Haloperidol versus placebo for schizophrenia.
Haloperidol was developed in the late 1950s for use in the field of anaesthesia. Research subsequently demonstrated effects on hallucinations, delusions, aggressiveness, impulsiveness and states of excitement and led to the introduction of haloperidol as an antipsychotic. To evaluate the clinical effects of haloperidol for the management of schizophrenia and other similar serious mental illnesses compared with placebo. Initially, we electronically searched the databases of Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library (1998, Issue 4), The Cochrane Schizophrenia Group's Register (December 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH. We also checked references of all identified studies for further trial citations and contacted the authors of trials and pharmaceutical companies for further information and archive material.For the 2012 update, on 15 May 2012, we searched the Cochrane Schizophrenia Group's Trials Register. We included all relevant randomised controlled trials comparing the use of haloperidol (any oral dose) with placebo for those with schizophrenia or other similar serious, non-affective psychotic illnesses (however diagnosed). Our main outcomes of interest were death, loss to follow-up, clinical and social response, relapse and severity of adverse effects. We evaluated data independently and extracted, re-inspected and quality assessed the data. We analysed dichotomous data using risk ratio (RR) and calculated their 95% confidence intervals (CI). For continuous data, we calculated mean differences (MD). We excluded continuous data if loss to follow-up was greater than 50% and inspected data for heterogeneity. We used a fixed-effect model for all analyses. For the 2012 update, we assessed risk of bias of included studies and used the GRADE approach to create a 'Summary of findings' table. Twenty-five trials randomising 4651 people are now included in this review. We chose seven main outcomes of interest for the 'Summary of findings' table. More people allocated haloperidol improved in the first six weeks of treatment than those given placebo (4 RCTs n = 472, RR 0.67 CI 0.56 to 0.80, moderate quality evidence). A further eight trials also found a difference favouring haloperidol across the six weeks to six months period (8 RCTs n = 307 RR 0.67 CI 0.58 to 0.78, moderate quality evidence). Relapse data from two trials favoured haloperidol at < 52 weeks but the evidence was very low quality (2 RCTs n = 70, RR 0.69 CI 0.55 to 0.86). Moderate quality evidence showed about half of those entering studies failed to complete the short trials (six weeks to six months), although, at up to six weeks, 16 studies found a difference that marginally favoured haloperidol (n = 1812, RR 0.87 CI 0.80 to 0.95). Adverse effect data does, nevertheless, support clinical impression that haloperidol is a potent cause of movement disorders, at least in the short term. Moderate quality evidence indicates that haloperidol caused parkinsonism (5 RCTs n = 485, RR 5.48 CI 2.68 to 11.22), akathisia (6 RCTs n = 695, RR 3.66 CI 2.24 to 5.97, and acute dystonia (5 RCTs n = 471, RR 11.49 CI 3.23 to 10.85). Discharge from hospital was equivocal between groups (1 RCT n = 33, RR 0.85 CI 0.47 to 1.52, very low quality evidence). Data were not reported for death and patient satisfaction. Haloperidol is a potent antipsychotic drug but has a high propensity to cause adverse effects. Where there is no treatment option, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. However, where a choice of drug is available, people with schizophrenia and clinicians may wish to prescribe an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias. Haloperidol should be less favoured as a control drug for randomised trials of new antipsychotics.


Preparation and Characterization of an Oral Vaccine Formulation Using Electrosprayed Chitosan Microparticles.
Chitosan particles loaded with the antigen ovalbumin (OVA) and the adjuvant Quil-A were produced by electrospray, using mixtures of water/ethanol/acetic acid as a solvent. Three different chitosans designed as HMC+70, HMC+85, and HMC+90 (called as 705010, 855010, and 905010) were tested and its efficacy to be used in oral vaccine delivery applications was investigated. The morphology, size, and zeta potential of the produced particles were investigated, together with the encapsulation efficiency and release of OVA from the three chitosan formulations. Moreover, the mucoadhesion and cytotoxicity of the chitosan microparticles was examined. All the three formulations with OVA and Quil-A were in the micrometer size range and had a positive zeta potential between 46 and 75 mV. Furthermore, all the three formulations displayed encapsulation efficiencies above 80% and the release of OVA over a period of 80 h was observed to be between 38 and 47%. None of the developed formulations exhibited high mucoadhesive properties, either cytotoxicity. The formulation prepared with HMC+70, OVA, and Quil-A had the highest stability within 2 h in buffer solution, as measured by dynamic light scattering. The electrosprayed formulation consisting of HMC+70 with OVA and Quil-A showed to be the most promising as an oral vaccine system.


Comparing sensitivity and specificity of screening mammography in the United States and Denmark.
Delivery of screening mammography differs substantially between the United States (US) and Denmark. We evaluated whether there are differences in screening sensitivity and specificity. We included screens from women screened at age 50-69 years during 1996-2008/2009 in the US Breast Cancer Surveillance Consortium (BCSC) (n = 2,872,791), and from two population-based mammography screening programs in Denmark (Copenhagen, n = 148,156 and Funen, n = 275,553). Women were followed-up for 1 year. For initial screens, recall rate was significantly higher in BCSC (17.6%) than in Copenhagen (4.3%) and Funen (3.1%). Sensitivity was fairly similar in BCSC (91.8%) and Copenhagen (90.5%) and Funen (92.5%). At subsequent screens, recall rates were 8.8%, 1.8% and 1.4% in BCSC, Copenhagen and Funen, respectively. The BCSC sensitivity (82.3%) was lower compared with that in Copenhagen (88.9%) and Funen (86.9%), but when stratified by time since last screen, the sensitivity was similar. For both initial and subsequent screenings, the specificity of screening in BCSC (83.2% and 91.6%) was significantly lower than that in Copenhagen (96.6% and 98.8%) and Funen (97.9% and 99.2%). By taking time since last screen into account, it was found that American and Danish women had the same probability of having their asymptomatic cancers detected at screening. However, the majority of women free of asymptomatic cancers experienced more harms in terms of false-positive findings in the US than in Denmark.


The human oral microbiome.
The human oral cavity contains a number of different habitats, including the teeth, gingival sulcus, tongue, cheeks, hard and soft palates, and tonsils, which are colonized by bacteria. The oral microbiome is comprised of over 600 prevalent taxa at the species level, with distinct subsets predominating at different habitats. The oral microbiome has been extensively characterized by cultivation and culture-independent molecular methods such as 16S rRNA cloning. Unfortunately, the vast majority of unnamed oral taxa are referenced by clone numbers or 16S rRNA GenBank accession numbers, often without taxonomic anchors. The first aim of this research was to collect 16S rRNA gene sequences into a curated phylogeny-based database, the Human Oral Microbiome Database (HOMD), and make it web accessible (www.homd.org). The HOMD includes 619 taxa in 13 phyla, as follows: Actinobacteria, Bacteroidetes, Chlamydiae, Chloroflexi, Euryarchaeota, Firmicutes, Fusobacteria, Proteobacteria, Spirochaetes, SR1, Synergistetes, Tenericutes, and TM7. The second aim was to analyze 36,043 16S rRNA gene clones isolated from studies of the oral microbiota to determine the relative abundance of taxa and identify novel candidate taxa. The analysis identified 1,179 taxa, of which 24% were named, 8% were cultivated but unnamed, and 68% were uncultivated phylotypes. Upon validation, 434 novel, nonsingleton taxa will be added to the HOMD. The number of taxa needed to account for 90%, 95%, or 99% of the clones examined is 259, 413, and 875, respectively. The HOMD is the first curated description of a human-associated microbiome and provides tools for use in understanding the role of the microbiome in health and disease.


Genome-Wide Association Study of Growth and Body-Shape-Related Traits in Large Yellow Croaker (Larimichthys crocea) Using ddRAD Sequencing.
Large yellow croaker (Larimichthys crocea) is an economically important marine fish species of China. Due to overfishing and marine pollution, the wild stocks of this croaker have collapsed in the past decades. Meanwhile, the cultured croaker is facing the difficulties of reduced genetic diversity and low growth rate. To explore the molecular markers related to the growth traits of croaker and providing the related SNPs for the marker-assisted selection, we used double-digest restriction-site associated DNA (ddRAD) sequencing to dissect the genetic bases of growth traits in a cultured population and identify the SNPs that associated with important growth traits by GWAS. A total of 220 individuals were genotyped by ddRAD sequencing. After quality control, 27,227 SNPs were identified in 220 samples and used for GWAS analysis. We identified 13 genome-wide significant associated SNPs of growth traits on 8 chromosomes, and the beta P of these SNPs ranged from 0.01 to 0.86. Through the definition of candidate regions and gene annotation, candidate genes related to growth were identified, including important regulators such as fgf18, fgf1, nr3c1, cyp8b1, fabp2, cyp2r1, ppara, and ccm2l. We also identified SNPs and candidate genes that significantly associated with body shape, including bmp7, col1a1, col11a2, and col18a1, which are also economically important traits for large yellow croaker aquaculture. The results provided insights into the genetic basis of growth and body shape in large yellow croaker population and would provide reliable genetic markers for molecular marker-assisted selection in the future. Meanwhile, the result established a basis for our subsequent fine mapping and related gene study.


Assessing the impact of health literacy on education retention of stroke patients.
Inadequate health literacy is a pervasive problem with major implications for reduced health status and health disparities. Despite the role of focused education in both primary and secondary prevention of stroke, the effect of health literacy on stroke education retention has not been reported. We examined the relationship of health literacy to the retention of knowledge after recommended stroke education. This prospective cross-sectional study was conducted at an urban safety-net hospital. Study subjects were patients older than 18 admitted to the hospital stroke unit with a diagnosis of acute ischemic stroke who were able to provide informed consent to participate (N = 100). Health literacy levels were measured by using the short form of Test of Functional Health Literacy in Adults. Patient education was provided to patients at an inpatient stroke unit by using standardized protocols, in compliance with Joint Commission specifications. The education outcomes for poststroke care education, knowledge retention, was assessed for each subject. The effect of health literacy on the Stroke Patient Education Retention scores was assessed by using univariate and multivariate analyses. Of the 100 participating patients, 59% had inadequate to marginal health literacy. Stroke patients who had marginal health literacy (mean score, 7.45; standard deviation [SD], 1.9) or adequate health literacy (mean score, 7.31; SD, 1.76) had statistically higher education outcome scores than those identified as having inadequate health literacy (mean score, 5.58; SD, 2.06). Results from multivariate analysis indicated that adequate health literacy was most predictive of education outcome retention. This study demonstrated a clear relationship between health literacy and stroke education outcomes. Studies are needed to better understand the relationship of health literacy to key educational outcomes for primary or secondary prevention of stroke and to refine stroke education for literacy levels of high-risk populations.


Minor impact of ocean acidification to the composition of the active microbial community in an Arctic sediment.
Effects of ocean acidification on the composition of the active bacterial and archaeal community within Arctic surface sediment was analysed in detail using 16S rRNA 454 pyrosequencing. Intact sediment cores were collected and exposed to one of five different pCO(2) concentrations [380 (present day), 540, 750, 1120 and 3000 μatm] and RNA extracted after a period of 14 days exposure. Measurements of diversity and multivariate similarity indicated very little difference between pCO(2) treatments. Only when the highest and lowest pCO(2) treatments were compared were significant differences evident, namely increases in the abundance of operational taxonomic units most closely related to the Halobacteria and differences to the presence/absence structure of the Planctomycetes. The relative abundance of members of the classes Planctomycetacia and Nitrospira increased with increasing pCO(2) concentration, indicating that these groups may be able to take advantage of changing pH or pCO(2) conditions. The modest response of the active microbial communities associated with these sediments may be due to the low and fluctuating pore-water pH already experienced by sediment microbes, a result of the pH buffering capacity of marine sediments, or due to currently unknown factors. Further research is required to fully understand the impact of elevated CO(2) on sediment physicochemical parameters, biogeochemistry and microbial community dynamics.


Physical activity in relation to body size and composition in women in UK Biobank.
Physical activity is thought to protect against obesity, but the evidence is limited and few large studies of this topic have direct, objective measures of several different anthropometric variables. We examined the association of self-reported physical activity with measures of total and central adiposity. Our cross-sectional study included 38,201 premenopausal and 94,592 postmenopausal healthy women aged 40 to 70 years in UK Biobank, recruited from 2006 to 2010. Means for total and vigorous physical activity were 31.3 (SD, 30.8) and 9.7 (SD, 14.8) metabolic equivalent h/wk, respectively, for premenopausal and 34.4 (SD, 33.1) and 8.9 (SD, 15.6) metabolic equivalent h/wk, respectively, for postmenopausal women. Multiple linear regression models showed that in both premenopausal and postmenopausal women, body mass index, body fat mass and percentage, trunk fat mass and percentage, waist and hip circumference, and waist-to-hip ratio were lower in women with higher physical activity (P < .0001). Within each category of total physical activity, a larger proportion of vigorous physical activity was associated with lower adiposity (P < .0001). These findings support the roles of a physically active lifestyle and vigorous exercise in maintaining healthy body size and composition. Higher exercise intensity may be associated with lower adiposity, beyond the influence of exercise frequency and duration.


Saccharomyces boulardii viability and efficacy in horses with antimicrobial-induced diarrhoea.
Saccharomyces boulardii has been successfully used in the prevention and treatment of antimicrobial-associated diarrhoea in humans. We hypothesised that a viable, dried lyophilised preparation of S boulardii would survive in the gastrointestinal tract of horses with antimicrobial-associated enterocolitis, and significantly decrease the duration of diarrhoea. Twenty-one horses, over one year of age, with antimicrobial-associated diarrhoea of up to 72 hours duration, were consecutively randomised in a controlled prospective study. The treatment group received S boulardii (25 g, orally, every 12 hours) until the cessation of clinical signs. S boulardii was successfully cultured in 58.3 per cent of treatment horses on day 3. No statistically significant differences were found in days to return to normal faecal consistency; resolution of watery diarrhoea; return to normal heart rate, respiratory rate and temperature; resolution of leucopaenia; attitude improvement; appetite improvement; and survival at discharge. This is the first study to demonstrate survival of S boulardii in horses with gastrointestinal illness. Further study of the efficacy and safety of S boulardii in horses with antimicrobial-associated diarrhoea in a larger group is warranted.


Ultrafast charge separation dynamics in opaque, operational dye-sensitized solar cells revealed by femtosecond diffuse reflectance spectroscopy.
Efficient dye-sensitized solar cells are based on highly diffusive mesoscopic layers that render these devices opaque and unsuitable for ultrafast transient absorption spectroscopy measurements in transmission mode. We developed a novel sub-200 femtosecond time-resolved diffuse reflectance spectroscopy scheme combined with potentiostatic control to study various solar cells in fully operational condition. We studied performance optimized devices based on liquid redox electrolytes and opaque TiO2 films, as well as other morphologies, such as TiO2 fibers and nanotubes. Charge injection from the Z907 dye in all TiO2 morphologies was observed to take place in the sub-200 fs time scale. The kinetics of electron-hole back recombination has features in the picosecond to nanosecond time scale. This observation is significantly different from what was reported in the literature where the electron-hole back recombination for transparent films of small particles is generally accepted to occur on a longer time scale of microseconds. The kinetics of the ultrafast electron injection remained unchanged for voltages between +500 mV and -690 mV, where the injection yield eventually drops steeply. The primary charge separation in Y123 organic dye based devices was clearly slower occurring in two picoseconds and no kinetic component on the shorter femtosecond time scale was recorded.


Statistical learning using real-world scenes: extracting categorical regularities without conscious intent.
Recent work has shown that observers can parse streams of syllables, tones, or visual shapes and learn statistical regularities in them without conscious intent (e.g., learn that A is always followed by B). Here, we demonstrate that these statistical-learning mechanisms can operate at an abstract, conceptual level. In Experiments 1 and 2, observers incidentally learned which semantic categories of natural scenes covaried (e.g., kitchen scenes were always followed by forest scenes). In Experiments 3 and 4, category learning with images of scenes transferred to words that represented the categories. In each experiment, the category of the scenes was irrelevant to the task. Together, these results suggest that statistical-learning mechanisms can operate at a categorical level, enabling generalization of learned regularities using existing conceptual knowledge. Such mechanisms may guide learning in domains as disparate as the acquisition of causal knowledge and the development of cognitive maps from environmental exploration.


American Headache Society Survey About Urgent and Emergency Management of Headache Patients.
Emergency department (ED) visits for migraine are burdensome to patients and to the larger healthcare system and society. Thus, it is important to determine strategies used to prevent ED visits and the common communication patterns between headache specialists and the ED team. We sought to understand: (1) Whether headache specialists use headache management protocols. (2) The strategies they use to try and reduce the number of ED visits for headache. (3) Whether protocols are used in the EDs with which they are affiliated. (4) The level of satisfaction with the coordination of care between headache physicians and the ED. We surveyed via SurveyMonkey members of the American Headache Society Emergency Department/Refractory/Inpatient (EDRI) Section to understand their practice regarding patients who call their office to be seen urgently, and to understand their communication with their local EDs. There were 96 eligible AHS members, 50 of whom responded to questionnaires either by email or in person (52%). Of these, 59% of respondents reported giving rescue treatment to their patients to manage acute attacks. Fifty-four percent reported using standard protocols for outpatients not responding to usual acute treatments. In the event of a request for urgent care, 12% of specialists reported bringing patients into the office most or all of the time, and 20% reported sending patients to the ED some or most of the time for headache management. Thirty-six percent reported prescribing a new medicine and 30% reported providing telephone counseling some/most/all of the time. Sixty percent reported that their ED has a protocol for migraine management. Overall, 38% were usually or very satisfied with the headache care in the ED. A substantial number of headache specialists are dissatisfied with the care their patients receive in the ED. More standardized protocols for ED visits by patients with known headache disorders, and clear guidelines for communication between ED providers and treating physicians, along with better methods for follow-up following discharge from the ED, might appear to improve this issue.


Selectived and Reshaped Early Dominant Microbial Community in the Cecum With Similar Proportions and Better Homogenization and Species Diversity Due to Organic Acids as AGP Alternatives Mediate Their Effects on Broilers Growth.
Understanding the differences in microbial communities shaped by different food selective forces, especially during early post-hatch period, is critical to gain insight into how to select, evaluate, and improve antibiotic growth promoters (AGPs) alternatives in food animals. As a model system, commercial diet-administered OAs (DOAs) and water-administered OAs (WOAs) were used separately or in combination as Virginiamycin alternatives for broiler feeding during two growth phases: 1-21 days and 22-42 days. Among these three OA-treated groups, the DOA group was most similar to the AGP group in the composition and the proportion of these dominant bacterial communities at the level of phylum, family, and genus in cecal chyme of broilers. Sub-therapeutic Virginiamycin decreased the richness, homogenization, and species diversity of gut microbiota, especially in the early growth stage from days 1 to 21. Among these three OA supplementation schemes, it was clear that DOA supplementation was more likely to increase or maintain the richness, homogenization, species diversity, and predicted gene functions of cecal microbiota in treated broilers than either no supplementation or AGP supplementation during two experimental stages. The interference of DOA treatment with early colonization of probiotics and pathogens in broiler cecum was the most similar to AGP treatment, and OAs did not cause the occurrence of Virginiamycin-resistant strains of Enterococcus at the end of this trial. In terms of the predicted gene functions of the microbiota, AGP and DOA treatments provided a similar selective force for microbial metabolism functions in the cecum of broiler chickens, especially in the early growth stage. Noticeably, the relative abundance of some microbiome that was modified by Virginiamycin or DOA supplementation was significantly correlated with body weight gain and KEGG pathway analysis-annotated gene functions such as replication and repair, translation, nucleotide metabolism, and so on. With the comprehensive analysis of these results and practical application, shortened DOA supplementation, after optimization of the amount of addition, would be a suitable alternative to sub-therapeutic Virginiamycin. It was suggested that the programed intestinal microecology under such early selection forces and the effective addition time may be the key elements to focus on the designed alternate strategies of AGPs in food animals.


Independence of VNTR alleles defined as fixed bins.
An analysis is presented of data collected by the Federal Bureau of Investigation at six unlinked variable number of tandem repeats (VNTR) loci for the United States population. Databases have been constructed of VNTR profiles of Caucasians, Blacks and Hispanics from Florida, Texas and California. There was very little evidence for correlations between lengths for pairs of VNTR fragments, within or between loci. When the fragment lengths were amalgamated into discrete bins, there was also little evidence for disequilibrium over all genotypes, within or between loci, for the Caucasian database, although some disequilibrium was found for the Black and Hispanic databases. No disequilibrium was found for the Caucasian or Black databases when tests were confined to heterozygous individuals. In cases of global disequilibrium, local tests can be applied to specific genotypes. The results suggest that, at the bin level, frequencies of VNTR profiles can generally be estimated as the products of the frequencies of the constituent elements. This overcomes the problem of estimating population frequencies when any particular profile does not exist in the database. There is some evidence for different frequencies, at the individual bin level, between geographic samples within each of the Caucasian, Black and Hispanic databases, and considerable evidence for differences between the three databases. These differences are less evident for the frequencies of four-locus profiles.


Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.
Cigarette smoking is an established risk factor for pancreatic cancer. However, prospective data for most European countries are lacking, and epidemiologic studies on exposure to environmental tobacco smoke (ETS) in relation to pancreatic cancer risk are scarce. We examined the association of cigarette smoking and exposure to ETS with pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). This analysis was based on 465,910 participants, including 524 first incident pancreatic cancer cases diagnosed after a median follow-up of 8.9 years. Estimates of risk were obtained by Cox proportional hazard models and adjusted for weight, height, and history of diabetes mellitus. An increased risk of pancreatic cancer was found for current cigarette smokers compared with never smokers (HR = 1.71, 95% CI = 1.36-2.15), and risk increased with greater intensity and pack-years. Former cigarette smokers who quit for less than 5 years were at increased risk of pancreatic cancer (HR = 1.78, 95% CI = 1.23-2.56), but risk was comparable to never smokers after quitting for 5 years or more. Pancreatic cancer risk was increased among never smokers daily exposed to ETS (for many hours) during childhood (HR = 2.61, 95% CI = 0.96-7.10) and exposed to ETS at home and/or work (HR = 1.54, 95% CI = 1.00-2.39). These results suggest that both active cigarette smoking, as well as exposure to ETS, is associated with increased risk of pancreatic cancer and that risk is reduced to levels of never smokers within 5 years of quitting.


The relationship between exposure to alcohol-related content on Facebook and predictors of alcohol consumption among female emerging adults.
Consuming an unhealthy level of alcohol is a significant problem for some young women. Potential determinants of excess consumption include perceptions of usual consumption among peers-perceptions of what is "normal." The present study examined whether perceptions of social normative endorsement of drinking, operationalized by measures of perceived alcohol consumption of close friends (proximal norms), the consumption of the "average student" (distal norms), and the extent of alcohol-related content posted by peers on Facebook were related to alcohol-related attitudes and self-reported consumption. Female university students (n=129; Mage=21.48 years, SD=3.00) completed an online questionnaire assessing Facebook use, perceived alcohol-related norms, and self-reported alcohol attitudes and consumption. Perceptions of the consumption of the average female student were a negative predictor of attitudes. Positive alcohol attitudes, extent of own alcohol-related photographic posts on Facebook, average female student alcohol consumption, and report of male close friend consumption predicted self-report of own alcohol consumption. Interestingly, female close friend norms failed to predict consumption, whereas male close friend norms predicted consumption but not attitudes, suggesting the possibility of separate cognitive pathways for alcohol-related attitudes and behavior. This study builds on existing research by casting new light on predictors of alcohol-related attitudes, as well as describing the potential role of social networking sites such as Facebook in the formation of social norms and the modulation of drinking behavior.


Engineered hybrid spider silk particles as delivery system for peptide vaccines.
The generation of strong T-cell immunity is one of the main challenges for the development of successful vaccines against cancer and major infectious diseases. Here we have engineered spider silk particles as delivery system for a peptide-based vaccination that leads to effective priming of cytotoxic T-cells. The recombinant spider silk protein eADF4(C16) was fused to the antigenic peptide from ovalbumin, either without linker or with a cathepsin cleavable peptide linker. Particles prepared from the hybrid proteins were taken up by dendritic cells, which are essential for T-cell priming, and successfully activated cytotoxic T-cells, without signs of immunotoxicity or unspecific immunostimulatory activity. Upon subcutaneous injection in mice, the particles were taken up by dendritic cells and accumulated in the lymph nodes, where immune responses are generated. Particles from hybrid proteins containing a cathepsin-cleavable linker induced a strong antigen-specific proliferation of cytotoxic T-cells in vivo, even in the absence of a vaccine adjuvant. We thus demonstrate the efficacy of a new vaccine strategy using a protein-based all-in-one vaccination system, where spider silk particles serve as carriers with an incorporated peptide antigen. Our study further suggests that engineered spider silk-based vaccines are extremely stable, easy to manufacture, and readily customizable.


Long term changes in health-related quality of life for people with heart failure: the ECHOES study.
Heart failure (HF) impairs all aspects of health-related quality of life (HRQoL), but little is known about the effect of developing HF on HRQoL over time. We aimed to report changes in HRQoL over a 13-year period. HRQoL was measured in the Echocardiographic Heart of England Screening (ECHOES) study and the ECHOES-X follow-up study (N = 1618) using the SF-36 questionnaire (Version 1). Mixed modelling compared changes in HRQoL across diagnostic groups, adjusting for potential predictors and design variables. Patients who had developed HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF) at rescreening had significantly greater reduction in physical functioning (PF) and role physical (RP) scores compared with those without HF; adjusted mean difference in PF: HFrEF -16.1, [95% confidence interval (CI) -22.2 to -10.1]; HFpEF -14.6, (95% CI -21.2 to -8.1); in RP: HFrEF -20.7, (95% CI -31.8 to -9.7); HFpEF -19.3, (95% CI -31.0 to -7.6). Changes in HRQoL of those with a HF diagnosis at baseline and rescreen, with exception of role emotion, were similar to those without HF but started from a much lower baseline score. People with a new diagnosis of HF at rescreening had a significant reduction in HRQoL. Conversely, for those with HF detected on initial screening, little change was observed in HRQoL scores on rescreening. Further research is required to understand the development of HF over time and to test interventions designed to prevent decline in HRQoL, potentially through earlier diagnosis and treatment optimization.


Identification of polymorphic inversions from genotypes.
Polymorphic inversions are a source of genetic variability with a direct impact on recombination frequencies. Given the difficulty of their experimental study, computational methods have been developed to infer their existence in a large number of individuals using genome-wide data of nucleotide variation. Methods based on haplotype tagging of known inversions attempt to classify individuals as having a normal or inverted allele. Other methods that measure differences between linkage disequilibrium attempt to identify regions with inversions but unable to classify subjects accurately, an essential requirement for association studies. We present a novel method to both identify polymorphic inversions from genome-wide genotype data and classify individuals as containing a normal or inverted allele. Our method, a generalization of a published method for haplotype data 1, utilizes linkage between groups of SNPs to partition a set of individuals into normal and inverted subpopulations. We employ a sliding window scan to identify regions likely to have an inversion, and accumulation of evidence from neighboring SNPs is used to accurately determine the inversion status of each subject. Further, our approach detects inversions directly from genotype data, thus increasing its usability to current genome-wide association studies (GWAS). We demonstrate the accuracy of our method to detect inversions and classify individuals on principled-simulated genotypes, produced by the evolution of an inversion event within a coalescent model 2. We applied our method to real genotype data from HapMap Phase III to characterize the inversion status of two known inversions within the regions 17q21 and 8p23 across 1184 individuals. Finally, we scan the full genomes of the European Origin (CEU) and Yoruba (YRI) HapMap samples. We find population-based evidence for 9 out of 15 well-established autosomic inversions, and for 52 regions previously predicted by independent experimental methods in ten (9+1) individuals 34. We provide efficient implementations of both genotype and haplotype methods as a unified R package inveRsion.


Electron Transmission through Coordinating Atoms Embedded in Metal-Organic Nanoporous Networks.
On-surface metal-organic nanoporous networks generally refer to adatom coordinated molecular arrays, which are characterized by the presence of well-defined and regular nanopores. These periodic structures constructed using two types of components confine the surface electrons of the substrate within their nanocavities. However, the confining (or scattering) strength that individual building units exhibit is a priori unknown. Here, we study the modification of the substrate's surface electrons by the interaction with a Cu-coordinated TPyB metal-organic network formed on Cu(111) and disentangle the scattering potentials and confinement properties. By means of STM and angle-resolved photoemission spectroscopy we find almost unperturbed free-electron-like states stemming from the rather weak electron confinement that yields significant coupling between adjacent pores. Electron plane wave expansion simulations match the superlattice induced experimental electronic structure, which features replicating bands and energy renormalization effects. Notably, the electrostatic potential landscape obtained from our ab initio calculations suggests that the molecules are the dominant scattering entities while the coordination metal atoms sandwiched between them act as leaky channels. These metal atom transmission conduits facilitate and enhance the coupling among quantum dots, which are prone to be exploited to engineer the electronic structure of surface electron gases.


Flight of Rhyzopertha dominica (Coleoptera: Bostrichidae)-a Spatio-Temporal Analysis With Pheromone Trapping and Population Genetics.
The flight of the lesser grain borer, Rhyzopertha dominica (F.), near grain storages and at distances from them, was investigated to assess the potential of these beetles to infest grain and spread insecticide resistance genes. We caught R. dominica in pheromone-baited flight traps (and blank controls) set at storages, in fields away from storages, and in native vegetation across a 12-mo period. A functional set of highly polymorphic microsatellite markers was developed, enabling population genetic analyses on the trapped beetles. Pheromone-baited traps caught just as many R. dominica adults at least 1 km from grain storages as were caught adjacent to grain storages. Samples of beetles caught were genetically homogeneous across the study area (over 7,000 km2) in South Queensland, Australia. However, a change in genetic structure was detected at one bulk storage site. Subsequent analysis detected a heterozygous excess, which indicated a population bottleneck. Only a few beetles were caught during the winter months of June and July. To assess the mating status and potential fecundity of dispersing R. dominica females, we captured beetles as they left grain storages and quantified offspring production and life span in the laboratory. Nearly all (95%) of these dispersing females had mated and these produced an average of 242 offspring. We demonstrated that R. dominica populations in the study area display a high degree of connectivity and this is a result of the active dispersal of mated individuals of high potential fecundity.


Utilization and disparities in medication treatment for opioid use disorder among patients with comorbid opioid use disorder and chronic pain during the COVID-19 pandemic.
The COVID-19 pandemic's impact on utilization of medications for opioid use disorder (MOUD) among patients with opioid use disorder (OUD) and chronic pain is unclear. We analyzed New York State (NYS) Medicaid claims from pre-pandemic (August 2019-February 2020) and pandemic (March 2020-December 2020) periods for beneficiaries with and without chronic pain. We calculated monthly proportions of patients with OUD diagnoses in 6-month-lookback windows utilizing MOUD and proportions of treatment-naïve patients initiating MOUD. We used interrupted time series to assess changes in MOUD utilization and initiation rates by medication type and by race/ethnicity. Among 20,785 patients with OUD and chronic pain, 49.3% utilized MOUD (versus 60.3% without chronic pain). The pandemic did not affect utilization in either group but briefly disrupted initiation among patients with chronic pain (β=-0.009; 95% CI [-0.015, -0.002]). Overall MOUD utilization was not affected by the pandemic for any race/ethnicity but opioid treatment program (OTP) utilization was briefly disrupted for non-Hispanic Black individuals (β=-0.007 [-0.013, -0.001]). The pandemic disrupted overall MOUD initiation in non-Hispanic Black (β=-0.007 [-0.012, -0.002]) and Hispanic individuals (β=-0.010 [-0.019, -0.001]). Adults with chronic pain who were enrolled in NYS Medicaid before the COVID-19 pandemic had lower MOUD utilization than those without chronic pain. MOUD initiation was briefly disrupted, with disparities especially in racial/ethnic minority groups. Flexible MOUD policy initiatives may have maintained overall treatment utilization, but disparities in initiation and care continuity remain for patients with chronic pain, and particularly for racial/ethnic minoritized subgroups.


The use of motion analysis to measure pain-related behaviour in a rat model of degenerative tendon injuries.
Chronic tendinopathy is characterized with longstanding activity-related pain with degenerative tendon injuries. An objective tool to measure painful responses in animal models is essential for the development of effective treatment for tendinopathy. Gait analysis has been developed to monitor the inflammatory pain in small animals. We reported the use of motion analysis to monitor gait changes in a rat model of degenerative tendon injury. Intratendinous injection of collagenase into the left patellar tendon of Sprague Dawley rat was used to induce degenerative tendon injury, while an equal volume of saline was injected in the control groups. Motion analyses with a high speed video camera were performed on all rats at pre-injury, 2, 4, 8, 12 or 16 weeks post injection. In the end-point study, the rats were sacrificed to obtain tendon samples for histological examination after motion analyses. In the follow-up study, repeated motion analyses were performed on another group of collagenase-treated and saline-treated rats. The results showed that rats with injured patellar tendon exhibited altered walking gait as compared to the controls. The change in double stance duration in the collagenase-treated rats was reversible by administration of buprenorphrine (p=0.029), it suggested that the detected gait changes were associated with pain. Comparisons of end-point and follow-up studies revealed the confounding effects of training, which led to higher gait velocities and probably a different adaptive response to tendon pain in the trained rats. The results showed that motion analysis could be used to measure activity-related chronic tendon pain.


The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients.
Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.


Characterizing 18 Years of the Death With Dignity Act in Oregon.
Numerous states have pending physician-aided dying (PAD) legislation. Little research has been done regarding use of PAD, or ways to improve the process and/or results. To evaluate results of Oregon PAD, the longest running US program; to disseminate results; and to determine promising PAD research areas. A retrospective observational cohort study of 991 Oregon residents who had prescriptions written as part of the state's Death with Dignity Act. We reviewed publicly available data from Oregon Health Authority reports from 1998 to 2015, and made a supplemental information request to the Oregon Health Authority. Number of deaths from self-administration of lethal medication versus number of prescriptions written. A total of 1545 prescriptions were written, and 991 patients died by using legally prescribed lethal medication. Of the 991 patients, 509 (51.4%) were men and 482 (48.6%) were women. The median age was 71 years (range, 25-102 years). The number of prescriptions written increased annually (from 24 in 1998 to 218 in 2015), and the percentage of prescription recipients dying by this method per year averaged 64%. Of the 991 patients using lethal self-medication, 762 (77%) recipients had cancer, 79 (8%) had amyotrophic lateral sclerosis, 44 (4.5%) had lung disease, 26 (2.6%) had heart disease, and 9 (0.9%) had HIV. Of 991 patients, 52 (5.3%) were sent for psychiatric evaluation to assess competence. Most (953; 96.6%) patients were white and 865 (90.5%) were in hospice care. Most (118, 92.2%) patients had insurance and 708 (71.9%) had at least some college education. Most (94%) died at home. The estimated median time between medication intake and coma was 5 minutes (range, 1-38 minutes); to death it was 25 minutes (range, 1-6240 minutes). Thirty-three (3.3%) patients had known complications. The most common reasons cited for desiring PAD were activities of daily living were not enjoyable (89.7%) and losses of autonomy (91.6%) and dignity (78.7%); inadequate pain control contributed in 25.2% of cases. The number of PAD prescriptions written in Oregon has increased annually since legislation enactment. Patients use PAD for reasons related to quality of life, autonomy, and dignity, and rarely for uncontrolled pain. Many questions remain regarding usage and results, making this area suitable for cancer care delivery research.


Phytochemical screening and antibacterial activity of different solvent extracted samples of Arisaema jacquemontii.
The current research was carried out to assess the antibacterial activities and phytochemical analysis of the methanol, n-hexane, ethyl acetate, n-butanol soluble fractions and aqueous extracts of the tubers of Arisaema jacquemontii. All the extracts were tested for their antibacterial potential at 1, 2 and 3 mg disc-1 concentrations against 6 bacterial strains through disc diffusion suseptibility assay. The data suggested that different extracts showed varying degree of growth inhibition against the tested microbes. Statistical analysis revealed that n-hexane and ethyl acetate soluble fractions significantly inhibited the growth of all the bacterial strains at the tested concentrations. Moderate activities were recorded for n-butanol and methanolic extracted samples at different concentrations against all the tested strains of bacteria. P. aeruginosa, S. aureus and X. campestris showed resistance to all the tested concentrations of the aqueous extract. B. subtilis and K. pneumoniae were resistant at 1 and 2 mg disc-1 concentrations of the aqueous extract and 3 mg disc-1 of the same extract reduced the growth of the same bacteria. Phytochemical analysis of the different solvent extracted samples suggested the presence or absence of various metabolites including alkaloids, saponins, tannins, sterols, flavonoids, protein, carbohydrates and fats.


Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial.
In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation. Based on these findings, riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI. Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889.


Glycogen synthase kinase 3 beta (GSK-3 beta) as a therapeutic target in neuroAIDS.
Highly active antiretroviral therapy (HAART) has made a significant impact on the lives of people living with HIV-1 infection. The incidence of neurologic disease associated with HIV-1 infection of the CNS plummeted between 1996-2000, but unfortunately the number of people currently HIV-1 infected (i.e., prevalence) with associated cognitive impairment has been steadily rising. While the reasons for this may be multifactorial, the implication is clear: there is a pressing need for adjunctive therapy directed at reversing or preventing damage to vulnerable pathways in the central nervous system (CNS) from HIV-1 infection. Using a team of preclinical and clinical investigators, we have focused our efforts on defining how proinflammatory mediators and secretory neurotoxins from HIV-1 disrupt signaling of the survival-regulating enzyme, glycogen synthase kinase 3 beta (GSK-3beta). In a series of studies initiated using in vitro, then in vivo models of HIV-1-associated dementia (HAD), we have demonstrated the ability of the mood stabilizing and anticonvulsant drug, sodium valproate (VPA), that inhibits GSK-3beta activity and other downstream mediators, to reverse HIV-1-induced damage to synaptic pathways in the CNS. Based on these results, we successfully performed pharmacokinetic and safety and tolerability trials with VPA in a cohort of HIV-1-infected patients with neurologic disease. VPA was well tolerated in this population and secondary measures of brain metabolism, as evidenced by an increase in N-acetyl aspartate/creatine (NAA/Cr), further suggested that VPA may improve gray matter integrity in brain regions damaged by HIV-1. These findings highlight the therapeutic potential of GSK-3beta blockade.


Trends in reproductive behavior among young single women in Colombia and Peru: 1985-1999.
Using "calendar" data for single women aged 15-24 from successive Demographic and Health Surveys (DHS) conducted in Colombia and Peru during the 1990s, we document trends, year by year, in sexual activity, the use of contraceptives, and subsequent reproductive outcomes. We provide evidence of the important and hitherto largely untapped potential of DHS calendar data to draw complete sexual and reproductive profiles when data from various surveys are integrated. Over the period 1985-1999, young single women in both Colombia and Peru became sexually active at younger ages. The use of contraceptives, especially the use of condoms, increased but did not fully offset the rise in sexual activity, and thus the incidence of premarital conceptions rose among young single women. In both countries, sharp declines occurred in the proportion of premaritally conceived births that were reported as being wanted.


Kerr-lens mode locking with minimum nonlinearity using gain-matched output couplers.
Broadband Kerr-lens mode locking is demonstrated at greatly reduced mode-locking strength with a gain-matched output coupler that compensates for gain filtering. Already at very low pump powers, slightly above the cw lasing threshold, we are able to initiate robust mode locking and generate <8 fs output pulses from a Ti:sapphire laser with good beam quality. Because dielectric coatings offer flexible design capabilities, this approach is applicable to various lasers with different gain media to extract pulses covering the full gain spectrum with minimum saturable absorber action.


Differences in poisoning mortality in the United States, 2003-2007: epidemiology of poisoning deaths classified as unintentional, suicide or homicide.
Poisoning, specifically unintentional poisoning, is a major public health problem in the United States (U.S.). Published literature that presents epidemiology of all forms of poisoning mortalities (i.e., unintentional, suicide, homicide) together is limited. This report presents data and summarizes the evidence on poisoning mortality by demographic and geographic characteristics to describe the burden of poisoning mortality and the differences among sub-populations in the U.S. for a 5-year period. Using mortality data from the Center for Disease Control and Prevention's Web-based Injury Statistics Query and Reporting System, we presented the age-specific and age-adjusted unintentional and intentional (suicide, homicide) poisoning mortality rates by sex, age, race, and state of residence for the most recent years (2003-2007) of available data. Annual percentage changes in deaths and rates were calculated, and linear regression using natural log were used for time-trend analysis. There were 121,367 (rate=8.18 per 100,000) unintentional poisoning deaths. Overall, the unintentional poisoning mortality rate increased by 46.9%, from 6.7 per 100,000 in 2003 to 9.8 per100.000 in 2007, with the highest mortality rate among those aged 40-59 (rate=15.36), males (rate=11.02) and whites (rate=8.68). New Mexico (rate=18.2) had the highest rate. Unintentional poisoning mortality rate increased significantly among both sexes, and all racial groups except blacks (p<0.05 time-related trend for rate). Among a total of 29,469 (rate=1.97) suicidal poisoning deaths, the rate increased by 9.9%, from 1.9 per 100,000 in 2003 to 2.1 per 100,000 in 2007, with the highest rate among those aged 40-59 (rate=3.92), males (rate=2.20) and whites (rate=2.24). Nevada (rate=3.9) had the highest rate. Mortality rate increased significantly among females and whites only (p<0.05 time-related trend for rate). There were 463 (rate=0.03) homicidal poisoning deaths and the rate remained the same during 2003-2007. The highest rates were among aged 0-19 (rate=0.05), males (rate=0.04) and blacks (rate=0.06). Prevention efforts for poisoning mortalities, especially unintentional poisoning, should be developed, implemented and strengthened. Differences exist in poisoning mortality by age, sex, location, and these findings underscore the urgency of addressing this public health burden as this epidemic continues to grow in the U.S.


Enhancement of tumor growth and vascular density by transfection of vascular endothelial cell growth factor into MCF-7 human breast carcinoma cells.
Vascular endothelial growth factor (VEGF) is a secreted endothelial-specific growth factor that is angiogenic in vivo. It is commonly expressed in a range of carcinomas. The study was designed to investigate the effect of constitutive expression of VEGF on tumor formation by estrogen-dependent human MCF-7 breast carcinoma cells. A full-length complementary DNA encoding the shortest isoform of VEGF (VEGF121) was stably transfected into MCF-7 cells. Transfected clones were screened for VEGF121 messenger RNA (mRNA) expression by ribonuclease protection analysis and for secretion of VEGF121 protein by Western blot analysis. Secretion of biologically active VEGF121 by transfectants was confirmed by 1) a competitive radioreceptor-binding assay, 2) stimulation of the growth of microvascular endothelial cells in vitro, and 3) potent angiogenic activity in the rabbit corneal assay. Tumor models were then established by subcutaneously implanting wild-type or VEGF121-transfected MCF-7 cells, together with either mouse BALB/3T3 clone A31 fibroblasts or human MDA-435S breast carcinoma cells, into ovariectomized nude mice either with or without a separately implanted slow-release estrogen pellet. Tumor vascularity was quantitatively assessed by capillary vessel counting after staining with the pan-endothelial marker CD31. Stable VEGF121-overexpressing MCF-7 cells were isolated and designated V12 cells. When implanted into the rabbit cornea, V12 cells elicited a strong directional outgrowth of capillaries. The growth rate of V12 cells in vitro was indistinguishable from that of MCF-7 wild-type cells. V12 cells formed faster growing tumors than did wild-type cells (P < .01) when xenografted subcutaneously into nude mice with either 3T3 fibroblasts or MDA-435S cells. Tumors formed from V12 cells were more vascular (P < .01) and showed a heterogeneous distribution of vessels when compared with the homogeneous distribution seen in tumors formed from wild-type cells. VEGF121 overexpression had no effect on hormone dependence or tamoxifen sensitivity of tumor formation by MCF-7 cells in mice. No macroscopic evidence for metastasis from subcutaneous implants was obtained. VEGF121 expression by breast carcinoma cells confers a growth advantage in vivo but not in vitro. Tumors formed by V12 transfectants were more vascular than those formed by wild-type MCF-7 cells, and we surmise that the growth advantage arises from increased tumor vascularization induced by VEGF121. Tumor formation by V12 cells could provide a useful model for the assessment of anti-angiogenic drugs.


Deep brain stimulation: postoperative issues.
Numerous factors need to be taken into account when managing a patient with Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow-up care should be determined, including patient adjustments of stimulation, timing of follow-up visits and telephone contact with the patient, and stimulation and medication conditions during the follow-up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long-term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job-related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery.


The accessibility and acceptability of self-management support interventions for men with long term conditions: a systematic review and meta-synthesis of qualitative studies.
Self-management support interventions can improve health outcomes, but their impact is limited by the numbers of people able or willing to access them. Men's attendance at existing self-management support services appears suboptimal despite their increased risk of developing many of the most serious long term conditions. The aim of this review was to determine whether current self-management support interventions are acceptable and accessible to men with long term conditions, and explore what may act as facilitators and barriers to access of interventions and support activities. A systematic search for qualitative research was undertaken on CINAHL, EMBASE, MEDLINE, PsycINFO and Social Science Citation Index, in July 2013. Reference lists of relevant articles were also examined. Studies that used a qualitative design to explore men's experiences of, or perceptions towards, self-management support for one or more long term condition were included. Studies which focused on experiences of living with a long term condition without consideration of self-management support were excluded. Thirty-eight studies met the inclusion criteria. A meta-ethnography approach was employed to synthesise the findings. Four constructs associated with men's experience of, and perceptions towards, self-management support were identified: 1) need for purpose; 2) trusted environments; 3) value of peers; and 4) becoming an expert. The synthesis showed that men may feel less comfortable participating in self-management support if it is viewed as incongruous with valued aspects of their identity, particularly when activities are perceived to challenge masculine ideals associated with independence, stoicism, and control. Men may find self-management support more attractive when it is perceived as action-oriented, having a clear purpose, and offering personally meaningful information and practical strategies that can be integrated into daily life. Self-management support is most likely to be successful in engaging men when it is congruent with key aspects of their masculine identity. In order to overcome barriers to access and fully engage with interventions, some men may need self-management support interventions to be delivered in an environment that offers a sense of shared understanding, connectedness, and normality, and involves and/or is facilitated by men with a shared illness experience.


Rearrangements of minisatellites in the human telomerase reverse transcriptase gene are not correlated with its expression in colon carcinomas.
Telomerase activation is crucial in human carcinogenesis. The limiting component of telomerase, the catalytic subunit (hTERT), is undetectable in normal somatic cells but present in most tumor cells, including the earliest stages of colon carcinoma. The mechanisms involved in the differential expression in normal and tumor cells are not understood. In normal cells hTERT expression is shut down by a repressor, and upregulation could be a consequence of cis-acting changes in the hTERT gene, making it resistant to repression. We have identified a polymorphic and a monomorphic minisatellite in the second intron of the hTERT gene, and polymorphic one in intron 6. The polymorphic minisatellite in intron 2 contains binding sites for c-Myc, which has been shown to upregulate hTERT transcription. Screening colon carcinoma DNAs for rearrangements of hTERT minisatellites we detected no changes in 33 samples from tumors, most of which express hTERT. This indicates that size rearrangements of the hTERT minisatellites are not required for telomerase expression in colon carcinomas. Minor changes and one LOH were seen in five tumors.


Satellite detection of land-use change and effects on regional forest aboveground biomass estimates.
We used remote-sensing-driven models to detect land-cover change effects on forest aboveground biomass (AGB) density (Mg.ha(-1), dry weight) and total AGB (Tg) in Minnesota, Wisconsin, and Michigan USA, between the years 1992-2001, and conducted an evaluation of the approach. Inputs included remotely-sensed 1992 reflectance data and land-cover map (University of Maryland) from Advanced Very High Resolution Radiometer (AVHRR) and 2001 products from Moderate Resolution Imaging Spectroradiometer (MODIS) at 1-km resolution for the region; and 30-m resolution land-cover maps from the National Land Cover Data (NLCD) for a subarea to conduct nine simulations to address our questions. Sensitivity analysis showed that (1) AVHRR data tended to underestimate AGB density by 11%, on average, compared to that estimated using MODIS data; (2) regional mean AGB density increased slightly from 124 (1992) to 126 Mg ha(-1) (2001) by 1.6%; (3) a substantial decrease in total forest AGB across the region was detected, from 2,507 (1992) to 1,961 Tg (2001), an annual rate of -2.4%; and (4) in the subarea, while NLCD-based estimates suggested a 26% decrease in total AGB from 1992 to 2001, AVHRR/MODIS-based estimates indicated a 36% increase. The major source of uncertainty in change detection of total forest AGB over large areas was due to area differences from using land-cover maps produced by different sources. Scaling up 30-m land-cover map to 1-km resolution caused a mean difference of 8% (in absolute value) in forest area estimates at the county-level ranging from 0 to 17% within a 95% confidence interval.


Moving polewards in winter: a recent change in the migratory strategy of a pelagic seabird?
During the non-breeding period, many birds migrate to milder areas, found closer to the equator than their breeding sites. Opposite movements are very rare. In the Southern Ocean, the abundance of 13C declines markedly with more southern latitude, providing a characteristic 13C isoscape. This can be used as a tracer for the movement of seabirds between breeding and inter-breeding areas, by comparing stable isotope ratios of feathers grown at different times of the year. We studied seasonal movements of Thin-billed prions (Aves, Procellariiformes), breeding at the Subantarctic Falkland/Malvinas Islands, compared with those of Wilson's storm-petrels breeding in the Antarctic South Shetland Islands. The two species showed opposite migratory movements. While Wilson's storm-petrels moved to warmer waters north of the Drake Passage in winter, Thin-billed prions showed a reversed movement towards more polar waters. Carbon stable isotope ratios in recent and historical feathers indicated that poleward winter movements of Thin-billed prions were less common historically (45% in 1913-1915), and have only recently become dominant (92% in 2003-2005), apparently in response to warming sea temperatures. This study shows that pelagic seabirds can rapidly change migration strategies within populations, including migration towards more poleward waters in winter.


A randomized optical coherence tomography study of coronary stent strut coverage and luminal protrusion with rapamycin-eluting stents.
We used optical coherence tomography, which has a resolution of <20 microm, to analyze thin layers of neointima in rapamycin-eluting coronary stents. Lack of neointimal coverage has been implicated in the pathogenesis of drug-eluting coronary stent thrombosis. Angiography and intracoronary ultrasound lack the resolution to examine this. We conducted a randomized trial in patients receiving polymer-coated rapamycin-eluting stents (Cypher, Cordis, Johnson & Johnson, Miami, Florida) and nonpolymer rapamycin-eluting stents (Yukon, Translumina, Hechingen, Germany) to examine neointimal thickness, stent strut coverage, and protrusion at 90 days. Twenty-four patients (n = 12 for each group) underwent stent deployment and invasive follow-up at 90 days with optical coherence tomography. The primary end point was binary stent strut coverage. Coprimary end points were neointimal thickness and stent strut luminal protrusion. No patient had angiographic restenosis. For polymer-coated and nonpolymer rapamycin-eluting stents, respectively, mean (SD), neointimal thickness was 77.2 (25.6) microm versus 191.2 (86.7) mum (p < 0.001). Binary stent strut coverage was 88.3% (11.8) versus 97.2% (6.1) (p = 0.030). Binary stent strut protrusion was 26.5% (17.5) versus 4.8% (8.6) (p = 0.001). Mean neointimal thickness for the polymer-coated rapamycin-eluting stent was significantly less than the nonpolymer rapamycin-eluting stent but as a result coverage was not homogenous, with >10% of struts being uncovered. High-resolution imaging allowed development of the concept of the protrusion index, and >25% of struts protruded into the vessel lumen with the polymer-coated rapamycin-eluting stent compared with <5% with the nonpolymer rapamycin-eluting stent. These findings may have important implications for the risk of stent thrombosis and, therefore, future stent design. (An optical coherence tomography study to determine stent coverage in polymer coated versus bare metal rapamycin eluting stents. ORCA 1, from the Optimal Revascularization of the Coronary Arteries group; ISRCTN42475919).


Immunohistochemical detection of the epidermal growth factor receptor in paraffin-embedded human tissues.
Expression of the epidermal growth factor (EGF) receptor was evaluated by immunohistochemical staining of formalin-fixed, paraffin-embedded tumour tissues employing two antibodies raised to short synthetic peptides from the cytoplasmic domain of the molecule. Both antibodies gave concordant staining of a series of bladder cancers known to express or lack EGF receptors. There was no cross-reaction with the related c-erbB-2 protein, which was also over-expressed in some cases. Cancers with EGF receptor expression also expressed high levels of TGF-alpha, a receptor agonist.


The applicability of normalisation process theory to speech and language therapy: a review of qualitative research on a speech and language intervention.
The Bercow review found a high level of public dissatisfaction with speech and language services for children. Children with speech, language, and communication needs (SLCN) often have chronic complex conditions that require provision from health, education, and community services. Speech and language therapists are a small group of Allied Health Professionals with a specialist skill-set that equips them to work with children with SLCN. They work within and across the diverse range of public service providers. The aim of this review was to explore the applicability of Normalisation Process Theory (NPT) to the case of speech and language therapy. A review of qualitative research on a successfully embedded speech and language therapy intervention was undertaken to test the applicability of NPT. The review focused on two of the collective action elements of NPT (relational integration and interaction workability) using all previously published qualitative data from both parents and practitioners' perspectives on the intervention. The synthesis of the data based on the Normalisation Process Model (NPM) uncovered strengths in the interpersonal processes between the practitioners and parents, and weaknesses in how the accountability of the intervention is distributed in the health system. The analysis based on the NPM uncovered interpersonal processes between the practitioners and parents that were likely to have given rise to successful implementation of the intervention. In previous qualitative research on this intervention where the Medical Research Council's guidance on developing a design for a complex intervention had been used as a framework, the interpersonal work within the intervention had emerged as a barrier to implementation of the intervention. It is suggested that the design of services for children and families needs to extend beyond the consideration of benefits and barriers to embrace the social processes that appear to afford success in embedding innovation in healthcare.


Z-nucleotide accumulation in erythrocytes from Lesch-Nyhan patients.
5-Amino-4-imidazolecarboxamide riboside 5'-monophosphate (ZMP) is an intermediate in the purine de novo synthetic pathway that may be further metabolized to inosine 5'-monophosphate, degraded to the corresponding nucleoside (5-amino-4-imidazole-carboxamide riboside; Z-riboside), or phosphorylated to the corresponding 5'-triphosphate (ZTP). Accumulation of ZTP in microorganisms has been associated with depletion of folate intermediates that are necessary for the conversion of ZMP to inosine 5'-monophosphate and has been postulated to play a regulatory role in cellular metabolism. We have shown the presence of Z-nucleotides in erythrocytes derived from five individuals with the Lesch-Nyhan syndrome. Erythrocyte folate levels were within the normal range, although guanosine triphosphate levels were significantly reduced below those in normal controls (P less than 0.01). A small amount of Z-nucleotide accumulation was also found in one individual with partial deficiency of the enzyme hypoxanthine guanine phosphoribosyltransferase and in two individuals with other disorders of purine overproduction. In contrast, no Z-nucleotides were detected in 13 normal controls or in three individuals with hyperuricemia on allopurinol therapy. We conclude that Z-nucleotide formation may result from markedly increased rates of de novo purine biosynthesis. It is possible that metabolites of these purine intermediates may play a role in the pathogenesis of the Lesch-Nyhan syndrome.


Fixation of osteoporotic distal fibula fractures: A biomechanical comparison of locking versus conventional plates.
The increased use of locking plates to treat difficult fracture scenarios has been advocated in patients that have reduced bone mineral density. One of these difficult fracture patterns, fixation of the distal fragment of a distal fibula fracture, may depend on unicortical and cancellous bony purchase. This study investigated the construct stiffness afforded by using locking and conventional plating schema in a cadaveric model. Overall, the data indicate that a locking plate construct with two distal unicortical screws was mechanically equivalent to standard plating with 3 distal screws. In addition, fixation with the standard plates was dependent on bone mineral density (BMD) whereas the locking plate fixation was independent of BMD. The clinical implication of this study is that locking plates may be advantageous in patients with the most severe osteoporosis.


CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity.
Imatinib is currently used for the treatment of chronic myeloid leukemia (CML). The main metabolite CGP74588 has similar potency to that of imatinib and is a product of CYP3A4 and CYP3A5 metabolism. However, the clinical significance of the metabolism on therapeutic response and pharmacokinetics is still unclear. We designed this study to investigate the role of the CYP3A activity in the response to imatinib therapy. Fourteen CML patients were phenotyped for in vivo CYP3A activity using quinine as a probe drug. The plasma concentration ratio of quinine and its CYP3A metabolite was used for assessing CYP3A activity. The patients were divided into complete molecular responders with undetectable levels of BCR-ABL transcripts after 12 months of therapy and into partial molecular responders who had failed to achieve a complete molecular response. Patients that achieved complete molecular response showed significantly (Mann-Whitney U-test, p=0.013) higher in vivo CYP3A activity (median quinine metabolic ratio = 10.1) than patients achieving partial molecular response (median = 15.9). These results indicate a clinical significance of the CYP3A activity and its metabolic products in CML patients treated with imatinib.


Biomechanical and tomographic differences in the microarchitecture and strength of trabecular and cortical bone in the early stage of male osteoporosis.
Osteoporosis is a continuous process of loss of bone tissue. Compared to women, osteoporosis in men is associated with greater morbidity and mortality. In this study, we conducted tomographic and biomechanical evaluations of trabecular and cortical bone in the early stage of male osteoporosis. Male Wistar rats were subjected to orchiectomy and sham operation. Four weeks after being castrated, decreased levels of testosterone in plasma were found and resulted in concurrent bone loss. Separately, the orchiectomy led to significant tomographic alterations in the trabecular bone number, trabecular separation, and trabecular pattern factor. Data of a mechanistic compression test further showed that the orchiectomy diminished the maximum loading force, displacement at maximum load, energy at maximum load, and ultimate stress. Interestingly, orchiectomy-triggered changes in the maximum loading force and tomographic parameters were highly correlated. In contrast, tomographic and biomechanical analyses showed that 4 weeks after rats were orchiectomized, the thickness, area, maximum loading force, bone stiffness, energy at maximum load, and ultimate stress of the cortical bone were not changed. Taken together, this study showed specific differences in the microarchitecture and strength of trabecular bone in the early stage of male osteoporosis.


Somatic growth of a school-aged population from Mozambique: trend and biosocial meaning.
A cross-sectional study of children and adolescents from Maputo, Mozambique, was carried out in order to (1) describe the current growth status of children and adolescents from Maputo, (2) evaluate the relative status of the growth and development of youth from Maputo compared to WHO international standards, (3) assess the relationship between socioeconomic status and growth and development, and (4) assess the impact that the civil war (1980-1992) had on the health status of children and adolescents living in Maputo. The sample is composed of 2,271 subjects (1,098 boys and 1,173 girls), age 6 to 17 years. Somatic measures included height, weight, and skinfold thicknesses from which nutritional indicators were calculated and plotted against WHO norms. Subjects were divided into three groups according to their socioeconomic status. Data from a cross-sectional study done in the same areas in 1992 was used to analyze the impact of war. Beginning at 11 years, Maputo students are always shorter and weigh less than the WHO standards. BMI in boys from 11 years and in girls from 12 years is somewhat lower than the WHO norms. A social gradient is evident, favoring those students with higher socioeconomic status. Height, weight, BMI, fat mass, and lean body mass are always higher in the 1999 sample than in the 1992 study. We conclude that (1) there is a substantial difference in height and weight values of Maputo children and adolescents compared to WHO standards; (2) there is a clear advantage of being of higher socioeconomic status; (3) socioeconomic status, hygiene, and sanitation are the main factors responsible for the greater values of the 1999 sample; and (4) differences between the stature of students with higher socioeconomic status and the WHO norms are almost irrelevant. This last aspect reveals the importance of socioeconomic factors in determining the growth process, implying its importance in facilitating the "expression" of the genotypes available in the population.


Surgical techniques to minimize shoulder pain after laparoscopic cholecystectomy. A systematic review.
Laparoscopic cholecystectomy (LC) is the treatment of choice for symptomatic cholecystolithiasis. Despite the many advantages over open surgery, many patients complain about referred pain to the shoulder during the postoperative course. The purpose of this review was to evaluate different intraoperative surgical methods to minimize shoulder pain (SP). A search of the literature was conducted using PubMed, Excerpta Medica Database (EMBASE), and Cochrane database of systematic reviews. Eligibility criteria were: randomized clinical trials or meta-analysis evaluating intraoperative surgical methods applied to minimize incidence or severity of SP after LC. Only papers published in English were included. Data extracted were year of publication, number of participants and allocation, nonsignificant or significant effect on incidence or severity of SP. A total of 31 papers where included in the review. Seven, 8, and 12 papers investigated the effect of drains, abdominal wall lift (AWL), and low-pressure pneumoperitoneum respectively. Four papers investigated drain suction, active gas aspiration, low insufflation flow or N2O insufflation respectively. The interventions that overall showed a significant reduction on either the incidence or severity of SP were low-pressure pneumoperitoneum, low insufflation rate, and active gas aspiration. Drainage and AWL are not recommended to reduce SP after LC. Low-pressure pneumoperitoneum with carbon dioxide is the best documented intraoperative surgical method to minimize both the incidence and severity of SP after LC.


Interferons, serotonin and neurotoxicity.
Interferons are a class of cytokines profoundly affecting immune function. Several interferons are now synthesized and used clinically, notably for viral diseases and cancer. In addition to their desired immune effects, interferons cause a number of toxicities, including prominent effects on the nervous system. This literature review focused on the incidence of depression associated with interferon treatment. Possible neurochemical mechanisms and remedial strategies were also considered. Interferon treatment, particularly with the alpha subtype, is unquestionably linked with depression, but the strength of association is uncertain because of erratic ascertainment and pretreatment co-morbidity. A likely pathogenic mechanism has been described, involving interferon suppression of serotonin synthesis. Controlled treatment trials of interferon-induced depression are not yet available. Neurotoxicity substantially limits the use of interferons. At least some of the risk of depression appears to derive from their anti-serotonergic effects, consistent with the large body of evidence pointing to a general link between serotonin and affective illness. Vigilant detection and aggressive treatment of depression is necessary to optimize interferon treatment of many patients.


Unusual interferon gamma measurements with QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube tests.
Interferon gamma (IFN-γ) release assays, such as QuantiFERON®-TB Gold test (QFT-G) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect M. tuberculosis (Mtb) infection. Recognition of unusual IFN-γ measurements may help indicate inaccurate results. We examined QFT-G and QFT-GIT results from subjects who had two or more tests completed. We classified unusual IFN-γ measurements as: 1) High Nil Concentration (HNC) when IFN-γ concentration in plasma from unstimulated blood exceeded 0.7 IU/mL; 2) Low Mitogen Response (LMR) when Mitogen Response was <0.5 IU/mL; 3) Very Low Mitogen Response (VLMR) when Mitogen Response was ≤-0.5 IU/mL; and 4) Very Low Antigen Response (VLAR) when the response to a Mtb antigen was ≤-0.35 IU/mL and ≤-0.5 times the IFN-γ concentration in plasma from unstimulated blood. Among 5,309 results from 1,728 subjects, HNC occurred in 234 (4.4%) tests for 162 subjects, LMR in 108 (2.0%) tests for 85 subjects, VLMR in 22 (0.4%) tests for 21 subjects, and VLAR in 41 (0.8%) tests for 39 subjects. QFT-GIT had fewer HNC, VLMR, and VLAR (p = 0.042, 0.004, and 0.067 respectively); QFT-G had fewer LMR (p = 0.005). Twenty-four (51.6%) of 47 subjects with positive results and HNC were negative or indeterminate by all other tests. Thirteen (61.9%) of 21 subjects with positive results and LMR were negative or indeterminate by all other tests. Unusual IFN-γ measurements including HNC, LMR, VLMR, and VLAR were encountered in small numbers, and in most instances were not seen on simultaneously or subsequently performed tests. To avoid erroneous diagnosis of Mtb infection, IGRAs with unusual IFN-γ measurements should be repeated with another blood sample and interpreted with caution if they recur.


The Health Impact of Symptomatic Adult Spinal Deformity: Comparison of Deformity Types to United States Population Norms and Chronic Diseases.
A retrospective analysis of a prospective, multicenter database. The aim of this study was to evaluate the health impact of symptomatic adult spinal deformity (SASD) by comparing Standard Form Version 2 (SF-36) scores for SASD with United States normative and chronic disease values. Recent data have identified radiographic parameters correlating with poor health-related quality of life for SASD. Disability comparisons between SASD patients and patients with chronic diseases may provide further insight to the disease burden caused by SASD. Consecutive SASD patients, with no history of spine surgery, were enrolled into a multicenter database and evaluated for type and severity of spinal deformity. Baseline SF-36 physical component summary (PCS) and mental component summary (MCS) values for SASD patients were compared with reported U.S. normative and chronic disease SF-36 scores. SF-36 scores were reported as normative-based scores (NBS) and evaluated for minimally clinical important difference (MCID). Between 2008 and 2011, 497 SASD patients were prospectively enrolled and evaluated. Mean PCS for all SASD was lower than U.S. total population (ASD = 40.9; US = 50; P < 0.05). Generational decline in PCS for SASD patients with no other reported comorbidities was more rapid than U.S. norms (P < 0.05). PCS worsened with lumbar scoliosis and increasing sagittal vertical axis (SVA). PCS scores for patients with isolated thoracic scoliosis were similar to values reported by individuals with chronic back pain (45.5 vs 45.7, respectively; P > 0.05), whereas patients with lumbar scoliosis combined with severe sagittal malalignment (SVA >10 cm) demonstrated worse PCS scores than values reported by patients with limited use of arms and legs (24.7 vs 29.1, respectively; P < 0.05). SASD is a heterogeneous condition that, depending upon the type and severity of the deformity, can have a debilitating impact on health often exceeding the disability of more recognized chronic diseases. Health care providers must be aware of the types of SASD that correlate with disability to facilitate appropriate diagnosis, treatment, and research efforts. 3.


Bisdemethoxycurcumin Inhibits Adipogenesis in 3T3-L1 Preadipocytes and Suppresses Obesity in High-Fat Diet-Fed C57BL/6 Mice.
Obesity is caused by excessive accumulation of body fat and is closely related to complex metabolic diseases. Adipogenesis is a key process that is required in adipocyte hypertrophy in the development of obesity. Curcumin (Cur) has been reported to inhibit adipocyte differentiation, but the inhibitory effects of other curcuminoids present in turmeric, such as demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), on adipogenesis have not been investigated. Here, we investigated the effects of curcuminoids on adipogenesis and the molecular mechanisms of adipocyte differentiation. Among three curcuminoids, BDMC was the most effective suppressor of lipid accumulation in adipocytes. BDMC suppressed adipogenesis in the early stage primarily through attenuation of mitotic clonal expansion (MCE). In BDMC-treated preadipocytes, cell cycle arrest at the G0/G1 phase was found after initiation of adipogenesis and was accompanied by downregulation of cyclin A, cyclin B, p21, and mitogen-activated protein kinase (MAPK) signaling. The protein levels of the adipogenic transcription factors peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding proteins (C/EBP)α were also reduced by BDMC treatment. Furthermore, 0.5% dietary BDMC (w/w) significantly lowered body weight gain and adipose tissue mass in high-fat diet (HFD)-fed mice. The results of H&E staining showed that dietary BDMC reduced hypertrophy in adipocytes. These results demonstrate for the first time that BDMC suppressed adipogenesis in 3T3-L1 adipocytes and prevented HFD-induced obesity. Our results suggest that BDMC has the potential to prevent obesity.


Evaluation of the VA's Pilot Program in Institutional Reorganization Toward Primary and Ambulatory Care: Part II, A study of organizational stresses and dynamics.
Many academically affiliated hospitals are moving from an inpatient, subspecialty orientation in their patient care and educational programs toward a greater emphasis on ambulatory and primary care. Few studies have focused on the organizational, staffing, and management issues involved in implementing these changes. The authors carried out a qualitative evaluation of the process of change in an academic Department of Veterans Affairs hospital during implementation of a major ambulatory primary care program. They interviewed four top managers individually and 59 top and middle managers, house officers, and patients in focus groups in the spring of 1992, nine months after implementation of the key components of the program. Four raters independently evaluated written transcripts of focus-group sessions and identified themes. The main problems identified were difficulty with administrative integration between inpatient and outpatient services; need for training, retraining, and orientation; tensions due to changes in roles and organizational culture; and inefficiency due to the need for frequent negotiations in daily work life. These four problems reflected tensions associated with new demands imposed by matrix management, changing job descriptions, policies and procedures, and changing patterns of communication and record keeping. During the process of implementation of a primary care focus throughout a medical center, extra demands upon staff are inevitable and should be anticipated and planned for. Twelve key factors for successful organizational change are discussed.


Complete congruence between gene diversity estimates derived from genotypic data at enzyme and random amplified polymorphic DNA loci in black spruce.
Controversy still exists over the adaptive nature of variation of enzyme loci. In conifers, random amplified polymorphic DNAs (RAPDs) represent a class of marker loci that is unlikely to fall within or be strongly linked to coding DNA. We have compared the genetic diversity in natural populations of black spruce [Picea mariana (Mill.) B.S.P.] using genotypic data at allozyme loci and RAPD loci as well as phenotypic data from inferred RAPD fingerprints. The genotypic data for both allozymes and RAPDs were obtained from at least six haploid megagametophytes for each of 75 sexually mature individuals distributed in five populations. Heterozygosities and population fixation indices were in complete agreement between allozyme loci and RAPD loci. In black spruce, it is more likely that the similar levels of variation detected at both enzyme and RAPD loci are due to such evolutionary forces as migration and the mating system, rather than to balancing selection and overdominance. Furthermore, we show that biased estimates of expected heterozygosity and among-population differentiation are obtained when using allele frequencies derived from dominant RAPD phenotypes.


Bronchoscopic and bronchographic findings in 12 patients with sarcoidosis and severe or progressive airways obstruction.
Twelve patients (8 men), aged 33-67 (mean 49) years, with histologically proved sarcoidosis underwent bronchoscopy. All had symptoms, signs (wheeze in 11, high pitched inspiratory "squeaks" in six, stridor in three), and physiological abnormalities characteristic of severe or worsening airways obstruction. Eleven patients also underwent bronchography. At the time of bronchoscopy four patients had stage II, one stage III, and seven stage IV sarcoidosis. All patients had a peak expiratory flow (PEF) of 70% predicted or less and a maximum expiratory flow at 50% (MEF50) and 25% (MEF25) of vital capacity below 35% predicted. The ratio of their forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ranged from 37% to 65%. Fibreoptic bronchoscopy showed single or multiple areas of segmental bronchial stenoses in 10 patients, two of whom had stenotic webs. Bronchography showed that the sites and severity of stenoses were more widespread than suspected from the bronchoscopic findings. Five of the 11 patients undergoing bronchography had bronchiectasis, which was restricted to the upper lobes in three and a lower lobe in one and affected both upper and lower lobes in one patient. The bronchiectasis had not been suspected or diagnosed from the chest radiography or the bronchoscopy.


Community-acquired pneumonia.
Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.


Infection and autoimmunity in Sjogren's syndrome: a clinical study and comprehensive review.
Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by lymphocytic infiltration of the exocrine glands, and autoantibody production. Multiple environmental factors affecting an individual with a genetic susceptibility may trigger the development of SS. Herein, we aimed to evaluate links between the different pebbles in the mosaic of SS. Demographic, clinical data and blood samples were gathered from 82 consecutive patients with SS, and 139 healthy controls. Samples were analyzed for infectious serology and auto-antibodies as well as for relevant genetic mutations (TAP genes) and cytokines levels. An immune response (IgG) against Epstein-Barr virus (EBV) early antigen (EA) was positively associated with SS (OR 4; 95% CI: 1.82-8.83, p = 0.001) while a protective effect of IgG anti-cytomegalovirus (CMV) was observed (OR 0.3; 95%CI: 0.16-0.74, p = 0.009). Anti-Ro/SSA, anti-LA/SSB, anti-nuclear, anti-gliadin, anti-TTG-IgG and anti-RNP antibodies were statistically more prevalent among SS patients than controls. Notably, the presence of anti-Ro/SSA and anti La/SSB correlated with anti-EBVEA IgG (OR 3.1; 95%CI: 1.08-8.74) and (OR 3.9; 95%CI: 1.37-10.96) respectively. Autoantibodies, cytokines and several genetic markers correlated with clinical manifestation of SS. Our data suggest that infectious agents may play both a causative and protective role in the pathogenesis of SS. Moreover certain autoantibodies, cytokines and specific TAP alleles correlate with clinical manifestations of SS, and may enable better prediction and/or directed therapy once confirmed in future studies.


Latent profiles of multidimensional prosocial behaviors: An examination of prosocial personality groups.
The current study sought to determine how prosocial behaviors reflecting various motivations (altruistic and public prosocial behaviors) and situations (i.e., anonymous, compliant, dire, and emotional prosocial behaviors) jointly inform subtypes of prosocial personality groups. Undergraduates (N = 324, M age = 19.47 years, 80% female) completed a measure of these six prosocial behaviors (Prosocial Tendencies Measure-Revised). Latent profile analysis results supported a three-group solution: altruistic helpers (AH), public helpers (PH), and altruistic idealists (AI). The AH and AI profiles were defined by elevated altruistic prosocial behaviors, but the AH profile was higher on situational helping and socioemotive and sociocognitive correlates. The PH profile was characterized by elevated public prosocial behaviors and moderate levels of situational helping. These identified profiles support multiple competing ideas of the true nature of prosocial personality, but also introduce the possibility that some individuals idealize motives but fail to engage in behavior.


Improved identification of the palmar fibrocartilage of the navicular bone with saline magnetic resonance bursography.
Fibrocartilage degeneration is the earliest pathologic finding in navicular disease but remains difficult to detect, even with magnetic resonance (MR) imaging. We hypothesized that injection of the navicular bursa with saline would improve accuracy of MR imaging evaluation of palmar fibrocartilage. Thoracic limbs were collected from 11 horses within 6 h of death. Imaging was performed with a 1.5 T magnet using sagittal 2D proton density and transverse 3D FLASH sequences with fat saturation. For the purpose of determining sensitivity and specificity of the MR images, fibrocartilage was classified as normal or abnormal, based on combination of the findings of gross and microscopic pathology. Thickness of fibrocartilage was measured on histologic sections and corresponding transverse FLASH MR images before and after injection of saline. A paired Student's t-test was used for comparison of measurements. Partial thickness fibrocartilage loss was present in 6 of 22 limbs. Sensitivity of precontrast MR images for detection of lesions was 100% while specificity was 6%. Saline MR arthrography resulted in both sensitivity and specificity of 100% based on consensus review. Mean histologic fibrocartilage thickness was 0.75 +/- 0.12 mm. Mean fibrocartilage thickness on precontrast transverse FLASH images was 0.93 +/- 0.065 and 0.73 +/- 0.09 mm on postsaline images. The histologic cartilage thickness was signficantly different from that in precontrast images (P<0.001) but not in images acquired after saline injection (P = 0.716). Based on our results, and using pulse sequences as described herein, navicular fibrocartilage can only be evaluated reliably for the presence of partial thickness lesions after intrabursal injection of saline.


The use of colour vision measurement in the diagnosis of digoxin toxicity.
Colour vision has been measured, using the Farnsworth-Munsell 100-Hue test, in control subjects and in patients taking digoxin. In 10 patients with digitalis toxicity, of whom only two described symptomatic abnormalities, colour vision was impaired compared with that of both control subjects and non-toxic patients who had been taking digoxin for more than two months. Withdrawal of digoxin from toxic patients led to improved colour vision. Colour vision scores correlated well with (a) log plasma digoxin concentrations, and (b) various measures of the pharmacodynamic effects of cardiac glycosides on cation transport in the patients' own erythrocytes. These results suggest that colour vision assessment may be of use in screening for digitalis toxicity at the bedside and in assessing the degree of digitalis intoxication in an individual patient as an aid to clinical research.