Six Year Refractive Change among White Children and Young Adults: Evidence for Significant Increase in Myopia among White UK Children.
To determine six-year spherical refractive error change among white children and young adults in the UK and evaluate differences in refractive profiles between contemporary Australian children and historical UK data. Population-based prospective study. The Northern Ireland Childhood Errors of Refraction (NICER) study Phase 1 examined 1068 children in two cohorts aged 6-7 years and 12-13 years. Prospective data for six-year follow-up (Phase 3) are available for 212 12-13 year olds and 226 18-20 year olds in each cohort respectively. Cycloplegic refractive error was determined using binocular open-field autorefraction (Shin-Nippon NVision-K 5001, cyclopentolate 1%). Participants were defined by spherical equivalent refraction (SER) as myopic SER ≤-0.50D, emmetropic -0.50D<SER<+2.00 or hyperopic SER≥+2.00D. Proportion and incidence of myopia. The proportion of myopes significantly increased between 6-7 years (1.9%) and 12-13 years (14.6%) (p<0.001) but not between 12-13 and 18-20 years (16.4% to 18.6%, p = 0.51). The estimated annual incidence of myopia was 2.2% and 0.7% for the younger and older cohorts respectively. There were significantly more myopic children in the UK at age 12-13 years in the NICER study (16.4%) than reported in Australia (4.4%) (p<0.001). However by 17 years the proportion of myopia neared equivalence in the two populations (NICER 18.6%, Australia 17.7%, p = 0.75). The proportion of myopic children aged 12-13 years in the present study (2006-2008) was 16.4%, significantly greater than that reported for children aged 10-16 years in the 1960's (7.2%, p = 0.01). The proportion of hyperopes in the younger NICER cohort decreased significantly over the six year period (from 21.7% to 14.2%, p = 0.04). Hyperopes with SER ≥+3.50D in both NICER age cohorts demonstrated persistent hyperopia. The incidence and proportion of myopia are relatively low in this contemporary white UK population in comparison to other worldwide studies. The proportion of myopes in the UK has more than doubled over the last 50 years in children aged between 10-16 years and children are becoming myopic at a younger age. Differences between the proportion of myopes in the UK and in Australia apparent at 12-13 years were eliminated by 17 years of age.


Attenuation correction for small animal PET images: a comparison of two methods.
In order to extract quantitative parameters from PET images, several physical effects such as photon attenuation, scatter, and partial volume must be taken into account. The main objectives of this work were the evaluation of photon attenuation in small animals and the implementation of two attenuation correction methods based on X-rays CT and segmentation of emission images. The accuracy of the first method with respect to the beam hardening effect was investigated by using Monte Carlo simulations. Mouse- and rat-sized phantoms were acquired in order to evaluate attenuation correction in terms of counts increment and recovery of uniform activity concentration. Both methods were applied to mice and rat images acquired with several radiotracers such as(18)F-FDG, (11)C-acetate, (68)Ga-chloride, and (18)F-NaF. The accuracy of the proposed methods was evaluated in heart and tumour tissues using (18)F-FDG images and in liver, kidney, and spinal column tissues using (11)C-acetate, (68)Ga-chloride, and (18)F-NaF images, respectively. In vivo results from animal studies show that, except for bone scans, differences between the proposed methods were about 10% in rats and 3% in mice. In conclusion, both methods provide equivalent results; however, the segmentation-based approach has several advantages being less time consuming and simple to implement.


Evaluation of a Pharmacist-Driven Protocol to Reduce Inappropriate Use of Acid-Suppressive Medications In the Non-ICU Setting.
Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2 blockers) continue to be over utilized for stress ulcer prophylaxis (SUP). Our study aims to evaluate the effectiveness and feasibility of a pharmacist-driven termination protocol in a community teaching hospital to limit the inappropriate use of acid-suppressive medications in the non-intensive care unit (ICU) setting. Patient charts were evaluated for the appropriate use of PPIs or H2 blockers. A centralized pharmacist contacted healthcare providers for medication discontinuation if the acid suppressant use was deemed inappropriate. The primary outcome of the study was the number of patients who had acid-suppressive medication discontinued after the implementation of the pharmacist-driven termination protocol. Acid-suppressive medication was inappropriately prescribed for nine patients. It was discontinued for eight of those patients based on the pharmacist-driven termination protocol; this was a statistically significant decrease (P < 0.001). The pharmacist spent, on average, less than one minute on each patient's chart. Our study revealed that a pharmacist-driven termination protocol resulted in a 6% overall reduction rate in inappropriately used acid-suppressive medications, with little impact on pharmacist workflow. Implementing such a termination protocol could help to decrease the inappropriate use of acid-suppressive medications in an inpatient hospital service.


Preschool vision screening.
Although a good case for preschool screening for vision defects can be made there is very little evidence that existing programmes are effective in practice. A comparative trial of three different methods of preschool vision screening is described. Some 7000 children initially aged 5 months (younger cohorts) and 30 months (older cohorts) in three matched areas entered the trial during 1987. During 18 months of follow up new visual and ocular defects among these children were ascertained through ophthalmology outpatients and from optician records. Screening at 35 months by an orthoptist based in the community is superior to conventional health visitor surveillance at 30 months and to an agreed programme of primary care screening for squint at 30-36 months as judged by screening sensitivity (100% v 50% v 50%) and the incidence of treated target conditions (17 v 3 v 5 per 1000 person years). A notable feature in the area served by the orthoptist is that 13 children received treatment for straight eyed visual acuity loss from among 1000 children whereas there were no such cases among 2500 in the comparison areas. In the younger cohorts (that is, screening at age 5-9 months) all three programmes showed equally poor results, only one of the eight treated target conditions arising from all 3500 younger children being screen detected.


Glaucoma-Related Differences in Gaze Behavior When Negotiating Obstacles.
Safe navigation requires avoiding objects. Visual field loss may affect how one visually samples the environment, and may thus contribute to bumping into objects and falls. We tested the hypothesis that gaze strategies and the number of collisions differ between people with glaucoma and normally sighted controls when navigating around obstacles, particularly under multitasking situations. Twenty persons with moderate-severe glaucoma and 20 normally sighted controls walked around a series of irregularly spaced vertical obstacles under the following three conditions: walking with obstacles only, walking and counting backward to simulate a conversation, and walking while performing a concurrent visual search task to simulate locating a landmark. We quantified gaze patterns and the number of obstacle contacts. Compared with controls, people with glaucoma directed gaze closer to their current position (P < 0.05). They also directed a larger proportion of fixations (in terms of number and duration) to obstacles (P < 0.05). Despite this finding, considerably more people with glaucoma contacted an obstacle (P < 0.05). Multitasking led to changes in gaze behavior in both groups, and this was accompanied by a large increase in obstacle contacts among those with glaucoma (P < 0.05). Glaucoma alters gaze patterns when negotiating a series of obstacles and increases the likelihood of collisions. Multitasking in this situation exacerbates these changes. Understanding glaucoma-related changes in gaze behavior during walking in cluttered environments may provide critical insight for orientation and mobility specialists and guide the design of gaze training interventions to improve mobility.


[Glucotoxicity and lipotoxicity: factors in the pathogenesis and evolution of type 2 diabetes].
Glucose toxicity refers to the structural and functional damage in the beta cells and target tissues of insulin, caused by chronic hyperglycemia. These alterations cause a lower hormonal secretion and action (insulin resistance). Lipid toxicity refers to the damage caused by persistently high free fatty acid levels, as a consequence of triacylglycerol catabolism. Since elevated glucose and lipid levels cause a similar damage and interact, the term glucose and lipid toxicity refers to their additive effects. This toxicity can be implicated in the pathogenesis of type II diabetes and in the secondary failure of oral hypoglycemic drugs, leading to the requirement of insulin treatment. Insulin resistance with normal glucose levels, glucose intolerance and clinical diabetes are the three recognized stages in the development of type 2 diabetes. Considering that the first two stages are reversible, a good metabolic control to avoid glucose and lipid toxicity could revert or avoid the development of clinical diabetes.


Shifts in stability and control effectiveness during evolution of Paraves support aerial maneuvering hypotheses for flight origins.
The capacity for aerial maneuvering was likely a major influence on the evolution of flying animals. Here we evaluate consequences of paravian morphology for aerial performance by quantifying static stability and control effectiveness of physical models for numerous taxa sampled from within the lineage leading to birds (Paraves). Results of aerodynamic testing are mapped phylogenetically to examine how maneuvering characteristics correspond to tail shortening, forewing elaboration, and other morphological features. In the evolution of Paraves we observe shifts from static stability to inherently unstable aerial planforms; control effectiveness also migrated from tails to the forewings. These shifts suggest that a some degree of aerodynamic control and capacity for maneuvering preceded the evolution of a strong power stroke. The timing of shifts also suggests features normally considered in light of development of a power stroke may play important roles in control.


The Rural Household Multiple Indicator Survey, data from 13,310 farm households in 21 countries.
The Rural Household Multiple Indicator Survey (RHoMIS) is a standardized farm household survey approach which collects information on 758 variables covering household demographics, farm area, crops grown and their production, livestock holdings and their production, agricultural product use and variables underlying standard socio-economic and food security indicators such as the Probability of Poverty Index, the Household Food Insecurity Access Scale, and household dietary diversity. These variables are used to quantify more than 40 different indicators on farm and household characteristics, welfare, productivity, and economic performance. Between 2015 and the beginning of 2018, the survey instrument was applied in 21 countries in Central America, sub-Saharan Africa and Asia. The data presented here include the raw survey response data, the indicator calculation code, and the resulting indicator values. These data can be used to quantify on- and off-farm pathways to food security, diverse diets, and changes in poverty for rural smallholder farm households.


Clinical Parameters and Challenges of Managing Cervicofacial Necrotizing Fasciitis in a Sub-Saharan Tertiary Hospital.
Necrotizing fasciitis is a severe soft tissue infection. In our environment, patients presenting with this infection are usually financially incapacitated and, therefore, their management can be challenging. This paper aimed to document the pattern and challenges encountered in the management of cervicofacial necrotizing fasciitis (CNF) in the University College Hospital, Ibadan. Information such as biodata, site of infection, systemic conditions, widest span of defect, management provided, hospital stay, and outcome of management was prospectively collected on all patients with CNF who presented at the Department of Oral and Maxillofacial Surgery between January 2007 and December 2013. The patients were managed according to a devised protocol of antibiotic therapy, serial debridement and honey dressings. Twenty-four cases of CNF were seen. There were 9 males and 15 females while 70.9% of the patients belonged to the low socioeconomic class. The mean span of wound defect was 12.2 (±8.844) cm. The mean hospital stay was 27.8 (±23.1) days, and scar formation was the most common complication encountered. Our study represents the largest series of CNF from a Nigerian health facility presently. The management of necrotizing fascitis in the maxillofacial region poses a significant challenge to both the surgeon and the patient. However, the mortality rate of CNF in our center appears comparatively low.


Aggressive giant cystic lymphatic malformation in a newborn.
Lymphatic malformations are uncommon, benign and congenital malformations of the lymphatic system exhibiting lack of development of communication between the lymphatic and venous circulation. We report the unusual case of rapidly expanding giant lymphatic malformation of the torso, bilateral axillae and left upper extremity of a newborn. As the first-line treatment, aspiration and sclerotherapy with bleomycin were performed. The sclerotherapy failed to cause regression of the mass, and rapid expansion of the malformation necessitated surgery. Partial resection of the mass was performed. Clinical symptoms of respiratory distress resolved in the early postoperative period, and the patient became hemodynamically stable. However, intrathoracic invasion of the mass developed, leading to restriction of thoracic expansion, ending in death. In conclusion, surgical treatment of giant lymphatic malformations remains challenging.


GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia.
To investigate better GVHD prophylaxis in reduced intensity conditioning umbilical cord blood transplantation (RIC-UCBT), we compared transplant outcomes after UCBT among GvHD prophylaxes using the registry data. We selected patients transplanted for AML or ALL with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 748 first RIC-UCBT between 2000 and 2012 (MTX+ group, 446, MMF+ group, 302) were included. The cumulative incidence of neutrophil and platelet counts higher than 50 000/μL was significantly better in the MMF+ group (relative risk (RR), 1.55; P<0.001: RR, 1.34; P=0.003, respectively). In multivariate analyses, the risk of grade II-IV and III-IV acute GvHD was significantly higher in the MMF+ group than in the MTX+ group (RR, 1.75; P<0.001: RR, 1.97; P=0.004, respectively). In disease-specific analyses of AML, the risk of relapse of high-risk disease was significantly lower in the MMF+ group (RR, 0.69; P=0.009), whereas no significant difference was observed in the risk of relapse-free and overall survival in high-risk disease. In patients with standard-risk disease, no significant differences were noted in the risk of relapse or survival between the MTX+ and MMF+ groups. Collectively, these results suggest that MMF-containing prophylaxis may be preferable in RIC-UCBT, particularly for high-risk disease.


Subthalamic nucleus discharge patterns during movement in the normal monkey and Parkinsonian patient.
The pathophysiology of Parkinson disease (PD) is characterized by derangements in the discharge rates, bursting patterns, and oscillatory activity of basal ganglia (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns in humans with PD were compared with that in the normal monkey during performance of similar volitional movements. Single-unit STN recordings were collected while PD patients and animals moved a joystick in the direction of targets presented on a monitor. When discharge rates in all PD human and normal monkey neurons were compared, no significant differences were observed. However, when neurons were classified by peri-movement response type (i.e., excited, inhibited, or unresponsive to movement) statistical differences were demonstrated - most significantly among PD excited neurons. Analysis of burst activity demonstrated inter- and intra-burst activities were greater in the PD human compared to the monkey irrespective of neuronal response type. Moreover, simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies. During movement, discharge and burst rates were positively correlated, independent of subject or neuronal response type; however, rates and oscillatory activity were more strongly correlated in the PD human than the normal monkey. Interestingly, across all domains of analysis, STN neurons in PD demonstrated reduced response variability when compared to STN neurons in the normal monkey brain. Thus, the net effect of PD may be a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity.


Antarctic Rahnella inusitata: A Producer of Cold-Stable β-Galactosidase Enzymes.
There has been a recent increase in the exploration of cold-active β-galactosidases, as it offers new alternatives for the dairy industry, mainly in response to the current needs of lactose-intolerant consumers. Since extremophilic microbial compounds might have unique physical and chemical properties, this research aimed to study the capacity of Antarctic bacterial strains to produce cold-active β-galactosidases. A screening revealed 81 out of 304 strains with β-galactosidase activity. The strain Se8.10.12 showed the highest enzymatic activity. Morphological, biochemical, and molecular characterization based on whole-genome sequencing confirmed it as the first Rahnella inusitata isolate from the Antarctic, which retained 41-62% of its β-galactosidase activity in the cold (4 °C-15 °C). Three β-galactosidases genes were found in the R. inusitata genome, which belong to the glycoside hydrolase families GH2 (LacZ and EbgA) and GH42 (BglY). Based on molecular docking, some of these enzymes exhibited higher lactose predicted affinity than the commercial control enzyme from Aspergillus oryzae. Hence, this work reports a new Rahnella inusitata strain from the Antarctic continent as a prominent cold-active β-galactosidase producer.


Accumulation of contaminants in fish from wastewater treatment wetlands.
Increasing demands on water resources in arid environments make reclamation and reuse of municipal wastewater an important component of the water budget. Treatment wetlands can be an integral part of the water-reuse cycle providing both water-quality enhancement and habitat functions. When used for habitat, the bioaccumulation potential of contaminants in the wastewater is a critical consideration. Water and fish samples collected from the Tres Rios Demonstration Constructed Wetlands near Phoenix, Arizona, which uses secondary-treated wastewater to maintain an aquatic ecosystem in a desert environment, were analyzed for hydrophobic organic compounds (HOC) and trace elements. Semipermeable membrane devices (SPMD) were deployed to investigate uptake of HOC. The wetlands effectively removed HOC, and concentrations of herbicides, pesticides, and organic wastewater contaminants decreased 40-99% between inlet and outlet. Analysis of Tilapia mossambica and Gambusia affinis indicated accumulation of HOC, including p,p'-DDE and trans-nonachlor. The SPMD accumulated the HOC detected in the fish tissue as well as additional compounds. Trace-element concentrations in whole-fish tissue were highly variable, but were similar between the two species. Concentrations of HOC and trace elements varied in different fish tissue compartments, and concentrations in Tilapia liver tissue were greater than those in the whole organism or filet tissue. Bioconcentration factors for the trace elements ranged from 5 to 58,000 and for the HOC ranged from 530 to 150,000.


Comparison between the modelled response of primary motor cortex neurons to pulse-width modulated and conventional TMS stimuli.
In this study, the neural response to pulse-width modulated (PWM) transcranial magnetic stimulation (TMS) is estimated using a computational neural model which simulates the response of cortical neurons to TMS. The recently introduced programmable TMS uses PWM to approximate conventional resonance-based TMS pulses by fast switching between voltage levels. The effect of such stimulation on the six cortical layers is modelled by estimating the activation threshold of the neurons. Modelling results are compared between the novel device and that of conventional TMS stimuli generated by Magstim stimulators. The neural responses to the PWM pulses and the conventional stimuli show a high correlation, which validates the use of pulse-width modulated pulses in TMS.Clinical Relevance- This computational modelling study demonstrates an equivalent effect of PWM and conventional TMS pulses on the nervous system which paves the way to more flexibility in exploring and choosing stimulation parameters for TMS treatment.


Tumor physiology and charge dynamics of anticancer drugs: implications for camptothecin-based drug development.
Charge is an important characteristic of drug molecules, since ionization sites determine the pKa at a particular pH. The pKa in turn can affect many parameters, including solubility, dissolution rate, reaction kinetics, formulation, cell permeability, tissue distribution, renal elimination, metabolism, protein binding and receptor interactions. The impact of charge dynamics is amplified in human solid tumors that exhibit the glycolytic phenotype and associated acidic extracellular microenvironment. This phenotype is driven by hypoxia and creates a pH gradient in tumors that favors uptake of weak acids and exclusion of weak bases. Established anticancer drugs exhibit a range of pKa's and thus variable ability to exploit the tumor pH gradient. The camptothecins are a prime example as they represent a diverse class of approved anticancer drugs and drug candidates whose charge distribution varies with pH. An in silico method was used to predict charge distribution of camptothecins at physiological versus acidic pH in both the lactone and carboxylate forms. A significant amount of uncharged carboxylate was predicted at acidic pH that could enter tumor cells and accumulate in mitochondria to inhibit mitochondrial topoisomerase I. A model is presented to describe the charge dynamics of a new camptothecin analog and the impact on nuclear and mitochondrial mechanism(s) of action. This example illustrates the importance of integrating tumor physiology and charge dynamics into anticancer drug development.


Load-sensitive rat gastric vagal afferents encode volume but not gastric nutrients.
To assess nutrient sensitivity in a population of gastric load-sensitive vagal afferents, their neurophysiological activity was examined in anesthetized rats with inflated pyloric cuffs after gastric infusion of a range of volumes of nutrient and equiosmotic saline solutions. Responses to physiological saline loads (1, 2, 4, and 8 ml) were compared with responses elicited by the same volume range of carbohydrate (12.5% glucose), protein (12.5% peptone), and equiosmotic hypertonic (750 mosM) saline. The threshold load volume of physiological saline required to increase gastric vagal afferent activity was 1 ml. Thereafter, there was a dose-dependent relationship between increasing gastric volume and firing rate and between gastric volume and pressure. The dose-response relationships elicited by glucose, peptone, and equiosmotic hypertonic saline loads did not differ from those elicited by physiological saline loads. These data identify a population of gastric load-sensitive vagal afferents unresponsive to the chemical composition of gastric contents and are consistent with a role for vagal gastric volume signals but not gastric nutrient content in the negative feedback control of ingestion.


The effect of women's property rights on HIV: a search for quantitative evidence.
In recent years, efforts to reduce HIV transmission have begun to incorporate a structural interventions approach, whereby the social, political, and economic environment in which people live is considered an important determinant of individual behaviors. This approach to HIV prevention is reflected in the growing number of programs designed to address insecure or nonexistent property rights for women living in developing countries. Qualitative and anecdotal evidence suggests that property ownership may allow women to mitigate social, economic, and biological effects of HIV for themselves and others through increased food security and income generation. Even so, the relationship between women's property and inheritance rights (WPIR) and HIV transmission behaviors is not well understood. We explored sources of data that could be used to establish quantitative links between WPIR and HIV. Our search for quantitative evidence included (1) a review of peer-reviewed and "gray" literature reporting on quantitative associations between WPIR and HIV, (2) identification and assessment of existing data-sets for their utility in exploring this relationship, and (3) interviews with organizations addressing women's property rights in Kenya and Uganda about the data they collect. We found no quantitative studies linking insecure WPIR to HIV transmission behaviors. Data-sets with relevant variables were scarce, and those with both WPIR and HIV variables could only provide superficial evidence of associations. Organizations addressing WPIR in Kenya and Uganda did not collect data that could shed light on the connection between WPIR and HIV, but the two had data and community networks that could provide a good foundation for a future study that would include the collection of additional information. Collaboration between groups addressing WPIR and HIV transmission could provide the quantitative evidence needed to determine whether and how a WPIR structural intervention could decrease HIV transmission.


Breakthrough in purification of fossil pollen for dating of sediments by a new large-particle on-chip sorter.
Particle sorting is a fundamental method in various fields of medical and biological research. However, existing sorting applications are not capable for high-throughput sorting of large-size (>100 micrometers) particles. Here, we present a novel on-chip sorting method using traveling vortices generated by on-demand microjet flows, which locally exceed laminar flow condition, allowing for high-throughput sorting (5 kilohertz) with a record-wide sorting area of 520 micrometers. Using an activation system based on fluorescence detection, the method successfully sorted 160-micrometer microbeads and purified fossil pollen (maximum dimension around 170 micrometers) from lake sediments. Radiocarbon dates of sorting-derived fossil pollen concentrates proved accurate, demonstrating the method's ability to enhance building chronologies for paleoenvironmental records from sedimentary archives. The method is capable to cover urgent needs for high-throughput large-particle sorting in genomics, metabolomics, and regenerative medicine and opens up new opportunities for the use of pollen and other microfossils in geochronology, paleoecology, and paleoclimatology.


Critical role of cytosolic phospholipase A2{alpha} in bronchial mucus hypersecretion in CFTR-deficient mice.
Cystic fibrosis (CF) is due to mutations in the CF transmembrane conductance regulator gene CFTR. CF is characterised by mucus dehydration, chronic bacterial infection and inflammation, and increased levels of cytosolic phospholipase A2α (cPLA2α) products in airways. We aimed to examine the role of cPLA2α in the modulation of mucus production and inflammation in CFTR-deficient mice and epithelial cells. Mucus production was assessed using histological analyses, immuno-histochemistry and MUC5AC ELISA. cPLA2α activation was measured using an enzymatic assay and lung inflammation determined by histological analyses and polymorphonuclear neutrophil counts in bronchoalveolar lavages. In lungs from Cftr(-/-) mice, lipopolysaccharide induced mucus overproduction and MUC5AC expression associated with an increased cPLA2α activity. Mucus overproduction was mimicked by instillation of the cPLA2α product arachidonic acid, and abolished by either a cPLA2α null mutation or pharmacological inhibition. An increased cPLA2α activity was observed in bronchial explants from CF patients. CFTR silencing induced cPLA2α activation and MUC5AC expression in bronchial human epithelial cells. This expression was enhanced by arachidonic acid and reduced by cPLA2α inhibition. However, inhibition of CFTR chloride transport function had no effect on MUC5AC expression. Reduction of CFTR expression increased cPLA2α activity. This led to an enhanced mucus production in airway epithelia independent of CFTR chloride transport function. cPLA2α represents a suitable new target for therapeutic intervention in CF.


Emergency Department During Long Public Holidays.
The purpose of this study is to determine the impact of the expected increase in the volume of patient visits in the emergency department during holiday periods on physicians' tendencies regarding test and consultation requests as well as on the length of time patients stay in the emergency department. The study groups included all of the patients who visited the emergency department during the nine-day public holiday (Eid al-Adha, a religious festival of sacrifice) celebrations and a nine-day non-holiday "normal" period. The patients' demographic information, reasons for their visits, comorbid diseases, whether or not they had undergone laboratory and screening tests, consultations, length of stay, and the way their visits ended were compared statistically. Of the 6353 patients enrolled in the study, 3523 (55.5%) were seen in the emergency department during the holiday period, while 2830 (45.5%) were seen during the non-holiday period (p≤0.001). During the holiday period, there was a 1.9% decrease in laboratory test requests (p=0.108), a 7.7% increase in radiology examination requests (p≤0.001), and a 1.2% increase in consultation requests (p=0.063). The patients' length of stay during the holiday period was 55.9±75.3 minutes and was 56.3±71.9 minutes during the non-holiday period (p=0.819). The length of time for the patients who underwent tests or consultations was 88.6±92.8 minutes during the holiday period and 92.6±87.5 minutes during the non-holiday period (p=0.224). As expected, the number of patient visits to the emergency department increased during the holiday period, but this increase did not lead to a similar increase in test and consultation requests by the physicians, except for radiology examination requests. In addition, the length of time that patients stayed in the emergency department was not affected by the increase in the volume of patient visits during the holiday period.


Traumatic brain injury in Latin America: lifespan analysis randomized control trial protocol*.
Although in the developed world the intracranial pressure (ICP) monitor is considered the standard of care for patients with severe traumatic brain injury (TBI), its usefulness to direct treatment decisions has never been tested rigorously. The primary focus was to conduct a high-quality, randomized, controlled trial to determine whether ICP monitoring used to direct TBI treatment improves patient outcomes. By providing education, equipment, and structure, the project will enhance the research capacity of the collaborating investigators and will foster the collaborations established during earlier studies. Study centers were selected that routinely treated ICP based on clinical examination and computed tomography imaging using internal protocols. We randomized patients to either an ICP monitor group or an imaging and clinical examination group. Treatment decisions for the ICP monitor group are guided by ICP monitoring based on established guidelines. Treatment decisions for the imaging and clinical examination group are made using a single protocol derived from those previously being used at those centers. There are 2 study hypotheses: (1) patients with severe TBI whose acute care treatment is managed using ICP monitors will have improved outcomes and 2) incorporating ICP monitoring in the care of patients with severe TBI will minimize complications and decrease length of intensive care unit stay. This clinical trial tests the effectiveness of a management protocol based on technology considered pivotal to brain trauma treatment in the developed world: the ICP monitor. A randomized, controlled trial of ICP monitoring has never been performed-a critical gap in the evidence base that supports the role of ICP monitoring in TBI care. As such, the results of this randomized, controlled trial will have global implications regardless of the level of development of the trauma system.


Corticosteroids regulate brain hippocampal 5-HT1A receptor mRNA expression.
Using in situ hybridization techniques, the expression of 5-HT1A receptor mRNA was measured within the hippocampal formation after bilateral adrenalectomy (ADX). After 24 hr ADX, 5-HT1A receptor mRNA expression was significantly increased in all hippocampal subfields in ADX animals relative to sham-operated controls (SHAM). The magnitude of the increase was most pronounced within CA2 (127%) and CA3/4 (94%)-subfields of dorsal hippocampus, intermediate in the dentate gyrus (73%), and least within CA1 (60%). Administration of exogenous corticosterone (CORT) at the time of ADX maintained the level of 5-HT1A receptor mRNA expression within the range of SHAM animals. In vitro receptor autoradiographic analysis of 5-HT1A receptors in adjacent sections from the same animals indicated a simultaneous increase in 5-HT1A binding throughout the hippocampus in response to ADX. 5-HT1A binding increased to a similar extent (approximately 30%) in CA subfields and dentate gyrus but remained within SHAM levels in CORT-replaced animals. 5-HT1A receptor mRNA levels were also increased in hippocampal subregions of 1 week ADX animals relative to SHAM animals. Within both CA1 and CA2 subfields, the increments were approximately double those observed after 1 d ADX. 5-HT1A receptor binding was increased in every hippocampal subfield to a similar extent as that observed after 1 d ADX. Increases in both 5-HT1A receptor mRNA expression and 5-HT1A receptor binding were preventable by administration of exogenous CORT at the time of ADX. Hippocampal 5-HT1C receptor mRNA and D1 receptor mRNA expression were not significantly altered by either acute or chronic ADX treatment. These data indicate that adrenal steroids may selectively regulate hippocampal 5-HT1A receptors at the level of 5-HT1A receptor mRNA expression.


Bt crops producing Cry1Ac, Cry2Ab and Cry1F do not harm the green lacewing, Chrysoperla rufilabris.
The biological control function provided by natural enemies is regarded as a protection goal that should not be harmed by the application of any new pest management tool. Plants producing Cry proteins from the bacterium, Bacillus thuringiensis (Bt), have become a major tactic for controlling pest Lepidoptera on cotton and maize and risk assessment studies are needed to ensure they do not harm important natural enemies. However, using Cry protein susceptible hosts as prey often compromises such studies. To avoid this problem we utilized pest Lepidoptera, cabbage looper (Trichoplusia ni) and fall armyworm (Spodoptera frugiperda), that were resistant to Cry1Ac produced in Bt broccoli (T. ni), Cry1Ac/Cry2Ab produced in Bt cotton (T. ni), and Cry1F produced in Bt maize (S. frugiperda). Larvae of these species were fed Bt plants or non-Bt plants and then exposed to predaceous larvae of the green lacewing Chrysoperla rufilabris. Fitness parameters (larval survival, development time, fecundity and egg hatch) of C. rufilabris were assessed over two generations. There were no differences in any of the fitness parameters regardless if C. rufilabris consumed prey (T. ni or S. frugiperda) that had consumed Bt or non-Bt plants. Additional studies confirmed that the prey contained bioactive Cry proteins when they were consumed by the predator. These studies confirm that Cry1Ac, Cry2Ab and Cry1F do not pose a hazard to the important predator C. rufilabris. This study also demonstrates the power of using resistant hosts when assessing the risk of genetically modified plants on non-target organisms.


An Extensive Unified Thermo-Electric Module Characterization Method.
Thermo-Electric Modules (TEMs) are being increasingly used in power generation as a valid alternative to batteries, providing autonomy to sensor nodes or entire Wireless Sensor Networks, especially for energy harvesting applications. Often, manufacturers provide some essential parameters under determined conditions, like for example, maximum temperature difference between the surfaces of the TEM or for maximum heat absorption, but in many cases, a TEM-based system is operated under the best conditions only for a fraction of the time, thus, when dynamic working conditions occur, the performance estimation of TEMs is crucial to determine their actual efficiency. The focus of this work is on using a novel procedure to estimate the parameters of both the electrical and thermal equivalent model and investigate their relationship with the operating temperature and the temperature gradient. The novelty of the method consists in the use of a simple test configuration to stimulate the modules and simultaneously acquire electrical and thermal data to obtain all parameters in a single test. Two different current profiles are proposed as possible stimuli, which use depends on the available test instrumentation, and relative performance are compared both quantitatively and qualitatively, in terms of standard deviation and estimation uncertainty. Obtained results, besides agreeing with both technical literature and a further estimation method based on module specifications, also provides the designer a detailed description of the module behavior, useful to simulate its performance in different scenarios.


Orthotopic liver transplantation: postoperative complications and their management.
The Birmingham liver transplant programme started in 1982. Forty-six patients have been transplanted with a follow-up of 3 months or longer. Twenty-seven patients are still alive, of whom sixteen have lived for more than one year. The 30 day hospital mortality was 30.4 per cent and the actuarial predicted one year survival 55.5 per cent. Four patients have been regrafted for chronic rejection and graft failure. Thirteen patients have required surgery in the postoperative period for: bleeding (two), removal of abdominal packs (four), biliary leaks and obstruction (five), duodenal perforation (one) and small bowel obstruction (one). Acute rejection was common, occurring in 30 patients and progressing to chronic rejection in 4. Ten patients developed renal failure with an 80 per cent mortality and eleven patients developed grand mal fits. Severe bleeding (greater than 70 units) was associated with previous abdominal surgery and a high mortality (88.9 per cent). Opportunistic fungal infection carried a 100 per cent mortality. Although more than half of all transplanted patients will survive for more than one year, the postoperative period is still one of high morbidity and mortality.


betaTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis.
The BimEL tumor suppressor is a potent proapoptotic BH3-only protein. We found that, in response to survival signals, BimEL was rapidly phosphorylated on three serine residues in a conserved degron, facilitating binding and degradation via the F box protein betaTrCP. Phosphorylation of the BimEL degron was executed by Rsk1/2 and promoted by the Erk1/2-mediated phosphorylation of BimEL on Ser69. Compared to wild-type BimEL, a BimEL phosphorylation mutant unable to bind betaTrCP was stabilized and consequently potent at inducing apoptosis by the intrinsic mitochondrial pathway. Moreover, although non-small cell lung cancer (NSCLC) cells often become resistant to gefitinib (a clinically relevant tyrosine kinase inhibitor that induces apoptosis through BimEL), silencing of either betaTrCP or Rsk1/2 resulted in BimEL-mediated apoptosis of both gefitinib-sensitive and gefitinib-insensitive NSCLC cells. Our findings reveal that betaTrCP promotes cell survival in cooperation with the ERK-RSK pathway by targeting BimEL for degradation.


Postnatal development of laminar innervation patterns by monoaminergic fibers in monkey (Macaca fascicularis) primary visual cortex.
Immunohistochemical methods are used to characterize the distribution of noradrenergic and serotonergic fibers in primary visual cortex of cynomolgus monkeys (Macaca fascicularis) at various postnatal ages. Previous studies in adult squirrel monkeys have shown that serotonergic fibers are generally restricted to the upper four cortical laminae and are especially dense in layer IV, whereas noradrenergic fibers are especially dense in layers V and VI, moderate in layers I, II, and III, and virtually absent in layer IV (Morrison, J. H., S. L. Foote, M. E. Molliver, F. E. Bloom, and H. G. W. Lidov (1982) Proc. Natl. Acad. Sci. U.S.A. 2401-2405; Morrison, J. H., S. L. Foote, D. O'Connor, and F. E. Bloom (1982) Brain Res. Bull. 9: 309-319). Since these monoamines, especially norepinephrine, have been hypothesized to play an essential role in the developmental plasticity of visual cortex organization (e.g., Kasamatsu, T., and J. D. Pettigrew (1976) Science 194: 206-209; Pettigrew, J. D., and T. Kasamatsu (1978) Nature 271: 761-763), the present study examined the postnatal development of these innervation patterns, especially just before and just after the reported "critical period" for visual plasticity. A dense serotonergic innervation of layer IV is present at birth along with sparse innervation of other laminae. The adult pattern of serotonergic innervation, which is similar to that in the squirrel monkey but even more specifically laminated, becomes evident by 6 weeks of age. In the adult pattern, the most dense innervation remains in layers IVb and IVc. A much lower density of noradrenergic than of serotonergic fibers is evident at all ages examined. As with serotonin, the lowest density of fibers is observed at birth. By about 2 months of age these noradrenergic fibers have become more dense, and their laminar distribution is similar to that of adult cynomolgus which is similar to adult squirrel monkey. These studies indicate that: (1) both types of innervation display a continuum of development, with no abrupt changes, (2) serotonergic innervation is more dense than noradrenergic innervation at every age examined, (3) these two transmitter systems exhibit very different laminar innervation patterns as early as birth, and (4) the greater laminar specialization of area 17 in cynomolgus versus squirrel monkeys is accompanied by corresponding enhanced laminar specialization of these monoaminergic afferents.


miR-145 suppress the androgen receptor in prostate cancer cells and correlates to prostate cancer prognosis.
Androgen signalling through the androgen receptor (AR) is essential for prostate cancer initiation, progression and transformation to the lethal castration-resistant state. The aim of this study was to characterize the mechanisms by which miR-145 deregulation contribute to prostate cancer progression. The miR-145 levels, measured by quantitative reverse transcription-polymerase chain reaction, were found to inversely correlate with occurrence of metastases, survival and androgen deprivation therapy response in a well-characterized prostate cancer cohort. Introduction of ectopic miR-145 in prostate cancer cells generated an inhibitory effect on the AR at both transcript and protein levels as well as its activity and downstream targets prostate-specific antigen (PSA), kallikrein-related peptidase 2 and TMPRSS2. The regulation was shown to be mediated by direct binding using Ago2-specific immunoprecipitation, but there was also indication of synergetic AR activation. These findings were verified in clinical prostate specimens by demonstrating inverse correlations between miR-145 and AR expression as well as serum PSA levels. In addition, miR-145 was found to regulate androgen-dependent cell growth in vitro. Our findings put forward novel possibilities of therapeutic intervention, as miR-145 potentially could decrease both the stem cells and the AR expressing bulk of the tumour and hence reduce the transformation to the deadly castration-resistant form of prostate cancer.


Environment and Lifestyle: Their Influence on the Risk of RA.
Rheumatoid arthritis (RA) is a complex disease in which environmental agents are thought to interact with genetic factors that lead to triggering of autoimmunity. We reviewed environmental, hormonal, and dietary factors that have been suggested to be associated with the risk of RA. Smoking is the most robust factor associated with the risk of RA, with a clear gene-environment interaction. Among other inhalants, silica may increase the risk of RA in men. There is less evidence for pesticides, pollution, and other occupational inhalants. Regarding female hormonal exposures, there is some epidemiological evidence, although not consistent in the literature, to suggest a link between hormonal factors and the risk of RA. Regarding dietary factors, available evidence is conflicting. A high consumption of coffee seems to be associated with an increased risk of RA, whereas a moderate consumption of alcohol is inversely associated with the risk of RA, and there is less evidence regarding other food groups. Dietary pattern analyses (Mediterranean diet, the inflammatory potential of the diet, or diet quality) suggested a potential benefit of dietary modifications for individuals at high risk of RA. To date, smoking and silica exposure have been reproducibly demonstrated to trigger the emergence of RA. However, many other environmental factors have been studied, mostly with a case-control design. Results were conflicting and studies rarely considered potential gene-environment interactions. There is a need for large scale prospective studies and studies in predisposed individuals to better understand and prevent the disease and its course.


Cognitive impairment in remission in bipolar affective disorder.
Although the traditional view of bipolar affective disorder is that the majority of patients have full remission between episodes, recent evidence suggests that residual cognitive deficits are present. The aim of this study was to determine whether memory and executive deficits were present in a well-defined clinically remitted group of patients. This was a case-control study of bipolar patients in remission (N = 18). Subjects had to fulfil stringent clinical criteria for inclusion into the study and had to have been in remission for at least 4 months. Subjects also had no history of substance dependence. The cognitive battery examined memory and executive function. Patients in excellent clinical remission and who reported good social adaptation showed imipairment on tests of visuospatial recognition memory. Accuracy on four tests of executive function was not impaired in patients in remission compared with controls, although response latency on these executive tests was still impaired. As our group and others have shown, patients with mania and unipolar depression show generalized impairment on tests of memory and executive function. In comparison, this study has demonstrated that patients in remission show a relatively specific impairment in memory with recovery of accuracy measures on executive function task. The increased response latency on the executive tasks suggests a possible small residual impairment. These findings suggest that in netIroanatomical terms, more posterior cortical function (temporal lobe) has not improved but there is at least some recovery of frontal lobe function in remission.


Integrative analysis of epigenetic modulation in melanoma cell response to decitabine: clinical implications.
Decitabine, an epigenetic modifier that reactivates genes otherwise suppressed by DNA promoter methylation, is effective for some, but not all cancer patients, especially those with solid tumors. It is commonly recognized that to overcome resistance and improve outcome, treatment should be guided by tumor biology, which includes genotype, epigenotype, and gene expression profile. We therefore took an integrative approach to better understand melanoma cell response to clinically relevant dose of decitabine and identify complementary targets for combined therapy. We employed eight different melanoma cell strains, determined their growth, apoptotic and DNA damage responses to increasing doses of decitabine, and chose a low, clinically relevant drug dose to perform whole-genome differential gene expression, bioinformatic analysis, and protein validation studies. The data ruled out the DNA damage response, demonstrated the involvement of p21(Cip1) in a p53-independent manner, identified the TGFbeta pathway genes CLU and TGFBI as markers of sensitivity to decitabine and revealed an effect on histone modification as part of decitabine-induced gene expression. Mutation analysis and knockdown by siRNA implicated activated beta-catenin/MITF, but not BRAF, NRAS or PTEN mutations as a source for resistance. The importance of protein stability predicted from the results was validated by the synergistic effect of Bortezomib, a proteasome inhibitor, in enhancing the growth arrest of decitabine in otherwise resistant melanoma cells. Our integrative analysis show that improved therapy can be achieved by comprehensive analysis of cancer cells, identified biomarkers for patient's selection and monitoring response, as well as targets for improved combination therapy.


A large psammomatoid ossifying fibroma with proptosis: A case report.
The psammomatoid ossifying fibroma (POF) is a rare and benign fibro-osseous lesion predominantly affecting the paranasal sinuses and orbits of children and young adults. The diagnosis and management of the lesion remains challenging. The present study reported a rare case of a large POF in a 39-year-old male patient. The patient had a 30 year history of a slowly growing tumor and this had resulted in right craniofacial deformity, as well as right lateral displacement of the eye ball. Due to the large tumor size, surgical removal of the lesion was the predominant treatment. At 5 months after complete surgical resection, the patient was free from any symptoms. The radiological and histological findings, as well as the surgical management, were presented and the relevant literature was reviewed.


Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV.
Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. The data on the global outbreak of "2019-nCoV, SARS-CoV, and MERS-CoV" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.


[A Case of Extrahepatic Bile Duct Carcinoid Tumor Involving Diagnostic Difficulties].
A patient in his 60s had undergone laparoscopic anterior resection for the treatment of carcinoma of the rectum in February 2016. Histopathologic examination revealed the lesion as a pT2(MP)n(-)M0, fStage Ⅰrectal cancer. One year post-surgery, contrast-enhanced computed tomography(CT)revealed enhancement of parts of the intrapancreatic distal bile ducts. Magnetic resonance cholangiopancreatography(MRCP)showed filling defects at the same site. Magnetic resonance imaging( MRI)with an endorectal coil(ERC)was then performed to identify reproducible bile duct filling defects. Neither cytology nor biopsy yielded any findings that definitely indicated malignancy. Intraductal ultrasonography(IDUS)led to the suspicion of a nonepithelial tumor or an enlarged lymph node. Repeated biopsies via ERC were performed based on the absence of evidence of malignancy and revealed the presence of some atypical cells within the lesions. Although no definitive diagnosis could be made, the patient was scheduled for surgery in June 2017 after obtaining his consent. Upon taping of the common bile duct during surgery, a tumor was palpable on the dorsal aspect of the pancreas. The bile duct tumor was completely excised and submitted for intraoperative diagnosis; the pancreatic dorsal aspect appeared to be totally split. There was no evidence of atypia in the neoplasm, which was therefore considered to be benign; however, malignancy could not be completely ruled out because the patient had presented with elevated serum levels of carbohydrate antigen(CA)19-9 once before the operation. After intraoperative consultation with the patient's family members, who were reluctant to provide consent for pancreaticoduodenectomy, we completed the operation with resection of the bile duct tumor, followed by choledochojejunostomy. The tumor was found to be chromogranin A(+), cluster of differentiation(CD)56(+/-), CA19-9(+, solely ductal structure), carcinoembryonic antigen(CEA)(+, solely ductal structure), and intranuclear p53(-), with an MIB- 1 index of<2%. With regard to neuroendocrine markers, a region that could potentially have been a carcinoid tumor, based on the findings on hematoxylin and eosin(HE)staining, and a lumenized superficial region showed positivity in toto. Therefore, the lesion as a whole was diagnosed as a G1 carcinoid neuroendocrine tumor(NET). However, the superficial lumenized layer was positive for both CA19-9 and CEA; therefore, the tumor was thought to concurrently have epithelial characteristics. The lateral stumpwas negative, while the status of the ablated region remained unclear. After discussing the histopathologic examination results with the patient and his family members, the patient's follow-upwas decided to consist of periodic checkups without any further surgical intervention. The patient has since remained free of recurrence. Carcinoid tumor of the bile duct is extremely rare but should be considered in cases involving bile duct tumors that show enhancement on imaging prior to surgery and for which no definitive diagnosis can be established despite repeated biopsy explorations.


Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines.
Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.


Olfactory receptor and circuit evolution promote host specialization.
The evolution of animal behaviour is poorly understood1,2. Despite numerous correlations between interspecific divergence in behaviour and nervous system structure and function, demonstrations of the genetic basis of these behavioural differences remain rare3-5. Here we develop a neurogenetic model, Drosophila sechellia, a species that displays marked differences in behaviour compared to its close cousin Drosophila melanogaster6,7, which are linked to its extreme specialization on noni fruit (Morinda citrifolia)8-16. Using calcium imaging, we identify olfactory pathways in D. sechellia that detect volatiles emitted by the noni host. Our mutational analysis indicates roles for different olfactory receptors in long- and short-range attraction to noni, and our cross-species allele-transfer experiments demonstrate that the tuning of one of these receptors is important for species-specific host-seeking. We identify the molecular determinants of this functional change, and characterize their evolutionary origin and behavioural importance. We perform circuit tracing in the D. sechellia brain, and find that receptor adaptations are accompanied by increased sensory pooling onto interneurons as well as species-specific central projection patterns. This work reveals an accumulation of molecular, physiological and anatomical traits that are linked to behavioural divergence between species, and defines a model for investigating speciation and the evolution of the nervous system.


Toxicity of methylmercury injected into eggs when dissolved in water versus corn oil.
In a previous study, the embryotoxicity of methylmercury dissolved in corn oil was compared among 26 species of birds. Corn oil is not soluble in the water-based matrix that constitutes the albumen of an egg. To determine whether the use of corn oil limited the usefulness of this earlier study, a comparison was made of the embryotoxicity of methylmercury dissolved in corn oil versus water. Mallard (Anas platyrhynchos) and chicken (Gallus gallus) eggs were injected with methylmercury chloride dissolved in corn oil or water to achieve concentrations of 0, 0.2, 0.4, 0.8, and 1.6 µg/g mercury in the egg on a wet weight basis. Hatching success at each dose of mercury was compared between the two solvents. For mallards, 16.4% of the eggs injected with 1.6 µg/g mercury dissolved in water hatched, which was statistically lower than the 37.6% hatch rate of eggs injected with 1.6 µg/g mercury dissolved in corn oil, but no differences in hatching success were observed between corn oil and water at any of the other doses. With chicken eggs, no significant differences occurred in percentage hatch of eggs between corn oil and water at any of the mercury doses. Methylmercury dissolved in corn oil seems to have a toxicity to avian embryos similar to that of does methylmercury dissolved in water. Consequently, the results from the earlier study that described the toxicity of methylmercury dissolved in corn oil to avian embryos were probably not compromised by the use of corn oil as a solvent.


Reaching Latinas with Our Bodies, Ourselves and the Guía de Capacitación para Promotoras de Salud: health education for social change.
As the cultural and linguistic diversity of the United States continues to grow and population shifts transform the communities where we live and work, health care providers continue to face challenges to deliver health services in demographically redefined terrains. This report describes the development of a Spanish-language training guide for community health workers (Guía de Capacitación para Promotoras de Salud) based on the book Nuestros Cuerpos, Nuestras Vidas (NCNV), the Spanish-language translation and cultural adaptation of the classic women's health book Our Bodies, Ourselves. The guide aims to 1) provide a tool for addressing the health education needs of immigrant Latinas and 2) facilitate the use of the book NCNV as a health education tool in Latino communities. Thirty telephone interviews with individuals working in agencies and organizations serving Latinos and 2 focus groups with Latinas were conducted to select the topics included in the training guide, all of which were drawn directly from NCNV. The guide contains 11 modules organized into 6 workshops. The modules address 11 topics related to women's health, ranging from sexuality and pregnancy to domestic violence and mental health. An ecological framework is used to deliver the health information. The materials acknowledge the roles of history, environment, culture, economic conditions, migration history, and politics as key determinants of health and illness. The workshops are designed to train community health workers on the women's health topics contained in the guide and to equip them for the delivery of health education among immigrant Latinas.


Implicit theories about interrelations of anger components in 25 countries.
We were interested in the cross-cultural comparison of implicit theories of the interrelations of eight anger components (antecedents, body sensations, cognitive reactions, verbal expressions, nonverbal expressions, interpersonal responses, and primary and secondary self-control). Self-report scales of each of these components were administered to a total of 5,006 college students in 25 countries. Equivalence of the scales was supported in that scales showed acceptable congruence coefficients in almost all comparisons. A multigroup confirmatory factor model with three latent variables (labeled internal processes, behavioral outcomes, and self-control mechanisms) could well account for the interrelations of the eight observed variables; measurement and structural weights were invariant. Behavioral outcomes and self-control mechanisms were only associated through their common dependence on internal processes. Verbal expressions and cognitive reactions showed the largest cross-cultural differences in means, whereas self-control mechanisms scales showed the smallest differences. Yet, cultural differences between the countries were small. It is concluded that anger, as measured by these scales, shows more pronounced cross-cultural similarities than differences in terms of both interrelations and mean score levels.


Fourier transform infrared spectroscopy as a method to study lipid accumulation in oleaginous yeasts.
Oleaginous microorganisms, such as different yeast and algal species, can represent a sustainable alternative to plant oil for the production of biodiesel. They can accumulate fatty acids (FA) up to 70% of their dry weight with a predominance of (mono)unsaturated species, similarly to what plants do, but differently from animals. In addition, their growth is not in competition either with food, feed crops, or with agricultural land.Despite these advantages, the exploitation of the single cell oil system is still at an early developmental stage. Cultivation mode and conditions, as well as lipid extraction technologies, represent the main limitations. The monitoring of lipid accumulation in oleaginous microorganisms is consequently crucial to develop and validate new approaches, but at present the majority of the available techniques is time consuming, invasive and, when relying on lipid extraction, can be affected by FA degradation. In this work the fatty acid accumulation of the oleaginous yeasts Cryptococcus curvatus and Rhodosporidium toruloides and of the non-oleaginous yeast Saccharomyces cerevisiae (as a negative control) was monitored in situ by Fourier Transform Infrared Spectroscopy (FTIR). Indeed, this spectroscopic tool can provide complementary information to those obtained by classical techniques, such as microscopy, flow cytometry and gas chromatography. As shown in this work, through the analysis of the absorption spectra of intact oleaginous microorganisms it is possible not only to monitor the progression of FA accumulation but also to identify the most represented classes of the produced lipids. Here we propose FTIR microspectroscopy - supported by multivariate analysis - as a fast, reliable and non invasive method to monitor and analyze FA accumulation in intact oleaginous yeasts. The results obtained by the FTIR approach were in agreement with those obtained by the other classical methods like flow cytometry and gas chromatography. Moreover, the possibility to track lipid production in real time is highly desirable to support the initial screening of strains and media as well as to optimize the scaling up experiments, which are essential for a viable and successful development of an industrial production process.


Criminal law and HIV testing: empirical analysis of how at-risk individuals respond to the law.
This Note assesses the effect of laws that specifically criminalize behaviors that expose others to the human immunodeficiency virus (HIV). This Note examines the relationship between HIV testing decisions by high-risk individuals and the existence of these HIV-specific statutes, as well as the amount of media coverage related to them. One of the main reasons public health experts criticize criminalization of HIV-exposing behavior is that it may discourage at-risk individuals from undergoing HIV testing. This argument, however, remains empirically untested to date. This study quantitatively examines whether at-risk individuals living in jurisdictions with HIV-specific statutes are less likely to report having been tested for HIV in the past year compared to those living in jurisdictions without HIV-specific statutes. Regression analysis is conducted using data collected in the United States over a seven-year span. The results show that at-risk individuals residing in states with HIV-specific statutes are no less likely to report having been tested for HIV than those who live in other states. However, the number of people who reported that they had been tested for HIV is inversely correlated with the frequency of newspaper coverage of criminalization of HIV-exposing behavior. These findings imply that at-risk individuals' HIV testing is associated with media coverage of criminalizing HIV-exposing behavior. The negative impact that criminal law has on HIV testing rates could be a serious public health threat. Testing is often the initial step in public health interventions that most effectively modify the risky behavior of HIV-positive individuals. The adverse consequence of criminalization should weigh heavily in the design and application of criminal sanctions for HIV-exposing behavior. In addition, future research should further explore the relationships between criminalization, media coverage of criminalization, and HIV testing decisions for a more nuanced understanding of the consequences of criminalization.


A cell type-specific transcriptomic approach to map B cell and monocyte type I interferon-linked pathogenic signatures in Multiple Sclerosis.
Alteration in endogenous Interferon (IFN) system may profoundly impact immune cell function in autoimmune diseases. Here, we provide evidence that dysregulation in IFN-regulated genes and pathways are involved in B cell- and monocyte-driven pathogenic contribution to Multiple Sclerosis (MS) development and maintenance. In particular, by using an Interferome-based cell type-specific approach, we characterized an increased susceptibility to an IFN-linked caspase-3 dependent apoptotic cell death in both B cells and monocytes of MS patients that may arise from their chronic activation and persistent stimulation by activated T cells. Ongoing caspase-3 activation functionally impacts on MS monocyte properties influencing the STAT-3/IL-16 axis, thus, driving increased expression and massive release of the bio-active IL-16 triggering and perpetuating CD4+ T cell migration. Importantly, our analysis also identified a previously unknown multi-component defect in type I IFN-mediated signaling and response to virus pathways specific of MS B cells, impacting on induction of anti-viral responses and Epstein-barr virus infection control in patients. Taking advantage of cell type-specific transcriptomics and in-depth functional validation, this study revealed pathogenic contribution of endogenous IFN signaling and IFN-regulated cell processes to MS pathogenesis with implications on fate and functions of B cells and monocytes that may hold therapeutic potential.


Large scale screening for haemoglobin disorders in southern Vietnam: implications for avoidance and management.
In order to obtain an approximate assessment of the public health burden that will be posed by the inherited disorders of haemoglobin in southern Vietnam, several thousand individuals were screened for these conditions. A smaller sample was screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. The important haemoglobin disorders identified were beta thalassaemia, haemoglobin E and a variety of different forms of alpha thalassaemia. There were sufficient G6PD-deficient individuals to materially affect malaria control programme design. The most remarkable finding was wide variation in the gene frequencies of these conditions among the ethnic groups sampled. The approximate number of babies expected to be born with clinically significant haemoglobin disorders in Vietnam was estimated from the gene-frequency data. This study emphasizes the importance of wide-scale population screening, including ethnic subgroups, to establish the requirements for inherited haemoglobin disorder programmes in resource-limited settings.


Screening for type 2 diabetes is feasible, acceptable, but associated with increased short-term anxiety: a randomised controlled trial in British general practice.
To assess the feasibility and uptake of a diabetes screening programme; to examine the effects of invitation to diabetes screening on anxiety, self-rated health and illness perceptions. Randomised controlled trial in two general practices in Cambridgeshire. Individuals aged 40-69 without known diabetes were identified as being at high risk of having undiagnosed type 2 diabetes using patient records and a validated risk score (n = 1,280). 355 individuals were randomised in a 2 to 1 ratio into non-invited (n = 238) and invited (n = 116) groups. A stepwise screening programme confirmed the presence or absence of diabetes. Six weeks after the last contact (either test or invitation), a questionnaire was sent to all participants, including non-attenders and those who were not originally invited. Outcome measures included attendance, anxiety (short-form Spielberger State Anxiety Inventory-STAI), self-rated health and diabetes illness perceptions. 95 people (82% of those invited) attended for the initial capillary blood test. Six individuals were diagnosed with diabetes. Invited participants were more anxious than those not invited (37.6 vs. 34.1 STAI, p-value = 0.015), and those diagnosed with diabetes were considerably more anxious than those classified free of diabetes (46.7 vs. 37.0 STAI, p-value = 0.031). Non-attenders had a higher mean treatment control sub-scale (3.87 vs. 3.56, p-value = 0.016) and a lower mean emotional representation sub-scale (1.81 vs. 2.68, p-value = 0.001) than attenders. No differences in the other five illness perception sub-scales or self-rated health were found. Screening for type 2 diabetes in primary care is feasible but may be associated with higher levels of short-term anxiety among invited compared with non-invited participants.


Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells.
Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.


[Secondary prevention of myocardial infarct].
Preventive measures are the most powerful measures to treat manifestations of ischemic cardiopathy. Secondary prevention of myocardial infarction involves the following intervention areas: a) Limitation of adverse physiological and emotional consequences of the acute illness; b) Identification of the patients particularly exposed to the risk of new episodes of ischemic cardiopathy or to their consequences, namely reinfarction and sudden death; c) Institution of therapeutic attitudes, surgical or medical, that can prolong life and can oppose functional deterioration and prevent symptoms; d) Institution of measures that can oppose the progression of the initial disease that is, in almost all cases, atherosclerosis. Measures that can oppose the progression of cardiac disease and its consequences after an episode of myocardial infarction, and measures that can oppose the evolution of atherosclerosis are described in this article. The measures that can influence the risk factors after an episode of myocardial infarction are briefly commented: characteristics related to life style and physical exercise; smoking habits; plasmatic lipid levels; high blood pressure; and therapeutic substitution with estrogens after menopause. Pharmacological interventions in secondary prevention of myocardial infarction are described, namely with the following groups of substances: beta-adrenergic blocking agents; platelet active agents; anticoagulants; and angiotensin-converting enzyme inhibitors.


Hormone levels and mammary epithelial cell proliferation in rats treated with a regimen of estradiol and progesterone that mimics the preventive effect of pregnancy against mammary cancer.
Women who bear their first child by their late teens have about half the risk of developing breast cancer relative to nulliparous women. The rat is a good model for studying the role of hormones in breast cancer since, for example, young rats become nearly refractory to mammary carcinogenesis after delivering a litter of pups. Short term administration of estradiol and progesterone (E & P) provides virgin rats protection from mammary carcinogenesis as effectively as pregnancy. The purpose of these studies were twofold: first, to evaluate potential long-term toxicity of the E & P treatments and second, to compare hormone treated rats and pregnant rats with respect to circulating E & P levels as well as mammary epithelial cell proliferation and differentiation. To test for toxicity, rats were treated with E & P (20 micrograms and 4 mg, respectively) or vehicle by s.c. injections 5 times per week for 5 weeks beginning at 40 days of age. The animals were weighed biweekly and sacrificed at 500 days of age when detailed necropsies were performed. No significant difference in weight gain was observed between the two groups nor was any toxicity grossly observable in the hormone-treated rats. Furthermore, there was no increase in the number of spontaneous mammary or pituitary tumors in the E & P treated group relative to controls. To evaluate serum hormone titers and mammary proliferation, rats were treated with steroids or vehicle daily beginning at 65 days of age. At 6 and 24 hours after the 1st, 14th and 35th injection, serum E & P were measured by RIA and mammary epithelial cell proliferation by immunohistochemistry (PCNA). At 6 hours after each injection, E & P levels were 3 to 5 fold those observed late in pregnancy. By 24 hours, however, E & P levels subsided to late pregnancy levels or lower. The mammary epithelial cell proliferation index in either E & P treated or late pregnant rats was 6 to 14%. Histologic sections and wholemounts of mammary glands showed a similar degree of differentiation between rats treated with E & P for 14 days or longer and late pregnant rats. These data further suggest that E & P treatments are a non-toxic means of mimicking the protective effect of pregnancy against mammary cancer and that pregnancy or hormone treatments may achieve this prophylaxis through a differentiation mechanism.


Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease.
The genetic influence on disease course in inflammatory bowel disease (IBD) remains unknown. We therefore aimed to study longitudinal concordance for clinical characteristics and longitudinal stability using the Montreal Classification in an IBD twin population. A total of 158 twins with ulcerative colitis (UC) (18 belonging to 9 concordant monozygotic pairs) and 141 twins with Crohn's disease (CD) (34 belonging to 17 concordant monozygotic pairs) were enrolled. Medical notes were scrutinized for clinical characteristics at diagnosis and after 10 years. Using the binominal distribution, we tested the hypothesis that clinical characteristics were independent within individuals in disease concordant monozygotic pairs. In CD, location was identical in 11/17 monozygotic concordant pairs at diagnosis (P = 0.008) and in 11/16 pairs after 10 years (P = 0.02). Behavior at diagnosis was identical in 13/17 pairs (P = 0.03) and in 11/16 pairs after 10 years (P = 0.01). Monozygotic UC twins were concordant (within 5 years) for age at diagnosis (6/9 pairs; P < 0.001) and symptomatic onset (4/9 pairs; P = 0.02) but not for extent of disease at diagnosis or after 10 years. The Montreal Classification did not demonstrate longitudinal stability, either regarding location or behavior of CD or extent of UC. The high phenotypic concordance, both at diagnosis and longitudinally, in monozygotic twins with CD supports a genetic influence not only on disease occurrence but also on disease course. This contrasts with UC, where the genetic impact appears less. Montreal Classification characteristics changed over time and should be used cautiously.


Algorithm for localized adaptive diffuse optical tomography and its application in bioluminescence tomography.
A reconstruction algorithm for diffuse optical tomography based on diffusion theory and finite element method is described. The algorithm reconstructs the optical properties in a permissible domain or region-of-interest to reduce the number of unknowns. The algorithm can be used to reconstruct optical properties for a segmented object (where a CT-scan or MRI is available) or a non-segmented object. For the latter, an adaptive segmentation algorithm merges contiguous regions with similar optical properties thereby reducing the number of unknowns. In calculating the Jacobian matrix the algorithm uses an efficient direct method so the required time is comparable to that needed for a single forward calculation. The reconstructed optical properties using segmented, non-segmented, and adaptively segmented 3D mouse anatomy (MOBY) are used to perform bioluminescence tomography (BLT) for two simulated internal sources. The BLT results suggest that the accuracy of reconstruction of total source power obtained without the segmentation provided by an auxiliary imaging method such as x-ray CT is comparable to that obtained when using perfect segmentation.


Nonsurgical Facial Rejuvenation Procedures in Patients Under 50 Prior to Undergoing Facelift: Habits, Costs, and Results.
Facial rejuvenation in patients younger than 50 years of age has experienced an unprecedented growth with multimodality nonsurgical and less invasive rhytidectomy techniques. To analyze the nonsurgical treatment habits of patients prior to undergoing rhytidectomy at <50 years of age. Retrospective study to enlist patients who underwent primary rhytidectomy at age <50 years between January 1, 2003 and December 31, 2013 by the senior author (AAJ) to complete a survey. One hundred and fifty-seven patients were surveyed. Patients had nonsurgical rejuvenation starting at an average age of 37 years and rhytidectomy at an average age of 44 years. Thirty-two percent of responders had injectable treatments prior to their facelift, reporting a mean of 7 rounds of injectable treatments prior to pursuing rhytidectomy. Sixteen percent of responders had laser skin resurfacing undergoing 4 separate treatments prior to rhytidectomy, and 10% had energy-based facial tightening treatments one time prior to their rhytidectomy. Average expenditure on nonsurgical treatments prior to rhytidectomy was $7000 cumulatively. Fifty-nine percent of patients who went on to rhytidectomy did not report regret over this cost expenditure. Patients reported that they appeared 4 years younger after nonsurgical intervention, and 8 years younger after their facelift, a statistically significant difference (P = .048). Patients undergoing rhytidectomy <50 years old begin less invasive facial rejuvenation treatments at an even earlier age. The majority of these patients did not regret the costs associated with noninvasive treatments, even though they saw that rhytidectomy provided a greater rejuvenation effect. Rhytidectomy surgeons should incorporate nonsurgical techniques into their practice to best serve the needs of the modern aging face patient.


Protease-sensitive synthetic prions.
Prions arise when the cellular prion protein (PrP(C)) undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc). Frequently, PrP(Sc) is protease-resistant but protease-sensitive (s) prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec) PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164), denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174) did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc) and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc). These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc).


Anxious, threatened, and also unethical: how anxiety makes individuals feel threatened and commit unethical acts.
People often experience anxiety in the workplace. Across 6 studies, we show that anxiety, both induced and measured, can lead to self-interested unethical behavior. In Studies 1 and 2, we find that compared with individuals in a neutral state, anxious individuals are more willing (a) to participate in unethical actions in hypothetical scenarios and (b) to engage in more cheating to make money in situations that require truthful self-reports. In Studies 3 and 4, we explore the psychological mechanism underlying unethical behaviors when experiencing anxiety. We suggest and find that anxiety increases threat perception, which, in turn, results in self-interested unethical behaviors. Study 5 shows that, relative to participants in the neutral condition, anxious individuals find their own unethical actions to be less problematic than similar actions of others. In Study 6, data from subordinate-supervisor dyads demonstrate that experienced anxiety at work is positively related with experienced threat and unethical behavior. We discuss the theoretical and practical implications of our findings.


Study of Flare Assessment in Systemic Lupus Erythematosus Based on Paper Patients.
To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features. Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.


Beneficial effect of pistachio consumption on glucose metabolism, insulin resistance, inflammation, and related metabolic risk markers: a randomized clinical trial.
To examine whether a pistachio-rich diet reduces the prediabetes stage and improves its metabolic risk profile. Prediabetic subjects were recruited to participate in this Spanish randomized clinical trial between 20 September 2011 and 4 February 2013. In a crossover manner, 54 subjects consumed two diets, each for 4 months: a pistachio-supplemented diet (PD) and a control diet (CD). A 2-week washout period separated study periods. Diets were isocaloric and matched for protein, fiber, and saturated fatty acids. A total of 55% of the CD calories came from carbohydrates and 30% from fat, whereas for the PD, these percentages were 50 and 35%, respectively (including 57 g/day of pistachios). Fasting glucose, insulin, and HOMA of insulin resistance decreased significantly after the PD compared with the CD. Other cardiometabolic risk markers such as fibrinogen, oxidized LDL, and platelet factor 4 significantly decreased under the PD compared with the CD (P < 0.05), whereas glucagon-like peptide-1 increased. Interleukin-6 mRNA and resistin gene expression decreased by 9 and 6%, respectively, in lymphocytes after the pistachio intervention (P < 0.05, for PD vs. CD). SLC2A4 expression increased by 69% in CD (P = 0.03, for PD vs. CD). Cellular glucose uptake by lymphocytes decreased by 78.78% during the PD (P = 0.01, PD vs. CD). Chronic pistachio consumption is emerging as a useful nutritional strategy for the prediabetic state. Data suggest that pistachios have a glucose- and insulin-lowering effect, promote a healthier metabolic profile, and reverse certain metabolic deleterious consequences of prediabetes.


Identifying the future needs for long-term USDA efforts in agricultural animal genomics.
Agricultural animal research has been immensely successful over the past century in developing technology and methodologies that have dramatically enhanced production efficiency of the beef, dairy, swine, poultry, sheep, and aquaculture industries. In the past two decades, molecular biology has changed the face of agricultural animal research, primarily in the arena of genomics and the relatively new offshoot areas of functional genomics, proteomics, transcriptomics, metabolomics and metagenomics. Publication of genetic and physical genome maps in the past 15 years has given rise to the possibility of being able finally to understand the molecular nature of the genetic component of phenotypic variation. While quantitative geneticists have been remarkably successful in improving production traits, genomic technology holds potential for being able to lead to more accurate and rapid animal improvement, especially for phenotypic traits that are difficult to measure.Recently, the agricultural research community has been able to capitalize on the infrastructure built by the human genome project by sequencing two of the major livestock genomes (Gallus domesticus and Bos Taurus). The 2005 calendar year is truly unprecedented in the history of agricultural animal research since draft genome sequences were completed for chickens and cattle. In addition, sequencing the swine and equine genome was initiated in early 2006. We now have in place a powerful toolbox for understanding the genetic variation underlying economically important and complex phenotypes. Over the past few years, new challenges have emerged for animal agriculture. Enhancements in production efficiency have not come without some negative side effects on animal well-being and longevity in production environments, including losses in reproductive efficiency, increased stress susceptibility, increased animal waste issues, and increased susceptibility to animal metabolic and infectious diseases. When considered in concert with societal concerns in the areas of natural resource conservation and protection, animal welfare, and food safety, it is clear that publicly supported agricultural research must be focused on enhancing the functionality and well-being of livestock and poultry in environmentally neutral production systems in the future. Realizing the great potential for animal genomics to address these and other issues, a workshop was convened by the U. S. Department of Agriculture (USDA) in Washington, DC in September of 2004. The workshop was entitled "Charting the Road Map for Long Term USDA Efforts in Agricultural Animal Genomics". This paper summarizes the proceedings of the workshop and the resulting recommendations. The need for a cohesive, comprehensive long-term plan for all of USDA's research efforts in animal genomics was evident at the workshop, requiring further integration of the efforts of the USDA's Cooperative State Research, Education, and Extension Service (CSREES) and the USDA's Agricultural Research Service (ARS) to achieve the greatest return on investment.


Lifetime physical and sexual abuse, substance abuse, depression, and suicide attempts among Native American women.
Although there is preliminary evidence that violence against women and children may be particularly prevalent in some Native American communities, associations between abuse and substance abuse, mental health problems, and suicide attempts have rarely been studied in this population. This study examined lifetime and current physical and sexual abuse among 30 Native American women. Nearly half had experienced physical and/or sexual abuse as children, over half were sexually abused at some time in their lives, and over three-fourths were abused by a partner. All but four women (87%) had experience physical or sexual abuse in their lifetime. Significant relationships were found among childhood abuse, substance abuse, and adult revictimization, and among cumulative lifetime abuse events, substance abuse, and depression. Further research is needed to examine abuse and relationships between abuse and health sequelae in Native American populations. An accelerated public health and community response is needed to address abuse issues in this community.


IL-17/Th17 pathway is activated in acne lesions.
The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy.


Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes.
NKT cell activation by alpha-galactosylceramide (alpha-GalCer) inhibits autoimmune diabetes in NOD mice, in part by inducing recruitment to pancreatic lymph nodes (PLNs) of mature dendritic cells (DCs) with disease-protective effects. However, how activated NKT cells promote DC maturation, and what downstream effect this has on diabetogenic T cells was unknown. Activated NKT cells were found to produce a soluble factor(s) inducing DC maturation. Initially, there was a preferential accumulation of mature DCs in the PLNs of alpha-GalCer-treated NOD mice, followed by a substantial increase in T cells. Adoptive transfer of a diabetogenic CD8 T cell population (AI4) induced a high rate of disease (75%) in PBS-treated NOD recipients, but not in those pretreated with alpha-GalCer (8%). Significantly, more AI4 T cells accumulated in PLNs of alpha-GalCer than PBS-treated recipients, while no differences were found in mesenteric lymph nodes from each group. Compared with those in mesenteric lymph nodes, AI4 T cells entering PLNs underwent greater levels of apoptosis, and the survivors became functionally anergic. NKT cell activation enhanced this process. Hence, activated NKT cells elicit diabetes protection in NOD mice by producing a soluble factor(s) that induces DC maturation and accumulation in PLNs, where they subsequently recruit and tolerize pathogenic T cells.