[Investigating actual conditions to clarify issues accompanying SMARPP].
Serigaya Methamphetamine Relapse Prevention Program (SMARPP) is an effective treatment program for drug-dependent patients that has been introduced by many psychiatric institutions. To conduct SMARPP effectively, the issues accompanying this program need to be clarified. Recently, an investigation was conducted on the healthcare/medical institutions that introduced this program and the results are reported in this study. Of healthcare/medical institutions that have introduced SMARPP as of June 2012, 35 were selected as subjects. Responses were collected from 26 institutions. Responses were also collected from 165 healthcare professionals who have conducted SMARPP at the 26 institutions. About 35% of the institutions were not medical institutions specializing in treatment of drug dependence. Of the healthcare professionals who have conducted the program, 26.7% (n = 44) completed a SMARPP training course; with most of them having no opportunity to participate in a training course before conducting it. Forty-three percent of them (n = 71) conducted the program once a week. The staff in charge of SMARPP reported participants' troublesome words and actions that they confronted. There were 60 cases in which the staff found it difficult to answer the participant's question, 91 cases in which they found it difficult to respond to the participant's behavior, and 98 cases in which they found it difficult to lead the meeting. Most of these words and actions seemed to reflect .'resistance' that was recognized in the course of treatment of drug dependence/alcoholism. The 'resistance' can be categorized into the following two types: 'resistance' to staying away from drug/alcohol which is also called 'suction talk' and 'resistance' reflecting 'discord' in the treatment relationship. Because physicians and psychologists were generally in charge of meetings, they frequently found it difficult to cope with troublesome situations. More healthcare professionals with the experience of treatment of drug dependence/alcoholism recognized difficulty in coping with them. This is probably because, unlike the conventional treatment for dependence emphasizing guiding or educational aspect, SMARPP is an intervention focusing on raising awareness. As a method of intervention for the participants in SMARPP, the intervention that does not control patients' 'resistance,' characteristic of motivational interviewing, seems to be effective.


Nutrient intake and food consumption among medical students in Greece assessed during a Clinical Nutrition course.
The objective of this study was to determine nutrient intake and food consumption patterns among medical students at the University of Crete, Greece. As part of the Clinical Nutrition course from 1989 to 2001, a total of 951 third-year medical students (500 male, 451 female) aged 22+/-2 years underwent dietary interview, during which individual 24-h dietary recalls were taken. The students also completed a questionnaire on smoking habits, and anthropometric measurements were performed. The Mann-Whitney test was applied to assess differences in nutrient and food group intake between lower and higher fat eaters. Analysis of covariance was used to study relationships between nutrient intakes and tobacco use, adjusting for gender, age, and body mass index. The mean daily energy intake was 2493 kcal (10437 kJ) for males and 1675 kcal (7012 kJ) for females. The contribution of total fat to energy intake was 40% in each gender. Lower fat eaters (</=34.3% of total energy) had higher intakes of fiber (P<0.01), vitamin C (P<0.01) and fruits (P<0.05), and a lower consumption of red meat (P<0.01) than students in the upper fat quartile (>/=46.0% of total energy). Smokers had higher intakes of energy (P<0.05) and saturated fatty acids (P<0.01), and lower intakes of fiber (P<0.001), folate (P<0.05) and vitamin C (P<0.001) than non-smokers/ex-smokers. Our results indicate a need for Greek medical students to improve their dietary and health habits. Dietary assessment could be used to enhance nutrition education in medical schools.


Investigating patterns in the spermiation response of eight Australian frogs administered human chorionic gonadotropin (hCG) and luteinizing hormone-releasing hormone (LHRHa).
Exogenous LHRHa and hCG are routinely employed to induce spermiation in vivo in anurans. To date, however, few studies have directly compared the efficacy of these two hormones. The aim of this study was threefold. First to quantify the spermiation response of eight Australian anuran species (Crinia glauerti, Crinia georgiana, Crinia pseudinsignifera, Geocrinia rosea, Heleioporus albopunctatus, Heleioporuseyrei, Neobatrachus pelobatoides and Pseudophryne guentheri) administered LHRHa and hCG. Second, to determine whether variance in spermiation responses is related to a species' reproductive mode (aquatic vs. terrestrial) or family (Limnodynastidae vs. Myobatrachidae). Third, to compare the quantity and quality of spermatozoa obtained via hormone administration (LHRHa and hCG) to spermatozoa obtained via testis removal and maceration. There was no significant difference in the viability of spermatozoa obtained from hCG or LHRHa administration in any of the eight study species. The sperm viability of samples ranged from 28-84% in C. georgiana and G. rosea, respectively. The hormone that induced the release of the highest number of spermatozoa differed among species, with all five species belonging to the family Myobatrachidae responding better to LHRHa, and the three species from the family Lymnodynastidae releasing a greater number of spermatozoa in response to hCG. Importantly, these results provide the first preliminary evidence that hCG and LHRHa efficacy in anurans may be predicted by phylogeny. Understanding such broad-scale patterns in the response of anurans to exogenous hormones will expedite the application of assisted reproductive technologies to novel species.


Genetic analysis of completely sequenced disease-associated MHC haplotypes identifies shuffling of segments in recent human history.
The major histocompatibility complex (MHC) is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorphic regions of the human genome such as the MHC are, however, somewhat refractory to some whole-genome analysis methods. To address this issue, we are employing a bacterial artificial chromosome (BAC) cloning strategy to sequence entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3-DQ2) and compare it with the MHC reference haplotype and with a second haplotype, COX (HLA-A1-B8-Cw7-DR3-DQ2), that shares the same HLA-DRB1, -DQA1, and -DQB1 alleles. We have defined the complete gene, splice variant, and sequence variation contents of all three haplotypes, comprising over 259 annotated loci and over 20,000 single nucleotide polymorphisms (SNPs). Certain coding sequences vary significantly between different haplotypes, making them candidates for functional and disease-association studies. Analysis of the two DR3 haplotypes allowed delineation of the shared sequence between two HLA class II-related haplotypes differing in disease associations and the identification of at least one of the sites that mediated the original recombination event. The levels of variation across the MHC were similar to those seen for other HLA-disparate haplotypes, except for a 158-kb segment that contained the HLA-DRB1, -DQA1, and -DQB1 genes and showed very limited polymorphism compatible with identity-by-descent and relatively recent common ancestry (<3,400 generations). These results indicate that the differential disease associations of these two DR3 haplotypes are due to sequence variation outside this central 158-kb segment, and that shuffling of ancestral blocks via recombination is a potential mechanism whereby certain DR-DQ allelic combinations, which presumably have favoured immunological functions, can spread across haplotypes and populations.


A randomized trial of hyperglycemic control in pediatric intensive care.
Whether an insulin infusion should be used for tight control of hyperglycemia in critically ill children remains unclear. We randomly assigned children (≤16 years of age) who were admitted to the pediatric intensive care unit (ICU) and were expected to require mechanical ventilation and vasoactive drugs for at least 12 hours to either tight glycemic control, with a target blood glucose range of 72 to 126 mg per deciliter (4.0 to 7.0 mmol per liter), or conventional glycemic control, with a target level below 216 mg per deciliter (12.0 mmol per liter). The primary outcome was the number of days alive and free from mechanical ventilation at 30 days after randomization. The main prespecified subgroup analysis compared children who had undergone cardiac surgery with those who had not. We also assessed costs of hospital and community health services. A total of 1369 patients at 13 centers in England underwent randomization: 694 to tight glycemic control and 675 to conventional glycemic control; 60% had undergone cardiac surgery. The mean between-group difference in the number of days alive and free from mechanical ventilation at 30 days was 0.36 days (95% confidence interval [CI], -0.42 to 1.14); the effects did not differ according to subgroup. Severe hypoglycemia (blood glucose, <36 mg per deciliter [2.0 mmol per liter]) occurred in a higher proportion of children in the tight-glycemic-control group than in the conventional-glycemic-control group (7.3% vs. 1.5%, P<0.001). Overall, the mean 12-month costs were lower in the tight-glycemic-control group than in the conventional-glycemic-control group. The mean 12-month costs were similar in the two groups in the cardiac-surgery subgroup, but in the subgroup that had not undergone cardiac surgery, the mean cost was significantly lower in the tight-glycemic-control group than in the conventional-glycemic-control group: -$13,120 (95% CI, -$24,682 to -$1,559). This multicenter, randomized trial showed that tight glycemic control in critically ill children had no significant effect on major clinical outcomes, although the incidence of hypoglycemia was higher with tight glucose control than with conventional glucose control. (Funded by the National Institute for Health Research, Health Technology Assessment Program, U.K. National Health Service; CHiP Current Controlled Trials number, ISRCTN61735247.).


Ciprofloxacin-induced urticaria and tenosynovitis: a case report.
Tendon disorders are rare events associated with fluoroquinolone congestion. Skin reactions are more frequent than tendon disorders. We reported this case as the combination of ciprofloxacin-induced urticaria and tenosynovitis has been unreported in young women. A 28-year-old woman without underlying disease developed urticarias and tendinopathy 4 days after the initiation of ciprofloxacin treatment for urinary infection. MRI of the left foot revealed increased synovial fluid surrounding the tendon of the flexor hallucis longus muscle representing tenosynovitis. Ciprofloxacin was ceased due to the possibility of ciprofloxacin-induced tendinopathy and urticaria. Complete resolution of her symptoms and findings occurred 3 days after discontinuation of ciprofloxacin without any additional treatment. Early discontinuation of fluoroquinolone therapy when tendinopathy is suspected is the basis of therapy. So, it should be kept in mind that fluoroquinolone-induced tendinopathy may occur in an otherwise healthy young patient with no risk factors and in a site other than the Achilles tendon.


Interpreting cerebrospinal fluid pleocytosis in HIV in the era of potent antiretroviral therapy.
Cerebrospinal fluid (CSF) pleocytosis may be seen in asymptomatic HIV-infected individuals. This finding complicates interpretation of CSF abnormalities when such individuals are evaluated for other central nervous system infections. The goal of this study was to determine the relationship between CSF pleocytosis, central nervous system (CNS) antiretroviral penetration, adherence to antiretroviral medication regimens, neurological symptoms and performance on neuropsychological tests. Clinically stable HIV-infected individuals at any peripheral blood CD4+ T cell count or any plasma viral load were asked to attend study visits at entry and every 6 months thereafter for at least one year. At each visit, they underwent a standardized neurological and medication history; neurological examination; a brief neuropsychological test battery: venipuncture; lumbar puncture; and assessment of medication adherence. Generalized estimating equations (GEE) were used to assess the relationships between CSF pleocytosis and other variables. CSF pleocytosis was independently and significantly related to lack of current antiretroviral use (OR 5.9, 95% CI 1.8-18.6, p = 0.003), CD4 count > 200/ul (OR 23.4, 95% CI 3.1-177.3, p = 0.002) and detectable plasma HIV RNA (OR 3.3, 95% CI 1.1-9.4, p = 0.03). At visits where antiretrovirals were used, and taking into account detectable plasma HIV RNA, an antiretroviral regimen that contained two or more agents with good CNS penetration conferred a trend toward lower odds of CSF pleocytosis (OR 0.45, 95% CI 0.18-1.12, p = 0.087). CSF pleocytosis is a characteristic of HIV disease that varies significantly with easily identifiable clinical and laboratory features. Use of antiretroviral agents decreases the odds of pleocytosis. This association may be stronger when the regimen contains two or more agents with good CNS penetration.


Hepatitis B/C and HIV in sub-Saharan Africa: an association between highly prevalent infectious diseases. A systematic review and meta-analysis.
Hepatitis B virus (HBV), hepatitis C virus (HCV), and the human immunodeficiency virus (HIV) are endemic in Africa. However, hepatitis co-infection rates among HIV-infected individuals remain controversial. The aim of this review was to determine the prevalence of HBV and HCV in HIV-infected patients in sub-Saharan Africa and to analyze whether HIV is associated with a higher HBV/HCV prevalence in that region. We performed a systematic review and meta-analysis. Studies reporting HBV and HCV prevalence data amongst HIV-infected patients in sub-Saharan Africa were included. Weighted means and medians across studies were calculated. Studies including an HIV-negative control group were used for meta-analysis. Risk ratios (RRs) were calculated using a random effects model. Sixty studies were included. Among HIV-infected individuals, mean HBsAg and anti-HCV prevalence rates were 15% and 7%, respectively. RRs for a positive HBsAg and a positive anti-HCV were 1.40 (95% confidence interval (CI) 1.16-1.69) and 1.60 (95% CI 1.05-2.45) for HIV-infected, as compared to HIV-uninfected, patients. Many HIV-positive individuals in sub-Saharan Africa are HBV or HCV co-infected. HIV is associated with a higher prevalence of both HBV and HCV in this region. However, this association is less evident than that observed in Western countries and varies between studies.


Regulation of Ca2+ release by InsP3 in single guinea pig hepatocytes and rat Purkinje neurons.
The repetitive spiking of free cytosolic [Ca2+] ([Ca2+]i) during hormonal activation of hepatocytes depends on the activation and subsequent inactivation of InsP3-evoked Ca2+ release. The kinetics of both processes were studied with flash photolytic release of InsP3 and time resolved measurements of [Ca2+]i in single cells. InsP3 evoked Ca2+ flux into the cytosol was measured as d[Ca2+]i/dt, and the kinetics of Ca2+ release compared between hepatocytes and cerebellar Purkinje neurons. In hepatocytes release occurs at InsP3 concentrations greater than 0.1-0.2 microM. A comparison with photolytic release of metabolically stable 5-thio-InsP3 suggests that metabolism of InsP3 is important in determining the minimal concentration needed to produce Ca2+ release. A distinct latency or delay of several hundred milliseconds after release of low InsP3 concentrations decreased to a minimum of 20-30 ms at high concentrations and is reduced to zero by prior increase of [Ca2+]i, suggesting a cooperative action of Ca2+ in InsP3 receptor activation. InsP3-evoked flux and peak [Ca2+]i increased with InsP3 concentration up to 5-10 microM, with large variation from cell to cell at each InsP3 concentration. The duration of InsP3-evoked flux, measured as 10-90% risetime, showed a good reciprocal correlation with d[Ca2+]i/dt and much less cell to cell variation than the dependence of flux on InsP3 concentration, suggesting that the rate of termination of the Ca2+ flux depends on the free Ca2+ flux itself. Comparing this data between hepatocytes and Purkinje neurons shows a similar reciprocal correlation for both, in hepatocytes in the range of low Ca2+ flux, up to 50 microM. s-1 and in Purkinje neurons at high flux up to 1,400 microM. s-1. Experiments in which [Ca2+]i was controlled at resting or elevated levels support a mechanism in which InsP3-evoked Ca2+ flux is inhibited by Ca2+ inactivation of closed receptor/channels due to Ca2+ accumulation local to the release sites. Hepatocytes have a much smaller, more prolonged InsP3-evoked Ca2+ flux than Purkinje neurons. Evidence suggests that these differences in kinetics can be explained by the much lower InsP3 receptor density in hepatocytes than Purkinje neurons, rather than differences in receptor isoform, and, more generally, that high InsP3 receptor density promotes fast rising, rapidly inactivating InsP3-evoked [Ca2+]i transients.


Biodiversity increases multitrophic energy use efficiency, flow and storage in grasslands.
The continuing loss of global biodiversity has raised questions about the risk that species extinctions pose for the functioning of natural ecosystems and the services that they provide for human wellbeing. There is consensus that, on single trophic levels, biodiversity sustains functions; however, to understand the full range of biodiversity effects, a holistic and multitrophic perspective is needed. Here, we apply methods from ecosystem ecology that quantify the structure and dynamics of the trophic network using ecosystem energetics to data from a large grassland biodiversity experiment. We show that higher plant diversity leads to more energy stored, greater energy flow and higher community-energy-use efficiency across the entire trophic network. These effects of biodiversity on energy dynamics were not restricted to only plants but were also expressed by other trophic groups and, to a similar degree, in aboveground and belowground parts of the ecosystem, even though plants are by far the dominating group in the system. The positive effects of biodiversity on one trophic level were not counteracted by the negative effects on adjacent levels. Trophic levels jointly increased the performance of the community, indicating ecosystem-wide multitrophic complementarity, which is potentially an important prerequisite for the provisioning of ecosystem services.


Host site of activity and cytological effects of histone-like proteins on the parasitic dinoflagellate Amyloodinium ocellatum.
Histone-like proteins (HLPs) are broad-spectrum, endogenously produced antibiotics which we have isolated from tissues of rainbow trout Oncorhynchus mykiss and hybrid striped bass (Morone saxatilis male x M. chrysops female). Here, we show that HLP-1, which has high sequence homology to histone H2B, equally inhibited both young and mature trophonts of the important ectoparasite Amyloodinium ocellatum. In addition to direct killing of Amyloodinium trophonts, there was evidence that HLP-1 from both rainbow trout and hybrid striped bass caused severe developmental abnormalities, including delayed development, in both the parasitic trophont stage as well as the reproductive tomont stage. The deleterious effects of HLP-1 also were manifested in what appeared to be 'delayed mortality', where parasites of normal appearance would die later in development. Similar serious damage was also seen with calf histone H2B and the unrelated peptide antibiotic magainin 2. A comparison of the antibiotic activity in mucus versus epidermis compartments of the skin of hybrid striped bass suggested that the majority of antibiotic (including HLP-1) activity resided in the epidermis, although some activity was present in the mucus. These data suggest that normal, nonimmune fish skin contains potent defenses against protozoan ectoparasites and that the effects of these defenses may extend beyond their transient interactions with the parasites, which has important implications for this host-parasite relationship.


Ground reaction forces at different speeds of human walking and running.
In this study the variation in ground reaction force parameters was investigated with respect to adaptations to speed and mode of progression, and to type of foot-strike. Twelve healthy male subjects were studied during walking (1.0-3.0 m s-1) and running (1.5-6.0 m s-1). The subjects were selected with respect to foot-strike pattern during running. Six subjects were classified as rearfoot strikers and six as forefoot strikers. Constant speeds were accomplished by pacer lights beside an indoor straightway and controlled by means of a photo-electronic device. The vertical, anteroposterior and mediolateral force components were recorded with a force platform. Computer software was used to calculate durations, amplitudes and impulses of the reaction forces. The amplitudes were normalized with respect to body weight (b.w.). Increased speed was accompanied by shorter force periods and larger peak forces. The peak amplitude of the vertical reaction force in walking and running increased with speed from approximately 1.0 to 1.5 b.w. and 2.0 to 2.9 b.w. respectively. The anteroposterior peak force and mediolateral peak-to-peak force increased about 2 times with speed in walking and about 2-4 times in running (the absolute values were on average about 10 times smaller than the vertical). The transition from walking to running resulted in a shorter support phase duration and a change in the shape of the vertical reaction force curve. The vertical peak force increased whereas the vertical impulse and the anteroposterior impulses and peak forces decreased. In running the vertical force showed an impact peak at touch-down among the rearfoot strikers but generally not among the forefoot strikers. The first mediolateral force peak was laterally directed (as in walking) for the rearfoot strikers but medially for the forefoot strikers. Thus, there is a change with speed in the complex interaction between vertical and horizontal forces needed for propulsion and equilibrium during human locomotion. The differences present between walking and running are consequences of fundamental differences in motor strategies between the two major forms of human progression.


The psychological effects of improvised explosive devices (IEDs) on UK military personnel in Afghanistan.
To explore the psychological consequences of improvised explosive device (IED) exposure as IEDs have been the greatest threat to UK military personnel in Afghanistan though the mental health consequences of IED exposure are largely unknown. Deployed UK military personnel completed a survey while deployed in Afghanistan. Combat personnel and those dealing specifically with the IED threat were compared with all other deployed personnel; the relationship between IED exposure, general combat experiences, Post Traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C) and General Health Questionnaire scores were evaluated. The response rate was 98% (n=2794). Half reported IED-related concerns, a third experienced exploding IEDs and a quarter gave medical aid to IED casualties. Combat and counter-IED threat personnel had higher levels of IED exposure than other deployed personnel. 18.8% of personnel who witnessed exploding IEDs scored positive for common mental disorder (General Health Questionnaire-12 scores ≥4) and 7.6% scored positive for probable PTSD symptoms (PTSD Checklist-Civilian Version scores ≥44). After adjusting for general combat exposure and other observed confounders, PTSD symptoms were associated with IED exposure whereas common mental disorder symptoms were not. IED exposure, IED-related concerns and functional impairment accumulated during deployment but functional impairment was related to factors other than IED exposure alone. In Afghanistan, a substantial proportion of personnel were exposed to exploding IEDs however, the majority of exposed personnel were psychologically healthy. Psychological effects were similar for combat personnel and those dealing specifically with the IED threat but both groups were at greater psychological risk than other deployed personnel.


Failed metal-on-metal hip arthroplasties: a spectrum of clinical presentations and operative findings.
A number of recent reports have described novel failure mechanisms of metal-on-metal bearings in total and resurfacing hip arthroplasty. Hip arthroplasties with metal-on-metal articulations are also subject to the traditional methods of failure seen with different bearing couples. There is currently little information in the literature to help guide timely clinical evaluation and management of these patients. We therefore describe the (1) clinical presentations; (2) reasons for failure; (3) operative findings; and (4) histologic findings in patients with failed metal-on-metal hip arthroplasties. We retrospectively identified all 37 patients (37 hips) with metal on metal total hip or resurfacing arthroplasties who underwent revision over the past 3 years at our institution. Relevant clinical, radiographic, laboratory, intraoperative, and histopathologic findings were analyzed for all patients. Of the 37 patients, 10 were revised for presumed hypersensitivity specific to the metal-on-metal articulation. This group included eight patients with tissue histology confirming chronic inflammation with lymphocytic infiltration, eight with aseptic loosening of a monoblock screwless uncemented acetabular component, two with iliopsoas impingement associated with a large-diameter femoral head, and three with femoral neck fracture after resurfacing arthroplasty; the remainder of the patients were revised for infection, instability, component malposition, and periprosthetic fracture. Increased awareness of the modes of failure will bring to light the potential complications particular to metal-on-metal articulations while placing these complications into the context of failures associated with all hip arthroplasties. This novel clinical information should be valuable for the practicing surgeon faced with this patient population. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Ocean currents modify the coupling between climate change and biogeographical shifts.
Biogeographical shifts are a ubiquitous global response to climate change. However, observed shifts across taxa and geographical locations are highly variable and only partially attributable to climatic conditions. Such variable outcomes result from the interaction between local climatic changes and other abiotic and biotic factors operating across species ranges. Among them, external directional forces such as ocean and air currents influence the dispersal of nearly all marine and many terrestrial organisms. Here, using a global meta-dataset of observed range shifts of marine species, we show that incorporating directional agreement between flow and climate significantly increases the proportion of explained variance. We propose a simple metric that measures the degrees of directional agreement of ocean (or air) currents with thermal gradients and considers the effects of directional forces in predictions of climate-driven range shifts. Ocean flows are found to both facilitate and hinder shifts depending on their directional agreement with spatial gradients of temperature. Further, effects are shaped by the locations of shifts in the range (trailing, leading or centroid) and taxonomic identity of species. These results support the global effects of climatic changes on distribution shifts and stress the importance of framing climate expectations in reference to other non-climatic interacting factors.


Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease.
In one genetic study, the high temperature requirement A2 (HTRA2) mitochondrial protein has been associated with increased risk for sporadic Parkinson disease (PD). One missense mutation, p.Gly399Ser, in its C-terminal PDZ domain (from the initial letters of the postsynaptic density 95, PSD-95; discs large; and zonula occludens-1, ZO-1 proteins [Kennedy, 1995]) resulted in defective protease activation, and induced mitochondrial dysfunction when overexpressed in stably transfected cells. Here we examined the contribution of genetic variability in HTRA2 to PD risk in an extended series of 266 Belgian PD patients and 273 control individuals. Mutation analysis identified a novel p.Arg404Trp mutation within the PDZ domain predicted to freeze HTRA2 in an inactive form. Moreover, we identified six patient-specific variants in 5' and 3' regulatory regions that might affect HTRA2 expression as supported by data of luciferase reporter gene analyses. Our study confirms a role of the HTRA2 mitochondrial protein in PD susceptibility through mutations in its functional PDZ domain. In addition, it extends the HTRA2 mutation spectrum to functional variants possibly affecting transcriptional activity. The latter underpins a previously unrecognized role for altered HTRA2 expression as a risk factor relevant to parkinsonian neurodegeneration.


A comparison of the hemodynamic effects of endothelin-1 and sarafotoxin S6b in conscious rats.
The hemodynamic effects of sarafotoxin S6b (SRT) and endothelin-1 (ET-1) were studied in conscious, freely moving rats. Intravenous bolus administration of ET-1 produced an initial transient depressor response and skeletal muscle (hindquarters) vasodilation. This depressor activity was not observed after i.v. SRT except at a high dose. The initial fall in blood pressure was followed by a sustained pressor response and an increase in total peripheral resistance which were mediated, at least partially, by visceral (mesenteric) and skeletal muscle (hindquarters) vasoconstriction. The durations of the pressor responses and times required to achieve the peak pressor effects (peak time) were greater for ET-1 as compared to SRT. The results of qualitatively similar sustained hemodynamic effects and the strong correlation between the amplitude of the responses to ET-1 and SRT in individual rats suggest that the sustained pressor responses to these peptides are mediated by the same receptors, although the potency was significantly greater for ET-1 than for SRT. Furthermore, the initial depressor and sustained pressor responses appear to be mediated by distinct receptor subtypes inasmuch as the same dose of ET-1 was required for both vasodilator and vasoconstrictor activity but a higher dose of SRT was required to elicit its vasodilator as compared to constrictor effects. Thus, SRT may have relatively lower affinity for receptors mediating its initial hemodynamic responses whereas ET-1 binds with equal affinity to both receptors. These potent and vascular specific hemodynamic actions suggest a role of endothelin in regulating cardiovascular function.


Emotion recognition from posed and spontaneous dynamic expressions: Human observers versus machine analysis.
The majority of research on the judgment of emotion from facial expressions has focused on deliberately posed displays, often sampled from single stimulus sets. Herein, we investigate emotion recognition from posed and spontaneous expressions, comparing classification performance between humans and machine in a cross-corpora investigation. For this, dynamic facial stimuli portraying the six basic emotions were sampled from a broad range of different databases, and then presented to human observers and a machine classifier. Recognition performance by the machine was found to be superior for posed expressions containing prototypical facial patterns, and comparable to humans when classifying emotions from spontaneous displays. In both humans and machine, accuracy rates were generally higher for posed compared to spontaneous stimuli. The findings suggest that automated systems rely on expression prototypicality for emotion classification and may perform just as well as humans when tested in a cross-corpora context. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Medication adherence among men who have sex with men at risk for HIV infection in the United States: implications for pre-exposure prophylaxis implementation.
Pre-exposure prophylaxis (PrEP) is a promising HIV prevention approach for men who have sex with men (MSM), however non-adherence could limit its effectiveness. Understanding the experiences of HIV-uninfected MSM taking routine medications can provide valuable insights into open label PrEP adherence in real world settings and guide development of PrEP adherence interventions. In this study, we examined self-reported medication-taking experiences and facilitators and barriers of medication adherence among a geographically-diverse online sample of HIV-uninfected US MSM. Among 1480 participants, 806 (54%) reported taking medications regularly, of whom 80% reported taking medications for treatment and 55% for prevention purposes. Facilitators of medication adherence included establishing a routine, keeping medication visible, and using a pill-box; barriers included forgetting, changes in routine, and being busy or away from home. Only 45% rated their medication-taking ability as excellent, and 36% reported not missing any doses in the past 30 days. In multivariable analyses, older men and those not reporting any adherence barriers were more likely to report excellent adherence, and men willing to use PrEP were more likely to report perfect 30-day adherence. Counseling strategies to build pill-taking routines and support younger MSM are suggested to maximize the public health impact of PrEP.


Molecularly Imprinted Electropolymer for a Hexameric Heme Protein with Direct Electron Transfer and Peroxide Electrocatalysis.
For the first time a molecularly imprinted polymer (MIP) with direct electron transfer (DET) and bioelectrocatalytic activity of the target protein is presented. Thin films of MIPs for the recognition of a hexameric tyrosine-coordinated heme protein (HTHP) have been prepared by electropolymerization of scopoletin after oriented assembly of HTHP on a self-assembled monolayer (SAM) of mercaptoundecanoic acid (MUA) on gold electrodes. Cavities which should resemble the shape and size of HTHP were formed by template removal. Rebinding of the target protein sums up the recognition by non-covalent interactions between the protein and the MIP with the electrostatic attraction of the protein by the SAM. HTHP bound to the MIP exhibits quasi-reversible DET which is reflected by a pair of well pronounced redox peaks in the cyclic voltammograms (CVs) with a formal potential of -184.4 ± 13.7 mV vs. Ag/AgCl (1 M KCl) at pH 8.0 and it was able to catalyze the cathodic reduction of peroxide. At saturation the MIP films show a 12-fold higher electroactive surface concentration of HTHP than the non-imprinted polymer (NIP).


Horner's syndrome secondary to tube thoracostomy.
Tube thoracostomy is a common therapeutic approach applied in medical practice. Certain complications of this procedure have been described in the literature. Oculosympathetic paresis, or Horner's syndrome, occurs from the interruption of second order preganglionic neurons and manifests as miosis, ptosis, hemifacial anhidrosis and enophthalmos. Iatrogenic Horner's syndrome, on the other hand, very rarely couples with tube thoracostomy. Only seven cases have been described in the literature, two of whom were in the pediatric age group. Herein we present a three-year-old girl operated for diaphragmatic hernia who later developed Horner's syndrome at the same side of the thorax tube. Upon the development of the pathology, the tube was repositioned and after one month only a slight ptosis persisted. Our patient seems to be the third case described in the literature. The clinical significance of this pathology is assessed in this report.


Physical activity and fat-free mass during growth and in later life.
Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass. A study is presented of the association between FFM and physical activity in relation to age. In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution. PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively. If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults.


Matching species traits to projected threats and opportunities from climate change.
Climate change can lead to decreased climatic suitability within species' distributions, increased fragmentation of climatically suitable space, and/or emergence of newly suitable areas outside present distributions. Each of these extrinsic threats and opportunities potentially interacts with specific intrinsic traits of species, yet this specificity is seldom considered in risk assessments. We present an analytical framework for examining projections of climate change-induced threats and opportunities with reference to traits that are likely to mediate species' responses, and illustrate the applicability of the framework. Sub-Saharan Africa. We applied the framework to 195 sub-Saharan African amphibians with both available bioclimatic envelope model projections for the mid-21st century and trait data. Excluded were 500 narrow-ranging species mainly from montane areas. For each of projected losses, increased fragmentation and gains of climate space, we selected potential response-mediating traits and examined the spatial overlap with vulnerability due to these traits. We examined the overlap for all species, and individually for groups of species with different combinations of threats and opportunities. In the Congo Basin and arid Southern Africa, projected losses for wide-ranging amphibians were compounded by sensitivity to climatic variation, and expected gains were precluded by poor dispersal ability. The spatial overlap between exposure and vulnerability was more pronounced for species projected to have their climate space contracting in situ or shifting to distant geographical areas. Our results exclude the potential exposure of narrow-ranging species to shrinking climates in the African tropical mountains. We illustrate the application of a framework combining spatial projections of climate change exposure with traits that are likely to mediate species' responses. Although the proposed framework carries several assumptions that require further scrutiny, its application adds a degree of realism to familiar assessments that consider all species to be equally affected by climate change-induced threats and opportunities.


Movement in Aesthetic Experiences: What We Can Learn from Parkinson Disease.
Visual art offers cognitive neuroscience an opportunity to study how subjective value is constructed from representations supported by multiple neural systems. A surprising finding in aesthetic judgment research is the functional activation of motor areas in response to static, abstract stimuli, like paintings, which has been hypothesized to reflect embodied simulations of artists' painting movements, or preparatory approach-avoidance responses to liked and disliked artworks. However, whether this motor involvement functionally contributes to aesthetic appreciation has not been addressed. Here, we examined the aesthetic experiences of patients with motor dysfunction. Forty-three people with Parkinson disease and 40 controls made motion and aesthetics judgments of high-motion Jackson Pollock paintings and low-motion Piet Mondrian paintings. People with Parkinson disease demonstrated stable and internally consistent preferences for abstract art, but their perception of movement in the paintings was significantly lower than controls in both conditions. The patients also demonstrated enhanced preferences for high-motion art and an altered relationship between motion and aesthetic appreciation. Our results do not accord well with a straightforward embodied simulation account of aesthetic experiences, because artworks that did not include visual traces of the artist's actions were still experienced as lower in motion by Parkinson patients. We suggest that the motor system may be involved in integrating low-level visual features to form abstract representations of movement rather than simulations of specific bodily actions. Overall, we find support for hypotheses linking motor responses and aesthetic appreciation and show that altered neural functioning changes the way art is perceived and valued.


Applying the mental models framework to carbon monoxide risk in northern Mexico.
Low-income residents of northern Mexico rely on unvented heaters during the winter, a practice that puts them at elevated risk for carbon monoxide intoxication. The goal of this study is to develop a communication protocol for carbon monoxide intoxication risks among the primarily low socioeconomic status population of Ciudad Juárez, Chihuahua, Mexico. The mental models risk communication approach was used to identify important gaps in public understanding. This approach consists of step-by-step assessment of information needs and effectiveness of risk communication efforts by using interviews and surveys. The mental models process uncovered a key technical misunderstanding, the subject population's belief that carbon monoxide can be seen or smelled, which may result in a risk-prone behavior: failure to use a carbon monoxide detector. A communication protocol was designed to address this and other knowledge gaps, and it produced significant improvements in subjects' knowledge in a pretest/posttest evaluation. The mental models process was successful in developing a communication instrument capable of improving knowledge in the subject population. Future research needs include assessing the extent to which this instrument succeeds in changing behavior and reducing the risk of carbon monoxide intoxication. Future interventional efforts may focus on encouraging people to use carbon monoxide detectors.


Coping, stress, and negative childhood experiences: The link to psychopathology, self-harm, and suicidal behavior.
Early life experiences, such as childhood adversities or poor parenting practices, can impact on the ability to cope with stressors across the lifespan. Furthermore, poor coping skills can lead to the development of mental illnesses, self-harm, and suicidal behavior. This study aimed to examine demographic differences in stress levels and to determine if those who had endured negative childhood experiences would be more likely to develop psychological problems and display suicidal behavior when current stress levels were accounted for. The study also explored the link between coping and mental health problems. Finally, it aimed to predict risk and protective factors related to good coping skills. The study utilized data obtained from the Ulster University Student Wellbeing Study, conducted across four university campuses in Northern Ireland in 2015 (n = 716) as part of the World Health Organization World Mental Health (WMH) International College Student Initiative. Mental health problems and early childhood experiences were examined using questions adapted from the WMH Composite International Diagnostic Interview, with self-harm and suicidal behavior measured using the Self-Injurious Thoughts and Behaviors Interview (SITBI). Females, non-heterosexuals, and older students experienced more current stress. When current stress levels were high, childhood adversities and parental overcontrol and overindulgence were related to higher rates of mental health problems, self-harm, and suicidal behavior. Poor coping skills were associated with negative mental health outcomes. Social support and good emotion-regulation strategies were related to effective coping, while parental overcontrol and overindulgence, female gender, and younger age were related to poorer coping. The study highlights the importance of developing good coping skills to deal with life stressors, thereby minimizing the risk of psychological problems and suicidal behavior. The findings provide support for initiatives to help parents improve their parenting skills and other programs to help young people cope with stress, and to develop social networks and adaptive emotion-regulation strategies.


An integrative review exploring the physical and psychological harm inherent in using restraint in mental health inpatient settings.
In Western society, policy and legislation seeks to minimize restrictive interventions, including physical restraint; yet research suggests the use of such practices continues to raise concerns. Whilst international agreement has sought to define physical restraint, diversity in the way in which countries use restraint remains disparate. Research to date has reported on statistics regarding restraint, how and why it is used, and staff and service user perspectives about its use. However, there is limited evidence directly exploring the physical and psychological harm restraint may cause to people being cared for within mental health inpatient settings. This study reports on an integrative review of the literature exploring available evidence regarding the physical and psychological impact of restraint. The review included both experimental and nonexperimental research papers, using Cooper's (1998) five-stage approach to synthesize the findings. Eight themes emerged: Trauma/retraumatization; Distress; Fear; Feeling ignored; Control; Power; Calm; and Dehumanizing conditions. In conclusion, whilst further research is required regarding the physical and psychological implications of physical restraint in mental health settings, mental health nurses are in a prime position to use their skills and knowledge to address the issues identified to eradicate the use of restraint and better meet the needs of those experiencing mental illness.


Force measurements of the alpha5beta1 integrin-fibronectin interaction.
The interaction of the alpha(5)beta(1) integrin and its ligand, fibronectin (FN), plays a crucial role in the adhesion of cells to the extracellular matrix. An important intrinsic property of the alpha(5)beta(1)/FN interaction is the dynamic response of the complex to a pulling force. We have carried out atomic force microscopy measurements of the interaction between alpha(5)beta(1) and a fibronectin fragment derived from the seventh through tenth type III repeats of FN (i.e., FN7-10) containing both the arg-gly-asp (RGD) sequence and the synergy site. Direct force measurements obtained from an experimental system consisting of an alpha(5)beta(1) expressing K562 cell attached to the atomic force microscopy cantilever and FN7-10 adsorbed on a substrate were used to determine the dynamic response of the alpha(5)beta(1)/FN7-10 complex to a pulling force. The experiments were carried out over a three-orders-of-magnitude change in loading rate and under conditions that allowed for detection of individual alpha(5)beta(1)/FN7-10 interactions. The dynamic rupture force of the alpha(5)beta(1)/FN7-10 complex revealed two regimes of loading: a fast loading regime (>10,000 pN/s) and a slow loading regime (<10,000 pN/s) that characterize the inner and outer activation barriers of the complex, respectively. Activation by TS2/16 antibody increased both the frequency of adhesion and elevated the rupture force of the alpha(5)beta(1)/wild type FN7-10 complex to higher values in the slow loading regime. In experiments carried out with a FN7-10 RGD deleted mutant, the force measurements revealed that both inner and outer activation barriers were suppressed by the mutation. Mutations to the synergy site of FN, however, suppressed only the outer barrier activation of the complex. For both the RGD and synergy deletions, the frequency of adhesion was less than that of the wild type FN7-10, but was increased by integrin activation. The rupture force of these mutants was only slightly less than that of the wild type, and was not increased by activation. These results suggest that integrin activation involved a cooperative interaction with both the RGD and synergy sites.


Face it or hide it: parental socialization of reappraisal and response suppression.
Mastery of cognitive emotion regulation strategies is an important developmental task. This paper focuses on two strategies that occur from preschool age onwards (Stegge and Meerum Terwogt, 2007): reappraisal and response suppression. Parental socialization of these strategies was investigated in a sample of N = 219 parents and their children. Informed by the tripartite model of family impact on children's emotion regulation, direct relations of emotion socialization components (modeling and reactions to the child's negative emotions) and indirect relations of parental emotion-related beliefs (such as parental emotion regulation self-efficacy) were examined. Data on emotion socialization components and parental beliefs on emotion regulation were collected via self-report. Data on children's emotion regulation strategies were collected via parent report. Findings showed direct effects of parental modeling and parenting practices on children's emotion regulation strategies, with distinct socialization paths for reappraisal and response suppression. An indirect effect of parental emotion regulation self-efficacy on children's reappraisal was found. These associations were not moderated by parent sex. Findings highlight the importance of both socialization components and parental emotion-related beliefs for the socialization of cognitive emotion regulation strategies and suggest a domain-specific approach to the socialization of emotion regulation strategies.


Differential transcriptional analysis of the cyanobacterium Cyanothece sp. strain ATCC 51142 during light-dark and continuous-light growth.
We analyzed the metabolic rhythms and differential gene expression in the unicellular, diazotrophic cyanobacterium Cyanothece sp. strain ATCC 51142 under N(2)-fixing conditions after a shift from normal 12-h light-12-h dark cycles to continuous light. We found that the mRNA levels of approximately 10% of the genes in the genome demonstrated circadian behavior during growth in free-running (continuous light) conditions. The genes for N(2) fixation displayed a strong circadian behavior, whereas photosynthesis and respiration genes were not as tightly regulated. One of our main objectives was to determine the strategies used by these cells to perform N(2) fixation under normal day-night conditions, as well as under the greater stress caused by continuous light. We determined that N(2) fixation cycled in continuous light but with a lower N(2) fixation activity. Glycogen degradation, respiration, and photosynthesis were also lower; nonetheless, O(2) evolution was about 50% of the normal peak. We also demonstrated that nifH (encoding the nitrogenase Fe protein), nifB, and nifX were strongly induced in continuous light; this is consistent with the role of these proteins during the assembly of the enzyme complex and suggested that the decreased N(2) fixation activity was due to protein-level regulation or inhibition. Many soluble electron carriers (e.g., ferredoxins), as well as redox carriers (e.g., thioredoxin and glutathione), were strongly induced during N(2) fixation in continuous light. We suggest that these carriers are required to enhance cyclic electron transport and phosphorylation for energy production and to maintain appropriate redox levels in the presence of elevated O(2), respectively.


Optical Density of Subretinal Fluid in Retinal Detachment.
To investigate the changes over time in optical density (OD) characteristics of subretinal fluid (SRF) in rhegmatogenous retinal detachment (RRD) and their clinical relevance. The study included patients with first-onset RRD and no history of intraocular illness who underwent optical coherence tomography (OCT) and whose OCT scans showed sufficient SRF for sampling (08/2013-09/2014). The highest quality B-scan (as graded by the OCT image acquisition software) containing SRF was analyzed. Optical density measurements were obtained using ImageJ. Optical density ratios (ODRs) were calculated as SRF OD divided by vitreous OD. Time from onset of RRD was determined by first signs of visual loss as described in the patient's anamnesis. Patients were divided into three groups by RRD duration: acute (≤1 week), subacute (between 1 week and 1 month), and chronic (>1 month). Thirty-five eyes (34 patients) met the inclusion criteria. The ODR measurement was significantly associated with RRD duration. The ODR had a significant (P < 0.0001) association with the 3-month postoperative visual acuity (VA). Vitreous OD did not differ significantly between the three groups. The increase over time in the ODR of the SRF in RRD might reflect a change in SRF composition and state of the retina. This, together with a significant association between preoperative ODR values and postoperative VA suggest its potential as a biological prognostic marker.


Open-ended interview questions and saturation.
Sample size determination for open-ended questions or qualitative interviews relies primarily on custom and finding the point where little new information is obtained (thematic saturation). Here, we propose and test a refined definition of saturation as obtaining the most salient items in a set of qualitative interviews (where items can be material things or concepts, depending on the topic of study) rather than attempting to obtain all the items. Salient items have higher prevalence and are more culturally important. To do this, we explore saturation, salience, sample size, and domain size in 28 sets of interviews in which respondents were asked to list all the things they could think of in one of 18 topical domains. The domains-like kinds of fruits (highly bounded) and things that mothers do (unbounded)-varied greatly in size. The datasets comprise 20-99 interviews each (1,147 total interviews). When saturation was defined as the point where less than one new item per person would be expected, the median sample size for reaching saturation was 75 (range = 15-194). Thematic saturation was, as expected, related to domain size. It was also related to the amount of information contributed by each respondent but, unexpectedly, was reached more quickly when respondents contributed less information. In contrast, a greater amount of information per person increased the retrieval of salient items. Even small samples (n = 10) produced 95% of the most salient ideas with exhaustive listing, but only 53% of those items were captured with limited responses per person (three). For most domains, item salience appeared to be a more useful concept for thinking about sample size adequacy than finding the point of thematic saturation. Thus, we advance the concept of saturation in salience and emphasize probing to increase the amount of information collected per respondent to increase sample efficiency.


Film Extrusion of Crambe abyssinica/Wheat Gluten Blends.
Crambe abyssinica is a plant with potential for use in industrial (non-food) plant oil production. The side stream from this oil production is a high-protein crambe meal that has limited value, as it is not fit for food or feed use. However, it contains proteins that could potentially make it a suitable raw material for higher-value products. The purpose of this study was to find methods of making this side stream into extruded films, showing that products with a higher value can be produced. The study mainly considered the development of material compositions and methods of preparing and extruding the material. Wheat gluten was added as a supportive protein matrix material, together with glycerol as a plasticizer and urea as a denaturant. The extrudate was evaluated with respect to mechanical (tensile testing) and oxygen barrier properties, and the extrudate structure was revealed visually and by scanning electron microscopy. A denser, more homogeneous material had a lower oxygen transmission rate, higher strength, and higher extensibility. The most homogeneous films were made at an extruder die temperature of 125-130 °C. It is shown here that a film can be extruded with promising mechanical and oxygen barrier properties, the latter especially after a final compression molding step.


A nationwide survey on the epidemiology and clinical features of eosinophilic granulomatosis with polyangiitis (Churg-Strauss) in Japan.
We conducted a cross-sectional nationwide survey to determine eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) prevalence and clinical features in Japan. Data for EGPA patients in 2008 were collected from 1,564 hospitals. In total, 965 patients were reported from 365 departments. In a second survey, clinical data for 473 patients were obtained. We estimated that 1,866 (95% CI: 1,640-2,092) patients have EGPA in Japan (prevalence, 17.8/1,000,000). Of the 473 patients in the second survey, 315 fulfilled American College of Rheumatology (ACR) criteria or Lanham's criteria for EGPA. The mean age (± SD) of the 315 at onset was 55 ± 14 years, male to female ratio 1:2. 93% of patients had neurological manifestations, which were the organ system most frequently involved. Among 277 patients tested for myeloperoxidase (MPO)-/p anti-neutrophil cytoplasmic antibody (ANCA), 139 (50%) were positive, while only 6 of 238 were positive for proteinase3 (PR3)-/cANCA. MPO-ANCA-positive patients had renal involvement, mucous membrane or ophthalmological symptoms, and ENT symptoms more frequently, whereas cutaneous lesions and cardiovascular involvement were less common. The prevalence of EGPA and the frequency of MPO-/p-ANCA-positivity in Japanese EGPA patients were mostly similar to those of Western countries. However, female predominance and a high frequency of neurological manifestations characterized Japanese patients.


Infection of Acanthamoeba castellanii by Chlamydia pneumoniae.
Chlamydia pneumoniae is an intracellular respiratory pathogen, which, similar to Legionella, might have developed mechanisms to escape the intracellular bactericidal activity of both human host cells and amoeba. We therefore investigated the intracellular growth and survival of C. pneumoniae in Acanthamoeba castellanii by using cell culture, immunofluorescence microscopy, and electron microscopy. A castellanii was incubated with purified elementary bodies of C. pneumoniae TW 183 at a concentration of 10(6) inclusion-forming units (IFU)/ml to give a ratio of approximately 1 IFU of C. pneumoniae per amoeba. Quantitative determination of chlamydial growth within A. castellanii revealed viable and infective C. pneumoniae in the range of 10(4) to 10(5) IFU/ml between days 7 and 14 postinfection. Immunofluorescence analysis and transmission electron microscopy with subsequent immunogold staining confirmed evidence of infection of the amoebae by C. Pneumoniae and additionally revealed that C. pneumoniae entered the typical growth cycle. Our results show that amoebae allow the survival of C. pneumoniae, suggesting that amoebae may serve as an additional reservoir for Chlamydia or Chlamydia-related organisms.


Measuring experimental cyclohexane-water distribution coefficients for the SAMPL5 challenge.
Small molecule distribution coefficients between immiscible nonaqueuous and aqueous phases-such as cyclohexane and water-measure the degree to which small molecules prefer one phase over another at a given pH. As distribution coefficients capture both thermodynamic effects (the free energy of transfer between phases) and chemical effects (protonation state and tautomer effects in aqueous solution), they provide an exacting test of the thermodynamic and chemical accuracy of physical models without the long correlation times inherent to the prediction of more complex properties of relevance to drug discovery, such as protein-ligand binding affinities. For the SAMPL5 challenge, we carried out a blind prediction exercise in which participants were tasked with the prediction of distribution coefficients to assess its potential as a new route for the evaluation and systematic improvement of predictive physical models. These measurements are typically performed for octanol-water, but we opted to utilize cyclohexane for the nonpolar phase. Cyclohexane was suggested to avoid issues with the high water content and persistent heterogeneous structure of water-saturated octanol phases, since it has greatly reduced water content and a homogeneous liquid structure. Using a modified shake-flask LC-MS/MS protocol, we collected cyclohexane/water distribution coefficients for a set of 53 druglike compounds at pH 7.4. These measurements were used as the basis for the SAMPL5 Distribution Coefficient Challenge, where 18 research groups predicted these measurements before the experimental values reported here were released. In this work, we describe the experimental protocol we utilized for measurement of cyclohexane-water distribution coefficients, report the measured data, propose a new bootstrap-based data analysis procedure to incorporate multiple sources of experimental error, and provide insights to help guide future iterations of this valuable exercise in predictive modeling.


Incubating the research independence of a medical scientist training program graduate: a case study.
Physician-scientists play a critical role in discovering new biological knowledge and translating findings into medical practices that can improve clinical outcomes. Collectively, the National Institutes of Health (NIH) and its affiliated Medical Scientist Training Programs (MSTPs) invest upwards of $500,000 to fully train each of the 900+ MD/PhD students enrolled in these programs. Nevertheless, graduates face the challenges of navigating fragmented intervals of clinical training and research engagement, reinitiating research upon completing their residencies, managing financial pressures, and competing for funding following what is typically four or more years of research inactivity. Together, these barriers contribute to the high attrition rate of MSTP graduates from research careers. The authors designed and implemented (2009-2014), for a single trainee, an alternative postgraduate training model characterized by early research engagement, strategic mentoring, unyoked clinical and research milestones, and dedicated financial support. The pilot training experiment was so successful that the trainee secured an NIH project grant and completed his transition to research independence 3.5 years after starting the experimental training schedule-nearly 9 years earlier (based on age) than is typical for MD/PhDs transitioning from mentored to independent research. This success has demonstrated that unyoking research engagement from conventional calendar-based clinical training milestones is a feasible, effective means of incubating research independence in MSTP graduates. The authors encourage the design and application of similar unconventional approaches that interweave residency training with ongoing research activity for appropriate candidates, especially in subspecialties with increased MSTP graduate enrollment.


Nonhealing Wounds Caused by Brown Spider Bites: Application of Hyperbaric Oxygen Therapy.
Bites by Loxosceles spiders (also known as recluse spiders or brown spiders) can cause necrotic ulcerations of various sizes and dimensions. The current standard of care for brown spider bites includes analgesics, ice, compression, elevation, antihistamines, and surgical debridement. Hyperbaric oxygen therapy (HBOT) in the treatment of brown spider bites has been administered in the early stage of ulceration, or 2 to 6 days after the bite. Unfortunately, the diagnosis of spider bite-related ulcers is often delayed and weeks or months may elapse before HBOT is considered. To evaluate the effect of HBOT on nonhealing wounds caused by brown spider bites in the late, chronic, nonhealing stage. Analysis of 3 patients with brown spider-bite healing wounds treated at The Sagol Center for Hyperbaric Medicine and Research in Israel. Patients presented 2 to 3 months after failure of other therapies including topical dressings, antibiotics, and corticosteroids. All patients were treated with daily 2 ATA (atmospheres absolute) with 100% oxygen HBOT sessions. All 3 patients were previously healthy without any chronic disease. Their ages were 30, 42, and 73 years. They were treated once daily for 13, 17, and 31 sessions, respectively. The wounds of all 3 patients healed, and there was no need for additional surgical intervention. There were no significant adverse events in any of the patients. Microvascular injury related to brown spider bites may culminate in ischemic nonhealing wounds even in a relatively young, healthy population. Hyperbaric oxygen therapy should be considered as a valuable therapeutic tool even months after the bite.


Tissue-wide coordination of epithelium-to-neural stem cell transition in the Drosophila optic lobe requires Neuralized.
Many tissues are produced by specialized progenitor cells emanating from epithelia via epithelial-to-mesenchymal transition (EMT). Most studies have so far focused on EMT involving single or isolated groups of cells. Here we describe an EMT-like process that requires tissue-level coordination. This EMT-like process occurs along a continuous front in the Drosophila optic lobe neuroepithelium to produce neural stem cells (NSCs). We find that emerging NSCs remain epithelial and apically constrict before dividing asymmetrically to produce neurons. Apical constriction is associated with contractile myosin pulses and involves RhoGEF3 and down-regulation of the Crumbs complex by the E3 ubiquitin ligase Neuralized. Anisotropy in Crumbs complex levels also results in accumulation of junctional myosin. Disrupting the regulation of Crumbs by Neuralized lowered junctional myosin and led to imprecision in the integration of emerging NSCs into the front. Thus, Neuralized promotes smooth progression of the differentiation front by coupling epithelium remodeling at the tissue level with NSC fate acquisition.


Yield of diagnostic tests and its impact on cost in adult patients with syncope presenting to a community hospital.
Total annual costs for syncope-related hospitalizations were $2.4 billion in 2000. The aim of this study was to examine the type and number of tests ordered for patients admitted with syncope and whether these tests helped establish the cause. We studied the records of 1038 patients coded as "syncope" in billing records, and 167 fulfilled the eligibility criteria. The main outcome measures were the diagnostic yield of the ordered tests, the incremental cost/incremental benefit, and the number of admissions that can be averted if risk stratification were used in the evaluation. The etiology of the syncope was identified in 48.3% of the patients. Postural blood pressure measurement has the highest diagnostic yield at 58.7%, whereas history taking diagnosed 19.7% of cases. The diagnostic yields of telemetry, electrocardiogram, radionuclide stress test, echocardiography, and troponin measurement were 4.76%, 4.24%, 3.44%, 0.94%, and 0.62%, respectively. Chest x-ray, carotid ultrasonography, 24-hour Holter monitoring, brain computed tomography, and brain magnetic resonance imaging did not yield the diagnosis in any of the patients. Only 1.9% of the money spent in the evaluation of syncope was effective in leading to a definitive diagnosis. The orthostatic blood pressure measurement was ranked first in the incremental cost/incremental benefit ratio and the radionuclide stress test was ranked last (17.03 vs 42,369.0, respectively). Approximately 6% of the patients did not meet the admission criteria. Physicians ordered unnecessary tests that have a low yield and are not cost-effective. A standardized algorithmic approach should be the cornerstone in the evaluation of syncope.


Large-scale geographical variation in eggshell metal and calcium content in a passerine bird (Ficedula hypoleuca).
Birds have been used as bioindicators of pollution, such as toxic metals. Levels of pollutants in eggs are especially interesting, as developing birds are more sensitive to detrimental effects of pollutants than adults. Only very few studies have monitored intraspecific, large-scale variation in metal pollution across a species' breeding range. We studied large-scale geographic variation in metal levels in the eggs of a small passerine, the pied flycatcher (Ficedula hypoleuca), sampled from 15 populations across Europe. We measured 10 eggshell elements (As, Cd, Cr, Cu, Ni, Pb, Zn, Se, Sr, and Ca) and several shell characteristics (mass, thickness, porosity, and color). We found significant variation among populations in eggshell metal levels for all metals except copper. Eggshell lead, zinc, and chromium levels decreased from central Europe to the north, in line with the gradient in pollution levels over Europe, thus suggesting that eggshell can be used as an indicator of pollution levels. Eggshell lead levels were also correlated with soil lead levels and pH. Most of the metals were not correlated with eggshell characteristics, with the exception of shell mass, or with breeding success, which may suggest that birds can cope well with the current background exposure levels across Europe.


The accuracy of human population maps for public health application.
Human population totals are used for generating burden of disease estimates at global, continental and national scales to help guide priority setting in international health financing. These exercises should be aware of the accuracy of the demographic information used. The analysis presented in this paper tests the accuracy of five large-area, public-domain human population distribution data maps against high spatial resolution population census data enumerated in Kenya in 1999. We illustrate the epidemiological significance, by assessing the impact of using these different human population surfaces in determining populations at risk of various levels of climate suitability for malaria transmission. We also describe how areal weighting, pycnophylactic interpolation and accessibility potential interpolation techniques can be used to generate novel human population distribution surfaces from local census information and evaluate to what accuracy this can be achieved. We demonstrate which human population distribution surface performed best and which population interpolation techniques generated the most accurate bespoke distributions. Despite various levels of modelling complexity, the accuracy achieved by the different surfaces was primarily determined by the spatial resolution of the input population data. The simplest technique of areal weighting performed best. Differences in estimates of populations at risk of malaria in Kenya of over 1 million persons can be generated by the choice of surface, highlighting the importance of these considerations in deriving per capita health metrics in public health. Despite focussing on Kenya the results of these analyses have general application and are discussed in this wider context.


Potential Mechanisms Driving Population Variation in Spatial Memory and the Hippocampus in Food-caching Chickadees.
Harsh environments and severe winters have been hypothesized to favor improvement of the cognitive abilities necessary for successful foraging. Geographic variation in winter climate, then, is likely associated with differences in selection pressures on cognitive ability, which could lead to evolutionary changes in cognition and its neural mechanisms, assuming that variation in these traits is heritable. Here, we focus on two species of food-caching chickadees (genus Poecile), which rely on stored food for survival over winter and require the use of spatial memory to recover their stores. These species also exhibit extensive climate-related population level variation in spatial memory and the hippocampus, including volume, the total number and size of neurons, and adults' rates of neurogenesis. Such variation could be driven by several mechanisms within the context of natural selection, including independent, population-specific selection (local adaptation), environment experience-based plasticity, developmental differences, and/or epigenetic differences. Extensive data on cognition, brain morphology, and behavior in multiple populations of these two species of chickadees along longitudinal, latitudinal, and elevational gradients in winter climate are most consistent with the hypothesis that natural selection drives the evolution of local adaptations associated with spatial memory differences among populations. Conversely, there is little support for the hypotheses that environment-induced plasticity or developmental differences are the main causes of population differences across climatic gradients. Available data on epigenetic modifications of memory ability are also inconsistent with the observed patterns of population variation, with birds living in more stressful and harsher environments having better spatial memory associated with a larger hippocampus and a larger number of hippocampal neurons. Overall, the existing data are most consistent with the hypothesis that highly predictable differences in winter climate drive the evolution and maintenance of differences among populations both in cognition and in the brain via local adaptations, at least in food-caching parids.


Can Low-Income Americans Afford a Healthy Diet?
Many nutritional professionals believe that all Americans, regardless of income, have access to a nutritious diet of whole grains, lean meats, and fresh vegetables and fruit. In reality, food prices pose a significant barrier for many consumers who are trying to balance good nutrition with affordability. The Thrifty Food Plan (TFP), commonly cited as a model of a healthy low-cost diet, achieves cost goals by relaxing some nutrition constraints and by disregarding the usual eating habits of the American population. Diet optimization techniques, when sensitive to cost and social norms, can help identify affordable, good tasting, nutrient-rich foods that are part of the mainstream American diet.


A theoretical investigation of the long-haul RZ-DPSK system performance using DFF and NZDSF.
Transmission performances of 6,000 km RZ-DPSK system using dispersion flattened fiber (DFF) and non-zero dispersion shifted fiber (NZDSF) were theoretically investigated and compared. Both fibers showed similar performance when the repeater output power was small, but the DFF showed superior performance in the higher repeater output power regime. The result shows that the merit of the DFF is fully utilized when the repeater output power is high enough.


CanWalk: study protocol for a randomized feasibility trial of a walking intervention for people with recurrent or metastatic cancer.
Increasing numbers of people in the UK are living with recurrent or metastatic cancer, many of whom experience reduced quality of life resulting from the physical and psychosocial consequences of cancer and its treatment. While drug treatments are important at alleviating some symptoms, there is increasing evidence of the benefits of exercise in enhancing quality of life and health outcomes. Walking is an inexpensive and accessible form of exercise. To our knowledge, no studies have investigated whether a walking intervention is sufficient to enhance quality of life and alleviate symptoms in people with recurrent or metastatic cancer across a range of tumor types. This paper describes the CanWalk study protocol, which aims to assess the feasibility and acceptability of undertaking a randomized controlled trial of a community-based walking program to enhance quality of life and well-being in people with recurrent or metastatic cancer. A mixed methods feasibility study includes an exploratory two-center randomized controlled trial and qualitative interviews. A minimum of 60 participants will be recruited from two London NHS Trusts and randomized 1:1 between the walking intervention and standard care using minimization. The walking intervention consists of the initial provision of written/online information followed by a short motivational interview. Participants are instructed to walk for 30 min on alternate days and attend an organized volunteer-led walk once a week. Half of all participants will be asked to use a pedometer. Postal questionnaires will be completed at baseline (pre-randomization) and at 6, 12 and 24 weeks. A subsample of participants and stakeholders will be interviewed at the end of the study. Primary outcomes will be the acceptability and feasibility of the intervention and trial. A range of secondary outcome assessments needed to design a main study, including estimates of recruitment, adherence and variability in quality of life, will be evaluated. Data from this study will be used to refine the walking intervention, investigate the acceptability of the intervention and study design, and determine the most appropriate outcome measures thereby providing estimates of the factors needed to design the main study. ISRCTN42072606.


Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in Eμ-TCL1 mouse model.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States. The tissue microenvironment, specifically the lymph nodes, influences the biological and clinical behavior of CLL cells. Gene expression profiling of CLL cells from peripheral blood, bone marrow, and lymph nodes revealed Cav-1 as one of the genes that might be involved in the pathogenesis of CLL. We have previously reported that the knockdown of Cav-1 in primary CLL cells exhibits a significant decrease in cell migration and immune synapse formation. However, the precise role of Cav-1 in CLL initiation and progression in vivo is not known. Therefore, we decreased the expression of Cav-1 in vivo by breeding Eμ-TCL1 with cav-1 knockout mice. We observed a significant decrease in the number of CLL cells and rate of proliferation of CLL cells in spleen, liver, and bone marrow from Eμ-TCL1-Cav1(-/+) and Eμ-TCL1-Cav1(-/-) mice as compared with Eμ-TCL1 mice. In addition, there was a significant increase in survival of Eμ-TCL1-Cav1(-/+) and Eμ-TCL1-Cav1(-/-) compared with Eμ-TCL1 mice. Mechanistically, we observed a decrease in MAPK-Erk signaling measured by p-Erk levels in Eμ-TCL1-Cav1(-/+) mice when compared with Eμ-TCL1-Cav(wt/wt). Together these results indicate that decreased Cav-1 in Eμ-TCL1 mice significantly delays the onset of CLL and decreases leukemic progression by inhibiting MAPK-Erk signaling, suggesting a role for Cav-1 in the proliferation and progression of CLL.


Ethanol sensitivity in ATP-gated P2X receptors is subunit dependent.
P2X receptors are ligand-gated cation channels that are gated by synaptically released extracellular adenosine 5'-triphosphate (ATP). P2X receptors are inhibited by ethanol; however, few investigations have focused on ethanol's effects in P2X receptors. Recently, recombinant homomeric P2X4 receptors were reported to be sensitive to ethanol's inhibitory action, whereas recombinant P2X3 receptors were insensitive to ethanol. The two recombinant studies were conducted in different expression systems by using different techniques; therefore, questions remain. The present study tests the hypothesis that ethanol sensitivity in P2X receptors is subunit dependent. The effects of ethanol (25-200 mM +/- ATP) on rat recombinant homomeric P2X2 and P2X4 receptors expressed in Xenopus oocytes were tested by using two-electrode voltage clamp techniques. Ethanol inhibited EC10 ATP-gated currents significantly less in P2X2 versus P2X4 receptors. A second study found that ethanol right-shifted the ATP concentration-response curve in P2X2 receptors, which significantly increased the EC50 for ATP without altering the Hill slope or maximal current response to ATP. These latter characteristics of ethanol action in P2X2 receptors agree with previous work in P2X4 receptors. There was no effect of ethanol when tested in the absence of ATP. The findings are the first to show (1) ethanol inhibition of ATP-activated currents on P2X2 receptors, (2) differences in ethanol sensitivity between homomeric P2X receptors when tested under matched conditions, and (3) evidence that suggests similar mechanisms of ethanol action for P2X2 and P2X4 receptors. These findings provide the first direct support for the hypothesis that ethanol sensitivity in P2X receptors is subunit dependent.


Genetic and mass spectrometry analyses of the unusual type IV-like pili of the archaeon Methanococcus maripaludis.
The structure of pili from the archaeon Methanococcus maripaludis is unlike that of any bacterial pili. However, genetic analysis of the genes involved in the formation of these pili has been lacking until this study. Pili were isolated from a nonflagellated (ΔflaK) mutant and shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to consist primarily of subunits with an apparent molecular mass of 17 kDa. In-frame deletions were created in three genes, MMP0233, MMP0236, and MMP0237, which encode proteins with bacterial type IV pilin-like signal peptides previously identified by in silico methodology as likely candidates for pilus structural proteins. Deletion of MMP0236 or MMP0237 resulted in mutant cells completely devoid of pili on the cell surface, while deletion of the third pilin-like gene, MMP0233, resulted in cells greatly reduced in the number of pili on the surface. Complementation with the deleted gene in each case returned the cells to a piliated state. Surprisingly, mass spectrometry analysis of purified pili identified the major structural pilin as another type IV pilin-like protein, MMP1685, whose gene is located outside the first pilus locus. This protein was found to be glycosylated with an N-linked branched pentasaccharide glycan. Deletion and complementation analysis confirmed that MMP1685 is required for piliation.


Body Position Influences Which Neural Structures Are Recruited by Lumbar Transcutaneous Spinal Cord Stimulation.
Transcutaneous stimulation of the human lumbosacral spinal cord is used to evoke spinal reflexes and to neuromodulate altered sensorimotor function following spinal cord injury. Both applications require the reliable stimulation of afferent posterior root fibers. Yet under certain circumstances, efferent anterior root fibers can be co-activated. We hypothesized that body position influences the preferential stimulation of sensory or motor fibers. Stimulus-triggered responses to transcutaneous spinal cord stimulation were recorded using surface-electromyography from quadriceps, hamstrings, tibialis anterior, and triceps surae muscles in 10 individuals with intact nervous systems in the supine, standing and prone positions. Single and paired (30-ms inter-stimulus intervals) biphasic stimulation pulses were applied through surface electrodes placed on the skin between the T11 and T12 inter-spinous processes referenced to electrodes on the abdomen. The paired stimulation was applied to evaluate the origin of the evoked electromyographic response; trans-synaptic responses would be suppressed whereas direct efferent responses would almost retain their amplitude. We found that responses to the second stimulus were decreased to 14%±5% of the amplitude of the response to the initial pulse in the supine position across muscles, to 30%±5% in the standing, and to only 80%±5% in the prone position. Response thresholds were lowest during standing and highest in the prone position and response amplitudes were largest in the supine and smallest in the prone position. The responses obtained in the supine and standing positions likely resulted from selective stimulation of sensory fibers while concomitant motor-fiber stimulation occurred in the prone position. We assume that changes of root-fiber paths within the generated electric field when in the prone position increase the stimulation thresholds of posterior above those of anterior root fibers. Thus, we recommend conducting spinal reflex or neuromodulation studies with subjects lying supine or in an upright position, as in standing or stepping.


Incidence and clinical decision making for the Wada test over one decade: 1997-2007.
The objective of this study was to review the percentage of Wada tests performed on patients with intractable temporal lobe epilepsy undergoing surgery at a single epilepsy centre over the last decade, and to identify clinical features which are more likely associated with decision making in favour of Wada testing. We retrospectively reviewed all temporal lobe resections performed between 1997 and 2007 at the Cleveland Clinic Epilepsy Center. A total of 410 Wada tests were conducted on 777 patients undergoing temporal lobectomy (TL). Left temporal resection was performed in 55% of cases. The most frequent pathological diagnoses were hippocampal sclerosis (42%) and non-specific gliosis (26%). Overall, Wada test frequency in patients undergoing presurgical evaluation decreased over time. In 1997, 47 of 58 (81%) TL patients underwent Wada testing compared to 11 of 76 (14.4%) in 2007. Patients with left temporal lobe epilepsy, and/or those referred for subdural electrode placement, were significantly more likely to undergo Wada testing. The most common types of surgery were antero-medial temporal resection with removal of mesial structures (59%) and temporal resection without mesial structure removal (32%). Patients with left temporal epilepsy and Wada testing were significantly more likely to undergo resection of mesial cortex. Wada testing has declined over the last decade in this single centre study. Patients with left, likely dominant, temporal lobe epilepsy and those with subdural evaluations were more likely to undergo Wada testing. We speculate that the emergence of alternative noninvasive language lateralization techniques, along with concerns about the reliability of results and awareness of complication risks, are major reasons for the decline.


Urothelial Carcinomas With Trophoblastic Differentiation, Including Choriocarcinoma: Clinicopathologic Series of 16 Cases.
Trophoblastic differentiation (including choriocarcinoma) arising in urothelial carcinoma has been described in numerous case reports, but never in a single series. We present a series of these tumors, describing the morphologic spectrum, applying traditional and novel immunohistochemical stains, and characterizing clinical follow-up. We identified 16 cases, arising predominantly in the bladder (N=14), but also the ureter (N=1) and prostatic urethra (N=1). Six of our cases (38%) contained invasive urothelial carcinoma with admixed syncytiotrophoblasts, 8 cases (50%) consisted of invasive urothelial carcinoma with choriocarcinoma, 1 case (6%) showed urothelial carcinoma in situ with associated choriocarcinoma, and 1 case (6%) consisted of pure choriocarcinoma. Other subtypes of variant morphology were seen in 5 of our cases (31%) and included squamous, glandular, lipoid, chordoid/myxoid, and sarcomatoid features. Given the limited specificity of human chorionic gonadotropin immunohistochemistry, we also studied the expression of a novel specific trophoblastic marker, hydroxyl-δ-5-steroid dehydrogenase, as well as Sal-like protein 4. Human chorionic gonadotropin expression was seen in nearly all cases (93%) but was often not limited to the trophoblastic component, staining the urothelial component also in 85% of the cases. Expression of hydroxyl-δ-5-steroid dehydrogenase was more sensitive and more specific, staining 100% of the cases and limited to trophoblasts in all but 1 case. Sal-like protein 4 expression was variable, staining trophoblast in only 50% of cases and staining the urothelial carcinoma component in 43% of those positive cases. Most of our tumors presented at a high stage and were associated with poor clinical outcomes, with at least muscle-invasive disease (pT2) in 10 of the 14 bladder tumors (71%), periureteric fat invasion in the ureter tumor (pT3), distant metastases in 7 of 16 cases (44%) and death of disease in 3 of the 15 patients with follow-up (20%). Our study describes a series of urothelial carcinomas with trophoblastic differentiation, demonstrating the morphologic spectrum of this entity, its frequent association with other subtypes of variant morphology, its characteristic immunoprofile, and its aggressive clinical behavior.


Central and peripheral haemodynamic responses to high carbohydrate and high fat meals in human cardiac transplant recipients.
1. Patients with autonomic dysfunction and elderly people with an age-related decline in autonomic function can suffer from a fall in blood pressure after eating. While the cardiovascular changes after eating and the effect of meal composition on these changes are well established, the underlying mechanisms are less clear. 2. This study assessed the cardiac, circulatory and humoral responses to ingestion of isoenergetic (2.5 MJ) high carbohydrate and high fat meals in nine orthotopic cardiac transplant recipients, who before transplantation had significant circulatory, metabolic and autonomic abnormalities and after transplantation had complete or partial extrinsic cardiac denervation, and compared them to the responses seen in nine healthy age-matched control subjects. 3. All variables were measured non-invasively. Cardiac transplant recipients, despite cardiac denervation, showed a normal heart rate response to high carbohydrate and high fat meals (maximal increase at 30 min postprandially + 7.8 +/- 1.1 and + 63 +/- 1.4 beats/min respectively), a normal cardiac output response to the high carbohydrate meal (maximal increase at 30 min + 1.16 +/- 0.25 l/min), but a significantly attenuated cardiac output response to the high fat meal. Cardiac transplant recipients had attenuated superior mesenteric artery blood flow responses after both meals (P < 0.05) and an attenuated calf vascular resistance response after the high fat meal (P < 0.01). Throughout the study after both meals, cardiac transplant recipients maintained blood pressure. 4. This study demonstrates that cardiac transplant recipients, despite partial or complete cardiac denervation, have a normal chronotropic response to food and a normal cardiac output response to a high carbohydrate meal. The attenuated cardiac output response to a high fat meal did not compromise blood pressure, due at least in part to decreased splanchnic vasodilatation.


Driven to less distraction: rTMS of the right parietal cortex reduces attentional capture in visual search.
In visual search, the presence of a highly salient color singleton can slow or facilitate search for a shape target depending on whether the singleton is a distractor or coincides with the target. This is consistent with an attentional shift (attentional capture) to the salient item. This attentional capture can be driven by bottom-up or top-down processes or both. We investigated the role of the parietal cortex in attentional capture by a singleton using repetitive transcranial magnetic stimulation. Following disruption to the right posterior parietal cortex by sustained transcranial magnetic stimulation, the reaction time (RT) cost of the singleton distractor was reduced. At least part of this lessening of singleton distraction was due to the elimination of priming (top-down) effects between target and distractor singletons on consecutive trials. In Experiment 2, we presented the different conditions in separate blocks meaning any effects of the distractor can most likely be attributed to bottom-up processes. Nevertheless, there was still a decrease in RT interference from the distractor so that a reduction in priming cannot provide a full account of the results. The data are consistent with previous work positing that the right parietal cortex directs attention to salient stimuli (e.g., Constantinidis 2005, Mevorach et al. 2006), while also suggesting a role for the right parietal cortex in the integration of bottom-up salience information with memories for salient features on prior trials.


Two phases of offline learning in contour integration.
We demonstrate daytime and overnight offline modulations of perceptual learning in a visual integration task. We employed a contour integration task, which requires longer range spatial integration than the more commonly used texture discrimination task, yet, still addresses the earliest cortical processing levels. In order to dissociate the effect of daytime and overnight offline modulations on perceptual learning, we introduced a 12-h shift between the practice times of two groups of subjects. Throughout the five practice sessions, the 12-h shift resulted in stepwise modulation of a typical learning curve, with a phase shift between the two groups. Between sessions (offline) improvement during the day was relatively small and only occurred in the first few sessions, while it was always significant after a night of sleep. Our results extend the body of evidence on the potential role of sleep in perceptual learning and generalize it to integrative visual processes. We have clearly distinguished two phases of learning: both daytime and overnight improvements in the initial phase, and only overnight improvements in the later phase.


Bolus fluorouracil induced syncope and pulseless ventricular tachycardia: a case report.
5-fluorouracil is an anti-cancer drug commonly used in oncology practice. Typical side effects are myelosupression, nausea, vomiting, diarrhea and stomatitis. Cardiotoxicity is the other toxicity. Cardiac side effects are ST segment changes, rhythm abnormalities, supraventricular and ventricular dysrhytmias. Pulseless ventricular tachycardia and ventricular fibrillation releated with bolus fluorouracil were not detected in the literature. Here we discussed a 46 year-old male patient that has no known cardiac history. After bolus fluorouracil administration, syncope and pulseless ventricular tachycardia developed in this patient. There are a few explanations about the cardiotoxicity of fluorouracil. One of these is the effect on nitric oxide. It causes a reduction in the levels of endothelial NO and this leads coronary vasospasm. Another explanation is protein kinase C mediated vasospasm. In animal studies toxic myocarditis like lesions were detected with fluorouracil infusions. Finally both myocardit and vasospasm may lead cardiac problems like sudden cardiac deaths. Bolus 5-fluorouracil is as cardiotoxic as 5-fluorouracil infusion and we must be careful about the arrhytmia after the bolus administration.


Comparison of Oncentra® Brachy IPSA and graphical optimisation techniques: a case study of HDR brachytherapy head and neck and prostate plans.
There are a number of different dwell positions and time optimisation options available in the Oncentra® Brachy (Elekta Brachytherapy Solutions, Veenendaal, The Netherlands) brachytherapy treatment planning system. The purpose of this case study was to compare graphical (GRO) and inverse planning by simulated annealing (IPSA) optimisation techniques for interstitial head and neck (HN) and prostate plans considering dosimetry, modelled radiobiology outcome and planning time. Four retrospective brachytherapy patients were chosen for this study, two recurrent HN and two prostatic boosts. Manual GRO and IPSA plans were generated for each patient. Plans were compared using dose-volume histograms (DVH) and dose coverage metrics including; conformity index (CI), homogeneity index (HI) and conformity number (CN). Logit and relative seriality models were used to calculate tumour control probability (TCP) and normal tissue complication probability (NTCP). Approximate planning time was also recorded. There was no significant difference between GRO and IPSA in terms of dose metrics with mean CI of 1.30 and 1.57 (P > 0.05) respectively. IPSA achieved an average HN TCP of 0.32 versus 0.12 for GRO while for prostate there was no significant difference. Mean GRO planning times were greater than 75 min while average IPSA planning times were less than 10 min. Planning times for IPSA were greatly reduced compared to GRO and plans were dosimetrically similar. For this reason, IPSA makes for a useful planning tool in HN and prostate brachytherapy.