Self-injurious skin picking: clinical characteristics and comorbidity.
Repetitive skin picking, a self-injurious behavior that may cause severe tissue damage, has received scant empirical attention. The authors examined the demographics, phenomenology, and associated psychopathology in a series of 31 subjects with this problem. Subjects were administered the Structured Clinical Interview for DSM-IV for Axis I and Axis II disorders. They also completed several mood questionnaires and a new self-report inventory designed to assess phenomenology, triggers, cognitions, emotions, and consequences associated with skin picking. The mean age at onset on self-injurious skin picking was 15 years, and the mean duration of illness was 21 years. All subjects picked at more than one body area, and the most frequent sites of skin picking were pimples and scabs (87%). The most common comorbid Axis I diagnoses were obsessive-compulsive disorder (OCD; 52%), alcohol abuse/dependence (39%), and body dysmorphic disorder (32%). Forty-eight percent (N = 15) of the subjects met criteria for at least one mood disorder, and 65% (N = 20) for at least one anxiety disorder. The most common Axis II disorders were obsessive-compulsive personality disorder (48%) and borderline personality disorder (26%). Self-injurious skin picking is a severe and chronic psychiatric and dermatologic problem associated with high rates of psychiatric comorbidity. It may be conceptualized as a variant of OCD or impulse-control disorder with self-injurious features and may, in some cases, represent an attempt to regulate intense emotions.


Widow(er) poverty and out-of-pocket medical expenditures near the end of life.
Elderly widows are three times as likely to live in poverty as older married people. This study investigates the gap in poverty, income, and wealth between these groups. Focus is placed on the role played by out-of-pocket medical expenditures spent on dying spouses. A national panel survey of people age 70 and older in 1993 was used. Income, poverty, wealth, and out-of-pocket expenditures were examined before and after widowhood, with comparisons made with couples not experiencing a death. Forty-four percent of the difference in economic status between widow(er)s and married elderly persons was due to disparities in economic status that existed prior to widowhood. The remaining 56% was due to factors more directly related to the death of a spouse, including the loss of income and expenses associated with dying. On average, out-of-pocket medical expenditures in the final 2 years of life were equal to 30% of the couple's annual income. For couples in the bottom quarter of the income distribution, these expenditures were 70% of their income. As policy makers continue to debate expansions and reforms of Medicare, the potential effects of these reforms on economic well-being, particularly among widows, should be considered.


Screening for depression: Psychometric properties of the German version of the Glasgow depression scale for people with a learning disability (individual and carer version).
Adults with intellectual disabilities should participate in the diagnostics of their mental health. The Glasgow Depression Scale for people with a Learning Disability (GDS-LD) and its Carer Supplement (GDS-CS) were translated into German and tested. Internal consistency, criterion validity and inter-test reliability were tested in 64 adults with borderline, mild or moderate intellectual disabilities and their carers. Convergent validity was analysed in 57 adults without intellectual disabilities. Internal consistency was good (α = 0.81) for GDS-LD and acceptable (α = 0.72) for GDS-CS. The GDS-LD did not differentiate between groups with and without depression. The GDS-CS significantly differentiated between these groups. Convergent validity of the GDS-LD was high. The correlation of GDS-LD and GDS-CS was non-significant. In its present form the German version of the GDS-LD does not meet the psychometric properties to be used in clinical practice. This leads to the broader question, how to measure depression in people with learning disabilities with the knowledge of the fallibility of existing measures when utilised with this clinical cohort. Also, future studies need to investigate the role of self-rating.


Toward a Universal Readout for 18F-Labeled Amyloid Tracers: The CAPTAINs Study.
To date, 3 18F-labeled PET tracers have been approved for assessing cerebral amyloid plaque pathology in the diagnostic workup of suspected Alzheimer disease (AD). Although scanning protocols are relatively similar across tracers, U.S. Food and Drug Administration- and the European Medicines Agency-approved visual rating protocols differ among the 3 tracers. This proof-of-concept study assessed the comparability of the 3 approved visual rating protocols to classify a scan as amyloid-positive or -negative, when applied by groups of experts and nonexperts to all 3 amyloid tracers. Methods: In an international multicenter approach, both expert (n = 4) and nonexpert raters (n = 3) rated scans acquired with 18F-florbetaben, 18F-florbetapir and 18F-flutemetamol. Scans obtained with each tracer were presented for reading according to all 3 approved visual rating protocols. In a randomized order, every single scan was rated by each reader according to all 3 protocols. Raters were blinded for the amyloid tracer used and asked to rate each scan as positive or negative, giving a confidence judgment after each response. Percentage of visual reader agreement, interrater reliability, and agreement of each visual read with binary quantitative measures (fixed SUV ratio threshold for positive or negative scans) were computed. These metrics were analyzed separately for expert and nonexpert groups. Results: No significant differences in using the different approved visual rating protocols were observed across the different metrics of agreement in the group of experts. Nominal differences suggested that the 18F-florbetaben visual rating protocol achieved the highest interrater reliability and accuracy especially under low confidence conditions. For the group of nonexpert raters, significant differences between the different visual rating protocols were observed with overall moderate-to-fair accuracy and with the highest reliability for the 18F-florbetapir visual rating protocol. Conclusion: We observed high interrater agreement despite applying different visual rating protocols for all 18F-labeled amyloid tracers. This implies that the results of the visual interpretation of amyloid imaging can be well standardized and do not depend on the rating protocol in experts. Consequently, the creation of a universal visual assessment protocol for all amyloid imaging tracers appears feasible, which could benefit especially the less-experienced readers.


Analysis of the muscle tissue of Wistar rats submitted to the sciatic nerve compression model and cryotherapy.
To evaluate the effects of right sciatic nerve compression and cryotherapy on muscle tissue. We used 42 male Wistar rats, subdivided in the following Groups Control, Injury 3, Injury 8 and Injury 15 submitted to nerve compression and euthanized in the 3rd, 8th and 15th day after surgery. The Cryotherapy Injury 3 was entailed treatment with cryotherapy by immersion of the animal in recipient for 20 minutes during 1 day, then animals were euthanized at the 3rd day after surgery, and the Cryotherapy Injury 8 and the Cryotherapy Injury 15 was treated for 6 days, and euthanized at the 8th and 15th day after surgery. Functional evaluation was performed by the grasping strength of the right pelvic limb. The right tibialis anterior muscles were evaluated for mass, smaller diameter and cross-sectional area. In the Cryotherapy Injury 8 and the Cryotherapy Injury 15 groups, the hydroxyproline was dosed in the right soles. In the compression there was a significant difference in the Injury Groups compared with the Control Group (p<0.05). In the smaller diameter, the compression in Control Group was higher than Injury 8 (p=0.0094), Injury 15 (p=0.002) and Cryotherapy Injury 15 (p<0.001) groups. The comparison between groups with euthanasia in the same post-operative period, a significant difference (p=0.0363) was seen in day 8th after surgery, and this result in Cryotherapy Injury Group was greater than Injury Group. In the fiber area, Control Group was also higher than the Injury 8 (p=0.0018), the Injury 15 (p<0.001) and the Cryotherapy Injury 15 (p<0.001). In hydroxyproline, no significant difference was seen between groups. Nerve damage resulted in decreased muscle strength and trophism, the cryotherapy delayed hypotrophy, but this effect did not persist after cessation of treatment.


Molecular events linking cholesterol to Alzheimer's disease and inclusion body myositis in a rabbit model.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by cognitive impairment and dementia, resulting from progressive synaptic dysfunction, loss and neuronal cell death. Inclusion body myositis (IBM) is a skeletal muscle degenerative disease, displaying progressive proximal and distal muscle weakness, in association with muscle fiber atrophy, degeneration and death. Studies have shown that the late onset version of AD (LOAD) and sporadic IBM (sIBM) in muscle share many pathological features, including the presence of extracellular plaques of β-amyloid peptides and intracellular tangles of hyperphosphorylated tau proteins. High blood cholesterol is suggested to be a risk factor for LOAD. Many neuropathological changes of LOAD can be reproduced by feeding rabbits a 2% enriched cholesterol diet for 12 weeks. The cholesterol fed rabbit model also simultaneously develops sIBM like pathology, which makes it an ideal model to study the molecular mechanisms common to the development of both diseases. In the present study, we determined the changes of gene expression in rabbit brain and muscle during the progression of LOAD and sIBM pathology using a custom rabbit nucleotide microarray, followed by qRT-PCR analyses. Out of 869 unique transcripts screened, 47 genes showed differential expression between the control and the cholesterol-treated group during the 12 week period and 19 changed transcripts appeared to be common to LOAD and sIBM. The most notable changes are the upregulation of the hemoglobin gene family and the downregulation of the genes required for mitochondrial oxidative phosphorylation in both brain and muscle tissues throughout the time course. The significant overlap on the changes of gene expression in the brain and muscle of rabbits fed with cholesterol-enriched diet supports the notion that LOAD and sIBM may share a common etiology.


Assessment of water droplet evaporation mechanisms on hydrophobic and superhydrophobic substrates.
Evaporation rates are predicted and important transport mechanisms identified for evaporation of water droplets on hydrophobic (contact angle ~110°) and superhydrophobic (contact angle ~160°) substrates. Analytical models for droplet evaporation in the literature are usually simplified to include only vapor diffusion in the gas domain, and the system is assumed to be isothermal. In the comprehensive model developed in this study, evaporative cooling of the interface is accounted for, and vapor concentration is coupled to local temperature at the interface. Conjugate heat and mass transfer are solved in the solid substrate, liquid droplet, and surrounding gas. Buoyancy-driven convective flows in the droplet and vapor domains are also simulated. The influences of evaporative cooling and convection on the evaporation characteristics are determined quantitatively. The liquid-vapor interface temperature drop induced by evaporative cooling suppresses evaporation, while gas-phase natural convection acts to enhance evaporation. While the effects of these competing transport mechanisms are observed to counterbalance for evaporation on a hydrophobic surface, the stronger influence of evaporative cooling on a superhydrophobic surface accounts for an overprediction of experimental evaporation rates by ~20% with vapor diffusion-based models. The local evaporation fluxes along the liquid-vapor interface for both hydrophobic and superhydrophobic substrates are investigated. The highest local evaporation flux occurs at the three-phase contact line region due to proximity to the higher temperature substrate, rather than at the relatively colder droplet top; vapor diffusion-based models predict the opposite. The numerically calculated evaporation rates agree with experimental results to within 2% for superhydrophobic substrates and 3% for hydrophobic substrates. The large deviations between past analytical models and the experimental data are therefore reconciled with the comprehensive model developed here.


Instructional Training Compared with Self-Study for Pulmonary Function Test Interpretation.
Pulmonary diseases have considerable prognostic relevance for all-cause mortality. Most patients with lung diseases such as chronic obstructive pulmonary disease are treated by general practitioners. Understanding the clinical consequences such as pulmonary hyperinflation or reduced diffusion capacity is important for the management and prognosis of patients with chronic respiratory disorders. Therefore, the interpretation of pulmonary function testing (PFT) results needs to see more emphasis in the medical education curriculum. To develop PFT training for final-year medical students and to compare the efficacy of instructional training to self-reliant textbook study. A two-armed randomized control trial compares learning outcomes in PFT interpretation. A total of 25 final-year medical students were selected at random into the 1) instructional training group or 2) self-reliant textbook study group on PFT interpretation. The learning time for both groups was 2 hours. The duration of the written pre- and post-training examinations was 60 minutes each. Both exams had a knowledge section (30 questions, maximum 120 points) and a skills section (11 case studies, maximum 75 points). The instructional training group acquired significantly more knowledge and, in particular, higher skill levels when compared with the self-reliant reading group. In the reading group, knowledge scores increased from 48 to 60% (12%) and skills scores increased from 14 to 22% (8%), whereas in the instructional group, knowledge increased from 47 to 71% (24%) and skills from 18 to 58% (40%). A multivariate analysis (Pillai's Trace: 0.633; P < 0.001) as well as follow-up univariate analyses reveal that these differences are statistically significant (knowledge: F = 8.811, df = 1, P = 0.007; skills F = 33.965, df = 1, P < 0.001). Interestingly, there was no significant group effect in the pure knowledge gain about respiratory disorders per se. The self-reliant study group was less able to translate their newly acquired knowledge into interpretation of comprehensive PFT reports. A mandatory 2-hour instructional training greatly enhances the students' knowledge and skills about PFT interpretation. Obligatory PFT instructional training should therefore be included in the students' curriculum.


Defining dementia: social and historical background of Alzheimer disease.
Though Alzheimer disease (AD) has been recognized as a distinct entity since 1907, scientific understanding of, and public interest in, the disease remained very limited until the 1970s. The perception of AD as a significant problem has been substantially affected by cultural and demographic changes and by interest group and federal government initiatives. The recognition of AD has transformed senility from an expected stage of life into a "disease." It has also increased fear both of the individual effects of having AD and of the social consequences of AD in the population. Both the biotechnology industry and AD activist organizations will play a role in the social implications of genetic testing for AD.


Interpretability of the audiogram by audiologists and physician non-specialists.
The audiogram is frequently used by hearing specialists communicate test results to non-specialists, such as physicians. However, it relies on uncommon terminology and interpreting unusual graphical elements to extract information. In this study, we examine whether the audiogram can be accurately interpreted by specialists and non-specialists. We used an online questionnaire to assess the interpretability of an audiogram by audiologists and primary-care physicians. Participants viewed a sample audiogram and submitted their answers via an online survey system. We recruited actively practicing primary care physicians (n = 100) and actively practicing audiologists (n = 67). We only accepted respondents from the United States. The audiogram was not easily interpreted by physicians, with a median score of 4/9. Fewer than 25% could accurately report a threshold correctly. Audiologists were more accurate than physicians (median score 7/9, Wilcoxon two-sample p < 0.001, r = 0.648). The audiogram is difficult for non-specialists to interpret. Clinicians are advised to supplement or supplant the audiogram in interprofessional communication. The development of tools to facilitate interprofessional communication between audiologists and physicians could have positive effects on physician awareness of hearing loss, and even downstream influences on patient behaviour and outcomes.


Intramolecular recombination between transfected repeated sequences in mammalian cells is nonconservative.
When plasmids carrying a fragmented gene with segments present as direct repeats are introduced into mammalian cells, recombination or gene conversion between the repeated sequences can reconstruct the gene. Intramolecular recombination leads to the deletion of the intervening sequences and the loss of one copy of the repeat. This process is known to be stimulated by double-strand breaks. Two current models for recombination in eucaryotic cells propose that the reaction is initiated by double-strand breaks, but differ in their predictions as to the fate of the intervening sequences. One model suggests that these sequences are always lost, while the other indicates that the reaction will be conservative as a function of the position of the double-strand break. We have constructed a plasmid in which two overlapping portions of the simian virus 40 early region, which contains the origin and T-antigen gene, are present as direct repeats separated by sequences containing a plasmid with a simian virus 40 origin of replication. Recombination across the repeated segments could produce a plasmid with an origin of replication and/or a plasmid with a gene for a functional T-antigen which would drive the replication of both. Introduction of this construction into African green monkey kidney cells, without coinfection, establishes a condition in which the products of the recombination or gene conversion can be interpreted unambiguously. We find that the majority of the reconstruction reactions are nonconservative.


Early retinopathy in the Bernese Mountain Dog in France: preliminary observations.
The objective of the study was to describe a form of early retinopathy in the Bernese Mountain Dog in France. Sixty-two Bernese Mountain Dogs (38 males and 24 females), whose ages ranged from 2 months to 9 years, were examined over a period of 3 years. Visual behavior, pupillary light reflexes, menace responses and ocular fundi were evaluated in all animals. Electroretinography (ERG) was performed on six of the affected dogs after dark adaptation. Fluorescein angiography (FA) was performed on one affected dog. Whenever possible, the pedigrees of the affected dogs were evaluated. A histological examination of the retina was performed on one of the affected dogs. Eight dogs (seven males and one female) were diagnosed with retinopathy with an early onset of clinical signs. (Four dogs were aged between 3 months and 1 year, two dogs were aged 2 and 3.5 years, and one dog was 7 years old.) Night vision was impaired in most of the dogs. Retinopathy was characterized ophthalmoscopically by a bilateral, symmetrical horizontal zone of tapetal hyper-reflectivity adjacent to and above the optic disc, and sometimes by peri-papillary hyper-reflectivity. ERG changes included a reduction in b-wave amplitude varying from one case to another. Fluoroscein angiography demonstrated an ischemic-type alteration with epitheliopathy opposite the hyper-reflective zone. Pedigree examinations suggested a familial predisposition. The histological examination indicated photoreceptor degeneration that was more pronounced in the central tapetal zone. In France, retinopathy in the Bernese Mountain Dog involves an early retinal degeneration that produces specific manifestations of the ocular fundus, night visual impairment or blindness, and has familial transmission.


The electronic structure of organic-inorganic hybrid compounds: (NH₄)₂CuCl₄, (CH₃NH₃)₂CuCl₄ and (C₂H₅NH₃)₂CuCl₄.
Hybrid organic-inorganic compounds are an intriguing class of materials that have been experimentally studied over the past few years because of a potential broad range of applications. The electronic and magnetic properties of three organic-inorganic hybrid compounds with compositions (NH4)2CuCl4, (CH3NH3)2CuCl4 and (C2H5NH3)2CuCl4 are investigated for the first time with density functional theory plus on-site Coulomb interaction. A strong Coulomb interaction on the copper causes a relatively weak exchange coupling within the layers of the octahedral network, in good agreement with experiment. The character of the exchange interaction (responsible for magnetic behavior) is analyzed. The calculations reveal that (C2H5NH3)2CuCl4 has the strongest Jahn-Teller (JT) distortion in comparison with the two other compounds. The easy axis of magnetization is investigated, showing a weak anisotropic interaction between inter-layer Cu(2+) ions in the (C2H5NH3)2CuCl4 structure. Orbital ordering is concluded from our partial density of states calculations: a cooperation of the JT distortion with an antiferro-distortive pattern.


Plasma therapy of primary rat mammary carcinoma: dependence of consumption of C3 during absorption of plasma with sepharose derivatives on the anticoagulant.
A previous study demonstrated inhibition of growth of primary rat mammary carcinomas after infusion of tumor-bearer plasma absorbed against Sepharose derivatives. In this report we have quantitated changes in individual complement components that occur during absorption of rat plasma with Sepharose derivatives and defined optimal conditions for consumption of the third component of complement (C3) (other complement components defined similarly). The concentration of functionally active C1 to C9 was measured before and after absorption in plasmas from both normal rats and rats with mammary tumors. C3 activity in plasmas from normal and tumor-bearing rats was reduced (consumed) during absorption under appropriate conditions with Sepharose 4B, inactivated CNBr Sepharose, or Protein A-Sepharose. The concentration of functionally active C1 and C4 did not decrease significantly during absorption with Sepharose derivatives. Consumption of C3 in rat plasma was influenced by the anticoagulant and by the time and temperature of incubation with Sepharose derivative. C3 consumption in rat plasma anticoagulated with acid citrate dextrose solution was variable; addition of Mg2+ (5 mM) to plasma anticoagulated with acid citrate dextrose solution augmented C3 consumption. There was no C3 consumption in plasma anticoagulated with ethylenedinitrilotetraacetic acid (a chelator of calcium and magnesium). In contrast, this reduction was observed in plasma anticoagulated with [(ethylenebis(oxyethylenenitrilo)]tetraacetic acid (a chelator of calcium). The results demonstrate optimal conditions for activation of the alternative pathway of complement during absorption of rat plasma with Sepharose derivatives and suggest in vivo experiments to define the role of this pathway in inhibition of growth of mammary tumors.


Short-Term Exposure to Ambient Air Pollution and Biomarkers of Systemic Inflammation: The Framingham Heart Study.
The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area. We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameter<2.5 µm), black carbon, sulfate, nitrogen oxides, and ozone before the examination visits. We used linear mixed effects models for C-reactive protein and tumor necrosis factor receptor 2, which were measured up to twice for each participant; we used linear regression models for interleukin-6, fibrinogen, and tumor necrosis factor α, which were measured once. We adjusted for demographics, socioeconomic position, lifestyle, time, and weather. The 3- to 7-day moving averages of fine particulate matter (diameter<2.5 µm) and sulfate were positively associated with C-reactive protein concentrations. A 5 µg/m3 higher 5-day moving average fine particulate matter (diameter<2.5 µm) was associated with 4.2% (95% confidence interval: 0.8, 7.6) higher circulating C-reactive protein. Positive associations were also observed for nitrogen oxides with interleukin-6 and for black carbon, sulfate, and ozone with tumor necrosis factor receptor 2. However, black carbon, sulfate, and nitrogen oxides were negatively associated with fibrinogen, and sulfate was negatively associated with tumor necrosis factor α. Higher short-term exposure to relatively low levels of ambient air pollution was associated with higher levels of C-reactive protein, interleukin-6, and tumor necrosis factor receptor 2 but not fibrinogen or tumor necrosis factor α in individuals residing in the greater Boston area.


Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol.
The mitochondrion is well known for its key role in energy transduction. However, it is less well appreciated that it is also a focal point of iron metabolism. Iron is needed not only for heme and iron sulfur cluster (ISC)-containing proteins involved in electron transport and oxidative phosphorylation, but also for a wide variety of cytoplasmic and nuclear functions, including DNA synthesis. The mitochondrial pathways involved in the generation of both heme and ISCs have been characterized to some extent. However, little is known concerning the regulation of iron uptake by the mitochondrion and how this is coordinated with iron metabolism in the cytosol and other organelles (e.g., lysosomes). In this article, we discuss the burgeoning field of mitochondrial iron metabolism and trafficking that has recently been stimulated by the discovery of proteins involved in mitochondrial iron storage (mitochondrial ferritin) and transport (mitoferrin-1 and -2). In addition, recent work examining mitochondrial diseases (e.g., Friedreich's ataxia) has established that communication exists between iron metabolism in the mitochondrion and the cytosol. This finding has revealed the ability of the mitochondrion to modulate whole-cell iron-processing to satisfy its own requirements for the crucial processes of heme and ISC synthesis. Knowledge of mitochondrial iron-processing pathways and the interaction between organelles and the cytosol could revolutionize the investigation of iron metabolism.


Carcinoembryonic antigen and alpha-fetoprotein expression and monoclonal antibody targeting in a human hepatoma/nude mouse model.
Hep G2, a human hepatocellular carcinoma, was grown s.c. in nude mice, as well as in tissue culture. This line retains the normal liver parenchymal cell capacity to synthesize human plasma proteins such as albumin, but there is no indication that it harbors the hepatitis B virus. We have detected the oncofetal antigens alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in both Hep G2 xenografts and spent tissue culture media by Ouchterlony double diffusion assays, enzyme-linked immunosorbent assay, and immunohistology. By enzyme-linked immunosorbent assay, the AFP levels were 544.9 ng/ml in the cell culture and 1.6 microgram/g in saline extracts of the xenograft. The CEA levels were 35.2 ng/ml in the cell culture and 5.4 micrograms/g in the xenograft. The biodistribution of a radioiodinated anti-AFP murine monoclonal antibody and an anti-CEA monoclonal antibody were studied separately in nude mice bearing s.c. Hep G2 xenografts in comparison to an isotype-matched irrelevant IgG (Ag8). Anti-CEA antibody showed a preferential localization for Hep G2, but anti-AFP antibody did not. Immunohistochemical studies of the Hep G2 tumor, using biotinylated anti-AFP and anti-CEA, indicate both cytoplasmic and luminal staining of CEA and AFP in the tumor. These results suggest that Hep G2 may be a useful cell line for radioimmunodetection and radioimmunotherapy studies using anti-CEA and possibly anti-AFP monoclonal antibodies.


Arterial hypertension treated by angioplasty (Dotter). A serious complication.
Typical renovascular hypertension in a middle-aged woman was treated by percutaneous transluminal angioplasty. The initial result was good, but cerebral complications developed within 2 weeks. Examination of the major neck vessels before undertaking treatment leading to a permanent reduction in the blood pressure, is recommended.


[Effect of sulfur administration on lipid levels, antioxidant status and peroxide concentration in health resort patients].
The aim of the study was to test the effect of drinking sulphurous mineral water on lipid status and antioxidative balance in patients with degenerative arthroses during a 3-week stay in a health resort. Two groups of patients with and without drinking sulphurous water were investigated. Lipid levels, glutathione peroxidase, superoxidedismutase, antioxidative status, and peroxide concentration in plasma were measured. In both groups similar alterations of the activities of antioxidative enzymes as well as peroxide concentrations could be detected. Possible specific effects of drinking sulphurous mineral water have to be investigated in further studies.


Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation.
To identify the key molecules that regulate differentiation of hematopoietic cells, we carried out retrovirus-mediated functional screening for cDNAs whose expression suppresses IL-6-induced differentiation of mouse myeloid leukemic M1 cells. From this screening, we obtained a full length cDNA encoding a mouse homologue of human MgcRacGAP. Overexpression of the anti-sense MgcRacGAP profoundly inhibited IL-6-induced macrophage-differentiation of M1 cells. On the other hand, overexpression of the full-length form of MgcRacGAP alone enhanced macrophage differentiation of M1 cells in response to IL-6, and induced macrophage differentiation of HL-60 leukemic cells. To determine how this protein regulates differentiation and proliferation, an antibody against MgcRacGAP was prepared. Immunohistochemical studies revealed that MgcRacGAP mainly localizes in the nucleus in interphase, accumulates on the mitotic spindle in metaphase, and is condensed in the midbody during cytokinesis. Overexpression of an N-terminal domain deletion mutant, which lacks the ability to localize to the midbody through association with tubulins, or a GAP-inactive mutant resulted in the formation of multinucleated cells in HeLa cells as well as in hemopoietic cells. Interestingly, MgcRacGAP in the midbody was phosphorylated probably on serine and threonine residues. These results indicate that MgcRacGAP regulates cytokinesis and cellular differentiation as a regulator of Rho family of GTPase and suggest that this process is controlled by some serine/threonine kinases.


Comparison of recruitment and retention among demographic subgroups in a large diverse population study of diet.
We examined the feasibility of conducting a longitudinal study of diet among diverse populations by comparing rates of response throughout recruitment and retention phases by demographic and other characteristics. Using quota sampling, participants were recruited from 3 geographically and demographically diverse integrated health systems in the United States. Overall, 12,860 adults, ages 20-70, were invited to participate via mail. Participation first required accessing the study's website and later meeting eligibility criteria via telephone interview. Enrollees were asked to provide two 24-hour dietary recalls, either interviewer-administered or self-administered on the web, over 6 weeks. Stepped monetary incentives were provided. Rates for accessing the study website ranged from 6% to 23% (9% overall) across sites. Site differences may reflect differences in recruitment strategy or target samples. Of those accessing the website, enrollment was high (≥ 87%). Of the 1185 enrollees, 42% were non-Hispanic white, 34% were non-Hispanic black, and 24% were Hispanic. Men and minorities had lower enrollment rates than women and non-Hispanic whites, partially due to less successful telephone contact for eligibility screening. Once enrolled, 90% provided 1 recall and 80% provided both. Women had higher retention rates than men, as did older compared to younger participants. Retention rates were similar across race/ethnicity groups. While study recruitment remains challenging, once recruited most participants, regardless of race/ethnicity, completed two 24-hour dietary recalls, both interviewer-administered and self-administered on the web. This study demonstrates the feasibility of collecting multiple 24-hour recalls including less expensive automated self-administered recalls among diverse populations.


Opioid Overdose History, Risk Behaviors, and Knowledge in Patients Taking Prescribed Opioids for Chronic Pain.
More than 100 million adults in the United States experience chronic pain, and prescription opioids are the third most widely prescribed class of medications. Current opioid overdose prevention efforts almost exclusively target illicit opioid users, and little is known about the experience of overdose among patients being treated for chronic pain (CP) with a prescription opioid. Patients experiencing CP for three or more months and receiving a prescription opioid for pain management (N = 502) completed a self-report survey that asked questions about opioid overdose history, past 30-day risk factors, and knowledge of opioid overdose, overdose risk, and naloxone. Approximately one in five CP participants reported experiencing a lifetime overdose. CP participants reported engaging in several behaviors associated with overdose risk and were unlikely to have been trained to administer naloxone. Fewer than 50% of participants answered any knowledge item correctly. The likelihood of having experienced an overdose increased as the scores on the SOAPP-R and DSM-5 opioid use disorder checklist increased, and a SOAPP-R score of 7 or higher or meeting DSM-5 mild opioid use disorder criteria were significantly associated with reporting a lifetime overdose (85% and 84% of participants who experienced an overdose, respectively). Opioid overdose occurs at a high rate among CP participants, and this group is relatively uninformed about risk factors for overdose. Established SOAPP-R and DSM thresholds provide an opportunity to identify participants at elevated risk for having experienced an opioid overdose. These data support development of additional concentrated efforts to prevent overdose among chronic pain patients.


Neuroanatomy of Cerebellar Mutism Syndrome: The Role of Lesion Location.
Approximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar deep nuclei and superior cerebellar peduncles, which we refer to as the cerebellar outflow pathway, is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort. We evaluated the relationship between lesion location and the development of CMS in an observational study of 56 pediatric patients who underwent cerebellar tumor resection. We hypothesized that individuals that developed CMS after surgery (CMS+), relative to those that did not (CMS-) would have lesions that preferentially intersected with: 1) the cerebellar outflow pathway, and 2) a previously generated 'lesion-symptom map' of CMS. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/). We found supporting evidence for both hypotheses. Compared with CMS- patients, CMS + patients (n = 10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen's d = .73, p = .05), and the CMS lesion-symptom map (Cohen's d = 1.1, p = .004). These results strengthen the association of lesion location with risk of developing CMS and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to pediatric cerebellar tumors.


Short- and Long-Term Mortality for Patients With and Without a Cancer Diagnosis Following Pulmonary Embolism in Denmark, 2000 to 2020: A Nationwide Study.
New treatment regimens have been introduced in the past 20 years, which may influence the short- and long-term prognosis for patients with and without a cancer diagnosis following pulmonary embolism. However, newer studies investigating these trends are lacking. Therefore, we aimed to investigate the 30- and 31- to 365-day mortality following pulmonary embolism. Using the Danish nationwide registries, patients with a diagnosis of pulmonary embolism between 2000 and 2020 were included. Age- and sex-standardized 30- and 31- to 365-day mortality was calculated and stratified by cancer status. In total, 60 614 patients (29.6% with recent cancer; mean age, 68.2 years) were included. The 30-day mortality for patients with no recent cancer decreased from 19.1% (95% CI, 17.9%-20.4%) in 2000 to 7.3% (95% CI, 6.7%-8.0%) in 2018 to 2020 (hazard ratio [HR], 0.36 [95% CI, 0.32-0.40]; P<0.001). The 30-day mortality for patients with recent cancer decreased from 32.2% (95% CI, 28.8%-36.6%) to 14.1% (95% CI, 12.7%-15.5%) (HR, 0.38 [95% CI, 0.33-0.44]; P<0.001). The 31- to 365-day mortality for patients with no recent cancer decreased from 12.5% (95% CI, 11.4%-13.6%) to 9.4% (95% CI, 8.6%-10.2%) (HR, 0.73 [95% CI, 0.64-0.83]; P<0.001).The 31- to 365-day mortality for patients with recent cancer remained stable: 39.4% (95% CI, 35.1%-43.7%) to 38.3% (95% CI, 35.9%-40.6%) (HR, 0.97 [95% CI, 0.84-1.12]; P=0.69). From 2000 to 2020, improvements were observed in 30-day mortality following pulmonary embolism regardless of cancer status. For patients with recent cancer, 31- to 365-day mortality did not improve, whereas a minor improvement was observed for patients without recent cancer.


Primary Care Sports Medicine Fellowship: AMSSM Proposed Standards of Excellence.
The American Medical Society for Sports Medicine (AMSSM) recognizes a need to provide direction and continually enhance the quality of sports medicine fellowship training programs. This document was developed to be an educational resource for sports medicine physicians who teach in a 1-year primary care sports medicine fellowship training program. It is meant to provide high standards and targets for fellowship training programs that choose to reassess their curriculum and seek to make improvements.


Homogenization of bi-anisotropic metasurfaces.
Ultrathin metamaterial layers are modeled by a homogeneous bi-anisotropic film to represent various kinds of broken symmetries in photonic nanostructures, and specifically in optical metamaterials and metasurfaces. Two algorithms were developed to obtain the electromagnetic (EM) wave response from a metasurface (direct solver) or the metasurface parameters from the EM wave response (inverse solver) for a bi-anisotropic, subwavelength-thick nanostructured film. The algorithm is applied to two different metasurfaces to retrieve their effective homogeneous bi-anisotropic parameters. The effective layer of the same physical thickness is shown to produce the same response to plane wave excitation as the original metasurface.


"Understanding growth convergence in India (1981-2010): Looking beyond the usual suspects".
The literature on growth convergence has focused to a great extent on the role of initial incomes as a primary determinant of long-term growth outcomes. Expanded versions of growth models have used other explanators to unpack the growth process. In this paper we add to the literature in two significant ways: (a) we use socioeconomic variables that are sometimes overlooked in explaining growth (such as, political stability and political alliance, social heterogeneity, and demographic distribution), and (b) we demonstrate that earlier analyses may be overlooking the problem of normality and endogeneity in regression models (and we provide alternate methods like instrumental variable and distribution dynamics to control for these). In this paper we analyze the per capita income growth at the subnational level in India for the period 1981-82 to 2010-11 using an expanded growth framework. We find that initial incomes, the ratio of working age group to total population, political stability and alliance, and the extent of development expenditure play a positive and significant role in predicting growth. We also find that, contrary to popular belief, the presence of marginalized groups-namely Scheduled Castes and Scheduled Tribes-have not been a hindrance to growth of per capita incomes in states. Our findings on the influence of social institutions may have significant implications for a public policy of affirmative action in India. The results on the impact of development expenditure on growth is also important for states seeking to increase their growth rates through policy intervention.


Use of multiple assays subject to detection limits with regression modeling in assessing the relationship between exposure and outcome.
The goal of many studies in environmental epidemiology is to assess the relationship between chemical exposure and disease outcome. Often various assays can be used to measure a particular environmental exposure, with some assays being more invasive or expensive than others. We consider the situation in which 2 assays can be used to measure an environmental exposure. The first assay has measurement error and is subject to a lower detection limit (LOD), and the second assay has less measurement error and is not subject to a lower LOD. In this situation, the first assay is less invasive or less expensive and is measured in all study participants, whereas the second assay is more invasive or more expensive and is only measured in a subset of individuals. We develop a flexible class of regression models that incorporates both sets of assay measurements and allows for continuous or binary outcomes. We explore different design strategies for selecting the subset of patients in whom to measure the second assay. One design strategy is to measure the second more invasive or expensive assay only when the first assay is below LOD. We compare these designs with a simple design in which the second assay is measured in a random subset of patients without regard to the results of the first assay. We develop estimation approaches for these regression models. We demonstrate through simulations that there are efficiency advantages of measuring the second assay in at least a fraction of cases in which the first assay is above LOD. We illustrate the methodology by using data from a study examining the effect of environmental polychlorinated biphenyl exposure on the risk of endometriosis. The proposed methodology has good statistical properties and will be a useful methodological technique for studying the effect of exposure on outcome when exposure assays are subject to LOD.


Nitric oxide reactivity and mechanisms involved in its biological effects.
Nitric oxide (NO) is implicated in many different biological functions. This is due to its widespread distribution in tissue and to its ability to react with a range of molecules in the organism, of which haemoglobin (Hb), soluble guanylyl cyclase (GC), and superoxide anion are of particular note. In this review we describe the biological pathways of NO and their involvement in its physiological effects and toxicity. This endothelial factor rapidly diffuses into the vascular compartment, and the reaction with the Hb haem group is the main metabolic pathway for endogenous NO. Hb is, therefore, a scavenger for this mediator, which prevents it from reaching the tissue components. NO also reacts with the GC haem group, and this combination is fundamental to its acute vasorelaxing effect. Although molecular oxygen plays a very small part in the oxidization process of NO in biological systems, NO reacts with the superoxide anion to generate peroxynitrite at a rate that is limited only by its diffusion coefficient. This reaction is important in pathological conditions because the peroxynitrite thus formed is a selective oxidant and nitrating agent that interacts with numerous biological molecules, thereby damaging them. In addition, of particular note are the interactions of NO with thiol groups, which may mediate several relevant effects in the organism. NO may also activate endogenous ribosyltransferases, which facilitate the transfer of adenosine diphosphate-ribose groups from nicotine adenine dinucleotide to the G protein amino acid residues. These last two processes may also be involved in the control of arterial tone and more precisely so when chronic NO production takes place.


Reduction of 14C-norepinephrine metabolism in rabbit aorta by vasodilators.
In the present study, both of the major enzymes, monoamine oxidase and catechol-o-methyltransferase, involved in the degradation of norepinephrine were examined indirectly in segments of rabbit aorta by exposure of tissues to 14C-norepinephrine and subsequent isolation of metabolites from homogenates by chromatographic techniques. Segments of aorta were preincubated with vasodilators to examine their influence on accumulation and metabolism of 14C-norepinephrine. The accumulation of labeled norepinephrine by aortae was enhanced after preincubation with hydrochlorothiazide or diazoxide, and reduced after preincubation with sodium nitroprusside or nitroglycerin. However, the fraction of accumulated 14C-norepinephrine which was degraded was significantly reduced after exposure to all four vasodilators. These results suggest that a decrease in degradation of norepinephrine in vascular smooth muscle can be observed (1) in vitro and (2) fairly rapidly after exposure to vasodilators.


Hypertension, Diabetes and Neurodegenerative Diseases: Is there a Clinical Link through the Ca2+/cAMP Signalling Interaction?
Hypertension, diabetes and neurodegenerative diseases are among the most prevalent medical problems around the world, costing millions of dollars to the medical health systems. Indeed, hypertension has been associated with higher risk for decline of cognition, as evidenced in patients with Alzheimer´s disease (AD). Furthermore, there is a clear relationship between hypertension and diabetes, reflecting substantial overlap in their etiology. Calcium (Ca2+) channel blockers (CCBs) have been classically prescribed for treating hypertension because of their mechanism of action due to reducing the influx of Ca2+ into the smooth muscles cells. In addition, many clinical and experimental studies have been demonstrating pleiotropic effects for CCBs. For instance, in hypertensive patients treated with CCBs, it can be observed lower incidence of neurodegenerative diseases such as AD. The virtual mechanism of action could be attributed to a restoration and maintenance of Ca2+ homeostasis, which is dysregulated in the neurodegenerative diseases, including also a reduction of neuronal apoptosis as part of these CCBs pleiotropic effects. Similarly, in hypertensive patients treated with CCBs, it can be observed an improvement of diabetes status such as glycemic control. A possible mechanism of action under debate could be attributed to a restoration of insulin secretion, then achieving glycemic control, and reduction of pancreatic β-cell apoptosis. Considering the discovery of our group entitled "calcium paradox" due to Ca2+/cAMP signalling interaction, in this review I discussed the virtual involvement of this interaction in the pleiotropic effects of CCBs, including the possible role of the Ca2+/cAMP signalling interaction in the association between hypertension and higher risk for the decline of cognition, and diabetes.


Increased ω-3 polyunsaturated fatty acid/arachidonic acid ratios and upregulation of signaling mediator in individuals with autism spectrum disorders.
The investigation of links between the ratio of omega-3/omega-6 PUFAs and neuronal signaling is a research priority in autism spectrum disorders (ASD). We examine the relationships between the plasma ratios of docosahexaenoid acid (DHA)/arachidonic acid (AA) and eicopentaenoic acid (EPA)/AA and biomarkers of AA-related signaling mediators such as ceruloplasmin, transferrin and superoxide dismutase, in the behavioral symptoms of 28 individuals with ASD (mean age 13.5±4.6years) and 21 age- and gender-matched normal healthy controls (mean age 13.9±5.7years). Behavioral symptoms were assessed using the Aberrant Behavior Checklists (ABC). We conducted controlling for dietary intake and assessed the dietary intake of nutrients. There were no significant differences in intake of nutrients such as omega-3 and omega-6 PUFAs, saturated and unsaturated fatty acid, DHA, AA, iron and copper. Plasma EPA, DHA, and arachidic acid levels, and plasma DHA/AA and EPA/AA ratios were significantly higher, while plasma AA and adrenic acid were significantly lower in the 28 individuals with ASD than in the 21 normal controls. The ABC scores were significantly higher in the ASD group compared to the control group. The plasma ceruloplasmin levels in the ASD group were significantly reduced compared to those in the control group. Increased plasma DHA/AA and EPA/AA ratios may be related to low plasma levels of ceruloplasmin which has neuroprotective properties. Reduced plasma ceruloplasmin levels may diminish the protective capacity against brain damage, and may contribute to the pathophysiology of behavioral symptoms in individuals with ASD.


[Adult leg development of Tenebrio molitor: I. Experimental analysis of the restoration process during morphogenesis (author's transl)].
The leg of the last instar larva, and especially the pharate pupa, of Tenebrio molitor (Coleoptera) shows considerable restoration ability. Restoration refers to the regeneration of leg structures removed during the last larval instar. This process involves only those tissues adjacent to the cut surface. At each level of the leg, amputation before a characteristic time leads to the restoration of a complete leg, but thereafter the new segments formed are hypomorphic or just lobes. After an amputation close to the pupal ecdysis, fragments are obtained, and these incomplete structures show that the restoration process has ceased. Just before the pupal ecdysis the leg is withdrawn from the cuticle, so a very late amputation does not effect the leg tissue and a complete pupal and adult leg is formed. The whole of the larval leg participates in adult leg morphogenesis, and histological techniques demonstrate a great correspondence between larval and adult leg segments. The larval trochanter, however, forms the adult trochanter and the proximal part of the femur. The larval tibia forms the adult tibia plus tarsus, except for the adult claws which develop from the larval tarsal claw.


Effectiveness of a practice-based intervention to increase vaccination rates and reduce missed opportunities.
Although provider feedback and recall/reminder systems have been shown to increase vaccination rates for children, little is known about the effectiveness of less intensive interventions. To determine whether provider prompting at acute care visits in an urban hospital-based outpatient clinic can increase vaccination rates and decrease missed opportunities. Study participants, 3 years or younger, were identified from a managed care organization as receiving primary care at the clinic. Eligibility criteria included 1 or more visits to the clinic without regard to continuity of enrollment. Patients' vaccination records were generated at nursing triage and attached to the encounter sheet. Vaccination and visit data were abstracted from medical records, and comparisons were made between baseline (n = 521) and postintervention (n = 642) groups for up-to-date vaccination rates, missed opportunity rates, and mean numbers of visits. Up-to-date rates at the age of 24 months for 4 diphtheria and tetanus toxoids and pertussis, 3 polio, 1 measles-mumps-rubella, 3 hepatitis B, and 3 Haemophilus influenzae type b vaccines changed from 70% to 78% (P =.07). Up-to-date rates increased significantly to 87% among the subset of children continuously enrolled in the managed care organization and the practice (P<.01). Overall, mean numbers of visits were similar. Missed opportunity rates among children not up-to-date for 4 diphtheria and tetanus toxoids and pertussis, 3 polio, 1 measles-mumps-rubella, 3 hepatitis B, and 3 Haemophilus influenzae type b vaccines at the age of 24 months declined from 65% to 45% (P =.04). Similar trends were noted at the age of 10 months. In the absence of increased funding, minor changes in standard operating procedures may improve vaccination delivery. Further improvements may require efforts to ensure continuity of provider and plan assignment.


Badminton injuries.
In a one year period, from 1 January 1986 to 31 December 1986, 4303 patients with sports injuries were treated at Aarhus Amtssygehus and Aarhus Kommunehospital. The mean age was 21.6 years (range 7-72 years) and 2830 were men. Two hundred and seventeen badminton injuries occurred in 208 patients (136 men) with a mean age of 29.6 years (range 7-57 years), constituting 4.1 percent of all sport injuries in Aarhus. Joints and ligaments were injured in 58.5 percent of the patients, most frequently located in the lower limb and significantly more often among patients younger than 30 years of age. Muscle injury occurred in 19.8 percent of the patients. This type of injury was significantly more frequent among patients older than 30 years of age. Most injuries were minor. However, 6.8 percent of the patients were hospitalized and 30.9 percent received additional treatment by a physician. As the risk of injury varies with age, attempts to plan training individually and to institute prophylactic measures should be made.


Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.
Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely β-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic β-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 μM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and β-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which should be proved by further experiments.


Sea-air exchange of bromoanisoles and methoxylated bromodiphenyl ethers in the Northern Baltic.
Halogenated natural products in biota of the Baltic Sea include bromoanisoles (BAs) and methoxylated bromodiphenyl ethers (MeO-BDEs). We identified biogenic 6-MeO-BDE47 and 2'-MeO-BDE68 in Baltic water and air for the first time using gas chromatography - high resolution mass spectrometry. Partial pressures in air were related to temperature by: log p/Pa=m/T(K)+b. We determined Henry's law constants (HLCs) of 2,4-dibromoanisole (2,4-DiBA) and 2,4,6-tribromoanisole (2,4,6-TriBA) from 5 to 30°C and revised our assessment of gas exchange in the northern Baltic. The new water/air fugacity ratios (FRs) were lower, but still indicated net volatilization in May-June for 2,4-DiBA and May - September for 2,4,6-TriBA. The net flux (negative) of BAs from Bothnian Bay (38,000km2) between May - September was revised from -1319 to -532kg. FRs of MeO-BDEs were >1, suggesting volatilization, although this is tentative due to uncertainties in their HLCs and binding to dissolved organic carbon.


What do government agencies consider in the debate over added sugars?
The place of sugars in the U.S. diet is vigorously debated with much attention on added sugars, those added during processing or preparation of foodstuffs, particularly as they relate to obesity. Federal government agencies have different responsibilities related to the food supply including research, food safety, nutrition assistance, and labeling; therefore, the interpretation of evidence differs depending on the role of the agency. Some common references for government agency positions are the dietary reference intakes and the Dietary Guidelines for Americans, which together form the foundation for much of federal nutrition policy. Sugar consumption has increased in proportion to intake of other nutrients since 1980, when obesity began to increase substantially. Median intake of added sugars is ~12% of energy, whereas total sugar intake is ~22% of energy. Although there are differences in the way in which individual monosaccharides are metabolized, they are rarely consumed alone. A key issue related to obesity is likely the increased number of eating occasions and portion size for many indulgent foods; grain-based snacks have become the largest source of energy in the U.S. diet. There are currently insufficient data to justify a decision on regulation or taxation of sugar-containing foods and the like because the approach must be weighed against personal freedoms; the list of foods associated with obesity includes many commonly eaten items, and it is not likely that they are all causally related. Government should consider the totality of the evidence including the strength of the relationship of sugar intake with various health outcomes.


Predictors of Postoperative Seizure Recurrence: A Longitudinal Study of Temporal and Extratemporal Resections.
Objective. We investigated the longitudinal outcome of resective epilepsy surgery to identify the predictors of seizure recurrence. Materials and Methods. We retrospectively analyzed patients who underwent resections for intractable epilepsy over a period of 7 years. Multiple variables were investigated as potential predictors of seizure recurrence. The time to first postoperative seizure was evaluated using survival analysis and univariate analysis at annual intervals. Results. Among 70 patients, 54 (77%) had temporal and 16 (23%) had extratemporal resections. At last follow-up (mean 48 months; range 24-87 months), the outcome was Engel class I in 84% (n = 59) of patients. Seizure recurrence followed two patterns: recurrence was "early" (within 2 years) in 82% of patients, of whom 83% continued to have seizures despite optimum medical therapy; recurrence was "late" (after 2 years) in 18%, of whom 25% continued to have seizures subsequently. Among the variables of interest, only resection site and ictal EEG remained as independent predictors of seizure recurrence over the long term (p < 0.05). Extratemporal resection and discordance between ictal EEG and resection area were associated with 4.2-fold and 5.6-fold higher risk of seizure recurrence, respectively. Conclusions. Extratemporal epilepsy and uncertainty in ictal EEG localization are independent predictors of unfavorable outcome. Seizure recurrence within two years of surgery indicates poor long-term outcome.


Selective etching of injection molded zirconia-toughened alumina: Towards osseointegrated and antibacterial ceramic implants.
Due to their outstanding mechanical properties and excellent biocompatibility, zirconia-toughened alumina (ZTA) ceramics have become the gold standard in orthopedics for the fabrication of ceramic bearing components over the last decade. However, ZTA is bioinert, which hampers its implantation in direct contact with bone. Furthermore, periprosthetic joint infections are now the leading cause of failure for joint arthroplasty prostheses. To address both issues, an improved surface design is required: a controlled micro- and nano-roughness can promote osseointegration and limit bacterial adhesion whereas surface porosity allows loading and delivery of antibacterial compounds. In this work, we developed an integrated strategy aiming to provide both osseointegrative and antibacterial properties to ZTA surfaces. The micro-topography was controlled by injection molding. Meanwhile a novel process involving the selective dissolution of zirconia (selective etching) was used to produce nano-roughness and interconnected nanoporosity. Potential utilization of the porosity for loading and delivery of antibiotic molecules was demonstrated, and the impact of selective etching on mechanical properties and hydrothermal stability was shown to be limited. The combination of injection molding and selective etching thus appears promising for fabricating a new generation of ZTA components implantable in direct contact with bone. Zirconia-toughened alumina (ZTA) is the current gold standard for the fabrication of orthopedic ceramic components. In the present work, we propose an innovative strategy to provide both osseointegrative and antibacterial properties to ZTA surfaces: we demonstrate that injection molding allows a flexible design of surface micro-topography and can be combined with selective etching, a novel process that induces nano-roughness and surface interconnected porosity without the need for coating, avoiding reliability issues. These surface modifications have the potential to improve osseointegration. Furthermore, our results show that the porosity can be used for drug delivery and suggest that the etched surface could reduce bacterial adhesion.


Major hepatic resections for neoplasia in children.
In a consecutive series from 1968 to 1978, 11 hepatic resections encompassing at least two hepatic segments were carried out for neoplasia in pediatric patients varying in age from 7 days to 14 years. There were no operative deaths. These resections consisted of four right lobectomies, three extended right lobectomies, one right lobectomy with right nephrectomy and inferior vena caval resection, two left lobectomies, and one left extended lobectomy. Diagnoses were hepatoblastoma in six patients, Wilms' tumor invading the liver in two, hemangioendothelioma in two, and malignant mesenchymoma in one. Selective angiography and technetium Tc 99m sulfur colloid scintigraphy were important preoperative aids. Complications were infrequent and there were no major infections or biliary fistulas. There was one death eight months postoperatively due to recurrent hepatoblastoma. Vigorous hepatic regeneration occurred in all instances. Major hepatic resections are well tolerated in children and allow good subsequent development.


Plant-based corosolic acid: future anti-diabetic drug?
Diabetes is one of the nation's most prevalent, debilitating and costly diseases. For diabetes, frequent insulin treatment is very expensive and may increase anti-insulin antibody production, which may cause unwanted side effects. Corosolic acid may also have some efficacy in the treatment of diabetes, but without induction of anti-insulin antibodies. Recently, corosolic acid from Lagerstroemia speciosa L. leaf extracts has been reported to act via an indirect mechanism (unlike insulin) in animal experiments. The insulin-complementary anti-diabetic therapeutic value observed in these Japanese preliminary clinical trials has led to renewed interest in the biosynthesis of this compound. So far, there has been no clear evidence for a corosolic acid biosynthetic pathway in plants. This article provides possible roles of corosolic acid and hypothetical information on the biosynthetic pathway in plants.


Secreted Metabolome of ALS-Related hSOD1(G93A) Primary Cultures of Myocytes and Implications for Myogenesis.
Amyotrophic lateral sclerosis (ALS) is a motor neuron (MN) disease associated with progressive muscle atrophy, paralysis, and eventually death. Growing evidence demonstrates that the pathological process leading to ALS is the result of multiple altered mechanisms occurring not only in MNs but also in other cell types inside and outside the central nervous system. In this context, the involvement of skeletal muscle has been the subject of a few studies on patients and ALS animal models. In this work, by using primary myocytes derived from the ALS transgenic hSOD1(G93A) mouse model, we observed that the myogenic capability of such cells was defective compared to cells derived from control mice expressing the nonpathogenic hSOD1(WT) isoform. The correct in vitro myogenesis of hSOD1(G93A) primary skeletal muscle cells was rescued by the addition of a conditioned medium from healthy hSOD1(WT) myocytes, suggesting the existence of an in trans activity of secreted factors. To define a dataset of molecules participating in such safeguard action, we conducted comparative metabolomic profiling of a culture medium collected from hSOD1(G93A) and hSOD1(WT) primary myocytes and report here an altered secretion of amino acids and lipid-based signaling molecules. These findings support the urgency of better understanding the role of the skeletal muscle secretome in the regulation of the myogenic program and mechanisms of ALS pathogenesis and progression.


Pharmacodynamic analysis of eribulin safety in breast cancer patients using real-world postmarketing surveillance data.
Postmarketing surveillance is useful to collect safety data in real-world clinical settings. In this study, we applied postmarketing real-world data on a mechanistic model analysis for neutropenic profiles of eribulin in patients with recurrent or metastatic breast cancer. Demographic and safety data were collected using an active surveillance method from eribulin-treated recurrent or metastatic breast cancer patients. Changes in neutrophil counts over time were analyzed using a mechanistic pharmacodynamic model. Pathophysiological factors that might affect the severity of neutropenia were investigated, and neutropenic patterns were simulated for different treatment schedules. Clinical and laboratory data were collected from 401 patients (5199 neutrophil count measurements) who had not received granulocyte colony-stimulating factor and were eligible for pharmacodynamic analysis. The estimated mean parameters were as follows: mean transit time = 104.5 h, neutrophil proliferation rate constant = 0.0377 h-1 , neutrophil elimination rate constant = 0.0295 h-1 , and linear coefficient of drug effect = 0.0413 mL/ng. Low serum albumin levels and low baseline neutrophil counts were associated with severe neutropenia. The probability of grade ≥3 neutropenia was predicted to be 69%, 27%, and 27% for patients on standard, biweekly, and triweekly treatment scenarios, respectively, based on virtual simulations using the developed pharmacodynamic model. In conclusion, this is the first application of postmarketing surveillance data to a model-based safety analysis. This analysis of safety data reflecting authentic clinical settings will provide useful information on the safe use and potential risk factors of eribulin.


A sensor-weighted overlapping-sphere head model and exhaustive head model comparison for MEG.
The spherical head model has been used in magnetoencephalography (MEG) as a simple forward model for calculating the external magnetic fields resulting from neural activity. For more realistic head shapes, the boundary element method (BEM) or similar numerical methods are used, but at greatly increased computational cost. We introduce a sensor-weighted overlapping-sphere (OS) head model for rapid calculation of more realistic head shapes. The volume currents associated with primary neural activity are used to fit spherical head models for each individual MEG sensor such that the head is more realistically modelled as a set of overlapping spheres, rather than a single sphere. To assist in the evaluation of this OS model with BEM and other head models, we also introduce a novel comparison technique that is based on a generalized eigenvalue decomposition and accounts for the presence of noise in the MEG data. With this technique we can examine the worst possible errors for thousands of dipole locations in a realistic brain volume. We test the traditional single-sphere model, three-shell and single-shell BEM, and the new OS model. The results show that the OS model has accuracy similar to the BEM but is orders of magnitude faster to compute.


Factors affecting formation of adventitious branches in the seaweeds Fucus vesiculosus and F. radicans.
In the brackish Baltic Sea, shedding of adventitious branches is central to asexual recruitment of new thalli in the brown algae Fucus vesiculosus and F. radicans. To test which factors influence the formation of adventitious branches in brackish and in more marine conditions, we sampled 29 Fucus sites in the Baltic Sea (salinity 3-11) and 18 sites from the Danish straits, Kattegat, Skagerrak, and the North Sea (salinity 15-35). Separately for each area, we used structural equation modelling to determine which of eight predictor factors (phosphate, nitrate, chlorophyll-a (as a proxy for turbidity), temperature, salinity, oxygen, grazing pressure, and thallus area) best explained observed numbers of adventitious branches. In more marine waters, high yearly average values of phosphate, salinity and turbidity had positive effects on the formation of adventitious branches. In brackish-waters, however, high numbers of adventitious branches were found in areas with low yearly average values of temperature, salinity and oxygen. Grazing intensity had no significant effect in either of the two study areas, contrasting findings from studies in other areas. In areas with both sexually and asexually reproducing Fucus individuals, clones had on average more adventitious branches than unique genotypes, although there was strong variation among clonal lineages. This study is the first to investigate multiple potential drivers of formation of adventitious branches in natural populations of Fucus. Our results suggest that several different factors synergistically and antagonistically affect the growth of adventitious branches in a complex way, and that the same factor (salinity) can have opposing effects in different areas.


Analysis of high dimensional data using pre-defined set and subset information, with applications to genomic data.
Based on available biological information, genomic data can often be partitioned into pre-defined sets (e.g. pathways) and subsets within sets. Biologists are often interested in determining whether some pre-defined sets of variables (e.g. genes) are differentially expressed under varying experimental conditions. Several procedures are available in the literature for making such determinations, however, they do not take into account information regarding the subsets within each set. Secondly, variables (e.g. genes) belonging to a set or a subset are potentially correlated, yet such information is often ignored and univariate methods are used. This may result in loss of power and/or inflated false positive rate. We introduce a multiple testing-based methodology which makes use of available information regarding biologically relevant subsets within each pre-defined set of variables while exploiting the underlying dependence structure among the variables. Using this methodology, a biologist may not only determine whether a set of variables are differentially expressed between two experimental conditions, but may also test whether specific subsets within a significant set are also significant. The proposed methodology; (a) is easy to implement, (b) does not require inverting potentially singular covariance matrices, and (c) controls the family wise error rate (FWER) at the desired nominal level, (d) is robust to the underlying distribution and covariance structures. Although for simplicity of exposition, the methodology is described for microarray gene expression data, it is also applicable to any high dimensional data, such as the mRNA seq data, CpG methylation data etc.


Failures of perception in the low-prevalence effect: Evidence from active and passive visual search.
In visual search, rare targets are missed disproportionately often. This low-prevalence effect (LPE) is a robust problem with demonstrable societal consequences. What is the source of the LPE? Is it a perceptual bias against rare targets or a later process, such as premature search termination or motor response errors? In 4 experiments, we examined the LPE using standard visual search (with eye tracking) and 2 variants of rapid serial visual presentation (RSVP) in which observers made present/absent decisions after sequences ended. In all experiments, observers looked for 2 target categories (teddy bear and butterfly) simultaneously. To minimize simple motor errors, caused by repetitive absent responses, we held overall target prevalence at 50%, with 1 low-prevalence and 1 high-prevalence target type. Across conditions, observers either searched for targets among other real-world objects or searched for specific bears or butterflies among within-category distractors. We report 4 main results: (a) In standard search, high-prevalence targets were found more quickly and accurately than low-prevalence targets. (b) The LPE persisted in RSVP search, even though observers never terminated search on their own. (c) Eye-tracking analyses showed that high-prevalence targets elicited better attentional guidance and faster perceptual decisions. And (d) even when observers looked directly at low-prevalence targets, they often (12%-34% of trials) failed to detect them. These results strongly argue that low-prevalence misses represent failures of perception when early search termination or motor errors are controlled.


Formation of Coherent 1H-1T Heterostructures in Single-Layer MoS2 on Au(111).
Heterojunctions of semiconductors and metals are the fundamental building blocks of modern electronics. Coherent heterostructures between dissimilar materials can be achieved by composition, doping, or heteroepitaxy of chemically different elements. Here, we report the formation of coherent single-layer 1H-1T MoS2 heterostructures by mechanical exfoliation on Au(111), which are chemically homogeneous with matched lattices but show electronically distinct semiconducting (1H phase) and metallic (1T phase) character, with the formation of these heterojunctions attributed to a combination of lattice strain and charge transfer. The exfoliation approach employed is free of tape residues usually found in many exfoliation methods and yields single-layer MoS2 with millimeter (mm) size on the Au surface. Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), scanning tunneling microscopy (STM), and scanning tunneling spectroscopy (STS) have collectively been employed to elucidate the structural and electronic properties of MoS2 monolayers on Au substrates. Bubbles in the MoS2 formed by the trapping of ambient adsorbates beneath the single layer during deposition, have also been observed and characterized. Our work here provides a basis to produce two-dimensional heterostructures which represent potential candidates for future electronic devices.


Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy.
While platelet-activating factor (PAF) is produced in various diseases associated with bone resorption, its functions in bone metabolism remain unknown. Using PAF receptor-deficient mice, we evaluated the role of PAF in the development of bone resorption following ovariectomy, a model of postmenopausal osteoporosis. Through observations of bone mineral density and histomorphometric parameters, it was found that bone resorption was markedly attenuated in PAF receptor-deficient mice, indicating that PAF links estrogen depletion and osteoporosis in vivo. Osteoclasts expressed higher amounts of the enzymes required for PAF biosynthesis than osteoblasts. TNF-alpha and IL-1beta increased the acetyl-coenzyme A:lyso-PAF acetyltransferase activity in osteoclasts. Osteoclasts, but not osteoblasts, expressed the functional PAF receptor. PAF receptor stimulation prolonged the survival of osteoclasts in vitro. Furthermore, osteoclasts treated with a PAF receptor antagonist, and also those from PAF receptor-deficient mice, showed reductions in survival rate and Ca resorption activity. Consistently, in organ cultures, bone resorption was significantly suppressed by a PAF receptor antagonist treatment or genetic PAF receptor deficiency. Thus, these results suggest that, through the inflammatory cytokines, estrogen depletion enhances PAF production as a unique autocrine factor for osteoclast functions. Inhibition of PAF function might pave the way for a new strategy to prevent postmenopausal bone loss without disturbing osteoblast functions.


Cholestasis caused by lipid emulsions.
Liver function was observed in 35 patients receiving intravenous feeding for more than three weeks. A progressive cholestatic jaundice occurred in ten of 18 patients receiving a lipid emulsion in a dose of 3 grams per kilogram per day. Only one of 17 patients receiving a dose of 1 gram per kilogram per day showed evidence of cholestasis. Neither the type of amino acid preparation used nor the dosage appeared to be a factor. Similarly, the contribution to calories from dextrose did not influence the frequency of cholestasis. The cholestatic jaundice improved with the return to normal of liver function when the lipid emulsion dosage was reduced or intravenous feeding was discontinued.


Transforming growth factor-beta1 and prostate cancer.
Transforming growth factor-beta1 (TGF-beta1) is an important regulator of the normal and malignant prostate. In the non-malignant prostate, TGF-beta1 stimulates cell differentiation, inhibits epithelial cell proliferation and induces epithelial cell death. TGF-beta1 is secreted into semen and here it is an important immunosuppressive factor. Prostate cancer cells express high levels of TGF-beta1 and it seems to enhance prostate cancer growth and metastasis by stimulating angiogenesis and by inhibiting immune responses directed against tumour cells. Prostate cancer cells frequently lose their TGF-beta receptors and acquire resistance to the anti-proliferative and pro-apoptotic effects of TGF-beta1. Accordingly, high expression of TGF-beta1 and loss of TGF-beta receptor expression have been associated with a particularly bad prognosis in human prostate cancer patients. TGF-beta1 also seems to be a mediator of castration-induced apoptosis in androgen dependent normal and malignant prostate epithelial cells. The ability of some prostate tumours to avoid castration-induced apoptosis is however not simply due to loss of TGF-beta receptor type I or II expression in the tumour cells, but may also be related to an inability of these cells to up-regulate TGF-beta receptor levels in response to castration or possibly due to defects downstream of the receptors. Short-term therapy-induced changes in the TGF-beta system in prostate tumours can probably be used to predict the long-term response to androgen ablation treatment. Further investigations into the TGF-beta system in the prostate are, however, needed to elucidate how alterations in this system affect the behaviour of prostate tumours, and if this system can be manipulated for therapeutical purposes.


Tobacco preventive measures by dental care staff. An attempt to reduce the use of tobacco among adolescents.
The purpose of the present study was to investigate the tobacco habits of children and adolescents within the catchment area of a public dental clinic before and after information about tobacco was given by dental care staff. The study was carried out over a three-year period on all 12- to 19-year-olds who came to the clinic for check-ups, 919, 933 and 859 individuals during each respective year. In the first year epidemiological data regarding use of tobacco were registered. Starting with the second year of the study coordinated information was given about the detrimental health effects of tobacco use. This consisted of individual information during the check-up, waiting-room information, and tobacco information in connection with dental health education in school. Use of tobacco was observed from the age of 14. Use was similar among boys and girls and increased with age. The proportion of tobacco users was 10.3%, 11.5%, and 7.3% for the respective years of the study. Statistical analysis shows that the reduction between the second and third year of the study is significant (p < 0.05). The result supports the hypothesis that tobacco information conveyed by dental care staff can influence the tobacco habits of children and adolescents.


Disorders of blood pressure regulation-role of catecholamine biosynthesis, release, and metabolism.
Catecholamines (epinephrine and norepinephrine) are synthesised and produced by the adrenal medulla and postganglionic nerve fibres of the sympathetic nervous system. It is known that essential hypertension has a significant neurogenic component, with the rise in blood pressure mediated at least in part by overactivity of the sympathetic nervous system. Moreover, novel therapeutic strategies aimed at reducing sympathetic activity show promise in the treatment of hypertension. This article reviews recent advances within this rapidly changing field, particularly focusing on the role of genetic polymorphisms within key catecholamine biosynthetic enzymes, cofactors, and storage molecules. In addition, mechanisms linking the sympathetic nervous system and other adverse cardiovascular states (obesity, insulin resistance, dyslipidaemia) are discussed, along with speculation as to how recent scientific advances may lead to the emergence of novel antihypertensive treatments.


Time Course of Immune Response and Immunomodulation During Normal and Delayed Healing of Musculoskeletal Wounds.
Single trauma injuries or isolated fractures are often manageable and generally heal without complications. In contrast, high-energy trauma results in multi/poly-trauma injury patterns presenting imbalanced pro- and anti- inflammatory responses often leading to immune dysfunction. These injuries often exhibit delayed healing, leading to fibrosis of injury sites and delayed healing of fractures depending on the intensity of the compounding traumas. Immune dysfunction is accompanied by a temporal shift in the innate and adaptive immune cells distribution, triggered by the overwhelming release of an arsenal of inflammatory mediators such as complements, cytokines and damage associated molecular patterns (DAMPs) from necrotic cells. Recent studies have implicated this dysregulated inflammation in the poor prognosis of polytraumatic injuries, however, interventions focusing on immunomodulating inflammatory cellular composition and activation, if administered incorrectly, can result in immune suppression and unintended outcomes. Immunomodulation therapy is promising but should be conducted with consideration for the spatial and temporal distribution of the immune cells during impaired healing. This review describes the current state of knowledge in the spatiotemporal distribution patterns of immune cells at various stages during musculoskeletal wound healing, with a focus on recent advances in the field of Osteoimmunology, a study of the interface between the immune and skeletal systems, in long bone fractures. The goals of this review are to (1) discuss wound and fracture healing processes of normal and delayed healing in skeletal muscles and long bones; (2) provide a balanced perspective on temporal distributions of immune cells and skeletal cells during healing; and (3) highlight recent therapeutic interventions used to improve fracture healing. This review is intended to promote an understanding of the importance of inflammation during normal and delayed wound and fracture healing. Knowledge gained will be instrumental in developing novel immunomodulatory approaches for impaired healing.


Analyses of p53 expression pattern and BRCA mutations in patients with double primary breast and ovarian cancer.
To analyze the somatic pattern of p53 expression and BRCA germline mutation status in Israeli patients with both ovarian (OvCa) and breast cancer (BrCa). The study group comprised 43 Israeli patients with OvCa, all of whom had previous primary BrCa. p53 immunohistochemistry (IHC) on all available archival tissues and genotyping for the three predominant Jewish germline BRCA1-2 mutations were carried out. Samples from 64 patients with solitary OvCa and 61 with solitary BrCa were similarly analyzed as controls. p53 expression pattern and the immunopositivity rate were similar in the ovarian and breast tumors within the study group and in the two control groups: positive p53 staining was detected in 68% of ovarian tumors in the study group compared with 71.9% in the controls, and in 19.4% of the BrCa tissues versus 21.3% in the controls. Within the study group, advanced stage OvCa had a higher rate of p53 expression (84%) compared to early stage disease (38.5%) (P = 0.006). This difference was not apparent in the solitary OvCa control group. OvCa in BRCA1-2 mutation carriers from the study group were more likely to display positive p53 staining (79%), especially in tumors diagnosed before the age of 60 (90%) compared with the OvCa of noncarriers (60%), but this difference was statistically insignificant. The p53 expression rate in BrCa samples from the study group was not associated with BRCA1-2 mutation status. Positive p53 expression, detected by IHC, in OvCa patients with previous primary BrCa is significantly higher in advanced stage disease in BRCA1-2 mutation carriers. There is a higher positive p53 expression somatically in OvCa in BRCA1-2 carriers in whom OvCa was diagnosed before the age of 60 years, although this trend is not statistically significant. These observations suggest that somatic p53 inactivation may be an important event in ovarian tumorigenesis in this subset of patients.


Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase) deduced from a complementary DNA.
Neutral endopeptidase (EC 126.96.36.199) is a major constituent of kidney brush border membranes. It is also present in the brain where it has been shown to be involved in the inactivation of opioid peptides, methionine- and leucine-enkephalins. For this reason this enzyme is often called 'enkephalinase'. In order to characterize the primary structure of the enzyme, oligonucleotide probes were designed from partial amino acid sequences and used to isolate clones from kidney cDNA libraries. Sequencing of the cDNA inserts revealed the complete primary structure of the enzyme. Neutral endopeptidase consists of 750 amino acids. It contains a short N-terminal cytoplasmic domain (27 amino acids), a single membrane-spanning segment (23 amino acids) and an extracellular domain that comprises most of the protein mass. The comparison of the primary structure of neutral endopeptidase with that of thermolysin, a bacterial Zn-metallopeptidase, indicates that most of the amino acid residues involved in Zn coordination and catalytic activity in thermolysin are found within highly honmologous sequences in neutral endopeptidase.


Estimating the Combined Effects of Natural and Built Environmental Exposures on Birthweight among Urban Residents in Massachusetts.
Intrauterine growth has health implications both in childhood and adulthood. Birthweight is partially determined by prenatal environmental exposures. We aim to identify important predictors of birthweight out of a set of environmental, built environment exposures, and socioeconomic environment variables during pregnancy (i.e., fine particulate matter (PM2.5), temperature, greenness, walkability, noise, and economic indices). We included all singleton live births of mothers who resided in urban census block-groups and delivered in Massachusetts between 2001 and 2011 (n = 640,659). We used an elastic-net model to select important predictors of birthweight and constructed a multivariate model including the selected predictors, with adjustment for confounders. We additionally used a weighted quantile sum regression to assess the contribution of each exposure to differences in birthweight. All exposures were selected as important predictors of birthweight. In the multivariate model, lower birthweight was significantly associated with lower greenness and with higher temperature, walkability, noise, and segregation of the "high income" group. Treating the exposures individually, nighttime noise had the highest weight in its contribution to lower birthweight. In conclusion, after accounting for individual confounders, maternal environmental exposures, built environment exposures, and socioeconomic environment during pregnancy were important predictors of birthweight, emphasizing the role of these exposures in fetal growth and development.


The role of semantic memory in prospective memory and episodic future thinking: new insights from a case of semantic dementia.
Prospective memory (PM), the ability to remember to execute planned actions, and episodic future thinking (EFT), the ability to imagine future personal events, are two core aspects of future-oriented cognition. The present study aimed for the first time at examining the role of semantic memory loss in PM and EFT in a single case patient (SL) at the early stage of semantic dementia.First, we investigated various types of PM as well as episodic memory of new events using a validated ecological assessment via virtual reality. Second, we examined EFT using a temporally extended version of the TEMPau task, which measures episodic aspects of remembering the past and imagining the future taking temporal distance into account.Patient SL was deficient in semantically linked event-based PM and was unable to provide any EFT for the most distant period but was preserved in other types of PM and near and intermediate EFT.These findings provide new evidence on the role of semantic memory in PM depending on the type of intention and in EFT depending on the temporal distance mirroring autobiographical memory. Finally, they point out a specific link between PM and near EFT in future-oriented cognition.


Enhanced angular current intensity from Schottky emitters.
Even though the Schottky emitter is a high-brightness source of choice for electron beam systems, its angular current intensity is substantially lower than that of thermionic cathodes, rendering the emitter impractical for applications that require high beam current. In this study, two strategies were attempted to enhance its angular intensity, and their experimental results are reported. The first scheme is to employ a higher extraction field for increasing the brightness. However, the tip shape transformation was found to induce undesirably elevated emission from the facet edges at high fields. The second scheme exploits the fact that the angular intensity is proportional to the square of the electron gun focal length [Fujita, S. & Shimoyama, H. (2005) Theory of cathode trajectory characterization by canonical mapping transformation. J. Electron Microsc. 54, 331-343], which can be increased by scaling-up the emitter tip radius. A high angular current intensity (J(Omega) approximately 1.5 mA sr(-1)) was obtained from a scaled-up emitter. Preliminary performance tests were conducted on an electron probe-forming column by substituting the new emitter for the original tungsten filament gun. The beam current up to a few microamperes was achieved with submicron spatial resolution.


Frozen elephant trunk surgery-the Bologna's experience.
Different approaches are available to treat patients with complex and extensive diseases of the thoracic aorta. This study aims to report and comment on our experience with the frozen elephant trunk (FET) technique. Between January 2007 and July 2012, 122 patients (male: 86.9%; mean age: 61 years) underwent extensive thoracic aorta surgery using the FET approach with an E-vita open prosthesis. The most frequent indications for surgery included residual type A chronic dissection (45.9%), extensive degenerative aneurysm of the thoracic aorta (27%), and type A acute aortic dissection (7.4%). Sixty-nine patients had already undergone cardiac/aortic interventions through a median sternotomy. A total of 60 associated procedures were performed, with 76.6% on the aortic root. Selective antegrade cerebral perfusion and moderate hypothermia were used in all cases. Overall, hospital mortality was 15.2%. Post-operatively, 7.4% and 9.0% of patients were complicated by permanent neurologic dysfunction and spinal cord injury, respectively. For the surviving patients, 1- and 3-year freedom from all-cause mortality was (91.7±2.8)% and (79.1±6.1)%, respectively. 1- and 3-year freedom from re-intervention was (83.1±3.5)% and (74.1±4.3)%, respectively. In our experience, FET surgery allowed treatment of complex patients with extensive thoracic aortic diseases with satisfactory short- and mid-term results. Acute and chronic dissections represent interesting subsets for FET application. While further larger and longer-term studies are required to show the survival benefits of the FET technique versus other types of management, new strategies for spinal cord injury (paraplegia/paraparesis) reduction should also be researched.


SOMNAMBULISM: ALL-NIGHT ELECTROENCEPHALOGRAPHIC STUDIES.
Using special techniques allowing for subject mobility, we obtained continuous electroencephalographic recordings of known sleepwalkers. Somnambulistic incidents occurred during periods of slow-wave sleep. The incidents were not related temporally to dream periods, nor did they affect the total time or the percentage of time spent dreaming during the nights on which the subjects were studied.


Practice patterns in treating high-risk patients with hyperlipidemia at a northeast Tennessee university clinic.
This study was conducted to test the hypothesis that internal medicine residents at a northeast Tennessee university clinic were not compliant with the latest National Cholesterol Educational Program Adult Treatment Panel (NCEP-ATP) guidelines in treating hyperlipidemia in patients with diabetes and coronary artery disease. A retrospective medical record survey was conducted to evaluate residents' pattern in lowering low-density lipoprotein (LDL) cholesterol to below 100 mg/dL in patients with diabetes and coronary artery disease. The survey covered a 5-year period, from July 1998 to June 2003, and included 15 randomly chosen residents who were in training for 3 consecutive years. Charts were randomly selected from residents' clinics using International Classification of Diseases-9 codes for coronary artery disease or diabetes mellitus with hyperlipidemia. Five hundred fifty charts were reviewed. Only 41 (7.45%) met the inclusion criteria. Analysis of data using Epi-Info 2002 (Centers for Disease Control and Prevention, Atlanta, GA) revealed that only 68.3% of patients with diabetes and coronary artery disease reached target LDL cholesterol levels. Of the patients who reached target levels, only 42.9% maintained them. Analysis of variance and chi-square tests revealed that the frequency of cholesterol measurement, but not the frequency of physicians' visits, was associated with a higher likelihood of reaching the target LDL level. There was a suboptimal compliance among internal medicine residents in the frequency of screening for, reaching, and maintaining the target LDL cholesterol level, according to the latest NCEP-ATP guidelines, among high-risk patients with hyperlipidemias.