has been developed for the objective assessment of vertebral 'squaring' based on quantitative morphometric analysis of vertebral 'concavity' in lateral radiographs of the lumbar spine. The reference range for vertebral concavity was defined as greater than 1.0-4.0 mm from measurements of 255 radiologically normal lumbar vertebrae in 51 patients with non-specific back pain. Evidence of vertebral squaring, as defined by concavity measurements of 1 mm or less, was found in 28% of vertebrae from 103 patients with ankylosing spondylitis and 8% of vertebrae from 10 patients with Reiter's syndrome. Assessment of vertebral squaring by the concavity measurement was more reproducible than subjective analysis in the diagnosis of vertebral squaring; in a subgroup of 30 patients with seronegative spondyloarthropathy, the interobserver agreement on the presence or absence of vertebral squaring as assessed by two independent clinicians was 84%, compared with 94% using the concavity measurement. Corresponding values for intraobserver agreement were 79% for subjective analysis and 84% for the concavity measurement. The vertebral concavity measurement is performed simply, rapidly (about three minutes for five lumbar vertebrae), and requires no special experience or equipment. As a result of this, the technique may be of value in the radiological diagnosis of ankylosing spondylitis and in assessing changes in vertebral squaring in individual patients with time.


Effectiveness of Lumbar Facet Joint Blocks and Predictive Value before Radiofrequency Denervation: The Facet Treatment Study (FACTS), a Randomized, Controlled Clinical Trial.
WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: With facet interventions under scrutiny, the authors' objectives were to determine the effectiveness of different lumbar facet blocks and their ability to predict radiofrequency ablation outcomes. A total of 229 participants were randomized in a 2:2:1 ratio to receive intraarticular facet injections with bupivacaine and steroid, medial branch blocks, or saline. Those with a positive 1-month outcome (a 2-point or more reduction in average pain score) and score higher than 3 (positive satisfaction) on a 5-point satisfaction scale were followed up to 6 months. Participants in the intraarticular and medial branch block groups with a positive diagnostic block (50% or more relief) who experienced a negative outcome proceeded to the second phase and underwent radiofrequency ablation, while all saline group individuals underwent ablation. Coprimary outcome measures were average reduction in numerical rating scale pain score 1 month after the facet or saline blocks, and average numerical rating scale pain score 3 months after ablation. Mean reduction in average numerical rating scale pain score at 1 month was 0.7 ± 1.6 in the intraarticular group, 0.7 ± 1.8 in the medial branch block group, and 0.7 ± 1.5 in the placebo group; P = 0.993. The proportions of positive blocks were higher in the intraarticular (54%) and medial branch (55%) groups than in the placebo group (30%; P = 0.01). Radiofrequency ablation was performed on 135 patients (45, 48, and 42 patients from the intraarticular, medial branch, and saline groups, respectively). The average numerical rating scale pain score at 3 months was 3.0 ± 2.0 in the intraarticular, 3.2 ± 2.5 in the medial branch, and 3.5 ± 1.9 in the control group (P = 0.493). At 3 months, the proportions of positive responders in the intraarticular, medial branch block, and placebo groups were 51%, 56%, and 24% for the intraarticular, medial branch, and placebo groups, respectively (P = 0.005). This study establishes that facet blocks are not therapeutic. The higher responder rates in the treatment groups suggest a hypothesis that facet blocks might provide prognostic value before radiofrequency ablation.


Trichinella spiralis: genomic application to control a zoonotic nematode.
The nematode Trichinella spiralis and related species are zoonotic food-borne pathogens of humans. The muscle larval stage of this parasite establishes a chronic infection in skeletal muscle cells of humans who acquire trichinellosis. Muscle larvae also reside in skeletal muscles of animals, swine in particular, and other food animals, including game animals. These muscle larvae are the source of zoonotic transmission to humans. Once established, muscle larvae become less susceptible to anthelmintics that are effective against other stages of the parasite. Very little information exists to guide discovery of new drug targets and improved methods of eliminating muscle larvae established in muscle cells of humans or food animals. Here we discuss progress that has been made on sequencing the genome of T. spiralis. This informational resource should prove valuable for dissecting molecular characteristics of this parasite that warrant investigation as targets for chemotherapy. The availability of the T. spiralis genome has made possible the comparison of genomes from nematodes that span the evolutionary extremes of the phylum Nematoda. We describe a pan-phylum comparison of genomes that is underway. This comparative genomics approach is expected to identify molecular characteristics that are conserved among all nematodes, and hence applicable to nematode pathogens throughout the phylum, including species from the genus Trichinella. T. spiralis expression data for muscle larvae has been integrated with genome sequences to identify specific genes and proteins with relevance to control of this stage of the parasite. Examples are discussed in which genomic information may advance understanding of T. spiralis biology and new methods for treating infections by this parasite.


Comparison of Rates of Bleeding and Vascular Complications Before, During, and After Trial Enrollment in the SAFE-PCI Trial for Women.
SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women), a randomized controlled trial comparing radial and femoral access in women undergoing cardiac catheterization or percutaneous coronary intervention (PCI), was terminated early for lower than expected event rates. Whether this was because of patient selection or better access site practice among trial patients is unknown. SAFE-PCI was conducted within the National Cardiovascular Data Registry CathPCI registry. Using the National Cardiovascular Research Infrastructure Identification, PCI date, and age, patients enrolled in SAFE-PCI were compared with trial-eligible female CathPCI registry patients 1 year before, during, and 1 year after SAFE-PCI enrollment. Patient and procedure characteristics, predicted bleeding and mortality, and post-PCI bleeding were compared between groups. Enrolled SAFE-PCI patients and registry patients from the 3 time periods were linked to Centers for Medicare and Medicaid Services data to compare 30-day death and unplanned revascularization rates. At 54 SAFE-PCI sites, there were 496 SAFE-PCI trial patients with a PCI visit within the CathPCI registry. There were 24 958 registry patients from 1 year before and 1 year after SAFE-PCI enrollment and 15 904 trial-eligible registry patients during trial enrollment. Trial patients were younger, had lower predicted bleeding and mortality, and had lower rates of post-PCI bleeding within 72 hours compared with registry patients. Among 12 212 Centers for Medicare and Medicaid Services-linked patients, there were no significant differences in 30-day death and unplanned revascularization among the 4 groups. Lower predicted risk of bleeding and mortality among SAFE-PCI trial patients compared with registry patients suggests that lower-risk patients were selectively enrolled for the trial. These data demonstrate how registry-based randomized trials may offer methods for enrollment feedback to curb selection bias in recruitment. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01406236.


Raising the Stakes: Loss of Efflux Pump Regulation Decreases Meropenem Susceptibility in Burkholderia pseudomallei.
Burkholderia pseudomallei, the causative agent of the high-mortality disease melioidosis, is a gram-negative bacterium that is naturally resistant to many antibiotics. There is no vaccine for melioidosis, and effective eradication is reliant on biphasic and prolonged antibiotic administration. The carbapenem drug meropenem is the current gold standard option for treating severe melioidosis. Intrinsic B. pseudomallei resistance toward meropenem has not yet been documented; however, resistance could conceivably develop over the course of infection, leading to prolonged sepsis and treatment failure. We examined our 30-year clinical collection of melioidosis cases to identify B. pseudomallei isolates with reduced meropenem susceptibility. Isolates were subjected to minimum inhibitory concentration (MIC) testing toward meropenem. Paired isolates from patients who had evolved decreased susceptibility were subjected to whole-genome sequencing. Select agent-compliant genetic manipulation was carried out to confirm the molecular mechanisms conferring resistance. We identified 11 melioidosis cases where B. pseudomallei isolates developed decreased susceptibility toward meropenem during treatment, including 2 cases not treated with this antibiotic. Meropenem MICs increased from 0.5-0.75 µg/mL to 3-8 µg/mL. Comparative genomics identified multiple mutations affecting multidrug resistance-nodulation-division (RND) efflux pump regulators, with concomitant overexpression of their corresponding pumps. All cases were refractory to treatment despite aggressive, targeted therapy, and 2 were associated with a fatal outcome. This study confirms the role of RND efflux pumps in decreased meropenem susceptibility in B. pseudomallei. These findings have important ramifications for the diagnosis, treatment, and management of life-threatening melioidosis cases.


Effects of animal position and number of repeated measurements on selected two-dimensional and M-mode echocardiographic variables in healthy dogs.
To evaluate the effects of positioning and number of repeated measurements on intra- and interobserver variability of echocardiographic measurements in dogs. Prospective study. 4 healthy dogs. Each observer performed 24 examinations, separately assessing each dog 6 nonconsecutive times (3 times with the dog in lateral recumbency and 3 with the dog in a standing position). Variables evaluated included M-mode measurements of left ventricular end-diastolic and left ventricular end-systolic diameters, left ventricular free-wall thickness in diastole and systole, interventricular septal thickness in diastole and systole, left ventricular shortening fraction, and 2-dimensional measurements of the left atrial diameter-to-aortic diameter ratio. All coefficients of variation (range, 3.4% to 26.6%) were similar between operators and positions and were < 15% for 27 of 32 values. For both operators, repeatability of the measurements was better for left ventricular end-systolic diameter, left ventricular free-wall thickness in diastole, left ventricular free-wall thickness in systole, and the left atrial diameter-to-aortic diameter in the standing position, and similar for both positions for shortening fraction and left ventricular end-diastolic diameter. No effect of cardiac cycle was observed. Within-day variability of conventional echocardiography performed with the dog in the standing position was at least as good as that obtained with the dog in lateral recumbency for most measured variables. Single measurements of each variable may be sufficient for trained observers examining dogs that do not have an arrhythmia. The standing position should be used, particularly for stressed or dyspneic dogs.


High-density lipoprotein particle concentration and subclinical atherosclerosis of the carotid arteries in Japanese men.
The association of high-density lipoprotein particle (HDL-P) with atherosclerosis may be stronger than that of HDL-cholesterol (HDL-C) and independent of conventional cardiovascular risk factors. Whether associations persist in populations at low risk of coronary heart disease (CHD) remains unclear. This study examines the associations of HDL-P and HDL-C with carotid intima-media thickness (cIMT) and plaque counts among Japanese men, who characteristically have higher HDL-C levels and a lower CHD burden than those in men of Western populations. We cross-sectionally examined a community-based sample of 870 Japanese men aged 40-79 years, free of known clinical cardiovascular disease (CVD) and not on lipid-lowering medication. Participants were randomly selected among Japanese living in Kusatsu City in Shiga, Japan. Both HDL-P and HDL-C were inversely and independently associated with cIMT in models adjusted for conventional CHD risk factors, including low-density lipoprotein cholesterol (LDL-C) and diabetes. HDL-P maintained an association with cIMT after further adjustment for HDL-C (P < 0.01), whereas the association of HDL-C with cIMT was noticeably absent after inclusion of HDL-P in the model. In plaque counts of the carotid arteries, HDL-P was significantly associated with a reduction in plaque count, whereas HDL-C was not. HDL-P, in comparison to HDL-C, is more strongly associated with measures of carotid atherosclerosis in a cross-sectional study of Japanese men. Findings demonstrate that, HDL-P is a strong correlate of subclinical atherosclerosis even in a population at low risk for CHD.


Self-report of diabetes and claims-based identification of diabetes among Medicare beneficiaries.
This report compares self-reported diabetes in the National Health Interview Survey (NHIS) with diabetes identified using the Medicare Chronic Condition (CC) Summary file. NHIS records have been linked with Medicare data from the Centers for Medicare & Medicaid Services. The CC Summary file, one of several linked files derived from Medicare claims data, contains indicators for chronic conditions based on an established algorithm. This analysis was limited to 2005 NHIS participants aged 65 and over whose records were linked to 2005 Medicare data. Linked NHIS participants had at least 1 month of fee-for-service Medicare coverage in 2005. Concordance between self-reported diabetes and the CC Summary indicator for diabetes is compared and described by demographics, socioeconomic status, health status indicators, and geographic characteristics. Of the Medicare beneficiaries in the 2005 NHIS, 20.0% self-reported diabetes and 27.8% had an indicator for diabetes in the CC Summary file. Of those who self-reported diabetes in NHIS, the percentage with a CC Summary indicator for diabetes was high (93.1%). Of those with a CC Summary indicator for diabetes, the percentage self-reporting diabetes was comparatively lower (67.0%). Statistically significant differences by subgroup existed in the percentage concordance between the two sources. Of those with self-reported diabetes, the percentage with a CC Summary indicator differed by sex and age. Of those with a CC Summary indicator for diabetes, the percentage with self-reported diabetes differed by age, self-rated health, number of self-reported conditions, and geographic location. Among Medicare beneficiaries who self-reported diabetes in NHIS, a high concordance was observed with identification of diabetes in the CC Summary file. However, among Medicare beneficiaries with an indicator for diabetes in the CC Summary file, concordance with self-reported diabetes in NHIS is comparatively lower. Differences exist by subgroup.


Socioeconomic status overrides age and gender in determining health-seeking behaviour in rural Bangladesh.
To study the health-seeking behaviour of elderly members (aged > 60 years) of households in rural Bangladesh, to ascertain how their behaviour differs from that of younger people (aged 20-59 years) living in the same household and to explore the determinants of health-seeking behaviour. Structured interviews were conducted to elicit information on the health-seeking behaviour of household members aged > 20 years. Respondents were asked about major illnesses occurring within 15 days prior to the interview. The sample consisted of 966 households that had at least one resident who was aged > 60 (32% of 3031 households). We found no major differences in health-seeking behaviour between elderly people and younger adults. On average about 35% (405/1169) of those who reported having been ill during the previous 15 days in both age groups chose self-care/self-treatment; for both age groups the most commonly consulted type of provider was a paraprofessional such as a village doctor, a medical assistant or a community health worker. A household's poverty status emerged as a major determinant of health-seeking behaviour. The odds ratio (OR) that individuals from poor households would seek treatment from unqualified allopathic practitioners was 0.6 (95% confidence interval (CI) = 0.40-0.78); the odds ratio that individuals from poor households would seek treatment from qualified allopathic practitioners was 0.7 (95% CI = 0.60-0.95). For self-care or self-treatment it was 1.8 (95% CI = 1.43-2.36). Patients' level of education affected whether they avoided self-care/self-treatment and drugstore salespeople (who are usually unlicensed and untrained but who diagnose illnesses and sell medicine) and instead chose a formal allopathic practitioner (OR = 1.5; 95% CI = 1.15-1.96). When a household's poverty status was controlled for, there were no differences in age or gender in terms of health-care expenditure. We found that socioeconomic indicators were the single most pervasive determinant of health-seeking behaviour among the study population, overriding age and sex, and in case of health-care expenditure, types of illness as well.


Pattern and process in Amazon tree turnover, 1976-2001.
Previous work has shown that tree turnover, tree biomass and large liana densities have increased in mature tropical forest plots in the late twentieth century. These results point to a concerted shift in forest ecological processes that may already be having significant impacts on terrestrial carbon stocks, fluxes and biodiversity. However, the findings have proved controversial, partly because a rather limited number of permanent plots have been monitored for rather short periods. The aim of this paper is to characterize regional-scale patterns of 'tree turnover' (the rate with which trees die and recruit into a population) by using improved datasets now available for Amazonia that span the past 25 years. Specifically, we assess whether concerted changes in turnover are occurring, and if so whether they are general throughout the Amazon or restricted to one region or environmental zone. In addition, we ask whether they are driven by changes in recruitment, mortality or both. We find that: (i) trees 10 cm or more in diameter recruit and die twice as fast on the richer soils of southern and western Amazonia than on the poorer soils of eastern and central Amazonia; (ii) turnover rates have increased throughout Amazonia over the past two decades; (iii) mortality and recruitment rates have both increased significantly in every region and environmental zone, with the exception of mortality in eastern Amazonia; (iv) recruitment rates have consistently exceeded mortality rates; (v) absolute increases in recruitment and mortality rates are greatest in western Amazonian sites; and (vi) mortality appears to be lagging recruitment at regional scales. These spatial patterns and temporal trends are not caused by obvious artefacts in the data or the analyses. The trends cannot be directly driven by a mortality driver (such as increased drought or fragmentation-related death) because the biomass in these forests has simultaneously increased. Our findings therefore indicate that long-acting and widespread environmental changes are stimulating the growth and productivity of Amazon forests.


Molecular mechanisms for activation of the agouti-related protein and stimulation of appetite.
The agouti-related protein (Agrp) is a powerful orexigenic peptide, but little is known about its transcriptional regulation. The objective of this study was to determine molecular mechanisms for the activation of hypothalamic Agrp and identify compounds that stimulate appetite. We used promoter analyses methods, hypothalamic cell culture and transfection, immunohistochemistry, luciferase-expressing transgenic mice, in vivo bioluminescence, anitisense RNA, mouse feeding studies, indirect calorimetry, real-time PCR, and Western blots. We found that the Krüppel-like factor 4 (Klf4) is a potent activator of Agrp by binding to a specific CACCC-box in its minimal promoter. We also found that an extract of tarragon, termed PMI-5011, activated hypothalamic Klf4 and Agrp. In vivo, PMI-5011 increased Agrp promoter activity in luciferase-expressing transgenic mice, increased hypothalamic Klf4 and Agrp expression, increased hypothalamic Orexin and melanin-concentrating hormone, increased food intake, reduced circulating insulin and leptin levels, attenuated energy expenditure, and enhanced body weight but only when using a high-fat diet. These data show that Klf4 augmented hypothalamic Agrp by binding to a specific CACCC-box onto its minimal promoter. In addition, the tarragon extract PMI-5011 activated Klf4 and orexigenic neuropeptides and reduced peripheral insulin and leptin levels leading to positive energy balance.


Clinical evaluation of freeze-dried block allografts for alveolar ridge augmentation: a case series.
Various grafting materials have been used in guided bone regeneration procedures to augment alveolar ridges deficient in horizontal or vertical dimensions or both. Autogenous block grafts from intraoral and extraoral sites have been used for ridge augmentation with encouraging results. However, the risk of vascular and neurologic injury at the donor site as well as postoperative patient morbidity have been reported following these surgical procedures. The use of a cancellous block allograft could be one alternative to avoid potential donor site complications. Five deficient alveolar ridges in three patients were each grafted with a freeze-dried cancellous block allograft and a resorbable barrier membrane. Ridge measurements taken at baseline, graft placement, and a 6-month reentry surgery demonstrated an increase in alveolar ridge width from 2 to 4 mm. These gains in ridge width compare favorably with other guided bone regeneration studies, suggesting that a freeze-dried cancellous block allograft in conjunction with a resorbable membrane may be an acceptable alternative to the autogenous block graft in the treatment of compromised alveolar ridge deficiencies.


What are athletes' perceptions of rehabilitation outcome 1 year after hip arthroscopy?
Hip arthroscopy is a minimally invasive surgical procedure. Femoroacetabular impingement (FAI) is being increasingly recognized as a cause of hip pain in athletes and is a growing indication for arthroscopic surgery. Few studies have attempted to address patient views on outcome after arthroscopy, and no qualitative studies have been carried out to date. To explore athletes' perceptions of rehabilitation outcome, the rehabilitative process, and return to sport and to gain insight into factors that affected this process. A retrospective qualitative approach was adopted using semistructured interviews. Eight eligible participants were interviewed. Each had been treated with hip arthroscopy for FAI from September to November 2010. Data were audiotaped, transcribed verbatim, and analyzed using thematic analysis. Three main themes emerged. (1) The ability to participate in sport; athletes were relatively satisfied with outcome despite some limitations in sporting ability. (2) Perceptions of hip problems; there was a lack of understanding and an association of hip problems with older people among the general public. (3) Athletes' perception of rehabilitation; athletes were dissatisfied with the rehabilitation and sought greater physiotherapy input. Overall, athletes were relatively satisfied with their outcome 1 y after hip arthroscopy, despite some having to adapt their sporting activities. Key areas that need to be addressed in future research include factors affecting outcomes of hip arthroscopy, longer-term outcomes, perception of FAI among the public and health practitioners, and the development of a standardized evidence-based rehabilitation protocol.


Robotics in Pediatric Urology.
Robotic surgery has been slow to be fully accepted in the world of pediatric urology largely because of its initial application directed towards adult use and because of the inherent high cost associated with it. However, as previously shown, it has now become the gold standard for adolescent pyeloplasty in The United States. As the adoption of robotic surgery in children has become more widespread, its use has been applied to a broader spectrum of procedures with similar success rates to standard laparoscopy. These procedures include nephrectomy, heminephrectomy, ureteral reimplantation, and ureteroureterostomy. However, it has also shown feasibility and comparable success when compared to open surgery in procedures that were previously deemed too complex to be done by standard laparoscopy. For example, bladder neck reconstruction with Mitrofanoff and Malone procedure as well as bladder augmentation. This review objective is to provide an overview of robotic surgery in pediatric urology, with a focus on the more common cases such as pyeloplasty and reimplantation as well as more complex bladder reconstruction procedures.


Australian shelf sediments reveal shifts in Miocene Southern Hemisphere westerlies.
Global climate underwent a major reorganization when the Antarctic ice sheet expanded ~14 million years ago (Ma) (1). This event affected global atmospheric circulation, including the strength and position of the westerlies and the Intertropical Convergence Zone (ITCZ), and, therefore, precipitation patterns (2-5). We present new shallow-marine sediment records from the continental shelf of Australia (International Ocean Discovery Program Sites U1459 and U1464) providing the first empirical evidence linking high-latitude cooling around Antarctica to climate change in the (sub)tropics during the Miocene. We show that Western Australia was arid during most of the Middle Miocene. Southwest Australia became wetter during the Late Miocene, creating a climate gradient with the arid interior, whereas northwest Australia remained arid throughout. Precipitation and river runoff in southwest Australia gradually increased from 12 to 8 Ma, which we relate to a northward migration or intensification of the westerlies possibly due to increased sea ice in the Southern Ocean (5). Abrupt aridification indicates that the westerlies shifted back to a position south of Australia after 8 Ma. Our midlatitude Southern Hemisphere data are consistent with the inference that expansion of sea ice around Antarctica resulted in a northward movement of the westerlies. In turn, this may have pushed tropical atmospheric circulation and the ITCZ northward, shifting the main precipitation belt over large parts of Southeast Asia (4).


Workforce development and effective evaluation of projects.
The success of a project or programme is typically determined in relation to outputs. However, there is a commitment among UK public services to spending public funds efficiently and on activities that provide the greatest benefit to society. Skills for Health recognised the need for a tool to manage the complex process of evaluating project benefits. An integrated evaluation framework was developed to help practitioners identify, describe, measure and evaluate the benefits of workforce development projects. Practitioners tested the framework on projects within three NHS trusts and provided valuable feedback to support its development. The prospective approach taken to identify benefits and collect baseline data to support evaluation was positively received and the clarity and completeness of the framework, as well as the relevance of the questions, were commended. Users reported that the framework was difficult to complete; an online version could be developed, which might help to improve usability. Effective implementation of this approach will depend on the quality and usability of the framework, the willingness of organisations to implement it, and the presence or establishment of an effective change management culture.


Fecal Shedding of 2 Novel Live Attenuated Oral Poliovirus Type 2 Vaccine Candidates by Healthy Infants Administered Bivalent Oral Poliovirus Vaccine/Inactivated Poliovirus Vaccine: 2 Randomized Clinical Trials.
Primary intestinal immunity through viral replication of live oral vaccine is key to interrupt poliovirus transmission. We assessed viral fecal shedding from infants administered Sabin monovalent poliovirus type 2 vaccine (mOPV2) or low and high doses of 2 novel OPV2 (nOPV2) vaccine candidates. In 2 randomized clinical trials in Panama, a control mOPV2 study (October 2015 to April 2016) and nOPV2 study (September 2018 to October 2019), 18-week-old infants vaccinated with bivalent oral poliovirus vaccine/inactivated poliovirus vaccine received 1 or 2 study vaccinations 28 days apart. Stools were assessed for poliovirus RNA by polymerase chain reaction (PCR) and live virus by culture for 28 days postvaccination. Shedding data were available from 621 initially reverse-transcription PCR-negative infants (91 mOPV2, 265 nOPV2-c1, 265 nOPV2-c2 recipients). Seven days after dose 1, 64.3% of mOPV2 recipients and 31.3%-48.5% of nOPV2 recipients across groups shed infectious type 2 virus. Respective rates 7 days after dose 2 decreased to 33.3% and 12.9%-22.7%, showing induction of intestinal immunity. Shedding of both nOPV2 candidates ceased at similar or faster rates than mOPV2. Viral shedding of either nOPV candidate was similar or decreased relative to mOPV2, and all vaccines showed indications that the vaccine virus was replicating sufficiently to induce primary intestinal mucosal immunity.


Influence of cavity preparation and curing method on the marginal seal of resin composite restorations: an in vitro evaluation.
To evaluate the influence of cavity design and photocuring method on the marginal seal of resin composite restorations. Seventy-two bovine teeth were divided into 2 groups: group 1 received box-type cavity preparations, and group 2 received plate-type preparations. Each group was divided into 3 subgroups. After etching and bonding, Z250 resin composite (3M Espe) was applied in 2 equal increments and cured with 1 of 3 techniques: (1) conventional curing for 30 seconds at 650 mW/cm2; (2) 2-step photocuring, in which the first step was performed 14 mm from the restoration for 10 seconds at 180 mW/cm2 and the second step was performed in direct contact for 20 seconds at 650 mW/cm2; or (3) progressive curing using Jetlite 4000 (J. Morita) for 8 seconds at 125 mW/cm2 and then 22 seconds at 125 mW/cm2 up to 500 mW/cm2. The specimens were thermocycled for 500 cycles and then submitted to dye penetration with a 50% silver nitrate solution. Microleakage was assessed using a stereomicroscope. Data were analyzed using analysis of variance and Tukey test (5% level of significance). A statistically significant difference was found between groups when a double interaction between photocuring and cavity preparation was considered (P = .029). No one type of cavity preparation or photocuring method prevented micro-leakage. The plate-type preparation showed the worst dye penetration when conventional and progressive photocuring methods were used. The best results were found using the 2-step photocuring with the plate-type preparation.


N-methylpyridinium, a degradation product of trigonelline upon coffee roasting, stimulates respiratory activity and promotes glucose utilization in HepG2 cells.
N-Methylpyridinium (NMP) is a thermal degradation product of trigonelline formed upon coffee roasting and hypothesized to exert several health benefits in humans. Since for trigonelline evidence for hypoglycemic effects exists, we examined whether NMP also affects mechanisms of glucose utilization and cellular energy formation. For this purpose, the impact of trigonelline and NMP on respiratory activity, extracellular acidification, cellular adenosine nucleotides, energy supply from fatty acids and glucose as well as thermogenesis in HepG2 cells was analyzed. A 24 hour incubation with nanomolar concentrations of NMP enhanced oxygen consumption rates, resulting in increased ATP levels. Glucose was identified as the prevalent energy substrate as its uptake was augmented up to 18.1% ± 7.44% by NMP at 0.09 μM, whereas the uptake of fatty acids decreased upon NMP treatment. Cellular glucose uptake was also stimulated by trigonelline administration; however, a shift to the anaerobic energy production pathway was monitored. Both pyridine derivatives induced thermogenesis, although trigonelline presumably promoted proton leaks, while NMP increased the concentration of the uncoupling protein-2. We provide evidence that both compounds appear to stimulate cellular energy metabolism in HepG2 cells. Human intervention studies are warranted to ensure these effects in vivo.


Complications of circumcision in male neonates, infants and children: a systematic review.
Approximately one in three men are circumcised globally, but there are relatively few data on the safety of the procedure. The aim of this paper is to summarize the literature on frequency of adverse events following pediatric circumcision, with a focus on developing countries. PubMed and other databasess were searched with keywords and MeSH terms including infant/newborn/pediatric/child, circumcision, complications and adverse events. Searches included all available years and were conducted on November 6th 2007 and updated on February 14th 2009. Additional searches of the Arabic literature included searches of relevant databases and University libraries for research theses on male circumcision.Studies were included if they contained data to estimate frequency of adverse events following neonatal, infant and child circumcision. There was no language restriction. A total of 1349 published papers were identified, of which 52 studies from 21 countries met the inclusion criteria. The Arabic literature searches identified 46 potentially relevant papers, of which six were included. Sixteen prospective studies evaluated complications following neonatal and infant circumcision. Most studies reported no severe adverse events (SAE), but two studies reported SAE frequency of 2%. The median frequency of any complication was 1.5% (range 0-16%). Child circumcision by medical providers tended to be associated with more complications (median frequency 6%; range 2-14%) than for neonates and infants. Traditional circumcision as a rite of passage is associated with substantially greater risks, more severe complications than medical circumcision or traditional circumcision among neonates. Studies report few severe complications following circumcision. However, mild or moderate complications are seen, especially when circumcision is undertaken at older ages, by inexperienced providers or in non-sterile conditions. Pediatric circumcision will continue to be practiced for cultural, medical and as a long-term HIV/STI prevention strategy. Risk-reduction strategies including improved training of providers, and provision of appropriate sterile equipment, are urgently needed.


Clinical profile, comorbidity, and treatment history in 123 hair pullers: a survey study.
Trichotillomania, characterized by an irresistible urge to pull one's hair, may be more prevalent than previously believed. Despite increasing attention devoted to this topic in the recent literature, there are few studies based on large samples that are potentially generalizable to a community population. Surveys addressing clinical profile, comorbidity, and treatment history were mailed to all responders to a nationally distributed magazine article on trichotillomania. Out of 772 surveys sent, 123 completed surveys were returned. While there was a predominance of females in the whole sample, female-to-male prevalence was lower in children than adults. Onset was predominantly in childhood (mean age = 11 years), most frequently in middle childhood and least frequently before age 6. Subjects pulled hair from a variety of sites, including scalp, eyelashes, eyebrows, pubic region, face, and body, but the highest incidence and severity involved scalp hair. Children under 6 were more likely than other age groups to pull scalp hair and possibly less likely to pull other hair. In adults, symptom profile was not associated with age at onset. While subjects reported high rates of comorbid conditions in both self and family, trichotillomania was reportedly formally diagnosed in only 40% of the subjects. Although subjects reported a range of treatments, the majority (58%) reported no treatment history. Finally, only minimal improvement was reported for all modalities, with no significant difference in response to psychotherapy, behavior therapy, clomipramine, or fluoxetine. Trichotillomania is a chronic illness that may be difficult to treat. Controlled studies on comorbidity, epidemiology, treatment-seeking patterns, and long-term treatment response are needed.


Functional outcomes following ankle arthrodesis in males with haemophilia: analyses using the CDC's Universal Data Collection surveillance project.
In persons with haemophilia (PWH), repeated ankle haemarthroses lead to pain, loss of joint range of motion (ROM), and limitations in activity and participation in society. PWH are offered ankle arthrodesis (AA) to eliminate pain. In our experience, PWH are hesitant to proceed to AA due to concerns regarding gait anomalies, functional decline and complete loss of ROM. The aim of this study was to report outcomes in ROM, assistive device (AD)/wheelchair use, activity scale and work/school absenteeism for participants in the CDC's Universal Data Collection surveillance project (UDC) pre- and post- AA. Males with haemophilia enrolled in the UDC with first report of AA (1998-2010) were selected. Descriptive statistics were calculated using data from the annual study visit pre-AA and the follow-up visit (~12-24 months) post-AA. The 68 subjects who fulfilled the criteria were: mean age 36.9 years (SD = 12.9); 85.3% white; 85.3% haemophilia A; 72% severe, 20.6% moderate; and 10.3% with inhibitor once during the study period. Mean loss in total arc of ankle motion was 17.02° (SD = 21.8, P ≤ 0.01) pre- compared to post-AA. For 61.8%, there was no change in use of AD for ambulation/mobility. For 85.3%, there was no change in use of a wheelchair. On a self-reported activity scale, 11.8% improved, 8.8% worsened and 79.4% did not change. Work/school absenteeism averaged 2.7 (SD = 6.4) pre- and 1.5 (SD = 6.4, P = 0.26) days per year post-AA. While ankle ROM was significantly reduced post-AA, for most subjects, there was no change in use of AD/wheelchair for ambulation/mobility. Physical activity was maintained and work/school absenteeism remained stable.


Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies.
Prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association. We will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model. Formal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal. CRD42018091627.


Prefrontal cortex regulates inhibition and excitation in distributed neural networks.
Prefrontal cortex provides both inhibitory and excitatory input to distributed neural circuits required to support performance in diverse tasks. Neurological patients with prefrontal damage are impaired in their ability to inhibit task-irrelevant information during behavioral tasks requiring performance over a delay. The observed enhancements of primary auditory and somatosensory cortical responses to task-irrelevant distractors suggest that prefrontal damage disrupts inhibitory modulation of inputs to primary sensory cortex, perhaps through abnormalities in a prefrontal-thalamic sensory gating system. Failure to suppress irrelevant sensory information results in increased neural noise, contributing to the deficits in decision making routinely observed in these patients. In addition to a critical role in inhibitory control of sensory flow to primary cortical regions, and tertiary prefrontal cortex also exerts excitatory input to activity in multiple sub-regions of secondary association cortex. Unilateral prefrontal damage results in multi-modal decreases in neural activity in posterior association cortex in the hemisphere ipsilateral to damage. This excitatory modulation is necessary to sustain neural activity during working memory. Thus, prefrontal cortex is able to sculpt behavior through parallel inhibitory and excitatory regulation of neural activity in distributed neural networks.


Massive upregulation of the Fas ligand in lpr and gld mice: implications for Fas regulation and the graft-versus-host disease-like wasting syndrome.
Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of T cells with an unusual double negative (DN) (CD4-CD8-) phenotype. Previous studies have shown that these abnormal cells are capable of inducing redirected lysis of certain Fc receptor-positive target cells. Since the Fas ligand (FasL) has recently been shown to be partly responsible for T cell-mediated cytotoxicity, lymph node cells from lpr and gld mice were examined for the expression of FasL mRNA. Northern blot analysis revealed that lymph node cells obtained from lpr and gld mice had a striking increase in the level of expression of FasL mRNA predominantly due to expression in the DN T cells. Furthermore, lpr, but not gld lymph node cells killed the B cell line, A20, in a Fas-dependent manner. These findings indicate that Fas mutations result in a massive up-regulation of FasL which, most likely, results from repetitive exposure to (self) antigen. This phenomenon could explain the lpr-induced wasting syndrome observed when lpr bone marrow-derived cells are adoptively transferred to wild-type recipients.


Isoprene emissions influence herbivore feeding decisions.
Isoprene (C(5)H(8), 2-methyl 1,3-butadiene) is synthesized and emitted by many, but not all, plants. Unlike other related volatile organic compounds (monoterpenes and sesquiterpenes), isoprene has not been shown to mediate plant-herbivore interactions. Here, for the first time, we show, in feeding choice tests using isoprene-emitting transgenic tobacco plants (Nicotiana tabacum cv. Samsun) and non-emitting azygous control plants, that isoprene deters Manduca sexta caterpillars from feeding. This avoidance behaviour was confirmed using an artificial (isoprene-emitting and non-emitting control) diet. Both in vivo and in vitro experiments showed that isoprene can activate feeding avoidance behaviour in this system with a dose-response effect on caterpillar behaviour and an isoprene emission threshold level of <6 nmol m(-2) s(-1).


Epidemiological monitoring: methods for analysing routinely-collected data.
Morbidity and mortality statistics are routinely collected in many countries. These data may be arranged in a number of ways, for example, classified by area of residence, or occupation of the person concerned, or by the time-period during which the relevant event occurred. Judicious use of such data enables disease to be monitored and may draw attention to the adverse effects of harmful agents in the environment. This paper describes the different methods of analysing data for such purposes, giving examples of their application and discussing their relative merits. Particular reference is made to the data-collecting systems in England and Wales and to the statistical aspects of monitoring disease.


Cell differentiation of gonadotropin-releasing hormone neurons and alternative RNA splicing of the gonadotropin-releasing hormone transcript.
Two different, yet related issues regarding gonadotropin-releasing hormone (GnRH), i.e. the development and differentiation of hypothalamic GnRH neurons and the alternative RNA splicing of GnRH gene transcripts, are addressed in the present review. Using the immortalized GnRH-producing GT1 cell line, we found that activation of protein kinase C (PKC) with 12-O-tetradecanoylphorbol-13-acetate induces morphological and functional differentiation of these neurons. Specific isoforms of PKC are involved in neurite growth, cell migration and synaptic contacts and involve different signaling pathways. Using an in vitro splicing assay with HeLa nuclear extract, we found that excision of the first intron of the GnRH primary transcript is attenuated in non-GnRH-producing cells, but not in GnRH-producing cells such as GT1. This attenuation was relieved by exonic splicing enhancers located in the GnRH exons 3 and 4. Interestingly, addition of nuclear extract derived from GT1 cells further increased the excision rate of intron A, indicating that GnRH neurons contain TRANS-acting splicing factors. Extensive biochemical analysis indicates that Tra2alpha, a serine/arginine-rich RNA-binding protein, and other cofactors are likely involved in mediating neuron-specific excision of intron A from the GnRH primary transcript. An understanding of the GnRH neuron-specific splicing machinery provides critical insight into the molecular mechanism of GnRH gene regulation and consequently of mammalian reproductive development.


Hydroxyapatite-ciprofloxacin delivery system: Synthesis, characterisation and antibacterial activity.
The main objective of this study was to synthesize hydroxyapatite-ciprofloxacin composites using a chemical precipitation method and to evaluate the properties and in vitro release profile of the drug from the hydroxyapatite-ciprofloxacin composites. Composite characterization was achieved by FT-IR, XRD and DLS. Ciprofloxacin determination was accomplished by HPLC, resulting in good incorporation efficiency of the drug (18.13 %). The in vitro release study (Higuchi model C = K t1/2 and Ritger-Peppas model, C = K t0.6) showed a diffusion-controlled mechanism. The antibacterial activity showed that the bacterial growth inhibition zones were approximately equal for the synthesis composites and for the mechanical mixture on the Staphylococcus aureus germ. The use of hydroxyapatite, which is a biocompatible, bioactive and osteoconductive material, with ciprofloxacin, which has good antibacterial activity in this composite, makes it suitable for the development of bone grafts. Furthermore, the synthesis process allows a slow local release of the drug.


Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin.
To determine incidence of dementia in type 2 diabetic (T2DM) patients, and whether there are adverse or favorable effects of oral agents (OA) in DM, we obtained a representative cohort of 800,000 from Taiwan's National Health Insurance database. Those who, as of on January 1, 2000, were 50 years or older and dementia free (n = 127,209) were followed until December 31, 2007, in relation to absence (n = 101,816) or presence (n = 25,393) of T2DM, and whether any OA was used. Dementia was ascertained by ICD9-CM or A-code. Dementia incidence densities (DID) and fully adjusted Cox proportional hazard models were used to estimate association between dementia, DM, and OA. Notably, DID (per 10,000 person-years)was markedly increased with DM (without medication), compared to DM free subjects (119 versus 46). Using non-DM as reference, the adjusted hazard ratios (HRs) (95% confidence interval) for DM without and with OA were 2.41 (2.17–2.66) and 1.62 (1.49–1.77), respectively. For T2DM, compared with no medication, sulfonylureas alone reduced the HR from 1 to 0.85 (0.71–1.01), metformin alone to 0.76 (0.58–0.98), while with combined oral therapy the HR was 0.65 (0.56–0.74). Adjustments included cerebrovascular diseases so that non-stroke related dementias were found to be decreased in DM with sulfonylurea and metformin therapy. T2DM increases the risk of dementia more than 2-fold. On the other hand, sulfonylureas may decrease the risk of dementia, as does metformin; together, these 2 OAs decrease the risk of dementia in T2DM patients by 35% over 8 years.


Looking at eye gaze processing and its neural correlates in infancy-implications for social development and autism spectrum disorder.
The importance of eye gaze as a means of communication is indisputable. However, there is debate about whether there is a dedicated neural module, which functions as an eye gaze detector and when infants are able to use eye gaze cues in a referential way. The application of neuroscience methodologies to developmental psychology has provided new insights into early social cognitive development. This review integrates findings on the development of eye gaze processing with research on the neural mechanisms underlying infant and adult social cognition. This research shows how a cognitive neuroscience approach can improve our understanding of social development and autism spectrum disorder.


Assessment of Exercise Intensity for Uphill Walking in Healthy Adults Performed Indoors and Outdoors.
Borg's rating of perceived exertion (BRPE) scale is a simple, but subjective tool to grade physical strain during exercise. As a result, it is widely used for the prescription of exercise intensity, especially for cardiovascular disease prevention. The purpose of this study was to assess and compare relationships between BRPE and physiological measures of exercise intensity during uphill walking indoors and outdoors. 134 healthy participants [median age: 56 years (IQR 52-63)] completed a maximal graded walking test indoors on a treadmill using the modified Bruce protocol, and a submaximal 1 km outdoor uphill cardio-trekking test (1 km CTT). Heart rate (HR) and oxygen consumption (V̇O2) were continuously measured throughout both tests. BRPE was simultaneously assessed at the end of each increment on the treadmill, while the maximal BRPE value was noted at the end of the 1 km CTT. On the treadmill, BRPE correlated very high with relative HR (%HRmax) (ρ = 0.88, p < 0.001) and V̇O2 (%V̇O2max) (ρ = 0.89, p < 0.001). During the 1 km CTT, a small correlation between BRPE and %HRmax (ρ = 0.24, p < 0.05), respectively %V̇O2max was found (ρ = 0.24, p < 0.05). Criterion validity of BRPE during uphill walking depends on the environment and is higher during a treadmill test compared to a natural environment. Adding sensor-based, objective exercise-intensity parameters such as HR holds promise to improve intensity prescription and health safety during uphill walking in a natural environment.


Development of LT-HSC-Reconstituted Non-Irradiated NBSGW Mice for the Study of Human Hematopoiesis In Vivo.
Humanized immune system (HIS) mouse models are useful tools for the in vivo investigation of human hematopoiesis. However, the majority of HIS models currently in use are biased towards lymphocyte development and fail to support long-term multilineage leucocytes and erythrocytes. Those that achieve successful multilineage reconstitution often require preconditioning steps which are expensive, cause animal morbidity, are technically demanding, and poorly reproducible. In this study, we address this challenge by using HSPC-NBSGW mice, in which NOD,B6.SCID IL-2rγ-/-KitW41/W41 (NBSGW) mice are engrafted with human CD133+ hematopoietic stem and progenitor cells (HSPCs) without the need for preconditioning by sublethal irradiation. These HSPCs are enriched in long-term hematopoietic stem cells (LT-HSCs), while NBSGW mice are permissive to human hematopoietic stem cell (HSC) engraftment, thus reducing the cell number required for successful HIS development. B cells reconstitute with the greatest efficiency, including mature B cells capable of class-switching following allogeneic stimulation and, within lymphoid organs and peripheral blood, T cells at a spectrum of stages of maturation. In the thymus, human thymocytes are identified at all major stages of development. Phenotypically distinct subsets of myeloid cells, including dendritic cells and mature monocytes, engraft to a variable degree in the bone marrow and spleen, and circulate in peripheral blood. Finally, we observe human erythrocytes which persist in the periphery at high levels following macrophage clearance. The HSPC-NBSGW model therefore provides a useful platform for the study of human hematological and immunological processes and pathologies.


Human sensorimotor communication: a theory of signaling in online social interactions.
Although the importance of communication is recognized in several disciplines, it is rarely studied in the context of online social interactions and joint actions. During online joint actions, language and gesture are often insufficient and humans typically use non-verbal, sensorimotor forms of communication to send coordination signals. For example, when playing volleyball, an athlete can exaggerate her movements to signal her intentions to her teammates (say, a pass to the right) or to feint an adversary. Similarly, a person who is transporting a table together with a co-actor can push the table in a certain direction to signal where and when he intends to place it. Other examples of "signaling" are over-articulating in noisy environments and over-emphasizing vowels in child-directed speech. In all these examples, humans intentionally modify their action kinematics to make their goals easier to disambiguate. At the moment no formal theory exists of these forms of sensorimotor communication and signaling. We present one such theory that describes signaling as a combination of a pragmatic and a communicative action, and explains how it simplifies coordination in online social interactions. We cast signaling within a "joint action optimization" framework in which co-actors optimize the success of their interaction and joint goals rather than only their part of the joint action. The decision of whether and how much to signal requires solving a trade-off between the costs of modifying one's behavior and the benefits in terms of interaction success. Signaling is thus an intentional strategy that supports social interactions; it acts in concert with automatic mechanisms of resonance, prediction, and imitation, especially when the context makes actions and intentions ambiguous and difficult to read. Our theory suggests that communication dynamics should be studied within theories of coordination and interaction rather than only in terms of the maximization of information transmission.


FACTORS RELATED TO THE REDUCTION OF THE RISK OF COMPLICATIONS IN COLORECTAL SURGERY WITHIN PERIOPERATIVE CARE RECOMMENDED BY THE ACERTO PROTOCOL.
Perioperative care multimodal protocol significantly improve outcome in surgery. To investigate risk factors to various endpoints in patients submitted to elective colorectal operations under the ACERTO protocol. Cohort study analyzing through a logistic regression model able to assess independent risk factors for morbidity and mortality, patients submitted to elective open colon and/or rectum resection and primary anastomosis who were either exposed or non-exposed to demographic, clinical, and ACERTO interventions. Two hundred thirty four patients were analyzed and submitted to 156 (66.7%) rectal and 78 (33.3%) colonic procedures. The length of hospital postoperative stay (LOS) ≥ 7 days was related to rectal surgery and high NNIS risk index; preoperative fasting ≤4 h (OR=0.250; CI95=0.114-0.551) and intravenous volume of crystalloid infused > 30ml/kg/day (OR=0.290; CI95=0.119-0.706). The risk of postoperative site infection (SSI) was approximately four times greater in malnourished; eight in rectal surgery and four in high NNIS index. The duration of preoperative fasting ≤4 h was a protective factor by reducing by 81.3% the risk of surgical site infection (SSI). An increased risk for anastomotic fistula was found in malnutrition, rectal surgery and high NNIS index. Conversely, preoperative fasting ≤4 h (OR=0.11; CI95=0.05-0.25; p<0.0001) decreased the risk of fistula. Factors associated with pneumonia-atelectasis were cancer and rectal surgery, while preoperative fasting ≤ 4 h (OR=0.10; CI95=0.04-0.24; p<0.0001) and intravenous crystalloid ≤ 30 ml/kg/day (OR=0.36; CI95=0.13-0.97, p=0.044) shown to decrease the risk. Mortality was lower with preoperative fasting ≤4 h and intravenous crystalloids infused ≤30 ml/kg/day. This study allows to conclude that rectal procedures, high NNIS index, preoperative fasting higher than 4 h and intravenous fluids greater than 30 ml/kg/day during the first 48 h after surgery are independent risk factors for: 1) prolonged LOS; 2) surgical site infection and anastomotic fistula associated with malnutrition; 3) postoperative pneumonia-atelectasis; and 4) postoperative mortality.


Association between benzodiazepines use and risk of hip fracture in the elderly people: A meta-analysis of observational studies.
Hip fracture is one of the leading causes of disability, cost, morbidity, and mortality. Several studies reported that benzodiazepines (BDZs) have been associated with an increased risk of hip fracture in older individuals. The aim of this study was to evaluate the magnitude of hip fracture risk with BDZs. A systematic literature search on EMBASE, PubMed, Google Scholar, Scopus was performed between January 1, 1980, and March 31, 2019. The search strategy was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, and an observational study design was mandatory for articles inclusion. Data were extracted by two authors independently and a random effect model was used to evaluate effect size. The random-effects model (DerSimonian-Laird) was utilized to obtain the overall risk ratio (RR) and its 95% CI for all studies. The Newcastle Ottawa Scale (NOS) was also used to assess the quality of each study. Of 2315 studies screened, 33 (20 cohorts and 13 case-control) with 169,660 hip fracture cases were included in our analysis. In BDZs users, compared with non-users, the RR for hip fracture was 1.34 (95%CI: 1.26-1.44). The RR for long- and short-short acting BDZs and hip fracture risk were 1.31 (95%CI: 1.18-1.45, P<0.0001), and 1.15 (95%CI: 1.08-1.22, P<0.0001), respectively. When stratified by type of users, the current and recent users of BDZs had higher risk of hip fracture (RR: 1.83, 95% CI: 1.46-2.28, P<0.0001 and RR: 1.61, 95% 1.30-1.99, P<0.0001) whereas there was no increased risk of hip fracture in past BDZs users (RR: 1.18, 95%CI: 1.07-1.29, P<0.0001). Our meta-analysis showed an increased risk of hip fracture in patients with BDZs compared with non-users. Physicians should be aware of the unwanted consequence of BDZs when they will prescribe BDZs for their patients, especially elderly patients because hip fractures are highly prevalent in the elderly population.


Age and sex effects on corpus callosum morphology across the lifespan.
The corpus callosum (CC) is the largest interhemispheric white matter tract in the human brain, and is characterized by pronounced differences in morphology among individuals. There are limited data, however, regarding typical development, sex differences, and the neuropsychological correlates of individual differences within CC subregions. Magnetic resonance (MR) imaging exams were collected in a large cohort (N = 305) of healthy individuals (ages 8-68). We used a highly reliable program to automatically identify the midsagittal plane and obtain CC subregion measures according to approaches described by Witelson [1989]: Brain 112:799-835 and Hampel et al. [1998]: Arch Neurol 55:193-198 and a measure of whole CC shape (i.e., circularity). CC measurement parameters, including area, perimeter, length, circularity, and CC subregion area values were generally characterized by inverted U-shaped curves across the observed age range. Peak values for CC subregions were observed between ages 32 and 45, and descriptive linear correlations were consistent with sharper area changes in development. We also observed differing age-associated changes across the lifespan between males and females in the CC subregion corresponding to the genu (Witelson's subregion 2), as well as CC circularity. Mediation analysis using path modeling indicated that genu area mediated the relationship between age and processing speed for females, and the relationship between age and visual learning and executive functioning for males. Taken together, our findings implicate sex differences in CC morphology across the lifespan that are localized to the genu, which appear to mediate neuropsychological functions.


First Report of Phytophthora nicotianae on Bulb Onion in the United States.
Phytophthora nicotianae (synonym P. parasitica) Breda de Haan was isolated from recently harvested onion bulbs (Allium cepa) in cold storage from a commercial field in southern New Mexico. Deteriorating, water-soaked tissue from the center of four bulbs was plated onto water agar and incubated at room temperature. After 72 h, cultures of Phytophthora (identified by the presence of coenocytic hyphae and papillate sporangia) were isolated and transferred to V8 agar amended with ampicillin (250 mg/liter), rifampicin (10 mg/liter), and pimaricin (0.2% wt/vol). Isolates were identified as P. nicotianae based on morphological characteristics and DNA analysis. Sporangia were sharply papilliate, noncaducous, and ovoid to spherical. The average sporangium size was 45.9 × 39.9 μm with a length-to-width ratio of 1.15. Clamydospores, both terminal and intercalary, were spherical to ovoid and averaged 37.2 × 35.2 μm (2). PCR from whole-cell extracts was performed on four cultured isolates from the infected onion tissue using previously described primers ITS4 and ITS6, which amplify the 5.8S rDNA and ITS1 and ITS2 internal transcribed spacers (1,4). A band of approximately 890 bp was amplified and directly sequenced (GenBank Accession No. HQ398876). A BLAST search of the NCBI total nucleotide collection revealed a 100% similarity to multiple P. nicotianae isolates previously sequenced (1). To confirm the pathogenicity of the isolates, onion seedlings were inoculated with 25 ml of P. nicotionae zoospore solution (15,000 zoospores/ml). Necrosis of leaf tissue and seedling death was observed 5 days postinoculation. P. nicotianae was reisolated from the infected onion seedlings and the ITS region was sequenced to confirm its identity. P. nicotianae was previously reported in bulb onion from Australia, Taiwan (Formosa), and Zimbabwe (Rhodesia) (2). P. nicotianae was reported on bunching onions (A. fistulosum) in Hawaii in 1989 (3). Onions are an important crop in New Mexico with a total production value of 47 million dollars in 2008 (NM Agriculture Statistics 2008). This discovery of a potentially significant postharvest disease poses a threat to the onion industry in New Mexico. To our knowledge, this is the first report of P. nicotianae in bulb onion in the United States and the first report of P. nicotianae in New Mexico on any crop. References: (1) D. E. L. Cooke and J. M. Duncan. Mycol. Res. 101:667, 1997. (2) D. C. Erwin and O. K. Ribeiro. Page 56 in: Phytophthora Diseases Worldwide. The American Phytopathological Society, St Paul, MN, 1996. (3) R. D. Raabe et al. Information Text Series No. 22. University of Hawaii. Hawaii Inst. Trop. Agric. Human Resources, 1981. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.


The Epidemiology of Injuries Across the Weight-Training Sports.
Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12-0.7 injuries per lifter per year; 0.24-1 injury per 1000 h), with strongman (4.5-6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure.


Glutamate utilization promotes meningococcal survival in vivo through avoidance of the neutrophil oxidative burst.
Polymorphonuclear neutrophil leucocytes (PMNs) are a critical part of innate immune defence against bacterial pathogens, and only a limited subset of microbes can escape killing by these phagocytic cells. Here we show that Neisseria meningitidis, a leading cause of septicaemia and meningitis, can avoid killing by PMNs and this is dependent on the ability of the bacterium to acquire L-glutamate through its GltT uptake system. We demonstrate that the uptake of available L-glutamate promotes N. meningitidis evasion of PMN reactive oxygen species produced by the oxidative burst. In the meningococcus, L-glutamate is converted to glutathione, a key molecule for maintaining intracellular redox potential, which protects the bacterium from reactive oxygen species such as hydrogen peroxide. We show that this mechanism contributes to the ability of N. meningitidis to cause bacteraemia, a critical step in the disease process during infections caused by this important human pathogen.


Gut check: reappraisal of disgust helps explain liberal-conservative differences on issues of purity.
Disgust plays an important role in conservatives' moral and political judgments, helping to explain why conservatives and liberals differ in their attitudes on issues related to purity. We examined the extent to which the emotion-regulation strategy reappraisal drives the disgust-conservatism relationship. We hypothesized that disgust has less influence on the political and moral judgments of liberals because they tend to regulate disgust reactions through emotional reappraisal more than conservatives. Study 1a found that a greater tendency to reappraise disgust was negatively associated with conservatism, independent of disgust sensitivity. Study 1b replicated this finding, demonstrating that the effect of reappraisal is unique to disgust. In Study 2, liberals condemned a disgusting act less than conservatives, and did so to the extent that they reappraised their initial disgust response. Study 3 manipulated participants' use of reappraisal when exposed to a video of men kissing. Conservatives instructed to reappraise their emotional reactions subsequently expressed more support for same-sex marriage than conservatives in the control condition, demonstrating attitudes statistically equivalent to liberal participants.


Field cage studies and progressive evaluation of genetically-engineered mosquitoes.
A genetically-engineered strain of the dengue mosquito vector Aedes aegypti, designated OX3604C, was evaluated in large outdoor cage trials for its potential to improve dengue prevention efforts by inducing population suppression. OX3604C is engineered with a repressible genetic construct that causes a female-specific flightless phenotype. Wild-type females that mate with homozygous OX3604C males will not produce reproductive female offspring. Weekly introductions of OX3604C males eliminated all three targeted Ae. aegypti populations after 10-20 weeks in a previous laboratory cage experiment. As part of the phased, progressive evaluation of this technology, we carried out an assessment in large outdoor field enclosures in dengue endemic southern Mexico. OX3604C males were introduced weekly into field cages containing stable target populations, initially at 10:1 ratios. Statistically significant target population decreases were detected in 4 of 5 treatment cages after 17 weeks, but none of the treatment populations were eliminated. Mating competitiveness experiments, carried out to explore the discrepancy between lab and field cage results revealed a maximum mating disadvantage of up 59.1% for OX3604C males, which accounted for a significant part of the 97% fitness cost predicted by a mathematical model to be necessary to produce the field cage results. Our results indicate that OX3604C may not be effective in large-scale releases. A strain with the same transgene that is not encumbered by a large mating disadvantage, however, could have improved prospects for dengue prevention. Insights from large outdoor cage experiments may provide an important part of the progressive, stepwise evaluation of genetically-engineered mosquitoes.


Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models.
Obesity is important for the development of type-2 diabetes as a result of obesity-induced insulin resistance accompanied by impaired compensation of insulin secretion from pancreatic beta cells. Here, based on a randomized pilot clinical trial, we report that intranasal oxytocin administration over an 8-week period led to effective reduction of obesity and reversal of related prediabetic changes in patients. Using mouse models, we further systematically evaluated whether oxytocin and its analogs yield therapeutic effects against prediabetic or diabetic disorders regardless of obesity. Our results showed that oxytocin and two analogs including [Ser4, Ile8]-oxytocin or [Asu1,6]-oxytocin worked in mice to reverse insulin resistance and glucose intolerance prior to reduction of obesity. In parallel, using streptozotocin-induced diabetic mouse model, we found that treatment with oxytocin or its analogs reduced the magnitude of glucose intolerance through improving insulin secretion. The anti-diabetic effects of oxytocin and its analogs in these animal models can be produced similarly whether central or peripheral administration was used. In conclusion, oxytocin and its analogs have multi-level effects in improving weight control, insulin sensitivity and insulin secretion, and bear potentials for being developed as therapeutic peptides for obesity and diabetes.


Is Lipoprotein-Associated Phospholipase A2 a Link between Inflammation and Subclinical Atherosclerosis in Rheumatoid Arthritis?
Lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation, is associated with cardiovascular disease. This prospective study of an inception cohort aimed to investigate whether the level of Lp-PLA2 is associated with subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Patients from northern Sweden diagnosed with early RA were consecutively recruited into an ongoing prospective study. From these, all patients ≤60 years (n = 71) were included for measurements of subclinical atherosclerosis at inclusion (T0) and five years later (T5). Forty age- and sex-matched controls were included. The patients were clinically assessed, SCORE, Reynolds Risk Score, and Larsen score were calculated, and blood samples were drawn from all individuals at T0 and T5. There was no significant difference in the level of Lp-PLA2 between patients with RA and controls (p > 0.05). In simple linear regression models among patients with RA, Lp-PLA2 at T0 was significantly associated with intima media thickness (IMT) at T0 and T5, flow mediated dilation (FMD) at T0 and T5, ever smoking, male sex, HDL-cholesterol (inversely), non-HDL-cholesterol, SCORE, Reynolds Risk Score, and Larsen score (p < 0.05). CONCLUSION. In this cohort of patients with early RA, the concentration of Lp-PLA2 was associated with both subclinical atherosclerosis and disease severity.


Neuro-oncology in the Philippines: a scoping review on the state of medical practice, deterrents to care and therapeutic gaps.
Neoplasms of the brain and spine are relatively uncommon compared to breast, lung and gastrointestinal tumours, which occur at higher rates in the Asian population. Updated guidelines in diagnosis and treatment of neuro-oncologic diseases recommend advanced molecular-based precision-medicine; thus the need for increasingly individualised regimens. It is, therefore, necessary to determine whether there are areas of improvement in the provision of care to these patients, especially in low- to middle-income economies like the Philippines. In this study, we identified gaps in the delivery of medical care to Filipino patients with tumours of the central nervous system. We performed a scoping review on the available literature on clinical experience with treatment of neuro-oncologic cases from the Philippines and performed qualitative analysis viewed through the lens of the existing healthcare system. The medical practice of neuro-oncology in the Philippines lacks robust local data on epidemiology and treatment outcomes. There are existing legislative frameworks to support adequate healthcare delivery and financing to brain tumour patients. However, inequities in the geographic distribution of infrastructure, manpower and medications are roadblocks for accessibility to neuro-oncologic services like specialised molecular markers, neurosurgical procedures, sustained chemotherapy and radiation therapy centres. There are significant treatment gaps in the care of neuro-oncologic patients in the Philippines that need to be addressed. Early detection and initiation of prognosis-changing therapeutics through reduction of out-of-pocket expenses, access to readily available diagnostic tools and sustainability of management regimens are the main areas that necessitate strengthened partnership between the public and private sectors of Philippine society.


Racial, Ethnic, and Age Disparities in Incidence and Survival of Intrahepatic Cholangiocarcinoma in the United States; 1995-2014.
Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014). We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality. Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year allcause mortality (HR = 1.11, 95%CI: 1.05-1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07-1.24). Survival rates were poor also for individuals age 45 years or older, men, and Blacks and American Indians/Alaska Natives. The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.


Mo/Y multilayer mirrors for the 8-12-nm wavelength region.
Mo/Y multilayer mirrors were deposited by dc magnetron sputtering under different deposition conditions. They were characterized by reflectance measurements at normal and grazing angles of incidence, by transmission electron microscopy, and by Auger depth profiling. Normal-incidence peak reflectances of 34% and 22% were measured at wavelengths of 11.5 and 8.1 nm, respectively. Interface roughness and contamination of the layers during deposition limit the peak reflectance of these Mo/Y mirrors.


Examination of injected specimens by confocal laser scanning microscopy and scanning electron microscopy.
Although corrosion casts commonly examined by scanning electron microscopy (SEM) offer good insights into the general arrangement of the microvasculature of certain organs, no information can be obtained from such specimens on special morphological data or dynamic events. Thus, most investigators are obliged to make their interpretations of cast structures only on the basis of indirect criteria. A synopsis, which considers the most important data in that respect, is given for the blood and lymphatic microvessels. Moreover, a methodological approach is introduced, based on the application of fluorescent resin, which allows the examination of cast structures in uncorroded specimens together with the surrounding tissue by confocal laser scanning microscopy (CLSM). When two differently stained resins are injected at different sites, e.g., Mercox-fluorescent yellow into an artery and Mercox-rhodamine into the interstice, blood vessels and lymphatics can be well distinguished. In lymph nodes, the system of lymphoid spaces and that of intranodal sinuses can be separately represented with the same technique. Applications and advantages of the CLSM method, which is a useful tool for an extended interpretation of corrosion casts in SEM, are shown in cast specimens from tongue, skin, and liver in rats. In this study, both corroded and uncorroded specimens were considered. In addition, a new approach is demonstrated which combines casting technique and fluorescence microscopy with investigations carried out under experimental conditions. This allows the examination of microvascular casts together with labelled cells in liver and spleen in a state of phagocytosis.


New windows on the mechanism of action of K(ATP) channel openers.
K(ATP) channel openers are a diverse group of drugs with a wide range of potential therapeutic uses. Their molecular targets, the K(ATP) channels, exhibit tissue-specific responses because they possess different types of regulatory sulfonylurea receptor subunits. It is well recognized that complex interactions occur between K(ATP) channel openers and nucleotides, but the cloning of the K(ATP) channel has introduced a new dimension to the study of these events and has furthered our understanding of the molecular basis of the action of K(ATP) channel openers.


Differences in ion release after ceramic-on-ceramic and metal-on-metal total hip replacement. Medium-term follow-up.
Modern metal-on-metal bearings produce less wear debris and osteolysis, but have the potential adverse effect of release of ions. Improved ceramic-on-ceramic bearings have the lowest wear of all, but the corrosion process has not been analysed. Our aim was to measure the serum ion release (ng/ml) in 23 patients having stable hip prostheses with a ceramic-on-ceramic coupling (group A) and to compare it with the release in 42 patients with a metal-on-metal bearing (group B) in the medium term. Reference values were obtained from a population of 47 healthy subjects (group C). The concentrations of chromium, cobalt, aluminium and titanium were measured. There was a significant increase of cobalt, chromium and aluminium levels (p < 0.05) in group B compared with groups A and C. Group A did not differ significantly from the control group. Despite the apparent advantage of a metal-on-metal coupling, especially in younger patients with a long life expectancy, a major concern arises regarding the extent and duration of ion exposure. For this reason, the low corrosion level in a ceramic-on-ceramic coupling could be advantageous.


Co-orientation of replication and transcription preserves genome integrity.
In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this bias in the bacterium Bacillus subtilis slows replication elongation, and we proposed that this effect contributes to the evolutionary pressure selecting the transcription-replication co-orientation bias. This selection might have been based purely on selection for speedy replication; alternatively, the slowed replication might actually represent an average of individual replication-disruption events, each of which is counter-selected independently because genome integrity is selected. To differentiate these possibilities and define the precise forces driving this aspect of genome organization, we generated new strains with inversions either over approximately 1/4 of the chromosome or at ribosomal RNA (rRNA) operons. Applying mathematical analysis to genomic microarray snapshots, we found that replication rates vary dramatically within the inverted genome. Replication is moderately impeded throughout the inverted region, which results in a small but significant competitive disadvantage in minimal medium. Importantly, replication is strongly obstructed at inverted rRNA loci in rich medium. This obstruction results in disruption of DNA replication, activation of DNA damage responses, loss of genome integrity, and cell death. Our results strongly suggest that preservation of genome integrity drives the evolution of co-orientation of replication and transcription, a conserved feature of genome organization.


'Do as we say, not as we do:' a cross-sectional survey of injuries in injury prevention professionals.
As the leading cause of death and among the top causes of hospitalisation in Canadians aged 1-44 years, injury is a major public health concern. Little is known about whether knowledge, training and understanding of the underlying causes and mechanisms of injury would help with one's own prevention efforts. Based on the Theory of Planned Behaviour, we hypothesised that injury prevention professionals would experience fewer injuries than the general population. An online cross-sectional survey was distributed to Canadian injury prevention practitioners, researchers and policy makers to collect information on medically attended injuries. Relative risk of injury in the past 12 months was calculated by comparing the survey data with injury incidence reported by a comparable subgroup of adults from the (Canadian Community Health Survey (CCHS)) from 2009 to 2010. We had 408 injury prevention professionals complete the survey: 344 (84.5%) women and 63 (15.5%) men. In the previous 12 months, 86 individuals reported experiencing at least one medically attended injury (21,235 people per 100,000 people); with sports being the most common mechanism (41, 33.6%). Fully 84.8% individuals from our sample believed that working in the field had made them more careful. After accounting for age distribution, education level and employment status, injury prevention professionals were 1.69 (95% CI 1.41 to 2.03) times more likely to be injured in the past year. Despite their convictions of increasing their own safety behaviour and that of others, injury prevention professionals' knowledge and training did not help them prevent their own injuries.


Chloroplast transformation in Chlamydomonas with high velocity microprojectiles.
Bombardment of three mutants of the chloroplast atpB gene of Chlamydomonas reinhardtii with high-velocity tungsten microprojectiles that were coated with cloned chloroplast DNA carrying the wild-type gene permanently restored the photosynthetic capacity of the algae. In most transformants of one of the mutants, a fragment with a 2.5-kilobase deletion was restored to normal size by a homologous replacement event; in about 25 percent of the transformants the restored restriction fragment was 50 to 100 base pairs smaller or larger than that of wild type. About one-fourth of the transformants of this mutant contained unintegrated donor plasmid when first examined. This plasmid persisted in four different transformants after 65 cell generations of continuous liquid culture but was lost from all transformants maintained on plates of selective medium. The restored wild-type atpB gene remains in all transformants as an integral part of the chloroplast genome and is expressed and inherited normally.


Investigation of FGFR2-IIIC signaling via FGF-2 ligand for advancing GCT stromal cell differentiation.
Giant cell tumor of bone (GCT) is an aggressive bone tumor consisting of multinucleated osteoclast-like giant cells and proliferating osteoblast-like stromal cells. The signaling mechanism involved in GCT stromal cell osteoblastic differentiation is not fully understood. Previous work in our lab reported that GCT stromal cells express high levels of TWIST1, a master transcription factor in skeletal development, which in turn down-regulates Runx2 expression and prevents terminal osteoblastic differentiation in these cells. The purpose of this study was to determine the upstream regulation of TWIST1 in GCT cells. Using GCT stromal cells obtained from patient specimens, we demonstrated that fibroblast growth factor receptor (FGFR)-2 signaling plays an essential role in bone development and promotes differentiation of immature osteoblastic cells. Fibroblast growth factor (FGF)-2 stimulates FGFR-2 expression, resulting in decreased TWIST1 expression and increased Runx2, alkaline phosphastase (ALP) and osteopontin (OPN) expression. Inhibition of FGFR-2 through siRNA decreased the expression of ALP, Runx2 and OPN in GCT stromal cells. Our study also confirmed that FGF-2 ligand activates downstream ERK1/2 signaling and pharmacological inhibition of the ERK1/2 signaling pathway suppresses FGF-2 stimulated osteogenic differentiation in these cells. Our results indicate a significant role of FGFR-2 signaling in osteoblastic differentiation in GCT stromal cells.


Efficient surface functionalization of wound dressings by a phytoactive nanocoating refractory to Candida albicans biofilm development.
The present study reports the fabrication and characterization of a novel nanostructured phyto-bioactive coated rayon/polyester wound dressing (WD) surface refractory to Candida albicans adhesion, colonization and biofilm formation, based on functionalized magnetite nanoparticles and Anethum graveolens (AG) and Salvia officinalis (SO) essential oils (EOs). TEM, XRD, TGA, FT-IR were used for the characterization of the fabricated nanobiocoated WDs. Using magnetic nanoparticles for the stabilization and controlled release of EOs, the activity of natural volatile compounds is significantly enhanced and their effect is stable during time. For this reason the nanobiocoated surfaces exhibited a longer term anti-biofilm effect, maintained for at least 72 h. Besides their excellent anti- adherence properties, the proposed solutions exhibit the advantage of using vegetal natural compounds, which are less toxic and easily biodegradable in comparison with synthetic antifungal drugs, representing thus promising approaches for the development of successful ways to control and prevent fungal biofilms associated infections.


Do HMOs affect educational disparities in health care?
We wanted to examine how membership in a health maintenance organization (HMO) is related to delivery of preventive clinical services to patients with different educational levels. We conducted a cross-sectional analysis of the 1996-1997 Community Tracking Study Household Survey among adults aged 18 to 64 years with private or Medicaid health insurance. We examined interactions between respondent educational level and HMO membership for the following measures: having a regular source of care and, in the past year, having had a physician visit, a mental health visit, a mammogram (women > or = 50 years), an influenza vaccination (ages > or = 55 years), or smoking cessation counseling (smokers). After adjustment for sociodemographic factors, community size, insurance type, physical and mental health status, and smoking, respondents with less education were significantly less likely to have had a physician visit or mental health visit, mammogram, or influenza vaccination in the past year. Disparities in receipt of preventive care by educational level were smaller among HMO members. Differences in disparities between HMO members and non-HMO members reached statistical significance for influenza vaccination and showed a trend for mental health visits (P = .06). Moreover, HMO members with less than 12 years of education received services at levels comparable to non-HMO members with more education. There are appreciable disparities in receipt of preventive care by education among nonelderly insured persons. HMO membership is associated with smaller disparities for some services. Those with the lowest levels of education appeared to benefit the most from HMO membership.