Smoking prevents the expected postprandial increase in intestinal blood flow: a Doppler sonographic study.
To assess whether cigarette smoking had an effect on superior mesenteric artery postprandial blood flow. Forty-six subjects were studied in 3 groups with Doppler sonography. Group A consisted of nonsmokers; groups B and C consisted of smokers. In group B, subjects were allowed to smoke cigarettes postprandially, whereas in group C, postprandial smoking was prohibited. A baseline Doppler evaluation was performed in the fasting state, and consecutive Doppler evaluations were performed postprandially with 30-min intervals for 120 minutes. Doppler sonographic measurements of the superior mesenteric artery, including peak systolic and end-diastolic velocities, resistive index, and diameter, were calculated. Statistical analysis was performed by analysis of variance. All groups showed significant changes with time for all parameters (P < .001 for all). The changes in time were significantly different at 90 and 120 minutes for peak systolic velocity, at 90 minutes for end-diastolic velocity, and at 120 minutes for diameter between groups. Group B had the greatest differences. Compared with group A, changes in peak systolic velocity at 90 to 120 minutes were significantly lower in group B (P = .007 and .006, respectively), and compared with groups A and C, changes in end-diastolic velocity at 90 minutes (P = .006 and .004, respectively) and diameter at 120 minutes (P = .007 and .011, respectively) were significantly lower in group B. Smoking immediately after meals was associated with a superior mesenteric artery blood flow increase that was lower than expected, which may explain the belief that smoking reduces body weight. Postprandial smoking may have undesired results in patients with chronic intestinal ischemia.


Heterostructure WSe2-Ga2O3 Junction Field-Effect Transistor for Low-Dimensional High-Power Electronics.
Layered materials separated from each bulk crystal can be assembled to form a strain-free heterostructure by using the van der Waals interaction. We demonstrated a heterostructure n-channel depletion-mode β-Ga2O3 junction field-effect transistor (JFET) through van der Waals bonding with an exfoliated p-WSe2 flake. Typical diode characteristics with a high rectifying ratio of ∼105 were observed in a p-WSe2/n-Ga2O3 heterostructure diode, where WSe2 and β-Ga2O3 were obtained by mechanically exfoliating each crystal. Layered JFETs exhibited an excellent IDS- VDS output as well as IDS- VGS transfer characteristics with a high on/off ratio (∼108) and low subthreshold swing (133 mV/dec). Saturated output currents were observed with a threshold voltage of -5.1 V and a three-terminal breakdown voltage of +144 V. Electrical performances of the fabricated heterostructure JFET were maintained at elevated temperatures with outstanding air stability. Our WSe2-Ga2O3 heterostructure JFET paves the way to the low-dimensional high-power devices, enabling miniaturization of the integrated power electronic systems.


A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality.
We describe a new mitochondrial DNA mutation in a male infant who presented clinical and magnetic resonance imaging features of Leigh syndrome and died at the age of 9 mo. The patient's development was reportedly normal in the first months of life. At the age of 5 mo, he presented severe generalized hypotonia, nystagmus, and absent eye contact. Laboratory examination showed increased lactate and pyruvate in both serum and cerebrospinal fluid. Brain magnetic resonance imaging revealed multiple necrotic lesions in the basal ganglia, brain stem, and thalamus. Muscle histopathology was unremarkable, whereas respiratory chain enzyme analysis revealed a severe complex I deficiency. The patient died after an acidotic coma at age 9 mo. Sequence analysis of the entire mtDNA disclosed a new T10158C mutation with variable tissue heteroplasm (muscle: 83%; blood: 48%). The mutation was undetectable in the blood of his unaffected mother. The transition changes a serine residue into a proline, in a highly conserved region of the NADH dehydrogenase subunit 3 (ND3). This is the first description of a mitochondrial ND3 gene in Leigh syndrome with early lethality.


A 360-degree floating 3D display based on light field regeneration.
Using light field reconstruction technique, we can display a floating 3D scene in the air, which is 360-degree surrounding viewable with correct occlusion effect. A high-frame-rate color projector and flat light field scanning screen are used in the system to create the light field of real 3D scene in the air above the spinning screen. The principle and display performance of this approach are investigated in this paper. The image synthesis method for all the surrounding viewpoints is analyzed, and the 3D spatial resolution and angular resolution of the common display zone are employed to evaluate display performance. The prototype is achieved and the real 3D color animation image has been presented vividly. The experimental results verified the representability of this method.


Nurse staffing and hospital ownership in California.
The purpose of this study is to describe the relationship between nurse staffing and owner type or specific corporate owner in California acute care hospitals. Little empirical data exist regarding nurse staffing as it relates to owner type or specific corporate owner. With minimum staffing ratios scheduled to be implemented in January 2004, this study provides baseline data for evaluating the impact of minimum staffing ratios in California. The study design is descriptive and cross-sectional. Data used in this study are for short-term general hospitals that reported to the California Office of Statewide Health Planning and Development database for fiscal years ending in 1997 through 1999. Six regression models were estimated using pooled data from the 3 years of data. The most consistent significant findings are: increased patient days or patient discharges predict increased registered nurse (RN) hours; lower RN wages predict increased RN hours; higher technology scores predict increased RN hours; and in 1998 there was an across-the-board decrease in RN hours. Other significant findings include that for-profit hospitals and for-profit systems had fewer RN productive hours for medical-surgical nursing, and select corporate owners, unrelated to profit status, had consistently fewer RN productive hours for medical-surgical nursing. For-profit hospitals and systems behaved differently in the healthcare market environment of the late 1990s. Select nonprofit systems were also using significantly less RN staffing. Other findings support the implication that as technology sophistication increases, there will be a need for increased RN hours to manage the advanced technology. This runs counter to the argument that increasing technology will decrease the need for RN hours. Finally, as discharges go up, the need for RN hours increases.


Narratives in Two Languages: Storytelling of Bilingual Cantonese-English Preschoolers.
The aim of this study was to compare narratives generated by 4-year-old and 5-year-old children who were bilingual in English and Cantonese. The sample included 47 children (23 who were 4 years old and 24 who were 5 years old) living in Toronto, Ontario, Canada, who spoke both Cantonese and English. The participants spoke and heard predominantly Cantonese in the home. Participants generated a story in English and Cantonese by using a wordless picture book; language order was counterbalanced. Data were transcribed and coded for story grammar, morphosyntactic quality, mean length of utterance in words, and the number of different words. Repeated measures analysis of variance revealed higher story grammar scores in English than in Cantonese, but no other significant main effects of language were observed. Analyses also revealed that older children had higher story grammar, mean length of utterance in words, and morphosyntactic quality scores than younger children in both languages. Hierarchical regressions indicated that Cantonese story grammar predicted English story grammar and Cantonese microstructure predicted English microstructure. However, no correlation was observed between Cantonese and English morphosyntactic quality. The results of this study have implications for speech-language pathologists who collect narratives in Cantonese and English from bilingual preschoolers. The results suggest that there is a possible transfer in narrative abilities between the two languages.


Retinoic acid receptor alpha drives cell cycle progression and is associated with increased sensitivity to retinoids in T-cell lymphoma.
Peripheral T-cell lymphomas (PTCLs) are aggressive non-Hodgkin lymphomas with generally poor outcomes following standard therapy. Few candidate therapeutic targets have been identified to date. Retinoic acid receptor alpha (RARA) is a transcription factor that modulates cell growth and differentiation in response to retinoids. While retinoids have been used to treat some cutaneous T-cell lymphomas (CTCLs), their mechanism of action and the role of RARA in CTCL and other mature T-cell lymphomas remain poorly understood. After identifying a PTCL with a RARAR394Q mutation, we sought to characterize the role of RARA in T-cell lymphoma cells. Overexpressing wild-type RARA or RARAR394Q significantly increased cell growth in RARAlow cell lines, while RARA knockdown induced G1 arrest and decreased expression of cyclin-dependent kinases CDK2/4/6 in RARAhigh cells. The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. Genes down-regulated in transcriptome data were enriched for cell cycle and G1-S transition. Finally, RARA overexpression augmented chemosensitivity to retinoids. In conclusion, RARA drives cyclin-dependent kinase expression, G1-S transition, and cell growth in T-cell lymphoma. Synthetic retinoids inhibit these functions in a dose-dependent fashion and are most effective in cells with high RARA expression, indicating RARA may represent a therapeutic target in some PTCLs.


[SOCIODEMOGRAPHIC FACTORS AND ADEQUACY OF PRENATAL CARE ASSOCIATED PERINATAL MORTALITY IN COLOMBIAN PREGNANT WOMEN].
an adequate monitoring and the compliance of the nutritional requirements are essential for fetal development and successful control of pregnancy outcomes. This study aimed to determine the association between sociodemographic factors and the pre-birth monitoring associated with perinatal mortality in pregnant women from Colombia. this was a cross-sectional analysis from the 2010 Colombian Demographic and Health Survey and the National Nutritional Survey that included 14 754 pregnant women between 13 and 44 years old. Sociodemographic factors included: new born sex, geographic region, socioeconomic status (SISBEN), pre-birth monitoring (weight control, uterus height, blood pressure, fetal cardiac activity, biochemistry essays, urine analysis) and the supplementation of iron, calcium and folic acid, were collected by structured questionnaire. Associations were established through multivariable and binary regression models. sociodemographic factors such as living in high-density cities, pacific and western regions and low socioeconomic status (SISBEN I) showed a highest perinatal mortality with rates of 1.7%, 1.5%, 1.4% and 1.4%, respectively. After adjustment by new born sex, geographic region and SISBEN score, an adequate monitoring of weight control (OR = 5.12), blood pressure (OR = 5.18), biochemistry essays (OR = 2.19), supplementation of iron (OR = 2.09), calcium (OR=1.73) and folic acid (OR = 2.73) were associated as facilitators of perinatal mortality. perinatal mortality is determined by the sociodemographic factors and pre-birth follow-up included in this study. Government and decision makers can take these results to garbage actions aiming to improve pregnancy monitoring.


Seasonality of Coliform Bacteria Detection Rates in New Jersey Domestic Wells.
It is important that indicators of fecal pollution are reliable. Coliform bacteria are a commonly used indicator of fecal pollution. As other investigators have reported elsewhere, we observed a seasonal pattern of coliform bacteria detections in domestic wells in New Jersey. Examination of a statewide database of 10 years of water quality data from 93,447 samples, from 78,207 wells, generated during real estate transactions, revealed that coliform bacteria were detected in a higher proportion of wells during warm weather months. Further examination of the seasonal pattern of other data, including well water pH, precipitation, ground and surface water temperatures, surface water coliform bacteria concentrations, and vegetation, resulted in the hypothesis that these bacteria may be derived from nonfecal (or environmentally adapted) as well as fecal sources. We provide evidence that the coliform seasonality may be the result of seasonal changes in groundwater extraction volumes (and to a lesser extent precipitation), and temperature-driven changes in the concentration of surface or near-surface coliform sources. Nonfecal coliform sources may not indicate the presence of fecal wastes and hence the potential presence of pathogens, or do so in an inconsistent fashion. Additional research is needed to identify the sources of the coliforms detected in groundwater.


Isolation of a lectin binding rhamnogalacturonan-I containing pectic polysaccharide from pumpkin.
A rhamnogalacturonan-I (RG-I) containing pectic polysaccharide (PPc) was isolated from pumpkin following a low-temperature alkali treatment and a combination of gradual alcohol precipitation and ion-exchange. Monosaccharide compositional analysis of PPc revealed the presence of rhamnose, galacturonic acid, galactose, and arabinose in a molar ratio of 7.4: 25: 28: 2.6. Structural and linkage analysis by 1D NMR (1H NMR and 13C NMR), and 2D NMR (COSY, TOCSY, HSQC, and elevated temperature HMBC) suggested that PPc was a RG-I-like pectic polysaccharide, branched at the C-4 of some of the (about 29% of) rhamnosyl units, with relatively long β-1,4-d-galactan side chains to which were attached, through the C-3 of β-d-Gal, terminal non reducing α-Araf units. The results of surface plasmon resonance (SPR) show that PPc binds to two types of lectin, Ricinus communis agglutinin 120 (RCA120) and Galectin-3 (Gal-3). These binding studies show quick association and slow dissociation with a moderate binding affinity between PPc and Gal-3 of 1.26μM. The interaction between PPc and Gal-3 suggest the potential use of pumpkin pectic polysaccharide as a Gal-3 inhibitor in functional food or drug development applications.


Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation.
Hyperoxia causes cell injury and death associated with reactive oxygen species formation and inflammatory responses. Recent studies show that hyperoxia-induced cell death involves apoptosis, necrosis, or mixed phenotypes depending on cell type, although the underlying mechanisms remain unclear. Using murine lung endothelial cells, we found that hyperoxia caused cell death by apoptosis involving both extrinsic (Fas-dependent) and intrinsic (mitochondria-dependent) pathways. Hyperoxia-dependent activation of the extrinsic apoptosis pathway and formation of the death-inducing signaling complex required NADPH oxidase-dependent reactive oxygen species production, because this process was attenuated by chemical inhibition, as well as by genetic deletion of the p47(phox) subunit, of the oxidase. Overexpression of heme oxygenase-1 prevented hyperoxia-induced cell death and cytochrome c release. Likewise, carbon monoxide, at low concentrations, markedly inhibited hyperoxia-induced endothelial cell death by inhibiting cytochrome c release and caspase-9/3 activation. Carbon monoxide, by attenuating hyperoxia-induced reactive oxygen species production, inhibited extrinsic apoptosis signaling initiated by death-inducing signal complex trafficking from the Golgi apparatus to the plasma membrane and downstream activation of caspase-8. We also found that carbon monoxide inhibited the hyperoxia-induced activation of Bcl-2-related proteins involved in both intrinsic and extrinsic apoptotic signaling. Carbon monoxide inhibited the activation of Bid and the expression and mitochondrial translocation of Bax, whereas promoted Bcl-X(L)/Bax interaction and increased Bad phosphorylation. We also show that carbon monoxide promoted an interaction of heme oxygenase-1 with Bax. These results define novel mechanisms underlying the antiapoptotic effects of carbon monoxide during hyperoxic stress.


A Small Molecule Targeting the Transmembrane Domain of Death Receptor p75NTR Induces Melanoma Cell Death and Reduces Tumor Growth.
Small molecules offer powerful ways to alter protein function. However, most proteins in the human proteome lack small-molecule probes, including the large class of non-catalytic transmembrane receptors, such as death receptors. We hypothesized that small molecules targeting the interfaces between transmembrane domains (TMDs) in receptor complexes may induce conformational changes that alter receptor function. Applying this concept in a screening assay, we identified a compound targeting the TMD of death receptor p75NTR that induced profound conformational changes and receptor activity. The compound triggered apoptotic cell death dependent on p75NTR and JNK activity in neurons and melanoma cells, and inhibited tumor growth in a melanoma mouse model. Due to their small size and crucial role in receptor activation, TMDs represent attractive targets for small-molecule manipulation of receptor function.


Association between child-care and acute diarrhea: a study in Portuguese children.
To quantify the influence of the type of child-care on the occurrence of acute diarrhea with special emphasis on the effect of children grouping during care. From October 1998 to January 1999 292 children, aged 24 to 36 months, recruited using a previously assembled cohort of newborns, were evaluated. Information on the type of care and occurrence of diarrhea in the previous year was obtained from parents by telephone interview. The Chi2 and Kruskal-Wallis tests were used to compare proportions and quantitative variables, respectively. The risk of diarrhea was estimated through the calculation of incident odds ratios (OR) and their respective 95% confidence intervals (95% CI), crude and adjusted by unconditional logistic regression. Using as reference category children cared individually at home, the adjusted ORs for diarrhea occurrence were 3.18, 95% CI [1.49, 6.77] for children cared in group at home, 2.28, 95% CI [0.92, 5.67] for children cared in group in day-care homes and 2.54, 95% CI [1.21, 5.33] for children cared in day-care centers. Children that changed from any other type of child-care setting to child-care centers in the year preceding the study showed a risk even higher (OR 7.65, 95% CI [3.25, 18.02]). Group care increases the risk of acute diarrhea whatsoever the specific setting.


Psychological detachment from work during non-work time: linear or curvilinear relations with mental health and work engagement?
This study examined whether a higher level of psychological detachment during non-work time is associated with better employee mental health (Hypothesis 1), and examined whether psychological detachment has a curvilinear relation (inverted U-shaped pattern) with work engagement (Hypothesis 2). A large cross-sectional Internet survey was conducted among registered monitors of an Internet survey company in Japan. The questionnaire included scales for psychological detachment, employee mental health, and work engagement as well as for job characteristics and demographic variables as potential confounders. The hypothesized model was tested with moderated structural equation modeling techniques among 2,234 respondents working in the tertiary industries with regular employment. Results showed that psychological detachment had curvilinear relations with mental health as well as with work engagement. Mental health improved when psychological detachment increased from a low to higher levels but did not benefit any further from extremely high levels of psychological detachment. Work engagement showed the highest level at an intermediate level of detachment (inverted U-shaped pattern). Although high psychological detachment may enhance employee mental health, moderate levels of psychological detachment are most beneficial for his or her work engagement.


New synthesis method of HA/P(D,L)LA composites: study of fibronectin adsorption and their effects in osteoblastic behavior for bone tissue engineering.
A novel synthetic method to synthesize hydroxyapatite/poly (D,L) lactic acid biocomposite is presented in this study by mixing only the precursors hydroxyapatite and (D,L) LA monomer without adding neither solvent nor catalyst. Three compositions were successfully synthesized with the weight ratios of 1/1, 1/3, and 3/5 (hydroxyapatite/(D,L) lactic acid), and the grafting efficiency of poly (D,L) lactic acid on hydroxyapatite surface reaches up to 84 %. Scanning electron microscopy and Fourier transform infrared spectroscopy showed that the hydroxyapatite particles were successfully incorporated into the poly (D,L) lactic acid polymer and X ray diffraction analysis showed that hydroxyapatite preserved its crystallinity after poly (D,L) lactic acid grafting. Differential scanning calorimetry shows that Tg of hydroxyapatite/poly (D,L) lactic acid composite is less than Tg of pure poly (D,L) lactic acid, which facilitates the shaping of the composite obtained. The addition of poly (D,L) lactic acid improves the adsorption properties of hydroxyapatite for fibronectin extracellular matrix protein. Furthermore, the presence of poly (D,L) lactic acid on hydroxyapatite surface coated with fibronectin enhanced pre-osteoblast STRO-1 adhesion and cell spreading. These results show the promising potential of hydroxyapatite/poly (D,L) lactic acid composite as a bone substitute material for orthopedic applications and bone tissue engineering.


Enhanced allergic tissue injury in Goodpasture's syndrome by intercurrent bacterial infection.
Studies of 16 relapses in seven patients receiving treatment for Goodpasture's syndrome showed that intercurrent bacterial infection seemed to be the precipitating event in 13 cases, whereas a rising antibody titre to glomerular basement membrane was responsible in only one. This association between infection and relapse in Goodpasture's syndrome has several implications for the pathogenesis of antibody-mediated tissue damage, and, clearly, more experiments are needed. Whatever the explanation, however, prevention and early diagnosis and treatment of infection in anti-GBM disease are important.


How a masculine work ethic and economic circumstances affect uptake of HIV treatment: experiences of men from an artisanal gold mining community in rural eastern Uganda.
Current data from Uganda indicate that, compared to women, men are under-represented in HIV treatment, seek treatment later and have a higher mortality while on antiretroviral therapy (ART). By focusing on a masculine work ethic as one of the most predominant expressions of masculinity, this study explores why for some men HIV treatment enhances their masculinity while for others it undermines masculine work identity, leading them to discontinue the treatment. Participant observation and 26 in-depth interviews with men were conducted in a gold mining village in Eastern Uganda between August 2009 and August 2010. Interviewees included men who were taking HIV treatment, who had discontinued treatment, who suspected HIV infection but had not sought testing, or who had other symptoms unrelated to HIV infection. Many participants reported spending large proportions of their income, alleviating symptoms prior to confirming their HIV infection. This seriously undermined their sense of masculinity gained from providing for their families. Disclosing HIV diagnosis and treatment to employers and work colleagues could reduce job offers and/or collaborative work, as colleagues feared working with "ill" people. Drug side-effects affected work, leading some men to discontinue the treatment. Despite being on ART, some men believed their health remained fragile, leading them to opt out of hard work, contradicting their reputation as hard workers. However, some men on treatment talked about "resurrecting" due to ART and linked their current abilities to work again to good adherence. For some men, it was work colleagues who suggested testing and treatment-seeking following symptoms. The central role of a work ethic in expressing masculinity can both encourage and discourage men's treatment-seeking for AIDS. HIV testing and treatment may be sought in order to improve health and get back to work, thereby in the process regaining one's masculine reputation as a hard worker and provider for one's family. However, disclosure can affect opportunities for work and drug side-effects disrupt one's ability to labour, undermining the sense of masculinity gained from work. HIV support organizations need to recognize how economic and gender concerns impact on treatment decisions and help men deal with work-related fears.


Outcomes of transplantation using organs from a donor infected with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae.
Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi-organ infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Recipient 1 underwent simultaneous liver and kidney transplantation for alpha-1 antitrypsin deficiency and alcohol-related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC-producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living-donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC-producing K. pneumoniae. Culture of the preservation fluid containing the vein graft was positive for KPC-producing K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed-field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC-producing K. pneumoniae. All transplant recipients had good short-term outcomes. These cases highlight the importance of inter-institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug-resistant organisms.


The expanding indications of transcatheter aortic valve implantation.
Transcatheter aortic valve implantation (TAVI), also known as transcatheter aortic valve replacement, is increasingly performed worldwide and is a technology that is here to stay. It has become the treatment of choice for inoperable patients and an alternative option for patients at high surgical risk with severe aortic stenosis. Early results of TAVI in intermediate-risk patients appear promising although larger randomized trial results are awaited before the widespread adoption of this technology in this big pool of patients. In patients with bicuspid aortic stenosis and degenerated surgical bioprostheses, TAVI has been shown to be feasible and relatively safe, though certain important considerations remain. Indications for TAVI are likely to grow as newer generation and improved devices and delivery systems become available.


Differentiation of NUT midline carcinoma by epigenomic reprogramming.
NUT midline carcinoma (NMC) is a lethal pediatric tumor defined by the presence of BRD-NUT fusion proteins that arrest differentiation. Here we explore the mechanisms underlying the ability of BRD4-NUT to prevent squamous differentiation. In both gain-of and loss-of-expression assays, we find that expression of BRD4-NUT is associated with globally decreased histone acetylation and transcriptional repression. Bulk chromatin acetylation can be restored by treatment of NMC cells with histone deacetylase inhibitors (HDACi), engaging a program of squamous differentiation and arrested growth in vitro that closely mimics the effects of siRNA-mediated attenuation of BRD4-NUT expression. The potential therapeutic utility of HDACi differentiation therapy was established in three different NMC xenograft models, where it produced significant growth inhibition and a survival benefit. Based on these results and translational studies performed with patient-derived primary tumor cells, a child with NMC was treated with the FDA-approved HDAC inhibitor, vorinostat. An objective response was obtained after five weeks of therapy, as determined by positron emission tomography. These findings provide preclinical support for trials of HDACi in patients with NMC.


Response of kaolin ACT to heparin: evaluation with an automated assay and higher heparin doses.
Because previous reports suggest that the linear relationship between celite activated clotting time (ACT) values and heparin sodium is disrupted if values exceed 500 to 600 seconds, this study was designed to evaluate the relationship of kaolin activated clotting time (ACT) values to high in vitro heparin concentrations. In addition, the relationship of kaolin ACT to heparin concentration as determined manually was compared with that obtained with an automated heparin dose response assay. Blood specimens were obtained prior to and after heparin administration from 41 cardiac surgical patients requiring cardiopulmonary bypass in this institutional human studies committee-approved study. Five ACT instruments were used to evaluate the response of kaolin ACT to manually added heparin at two anticoagulation levels: low range (ACT values of less than 500 seconds) and high range (ACT values of 500 seconds or greater). Specimens were also used to measure kaolin ACT values at three heparin concentrations with an automated heparin dose response assay (HDR) using a Hepcon instrument. A greater response of kaolin ACT to heparin was seen with high-range ACT values than low-range ACT values as illustrated by greater (p = 0.002) mean slope values (low range, 99 +/- 30 s/U/ mL; high range, 128 +/- 50 s/U/ml). Good correlations were obtained between heparin concentration and either low- or high-range ACT values as demonstrated by mean correlation coefficients (low range, 0.992; high range 0.982). The response of low-range kaolin ACT values to heparin was greater than that obtained with the automated heparin dose response assay as illustrated by greater (p = 0.005) mean slope values (low range, 99 +/- 30 s/U/mL; HDR, 82 +/- 21 s/U/mL). Good correlations were observed for the relationship between heparin and ACT values obtained with the HDR assay (r = 0.998). A variable response of kaolin ACT to heparin among patients was demonstrated in our study, especially when ACT values exceeded 500 seconds. We found that the response of kaolin ACT to higher heparin concentrations was acceptable for clinical monitoring based on good correlations obtained in individual patients. The HDR assay generally overestimates a patient's heparin requirements; most likely, this is due to a lower response of kaolin ACT to heparin concentration that is reflected in this assay. Because and exceptional correlation can be obtained between kaolin ACT values and heparin concentration using the assay, this automated assay can identify heparin-resistant patients who may need further treatment.


Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome.
Fatal arrhythmias from occult long QT syndrome may be responsible for some cases of sudden infant death syndrome (SIDS). Because patients who have long QT syndrome with sodium channel gene (SCN5A) defects have an increased frequency of cardiac events during sleep, and a recent case is reported of a sporadic SCN5A mutation in an infant with near SIDS, SCN5A has emerged as the leading candidate ion channel gene for SIDS. To determine the prevalence and functional properties of SCN5A mutations in SIDS. Postmortem molecular analysis of 93 cases of SIDS or undetermined infant death identified by the Medical Examiner's Office of the Arkansas State Crime Laboratory between September 1997 and August 1999. Genomic DNA was extracted from frozen myocardium and subjected to SCN5A mutational analyses. Missense mutations were incorporated into the human heart sodium channel alpha subunit by mutagenesis, transiently transfected into human embryonic kidney cells, and characterized electrophysiologically. Molecular and functional characterization of SCN5A defects. Two of the 93 cases of SIDS possessed SCN5A mutations: a 6-week-old white male with an A997S missense mutation in exon 17 and a 1-month old white male with an R1826H mutation in exon 28. These 2 distinct mutations occurred in highly conserved regions of the sodium channel and were absent in 400 control patients (800 alleles). Functionally, the A997S and R1826H mutant channels expressed a sodium current characterized by slower decay and a 2- to 3-fold increase in late sodium current. Approximately 2% of this prospective, population-based cohort of SIDS cases had an identifiable SCN5A channel defect, suggesting that mutations in cardiac ion channels may provide a lethal arrhythmogenic substrate in some infants at risk for SIDS.


[America Manna: women and migration in a global perspective].
This article considers the role of migrant women in light of the contribution to the demographic, social, and economic development of the receiving country. The high level of development for these areas has always been fostered by the ready availability of a salaried work force and its easy replacement. The cost of labor in the country of origin is different from that in the receiving country and thus often results in a parallel work force and fosters forms of discrimination. With the crisis of the "rotation" model in the 1970s, the cost of replacing the work force has been concentrated in the countries of origin while official politics, which limited the immigration of family members, placed a greater burden on the women and the children of the emigrants, and increased the danger of their gradual marginalization.


Comparison of different adult stem cell types for treatment of myocardial ischemia.
A comparative analysis of the efficacy of different cell candidates for the treatment of heart disease remains to be described. This study is designed to evaluate the therapeutic efficacy of 4 cell types in a murine model of myocardial infarction. Bone marrow mononuclear cells (MN), mesenchymal stem cells (MSC), skeletal myoblasts (SkMb), and fibroblasts (Fibro) expressing firefly luciferase (Fluc) and green fluorescence protein (GFP) were characterized by flow cytometry, bioluminescence imaging (BLI), and luminometry. Female FVB mice (n=70) underwent LAD ligation and intramyocardially received one cell type (5x10(5)) or PBS. Cell survival was measured by BLI and by TaqMan PCR. Cardiac function was assessed by echocardiography and invasive hemodynamic measurements. Fluc expression correlated with cell number in all groups (r(2)>0.93). In vivo BLI revealed acute donor cell death of MSC, SkMb, and Fibro within 3 weeks after transplantation. By contrast, cardiac signals were still present after 6 weeks in the MN group, as confirmed by TaqMan PCR (P<0.01). Echocardiography showed significant preservation of fractional shortening in the MN group compared to controls (P<0.05). Measurements of left ventricular end-systolic/diastolic volumes revealed that the least amount of ventricular dilatation occurred in the MN group (P<0.05). Histology confirmed the presence of MN, although there was no evidence of transdifferentiation by donor MN into cardiomyocytes. This is the first study to show that compared to MSC, SkMB, and Fibro, MN exhibit a more favorable survival pattern, which translates into a more robust preservation of cardiac function.


Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model.
Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect.


Identification of novel ATP13A2 interactors and their role in α-synuclein misfolding and toxicity.
Lysosomes are responsible for degradation and recycling of bulky cell material, including accumulated misfolded proteins and dysfunctional organelles. Increasing evidence implicates lysosomal dysfunction in several neurodegenerative disorders, including Parkinson's disease and related synucleinopathies, which are characterized by the accumulation of α-synuclein (α-syn) in Lewy bodies. Studies of lysosomal proteins linked to neurodegenerative disorders present an opportunity to uncover specific molecular mechanisms and pathways that contribute to neurodegeneration. Loss-of-function mutations in a lysosomal protein, ATP13A2 (PARK9), cause Kufor-Rakeb syndrome that is characterized by early-onset parkinsonism, pyramidal degeneration and dementia. While loss of ATP13A2 function plays a role in α-syn misfolding and toxicity, the normal function of ATP13A2 in the brain remains largely unknown. Here, we performed a screen to identify ATP13A2 interacting partners, as a first step toward elucidating its function. Utilizing a split-ubiquitin membrane yeast two-hybrid system that was developed to identify interacting partners of full-length integral membrane proteins, we identified 43 novel interactors that primarily implicate ATP13A2 in cellular processes such as endoplasmic reticulum (ER) translocation, ER-to-Golgi trafficking and vesicular transport and fusion. We showed that a subset of these interactors modified α-syn aggregation and α-syn-mediated degeneration of dopaminergic neurons in Caenorhabditis elegans, further suggesting that ATP13A2 and α-syn are functionally linked in neurodegeneration. These results implicate ATP13A2 in vesicular trafficking and provide a platform for further studies of ATP13A2 in neurodegeneration.


Estrogen replacement therapy after breast cancer: a 12-year follow-up.
In the United States, estrogen replacement therapy (ERT) is discouraged in breast cancer survivors because of concerns that hormones may reactivate the disease. Because ERT can improve quality of life and decrease morbidity from osteoporosis and cardiovascular disease, however, this policy is increasingly being challenged. From February to August 1995, 607 breast cancer survivors were interviewed concerning ERT usage. Sixty-four patients indicated they received some form of ERT after their breast cancer diagnosis. Medical records for these patients were analyzed for disease stage, surgical treatment, adjuvant treatment, estrogen and progesterone receptor status, date of initiation of ERT, type of ERT, recurrence, and final outcome. Patients receiving ERT were followed prospectively. Eight patients were excluded because they had used only vaginal cream ERT. The remaining 56 received ERT as conjugated estrogens, an estradiol patch, estropipate, or birth control pills. The median follow-up from diagnosis was 12.8 years (range, 4.7-38.9 years). The median time on ERT since diagnosis was 6.4 years (range, 1.0-20.9 years); 38% of the patients initiated ERT within 2 years of diagnosis. Estrogen receptors were positive in 28 (74%) of the 38 cases with available information. Pathological disease stage at time of diagnosis and treatment was 0 in 15 cases (27%), I in 27 (48%), and II in 14 (25%). Twenty-six patients (47%) received adjuvant chemotherapy or hormonal therapy. One local recurrence and one contralateral breast cancer occurred during the follow-up period (13.5 and 9.6 years, respectively), with no regional or distant recurrences, for a 15-year actuarial disease-free survival rate of 92.5%. There were no breast cancer deaths. Use of ERT in a cohort of breast cancer survivors with tumors of generally good prognosis was not associated with increased breast cancer events compared with non-ERT users, even over a long follow-up period.


Hip damage occurs at the zone of femoroacetabular impingement.
Although current concepts of anterior femoroacetabular impingement predict damage in the labrum and the cartilage, the actual joint damage has not been verified by computer simulation. We retrospectively compared the intraoperative locations of labral and cartilage damage of 40 hips during surgical dislocation for cam or pincer type femoroacetabular impingement (Group I) with the locations of femoroacetabular impingement in 15 additional hips using computer simulation (Group II). We found no difference between the mean locations of the chondrolabral damage of Group I and the computed impingement zone of Group II. The standard deviation was larger for measures of articular damage from Group I in comparison to the computed values of Group II. The most severe hip damage occurred at the zone of highest probability of femoroacetabular impact, typically in the anterosuperior quadrant of the acetabulum for both cam and pincer type femoroacetabular impingements. However, the extent of joint damage along the acetabular rim was larger intraoperatively than that observed on the images of the 3-D joint simulations. We concluded femoroacetabular impingement mechanism contributes to early osteoarthritis including labral lesions. Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.


Prediction models for cardiovascular disease risk in the general population: systematic review.
To provide an overview of prediction models for risk of cardiovascular disease (CVD) in the general population. Systematic review. Medline and Embase until June 2013. Studies describing the development or external validation of a multivariable model for predicting CVD risk in the general population. 9965 references were screened, of which 212 articles were included in the review, describing the development of 363 prediction models and 473 external validations. Most models were developed in Europe (n=167, 46%), predicted risk of fatal or non-fatal coronary heart disease (n=118, 33%) over a 10 year period (n=209, 58%). The most common predictors were smoking (n=325, 90%) and age (n=321, 88%), and most models were sex specific (n=250, 69%). Substantial heterogeneity in predictor and outcome definitions was observed between models, and important clinical and methodological information were often missing. The prediction horizon was not specified for 49 models (13%), and for 92 (25%) crucial information was missing to enable the model to be used for individual risk prediction. Only 132 developed models (36%) were externally validated and only 70 (19%) by independent investigators. Model performance was heterogeneous and measures such as discrimination and calibration were reported for only 65% and 58% of the external validations, respectively. There is an excess of models predicting incident CVD in the general population. The usefulness of most of the models remains unclear owing to methodological shortcomings, incomplete presentation, and lack of external validation and model impact studies. Rather than developing yet another similar CVD risk prediction model, in this era of large datasets, future research should focus on externally validating and comparing head-to-head promising CVD risk models that already exist, on tailoring or even combining these models to local settings, and investigating whether these models can be extended by addition of new predictors.


Association of Low Vitamin D Levels With Noninfectious Anterior Uveitis.
Vitamin D plays an important role in both the innate and adaptive immune systems. It has been shown to contribute to the etiology of T-cell-mediated autoimmune diseases through the upregulation of type 2 anti-inflammatory T helper cells and the suppression of type 1 T helper cells. Noninfectious uveitis is postulated to be caused by immune dysfunction. To determine whether there is an association between vitamin D levels and noninfectious anterior uveitis. This was a case-control study. We identified patients with and without noninfectious uveitis using the Massachusetts Eye and Ear Infirmary Ocular Inflammation Database and electronic medical records from March 1, 2008, to December 12, 2015, at the Massachusetts Eye and Ear Infirmary Uveitis and Comprehensive Ophthalmology Clinics. One hundred patients with noninfectious anterior uveitis and 100 patients without uveitis were recruited. Patients with noninfectious uveitis were diagnosed by fellowship-trained uveitis specialists after exclusion of infectious causes and neoplastic masquerades of uveitis. All patients included had a total 25-hydroxyvitamin D level recorded. Multivariate regression models were constructed to determine the association between vitamin D levels and the presence of uveitis. Presence of noninfectious anterior uveitis. We identified 100 patients (64 white, 8 African American, 25 Asian, and 3 Hispanic) with a mean (SD) age of 51.8 (15.9) years (26 men) and 100 control individuals (58 white, 23 African American, 8 Asian, and 11 Hispanic) with a mean (SD) age of 53.6 (16.2) years (27 men). Hypovitaminosis D was associated with noninfectious uveitis in the univariate analysis (odds ratio, 2.53; 95% CI, 1.42-4.51; P = .002). The association in multivariate regression after adjusting for age, sex, and race/ethnicity was 2.96 (95% CI, 1.60-5.50; P = .001) The odds of developing uveitis were 4% lower for every 1-ng/mL increase in vitamin D level (odds ratio, 0.96; 95% CI, 0.93-0.99; P = .01) in the main multivariate analysis. In this retrospective study, lower vitamin D levels were associated with an increased risk of noninfectious anterior uveitis. However, this does not confirm a causal effect.


Detection of marine birnavirus genome in zooplankton collected from the Uwa Sea, Japan.
Marine birnaviruses (MABVs) infect a wide range of fish and shellfish, yet their mode of transmission is still unclear. To determine whether marine plankton serve as a vector for MABVs, we examined plankton collected from the Uwa Sea, Japan. The phytoplankton and zooplankton were collected monthly, at depths of 0 and 40 m, from May to November 2001. Detection of the MABV genome was carried out using 2-step PCR and virus isolation. Viral genome was detected in zooplankton collected at 0 m depth in September and at 40 m depth in November. The virus could not be isolated in the PCR-positive samples. These results suggest that zooplankton may act as a vector of MABVs, although the infective and/or accumulated virus titer in zooplankton was low.


Improving antenatal care to prevent adverse pregnancy outcomes caused by syphilis.
Evaluation of: Hawkes S, Matin N, Broutet N, Low N. Effectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis. Lancet Infect. Dis. 11(9), 684-691 (2011). Untreated maternal syphilis continues to be an important risk factor for adverse pregnancy outcomes in many developing countries, resulting in spontaneous abortion, stillbirth, premature delivery or perinatal death. In this systematic review and meta-analysis, Hawkes et al. review the effectiveness of interventions to increase the uptake of syphilis screening and treatment in pregnancy. The ten studies they review, published between 1986 and 2008, have a total sample size of more than 41,000. Overall, they showed that interventions to improve the uptake of antenatal screening for syphilis in pregnancy could reduce the syphilis-attributable incidence of stillbirth and perinatal death by 50%. As prevention of congenital syphilis costs less than US$1.50 per woman screened, the investment to scale up antenatal screening programs would be cost effective, would significantly improve pregnancy outcomes and reduce neonatal mortality.


Crimean-Congo Hemorrhagic Fever Virus Past Infections Are Associated with Two Innate Immune Response Candidate Genes in Dromedaries.
Dromedaries are an important livestock, used as beasts of burden and for meat and milk production. However, they can act as an intermediate source or vector for transmitting zoonotic viruses to humans, such as the Middle East respiratory syndrome coronavirus (MERS-CoV) or Crimean-Congo hemorrhagic fever virus (CCHFV). After several outbreaks of CCHFV in the Arabian Peninsula, recent studies have demonstrated that CCHFV is endemic in dromedaries and camel ticks in the United Arab Emirates (UAE). There is no apparent disease in dromedaries after the bite of infected ticks; in contrast, fever, myalgia, lymphadenopathy, and petechial hemorrhaging are common symptoms in humans, with a case fatality ratio of up to 40%. We used the in-solution hybridization capture of 100 annotated immune genes to genotype 121 dromedaries from the UAE tested for seropositivity to CCHFV. Through univariate linear regression analysis, we identified two candidate genes belonging to the innate immune system: FCAR and CLEC2B. These genes have important functions in the host defense against viral infections and in stimulating natural killer cells, respectively. This study opens doors for future research into immune defense mechanisms in an enzootic host against an important zoonotic disease.


Survival and cardiac event rates in the first year after emergency coronary angioplasty for acute myocardial infarction.
One year survival and event-free survival rates were analyzed in 342 patients with acute myocardial infarction who were consecutively enrolled in a treatment protocol of early intravenous thrombolytic therapy followed by emergency coronary angioplasty. Ninety-four percent of the patients achieved successful reperfusion, including 4% with failed angioplasty whose perfusion was maintained by means of a reperfusion catheter before emergency bypass surgery. The procedural mortality rate was 1.2% and the total in-hospital mortality rate was 11%. Ninety-two percent of surviving nonsurgical patients who underwent repeat cardiac catheterization were discharged from the hospital with an open infarct-related artery. The related cumulative 1 year survival rate for all patients managed with this treatment strategy was 87%, and the cardiac event-free survival rate was 84%. The 1 year survival for hospital survivors was 98% and the infarct-free survival rate was 94%. Multivariable analysis identified the following factors as independent predictors of subsequent cardiovascular death: cardiogenic shock, greater age, lower ejection fraction, female gender and a closed infarct-related vessel on the initial coronary angiogram. Among patients with cardiogenic shock, despite a 42% in-hospital mortality rate, only 4% died during the first year after hospital discharge. Similarly, the in-hospital and 1 year postdischarge mortality rates were 19 and 4%, respectively, for patients with an initial ejection fraction less than 40, and 25 and 3%, respectively, for patients greater than 65 years. An aggressive treatment strategy including early thrombolytic therapy, emergency cardiac catheterization, coronary angioplasty and, when necessary, bypass surgery resulted in a high rate of infarct vessel patency.(ABSTRACT TRUNCATED AT 250 WORDS)


Secondary cartilage revealed in a non-avian dinosaur embryo.
The skull and jaws of extant birds possess secondary cartilage, a tissue that arises after bone formation during embryonic development at articulations, ligamentous and muscular insertions. Using histological analysis, we discovered secondary cartilage in a non-avian dinosaur embryo, Hypacrosaurus stebingeri (Ornithischia, Lambeosaurinae). This finding extends our previous report of secondary cartilage in post-hatching specimens of the same dinosaur species. It provides the first information on the ontogeny of avian and dinosaurian secondary cartilages, and further stresses their developmental similarities. Secondary cartilage was found in an embryonic dentary within a tooth socket where it is hypothesized to have arisen due to mechanical stresses generated during tooth formation. Two patterns were discerned: secondary cartilage is more restricted in location in this Hypacrosaurus embryo, than it is in Hypacrosaurus post-hatchlings; secondary cartilage occurs at far more sites in bird embryos and nestlings than in Hypacrosaurus. This suggests an increase in the number of sites of secondary cartilage during the evolution of birds. We hypothesize that secondary cartilage provided advantages in the fine manipulation of food and was selected over other types of tissues/articulations during the evolution of the highly specialized avian beak from the jaws of their dinosaurian ancestors.


Comparative Analysis of Calcium Silicate-based Root Filling Materials Using an Open Apex Model.
Many new calcium silicate-based root filling materials have emerged in the market; however, their performance in the orthograde obturation of an open apex has not been evaluated. The purpose of this study was to compare the marginal adaptation of ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), NeoMTA Plus (Avalon Biomed Inc, Bradenton, FL), and Endosequence BC RRM-Fast Set Putty (BC RRM-FS; Brasseler USA, Savannah, GA) after orthograde placement in roots with open apices. Palatal roots of maxillary molars were instrumented to create divergent open apices and divided into 4 groups for orthograde obturation: ProRoot MTA, NeoMTA Plus, BC RRM-FS, and BC RRM-FS + BC Sealer. Using a scanning electron microscope, the quality of material adaptation at the anatomic apex was evaluated by 5 blinded examiners; 3 mm of the root end was sectioned, and gap distance was measured at the material-dentin interface. Statistical analyses were performed using the Kruskal-Wallis test. There were no significant differences in marginal adaptation among the 4 groups at the level of the anatomic apex (P = .175). BC RRM-FS + BC Sealer had a significantly smaller gap size after 3-mm root end resection compared with the other 3 groups (P < .01). No differences were observed among the other 3 materials. All materials showed comparable marginal adaptation at the anatomic apex when used for orthograde obturation of open apices. Application of BC Sealer before the delivery of BC RRM-FS Putty enhanced the quality of adaptation coronal to the apex.


Dissolution and transport of 2,4-DNT and 2,6-DNT from M1 propellant in soil.
Live-fire training exercises can result in particulate propellant contamination on military training ranges and can potentially contaminate ground water. This study was conducted to evaluate dissolution of the 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) from the propellant formulation, M1 (87.6% nitrocellulose, 7.3% 2,4-DNT, 0.57% 2,6-DNT, 1.06% diphenylamine, 3.48% dibutyl phthalate) and their subsequent transport in soil. Batch dissolution studies were followed by saturated column transport experiments. Neat, dissolved 2,4-DNT, and M1 in solid and dissolved forms were used as influent to columns filled with Plymouth loamy sand (mesic, coated Typic Quartzipsamments) from Camp Edwards, MA. Dissolution rates and other fate and transport parameters were determined using the HYDRUS-1D code. M1 dissolution was limited by DNT diffusion from the interior of the pellet, resulting in an exponential decrease in dissolution rate with time. The HYDRUS-1D model accurately described release and transport of 2,4- and 2,6-DNT from M1 propellant. Dissolution rates for M1 in the stirred reactor and column studies were similar, indicating that batch dissolution rates are potentially useful to represent field conditions.


Nuclear spin-hyperpolarization generated in a flavoprotein under illumination: experimental field-dependence and theoretical level crossing analysis.
The solid-state photo-chemically induced dynamic nuclear polarization (photo-CIDNP) effect generates non-equilibrium nuclear spin polarization in frozen electron-transfer proteins upon illumination and radical-pair formation. The effect can be observed in various natural photosynthetic reaction center proteins using magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, and in a flavin-binding light-oxygen-voltage (LOV) domain of the blue-light receptor phototropin. In the latter system, a functionally instrumental cysteine has been mutated to interrupt the natural cysteine-involving photochemistry allowing for an electron transfer from a more distant tryptophan to the excited flavin mononucleotide chromophore. We explored the solid-state photo-CIDNP effect and its mechanisms in phototropin-LOV1-C57S from the green alga Chlamydomonas reinhardtii by using field-cycling solution NMR. We observed the 13C and, to our knowledge, for the first time, 15N photo-CIDNP signals from phototropin-LOV1-C57S. Additionally, the 1H photo-CIDNP signals of residual water in the deuterated buffer of the protein were detected. The relative strengths of the photo-CIDNP effect from the three types of nuclei, 1H, 13C and 15N were measured in dependence of the magnetic field, showing their maximum polarizations at different magnetic fields. Theoretical level crossing analysis demonstrates that anisotropic mechanisms play the dominant role at high magnetic fields.


Compensatory gait mechanics in patients with unilateral knee arthritis.
Few studies exist on gait adaptation caused by knee osteoarthritis (OA), and those have only explored adaptations of the kinematics and kinetics of the knee joint itself. We characterize ankle, knee, hip, and low back mechanical energy expenditures (MEE) and compensations (MEC) during gait in patients with knee OA. Thirteen elderly patients with unilateral knee OA and 10 matched healthy elderly controls were studied during preferred and paced speed gait. Gait speed, step length, and lower extremity and low back joint MEE and MEC were compared between groups. Patients with knee OA had lower, but not significantly different, walking speed and step length compared to the controls, and had significantly different joint kinetic profiles. Patients had reduced ankle power at terminal stance, lacked a second positive peak in knee power, and had increased power absorption at the hip. Abnormal knee kinematics were exaggerated when walking at a paced speed, but hip kinetics normalized among patients with OA. Reduced ankle plantar-flexion power in patients with knee OA was probably due to disrupted transfer of energy through the knee. Lack of concentric knee power supports prior studies' conclusions that patients with knee OA avoid using their quadriceps to stabilize the knee, probably to reduce articular loads. Patients with knee OA increase eccentric hip power due to increased hip extension caused by abnormal knee kinematics, potentially increasing hip articular forces. This passive mechanism, however, may assist in the advancement of the leg into swing phase.


Silicon-based nanotheranostics.
With the rapid expansion of nanoscience and nanotechnology in interdisciplinary fields, multifunctional nanomaterials have attracted particular attention. Recent advances in nanotherapeutics for cancer applications provided diverse groups of synthetic particles with defined cellular and biological functions. The advance of nanotechnology significantly increased the number of possibilities for the construction of diverse biological tools. Such materials are destined to be of great importance because of the opportunity to combine the biotechnological potential of nanoparticles together with the recognition, sensitivity and modulation of cellular pathways or genes when applied to living organisms. In this mini review three main types of Si-based nanomaterials are highlighted in the area of their application for therapy and imaging: porous silicon nanoparticles (pSiNPs), mesoporous silica nanoparticles (MSNs), focusing on their nanoconstructs containing coordination compounds, and periodic mesoporous silica nanoparticles (PMONPs). Moreover, a critical discussion on the research efforts in the construction of nanotheranostics is presented.


Oral human papillomavirus (HPV) infection in HPV-positive patients with oropharyngeal cancer and their partners.
To better understand oral human papillomavirus (HPV) infection and cancer risk among long-term sexual partners of patients with HPV-positive oropharyngeal cancer (HPV-OPC). An oral rinse sample, risk factor survey, cancer history, and oral examination (partners only) were collected from patients with HPV-OPC and their partners. Oral rinse samples were evaluated for 36 types of HPV DNA using PGMY 09/11 primers and line-blot hybridization and HPV16 copy number using quantitative polymerase chain reaction. Oral HPV prevalence was compared with infection among those age 45 to 65 years using National Health and Nutrition Examination Survey (NHANES) 2009-2010. A total of 164 patients with HPV-OPC and 93 of their partners were enrolled. Patients were primarily men (90%), were never-smokers (51%), and had performed oral sex (97%), with a median age of 56 years; they had a high prevalence of oncogenic oral HPV DNA (61%) and oral HPV16 DNA (54%) at enrollment. Female partners had comparable oncogenic oral HPV prevalence compared with members of the general population of the same age (1.2% v 1.3%). Among the six male partners, no oncogenic oral HPV infections were detected. No precancers or cancers were identified during partner oral cancer screening examinations. However, a history of cervical disease was reported by nine partners (10.3%) and two female patients (11.8%), and three patients (2.0%) reported a previous partner who developed invasive cervical cancer. Oral HPV16 DNA is commonly detected among patients with HPV-OPC at diagnosis, but not among their partners. Partners of patients with HPV-OPC do not seem to have elevated oral HPV infection compared with the general population.


Aichi virus infection in elderly people in Sweden.
Aichi virus (AiV), genus Kobuvirus, family Picornaviridae, is associated with gastroenteritis in humans. Previous studies have shown high seroprevalence but low incidence (0.9-4.1%) in clinical samples. We report here the first detection of AiV in Sweden. Two hundred twenty-one specimens from hospitalized patients with diarrhea, who were negative for other enteric viruses, were included in the study. AiV were detected in three specimens, all from elderly patients. Phylogenetic analysis revealed that the three Swedish isolates belonged to genotype A and were genetically closest to European and Asian strains of AiV.


Carbohydrate-based block copolymer systems: directed self-assembly for nanolithography applications.
Self-assembly of block copolymers (BCPs) provides an attractive nanolithography approach, which looks especially promising for fabrication of regular structures with characteristic sizes below 10 nm. Nevertheless, directed self-assembly (DSA) and pattern transfer for BCPs with such small features remain to be a challenge. Here we demonstrate DSA of the maltoheptaose-block-polystyrene (MH1,2k-b-PS4,5k) BCP system using graphoepitaxy. BCP thin films were self-organized by solvent vapor annealing in tetrahydrofuran (THF) and water into sub-10 nm scale cylinders of the maltoheptaose (MH) block oriented horizontally or perpendicularly to the surface in a polystyrene (PS) matrix. The guiding patterns for graphoepitaxy were made by the electron beam lithography (EBL) and lift-off process with the distance gradually varying between 0 and 200 nm. Atomic force microscopy (AFM) investigation of MH1,2k-b-PS4,5k BCP DSA patterns revealed good ordering of vertical and horizontal cylindrical MH arrays for DSA lines with 150-200 nm separation. Reactive ion etching (RIE) of MH1,2k and PS4,5k thin films in O2 and CF4 plasma showed up to 14 times higher etch rate of MH compared to PS. These results indicate that MH1,2k-b-PS4,5k is a promising BCP for nanolithographic applications below 10 nm.


A quantitative trait locus influencing BMI maps to the region of the beta-3 adrenergic receptor.
The beta-3 adrenergic receptor (ADRB3) has been implicated as a regulator of energy expenditure, and a polymorphism in codon 64 of this gene (Trp64Arg) has been associated in some studies with obesity and insulin resistance. However, many studies have failed to detect an effect of this variant, and the importance of the Trp64Arg variant in human obesity remains controversial. We performed a quantitative linkage analysis of the ADRB3 and obesity, using 12 markers (including the intragenic Trp64Arg polymorphism) spanning a 57-cM region of chromosome 8. The study population consisted of 470 individuals from 10 large multigenerational families of Mexican-American ancestry residing in San Antonio, TX. In two-point analysis, logarithm of odds (LOD) scores >1.0 were observed for six markers surrounding ADRB3 in a 33-cM region spanned by markers D8S1477 and D8S1136. The multipoint LOD score was 3.21, occurring between markers D8S1121 and ADRB3, approximately 2-3 cM from ADRB3. Adjusting for the presence of the Arg64 allele or excluding from the analysis the 11 individuals homozygous for the Arg64 allele did not reduce the evidence for linkage. A genome scan was conducted at 10 cM map density to detect other loci influencing variation in BMI. Multipoint LOD scores >1.0 were observed in four other regions, including two on chromosome 17, one on chromosome 6q, and one on chromosome 2p. These data suggest that the ADRB3 should continue to be regarded as a strong candidate gene for obesity even though evidence for an effect of the Trp64Arg polymorphism could not be established. It is also possible that a gene closely linked to ADRB3 may influence susceptibility to obesity.


Primary Hyperventilation in the Emergency Department: A First Overview.
Primary hyperventilation is defined as a state of alveolar ventilation in excess of metabolic requirements, leading to decreased arterial partial pressure of carbon dioxide. The primary aim of this study was to characterise patients diagnosed with primary hyperventilation in the ED. Our retrospective cohort study comprised adult (≥16 years) patients admitted to our ED between 1 January 2006 and 31 December 2012 with the primary diagnosis of primary (=psychogenic) hyperventilation. A total of 616 patients were eligible for study. Participants were predominantely female (341 [55.4%] female versus 275 [44.6%] male respectively, p <0.01). The mean age was 36.5 years (SD 15.52, range 16-85). Patients in their twenties were the most common age group (181, 29.4%), followed by patients in their thirties (121, 19.6%). Most patients presented at out-of-office hours (331 [53.7%]. The most common symptom was fear (586, 95.1%), followed by paraesthesia (379, 61.5%) and dizziness (306, 49.7%). Almost a third (187, 30.4%) of our patients had previously experienced an episode of hyperventilation and half (311, 50.5%) of patients had a psychiatric co-morbidity. Hyperventilation is a diagnostic chimera with a wide spectrum of symptoms. Patients predominantly are of young age, female sex and often have psychiatric comorbidities. The severity of symptoms accompanied with primary hyperventilation most often needs further work-up to rule out other diagnosis in a mostly young population. In the future, further prospective multicentre studies are needed to evaluate and establish clear diagnostic criteria for primary hyperventilation and possible screening instruments.


Comparison of culture and a novel 5' Taq nuclease assay for direct detection of Campylobacter fetus subsp. venerealis in clinical specimens from cattle.
A Campylobacter fetus subsp. venerealis-specific 5' Taq nuclease PCR assay using a 3' minor groove binder-DNA probe (TaqMan MGB) was developed based on a subspecies-specific fragment of unknown identity (S. Hum, K. Quinn, J. Brunner, and S. L. On, Aust. Vet. J. 75:827-831, 1997). The assay specifically detected four C. fetus subsp. venerealis strains with no observed cross-reaction with C. fetus subsp. fetus-related Campylobacter species or other bovine venereal microflora. The 5' Taq nuclease assay detected approximately one single cell compared to 100 and 10 cells in the conventional PCR assay and 2,500 and 25,000 cells from selective culture from inoculated smegma and mucus, respectively. The respective detection limits following the enrichments from smegma and mucus were 5,000 and 50 cells/inoculum for the conventional PCR compared to 500 and 50 cells/inoculum for the 5' Taq nuclease assay. Field sampling confirmed the sensitivity and the specificity of the 5' Taq nuclease assay by detecting an additional 40 bulls that were not detected by culture. Urine-inoculated samples demonstrated comparable detection of C. fetus subsp. venerealis by both culture and the 5' Taq nuclease assay; however, urine was found to be less effective than smegma for bull sampling. Three infected bulls were tested repetitively to compare sampling tools, and the bull rasper proved to be the most suitable, as evidenced by the improved ease of specimen collection and the consistent detection of higher levels of C. fetus subsp. venerealis. The 5' Taq nuclease assay demonstrates a statistically significant association with culture (chi2 = 29.8; P < 0.001) and significant improvements for the detection of C. fetus subsp. venerealis-infected animals from crude clinical extracts following prolonged transport.


Design of broadband LP01↔LP02 mode converter based on special dual-core fiber for dispersion compensation.
A novel broadband LP01↔LP02 mode converter for dispersion compensation based on special dual-core fiber is theoretically investigated by using the coupled-mode theory. The simulated mode converter has ∼22 nm bandwidth with a conversion efficiency of over 80%. Furthermore, this noncomplete conversion only introduces the insertion loss rather than multipath interference resulting from the residual LP01 mode. Finally, one optimal scheme for broadening the bandwidth of high-efficiency conversion has been proposed by longitudinally tapering the dual-core fiber. The simulation results show that the conversion bandwidth can be improved to ∼31 nm by tapering with a scaling range of only 2%.


Laparoscopic gastrostomy: a safe method for obtaining enteral access.
Laparoscopic gastrostomy is a relatively new procedure which does not require a laparotomy but which allows direct visualization of the gastrostomy tube entering the stomach and the stomach-parietal peritoneum interface. The role of the laparoscopically placed gastrostomy for enteral access has yet to be defined. Our aim was to compare laparoscopic gastrostomy with open surgical gastrostomy to determine the effectiveness and safety of laparoscopic gastrostomy as a method for obtaining long term enteral access. We reviewed the records of 32 patients (December 1992 to April 1994) who had laparoscopic gastrostomy (group I) and 37 patients (January 1987 to December 1993) who had open gastrostomy (group II). The indications, length of operation, and morbidity and mortality rates in both groups were compared. The underlying diseases and indications for gastrostomy placement were similar in both groups. Both groups included primarily patients who were not candidates for upper endoscopy. Operative time was significantly shorter in the laparoscopic gastrostomy group (38 +/- 7 min) than in the open gastrostomy group (62 +/- 19), P < 0.0001. Major complication for laparoscopic gastrostomy was 6% and for open gastrostomy was 11%. There was no procedure-related mortality in group I and three patients in group II died in the immediate postoperative period. Major morbidity and mortality rates were not significantly different between the two groups. Laparoscopic gastrostomy is a safe and effective alternative to open gastrostomy, particularly in patients unable to undergo upper endoscopy or in patients undergoing a concomitant laparoscopic procedure.


Use-dependent cortical processing from fingertips in touchscreen phone users.
Cortical activity allotted to the tactile receptors on fingertips conforms to skilful use of the hand. For instance, in string instrument players, the somatosensory cortical activity in response to touch on the little fingertip is larger than that in control subjects. Such plasticity of the fingertip sensory representation is not limited to extraordinary skills and occurs in monkeys trained to repetitively grasp and release a handle as well. Touchscreen phones also require repetitive finger movements, but whether and how the cortex conforms to this is unknown. By using electroencephalography (EEG), we measured the cortical potentials in response to mechanical touch on the thumb, index, and middle fingertips of touchscreen phone users and nonusers (owning only old-technology mobile phones). Although the thumb interacted predominantly with the screen, the potentials associated with the three fingertips were enhanced in touchscreen users compared to nonusers. Within the touchscreen users, the cortical potentials from the thumb and index fingertips were directly proportional to the intensity of use quantified with built-in battery logs. Remarkably, the thumb tip was sensitive to the day-to-day fluctuations in phone use: the shorter the time elapsed from an episode of intense phone use, the larger the cortical potential associated with it. Our results suggest that repetitive movements on the smooth touchscreen reshaped sensory processing from the hand and that the thumb representation was updated daily depending on its use. We propose that cortical sensory processing in the contemporary brain is continuously shaped by the use of personal digital technology.


Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging.
We report an all-fiber-optic scanning, multimodal endomicroscope capable of simultaneous optical coherence tomography (OCT) and two-photon fluorescence (TPF) imaging. Both imaging modalities share the same miniature fiber-optic scanning endomicroscope, which consists of a double-clad fiber with a core operating in single mode at both the OCT (1310 nm) and two-photon excitation (1550 nm) wavelengths, a piezoelectric two-dimensional fiber-optic beam scanner, and a miniature aspherical compound lens suitable for simultaneous acquisition of en face OCT and TPF images. A fiber-optic wavelength division multiplexer was employed in the integrated platform to combine the low coherence OCT light source and the femtosecond two-photon excitation laser into the same optical path. Preliminary imaging results of cell cultures and mouse tissue ex vivo demonstrate the feasibility of simultaneous real-time OCT and TPF imaging in a scanning endomicroscopy setting for the first time.


Continuing education at the cutting edge: promoting transformative knowledge translation.
As the evidence-based practice movement gains momentum, continuing education practitioners increasingly confront the challenge of developing and conducting opportunities for achieving research uptake. Recent thinking invites new approaches to continuing education for health professionals, with due consideration of what knowledge merits uptake by practitioners, who should play what role in the knowledge transfer process, and what educational approach should be used. This article presents an innovative theory-based strategy that encompasses this new perspective. Through a facilitated experience of perspective transformation, clinicians are engaged in an on-the-job process of developing a deeply felt interest in research findings relevant to everyday practice, as well as ownership of that knowledge and its application. The strategy becomes a sustainable, integrated part of clinical practice, fitting naturally within its dynamic, unique environment, context, and climate and overcoming the barrier of time. Clinician experience of a top-down push toward prescribed practice change is avoided. With an expanded role encompassing facilitation of active learning partnerships for practice change, the continuing educator fosters a learning organization culture across the institution. The resultant role changes and leadership and accountability issues are elaborated.


A novel carbon coating technique for foil bolometers.
Naked foil bolometers can reflect a significant fraction of incident energy and therefore cannot be used for absolute measurements. This paper outlines a novel coating approach to address this problem by blackening the surface of gold foil bolometers using physical vapour deposition. An experimental bolometer was built containing four standard gold foil bolometers, of which two were coated with 100+ nm of carbon. All bolometers were collimated and observed the same relatively high temperature, ohmically heated plasma. Preliminary results showed 13%-15% more incident power was measured by the coated bolometers and this is expected to be much higher in future TCV detached divertor experiments.


Head and neck cancers in developing countries.
Head and neck cancers are the most common cancers in developing countries, especially in Southeast Asia. Head and neck cancers are more common in males compared to females. This is mainly attributed to tobacco, areca nut, alcohol, etc. Oral cancers are most common amongst all head and neck squamous cell cancers (HNSCC). HNSCC in the developing world differ from those in the Western world in terms of age, site of disease, etiology, and molecular biology. Poverty, illiteracy, advanced stage at presentation, lack of access to health care, and poor treatment infrastructure pose a major challenge in management of these cancers. The annual GDP (gross domestic product) spent on health care is very low in developing countries compared to the developed countries. Cancer treatment leads to a significant financial burden on the cancer patients and their families. Several health programs have been implemented to curb this rising burden of disease. The main aims of these health programs are to increase awareness among people regarding tobacco and to improve access to health care facilities, early diagnosis, treatment, and palliative care.


Inflammatory Response in Relation to COVID-19 and Other Prothrombotic Phenotypes.
The haemostatic system acts in concert with inflammation, so that after inflammatory response various mediators activate the haemostatic system through endothelial dysfunction, platelet activation and coagulation promoting thrombosis, which is termed thromboinflammation. In this process, the inflammasome acquires special relevance; its stimulation promotes innate and adaptive immune responses. Inflammasome activation plays an important physiopathological role in several disorders with inflammatory and thrombotic phenomena. The role of thromboinflammation has become relevant in the COVID-19 pandemic, in which a cytokine storm has been described as one of the responsible mechanisms.


Gordon McVie: his legacy as a blueprint for cancer advocates as we strive towards the 2030 global health and sustainable development goals.
Cancer prevention and control services worldwide must actively rebuild and contribute to improved health systems resilience alongside and beyond the COVID-19 (SARS-CoV-2 coronavirus disease) pandemic, especially in low- and middle-income countries. Cancer advocacy groups should respond to this unprecedented challenge as an opportunity to bolster community and patient involvement in research and clinical practice that is adjusted to local needs and circumstances. This short communication provides a synthesis of these critical challenges and, stemming from the pioneering activities of Gordon McVie on patient empowerment, urges policy makers and researchers to develop new implementation strategies that start from the social, economic and health consequences of the COVID-19 pandemic to overcome roadblocks in the access to cancer care. We propose that developing the domain of collaborative implementation research in national cancer control plans will be the key to consolidate patient-centred services with both an equity lens and a focus on integration of new technologies as all countries drive towards the 2030 goals of universal health coverage.


Salmonella typhimurium aroA- infection in gene-targeted immunodeficient mice: major role of CD4+ TCR-alpha beta cells and IFN-gamma in bacterial clearance independent of intracellular location.
Due to the dependency on aromatic precursors, the growth of Salmonella typhimurium aroA- is limited in immunocompetent mice. Here we show that H-21-A beta-/- mice (lacking MHC class II molecules and thus devoid of mature CD4+ TCR-alpha beta cells), TCR-beta-/- mice (devoid of TCR-alpha beta cells), and IFN-gamma R-/- mice (unresponsive to IFN-gamma) are highly susceptible to S. typhimurium aroA- infection compared with heterozygous controls. In contrast, beta 2m-deficient mice (lacking surface MHC class I and thus devoid of conventional CD8+ T cells) or TCR-delta-/- mice (devoid of TCR-gamma delta cells) were equally as resistant to S. typhimurium aroA- infection as their heterozygous littermates. These findings emphasize the vital role of CD4+ TCR-alpha beta cells and IFN-gamma in resistance against S. typhimurium aroA-. Sublethal inocula of S. typhimurium aroA- led to permanent infection in H-21-A beta-/- mice, suggesting that bacterial starvation is insufficient for sterile clearance in immunocompetent mice and that MHC class II-dependent immune mechanisms are required for pathogen eradication. The TCR-beta-/- mice suffered from salmonellosis more severely than the MHC class II-deficient mutants, suggesting an auxiliary function of CD8+ T cells. Recombinant S. typhimurium aroA-, secreting listeriolysin (Hly) of Listeria monocytogenes, are capable of escaping from the phagosome into the cytosol of the host cell. However, the course of infection of these recombinant S. typhimurium SL7207 Hlys and control strains did not differ in beta 2m-/- mutants. This finding argues against direct correlation of cytosolic location of S. typhimurium SL7207 Hlys with CD8+ T cell dependency of protection.


Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study.
Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) have profound immune defects and limited treatment options. Given the dramatic activity of lenalidomide in other B-cell malignancies and its pleotropic immunomodulatory effects, we conducted a phase II trial of this agent in CLL. Patients with relapsed or refractory B-cell CLL (B-CLL) were eligible if they required treatment as per the National Cancer Institute Working Group 1996 guidelines. Lenalidomide was administered orally at 25 mg on days 1 through 21 of a 28-day cycle. Response was assessed after each cycle. Patients were to continue treatment until disease progression, unacceptable toxicity, or complete remission. Rituximab was added to lenalidomide on disease progression. Forty-five patients were enrolled, with a median age of 64 years. Sixty-four percent of the patients had Rai stage III or IV disease, and 51% were refractory to fludarabine. The overall response rate was 47%, with 9% of the patients attaining a complete remission. Fatigue, thrombocytopenia, and neutropenia were the most common adverse effects noted in 83%, 78%, and 78% of the patients, respectively. Lenalidomide is clinically active in patients with relapsed or refractory B-CLL. These findings are encouraging and warrant further investigation of this agent in the treatment of this disorder.


Endoplasmic reticulum-plasma membrane contact sites integrate sterol and phospholipid regulation.
Tether proteins attach the endoplasmic reticulum (ER) to other cellular membranes, thereby creating contact sites that are proposed to form platforms for regulating lipid homeostasis and facilitating non-vesicular lipid exchange. Sterols are synthesized in the ER and transported by non-vesicular mechanisms to the plasma membrane (PM), where they represent almost half of all PM lipids and contribute critically to the barrier function of the PM. To determine whether contact sites are important for both sterol exchange between the ER and PM and intermembrane regulation of lipid metabolism, we generated Δ-super-tether (Δ-s-tether) yeast cells that lack six previously identified tethering proteins (yeast extended synatotagmin [E-Syt], vesicle-associated membrane protein [VAMP]-associated protein [VAP], and TMEM16-anoctamin homologues) as well as the presumptive tether Ice2. Despite the lack of ER-PM contacts in these cells, ER-PM sterol exchange is robust, indicating that the sterol transport machinery is either absent from or not uniquely located at contact sites. Unexpectedly, we found that the transport of exogenously supplied sterol to the ER occurs more slowly in Δ-s-tether cells than in wild-type (WT) cells. We pinpointed this defect to changes in sterol organization and transbilayer movement within the PM bilayer caused by phospholipid dysregulation, evinced by changes in the abundance and organization of PM lipids. Indeed, deletion of either OSH4, which encodes a sterol/phosphatidylinositol-4-phosphate (PI4P) exchange protein, or SAC1, which encodes a PI4P phosphatase, caused synthetic lethality in Δ-s-tether cells due to disruptions in redundant PI4P and phospholipid regulatory pathways. The growth defect of Δ-s-tether cells was rescued with an artificial "ER-PM staple," a tether assembled from unrelated non-yeast protein domains, indicating that endogenous tether proteins have nonspecific bridging functions. Finally, we discovered that sterols play a role in regulating ER-PM contact site formation. In sterol-depleted cells, levels of the yeast E-Syt tether Tcb3 were induced and ER-PM contact increased dramatically. These results support a model in which ER-PM contact sites provide a nexus for coordinating the complex interrelationship between sterols, sphingolipids, and phospholipids that maintain PM composition and integrity.


Realizing and Maintaining Capabilities: Late Life as a Social Project.
One central and unfortunately unavoidable characteristic of the aging process is its association with chronic physiological deterioration. Frailty, cognitive impairment, and physical conditions such as cardiovascular disease and vision and hearing loss are more frequent in this phase of life, and these conditions translate into an increasing need for care and support of multiple kinds. In traditional bioethical scholarship, these distinctive features of aging have been examined predominantly through a health-focused lens. My main contention in this essay, however, is that viewing aging within bioethics as primarily a health problem, to be addressed through frameworks for decision-making or for resource allocation, is inadequate. My aim is to consider how the health conditions associated with aging affect older people's lives in a much more expansive way than has typically been acknowledged. Just as importantly, I intend to show how shifting our bioethical imagination in this way raises different and challenging questions about what a good life in late life consists in and about what is owed to older people, in their personal and social lives, as a matter of justice.


12/15-Lipoxygenase-derived lipid metabolites induce retinal endothelial cell barrier dysfunction: contribution of NADPH oxidase.
The purpose of the current study was to evaluate the effect of 12/15-lipoxygenase (12/15-LOX) metabolites on retinal endothelial cell (REC) barrier function. FITC-dextran flux across the REC monolayers and electrical cell-substrate impedance sensing (ECIS) were used to evaluate the effect of 12- and 15-hydroxyeicosatetreanoic acids (HETE) on REC permeability and transcellular electrical resistance (TER). Effect of 12- or 15-HETE on the levels of zonula occludens protein 1 (ZO-1), reactive oxygen species (ROS), NOX2, pVEGF-R2 and pSHP1 was examined in the presence or absence of inhibitors of NADPH oxidase. In vivo studies were performed using Ins2(Akita) mice treated with or without the 12/15-LOX inhibitor baicalein. Levels of HETE and inflammatory mediators were examined by LC/MS and Multiplex Immunoassay respectively. ROS generation and NOX2 expression were also measured in mice retinas. 12- and 15- HETE significantly increased permeability and reduced TER and ZO-1 expression in REC. VEGF-R2 inhibitor reduced the permeability effect of 12-HETE. Treatment of REC with HETE also increased ROS generation and expression of NOX2 and pVEGF-R2 and decreased pSHP1 expression. Treatment of diabetic mice with baicalein significantly decreased retinal HETE, ICAM-1, VCAM-1, IL-6, ROS generation, and NOX2 expression. Baicalein also reduced pVEGF-R2 while restored pSHP1 levels in diabetic retina. Our findings suggest that 12/15-LOX contributes to vascular hyperpermeability during DR via NADPH oxidase dependent mechanism which involves suppression of protein tyrosine phosphatase and activation of VEGF-R2 signal pathway.


Evolution of the genus Mimivirus based on translation protein homology and its implication in the tree of life.
The natural history of mimiviruses (i.e., viruses that are members of the Mimivirus genus) is a challenge for modern biology. A new domain of life to include these organisms has been proposed from analysis of gene conservation. We analyzed the evolutionary relationship of proteins involved in the translation system, and our data show that mimiviruses are a sister group of Eukarya. New data about the origins of Eukarya, in which Eukarya appears as a branch derived from the Archaea domain, were discussed, and we suggest that the mimiviruses emerged from the initial population that gave origin to Eukarya and that, in this way are not part of a new domain of life.


Effects of mountain pine beetle on fuels and expected fire behavior in lodgepole pine forests, Colorado, USA.
In Colorado and southern Wyoming, mountain pine beetle (MPB) has affected over 1.6 million ha of predominantly lodgepole pine forests, raising concerns about effects of MPB-caused mortality on subsequent wildfire risk and behavior. Using empirical data we modeled potential fire behavior across a gradient of wind speeds and moisture scenarios in Green stands compared three stages since MPB attack (Red [1-3 yrs], Grey [4-10 yrs], and Old-MPB [∼30 yrs]). MPB killed 50% of the trees and 70% of the basal area in Red and Grey stages. Across moisture scenarios, canopy fuel moisture was one-third lower in Red and Grey stages compared to the Green stage, making active crown fire possible at lower wind speeds and less extreme moisture conditions. More-open canopies and high loads of large surface fuels due to treefall in Grey and Old-MPB stages significantly increased surface fireline intensities, facilitating active crown fire at lower wind speeds (>30-55 km/hr) across all moisture scenarios. Not accounting for low foliar moistures in Red and Grey stages, and large surface fuels in Grey and Old-MPB stages, underestimates the occurrence of active crown fire. Under extreme burning conditions, minimum wind speeds for active crown fire were 25-35 km/hr lower for Red, Grey and Old-MPB stands compared to Green. However, if transition to crown fire occurs (outside the stand, or within the stand via ladder fuels or wind gusts >65 km/hr), active crown fire would be sustained at similar wind speeds, suggesting observed fire behavior may not be qualitatively different among MPB stages under extreme burning conditions. Overall, the risk (probability) of active crown fire appears elevated in MPB-affected stands, but the predominant fire hazard (crown fire) is similar across MPB stages and is characteristic of lodgepole pine forests where extremely dry, gusty weather conditions are key factors in determining fire behavior.


Using the electronic medical record to identify community-acquired pneumonia: toward a replicable automated strategy.
Timely information about disease severity can be central to the detection and management of outbreaks of acute respiratory infections (ARI), including influenza. We asked if two resources: 1) free text, and 2) structured data from an electronic medical record (EMR) could complement each other to identify patients with pneumonia, an ARI severity landmark. A manual EMR review of 2747 outpatient ARI visits with associated chest imaging identified x-ray reports that could support the diagnosis of pneumonia (kappa score = 0.88 (95% CI 0.82∶0.93)), along with attendant cases with Possible Pneumonia (adds either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain) or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the provider). The x-ray reports served as a reference to develop a text classifier using machine-learning software that did not require custom coding. To identify pneumonia cases, the classifier was combined with EMR-based structured data and with text analyses aimed at ARI symptoms in clinical notes. 370 reference cases with Possible Pneumonia and 250 with Pneumonia-in-Plan were identified. The x-ray report text classifier increased the positive predictive value of otherwise identical EMR-based case-detection algorithms by 20-70%, while retaining sensitivities of 58-75%. These performance gains were independent of the case definitions and of whether patients were admitted to the hospital or sent home. Text analyses seeking ARI symptoms in clinical notes did not add further value. Specialized software development is not required for automated text analyses to help identify pneumonia patients. These results begin to map an efficient, replicable strategy through which EMR data can be used to stratify ARI severity.


Comparison of the nonstructural protein, NS3, of tick-borne and insect-borne orbiviruses.
The complete nucleotide sequence of the smallest RNA segment (segment 10) of Broadhaven (BRD) virus, a tick-borne orbivirus, was determined from a full-length cDNA clone. The genome segment is 702 nucleotides in length and has a coding capacity for two proteins of either 205 or 199 amino acids, having net charges of +16.5 and +17.5, respectively, at neutral pH. Comparison of the sequence of RNA segment 10 of BRD, bluetongue, African horse sickness, and Palyam viruses revealed amino acid homology of 20 to 30% between the four orbiviruses, with one conserved region of 40 to 50% homology which, in segment 10 of BRD virus, is found between residues 26 and 71.


Spontaneous arousals in supine infants while swaddled and unswaddled during rapid eye movement and quiet sleep.
Supine sleep is recommended for infants to decrease the risk of sudden infant death syndrome, but many parents report that their infants seem uncomfortable supine. Many cultures swaddle infants for sleep in the supine position. Swaddled infants are said to "sleep better"; presumably they sleep longer or with fewer arousals. However, there have been no studies of the effect of swaddling on spontaneous arousals during sleep. Arousal is initiated in brainstem centers and manifests as a sequence of reflexes: from sighs to startles and then to thrashing movements. Such "brainstem arousals" may progress to full arousal, but most do not. Twenty-six healthy infants, aged 80 +/- 7 days, were studied during normal nap times. Swaddled (cotton spandex swaddle) and unswaddled trials were alternated for each infant. Sleep state (rapid eye movement [REM] or quiet sleep [QS]) was determined by behavioral criteria (breathing pattern, eye movements) and electroencephalogram/electrooculogram (10 infants). Respitrace, submental and biceps electromyogram, and video recording were used to detect startles and sighs (augmented breaths). Full arousals were classified by eye opening and/or crying. Frequencies of sighs, startles, and full arousals per hour were calculated. Progression of events was calculated as percentages in each sleep state, as was duration of sleep state. Swaddling decreased startles in QS and REM, full arousal in QS, and progression of startle to arousal in QS. It resulted in shorter arousal duration during REM sleep and more REM sleep. Swaddling has a significant inhibitory effect on progression of arousals from brainstem to full arousals involving the cortex in QS. Swaddling decreases spontaneous arousals in QS and increases the duration of REM sleep, perhaps by helping infants return to sleep spontaneously, which may limit parental intervention. For these reasons, a safe form of swaddling that allows hip flexion/abduction and chest wall excursion may help parents keep their infants in the supine sleep position and thereby prevent the sudden infant death syndrome risks associated with the prone sleep position.