Errors in medical interpretation and their potential clinical consequences in pediatric encounters.
About 19 million people in the United States are limited in English proficiency, but little is known about the frequency and potential clinical consequences of errors in medical interpretation. To determine the frequency, categories, and potential clinical consequences of errors in medical interpretation. During a 7-month period, we audiotaped and transcribed pediatric encounters in a hospital outpatient clinic in which a Spanish interpreter was used. For each transcript, we categorized each error in medical interpretation and determined whether errors had a potential clinical consequence. Thirteen encounters yielded 474 pages of transcripts. Professional hospital interpreters were present for 6 encounters; ad hoc interpreters included nurses, social workers, and an 11-year-old sibling. Three hundred ninety-six interpreter errors were noted, with a mean of 31 per encounter. The most common error type was omission (52%), followed by false fluency (16%), substitution (13%), editorialization (10%), and addition (8%). Sixty-three percent of all errors had potential clinical consequences, with a mean of 19 per encounter. Errors committed by ad hoc interpreters were significantly more likely to be errors of potential clinical consequence than those committed by hospital interpreters (77% vs 53%). Errors of clinical consequence included: 1) omitting questions about drug allergies; 2) omitting instructions on the dose, frequency, and duration of antibiotics and rehydration fluids; 3) adding that hydrocortisone cream must be applied to the entire body, instead of only to facial rash; 4) instructing a mother not to answer personal questions; 5) omitting that a child was already swabbed for a stool culture; and 6) instructing a mother to put amoxicillin in both ears for treatment of otitis media. Errors in medical interpretation are common, averaging 31 per clinical encounter, and omissions are the most frequent type. Most errors have potential clinical consequences, and those committed by ad hoc interpreters are significantly more likely to have potential clinical consequences than those committed by hospital interpreters. Because errors by ad hoc interpreters are more likely to have potential clinical consequences, third-party reimbursement for trained interpreter services should be considered for patients with limited English proficiency.


Musculoskeletal trauma and all-cause mortality in India: a multicentre prospective cohort study.
There is little data in low-income and middle-income countries (LMICs) quantifying the burden of fractures and describing current practices. The aim of the study was describe the severity of musculoskeletal injuries in LMICS and identify modifiable factors that predict subsequent early all-cause mortality. We did a multicentre, prospective, observational study of patients who presented to 14 hospitals across India for musculoskeletal trauma (fractures or dislocations). Patients were recruited during an 8-week period, between November, 2011, and June, 2012, and were followed for 30-days or hospital discharge, whichever occurred first. Primary outcome was all-cause mortality with secondary outcomes of reoperation and infection. Logistic regression analyses were conducted to identify factors associated with all-cause mortality. We enrolled 4822 patients, but restricted analyses to 4612 (96%) patients who had complete follow-up. The majority (56·2% younger than 40 years old) of trauma patients were young (mean age 40·9 years [SD 16·9]) and 3148 (68%) were men. 2344 (518%) patients sustained trauma as a result of a road traffic accident. The most common musculoskeletal injury was a fracture (4514 [98%]) and 707 patients (15%) incurred an open fracture. Less than a third of musculoskeletal trauma patients (1374 [29%]) were transported to hospital by ambulance, and one in six patients (18%) arrived at the hospital later than 24 h after sustaining their injury. Over a third (239 [35%] of 707) of open fractures were definitively stabilised later than 24 h. 30-day mortality was 1·7% (95% CI 1·4-2·2) for all patients and 2·1% (95% CI 1·5-2·7) among road traffic victims (p=0·005). Musculoskeletal trauma severity including the number of fractures (3·1 [95% CI 2·4-3·9]) and presence of an open fracture (2·1 [95% CI 1·2-3·4]) significantly increased the odds of all-cause mortality. Musculoskeletal trauma severity, particularly road related, is a key predictor of subsequent mortality. Improvement in road safety policies, and improvements in access to emergency medical services and timely orthopaedic care are critical to mitigate the burden of injury worldwide. Regional Medical Associates, AO International, Hamilton Health Sciences Trauma Fund.


What Is Citizen Science?--A Scientometric Meta-Analysis.
The concept of citizen science (CS) is currently referred to by many actors inside and outside science and research. Several descriptions of this purportedly new approach of science are often heard in connection with large datasets and the possibilities of mobilizing crowds outside science to assists with observations and classifications. However, other accounts refer to CS as a way of democratizing science, aiding concerned communities in creating data to influence policy and as a way of promoting political decision processes involving environment and health. In this study we analyse two datasets (N = 1935, N = 633) retrieved from the Web of Science (WoS) with the aim of giving a scientometric description of what the concept of CS entails. We account for its development over time, and what strands of research that has adopted CS and give an assessment of what scientific output has been achieved in CS-related projects. To attain this, scientometric methods have been combined with qualitative approaches to render more precise search terms. Results indicate that there are three main focal points of CS. The largest is composed of research on biology, conservation and ecology, and utilizes CS mainly as a methodology of collecting and classifying data. A second strand of research has emerged through geographic information research, where citizens participate in the collection of geographic data. Thirdly, there is a line of research relating to the social sciences and epidemiology, which studies and facilitates public participation in relation to environmental issues and health. In terms of scientific output, the largest body of articles are to be found in biology and conservation research. In absolute numbers, the amount of publications generated by CS is low (N = 1935), but over the past decade a new and very productive line of CS based on digital platforms has emerged for the collection and classification of data.


Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study.
Observational studies and small intervention studies suggest alcohol raises gamma-glutamyltransferase (GGT). We used Mendelian randomization to assess the causal effect of alcohol use on GGT in older Chinese people. An instrumental variable (IV) analysis in 2,321 men and 2,757 women aged 50+ years from phase 3 of the Guangzhou Biobank Cohort Study with ALDH2 (rs671) genotyped, alcohol use and GGT available was used to assess the causal effect of alcohol use on GGT. Rs671 was used as an IV and F-statistics was used to test for weak instrument hypothesis. An F-statistic of ≥10 indicates the IV is not weak. In men, the F-statistic for rs671 on alcohol use was 70. Using IV analysis alcohol use increased GGT by 10.60 U/L per alcohol unit (10 gram ethanol) per day (95% confidence interval (CI) 6.58 to 14.62). The estimate was lower in observational multivariate regression: 3.48 U/L GGT per alcohol unit per day (95% CI 2.84 to 4.11) adjusted for age, education, physical activity and smoking. In women, rs671 was not associated with alcohol or GGT and the F-statistic was 7 precluding IV analysis. In Mendelian randomization, we found confirmative evidence that alcohol use increases GGT among Southern Chinese men. Moreover, we found that the ALDH2 variant rs671 was not associated with GGT among Southern Chinese women who generally consume very low levels of alcohol. Taken together our findings strongly suggest that alcohol increases GGT, although we cannot rule out the possibility that other unknown factors may cause a different relation between alcohol and GGT in other populations.


The epidemic of foot-and-mouth disease in Saskatchewan, Canada, 1951-1952.
The epidemic of foot-and-mouth disease in Saskatchewan in 1951 and 1952 was studied in order to determine origins of outbreaks and methods of spread. The epidemic was initially considered to be vesicular stomatitis and foot-and-mouth disease was not recognized until February 1952, three months after the initial infection. The reports prepared at that time were reviewed in order to obtain details of the numbers of animals infected and the source and date of infection for the outbreaks. Methods of spread were rated according to their likelihood. The introduction of infection by an immigrant through his clothes as well as by sausage was possible. The sequence of events from the first outbreak to the spread from a feedlot/packing plant and from a dairy farm, which failed to report the disease, were clarified. Methods of spread included movement of animals, animal products and people and the airborne route. Milk delivery and artificial insemination did not result in spread of infection. The quarantine of affected farms reduced spread by animals and deterred visits by people. The original diagnosis of vesicular stomatitis was due to misinterpretation of a lesion in an inoculated horse. Laboratory tests established the presence of foot-and-mouth disease. The limited extent of the epidemic, despite the delay in diagnosis, is attributed to (i) the low density of cattle, (ii) few infected pigs and hence less airborne virus and (iii) absence of waste food feeding and milk collection in addition to the limited quarantine imposed.


Childhood behaviour problems show the greatest gap between DNA-based and twin heritability.
For most complex traits, DNA-based heritability ('SNP heritability') is roughly half that of twin-based heritability. A previous report from the Twins Early Development Study suggested that this heritability gap is much greater for childhood behaviour problems than for other domains. If true, this finding is important because SNP heritability, not twin heritability, is the ceiling for genome-wide association studies. With twice the sample size as the previous report, we estimated SNP heritabilities (N up to 4653 unrelated individuals) and compared them with twin heritabilities from the same sample (N up to 4724 twin pairs) for diverse domains of childhood behaviour problems as rated by parents, teachers, and children themselves at ages 12 and 16. For 37 behaviour problem measures, the average twin heritability was 0.52, whereas the average SNP heritability was just 0.06. In contrast, results for cognitive and anthropometric traits were more typical (average twin and SNP heritabilities were 0.58 and 0.28, respectively). Future research should continue to investigate the reasons why SNP heritabilities for childhood behaviour problems are so low compared with twin estimates, and find ways to maximise SNP heritability for genome-wide association studies.


Increasing nurses' person-centeredness.
In a two-phased study, two samples of registered nurses listened to audiotaped disclosure statements from simulated patients and responded to each statement "in as helpful a manner as possible." Their responses were judged for degree of "person-centeredness." Nurses in sample one (N=24) received no intervention between the two phases of the study; nurses in sample two (N=20), after completing phase I, listened to a brief message designed to enhance the helpfulness of their responses. No differences were found for the phase I person-centeredness scores; the nurses who received the intervention showed significant improvement in their degree of person-centeredness as compared to those who did not receive the intervention. Implications of these results are discussed.


Autochthonous Dengue Fever in 2 Patients, Rome, Italy.
Since August 2023, outbreaks of dengue virus (DENV) infection have occurred in Italy. We report 2 autochthonous case-patients and their extended follow-up. Despite persistent DENV detected in blood by PCR, results for antigenomic DENV RNA were negative after day 5, suggesting that a 5-day isolation period is adequate to avoid secondary cases.


Sudden death and use of stimulant medications in youths.
The authors sought to determine whether a significant association exists between the use of stimulants and the rare event of sudden unexplained death in children and adolescents. A matched case-control design was performed. Mortality data from 1985-1996 state vital statistics were used to identify 564 cases of sudden death occurring at ages 7 through 19 years across the United States along with a matched group of 564 young people who died as passengers in motor vehicle traffic accidents. The primary exposure measure was the presence of amphetamine, dextroamphetamine, methamphetamine, or methylphenidate according to informant reports or as noted in medical examiner records, toxicology results, or death certificates. In 10 (1.8%) of the sudden unexplained deaths it was determined that the youths were taking stimulants, specifically methylphenidate; in contrast, use of stimulants was found in only two subjects in the motor vehicle accident comparison group (0.4%), with only one involving methylphenidate use. A significant association of stimulant use with sudden unexplained death emerged from the primary analysis, which was based on exact conditional logistic regression (odds ratio=7.4, 95% CI=1.4 to 74.9). A comprehensive series of sensitivity analyses yielded qualitatively similar findings. This case-control study provides support for an association between the use of stimulants and sudden unexplained death among children and adolescents. Although sudden unexplained death is a rare event, this finding should be considered in the context of other data about the risk and benefit of stimulants in medical treatment.


Calorimetric measurement of the energy difference between two solid surface phases.
A recently designed single-crystal surface calorimeter has been deployed to measure the energy difference between two solid surface structures. The clean Pt{100} surface is reconstructed to a stable phase in which the surface layer of platinum atoms has a quasi-hexagonal structure. By comparison of the heats of adsorption of CO and of C(2)H(4) on this stable Pt{100}-hex phase with those on a metastable Pt{100}-(1x1) surface, the energy difference between the two clean phases was measured as 20 +/- 3 and 25 +/- 3 kilojoules per mole of surface platinum atoms.


Management and 6-month outcomes in elderly and very elderly patients with high-risk non-ST-elevation acute coronary syndromes: The Global Registry of Acute Coronary Events.
To test the hypothesis that increasing age in patients presenting with high-risk non-ST-segment elevation acute coronary syndromes (NSTE-ACS) does not adversely influence the benefit of an early invasive strategy on major adverse events at 6 months. We report clinical outcomes in young (<70), elderly (70-80), and very elderly (>80 years) patients with high-risk NSTE-ACS enrolled in GRACE between 1999 and 2006. Six month data were available in 18 466 patients (27% elderly, 16% very elderly). Elderly and very elderly patients were less likely to receive evidence-based treatments at discharge and had a longer hospital stay (6 vs. 5 days). Angiography was performed more frequently in younger patients (67 vs. 33% in very elderly, 55% in elderly; P < 0.0001). Multiple logistic regression analysis confirmed the benefit of revascularization on the primary study endpoint (6-month stroke, death, myocardial infarction) in young [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.56-0.86], elderly (0.60, 0.47-0.76), and very elderly (0.72, 0.54-0.95) patients. Revascularization was associated with reductions in 6-month mortality (OR 0.52, 95% CI 0.37-0.72 in young; 0.38, 0.26-0.54 in elderly; 0.68, 0.49-0.95 in very elderly). Stroke risk in hospital or at 6 months was not increased by revascularization. Following presentation with high-risk NSTE-ACS, an evidence-based approach to management was noted less frequently with advancing patient age. Angiography, in particular, was less likely to be undertaken. Revascularization, however, when performed, was associated with significant benefits at 6 months, independent of age, and did not increase risk of stroke.


Dual Antiplatelet Therapy Continuation Beyond 1 Year After Drug-Eluting Stents: A Meta-Analysis of Randomized Trials.
The benefits and harms of dual antiplatelet therapy (DAPT) continuation beyond 1 year after drug-eluting stent implantation as compared with 1-year DAPT remain controversial. We searched for randomized trials that compared longer than 1-year DAPT versus 1-year DAPT after drug-eluting stenting. A meta-analysis was performed by using standard frequentist and random-effects Bayesian approaches. Four trials comprising 17 650 participants were included. Compared with 1-year DAPT, extended DAPT did not affect all-cause mortality (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.79-1.5; P=0.53) or cardiovascular mortality (OR, 1.03; 95% CI, 0.72-1.46; P=0.88). Extended DAPT was associated with a reduction in the risk of myocardial infarction (OR, 0.56; 95% CI, 0.43-0.73; P<0.001), nonsignificant reductions of stent thrombosis (OR, 0.46; 95% CI, 0.16-1.27; P=0.13), similar risk of stroke (OR, 0.91; 95% CI, 0.65-1.26; P=0.56), and an increased risk of major bleeding (OR, 1.49; 95% CI, 1.06-2.11; P=0.02). By using Bayesian meta-analysis, we found moderate evidence of a reduction of myocardial infarction (OR, 0.62; 95% credible intervals, 0.39-1.05) and weak evidence of an increase in major bleeding (OR, 1.66; 95% credible intervals, 0.89-3.09) associated with extended DAPT. In this meta-analysis, extended DAPT beyond 1 year prevented myocardial infarctions and increased major bleedings, but the strength of evidence for these effects was not strong. DAPT continuation beyond 1 year showed no effects on mortality.


100th Anniversary of Macromolecular Science Viewpoint: Opportunities in the Physics of Sequence-Defined Polymers.
Polymer science has been driven by ever-increasing molecular complexity, as polymer synthesis expands an already-vast palette of chemical and architectural parameter space. Copolymers represent a key example, where simple homopolymers have given rise to random, alternating, gradient, and block copolymers. Polymer physics has provided the insight needed to explore this monomer sequence parameter space. The future of polymer science, however, must contend with further increases in monomer precision, as this class of macromolecules moves ever closer to the sequence-monodisperse polymers that are the workhorses of biology. The advent of sequence-defined polymers gives rise to opportunities for material design, with increasing levels of chemical information being incorporated into long-chain molecules; however, this also raises questions that polymer physics must address. What properties uniquely emerge from sequence-definition? Is this circumstance-dependent? How do we define and think about sequence dispersity? How do we think about a hierarchy of sequence effects? Are more sophisticated characterization methods, as well as theoretical and computational tools, needed to understand this class of macromolecules? The answers to these questions touch on many difficult scientific challenges, setting the stage for a rich future for sequence-defined polymers in polymer physics.


Rubella seroprevalence among pregnant women in Burkina Faso.
Despite the serious consequences of rubella infection during early pregnancy, very little is known about the rubella seroprevalence in a number of African countries including Burkina Faso. Between December 2007 and March 2008 serum samples were collected from 341 pregnant women in Bobo (n = 132, urban area) and Houndé (n = 209, rural area) and were tested for rubella-specific IgG antibodies with a commercial ELISA kit. An overall seropositivity rate of 95.0% (324/341) was found, with a higher percentage in the urban population and in the oldest age group. Considering an antibody titer of at least 10 International Units per ml as protective, the overall immunity rate in the cohort of pregnant women was 93.3% (318/341). The high overall seropositivity rate in the absence of routine immunization suggests a continuous transmission of endemic rubella virus in Burkina Faso, posing a threat to non-immune pregnant women.


Unique biology of Mcl-1: therapeutic opportunities in cancer.
Accumulating evidence suggests that Mcl-1 plays a critical pro-survival role in the development and maintenance of both normal and malignant tissues. Regulation of Mcl-1 expression occurs at multiple levels, allowing for either the rapid induction or elimination of the protein in response to different cellular events. This suggests that Mcl-1 can play an early role in response to signals directing either cell survival or cell death. Deregulation of pathways regulating Mcl-1 that result in its over-expression likely contribute to a cell's inability to properly respond to death signals possibly leading to cell immortalization and tumorigenic conversion. Correspondingly, Mcl-1 has been shown to be up-regulated in numerous hematological and solid tumor malignancies. Moreover, this up-regulation appears to be a factor in the resistance of some cancer types to conventional cancer therapies. Mechanisms that abrogate the pro-survival function of Mcl-1 either by diminishing its levels or inactivating its functional BH3 groove have shown promise for the combinational treatment with existing cancer therapies and as single agents in certain malignancies. Here we review the various pathways that regulate Mcl-1 expression and describe agents that are currently under development to modulate Mcl-1 activity for therapeutic benefit in oncology.


Legionella pneumophila-mediated host posttranslational modifications.
Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease. During infections, L. pneumophila releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the host. Notably, certain effector proteins mediate posttranslational modifications (PTMs), serving as useful approaches exploited by L. pneumophila to modify host proteins. Some effectors catalyze the addition of host protein PTMs, while others mediate the removal of PTMs from host proteins. In this review, we summarize L. pneumophila effector-mediated PTMs of host proteins, including phosphorylation, ubiquitination, glycosylation, AMPylation, phosphocholination, methylation, and ADP-ribosylation, as well as dephosphorylation, deubiquitination, deAMPylation, deADP-ribosylation, dephosphocholination, and delipidation. We describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.


A nonsense mutation in MLH1 causes exon skipping in three unrelated HNPCC families.
Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 are responsible for the majority of hereditary nonpolyposis colorectal cancer (HNPCC) families. A common mutation mechanism is to disrupt MLH1 and MSH2 mRNA splicing. The disruption creates aberrant mRNAs lacking specific coding exons (exon skipping). Here, we report a novel skipping of MLH1 exon 12 caused by an AAG to TAG nonsense mutation at codon 461 in three HNPCC families of North American origins. The nonsense codon was found in a conserved haplotype in the three unrelated families and seems to represent a founder mutation. The skipping created an aberrant MLH1 mRNA transcript lacking exon 12. The effect of the codon 461 nonsense mutation on exon 12 skipping is evident even though it was placed in a minigene construct containing entirely different coding sequences. Notably, the effect of the nonsense mutation on exon skipping is incomplete. Accordingly, a second aberrant MLH1 transcript encompassing the nonsense codon is also produced. Whereas the latter transcript is unstable, presumably because of nonsense-mediated mRNA decay, neither of the aberrant transcripts seems to affect the stability of wild-type MLH1 mRNA. This study demonstrates that the germ-line nonsense mutation at codon 461 of MLH1 disrupts normal MLH1 mRNA processing, and that exon skipping underlies pathogenesis in these HNPCC families.


Casualties: narrative and images of the war on Iraq.
The Iraqi people have endured an excess burden of morbidity and mortality during the past 15 years due to war and sanctions, with the March 2003 Anglo-American assault on and subsequent occupation of Iraq representing the most recent chapter. Children have been disproportionately affected; many have died from infectious disease, malnutrition, and lack of access to health care. There have been significant differences in the availability of narrative accounts and images of this suffering, reflective of the need of those who wage wars and impose sanctions to keep the public uninformed. This article suggests that public health and medical practitioners have a responsibility to seek out such accounts and images. The authors explore possible responses to narrative and images of this suffering, and outline the sorts of responses engendered by three perspectives-charity, development, and social justice. The suffering of the people of Iraq should spur a response from the health community to alleviate the situation and prevent unnecessary suffering.


Targeting the NLRP3 Inflammasome to Reduce Diet-Induced Metabolic Abnormalities in Mice.
Although the molecular links underlying the causative relationship between chronic low-grade inflammation and insulin resistance are not completely understood, compelling evidence suggests a pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Here we tested the hypothesis that either a selective pharmacological inhibition or a genetic downregulation of the NLRP3 inflammasome results in reduction of the diet-induced metabolic alterations. Male C57/BL6 wild-type mice and NLRP3-/- littermates were fed control diet or high-fat, high-fructose diet (HD). A subgroup of HD-fed wild-type mice was treated with the NLRP3 inflammasome inhibitor BAY 11-7082 (3 mg/kg intraperitoneally [IP]). HD feeding increased plasma and hepatic lipids and impaired glucose homeostasis and renal function. Renal and hepatic injury was associated with robust increases in profibrogenic markers, while only minimal fibrosis was recorded. None of these metabolic abnormalities were detected in HD-fed NLRP3-/- mice, and they were dramatically reduced in HD-mice treated with the NLRP3 inflammasome inhibitor. BAY 11-7082 also attenuated the diet-induced increase in NLRP3 inflammasome expression, resulting in inhibition of caspase-1 activation and interleukin (IL)-1β and IL-18 production (in liver and kidney). Interestingly, BAY 11-7082, but not gene silencing, inhibited nuclear factor (NF)-κB nuclear translocation. Overall, these results demonstrate that the selective pharmacological modulation of the NLRP3 inflammasome attenuates the metabolic abnormalities and the related organ injury/dysfunction caused by chronic exposure to HD, with effects similar to those obtained by NLRP3 gene silencing.


Life Cycle, Ultrastructure, and Host Specificity of the North American Isolate of Pasteuria that Parasitizes the Soybean Cyst Nematode, Heterodera glycines.
Light and transmission electron microscopy were used to investigate the life cycle and ultrastructure of an undescribed isolate of Pasteuria that parasitizes the soybean cyst nematode, Heterodera glycines. Studies also were conducted to determine the host specificity of Pasteuria. The endospores that attached to the cuticle of second-stage juveniles (J2) of H. glycines in soil did not germinate until the encumbered nematodes invaded soybean roots. Thereafter, the bacterium developed and completed its life cycle only in females. The stages of endosporogenesis were typical of Pasteuria spp. The mature endospore, like that of P. nishizawae, the only other Pasteuria known to infect H. glycines, produces an epicortical layer that completely surrounds the cortex, an outer spore coat that tapers progressively from the top to the base of the central body, and a double basal adhesion layer. However, subtle differences exist between the Pasteuria from North America and P. nishizawae with regard to size of the central body, nature and function of the mesosomes observed in the earlier stages of endosporogenesis, and appearance of the fibers lining the basal adhesion layer and the exosporium of the mature endospore. Endospores of the North American Pasteuria attached to J2 of H. schachtii, H. trifolii, and H. lespedezae but not to Meloidogyne arenaria race 1, Tylenchorhynchus nudus, and Labronema sp. Results from this study indicate that the North American Pasteuria is more similar to P. nishizawae than to any other known member of the genus. Additional evidence from comparative analysis of 16S rDNA sequences is needed to clarify whether these two Pasteuria belong to the same species.


Recombination and introgression of nuclear and chloroplast genomes between the peat mosses, Sphagnum capillifolium and Sphagnum quinquefarium.
Haploid hybrid gametophytes are often present at low frequencies in sympatric populations of Sphagnum capillifolium and Sphagnum quinquefarium. We used intersimple sequence repeat (ISSR) markers and polymerase chain reaction-restriction fragment length polymorphism of the trnL(UAA) intron of the chloroplast genome to reveal the nuclear and chloroplast composition of mature hybrid gametophytes from natural populations and of gametophytes derived from spores of hybrid sporophytes collected in nature. Asymmetrical nuclear inheritance was found in the progeny of the hybrid sporophytes, indicating that only spores with a low level of recombination of parental genomes were viable. A similarly skewed nuclear composition was found among the naturally occurring hybrid gametophytes. All hybrid genomes contained a larger proportion of S. capillifolium ISSR markers, combined with only two to five S. quinquefarium markers together with a chloroplast haplotype derived from S. quinquefarium. In this way, a pattern resembling introgression is created within a single generation. Some individuals possessed nuclear genomes typical for S. capillifolium in combination with the chloroplast haplotype of S. quinquefarium, possibly indicating backcrossing. Our results indicate that hybridization between S. capillifolium and S. quinquefarium is relatively common, but the resistance of large parts of the genome against heterospecific genes maintains the genetic distinctness of the species. Further evolutionary and phylogenetic consequences of restricted interspecific gene exchange are discussed.


Characterization of cytolethal distending toxin of campylobacter species isolated from captive macaque monkeys.
An association between certain Campylobacter species and enterocolitis in humans and nonhuman primates is well established, but the association between cytolethal distending toxin and disease is incompletely understood. The purpose of the present study was to examine Campylobacter species isolated from captive conventionally raised macaque monkeys for the presence of the cdtB gene and for cytolethal distending toxin activity. The identity of each isolate was confirmed on the basis of phenotypic and genotypic analyses. The presence of cytolethal distending toxin was confirmed on the basis of characteristic morphological changes in HeLa cells incubated with filter-sterilized whole-cell lysates of reference and monkey Campylobacter isolates and examinations by light microscopy, confocal microscopy, and flow cytometry. Although cdtB gene sequences were found in both Campylobacter jejuni and Campylobacter coli, the production of cytolethal distending toxin correlated positively (P < 0.0001) only with C. jejuni. We concluded that cytolethal distending toxin activity is a characteristic of C. jejuni. Our C. jejuni cdtB gene-specific PCR assay might be of assistance for differentiating toxigenic C. jejuni from C. coli in clinical laboratories.


Is self-generated thought a means of social problem solving?
Appropriate social problem solving constitutes a critical skill for individuals and may rely on processes important for self-generated thought (SGT). The aim of the current study was to investigate the link between SGT and social problem solving. Using the Means-End Problem Solving task (MEPS), we assessed participants' abilities to resolve daily social problems in terms of overall efficiency and number of relevant means they provided to reach the given solution. Participants also performed a non-demanding choice reaction time task (CRT) and a moderately-demanding working memory task (WM) as a context in which to measure their SGT (assessed via thought sampling). We found that although overall SGT was associated with lower MEPS efficiency, it was also associated with higher relevant means, perhaps because both depend on the capacity to generate cognition that is independent from the hear and now. The specific content of SGT did not differentially predict individual differences in social problem solving, suggesting that the relationship may depend on SGT regardless of its content. In addition, we also found that performance at the WM but not the CRT was linked to overall better MEPS performance, suggesting that individuals good at social processing are also distinguished by their capacity to constrain attention to an external task. Our results provide novel evidence that the capacity for SGT is implicated in the process by which solutions to social problems are generated, although optimal problem solving may be achieved by individuals who display a suitable balance between SGT and cognition derived from perceptual input.


The use of antenatal and postnatal care: perspectives and experiences of women and health care providers in rural southern Tanzania.
Although antenatal care coverage in Tanzania is high, worrying gaps exist in terms of its quality and ability to prevent, diagnose or treat complications. Moreover, much less is known about the utilisation of postnatal care, by which we mean the care of mother and baby that begins one hour after the delivery until six weeks after childbirth. We describe the perspectives and experiences of women and health care providers on the use of antenatal and postnatal services. From March 2007 to January 2008, we conducted in-depth interviews with health care providers and village based informants in 8 villages of Lindi Rural and Tandahimba districts in southern Tanzania. Eight focus group discussions were also conducted with women who had babies younger than one year and pregnant women. The discussion guide included information about timing of antenatal and postnatal services, perceptions of the rationale and importance of antenatal and postnatal care, barriers to utilisation and suggestions for improvement. Women were generally positive about both antenatal and postnatal care. Among common reasons mentioned for late initiation of antenatal care was to avoid having to make several visits to the clinic. Other concerns included fear of encountering wild animals on the way to the clinic as well as lack of money. Fear of caesarean section was reported as a factor hindering intrapartum care-seeking from hospitals. Despite the perceived benefits of postnatal care for children, there was a total lack of postnatal care for the mothers. Shortages of staff, equipment and supplies were common complaints in the community. Efforts to improve antenatal and postnatal care should focus on addressing geographical and economic access while striving to make services more culturally sensitive. Antenatal and postnatal care can offer important opportunities for linking the health system and the community by encouraging women to deliver with a skilled attendant. Addressing staff shortages through expanding training opportunities and incentives to health care providers and developing postnatal care guidelines are key steps to improve maternal and newborn health.


Assessment of Thermal and Textural Characteristics and Consumer Preferences of Lemon and Strawberry Flavored Fish Oil Organogels.
In this study, strawberry and lemon flavored fish oil organogels (FOO) were prepared with beeswax as the organogelator. The physical, thermal and textural characteristics as well as the consumer preferences of the flavored organogels were determined in comparison with fish oil and FOO containing no flavor. Furthermore, the stability of the organogels was evaluated during 90 day storage at 4°C. The results revealed that, structurally stable fish oil organogels as spreadable products might be formed and that flavoring of the gels enhances consumer preference. Thus, flavoring of fish oil organogels could be a challenge in increasing the consumption of fish oil.


The intersection of gender and race/ethnicity in smoking behaviors among menthol and non-menthol smokers in the United States.
To determine whether menthol is related to initiation, quantity or quitting, we examined differences in smoking behaviors among menthol and non-menthol smokers, stratified by gender and race/ethnicity, and adjusting for age, income and educational attainment. Cross-sectional, using data from the 2005 National Health Interview Survey and Cancer Control Supplement. United States. Black, Hispanic and white women and men aged 25-64 years. For each group, we examined (i) proportion of menthol smokers (comparing current and former smokers); (ii) age of initiation, cigarettes smoked per day and quit attempt in the past year (comparing menthol and non-menthol current smokers); and (iii) time since quitting (comparing menthol and non-menthol former smokers). We calculated predicted values for each demographic group, adjusting for age, income and educational attainment. After adjusting for age, income and education, black (compared with Hispanic and white) and female (compared with male) smokers were more likely to choose menthol cigarettes. There was only one statistically significant difference in age of initiation, cigarettes smoked per day, quit attempts or time since quitting between menthol and non-menthol smokers: white women who smoked menthol cigarettes reported longer cessation compared with those who smoked non-menthol cigarettes. The results do not support the hypothesis that menthol smokers initiate earlier, smoke more or have a harder time quitting compared with non-menthol smokers. A menthol additive and the marketing of it, given the clear demographic preferences demonstrated here, however, may be responsible for enticing the groups least likely to smoke into this addictive behavior.


The association of serum adiponectin levels with histopathological variables in gastric cancer patients.
Adiponectin is a peptide hormone secreted from the adipose tissue, affecting the proliferation and insulin sensitivity in different cell types. The levels of adiponectin have been found to be decreased in hyperinsulinemia and insulin resistant states, such as obesity. The previous studies have suggested that plasma adiponectin levels are decreased in patients with endometrial and breast cancer. In our study, the relationship among serum adiponectin levels, demographic features and histopathological variables was evaluated in gastric cancer patients. Forty consecutive patients with gastric cancer who underwent gastrectomy with standard lymph node dissection were included and 43 healthy controls were included in this study. The serum levels of glucose, insulin, C-peptide, HbA1c and adiponectin were measured in both groups. We analyzed the correlation among these parameters and patients' demographic features, such as age, gender, body mass index (BMI) and histopathological variables such as tumor localization, stage, nodal status, histological grade, vascular and lymphatic invasion. The mean age was 60.05+9.72 in patients, while it was 38.6+12.73 in controls. The mean serum adiponectin levels were 12.62+7.9 and 10.07+6.72 ng/ml, respectively, in groups. There was no different in terms of adiponectin, C-peptide, HOMA-R level in both groups. On the other hand, BMI, glucose and insulin levels were significantly different in gastric cancer patients in comparison with the controls. There was no correlation among the levels of adiponectin, BMI, insulin and c-peptide levels in patient group (P>0.05). The adiponectin levels of woman were significantly lower than male patients (P=0.002). No relations were detected among tumor stage, tumor localization, nodal status, lymphatic and vascular invasion, and the levels of serum adiponectin (P>0.05). Interestingly, a positive correlation was found between tumor grade and plasma adiponectin levels (r=0.372; P=0.018). Our results suggest that plasma adiponectin levels were similar in both patients with gastric cancer and the controls. In addition, no correlation was found between adiponectin levels and demographic features and histopathological variables of patients. But, in undifferentiated tumors, plasma adiponectin level was significantly higher than well-differentiated grade tumors.


The phosphatidylinositol transfer protein RdgBβ binds 14-3-3 via its unstructured C-terminus, whereas its lipid-binding domain interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein).
PITPs [PI (phosphatidylinositol) transfer proteins] bind and transfer PI between intracellular membranes and participate in many cellular processes including signalling, lipid metabolism and membrane traffic. The largely uncharacterized PITP RdgBβ (PITPNC1; retinal degeneration type B β), contains a long C-terminal disordered region following its defining N-terminal PITP domain. In the present study we report that the C-terminus contains two tandem phosphorylated binding sites (Ser(274) and Ser(299)) for 14-3-3. The C-terminus also contains PEST sequences which are shielded by 14-3-3 binding. Like many proteins containing PEST sequences, the levels of RdgBβ are regulated by proteolysis. RdgBβ is degraded with a half-life of 4 h following ubiquitination via the proteasome. A mutant RdgBβ which is unable to bind 14-3-3 is degraded even faster with a half-life of 2 h. In vitro, RdgBβ is 100-fold less active than PITPα for PI transfer, and RdgBβ proteins (wild-type and a mutant that cannot bind 14-3-3) expressed in COS-7 cells or endogenous proteins from heart cytosol do not exhibit transfer activity. When cells are treated with PMA, the PITP domain of RdgBβ interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein; also known as AGTRAP) causing membrane recruitment. We suggest that RdgBβ executes its function following recruitment to membranes via its PITP domain and the C-terminal end of the protein could regulate entry to the hydrophobic cavity.


Pterin-based ornamental coloration predicts yolk antioxidant levels in female striped plateau lizards (Sceloporus virgatus).
1. Maternal investment in egg quality can have important consequences for offspring fitness. For example, yolk antioxidants can affect embryonic development as well as juvenile and adult phenotype. Thus, females may be selected to advertise their yolk antioxidant deposition to discriminatory males via ornamental signals, perhaps depending on the reproductive costs associated with signal production. 2. Female striped plateau lizards (Sceloporus virgatus) develop pterin-based orange colour patches during the reproductive season that influence male behaviour and that are positively associated with the phenotypic quality of the female and her offspring. Here, we assessed one potential developmental mechanism underlying the relationship between offspring quality and female ornamentation in S. virgatus, by examining the relationship between ornament expression and yolk antioxidant levels. 3. As expected, concentrations of the yolk antioxidants vitamin A, vitamin E and carotenoids (lutein and zeaxanthin) were strongly positively intercorrelated. Eggs from larger clutches had fewer antioxidants than eggs from smaller clutches, suggesting that females may be limited in antioxidant availability or use. Fertilized and unfertilized eggs did not differ in yolk antioxidant levels. 4. The size of a female's ornament was positively related to both the concentration and total amount of yolk antioxidants, and ornament colour was positively related to yolk antioxidant concentration. Thus, in S. virgatus, female ornaments may advertise egg quality. In addition, these data suggest that more ornamented females may produce higher-quality offspring, in part because their eggs contain more antioxidants. As the colour ornament of interest is derived from pterins, not carotenoids, direct resource trade-offs between ornaments and eggs may be eliminated, reducing reproductive costs associated with signalling. 5. This is the first example of a positive relationship between female ornamentation and yolk antioxidants in reptiles and may indicate the general importance of these patterns in oviparous vertebrates.


Effect of diaphragmatic contraction on intramuscular pressure and vascular impedance.
The purpose of the present study was to determine whether the diaphragm, like limb muscles, generates high levels of intramuscular pressure during contraction. Studies were performed on in situ diaphragm strips in 15 dogs. An isometric force transducer was used to measure strip tension, and intramuscular pressure was assessed using both wick and balloon catheter techniques. Tension and intramuscular pressures were recorded during a series of graded contractions elicited by electrically stimulating strips via intramuscular electrodes. Similar techniques were used to record the tension and intramuscular pressures developed during graded contractions of a limb muscle, the vastus medialis. Intramuscular pressure was linearly related to tension in both the diaphragm and vastus medialis. However, for a given level of tension development, vastus medialis pressures were two- to threefold greater than those developed within the diaphragm. For example, at a tension of 2 kg/cm2 vastus medialis and diaphragm intramuscular pressures were 105 +/- 11 and 25 +/- 4 mmHg, respectively, when assessed with wick catheters, and were 159 +/- 11 and 48 +/- 5 mmHg, respectively, when assessed by the balloon catheter technique. These differences may reflect the fact that thick rounded muscles, like the vastus, may be capable of generating higher intramuscular pressures than the thin sheetlike diaphragm. To determine whether intradiaphragmatic pressure swings were large enough to explain the vascular compression produced by contraction, we measured phrenic arterial impedance during contraction in nine animals. In these animals the inferior phrenic artery was cannulated and pump perfused at a constant flow rate. With contraction, phrenic arterial pressure rose; i.e., phrenic arterial impedance increased.(ABSTRACT TRUNCATED AT 250 WORDS)


First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention.
The ideal anticoagulant should prevent ischemic complications without increasing the risk of bleeding. Controlled anticoagulation is possible with the REG1 system, an RNA aptamer pair comprising the direct factor IXa inhibitor RB006 and its active control agent RB007. This phase 2a study included a roll-in group (n=2) treated with REG1 plus glycoprotein IIb/IIIa inhibitors followed by 2 groups randomized 5:1 to REG1 or unfractionated heparin. In group 1 (n=12), RB006 was partially reversed with RB007 after percutaneous coronary intervention and fully reversed 4 hours later. In group 2 (n=12), RB006 was fully reversed with RB007 immediately after percutaneous coronary intervention. Femoral sheaths were removed after complete reversal. Patients were pretreated with aspirin and clopidogrel. End points included major bleeding within 48 hours; composite of death, myocardial infarction, or urgent target vessel revascularization within 14 days; and pharmacodynamic measures. All cases were successful, with final Thrombolysis in Myocardial Infarction grade 3 flow and no angiographic thrombotic complications. There were 2 ischemic end points in the REG1 group and 1 in the unfractionated heparin group, with 1 major bleed in the unfractionated heparin group. Median activated clotting time values rose from 151 to 236 seconds after RB006. Administration of the partial RB007 dose reversed anticoagulation to an intermediate activated clotting time value of 186 seconds. Complete reversal with RB007 returned the median activated clotting time value to 144 seconds. Both reversal strategies enabled scheduled femoral sheath removal. This study demonstrates the clinical translation of a novel platform of anticoagulation targeting factor IXa and its active reversal to percutaneous coronary intervention and provides the basis for further investigation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00715455.


Integrin alpha6 maintains the structural integrity of the kidney collecting system.
Laminins are a major constituent of the basement membranes of the kidney collecting system. Integrins, transmembrane receptors formed by non-covalently bound α and β subunits, serve as laminin receptors, but their role in development and homeostasis of the kidney collecting system is poorly defined. Integrin α3β1, one of the major laminin receptors, plays a minor role in kidney collecting system development, while the role of α6 containing integrins (α6β1 and α6β4), the other major laminin receptors, is unknown. Patients with mutations in α6 containing integrins not only develop epidermolysis bullosa, but also have abnormalities in the kidney collecting system. In this study, we show that selectively deleting the α6 or β4 integrin subunits at the initiation of ureteric bud development in mice does not affect morphogenesis. However, the collecting system becomes dilated and dysmorphic as the mice age. The collecting system in both null genotypes was also highly susceptible to unilateral ureteric obstruction injury with evidence of excessive tubule dilatation and epithelial cell apoptosis. Mechanistically, integrin α6-null collecting duct cells are unable to withstand high mechanical force when adhered to laminin. Thus, we conclude that α6 integrins are important for maintaining the integrity of the kidney collecting system by enhancing tight adhesion of the epithelial cells to the basement membrane. These data give a mechanistic explanation for the association between kidney collecting system abnormalities in patients and epidermolysis bullosa.


Prognostic Impact of the ABCC11/MRP8 Polymorphism in Adjuvant Oral Chemotherapy with S-1 for Non-Small Cell Lung Cancer.
Postoperative 1-year administration of S-1, an oral derivative of 5-fluorouracil (5-FU), was shown to be feasible in lung cancer. The 5-year survival rates of postoperative patients treated with S-1 adjuvant chemotherapy and the prognostic impact of clinicopathological factors were examined. The data of 50 patients with curatively resected pathological stage IB to IIIA non-small cell lung cancer, who were treated with S-1 postoperatively, were analyzed. The prognostic impacts of 22 clinicopathological factors including expressions of the 5-FU pathway enzymes were evaluated. A single-nucleotide polymorphism (SNP), i.e. 538G>A (rs17822931), of ABCC11/MRP8, which encodes a 5-FU excretion enzyme that is known as an earwax type determinant, was also evaluated. The 5-year overall and relapse-free survival rates were 72.5 and 67.5%, respectively. A performance status ≥ 1, lymphatic vessel invasion, blood vessel invasion, and the A/A type of SNP538, which is responsible for the dry earwax type, were significantly associated with shorter relapse-free survivals. In 34 patients who showed a relative performance of 70% or more for chemotherapy, multivariate survival analysis indicated significant hazard ratios only for the A/A type of SNP538 (p = 0.007). S-1 has sufficient power as adjuvant chemotherapy. However, its effect might be small in the dry earwax type patient group in an adjuvant setting.


Photodynamic therapy vs radiofrequency ablation for Barrett's dysplasia: efficacy, safety and cost-comparison.
To compare effectiveness, safety, and cost of photodynamic therapy (PDT) and radiofrequency ablation (RFA) in treatment of Barrett's dysplasia (BD). Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared. Thirty-three patients with high-grade dysplasia (HGD) had treatment with porfimer sodium photosensitzer and 630 nm laser (130 J/cm), with maximum of 3 treatment sessions. Fifty-three patients with BD (47 with low-grade dysplasia -LGD, 6 with HGD) had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions. Both groups received proton pump inhibitors twice daily. Endoscopic biopsies were acquired at 2 and 12 mo after enrollment, with 4-quadrant biopsies every 1 cm of the original BE extent. A complete histological resolution response of BD (CR-D) was defined as all biopsies at the last endoscopy session negative for BD. Fisher's exact test was used to assess differences between the two study groups for primary outcomes. For all outcomes, a two-sided P value of less than 0.05 was considered to indicate statistical significance. Thirty (91%) PDT patients and 39 (74%) RFA were men (P = 0.05). The mean age was 70.7 ± 12.2 and 65.4 ± 12.7 (P = 0.10) year and mean length of BE was 5.4 ± 3.2 cm and 5.7 ± 3.2 cm (P = 0.53) for PDT and RFA patients, respectively. The CR-D was (18/33) 54.5% with PDT vs (47/53) 88.7% with RFA (P = 0.001). One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA. PDT was five times more costly than RFA at our institution. The two groups were not randomized and had different BD grading are the limitations of the study. In our experience, RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.


Perspectives of clients and providers on factors influencing opioid agonist treatment uptake among HIV-positive people who use drugs in Indonesia, Ukraine, and Vietnam: HPTN 074 study.
Opioid agonist treatment (OAT) is an effective method of addiction treatment and HIV prevention. However, globally, people who inject drugs (PWID) have insufficient OAT uptake. To expand OAT access and uptake, policymakers, program developers and healthcare providers should be aware of barriers to and facilitators of OAT uptake among PWID. As a part of the HPTN 074 study, which assessed the feasibility of an intervention to facilitate HIV treatment and OAT in PWID living with HIV in Indonesia, Ukraine, and Vietnam, we conducted in-depth interviews with 37 HIV-positive PWID and 25 healthcare providers to explore barriers to and facilitators of OAT uptake. All interviews were audio-recorded, transcribed, translated into English, and coded in NVivo for analysis. We developed matrices to identify emergent themes and patterns. Despite some reported country-specific factors, PWID and healthcare providers at all geographic locations reported similar barriers to OAT initiation, such as complicated procedures to initiate OAT, problematic clinic access, lack of information on OAT, misconceptions about methadone, financial burden, and stigma toward PWID. However, while PWID reported fear of drug interaction (OAT and antiretroviral therapy), providers perceived that PWID prioritized drug use over caring for their health and hence were less motivated to take up ART and OAT. Motivation for a life change and social support were reported to be facilitators. These results highlight a need for support for PWID to initiate and retain in drug treatment. To expand OAT in all three countries, it is necessary to facilitate access and ensure low-threshold, financially affordable OAT programs for PWID, accompanied with supporting interventions. PWID attitudes and beliefs about OAT indicate the need for informational campaigns to counter misinformation and stigma associated with addiction and OAT (especially methadone).


Patterns of nutrient dynamics in Adirondack lakes recovering from acid deposition.
With decreases in acid deposition, nitrogen : phosphorus (N:P) ratios in lakes are anticipated to decline, decreasing P limitation of phytoplankton and potentially changing current food web dynamics. This effect could be particularly pronounced in the Adirondack Mountains of New York State, a historic hotspot for effects of acid deposition. In this study, we evaluate spatial patterns of nutrient dynamics in Adirondack lakes and use these to infer potential future temporal trends. We calculated Mann-Kendall tau correlations among total phosphorus (TP), chlorophyll a, dissolved organic carbon (DOC), acid neutralizing capacity (ANC), and nitrate (NO3- ) concentrations in 52 Adirondack Long Term Monitoring (ALTM) program lakes using samples collected monthly during 2008-2012. We evaluated the hypothesis that decreased atmospheric N and S deposition will decrease P limitation in freshwater ecosystems historically impacted by acidification. We also compared these patterns among lake watershed characteristics (i.e., seepage or lacking a surface outlet, chain drainage, headwater drainage, thin glacial till, medium glacial till). We found that correlations (P < 0.05) were highly dependent upon the different hydrologic flowpaths of seepage vs. drainage lakes. Differentiations among watershed till depth were also important in determining correlations due to water interaction with surficial geology. Additionally, we found low NO3- :TP (N:P mass) values in seepage lakes (2.0 in winter, 1.9 in summer) compared to chain drainage lakes (169.4 in winter, 49.5 in summer) and headwater drainage lakes (97.0 in winter, 10.9 in summer), implying a high likelihood of future shifts in limitation patterns for seepage lakes. With increasing DOC and decreasing NO3- concentrations coinciding with decreases in acid deposition, there is reason to expect changes in nutrient dynamics in Adirondack lakes. Seepage lakes may become N-limited, while drainage lakes may become less P-limited, both resulting in increased productivity. Long-term measurements of TP and chlorophyll a from the Adirondacks are needed to inform how future decreases in atmospheric N and S deposition will influence the trophic status of lake ecosystems throughout the region.


The effects of α-lipoic acid against testicular ischemia-reperfusion injury in Rats.
Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis. α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect of α-lipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed that α-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally, α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats.


Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin's lymphoma.
Patients with non-Hodgkin's B-cell lymphoma who received an antitumor vaccine of idiotypic ig protein showed humoral and proliferative immune responses. Because immunity to some antigens, including tumor antigens and human pathogenic viruses, may be better correlated with the cytolytic cellular immune response, we evaluated 16 non-Hodgkin's lymphoma patients immunized with autologous idiotypic ig molecules for changes in tumor-specific cytotoxic T-lymphocyte precursor (CTLp) frequency using limiting dilution analysis. Eleven patients had a significant increase in tumor-specific CTLp. Eight of these 11 patients remain without evidence of disease or with stable minimal disease. In contrast, all five patients who did not have a significant change in tumor-specific CTLp have developed progressive disease. Patient vaccination with tumor associated protein antigens can increase tumor-specific CTLp frequencies. The correlation of increased tumor specific CTLp with freedom from progression is significant at P = .002. This study indicates that measurement of CTLp frequencies are relevant to the clinical evaluation of human tumor vaccines and suggests that cell-mediated cytolytic immune responses may be an important determinant of vaccine efficacy.


CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B cell maturation.
The CD45 transmembrane glycoprotein has been shown to be a protein phosphotyrosine phosphatase and to be important in signal transduction in T and B lymphocytes. We have employed gene targeting to create a strain of transgenic mice that completely lacks expression of all isoforms of CD45. The spleens from CD45-null mice contain approximately twice the number of B cells and one fifth the number of T cells found in normal controls. The increase in B cell numbers is due to the specific expansion of two B cell subpopulations that express high levels of immunoglobulin (IgM) staining. T cell development is significantly inhibited in CD45-null animals at two distinct stages. The efficiency of the development of CD4-CD8- thymocytes into CD4+ CD8+ thymocytes is reduced by twofold, subsequently the frequency of successful maturation of the double positive population into mature, single positive thymocytes is reduced by a further four- to fivefold. In addition, we demonstrate that CD45-null thymocytes are severely impaired in their apoptotic response to cross-linking signals via T cell receptor (TCR) in fetal thymic organ culture. In contrast, apoptosis can be induced normally in CD45-null thymocytes by non-TCR-mediated signals. Since both positive and negative selection require signals through the TCR complex, these findings suggest that CD45 is an important regulator of signal transduction via the TCR complex at multiple stages of T cell development. CD45 is absolutely required for the transmission of mitogenic signals via IgM and IgD. By contrast, CD45-null B cells proliferate as well as wild-type cells to CD40-mediated signals. The proliferation of B cells in response to CD38 cross-linking is significantly reduced but not abolished by the CD45-null mutation. We conclude that CD45 is not required at any stage during the generation of mature peripheral B cells, however its loss reveals a previously unrecognized role for CD45 in the regulation of certain subpopulations of B cells.


Prevalence and determinants of sunbed use in thirty European countries: data from the Euromelanoma skin cancer prevention campaign.
Although considered as a first-group carcinogen, indoor tanning is a common practice in Europe. Euromelanoma is a pan-European skin cancer prevention campaign. To compare several European countries in terms of the prevalence and determinants of sunbed use. Participants in the Euromelanoma campaigns filled in questionnaires containing demographics and risk factors, including type/duration of sunbed use. Multivariate analyses adjusted for age, gender, education, skin type and year of survey were employed to assess factors independently associated with sunbed use in each country. In total, 227 888 individuals (67.4% females, median age 44, 63.4% highly educated, 71.9% skin types III-VI) from 30 countries participated. Overall, the prevalence of sunbed ever use was 10.6% (≤19-year-olds: 5.9%; 20 to 35-year-olds: 17.0%; >35-year-olds: 8.3%). Females displayed a higher prevalence than males in all countries. Balkan countries displayed the highest female/male ratios (≥4). Sunbed use was significantly more prevalent among skin type III-VI (14/30 countries) and highly educated participants (11/30 countries). Significant correlations were found between sunbed use prevalence and countries' latitude (P < 0.001) and sunshine (P = 0.002); Italy and Spain represented exceptions towards excessive exposure. Very different prevalence rates were found for Spain (19.3%) and Portugal (2.0%). Scandinavian countries ranked highest in sunbed use among ≤19-year-olds, Baltic countries among 20 to 35-year-olds. Sunbed use prevalence was higher in northern, sun-deprived countries, with the exception of Italy and Spain. The main determinants of sunbed use were age (young adults) and gender (females), whereas education and skin type had a less relevant effect. Geographic particularities were found in four regions: Iberian (prevalence ten times higher in Spain than Portugal), Balkan (prevalence disproportionately higher among women), Baltic (highest prevalence among young adults) and Scandinavian (highest prevalence among adolescents). These data have public health relevance for future interventions aimed at reducing sunbed use in Europe.


Biologics in Achilles tendon healing and repair: a review.
Injuries of the Achilles tendon are relatively common with potentially devastating outcomes. Healing Achilles tendons form a fibrovascular scar resulting in a tendon which may be mechanically weaker than the native tendon. The resulting strength deficit causes a high risk for reinjury and other complications. Treatments using biologics aim to restore the normal properties of the native tendon and reduce the risk of rerupture and maximize tendon function. The purpose of this review was to summarize the current findings of various therapies using biologics in an attempt to improve the prognosis of Achilles tendon ruptures and tendinopathies. A PubMed search was performed using specific search terms. The search was open for original manuscripts and review papers limited to publication within the last 10 years. From these searches, papers were included in the review if they investigated the effects of biological augmentation on Achilles tendon repair or healing. Platelet-rich plasma may assist in the healing process of Achilles tendon ruptures, while the evidence to support its use in the treatment of chronic Achilles tendinopathies remains insufficient. The use of growth factors such as hepatocyte growth factor, recombinant human platelet-derived growth factor-BB, interleukin-6, and transforming growth factor beta as well as several bone morphogenetic proteins have shown promising results for Achilles tendon repair. In vitro and preclinical studies have indicated the potential effectiveness of bone marrow aspirate as well. Stem cells also have positive effects on Achilles tendon healing, particularly during the early phases. Polyhydroxyalkanoates (PHA), decellularized tendon tissue, and porcine small intestinal submucosa (SIS) are biomaterials which have shown promising results as scaffolds used in Achilles tendon repair. The application of biological augmentation techniques in Achilles tendon repair appears promising; however, several techniques require further investigation to evaluate their clinical application.


Semiclassical transport in nearly symmetric quantum dots. I. Symmetry breaking in the dot.
We apply the semiclassical theory of transport to quantum dots with exact and approximate spatial symmetries; left-right mirror symmetry, up-down mirror symmetry, inversion symmetry, or fourfold symmetry. In this work-the first of a pair of articles-we consider (a) perfectly symmetric dots and (b) nearly symmetric dots in which the symmetry is broken by the dot's internal dynamics. The second article addresses symmetry-breaking by displacement of the leads. Using semiclassics, we identify the origin of the symmetry-induced interference effects that contribute to weak localization corrections and universal conductance fluctuations. For perfect spatial symmetry, we recover results previously found using the random-matrix theory conjecture. We then go on to show how the results are affected by asymmetries in the dot, magnetic fields, and decoherence. In particular, the symmetry-asymmetry crossover is found to be described by a universal dependence on an asymmetry parameter gamma_{asym} . However, the form of this parameter is very different depending on how the dot is deformed away from spatial symmetry. Symmetry-induced interference effects are completely destroyed when the dot's boundary is globally deformed by less than an electron wavelength. In contrast, these effects are only reduced by a finite amount when a part of the dot's boundary smaller than a lead-width is deformed an arbitrarily large distance.


Intra- and Extracranial MR Venography: Technical Notes, Clinical Application, and Imaging Development.
Scientific debate over chronic cerebrospinal venous insufficiency (CCSVI) has drawn attention to venous system involvement in a series of pathologic brain conditions. In the last few decades, the MRI venography (MRV) field has developed a number of valuable sequences to better investigate structural anatomy, vessel patency, and flow characteristics of venous drainage in the intra- and extracranial systems. A brief two-tier protocol is proposed to encompass the study of intra- and extracranial venous drainage with and without contrast administration, respectively. Contrast-enhanced protocol is based on time-resolved contrast-enhanced MRV of the whole region plus extracranial flow quantification through 2D Cine phase contrast (PC); non-contrast-enhanced protocol includes intracranial 3D PC, extracranial 2D time of flight (TOF), and 2D Cine PC flow quantification. Total scanning time is reasonable for clinical applications: approximately seven minutes is allocated for the contrast protocol (most of which is due to 2D Cine PC), while the noncontrast protocol accounts for around twenty minutes. We believe that a short though exhaustive MRI scan of the whole intra- and extracranial venous drainage system can be valuable for a variety of pathologic conditions, given the possible venous implication in several neurological conditions.


A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency: a case report.
A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.


Recent patents and trends in orally disintegrating tablets.
Orally disintegrating tablets (ODTs) offer many advantages over the conventional oral dosage forms in terms of convenience and ease of use. Over the last decade, substantial advances in the formulation of ODTs have been achieved in academia and industry that resulted in the emerging of a large number of patents. The aim of this review is to summarise the most recent patents in ODT formulations and highlight their motivations, inventive steps and significances in the development of ODT formulations. Five major techniques have been applied in manufacturing of ODTs, namely conventional tablet press, moulding, freeze drying, tablet loading and pulverization, with majority of the patents dedicated to the use of conventional tablet pressing. The patents have addressed various issues concerning the manufacturing of robust and practical ODT formulations by disclosing new manufacturing techniques, advantageous materials, and innovative formulation steps. However, future developments are required to reduce the cost and widening the application of the new manufacturing techniques, while simplifying and shortening the formulation steps will be crucial in the well established ones.


A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study.
To determine the most cost-effective method of screening for atrial fibrillation (AF) in the population aged 65 years and over, as well as its prevalence and incidence in this age group. Also to evaluate the relative cost-effectiveness of different methods of recording and interpreting the electrocardiogram (ECG) within a screening programme. Multicentred randomised controlled trial. Purposefully selected general practices were randomly allocated to 25 intervention practices and 25 control practices. Fifty primary care centres across the West Midlands, UK. Patients aged 65 years and over. GPs and practice nurses in the intervention practices received education on the importance of AF detection and ECG interpretation. Patients in the intervention practices were randomly allocated to systematic (n = 5000) or opportunistic screening (n = 5000). Prospective identification of pre-existing risk factors for AF within the screened population enabled comparison between targeted screening of people at higher risk of AF and total population screening. AF detection rates in systematically screened and opportunistically screened populations in the intervention practices were compared with AF detection rate in 5000 patients in the control practices. The screening period was 12 months. Baseline prevalence of AF was 7.2%, with a higher prevalence in males (7.8%) and patients aged 75 years and over (10.3%). The control population demonstrated higher baseline prevalence (7.9%) than either the systematic (6.9%) or opportunistic (6.9%) intervention population. In the control population 47 new cases were detected (incidence 1.04% per year). In the opportunistic arm 243 patients without a baseline diagnosis of AF were found to have an irregular pulse, with 177 having an ECG, yielding 31 new cases (incidence 0.69% per year). A further 44 cases were detected outside the screening programme (overall incidence 1.64% per year). In the systematic arm 2357 patients had an ECG yielding 52 new cases (incidence 1.1% per year). Of these, 31 were detected by targeted screening and a further 21 by total population screening. A further 22 cases were detected outside the screening programme (overall incidence 1.62% per year). In terms of ECG interpretation, computerised decision support software (CDSS) gave a sensitivity of 87.3%, a specificity of 99.1% and a positive predictive value (PPV) of 89.5% compared with the gold standard (cardiologist reporting). GPs and practice nurses performed less well. The only difference in performance between intervention populations and controls was that practice nurses from the control arm performed less well than with intervention practice nurses on interpretation of limb-lead (PPV 38.8% versus 20.8%) and single-lead (PPV 37.7% versus 24.0%) ECGs. The within-trial economic evaluation results showed the lowest incremental cost to be for the opportunistic arm, with an incremental cost-effectiveness ratio of 337 pounds Sterling for each additional case detected compared to the control arm. Opportunistic screening dominated both more intensive screening strategies. Model-based analyses showed small differences in cost and quality-adjusted life-years for different methods and intensities of screening, but annual opportunistic screening resulted in the lowest number of ischaemic strokes and greatest proportion of cases of AF diagnosed. Probabilistic sensitivity results indicated that there was a probability of approximately 60% that screening from the age of 65 years was cost-effective in both men and women. The results of the study indicated that in terms of a screening programme for atrial fibrillation in patients 65 and over, the only strategy that improved on routine practice was opportunistic screening, model-based analyses indicated that there was a probability of approximately 60% of annual opportunistic screening being cost effective. It is suggested that the following topics are worthy of further investigation: the effect of the implementation of a screening programme for AF on the uptake and maintenance of anticoagulation in patients aged 65 years and over; an evaluation of the role of CDSS in the diagnosis of cardiac arrythmias; the best method for routinely detecting paroxysmal AF; ways of improving healthcare professionals' performance in ECG interpretation; development of a robust economic model to incorporate data on new therapeutic agents for use as thromboprophylactic agents for patients with AF, and an evaluation of the relative risk of stroke for patients with incident as opposed to prevalent AF.


The extracellular matrix glycoprotein elastin microfibril interface located protein 2: a dual role in the tumor microenvironment.
We have recently reported that elastin microfibril interface located protein 2 (EMILIN2), an extracellular matrix (ECM) glycoprotein, triggers cell death through a direct binding to death receptors. EMILIN2 thus influences cell viability through a mechanism that is unique for an ECM molecule. In the present work, we report an additional function for this molecule. First, we identify the region responsible for the proapoptotic effects, a 90-amino acid residue-long coiled-coil fragment toward the N-terminus of the molecule. The fragment recapitulates EMILIN2 proapoptotic mechanisms. In addition, using either the full molecule or the active fragment, for the first time, we demonstrate a significant antitumoral effect in vivo, likely due to a decrease in tumor cell viability. Unexpectedly, tumors treated with EMILIN2 or the deletion mutant display a significant increase of tumor angiogenesis. In view of this novel finding, the cotreatment of the growing tumors with an antiangiogenic drug led, in most cases, to a complete regression of tumor growth. These results grant further support to recent findings that pinpoint the microenvironment as an important regulator of cell fate under both physiological and pathological conditions and disclose the possibility of using EMILIN2 fragments as potent antineoplastic tools for cancer treatment.


β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties.
Natural bicyclic sesquiterpenes, β-caryophyllene (BCP) and β-caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described. BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB2 ), but not cannabinoid receptor type 1 (CB1 ). In opposite, BCP oxidation derivative, BCPO, does not exhibit CB1/2 binding, thus the mechanism of its action is not related to endocannabinoid system (ECS) machinery. It is known that BCPO alters several key pathways for cancer development, such as mitogen-activated protein kinase (MAPK), PI3K/AKT/mTOR/S6K1 and STAT3 pathways. In addition, treatment with this compound reduces the expression of procancer genes/proteins, while increases the levels of those with proapoptotic properties. The selective activation of CB2 may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with CB1 stimulation. Thus, BCP as selective CB2 activator may be taken into account as potential natural analgesic drug. Moreover, due to the fact that chronic pain is often an element of cancer disease, the double activity of BCP, anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology. This review is focused on anticancer and analgesic activities of BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.


Molecular genetic analysis of the nested Drosophila melanogaster lamin C gene.
Lamins are intermediate filaments that line the inner surface of the nuclear envelope, providing structural support and making contacts with chromatin. There are two types of lamins, A- and B-types, which differ in structure and expression. Drosophila possesses both lamin types, encoded by the LamC (A-type) and lamin Dm0 (B-type) genes. LamC is nested within an intron of the essential gene ttv. We demonstrate that null mutations in LamC are lethal, and expression of a wild-type LamC transgene rescues lethality of LamC but not ttv mutants. Mutations in the human A-type lamin gene lead to diseases called laminopathies. To determine if Drosophila might serve as a useful model to study lamin biology and disease mechanisms, we generated transgenic flies expressing mutant LamC proteins modeled after human disease-causing lamins. These transgenic animals display a nuclear lamin aggregation phenotype remarkably similar to that observed when human mutant A-type lamins are expressed in mammalian cells. LamC aggregates also cause disorganization of lamin Dm0, indicating interdependence of both lamin types for proper lamina assembly. Taken together, these data provide the first detailed genetic analysis of the LamC gene and support using Drosophila as a model to study the role of lamins in disease.


Optical measurement of the viscoelastic and biochemical responses of living cells to mechanical perturbation.
We have developed an optical method for real-time monitoring of cellular motion in a natural environment with nanometer resolution. From the motion driven by small optical forces, we measured dynamic viscoelastic responses of living cells in the linear reversible region. Cytoplasmic gel-to-sol transition that was due to the disruption of the actin-filament framework was detected, and a linear release of Ca(2+) from intracellular storage that was related to submicrometer cell deformation was observed. The method was shown to be a powerful tool for studying the natural response of cells to mechanical perturbation.


Parental history and lifestyle behaviors in relation to mortality from stroke among Japanese men and women: the Japan Collaborative Cohort Study.
We assessed the impact of parental history of stroke on stroke mortality, as well as the effect modification between lifestyle and stroke mortality, among Japanese. In this community-based, prospective cohort study, 22,763 men and 30,928 women aged 40 to 79 years with no history of cardiovascular disease or cancer at baseline (1988-1990) were followed through 2008. We examined the association between parental history of stroke and stroke mortality and estimated the impact of the combination of lifestyle and parental history on stroke mortality in offspring. During a mean follow-up period of 15.9 years, there were 1502 stroke deaths. In both sexes, participants with a parental history of stroke had a higher risk of stroke mortality as compared with those without such a history. The respective multivariable hazard ratio (95% CI) and population attributable fraction were 1.28 (1.10-1.49) and 5.4% in men, 1.22 (1.04-1.43) and 4.3% in women, and 1.25 (1.12-1.40) and 4.8% in all participants, for offspring with a maternal and/or paternal history of stroke. There was an inverse association between healthy-lifestyle score and stroke mortality, irrespective of parental history of stroke. The overall multivariable hazard ratio for the highest (6-8) versus the lowest (0-3) score categories was 0.56 (95% CI, 0.43-0.72) for participants with a maternal and/or paternal history of stroke and 0.44 (0.36-0.53) for those without such a history. Parental history of stroke was associated with stroke mortality in offspring. The inverse association between healthy lifestyle behaviors and stroke mortality, regardless of parental history, suggests that lifestyle modification is beneficial, even among individuals with a parental history of stroke.


Conducting polymers, dual neurotrophins and pulsed electrical stimulation--dramatic effects on neurite outgrowth.
In this study the synergistic effect of delivering two neurotrophins simultaneously to encourage neuron survival and neurite elongation was explored. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were incorporated into polypyrrole (PPy) during electrosynthesis and the amounts incorporated and released were determined using iodine-125 ((125)I) radio-labelled neurotrophins. Neurite outgrowth from cochlear neural explants grown on the conducting polymer was equivalent to that on tissue culture plastic but significantly improved with the incorporation of NT-3 and BDNF. Neurite outgrowth from explants grown on polymers containing both NT-3 and BDNF showed significant improvement over PPy doped only with NT-3, due to the synergistic effect of both neurotrophins. Neurite outgrowth was significantly improved when the polymer containing both neurotrophins was electrically stimulated. It is envisaged that when applied to the cochlear implant, these conducting and novel polymer films will provide a biocompatible substrate for storage and release of neurotrophins to help protect auditory neurons from degradation after sensorineural hearing loss and encourage neurite outgrowth towards the electrodes.


Analysis of YouTube as a Source of Information for Diabetic Foot Care.
Increasing amounts of diabetes-focused content is being posted to YouTube with little regulation as to the quality of the content. Diabetic education has been shown to reduce the risk of ulceration and amputation. YouTube is a frequently visited site for instructional and demonstrational videos posted by individuals, advertisers, companies, and health-care organizations. We sought to evaluate the usefulness of diabetic foot care video information on YouTube. YouTube was queried using the keyword phrase diabetic foot care. Original videos in English, with audio, less than 10 min long within the first 100 video results were evaluated. Two reviewers classified each video as useful or nonuseful/misleading. A 14-point usefulness criteria checklist was used to further categorize videos as most useful, somewhat useful, or nonuseful/misleading. Video sources were categorized by user type, and additional video metrics were collected. Of 87 included videos, 56 (64.4%), were classified as useful and 31 (35.6%) as nonuseful/misleading. A significant difference in the mean length of useful videos vs nonuseful/misleading videos was observed (3.33 versus 1.73 min; P < .0001). There was no significant difference in terms of popularity metrics (likes, views, subscriptions, etc) between useful and nonuseful/misleading videos. This study demonstrates that although most diabetic foot care videos on YouTube are useful, many are still nonuseful/misleading. More concerning is the lack of difference in popularity between useful and nonuseful videos. Podiatric physicians should alert patients to possibly misleading information and offer a curated list of videos.


Light dependency of nitrogen fixation in a coastal cyanobacterial mat.
The fixation of nitrogen in cyanobacterial mats situated along the littoral gradient on a Dutch barrier island was investigated by using a high-resolution online, near-real-time acetylene reduction assay. Light-response curves of nitrogenase activity yielded a variety of physiological parameters that changed during a day-night cycle. The fitted parameters were used to calculate nitrogen fixation from the incident natural irradiance over several days in two different mat types. Mats occurring in the higher regions of the littoral were composed of a diverse community of cyanobacteria, consisting of both heterocystous and non-heterocystous filamentous species, whereas closer to the low water mark the mats contained mainly non-heterocystous filamentous cyanobacteria. Although the daily cycles of nitrogenase activity differed considerably between the two types of mats, the daily integrated rates of nitrogen fixation were the same. Moreover, the daily integrated nitrogen fixation seemed to be independent from the daily incident photon flux. The measurements further suggest that different types of diazotrophic cyanobacteria become active at different times of the day and that the composition of the mat community affects maximal and daily patterns of nitrogenase activity. Notwithstanding the apparent light independence of nitrogen fixation, the light-response curves as well as light action spectra unequivocally showed that cyanobacteria were the predominant nitrogen-fixing organisms in these mats. It is concluded that the diversity of nitrogen-fixing cyanobacteria leads to an optimization of this process.


Constrictive bronchiolitis obliterans following gold therapy for psoriatic arthritis.
A 41 year old male with psoriatic arthritis developed progressive dyspnoea and airflow obstruction following 4 months of intramuscular gold therapy. Open lung biopsy revealed bronchiolitis obliterans of the constrictive type. This case suggests a possible aetiological role for gold in the pathogenesis of constrictive bronchiolitis obliterans, or alternatively an association between psoriatic arthritis and this inflammatory airway condition.


Natural killer cell function in human lung is compartmentalized.
Natural killer (NK) cells are a subpopulation of lymphocytes capable of killing a variety of neoplastic targets. NK can limit pulmonary metastases in animal models and could be important mediators of tumor defense in human lung. Previous studies in humans have suggested, however, that pulmonary NK cells obtained by bronchoalveolar lavage (BAL) are functionally inert. We purified lymphocytes from human lung tissue and compared the NK activity of these cells with lymphocytes purified from peripheral blood. The activity of NK cells obtained from minced whole lung specimens was comparable to that found in peripheral blood. Monoclonal antibodies to 2 markers found on peripheral blood large granular lymphocytes (LGL) were utilized to determine the phenotype of pulmonary NK cells. Lymphocytes expressing Leu 11b were responsible for pulmonary NK activity as all NK function was abrogated by pretreatment with anti-Leu 11b and complement. In contrast, lymphocytes expressing Leu 7 had little NK activity. Although the frequency of lymphocytes expressing Leu 7 or Leu 11 in blood was comparable, there were significantly more (p less than 0.001) Leu 7+ lymphocytes in the lung than Leu 11+ cells. Immunofluorescent staining of lung tissue demonstrated that LGL expressing Leu 11 were confined largely to the lung interstitium, whereas LGL expressing Leu 7 were frequently located in alveoli and larger airways. These findings suggest that NK function is present in the human lung and that it is compartmentalized with the NK-active Leu 11+ lymphocytes located primarily in the lung interstitium.


The validity of "conceptual span" as a measure of working memory capacity.
Three experiments tested whether a modified version of the Clustered Conceptual Span task (H. J. Haarmann, E. J. Davelaar, & M. Usher, 2003), which ostensibly requires active maintenance of semantic representations, predicted individual differences in higher-order cognitive abilities better than short-term memory (STM) span tasks or nonsemantic versions of the "Conceptual" task did. Nonsemantic Conceptual tasks presented short word lists clustered by color, first letter, or initial vowel sound, and cued subjects to recall only 1 of 3 clusters from each list; the Semantic task clustered words by taxonomic category. The Semantic Conceptual task generally failed to predict incremental variance in either verbal abilities or general fluid intelligence beyond the other Conceptual tasks or STM span tasks. Although the Semantic task showed a stronger relation to working memory span tasks than did the nonsemantic tasks (Experiment 3), that stronger relation did not translate into strong prediction of cognitive individual differences.


Intranasal mesenchymal stem cell therapy to boost myelination after encephalopathy of prematurity.
Encephalopathy of prematurity (EoP) is a common cause of long-term neurodevelopmental morbidity in extreme preterm infants. Diffuse white matter injury (dWMI) is currently the most commonly observed form of EoP. Impaired maturation of oligodendrocytes (OLs) is the main underlying pathophysiological mechanism. No therapies are currently available to combat dWMI. Intranasal application of mesenchymal stem cells (MSCs) is a promising therapeutic option to boost neuroregeneration after injury. Here, we developed a double-hit dWMI mouse model and investigated the therapeutic potential of intranasal MSC therapy. Postnatal systemic inflammation and hypoxia-ischemia led to transient deficits in cortical myelination and OL maturation, functional deficits and neuroinflammation. Intranasal MSCs migrated dispersedly into the injured brain and potently improved myelination and functional outcome, dampened cerebral inflammationand rescued OL maturation after dWMI. Cocultures of MSCs with primary microglia or OLs show that MSCs secrete factors that directly promote OL maturation and dampen neuroinflammation. We show that MSCs adapt their secretome after ex vivo exposure to dWMI milieu and identified several factors including IGF1, EGF, LIF, and IL11 that potently boost OL maturation. Additionally, we showed that MSC-treated dWMI brains express different levels of these beneficial secreted factors. In conclusion, the combination of postnatal systemic inflammation and hypoxia-ischemia leads to a pattern of developmental brain abnormalities that mimics the clinical situation. Intranasal delivery of MSCs, that secrete several beneficial factors in situ, is a promising strategy to restore myelination after dWMI and subsequently improve the neurodevelopmental outcome of extreme preterm infants in the future.


(31)P NMR phospholipid profiling of soybean emulsion recovered from aqueous extraction.
The quantity and composition of phospholipids in full-fat soybean flour, flakes, and extruded flakes and in the cream fraction recovered after aqueous extraction (AEP) and enzyme-assisted aqueous extraction (EAEP) of these substrates were studied with (31)P NMR. Extruded flakes had significantly more phosphatidic acid (PA) than flakes and flour prior to aqueous extraction. The PA content of the cream recovered after AEP and EAEP of extruded flakes was similar to that of the starting material, whereas the PA content of the creams from flour and flakes significantly increased. Changes in the PA content could be explained by the action of phospholipase D during the processing step and aqueous extraction. Total phospholipids in the oil recovered from the creams varied from 0.09 to 0.75%, and free oil yield, which is an indicator of cream stability, varied from 6 to 78%. Total phospholipid did not correlate with emulsion stability when it was lower than 0.20%. Inactivation of phospholipase D prior to aqueous extraction of flour resulted in a cream emulsion less stable toward enzymatic demulsification and containing less PA and total phospholipids than untreated flour. The phospholipid distributions in the cream, skim, and insolubles obtained from AEP flour were 7, 51, and 42%, respectively.