Quantitative relationship between cholesterol distribution and ordering of lipids in asymmetric lipid bilayers.
The plasma membrane of eukaryotic cells is known to be compositionally asymmetric. Certain phospholipids, such as sphingomyelin and phosphatidylcholine species, are predominantly localized in the outer leaflet, while phosphatidylethanolamine and phosphatidylserine species primarily reside in the inner leaflet. While phospholipid asymmetry between the membrane leaflets is well established, there is no consensus about cholesterol distribution between the two leaflets. We have performed a systematic study, via molecular simulations, of how the spatial distribution of cholesterol molecules in different "asymmetric" lipid bilayers are affected by the lipids' backbone, head-type, unsaturation, and chain-length by considering an asymmetric bilayer mimicking the plasma membrane lipids of red blood cells, as well as seventeen other asymmetric bilayers comprising of different lipid types. Our results reveal that the distribution of cholesterol in the leaflets is solely a function of the extent of ordering of the lipids within the leaflets. The ratio of the amount of cholesterol matches the ratio of lipid order in the two leaflets, thus providing a quantitative relationship between the two. These results are understood by the observation that asymmetric bilayers with equimolar amount of lipids in the two leaflets develop tensile and compressive stresses due to differences in the extent of lipid order. These stresses are alleviated by the transfer of cholesterol from the leaflet in compressive stress to the one in tensile stress. These findings are important in understanding the biology of the cell membrane, especially with regard to the composition of the membrane leaflets.


Safe to walk? Neighborhood safety and physical activity among public housing residents.
Despite its health benefits, physical inactivity is pervasive, particularly among those living in lower-income urban communities. In such settings, neighborhood safety may impact willingness to be regularly physically active. We examined the association of perceived neighborhood safety with pedometer-determined physical activity and physical activity self-efficacy. Participants were 1,180 predominantly racial/ethnic minority adults recruited from 12 urban low-income housing complexes in metropolitan Boston. Participants completed a 5-d pedometer data-collection protocol and self-reported their perceptions of neighborhood safety and self-efficacy (i.e., confidence in the ability to be physically active). Gender-stratified bivariate and multivariable random effects models were estimated to account for within-site clustering. Most participants reported feeling safe during the day, while just over one-third (36%) felt safe at night. We found no association between daytime safety reports and physical activity among both men and women. There was also no association between night-time safety reports and physical activity among men (p = 0.23) but women who reported feeling unsafe (versus safe) at night showed significantly fewer steps per day (4,302 versus 5,178, p = 0.01). Perceiving one's neighborhood as unsafe during the day was associated with significantly lower odds of having high physical activity self-efficacy among both men (OR 0.40, p = 0.01) and women (OR 0.68, p = 0.02). Residing in a neighborhood that is perceived to be unsafe at night is a barrier to regular physical activity among individuals, especially women, living in urban low-income housing. Feeling unsafe may also diminish confidence in the ability to be more physically active. Both of these factors may limit the effectiveness of physical activity promotion strategies delivered in similar settings.


Inherited microbial symbionts increase herbivore abundances and alter arthropod diversity on a native grass.
Some microbial symbionts of plants are maternally inherited and thus functionally increase genetic and phenotypic variation within plant populations. This variation, coupled with that of the host plant and environment, may alter abundances, diversity, and trophic structure of associated plant and animal communities. Fungal endophytes in the genus Neotyphodium are vertically transmitted, asexual microbial symbionts of grasses that remain asymptomatic and rely upon their hosts for resources and transmission via seeds, often providing benefits to their hosts, including protection against herbivores. Endophyte infections may influence associated arthropod communities in agronomic grasses, but the long-term effects of endophytes and variation in host genotype and resource availability on arthropod communities in native grass populations are unknown. We conducted a long-term field experiment with four maternal genotypes of an infected (E+) native grass (Festuca arizonica) from whence the endophyte was experimentally removed (E-) and water availability was controlled, to test the effects of infection, plant genotype, and resources on abundances, biomass, diversity (richness and evenness), and trophic structure of the arthropod community. Generally, E+ grasses harbored more arthropods, including more herbivores, predators, and detritivores, suggesting that the effects of endophytes cascaded upward through trophic levels in terms of abundances, at least in early ontogeny of the host. That E+ plants harbored more herbivorous insects than E- plants suggests that infection does not increase but instead decreases resistance to herbivores, contrary to prevailing concepts of endophytes as defensive mutualists. Infection did not alter overall species richness of the arthropod community or richness of herbivores but reduced natural enemy richness, especially that of parasites, and increased richness of detritivores. Reduced richness and shifts in evenness of natural enemies on E+ plants suggest that endophytes may disproportionately affect diversity at higher trophic levels and may partially explain increases in abundances of herbivorous insects on E+ plants. Biomass of predators, detritivores, and omnivores increased on plants with supplemented water, and arthropod and herbivore biomass varied by plant genotype. Symbiont-mediated phenotypic variation interacts with variation from plant genotype and environmental factors to alter arthropod abundances and diversity, and these effects shift with ontogeny of the host.


Feasibility and safety of transcaval transcatheter aortic valve implantation: a multicentre European registry.
A transfemoral transarterial approach is considered the preferable access route for transcatheter aortic valve implantation (TAVI), followed by a transaxillary/subclavian TAVI approach. However, these approaches may not be an option in all patients. This study aimed to report the initial European experience with transfemoral transcaval TAVI. Data on 50 patients treated by transcaval TAVI in five European centres were collected and analysed according to the Valve Academic Research Consortium (VARC)-2 definitions. The study population had a mean age of 78.7±8.0 years and a high surgical risk profile (median STS risk score 6.1%, interquartile range 3.0-11.2%). Transcaval access was successful in 49 out of 50 patients and device success was obtained in 94% of cases. Closure of the caval-aortic puncture site with a nitinol cardiac occluder was successful in all cases without need for emergent surgery. One patient received additional sealing of the aortic puncture site with a covered stent one day post TAVI due to a gradual haemoglobin drop of 3 g/dL. VARC-2-defined life-threatening bleeding and major vascular complications possibly related to transcaval access were 4% and 10%, respectively. There were no bleeding or vascular complications after discharge. At 30 days, the clinical efficacy endpoint was reached in 88% of patients. Transfemoral transcaval access proved to be a feasible and safe TAVI approach for high-risk patients with severe aortic stenosis not suitable for transfemoral or transaxillary/subclavian transarterial access.


Synergistic antimicrobial action and effect of active chitosan-gelatin biopolymeric films containing Thymus vulgaris, Ocimum basilicum and Origanum majorana essential oils against Escherichia coli and Staphylococcus aureus.
To replace synthetic preservatives and expand green consumption, several essential oils have been tested in foods and food packaging due to their antimicrobial properties. This study aimed to analyze the synergistic antimicrobial action of a chitosan-gelatin based active biopolymers with the addition of essential oils (EOs). The antimicrobial agents were tested against foodborne microorganisms Staphylococcus aureus and Escherichia coli strains. The antibacterial activity of Thymus vulgaris, Ocimum basilicum, Origanum majorana, and the synergistic interactions among them were assessed according to the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the microdilution method. Chitosan-gelatin based active biopolymers were developed, and 23% (w/w) of each essential oil and combined oils were added. The antimicrobial effect of active films was measured using the disk diffusion method. Active films with the addition of essential oils have potential applications as active packaging agents, especially those that demonstrated inhibition zones. Combined EOs can be used to enhance the antimicrobial activity, ensuring reduced doses used in active packaging and decreasing the association with adverse sensory characteristics.


Increased police patrols for preventing alcohol-impaired driving.
Road traffic injuries cause 1.2 million deaths worldwide each year. Alcohol consumption increases the risk of traffic crashes, especially fatal crashes. Increased police patrols aim to increase both the perceived and actual likelihood of being caught driving while alcohol-impaired, potentially reducing alcohol-related driving, crashes and injuries. To assess the effects on injuries and crashes of increased police patrols that target alcohol-impaired driving. We searched the Cochrane Injuries Group Specialised Register (5/2006), CENTRAL (The Cochrane Library 2006, Issue 2), MEDLINE (1966 to 5/2006), TRANSPORT (1968 to 5/2006), C2-SPECTR (2/2005), NCJRS (1/1951 to 5/2006), PsycINFO (1872 to 5/2006), Social Science Citation Index (1974 to 5/2006), SIGLE (1980 to 2/2006), Science Citation Index Expanded (1970 to 5/2006), Dissertation Abstracts (1870 to 5/2006), NTIS (1964 to 12/2004), conference proceedings, and reference lists. We contacted authors of eligible studies. Randomized controlled trials, controlled trials, controlled before and after studies, interrupted time series (ITS) studies, and controlled ITS studies evaluating increased police patrols, either alone or combined with other interventions, targeting alcohol-impaired motor vehicle drivers. Two investigators independently screened citations, extracted data, and assessed quality criteria. We compared intervention and no-intervention geographical areas or time periods. We re-analyzed study data as required. Results are presented narratively. The 32 eligible studies included one randomized controlled trial, eight controlled before-after studies, 14 controlled ITS studies, six ITS studies, and three studies with both ITS and controlled before-after analyses. Most interventions targeted only alcohol-impaired driving (69%) and included additional interventions such as media campaigns or special training for police officers (91%). Only two studies reported sufficient information to assess study quality completely. Two-thirds of studies were scored 'not adequate' on at least one feature. Five of six studies evaluating traffic fatalities reported reductions with the intervention, but differences were statistically significant in only one study. Effects of intervention on traffic injuries were inconsistent in the six studies evaluating this outcome, and no results were statistically significant. All four controlled studies evaluating fatal crashes reported reductions with the intervention, which were statistically significant in one study. All 12 controlled studies assessing injury crashes reported greater reductions with the intervention, though effects were minimal or not significant in several studies. ITS studies showed less consistent effects on fatal crashes (three studies) and injury crashes (four studies), and effect estimates were typically imprecise. Thirteen of 20 studies showed reductions in total crashes and about two-thirds of these were statistically significant. Studies examining increased police patrol programs were generally consistent in reporting beneficial effects on traffic crashes and fatalities, but study quality and reporting were often poor. Methodological limitations included inadequate sample size, dissimilar baseline measures, contamination, and inadequate data analysis. Thus existing evidence, although supportive, does not firmly establish whether increased police patrols, implemented with or without other intervention elements, reduce the adverse consequences of alcohol-impaired driving.


Animal-assisted interventions in internal and rehabilitation medicine: a review of the recent literature.
While conventional wisdom has always affirmed the value of animals in promoting human well-being, only recently has their therapeutic role in medicine become the focus of dedicated research. Therapeutic modalities that use animals as a tool for improving the physical, emotional, cognitive and/or social functioning of humans are called animal-assisted interventions (AAI), and are classified into: animal-assisted activities (AAA); animal-assisted therapy (AAT); and service animal programs (SAP). The aim of this review is to analyze the papers published between 2001 and 2010 in the most influential medical journals dealing with AAI, and discuss their findings in the light of what may be of interest for internal medicine and rehabilitation. A total of 35 articles met the strict inclusion criteria for this review: 18 papers dealing with AAA, 8 with AAT, and 9 with SAP. The therapeutic outcomes associated with AAA are: enhancement of socialization; reduction of stress, anxiety and loneliness; improvement in mood and general well-being; and development of leisure/recreation skills. Regarding AAT, horses are often used as a complementary strategy to facilitate the normalization of muscle tone and improve motor skills in children with cerebral palsy and persons with lower limb spasticity. Finally, most SAP utilize dogs, that assist people with various disabilities in performing everyday activities, thus reducing their dependence on other persons. Further studies are needed to better define the fields and programs for the therapeutic use of animals and to increase their utilization in medicine, as a promising, complementary and natural means to improve both functional autonomy and quality of life.


Myocardial injury after noncardiac surgery.
Recent investigations have substantially improved our understanding of myocardial injury after noncardiac surgery (MINS). MINS is defined as a prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. MINS occurs in 8% of adults undergoing major noncardiac surgery and is diagnosed with an elevated postoperative troponin measurement. MINS is associated with significant morbidity, and approximately 10% of patients experiencing MINS will die within 30 days. There is a dose-graded response in mortality and time to death with increasing levels of postoperative troponin elevations. Most patients (>80%) suffering from MINS will not experience an ischemic symptom. Without troponin monitoring, the majority of MINS events would go undetected. To avoid missing these prognostically relevant events, guidelines now recommend perioperative troponin monitoring in high-risk patients having noncardiac surgery. In patients who suffer MINS, risk-adjusted observational data suggest that aspirin and a statin can reduce the risk of 30-day mortality. Among adults, MINS is the most common cardiovascular complication that occurs after noncardiac surgery. Given that worldwide 200 million adult patients undergo major noncardiac surgery each year, at least 8 million of these patients will suffer MINS making this a substantial public health problem.


Metformin Monotherapy Downregulates Diabetes-Associated Inflammatory Status and Impacts on Mortality.
Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNFα, sTNFRI, and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality.


A twofold excess mortality among black compared with white IDDM patients in Allegheny county, Pennsylvania. Pittsburgh DERI Mortality Study Group.
To examine the long-term mortality experience of blacks who develop IDDM in childhood. The 11-25-year mortality status of individuals with IDDM who participated in the Diabetes Epidemiology Research International (DERI) Mortality Study was verified as of 1 January 1990 for 1,008 (94%) of the 1,076 individuals in the study. Life-table analysis was performed, and race-specific rates were determined for the final sample. Among black patients, 14.9% died compared with 6.6% of the white patients after a maximum of 25 years of follow-up. African-Americans experienced an age-adjusted mortality rate that was over twice that of whites for the entire period (9.4 vs. 3.8 per 1,000 person-years, respectively; P < 0.05) and at each 5-year interval of follow-up. Among blacks, the mortality rate for females (15.9/1,000 person-years) was 8.4 times (P < 0.05) that of males (1.9/1,000 person-years). In contrast, this sex difference was not seen among whites. Acute complications of diabetes accounted for 40% of the mortality in the black patients, while only 23% of the white patients died from acute causes. The data suggest that some of the excess mortality in black IDDM patients may be preventable.


Method for first-order design of a transfer optics system to throughput match a Fourier transform spectrometer to a sample cell without use of a field lens at the cell input.
The realization that the usual optical geometry of an absorption cell is the frustrum of a cone and that a requirement can be put on any transfer optics system that eliminates the need for a field lens at the cell input leads to a powerful method of first-order optical system design through (1) determination of a required ray transfer matrix, unique except for sign, which requires a single concave spherical mirror (or lens) to implement and (2) getting additional degrees of freedom to make the system more practical at the expense of additional spherical mirrors (or lenses). Two successful applications of the method are described.


Imaging in the Diagnosis and Monitoring of Children with Idiopathic Scoliosis.
The paper reviews the current imaging methods in the diagnosis and monitoring of patients with adolescent idiopathic scoliosis. Radiography is generally used in the initial diagnosis of the condition. Postero-anterior erect full spine radiograph is generally prescribed, and is supplemented by lateral full spine radiograph when indicated. To reduce the radiation hazard, only the area of interest should be exposed, and follow-up radiographs should be taken with as few projections as possible. When available, EOS® stereoradiography should be used. The radiation of the microdose protocol is 45 times less than that of the conventional radiography. Surface topography offers another approach to monitoring changes of curvatures in AIS patients. Recently, 3D ultrasound has been found to be able to measure the Cobb angle accurately. Yet, it is still in the early developmental stages. The inherent intrinsic and external limitations of the imaging system need to be resolved before it can be widely used clinically. For AIS patients with atypical presentation, computed tomography (CT) and/or magnetic resonance imaging (MRI) may be required to assess for any underlying pathology. As CT is associated with a high radiation dose, it is playing a diminishing role in the management of scoliosis, and is replaced by MRI, which is also used for pre-operative planning of scoliosis. The different imaging methods have their limitations. The EOS® stereoradiography is expensive and is not commonly available. The surface topography does not enable measurement of Cobb angle, particularly when the patient is in-brace. The 3D ultrasound scanning has inherent intrinsic technical limitation and cannot be used in all subjects. Radiography, however, enables diagnosis and monitoring of the adolescent idiopathic scoliosis (AIS). It is thus the gold standard in the evaluation and management of scoliosis curves.


Role of tumor-derived fibroblasts in the growth of primary cultures of human breast-cancer cells: effects of epidermal growth factor and the somatostatin analogue octreotide.
In the present study we have investigated the role of human breast-cancer-derived fibroblasts in the proliferation of primary cultures of epithelial cells derived from the same tumor. For this purpose, a co-culture system, using Transwell tissue-culture inserts with microporous membranes was employed. Fibroblasts and epithelial cells were enriched according to differences in their density on Percoll density gradients. The co-culture system was first established using MCF-7 breast cancer cells and a human fibroblast line (HF cells). Insulin, 17 beta-estradiol, EGF and HF cells all significantly stimulated the growth of MCF-7 breast cancer cells. The stimulatory effects of insulin, E2 and EGF were additive to the stimulatory effect of HF cells. These data suggest that (unique) factor(s), other than the above-mentioned growth-promoting compounds, are responsible for the growth-promoting effects of fibroblasts. In half of the human breast cancers investigated, tumor-derived fibroblasts stimulated tumor-derived epithelial cell proliferation. EGF significantly stimulated epithelial cell proliferation in 4 out of 6 cultures. The stimulatory effects of fibroblasts and EGF were additive or synergistic, and were observed in the additional presence of FCS, again suggesting production of unique factor(s) by the fibroblasts. In one culture the fibroblasts significantly inhibited epithelial tumor-cell proliferation. Conversely, the epithelial cells significantly stimulated proliferation of fibroblasts in 3 out of 3 cultures. The somatostatin analogue octreotide significantly inhibited epithelial cell proliferation by 46% in one tumor-cell culture in the absence, but not in the presence, of fibroblasts. In one culture, octreotide significantly inhibited the proliferation of fibroblasts co-cultured with epithelial cells.


The flux-flux correlation function for anharmonic barriers.
The flux-flux correlation function formalism is a standard and widely used approach for the computation of reaction rates. In this paper we introduce a method to compute the classical and quantum flux-flux correlation functions for anharmonic barriers essentially analytically through the use of the classical and quantum normal forms. In the quantum case we show that for a general f degree-of-freedom system having an index one saddle the quantum normal form reduces the computation of the flux-flux correlation function to that of an effective one-dimensional anharmonic barrier. The example of the computation of the quantum flux-flux correlation function for a fourth order anharmonic barrier is worked out in detail, and we present an analytical expression for the quantum mechanical microcanonical flux-flux correlation function. We then give a discussion of the short-time and harmonic limits.


The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review.
Granulocyte colony-stimulating factors (G-CSF) are commonly used in clinical practice to prevent febrile neutropenia (FN). US and EU prescribing information and treatment guidelines from the NCCN, ASCO, and EORTC specify that pegfilgrastim, a long-acting (LA) G-CSF, should be administered at least 24 h after myelosuppressive chemotherapy. Nevertheless, many patients receive LA G-CSFs on the same day as chemotherapy. This systematic literature review evaluated the relative merits of same-day versus next-day dosing of LA G-CSFs. A broad Ovid MEDLINE® and Embase® literature search was conducted that examined all publications indexed before May 9, 2016 that compared same-day versus next-day LA G-CSF administration. A congress abstract literature search included congresses from January 1, 2011 to April 6, 2016. The parameters for this review were prospectively delineated in a research protocol and adhered to the PRISMA Guidelines. The first part of the systematic literature search identified 1736 publications. After elimination of duplicates, title/abstract screening was conducted on 1440 records, and full text review was conducted on 449 publications. Eleven publications met all criteria and are included in this systematic review; of these, four included data from randomized or single arm prospective studies, and seven were retrospective studies. In most studies included in this review and across a variety of tumor types, administration of pegfilgrastim at least 24 h after myelosuppressive chemotherapy resulted in improved patient outcomes. Data from multiple publications support administration of pegfilgrastim at least 1 day after chemotherapy.


Correlation of the expression of CD32 and CD180 receptors on CLL cells and MEC1 cell line.
Chronic Lymphocytic Leukemia (CLL) presents with clonal expansion and accumulation of CD5+CD19+CD23+ cells in peripheral lymphoid organs and tissues and in bone marrow. CLL is supposedly driven by exogenous and/or endogenous (auto)antigen(s) and there is increasing evidence that CLL cells receive microenvironmental signals which support their growth, survival and expansion in vivo. We have previously shown that powerful signals are received by CLL cells through CD180 orphan toll-like receptor. Additional accessory signals could be generated through FcγRII (CD32), since both are expressed on CLL cells as well as on control B cells. Here we studied correlation of the expression of CD32 and CD180 on CLL cells as well as on MEC1 cell line. Peripheral blood mononuclear cells (PBMC) from CLL patients and age-matched healthy volunteers were separated, stained with appropriate antibodies to CD19, CD32 and CD180 and analysed by flow cytometry. CD32 and CD180 expression on MEC1 cells was studied at different time-points. The data was statistically analysed using the Mann-Whitney non-parametrical test. Our data indicates that expression of CD32 is significantly increased on CLL cells compared to control B cells as well as in long-term MEC1 cell culture. In contrast, CD180 expression on MEC1 cells significantly decreased throughout 0-96h of MEC1 cell culture. We have recently shown that CD180 ligation can redirect sIgM-mediated signaling from pro-survival to pro-apoptotic. This data indicates that a drop in the expression of CD180 on cycling CLL cells might lead to a weakening of this effect and enhance further survival and expansion of CLL cells in proliferative centres of lymphoid tissues. Since MEC1 cells are derived from a CLL patient with mutated IGVH genes (M-CLL) negative correlation between CD180 and CD32 expression on cycling MEC1 cells could be limited to M-CLL.


Intracellular Na+ activates a K+ channel in mammalian cardiac cells.
In a wide variety of cells, various intracellular agents, such as Ca2+, ATP and cyclic nucleotides, regulate ionic conductances of the membrane. In cardiac cells, the intracellular Na+ concentration [( Na+]i) frequently increases when a disturbance occurs in the electrogenic Na-K pump activity or the Na-Ca exchange mechanism. We have investigated a possible role of [Na+]i in controlling ion channels by using a patch-clamp method, and have found a K+ channel that is gated by [Na+]i greater than 20 mM, but not by the intracellular Ca2+ concentration (approximately 10(-4) M). We report here that the channel has a unitary conductance of 207 +/- 19 pS (n = 16) with K+ concentrations of 150 mM outside and 49 mM inside, and shows no detectable voltage-dependent kinetics. The Na+-activated K+ channel represents a novel class of ionic channel.


Impact of metabolic syndrome on cognition and brain: a selected review of the literature.
Metabolic syndrome (MetS), a clustering of risk factors for type 2 diabetes mellitus and cardiovascular disease, has been associated with cognitive dysfunction and brain abnormalities. This review describes the literature on the impact of MetS on brain and cognition and suggests directions for future research. A literature search for reports of MetS and cognition and brain imaging was conducted for both nonelderly adults and adolescents. No studies were found describing MetS and brain or cognition among adolescents; therefore, we also included studies investigating individual components of MetS in this age group. Most studies found associations between MetS and cognitive dysfunction. Multiple cognitive domains were affected by MetS in adults. In adolescents, the majority of findings were in executive functioning. Brain imaging literature in adults implicated MetS in ischemic stroke, white matter alterations, and altered brain metabolism. For adolescents, individual MetS factors were linked to volume losses in the hippocampus and frontal lobes. MetS negatively impacts cognitive performance and brain structure. Potential explanatory models include impaired vascular reactivity, neuroinflammation, oxidative stress, and abnormal brain lipid metabolism. We posit that insulin resistance-associated impairment in cerebrovascular reactivity is an important mechanism underlying brain deficits seen in MetS.


The Cognitive Psychopathology of Internet Gaming Disorder in Adolescence.
Adolescents are known to be an at-risk population for developing Internet gaming disorder (IGD). A recent clinical model has proposed that adolescents with IGD may endorse a unique set of maladaptive beliefs that underlie persistent and excessive involvement in Internet gaming activities. These include (a) beliefs about game reward value and tangibility, (b) maladaptive and inflexible rules about gaming behaviour, (c) over-reliance on gaming to meet self-esteem needs, and (d) gaming as a method of gaining social acceptance. A sample of 824 adolescents (402 male and 422 female) were recruited from multiple secondary schools and administered a survey that included measures of IGD symptomatology, problematic Internet gaming cognition, and psychological distress. The results showed that adolescents with IGD report significantly more maladaptive gaming beliefs than adolescents without IGD, including those who play Internet games for more than 30 h per week. The size of observed effects were large. The strong association between gaming cognitions and IGD symptoms still held after controlling for measures of gaming activity and psychological distress. These findings indicate that adolescents with IGD have distinct problematic thoughts about gaming, and highlight the importance of addressing these cognitions in therapeutic interventions for the disorder.


Tolerance for 8-oxoguanine but not thymine glycol in alignment-based gap filling of partially complementary double-strand break ends by DNA polymerase lambda in human nuclear extracts.
Ionizing radiation induces various clustered DNA lesions, including double-strand breaks (DSBs) accompanied by nearby oxidative base damage. Previous work showed that, in HeLa nuclear extracts, DSBs with partially complementary 3' overhangs and a one-base gap in each strand are accurately rejoined, with the gaps being filled by DNA polymerase lambda. To determine the possible effect of oxidative base damage on this process, plasmid substrates were constructed containing overhangs with 8-oxoguanine or thymine glycol in base-pairing positions of 3-base (-ACG or -GTA) 3' overhangs. In this context, 8-oxoguanine was well tolerated by the end-joining machinery when present at one end of the break, but not when present at both ends. Thymine glycol was less well tolerated than 8-oxoguanine, reducing gap filling and accurate rejoining by at least 10-fold. The results suggest that complex DSBs can be accurately rejoined despite the presence of accompanying base damage, but that nonplanar bases constitute a major barrier to this process and promote error-prone joining. A chimeric DNA polymerase, in which the catalytic domain of polymerase lambda was replaced with that of polymerase beta, could not substitute for polymerase lambda in these assays, suggesting that this domain is specifically adapted for gap filling on aligned DSB ends.


Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting.
An elevated preoperative white blood cell count has been associated with a worse outcome after coronary artery bypass grafting (CABG). Leukocyte subtypes, and particularly the neutrophil-lymphocyte (N/L) ratio, may however, convey superior prognostic information. We hypothesized that the N/L ratio would predict the outcome of patients undergoing surgical revascularization. Baseline clinical details were obtained prospectively in 1938 patients undergoing CABG. The differential leukocyte was measured before surgery, and patients were followed-up 3.6 years later. The primary end point was all-cause mortality. The preoperative N/L ratio was a powerful univariable predictor of mortality (hazard ratio [HR] 1.13 per unit, P < .001). In a backward conditional model, including all study variables, it remained a strong predictor (HR 1.09 per unit, P = .004). In a further model, including the European system for cardiac operative risk evaluation, the N/L ratio remained an independent predictor (HR 1.08 per unit, P = .008). Likewise, it was an independent predictor of cardiovascular mortality and predicted death in the subgroup of patients with a normal white blood cell count. This excess hazard was concentrated in patients with an N/L ratio in the upper quartile (>3.36). An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.


Isolation of sulfate-reducing bacteria from human thoracoabdominal pus.
To evaluate the prevalence of sulfate-reducing bacteria in septic processes, we searched for these bacteria by culture in 100 consecutive abdominal and pleural pus specimens. Twelve isolates were obtained from abdominal samples and were identified by a multiplex PCR as Desulfovibrio piger (formerly Desulfomonas pigra) (seven strains), Desulfovibrio fairfieldensis (four strains), and Desulfovibrio desulfuricans (one strain).


COL-3, a chemically modified tetracycline, inhibits lipopolysaccharide-induced microglia activation and cytokine expression in the brain.
Microglia activation results in release of proinflammatory molecules including cytokines, which contribute to neuronal damage in the central nervous system (CNS) if not controlled. Tetracycline antibiotics such as minocycline inhibit microglial activation and cytokine expression during CNS inflammation. In the present study we found that administration of chemically modified tetracycline-3 (COL-3), inhibits lipopolysaccharide (LPS)-induced microglial and p38 MAPK activation, as well as the increase in TNF-α, but not IL-1β expression, in the brains of BALB/c mice. COL-3 has been described to have no antibacterial activity. We observed that COL-3 had no activity against a Gram-negative bacteria, Escherichia coli; however surprisingly, COL-3 had antibacterial activity against a Gram-positive bacteria Staphylococcus aureus, with a minimum inhibitory concentration of 1 mg/ml. Our data show that COL-3 has some antibacterial activity against S. aureus, inhibits LPS-induced neuroinflammation, and displays potential as a therapeutic agent for treatment of conditions involving CNS inflammation.


Secondary bone/soft tissue sarcoma in childhood cancer survivors: a nationwide hospital-based case-series study in Japan.
Secondary cancer is the most life-threatening late effect of childhood cancer. We investigated the clinical features of secondary bone/soft tissue sarcoma among childhood cancer survivors (CCSs). We conducted a retrospective case-series study of 10 069 CCSs newly diagnosed with cancer between 1980 and 2009 across 15 Japanese hospitals. Twenty-one cases of pathologically diagnosed secondary bone/soft tissue sarcoma were selected, and the respective clinical courses were determined using additional questionnaires. The primary cancers included retinoblastoma (n = 7), acute lymphoblastic leukemia (n = 5), lymphoma (n = 5), osteosarcoma (n = 1), rhabdomyosarcoma (n = 1), brain tumor (n = 1) and Langerhans cell histiocytosis (n = 1). The median age at the primary cancer diagnosis was 2.9 years, and the male-to-female ratio was 16:5. The histological classifications of the secondary sarcoma included osteosarcoma (n = 10), malignant peripheral nerve sheath tumor (n = 4), rhabdomyosarcoma (n = 3), Ewing's sarcoma (n = 3) and primitive neuroectodermal tumor (n = 1). The median latency period to the secondary sarcoma was 10.2 years. Significant risk factors for secondary sarcoma in the multivariate Cox regression model included a history of retinoblastoma as the primary cancer (hazard ratio [HR], 20.9; 95% confidence interval [CI], 5.70-76.5) and autologous stem cell transplantation (SCT) (HR, 2.56; 95% CI, 1.08-6.03). Seventeen CCSs with secondary sarcoma underwent radiation, and nine, hematopoietic SCT. Twelve CCSs with secondary sarcoma achieved disease-free survival, while CCSs with hematological cancer or relapsed primary cancer who developed secondary sarcoma had the worst prognoses. The prognoses of CCSs with secondary sarcoma may depend on the primary cancer or prior relapse of primary cancer.


A selective 3-acylation of tetramic acids and the first synthesis of ravenic acid.
3-Acyltetramic acids, including delicate 3-oligoenoyl derivatives, such as the Penicillium metabolite ravenic acid, were prepared in two high-yielding steps. Reaction of tetramic acids with the ylide Ph(3)PCCO afforded exclusively the corresponding 3-acylylidenetetramic acids. These were amenable to Wittig olefinations with aliphatic, aromatic, saturated and unsaturated aldehydes after deprotonation with KOtBu. Due to its simplicity, selectivity and tolerance of pH-sensitive groups this method is superior to the established acylation protocols by Jones and Yoshii. It is also applicable to the synthesis of 3-acyltetronic acids. The new 3-oligoenoyl tetramic acids exhibited structure-dependent antimicrobial and cytotoxic activity.


Protein-mediated dethreading of a biotin-functionalised pseudorotaxane.
In this article, we describe the synthesis of new biotin-functionalised naphthalene derivatives 3 and 4 and their complexation behaviour with avidin and neutravidin using a range of analytical techniques. We have shown using 2-(4'-hydroxyazobenzene)benzoic acid displacement and ITC experiments, that compounds 3 and 4 have the propensity to form reasonably high-affinity bioconjugates with avidin and neutravidin. We have also demonstrated using (1)H NMR, UV-vis and fluorescence spectroscopy that the naphthalene moiety of 3 and 4 facilitates the formation of pseudorotaxane-like structures with 1 in water. We have then investigated the ability of avidin and neutravidin to modulate the complexation between 1 and 3 or 4. UV-vis and fluorescence spectroscopy has shown that in both cases the addition of the protein disrupts complexation between the naphthalene moieties of 3 and 4 with 1.


Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome.
Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.


Effect of phenobarbital and cimetidine on experimental cyclosporine nephrotoxicity: preliminary observations.
Cyclosporine is metabolized by the hepatic microsomal cytochrome P-450 mixed function oxidases. To determine the effects of inducers and inhibitors of this enzyme on nephrotoxicity, male Fischer 344 rats were treated with cyclosporine in doses of 25 mg/kg and 40 mg/kg by daily gavage for 14 days. Groups of animals were given phenobarbital 75 mg/kg i.p., cimetidine 75 mg/kg i.p., or .9% saline i.p. for 3 days prior to starting cyclosporine and throughout therapy. Animals treated with the oil vehicle for cyclosporine served as controls. Animals receiving cyclosporine together with phenobarbital hat better preservation of glomerular filtration rate than did other cyclosporine-treated animals. Cimetidine did not enhance cyclosporine nephrotoxicity. Direct tubular toxicity was not evident using cortical slice transport of tetraethylammonium, fractional excretion of sodium and light microscopy as markers. If phenobarbital protects from cyclosporine nephrotoxicity because of its enzyme inducing action, it would follow that the parent drug and not a toxic metabolite mediates renal dysfunction. Based on the decreased glomerular filtration rate in the absence of overt tubular damage the major mechanism of cyclosporine nephrotoxicity is probably related to vascular or glomerular effects of the drug.


Effects of freeze-thaw cycles on methanogenic hydrocarbon degradation: Experiment and modeling.
Cold regions are warming much faster than the global average, resulting in more frequent and intense freeze-thaw cycles (FTCs) in soils. In hydrocarbon-contaminated soils, FTCs modify the biogeochemical and physical processes controlling petroleum hydrocarbon (PHC) biodegradation and the associated generation of methane (CH4) and carbon dioxide (CO2). Thus, understanding the effects of FTCs on the biodegradation of PHCs is critical for environmental risk assessment and the design of remediation strategies for contaminated soils in cold regions. In this study, we developed a diffusion-reaction model that accounts for the effects of FTCs on toluene biodegradation, including methanogenic biodegradation. The model is verified against data generated in a 215 day-long batch experiment with soil collected from a PHC contaminated site in Ontario, Canada. The fully saturated soil incubations with six different treatments were exposed to successive 4-week FTCs, with temperatures oscillating between -10 °C and +15 °C, under anoxic conditions to stimulate methanogenic biodegradation. We measured the headspace concentrations and 13C isotope compositions of CH4 and CO2 and analyzed the porewater for pH, acetate, dissolved organic and inorganic carbon, and toluene. The numerical model represents solute diffusion, volatilization, sorption, as well as a reaction network of 13 biogeochemical processes. The model successfully simulates the soil porewater and headspace concentration time series data by representing the temperature dependencies of microbial reaction and gas diffusion rates during FTCs. According to the model results, the observed increases in the headspace concentrations of CH4 and CO2 by 87% and 136%, respectively, following toluene addition are explained by toluene fermentation and subsequent methanogenesis reactions. The experiment and the numerical simulation show that methanogenic degradation is the primary toluene attenuation mechanism under the electron acceptor-limited conditions experienced by the soil samples, representing 74% of the attenuation, with sorption contributing to 11%, and evaporation contributing to 15%. Also, the model-predicted contribution of acetate-based methanogenesis to total produced CH4 agrees with that derived from the 13C isotope data. The freezing-induced soil matrix organic carbon release is considered as an important process causing DOC increase following each freezing period according to the calculations of carbon balance and SUVA index. The simulation results of a no FTC scenario indicate that, in the absence of FTCs, CO2 and CH4 generation would decrease by 29% and 26%, respectively, and that toluene would be biodegraded 23% faster than in the FTC scenario. Because our modeling approach represents the dominant processes controlling PHC biodegradation and the associated CH4 and CO2 fluxes, it can be used to analyze the sensitivity of these processes to FTC frequency and duration driven by temperature fluctuations.


Reactive spindle cell nodules of the breast after core biopsy or fine-needle aspiration.
Reactive spindle cell nodules (RSCNs) arising postoperatively or after fine-needle aspiration (FNA) have been reported previously in the genitourinary tract and thyroid. We describe 18 cases of similar lesions in breast, associated with a history of core needle biopsy or FNA. The majority of the RSCNs (15 cases) were associated with papillary lesions or complex sclerosing lesions. The RSCNs were nonencapsulated and relatively nodular, measuring 1.5 to 9 mm. They were composed of spindle cells with mild to moderate nuclear pleomorphism and a low mitotic count. A network of small blood vessels, macrophages, and lymphocytes was present in all cases. Immunohistochemically, the spindle cells expressed smooth and specific muscle actins, supporting a myofibroblastic origin. The association of RSCNs with needle trauma to fibrosclerotic lesions, such as complex sclerosing lesions and papillary lesions that regularly have myofibroblasts, suggests an exuberant reparative cause. Recognition of this reactive process will avoid overdiagnosis of mammary spindle cell malignant neoplasm.


Production of CXC and CC chemokines by human antigen-presenting cells in response to Lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever.
The pathogenesis of Lassa fever (LF), a hemorrhagic fever endemic to West Africa, remains unclear. We previously compared Lassa virus (LASV) with its genetically close, but nonpathogenic homolog Mopeia virus (MOPV) and demonstrated that the strong activation of antigen-presenting cells (APC), including type I IFN production, observed in response to MOPV probably plays a crucial role in controlling infection. We show here that human macrophages (MP) produce large amounts of CC and CXC chemokines in response to MOPV infection, whereas dendritic cells (DC) release only moderate amounts of CXC chemokines. However, in the presence of autologous T cells, DCs produced CC and CXC chemokines. Chemokines were produced in response to type I IFN synthesis, as the levels of both mediators were strongly correlated and the neutralization of type I IFN resulted in an inhibition of chemokine production. By contrast, LASV induced only low levels of CXCL-10 and CXCL-11 production. These differences in chemokine production may profoundly affect the generation of virus-specific T-cell responses and may therefore contribute to the difference of pathogenicity between these two viruses. In addition, a recombinant LASV (rLASV) harboring the NP-D389A/G392A mutations, which abolish the inhibition of type I IFN response by nucleoprotein (NP), induced the massive synthesis of CC and CXC chemokines in both DC and MP, confirming the crucial role of arenavirus NP in immunosuppression and pathogenicity. Finally, we confirmed, using PBMC samples and lymph nodes obtained from LASV-infected cynomolgus monkeys, that LF was associated with high levels of CXC chemokine mRNA synthesis, suggesting that the very early synthesis of these mediators may be correlated with a favourable outcome.


Randomized Placebo-Controlled Trial of Intravenous Immunoglobulin in Autoimmune LGI1/CASPR2 Epilepsy.
Drug-resistant seizures are common in patients with leucine-rich, glioma-inactivated 1 (LGI1)-IgG associated and contactin-associated protein-like 2 (CASPR2)-IgG associated encephalitis. We performed the first randomized double-blind placebo-controlled trial to evaluate efficacy of intravenous immunoglobulin (IVIG) in reducing seizure frequency. Our enrollment goal was 30 LGI1/CASPR2-IgG-seropositive adult patients with ≥2 seizures per week. Patients were randomized to receive IVIG (0.5g/kg day 1, 1g/kg day 2, 0.6g/kg weeks 3 and 5) or volume-matched intravenous normal saline. Following the blinded phase, the nonresponders in the placebo group received IVIG. The primary clinical outcome was 50% reduction in seizure frequency from baseline to 5 weeks. After enrollment of 17 patients (LGI1-IgG, 14; CASPR2-IgG, 3) over 34 months, the study was terminated due to slow enrollment. Six of 8 patients in the IVIG group were responders, compared to 2 of 9 in the placebo group (p = 0.044, odds ratio = 10.5, 95% confidence interval = 1.1-98.9). For the LGI1-IgG seropositive subgroup, 6 of 8 patients in the IVIG group were responders, compared to zero of 6 in the placebo group. Two LGI1-IgG-seropositive patients receiving IVIG, but none receiving placebo, were seizure-free at the end of the blinded phase. Four of the 6 patients entering the open-label IVIG arm reported ≥50% reduction in seizure frequency. There were no correlations with LGI1/CASPR2-IgG1-4 subclasses. Superiority of IVIG to placebo reached statistical significance for the primary endpoint for all patients and the subset with LGI1-IgG. These results have to be interpreted with the caveat that the study did not reach its originally selected sample size. ANN NEUROL 2020;87:313-323.


A randomized controlled multicenter trial of individual placement and support for patients with moderate-to-severe mental illness.
Objectives The aim of this study was to evaluate the effectiveness of individual placement and support (IPS) for people struggling with work participation due to moderate-to-severe mental illness. The study was conducted in Norway, a setting characterized by a comprehensive welfare system and strong employment protection legislation. Methods A randomized controlled multicenter trial including 410 participants was conducted. The intervention group received IPS according to the IPS manual. The control group received high-quality usual care. The main outcome was competitive employment at 12- and 18-months follow-up, based on objective registry data. Changes in mental health and health-related quality of life were secondary outcomes. Results At 12-months follow-up, 36.6% of participants in the IPS group and 27.1% of participants in the control group were in competitive employment, while the difference was slightly higher (37.4% versus 27.1%) at 18-months follow-up. Furthermore, IPS yielded positive effects on all the secondary outcomes compared to the control group (all P<0.05). Conclusions The IPS model of supported employment was superior to high-quality usual care on both vocational and non-vocational outcomes for people with moderate-to-severe mental illness, even in a policy context characterized by high job security and a comprehensive welfare system.


Direct neural sensory feedback and control of a prosthetic arm.
Evidence indicates that user acceptance of modern artificial limbs by amputees would be significantly enhanced by a system that provides appropriate, graded, distally referred sensations of touch and joint movement, and that the functionality of limb prostheses would be improved by a more natural control mechanism. We have recently demonstrated that it is possible to implant electrodes within individual fascicles of peripheral nerve stumps in amputees, that stimulation through these electrodes can produce graded, discrete sensations of touch or movement referred to the amputee's phantom hand, and that recordings of motor neuron activity associated with attempted movements of the phantom limb through these electrodes can be used as graded control signals. We report here that this approach allows amputees to both judge and set grip force and joint position in an artificial arm, in the absence of visual input, thus providing a substrate for better integration of the artificial limb into the amputee's body image. We believe this to be the first demonstration of direct neural feedback from and direct neural control of an artificial arm in amputees.


Uniportal video-assisted thoracoscopic lobectomy: an alternative to conventional thoracoscopic lobectomy in lung cancer surgery?
Although the standard video-assisted thoracoscopic surgery (VATS) approach is generally performed through two to four incisions, uniportal VATS pulmonary resection has recently been reported to be a promising, less invasive alternative. To evaluate the adequacy of uniportal VATS lobectomy as an alternative to conventional VATS lobectomy in lung cancer, we analysed and compared the outcomes of uniportal and conventional VATS lobectomies. Retrospective observational data for patients who underwent VATS lobectomy at Samsung Medical Center between January 2013 and February 2014 due to a diagnosis of lung cancer were collected. Perioperative factors such as operative time, postoperative chest tube duration, postoperative hospital stay, complication rate, conversion rate, reoperation rate and mortality were compared between the uniportal and conventional VATS groups. A total of 90 uniportal VATS lobectomies and 60 conventional VATS lobectomies were attempted. Fifty-eight (64.5%) cases were completed as uniportal VATS lobectomies, and 51 (85%) cases as conventional VATS lobectomies. There were 32 (35.5%) conversions of uniportal VATS lobectomy cases, including four conversions to three-port VATS, 18 to two-port VATS and 10 to open thoracotomy. No differences in postoperative complications, postoperative 30-day mortality or reoperation rate were noted between the two groups. There was no difference in operative time, number of removed lymph nodes, chest tube duration or length of postoperative hospital stay between the uniportal VATS group and conventional VATS group. The similar perioperative results of uniportal VATS lobectomy compared with conventional VATS lobectomy suggest that uniportal VATS is a viable alternative approach to the conventional VATS approach in selected patients, especially in patients with early peripheral lung cancer with good anatomy and in good general condition.


Sterols: a tracer of organic matter in combined sewers.
The important organic pollution of combined wet weather flows (WWF), its acute impact on receiving waters have been widely demonstrated. The main three possibly origins for this organic pollution are: runoff water (streets and roofs), wastewater and erosion of sewer sediments in combined sewer system. This work, for tracing the origin of organic particles bound in combined sewer system, has been focused on the innovative use of sterols. So, eight sterols have been selected and analysed for each kind of sample. Results are represented in contents of sterols (microg g(-1)) and in sterol profiles (%). The comparison of contents and profiles leads the separation between two groups: runoff water, characterized by the total absence of coprostanol, epicoprostanol and coprostanone, and the group of sewer deposits (gross bed sediment (GBS), organic layer (OL), biofilms) and wastewater. Moreover, sewer deposits and wastewater can be distinguished by their sterol contents and profiles. To evaluate their contribution to WWF a comparison between sterol signatures is done which shows that these effluents have a strong similarity in profiles and in contents of sterols to the organic layer.


Amplitude equations for collective spatio-temporal dynamics in arrays of coupled systems.
We study the coupling induced destabilization in an array of identical oscillators coupled in a ring structure where the number of oscillators in the ring is large. The coupling structure includes different types of interactions with several next neighbors. We derive an amplitude equation of Ginzburg-Landau type, which describes the destabilization of a uniform stationary state and close-by solutions in the limit of a large number of nodes. Studying numerically an example of unidirectionally coupled Duffing oscillators, we observe a coupling induced transition to collective spatio-temporal chaos, which can be understood using the derived amplitude equations.


"Teaching is like nightshifts …": a focus group study on the teaching motivations of clinicians.
To ensure the highest quality of education, medical schools have to be aware of factors that influence the motivation of teachers to perform their educational tasks. Although several studies have investigated motivations for teaching among community-based practitioners, there is little data available for hospital-based physicians. This study aimed to identify factors influencing hospital-based physicians' motivations to teach. We conducted 3 focus group discussions with 15 clinical teachers from the Medical Faculty at Hamburg University. Using a qualitative inductive approach, we extracted motivation-related factors from the transcripts of the audio-recorded discussions. Three main multifaceted categories influencing the motivation of teachers were identified: the teachers themselves, the students, and the medical faculty as an organization. Participants showed individual sets of values and beliefs about their roles as teachers as well as personal notions of what comprises a "good" medical education. Their personal motives to teach comprised a range of factors from intrinsic, such as the joy of teaching itself, to more extrinsic motives, such as the perception of teaching as an occupational duty. Teachers were also influenced by the perceived values and beliefs of their students, as well as their perceived discipline and motivation. The curriculum organization and aspects of leadership, human resource development, and the evaluation system proved to be relevant factors as well, whereas extrinsic incentives had no reported impact. Individual values, beliefs, and personal motives constitute the mental framework upon which teachers perceive and assess motivational aspects for their teaching. The interaction between these personal dispositions and faculty-specific organizational structures can significantly impair or enhance the motivation of teachers and should therefore be accounted for in program and faculty development.


[Related factors of sperm DNA damage: Advances in studies].
The detection of sperm DNA damage, as an important supplement to semen routine examination strategies, has been applied in some clinical andrology laboratories. What factors may lead to sperm DNA damage remains one of the concerns among many andrologists. Present studies show a variety of factors of sperm DNA damage, including age, environmental pollutants such as organophosphorus and organochloride pesticides, plasticizer, heavy metals such as lead, carcinogens such as polycyclic aromatic hydrocarbons (c-PAHs) and zearalenone (ZEA), male reproductive system diseases or systemic diseases such as varicocele, infection, tumor, spermatogenesis and maturation dysfunction, spinal cord injury and endocrine disorders, seasons and temperature, lifestyle, abstinence time, semen refrigeration, semen handling in vitro, and certain medications. Among them, spermatogenesis and sperm maturation dysfunction may be the most secretive factors, which are involved in the molecular mechanisms of sperm chromatin packaging and restructuring, such as the transformation of histone to protamine, single nucleotide polymorphism of genes, and the role of telomere, which may be one of the hotspots in the future studies of sperm DNA damage. Relevant researches in the future are expected to focus on the prevention of sperm DNA damage and clarification of its specific pathogenic mechanisms so as to provide some evidence for its treatment.


Thoracoscopic sympathetic clipping for hyperhidrosis: long-term results and reversibility.
The study objectives were to assess 1) postoperative satisfaction and the occurrence of compensatory sweating after endoscopic thoracic sympathetic clipping in a consecutive series of patients and 2) the reversibility of adverse effects by removing the surgical clips. Between June 1998 and March 2006, 727 patients undergoing bilateral endoscopic thoracic sympathetic clipping for hyperhidrosis or facial blushing were prospectively followed for postoperative satisfaction and subjective compensatory sweating. The effect of removing the surgical clips was assessed in 34 patients who underwent a subsequent reversal procedure after endoscopic thoracic sympathetic clipping. Satisfaction and compensatory sweating were assessed using a visual analogue scale ranging from 0 to 10, with 10 indicating the highest degree. Follow-up was complete in 666 patients (92%). The median age was 26.9 years, and 383 (53%) were men. The level of sympathetic clipping was T2 in 399 patients (55%), T2+3 in 55 patients (8%), and T3+4 in 273 patients (38%). Median follow-up was 10.4 months (range 0-83 months). Excellent satisfaction (8-10 on visual analogue scale) was seen at last follow-up in 288 (74%) of the T2 group, 33 (62%) of the T2+3 group, and 184 (85%) of the T3+4 group. Postoperative satisfaction was significantly higher in the T3+4 group when compared with the T2 or T2+3 groups (P < .01). Severe compensatory sweating (8-10 on the visual analogue scale) was reported in 42 (13%) of the T2 group, 11 (28%) of the T2+3 group, and 17 (8%) of the T3+4 group. Postoperative compensatory sweating was significantly lower in the T3+4 group when compared with the T2 or T2+3 groups (P < .05). Thirty-four patients have subsequently undergone removal of the surgical clips after endoscopic thoracic sympathetic clipping. Follow-up was complete in 31 patients. The reasons for removal included severe compensatory sweating in 32 patients, anhydrosis of the upper limb in 4 patients, lack of improvement or recurrence of hyperhidrosis in 5 patients, and other adverse symptoms in 5 patients. The reversal procedure was done after a median time of 11.0 months (range 1-57 months) after endoscopic thoracic sympathetic clipping. The initial level of clipping was T2 in 21 patients, T2+3 in 7 patients, and T3+4 in 6 patients. There was a trend toward fewer subsequent reversal procedures in the T3+4 group when compared with the T2 or T2+3 groups (P = .06). Fifteen patients (48%) reported a substantial decrease in their compensatory sweating (5-10 on the visual analogue scale) after reversal. Thirteen patients (42%) reported that their initial hyperhidrosis or facial blushing has remained well controlled (8-10 on the visual analogue scale) after reversal. There was no significant relationship between the original level of clipping and the interval between endoscopic thoracic sympathetic clipping and the subsequent reversal and reversibility of symptoms. When compared with endoscopic thoracic sympathetic clipping at the T2 or T2+3 levels, endoscopic thoracic sympathetic clipping at the T3+4 level was associated with a higher satisfaction rate, a lower rate of severe compensatory sweating, and a trend toward fewer subsequent reversal procedures. Subjective reversibility of adverse effects after endoscopic thoracic sympathetic clipping was seen in approximately half of the patients who underwent endoscopic removal of surgical clips. Although yet to be supported by electrophysiologic studies, reversal of sympathetic clipping seems to provide acceptable results and should be considered in selected patients.


Psychiatric and psychological morbidity as a function of adaptive disability in preschool children with aggressive and hyperactive-impulsive-inattentive behavior.
Children with high levels of aggressive-hyperactive-impulsive-inattentive behavior (AHII; n = 154) were subdivided into those with (n = 38) and without (n = 116) adaptive disability (+AD/-AD) defined as a discrepancy between expected versus actual adaptive functioning. They were compared to each other and a control group of 47 normal children. Both AHII groups were more likely to have attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder than control children; more symptoms of general psychopathology; greater social skills deficits; more parental problems; and lower levels of academic achievement skills. Compared to AHII - AD children, AHII + AD children had (1) more conduct disorder; (2) greater inattention and aggression symptoms; (3) more social problems, less academic competence, and poorer self-control at school; (4) more severe and pervasive behavior problems across multiple home and school settings; and (5) parents with poorer child management practices. Thus, adaptive disability has utility as a marker for more severe and pervasive impairments in AHII children.


Urokinase-type plasminogen activator receptor: a beacon of malignancy?
Discriminating between benign and malignant disease is a pivotal diagnostic issue in the care of women with pelvic masses. Identification of serum biomakers that can rellably make the distinction would aid in the proper referral for patient care and may provide leads in the development of early detection strategies.


Inhibition of deoxyglucose uptake in MCF-7 breast cancer cells by 2-methoxyestrone and 2-methoxyestrone-3-O-sulfamate.
Most cancer cells are dependent on glucose uptake to fulfil their energy requirements. In the present investigation we have examined the ability of 2-methoxyestrone (2-MeOE1), 2-methoxyestradiol (2-MeOE2), 2-methoxyestrone-3-O-sulfamate (2-MeOEMATE), and a number of related compounds, to inhibit 2-deoxy-D-[1-(3)H]-glucose uptake in MCF-7 breast cancer cells. Glucose uptake was shown to be linear with respect to cell number and time over a 5-35min period. 2-MeOE2, 2-MeOE1 and 2-MeOEMATE inhibited glucose uptake by 25-49% at 10 microM. 2-Hydroxyestradiol and estrone sulfate had little effect on glucose uptake, whereas estrone glucuronide inhibited uptake by 29%. There is evidence that 2-methoxyestrogens may exert an anti-mitotic effect on cells by stabilizing microtubules in a similar manner to that of paclitaxel. We therefore examined the effect of exposing cells to 2-MeOEMATE or paclitaxel for 24 h on basal or insulin stimulated glucose uptake. Using these conditions, 2-MeOEMATE and paclitaxel inhibited basal glucose uptake by 50 and 22%, respectively, and insulin stimulated uptake by 36 and 51%, respectively. The development of drugs that can inhibit glucose uptake could have therapeutic potential for the treatment of breast cancer.


The promise of competency-based education in the health professions for improving global health.
Competency-based education (CBE) provides a useful alternative to time-based models for preparing health professionals and constructing educational programs. We describe the concept of 'competence' and 'competencies' as well as the critical curricular implications that derive from a focus on 'competence' rather than 'time'. These implications include: defining educational outcomes, developing individualized learning pathways, setting standards, and the centrality of valid assessment so as to reflect stakeholder priorities. We also highlight four challenges to implementing CBE: identifying the health needs of the community, defining competencies, developing self-regulated and flexible learning options, and assessing learners for competence. While CBE has been a prominent focus of educational reform in resource-rich countries, we believe it has even more potential to align educational programs with health system priorities in more resource-limited settings. Because CBE begins with a careful consideration of the competencies desired in the health professional workforce to address health care priorities, it provides a vehicle for integrating the health needs of the country with the values of the profession.


Deodorants and antiperspirants affect the axillary bacterial community.
The use of underarm cosmetics is common practice in the Western society to obtain better body odor and/or to prevent excessive sweating. A survey indicated that 95 % of the young adult Belgians generally use an underarm deodorant or antiperspirant. The effect of deodorants and antiperspirants on the axillary bacterial community was examined on nine healthy subjects, who were restrained from using deodorant/antiperspirant for 1 month. Denaturing gradient gel electrophoresis was used to investigate the individual microbial dynamics. The microbial profiles were unique for every person. A stable bacterial community was seen when underarm cosmetics were applied on a daily basis and when no underarm cosmetics were applied. A distinct community difference was seen when the habits were changed from daily use to no use of deodorant/antiperspirant and vice versa. The richness was higher when deodorants and antiperspirants were applied. Especially when antiperspirants were applied, the microbiome showed an increase in diversity. Antiperspirant usage led toward an increase of Actinobacteria, which is an unfavorable situation with respect to body odor development. These initial results show that axillary cosmetics modify the microbial community and can stimulate odor-producing bacteria.


A dynamic context model of interactive behavior.
A dynamic context model of interactive behavior was developed to explain results from two experiments that tested the effects of interaction costs on encoding strategies, cognitive representations, and response selection processes in a decision-making and a judgment task. The model assumes that the dynamic context defined by the mixes of internal and external representations and processes are sensitive to the interaction cost imposed by the task environment. The model predicts that changes in the dynamic context may lead to systematic biases in cognitive representations and processes that eventually influence decision-making and judgment outcomes. Consistent with the predictions by the model, results from the experiments showed that as interaction costs increased, encoding strategies and cognitive representations shifted from perception-based to memory-based. Memory-based comparisons of the stimuli enhanced the similarity and dominance effects, and led to stronger systematic biases in response outcomes in a choice task. However, in a judgment task, memory-based representations enhanced only the dominance effects. Results suggested that systematic response biases in the dominance context were caused by biases in the cognitive representations of the stimuli, but response biases in the similarity context were caused by biases in the comparison process induced by the choice task. Results suggest that changes in interaction costs not only change whether information was assessed from the external world or from memory but also introduce systematic biases in the cognitive representation of the information, which act as biased inputs to the subsequent decision-making and judgment processes. Results are consistent with the idea of interactive cognition, which proposes that representations and processes are contingent on the dynamic context defined by the information flow between the external task environment and internal cognition.


SGLT1 is required for the survival of triple-negative breast cancer cells via potentiation of EGFR activity.
Sodium/glucose cotransporter 1 (SGLT1), an essential active glucose transport protein that helps maintain high intracellular glucose levels, was previously shown to interact with epidermal growth factor receptor (EGFR); the SGLT1-EGFR interaction maintains intracellular glucose levels to promote survival of cancer cells. Here, we explore the role of SGLT1 in triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer. We performed TCGA analysis coupled to in vitro experiments in TNBC cell lines as well as in vivo xenografts established in the mammary fat pad of female nude mice. Tissue microarrays of TNBC patients with information of clinical-pathological parameters were also used to investigate the expression and function of SGLT1 in TNBC. We show that high levels of SGLT1 are associated with greater tumour size in TNBC. Knockdown of SGLT1 compromises cell growth in vitro and in vivo. We further demonstrate that SGLT1 depletion results in decreased levels of phospho-EGFR, and as a result, the activity of downstream signalling pathways (such as AKT and ERK) is inhibited. Hence, targeting SGLT1 itself or the EGFR-SGLT1 interaction may provide novel therapeutics against TNBC.


Finished Genome Sequences of Xanthomonas fragariae, the Cause of Bacterial Angular Leaf Spot of Strawberry.
Xanthomonas fragariae is a foliar pathogen of strawberry that is of significant concern to nursery production of strawberry transplants and field production of strawberry fruit. Long-read sequencing was employed to generate finished genomes for two isolates (each with one chromosome and two plasmids) from symptomatic plants in northern California.


PARL Leu262Val is not associated with fasting insulin levels in UK populations.
PARL, the gene encoding presenilins-associated rhomboid-like protein, maps to chromosome 3q27 within a quantitative trait locus that influences components of the metabolic syndrome. Recently, an amino acid substitution (Leu262Val, rs3732581) in PARL was associated with fasting plasma insulin levels in a US white population (N=1031). This variant was also found to modify the positive association between age and fasting insulin. The aim of this study was to test whether these findings could be replicated in two UK population-based cohorts. Participants from the Medical Research Council Ely and Hertfordshire cohort studies were genotyped for this variant using a SNaPshot primer extension assay and Taqman assay respectively. Full phenotypic and genotypic data were available for 3,666 study participants. Based on a dominant model, we found no association between the Leu262Val polymorphism and fasting insulin levels (p=0.79) or BMI (p=0.98). We did not observe the previously reported interaction between age and genotype on fasting insulin (p=0.14). Despite having greater statistical power, our data do not support the previously reported association between PARL Leu262Val and fasting plasma insulin levels, a measure of insulin resistance. Our findings indicate that this variant is unlikely to be an important contributor to insulin resistance in UK populations.


The relationship between isthmic and degenerative spondylolisthesis and the configuration of the lamina and facet joints.
Advanced degenerative change in the facet joints leads to displacement of the vertebral body, and the configuration of facet joints and lamina is closely related to the development of degenerative spondylolisthesis. For this study 103 patients and 25 controls were examined with respect to the configuration of the lamina, anteroposterior diameter of the vertebral canal, interarticular distance, interlaminar distance, disc degeneration, and degree of arthritic changes of facet joint, all as shown of plain radiography, and facet angle, interfacet distance, and contour of the canal side of the inferior articular process and lamina, as shown on computed axial tomography. The results of this study showed that those patients with a narrow facet angle were more likely to have developed degenerative spondylolisthesis. If the sum of both facet angles was less than 77.9 degree, the risk of development of degenerative spondylolisthesis was 2.5 times higher than if the sum was greater than 77.9 degree. Those with type N lamina, detected on plain radiographs, were especially likely to have developed degenerative spondylolisthesis. This suggested that degenerative spondylolisthesis may be due to the less effective check mechanism preventing a vertebra from slipping forward on the vertebra below. We recommend fusion of the degenerated spinal segments when operation is considered in cases of acute facet angle with symptoms.


Combined in Situ Photoluminescence and X-ray Scattering Reveals Defect Formation in Lead-Halide Perovskite Films.
Lead-halide perovskites have established a firm foothold in photovoltaics and optoelectronics due to their steadily increasing power conversion efficiencies approaching conventional inorganic single-crystal semiconductors. However, further performance improvement requires reducing defect-assisted, nonradiative recombination of charge carriers in the perovskite layers. A deeper understanding of perovskite formation and associated process control is a prerequisite for effective defect reduction. In this study, we analyze the crystallization kinetics of the lead-halide perovskite MAPbI3-xClx during thermal annealing, employing in situ photoluminescence (PL) spectroscopy complemented by lab-based grazing-incidence wide-angle X-ray scattering (GIWAXS). In situ GIWAXS measurements are used to quantify the transition from a crystalline precursor to the perovskite structure. We show that the nonmonotonous character of PL intensity development reflects the perovskite phase volume, as well as the occurrence of the defects states at the perovskite layer surface and grain boundaries. The combined characterization approach enables easy determination of defect kinetics during perovskite formation in real-time.


Early detection of cervical neoplasia by Raman spectroscopy.
Early detection of malignant tumours, or their precursor lesions, improves patient outcome. High risk human papillomavirus (HPV), particularly HPV16, infection can lead to the development of uterine cervical neoplasia, and therefore, the identification in clinical samples of the effects of HPV infection may have clinical value. In this report, we apply Raman microspectroscopy to live and fixed cultured cells to discriminate between defined cell types. Raman spectra were acquired from primary human keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16-containing cervical carcinoma-derived cell line. Averaged Raman spectra showed variations, mostly in peaks originating from DNA and proteins, consistent with HPV gene expression and cellular changes associated with neoplasia, in both live and fixed cells. Principal component analysis produced good discrimination between the cell types, with sensitivities of up to 100% for the comparison of fixed PHK and CaSki. These results demonstrate the ability of Raman spectroscopy to discriminate between cell types representing different stages of cervical neoplasia. More specifically, this technique was able to identify cells expressing the HPV 16 E7 gene accurately and objectively, suggesting that this approach may be of value in diagnosis. Moreover, the ability to detect the effects of the virus in fixed samples also demonstrates the compatibility of Raman spectroscopy with current cervical screening methods. (c) 2007 Wiley-Liss, Inc.


Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma associated herpesvirus.
Tumors associated with Kaposi's sarcoma-associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Virtually all of the tumor cells in these cancers are latently infected and dependent on the virus for survival. Latent viral proteins maintain the viral genome and are required for tumorigenesis. Current prevention and treatment strategies are limited because they fail to specifically target the latent form of the virus, which can persist for the lifetime of the host. Thus, targeting latent viral proteins may prove to be an important therapeutic modality for existing tumors as well as in tumor prevention by reducing latent virus load. Here, we describe a novel fluorescence-based screening assay to monitor the maintenance of the Kaposi's sarcoma-associated herpesvirus genome in B lymphocyte cell lines and to identify compounds that induce its loss, resulting in tumor cell death.


The shift in stages of the nutrition transition in the developing world differs from past experiences!
This paper explores the unique nutrition transition shifts in diet and activity patterns from the period termed the receding famine pattern to the one dominated by nutrition-related non-communicable diseases (NR-NCDs). The paper examines the speed and timing of these changes; unique components, such as the issue of finding both under- and overnutrition in the same household; potential exacerbating biological relationships that contribute to differences in the rates of change; and political issues. The focus is on lower- and middle-income countries of Asia, Africa, the Middle East and Latin America. These changes are occurring at great speed and at earlier stages of these countries' economic and social development. There are some unique issues that relate to body composition and potential genetic factors. The significance of the high number of persons exposed to heavy insults during pregnancy and infancy (foetal origins hypothesis) and the subsequent rapid shifts in energy imbalance remains to be understood. Countries that are still addressing major concerns of undernutrition are not ready to address these NR-NCDs. The developing world needs to give far greater emphasis to addressing the prevention of the adverse health consequences of this shift to the nutrition transition stage of degenerative diseases.


School-day and overall physical activity among youth.
Increasing school-day physical activity through policy and programs is commonly suggested to prevent obesity and improve overall child health. However, strategies that focus on school-day physical activity may not increase total physical activity if youth compensate by reducing physical activity outside of school. Objectively measured, nationally representative physical activity data were used to test the hypothesis that higher school-day physical activity is associated with higher overall daily physical activity in youth. Accelerometer data from 2003-2004/2005-2006 National Health and Nutrition Examination Surveys were analyzed in 2012 to estimate physical activity levels during the school day (8AM-3PM) among youth aged 6-19 years (n=2548). Fixed-effects regressions were used to estimate the impact of changes in school-day minutes of moderate-to-vigorous physical activity (MVPA) on changes in total daily MVPA. Each additional minute of school-day MVPA was associated with an additional 1.14 minutes (95% CI=1.04, 1.24; p<0.001) of total daily MVPA, or 0.14 additional minutes (95% CI=0.04, 0.24; p=0.008) outside the school day, controlling for total daily accelerometer wear time and age, gender, race/ethnicity, and other non-time varying covariates. There were no differences in the effect of school-day MVPA on total MVPA by age group, gender, race/ethnicity, poverty status, or degree of change in MVPA. Higher school-day MVPA was associated with higher daily MVPA among U.S. youth with no evidence for same-day "compensation." Increasing school-based physical activity is a promising approach that can improve total daily physical activity levels of youth.


Ultrastructure of hypertensive rat aorta. Increased basement membrane-like material.
To determine the effect of elevated blood pressure on the ultrastructure of rat aorta, hypertension (average mean pressure 163 +/- 17 mm Hg) was produced by suprarenal aortic coarctation. After 3 weeks, the subendothelium of the hypertensive thoracic aorta showed significantly increased volume measurements for mononuclear leukocytes and basement membrane-like material compared with the sham-operated control group. Focal areas of rarefaction of the subendothelial extracellular material were associated with the nearby presence of mononuclear leukocytes. None of these alterations were found in the normotensive abdominal aorta. The tunica media of hypertensive thoracic aorta also contained significantly increased basement membrane-like material. This new finding in an animal hypertension model is the direct result of the quantitative morphological approach employed in this study. In some rats, the partially constricting aortic ligature compromised the right renal artery leading to ischemic atrophy of the right kidney and hyperreninemia in addition to hypertension. In this group, excluded from the previous analysis and evaluated separately, subendothelial thickening and accumulation of basement membrane-like material in the thoracic aorta were greatly increased compared with the control group and other hypertensive rats. This result could not be attributed to an effect of blood pressure alone and might have been caused in part by humoral factors. Basement membrane accumulation appears to be an important early response of the arterial wall to hypertension or other factors in this rat model.


Thin film Ag superlens towards lab-on-a-chip integration.
A thin metal film near-field superlens, as originally suggested by Pendry and realized by Fang et al. and Melville et al., is investigated with emphasis on materials suitable for integration on a lab-on-a-chip platform. A chemically resistant cyclo-olefin copolymer (COC), mr-I-T85 from microresist technology, is applied as dielectric matrix/spacer for an Ag thin film superlens. The superlens successfully resolves 80 nm half-pitch gratings when illuminated with UV radiation at a free space wavelength of 365 nm. The superlens design, fabrication and characterization is discussed.


Specific Autobiographical Recall Mediates Impact of Cognition and Depression on Independence Function and Well-Being in Older Adults.
Autobiographical memory specificity has been associated with cognitive function, depression, and independence in older adults. This longitudinal study of 162 older adults moving to active supported living environments tracks changes in the role of the ability to recall specific autobiographical memory as a mediator between underlying cognitive function, or depression, and outcome perceived health or independence (e.g., Instrumental Activities of Daily Living, IADLs), across 18 months, as compared with controls not moving home. Clear improvements across time in autobiographical specificity were seen for residents but not controls, supporting the role of a socially active environment, and confirmed by correlation with number of activities reported in diaries, although the impact of diary activities on the effect of time on autobiographical specificity was not found. The role of autobiographical specificity in mediating general cognition and outcome functional limitations was clear for social limitations at 12 and 18 months, but its role in mediating effects of executive function and perceived health persisted throughout. The role of specificity in mediating between depression and perceived health, IADLs, and Functional Limitations persisted throughout. Analysis examining autobiographical specificity and depression as joint mediators between cognition and independence showed a forward effect such that higher specificity scores reduced the negative mediation effect of depression on independence. Finally, data showed the reduction of many of these mediations over time, supporting the role of autobiographical memory in times of change in a person's social situation. Data support potential autobiographical memory intervention development.


Aryl hydrocarbon receptor deficiency enhanced airway inflammation and remodeling in a murine chronic asthma model.
The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Recent studies have shown that AhR is a novel master regulator of the mucosal immune system, including lungs and intestine. To elucidate the role of AhR in chronic severe asthma, AhR wild-type and knockout mice (AhR-/- ) were sensitized and challenged with ovalbumin for 4 weeks. To uncover the underlying mechanisms, inflammatory cells profile and cytokines production were analyzed in bronchial lavage fluid (BALF) and lung tissue. Compared to wild-type mice, AhR-/- mice had exacerbated asthma symptoms, including airway inflammation, mucus production, airway hyperresponsiveness, and airway remodeling. BALF monocytes, neutrophils, eosinophils, and lymphocytes were all enhanced in OVA-immunized AhR-/- mice. In OVA-immunized AhR-/- mice, T helper (Th) 17 cell-specific cytokine IL-17A, as well as airway remodeling factors, including epithelial-mesenchymal transition (EMT) markers and vascular endothelial growth factor (VEGF), were all enhanced in lung tissue. Moreover, human cohort studies showed that AhR gene expression in bronchial epithelial cells decreases in severe asthma patients. Loss of AhR leads to worsening of allergic asthma symptoms, indicating its importance in maintaining normal lung function and mediating disease severity.


Phosphoproteins and protein-kinase activity in isolated envelopes of pea (Pisum sativum L.) chloroplasts.
A protein kinase was found in envelope membranes of purified pea (Pisum sativum L.) chloroplasts. Separation of the two envelope membranes showed that most of the enzyme activity was localized in the outer envelope. The kinase was activated by Mg(2+) and inhibited by ADP and pyrophosphate. It showed no response to changes in pH in the physiological range (pH 7-8) or conventional protein substrates. Up to ten phosphorylated proteins could be detected in the envelope-membrane fraction. The molecular weights of these proteins, as determined by polyacrylamide-gel electrophoresis were: two proteins higher than 145 kDa, 97, 86, 62, 55, 46, 34 and 14 kDa. The 86-kDa band being the most pronounced. Experiments with separated inner and outer envelopes showed that most labeled proteins are also localized in the outer-envelope fraction. The results indicate a major function of the outer envelope in the communication between the chloroplast and the parent cell.


A case study of liberation among Latino immigrant families who have children with disabilities.
Latino immigrant families with children with disabilities experience multiple sources of oppression during their settlement process in the United States. Unfair social structures and dominant cultural values and norms and the way they influence the immigrants' personal life stories generate a cycle of oppression very difficult to break. This paper presents a case study of how a group of Latino parents carried out a process of liberation fueled by the generation of empowering community narratives (critical awareness leading to transformative action) that resulted from a community-university partnership. Participants initiated a process that led them to discover their own stories of oppression and create new stories; to deconstruct the dominant cultural narratives and modify existing ones; and to understand contexts for power sharing. This joint reflection and increased awareness propelled group members to take action by founding a grassroots organization to redress some of the injustices that were partly responsible for their oppression, thus generating shifts at the personal, relational, and collective levels. In light of the theory of liberation, we discuss the participants' development of critical awareness that led them to take action to address their unmet needs.


Neurosurgery workforce in Canada, 1996 to 2011. Canadian Neurosurgical Society.
To determine the number of neurosurgeons in clinical practice in Canada on Jan. 1, 1996, and their practice profile and to determine requirements for 2001 and 2011. Telephone survey and national mail survey. Canada. All 174 neurosurgeons in Canada engaged in active clinical practice on Jan. 1, 1996, and all residents enrolled in neurosurgery training programs in Canada during the 1995-96 academic year. Demographic characteristics, full-time equivalents, workload, attrition, reasons for exit, vacancies, supply and shortfall. All 174 neurosurgeons responded to the survey. There is a chronic shortage of 25 neurosurgeons in Canada. Sixty-two established neurosurgeons will have stopped practice by 2001 and 181 by 2011. They will need to be replaced, for a total requirement of 87 and 206 neurosurgeons by 2001 and 2011 respectively. Canadian neurosurgery training programs can currently generate only up to 69 and 177 graduates by 2001 and 2011 respectively. During the period 1985-95, 50% of neurosurgery graduates emigrated from Canada within 2 years of obtaining certification, creating potential deficits of up to 52 and 117 neurosurgeons by 2001 and 2011 respectively. Strategies need to be developed quickly to address not only the chronic shortfall but also the attrition of established neurosurgeons. Strategies to increase and retain the number of Canadian neurosurgery graduates are also needed.


How can elderly apolipoprotein E ε4 carriers remain free from dementia?
Apolipoprotein E (APOE) ε4 is a major risk factor for Alzheimer's disease (AD) and dementia, but not all ε4 carriers develop dementia. We sought to identify factors that may play a role in modifying the risk of dementia due to ε4. A cognitively intact cohort (n = 932, age ≥ 75) was followed for 9 years to detect incident dementia cases. At baseline, information on education, leisure activities, and vascular risk factors was collected, and APOE was genotyped. During the follow-up, 324 subjects developed dementia, including 247 AD cases. The hazard ratio (HR, 95% confidence interval [95% CI]) of dementia related to the ε4 was 1.39 (1.11-1.76), while the risk was reduced when ε4 carriers had high education, no vascular risk factors, or high score of leisure activities. Among ε4 carriers, the multiadjusted HRs of dementia that were associated with high education, high level of leisure activities, and absence of vascular risk factors were 0.59 (0.40-0.87), 0.49 (0.29-0.85), and 0.61 (0.41-0.90), respectively. The ε4 carriers with these factors had about 1.2 years delayed time to dementia onset compared with those without these factors. High education, active leisure activities, or maintaining vascular health seems to reduce the risk of dementia related to APOE ε4. The ε4 carriers with these characteristics appear to have similar dementia-free survival time to non-ε4 carriers.