Comparison study of intense pulsed light versus a long-pulse pulsed dye laser in the treatment of facial skin rejuvenation.
Currently, various nonablative skin resurfacing techniques are being used to rejuvenate facial skin, including lasers and intense pulsed light (IPL). There are few direct comparison studies between IPLs and lasers. The objective of our study is to compare the effectiveness of intense pulsed light versus a long-pulse pulsed dye laser (LPDL) in the treatment of facial skin rejuvenation. Ten Asian patients with Fitzpatrick skin types III-IV were enrolled in this study. One half of the face was treated with IPL (6 treatment sessions) and the other side was treated by LPDL (3 treatment sessions). An LPDL with a wavelength of 595 nm and spot size of 7 mm was used. Utilizing the compression method, lentigines were treated using a PDL with a fluence between 9-12 J/cm and a pulse duration of 1.5 ms. Wrinkles were treated with fluences between 10 to 12 J/cm and a pulse duration of 20 ms, using a pulse-stacking technique. An IPL with a type B handpiece was used. Lentigines and wrinkles were treated with fluences between 27 to 40 J/cm and a pulse duration of 20 ms. The improvement of lentigines was 62.3% and 81.1% for IPL and LPDL respectively. There was no significant difference between IPL and LPDL in wrinkle reduction. There was no scarring or pigmentary change seen with either device. Both IPL and LPDL are effective for facial skin rejuvenation in Asians, but LPDL treatment is significantly better than IPL treatment in the treatment of lentigines. The use of the compression technique may allow this LPDL to be used effectively for facial rejuvenation and with fewer treatment sessions, when compared with the IPL.


A rare case of dengue encephalitis.
Dengue fever has a variable clinical spectrum ranging from asymptomatic infection to life-threatening dengue haemorrhagic fever and dengue shock syndrome. However, neurological complications, in general, are unusual. Dengue encephalopathy is not an unknown entity; however, dengue encephalitis, a direct neuronal infiltration by the dengue virus, is an extremely rare disease. Although dengue is classically considered a non-neurotropic virus, there is increasing evidence for dengue viral neurotropism, suggesting that, in a proportion of cases, there may be an element of direct viral encephalitis. An MRI brain rarely shows focal abnormalities in dengue encephalitis. We report an interesting case of dengue encephalitis during an outbreak in Delhi, India. The diagnosis was confirmed by blood and cerebrospinal fluid dengue serology and (NS1) antigen assay. The case showed extensive lesions involving the midbrain, cerebellum, thalamus and medial temporal region on both sides of the MRI brain, which is an uncommon manifestation of dengue fever.


In vitro and in vivo activity of ribavirin against Andes virus infection.
Pathogenic hantaviruses are a closely related group of rodent-borne viruses which are responsible for two distinct diseases in humans, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome (HPS, otherwise known as hantavirus cardiopulmonary syndrome, HCPS). The antiviral effect of ribavirin against Old World hantaviruses, most notably Hantaan virus, is well documented; however, only a few studies have addressed its inhibitory effect on New World hantaviruses. In the present study, we demonstrate that ribavirin is highly active against Andes virus (ANDV), an important etiological agent of HPS, both in vitro and in vivo using a lethal hamster model of HPS. Treatment of ANDV infected Vero E6 cells with ribavirin resulted in dose-dependent reductions in viral RNA and protein as well as virus yields with a half maximal inhibitory concentration between 5 and 12.5 µg ml(-1). In hamsters, treatment with as little as 5 mg kg(-1) day(-1) was 100% effective at preventing lethal HPS disease when therapy was administered by intraperitoneal injection from day 1 through day 10 post-infection. Significant reductions were observed in ANDV RNA and antigen positive cells in lung and liver tissues. Ribavirin remained completely protective when administered by intraperitoneal injections up to three days post-infection. In addition, we show that daily oral ribavirin therapy initiated 1 day post-infection and continuing for ten days is also protective against lethal ANDV disease, even at doses of 5 mg kg(-1) day(-1). Our results suggest ribavirin treatment is beneficial for postexposure prophylaxis against HPS-causing hantaviruses and should be considered in scenarios where exposure to the virus is probable. The similarities between the results obtained in this study and those from previous clinical evaluations of ribavirin against HPS, further validate the hamster model of lethal HPS and demonstrate its usefulness in screening antiviral agents against this disease.


Therapist success and its determinants.
This study examined the relatively unexplored contribution of the therapist's performance in determining outcomes of treatment. Nine therapists were studied: three performed supportive-expressive psychotherapy; three, cognitive-behavioral psychotherapy; and three, drug counseling. Profound differences were discovered in the therapists' success with the patients in their case loads. Four potential determinants of these differences were explored: patient factors; therapist factors; patient-therapist relationship factors; and therapy factors. Results showed that patient characteristics within each case load (after random assignments) were similar and disclosed no differences that would have explained the differences in success; therapist's personal qualities were correlated with outcomes but not significantly (mean r = .32); an early-in-treatment measure of the patient-therapist relationship, the Helping Alliance Questionnaire, yielded significant correlations with outcomes (mean r = .65); among the therapy techniques, "purity" provided significant correlations with outcomes (mean r = .44), both across therapists and within each therapist's case load. The three therapist-related factors were moderately associated with each other.


The invisible brain injury: the importance of identifying deficits following brain injury in children with intellectual disability.
Traumatic brain injury (TBI) is common during childhood. However, most of the extant literature about outcomes following childhood TBI is based on children who were functioning "normally" prior to the injury event. But, with the increasing community integration of children with Intellectual Disability (ID) there is an urgent need for specific information regarding problems following TBI for this group. Using a case study, this paper presents an overview of problems faced by these children who subsequently experience a TBI event, and examines questions pertinent to this dual diagnosis. In the case study presented, despite supposedly having access to an internationally acclaimed comprehensive no fault accident compensation and rehabilitation system, a lack of assessment, intervention and support was evident for both the child and the family following a severe TBI because he had pre-existing ID. This case study highlights the need for clinicians to consider the impact of TBI for children with ID, to avoid incorrectly attributing TBI symptoms to pre-existing problems. Children with ID are at increased risk; appropriate treatment plans are vital to maximize quality of life for them and their caregivers.


Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy.
Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.


Voting behavior is reflected in amygdala response across cultures.
Voting to determine one's leaders is among the most important decisions we make, yet little is known about the brain's role in how we come to these decisions. Behavioral studies have indicated that snap judgments of political candidates' faces can predict election outcomes but that the traits that lead to these judgments differ across cultures. Here we sought to investigate the neural basis for these judgments. American and Japanese natives performed simulated voting judgments of actual American and Japanese political candidates while neural activity was measured using functional magnetic resonance imaging (fMRI). Candidates for whom participants chose to vote elicited stronger responses in the bilateral amygdala than candidates for whom participants chose not to vote. This was true regardless of either the participant's culture or the target's culture, suggesting that these voting decisions provoked the same neural response cross-culturally. In addition, we observed a participant culture by target culture interaction in the bilateral amygdala. American and Japanese participants both showed a stronger response to cultural outgroup faces than they did to cultural in group faces, however this was unrelated to their voting decisions. These data provide insight to the mechanisms that underlie our snap judgments of others when making voting decisions and provide a neural correlate to cross-cultural consensus in social inferences.


Risk factors for stress fractures in female track-and-field athletes: a retrospective analysis.
The incidence and nature of stress fractures and the relationship of potential risk factors to stress-fracture history were investigated retrospectively in a group of 53 female competitive track-and-field athletes. Forty-five stress fractures, diagnosed by clinical findings and bone scan, radiograph, or CT scan, were reported in 22 women. Tibial fractures were the most common (33%). There was no significant difference in bone mineral density at the lumbar spine and tibia/fibula or in percentage body fat and total lean mass when comparing the groups with and without a stress-fracture history. Athletes with a past stress fracture were significantly older at menarche and were more likely to have experienced a history of menstrual disturbance (p < 0.05). Analysis of dietary behavior found that athletes with stress fractures scored significantly higher on the EAT-40 test and were more likely to engage in restrictive eating patterns and dieting. Multiple logistic regression showed that athletes with a history of oligomenorrhea were six times more likely to have sustained a stress fracture in the past, while those who were careful about their weight were eight times more likely. Prevention and treatment of stress fractures in female athletes should include a thorough assessment of menstrual characteristics and dietary patterns.


Functional conjugated pyridines via main-group element tuning.
Pyridine-based materials have seen widespread attention for the development of n-type organic materials. In recent years, the incorporation of main-group elements has also explored significant advantages for the development and tunability of organic conjugated materials. The unique chemical and electronic structure of main-group elements has led to several enhancements in conventional organic materials. This Feature article highlights recent main-group based pyridine materials by discussing property enhancements and application in organic electronics.


Accuracy of genomic predictions for feed efficiency traits of beef cattle using 50K and imputed HD genotypes.
The accuracy of genomic predictions can be used to assess the utility of dense marker genotypes for genetic improvement of beef efficiency traits. This study was designed to test the impact of genomic distance between training and validation populations, training population size, statistical methods, and density of genetic markers on prediction accuracy for feed efficiency traits in multibreed and crossbred beef cattle. A total of 6,794 beef cattle data collated from various projects and research herds across Canada were used. Illumina BovineSNP50 (50K) and imputed Axiom Genome-Wide BOS 1 Array (HD) genotypes were available for all animals. The traits studied were DMI, ADG, and residual feed intake (RFI). Four validation groups of 150 animals each, including Angus (AN), Charolais (CH), Angus-Hereford crosses (ANHH), and a Charolais-based composite (TX) were created by considering the genomic distance between pairs of individuals in the validation groups. Each validation group had 7 corresponding training groups of increasing sizes ( = 1,000, 1,999, 2,999, 3,999, 4,999, 5,998, and 6,644), which also represent increasing average genomic distance between pairs of individuals in the training and validations groups. Prediction of genomic estimated breeding values (GEBV) was performed using genomic best linear unbiased prediction (GBLUP) and Bayesian method C (BayesC). The accuracy of genomic predictions was defined as the Pearson's correlation between adjusted phenotype and GEBV (), unless otherwise stated. Using 50K genotypes, the highest average achieved in purebreds (AN, CH) was 0.41 for DMI, 0.34 for ADG, and 0.35 for RFI, whereas in crossbreds (ANHH, TX) it was 0.38 for DMI, 0.21 for ADG, and 0.25 for RFI. Similarly, when imputed HD genotypes were applied in purebreds (AN, CH), the highest average was 0.14 for DMI, 0.15 for ADG, and 0.14 for RFI, whereas in crossbreds (ANHH, TX) it was 0.38 for DMI, 0.22 for ADG, and 0.24 for RFI. The of GBLUP predictions were greatly reduced with increasing genomic average distance compared to those from BayesC predictions. The results indicate that 50K genotypes, used with BayesC, are more effective for predicting GEBV in purebred cattle. Imputed HD genotypes found utility when dealing with composites and crossbreds. Formulation of a fairly large training set for genomic predictions in beef cattle should consider the genomic distance between the training and target populations.


Liver damage during organ donor procurement in donation after circulatory death compared with donation after brain death.
During the past decade the number of livers recovered and transplanted from donation after circulatory death (DCD) donors has increased significantly. As reported previously, injuries are more frequent during kidney procurement from DCD than from donation after brain death (DBD) donors. This aim of this study was to compare outcomes between DCD and DBD with respect to liver injuries. Data on liver injuries in organs procured between 2000 and 2010 were obtained from the UK Transplant Registry. A total of 7146 livers were recovered from deceased donors during the study, 628 (8·8 per cent) from DCD donors. Injuries occurred in 1001 procedures (14·0 per cent). There were more arterial (1·6 versus 1·0 per cent), portal (0·5 versus 0·3 per cent) and caval (0·3 versus 0·2 per cent) injuries in the DBD group than in the DCD group, although none of these findings was statistically significant. Capsular injuries occurred more frequently in DCD than DBD (15·6 versus 11·4 per cent; P = 0·002). There was no significant difference between DCD and DBD groups in liver discard rates related to damage. There were no differences in terms of vascular injuries between DCD and DBD livers, although capsular injuries occurred more frequently in DCD organs. Continuing the trend for increased frequency of DCD liver recovery, and ensuring that there is an adequately skilled surgical team available for procurement, is vital to improving the utilization of DCD livers.


Osteology of the Late Triassic aetosaur Scutarx deltatylus (Archosauria: Pseudosuchia).
Aetosaurians are some of the most common fossils collected from the Upper Triassic Chinle Formation of Arizona, especially at the Petrified Forest National Park (PEFO). Aetosaurians collected from lower levels of the park include Desmatosuchus spurensis, Paratypothorax, Adamanasuchus eisenhardtae, Calyptosuchus wellesi, and Scutarx deltatylus. Four partial skeletons collected from the park between 2002 and 2009 represent the holotype and referred specimens of Scutarx deltatylus. These specimens include much of the carapace, as well as the vertebral column, and shoulder and pelvic girdles, and a new naming convention proposed for osteoderms descriptions better differentiates portions of the carapace and ventral armor. A partial skull from the holotype specimen represents the first aetosaur skull recovered and described from Arizona since the 1930s. The key morphological feature distinguishing Scutarx deltatylus is the presence of a prominent, triangular boss located in the posteromedial corner of the dorsal surface of the dorsal paramedian osteoderms. Scutarx deltatylus can be distinguished from closely related forms Calyptosuchus wellesi and Adamanasuchus eisenhardtae not only morphologically, but also stratigraphically. Thus, Scutarx deltatylus is potentially an index taxon for the upper part of the Adamanian biozone.


Speckle Tracking Echocardiography for the Assessment of the Athlete's Heart: Is It Ready for Daily Practice?
To describe the use of speckle tracking echocardiography (STE) in the biventricular assessment of athletes' heart (AH). Can STE aid differential diagnosis during pre-participation cardiac screening (PCS) of athletes? Data from recent patient, population and athlete studies suggest potential discriminatory value of STE, alongside standard echocardiographic measurements, in the early detection of clinically relevant systolic dysfunction. STE can also contribute to subsequent prognosis and risk stratification. Despite some heterogeneity in STE data in athletes, left ventricular global longitudinal strain (GLS) and right ventricular longitudinal strain (RV ɛ) indices can add to differential diagnostic protocols in PCS. STE should be used in addition to standard echocardiographic tools and be conducted by an experienced operator with significant knowledge of the AH. Other indices, including left ventricular circumferential strain and twist, may provide insight, but further research in clinical and athletic populations is warranted. This review also raises the potential role for STE measures performed during exercise as well as in serial follow-up as a method to improve diagnostic yield.


Total neoadjuvant therapy for rectal cancer: An emerging option.
The treatment of locally advanced rectal cancer (LARC) has benefited from improved surgical techniques and from the implementation of neoadjuvant chemoradiotherapy (CRT), which have markedly decreased the rates of local recurrence. However, distant metastatic disease remains the most significant cause of death for these patients. Although adjuvant chemotherapy (ChT) after neoadjuvant CRT and definitive surgery is commonly recommended, the value of adjuvant systemic therapy remains less clear. Trials evaluating adjuvant ChT for rectal cancer have been handicapped by poor compliance rates and inconsistent survival results. Shifting systemic therapy delivery to the neoadjuvant setting has the promise to improve compliance rates, reduce toxicity, and decrease distant relapse rates. Recently, multiple prospective trials have reported on the use of total neoadjuvant therapy (TNT) for patients with LARC, incorporating both ChT and CRT in the neoadjuvant setting. Here, the authors review the promising results from those trials. Because the studies have largely focused on pathologic outcomes (primarily pathologic complete response rates), ongoing phase 2 and 3 trials are now underway assessing the long-term disease-related outcomes with TNT. In addition to improving survival, TNT has the potential to increase the pool of patients with LARC who are eligible for organ preservation, which is also being evaluated. Cancer 2017;123:1497-1506. © 2017 American Cancer Society.


Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung.
Hypersecretion of airway mucus is a characteristic feature of chronic airway diseases like cystic fibrosis (CF) and leads via impairment of the muco-ciliary clearance and bacterial superinfection to respiratory failure. The major components of the mucus matrix forming family of mucins in the airways are MUC5AC and MUC5B. To investigate the expression of these glycoproteins in CF, immunohistochemistry was carried out on trachea, bronchi and peripheral lung obtained from CF patients and compared to normal lung tissues. MUC5AC immunohistochemistry demonstrated signals in goblet cells of the epithelial lining. Also, goblet cells inside glandular secretory ducts revealed MUC5AC-positive staining. In comparison to those from normal subjects, CF sections were characterized by inflammatory changes and goblet cell hyperplasia, resulting in increased numbers of MUC5AC-positive cells. Immunohistochemical staining for MUC5B showed abundant staining of submucosal glands and epithelial goblet cells. Inside the glands, the immunoreactivity was restricted to glandular mucous cells. MUC5AC and MUC5B are expressed in the same histological pattern in CF compared to normal tissues with an increase of MUC5AC-positive cells due to goblet cell hyper- and metaplasia.


Genetic analysis of transvection effects involving cis-regulatory elements of the Drosophila Ultrabithorax gene.
The Ultrabithorax (Ubx) gene of Drosophila melanogaster contains two functionally distinguishable regions: the protein-coding Ubx transcription unit and, upstream of it, the transcribed but nonprotein-coding bxd region. Numerous recessive, partial loss-of-function mutations which appear to be regulatory mutations map within the bxd region and within the introns of the Ubx transcription unit. In addition, mutations within the Ubx unit exons are known and most of these behave as null alleles. Ubx1 is one such allele. We have confirmed that, although the Ubx1 allele does not produce detectable Ubx proteins (UBX), it does retain other genetic functions detectable by their effects on the expression of a paired, homologous Ubx allele, i.e., by transvection. We have extended previous analyses made by E. B. Lewis by mapping the critical elements of the Ubx gene which participate in transvection effects. Our results show that the Ubx1 allele retains wild-type functions whose effectiveness can be reduced (1) by additional cis mutations in the bxd region or in introns of the Ubx transcription unit, as well as (2) by rearrangements disturbing pairing between homologous Ubx genes. Our results suggest that those remnant functions in Ubx1 are able to modulate the activity of the allele located in the homologous chromosome. We discuss the normal cis regulatory role of these functions involved in trans interactions between homologous Ubx genes, as well as the implications of our results for the current models on transvection.


Right ventromedial prefrontal cortex: a neuroanatomical correlate of impulse control in boys.
Emerging data on the neural mechanisms of impulse control highlight brain regions involved in emotion and decision making, including the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC) and amygdala. Variation in the development of these regions may influence one's propensity for impulsivity and, by extension, one's vulnerability to disorders involving low impulse control (e.g. substance abuse). Here we test the hypothesis that lower impulse control is associated with structural differences in these regions, particularly on the right side, in 61 normal healthy boys aged 7-17. We assessed parent- and teacher-reported behavioral ratings of impulse control (motor impulsivity and non-planning behavior) in relation to vmPFC, ACC and amygdala volume, measured using structural magnetic resonance imaging and FreeSurfer. A regression analysis showed that the right vmPFC was a significant predictor of impulse control ratings. Follow-up tests showed (i) a significant correlation between low impulse control and decreased right vmPFC volume, especially the medial sector of the vmPFC and (ii) significantly lower right vmPFC volume in a subgroup of 20 impulsive boys relative to 20 non-impulsive boys. These results are consistent with the notion that right vmPFC provides a neuroanatomical correlate of the normal variance in impulse control observed in boys.


Toward complete oral cavity cancer resection using a handheld diffuse reflectance spectroscopy probe.
This ex-vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy tissue, with the aim to develop a technology that can assess resection margins for the presence of tumor cells during oral cavity cancer surgery. Diffuse reflectance spectra were acquired on fresh surgical specimens from 28 patients with oral cavity squamous cell carcinoma. The spectra (400 to 1600 nm) were detected after illuminating tissue with a source fiber at 0.3-, 0.7-, 1.0-, and 2.0-mm distances from a detection fiber, obtaining spectral information from different sampling depths. The spectra were correlated with histopathology. A total of 76 spectra were obtained from tumor tissue and 110 spectra from healthy muscle tissue. The first- and second-order derivatives of the spectra were calculated and a classification algorithm was developed using fivefold cross validation with a linear support vector machine. The best results were obtained by the reflectance measured with a 1-mm source-detector distance (sensitivity, specificity, and accuracy are 89%, 82%, and 86%, respectively). DRS can accurately discriminate tumor from healthy tissue in an ex-vivo setting using a 1-mm source-detector distance. Accurate validation methods are warranted for larger sampling depths to allow for guidance during oral cavity cancer excision.


[Personal satisfaction as a component of adult's quality of life in Medellin].
Determining personal satisfaction as the main component of the quality of life of men and women aged 20 to 64 in Medellin during 2005. This was a cross/sectional descriptive population study. Its primary source of information consisted of two samples (659 men and 683 women) representing 523,705 and 651,704 people respectively, according to population expansion factors, selected via probabilistic complex sampling, stratified by socioeconomic level, clustering, city blocks, houses and people. The quality of life for adults in Medellin is mainly represented by personal and economic aspects, their housing's physical environment and social security. The aspects analysed in this study were evaluated above 75%; personal abilities and capability produced the greatest satisfaction, whilst the economic situation and social security produced least satisfaction. There were no significant differences according to gender regarding personal satisfaction concerning various aspects of life. This study's contribution to knowledge lies in making evident the need to integrate each person's subjectivity, opinions and individual perception of his/her own life, since these are the main components in evaluating an individual's quality of life.


A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis.
Severe sepsis is characterized by an initial hyper-inflammatory response that may progress to an immune-suppressed state associated with increased susceptibility to nosocomial infection. Analysis of samples obtained from patients who died of sepsis has identified expression of specific inhibitory receptors expressed on lymphocytes that are associated with cell exhaustion. The objective of this study was to prospectively determine the pattern of expression of these receptors and immune cell function in patients with acute sepsis. Twenty-four patients with severe sepsis were enrolled within 24 hours of the onset of sepsis, as were 12 age-matched healthy controls. Peripheral blood was obtained at enrollment and again seven days later. Immune cell subsets and receptor expression were extensively characterized by quantitative flow cytometry. Lymphocyte function was assayed by stimulated cytokine secretion and proliferation assays. Results were also correlated to clinical outcome. At the onset of severe sepsis, patients had decreased circulating innate and adaptive immune cells and elevated lymphocyte expression of receptors associated with cell activation compared to controls. Samples analyzed seven days later demonstrated increased expression of the inhibitory receptors CTLA4, TIM-3 and LAG-3 on T lymphocytes accompanied by decreased expression of the IL-7 receptor. Functional assays revealed impaired secretion of interferon γ following stimulation in vitro, which was reversible by incubation overnight in fresh media. Impaired secretion of IFNγ correlated with death or development of secondary infection. Lymphocytes from patients with acute sepsis upregulate expression of receptors associated with cell exhaustion, which may contribute to the immune suppressed state that occurs in protracted disease. Therapy that reverses T cell exhaustion may restore immune function in immunocompromised patients and improve survival in sepsis.


The effects of HIV/AIDS on the clinical profile and outcomes post pericardiectomy of patients with constrictive pericarditis: a retrospective review.
The clinical profile and surgical outcomes of patients with constrictive pericarditis were compared in HIV-positive and -negative individuals. This study was a retrospective analysis of patients diagnosed with constrictive pericarditis at Inkosi Albert Luthuli Central Hospital, Durban, over a 10-year period (2004-2014). Of 83 patients with constrictive pericarditis, 32 (38.1%) were HIV positive. Except for pericardial calcification, which was more common in HIV-negative subjects (n = 15, 29.4% vs n = 2, 6.3%; p = 0.011), the clinical profile was similar in the two groups. Fourteen patients died preoperatively (16.9%) and three died peri-operatively (5.8%). On multivariable analysis, age (OR 1.17; 95% CI: 1.03-1.34; p = 0.02), serum albumin level (OR 0.63; 95% CI: 0.43-0.92; p = 0.016), gamma glutamyl transferase level (OR 0.97; 95% CI: 0.94-0.1.0; p = 0.034) and pulmonary artery pressure (OR 1.49; 95% CI: 1.07-2.08; p = 0.018) emerged as independent predictors of pre-operative mortality rate. Peri-operative complications occurred more frequently in HIV-positive patients [9 (45%) vs 6 (17.6%); p = 0.030]. Without surgery, tuberculous constrictive pericarditis was associated with a high mortality rate. Although peri-operative complications occurred more frequently, surgery was not associated with increased mortality rates in HIV-positive subjects.


Role of the TGF-β pathway in dedifferentiation of human mature adipocytes.
Dedifferentiation of adipocytes contributes to the generation of a proliferative cell population that could be useful in cellular therapy or tissue engineering. Adipocytes can dedifferentiate into precursor cells to acquire a fibroblast-like phenotype using ceiling culture, in which the buoyancy of fat cells is exploited to allow them to adhere to the inner surface of a container. Ceiling culture is usually performed in flasks, which limits the ability to test various culture conditions. Using a new six-well plate ceiling culture approach, we examined the relevance of TGF-β signaling during dedifferentiation. Adipose tissue samples from patients undergoing bariatric surgery were digested with collagenase, and cell suspensions were used for ceiling cultures. Using the six-well plate approach, cells were treated with SB431542 (an inhibitor of TGF-β receptor ALK5) or human TGF-β1 during dedifferentiation. Gene expression was measured in these cultures and in whole adipose tissue, the stromal-vascular fraction (SVF), mature adipocytes, and dedifferentiated fat (DFAT) cells. TGF-β1 and collagen type I alpha 1 (COL1A1) gene expression was significantly higher in DFAT cells compared to whole adipose tissue samples and SVF cells. TGF-β1, COL1A1, and COL6A3 gene expression was significantly higher at day 12 of dedifferentiation compared to day 0. In the six-well plate model, treatment with TGF-β1 or SB431542, respectively, stimulated and inhibited the TGF-β pathway as shown by increased TGF-β1, TGF-β2, COL1A1, and COL6A3 gene expression and decreased expression of TGF-β1, COL1A1, COL1A2, and COL6A3, respectively. Treatment of DFAT cells with TGF-β1 increased the phosphorylation level of SMAD 2 and SMAD 3. Thus, a new six-well plate model for ceiling culture allowed us to demonstrate a role for TGF-β in modulating collagen gene expression during dedifferentiation of mature adipocytes.


Tumor protein p63/nuclear factor κB feedback loop in regulation of cell death.
Tumor protein (TP)-p53 family members often play proapoptotic roles, whereas nuclear factor κB (NF-κB) functions as a proapoptotic and antiapoptotic regulator depending on the cellular environment. We previously showed that the NF-κB activation leads to the reduction of the TP63 isoform, ΔNp63α, thereby rendering the cells susceptible to cell death upon DNA damage. However, the functional relationship between TP63 isotypes and NF-κB is poorly understood. Here, we report that the TAp63 regulates NF-κB transcription and protein stability subsequently leading to the cell death phenotype. We found that TAp63α induced the expression of the p65 subunit of NF-κB (RELA) and target genes involved in cell cycle arrest or apoptosis, thereby triggering cell death pathways in MCF10A cells. RELA was shown to concomitantly modulate specific cell survival pathways, making it indispensable for the TAp63α-dependent regulation of cell death. We showed that TAp63α and RELA formed protein complexes resulted in their mutual stabilization and inhibition of the RELA ubiquitination. Finally, we showed that TAp63α directly induced RelA transcription by binding to and activating of its promoter and, in turn, leading to activation of the NF-κB-dependent cell death genes. Overall, our data defined the regulatory feedback loop between TAp63α and NF-κB involved in the activation of cell death process of cancer cells.


Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release.
The responses of cloned human NK cells (ERNK57) to seven CC chemokines (monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and 1309) and two CXC chemokines (IL-8 and IP-10) were studied. Except for 1309, all CC chemokines induced chemotaxis of the NK cells in vitro, whereas the CXC chemokines were inactive. Maximal activity was obtained at 1 nM for MCP-1 and 10 to 100 nM for the other CC chemokines. The response showed a typically bimodal concentration dependence in all cases, except for RANTES, which induced a linear increase of migration over the concentration range of 0.1 to 1000 nM. A transient rise of the cytosolic-free Ca2+ concentration ([Ca2+]i), which is characteristic for chemokine-stimulated leukocytes, was observed in NK cells after stimulation with all six active chemokines. Since granule exocytosis is required for NK cell-dependent target killing, the effect of CC chemokines on exocytosis was tested. All CC chemokines that induced chemotaxis and [Ca2+]i changes also induced the release of granzyme A and N-acetyl-beta-D-glucosaminidase from cloned and blood NK cells, as well as CD8+ T cells after pretreatment with cytochalasin B. Maximum release was obtained from NK cells, and amounted to 35% and 13% of the total content of granzyme A and N-acetyl-beta-D-glucosaminidase, respectively. The capacity of cloned NK cells and CD8+ T cells to respond to chemokines depended on the time in culture after stimulation with PHA in the presence of irradiated feeder cells, and maximum responses were observed after 10 to 16 days. Our results demonstrate that CC chemokines activate NK cells, and are, therefore, not only attractants for monocytes, T lymphocytes, and eosinophil and basophil granulocytes.


A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity.
As part of a large scale effort to discover novel secreted proteins, a cDNA encoding a novel cytokine was identified. Alignments of the sequence of the new protein, designated IL-17B, suggest it to be a homolog of the recently described T cell-derived cytokine, IL-17. By Northern analysis, EST distribution and real-time quantitative polymerase chain reaction analysis, mRNA was detected in many cell types. A novel type I transmembrane protein, identified in an EST data base by homology to IL-17R, was found to bind specifically IL-17B, as determined by surface plasmon resonance analysis, flow cytometry, and co-immunoprecipitation experiments. Readily detectable transcription of IL-17BR was restricted to human kidney, pancreas, liver, brain, and intestines and only a few of the many cell lines tested. By using a rodent ortholog of IL-17BR as a probe, IL-17BR message was found to be drastically up-regulated during intestinal inflammation elicited by indomethacin treatment in rats. In addition, intraperitoneal injection of IL-17B purified from Chinese hamster ovary cells caused marked neutrophil migration in normal mice, in a specific and dose-dependent manner. Together these results suggest that IL-17B may be a novel proinflammatory cytokine acting on a restricted set of target cell types. They also demonstrate the strength of genomic approaches in the unraveling of novel biological pathways.


Short-term Music Training Enhances Complex, Distributed Neural Communication during Music and Linguistic Tasks.
Musical training is frequently associated with benefits to linguistic abilities, and recent focus has been placed on possible benefits of bilingualism to lifelong executive functions; however, the neural mechanisms for such effects are unclear. The aim of this study was to gain better understanding of the whole-brain functional effects of music and second-language training that could support such previously observed cognitive transfer effects. We conducted a 28-day longitudinal study of monolingual English-speaking 4- to 6-year-old children randomly selected to receive daily music or French language training, excluding weekends. Children completed passive EEG music note and French vowel auditory oddball detection tasks before and after training. Brain signal complexity was measured on source waveforms at multiple temporal scales as an index of neural information processing and network communication load. Comparing pretraining with posttraining, musical training was associated with increased EEG complexity at coarse temporal scales during the music and French vowel tasks in widely distributed cortical regions. Conversely, very minimal decreases in complexity at fine scales and trends toward coarse-scale increases were displayed after French training during the tasks. Spectral analysis failed to distinguish between training types and found overall theta (3.5-7.5 Hz) power increases after all training forms, with spatially fewer decreases in power at higher frequencies (>10 Hz). These findings demonstrate that musical training increased diversity of brain network states to support domain-specific music skill acquisition and music-to-language transfer effects.


The Drosophila homeotic target gene centrosomin (cnn) encodes a novel centrosomal protein with leucine zippers and maps to a genomic region required for midgut morphogenesis.
The products of the homeotic genes in Drosophila are transcription factors that are necessary to impose regional identity along the anterior-posterior axis of the developing embryo. However, the target genes under homeotic regulation that control this developmental process are largely unknown. We have utilized an immunopurification method to clone target genes of the Antennapedia protein (ANTP). We present here the characterization of centrosomin (cnn), one of the target genes isolated using this approach. The spatial and temporal expression of the cnn gene in the developing visceral mesoderm (VM) of the midgut and the central nervous system (CNS) of wild-type and homeotic mutant embryos is consistent with the idea that cnn is a homeotic target. In the VM, Antp and abdominal-A (abd-A) negatively regulate cnn, while Ultrabithorax (Ubx) shows positive regulation. In the CNS, cnn is regulated positively by Antp and negatively by Ubx and abd-A. Characterization of a cDNA encoding CNN predicts a novel structural protein with three leucine zipper motifs and several coiled-coil domains exhibiting limited homology to the rod portion of myosin. Immunocytochemical results demonstrate that the cnn encoded protein is localized to the centrosome and the accumulation pattern is coupled to the nuclear and centrosome duplication cycles of cleavage. In addition, evidence suggests that the expression of the cnn gene in the VM correlates with the morphogenetic function of Ubx in that tissue, i.e., the formation of the second midgut construction. The centrosomal localization of CNN and the involvement of microtubules in midgut morphogenesis suggest that this protein may participate in mitotic spindle assembly and the mechanics of morphogenesis through an interaction with microtubules, either directly or indirectly.


Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.
Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension < 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics.


Water-Permeable Dialysis Membranes for Multi-Layered Microdialysis System.
This paper presents the development of water-permeable dialysis membranes that are suitable for an implantable microdialysis system that does not use dialysis fluid. We developed a microdialysis system integrating microfluidic channels and nanoporous filtering membranes made of polyethersulfone (PES), aiming at a fully implantable system that drastically improves the quality of life of patients. Simplicity of the total system is crucial for the implantable dialysis system, where the pumps and storage tanks for the dialysis fluid pose problems. Hence, we focus on hemofiltration, which does not require the dialysis fluid but water-permeable membranes. We investigated the water permeability of the PES membrane with respect to the concentrations of the PES, the additives, and the solvents in the casting solution. Sufficiently, water-permeable membranes were found through in vitro experiments using whole bovine blood. The filtrate was verified to have the concentrations of low-molecular-weight molecules, such as sodium, potassium, urea, and creatinine, while proteins, such as albumin, were successfully blocked by the membrane. We conducted in vivo experiments using rats, where the system was connected to the femoral artery and jugular vein. The filtrate was successfully collected without any leakage of blood inside the system and it did not contain albumin but low-molecular-weight molecules whose concentrations were identical to those of the blood. The rat model with renal failure showed 100% increase of creatinine in 5 h, while rats connected to the system showed only a 7.4% increase, which verified the effectiveness of the proposed microdialysis system.


A parallel-group, randomized controlled trial into the effectiveness of Mindfulness-Based Compassionate Living (MBCL) compared to treatment-as-usual in recurrent depression: Trial design and protocol.
Mindfulness Based Cognitive Therapy (MBCT) has been shown to reduce the risk of relapse in patients with recurrent depression, but relapse rates remain high. To further improve outcome for this group of patients, follow-up interventions may be needed. Compassion training focuses explicitly on developing self-compassion, one of the putative working mechanisms of MBCT. No previous research has been done on the effectiveness of compassion training following MBCT in patients with recurrent depression. To investigate the effectiveness of Mindfulness-Based Compassionate Living (MBCL) in reducing (residual) depressive symptoms in patients with recurrent depression who previously participated in MBCT. A randomized controlled trial comparing MBCL in addition to treatment as usual (TAU) with TAU only, in patients suffering from recurrent depressive episodes who completed an MBCT course in the past. Assessments will take place at baseline, post-treatment and at six months follow-up. After the control period, patients randomized to the TAU condition will be offered MBCL as well. Primary outcome measure is severity of depressive symptoms according to the Beck Depression Inventory-II (BDI-II) at post-treatment. Secondary outcome measures are presence or absence of DSM-IV depressive disorder, rumination, self-compassion, mindfulness skills, positive affect, quality of life, experiential avoidance and fear of self-compassion. Our study is the first randomized controlled trial to examine the effectiveness of compassion training following MBCT in a recurrently depressed population. ClinicalTrials.gov: NCT02059200, registered 30 January 2014.


Paternal Inheritance of Bisphenol A Cardiotoxic Effects: The Implications of Sperm Epigenome.
Parental exposure to bisphenol A (BPA) has been linked to a greater incidence of congenital diseases. We have demonstrated that BPA induces in zebrafish males an increase in the acetylation of sperm histones that is transmitted to the blastomeres of the unexposed progeny. This work is aimed to determine whether histone hyperacetylation promoted by paternal exposure to BPA is the molecular mechanism underlying the cardiogenesis impairment in the descendants. Zebrafish males were exposed to 100 and 2000 µg/L BPA during early spermatogenesis and mated with non-exposed females. We analyzed in the progeny the expression of genes involved in cardiogenesis and the epigenetic profile. Once the histone hyperacetylation was confirmed, treatment with epigallocatechin gallate (EGCG), an inhibitor of histone acetyltransferases, was assayed on F1 embryos. Embryos from males exposed to 2000 µg/L BPA overexpressed the transcription factor hand2 and the receptor esr2b, showing their own promoters-as well as that of kat6a-an enrichment in H3K9ac. In embryos treated with EGCG, both gene expression and histone acetylation (global and specific) returned to basal levels, and the phenotype was recovered. As shown by the results, the histone hyperacetylated landscape promoted by BPA in the sperm alters the chromatin structure of the progeny, leading to the overexpression of the histone acetyltransferase and genes involved in cardiogenesis.


Emergency room closed reduction versus in situ splinting in the treatment of paediatric supracondylar humerus fractures.
Displaced supracondylar humerus fractures are treated with open or closed reduction and percutaneous pinning. In 2012, our management of patients with a displaced fracture changed from closed reduction in the emergency department (ED) to in situ splinting prior to closed reduction and pinning in the operating room (OR). The purpose of this study was to investigate if outcomes or complications differ between these two management methods. Patients less than ten years old with a Gartland type II or III supracondylar humerus fracture between 2008 and 2016 were included. Cases of polytrauma were excluded. Radiographic outcomes were assessed at follow-up. The Fisher's exact test was used for categorical variables and the Wilcoxon rank sums tests for continuous variables. In all, 157 patients were included, 89 with reduction in the ED and 68 without. There was no significant difference between the groups related to demographic factors or fracture characteristics. Patients managed without reduction in the ED had a lower average delay from ED to OR compared with those treated with reduction (16 hours versus 22 hours, p < 0.005) and a shorter hospital length of stay (34 hours versus 40 hours, p < 0.005). No difference in complications or outcomes was found between patients with Type II or III supracondylar fractures treated initially with or without closed reduction in the ED. Patients treated without ED reduction were taken to the OR sooner and remained in the hospital for a shorter period of time. Splinting in situ reduces anaesthesia exposure without increasing postoperative complications or suboptimal outcomes. Level III, retrospective comparative study.


Trends in food availability determined by the Food and Agriculture Organization's food balance sheets in Mediterranean Europe in comparison with other European areas.
The aims of this study were to assess the changes that have occurred in food patterns in Europe over the last 40 years based on food availability data and to compare the stability of the traditional Mediterranean diet in the south of Europe in this period. An ecological study carried out on the basis of Food and Agriculture Organization food balance sheets for three geographical areas of Europe (Mediterranean, north and east) over two time periods: 1961-1963 and 1998-2000. The average availability of total energy, energy provided from macronutrients and food groups was calculated for each area and each period studied. Over the last 40 years total energy availability and energy availability from lipids have increased considerably in the three European areas, while the percentage of energy from carbohydrates has fallen. The greatest changes have occurred in Mediterranean Europe, with an increase of 20.1% in total energy availability, an increase of 48.1% in energy availability from lipids and a fall of 20.5% from carbohydrates. Moreover, Mediterranean Europe showed a significant fall in the energy supplied by cereals (29.9%) and wine (55.2%), while the contribution of milk (77.8%) and dairy products (23.6%) increased. The results of this study suggest that European Mediterranean countries should take nutrition policy action to maintain their traditional healthy food pattern, with a cultural added value. This implies actions at all levels, including raising awareness of consumers, collaboration with the food sector and a call to set the agenda of the concerned politicians and stakeholders.


Staying physically active after spinal cord injury: a qualitative exploration of barriers and facilitators to exercise participation.
While enhancing physical activity has been an essential goal of public health officials, people with physical impairments such as spinal cord injury (SCI) are more likely to live a sedentary lifestyle. Exercise has been shown to decrease the risk for many of the secondary conditions associated with SCI, including osteoporosis, cardiovascular disease, pressure ulcers, urinary tract infections, diabetes and arthritis, yet this population is rarely a target for health promotion efforts. This paper examines the self-reported exercise experiences of people with SCI using a qualitative-exploratory design. We enrolled 26 individuals with SCI (15 self-described 'exercisers' and 11 'non-exercisers') from a non-random pool of survey responders. Semi-structured phone interviews were conducted to record participants' experiences with exercise pre/post injury, barriers and facilitators to being active and perceived health impact. Regardless of exercise status, all participants reported physical activity prior to injury and expressed interest in becoming active or maintaining an active lifestyle. Participants identified a range of both motivational and socio-environmental factors that were either facilitating or constraining of such a lifestyle. Non-exercisers identified barriers to exercise, including a perceived low return on physical investment, lack of accessible facilities, unaffordable equipment, no personal assistance and fear of injury. Exercisers identified facilitators, including personal motivation, independence, availability of accessible facilities and personal assistants, fear of health complications, and weight management. Exercisers associated a greater range of specific health benefits with being active than non-exercisers. Despite motivation and interest in being exercise active, people with SCI face many obstacles. Removal of barriers coupled with promotion of facilitating factors, is vital for enhancing opportunities for physical activity and reducing the risk of costly secondary conditions in this population.


An iterative L1-based image restoration algorithm with an adaptive parameter estimation.
Regularization methods for the solution of ill-posed inverse problems can be successfully applied if a right estimation of the regularization parameter is known. In this paper, we consider the L(1)-regularized image deblurring problem and evaluate its solution using the iterative forward-backward splitting method. Based on this approach, we propose a new adaptive rule for the estimation of the regularization parameter that, at each iteration, dynamically updates the parameter value, following the evolution of the objective functional. The iterative algorithm automatically stops, without requiring any assumption about the perturbation process, when the parameter has reached a seemingly near optimal value. In spite of the fact that the optimality of this value has not yet been theoretically proved, a large number of numerical experiments confirm that the proposed rule yields restoration results competitive with those of the best state-of-the-art algorithms.


Effect of long-term cannabis use on axonal fibre connectivity.
Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The aim of this study was to examine axonal fibre pathways across the brain for evidence of microstructural alterations associated with long-term cannabis use and to test whether age of regular cannabis use is associated with severity of any microstructural change. To this end, diffusion-weighted magnetic resonance imaging and brain connectivity mapping techniques were performed in 59 cannabis users with longstanding histories of heavy use and 33 matched controls. Axonal connectivity was found to be impaired in the right fimbria of the hippocampus (fornix), splenium of the corpus callosum and commissural fibres. Radial and axial diffusivity in these pathways were associated with the age at which regular cannabis use commenced. Our findings indicate long-term cannabis use is hazardous to the white matter of the developing brain. Delaying the age at which regular use begins may minimize the severity of microstructural impairment.


A new combined method of stable isotope-labeling derivatization-ultrasound-assisted dispersive liquid-liquid microextraction for the determination of neurotransmitters in rat brain microdialysates by ultra high performance liquid chromatography tandem mass spectrometry.
In this work, for the first time, a new hyphenated technique of stable isotope-labeling derivatization-ultrasound-assisted dispersive liquid-liquid microextraction has been developed for the simultaneous determination of monoamine neurotransmitters (MANTs) and their biosynthesis precursors and metabolites. The developed method was based on ultra high performance liquid chromatography tandem mass spectrometry detection using multiple-reaction monitoring mode. A pair of mass spectrometry sensitizing reagents, d0-10-methyl-acridone-2-sulfonyl chloride and d3-10-methyl-acridone-2-sulfonyl chloride, as stable isotope probes was utilized to facilely label neurotransmitters, respectively. The heavy labeled MANTs standards were prepared and used as internal standards for quantification to minimize the matrix effects in mass spectrometry analysis. Low toxic bromobenzene (extractant) and acetonitrile (dispersant) were utilized in microextraction procedure. Under the optimized conditions, good linearity was observed with the limits of detection (S/N>3) and limits of quantification (S/N>10) in the range of 0.002-0.010 and 0.015-0.040nmol/L, respectively. Meanwhile, it also brought acceptable precision (4.2-8.8%, peak area RSDs %) and accuracy (recovery, 96.9-104.1%) results. This method was successfully applied to the simultaneous determination of monoamine neurotransmitters and their biosynthesis precursors and metabolites in rat brain microdialysates of Parkinson's disease and normal rats. This provided a new method for the neurotransmitters related studies in the future.


Merging species? Evidence for hybridization between the eel parasites Anguillicola crassus and A. novaezelandiae (Nematoda, Anguillicolidea).
The eel parasitic nematodes Anguillicola crassus (originating from Asia) and Anguillicola novaezelandiae (originating from New Zealand) were both introduced to Europe, but occurred in sympatry only in Lake Bracciano in Italy, where they both infected the European eel (Anguilla anguilla). A. novaezelandiae was introduced to the lake in 1975 and disappeared soon after A. crassus was also found there in 1993. We tested the hypothesis if hybridization of the two species might be an explanation for the findings at Lake Bracciano. After laboratory infection of one European eel with 10 third stage larvae of each parasite, two living female and 4 male adults of each species were found to co-occur in the swim bladder after 222 days post exposure. In 9 out of 17 eggs, isolated in total from uteri of the two A. novaezelandiae females, alleles were detected by microsatellite analysis that are characteristic for A. crassus, suggesting the hybrid origin of these eggs. In contrast, none of the eggs isolated from A. crassus females possessed alleles different from those found in A. crassus adults, but it was revealed that one female can be inseminated by several males. Our results show that A. crassus and A. novaezelandiae can co-infect a single eel and can mature together in the same swim bladder. We also provide evidence for the possibility of hybridization of A. crassus males with A. novaezelandiae females. Therefore, hybridization might be an explanation for the disappearance of A. novaezelandiae from Lake Bracciano.


Serum prostate specific antigen is a strong predictor of future prostate growth in men with benign prostatic hyperplasia. PROSCAR long-term efficacy and safety study.
We analyze patterns of prostate growth in men diagnosed with benign prostatic hyperplasia (BPH) and treated with placebo during 4 years, and determine which baseline parameters were the strongest predictors of growth. A total of 3,040 men were enrolled in the 4-year randomized, placebo controlled Proscar Long-Term Efficacy and Safety study. Of these men a subgroup of 10% underwent pelvic magnetic resonance imaging prostate volume measurement at baseline and yearly thereafter. Absolute and percent volume changes during 4 years were calculated in the 164 placebo treated men in the subgroup. The ability of age, baseline prostate volume and prostate specific antigen (PSA) to predict prostate growth in placebo treated patients was assessed by multiple linear regression analyses, receiver operator characteristics curves, and evaluations of growth stratified by tertiles of baseline serum PSA and decades of life. In placebo treated patients a steady increase in mean plus or minus standard deviation prostate volume from year to year was noted (2.5+/-6.1, 4.9+/-6.8, 6.4+/-8.5 and 7.2+/-8.8 ml. at years 1, 2, 3 and 4, respectively). Mean volume changes at 4 years ranged from -9 to +30 ml. Mean percent change from baseline ranged from 12.5% to 16.6% for men 50 to 59 years old to those 70 to 79 years old. Baseline serum PSA was a strong predictor of growth with 7.4% to 22.0% change at 4 years from the lowest to highest PSA tertiles. Annualized growth rates from baseline were 0.7 ml. per year for PSA 0.2 to 1.3, 2.1 for PSA 1.4 to 3.2 and 3.3 for PSA 3.3 to 9.9 ng./ml. Multiple linear regression analysis showed that serum PSA was a stronger predictor of prostate growth than age or baseline prostate volume. All but 1 man with baseline serum PSA greater than 2.0 ng./ml. had prostate growth during 4 years, and 32.6% of men with serum PSA less than 2.0 exhibited a decrease in volume. Serum PSA is a stronger predictor of growth of the prostate in placebo treated patients than age or baseline prostate volume. Since prostate volume is a risk factor for acute urinary retention and the need for BPH related surgery, the ability of PSA to predict prostate growth may be an important factor when considering individual treatment options for BPH. Such use of PSA represents a shift in paradigm away from focusing solely on symptoms of BPH toward a more comprehensive approach with consideration of predicting and preventing risk factors of BPH related outcomes.


Tubulin and microtubules in cochlear hair cells: comparative immunocytochemistry and ultrastructure.
The distribution of tubulin has been investigated in surface preparations of the guinea pig organ of Corti using indirect immunofluorescence microscopy. Two different monoclonal antibodies to tubulin produce similar distinct patterns of labelling in hair cells. Labelling is greater in inner hair cells than outer hair cells. It occurs in rings around the cell apex, and in a meshwork below and channels through, the cuticular plate. In outer hair cells from the apical region of the cochlea, labelling occurs around the location of a basalward protrusion of the cuticular plate. These patterns correlate with the location of microtubules observed using transmission electron microscopy. A large patch of labelling occurs on the strial side of the cell corresponding to the largest channel through the cuticular plate and the kinociliary basal body. Strands of labelling are seen running parallel to the long axis of the cell between the subcuticular and synaptic region. Many more of these strands are seen in the inner hair cell than the outer hair cell and may correspond to tracks of microtubules transporting neurotransmitter vesicles or other organelles. In outer hair cells, intense labelling and many microtubules are seen in the subnuclear region. The possible roles of the different microtubule arrangements are discussed.


Relative toxicity of analgesics commonly used for intentional self-poisoning: A study of case fatality based on fatal and non-fatal overdoses.
Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. Using data for 2005-2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine (co-codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. Compared to paracetamol and based on single drug deaths the case fatality index of dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19-16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38-4.85) and codeine (OR 2.21, 95% CI 1.81-2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.


Treatment of oilfield wastewater by combined process of micro-electrolysis, Fenton oxidation and coagulation.
In this study, a combined process was developed that included micro-electrolysis, Fenton oxidation and coagulation to treat oilfield fracturing wastewater. Micro-electrolysis and Fenton oxidation were applied to reduce chemical oxygen demand (COD) organic load and to enhance organic components gradability, respectively. Orthogonal experiment were employed to investigate the influence factors of micro-electrolysis and Fenton oxidation on COD removal efficiency. For micro-electrolysis, the optimum conditions were: pH, 3; iron-carbon dosage, 50 mg/L; mass ratio of iron-carbon, 2:3; reaction time, 60 min. For Fenton oxidation, a total reaction time of 90 min, a H2O2 dosage of 12 mg/L, with a H2O2/Fe2+ mole ratio of 30, pH of 3 were selected to achieve optimum oxidation. The optimum conditions in coagulation process: pH, cationic polyacrylamide dosage, mixing speed and time is 4.3, 2 mg/L, 150 rpm and 30 s, respectively. In the continuous treatment process under optimized conditions, the COD of oily wastewater fell 56.95%, 46.23%, 30.67%, respectively, from last stage and the total COD removal efficiency reached 83.94% (from 4,314 to 693 mg/L). In the overall treatment process under optimized conditions, the COD of oily wastewater was reduced from 4,314 to 637 mg/L, and the COD removal efficiency reached 85.23%. The contribution of each stage is 68.45% (micro-electrolysis), 24.07% (Fenton oxidation), 7.48% (coagulation), respectively. Micro-electrolysis is the uppermost influencing process on COD removal. Compared with the COD removal efficiency of three processes on raw wastewater under optimized conditions: the COD removal efficiency of single micro-electrolysis, single Fenton oxidation, single coagulation is 58.34%, 44.88% and 39.72%, respectively. Experiments proved the effect of combined process is marvelous and the overall water quality of the final effluent could meet the class III national wastewater discharge standard of petrochemical industry of China (GB8978-1996).


Formamide-Free Genomic in situ Hybridization Allows Unambiguous Discrimination of Highly Similar Parental Genomes in Diploid Hybrids and Allopolyploids.
Polyploidy and hybridization play an important role in plant diversification and speciation. The application of genomic in situ hybridization (GISH) allows the identification of parental genomes in hybrids, thus elucidating their origins and allowing for analysis of their genomic evolution. The performance of GISH depends on the similarity of the parental genomes and on the age of hybrids. Here, we present the formamide-free GISH (ff-GISH) protocol applied to diploid and polyploid hybrids of monocots (Prospero, Hyacinthaceae) and dicots (Melampodium, Asteraceae) differing in similarity of the parental genomes and in chromosome and genome sizes. The efficiency of the new protocol is compared to the standard GISH protocol. As a result, ff-GISH allowed efficient labeling and discrimination of the parental chromosome sets in diploid and allopolyploid hybrids in Prospero autumnale species complex. In contrast, the standard GISH protocol failed to differentiate the parental genomes due to high levels of similar repetitive DNA. Likewise, an unambiguous identification of parental genomes in allotetraploid Melampodium nayaritense (Asteraceae) was possible after ff-GISH, whereas the standard GISH hybridization performance was suboptimal. The modified method is simple and non-toxic and allows the discrimination of very similar parental genomes in hybrids. This method lends itself to modifications and improvements and can also be used for FISH.


Incidence and clinical features of asymptomatic meningiomas.
The increased use of computerized tomography (CT) and magnetic resonance (MR) technology has led to an increase in the detection of asymptomatic meningiomas, although the surgical indication for these tumors remains undetermined. The authors investigated the incidence of asymptomatic meningiomas and their clinical features. An epidemiological survey was conducted of primary intracranial tumors diagnosed in Kumamoto Prefecture between 1989 and 1996. Follow-up neuroradiological imaging and clinical studies for asymptomatic meningiomas were performed. Primary intracranial tumors were diagnosed in 1,563 residents. Of these lesions, 504 (32.2%) were meningiomas, and of these meningiomas 196 (38.9%) were asymptomatic. The incidence of asymptomatic meningiomas was significantly higher in individuals older than 70 years of age. Furthermore, the incidence of asymptomatic meningiomas was significantly higher in female than in male patients. Of the asymptomatic meningiomas in 196 patients, 87 (44.4%) were surgically removed, whereas 109 (55.6%) were treated conservatively. Of these conservatively treated patients, 63 received follow-up care for more than 1 year. In 20 of these 63 cases, the tumors increased in size over the 27.8-month average follow-up period (range 12-87 months), whereas in the other 43 cases, the tumor size did not increase during a 36.6-month average follow-up period (range 12-96 months). There was no significant difference with respect to age, tumor size, and male/female ratio between the patient group in which the tumor size increased and the group in which it did not increase during the follow-up period. Asymptomatic meningiomas that evidenced calcification on CT scans and/or hypointensity on T2-weighted MR images appear to have a slower growth rate. Among patients older than age 70 years who underwent operation for asymptomatic meningioma, the neurological morbidity rate was 23.3%; it was 3.5% among younger patients. This indicates that the advisability of surgery in elderly patients with asymptomatic meningiomas must be considered very carefully.


PARP1 is required for chromosomal translocations.
Chromosomal translocations are common contributors to malignancy, yet little is known about the precise molecular mechanisms by which they are generated. Sequencing translocation junctions in acute leukemias revealed that the translocations were likely mediated by a DNA double-strand break repair pathway termed nonhomologous end-joining (NHEJ). There are major 2 types of NHEJ: (1) the classical pathway initiated by the Ku complex, and (2) the alternative pathway initiated by poly ADP-ribose polymerase 1 (PARP1). Recent reports suggest that classical NHEJ repair components repress translocations, whereas alternative NHEJ components were required for translocations. The rate-limiting step for initiation of alternative NHEJ is the displacement of the Ku complex by PARP1. Therefore, we asked whether PARP1 inhibition could prevent chromosomal translocations in 3 translocation reporter systems. We found that 2 PARP1 inhibitors or repression of PARP1 protein expression strongly repressed chromosomal translocations, implying that PARP1 is essential for this process. Finally, PARP1 inhibition also reduced both ionizing radiation-generated and VP16-generated translocations in 2 cell lines. These data define PARP1 as a critical mediator of chromosomal translocations and raise the possibility that oncogenic translocations occurring after high-dose chemotherapy or radiation could be prevented by treatment with a clinically available PARP1 inhibitor.


Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression.
Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and CS treatment induced increased expression of Duox-1, and silencing of Doux-1 improved the rate of cell wound repair induced by CSE treatment. Nuli-1 cells pretreated with thapsigargin but not calcium ionophore exhibited increased Duox-1 mRNA expression. CSE treatment stimulated PKCα activation, which was effectively blocked by pretreatment with diphenylene iodonium, a NADPH oxidase inhibitor. Compared to control, lungs from CS-exposed mice showed a significant increase in PKCα activity and Duox-1 expression. Collectively, the data demonstrated that CS exposure upregulates expression of Duox-1 protein. This further leads to H2O2 production and PKCα activation, inhibiting A2AAR-stimulated wound repair.


Climbing Brain Levels of Organisation from Genes to Consciousness.
Given the tremendous complexity of brain organisation, here I propose a strategy that dynamically links stages of brain organisation from genes to consciousness, at four privileged structural levels: genes; transcription factors (TFs)-gene networks; synaptic epigenesis; and long-range connectivity. These structures are viewed as nested and reciprocally inter-regulated, with a hierarchical organisation that proceeds on different timescales during the course of evolution and development. Interlevel bridging mechanisms include intrinsic variation-selection mechanisms, which offer a community of bottom-up and top-down models linking genes to consciousness in a stepwise manner.


Fracture of the knee endoprosthesis. Report of three cases of tibial component failure.
Three cases of total knee replacement, in which the polyethylene tibial component was fractured, are presented. Two were Attenborough prostheses and the third was a Townley prosthesis. In all cases there were radiographic signs of loosening before the fracture occurred. They were all successfully reoperated with an arthrodesis, using the long Küntscher nail technique.


Antiallergic effect of flavonoid glycosides obtained from Mentha piperita L.
Six flavonoid glycosides, eriocitrin (1), narirutin (2), hesperidin (3), luteolin-7-O-rutinoside (4), isorhoifolin (5), diosmin (6), rosmarinic acid (7) and 5,7-dihydroxycromone-7-O-rutinoside (8), were isolated from the aerial part of Mentha piperita L. Among these compounds, compound 4 showed a potent inhibitory effect on histamine release induced by compound 48/80 and antigen-antibody reaction. This compound was more effective than luteolin and luteolin-7-O-glucoside in inhibiting histamine release from rat peritoneal mast cells. Compound 4 also caused a dose-related inhibition of the antigen-induced nasal response and significant effects were observed at doses of 100 and 300 mg/kg. These results indicate that compound 4 may be clinically useful in alleviating the nasal symptoms of allergic rhinitis.


Taxonomy and evolutionary relationships within species of section Rimosae (Inocybe) based on ITS, LSU and mtSSU sequence data.
The present study aimed at elucidating the structure of Inocybe subg. Inosperma sect. Rimosae but included also representatives from subg. Mallocybe and the genus Auritella. Phylogenetic relationships were inferred using ITS, LSU and mtSSU sequence data. The analyses recovered the ingroup as a monophyletic, strongly supported clade. The results indicate that recognizing Auritella on the genus level renders Inocybe paraphyletic. The species traditionally placed in sect. Rimosae were found to be distributed over two strongly supported clades, Maculata and Rimosae s.s. The Maculata clade clusters with sect. Cervicolores and the two represent subg. Inosperma in a strict sense. Rimosae s.s. emerges as an independent, supported clade well separated from Inosperma s.s. Twenty-one terminal groups were correlated with morphologically distinct species. In addition several taxa on single branches and minor less supported clades were recovered. A key to the identified species of the Maculata and Rimosae s.s. clades which occur in Northwest Europe is provided.