Surfactant-free sacrificial template synthesis of submicrometer-sized YVO4:Eu3+ hierarchical hollow spheres with tunable textual parameters and luminescent properties.
For the first time, well-dispersed submicrometer-sized YVO(4):Eu(3+) hollow spheres were successfully synthesized though a surfactant-free method by employing Y(OH)CO(3):Eu(3+) colloidal spheres as a sacrificial template and NH(4)VO(3) as a vanadium source. The synthetic process mainly consists of two steps, i.e., hydrothermal reaction and acid erosion. By simply changing the amount of NH(4)VO(3) added, the textural parameters of the as-obtained hollow spheres, such as the inner diameter and shell-thickness, can be easily tuned. Moreover, double-shelled hollow spheres could also be obtained when the amount of NH(4)VO(3) was increased to a certain extent. Particularly, the amorphous colloidal spheres of the template could be completely consumed when the amount of NH(4)VO(3) was in large excess, giving rise to the direct formation of uniform hollow spheres without acid erosion. The possible formation process is discussed in detail. Under ultraviolet excitation, the obtained hollow YVO(4):Eu(3+) phosphors showed strong red emissions, and the Commission Internationale d'Eclairage (CIE) coordinates of the YVO(4):Eu(3+) phosphors were closely related with the textural parameters such as the inner diameter, shell-thickness and number of shells, indicating a size-dependent characteristic.


Factors affecting the daily feed intake and feed conversion ratio of pigs in grow-finishing units: the case of a company.
The aim of this study was to use mathematical modeling to identify and quantify the main factors that affect daily feed intake (DFI) and feed conversion ratio (FCR) in grow-finishing (GF) pig units. We evaluated the production records of 93 GF farms between 2010 and 2013, linked to a company, working in a cooperative system, located in western Paraná State, Brazil. A total of 683 batches, consisting of approximately 495,000 animals, were used. Forty production factors related to the management, health, plant and equipment, nutrition, genetics and environment were considered. The number of pigs per pen, type of feeder, origin and sex (the last two variables were combined in the models) of the animals and initial and final body weights were included in the final models to predict DFI and FCR (dependent variables). Additionally, the duration of the GF phase was included for the parameter FCR. All factors included in the final models had significant effects for both dependent variables. There was a reduction in DFI (0.04 kg) (P < 0.001) and an improvement in FCR (6.0 points) (P < 0.001) in batches from pens with less than 20 animals compared with batches from pens with more than 20 animals. In barns with "other" feeder types (mostly the linear dump type) different of conical semiautomatic feeder, a reduction of DFI (0.03 kg) (P < 0.05) and improved FCR (3.0 points) (P < 0.05) were observed. Batches of barrows from units specialized for producing piglets (SPU) had higher DFI (approximately 0.02 kg) (P < 0.01) than batches of females and batches of mixed animals from SPU, and batches of mixed animals from farms not specialized for piglet production (farrow-to-finish farms). Batches of females from SPU and mixed batches from SPU had better FCR (5.0 and 3.0 points respectively) (P < 0.001 and P < 0.001, respectively) than batches of piglets originating from farrow-to-finish farms. The variables selected for the final models explained approximately 50 and 64 % of the total variance in DFI and FCR, respectively. The models are tools for the interpretation of the factors related to the evaluated parameters, aiding in the identification of critical aspects of production. The main parameters affecting DFI and FCR in this company during the GF period were the number of pigs per pen, the type of feeder used and the combination origin-sex of the animals.


[Lipids of a paraffin-oxidizing strain of Pseudomonas aeruginosa].
The qualitative and quantitative composition of lipids was studied in a paraffin-oxidizing Pseudomonas aeruginosa P-20 strain. The content of free lipids was 7% of the dry biomass weight in a medium with hexadecane and 6.7% in a medium with glucose. The content of bound lipids was 6.7 and 5.6%, respectively. Phospholipids and free fatty acids are main components of lipids in the both cases. Phospholipids are represented by diphosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl glycerol, and phosphatidyl choline. The fatty acids of free lipids consist by 72% of even acids with an unbranched carbon chain, among which palmitic and octadecenic acids prevail no matter what is the composition of a medium. 'Uneven' acids are represented mainly by nonadecenic acid: 17.8% in the medium with hexadecane and 15.9% in the medium with glucose. The content of unsaturated acids is 55.95% in 'hexadecane' cells and 44.89% in 'glucose' cells; octadecenic and nonadecenic acids predominate among unsaturated acids. Fatty acids covalently bound to cellular proteins and polysaccharides contain much less unsaturated compounds (particularly in cells grown in the medium with hexadecane) and more branched acids; C18:1, C16:0 and C17:0-branched acids predominate among them.


Ensuring continued progress in biomarkers for amyotrophic lateral sclerosis.
Multiple candidate biomarkers for amyotrophic lateral sclerosis (ALS) have emerged across a range of platforms. Replication of results, however, has been absent in all but a few cases, and the range of control samples has been limited. If progress toward clinical translation is to continue, the specific biomarker needs of ALS, which differ from those of other neurodegenerative disorders, as well as the challenges inherent to longitudinal ALS biomarker cohorts, must be understood. Appropriate application of multimodal approaches, international collaboration, presymptomatic studies, and biomarker integration into future therapeutic trials are among the essential priorities going forward.


Quality of life among patients receiving palliative care in South Africa and Uganda: a multi-centred study.
Quality of life (QOL) is a core outcome of palliative care, yet in African settings there is a lack of evidence on patients' levels of QOL. We aimed to describe QOL among patients with incurable, progressive disease receiving palliative care in South Africa and Uganda, to compare QOL in cancer and HIV, to determine how domains of QOL correlate with overall QOL, and compare levels of QOL in this population with those in other studies using the same tool. A cross-sectional survey was conducted using the Missoula Vitas Quality of Life Index (MVQOLI), a 26-item QOL questionnaire with five subscales (Function, Symptom, Interpersonal, Well being, Transcendent) covering physical, social, psychological and spiritual domains and one global QOL item. One item in each subscale assesses the subjective importance of the domain on a score from 1 (least important) to 5 (most important), used to weight the contribution of the subscale towards the Total QOL score. The tool was translated into 6 languages and administered to consecutively recruited patients at four facilities in South Africa and one in Uganda. 285 patients were recruited, with a mean age of 40.1; 197 (69.1%) were female. Patients' primary diagnoses were HIV (80.7%), cancer (17.9%) and other conditions (1.4%). The mean global QOL score was 2.81 (possible range 0 (worst) to 5 (best)); mean Total score 17.32 (possible range 0 to 30). Patients scored most poorly on Function (mean 0.21), followed by Well being (2.59), Symptoms (5.38), Transcendent (5.50), Interpersonal (9.53) (possible range for subscale scores -30 to 30). Most important to patients were: close relationships (mean 4.13), feeling at peace (4.12), sense of meaning in life (4.10), being active (3.84), physical comfort (2.58). Cancer patients were predominantly recruited at three of the sites; hence comparison with HIV-infected patients was restricted to these sites. HIV+ patients (n = 115) scored significantly worse than cancer patients (n = 50) on Well being (Z = -2.778, p = 0.005), Transcendence (Z = -2.693, p = 0.007) and Total QOL (Z = -2.564, p = 0.01). Global QOL score was most weakly correlated with Total QOL (r = 0.37) and the Transcendent subscale was most highly correlated (r = 0.77) (both p < 0.001). Patients receiving palliative care in South Africa and Uganda exhibited significantly poorer QOL compared to similar populations in the USA. Feeling at peace and having a sense of meaning in life were more important to patients than being active or physical comfort, and spiritual wellbeing correlated most highly with overall QOL. It is therefore vital to identify and meet the psychological and spiritual care needs of patients, as well as to assess and treat pain and other symptoms. Our finding that patients scored most poorly on the Function domain warrants further research.


Study Protocol--Improving Access to Kidney Transplants (IMPAKT): a detailed account of a qualitative study investigating barriers to transplant for Australian Indigenous people with end-stage kidney disease.
Indigenous Australians are slightly more than 2% of the total Australian population however, in recent years they have comprised between 6 and 10% of new patients beginning treatment for end-stage kidney disease (ESKD). Although transplant is considered the optimal form of treatment for many ESKD patients there is a pronounced disparity between the rates at which Indigenous ESKD patients receive transplants compared with their non-Indigenous counterparts. The IMPAKT (Improving Access to Kidney Transplants) Interview study investigated reasons for this disparity through a large scale, in-depth interview study involving patients, nephrologists and key decision-making staff at selected Australian transplant and dialysis sites. The design and conduct of the study reflected the multi-disciplinary membership of the core IMPAKT team. Promoting a participatory ethos, IMPAKT established partnerships with a network of hospital transplant units and hospital dialysis treatment centres that provide treatment to the vast majority of Indigenous patients across Australia. Under their auspices, the IMPAKT team conducted in-depth interviews in 26 treatment/service centres located in metropolitan, regional and remote Australia. Peer interviewing supported the engagement of Indigenous patients (146), and nephrologists (19). In total IMPAKT spoke with Indigenous and non-Indigenous patients (241), key renal nursing and other (non-specialist) staff (95) and a small number of relevant others (28). Data analysis was supported by QSR software. At each site, IMPAKT also documented educational programs and resources, mapped an hypothetical 'patient journey' to transplant through the local system and observed patient care and treatment routines. The national scope, inter-disciplinary approach and use of qualitative methods in an investigation of a significant health inequality affecting Indigenous people is, we believe, an Australian first. An exceptionally large cohort of Indigenous participants provided evaluative comment on their health services in relation to dialysis and transplant. Additionally, the data includes extensive parallel commentary from a cohort of specialists, nurses and other staff. The study considers a 'patient journey' to transplant within a diverse range of Australian treatment centre/workplace settings. The IMPAKT Interview study protocol may contribute to improvements in multi-disciplinary, flexible design health services research with hard to reach or vulnerable populations in Australia and elsewhere.


Myosin-X is dispensable for spindle morphogenesis and positioning in the mouse oocyte.
Off-center spindle positioning in mammalian oocytes enables asymmetric divisions in size, which are important for subsequent embryogenesis. The migration of the meiosis I spindle from the oocyte center to its cortex is mediated by F-actin. Specifically, an F-actin cage surrounds the microtubule spindle and applies forces to it. To better understand how F-actin transmits forces to the spindle, we studied a potential direct link between F-actin and microtubules. For this, we tested the implication of myosin-X, a known F-actin and microtubule binder involved in spindle morphogenesis and/or positioning in somatic cells, amphibian oocytes and embryos. Using a mouse strain conditionally invalidated for myosin-X in oocytes and by live-cell imaging, we show that myosin-X is not localized on the spindle, and is dispensable for spindle and F-actin assembly. It is not required for force transmission as spindle migration and chromosome alignment occur normally. More broadly, myosin-X is dispensable for oocyte developmental potential and female fertility. We therefore exclude a role for myosin-X in transmitting F-actin-mediated forces to the spindle, opening new perspectives regarding this mechanism in mouse oocytes, which differ from most mitotic cells.


An investigation of residential facility staff usage of touchscreen technology.
Older adults may become more familiar and interested in using touchscreen technology (TT). TT can be used to engage older adults living in residential aged care facilities (RACFs) and staff there can play an important role in supporting residents to use TT. However, before these are introduced, it is crucial to investigate their opinions in using TT with residents. A questionnaire based on the Technology Acceptance Model was administered to assess staff usage and confidence in using TT, their perceptions in TT ease-of-use and usefulness in helping them care for their residents. Perhaps unsurprisingly, results found that respondents were familiar using TT. More importantly, staff reported that they were interested in engaging residents with TT and nominated different training methods to support them such as group in-services. This project provides information about staff experience and acceptance of the use of TT for residents in RACFs.


Relocating race: introdution.
The essays here reconsider some of the basal assumptions in Nancy Stepan's now-classic The Idea of Race in Science (1982). Stepan's book focused, for the most part, on metropolitan scientists from 1800 to 1960. The present contributions seek to "relocate" race along one (at least) of three axes: discipline, geography, period. The aim overall is not so much to make the fairly obvious point that "racial" thinking was different in different times and places; rather, the essays seek to use accounts of the relocation of race to "make strange" our assumptions about the conditions of possibility for nineteenth- and early twentieth-century race science in its once-canonical form.


Community Perceptions of HIV Stigma, Discriminatory Attitudes, and Disclosure Concerns: A Health Facility-Based Study in Selected Health Districts of South Africa.
Research data about HIV stigma perceptions and discriminatory attitudes among the general population are limited. Furthermore, the willingness of HIV-negative individuals to engage with HIV prevention and disclosure interventions has not been established in South Africa. The study investigated community perceptions of stigma as well as discriminatory attitudes towards HIV disclosure to understand if and how these perceptions might influence the uptake of disclosure interventions. This facility-based study used a validated questionnaire to measure the four constructs of HIV stigma among 670 adults recruited from health districts of two provinces of South Africa. Of these, 72% were female, 87% had ever been tested for HIV, and 31% knew someone who has HIV. Stigma towards people living with HIV (PLHIV) is widespread in the general population. A high proportion (75%) endorsed disclosure concerns, 75% perceived stigma to be common, and 56% endorsed negative statements indicating perceived stigma in communities. Fear, moral and social judgement, and rejection underlined their perceptions about PLHIV. Almost half (45.7%) were unwilling to care for family members sick with AIDS, suggesting negative distancing reactions and discriminatory attitudes towards PLHIV. The widespread discriminatory attitudes and the perceived stigma that is evident in the general population might heighten the disclosure concerns endorsed, promote non-disclosure, and increase HIV transmission. To design interventions, it is crucial to be cognisant of disclosure concerns, discriminatory attitudes, and perceived stigma evident in communities. Thus, the findings underscore the need to increase efforts to challenge and reduce community drivers of negative discriminatory attitudes and perceived stigma.


Assessing grassland cultural ecosystem services supply and demand for promoting the sustainable realization of grassland cultural values.
Grasslands deliver essential providing and regulating ecosystem services, concomitantly with providing indispensable cultural services that merit profound consideration. However, grassland cultural ecosystem services (GCES) face a conspicuous knowledge lacuna due to the lack of a unified research framework and quantitative methodology. This study endeavors to fill this gap by quantifying the potential supply and actual demand of GCES, concurrently scrutinizing spatial congruencies and disparities between GCES supply and demand in Inner Mongolia Autonomous Region (IMAR), China. To achieve this, we integrated social survey data, Point of Interest (POI) data, social media data, the Social Values for Ecosystem Services (SolVES) model and GIS Getis-Ord Gi* statistical analysis. Our analysis unveiled grid-scale spatial patterns of GCES supply and demand, furnishing a nuanced high-low ranking of GCES. It transpired that scenic travel holds the highest potential supply of GCES with a high-value area proportion of 46.0 %, while grassland recuperation ranks the lowest. Notably, road accessibility emerged as the most crucial factor influencing GCES patterns. Furthermore, we observed a substantial misalignment in the GCES supply-demand relationship, with 65.99 % of IMAR experiencing excess supply compared to demand and only 20.66 % achieving equilibrium. At a 95 % significance level, hot spots (excess supply) and cold spots (excess demand) accounted for 26.03 % and 22 %, respectively. We propose targeted suggestions that regions with oversupply of GCES should channel efforts toward augmenting road accessibility, whereas regions grappling with excess demand should prioritize the judicious allocation of resources to avert surpassing the environmental carrying capacity. Our study furnished insights for decision-makers to formulate sustainable development plans pertaining to grassland culture.


Structural and thermodynamic insights into antibody light chain tetramer formation through 3D domain swapping.
Overexpression of antibody light chains in small plasma cell clones can lead to misfolding and aggregation. On the other hand, the formation of amyloid fibrils from antibody light chains is related to amyloidosis. Although aggregation of antibody light chain is an important issue, atomic-level structural examinations of antibody light chain aggregates are sparse. In this study, we present an antibody light chain that maintains an equilibrium between its monomeric and tetrameric states. According to data from X-ray crystallography, thermodynamic and kinetic measurements, as well as theoretical studies, this antibody light chain engages in 3D domain swapping within its variable region. Here, a pair of domain-swapped dimers creates a tetramer through hydrophobic interactions, facilitating the revelation of the domain-swapped structure. The negative cotton effect linked to the β-sheet structure, observed around 215 nm in the circular dichroism (CD) spectrum of the tetrameric variable region, is more pronounced than that of the monomer. This suggests that the monomer contains less β-sheet structures and exhibits greater flexibility than the tetramer in solution. These findings not only clarify the domain-swapped structure of the antibody light chain but also contribute to controlling antibody quality and advancing the development of future molecular recognition agents and drugs.


Warning Signs: Occult Diabetes and Dysglycemia in the Hand Surgery Patient Population.
Diabetes mellitus often exists for many years prior to diagnosis, and very little is known about the role of the prediagnosis stage of metabolic impairment in contributing to hand and upper-extremity pathology. The goal of this study is to determine the prevalence of undiagnosed glucose dysregulation in patients presenting with the 2 most commonly treated conditions of the hand and wrist. A retrospective study was performed of hand surgery patients with no established diagnosis of prediabetes or diabetes referred for a 2-hour glucose tolerance test according to American Diabetes Association criteria. Patients were divided into 3 groups: peripheral neuropathies, trigger finger, and controls with various upper-extremity diagnoses. Rates of undiagnosed prediabetes and diabetes were compared between groups, including subgroup analysis of patients based on unilateral or bilateral presentation. Binary logistic regression analysis was also used to calculate odds ratios for multiple variables. Patients with neuropathy had a significantly higher incidence of undiagnosed dysglycemia compared with the control group. Of those patients, 51.3% were prediabetic and 12.8% were diabetic. The control group had significantly lower rates. Within the bilateral neuropathy patients, 59.6% had prediabetes and 15.4% had diabetes, versus 34.6% with prediabetes and 7.7% with diabetes in the unilateral group. Hand surgeons encounter a patient population with high rates of undiagnosed prediabetes and diabetes, with some presentations as much as 6 times higher than the general population. Certain patient presentations should prompt appropriate diagnostic testing and referral, especially those presenting with bilateral compression neuropathy and elevated body mass index.


Mechanisms and consequences of intestinal dysbiosis.
The composition of the gut microbiota is in constant flow under the influence of factors such as the diet, ingested drugs, the intestinal mucosa, the immune system, and the microbiota itself. Natural variations in the gut microbiota can deteriorate to a state of dysbiosis when stress conditions rapidly decrease microbial diversity and promote the expansion of specific bacterial taxa. The mechanisms underlying intestinal dysbiosis often remain unclear given that combinations of natural variations and stress factors mediate cascades of destabilizing events. Oxidative stress, bacteriophages induction and the secretion of bacterial toxins can trigger rapid shifts among intestinal microbial groups thereby yielding dysbiosis. A multitude of diseases including inflammatory bowel diseases but also metabolic disorders such as obesity and diabetes type II are associated with intestinal dysbiosis. The characterization of the changes leading to intestinal dysbiosis and the identification of the microbial taxa contributing to pathological effects are essential prerequisites to better understand the impact of the microbiota on health and disease.


The primary structure of rat ribosomal protein S8.
The amino acid sequence of rat ribosomal protein S8 was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed from the NH2- and carboxyl-terminal amino acid sequences of the protein. Ribosomal protein S8 contains 207 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has a molecular weight of 23,928. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 7-9 copies of the S8 gene. Ribosomal protein S8 contains a possible internal repeat that has 12 or 13 residues, is basic, and occurs 5 times in the protein.


Dynamic subcellular localization of a respiratory complex controls bacterial respiration.
Respiration, an essential process for most organisms, has to optimally respond to changes in the metabolic demand or the environmental conditions. The branched character of their respiratory chains allows bacteria to do so by providing a great metabolic and regulatory flexibility. Here, we show that the native localization of the nitrate reductase, a major respiratory complex under anaerobiosis in Escherichia coli, is submitted to tight spatiotemporal regulation in response to metabolic conditions via a mechanism using the transmembrane proton gradient as a cue for polar localization. These dynamics are critical for controlling the activity of nitrate reductase, as the formation of polar assemblies potentiates the electron flux through the complex. Thus, dynamic subcellular localization emerges as a critical factor in the control of respiration in bacteria.


Structural basis of Zn(II) induced metal detoxification and antibiotic resistance by histidine kinase CzcS in Pseudomonas aeruginosa.
Pseudomonas aeruginosa (P. aeruginosa) is a major opportunistic human pathogen, causing serious nosocomial infections among immunocompromised patients by multi-determinant virulence and high antibiotic resistance. The CzcR-CzcS signal transduction system in P. aeruginosa is primarily involved in metal detoxification and antibiotic resistance through co-regulating cross-resistance between Zn(II) and carbapenem antibiotics. Although the intracellular regulatory pathway is well-established, the mechanism by which extracellular sensor domain of histidine kinase (HK) CzcS responds to Zn(II) stimulus to trigger downstream signal transduction remains unclear. Here we determined the crystal structure of the CzcS sensor domain (CzcS SD) in complex with Zn(II) at 1.7 Å resolution. This is the first three-dimensional structural view of Zn(II)-sensor domain of the two-component system (TCS). The CzcS SD is of α/β-fold in nature, and it senses the Zn(II) stimulus at micromole level in a tetrahedral geometry through its symmetry-related residues (His55 and Asp60) on the dimer interface. Though the CzcS SD resembles the PhoQ-DcuS-CitA (PDC) superfamily member, it interacts with the effector in a novel domain with the N-terminal α-helices rather than the conserved β-sheets pocket. The dimerization of the N-terminal H1 and H1' α-helices is of primary importance for the activity of HK CzcS. This study provides preliminary insight into the molecular mechanism of Zn(II) sensing and signaling transduction by the HK CzcS, which will be beneficial to understand how the pathogen P. aeruginosa resists to high levels of heavy metals and antimicrobial agents.


Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis.
Therapeutic vaccination with Copaxone (glatiramer acetate, Cop-1) protects motor neurons against acute and chronic degenerative conditions. In acute degeneration after facial nerve axotomy, the number of surviving motor neurons was almost two times higher in Cop-1-vaccinated mice than in nonvaccinated mice, or in mice injected with PBS emulsified in complete Freund's adjuvant (P < 0.05). In mice that express the mutant human gene Cu/Zn superoxide dismutase G93A (SOD1), and therefore simulate the chronic human motor neuron disease amyotrophic lateral sclerosis, Cop-1 vaccination prolonged life span compared to untreated matched controls, from 211 +/- 7 days (n = 15) to 263 +/- 8 days (n = 14; P < 0.0001). Our studies show that vaccination significantly improved motor activity. In line with the experimentally based concept of protective autoimmunity, these findings suggest that Cop-1 vaccination boosts the local immune response needed to combat destructive self-compounds associated with motor neuron death. Its differential action in CNS autoimmune diseases and neurodegenerative disorders, depending on the regimen used, allows its use as a therapy for either condition. Daily administration of Cop-1 is an approved treatment for multiple sclerosis. The protocol for non-autoimmune neurodegenerative diseases such as amyotrophic lateral sclerosis, remains to be established by future studies.


Prokaryotic expression and identification of scavenger receptor B2.
There is still no effective clinical antiviral drug against human enterovirus 71 (EV71) infection, which causes hand, foot and mouth disease (HFMD) in children. Scavenger receptor class B member 2 (SCARB2) is an important receptor of EV71 as it plays a vital role in the early steps of viral infection. In this study, recombinant SCARB2 protein was expressed and purified in a prokaryotic expression system, and was identified by western blot with a monoclonal antibody and mass spectrometry analysis. Detection of the sera from mice immunized with the recombinant SCARB2 protein using ELISA and western blot showed good immunogenicity of the recombinant protein. Furthermore, in the neutralization test cytopathic effect was significantly decreased when EV71 was incubated with the immune sera before infection. In summary, the SCARB2 protein was expressed successfully, and the immune sera showed obvious antiviral effect against EV71. This study provides useful information about the interaction mechanism between SCARB2 and EV71, and is also helpful for further clinical treatment research of HFMD.


A multichannel dampened flow system for studies on shear stress-mediated mechanotransduction.
Shear stresses are powerful regulators of cellular function and potent mediators of the development of vascular disease. We have designed and optimized a system allowing the application of flow to cultured cells in a multichannel format. By using a multichannel peristaltic pump, flow can be driven continuously in the system for long-term studies in multiple isolated flow loops. A key component of the system is a dual-chamber pulse dampener that removes the pulsatility of the flow without the need for having an open system or elevated reservoir. We optimized the design parameters of the pulse dampening chambers for the maximum reduction in flow pulsation while minimizing the fluid needed for each isolated flow channel. Human umbilical vein endothelial cells (HUVECs) were exposed to steady and pulsatile shear stress using the system. We found that cells under steady flow had a marked increased production of eNOS and formation of actin stress fibers in comparison to those under pulsatile flow conditions. Overall, the results confirm the utility of the device as a practical means to apply shear stress to cultured cells in the multichannel format and provide steady, long term flow to microfluidic devices.


Necrotising fasciitis of odontogenic origin.
Necrotising fasciitis (NF) is a rare infection of the fascial planes, which is less common in head and neck, because of the rarity and higher vascularity in the region. We report a case of necrotising fasciitis in a 43-year-old man, arising from a dental infection treated successfully by early diagnosis, prompt surgical management, antibiotic therapy and adjunctive hyperbaric oxygen (HBO) therapy. The diagnosis of descending NF must always be considered in a patient who presents with a history of oropharyngeal infection with evidence of neck swelling, chest pain, and dyspnea or respiratory distress. Aggressive surgical debridement of all involved tissue along with intravenous antibiotic therapy should be initiated before aerobic and anaerobic cultures are obtained. HBO may also be of some benefit in the treatment of this potentially fatal infection.


Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice.
Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study of parasitic and allergic disease.


Regulation of Ca2+/calmodulin-dependent protein kinase II by Ca2+/calmodulin-independent autophosphorylation.
The autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaM-KII) results in the generation of kinase activity that is largely Ca2+/CaM-independent. We report that continued Ca2+/CaM-independent autophosphorylation of CaM-KII results in the generation of distinct phosphopeptides as identified by high performance liquid chromatography and enzymatic properties that are different than those observed for Ca2+/CaM-dependent autophosphorylation. These Ca2+/CaM-independent properties include (a) increased catalytic activity, (b) higher substrate affinity for the phosphorylation of synapsin I, and (c) decreased CaM-binding to both CaM-KII subunits as analyzed by gel overlays. Our results indicate that the autophosphorylation of only one subunit per holoenzyme is required to generate the Ca2+/CaM-independent CaM-KII. We suggest a two-step process by which autophosphorylation regulates CaM-KII. Step I requires Ca2+/CaM and underlies initial kinase activation. Step II involves continued autophosphorylation of the Ca2+/CaM-independent kinase and results in increased affinity for its substrate synapsin I and decreased affinity for calmodulin. These results indicate a complex mechanism through which autophosphorylation of CaM-KII may regulate its activity in response to transient fluctuations in intracellular calcium.


Trypanosoma sp. infection in Boa constrictor snakes: morphological, hematological, clinical biochemistry, molecular, and phylogenetic characteristics.
There are few reports of Trypanosoma in snakes, as well as little information about its pathogenicity in these animals. Thus, the present study aimed to characterize Trypanosoma found in Boa constrictor snakes, to verify the influence of the parasitism on hematological and clinical biochemistry parameters, and to perform a phylogenetic study of the isolates. Blood samples from sixty-one boas were analyzed for the presence of trypanosomatids and by hematological and clinical biochemistry assays. The flagellates that were found in this analysis were used for cell culture, morphometry, and molecular analysis. Later, molecular typing phylogenetic studies were performed. Nine positive animals (14.75%) were identified by microscopy analysis. The hematological results showed that parasitized animals presented significantly lower levels of packed cell volume, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. In the leukogram, eosinophils and heterophils counts were higher in parasitized animals. Considering the molecular analyses, the isolates presented a higher identity of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the 18S small subunit ribosomal RNA (SSU rRNA) gene fragments with Trypanosoma serpentis. The phylogenetic tree, using the GAPDH, clustered all isolates with T. serpentis and Trypanosoma cascavelli. This is the first description of T. serpentis parasitizing boas and of the clinical changes caused by trypanosomatid infection in snakes.


[Use of I125 labelled poly(I). poly(C) for determination of antibodies to double-stranded RNA by immune complex absorption to nitrocellulose filters].
125I-labeled double-stranded polyribonucleotide complex was used for detection of antibodies to double-stranded RNA in sera from people and immunized animals by the method of immune complex adsorption by the nitrocellulose filters. The technique is simple and sensitive. Antibodies to double-stranded RNA WERE detected in sera from patients with different diseases and from normal individuals. Systemic lupus erythematosus sera contain as a rule higher amounts of antibodies to double-stranded RNA. Often these antibodies were measured together with those directed towards native and denatured DNA. Anti-double-stranded RNA antibodies from sera of immunised animals and patients with systemic lupus erythematosus are highly specific.


Amino acid motifs required for isolated beta cytoplasmic domains to regulate 'in trans' beta1 integrin conformation and function in cell attachment.
The role of beta cytoplasmic domains in regulating beta1 integrin conformation and function in cell attachment is not fully understood. In this study, we tested the ability of transiently expressed beta cytoplasmic domains connected to an extracellular reporter domain to regulate 'in trans' the conformation of endogenous beta1 integrins, and compared these effects on cell attachment. We found that chimeric receptors containing either the beta1, beta3 or beta5 cytoplasmic domains inhibited the expression of the conformationally dependent 9EG7 and 12G10 epitopes on endogenous beta1 integrins. In contrast, chimeric receptors containing the beta4 or alpha5 cytoplasmic domain, or a control receptor lacking a cytoplasmic domain, had no effect. This inhibition occurred in a dose-dependent manner that required high levels of expression of the chimeric receptor. These results suggest that beta1 integrin conformation can be regulated by conserved cytosolic interactions involving beta cytoplasmic domains. This is further supported by our findings that mutations within amino acid motifs conserved among these beta cytoplasmic domains, specifically the NXXY, NPXY and TST-like motifs, reduced the ability of these chimeric receptors to regulate beta1 integrin conformation. Interestingly, the chimeric receptors inhibited cell attachment in a similar dose-dependent manner and required intact NXXY, NPXY, and TST-like motifs. The beta1 chimera also inhibited the binding of soluble fibronectin to endogenous beta1 integrins. Thus, the concomitant inhibition in the expression of conformation-dependent integrin epitopes, cell attachment and ligand binding by the chimeras, suggests that the expression of the 9EG7 and 12G10 epitopes correlates with integrin function. However, Mn2+, which is an extracellular activator of integrin function, increased 9EG7 expression to basal levels in the presence of the beta1 chimera, but did not rescue cell attachment to the same extent. Thus, although the beta1 integrin conformation recognized by mAb 9EG7 may be required for cell attachment, it is not sufficient, suggesting that the beta chimeras may be inhibiting both ligand binding and post-ligand binding events required for cell attachment. In addition, the inhibitory effects of the chimeric receptors on cell attachment were not reversed by the addition of the pharmacological agents that inhibit intracellular signals previously shown to inhibit integrin function. This finding, together with the requirement for high levels of the chimeric receptors and the fact that mutations in the same conserved motifs in heterodimeric beta1 integrins have been reported to regulate beta1 integrin conformation and function in cell attachment, suggest that beta cytoplasmic domains regulate these processes by interacting with cytosolic factors and that the regulatory effect of the chimeras may be due to their ability to titrate proteins from endogenous integrins.


Current status of gadolinium toxicity in patients with kidney disease.
Gadolinium-based contrast (GBC) agents have recently been the subject of intense interest for physicians across numerous specialties. These agents are widely used as contrast for magnetic resonance imaging and have been generally considered safe. Early on, phase III trials and small studies in low-risk patients suggested a benign renal profile; however, more recent studies raised the possibility of nephrotoxicity, although it is not clear whether it approaches the incidence of nephropathy associated with iodinated radiocontrast. In 2006, reports of a rare systemic fibrosing condition called nephrogenic systemic fibrosis (NSF) were recently linked to exposure of patients with advanced kidney disease to GBC agents. Analysis of the data suggests that certain GBC agents are more likely to be associated with NSF. Also, not all patients with kidney disease are at risk for developing NSF, only those with advanced acute or chronic kidney disease. Avoidance of GBC exposure is the best approach for high-risk patients. When GBC is required to obtain optimal images, use of low dosages of more stable macrocyclic agents is safer and preferred. This article reviews the current status of GBC agents as nephrotoxins and causes of NSF and provides opinions on how to use these agents in patients with underlying kidney disease.


Reaching across the aisle: Cross-disciplinary collaboration in otolaryngology research.
Collaboration and diversity of expertise are increasingly emphasized in the production of successful research. However, the degree of cross-disciplinary collaboration in otolaryngology research is unknown. In this study, we quantify cross-disciplinary collaboration in otolaryngology publications. We retrospectively analyzed authorship and study characteristics for all original articles published from January 2014 to December 2016 in three key peer-reviewed otolaryngology journals: Laryngoscope, Otolaryngology-Head & Neck Surgery, and JAMA Otolaryngology-Head & Neck Surgery. Author affiliations and online searches were used to determine author's primary discipline. Subspecialty topic of article, study design, and funding sources were also recorded. Fisher exact test was used to compare characteristics of articles with and without cross-disciplinary authorship. A total of 2,378 articles were reviewed, of which 1,312 (55%) articles had one or more cross-disciplinary collaborators. Among articles with cross-disciplinary collaboration, the greatest representation of disciplines was from other medical specialties (1,109, 50.9%), epidemiology/biostatistics (266, 12.2%), pathology/histology (175, 8.0%), biologic sciences (168, 7.7%), and radiology/imaging (144, 6.6%). Cross-disciplinary studies had a significantly greater proportion of articles on the topic of head and neck compared to studies without collaboration (P < 0.0001). The proportion of funded studies was significantly greater among articles with collaboration compared to articles without collaboration (P < 0.0001). The majority of articles published during a 3-year period in three influential otolaryngology journals had cross-disciplinary collaboration. There is potential opportunity for further leveraging expertise, funding opportunities, and dissemination of key findings through collaborative research. NA Laryngoscope, 129:1800-1805, 2019.


The Perinatal Birth Environment: Communication Strategies and Processes for Adherence to a Standardized Guideline in Women Undergoing Second-Stage Labor With Epidural Anesthesia.
Key to any perinatal safety initiative is buy-in and strong leadership from obstetric and pediatric providers, advanced practice nurses, and labor and delivery nurses in collaboration with ancillary staff. In the fall of 2007, executives of a large Midwestern hospital system created the Zero Birth Injury Initiative. This multidisciplinary group sought to eliminate birth injury using the Institute of Healthcare Improvement Perinatal Bundles. Concurrently, the team implemented a standardized second-stage labor guideline for women who choose epidural analgesia for pain management to continue the work of eliminating birth injuries in second-stage labor. The purpose of this article was to describe the process of the modification and adaptation of a standardized second-stage labor guideline, as well as adherence rates of these guidelines into clinical practice. Prior to implementation, a Web-based needs assessment survey of providers was conducted. Most (77% of 180 respondents) believed there was a need for an evidence-based guideline to manage the second stage of labor. The guideline was implemented at 5 community hospitals and 1 academic health center. Data were prospectively collected during a 3-month period for adherence assessment at 1 community hospital and 1 academic health center. Providers adhered to the guideline in about 57% of births. Of patients whose provider followed the guideline, 75% of women were encouraged to delay pushing compared with only 28% of patients delayed pushing when the provider did not follow the guideline.


Temperature dependence of the frequency noise in a mid-IR DFB quantum cascade laser from cryogenic to room temperature.
We report on the measurement of the frequency noise power spectral density in a distributed feedback quantum cascade laser over a wide temperature range, from 128 K to 303 K. As a function of the device temperature, we show that the frequency noise behavior is characterized by two different regimes separated by a steep transition at ≈200 K. While the frequency noise is nearly unchanged above 200 K, it drastically increases at lower temperature with an exponential dependence. We also show that this increase is entirely induced by current noise intrinsic to the device. In contrast to earlier publications, a single laser is used here in a wide temperature range allowing the direct assessment of the temperature dependence of the frequency noise.


Analysis of human sperm karyotypes in testicular cancer patients before and after chemotherapy.
Sperm karyotype analysis was performed on testicular cancer patients before and after treatment with BEP (bleomycin, etoposide, and cisplatin). A total of 788 sperm chromosome complements was studied, 236 before chemotherapy (CT) and 552 post-CT. There was no significant difference in the total frequency of sperm chromosomal abnormalities pre-CT (10.2%) compared to post-CT (10.7%). Similarly, there were no significant differences in the frequencies of numerical abnormalities (2.5% pre-CT vs. 2.4% post-CT) or structural abnormalities (6.4% pre-CT vs. 7.4% post-CT). The percentage of X-bearing sperm was also not significantly different before (46.3%) and after CT (50.1%). The results in cancer patients were not significantly different from those in control donors. This study corroborates results from our previous analysis of these same men using multicolor fluorescence in situ hybridization for assessment of aneuploidy for chromosomes 1, 12, X, Y, and XY. Together, these two studies suggest that the sperm of men receiving BEP chemotherapy are not at increased risk of chromosomal abnormalities two or more years after treatment.


Amino acid residues in the cytoplasmic domain of the Mason-Pfizer monkey virus glycoprotein critical for its incorporation into virions.
Assembly of an infectious retrovirus requires the incorporation of the envelope glycoprotein complex during the process of particle budding. We have recently demonstrated that amino acid substitutions of a tyrosine residue in the cytoplasmic domain block glycoprotein incorporation into budding Mason-Pfizer monkey virus (M-PMV) particles and abrogate infectivity (C. Song, S. R. Dubay, and E. Hunter, J. Virol. 77:5192-5200, 2003). To investigate the contribution of other amino acids in the cytoplasmic domain to the process of glycoprotein incorporation, we introduced alanine-scanning mutations into this region of the transmembrane protein. The effects of the mutations on glycoprotein biosynthesis and function, as well as on virus infectivity, have been examined. Mutation of two cytoplasmic residues, valine 20 and histidine 21, inhibits viral protease-mediated cleavage of the cytoplasmic domain that is observed during virion maturation, but the mutant virions show only moderately reduced infectivity. We also demonstrate that the cytoplasmic domain of the M-PMV contains three amino acid residues that are absolutely essential for incorporation of glycoprotein into virions. In addition to the previously identified tyrosine at residue 22, an isoleucine at position 18 and a leucine at position 25 each mediate the process of incorporation and efficient release of virions. While isoleucine 18 may be involved in direct interactions with immature capsids, antibody uptake studies showed that leucine 25 and tyrosine 22 are part of an efficient internalization signal in the cytoplasmic domain of the M-PMV glycoprotein. These results demonstrate that the cytoplasmic domain of M-PMV Env, in part through its YXXL-mediated endocytosis and intracellular trafficking signals, plays a critical role in the incorporation of glycoprotein into virions.


The efficacy of ASL/ENGLISH bilingual education: considering public schools.
The study investigated the efficacy and viability of American Sign Language (ASL)/English bilingual education for public schools serving deaf and hard of hearing children. Prior research related to ASL/English bilingual education is reviewed. Quantitative data related to the reading comprehension achievement of 25 deaf and hard of hearing students that were collected for the study are analyzed. The subjects' school program is described in depth. Overall performance of the sample is discussed. A description of high and low gainers is included. A statistically significant correlation between years of ASL usage and reading achievement is identified. Implications for the implementation of ASL/English bilingual methodology are reviewed, and suggestions for future research are offered.


Adenosine-induced cell death: evidence for receptor-mediated signalling.
Adenosine modulates the proliferation, survival and apoptosis of many different cell types, ranging from epithelial, endothelial and smooth muscle cells, to cells of the immune and neural lineages. In this review, we critically discuss the available in vitro and in vivo data which support a role for adenosine in both development-associated apoptosis, and in diseases characterized by either pathologically increased cell death (e.g., ischemia, trauma and aging-associated neurodegeneration) or abnormally reduced spontaneous apoptosis (e.g., cancer). Particular emphasis is given to the possible role of extracellular adenosine receptors, since these may represent novel and attractive molecular targets for the pharmacological modulation of apoptosis. In some instances, adenosine-induced cell death has been demonstrated to require entry of the nucleoside inside cells; however, in many other cases, activation of specific adenosine extracellular receptors has been demonstrated. Of the four G protein-coupled adenosine receptors so far identified, the A2A and the A3 receptors have been specifically implicated in modulation of cell death. For the A3 receptor, results obtained by exposing both cardiomyocytes and brain astrocytes to graded concentrations of selective agonists suggest induction of both cell protection and cell death. Such opposite effects, which likely depend on the degree of receptor activation, may have important therapeutic implications in the pharmacological modulation of cardiac and brain ischemia. For the A2A receptor, recent intriguing data suggest a specific role in immune cell death and immunosuppression, which may be relevant to both adenosine-deaminase-immunodeficiency syndrome (a pathology characterized by accumulation of adenosine to toxic levels) and in tumors where induction of apoptosis via activation of specific extracellular receptors may be desirable. Finally, preliminary data suggest that, in a similar way to the adenosine-deaminase-immunodeficiency syndrome, the abnormal accumulation of adenosine in degenerative muscular diseases may contribute to muscle cell death. Although the role of adenosine receptors in this effect still remains to be determined, these data suggest that adenosine-induced apoptosis may also represent a novel pathogenic pathway in muscular dystrophies.


Effects of the antioxidants dihydrolipoic acid (DHLA) and probucol on xenobiotic-mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes in vitro(1).
The antioxidant effects of dihydrolipoic acid (DHLA) and probucol were investigated in a human erythrocytic in-vitro model of diabetic oxidative stress, where xenobiotics were used to form methaemoglobin. 4-Aminophenol mediated haemoglobin oxidation in non-diabetic erythrocytes was not affected by the presence of either DHLA or probucol. However, with diabetic cells, there were significant increases (P<0.01) in 4-aminophenol-mediated haemoglobin oxidation in the presence of DHLA. Methaemoglobin formed by nitrite in non-diabetic and diabetic cells was not altered by either DHLA or probucol except at one time point in diabetic cells. In non-diabetic as well as diabetic cells, methaemoglobin formed by MADDS-NHOH was significantly reduced at all three time points in the presence of DHLA (P<0.0001) but unaffected by probucol. In the presence of DHLA only, methaemoglobin formed by the products of rat microsomal oxidation of both 4-aminopropiophenone and benzocaine was markedly reduced for both xenobiotics in diabetic and non-diabetic cells (P<0.0001) compared with cells incubated in the absence of DHLA. There were no significant differences between total cellular thiol levels determined between diabetic and non-diabetic erythrocytes, nor did DHLA or probucol affect resting thiol levels. MADDS-NHOH caused a significant thiol depletion in diabetic cells, which was restored in the presence of DHLA. A further study is required to determine how DHLA attenuates the potent REDOX reactions that occur during hydroxylamine-mediated methaemoglobin formation.


Living alone and antidepressant medication use: a prospective study in a working-age population.
An increasing proportion of the population lives in one-person households. The authors examined whether living alone predicts the use of antidepressant medication and whether socioeconomic, psychosocial, or behavioral factors explain this association. The participants were a nationally representative sample of working-age Finns from the Health 2000 Study, totaling 1695 men and 1776 women with a mean age of 44.6 years. In the baseline survey in 2000, living arrangements (living alone vs. not) and potential explanatory factors, including psychosocial factors (social support, work climate, hostility), sociodemographic factors (occupational grade, education, income, unemployment, urbanicity, rental living, housing conditions), and health behaviors (smoking, alcohol use, physical activity, obesity), were measured. Antidepressant medication use was followed up from 2000 to 2008 through linkage to national prescription registers. Participants living alone had a 1.81-fold (CI = 1.46-2.23) higher purchase rate of antidepressants during the follow-up period than those who did not live alone. Adjustment for sociodemographic factors attenuated this association by 21% (adjusted OR = 1.64, CI = 1.32-2.05). The corresponding attenuation was 12% after adjustment for psychosocial factors (adjusted OR = 1.71, CI = 1.38-2.11) and 9% after adjustment for health behaviors (adjusted OR = 1.74, CI = 1.41-2.14). Gender-stratified analyses showed that in women the greatest attenuation was related to sociodemographic factors and in men to psychosocial factors. These data suggest that people living alone may be at increased risk of developing mental health problems. The public health value is in recognizing that people who live alone are more likely to have material and psychosocial problems that may contribute to excess mental health problems in this population group.


Target-enriched nanopore sequencing and de novo assembly reveals co-occurrences of complex on-target genomic rearrangements induced by CRISPR-Cas9 in human cells.
The CRISPR-Cas9 system is widely used to permanently delete genomic regions via dual guide RNAs. Genomic rearrangements induced by CRISPR-Cas9 can occur, but continuous technical developments make it possible to characterize complex on-target effects. We combined an innovative droplet-based target enrichment approach with long-read sequencing and coupled it to a customized de novo sequence assembly. This approach enabled us to dissect the sequence content at kilobase scale within an on-target genomic locus. We here describe extensive genomic disruptions by Cas9, involving the allelic co-occurrence of a genomic duplication and inversion of the target region, as well as integrations of exogenous DNA and clustered interchromosomal DNA fragment rearrangements. Furthermore, we found that these genomic alterations led to functional aberrant DNA fragments and can alter cell proliferation. Our findings broaden the consequential spectrum of the Cas9 deletion system, reinforce the necessity of meticulous genomic validations, and introduce a data-driven workflow enabling detailed dissection of the on-target sequence content with superior resolution.


A biomechanical investigation of ankle injury under excessive external foot rotation in the human cadaver.
Numerous studies on the mechanisms of ankle injury deal with injuries to the syndesmosis and anterior ligamentous structures but a previous sectioning study also describes the important role of the posterior talofibular ligament (PTaFL) in the ankle's resistance to external rotation of the foot. It was hypothesized that failure level external rotation of the foot would lead to injury of the PTaFL. Ten ankles were tested by externally rotating the foot until gross injury. Two different frequencies of rotation were used in this study, 0.5 Hz and 2 Hz. The mean failure torque of the ankles was 69.5+/-11.7 Nm with a mean failure angle of 40.7+/-7.3 degrees . No effects of rotation frequency or flexion angle were noted. The most commonly injured structure was the PTaFL. Visible damage to the syndesmosis only occurred in combination with fibular fracture in these experiments. The constraint of the subtalar joint in the current study may have affected the mechanics of the foot and led to the resultant strain in the PTaFL. In the real world, talus rotations may be affected by athletic footwear that may influence the location and potential for an ankle injury under external rotation of the foot.


Applying Serum Cytokine Levels to Predict Pain Severity in Cancer Patients.
Cancers originating in the breast, lung and prostate often metastasize to the bone, frequently resulting in cancer-induced bone pain that can be challenging to manage despite conventional analgesic therapy. This exploratory study's aim was to identify potential biomarkers associated with cancer-induced pain by examining a sample population of breast cancer patients undergoing bisphosphonate therapy. A secondary analysis of the primary study was performed to quantify serum cytokine levels for correlation to pain scores. Cytokines with statistically significant correlations were then input into a stepwise regression analysis to generate a predictive equation for a patient's pain severity. In an effort to find additional potential biomarkers, correlation analysis was performed between these factors and a more comprehensive panel of cytokines and chemokines from breast, lung, and prostate cancer patients. Statistical analysis identified nine cytokines (GM-CSF, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-12p70, IL-17A, and IL-23) that had significant negative correlations with pain scores and they could best predict pain severity through a predictive equation generated for this specific evaluation. After performing a correlation analysis between these factors and a larger panel of cytokines and chemokines, samples from breast, lung and prostate patients showed distinct correlation profiles, highlighting the clinical challenge of applying pain-associated cytokines related to more defined nociceptive states, such as arthritis, to a cancer pain state. Exploratory analyses such as the ones presented here will be a beneficial tool to expand insights into potential cancer-specific nociceptive mechanisms and to develop novel therapeutics.


[Pain school. Ambulatory treatment of patients on long-term sick leave due to muscular pain. A 1-year follow-up study].
55 patients with chronic musculoskeletal pain who had been on sick leave for at least six months took part in a four week outpatient treatment programme. The programme was multidisciplinary and consisted of a combination of physical activity, formal lectures about health matters and individual consultations with doctor, psychologist, social worker, nurse and sports instructor. Pretreatment Minnesota Multiphasic Personality Inventory and Health Locus of Control showed the patients to have a typical chronic pain profile. The tests did not discriminate between those who had a favourable outcome and those who did not. At one year follow-up, 21 of the 55 patients had returned to work despite unchanged subjective intensity of pain.


The effect of therapeutic music interventions on the behavior of hospitalized children in isolation: developing a contextual support model of music therapy.
The purpose of this study was to provide preliminary data that support or negate a contextual support model of music therapy. The contextual support model of music therapy, based on Skinner and Wellborn's (1994) motivational theory of coping, argues that therapeutic music environments possess elements of structure, autonomy support, and involvement that lead children to become more actively engaged with their environment. This study examined three basic suppositions of the theory: (a) that music interventions create supportive environments, (b) that music interventions increase children's active engagement, and (c) that relationships exist between supportive environments and engaging behavior. Ten pediatric oncology patients restricted to an isolated environment participated in the study. Participants, serving as their own controls, experienced four different environmental conditions. Each condition was videotaped to facilitate collection of environmental and behavioral data. Statistical analyses of these data revealed: (a) that the music environment possessed a significantly higher frequency of environmental support elements than other activities typically experienced by hospitalized children, (b) that therapeutic music interventions elicited significantly more engaging behaviors from hospitalized children than other hospital activities, (c) that positive behavioral effects of music interventions were not maintained in hospital experiences that followed the music session, and (d) that environmental support elements were related to some positive behaviors but these behaviors were not consistent across environments.


Modulation of HLA-DR in dry eye patients following 30 days of treatment with a lubricant eyedrop solution.
To determine the changes in dry eye disease (DED) severity and the percentage of cells expressing HLA-DR on the ocular surface following treatment with lubricant eyedrops containing polyethylene glycol and propylene glycol (PEG/PG) and the gelling agent hydroxypropyl guar (HP-Guar). Nineteen patients with DED used PEG/PG + HP-Guar eyedrops four times per day for 30 days. Assessments included DED severity (Ocular Surface Disease Index [OSDI], corneal staining, conjunctival staining, tear film break-up time [TFBUT], and Schirmer testing) and impression cytology of the conjunctiva with masked flow cytometry at baseline and at 30 days. There was a significant decrease in corneal staining (P<0.01), OSDI (P=0.02), and TFBUT (P<0.01) following treatment with PEG/PG + HP-Guar. Results from flow cytometry revealed a significant decrease in cells expressing HLA-DR (P=0.02). Treatment with PEG/PG + HP-Guar eyedrops showed improvement in dry eye severity and reduction in surface inflammation as indicated by a reduction in HLA-DR expression.


CHILDREN'S MENTAL HEALTH SERVICE USE AND MATERNAL MENTAL HEALTH: A PATH ANALYTIC MODEL.
OBJECTIVE: This observational study explores pathways towards any past year use of child mental health services. METHODS: Data from the 2002 National Survey of American Families were used to explore the relationship between past month maternal mental health and past year child mental health services use. Observations were limited to the 8072 most knowledgeable adults who were the mothers of target children aged 6-11. Logistic regressions were performed to determine the odds of any child mental health service use followed by path analyses using Maximum Likelihood estimation with robust standard errors. RESULTS: Multiple factors were associated with odds of any child mental health service use. In the path analytic model poor past month maternal mental health was associated with increased aggravation which in turn was associated with increased use of mental health visits. Negative child behaviors as reported by the mother were also associated with increased maternal aggravation and increased service use. CONCLUSIONS: Parental perception of child behaviors influences treatment seeking, both directly and indirectly through parental aggravation. Parental mental health influences tolerance for child behaviors. Findings are consistent with other studies. Interventions should address the entire family and their psychosocial circumstances through collaboration between multiple service sectors.


Real time monitoring of accelerated chemical reactions by ultrasonication-assisted spray ionization mass spectrometry.
Ultrasonication has been used to accelerate chemical reactions. It would be ideal if ultrasonication-assisted chemical reactions could be monitored by suitable detection tools such as mass spectrometry in real time. It would be helpful to clarify reaction intermediates/products and to have a better understanding of reaction mechanism. In this work, we developed a system for ultrasonication-assisted spray ionization mass spectrometry (UASI-MS) with an ~1.7 MHz ultrasonic transducer to monitor chemical reactions in real time. We demonstrated that simply depositing a sample solution on the MHz-based ultrasonic transducer, which was placed in front of the orifice of a mass spectrometer, the analyte signals can be readily detected by the mass spectrometer. Singly and multiply charged ions from small and large molecules, respectively, can be observed in the UASI mass spectra. Furthermore, the ultrasonic transducer used in the UASI setup accelerates the chemical reactions while being monitored via UASI-MS. The feasibility of using this approach for real-time acceleration/monitoring of chemical reactions was demonstrated. The reactions of Girard T reagent and hydroxylamine with steroids were used as the model reactions. Upon the deposition of reactant solutions on the ultrasonic transducer, the intermediate/product ions are readily generated and instantaneously monitored using MS within 1 s. Additionally, we also showed the possibility of using this reactive UASI-MS approach to assist the confirmation of trace steroids from complex urine samples by monitoring the generation of the product ions.


Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in colorectal cancer through ERK and β-arrestin pathways.
The CXC chemokine receptor 7 (CXCR7) has been reported to be involved in cell growth, metastasis and apoptosis in certain cancers. However, the function and molecular mechanisms of CXCR7 in human colorectal cancer (CRC) are still undefined. In the present study, sixty-eight cases of CRC tissues and corresponding adjacent non-cancer tissues (ANCT) were collected, and the expression of CXCR7 was assessed using immunohistochemistry (IHC) in biopsy samples. Furthermore, CXCR7 gene was silenced by small hairpin RNA-mediated lentiviral vector (Lv-shCXCR7), by transfection into human CRC cells (SW480 and HT-29). The levels of p-ERK, β-arrestin, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2) and caspase-3 (CAS-3) were detected by western blotting. Cell proliferative activities and invasive capability were respectively measured by MTT and Transwell assays. Cell apoptosis was analyzed by flow cytometry. The results demonstrated that CXCR7 expression was significantly upregulated in CRC tissues compared with the ANCT (54.4 vs. 36.8%, P=0.041), and correlated with Dukes staging and depth of invasion (P=0.007; P=0.002). Silencing of CXCR7 gene suppressed cell proliferation and invasion, and induced cell apoptosis in CRC cells with decreased expression of p-ERK, β-arrestin, PCNA and MMP-2 but increased expression of CAS-3. The tumor volumes in the SW480 subcutaneous tumor models treated with Lv-shCXCR7 were significantly smaller than those of the negative control (NC) and PBS groups (P<0.01). In conclusion, our findings indicate that upregulation of CXCR7 expression is associated with tumor invasion, and silencing of the CXCR7 gene represses the development of CRC cells through ERK and β-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of CRC.


Numerical model of tapered fiber Bragg gratings for comprehensive analysis and optimization of their sensing and strain-induced tunable dispersion properties.
A versatile numerical model for spectral transmission/reflection, group delay characteristic analysis, and design of tapered fiber Bragg gratings (TFBGs) is presented. This approach ensures flexibility with defining both distribution of refractive index change of the gratings (including apodization) and shape of the taper profile. Additionally, sensing and tunable dispersion properties of the TFBGs were fully examined, considering strain-induced effects. The presented numerical approach, together with Pareto optimization, were also used to design the best tanh apodization profiles of the TFBG in terms of maximizing its spectral width with simultaneous minimization of the group delay oscillations. Experimental verification of the model confirms its correctness. The combination of model versatility and possibility to define the other objective functions of Pareto optimization creates a universal tool for TFBG analysis and design.


Alcohol abuse risk factors and psychiatric disorders in pregnant women with a history of infertility.
To determine if a history of infertility is associated with alcohol abuse risk factors, depression, and other psychiatric disorders. Pregnant women awaiting their first prenatal visit completed a questionnaire and subsequently participated in an interview consisting of the Structured Clinical Interview for DSM-IIIR and the Family Alcohol and Drug Survey. The data obtained from women with a history of infertility were compared with the data from women without prior infertility. Eighty-nine pregnant women participated in the study, 27 with prior infertility and 62 without. Subjects were demographically similar, except that women with a history of infertility were slightly older than controls (34.7 vs. 31.1 years, p < 0.001). Pregnant women with a history of infertility reported needing significantly more drinks to get high, (3.3 vs. 2.7, p = 0.04) and were more likely to have clinically elevated tolerance, annoyance, cut-down, and eye-opener (T-ACE) alcohol tolerance scores (83.3% vs. 52.3%, p < 0.01) than women without such history. Major depression (lifetime) was diagnosed in 69.2% of infertility subjects compared with 30% of controls (p < 0.05). Lifetime simple phobia (23.1% vs. 10%, p < 0.01), generalized anxiety disorder (23.1% vs. 3%, p < 0.01), panic disorder (15.4% vs. 0%, p < 0.05), and bulimia (7.7% vs. 0%, p < 0.05) were also more common in women with a history of infertility compared with controls. Pregnant women with a history of infertility are at increased risk for alcohol abuse and are more likely to suffer from other psychiatric disorders than women without such history. Special attention to these issues is warranted when caring for pregnant women who were previously infertile.


Rheumatoid arthritis: pathogenesis and early recognition.
Rheumatoid arthritis (RA) is a chronic, destructive disease characterized by joint pain and swelling, which progresses in a substantial percentage of patients to invasion of bone and cartilage. If not successfully treated, progressive joint destruction results in loss of function, disability, and increased mortality. The time from onset of symptoms to joint destruction is frequently measured in months rather than years. Unfortunately, the time from disease onset to diagnosis and initiation of effective therapy is often prolonged, allowing development of irreversible joint destruction. In order to apply current knowledge to reduce the disability and death associated with progressive RA, the clinician must understand the pathophysiologic stages of the disease as reflected in symptoms, radiography, and biochemical markers. Prognostic factors relevant to RA severity, including factors relevant to RA severity, including serum markers and genetic traits, must also be known so that appropriate therapeutic strategies can be planned. Although current therapy cannot reliably alter the long-term outcome of RA, new approaches are promising. Patients at high risk or who fail to respond to conservative therapy are candidates for earlier, more aggressive strategies using single or possibly combination antirheumatic therapy.


Ketamine as a Rapid Sequence Induction Agent in the Trauma Population: A Systematic Review.
The choice of drug used to facilitate endotracheal intubation in trauma patients during rapid sequence induction (RSI) may have an impact on survival. Ketamine is commonly used in the hemodynamically unstable trauma patient although it has been associated with side effects. This review sought to investigate whether ketamine should be preferred over other induction agents for RSI in trauma patients. PubMed, Embase, and the Cochrane Library were systematically searched on September 19, 2016 for studies reporting RSI of adult trauma patients with ketamine compared with another induction agent (etomidate, propofol, thiopental, or midazolam). No language restrictions were applied. The primary outcome was 30-day mortality, and secondary outcomes included information on blood transfusions, length of hospital stay, and hospital mortality. Risk of bias was assessed using the Cochrane Risk of Bias assessment tool for randomized trials and the Risk of Bias in Non-Randomized Studies of Interventions for nonrandomized studies of intervention. A total of 4 studies were included. A cohort study from 1976 compared thiopental (n = 26) with ketamine (n = 14) for RSI in trauma patients. The primary outcome was number of blood transfusions, and no significant difference was found. Risk of bias was judged to be serious. A randomized controlled trial from 2009 compared etomidate (n = 57) with ketamine (n = 47) and found no significant difference in 28-day mortality (odds ratio [OR], 0.8 [0.4-2.0]). The trial was judged to have a low risk of bias. Two cohort studies from 2015 and 2017 also compared etomidate (n = 116 and n = 526) with ketamine (n = 145 and n = 442). No significant difference in hospital mortality between the groups was observed (OR, 1.11 [0.38-3.27] and OR, 1.41 [0.91-2.16], respectively). Both studies were judged to have a moderate risk of bias, thus excluding the possibility of a meaningful meta-analysis. The study from 2017 also reported number of units of blood transfused during the first 48 hours after trauma and length of hospital stay. No significant differences were observed (OR, 1.14 [0.87-1.49] and OR, 1.1 [0.95-1.27], respectively). Extremely few studies have compared induction agents for RSI in trauma patients. No significant differences have been found in mortality, length of hospital stay, or number of blood transfusions after induction with ketamine compared to other induction agents, but a clinically relevant benefit or harm cannot be excluded.


Integrative transcriptome meta-analysis reveals widespread sex-biased gene expression at the human fetal-maternal interface.
As males and females share highly similar genomes, the regulation of many sexually dimorphic traits is constrained to occur through sex-biased gene regulation. There is strong evidence that human males and females differ in terms of growth and development in utero and that these divergent growth strategies appear to place males at increased risk when in sub-optimal conditions. Since the placenta is the interface of maternal-fetal exchange throughout pregnancy, these developmental differences are most likely orchestrated by differential placental function. To date, progress in this field has been hampered by a lack of genome-wide information on sex differences in placental gene expression. Therefore, our motivation in this study was to characterize sex-biased gene expression in the human placenta. We obtained gene expression data for >300 non-pathological placenta samples from 11 microarray datasets and applied mapping-based array probe re-annotation and inverse-variance meta-analysis methods which showed that >140 genes (false discovery rate (FDR) <0.05) are differentially expressed between male and female placentae. A majority of these genes (>60%) are autosomal, many of which are involved in high-level regulatory processes such as gene transcription, cell growth and proliferation and hormonal function. Of particular interest, we detected higher female expression from all seven genes in the LHB-CGB cluster, which includes genes involved in placental development, the maintenance of pregnancy and maternal immune tolerance of the conceptus. These results demonstrate that sex-biased gene expression in the normal human placenta occurs across the genome and includes genes that are central to growth, development and the maintenance of pregnancy.


A low-Ca2+ response operon encodes the V antigen of Yersinia pestis.
Yersinia pestis has a virulence regulon called the low-Ca2+ response that is mediated by the plasmid pCD and manifested as regulation of growth and of expression of several virulence-associated properties by Ca2+ and temperature. We used Mu dI(Ap lac) to obtain a mutation in pCD1 of Y. pestis KIM that rendered the bacteria unable to express one of these properties, the V antigen. This mutant also had lost the Ca2+ requirement for growth at 37 degrees C and was avirulent in mice. Two-dimensional protein gel electrophoresis showed that the Mu dI(Ap lac) insertion had eliminated 13,000- and 18,000-molecular-weight proteins in addition to the V antigen. We mapped the Mu dI(Ap lac) insertion within pCD1, cloned the HindIII fragment spanning the insertion location, prepared two subclones of this fragment, and identified the proteins these clones expressed in Escherichia coli minicells. The data indicated that the V gene lies within an operon containing three genes; lcrG (encoding the 13,000-molecular-weight protein), lcrV (encoding the 38,000-molecular-weight V antigen), and lcrH (encoding the 18,000-molecular-weight protein). Therefore, the V operon contains the structural gene for V antigen, at least one virulence gene, and at least one Ca2+-dependence gene.


Systematic review of three decades of Spanish cardiovascular epidemiology: improving translation for a future of prevention.
In order to improve national cardiovascular disease (CVD) epidemiology and prevention, we systematically reviewed and analyzed the relevant literature produced in the last three decades for Spain. Systematic Review. We searched for all the articles aiming to monitor CVD clinical endpoints and risk factors in the Spanish general population that were indexed in MEDLINE and EMBASE. Based on international recommendations, we analyzed each article with a three-level scoring system (low to high) for the following criteria: data quality, representativeness and translation of results into preventive interventions. We reviewed 2565 articles, selecting 314 for in-depth analysis. Articles about diet, blood pressure, obesity and smoking represented 53% of all published CVD studies, whereas those about physical activity or psychosocial factors represented only 5%. Low data quality was found in 67% and 60% of the articles about physical activity and smoking, respectively. High data quality was found in 77% and 61% of the articles dedicated to diet and blood pressure, respectively. Representativeness was low for 41%, 31% and 25% of the studies focusing on diet, smoking and diabetes, respectively. Translation of research results into prevention scored lowest of all three criteria, as 41% of all 314 articles scored low. None of the articles on obesity, diabetes, lipids, physical activity or psychosocial factors identified any specific preventive intervention. Future Spanish CVD epidemiology research will benefit from improving not just the quality and representativeness of the data measured, but drastically improving the translation of research results into future preventive interventions. The lack of a translational focus remains the fundamental gap in CVD research.


Autosomal dominant supravalvular aortic stenosis: localization to chromosome 7.
Supravalvular aortic stenosis (SVAS) is a localized or diffuse congenital narrowing of the ascending aorta which may occur sporadically, as a familial defect, or in association with Williams syndrome. Familial cases suggest an autosomal dominant gene defect but the underlying molecular basis of SVAS is unknown. In this study, we sought to localize the genetic defect in familial SVAS by linkage analysis in a large three generation family. A total of 44 polymorphic markers were examined for linkage, including 17 Southern blot-based RFLPs, 2 PCR-based RFLPs, and 25 microsatellites, primarily of the (CA)n repeat type. We report linkage of the disease phenotype to a highly informative (CA)n repeat marker, Mfd 50, at locus D7S440 which has been localized to chromosome arm 7q. Using a 100% penetrance model, which was more conservative than lower values of penetrance, a peak LOD score of 4.66 at a recombination frequency of 0.043 was found. A number of candidate genes have been localized to this region, including collagen 1A2, laminin B1, and elastin. Based on our preliminary linkage data, the abnormal microscopic appearance of aortic elastic fibers in SVAS, and analogous animal and human diseases associated with elastic fiber and vascular abnormalities, there is indirect evidence suggesting elastin as a possible candidate gene for this disorder.


Isolation of catalase-deficient Escherichia coli mutants and genetic mapping of katE, a locus that affects catalase activity.
A number of catalase-deficient mutants of Escherichia coli which exhibit no assayable catalase activity were isolated. The only physiological difference between the catalase mutants and their parents was a 50- to 60-fold greater sensitivity to killing by hydrogen peroxide. For comparison, mutations in the xthA and recA genes of the same strains increased the sensitivity of the mutants to hydrogen peroxide by seven- and fivefold, respectively, showing that catalase was the primary defense against hydrogen peroxide. One class of mutants named katE was localized between pfkB and xthA at 37.8 min on the E. coli genome. A second class of catalase mutants was found which did not map in this region.


Open, randomized pilot study after first stroke: a 3.5-year follow-up.
Although care in stroke units has improved outcome in stroke patients, it is less clear whether specialized outpatient care after stroke can further improve the prognosis. We therefore conducted a pilot study comparing specialized long-term care with usual care after a first stroke. During a 2-year period, 549 patients were discharged alive from our stroke unit. Eighty-one patients were randomized to follow-up care at the stroke outpatient clinic (intervention group), and 82 patients were randomized to follow-up care with their general practitioner (control group). No differences in baseline variables were noted between the 2 groups. At the 12-month visit, there were no significant differences between the groups with respect to handicap, depression, and perceived health. During 3.5 years of follow-up, no differences in mortality, stroke recurrence rate, and unplanned hospitalizations were observed between the groups. In this small pilot study, specialized follow-up service for stroke patients was not superior to "usual care."


Pharmacokinetics of 2-ethyl-1,3-hexanediol. I. Systemic disposition following single intravenous doses in male Fischer 344 rats.
A determination of the systemic pharmacokinetics of [1,3-14C]-2-ethyl-1,3-hexanediol (EHD) was conducted following i.v. dosing of male Fischer 344 rats. Pharmacokinetic analyses of the plasma data indicated that there is dose linearity in the 1.5 to 150 mg/kg range, and that EHD is cleared from plasma in a biexponential manner according to first order transfer and elimination processes. The data show that EHD-derived radioactivity is very rapidly distributed and then is slowly eliminated (probably as EHD metabolites) over a 48-hr period after a single i.v. injection. EHD is not found in the urine as unchanged test material by HPLC analysis following these i.v. doses, indicating that this chemical is probably completely metabolized in the rat. The appearance of EHD-derived radioactivity in the urine also follows a first order behavior, as evidenced by calculations of rate constants which are similar to the terminal rate constants from plasma radioactivity data. Both U infinity-Ut and dU/dt analyses of urine radioactivity data demonstrated that first order rate constants can be derived from urinary excretion data and supported the overall conclusion that the elimination of EHD from the rat follows first order processes in this range of i.v. doses.


What is the revised Fear Survey Schedule for Children measuring?
This study was designed to investigate parameters of children's fear in terms of frequency of fearful thoughts and avoidance behaviour. It is suggested that current measures such as the Fear Survey Schedule for Children--Revised (FSSC-R) do not assess fearful behaviour in the sense of the occurrence of fearful responding in daily life, but rather reflect a negative affective response to the thought of occurrence of specific events. A modified version of the FSSC-R examined the frequency of fearful thoughts/feelings and avoidance activities amongst 376 children aged 7-12 yr. Contrary to predictions, it was found that children reported high levels of fearful thoughts and avoidance behaviour to those items identified as the greatest fears on the FSSC-R, namely fears of injury, illness, death and danger. These events were typically of low probability (e.g. earthquakes) and the question was raised as to what children are responding to when they are asked to rate their fearful responses. The same pattern of results was reflected in older compared to younger children. It is suggested that even when children are asked to rate frequency of fearful thoughts or avoidance behaviour, they tend to respond to fear questionnaire items according to their affective response to the image or thought of the stimulus situation rather than their actual fear responses. Both the FSSC-R and the modified version were found to discriminate between teacher nominated high and low fearful children and to correlate significantly with a self report measure of anxiety.


New insight into drug-DNA interactions at individual drug binding sites probed by RNA polymerase during active transcription of the DNA.
An in vitro transcription assay has been used to probe drug-DNA interactions during active transcription of the DNA. The method relies upon the formation of a stable, synchronized population of initiated transcripts comprising a short length of RNA, achieved by the absence of one nucleotide in the initiation mixture. Subsequent equilibration of the transcription complex with drug, followed by elongation of the initiated transcripts, yields lengths of RNA determined by transcription up to each drug-occupied site. A variety of site-specific phenomena have been observed, including delayed termination of transcription 5-10 bp downstream of actinomycin binding sites; 10-20% probability of termination at most echinomycin sites; drug residence-time-dependent termination of bacteriophage polymerases; enhanced residence time compared to physicochemical measurement of drug-DNA dissociation rates. The use of two counter-directed promoters separated by 100 bp results in a sensitive bidirectional transcription footprinting procedure able to resolve adjacent drug sites separated by only 1 bp. The significance of the method of in vitro transcription is the ability to quantitate a range of parameters describing individual drug sites in situations where multiple drug-DNA interactions exist.


Anesthetic management of robot-assisted thoracoscopic thymectomy.
Myasthenia gravis (MG) is a rare disorder involving neuromuscular junction. In conjunction with medical therapy, thymectomy is a known modality of treatment of MG and has shown to increase the probability of remission and overall symptomatic improvement. For minimally invasive thymectomy, video-.assisted thoracoscopic surgery has been the preferred surgical approach till recently. The robotic surgical procedure must necessarily bring new challenges to the anesthesiologists to effectively meet the specific requirements of the technique. At present, there is a paucity of literature regarding the anesthetic concerns of robotic assisted thymectomy, patient in question specifically posed a challenge since different maneuvers and techniques had to be tried to obtain optimum surgical conditions with stable ventilatory and hemodynamic parameters. Concerns of patient positioning and hemodynamic monitoring have also been discussed.


[The effect of drugs on free-radical oxidation].
Data available in the literature and the results of original investigations of the effect of drugs on the free-radical oxidation process are summarized. It is pointed out that the character of drug influence on the on the free-radical oxidation process must be taken into account in selecting drugs for the treatment of particular diseases.


Abortion surveillance - United States, 2006.
Since 1969, CDC has conducted abortion surveillance to document the number and characteristics of women obtaining legal induced abortions in the United States. 2006. Each year, CDC requests abortion data from the central health agencies of 52 reporting areas (the 50 states, New York City, and the District of Columbia); these data are provided to CDC voluntarily. In 2006, data were received from 49 reporting areas. For the purpose of trend analysis, data were evaluated from the 46 areas that reported data every year during 1996-2006. For 2006, a total of 846,181 abortions were reported to CDC. Among the 46 areas that provided data consistently during 1996-2006, a total of 835,134 abortions (98.7% of the total) were reported; the abortion rate was 16.1 abortions per 1,000 women aged 15-44 years, and the abortion ratio was 236 abortions per 1,000 live births. During the previous decade (1997-2006), reported abortion numbers, rates, and ratios decreased 5.7%, 8.8%, and 14.8%, respectively; most of these declines occurred before 2001. During the previous year (2005-2006), the total number of abortions increased 3.1%, and the abortion rate increased 3.2%; the abortion ratio was stable. In 2006, as during the previous decade (1997-2006), women aged 20-29 years accounted for the majority (56.8%) of abortions and had the highest abortion rates (29.9 abortions per 1,000 women aged 20-24 years and 22.2 abortions per 1,000 women aged 25-29 years); by contrast, abortion ratios were highest at the extremes of reproductive age. Adolescents aged 15-19 years accounted for 16.5% of all abortions in 2006 and had an abortion rate of 14.8 abortions per 1,000 adolescents aged 15-19 years; women aged >or=35 years accounted for a smaller percentage (12.1%) of abortions and had lower abortion rates (7.8 abortions per 1,000 women aged 35-39 years and 2.6 abortions per 1,000 women aged >or=40 years). During 1997-2006, the percentage of abortions and the abortion rate increased among women aged >or=35 years but declined among adolescents aged <or=19 years and among women aged 20-29 years. The majority (62.0%) of abortions in 2006 were performed at <or=8 weeks' gestation; few abortions were performed at 16-20 weeks' gestation (3.7%) or at >or=21 weeks' gestation (1.3%). During 1997-2006, the percentage of abortions performed at <or=8 weeks' gestation increased 11.7%; this increase largely was accounted for by procedures performed at <or=6 weeks' gestation, which increased 66.3%. In 2006, the greatest percentage (87.6%) of abortions were performed by curettage (including vacuum aspiration, sharp curettage, and dilation and evacuation procedures), followed by medical (nonsurgical) abortion (10.6%). Deaths of women associated with complications from abortions for 2006 are being investigated under CDC's Pregnancy Mortality Surveillance System. In 2005, the most recent year for which data were available, seven women were reported to have died as a result of complications from known legal induced abortions. No reported deaths were associated with known illegal induced abortions. Among the 46 areas that reported data consistently during 1996-2006, decreases in the total reported number, rate, and ratio of abortions were attributable primarily to reductions before 2001. During 2005-2006, the total number and rate of abortions increased. In 2005, as in the previous years, reported deaths related to abortions occurred only rarely. Abortion surveillance in the United States continues to provide the data needed to examine trends in the number and characteristics of women obtaining abortions. Policymakers and program planners can use these data to guide and evaluate efforts to prevent unintended pregnancies.


Role of corticosteroids in stable chronic obstructive pulmonary disease.
Evidence supporting or refuting the use of corticosteroids in the treatment of patients with chronic obstructive pulmonary disease (COPD) has only recently become available, and evidence is still missing for a number of important clinical issues. Results from four large studies on the long-term effects of inhaled corticosteroids on COPD and other controlled studies on the more short-term effects of inhaled corticosteroids provide evidence that regular treatment with these drugs is only appropriate for a limited group of patients with COPD. These include symptomatic COPD patients with documented spirometric response to inhaled corticosteroids or those with a forced expiratory volume in 1 second (FEV(1)) less than 50% predicted and repeated exacerbations requiring treatments with antibiotics or oral corticosteroids.


Trans fatty acids in adipose tissue and the food supply are associated with myocardial infarction.
Metabolic studies have clearly shown that trans fatty acids (TFAs) elevate LDL and lower HDL cholesterol. Epidemiologic studies showed a relation between TFA intake and the risk of myocardial infarction (MI), but studies examining adipose tissue TFAs have not uniformly confirmed this. We performed a case control study examining both adipose tissue levels and dietary intake of TFAs and first MI. Between 1995 and 1997, 209 cases of first MI completed a 300-item FFQ and 79 had an adipose tissue biopsy; 179 matched controls completed the FFQ and 167 had a biopsy. During the course of the study (mid-1996), TFAs were eliminated from margarines sold in Australia. Cases biopsied before mid-1996 had greater levels of trans 18:1(n-9) (32% P < 0.03) and trans 18:1(n-11) (23%, P < 0.001) than controls biopsied before mid-1996. After June 1996, there were no differences between cases and controls in any of the adipose tissue TFAs measured. Logistic regression showed that trans 18:1(n-11) (P = 0.03) was an independent predictor of a first MI. Cases consumed 0.5 g/d (P = 0.002) more TFAs than controls. Subjects in the highest quintile of TFA intake had an OR for first MI of 2.1 (95% CI, 1.1-4.3), which was not independent of saturated fat intake. Apparent TFA intake from margarine was related to adipose tissue 18:1t[(n-9) and (n-10)] in 1995 (r = 0.66, 0.66, respectively). We conclude that TFAs in adipose tissue are associated with an increased risk of coronary artery disease and rapidly disappear from adipose tissue when not included in margarines.


In vivo photoactivation without "light": use of Cherenkov radiation to overcome the penetration limit of light.
The poor tissue penetration of visible light has been a major barrier for optical imaging, photoactivatable conversions, and photodynamic therapy for in vivo targets with depths beyond 10 mm. In this report, as a proof-of-concept, we demonstrated that a positron emission tomography (PET) radiotracer, 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)FDG), could be used as an alternative light source for photoactivation. We utilized (18)FDG, which is a metabolic activity-based PET probe, as a source of light to photoactivate caged luciferin in a breast cancer animal model expressing luciferase. Bioluminescence produced from luciferin allowed for the real-time monitoring of Cherenkov radiation-promoted uncaging of the substrate. The proposed method may provide a very important option for in vivo photoactivation, in particular for activation of photosensitizers for photodynamic therapy and eventually for combining radioisotope therapy and photodynamic therapy.