Implementing the near- to far-field transformation in the finite-difference time-domain method.
When the finite-difference time-domain (FDTD) method is applied to light-scattering computations, the far fields can be obtained by means of integrating the near fields either over the volume bounded by the particle's surface or on a regular surface encompassing the scatterer. For light scattering by a sphere, the accurate near-field components on the FDTD-staggered meshes can be computed from the rigorous Lorenz-Mie theory. We investigate the errors associated with these near- to far-field transform methods for a canonical scattering problem associated with spheres. For a scatterer with a small refractive index, the surface-integral approach is more accurate than its volume counterpart for computation of the phase functions and extinction efficiencies; however, the volume-integral approach is more accurate for computation of other scattering matrix elements, such as P12, P32, and P43, especially for backscattering. If a large refractive index is involved, the results computed from the volume-integration method become less accurate, whereas the surface method still retains the same order of accuracy as in the situation for the small refractive index.


"Productivity" of Undergraduate Institutions: New analyses show that a college's output of doctors of philosophy depends largely on its input of students.
A new method for evaluating the "Ph.D. productivity" of undergraduate institutions was applied to a sample of 265 institutions. It was found that a college's actual Ph.D. output can be predicted relatively accurately from an "expected" output based on the sex, major fields, and intelligence level of its students. Public institutions were found to be significantly overproductive, and eastern men's colleges and universities were found to be significantly underproductive. Previous findings indicating that the faculty had a causative effect on productivity were not confirmed. These results suggest that Ph.D. productivity may not be a sensitive measure of the effectiveness of undergraduate institutions.


Modelling lateral beam quality variations in pencil kernel based photon dose calculations.
Standard treatment machines for external radiotherapy are designed to yield flat dose distributions at a representative treatment depth. The common method to reach this goal is to use a flattening filter to decrease the fluence in the centre of the beam. A side effect of this filtering is that the average energy of the beam is generally lower at a distance from the central axis, a phenomenon commonly referred to as off-axis softening. The off-axis softening results in a relative change in beam quality that is almost independent of machine brand and model. Central axis dose calculations using pencil beam kernels show no drastic loss in accuracy when the off-axis beam quality variations are neglected. However, for dose calculated at off-axis positions the effect should be considered, otherwise errors of several per cent can be introduced. This work proposes a method to explicitly include the effect of off-axis softening in pencil kernel based photon dose calculations for arbitrary positions in a radiation field. Variations of pencil kernel values are modelled through a generic relation between half value layer (HVL) thickness and off-axis position for standard treatment machines. The pencil kernel integration for dose calculation is performed through sampling of energy fluence and beam quality in sectors of concentric circles around the calculation point. The method is fully based on generic data and therefore does not require any specific measurements for characterization of the off-axis softening effect, provided that the machine performance is in agreement with the assumed HVL variations. The model is verified versus profile measurements at different depths and through a model self-consistency check, using the dose calculation model to estimate HVL values at off-axis positions. A comparison between calculated and measured profiles at different depths showed a maximum relative error of 4% without explicit modelling of off-axis softening. The maximum relative error was reduced to 1% when the off-axis softening was accounted for in the calculations.


Chromosome structure and pairing preferences in autotetraploid rye (Secale cereale).
The influence of chromosome structure upon pairing behaviour during meiosis was investigated by comparing four autotetraploid genotypes of rye (Secale cereale) containing homologous chromosome sets with different degrees of structural similarity. The series provided a range of genotypes that, at one extreme, contained structurally identical chromosome sets and, at the other extreme, sets that are certainly more heterozygous in the genic sense and probably also more diverse from a purely structural viewpoint. Relative frequencies of pairing configurations at meiotic prophase and metaphase I were compared by electron microscopy of whole-mount surface-spread synaptonemal complex complements and light microscopy of squash preparations. Despite unexpectedly low quadrivalent frequencies over all four genotypes, higher mean bivalent frequencies appeared to be associated with greater homologue diversity. In other words, greater structural divergence between chromosome sets appears to facilitate more efficient discrimination between homologous and identical chromosomes that drives the formation of bivalents. Statistical comparisons were not able to confirm in some cases the significance of the observed pattern of pairing behaviour.


Effect of treatment with betahistine dihydrochloride on the postural stability in patients with different duration of benign paroxysmal positional vertigo.
The effect of betahistine dihydrochloride on the postural stability after repositioning Epley's maneuver (EM) in patients with BPPV was evaluated by static posturography in open and closed eyes conditions. Ninety patients were divided into four groups by duration (less and above 60 days of BPPV) and by treatment (with and without treatment with betahistine). The investigation was made one hour after the positive Dix-Hallpike test, 10 and 20 days after the treatment with EM. "Sway velocity" (SV) was calculated to evaluate postural stability. The results show dependence between efficacy of treatment with betahistine applied after EM and duration of BPPV. Betahistine normalized postural stability of patients with duration of BPPV less than 60 days after 10 days of treatment and had less effect on patients with duration of BPPV above 60 days. We assume that after removing the otoconia betahistine plays an important role for improving blood flow in the inner ear. The short presence of otoconia didn't damage sensory receptor, and restoring the normal function of motion-sensitive hairs cells and stabilizing the posture was observed.


Advance care planning in the elderly.
Key components of advance care planning (ACP) for the elderly include choosing a surrogate decision maker, identifying personal values, communicating with surrogates and clinicians, documenting wishes in advance directives, and translating values and preferences for future medical care into medical orders. ACP often involves multiple brief discussions over time. This article outlines common benefits and barriers to ACP in primary care, and provides practical approaches to integrating key ACP components into primary care for older adults. Opportunities for multidisciplinary teams to incorporate ACP into brief clinic visits are highlighted.


Anesthetic effects from low concentrations of proparacaine and benoxinate.
Using double masking procedures, the response to McKay-Marg and Goldmann tonometry of 361 randomly selected patients was determined following the installation of a single dose of either 0.125, 0.25 or 0.5% proparacaine or 0.1, 0.2 or 0.4% benoxinate. Examiners graded the adequacy, patient tolerance and conjunctival hyperemia induced by the drop, while the subjects reported on the sting of the drop, awareness of the tonometer and discomfort after the procedure. The results indicate that 0.25% proparacaine is an effective anesthetic dose on all patients and that 0.2% benoxinate and 0.125% proparacaine would be effective on patients over age 40. The implication of these results is that significantly lower doses of anesthetic can be used which will result in less stinging, reduced hyperemia and shorter duration of action.


The localization of some coenzyme A-dependent enzymes in rat liver mitochondria.
1. CoA, acetyl-CoA, l-carnitine and acetyl-l-carnitine when added to rat liver mitochondria equilibrate with approximately two-thirds of the total intramitochondrial water. The mitochondrial space calculated to be freely permeable to these solutes was identical with that obtained for sucrose. 2. Acetyl-CoA is rapidly deacylated by rat liver mitochondria at 0 degrees C, and special precautions are required to measure its mitochondrial permeation. 3. Rat liver mitochondria were separated into fractions that correspond to the inner membrane, the outer membrane, and the soluble proteins of the matrix and intermembrane compartment. Soluble enzymes considered to be located in the matrix were citrate synthase (EC 184.108.40.206), palmitoyl-CoA dehydrogenase (EC 126.96.36.199), electron-transferring flavoprotein, medium-chain-length ATP-specific fatty acyl-CoA synthetase (EC 220.127.116.11), l-3-hydroxybutyryl-CoA dehydrogenase (EC 220.127.116.11) and 3-keto-acyl-CoA thiolase (EC 220.127.116.11). Carnitine palmitoyltransferase (EC 2.3.1.-) is largely associated with the inner-membrane fraction. A long-chain-length ATP-specific fatty acyl-CoA synthetase (EC 184.108.40.206) is associated with the outer-membrane fraction.


The role of the adrenal cortex in polycystic ovary syndrome.
Adrenal androgen excess affects approximately 25% of PCOS patients. The exact etiology of this excess in PCOS patients is unclear. Some evidence that adrenal androgen excess may be a genetic trait. The adrenal androgen response to ACTH is highly individualized, and the relative response seems to be constant over time. In addition, there is a strong familial component to adrenal androgen levels in normal individuals and PCOS patients. It is possible that the tendency to overproduce adrenal androgens is an inherited risk factor for the development of PCOS. Overall, few hyperandrogenic patients actually have isolated deficiencies of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11-hydroxylase. The ovarian hormonal secretion in PCOS can affect adrenal androgen secretion and metabolism, although this factor accounts for only part of this abnormality. More likely, the adrenal androgen excess results from a generalized hyperresponsiveness of the adrenal cortex to ACTH, but without an increase in CRH or ACTH sensitivity. Although glucocorticoid administration may improve the ovulatory function of these patients, the results are modest and cannot be predicted by the circulating androgen levels.


Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients.
The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of distinguishing tumour from normal tissue via conventional fluorescence intensity-based imaging. Here we show that, after systemic injection of the near-infrared dye indocyanine green in patients with various types of solid tumour, the fluorescence lifetime (FLT) of tumour tissue is longer than the FLT of non-cancerous tissue. This tumour-specific shift in FLT can be used to distinguish tumours from normal tissue with an accuracy of over 97% across tumour types, and can be visualized at the cellular level using microscopy and in larger specimens through wide-field imaging. Unlike fluorescence intensity, which depends on imaging-system parameters, tissue depth and the amount of dye taken up by tumours, FLT is a photophysical property that is largely independent of these factors. FLT imaging with indocyanine green may improve the accuracy of cancer surgeries.


Correlated biochemical and cytochemical studies of nicotinamide adenine dinucleotide phosphatase (NADPase) activity in ameloblasts using structural analogues of NADP.
The effects of altering the molecular structure of nicotinamide adenine dinucleotide phosphate (NADP) on enzymatic hydrolysis of the monoester phosphate group was examined at pH 5.0 in rat incisor ameloblasts using eight analogues of the oxidized form of the beta-isomer of NADP (beta-NADP+) modified in either the nicotinamide or adenine regions, or at the site for attachment of the monoester phosphate group to the molecule. Biochemical studies with whole homogenates of unfixed enamel organs revealed that the Michaelis-Menten constant (KM) and the maximum rate of dephosphorylation (Vmax) were different for these analogues relative to values estimated with beta-NADP+ as substrate. For example, the KM value was 3-fold higher and the Vmax value was lower by about 1/2 with the reduced form of the molecule as substrate. The KM value was about 2-fold higher but the Vmax value was about the same with an analogue lacking the nicotinamide group as substrate, while both the KM and the Vmax values were about 2-fold higher with an analogue containing an ethylene group covalently linked to adenine as substrate. In contrast, the KM value was markedly reduced (1/15) and the Vmax value was elevated (4-fold) using an analogue as substrate which contained the phosphate group attached at the 3'-position (3'-NADP+), rather than the 2'-position as in beta-NADP+ and other analogues. Cytochemical studies with glutaraldehyde-fixed enamel organs revealed that reaction product from hydrolysis of beta-NADP+ and other analogues containing the phosphate group attached at the natural 2'-position was localized within the intermediate saccules of the ameloblast Golgi apparatus. Reaction product from hydrolysis of 3'-NADP+, however, was localized at a different site, that is, within granules and membranous connections of the GERL system in the cell. Hence, 3'-NADP+ was not hydrolyzed by NADPase but by another enzyme tentatively identified as Coenzyme A phosphatase.


Immunologic and genetic links between spondylarthropathies and inflammatory bowel diseases.
Spondyloarthritis (SpA) is a well recognized extraintestinal manifestation of Inflammatory Bowel Diseases (IBDs), either Crohn's Disease(CD) or Ulcerative Colitis (UC). A much larger percentage of SpA patients have subclinical gut inflammation manifested either by endoscopic findings or by histology. The aim of the present article is to review clinical and experimental evidences regarding the immunological and genetic links between gut and joint inflammation in IBDs and SpA. A systematic review using PubMed database entering IBD and SpA as key words was performed. The association with HLA-B27 is less strong in IBD-associated SpA than in Idiopathic Ankylosing Spondylitis (AS) and there is some evidence for an association between gut inflammation in SpA and CD related CARD15 mutations. A common inflammatory pathogenic pathway has been suggested in gut and joint inflammation in IBD. Treatment of SpA associated with IBD has gained major advances in recent years with the advent of anti-TNF-alpha therapy. The adaptive immune response in IBD is thought to be strictly differentiated between Th1 and Th2 in CD and UC respectively. Recent findings, however, suggest that novel effector pathways could drive tissue damage. The most important pathway now emerging is the IL-23/IL-17 axis. Present and future advancements of knowledge on mechanisms of inflammation will likely lead to new therapeutic targets.


Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation.
Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection.


[Cutaneous manifestations of HIV].
The human immunodeficiency virus (HIV) is a lentivirus member of the Retroviridae family, the clinical spectrum of which includes: primary infection, clinically asymptomatic stage, early symptomatic infection, and advanced immunodeficiency. The latter can present with complications associated to opportunistic infections, malignancies, and/or neurological diseases. The cutaneous manifestations of HIV are extremely common and include those related with early HIV infection and other infectious diseases (bacterial, viral, fungal, and parasitic) and noninfectious etiologies. These manifestations may be the first signs of immunosuppression and can lead to the HIV diagnosis. The higher frequency of skin diseases occurs when the CD4 count is less than 250 cells/mm3. The knowledge of these defining cutaneous conditions in patients infected with HIV is essential for an early diagnosis of infection, for establishing an early antiretroviral treatment, and improving the prognosis of these patients.


A Nonviral piggyBac Transposon-Mediated Method to Generate Large-Scale CAR-NK Cells from Human Peripheral Blood Primary NK Cells.
With the inherent antitumor function and unique "off-the-shelf" potential, genetically engineered human natural killer (NK) cells with chimeric antigen receptors (CARs) bear great promise for the treatment of multiple hematological malignancies and solid tumors. Current methods of producing large-scale CAR-NK cells mainly rely on mRNA transfection and viral vector transduction. However, mRNA CAR-NK cells were not stable in CAR expression while viral vector transduction mostly ended up with low efficiency. In this chapter, we described an optimized protocol to generate CAR-NK cells by using the piggyBac transposon system via electroporation and to further expand these engineered CAR-NK cells in a large scale together with artificial antigen-presenting feeder cells. This method can stably engineer human primary NK cells with high efficiency and supply sufficient scale of engineered CAR-NK cells for the future possible clinical applications.


Intranasal Pressure Recording for Monitoring Mouse Respiration.
Respiration is a highly dynamic signal that influences voluntary behaviors including odor sampling and entrains rhythmic activity in the brain. Many techniques exist to record respiration with each exhibiting strengths and drawbacks given the ultimate goals of the respiration recording. Intranasal cannula implantation, coupled with pressure sensor recording, allows for temporal precision and detailed feature extraction of the respiratory waveform. Here we describe the implantation process and necessary recording equipment to effectively conduct intranasal pressure recording of respiration. This is an ideal method for understanding the dynamics of odor sampling in conjunction with olfactory sensory transmission.


Cannabis use and mania symptoms: a systematic review and meta-analysis.
Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. This review aimed to examine the impact of cannabis use on the incidence of manic symptoms and on their occurrence in those with pre-existing bipolar disorder. A systematic review of the scientific literature using the PRISMA guidelines. PsychINFO, Cochrane, Scopus, Embase and MEDLINE databases were searched for prospective studies. Six articles met inclusion criteria. These sampled 2391 individuals who had experienced mania symptoms. The mean length of follow up was 3.9 years. Studies support an association between cannabis use and the exacerbation of manic symptoms in those with previously diagnosed bipolar disorder. Furthermore, a meta-analysis of two studies suggests that cannabis use is associated with an approximately 3-fold (Odds Ratio: 2.97; 95% CI: 1.80-4.90) increased risk for the new onset of manic symptoms. We were only able to identify a small number of studies of variable quality, thus our conclusions remain preliminary. Our findings whilst tentative, suggest that cannabis use may worsen the occurrence of manic symptoms in those diagnosed with bipolar disorder, and may also act as a causal risk factor in the incidence of manic symptoms. This underscores the importance of discouraging cannabis use among youth and those with bipolar disorder to help prevent chronic psychiatric morbidity. More high quality prospective studies are required to fully elucidate how cannabis use may contribute to the development of mania over time.


Effect of nano-topographical features of Ti/TiO(2) electrode surface on cell response and electrochemical stability in artificial saliva.
The paper is a new approach which aims to evaluate the relation between surface aspects (wettability and roughness) of materials based on titanium with native passive TiO(2) as untreated samples and TiO(2) nanotubes as treated discs respectively, their electrochemical stability in artificial saliva, and fibroblast cell behavior. Ti/TiO(2) modified electrodes as nanotubes with 120 nm as diameter were obtained using an electrochemical method as anodizing and surface analysis as SEM, AFM and contact angle measurements were performed to obtain topographical features and wettability. The TiO(2) nanotube structured oxide films electrochemical growth increases the stability of titanium surfaces. The electrochemical behavior of the Ti/TiO(2) nanotube surface was evaluated by corrosion parameters obtained from Tafel plots and electrical parameters for proposed circuits from electrochemical impedance spectroscopy were analyzed. The cell results indicated a slight preference in terms of cell survival and adhesion for nanostructure TiO(2) with a more hydrophilic character and the electrochemical data revealed that such features are connected with better stability in artificial saliva. The roughness seems to be not conclusive for this case.


Spatial Patterns in the Distribution, Diversity and Abundance of Benthic Foraminifera around Moorea (Society Archipelago, French Polynesia).
Coral reefs are now subject to global threats and influences from numerous anthropogenic sources. Foraminifera, a group of unicellular shelled organisms, are excellent indicators of water quality and reef health. Thus we studied a set of samples taken in 1992 to provide a foraminiferal baseline for future studies of environmental change. Our study provides the first island-wide analysis of shallow benthic foraminifera from around Moorea (Society Archipelago). We analyzed the composition, species richness, patterns of distribution and abundance of unstained foraminiferal assemblages from bays, fringing reefs, nearshore and back- and fore-reef environments. A total of 380 taxa of foraminifera were recorded, a number that almost doubles previous species counts. Spatial patterns of foraminiferal assemblages are characterized by numerical abundances of individual taxa, cluster groups and gradients of species richness, as documented by cluster, Fisher α, ternary plot and Principal Component Analyses (PCA). The inner bay inlets are dominated by stress-tolerant, mostly thin-shelled taxa of Bolivina, Bolivinella, Nonionoides, Elongobula, and Ammonia preferring low-oxygen and/or nutrient-rich habitats influenced by coastal factors such as fresh-water runoff and overhanging mangroves. The larger symbiont-bearing foraminifera (Borelis, Amphistegina, Heterostegina, Peneroplis) generally live in the oligotrophic, well-lit back- and fore-reef environments. Amphisteginids and peneroplids were among the few taxa found in the bay environments, probably due to their preferences for phytal substrates and tolerance to moderate levels of eutrophication. The fringing reef environments along the outer bay are characterized by Borelis schlumbergeri, Heterostegina depressa, Textularia spp. and various miliolids which represent a hotspot of diversity within the complex reef-lagoon system of Moorea. The high foraminiferal Fisher α and species richness diversity in outer bay fringing reefs is consistent with the disturbance-mosaic (microhabitat heterogeneity) hypothesis. Calculations of the FORAM Index (FI), a single metric index to assess reef vitality, indicate that all fore- and most back-reef environments support active carbonate accretion and provide habitat suitability for carbonate producers dependent on algal symbiosis. Lowest suitability values were recorded within the innermost bays, an area where natural and increasing anthropogenic influences continue to impact the reefs. The presence of habitat specific assemblages and numerical abundance values of individual taxa show that benthic foraminifera are excellent recorders of environmental perturbations and good indicators useful in modern and ancient ecological and environmental studies.


Autonomic function in children with type 1 diabetes mellitus.
We investigated autonomic function in 58 children and young adults with Type 1 diabetes mellitus (aged 7-22 years, duration from 3 to 18, 8.6 +/- 3.4 years) and in 74 healthy controls (6-21 years) using power spectral analysis of blood pressure and heart rate in addition to conventional standard autonomic function tests: deep breathing, the Valsalva manoeuvre, and a standing test. None of the diabetic patients were symptomatic. Reproducibility of the tests was assessed by determining the coefficient of variation in 9 controls (7.8-37.7%). Thirteen per cent of the subjects had difficulty in adequately performing the Valsalva manoeuvre. After adjustment for age, sex, body mass index, and respiratory frequency, results of the Valsalva manoeuvre and deep breathing were not different between patients and controls and there was no significant postural reduction in systolic blood pressure (> or = 20 mmHg) in the patients. Heart rate variation in the supine position during natural breathing was low in patients, although power spectral analysis of heart rate variation did not show a significant decrease in the power density in the high and the low frequency in patients compared to healthy controls. Beat-to-beat blood pressure fluctuation was significantly lower in patients and correlated with metabolic control (mean annual haemoglobin A1c), but not with disease duration and was abnormal in 7 diabetic children (12%). In contrast, tests of vagal activity were not impaired in the patients in this age range. We concluded that vagal involvement in Type 1 diabetic patients determined by spectral analysis of R-R intervals in addition to conventional tests is uncommon, but that beat-to-beat blood pressure variation was more likely to be affected.


Volatile Fragility: New Employment Forms and Disrupted Employment Protection in The New Economy.
This research is based on empirical surveys conducted in two Chinese cities, Beijing and Chengdu, which examine employment relationships, labor protection and social protection in the new digital economy. Through these theoretically informed surveys on various forms of employment via online platforms, we have found that the organizational principles and functional patterns of employment have profoundly transformed in the epoch of digitalization. The traditional employment relationship characterized by written contracts with clearly defined entitlements and obligations for employers and employees have been increasingly substituted by new volatile, fluid and fragile employment forms, softening the labor rights and social rights of "digital employees" and strengthening social control over them through online evaluation systems supported by smart phones and apps. The employees engaged in the online sharing economy have become more individualized and atomized than ever before, resulting in the emergence of an unorganized and disenfranchised "digital working class."


Prospective risk factors for new-onset post-traumatic stress disorder in National Guard soldiers deployed to Iraq.
National Guard troops are at increased risk for post-traumatic stress disorder (PTSD); however, little is known about risk and resilience in this population. The Readiness and Resilience in National Guard Soldiers Study is a prospective, longitudinal investigation of 522 Army National Guard troops deployed to Iraq from March 2006 to July 2007. Participants completed measures of PTSD symptoms and potential risk/protective factors 1 month before deployment. Of these, 81% (n=424) completed measures of PTSD, deployment stressor exposure and post-deployment outcomes 2-3 months after returning from Iraq. New onset of probable PTSD 'diagnosis' was measured by the PTSD Checklist - Military (PCL-M). Independent predictors of new-onset probable PTSD were identified using hierarchical logistic regression analyses. At baseline prior to deployment, 3.7% had probable PTSD. Among soldiers without PTSD symptoms at baseline, 13.8% reported post-deployment new-onset probable PTSD. Hierarchical logistic regression adjusted for gender, age, race/ethnicity and military rank showed that reporting more stressors prior to deployment predicted new-onset probable PTSD [odds ratio (OR) 2.20] as did feeling less prepared for deployment (OR 0.58). After accounting for pre-deployment factors, new-onset probable PTSD was predicted by exposure to combat (OR 2.19) and to combat's aftermath (OR 1.62). Reporting more stressful life events after deployment (OR 1.96) was associated with increased odds of new-onset probable PTSD, while post-deployment social support (OR 0.31) was a significant protective factor in the etiology of PTSD. Combat exposure may be unavoidable in military service members, but other vulnerability and protective factors also predict PTSD and could be targets for prevention strategies.


Risk factors for nuclear, cortical and posterior subcapsular cataracts in the Chinese population of Singapore: the Tanjong Pagar Survey.
To describe risk factors for nuclear, cortical, and posterior subcapsular (PSC) cataracts in Chinese Singaporeans. A population based cross sectional study was carried out on ethnic Chinese men and women aged 40-81 years. A stratified, clustered, disproportionate (more weights to older people), random sampling procedure was used to initially select 2000 Chinese names of those aged 40-79 years from the 1996 electoral register in the Tanjong Pagar district in Singapore. Eligible subjects (n = 1717) were invited for a standardised ocular examination and interview at a centralised clinic, following which an abbreviated examination was conducted for non-respondents in their homes. Cataract was graded clinically using to the Lens Opacity Classification System (LOCS) III system. The main outcome measures were adjusted odds ratio for risk factors for specific cataract types (nuclear, cortical and PSC), any cataract and cataract surgery, examined in multiple logistic regression models. Out of the 1232 (71.8%) examined, 1206 (70.2%) provided lens data for this analysis. Increasing age was associated with all cataract types, any cataract, and cataract surgery. There was no significant sex difference in presence of any cataract, specific cataract types or cataract surgery. After controlling for age, sex, and other factors, diabetes was associated with cortical cataract (3.1; 95% CI: 1.6 to 6.1), PSC cataract (2.2; 95% CI 1.2 to 4.1), any cataract (2.0; 95% CI: 0.9 to 4.5), and cataract surgery (2.3; 95% CI: 1.3 to 4.1). Lower body mass index was associated with cortical cataract (1.8; 95% CI: 1.1 to 2.9; lowest versus highest quintile) and any cataract (2.3; 95% CI: 1.3 to 4.0). Current cigarette smoking was associated with nuclear cataract (1.7, 95% CI: 1.0 to 2.9; more than 10 cigarettes per day versus none). A non-professional occupation was associated with nuclear cataract (2.9; 95% CI: 1.5 to 5.8; for production or machine operators and 2.6; 95% CI: 1.2 to 5.5; for labourers or agricultural workers, both versus professionals). Lower education was associated with nuclear cataract (2.3; 95% CI: 1.0 to 5.2, none versus tertiary), while lower household income was associated with PSC cataract (4.7, 95% CI: 1.1 to 20.0; income <S$2000 versus >S$4000). Age related cataracts are associated with a variety of risk factors among Chinese people in Singapore, similar to those reported in European, Indian, and African derived populations. These data support common aetiological mechanisms for age related cataracts, irrespective of ethnic origin.


Investigation of translocation, DNA unwinding, and protein displacement by NS3h, the helicase domain from the hepatitis C virus helicase.
Helicases are motor proteins that are involved in DNA and RNA metabolism, replication, recombination, transcription, and repair. The motors are powered by ATP binding and hydrolysis. Hepatitis C virus encodes a helicase called nonstructural protein (NS3). NS3 possesses protease and helicase activities on its N-terminal and C-terminal domains, respectively. The helicase domain of NS3 is termed NS3h. In vitro, NS3h catalyzes RNA and DNA unwinding in a 3'-5' direction. The directionality of unwinding is thought to arise in part from the enzyme's ability to translocate along DNA, but translocation has not been shown explicitly. We examined the DNA translocase activity of NS3h by using single-stranded oligonucleotide substrates containing a fluorescent probe on the 5' end. NS3h can bind to the ssDNA and in the presence of ATP move toward the 5' end. When the enzyme encounters the fluorescent probe, a fluorescence change is observed that allows translocation to be characterized. Under conditions that favor binding of one NS3h per DNA substrate (100 nM NS3h and 200 nM oligonucleotide), we find that NS3h translocates on ssDNA at a rate of 46 +/- 5 nucleotides/s, and that it can move for 230 +/- 60 nucleotides before dissociating from the DNA. The translocase activity of some helicases is responsible for displacing proteins that are bound to DNA. We studied protein displacement by using a ssDNA oligonucleotide covalently linked to biotin on the 5' end. Upon addition of streptavidin, a "protein block" was placed in the pathway of the helicase. Interestingly, NS3h was unable to displace streptavidin from the end of the oligonucleotide, despite its ability to translocate along the DNA. The DNA unwinding activity of NS3h was examined using a 22 bp duplex DNA substrate under conditions that were identical to those used to study translocation. NS3h exhibited little or no DNA unwinding under single-cycle conditions, supporting the conclusion that NS3h is a relatively poor helicase in its monomeric form, as has been reported. In summary, NS3h translocates on ssDNA as a monomer, but the translocase activity does not correspond to comparable DNA unwinding activity or protein displacement activity under identical conditions.


Skin epidermis lacking the c-Myc gene is resistant to Ras-driven tumorigenesis but can reacquire sensitivity upon additional loss of the p21Cip1 gene.
The target gene(s) required for Myc-mediated tumorigenesis are still elusive. Here we show that while endogenous c-Myc is surprisingly dispensable for skin homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis is resistant to Ras-mediated DMBA/TPAinduced tumorigenesis. This is mechanistically linked to p21(Cip1), which is induced in tumors by the activated Ras-ERK pathway but repressed by c-Myc. Acute elimination of c-Myc in established tumors leads to the up-regulation of p21(Cip1), and epidermis lacking both p21(Cip1) and c-Myc reacquires normal sensitivity to DMBA/TPA-induced tumorigenesis. This identifies c-Myc-mediated repression of p21(Cip1) as a key step for Ras-driven epidermal tumorigenesis.


Low frequency of 5'-flanking insertion of human insulin gene in Japanese non-insulin-dependent diabetic subjects.
Polymorphism in the 5'-flanking region of the human insulin gene in 149 unrelated Japanese subjects [77 with non-insulin-dependent diabetes mellitus (NIDDM), 17 with insulin-dependent diabetes mellitus (IDDM), and 55 controls] was analyzed with Southern blot hybridization. We used the size of the hybridized fragments to classify the locus into three groups according to Bell's method (a short, class 1 allele averaging 570 base pairs; an intermediate-size, class 2 allele averaging 1320 base pairs, and a long, class 3 allele averaging 2470 base pairs in size). The allelic frequency of classes 2 and 3 in 298 alleles was 5.0% and in the 146 alleles of NIDDM, 7.8%. The value is lower than in Caucasians, American Blacks, and Pima Indians, and the results suggest that the 5'-flanking insertion is not a genetic marker in most NIDDM patients who are Japanese. However, the frequency of the 5'-flanking insertion in those who were not obese and had a family history of diabetes was higher than that of other NIDDM patients (P = .013), and the frequency in NIDDM patients with onset of diabetes at age less than or equal to 39 yr was lower than those whose onset was at age greater than or equal to 40 yr (P = .053). As NIDDM is a heterogeneous disorder, further analysis is needed. These results suggest that we cannot completely exclude the meaning of the insertion in NIDDM. On the other hand, the frequency in IDDM was 0%, lower than in NIDDM (P = .094). Because the number of subjects studied was small, this result is speculative.


A Descriptive Study of Decision-Making Conversations during Pediatric Intensive Care Unit Family Conferences.
Little is known about how decision-making conversations occur during pediatric intensive care unit (PICU) family conferences (FCs). Describe the decision-making process and implementation of shared decision making (SDM) during PICU FCs. Observational study. University-based tertiary care PICU, including 31 parents and 94 PICU healthcare professionals involved in FCs. We recorded, transcribed, and analyzed 14 PICU FCs involving decision-making discussions. We used a modified grounded theory and content analysis approach to explore the use of traditionally described stages of decision making (DM) (information exchange, deliberation, and determining a plan). We also identified the presence or absence of predefined SDM elements. DM involved the following modified stages: information exchange; information-oriented deliberation; plan-oriented deliberation; and determining a plan. Conversations progressed through stages in a nonlinear manner. For the main decision discussed, all conferences included a presentation of the clinical issues, treatment alternatives, and uncertainty. A minority of FCs included assessing the family's understanding (21%), assessing the family's need for input from others (28%), exploring the family's desired decision-making role (35%), and eliciting the family's opinion (42%). In the FCs studied, we found that DM is a nonlinear process. We also found that several SDM elements that could provide information about parents' perspectives and needs did not always occur, identifying areas for process improvement.


Thin carbon layer coated Ti(3+)-TiO2 nanocrystallites for visible-light driven photocatalysis.
Black TiO2 containing Ti(3+) attracts enormous attention due to its excellent visible-light driven photocatalytic activity. Herein, an in situ thermal decomposition approach to synthesize uniform thin carbon coated Ti(3+)-TiO2 nanocrystals is presented. During the oleic acid-assisted solvothermal process, the crystal size and morphology of TiO2 were controlled through oleic acid with carboxylic acid groups. Then the residual small quantities of oleic acid anchored on TiO2 were used as a carbon source, which could be in situ pyrolyzed into a carbon layer on TiO2 at high temperature and under an inert atmosphere. Meanwhile, Ti(4+) species were partly reduced into Ti(3+) states/oxygen vacancies on the surface of TiO2 due to the carbothermal reduction reaction for the carbon-encapsulated Ti(3+)-TiO2 structure. A series of characterizations indicated that the 20-25 nm TiO2 nanocrystals obtained were wrapped evenly by 1-2 nm carbon layers, which had an important effect on the energy band structure change of TiO2. The presence of the carbon layer also improves the Ti(3+) stability and the conduction behavior of the composites. The Ti(3+) states/oxygen vacancies created on the surface of TiO2 were responsible for the remarkable photogenerated charge separation and extended visible-light absorption range. Furthermore, Ti(3+) states/oxygen vacancies and the carbon layer together could enhance the adsorption ability of O2 so as to promote the photogenerated electrons captured by the adsorbed O2, leading to a great increase in the charge separation. As a result, the composites exhibit high photocatalytic performance for organic pollutants under visible light irradiation. This simple and new method may pave the way to practical applications for efficient photocatalytic degradation under visible light.


The effects of ionotropic agonists of excitatory amino acids on the release of arginine vasopressin in rat hypothalamic slices.
The effects of ionotropic excitatory amino acids agonists on the release of vasopressin from rat hypothalamic slices were studied. Incubation with increasing doses of NMDA, kainate or AMPA decreased the release of vasopressin in a dose-dependent manner. The values of the IC50 were 1.0, 9.6, or 3.7 x 10-8 M, respectively. The inhibitory effect of the various excitatory amino acids tested was blocked by coincubation with their respective antagonists. Vasopressin secretion was stimulated to 140.3 +/- 7.6% of controls when the slices were obtained from chronically (7 days) salt-loaded rats. Addition of 1 x 10-7 M NMDA or 1 x 10-6 M kainate to the incubation medium antagonized the salt loading-induced increase in vasopressin release. Incubation with 1 x 10-4 M tetrodotoxin did not change basal vasopressin release, but it blocked the decrease in vasopressin secretion induced by 1 x 10-7 M NMDA or 1 x 10-6 M kainate or 1 x 10-6 M AMPA. Incubation with 1 x 10-5 M phaclophen (a GABAB antagonist) and 1 x 10-5 M bicuculline (a GABAA antagonist) was without effect on basal vasopressin secretion while it reversed the inhibition of vasopressin release induced by 1 x 10-7 M NMDA. Incubation with 1 x 10-6 M GABA alone decreased vasopressin secretion to 64.6 +/- 6.9% of control values. The inhibitory effect of GABA did not change when 1 x 10-7 M NMDA was added to the incubation medium. These findings demonstrate that ionotropic excitatory amino acids agonists inhibit vasopressin secretion from hypothalamic slices. They strongly suggest that this inhibitory effect is mediated through local GABAergic interneurones.


[Identification and early nutritional support in hospitalized malnourished patients].
The prevalence of hyponutrition in hospitalized patients in our setting is 53%. The therapeutic approach is controversial. To determine whether an early nutritional intervention in hospitalized patients by means of oral nutritional support can improve their prognosis regarding decreased morbimortality and hospital stay. Randomized prospective study comprised by a treatment group and a control group of malnourished patients hospitalized at the Internal Medicine and Respiratory Medicine Departments. The nutritional diagnosis was made by using the Subjective Global Assessment. Groups B and C were assigned to receive the hospital diet according to their needs and pathology (control group) and the treatment group also received a standard nutritional supplement. We recorded the development of infections, pressure ulcers, hospitalization days, mortality, and weight. We performed more than 1,700 Subjective Global Assessments. Five hundred and thirty seven patients (264 treated and 273 controls) were followed-up until hospital discharge or death. We did not find statistically significant differences in mortality, hospital stay, or occurrence of complications between the treatment group and the control group. The treatment group presented statistically significant weight increase as compared with the control group. We could not demonstrate benefits when using the oral nutritional supplement in terms of mortality, hospital stay, infectious complications, or pressure ulcers. The significant weight increase in the treatment group allowed us concluding that the supplement effectively treated hyponutrition in this group. This new clinical status implies a better prognosis, as it has already been shown. However, this could not be observed by means of the study parameters. Long-term studies are required to determine for how long this nutritional improvement can be sustained, implying a better prognosis in the long run.


Current status of pulmonary metastasectomy from primary epithelial tumors.
The resection of pulmonary metastases can prolong the survival of selected patients and its therapeutic value is now accepted. The criteria for eligibility have also evolved. We reviewed the recent literature on pulmonary metastasectomy for various epithelial primary tumors and tried to establish better prognostic indicators for its surgical application. In addition to the welldefined requisites for pulmonary metastasectomy, other requirements include the absence of mediastinal lymph node involvement, a limited number of pulmonary metastatic lesions, a long disease-free interval, small metastasis, and no elevation of tumor markers, although the clinical importance of each factor varies among the primary tumors. On the other hand, with the development of video-assisted thoracoscopic surgery (VATS) and advances in thoracic imaging technology, VATS metastasectomy might become an accepted treatment for metastatic nodules located in the periphery of the lung, which can be easily removed by a wedge resection. Repeat surgery is also possible during follow-up after VATS.


Involvement of a Gr2a-Expressing Drosophila Pharyngeal Gustatory Receptor Neuron in Regulation of Aversion to High-Salt Foods.
Regulation of feeding is essential for animal survival. The pharyngeal sense organs can act as a second checkpoint of food quality, due to their position between external taste organs such as the labellum which initially assess food quality, and the digestive tract. Growing evidence provides support that the pharyngeal sensory neurons regulate feeding, but much is still unknown. We found that a pair of gustatory receptor neurons in the LSO, a Drosophila adult pharyngeal organ which expresses four gustatory receptors, is involved in feeding inhibition in response to high concentrations of sodium ions. RNAi experiments and mutant analysis showed that the gustatory receptor Gr2a is necessary for this process. This feeding preference determined by whether a food source is perceived as appetizing or not is influenced by nutritional conditions, such that when the animal is hungry, the need for energy dominates over how appealing the food source is. Our results provide experimental evidence that factors involved in feeding function in a context-dependent manner.


[Cultivation of Leptospira in a liquid culture medium with lysed rabbit blood].
A new method of the preparation of liquid culture medium for the cultivation of Leptospira has been developed on the basis of multiple freezing and thawing of defibrinated rabbit blood. A higher productivity of the new medium in comparison with the medium used in common practice has been established. The medium having a new composition is suitable for cultivation of Leptospira and the accumulation of biomass. The advantage of the medium made is in addition to high growth properties, the its economic efficiency and availability for practical laboratories.


Estimation of Ontogeny Functions for Renal Transporters Using a Combined Population Pharmacokinetic and Physiology-Based Pharmacokinetic Approach: Application to OAT1,3.
To date, information on the ontogeny of renal transporters is limited. Here, we propose to estimate the in vivo functional ontogeny of transporters using a combined population pharmacokinetic (popPK) and physiology-based pharmacokinetic (PBPK) modeling approach called popPBPK. Clavulanic acid and amoxicillin were used as probes for glomerular filtration, combined glomerular filtration, and active secretion through OAT1,3, respectively. The predictive value of the estimated OAT1,3 ontogeny function was assessed by PBPK predictions of renal clearance (CLR) of other OAT1,3 substrates: cefazolin and piperacillin. Individual CLR post-hoc values, obtained from a published popPK model on the concomitant use of clavulanic acid and amoxicillin in critically ill children between 1 month and 15 years, were used as dependent variables in the popPBPK analysis. CLR was re-parameterized according to PBPK principles, resulting in the estimation of OAT1,3-mediated intrinsic clearance (CLint,OAT1,3,invivo) and its ontogeny. CLint,OAT1,3,invivo ontogeny was described by a sigmoidal function, reaching half of adult level around 7 months of age, comparable to findings based on renal transporter-specific protein expression data. PBPK-based CLR predictions including this ontogeny function were reasonably accurate for piperacillin in a similar age range (2.5 months-15 years) as well as for cefazolin in neonates as compared to published data (%RMSPE of 21.2 and 22.8%, respectively and %PE within ±50%). Using this novel approach, we estimated an in vivo functional ontogeny profile for CLint,OAT1,3,invivo that yields accurate CLR predictions for different OAT1,3 substrates across different ages. This approach deserves further study on functional ontogeny of other transporters.


A systematic review of dynamometry and its role in hand trauma assessment.
The dynamometer was developed by American neurologists and came into general use in the late 19th century. It is still used in various ways as a diagnostic and prognostic tool in clinical settings. In this systematic review we assessed in detail the different uses of dynamometry, its reliability, different dynamometers used and the influence of rater experience by bringing together and evaluating all published literature in this field. It was found that dynamometry is applied in a wide range of medical conditions. Furthermore, the great majority of studies reported acceptable to high reliability of dynamometry. Jamar mechanical dynamometer was used most often in the studies reviewed. There were mixed results concerning the effect of rater experience. The factors influencing the results of dynamometry were identified as age, gender, body weight, grip strength, BMI, non/dominant hand, assessing upper/lower limbs, rater and patient's strength and the distance from the joint where the dynamometer is placed. This review provides an understanding of the relevance and significance of dynamometry which should serve as a starting point to guide its use in hand trauma assessment. On the basis of our findings, we suggest that hand dynamometry has a great potential, and could be used more often in clinical practice.


Novel and emerging targets for cholangiocarcinoma progression: therapeutic implications.
Cholangiocarcinoma (CCA) is a heterogeneous group of aggressive biliary malignancies. While surgery and liver transplantation are the only potentially curative modalities for early-stage disease, limited options are available for most patients with incurable-stage disease. Survival outcomes remain dismal. Recent molecular profiling efforts have led to improved understanding of the genomic landscape of CCA and to the identification of subgroups with distinct diagnostic, prognostic, and therapeutic implications. : We provide an updated review and future perspectives on features of cholangiocarcinogenesis that can be translated into therapeutic biomarkers and targets. We highlight the critical studies that have established current systemic chemotherapy and targeted therapeutics, while elaborating on novel targeted and immunotherapeutic approaches in development. Relevant literature and clinical studies were identified by searching PubMed and www.ClinicalTrials.gov. : While therapies targeting the various molecular subgroups of CCA are rapidly emerging and changing treatment paradigms, their success has been limited by the genetic heterogeneity of CCA and the plasticity of the targets. Novel strategies aiming to combine immunotherapy, chemotherapy, and molecularly targeted therapeutics will be required to offer durable clinical benefit and maximize survival.


Clinicopathologic study of Wegener's granulomatosis with special emphasis on early lesions in 10 Korean patients.
We reviewed ten cases of Wegener's granulomatosis with special emphasis on the characteristics of the early stage of Wegener's granulomatosis. All patients presented with nonspecific symptoms and signs, so that Wegener's granulomatosis was not initially considered. However, half of the patients had clinical or radiologic disease in the nose/or paranasal sinuses as the primary presenting problems and showed neutrophil microabscess surrounded by palisading epithelioid cells and irregularly arranged giant cells in the nasal biopsy as the most characteristic feature. Five of ten patients were believed to have a protracted superficial phenomenon before involvement of other organs, specifically the lung or kidney. Four of ten patients showed nonreactivity to ANCA test at the time of presentation. Although the number of cases reviewed in this study was small, the rate of nonreactivity to ANCA was higher than those of the larger series. The importance of early diagnosis of Wegener's granulomatosis can not be overemphasized in view of the fact that cases unrecognized clinicopathologically finally progress to full-blown systemic form of Wegener's granulomatosis with poor prognosis. The diagnosis of Wegener's granulomatosis should be based on a thorough and meticulous examination of its characteristic histologic changes in biopsied tissue particularly extravascular foci.


2-[2'-(Dimethylamino)ethyl]-1,2-dihydro- 3H-dibenz[de,h]isoquinoline-1,3-diones with substituents at positions 4, 8, 9, 10, and 11. Synthesis, antitumor activity, and quantitative structure-activity relationships.
New 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3- diones with substituents at the 4, 8, 9, 10, and 11 positions were synthesized. Diazonium salts prepared from aminoazonafides were key intermediates for many of the analogues. Six of the new compounds were more potent than azonafide in a panel of tumor cells including human melanoma and ovarian carcinoma and murine L1210 leukemias. Three of these compounds, the 10-OCH3, 10-OC2H5, and 10-F analogues, had better ratios of cardiotoxicity to tumor-cell toxicity than azonafide. Eight compounds were not cross-resistant with MDR L1210 leukemia, and the 10-CN analogue was more potent against solid tumor cells than leukemia cells. The 9-OH, 10-CN, and 10-F analogues had high potency against both sensitive and resistant cell lines of MFX 7 breast carcinoma and WiDr colon carcinoma and sensitivity A599 lung carcinoma. Advantages of the 10-Cl, 10-NH2, and 10-CN analogues over azonafide were apparent in P388 leukemia in mice, and the 10-CN analogue was more effective than doxorubicin in this assay. Quantitative structure-activity relationship studies revealed statistically significant correlations between DNA binding strength of 8- and 10-substituted azonafides, as measured by deltaTm, and toxicity to tumor cells. There also were correlations between substituent size, as measured by MR, and cytotoxicity for 9- and 10-substituted azonafides and between MR and deltaTm for 4- and 11-substituted azonafides. Lipophilicity of substituents (pi) correlated with cytotoxicity for 9-, 10-, and 11-substituted azonafides. These results lend support to a model in which DNA binding strength influences cytotoxic potency, and lipophilicity increases DNA binding whereas large substituents decrease it.


Opposite causal effects of birthweight on myocardial infarction and atrial fibrillation and the distinct mediating pathways: a Mendelian randomization study.
Previous observational studies have documented an inverse association of birthweight with myocardial infarction (MI) but a positive association with atrial fibrillation (AF). However, the causality of these associations and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of birthweight, incorporating both fetal and maternal genetic effects, on MI and AF, and identify potential mediators in their respective pathways. We performed Mendelian randomization (MR) analyses using genome-wide association study summary statistics for birthweight (N = 297,356 for own birthweight and 210,248 for offspring birthweight), MI (Ncase=61,000, Ncontrol=577,000), AF (Ncase=60,620, Ncontrol=970,216), and 52 candidate mediators (N = 13,848-1,295,946). Two-step MR was employed to identify and assess the mediation proportion of potential mediators in the associations of birthweight with MI and AF, respectively. As a complement, we replicated analyses for fetal-specific birthweight and maternal-specific birthweight. Genetically determined each 1-SD lower birthweight was associated with a 40% (95% CI: 1.22-1.60) higher risk of MI, whereas each 1-SD higher birthweight was causally associated with a 29% (95% CI: 1.16-1.44) higher risk of AF. Cardiometabolic factors, including lipids and lipoproteins, glucose and insulin, blood pressure, and fatty acids, each mediated 4.09-23.71% of the total effect of birthweight on MI, followed by body composition and strength traits (i.e., appendicular lean mass, height, and grip strength) and socioeconomic indicators (i.e., education and household income), with the mediation proportion for each factor ranging from 8.08 to 16.80%. By contrast, appendicular lean mass, height, waist circumference, childhood obesity, and body mass index each mediated 15.03-45.12% of the total effect of birthweight on AF. Both fetal-specific birthweight and maternal-specific birthweight were inversely associated with MI, while only fetal-specific birthweight was positively associated with AF. Psychological well-being and lifestyle factors conferred no mediating effect in either association. Cardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.


The targets of CAPRI rounds 20-27.
Eight CAPRI prediction rounds with a total of 15 targets were held in the years 2010-2012. Only five of the targets were protein assemblies comparable with those of earlier CAPRI rounds. In one target, the solvent positions at the interface had to be predicted; another was a protein-polysaccharide complex. The remainders were designed complexes issued from protein engineering experiments, and the prediction concerned either their structure or the binding affinity of the designed ligand. Affinity prediction was a new experiment in CAPRI, and a challenge for its participants. It pushed the community into developing novel procedures and score functions that will improve the performance of docking methods, help designing binders, and yield better structure-based estimates of the binding free energy of natural assemblies.


Effectiveness of home-based pulmonary rehabilitation for patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials.
The pulmonary rehabilitation program has become a cornerstone in the management of patients with chronic obstructive pulmonary disease (COPD). Programs based in hospital and treatment facilities, however, are inconvenient and underutilized. A home-based program is a promising alternative, but studies of its effectiveness have yielded inconsistent results. The purpose of this study is to evaluate the impact of home-based pulmonary rehabilitation programs on health-related quality of life (HRQoL) and other health outcomes in patients with COPD. Randomized controlled trials (RCTs) of home-based pulmonary rehabilitation programs published between February 1991 and February 2012 were retrieved from electronic databases (PubMed, Cochrane Library, Science Direct, China National Knowledge Infrastructure [CNKI], and Wanfang Database). Two reviewers independently assessed topical relevance and trial quality, extracted data for meta-analysis using the Review Manager v5.1 software, and contacted the original studies' authors for additional information. Eighteen trials, comprising 733 randomized patients, were included in the meta-analysis. COPD patients experienced significant relief in dyspnea status, measured by the Borg score (Fixed effects model, WMD = -0.92, 95% CI: -1.61~-0.23, p = .009) and baseline dyspnea index (BDI) (Fixed effects model, WMD = -1.77, 95% CI: -2.65~-0.89, p < .0001) after 12 weeks of home-based intervention. Home-based intervention also improved patients' HRQoL scores, measured by the Chronic Respiratory Questionnaire (CRQ) and St. George's Respiratory Questionnaire (SGRQ) (Fixed effects model, WMD = -11.33, 95% CI: -16.37~-6.29, p < .0001, SGRQ total scores after 12 weeks of intervention); exercise capacity (measured by the 6-minute walking distance test (6MWD) (Fixed effects model, WMD = 35.88, 95% CI: 9.38~62.38, p = .008, after 12 weeks of intervention); and pulmonary functions (measured by forced expiratory volume in one-second/forced vital capacity (FEV1 /FVC) [Random effects model, WMD = -10.72, 95% CI: -15.86~-5.58, p < .0001, after 12 weeks of intervention), as compared with the nonintervention control group; however, no statistically significant changes were seen in maximal workload, hospital admission, cost of care, or mortality between the two groups. Home-based pulmonary rehabilitation programs represent effective therapeutic intervention approaches for relieving COPD-associated respiratory symptoms and improving HRQoL and exercise capacity. Rigorously designed, large-scale RCTs are still needed to identify an optimal standard home-based pulmonary rehabilitation program.


Weight loss through adjustable gastric banding and improvement in daytime sleepiness: 2 year interim results of APEX study.
Obesity is one factor associated with an increased risk of obstructive sleep apnea (OSA). This study reports the investigator-reported resolution or improvement of OSA and improvements in sleep-related quality of life (QOL) 2 years after surgical placement of the LAP-BAND AP * (LBAP) system. The LBAP Experience (APEX) study is an ongoing 5 year, prospective, observational study assessing change in weight, comorbidities, and QOL after LBAP implantation. This is an interim analysis of patients with evaluable data at 24 months who had OSA at baseline. NCT00501085. At baseline, 117 of 395 patients (29.6%; mean body mass index [BMI], 45.0 kg/m2) reported OSA; of these, 57 had evaluable patient-reported outcome data at 2 years. Investigator-reported resolution or improvement of OSA was 69% and 86% at post-operative years 1 and 2, respectively. Patients reporting resolution, improvement, or no change in OSA experienced mean changes in BMI and percentage of weight loss of -9.7 kg/m(2)/-21.7%, -8.3 kg/m(2)/-18.7%, and -5.7 kg/m(2)/-13.2%, respectively (n = 54). Mean 2 year BMI was not statistically different between the groups (p = not significant). Mean scores for all Epworth Sleepiness Scale responses for the OSA population improved by -0.43 from baseline (p < 0.0001; n = 78) compared with -0.29 for patients without OSA at baseline (n = 177; p = 0.037 between groups). In addition, the overall study population experienced resolution and/or improvement in other obesity-related comorbidities, such as type 2 diabetes (96%) and hypertension (91%). These data support that surgically facilitated weight loss can improve sleep-related QOL and may result in resolution or improvement of OSA; the degree of weight loss may be related to these changes.


A Quartet of Elastic Stable Intramedullary Nails for More Challenging Pediatric Femur Fractures.
The insertion of 2 elastic stable intramedullary nails (ESINs) is a common treatment for pediatric femur fractures. However, the use of this technique in length-unstable or metadiaphyseal fractures has historically been associated with higher complication rates. To improve stability, the addition of a third ESIN has been assessed biomechanically and clinically, but the addition of a fourth nail has only been evaluated biomechanically. The purpose of this study is to report our surgical technique and radiographic outcomes using a quartet of ESINs in pediatric femur fractures. A retrospective review was performed of pediatric patients with length-unstable or metadiaphyseal femur fractures who were treated with 4 ESINs by a single surgeon from 2008 to 2013. Nails were inserted in a retrograde manner, 2 each from medial and lateral starting points. Patients were followed clinically and radiographically until the union and routine removal of hardware. Primary outcomes included fracture union, sagittal, and coronal plane alignment, and complications. Fourteen patients underwent quartet ESIN placement. Two patients were excluded: one for early loss to follow-up and another with a diagnosis of osteogenesis imperfecta. The average patient age was 9.3 years (range, 4 to 14 y) and weight was 47 kg (range, 21 to 95 kg). All fractures achieved radiographic union at mean 5.5 months (range, 2 to 9 mo). Hardware was removed at a mean of 9.4 months (range, 2 to 22 mo) following implantation. At final mean follow-up of 18 months, patients and families reported no functional limitations. There were no hardware failures or revision surgeries. There were no limb length discrepancies or malalignment at the time of final radiographic follow-up. There were 2 minor complications-1 patient with pain secondary to nail migration resulting in prominence at the knee and another with refracture following a fall. The stable refracture occurred before complete fracture union and hardware removal and went on to the union without the need for any additional treatment. Treatment with a quartet of ESINs should be considered for skeletally immature children with length-unstable or metadiaphyseal femur fractures. In this series, all fractures achieved union without major complications or hardware failure. This modification to traditional elastic nailing techniques is an option for the surgeon to consider as an alternative to rigid intramedullary nailing, submuscular plating, or external fixation. Level IV.


Efficient coding of subjective value.
Preference-based decisions are essential for survival, for instance, when deciding what we should (not) eat. Despite their importance, preference-based decisions are surprisingly variable and can appear irrational in ways that have defied mechanistic explanations. Here we propose that subjective valuation results from an inference process that accounts for the structure of values in the environment and that maximizes information in value representations in line with demands imposed by limited coding resources. A model of this inference process explains the variability in both subjective value reports and preference-based choices, and predicts a new preference illusion that we validate with empirical data. Interestingly, the same model explains the level of confidence associated with these reports. Our results imply that preference-based decisions reflect information-maximizing transmission and statistically optimal decoding of subjective values by a limited-capacity system. These findings provide a unified account of how humans perceive and valuate the environment to optimally guide behavior.


Gene and cell-based therapies for heart disease.
Heart disease remains the prevalent cause of premature death and accounts for a significant proportion of all hospital admissions. Recent developments in understanding the molecular mechanisms of myocardial disease have led to the identification of new therapeutic targets, and the availability of vectors with enhanced myocardial tropism offers the opportunity for the design of gene therapies for both protection and rescue of the myocardium. Genetic therapies have been devised to treat complex diseases such as myocardial ischemia, heart failure, and inherited myopathies in various animal models. Some of these experimental therapies have made a successful transition to clinical trial and are being considered for use in human patients. The recent isolation of endothelial and cardiomyocyte precursor cells from adult bone marrow may permit the design of strategies for repair of the damaged heart. Cell-based therapies may have potential application in neovascularization and regeneration of ischemic and infarcted myocardium, in blood vessel reconstruction, and in bioengineering of artificial organs and prostheses. We expect that advances in the field will lead to the development of safer and more efficient vectors. The advent of genomic screening technology should allow the identification of novel therapeutic targets and facilitate the detection of disease-causing polymorphisms that may lead to the design of individualized gene and cell-based therapies.


Association between increase in fixed penalties and road safety outcomes: A meta-analysis.
Studies that have evaluated the association between increases in traffic fine amounts (fixed penalties) and changes in compliance with road traffic law or the number of accidents are synthesised by means of meta-analysis. The studies were few and different in many respects. Nine studies were included in the meta-analysis of changes in compliance. Four studies were included in the meta-analysis of changes in accidents. Increasing traffic fines was found to be associated with small changes in the rate of violations. The changes were non-linear. For increases up to about 100%, violations were reduced. For larger increases, no reduction in violations was found. A small reduction in fatal accidents was associated with increased fixed penalties, varying between studies from less than 1-12%. The main pattern of changes in violations was similar in the fixed-effects and random-effects models of meta-analysis, meta-regression and when simple (non-weighted) mean values were computed. The main findings are thus robust, although most of the primary studies did not control very well for potentially confounding factors. Summary estimates of changes in violations or accidents should be treated as provisional and do not necessarily reflect causal relationships.


JC virus latency in the brain and extraneural organs of patients with and without progressive multifocal leukoencephalopathy.
JC virus (JCV) is latent in the kidneys and lymphoid organs of healthy individuals, and its reactivation in the context of immunosuppression may lead to progressive multifocal leukoencephalopathy (PML). Whether JCV is present in the brains or other organs of healthy people and in immunosuppressed patients without PML has been a matter of debate. We detected JCV large T DNA by quantitative PCR of archival brain samples of 9/24 (38%) HIV-positive PML patients, 5/18 (28%) HIV-positive individuals, and 5/19 (26%) HIV-negative individuals. In the same samples, we detected JCV regulatory region DNA by nested PCR in 6/19 (32%) HIV-positive PML patients, 2/11 (18%) HIV-positive individuals, and 3/17 (18%) HIV-negative individuals. In addition, JCV DNA was detected in some spleen, lymph node, bone, and kidney samples from the same groups. In situ hybridization data confirmed the presence of JCV DNA in the brains of patients without PML. However, JCV proteins (VP1 or T antigen) were detected mainly in the brains of 23/24 HIV-positive PML patients, in only a few kidney samples of HIV-positive patients, with or without PML, and rarely in the bones of HIV-positive patients with PML. JCV proteins were not detected in the spleen or lymph nodes in any study group. Furthermore, analysis of the JCV regulatory region sequences showed both rearranged and archetype forms in brain and extraneural organs in all three study groups. Regulatory regions contained increased variations of rearrangements correlating with immunosuppression. These results provide evidence of JCV latency in the brain prior to severe immunosuppression and suggest new paradigms in JCV latency, compartmentalization, and reactivation.


Prevention and regression of hypertension: role of renal microvascular protection.
Hypertension is a disease which affects over 26.4% of the world adult population, therefore novel approaches to the prevention and treatment of this disease need to be examined. Previous studies from our and other laboratories have shown that treatment of spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats with a renin-angiotensin system (RAS) inhibitor during the 'critical period' in hypertension development results in prevention of the later development of hypertension. In humans, Julius et al. reported similar findings in the landmark TROPHY study. Recently, we reported that 'pulse' treatment of SHR with high-dose angiotensin receptor blocker (ARB) is effective in causing sustained reduction of already established hypertension, even when the treatment was started after the 'critical period'. These results suggest the possibility that 'regression' of established hypertension may become feasible, and we have started a prospective, multicenter clinical study (STAR CAST study) to examine this possibility. In our animal studies, we found that treatment of rats during the 'critical period' with an ARB inhibits the development of renal arteriolar hypertrophy. Moreover, a high-dose angiotensin blocker caused a remarkable reversal of renal arteriolar hypertrophy in SHR, which was associated with changes in microvascular MMP expression. These results suggest that changes in the renal microvasculature may have an important role in the mechanisms of hypertension prevention and regression by ARB.


A preliminary report on regenerative healing in the equine tendon.
The concept of regenerative healing has been used to manipulate the healing process in experimental animals and clinically to augment bone healing in people after orthopedic operation. An implanted electrical device was used in an attempt to produce regenerative healing in experimentally created equine tendon injury. The bimetallic electrical implant did not produce regenerative healing under the conditions of this experiment. The mechanism of implantation and discussion of the results are included.


A novel NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein (CTBP; 5.1S) in rat liver: a comparison with 4.7S NADPH-dependent CTBP.
A novel NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) was purified by sequential fractionation of rat liver cytosol on Q-Sepharose, phenyl-Sepharose, red-Sepharose, and polyacrylamide gel electrophoresis under nondenaturing conditions. The CTBP had a sedimentation coefficient of 5.1S, a Stokes' radius of 35 A, and a calculated mol wt of 76,000. The apparently homogenous protein consisted of a dimer of a polypeptide chain with a mol wt of 38,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. NADPH increased both the affinity and maximal binding capacity for T3 in the 5.1S CTBP. The maximal activity to bind T3 was obtained by 3.0 x 10(-8) M NADPH. The calculated maximal affinity constant was 2.4 x 10(9) M-1, and the maximal binding capacity was 21,000 pmol T3/mg 5.1S CTBP. The order of affinity of iodothyronine analogs to the 5.1S CTBP was as follows: D-T3 greater than L-T3 greater than L-T4 greater than triiodothyroacetic acid. The optimal pH for T3 binding was 7.2-7.5. Ca2+, Mg2+, and Mn2+ (0.1-10 mM) did not influence T3 binding to CTBP. Zn2+ (1.0 mM), however, inhibited the binding. These results suggested that 5.1S NADPH-dependent CTBP, which is distinct from 4.7S CTBP that had been purified in our laboratory from rat kidney, is present in rat liver.


Growth hormone for in vitro fertilization.
In an effort to improve outcomes of in vitro fertilisation (IVF) cycles the use of growth hormone (GH) has been considered. Most studies investigate the role of GH in normally ovulating infertile women but there is also an interest in the effect of GH on women who respond poorly to ovulation induction and IVF. To assess the effectiveness of GH or growth hormone releasing (GRF) adjuvant therapy, primarily in terms of improving livebirth rate, for women undergoing ovulation induction prior to IVF in (a) patients with no previous history of poor response and (b) patients with a history of poor response. We searched the Cochrane Menstrual Disorders and Subfertility Group's trials register (24 March 2003), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1966 to Feb 2003), EMBASE (1988 to Feb 2003) and Biological Abstracts (1969 to Feb 2003). Reference lists of articles were also searched. All randomised controlled trials were included if they addressed the research question and provided outcome data for intervention and control subjects. Assessment of trial quality and extraction of relevant data was performed independently by two reviewers. Validity was assessed in terms of method of randomisation, completeness of follow-up and co-intervention. Nine studies (401 couples) were included. Three trials concerned patients with no history of poor response to IVF (91 women) and six investigated previous poor responders (302 women). There was no evidence that routine use of GH affected the outcome of livebirth (3 RCTs; OR 1.17, 95% CI 0.38 to 3.59). In women who had previously responded poorly to IVF there was no significant differences in livebirth when combining trials of GH and GRF (4 RCTs; OR 2.42, 95% CI 0.94 to 6.23). However when trials using GH were analysed separately there was an increase in livebirths (3 RCTs; OR 4.37, 95% CI 1.06 to 18.01). There was no significant differences in any adverse events, but these were poorly and inconsistently reported. Although the use of GH in previous poor responders has been found to show a significant improvement in livebirth rate, this result was only just significant. Also, this data is from just three small trials. Therefore, before recommending GH in IVF further research is necessary to fully define its role. Meanwhile GH should only be considered in the context of a clinical trial.


Tracheal injury following robotic thyroidectomy: A literature review of epidemiology, etiology, diagnosis, and treatment and 3 case reports.
Robotic thyroidectomy is one of the most advanced surgical procedures used to manage benign and malignant thyroid nodules. However, complication risks such as tracheal injury still exists. Tracheal injury in robotic thyroidectomy is difficult to detect and is one of the life-threatening complications. This study reviews the current literature on the tracheal injury following robotic thyroidectomy and also discusses our findings on 2060 cases of robotic thyroidectomy via Da Vinci Surgical System performed in our department and finally presents 3 cases treated in our center. PubMed and Web of Science database were searched using Medical Subject Headings (Mesh) related to "tracheal injury" and "robotic thyroidectomy". The search was conducted without publication date limits. We reviewed the literature and summarized common causes, diagnosis and therapeutic options of tracheal injury in robotic thyroidectomy, which has been described in comparison studies or retrospective studies. Tracheal injury is often diagnosed when patients suffer from dyspnea and usually leads to severe postoperative consequences. Tracheal injury can be suspected in all patients having subcutaneous emphysema, pneumomediastinum, pneumothorax or dyspnea after robotic thyroidectomy. Tracheoscopy is necessary to determine the location and size of tracheal injury. In patients whose condition is stable and the injury is contained, conservative treatment is feasible. Certainly, primary closure or tracheotomy is necessary for patients with serious respiratory difficulty or pneumothorax.


Coronary risk correlates with cerebral amyloid deposition.
This study investigated the hypothesis that vascular risk factors are amyloidogenic. Participants were 43 persons, most with normal cognition or mild cognitive impairment. Vascular risk was quantified using the Framingham Coronary Risk Profile (FCRP) score. Cerebral amyloid was measured by [(11)C]Pittsburgh compound B (PIB) positron emission tomography (PET) and quantified with a Global PIB index, which is the average of distribution volume ratios in selected cortical regions of interest. In a bivariate model FCRP accounted for 16% of the variance in PIB index (p < 0.008) and the positive association remained significant controlling for age and sex. The effect of FCRP was independent of apolipoprotein E (APOE) genotype, which was also associated as expected with PIB. Carotid intima-media thickness was not associated with PIB index. Effects of individual FCRP component risk factors, cholesterol, and glycemic status on PIB index were all nonsignificant, suggesting an aggregate effect of risk factors. Although this is a correlational observation it may represent a causal relationship as there are multiple, plausible, amyloidogenic mechanisms of vascular risk factors.


The effects of feed bunk competition on the feed sorting behavior of close-up dry cows.
The objectives of this research were to describe the feed sorting, feeding behavior, and feed intake of cows consuming a close-up ration and to determine if these behaviors are affected by competition for access to the feed bunk. Thirty-six dry Holstein cows, consuming a close-up total mixed ration diet, were assigned to 1 of 2 treatments: 1) noncompetitive (1 cow/feed bin) or 2) competitive (2 cows/feed bin). Dry matter intake, feeding behavior, and sorting behavior were monitored for each feed bin on 4 separate days during wk 2 and 3 before the anticipated calving dates of the cows. Fresh feed and orts were sampled daily from each bin and were subjected to particle size analysis. The particle size separator consisted of 3 screens (18, 9, and 1.18 mm) and a bottom pan resulting in 4 fractions (long, medium, short, and fine). Sorting was calculated as the actual intake of each particle size fraction expressed as a percentage of the predicted intake of that fraction. Regardless of treatment, the cows sorted against long particles and for short and fine particles. Competition at the feed bunk had no effect on the sorting behavior, dry matter intake, or feeding time of the cows, but did dramatically increase the feeding rate of the cows. The competitively fed cows also had fewer meals per day, and tended to have larger and longer meals. Our results suggest that increased competition at the feed bunk promotes feeding behavior patterns that will likely increase the between-cow variation in composition of total mixed ration consumed.


Brief communication: investigating the relationship between psychopathy and interoceptive awareness.
Psychopathy is a disorder that is characterized by marked emotional deficiencies. Because previous studies suggest that an individual's sensitivity to bodily signals--or "interoceptive awareness"--is associated with various components of emotional functioning, the authors expected this capacity to be reduced in psychopathic individuals. Therefore, the current study examined the relationship between psychopathy and interoceptive awareness by assessing heartbeat detection abilities in a group of 75 male personality disordered offenders, varying in their degree of psychopathy, as assessed with the Hare Psychopathy Checklist-Revised (PCL-R; Hare, 2003). Regression analyses revealed that PCL-R Facet 4, which reflects antisocial behavior, was predictive of reduced interoceptive awareness. These findings suggest that the expression of psychopathic behavior might be influenced by an attenuated sensitivity to one's own bodily signals.


Implementation and Evaluation of a Wiki Involving Multiple Stakeholders Including Patients in the Promotion of Best Practices in Trauma Care: The WikiTrauma Interrupted Time Series Protocol.
Trauma is the most common cause of mortality among people between the ages of 1 and 45 years, costing Canadians 19.8 billion dollars a year (2004 data), yet half of all patients with major traumatic injuries do not receive evidence-based care, and significant regional variation in the quality of care across Canada exists. Accordingly, our goal is to lead a research project in which stakeholders themselves will adapt evidence-based trauma care knowledge tools to their own varied institutional contexts and cultures. We will do this by developing and assessing the combined impact of WikiTrauma, a free collaborative database of clinical decision support tools, and Wiki101, a training course teaching participants how to use WikiTrauma. WikiTrauma has the potential to ensure that all stakeholders (eg, patients, clinicians, and decision makers) can all contribute to, and benefit from, evidence-based clinical knowledge about trauma care that is tailored to their own needs and clinical setting. Our main objective will be to study the combined effect of WikiTrauma and Wiki101 on the quality of care in four trauma centers in Quebec. First, we will pilot-test the wiki with potential users to create a version ready to test in practice. A rapid, iterative prototyping process with 15 health professionals from nonparticipating centers will allow us to identify and resolve usability issues prior to finalizing the definitive version for the interrupted time series. Second, we will conduct an interrupted time series to measure the impact of our combined intervention on the quality of care in four trauma centers that will be selected-one level I, one level II, and two level III centers. Participants will be health care professionals working in the selected trauma centers. Also, five patient representatives will be recruited to participate in the creation of knowledge tools destined for their use (eg, handouts). All participants will be invited to complete the Wiki101 training and then use, and contribute to, WikiTrauma for 12 months. The primary outcome will be the change over time of a validated, composite, performance indicator score based on 15 process performance indicators found in the Quebec Trauma Registry. This project was funded in November 2014 by the Canadian Medical Protective Association. We expect to start this trial in early 2015 and preliminary results should be available in June 2016. Two trauma centers have already agreed to participate and two more will be recruited in the next months. We expect that this study will add important and unique evidence about the effectiveness, safety, and cost savings of using collaborative platforms to adapt knowledge implementation tools across jurisdictions.


Characterizing different-flavored e-cigarette solutions from user-reported sensory attributes and appeal.
Scientists and regulators need parsimonious methods of characterizing flavored e-cigarettes which may vary widely in both chemical flavoring constituents and marketing descriptors. This laboratory experiment characterized user-reported appeal and experience of five cross-cutting sensory attributes (sweetness, bitterness, smoothness, harshness, coolness) of 10 common e-cigarette flavors. In a within-subject double-blind single-visit protocol, current nicotine/tobacco product users (N = 119) self-administered a single puff of each e-liquid flavor via a pod-style device and rated its appeal and sensory attributes on 0-100 scales. Custom-manufactured e-liquids, nicotine concentration: M (SD) = 23.4 (0.9) mg/mL, representative of commonly marketed fruit (green apple, strawberry), dessert (dark chocolate, vanilla), mint (peppermint, spearmint), nonmint cooling (menthol, koolada), and tobacco (subtle tobacco, full-flavored tobacco) flavor descriptors were used and their constituents were independently analyzed. Results largely demonstrated that a flavor's sensory attributes concorded with its marketed flavor descriptor. Among the 10 flavors, vanilla was rated sweetest (B[difference vs. mean of 9 other flavors] = 14.44, 95% CI [10.84, 18.03]), full-flavored tobacco was most bitter, B = 8.34, 95% CI [4.73, 11.96], subtle tobacco was most harsh, B = 5.69, 95% CI [1.70, 9.68], and peppermint scored highest in both smoothness, B = 6.98, 95% CI [3.13, 10.82], and coolness, B = 29.25, 95% CI [25.50, 33.01]. Flavors with higher appeal ratings tended to be sweeter, smoother, cooler, and less bitter and harsh. Chemical analysis found numerous flavoring constituents among study products without any clear differentiation of chemicals being present in particular flavor categories, which underscores the utility of using sensory ratings to characterize different-flavored e-cigarettes over and above constituent analyses. Characterizing e-cigarette flavors by subjective sensory attributes may be useful in future research and regulatory activities. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Prenatal Exposure to an Acute Stressor and Children's Cognitive Outcomes.
Exposure to environmental stressors is highly prevalent and unequally distributed along socioeconomic lines and may have enduring negative consequences, even when experienced before birth. Yet, estimating the consequences of prenatal stress on children's outcomes is complicated by the issue of confounding (i.e., unobserved factors correlated with stress exposure and with children's outcomes). I combine a natural experiment-a strong earthquake in Chile-with a panel survey to capture the effect of prenatal exposure on acute stress and children's cognitive ability. I find that stress exposure in early pregnancy has no effect on children's cognition among middle-class families, but it has a strong negative influence among disadvantaged families. I then examine possible pathways accounting for the socioeconomic stratification in the effect of stress, including differential exposure across socioeconomic status, differential sensitivity, and parental responses. Findings suggest that the interaction between prenatal exposures and socioeconomic advantage provides a powerful mechanism for the intergenerational transmission of disadvantage.


A Population- and Hospital-based Cross-sectional Study of Renal Function in Hidradenitis Suppurativa.
The chronic inflammatory skin diseases hidradenitis suppurativa (HS) and psoriasis have been linked to cardiovascular risk factors and the latter has also been linked to possible renal dysfunction. Since basement membrane thinning in the skin of HS patients has been described, we speculated whether similar basement membrane defects might occur in renal tissue. Our objective was to investigate a possible association between HS and renal dysfunction. We performed a hospital and population-based cross-sectional study using estimated Glomerular-Filtration-Rate (eGFR) to assess renal function. Thirty-two hospital individuals with HS, 430 population individuals with HS, and 20,780 population individuals without HS were (controls) identified. The age-, sex-, smoking-, BMI-, hypertension- and diabetes-adjusted analysis revealed a statistically significant higher eGFR for the hospital group with HS and a mean difference in eGFR of 6.81 (1.27-12.35) ml/min/1.73 m2 between the hospital group with HS and the population group without HS. The observed higher eGFR in the hospital group with HS indicates a possible association of HS and renal dysfunction.


Use of Food Services by Consumers in the SARS-CoV-2 Pandemic. How the Eating Habits of Consumers Changed in View of the New Disease Risk Factors?
The SARS-CoV-2 pandemic in 2020-2021 changed the eating habits of people around the world. The aim of this study is to understand the effects of COVID-19 on changing consumers' eating habits, including their concerns about food service nutrition in case of new disease risk factors. The survey conducted using the computer-assisted web-based interviewing method on a group of 1021 adult respondents in Poland. We collected information about consumer choices and habits related to use of food services during the pandemic. This research found that COVID-19 had an impact on consumers' use of food services, both on-site and take-away. Using cluster analysis, we identified five main groups of food service consumers. It was found that almost half of the respondent group did not change their diet during the pandemic, 20% of respondents changed their diet to a positive one, and 20% to a diet that was negative. For respondents the most important forms of protection against COVID-19 in catering establishments were hand disinfection (70.3%), table disinfection (70.4%), wearing of masks and visors by staff (68.2%), and the possibility of cashless payments (64.6%). Based on cluster analysis (eight consumer clusters), we stated that majority of respondents did not see any threats to using catering service during the pandemic. Only a small group (8.1%) of respondents were afraid of the possibility of getting sick with COVID-19. This study presented the effects of COVID-19 on consumer eating behavior in catering and their concerns with food services uses. Discovering consumer concerns can reduce risk, increase food safety and improve eating habits.


Genetic Load and Adaptive Potential of a Recovered Avian Species that Narrowly Avoided Extinction.
High genetic diversity is a good predictor of long-term population viability, yet some species persevere despite having low genetic diversity. Here we study the genomic erosion of the Seychelles paradise flycatcher (Terpsiphone corvina), a species that narrowly avoided extinction after having declined to 28 individuals in the 1960s. The species recovered unassisted to over 250 individuals in the 1990s and was downlisted from Critically Endangered to Vulnerable in the International Union for the Conservation of Nature Red List in 2020. By comparing historical, prebottleneck (130+ years old) and modern genomes, we uncovered a 10-fold loss of genetic diversity. Highly deleterious mutations were partly purged during the bottleneck, but mildly deleterious mutations accumulated. The genome shows signs of historical inbreeding during the bottleneck in the 1960s, but low levels of recent inbreeding after demographic recovery. Computer simulations suggest that the species long-term small Ne reduced the masked genetic load and made the species more resilient to inbreeding and extinction. However, the reduction in genetic diversity due to the chronically small Ne and the severe bottleneck is likely to have reduced the species adaptive potential to face environmental change, which together with a higher load, compromises its long-term population viability. Thus, small ancestral Ne offers short-term bottleneck resilience but hampers long-term adaptability to environmental shifts. In light of rapid global rates of population decline, our work shows that species can continue to suffer the effect of their decline even after recovery, highlighting the importance of considering genomic erosion and computer modeling in conservation assessments.


Development of heart rate in the precocial king quail Coturnix chinensis.
Our aim was to examine changes in heart rate (fh) during the embryonic and posthatching periods of the smallest precocial avian species, Coturnix chinensis. In experiment I, repeated measurements of mean fh were made for individual quail by ballistocardiogram (BCG) during incubation, and by both piezo-electric film and electrocardiogram (ECG) during the posthatching period (resting and thermoneutral conditions). Mean fh of all embryos increased during the second half of incubation and the first week posthatching, but a few embryos experienced a very brief period of decreased fh prior to internal pipping. After the first week, fh of posthatching quail was maintained at high levels (550-650 beats min-1), then decreased with age and increase in body mass. The maximal fh of quail chicks represents a greater posthatching increase in fh than is found in larger precocial chickens, this difference being attributable to the higher demands of thermoregulation at small body masses in the quail. In experiment II, the mean fh of quail embryos (day 2-16) was recorded by ECG, and embryonic stage, yolk-free embryo mass (wet and dry) and water content were measured. Mean fh was linearly related to embryo mass throughout incubation, except on the day prior to internal pipping, when the fh of a few embryos declined below this linear relationship. Measurements of instantaneous fh of late incubation embryos, young and adult quail all showed spontaneous fluctuations in fh. Two main frequency components of fh fluctuations were identified for the first time in an avian species. Low-frequency (mean 0.09 Hz, 12.6 s) and high-frequency (1.4 Hz, 0.9 s) oscillations in both young chicks and adult quail were detected and are considered to reflect baroreflex mediation of fh and respiratory sinus arrhythmia, respectively.