Structural chromosome abnormalities, increased DNA strand breaks and DNA strand break repair deficiency in dermal fibroblasts from old female human donors.
Dermal fibroblasts provide a paradigmatic model of cellular adaptation to long-term exogenous stress and ageing processes driven thereby. Here we addressed whether fibroblast ageing analysedex vivo entails genome instability. Dermal fibroblasts from human female donors aged 20-67 years were studied in primary culture at low population doubling. Under these conditions, the incidence of replicative senescence and rates of age-correlated telomere shortening were insignificant. Genome-wide gene expression analysis revealed age-related impairment of mitosis, telomere and chromosome maintenance and induction of genes associated with DNA repair and non-homologous end-joining, most notably XRCC4 and ligase 4. We observed an age-correlated drop in proliferative capacity and age-correlated increases in heterochromatin marks, structural chromosome abnormalities (deletions, translocations and chromatid breaks), DNA strand breaks and histone H2AX-phosphorylation. In a third of the cells from old and middle-aged donors repair of X-ray induced DNA strand breaks was impaired despite up-regulation of DNA repair genes. The distinct phenotype of genome instability, increased heterochromatinisation and (in 30% of the cases futile) up-regulation of DNA repair genes was stably maintained over several cell passages indicating that it represents a feature of geroconversion that is distinct from cellular senescence, as it does not encompass a block of proliferation.


Enhancement drugs: are there limits to what we should enhance and why?
Substances, such as alcohol, opiates and cannabis, have been used by humans for millennia. Today, a much wider range of substances are used for a range of purposes, including the enhancement of performance during university studies, sexual experiences, sports, exercise, at celebrations, socializing and the experience of art and music. Substance use is also associated with a range of harmful effects to the individual and society as a whole. Prohibitions, regulation, prevention and treatment have all been used to protect against this harm. In this commentary, it is argued that public health interventions should target relevant harms and not to evaluate which aspects of human endeavors and experiences should be enhanced and which should not. It is argued that interventions should directly target the harmful effects, using the best available evidence. Two examples are given of substances that may be altered to prevent serious harm--one for alcohol and one for cannabis. In the case of alcohol, the addition of dissolved oxygen could reduce both the risk of accidents and the risk of liver damage associated with alcohol consumption. In the case of cannabis, there is strong indication that the reduction of content Delta-tetrahydrocannabinol and the increase of cannabidiol could reduce the risk of psychoses and the addiction associated with its use. The aim of this article is to show that responsible regulation should not necessarily be restricted to preventing the use and/or (in the case of alcohol) a reduction in the amounts and frequency of its use, but should also aim to include a range of other strategies that could reduce the burden of illness associated with illicit substance use.


Man1, an inner nuclear membrane protein, regulates vascular remodeling by modulating transforming growth factor beta signaling.
A growing number of integral inner nuclear membrane (INM) proteins have been implicated in diverse cellular functions. Man1, an INM protein, has recently been shown to regulate transforming growth factor (Tgf) beta superfamily signaling by interacting with receptor-associated Smads. However, the in vivo roles of Man1 have not been fully characterized. Here, we show that Man1 regulates vascular remodeling by analyzing Man1-deficient embryos lacking the Smad interacting domain. Man1-deficient embryos die at midgestation because of defects in embryonic vasculature; the primary capillary plexus forms, but subsequent remodeling is perturbed. It has been proposed that the angiogenesis process is divided into two balanced phases, the activation and resolution/maturation phases, both of which are regulated by Tgfbeta1. We have demonstrated, in Man1-deficient embryos, the expression of Tgfb1 is upregulated and Smad2/3 signaling is abnormally activated, resulting in increased extracellular matrix deposition, a hallmark of the resolution phase of angiogenesis. We have also showed that the recruitment of mural cells to the vascular wall is severely disturbed in mutants, which may lead to disruption of intercellular communication between endothelial and mural cells required for proper vascular remodeling. These results have revealed a novel role for Man1 in angiogenesis and provide the first evidence that vascular remodeling can be regulated at the INM through the interaction between Man1 and Smads.


Differences in the processing of short-range apparent motion at small and large displacements.
Using random dot patterns we have compared performance on direction discrimination tasks for single and multi-step sequences of apparent motion at a range of displacement sizes. Performance was measured by varying the correlation between the frames. For "small" displacements we found that no improvement in performance occurs with stimulus duration (number of frames) if the movement of individual elements within the pattern was restricted to one step, whereas if elements undergo multiple steps, performance improves with duration. For "large" displacements, on the contrary, performance improves with increasing stimulus duration irrespective of whether individual elements are restricted to single steps. These results suggest that small and large displacements are processed in different ways. We review possible psychophysical and physiological correlates of this suggestion.


Chinese American adolescents: perceived parenting styles and adolescents' psychosocial health.
Asian Americans are one of the fastest-growing minority groups in the USA, and Chinese constitute the largest group. Evidence suggests that Asian American adolescents experience higher levels of depressive symptoms than their same-gender white counterparts. Quantitative findings suggest associations between parenting factors and Chinese American adolescents' mental health. A qualitative understanding regarding Chinese American adolescents' perceived parenting styles and its relationship with adolescents' psychosocial health is warranted. To gain an in-depth understanding of Chinese American adolescents' perceived parenting styles and how parenting styles might influence adolescents' psychosocial health. In this qualitative study, we recruited 15 Chinese American adolescents aged 12-17 years in a southwest metropolitan area. We conducted two focus group interviews. Participants also filled out a brief questionnaire that included their socio-demographic information, immigration history and level of acculturation. Participants reported perceiving that parents had high expectations about academic performance and moral values. They also perceived stricter family rules regarding choices of friends compared with their non-Asian peers. Parents tended to be more protective of girls than of boys. Both Chinese American boys and girls reported poor or ineffective communication with their parents, which contributed to increased conflict between parents and adolescents and emotional distress of the adolescents. The findings provide evidence for nurses to develop linguistically and culturally tailored resources (e.g. parent support groups, programs aimed to improving parent-child communication) or connect these families with existing resources to enhance parenting skills and consequently reduce emotional distress of their adolescent children.


Molecular and structural analysis of nuclear localizing anti-DNA lupus antibodies.
To determine the structure of three nuclear localizing lupus anti-DNA immunoglobulins (Igs) and to search for clues to mechanisms of cellular and/or nuclear access, their H- and L-chain variable region sequences were determined and subjected to three-dimensional modeling. Although the results indicate heterogeneity in their primary structures, the H chains are encoded by 3 members of the J558 VH gene family with a common tertiary conformation that is not shared by a J558-encoded nonnuclear localizing anti-DNA control Ig. Furthermore, at least two of the Igs share a conformational motif in the H-chain CDR3, and all three Igs contain multiple positively charged amino acids in their CDRs, resembling nuclear localization signals that direct protein nuclear import. Notably, each VH and VK gene is also found recurrently among previously described autoantibodies. Molecular analysis further indicates that both germline-encoded and significantly mutated V genes can generate nuclear localizing anti-DNA Ig.


Pneumococcal vaccination policy in Europe.
Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.


Scutellaria baicalensis, the golden herb from the garden of Chinese medicinal plants.
Scutellaria baicalensis Georgi, or Chinese skullcap, has been widely used as a medicinal plant in China for thousands of years, where the preparation from its roots is called Huang-Qin. It has been applied in the treatment of diarrhea, dysentery, hypertension, hemorrhaging, insomnia, inflammation and respiratory infections. Flavones such as baicalin, wogonoside and their aglycones baicalein wogonin are the major bioactive compounds extracted from the root of S. baicalensis. These flavones have been reported to have various pharmacological functions, including anti-cancer, hepatoprotection, antibacterial and antiviral, antioxidant, anticonvulsant and neuroprotective effects. In this review, we focus on clinical applications and the pharmacological properties of the medicinal plant and the flavones extracted from it. We also describe biotechnological and metabolic methods that have been used to elucidate the biosynthetic pathways of the bioactive compounds in Scutellaria.


First Report of Colletotrichum acutatum and C. fragariae Causing Bitter Rot of Apple in Uruguay.
Almost 50% of deciduous fruit produced in Uruguay are apples and bitter rot is ubiquitous in the apple-production regions in Uruguay. In rainy and hot seasons (25 to 32°C by day), severe outbreaks of bitter rot occur. In summer 2010, when apple rot incidence reached 70% in some orchards, fruit with typical symptoms of bitter rot were collected from orchards in the south-central region, the main apple-production area. Symptoms included 0.5 to 6.0 cm in diameter, circular, sunken, light brown-to-brown lesions on the fruit surface that contained black, pinhead-sized fruiting structures that produced orange-to-brown conidial masses under high relative humidity. Each lesion progressed to the core of the fruit in a V-shaped pattern. Single-conidial isolates from lesions were examined morphologically (3), and based on sequences of the internal transcribed spacer (ITS) rDNA determined using ITS1/ITS4 primers (4), three species were identified: Colletotrichum acutatum with white-to-pale orange colonies and one-celled, hyaline, fusiform to cylindrical conidia that averaged 14.5 (9.3 to 17.8) × 5.0 (6.9 to 4.0) μm (isolates C11 and C18, GenBank Nos. JN413081 and JN413082, respectively); C. fragariae with white-to-pale gray and/or dark gray colonies and one-celled, hyaline, cylindrical to fusiform conidia that averaged 20.5 (14.3 to 22.9) × 6.0 (4.6 to 7.6) μm (isolate C15 and C37, GenBank Nos. JN413083 and JN413084, respectively); and C. gloeosporioides with white-to-pale gray or gray colonies and one-celled, hyaline, cylindrical to fusiform conidia that averaged 16.5 (13.1 to 20.3) × 6.5 (3.7 to 7.6) μm (isolates C5 and C29, GenBank Nos. JN413079 and JN413080) when grown on potato dextrose agar (PDA) at 25°C. To confirm pathogenicity, two isolates of each Colletotrichum spp. were inoculated onto mature, asymptomatic fruit of cv. Pink Lady (eight fruit per isolate). Each fruit was surface disinfested with 70% ethanol, wounded with a sterile needle, and inoculated with 10 μl of a spore suspension (5 × 105 conidia/ml) of the appropriate isolate. Eight control fruit were each inoculated with 10 μl of sterile water. Inoculated fruit and the control fruit were placed in plastic bags (eight fruit per bag) and incubated at 25°C. Symptoms (sunken, brown lesions each with a V-shaped pattern extending to the core) developed on all inoculated fruit 2 to 4 days after inoculation. No lesions were observed on control fruit. When fungi were reisolated from lesions of inoculated fruit onto PDA and incubated at 25°C, colony and conidial morphology were identical to those of the original isolates, confirming Koch's postulates. This study confirms a previous report of C. gloeosporioides causing bitter rot on apple in Uruguay (1). C. acutaum and C. gloeosporioides are known to cause bitter rot on apple. C. fragariae has traditionally been associated with strawberry and recently with other host plants (2), but not with bitter rot of apple. To our knowledge, this is the first report of bitter rot of apple caused by C. fragariae, and the first report of this disease caused by C. acutatum and C. fragariae in Uruguay. References: (1) S. García. Page 49 in: Guía Para el Manejo Integrado de Plagas y Enfermedades en Frutales. INIA Las Brujas, Canelones, 1998. (2) S. J. MacKenzie et al. Plant Dis. 92:1432, 2008. (3) B. C. Sutton. The Coelomycetes. CAB International Publishing, New York, 1980. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.


Stereotactic body radiotherapy for organ-confined prostate cancer.
Improved understanding of prostate cancer radiobiology combined with advances in delivery of radiation to the moving prostate offer the potential to reduce treatment-related morbidity and maintain quality of life (QOL) following prostate cancer treatment. We present preliminary results following stereotactic body radiotherapy (SBRT) treatment for organ-confined prostate cancer. SBRT was performed on 304 patients with clinically localized prostate cancer: 50 received 5 fractions of 7 Gy (total dose 35 Gy) and 254 received 5 fractions of 7.25 Gy (total dose 36.25 Gy). Acute and late toxicity was assessed using the Radiation Therapy Oncology Group scale. The Expanded Prostate Cancer Index Composite questionnaire was used to assess QOL. Prostate-specific antigen response was monitored. At a median 30-month (26 - 37 month, range) follow-up there were no biochemical failures for the 35-Gy dose level. Acute Grade II urinary and rectal toxicities occurred in 4% of patients with no higher Grade acute toxicities. One Grade II late urinary toxicity occurred with no other Grade II or higher late toxicities. At a median 17-month (8 - 27 month, range) follow-up the 36.25 Gy dose level had 2 low- and 2 high-risk patients fail biochemically (biopsy showed 2 low- and 1 high-risk patients were disease-free in the gland). Acute Grade II urinary and rectal toxicities occurred in 4.7% (12/253) and 3.6% (9/253) of patients, respectively. For those patients with a minimum of 12 months follow-up, 5.8% (12/206) had late Grade II urinary toxicity and 2.9% (6/206) had late Grade II rectal toxicities. One late Grade III urinary toxicity occurred; no Grade IV toxicities occurred. For both dose levels at 17 months, bowel and urinary QOL returned to baseline values; sexual QOL decreased by 10%. The low toxicity and maintained QOL are highly encouraging. Additional follow-up is needed to determine long-term biochemical control and maintenance of low toxicity and QOL.


Is "isolated home" hypertension as opposed to "isolated office" hypertension a sign of greater cardiovascular risk?
The SHEAF (Self-Measurement of Blood Pressure at Home in the Elderly: Assessment and Follow-up) study is an observational study (from February 1998 to early 2002) designed to determine whether home blood pressure (BP) measurement has a greater cardiovascular prognostic value than office BP measurement among elderly (> or =60 years) French patients with hypertension. The objective of this present work is to describe the baseline characteristics of the treated patients in the SHEAF study from February 1998 to March 1999, placing special emphasis on "isolated office" and "isolated home" hypertension. Baseline office BP measurement was assessed using a mercury sphygmomanometer. Home BP measurement was performed over a 4-day period. A 140/90-mm Hg threshold was chosen to define office hypertension, and a 135/85-mm Hg threshold to define home hypertension. Of the 5211 hypertensive patients in the SHEAF study with a valid home BP measurement, 4939 received treatment with at least 1 antihypertensive drug. Patients with isolated office hypertension represented 12.5% of this population, while patients with isolated home hypertension represented 10.8%. The characteristics of the patients with isolated office hypertension were similar to those of patients with controlled hypertension. However, patients with isolated office hypertension had fewer previous cardiovascular complications. In contrast, rates of cardiovascular risk factors and history of cardiovascular disease in patients with isolated home hypertension resembled those in patients with uncontrolled hypertension. This retrospective analysis suggests that patients with isolated home hypertension belong to a high-risk subgroup. The 3-year follow-up of these patients will provide prospective data about the cardiovascular prognosis of these subgroups.


Clinical significance of human sperm-zona pellucida binding.
To assess the relationship between sperm morphology and motion parameters and sperm-zona pellucida (ZP) binding capacity under hemizona assay (HZA) conditions and to determine the discriminatory power of the HZA for the prediction of in vitro sperm fertilizing ability. Prospectively designed study. Academic tertiary centers. One hundred ninety-six couples undergoing IVF therapy participated in this study. Hemizona assay and IVF results were determined for each couple. Computerized sperm motion analysis, sperm morphology (strict) criteria), and HZA results were correlated with fertilization outcome. Among sperm parameters from the original ejaculates, morphology was the best predictor of sperm-ZP binding ability; hyperactivated motility was the best predictor of HZA results after swim-up separation of the motile sperm fractions. The HZA index provided the highest discriminatory power for fertilization success/failure, with an overall accuracy of 86%. Sperm morphology and hyperactivated motility showed a high correlation with the capacity of sperm to achieve tight binding to the ZP. The excellent positive and negative predictive values of the HZA for fertilization outcome provide additional support for the use of this functional bioassay in the decision-making process within the assisted reproduction setting.


Spontaneous cornual pregnancy after homolateral salpingectomy for an earlier tubal pregnancy: a case report and literature review.
Cornual pregnancy is an infrequent pathological condition with severe prognosis if not adequately recognized. Ipsilateral salpingectomy represents a unique risk factor for this clinical entity. This article reports a laparoscopically treated spontaneous cornual pregnancy after homolateral salpingectomy for an earlier tubal pregnancy in a condition of hemodynamic instability as a result of cornual rupture. We include a review of the literature, underlining the feasibility of a laparoscopic approach and new treatment options combining medical and surgical tools with specific attention to their impact on future fertility and on risk of uterine rupture in a future pregnancy.


Suppression of substrate inhibition in phenanthrene-degrading Mycobacterium by co-cultivation with a non-degrading Burkholderia strain.
In natural environments contaminated by recalcitrant organic pollutants, efficient biodegradation of such pollutants has been suggested to occur through the cooperation of different bacterial species. A phenanthrene-degrading bacterial consortium, MixEPa4, from polluted soil was previously shown to include a phenanthrene-degrading strain, Mycobacterium sp. EPa45, and a non-polycyclic aromatic hydrocarbon (PAH)-degrading strain, Burkholderia sp. Bcrs1W. In this study, we show that addition of phenanthrene to rich liquid medium resulted in the transient growth arrest of EPa45 during its degradation of phenanthrene. RNA-sequencing analysis of the growth-arrested cells showed the phenanthrene-dependent induction of genes that were predicted to be involved in the catabolism of this compound, and many other cell systems, such as a ferric iron-uptake, were up-regulated, implying iron deficiency of the cells. This negative effect of phenanthrene became much more apparent when using phenanthrene-containing minimal agar medium; colony formation of EPa45 on such agar was significantly inhibited in the presence of phenanthrene and its intermediate degradation products. However, growth inhibition was suppressed by the co-residence of viable Bcrs1W cells. Various Gram-negative bacterial strains, including the three other strains from MixEPa4, also exhibited varying degrees of suppression of the growth inhibition effect on EPa45, strongly suggesting that this effect is not strain-specific. Growth inhibition of EPa45 was also observed by other PAHs, biphenyl and naphthalene, and these two compounds and phenanthrene also inhibited the growth of another mycobacterial strain, M. vanbaalenii PYR-1, that can use them as carbon sources. These phenomena of growth inhibition were also suppressed by Bcrs1W. Our findings suggest that, in natural environments, various non-PAH-degrading bacterial strains play potentially important roles in the facilitation of PAH degradation by the co-residing mycobacteria.


Anti-tumor necrosis factor alpha therapy normalizes fibrinolysis impairment in patients with active rheumatoid arthritis.
Rheumatoid arthritis (RA) is associated with increased cardiovascular risk and involvement of inflammation, coagulation and fibrinolysis. Treatment with infliximab, a tumour necrosis factor-alpha (TNF-alpha) blocking chimeric monoclonal antibody, induces a long-term reduction of inflammation and coagulation, but its effect on fibrinolysis is still unknown. We carried out an observational study investigating plasma biomarkers of inflammation and fibrinolysis in RA patients before and after 14 weeks of infliximab treatment given according to the therapeutic guidelines for RA. We studied 20 selected patients with active RA and without any other atherosclerosis risk factor as well as 40 healthy controls. Patients, treated with a stable dose of methotrexate, received infliximab (3 mg/kg) at week 0, 2, 6 and 14. At week 0 and 14, we assessed clinical, inflammatory and fibrinolyitic parameters. At baseline, plasminogen activator inhibitor (PAI-1) antigen, PAI-1 activity and tissue-type plasminogen activator (t-PA) antigen were significantly higher in RA patients than in controls (p=0.01, p=0.001 and p=0.0001 respectively). After 14 weeks of infliximab treatment, the levels of PAI-1 antigen, PAI-1 activity and t-PA antigen significantly decreased till normalization (p=0.0001). Plasma levels of C reactive protein (CRP) and interleukin-6 (IL-6) were directly correlated with levels of PAI-1 antigen (p=0.011 and p=0.0001), PAI-1 activity (p=0.013 and p=0.027) and t-PA antigen (p=0.017 and p=0.040). This study provides evidence that TNF-alpha blockade by infliximab not only decreases inflammation, but also reduces the inhibition of fibrinolysis. Such a combined effect may be pivotal in reducing the whole thrombotic risk in these patients.


Not going with the flow: Locomotor activity does not constrain immunity in a wild fish.
Immunity is a central component of fitness in wild animals, but its determinants are poorly understood. In particular, the importance of locomotory activity as a constraint on immunity is unresolved. Using a piscine model (Gasterosteus aculeatus), we combined a 25-month observational time series for a wild lotic habitat with an open flume experiment to determine the influence of locomotor activity (countercurrent swimming) on natural variation in immune function. To maximize the detectability of effects in our flume experiment, we set flow velocity and duration (10 cm/s for 48 hr) just below the point at which exhaustion would ensue. Following this treatment, we measured expression in a set of immune-associated genes and infectious disease resistance through a standard challenge with an ecologically relevant monogenean infection (Gyrodactylus gasterostei). In the wild, there was a strong association of water flow with the expression of immune-associated genes, but this association became modest and more complex when adjusted for thermal effects. Our flume experiment, although statistically well-powered and based on a scenario near the limits of swimming performance in stickleback, detected no countercurrent swimming effect on immune-associated gene expression or infection resistance. The field association between flow rate and immune expression could thus be due to an indirect effect, and we tentatively advance hypotheses to explain this. This study clarifies the drivers of immune investment in wild vertebrates; although locomotor activity, within the normal natural range, may not directly influence immunocompetence, it may still correlate with other variables that do.


Affective Norms for Italian Words in Older Adults: Age Differences in Ratings of Valence, Arousal and Dominance.
In line with the dimensional theory of emotional space, we developed affective norms for words rated in terms of valence, arousal and dominance in a group of older adults to complete the adaptation of the Affective Norms for English Words (ANEW) for Italian and to aid research on aging. Here, as in the original Italian ANEW database, participants evaluated valence, arousal, and dominance by means of the Self-Assessment Manikin (SAM) in a paper-and-pencil procedure. We observed high split-half reliabilities within the older sample and high correlations with the affective ratings of previous research, especially for valence, suggesting that there is large agreement among older adults within and across-languages. More importantly, we found high correlations between younger and older adults, showing that our data are generalizable across different ages. However, despite this across-ages accord, we obtained age-related differences on three affective dimensions for a great number of words. In particular, older adults rated as more arousing and more unpleasant a number of words that younger adults rated as moderately unpleasant and arousing in our previous affective norms. Moreover, older participants rated negative stimuli as more arousing and positive stimuli as less arousing than younger participants, thus leading to a less-curved distribution of ratings in the valence by arousal space. We also found more extreme ratings for older adults for the relationship between dominance and arousal: older adults gave lower dominance and higher arousal ratings for words rated by younger adults with middle dominance and arousal values. Together, these results suggest that our affective norms are reliable and can be confidently used to select words matched for the affective dimensions of valence, arousal and dominance across younger and older participants for future research in aging.


Operative versus nonoperative interventions for common fractures of the clavicle: a meta-analysis of randomized controlled trials.
The popularity of surgery for acute displaced midshaft clavicle fractures has been fuelled by early randomized controlled trials (RCTs) showing improved rates of radiographic union and perceived functional benefits compared with nonoperative approaches. We performed a meta-analysis to determine the effect of operative and nonoperative interventions on the risk of secondary operation and complications and on long-term function. We search MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for reports of relevant RCTs published to Mar. 7, 2014. Two reviewers assessed eligibility of potential reports and the risk of bias of included trials. The Grading of Recommendations Assessment, Development and Evaluation approach was used to summarize the quality of evidence for all outcomes. We included 15 RCTs (9 trials comparing operative and nonoperative interventions, 5 comparing implants for operative treatment, and 1 comparing nonoperative treatments). Nonoperative treatments did not differ from operative treatments in the risk of secondary operation (risk ratio [RR] 1.16, 95% confidence interval [CI] 0.58 to 2.35) or all complications (RR 0.90, 95% CI 0.55 to 1.50). One in 4 patients had a complication regardless of the treatment approach. Differences in functional outcomes, although smaller than the threshold for minimal important differences at 1 year, favoured operative interventions (standardized mean difference 0.38, 95% CI 0 to 0.75). Evidence for the type of implant or approach to nonoperative treatment remained inconclusive. Current evidence does not support the routine use of internal fixation for the treatment of displaced midshaft clavicle fractures. Complication rates were high regardless of the treatment approach.


Visceral obesity is associated with high levels of serum squalene.
To investigate the impact of visceral obesity on cholesterol metabolism in normoglycemic offspring of patients with type 2 diabetes. The proportion of intra-abdominal fat (IAF) was measured by abdominal computer tomography, and serum cholesterol synthesis and absorption markers were determined by gas-liquid chromatography in 109 normoglycemic offspring of patients with type 2 diabetes. Insulin action was measured with the hyperinsulinemic euglycemic clamp. The gene encoding squalene synthase (farnesyl-diphosphate farnesyltransferase 1) was screened with the single-strand conformation polymorphism analysis and direct sequencing. Cholesterol synthesis markers correlated positively with IAF (r = 0.213 to 0.309, p < or = 0.027) and negatively with the rates of insulin-stimulated whole-body glucose uptake (r = -0.372 to -0.248, p < or = 0.010). However, serum squalene, the first measured precursor of cholesterol synthesis, showed a positive correlation with IAF (r = 0.309, p = 0.001) without any association with subcutaneous fat or insulin sensitivity. Variation in the farnesyl-diphosphate farnesyltransferase 1 gene did not explain elevated serum squalene levels in viscerally obese subjects. From the cholesterol absorption markers, cholestanol was associated negatively with IAF and positively with whole-body glucose uptake (p < 0.05). High serum squalene levels are associated with visceral obesity but not with subcutaneous obesity. Whether this finding is causally connected to visceral obesity remains to be established.


2018 update of the EULAR recommendations for the management of Behçet's syndrome.
Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.


Factors Affecting Visual Field Outcomes in the Idiopathic Intracranial Hypertension Treatment Trial.
To determine the prevalence of visual field (VF) performance failures (PF) and treatment failures (TFs), and identify factors associated with PFs in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). A total of 165 participants from 38 sites with idiopathic intracranial hypertension (IIH) and mild visual loss were randomized to either acetazolamide-plus diet or placebo-plus diet. The IIHTT Visual Field Reading Center evaluated 2950 Swedish Interactive Threshold Algorithm Standard 24-2 VFs from the enrolled participants. A TF was defined when the participant's VF mean deviation (MD) worsened ≥2 to 3 dB from the average baseline MD (range of -2 to -7 dB) with a second retest confirming the visual deterioration. A PF was determined when the participant's: 1) VF results met TF criteria but were not confirmed on retest, 2) deterioration was confirmed on retest but the IIHTT Adjudication Committee concluded a TF was clinically unlikely. TF was detected in 7/165 (4%) of the participants and PF was detected in 35/165 (21%) of the participants on at least 1 examination. Four of the 35 PFs were adjudicated for TF, however based on clinical review by the adjudication committee and a third retest, they were judged as PFs. Of the 2,950 total IIHTT VF examinations, 2.7% met PF criteria. PF was confirmed in 21% of subjects and in 2.7% of the total number of VF examinations and was reversible on repeat testing. We recommend retesting when perimetric worsening occurs in otherwise clinically stable or improving IIH patients.


Nodal signaling range is regulated by proprotein convertase-mediated maturation.
Tissue patterning is established by extracellular growth factors or morphogens. Although different theoretical models explaining specific patterns have been proposed, our understanding of tissue pattern establishment in vivo remains limited. In many animal species, left-right patterning is governed by a reaction-diffusion system relying on the different diffusivity of an activator, Nodal, and an inhibitor, Lefty. In a genetic screen, we identified a zebrafish loss-of-function mutant for the proprotein convertase FurinA. Embryological and biochemical experiments demonstrate that cleavage of the Nodal-related Spaw proprotein into a mature form by FurinA is required for Spaw gradient formation and activation of Nodal signaling. We demonstrate that FurinA is required cell-autonomously for the long-range signaling activity of Spaw and no other Nodal-related factors. Combined in silico and in vivo approaches support a model in which FurinA controls the signaling range of Spaw by cleaving its proprotein into a mature, extracellular form, consequently regulating left-right patterning.


"Hybrid Topics" - Facilitating the Interpretation of Topics Through the Addition of MeSH Descriptors to Bags of Words.
Extracting and understanding information, themes and relationships from large collections of documents is an important task for biomedical researchers. Latent Dirichlet Allocation is an unsupervised topic modeling technique using the bag-of-words assumption that has been applied extensively to unveil hidden thematic information within large sets of documents. In this paper, we added MeSH descriptors to the bag-of-words assumption to generate 'hybrid topics', which are mixed vectors of words and descriptors. We evaluated this approach on the quality and interpretability of topics in both a general corpus and a specialized corpus. Our results demonstrated that the coherence of 'hybrid topics' is higher than that of regular bag-of-words topics in the specialized corpus. We also found that the proportion of topics that are not associated with MeSH descriptors is higher in the specialized corpus than in the general corpus.


Glypican-3-Expressing Hepatocellular Carcinoma in a Non-Cirrhotic Patient with Nonalcoholic Steatohepatitis: Case Report and Literature Review.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Nonalcoholic steatohepatitis (NASH) is now considered as the major cause of cryptogenic cirrhosis, which can progress to HCC. Glypican-3 is a member of the Heparan Sulfate Proteoglycan (HSP) family that plays a role in cell growth, differentiation, and migration. Glypican-3 is significantly up-regulated in a majority of HCCs compared to normal and benign liver samples. Glypican-3 protein is detectable in around 40-53% of HCC patients whereas it is not detectable in the serum of healthy individuals. There are several reports of HCC arising in the setting of non-cirrhotic NASH. This report describes a case of HCC that expressed Glypican-3 and arose in a 47-year-old female with noncirrhotic NASH.


Regulation of airway ciliary activity by Ca2+: simultaneous measurement of beat frequency and intracellular Ca2+.
Airway ciliary activity is influenced by [Ca2+]i, but this mechanism is not fully understood. To investigate this relationship, ciliary activity and [Ca2+]i were measured simultaneously from airway epithelial ciliated cells. Ciliary beat frequency was determined, for each beat cycle, with phase-contrast optics and high-speed video imaging (at 240 images s-1) and correlated with [Ca2+]i determined, at the ciliary base, by fast imaging (30 images s-1) of fura-2 fluorescence. As a mechanically induced intercellular Ca2+ wave propagated through adjacent cells, [Ca2+]i was elevated from a baseline concentration of 45 to 100 nM, to a peak level of up to 650 nM. When the Ca2+ wave reached the ciliary base, the beat frequency rapidly increased, within a few beat cycles, from a basal rate of 6.4 to 11.6 Hz at 20-23 degrees C, and from 17.2 to 26.7 Hz at 37 degrees C. Changes in [Ca2+]i, above 350 nM, had no effect on the maximum beat frequency. We suggest that airway ciliary beat frequency is 1) controlled by a low range of [Ca2+]i acting directly at an axonemal site at the ciliary base and 2) that a maximum frequency is induced by a change in [Ca2+]i of approximately 250-300 nM.


Genome Sequencing of Ralstonia solanacearum CQPS-1, a Phylotype I Strain Collected from a Highland Area with Continuous Cropping of Tobacco.
Ralstonia solanacearum, an agent of bacterial wilt, is a highly variable species with a broad host range and wide geographic distribution. As a species complex, it has extensive genetic diversity and its living environment is polymorphic like the lowland and the highland area, so more genomes are needed for studying population evolution and environment adaptation. In this paper, we reported the genome sequencing of R. solanacearum strain CQPS-1 isolated from wilted tobacco in Pengshui, Chongqing, China, a highland area with severely acidified soil and continuous cropping of tobacco more than 20 years. The comparative genomic analysis among different R. solanacearum strains was also performed. The completed genome size of CQPS-1 was 5.89 Mb and contained the chromosome (3.83 Mb) and the megaplasmid (2.06 Mb). A total of 5229 coding sequences were predicted (the chromosome and megaplasmid encoded 3573 and 1656 genes, respectively). A comparative analysis with eight strains from four phylotypes showed that there was some variation among the species, e.g., a large set of specific genes in CQPS-1. Type III secretion system gene cluster (hrp gene cluster) was conserved in CQPS-1 compared with the reference strain GMI1000. In addition, most genes coding core type III effectors were also conserved with GMI1000, but significant gene variation was found in the gene ripAA: the identity compared with strain GMI1000 was 75% and the hrpII box promoter in the upstream had significantly mutated. This study provided a potential resource for further understanding of the relationship between variation of pathogenicity factors and adaptation to the host environment.


Dicopper(I) Complexes Incorporating Acetylide-Functionalized Pyridinyl-Based Ligands: Synthesis, Structural, and Photovoltaic Studies.
Heteroaryl incorporated acetylide-functionalized pyridinyl ligands (L1-L6) with the general formula Py-C≡C-Ar (Py = pyridine and Ar = thiophene-2-yl, 2,2' -bithiophene]-5-yl, 2,2' :5',2″ -terthiophene]-5-yl, thieno[2,3- b]thiophen-2-yl, quinoline-5-yl, benzo[c][1,2,5]thiadiazole-5-yl) have been synthesized by Pd(0)/Cu(I)-catalyzed cross-coupling reaction of 4-ethynylpyridine and the respective heteroaryl halide. Ligands L1-L6 were isolated in respectable yields and characterized by microanalysis, IR spectroscopy, 1H NMR spectroscopy, and ESI-MS mass spectrometry. A series of dinuclear Cu(I) complexes 1-10 have been synthesized by reacting L1-L6 with CuI and triphenylphosphine (PPh3) (R1) or with an anchored phosphine derivative, 4-(diphenylphosphino) benzoic acid (R2)/2-(diphenylphosphino)benzenesulfonic acid (R3), in a stoichiometric ratio. The complexes are soluble in common organic solvents and have been characterized by analytical, spectroscopic, and computational methods. Single-crystal X-ray structure analysis confirmed rhomboid dimeric structures for complexes 1, 2, 4, and 5, and a polymeric structure for 6. Complexes 1-6 showed oxidation potential responses close to 0.9 V vs Fc0/+, which were chemically irreversible and are likely to be associated with multiple steps and core oxidation. Preliminary photovoltaic (PV) results of these new materials indicated moderate power conversion efficiency (PCE) in the range of 0.15-1.56% in dye-sensitized solar cells (DSSCs). The highest PCE was achieved with complex 10 bearing the sulfonic acid anchoring functionality.


Fiber-optic bend sensor using LP21 mode operation.
A novel fiber-optic bending sensor based upon the propagation of LP21 mode is demonstrated. The sensor, comprised of an S-bend fiber on an elastic film, measures LP21 mode specklegram rotation, which increments linearly with bending angle by the stress-optic effect. The sensor is capable of experimentally achieving a sensitivity as high as 4.13 rad/m(-1). The theoretical analysis of the sensor, which is a combination of fiber coupled-mode theory and elastic-optic theory, validates the accuracy of the sensor. The sensor is also shown to be temperature-immune, and can detect both bending direction and bending angle with a large dynamic range. Furthermore, the sensor implementation incorporates inexpensive single-mode fiber at 650 nm for few-mode operation, enabling low-loss transmission and compatibility with existing interfaces.


Enzyme-adenylate structure of a bacterial ATP-dependent DNA ligase with a minimized DNA-binding surface.
DNA ligases are a structurally diverse class of enzymes which share a common catalytic core and seal breaks in the phosphodiester backbone of double-stranded DNA via an adenylated intermediate. Here, the structure and activity of a recombinantly produced ATP-dependent DNA ligase from the bacterium Psychromonas sp. strain SP041 is described. This minimal-type ligase, like its close homologues, is able to ligate singly nicked double-stranded DNA with high efficiency and to join cohesive-ended and blunt-ended substrates to a more limited extent. The 1.65 Å resolution crystal structure of the enzyme-adenylate complex reveals no unstructured loops or segments, and suggests that this enzyme binds the DNA without requiring full encirclement of the DNA duplex. This is in contrast to previously characterized minimal DNA ligases from viruses, which use flexible loop regions for DNA interaction. The Psychromonas sp. enzyme is the first structure available for the minimal type of bacterial DNA ligases and is the smallest DNA ligase to be crystallized to date.


A novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcripts.
miR-21 is the most commonly over-expressed microRNA (miRNA) in cancer and a proven oncogene. Hsa-miR-21 is located on chromosome 17q23.2, immediately downstream of the vacuole membrane protein-1 (VMP1) gene, also known as TMEM49. VMP1 transcripts initiate ∼ 130 kb upstream of miR-21, are spliced, and polyadenylated only a few hundred base pairs upstream of the miR-21 hairpin. On the other hand, primary miR-21 transcripts (pri-miR-21) originate within the last introns of VMP1, but bypass VMP1 polyadenylation signals to include the miR-21 hairpin. Here, we report that VMP1 transcripts can also bypass these polyadenylation signals to include miR-21, thus providing a novel and independently regulated source of miR-21, termed VMP1-miR-21. Northern blotting, gene-specific RT-PCR, RNA pull-down and DNA branching assays support that VMP1-miR-21 is expressed at significant levels in a number of cancer cell lines and that it is processed by the Microprocessor complex to produce mature miR-21. VMP1 and pri-miR-21 are induced by common stimuli, such as phorbol-12-myristate-13-acetate (PMA) and androgens, but show differential responses to some stimuli such as epigenetic modifying agents. Collectively, these results indicate that miR-21 is a unique miRNA capable of being regulated by alternative polyadenylation and two independent gene promoters.


Techno-Economic Analysis of Solar Water Heating Systems inTurkey.
In this study, solar water heater was investigated using meteorological and geographical data of 129 sites over Turkey. Three different collector types were compared in terms of absorber material (copper, galvanized sheet and selective absorber). Energy requirement for water heating, collector performances, and economical indicators were calculated with formulations using observed data. Results showed that selective absorbers were most appropriate in terms of coverage rate of energy requirement for water-heating all over Turkey. The prices of selective, copper and galvanized absorber type's heating systems in Turkey were 740.49, 615.69 and 490.89 USD, respectively. While payback periods (PBPs) of the galvanized absorber were lower, net present values (NPVs) of the selective absorber were higher than the rest. Copper absorber type collectors did not appear to be appropriate based on economical indicators.


Down-regulation of lncRNA XIST inhibits cell proliferation via regulating miR-744/RING1 axis in non-small cell lung cancer.
Long non-coding RNAs (lncRNAs) are known to be potential factors in promoting tumor progression. However, the function and mechanism of lncRNA XIST in non-small cell lung cancer (NSCLC) remains poorly understood. The expression levels of lncRNA XIST in NSCLC tissues and cell lines were detected with real-time PCR, and the correlation of the expression level of XIST with histopathological characteristics and prognosis was analyzed. The biological function of lncRNA XIST was validated through assays in vivo and in vitro The expression of lncRNA XIST was significantly up-regulated in NSCLC tissues. In addition, overexpression of XIST was positively correlated with the advanced clinical status of tumors, as well as poor overall survival and DFS. A tumor suppressive effect was presented via functional knockdown of lncRNA XIST. Up-regulation of XIST enhanced the proliferation, migration, and invasion ability of NSCLC cells both in vivo and in vitro Mechanically, it was indicated that XIST could serve as an endogenous competitive RNA modulating miR-744, leading to the miR-744/RING1 signaling pathway inhibition and Wnt/β-catenin signaling pathway activation. Taken together, it was confirmed here that XIST overexpression is associated with tumor progression phenotype and the newly discovered XIST/miR-744/RING1 axis, which could serve as a potential biomarker and therapeutic target for NSCLC.


Fourier analysis of human sagittal sutures.
To evaluate the complexity of human sagittal suture patterns and to investigate whether the suture complexity correlates with age. Geometric patterns of the sagittal sutures from 104 dry human skulls from the Terry Collection and 16 computed tomography images from the Bosma Collection, aged 2 months to 60 years, were digitized. The complexity of the patterns was presented by suture length, curved suture (or skull) length, and length ratio and the frequency and amplitude contents by the discrete Fourier transform (DFT) analysis. The suture length along the skull showed a positive correlation with age from 2 months to 10 years, reflecting the growth of the skull. The suture length ratio, R, a measure of the complexity of the suture pattern, had a similar trend to suture length (i.e., increased with age to about 10 years and leveled off afterward, accompanied by a large scatter). The major frequency from the DFT analysis indicated an age-related development in suture complexity from infants to about 10 years and no further change for individuals older than 10 years. Quantitative analyses of human sagittal suture using length, length ratio, and DFT indicated that there is a progressive increase in the complexity of sagittal sutural waveform with age, especially in the early ages. These findings agree with the observations from animal experiments that sagittal sutural waveform is the result of intrinsic tissue response to extrinsic forces such as those generated by the temporalis.


Subcutaneous interferon alpha 2a combined with cryotherapy vs cryotherapy alone in the treatment of primary anogenital warts: a randomised observer blind placebo controlled study.
To compare patient tolerance and treatment efficacy of subcutaneous interferon (IFN) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital (AG) warts. Randomised placebo controlled observer blind study. Statistical analysis was by chi square and Mann Whitney U tests. 60 patients with newly diagnosed AG warts. 29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy, respectively. Clinical presence or absence of AG warts. Patients wart-free at 8 weeks were asked to re-attend at 12 weeks; those with persistent warts at 8 weeks were withdrawn from the study. At 8 weeks 60.7% (17/28 patients) of the IFN group and 67.9% (19/28 patients) of the placebo group were clinically wart-free (not significant); corresponding figures at 12 week review were 29.6% (8/27 patients) and 40% (10/25 patients) respectively (not significant). There was no difference in treatment response between males and females. Recurrence of warts at three month review, in patients cleared of warts at 8 weeks, was seen in 50% (8/16) and 37.5% (6/16) of patients in the IFN and placebo groups respectively (not significant). Multiple warts and the presence of perianal/anal canal warts, either alone or concurrent with warts on the genitalia, at first clinic attendance, were adverse prognostic indicators (p less than 0.001, and p = 0.05 respectively). Cervical human papilloma virus (HPV) infection, exophytic or subclinical, was present in 58.3% and 77.2% of females in the IFN and placebo groups respectively, at trial entry. Although these lesions were not directly treated, colposcopic resolution was seen in 12.5% of affected women, in both treatment groups, by the end of the 7 week treatment period. Systemic side effects were significantly more common in the IFN than in the placebo group, 50% versus 10.7% of patients (p less than 0.01). Severe influenza like symptoms occurred, after the first three injections only, in one patient treated with IFN; all other reported side effects were mild. Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts. The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators.


Structural and mechanistic insights into Helicobacter pylori NikR activation.
NikR is a transcriptional metalloregulator central in the mandatory response to acidity of Helicobacter pylori that controls the expression of numerous genes by binding to specific promoter regions. NikR/DNA interactions were proposed to rely on protein activation by Ni(II) binding to high-affinity (HA) and possibly secondary external (X) sites. We describe a biochemical characterization of HpNikR mutants that shows that the HA sites are essential but not sufficient for DNA binding, while the secondary external (X) sites and residues from the HpNikR dimer-dimer interface are important for DNA binding. We show that a second metal is necessary for HpNikR/DNA binding, but only to some promoters. Small-angle X-ray scattering shows that HpNikR adopts a defined conformation in solution, resembling the cis-conformation and suggests that nickel does not trigger large conformational changes in HpNikR. The crystal structures of selected mutants identify the effects of each mutation on HpNikR structure. This study unravels key structural features from which we derive a model for HpNikR activation where: (i) HA sites and an hydrogen bond network are required for DNA binding and (ii) metallation of a unique secondary external site (X) modulates HpNikR DNA binding to low-affinity promoters by disruption of a salt bridge.


Qualitative and quantitative comparison of the cardiac effects of encainide and its three major metabolites in the dog.
We have evaluated the electrophysiologic effect of encainide and its three major metabolites, O-demethyl encainide, 3-methoxy-O-demethyl encainide and N-demethyl encainide in an anesthetized dog model. Our results support previous reports that O-demethyl encainide and 3-methoxy-O-demethyl encainide are both more potent than encainide in the depression of conduction. We also have shown that N-demethyl encainide is of about equal potency to encainide. Whereas the major differences between these compounds is primarily one of potency, there are some qualitative differences. Although O-demethyl encainide did not change the ventricular or atrial effective refractory periods significantly, 3-methoxy-O-demethyl encainide and N-demethyl encainide prolonged both. Encainide increased the atrial effective refractory period but did not produce significant changes in the ventricular refractory period. These data support previous suggestions of an important role for these metabolites as modulators of the clinical efficacy of encainide.


The histology of interstitial cystitis.
Several studies have reported histologic findings in interstitial cystitis (IC) bladder biopsy specimens. However, these studies used a variety of criteria to define IC, which may explain the variation noted in the histologic changes. Clinical experience shows that these biopsy specimens are often not helpful in confirming the diagnosis. Our study was designed to examine the histologic features identified in bladder biopsy specimens from patients with IC and compare them with biopsy specimens from a control population. Although IC patients as a group had a higher incidence and degree of denuded epithelium, ulceration, and submucosal inflammation, none of these findings was pathognomonic. In addition, these findings occurred only in interstitial cystitis patients with pyuria or small bladder capacity. The inflammatory infiltrate seen in IC was composed predominantly of lymphocytes, with increasing numbers of plasma cells as the degree of inflammation increased. There was no specific predilection for the inflammatory infiltrate to be perineural. Submucosal inflammation was associated with denuded epithelium, ulceration, pyuria, and a clinical response to therapy suggesting a pathophysiologic relationship. Epithelial and basement membrane thickness, submucosal edema, vascular ectasia, fibrosis, and detrusor muscle inflammation and fibrosis were not significantly different in the IC and control patients. These findings suggest that IC is a chronic submucosal inflammatory disease, at least in those patients with small bladder capacities or pyuria. IC is best diagnosed from its clinical features; the histologic changes identified in the bladder biopsy play a supportive role in this diagnosis. Mast cells play a limited role in the diagnosis of IC.


Quantitative reverse transcription-polymerase chain reaction of circulating thyroglobulin messenger ribonucleic acid for monitoring patients with thyroid carcinoma.
Patients with thyroid cancer are monitored for disease recurrence by measurement of serum thyroglobulin (Tg) and iodine-131 (131I) scanning. To enhance sensitivity and to circumvent antibodies that interfere with Tg immunoassays, we have developed RT-PCR assays that detect circulating thyroid messenger RNA (mRNA) transcripts. We now report results using a sensitive quantitative Tg mRNA assay (Taqman; ABI, Foster City, CA) in comparison with immunoassay in patients previously treated for thyroid cancer. We evaluated 107 patients: 84 during T4 therapy, 14 after T4 withdrawal, and 9 at both time points. All patients had near-total thyroidectomy, and 92% received postoperative 131I. Serum TSH, Tg protein, and Tg mRNA were measured. Patients were grouped based on most recent 131I scan or pathologically confirmed disease as having no detectable thyroid tissue (n = 33), thyroid bed uptake (n = 37), cervical/regional adenopathy (n = 21), or distant metastases (n = 16). During T4 therapy, median (range) Tg mRNA values (pg Tg Eq/microg thyroid RNA) for the groups were 1.5 (0-26.8), 9.4 (0.5-90.0), 15.4 (0.2-92), and 12.4 (1.9-16.6), respectively. Using a value of 3 pg Tg Eq/microg thyroid RNA as cut-point, Tg mRNA was positive in 38% of patients with no uptake, 75% with thyroid bed uptake, 84% with cervical/regional disease, and 94% with distant metastases. The median Tg mRNA value for patients with no uptake was lower than the median values for patients with thyroid bed uptake (P = 0.009) or with detectable thyroid tissue at any site (P = 0.010). Patients with negative 131I whole body scans were also less likely to have detectable Tg mRNA levels than were patients with thyroid bed uptake (P < 0.001) or any detectable thyroid tissue at any location (P < 0.001). Similar differences between these groups were seen after T4 withdrawal and for the 23 patients with circulating anti-Tg antibodies, when analyzed separately. Eight of the nine patients studied with low and high TSH concentrations displayed greater amounts of circulating Tg mRNA after T4 withdrawal. In three patients followed prospectively, the amount Tg mRNA correlated with the presence and absence of cervical metastases. In conclusion, we have demonstrated that a quantitative Tg mRNA assay can identify thyroid cancer patients with recurrent or residual thyroid tissue with greater sensitivity and similar specificity to Tg immunoassay during T4 therapy. The assay was unaffected by anti-Tg antibodies, responded to TSH-stimulation, and was reduced after surgical removal of metastases. These data suggest that this quantitative Tg mRNA assay may be a sensitive marker of tumor recurrence or response to therapy, particularly in patients with anti-Tg antibodies.


Biomaterials approaches in stem cell mechanobiology.
Multiple molecular and physical cues engage in complex interplay to afford the fine control over stem cell behavior that is required during tissue development, homeostasis, and repair. As a result of a close collaboration between biologists, engineers, and physicists over the past decade, the types of mechanical parameters which influence stem cells, along with the corresponding cellular outcomes, have started to emerge. Moreover, the field has begun to identify the molecular structures and mechanisms whereby stem cells sense physical signals and transduce them into biological response. In this chapter, we survey the existing knowledge of stem cell mechanobiology and discuss bioengineering approaches which hold the potential to address outstanding questions and concepts. In particular, we cover approaches which may help dissect the context-dependent influence of the physical environment, and resolve its interactions with molecular signals. We also describe platforms which could recreate the spatial and temporal variations in mechanics which are present in vivo and may play a role in patterning stem cell behaviors. Comprehensive understanding of the complex mechanical regulation of stem cell fate may bring us closer to taking full advantage of their vast regenerative potential.


Adaptation of Running Biomechanics to Repeated Barefoot Running: A Randomized Controlled Study.
Previous studies have shown that changing acutely from shod to barefoot running induces several changes to running biomechanics, such as altered ankle kinematics, reduced ground-reaction forces, and reduced loading rates. However, uncertainty exists whether these effects still exist after a short period of barefoot running habituation. The purpose was to investigate the effects of a habituation to barefoot versus shod running on running biomechanics. It was hypothesized that a habituation to barefoot running would induce different adaptations of running kinetics and kinematics as compared with a habituation to cushioned footwear running or no habituation. Controlled laboratory study. Young, physically active adults without experience in barefoot running were randomly allocated to a barefoot habituation group, a cushioned footwear group, or a passive control group. The 8-week intervention in the barefoot and footwear groups consisted of 15 minutes of treadmill running at 70% of VO2 max (maximal oxygen consumption) velocity per weekly session in the allocated footwear. Before and after the intervention period, a 3-dimensional biomechanical analysis for barefoot and shod running was conducted on an instrumented treadmill. The passive control group did not receive any intervention but was also tested prior to and after 8 weeks. Pre- to posttest changes in kinematics, kinetics, and spatiotemporal parameters were then analyzed with a mixed effects model. Of the 60 included participants (51.7% female; mean ± SD age, 25.4 ± 3.3 years; body mass index, 22.6 ± 2.1 kg·m-2), 53 completed the study (19 in the barefoot habituation group, 18 in the shod habituation group, and 16 in the passive control group). Acutely, running barefoot versus shod influenced foot strike index and ankle, foot, and knee angles at ground contact (P < .001), as well as vertical average loading rate (P = .003), peak force (P < .001), contact time (P < .001), flight time (P < .001), step length (P < .001), and cadence (P < .001). No differences were found for average force (P = .391). After the barefoot habituation period, participants exhibited more anterior foot placement (P = .006) when running barefoot, while no changes were observed in the footwear condition. Furthermore, barefoot habituation increased the vertical average loading rates in both conditions (barefoot, P = .01; shod, P = .003) and average vertical ground-reaction forces for shod running (P = .039). All other outcomes (ankle, foot, and knee angles at ground contact and flight time, contact time, cadence, and peak forces) did not change significantly after the 8-week habituation. Changing acutely from shod to barefoot running in a habitually shod population increased the foot strike index and reduced ground-reaction force and loading rates. After the habituation to barefoot running, the foot strike index was further increased, while the force and average loading rates also increased as compared with the acute barefoot running situation. The increased average loading rate is contradictory to other studies on acute adaptations of barefoot running. A habituation to barefoot running led to increased vertical average loading rates. This finding was unexpected and questions the generalizability of acute adaptations to long-term barefoot running. Sports medicine professionals should consider these adaptations in their recommendations regarding barefoot running as a possible measure for running injury prevention. DRKS00011073 (German Clinical Trial Register).


Digit ratio, color polymorphism and egg testosterone in the Australian painted dragon.
Variation in exposure to sex hormones during early development contributes to phenotypic plasticity in vertebrate offspring. As a proposed marker for prenatal sex hormone exposure and because of their association with various physiological and behavioral characteristics, digit ratio and/or digit length have received notable interest within the field of evolutionary ecology. However, the validity of digit measures as a proxy of prenatal sex hormone exposure is controversial and only few studies have provided direct evidence for the link between digit development and prenatal sex hormones. Here, we report morph- and sex-specific variation in digit ratio in wild painted dragon lizards (Ctenophorus pictus). Lizards expressing a yellow bib have significantly larger third-to-fourth toe ratios (3D:4D) than lizards without a bib. Males have significantly smaller 3D:4D than females. Furthermore, we show that experimental elevation of yolk testosterone significantly increases 3D:4D in hatchling painted dragon lizards, but has no influence on hatchling size. Our results provide direct and indirect evidence for the involvement of prenatal sex steroids in digit development and it is suggested that digit ratio may be used as a biomarker for prenatal steroid exposure in this reptilian species. As such, digit ratio may provide a useful tool to study temporal or spatial differences in the proximate hormonal mechanisms modulating physiological and behavioural phenotypes.


Exercise Intensity-Dependent Effects on Cognitive Control Function during and after Acute Treadmill Running in Young Healthy Adults.
The idea that physical activity differentially impacts upon performance of various cognitive tasks has recently gained increased interest. However, our current knowledge about how cognition is altered by acute physical activity is incomplete. To measure how different intensity levels of physical activity affect cognition during and after 1 bout of physical activity, 30 healthy, young participants were randomized to perform a not-X continuous performance test (CPT) during low (LI)- and moderate intensity (MI) running. The same participants were subsequently randomized to perform the not-X CPT post LI, MI, and high intensity (HI) running. In addition, exercise related mood changes were assessed through a self-report measure pre and post running at LI, MI, and HI. Results showed worsening of performance accuracy on the not-X CPT during one bout of moderate compared to low intensity running. Post running, there was a linear decrease in reaction time with increasing running intensity and no change in accuracy or mood. The decreased reaction times post HI running recovered back to baseline within 20 min. We conclude that accuracy is acutely deteriorated during the most straining physical activity while a transient intensity-dependent enhancement of cognitive control function is present following physical activity.


How can self-efficacy be increased? Meta-analysis of dietary interventions.
Targeting individuals' beliefs that they are able to eat healthily can improve dietary-related behaviours. However, the most effective behaviour change techniques (BCTs) to promote dietary self-efficacy have not been systematically reviewed. This research addressed this gap. Studies testing the effect of interventions on healthy eating and underlying dietary-related self-efficacy, within randomised controlled trials, were systematically reviewed in MEDLINE, EMBASE and PSYCINFO. Two reviewers independently coded intervention content in both intervention and comparison groups. Data pertaining to study quality were also extracted. Random effects meta-analysis was used to calculate an overall effect size on dietary self-efficacy for each study. The associations between 26 BCTs and self-efficacy effects were calculated using meta-regression. In some of the analyses, interventions that incorporated self-monitoring (tracking one's own food-related behaviour), provided feedback on performance, prompted review of behavioural goals, provided contingent rewards (rewarding diet success), or planned for social support/social change increased dietary self-efficacy significantly more than interventions that did not. Stress management was consistently associated with self-efficacy effects across all analyses. There was strong evidence for stress management and weaker evidence for a number of other BCTs. The findings can be used to develop more effective, theory- and evidence-based behavioural interventions.


Genetic evolution of equine influenza strains isolated in France from 2005 to 2010.
REASON FOR PERFORMING THIS STUDY: Equine influenza virus (EIV) is considered the most economically important equine respiratory pathogen worldwide. The H3N8 subtype, responsible for all outbreaks of equine influenza globally, evolves perpetually. Mutations in the genome of these viruses have the potential to modify their antigenic properties and recognition by pre-existing antibodies. The aim of this study was to determine the genetic evolution of EIV strains in France and to compare it with the evolution of strains isolated globally. Analysis of the sequence data was performed to investigate any possible links between the outbreaks. Retrospective genetic analysis study of archived material. Analyses were performed on the HA1 domain of haemagglutinin H3 of EIV isolated in a previous study carried out from November 2005 to October 2010. The nucleic acid sequence of 41 strains was analysed and translated. The French viruses were compared with 59 Clade 1 strains and 83 Clade 2 strains. Strains were aligned chronologically and on the basis of their geographical origin. The 16 Clade 1 strains are all derived from the outbreak that started in the Grosbois training yard in 2009. The virus genome appears to have been stable during the outbreak. The 25 Clade 2 strains were isolated over the 5-year period during which several mutations had emerged. Some strains incorporate a sporadic mutation, and others a mutation that may occur several times but does not persist. However, all strains are gradually moving towards definitive mutations. This study demonstrated that EIVs have evolved in France during this period in a similar manner to EIVs globally. The data lend support to the current World Animal Health Organisation recommendation that the vaccines contain a representative of both Clade 1 and Clade 2 of the Florida sublineage.


Twenty-four hour metabolic rate measurements utilized as a reference to evaluate several prediction equations for calculating energy requirements in healthy infants.
To date, only short-duration metabolic rate measurements of less than four hours have been used to evaluate prediction equations for calculating energy requirements in healthy infants. Therefore, the objective of this analysis was to utilize direct 24-hour metabolic rate measurements from a prior study to evaluate the accuracy of several currently used prediction equations for calculating energy expenditure (EE) in healthy infants. Data from 24-hour EE, resting (RMR) and sleeping (SMR) metabolic rates obtained from 10 healthy infants, served as a reference to evaluate 11 length-weight (LWT) and weight (WT) based prediction equations. Six prediction equations have been previously derived from 50 short-term EE measurements in the Enhanced Metabolic Testing Activity Chamber (EMTAC) for assessing 24-hour EE, (EMTACEE-LWT and EMTACEE-WT), RMR (EMTACRMR-LWT and EMTACRMR-WT) and SMR (EMTACSMR-LWT and EMTACSMR-WT). The last five additional prediction equations for calculating RMR consisted of the World Health Organization (WHO), the Schofield (SCH-LWT and SCH-WT) and the Oxford (OXFORD-LWT and OXFORD-WT). Paired t-tests and the Bland & Altman limit analysis were both applied to evaluate the performance of each equation in comparison to the reference data. 24-hour EE, RMR and SMR calculated with the EMTACEE-WT, EMTACRMR-WT and both the EMTACSMR-LWT and EMTACSMR-WT prediction equations were similar, p = NS, to that obtained from the reference measurements. However, RMR calculated using the WHO, SCH-LWT, SCH-WT, OXFORD-LWT and OXFORD-WT prediction equations were not comparable to the direct 24-hour metabolic measurements (p < 0.05) obtained in the 10 reference infants. Moreover, the EMTACEE-LWT and EMTACRMR-LWT were also not similar (p < 0.05) to direct 24-hour metabolic measurements. Weight based prediction equations, derived from short-duration EE measurements in the EMTAC, were accurate for calculating EE, RMR and SMR in healthy infants.


Energy performance indicators of wastewater treatment: a field study with 17 Portuguese plants.
The energy costs usually represent the second largest part of the running costs of a wastewater treatment plant (WWTP). It is therefore crucial to increase the energy efficiency of these infrastructures and to implement energy management systems, where quantitative performance metrics, such as performance indicators (PIs), play a key role. This paper presents energy PIs which cover the unit energy consumption, production, net use from external sources and costs, and the results used to validate them and derive their reference values. The results of a field study with 17 Portuguese WWTPs (5-year period) were consistent with the results obtained through an international literature survey on the two key parcels of the energy balance--consumption and production. The unit energy consumption showed an overall inverse relation with the volume treated, and the reference values reflect this relation for trickling filters and for activated sludge systems (conventional, with coagulation/filtration (C/F) and with nitrification and C/F). The reference values of electrical energy production were derived from the methane generation potential (converted to electrical energy) and literature data, whereas those of energy net use were obtained by the difference between the energy consumption and production.


High-speed dual color fluorescence lifetime endomicroscopy for highly-multiplexed pulmonary diagnostic applications and detection of labeled bacteria.
We present a dual-color laser scanning endomicroscope capable of fluorescence lifetime endomicroscopy at one frame per second (FPS). The scanning system uses a coherent imaging fiber with 30,000 cores. High-speed lifetime imaging is achieved by distributing the signal over an array of 1024 parallel single-photon avalanche diode detectors (SPADs), minimizing detection dead-time maximizing the number of photons detected per excitation pulse without photon pile-up to achieve the high frame rate. This also enables dual color fluorescence imaging by temporally shifting the dual excitation lasers, with respect to each other, to separate the two spectrally distinct fluorescent decays in time. Combining the temporal encoding, to provide spectral separation, with lifetime measurements we show a one FPS, multi-channel endomicroscopy platform for clinical applications and diagnosis. We demonstrate the potential of the system by imaging SmartProbe labeled bacteria in ex vivo samples of human lung using lifetime to differentiate bacterial fluorescence from the strong background lung autofluorescence which was used to provide structural information.


Optic neuropathy associated with the use of over-the-counter sexual enhancement supplements.
This case report details an association of the use of over-the-counter sexual enhancement supplements with atypical optic neuropathy. A 42-year-old man presented with right-sided headache and vision loss of the right eye, which deteriorated to a single quadrant of hand motion over 11 days. Serial orbital magnetic resonance imaging scans demonstrated progressive orbital optic nerve enhancement extending into the optic canal despite high-dose steroid treatment. The patient eventually admitted to using several over-the-counter sexual enhancement supplements prior to the onset of symptoms and throughout the course of his steroid treatment, which he subsequently discontinued. His vision improved to 20/200 with an expanded visual field. Anterior ischemic optic neuropathy has been reported in association with phosphodiesterase (PDE)-5 inhibitor use, but visual loss in association with unregulated sexual enhancement supplements has not been studied. While one case cannot establish association, our case is suggestive of potential dangers of over-the-counter sexual enhancement supplements, which may contain PDE-5 inhibitors, "male hormones," and "substances that enhance blood production." The case also underscores the importance of obtaining a careful history of supplements in patients with optic neuropathies.


THE RELATION OF THE TOXICITY OF DIPHTHERIA TOXIN TO ITS NEUTRALIZING VALUE UPON ANTITOXIN AT DIFFERENT STAGES IN THE GROWTH OF CULTURE.
Until recently diphtheria " toxin " was supposed to be a single definite substance and to have a definite toxicity in animals and neutralizing power for antitoxin. A fatal dose of toxin, without regard to the conditions under which it was produced or preserved, was supposed to require always the same quantity of antitoxin to neutralize it. Ehrlich's researches have completely done away with this theory, and have substituted for it one which assumes the toxin to be only at its origin a single definite chemical compound with definite physiological and antitoxic properties. According to Ehrlich the toxin is an unstable substance which readily loses its toxicity, while at the same time its affinity for antitoxin may be either increased or decreased. Its neutralization by antitoxin he considers to be due to a chemical union between the toxin and the antitoxin. The results of our experiments as detailed in this paper are fully in accord with those published by Ehrlich, as to the varying neutralizing value of a minimal fatal dose of " toxin "; they, however, go further and indicate roughly a general law in accordance with which these changes occur. The neutralizing value of a fatal dose of toxin is at its lowest in the culture fluid when the first considerable amounts of toxin have been produced. After a short period, during which the quantity of toxin in the fluid is increasing, the neutralizing value of the fatal dose begins to increase, at first rapidly, then more slowly. While the culture is still in vigorous growth and new toxin is being produced, the neutralizing value of the fatal dose fluctuates somewhat, but with a generally upward tendency. After the cessation of toxin production the neutralizing value of the fatal dose increases steadily until it becomes five to ten times its original amount. In our experiments the greatest value for L(+) was 126, the least 27. As at 6 hours L(+) was only 72 and at 28 hours only 91, we doubt whether L(+) ever reaches above 150, and therefore hardly expect Ehrlich's figures of 200 to be realized. When we seek to analyze the above-described process, we find certain facts which seem partly to explain it. Experiments have shown that filtered toxin, preserved for any length of time in conditions under which access of air occurs, gradually loses in both its toxicity and neutralizing power, and that it loses more rapidly in the former property than in the later. Thus, while the fatal dose of a toxin preserved for one year rose from .01 cc. to .55 cc., it lost only half as much in neutralizing value, one unit neutralizing at first 1 cc., at the end of the year 25 cc. These processes take place more rapidly at room temperature than in the ice chest, and in the incubator than in the room. In the fluid holding the living bacilli we have, therefore, after the first few hours of toxin formation, a double process going on, one of deterioration in the toxin already accumulated, which tends to increase the neutralizing value of the fatal dose, the other of new toxin formation, which probably tends to diminish the neutralizing value. The chemical changes produced by the growth of the bacilli in the bouillon tend to aid one or the other of these processes and so to make from hour to hour slight changes in the value of the fatal dose. Later, with the period of cessation of toxin production, the gradual deterioration of the toxicity alone continues, and the fatal dose gradually and steadily increases in its neutralizing value. Ehrlich's theories, as to the splitting up of " toxin " into toxoids having little or no toxicity but on the average full neutralizing power for antitoxin, have not in our opinion been substantiated by the results of these experiments. The difference between the amount of toxin mixed with a unit of antitoxin which causes the first symptoms and that causing death upon the fourth day would be, it is true, explained by his theory, but the failure of this difference to be greater where, by his theories, epitoxoids should be in great abundance prevents our acceptance of his views. The fact of the greater neutralization value of a fatal dose of a deteriorated toxin would be accounted for on his protoxoid theory. This, however, is not proof of its correctness, as other theories, such as the production by the diphtheria bacillus of two or more closely allied toxins, similar to the allied alkaloids produced by plants, would equally account for it, if we supposed the one which had the greater neutralization value was more resistant to destruction than the other. We only advance this theory to call attention to the fact that many theories can on paper explain a process without necessarily being thereby established. Even if his theories prove partially correct, we feel certain that his formula for standardizing toxins is founded upon error and cannot be employed for the purpose intended by him. While we do not believe, therefore, that he has changed the principles of testing antitoxin, yet we believe he has contributed greatly to uniformity in results by calling attention to the necessity of selecting a suitable toxin and by employing and distributing an antitoxin as a standard to test toxins by. In this way smaller testing stations can make their results correspond with those of the central station. In spite of the great variations in the neutralizing value of a fatal dose in different toxins, we do not believe there has been any such great difference in the toxins used by the different stations for testing purposes. Most laboratories have taken the culture fluid at about the time of its greatest toxicity, and the neutralizing value of a fatal dose of this toxin would seldom vary more than 10 per cent above or below the standard now adopted in Germany by the government testing station, this latter being presumably as close as possible to that used to establish the original Behring-EhrIich unit. Where error has been made, it has usually been by taking too old culture fluids, which would cause the antitoxin strength of samples tested to be estimated below and not above its real value. Culture 8, which is used not only by us but by many other laboratories in the United States and Europe, fortunately produces on the 6th day, the time at which the culture is usually removed, a toxin which grades Elirlich's antitoxin within five per cent of the strength given by him. We believe that by using such a bacillus, we can, after gaining a fuller knowledge of its characteristics, obtain a toxin of a known and suitable neutralizing value, and thus always correctly standardize an antitoxic serum. Meanwhile a fairly permanent antitoxin, such as Ehrlich provides, is of immense value in insuring a uniform though not necessarily correct standard among the different testing stations and in allowing of comparison between them.


Fibronectin has a dual role in locomotion and anchorage of primary chick fibroblasts and can promote entry into the division cycle.
Fibronectin (FN), which is already known to be a natural factor for fibroblast spreading on substrata, has now been shown to be essential for two distinct types of adhesion with different biological functions in chick heart fibroblasts, namely adhesion directed toward locomotion and toward stationary anchorage for growth. Manipulation of culture conditions and the use of antisera of differing specificities has demonstrated that both exogenous and cell-derived FN are important in each process. The organization of the fibronectin-containing matrix differs between the two states. Immunoelectron microscopy with a colloidal gold marker reveals the presence of small membrane-associated plaques of fibronectin in motile cells with associated submembranous specialization. A fibrillar matrix containing fibronectin is dominant in nonmotile, growing fibroblasts. The development of focal adhesions for stationary anchorage can be dramatically enhanced by addition of cell-derived FN at an appropriate stage, and this promotes entry into the growth cycle. New macromolecular synthesis in addition to FN is necessary for focal adhesion development but not for locomotion.


Avian SERPINB12 expression in the avian oviduct is regulated by estrogen and up-regulated in epithelial cell-derived ovarian carcinomas of laying hens.
Serine protease inhibitors (SERPINs) are involved in a variety of biological processes such as blood clotting, angiogenesis, immune system, and embryogenesis. Although, of these, SERPINB12 is identified as the latest member of clade B in humans, little is known of it in chickens. Thus, in this study, we investigated SERPINB12 expression profiles in various tissues of chickens and focused on effects of steroid hormone regulation of its expression. In the chicken oviduct, SERPINB12 mRNA and protein are abundant in the luminal (LE) and glandular (GE) epithelia of the magnum in response to endogenous or exogenous estrogen. Furthermore, SERPINB12 mRNA and protein increase significantly in GE of cancerous ovaries of laying hens with epithelia-derived ovarian cancer. Collectively, these results indicate that SERPINB12 is a novel estrogen-stimulated gene that is up-regulated by estrogen in epithelial cells of the chicken oviduct and that it is a potential biomarker for early detection of ovarian carcinomas in laying hens and women.


Digital subcarrier multiplexing for fiber nonlinearity mitigation in coherent optical communication systems.
In this work we experimentally investigate the improved intra-channel fiber nonlinearity tolerance of digital subcarrier multiplexed (SCM) signals in a single-channel coherent optical transmission system. The digital signal processing (DSP) for the generation and reception of the SCM signals is described. We show experimentally that the SCM signal with a nearly-optimum number of subcarriers can extend the maximum reach by 23% in a 24 GBaud DP-QPSK transmission with a BER threshold of 3.8 × 10(-3) and by 8% in a 24 GBaud DP-16-QAM transmission with a BER threshold of 2 × 10(-2). Moreover, we show by simulations that the improved performance of SCM signals is observed over a wide range of baud rates, further indicating the merits of SCM signals in baud-rate flexible agile transmissions and future high-speed optical transport systems.


Social media sharing of low-quality news sources by political elites.
Increased sharing of untrustworthy information on social media platforms is one of the main challenges of our modern information society. Because information disseminated by political elites is known to shape citizen and media discourse, it is particularly important to examine the quality of information shared by politicians. Here, we show that from 2016 onward, members of the Republican Party in the US Congress have been increasingly sharing links to untrustworthy sources. The proportion of untrustworthy information posted by Republicans versus Democrats is diverging at an accelerating rate, and this divergence has worsened since President Biden was elected. This divergence between parties seems to be unique to the United States as it cannot be observed in other western democracies such as Germany and the United Kingdom, where left-right disparities are smaller and have remained largely constant.


Changes in anger and aggression after treatment for PTSD in active duty military.
To examine whether treating posttraumatic stress disorder (PTSD) reduces anger and aggression and if changes in PTSD symptoms are associated with changes in anger and aggression. Active duty service members (n = 374) seeking PTSD treatment in two randomized clinical trials completed a pretreatment assessment, 12 treatment sessions, and a posttreatment assessment. Outcomes included the Revised Conflict Tactics Scale and state anger subscale of the State-Trait Anger Expression Inventory. Treatment groups were analyzed together. There were small to moderate pretreatment to posttreatment reductions in anger (standardized mean difference [SMD] = -0.25), psychological aggression (SMD = -0.43), and physical aggression (SMD = -0.25). The majority of participants continued to endorse anger and aggression at posttreatment. Changes in PTSD symptoms were mildly to moderately associated with changes in anger and aggression. PTSD treatments reduced anger and aggression with effects similar to anger and aggression treatments; innovative psychotherapies are needed.


Diagnostic performance of a commercial immunoblot assay for myositis antibody testing.
The objective of this study was to establish a population based reference range for a commercial immunoblot assay detecting myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs), and to assess the diagnostic performance of this reference range against the manufacturer's recommended ranges in a myositis patient cohort. A total of 124 patients from a myositis cohort and 197 healthy controls were serologically assessed using a commercial immunoblot containing eleven autoantigens (Jo-1, EJ, OJ, PL7, PL12, Mi-2, SRP, Ku, PMScl75, PMScl100 and Ro52) according to the manufacturer's instructions. Use of the manufacturer's reference ranges resulted in detection of MSAs in 19.4% of myositis patients and 9.1% of controls; MAAs were detected in 41.1% of myositis patients and 14.2% of controls. Reference values derived from the healthy control population resulted in significant differences in cut-off values for some autoantibodies, particularly Ro52 and PMScl75. Use of local reference ranges reduced detection of MSAs to 16.9% of myositis patients and 3% of healthy controls, with MAAs 23.4% of patients and 2% of healthy controls. Application of population based reference ranges resulted in significant differences in detection of MSAs and MAAs compared to the manufacturer's recommended ranges. Cut-off levels should be assessed to ensure suitability for the population tested.


Mast Cell Activation Syndrome.
Mast cell activation syndrome (MCAS) involves the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems, classified as primary, secondary, and idiopathic. Earlier criteria for MCAS diagnosis included episodic symptoms with mast cell mediators affecting two or more organ systems with urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope, tachycardia, wheezing, conjunctival injection, pruritus, nasal stuffiness, decrease in frequency, severity, or resolution of symptoms with anti-mediator therapy including H1/H2 receptor antagonists, anti-leukotrienes, or mast cell stabilizers. Laboratory data includes an increased validated urinary or serum markers of MCAS, documentation of an increase of the marker above the patient's baseline value during symptomatic periods on more than two occasions, or baseline serum tryptase levels that are persistently above 15 ng/mL. Laboratory data also includes an increase of the tryptase level above baseline value on one occasion. Other assays are 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha. A recent global classification is a response of clinical symptoms, a substantial transient increase in serum total tryptase or increase in other mast cell-derived mediators, histamine or PGD2 or urinary metabolites, and agents that attenuate production or mast cell mediator activities. "Spectrum of MCAS disorders" has been proposed, highlighting symptoms' diagnostic tests and treatments.


Inhibition of murine sarcoma virus induced transformation by adenovirus structural proteins.
The purified fibre and hexon of adenovirus 12 inhibit the transformation in tissue culture of murine sarcoma virus (msv-m) by as much as 80% and 70%, respectively, when they are added to cells 8 to 2o h before MSV-M infection. During a 12 h period, only about 6 to 8% of added radiolabelled viral proteins become associated with cells (or I-O mug protein bound/10(5) cells). No inhibition occurs when the proteins are added simultaneously with MSV-M or 90 min or 4 h after MSV-M. There is also a direct correlation between the extent of focus inhibition and the concentrations of viral proteins used. Concentrations of viral proteins used to inhibit cell transformation do not affect cell growth, but do reduce cell macromolecular synthesis.


The order of concurrent training does not affect soccer-related performance adaptations.
Despite the wealth of evidence regarding physical training strategies in soccer, there is little information regarding soccer-specific concurrent training and the effects of training order. The current study aimed to: i) quantify the effects of concurrent high-intensity run-based training (HIT) and strength- and power-based training (STR) on soccer-specific performance, and ii) investigate the order effect of completing HIT and STR either first or second within training sessions. Eighteen semi- and fully-professional players completed a battery of field- and gym-based tests before and after a 5-week pre-season training intervention. Players were pair-matched and completed 3 sessions per week of HIT followed by STR (n=9) or STR followed by HIT (n=9). ANCOVA tests revealed no differences between groups for changes in any of the measures (p>0.05). However, a training effect was observed for all measures (p<0.05), with 10-m sprint, 6×30-m repeated sprint, 40-m agility and Yo-Yo test performances improving by 1.8±2.6%, 1.3±1.8%, 1.0±1.5% and 19.4±23.4%, respectively (n=18). In conclusion, there was a positive effect of the concurrent training approach on key measures of soccer performance, but the order of completing HIT and STR appears inconsequential to performance adaptations.


Electronic coupling and catalytic effect on H2 evolution of MoS2/graphene nanocatalyst.
Inorganic nano-graphene hybrid materials that are strongly coupled via chemical bonding usually present superior electrochemical performance. However, how the chemical bond forms and the synergistic catalytic mechanism remain fundamental questions. In this study, the chemical bonding of the MoS2 nanolayer supported on vacancy mediated graphene and the hydrogen evolution reaction of this nanocatalyst system were investigated. An obvious reduction of the metallic state of the MoS2 nanolayer is noticed as electrons are transferred to form a strong contact with the reduced graphene support. The missing metallic state associated with the unsaturated atoms at the peripheral sites in turn modifies the hydrogen evolution activity. The easiest evolution path is from the Mo edge sites, with the presence of the graphene resulting in a decrease in the energy barrier from 0.17 to 0.11 eV. Evolution of H2 from the S edge becomes more difficult due to an increase in the energy barrier from 0.43 to 0.84 eV. The clarification of the chemical bonding and catalytic mechanisms for hydrogen evolution using this strongly coupled MoS2/graphene nanocatalyst provide a valuable source of reference and motivation for further investigation for improved hydrogen evolution using chemically active nanocoupled systems.