[Dietary fiber and OGTT: blood sugar variations after administration of a new purified glucomannane].
After having stressed the importance of fibres in the nutritional field, pointing out the inverse relationship between vegetal fibres consumption in various populations and diffusion of many diseases of the so-called "industrialized" societies (such as obesity, diabetes, dyslipidemias, atherosclerosis, cholelithiasis, cancer of the colon, etc.), the Authors report their experiment on a new experimental product based on glucomannane purified (PRL). The present study was carried out on 24 obese subjects (5 males and 19 females). The patients, normoglycemics in their basic condition, were submitted to OGTT with 75 g of glucose in the morning before eating and were subdivided into two groups, the first (Group A) characterized by the sequence OGTT + placebo; after a few days, by another OGTT + experimental product; the second characterized by the inverse sequence. Four tablets (glucomannane purified 5,2 g) and four tablets of placebo was the posology employed. The evaluation of the possible action of the product in reducing or slowing down the intestinal absorption of glucose was the aim of the research. The results obtained show that the administration of the product under study has led to a sharp decrease of the average glycemic values with variations per cent ranging from 13% to 16% in Group A, from 10% to 11% in Group B and from 7% to 12% in the two groups considered on the whole. In conclusion, the Authors wish an increased diffusion of dietary fibres and particularly of the glucomannanes in all those dysmetabolic forms having at their bases an unbalanced, hypercaloric alimentation, rich in refined aliments and poor in fibres.


A Case of Luscan-Lumish Syndrome: Possible Involvement of Enhanced GH Signaling.
Luscan-Lumish syndrome (LLS) is characterized by postnatal overgrowth, obesity, Chiari I malformation, seizures, and intellectual disability. SET domain-containing protein 2 (SETD2) is a histone methyltransferase, where mutations in the gene are associated with the development of LLS. However, mechanisms underlying LLS remain unclear. A 20-year-old man was referred to our hospital because of tall stature. His body height was 188.2 cm (+3.18 SD) and he showed obesity with a body mass index of 28.4 kg/m2. He exhibited acral overgrowth, jaw malocclusion, and prognathism, but no history of seizures, intellectual disability, or speech delay. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and nadir GH levels after administration of 75 g oral glucose were within normal range. Pituitary magnetic resonance imaging showed no pituitary adenoma, but Chiari I malformation. Whole exome sequencing analysis of the proband revealed a de novo heterozygous germline mutation in SETD2 (c.236T>A, p.L79H). Skin fibroblasts derived from the patient grew faster than those from his father and the control subject. In addition, these cells showed enhanced tyrosine phosphorylation and transcriptional activity of signal transducer and activator of transcription 5b (STAT5b) and increased IGF-1 expression induced by GH. This is a mild case of LLS with a novel mutation in SETD2 without neurological symptoms. LLS should be differentiated in a patient with gigantism without pituitary tumors. Although further investigation is necessary, this is the first study to suggest the involvement of aberrant GH signaling in the development of LLS.


Sensation/novelty seeking in psychotic disorders: A review of the literature.
The evaluation of personality traits is important for the better understanding of the person suffering from psychosis and for treatment individualization. However literature on patients' personality and character in such disorders is limited. The aim of this review was to summarize the literature on sensation/novelty seeking (SNS), a trait which is biologically based and highly heritable and is associated with dopamine activity, and refers to a person's tendency to seek varied, novel, complex, and intense sensations and experiences. A total of 38 studies were included in this review, involving 2808 patients and 2039 healthy controls. There is consistent evidence that this trait is independently associated with alcohol and substance abuse in patients with schizophrenia and related disorders. The estimation of SNS would help clinicians to identify patients at risk for abuse. There is also some evidence that higher SNS levels may relate to medication non-adherence and seem to increase the risk of patients' aggressive and violent behavior, but studies are scarce. SNS was found not to be related to suicidality, whereas in the fields of patients' quality of life and psychopathology results are contradictory, but most studies show no possible association. Several studies suggest that SNS is lower in psychotic patients compared to controls, whereas most yield no differences. The evidence for this trait as a potential endophenotype of schizophrenia is weak. SNS may be implicated in psychotic disorders' course and prognosis in several ways and should be always inquired for. This trait can be reliably measured with the use of easily applicable self-rated instruments, and patients' accounts could inform clinicians when planning management and delivering individualized treatment.


Does the upgrading of the radio communications network in health facilities reduce the delay in the referral of obstetric emergencies in Southern Malawi?
Mwanza, Phalombe and Zomba districts in the Southern Region of Malawi. Radios have been installed in many health centers in the Southern Region of Malawi but communication is often indirect. Messages get re-channeled from one health center to another before reaching district hospitals. In an attempt to strengthen the obstetric referral system, the Safe Motherhood Project installed a repeater-based VHF radio communication system in three pilot districts. The overall goal of the new network was to enable the health centers to communicate directly to their district health offices (DHOs) for an ambulance when they have an emergency obstetric complication for referral to the hospital. This study aimed to determine whether or not improving the radio communications system reduces the delay in referral of obstetric emergencies from health center to hospital. Data collection was conducted between 2001 and 2003 using a range of data collection methods. Radio communications register books were placed at each participating health center to record information on all women with emergency obstetric complications referred to the hospital for further management. An obstetric referral form was completed on each woman referred to the hospital. And using the same referral form, the referral hospital was required to give feedback to the health centers on discharge of the patient. Existing maternity registers or HMIS registers were reviewed to obtain additional information not captured in radio communication registers. Interviews with health center staff were conducted to obtain their communication experiences before and after the new network was installed. The average number of obstetric admissions per month and the proportion of referrals in the participating health centers significantly increased during the post-intervention period. Significantly more emergency obstetric referrals were collected under 1 hour between decision to refer by the midwife at the health center and arrival of transport from the DHO or base station in the post-intervention period than pre-intervention period (p<0.02). However, some patients still waited for more than 13 hours for transportation in the post-intervention period. The median time interval between decision to refer and arrival of transport was 3 h. versus 2 h. 3 min. in the pre- and post-intervention periods respectively. This study has demonstrated that the new VHF radio network system has, without doubt, improved the radio communication system in the three pilot districts. However, although the time interval between the decision to refer and arrival of transport significantly improved after the intervention, the majority of transportation still took too long, particularly for someone with postpartum hemorrhage. It is very important to improve the management/control of obstetric ambulances at district level so as to complement efforts of an improved radio communication system in reducing delays in the referral of obstetric emergencies.


A diverse range of gene products are effectors of the type I interferon antiviral response.
The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago, only a few have been characterized with respect to antiviral activity. For most ISG products, little is known about their antiviral potential, their target specificity and their mechanisms of action. Using an overexpression screening approach, here we show that different viruses are targeted by unique sets of ISGs. We find that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities. To conduct the screen, more than 380 human ISGs were tested for their ability to inhibit the replication of several important human and animal viruses, including hepatitis C virus, yellow fever virus, West Nile virus, chikungunya virus, Venezuelan equine encephalitis virus and human immunodeficiency virus type-1. Broadly acting effectors included IRF1, C6orf150 (also known as MB21D1), HPSE, RIG-I (also known as DDX58), MDA5 (also known as IFIH1) and IFITM3, whereas more targeted antiviral specificity was observed with DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT (also known as PBEF1), OASL, RTP4, TREX1 and UNC84B (also known as SUN2). Combined expression of pairs of ISGs showed additive antiviral effects similar to those of moderate type I interferon doses. Mechanistic studies uncovered a common theme of translational inhibition for numerous effectors. Several ISGs, including ADAR, FAM46C, LY6E and MCOLN2, enhanced the replication of certain viruses, highlighting another layer of complexity in the highly pleiotropic type I interferon system.


Discounting health and cost-effectiveness analysis: a response to Nord.
Nord (2011) criticizes standard arguments which assert that consistency requires that future health benefits must be discounted at the same rate as future costs in cost-effectiveness analysis (CEA). He suggests these arguments are misguided because they require transitivity of preferences across decision contexts and that it can be appropriate to discount health at different rates depending on the programs to be compared. I claim that rejecting transitivity is unwarranted and would sharply diminish the utility of CEA. Factors that tempt Nord to reject consistency can be accommodated by recognizing that CEA does not perfectly mimic normative social preferences because it omits factors (like distribution of health in a population) that can be normatively significant. A better approach is to maintain consistency in application of CEA but authorize decision makers to depart from rankings implied by CEA when justified and to explain which specific factors justify the decision. Finally, the assertion that health must be discounted at the same rate as costs requires the additional assumption that the dollar value of health does not change over time, a point that is not always recognized in standard arguments.


Allogeneic endometrial regenerative cells: an "Off the shelf solution" for critical limb ischemia?
Critical limb ischemia (CLI) is an advanced form of peripheral artery disease which is responsible for approximately 100,000 amputations per year in the US. Trials to date have reported clinical improvement and reduced need for amputation in CLI patients receiving autologous bone marrow or mobilized peripheral blood stem cells for stimulation of angiogenesis. While such treatments are currently entering Phase III trials, practical and scientific pitfalls will limit widespread implementation if efficacy is proven. Hurdles to be overcome include: a) reduced angiogenic potential of autologous cells in aged patients with cardiovascular risk factors; b) invasiveness/adverse effects of bone marrow extraction and G-CSF mobilization, respectively; and c) need for on-site cellular manipulation. The Endometrial Regenerative Cell (ERC) is a mesenchymal-like stem cell derived from the menstrual blood that is believed to be associated with endometrial angiogenesis. We discuss the possibility of using allogeneic ERCs as an "off the shelf" treatment for CLI based on the following properties: a) High levels of growth factors and matrix metalloprotease production; b) Ability to inhibits inflammatory responses and lack of immunogenicity; and c) Expandability to great quantities without loss of differentiation ability or karyotypic abnormalities.


Intra- and intermuscular variation in human quadriceps femoris architecture assessed in vivo.
Despite the functional importance of the human quadriceps femoris in movements such as running, jumping, lifting and climbing, and the known effects of muscle architecture on muscle function, no research has fully described the complex architecture of this muscle group. We used ultrasound imaging techniques to measure muscle thickness, fascicle angle and fascicle length at multiple regions of the four quadriceps muscles in vivo in 31 recreationally active, but non-strength-trained adult men and women. Our analyses revealed a reasonable similarity in the superficial quadriceps muscles, which is suggestive of functional similarity (at least during the uni-joint knee extension task) given that they act via a common tendon. The deep vastus intermedius (VI) is architecturally dissimilar and therefore probably serves a different function(s). Architecture varies significantly along the length of the superficial muscles, which has implications for the accuracy of models that assume a constant intramuscular architecture. It might also have consequences for the efficiency of intra- and intermuscular force transmission. Our results provide some evidence that subjects with a given architecture of one superficial muscle, relative to the rest of the subject sample, also have a similar architecture in other superficial muscles. However, this is not necessarily true for vastus lateralis (VL), and was not the case for VI. Therefore, the relative architecture of one muscle cannot confidently be used to estimate the relative architecture of another. To confirm this, we calculated a value of whole quadriceps architecture by four different methods. Regardless of the method used, we found that the absolute or relative architecture of one muscle could not be used as an indicator of whole quadriceps architecture, although vastus medialis, possibly in concert with VL and the anterior portion of VI, could be used to provide a useful snapshot. Importantly, our estimates of whole quadriceps architecture show a gender difference in whole quadriceps muscle thickness, and that muscle thickness is positively correlated with fascicle angle whereas fascicle length is negatively, although weakly, correlated with fascicle angle. These results are supportive of the validity of estimates of whole quadriceps architecture. These data are interpreted with respect to their implications for neural control strategies, region-specific adaptations in muscle size in response to training, and gender-dependent differences in the response to exercise training.


Clinical Inquiry-In women who have undergone breast cancer surgery, including lymph node removal, do blood pressure measurements taken in the ipsilateral arm increase the risk of lymphedema?
Throughout the healthcare industry fears of taking blood pressure in the arms of patients who have undergone breast cancer surgery have been propagated for decades and continue to be recommended by multiple medical societies and healthcare organizations. However, these precautions are not well based on evidence-based medicine and may have a more historical and traditional basis. The purpose of this study was to review current evidence-based research as well as current guidelines regarding ipsilateral blood pressure measurements in women who have undergone breast surgery for cancer including lymph node removal.


Estimated lower speed boundary at which the walk ratio constancy is broken in healthy adults.
[Purpose] The ratio of step length to cadence (walk ratio) is invariant over a wide range of speeds. However, no studies have investigated details of the change in the walk ratio at slow speeds. It is necessary to explore how walking behavior changes at a low speed to understand the slow walking observed in various conditions such as aging and pathological conditions. In this study, changes in the walk ratio at slow speeds were investigated, and a lower boundary was estimated at which the walk ratio constancy is broken. [Subjects and Methods] Twenty-one healthy adults were instructed to walk along a flat, straight walkway at five different speeds (fast, preferred, slightly slow, slow, and very slow). The walk ratio was calculated from the step length and cadence. [Results] As the walking speed decreased, the walk ratio and variance began to increase abruptly. The initial break in the walk ratio constancy was at approximately 62 m/min. In addition, the boundary of cadence was approximately 98 m/steps/min. [Conclusions] The study successfully determined a lower boundary at which the walk ratio constancy was broken, suggesting that different control strategies are used when walking at less than the gait speed at which constancy is broken in healthy adults. The finding provides valuable information for understanding slow walking observed in individuals with various pathological conditions.


A novel mechanism of body mass regulation.
While significant attention has been devoted to the identification of hormonal factors that control body mass, little attention has been paid to the role of mechanical loading on animal mass. Here, we provide evidence that intraperitoneal implantation of metabolically inert mass results in a compensatory reduction in tissue mass. Deer mice (Peromyscus maniculatus) were surgically implanted with weights of 1, 2 or 3 g. There was a resulting loss of tissue mass (total body mass minus implant mass) that was proportional to the mass of the implant. This reduction in tissue mass followed a reduction in food intake in animals with 3 g implants. Evaluation of body composition failed to identify any single component that contributed to the loss of tissue mass. Removal of implants led to a transient restoration of body mass to levels similar to the total body mass of those control animals in which the implant had not been removed. However, within 12 days of implant removal, body mass again declined to the level seen before implant removal. These results suggest the existence of a set point that is sensitive to changes in the perception of mass and that is transduced via neural pathways.


Synthesis and self-assembly behavior of a biodegradable and sustainable soybean oil-based copolymer nanomicelle.
Herein, we report a novel amphiphilic biodegradable and sustainable soybean oil-based copolymer (SBC) prepared by grafting hydrophilic and biocompatible hydroxyethyl acrylate (HEA) polymeric segments onto the natural hydrophobic soybean oil chains. FTIR, H(1)-NMR, and GPC measurements have been used to investigate the molecular structure of the obtained SBC macromolecules. Self-assembly behaviors of the prepared SBC in aqueous solution have also been extensively evaluated by fluorescence spectroscopy and transmission electron microscopy. The prepared SBC nanocarrier with the size range of 40 to 80 nm has a potential application in the biomedical field.


Design and synthesis of a long-wavelength latent fluorogenic substrate for salicylate hydroxylase: a useful fluorimetric indicator for analyte determination by dehydrogenase-coupled biosensors.
Salicylate hydroxylase (SHL) catalyzes the production of catechol (plus CO(2) and H(2)O) from salicylate, NADH, and O(2). Coimmobilization of SHL with a NAD(P)(+)-dependent dehydrogenase in front of a Clark-type oxygen electrode has been investigated in the development of a general type of dehydrogenase-based biosensors that can detect various biological analytes; however, currently, no fluorophores are available for these applications. We synthesized the first new long-wavelength latent fluorogenic substrate SHLF (3) for SHL. In the presence of NADH and under aerobic conditions, SHL catalyzes the decarboxylative hydroxylation of SHLF followed by a quinone-methide-type rearrangement reaction concomitant with the ejection of a fluorescence coumarin 2, which is spontaneous and irreversible at physiological temperatures in aqueous media. The fluorescence signal generated by this process is specific and, in the near red spectral region with an emission maximum at 595 nm, is suppressed by salicylic acid. The fluorescence response of SHLF is insensitive to various biological reactive oxygen species (ROS) and reductants. Furthermore, SHLF is a sensitive fluorimetric indicator for analyte determination in the SHL-coupled dehydrogenase assay in which NAD(+) is converted to NADH. This novel fluorescence assay detected 3-hydroxybutyrate and cholesterol in the nanomolar range and is more sensitive than the current SHL-dehydrogenase amperometric sensors, making it applicable to the construction of a fiber-optic fluorescence biosensor for clinical diagnostic uses.


Presence of functional vasopressin receptors in spinal ventral horn neurons of young rats: a morphological and electrophysiological study.
The objective of the present work was double. (i) Light microscopic autoradiography was used to determine the distribution of vasopressin and oxytocin binding sites in the spinal cord of rats. (ii) Whole-cell recordings were performed in lumbar spinal cord slices in order to assess whether these receptors are functional, whether they are located pre- or postsynaptically and whether they are present in motoneurons. In newborns, vasopressin binding sites of the V1a type were present in all laminae of the central gray at all segmental levels, whereas oxytocin binding sites were found only in the superficial layers of the dorsal horn. In adults, binding sites for both neuropeptides were also present, but were less dense. The dissociation constants for vasopressin were similar in newborns and adults. Whole-cell recordings showed that in identified motoneurons vasopressin exerted a direct effect, by inducing a membrane depolarization or by generating a sustained inward current, and an indirect effect, by enhancing glycinergic and GABAergic inhibitory transmission. Vasopressin-induced facilitation of inhibitory transmission could also be demonstrated in unidentified ventral horn neurons. All these effects were mediated by V1a but not V1b receptors. In some neurons, glycinergic transmission was also facilitated by a selective oxytocin receptor agonist. Our data, together with data obtained previously in brainstem motor nuclei, suggest that vasopressin of hypothalamic origin could play a role in motricity. The neuropeptide could act as a neuromodulator, because it would not directly activate motoneurons, but rather render them more responsive to incoming excitatory inputs. Vasopressin may thus act as a regulator of muscular force.


Transcriptomic analysis of 'Suli' pear (Pyrus pyrifolia white pear group) buds during the dormancy by RNA-Seq.
Bud dormancy is a critical developmental process that allows perennial plants to survive unfavorable environmental conditions. Pear is one of the most important deciduous fruit trees in the world, but the mechanisms regulating bud dormancy in this species are unknown. Because genomic information for pear is currently unavailable, transcriptome and digital gene expression data for this species would be valuable resources to better understand the molecular and biological mechanisms regulating its bud dormancy. We performed de novo transcriptome assembly and digital gene expression (DGE) profiling analyses of 'Suli' pear (Pyrus pyrifolia white pear group) using the Illumina RNA-seq system. RNA-Seq generated approximately 100 M high-quality reads that were assembled into 69,393 unigenes (mean length = 853 bp), including 14,531 clusters and 34,194 singletons. A total of 51,448 (74.1%) unigenes were annotated using public protein databases with a cut-off E-value above 10-5. We mainly compared gene expression levels at four time-points during bud dormancy. Between Nov. 15 and Dec. 15, Dec. 15 and Jan. 15, and Jan. 15 and Feb. 15, 1,978, 1,024, and 3,468 genes were differentially expressed, respectively. Hierarchical clustering analysis arranged 190 significantly differentially-expressed genes into seven groups. Seven genes were randomly selected to confirm their expression levels using quantitative real-time PCR. The new transcriptomes offer comprehensive sequence and DGE profiling data for a dynamic view of transcriptomic variation during bud dormancy in pear. These data provided a basis for future studies of metabolism during bud dormancy in non-model but economically-important perennial species.


High-speed rotational atherectomy using the radial artery approach and a sheathless guide: a single-centre comparison with the "conventional" femoral approach.
This study retrospectively compares the in-hospital outcomes for patients undergoing high-speed rotational atherectomy (HSRA) facilitated percutaneous coronary intervention (PCI) using either the radial or the femoral artery approach. From September 2008 to February 2013, 135 consecutive patients (75 femoral, 60 radial) underwent HSRA in our centre. A comparison of in-hospital outcomes was performed. For the radial approach, a 7.5 Fr sheathless guiding catheter (SGC) was used. The sizing of the burrs deployed was similar (1.75 [0.75-2.00] vs. 1.75 [1.25-2.5] mm, p=0.68) with no difference in screening time (15.5 [12.2-19.5] vs. 19 [14-26] min, p=0.068), major access-site bleeding complications (0.0% vs. 1.3%, p>0.99) and procedural success (100% vs. 91%, p=0.22) in the radial and the femoral group, respectively. However, in-hospital stay [1 (0-5) vs. 1 (0-20) days, p=0.04] was slightly higher following the femoral approach. A temporary wire was placed in 10% of femoral patients. No in-hospital death was observed. This study shows that the radial artery approach with the 7.5 Fr SGC is at least as safe and effective as the conventional femoral approach for performing HSRA-facilitated PCI.


Compositional averaging of continuum intensities in multielement compounds.
We find no physical basis for traditional mass-fraction weighted averaging of X-ray continuum measured in pure elements to estimate continuum production from compounds. Measurements of continuum from pairs of stable isotopes demonstrate that mass alone (the presence of more or fewer neutrons) has no effect on continuum production in electron probe microanalysis. Electron-fraction weighted averaging, which is based on the relative contribution of each constituent element to the electron (or proton) composition of a compound, proved superior to mass-fraction weighted averaging, in predicting the continuum of a compound from the measured continuum of its elements.


An exercise program in the treatment of fibromyalgia.
To assess the utility of an exercise program, which included aerobic, flexibility and strengthening elements, in the treatment of fibromyalgia (FM). FM is a chronic musculoskeletal condition characterized by diffuse musculoskeletal pain and aching. It has been suggested that aerobic exercise is helpful in its treatment. We studied 60 patients who met American College of Rheumatology criteria for FM and had no significant comorbidities. Measurements performed on each patient at the pre and poststudy assessment included the number of tender points (TP), total myalgic scores (TM), aerobic fitness (AF), flexibility and isokinetic strength. After initial evaluation patients were randomly assigned to either an exercise or a relaxation group. Each group met 3 times per week for 6 weeks for 1 h of supervised exercise or relaxation. All patients data were stored in a computerized database and statistical analysis was performed on all pre and poststudy assessments. Thirty-eight patients (18 exercise and 20 relaxation) completed the study. Analysis of our data showed no significant difference between the groups in their prestudy assessment. Poststudy assessments, however, showed a significant improvement between the exercise and relaxation groups in TP (p < 0.05), TM (p < 0.05), and AF (p < 0.05). Similar improvements were also found when the pre and poststudy assessment of the exercise group were compared. Exercise is helpful in the management of FM in the short term. It also shows that FM patients can undertake an exercise program which includes aerobic, flexibility, and strength training exercises without adverse effects. The long term utility of this type of exercise requires further evaluation.


The effect of mobility on HIV-related healthcare access and use for female sex workers: A systematic review.
Female sex workers (FSW) experience a high HIV burden and are often mobile. FSW access to HIV-related healthcare is essential for equitable welfare and to reduce new HIV infections. We systematically reviewed the literature on mobility and HIV-related healthcare access and use among FSW. Outcome measures included: HIV/STI testing, STI treatment, PrEP (initiation or adherence), and ART (initiation or adherence). We summarised the results with a narrative synthesis. From 7417 non-duplicated citations, nine studies from Canada (3), Guatamala, Honduras (2), India, South Africa, and Vietnam were included. Only one of the studies was designed to address mobility and healthcare access, and only six reported adjusted effect estimates. Mobility was measured over four time-frames (from 'current' to 'ever'), as having lived or worked elsewhere or in another town/province/country. Three studies from Canada, Guatemala, and India found mobility associated with increased odds of poor initial access to healthcare (adjusted odds ratios (AOR) from 1.33, 95% CI 1.02, 1.75, to 2.27, 95% CI 1.09, 4.76), and one from Vietnam found no association (odds ratio (OR): 0.92, 95% CI 0.65, 1.28). The study from South Africa found no association with initiating ART (risk ratio: 0.86, 95% CI 0.65, 1.14). Two studies from Canada and Honduras found increased odds of ART interruption (AOR 2.74, 95% CI 0.89, 8.42; 5.19, 95% CI 1.38, 19.56), while two other studies from Canada and Honduras found no association with detectable viral load (OR 0.84, 95% CI 0.08, 8.33; AOR 0.79, 95% CI 0.41, 1.69). We found that mobility is associated with reduced initial healthcare access and interruption of ART, consistent with literature from the general population. Discordance between effects on adherence and viral load may be due to measurement of mobility. Future research should carefully construct measures of mobility and consider a range of HIV-related healthcare outcomes.


Prevalence of antibodies to Toxoplasma gondii in raccoons (Procyon lotor) from an urban area of Northern Virginia.
Raccoons (Procyon lotor) are intermediate hosts for Toxoplasma gondii, and clinical toxoplasmosis in raccoons has been reported. A 2-yr serological survey was conducted to determine the prevalence of antibodies to T. gondii in raccoons collected from Fairfax County, Virginia, a suburban/urban area outside Washington, D.C. Serum samples from 256 raccoons were examined for T. gondii antibodies at a 1:50 dilution using the modified direct agglutination test. Results indicated that 216 (84.4%) of the raccoons had been exposed to T. gondii. Our results indicate that raccoons in this area of Virginia are frequently exposed to T. gondii. Domestic cats were common in the study area and may have served as a source of oocysts for raccoons and the food items of raccoons.


Measuring telomere length and telomere dynamics in evolutionary biology and ecology.
Telomeres play a fundamental role in the protection of chromosomal DNA and in the regulation of cellular senescence. Recent work in human epidemiology and evolutionary ecology suggests adult telomere length (TL) may reflect past physiological stress and predict subsequent morbidity and mortality, independent of chronological age.Several different methods have been developed to measure TL, each offering its own technical challenges. The aim of this review is to provide an overview of the advantages and drawbacks of each method for researchers, with a particular focus on issues that are likely to face ecologists and evolutionary biologists collecting samples in the field or in organisms that may never have been studied in this context before.We discuss the key issues to consider and wherever possible try to provide current consensus view regarding best practice with regard to sample collection and storage, DNA extraction and storage, and the five main methods currently available to measure TL.Decisions regarding which tissues to sample, how to store them, how to extract DNA, and which TL measurement method to use cannot be prescribed, and are dependent on the biological question addressed and the constraints imposed by the study system. What is essential for future studies of telomere dynamics in evolution and ecology is that researchers publish full details of their methods and the quality control thresholds they employ.


Replication of biotinylated human immunodeficiency viruses.
Previous work demonstrated recently the adaptation of the Escherichia coli biotin ligase BirA - biotin acceptor sequence (BAS) labeling system to produce human immunodeficiency virus type 1 viruses with biotinylated integrase (NLXIN(B)) and matrix (NLXMA(B)) proteins (Belshan et al., 2009). This report describes the construction of an HIV permissive cell line stably expressing BirA (SupT1.BirA). Consistent with the results in the previous report, NLXMA(B) replicated similar to wild-type levels and expressed biotinylated Gag and MA proteins in the SupT1.BirA cells, whereas the replication of NLXIN(B) was reduced severely. Three additional HIV type 2 (HIV-2) viruses were constructed with the BAS inserted into the vpx and vpr accessory genes. Two BAS insertions were made into the C-terminal half of the Vpx, including one internal insertion, and one at the N-terminus of Vpr. All three viruses were replication competent in the SupT1.BirA cells and their target proteins biotinylated efficiently and incorporated into virions. These results demonstrate the potential utility of the biotinylation system to label and capture HIV protein complexes in the context of replicating virus.


A detailed study of cholinium chloride and levulinic acid deep eutectic solvent system for CO2 capture via experimental and molecular simulation approaches.
Choline chloride + levulinic acid deep eutectic solvent is studied as a suitable material for CO2 capturing purposes. The most relevant physicochemical properties of this solvent are reported together with the CO2 solubility as a function of temperature. The corrosivity of this solvent is studied showing better performance than amine-based solvents. A theoretical study using both density functional theory and molecular dynamics approaches is carried out to analyze the properties of this fluid from the nanoscopic viewpoint, and their relationship with the macroscopic behavior of the system and its ability for CO2 capturing. The behavior of the liquid-gas interface is also studied and its role on the CO2 absorption mechanism is analyzed. The reported combined experimental and theoretical approach leads to a complete picture of the behavior of this new sorbent with regard to CO2, which together with its low cost, and the suitable environmental and toxicological properties of this solvent, lead to a promising candidate for CO2 capturing technological applications.


Disruption of Drosophila melanogaster lipid metabolism genes causes tissue overgrowth associated with altered developmental signaling.
Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of many developmental pathways is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is critical for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase. Both mutants cause Notch, Wingless, the Epidermal Growth Factor Receptor (EFGR), and Patched to accumulate abnormally in endosomal compartments. In mosaic animals, mutant tissues exhibit an unusual non-cell-autonomous effect whereby mutant cells are functionally rescued by secreted activities emanating from adjacent wildtype tissue. Strikingly, both mutants display prominent tissue overgrowth phenotypes that are partially attributable to altered Notch and Wnt signaling. Our analysis of the mutants demonstrates genetic links between abnormal lipid metabolism, perturbations in developmental signaling, and aberrant cell proliferation.


Leishmania DNA is rapidly degraded following parasite death: an analysis by microscopy and real-time PCR.
Control of human leishmaniases relies on appropriate diagnosis and reliable methods for monitoring chemotherapy. The current method used for estimation of parasite burden during chemotherapy patient follow-up as well as in pharmacological studies performed in experimental models involves PCR-based assays. Compared to time-consuming conventional methods, this type of Leishmania DNA detection-based method is extremely sensitive, but could fail in distinguishing viable Leishmania from slowly degenerating ones. We have used an in vitro model to monitor the duration of Leishmania DNA persistence in mouse macrophages following exposure to l-leucine ester, a molecule otherwise known to rapidly kill intracellular Leishmania amazonensis amastigotes. At 1h of post l-leucine ester exposure, more than 98% of amastigote-loaded macrophages harbored killed parasites and parasite remnants, as assessed by microscopy. This dramatic decrease in parasite load and the microscopic parasite follow-up over the 120 h time period studied were correlated with Leishmania DNA as quantified by real-time PCR. Our results indicate that kinetoplast and nuclear parasite DNA degradation occurs very rapidly after amastigote death. These data add further weight to the argument that PCR assays represent not only a robust method for diagnosis but can also be reliable for monitoring parasite size reduction rate post any intervention (Leishmania-targeting molecules, immunomodulators...).


Reflections of Oneself: Neurocognitive Evidence for Dissociable Forms of Self-Referential Recollection.
Research links the medial prefrontal cortex (mPFC) with a number of social cognitive processes that involve reflecting on oneself and other people. Here, we investigated how mPFC might support the ability to recollect information about oneself and others relating to previous experiences. Participants judged whether they had previously related stimuli conceptually to themselves or someone else, or whether they or another agent had performed actions. We uncovered a functional distinction between dorsal and ventral mPFC subregions based on information retrieved from episodic long-term memory. The dorsal mPFC was generally activated when participants attempted to retrieve social information about themselves and others, regardless of whether this information concerned the conceptual or agentic self or other. In contrast, a role was discerned for ventral mPFC during conceptual but not agentic self-referential recollection, indicating specific involvement in retrieving memories related to self-concept rather than bodily self. A subsequent recognition test for new items that had been presented during the recollection task found that conceptual and agentic recollection attempts resulted in differential incidental encoding of new information. Thus, we reveal converging fMRI and behavioral evidence for distinct neurocognitive forms of self-referential recollection, highlighting that conceptual and bodily aspects of self-reflection can be dissociated.


Are computers effective lie detectors? A meta-analysis of linguistic cues to deception.
This meta-analysis investigates linguistic cues to deception and whether these cues can be detected with computer programs. We integrated operational definitions for 79 cues from 44 studies where software had been used to identify linguistic deception cues. These cues were allocated to six research questions. As expected, the meta-analyses demonstrated that, relative to truth-tellers, liars experienced greater cognitive load, expressed more negative emotions, distanced themselves more from events, expressed fewer sensory-perceptual words, and referred less often to cognitive processes. However, liars were not more uncertain than truth-tellers. These effects were moderated by event type, involvement, emotional valence, intensity of interaction, motivation, and other moderators. Although the overall effect size was small, theory-driven predictions for certain cues received support. These findings not only further our knowledge about the usefulness of linguistic cues to detect deception with computers in applied settings but also elucidate the relationship between language and deception.


The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line.
The voltage gated potassium (K+) channels Eag and HERG have been implicated in the pathogenesis of various cancers, through association with cell cycle changes and programmed cell death. The role of these channels in the onset and progression of ovarian cancer is unknown. An understanding of mechanism by which Eag and HERG channels affect cell proliferation in ovarian cancer cells is required and therefore we investigated their role in cell proliferation and their effect on the cell cycle and apoptosis of ovarian cancer cells. The presence of Eag and HERG was determined in SK-OV-3 cells using immunofluorescence and western blotting. The effect of the Eag blockers (imipramine and clofilium) and HERG blockers (E-4031 and ergtoxin) on cell proliferation was assessed using the MTS assay with further investigation of their role in the cell cycle and apoptosis determined by flow cytometry. Eag and HERG channels were present in the cytoplasm and nuclei of SK-OV-3 cells. There was significant inhibition of proliferation of SK-OV-3 cells by imipramine (P < 0.001) and ergtoxin (P < 0.05) at 72 hours of culture. Incubation of cells with ergtoxin led to the accumulation of cells in the S and G2/M phase, while cells accumulated in S phase after incubation with E-4031, with no effect on apoptosis. Imipramine did not affect the cell cycle but increased the proportion of SK-OV-3 cells undergoing early apoptosis. Both Eag and HERG channels are expressed in SK-OV-3 ovarian cancer cells and have a role in cell proliferation. HERG channels affect the cell cycle while Eag channels are implicated in the inhibition of apoptosis of ovarian cancer cells. The family of Eag channels may represent a new therapeutic target for the treatment of ovarian cancer.


Strategies to reduce non-communicable diseases in the offspring: negative and positive in utero programming.
Non-communicable diseases (NCDs) are a major problem as they are the leading cause of death and represent a substantial economic cost. The 'Developmental Origins of Health and Disease Hypothesis' proposes that adverse stimuli at different life stages can increase the predisposition to these diseases. In fact, adverse in utero programming is a major origin of these diseases due to the high malleability of embryonic development. This review provides a comprehensive analysis of the scientific literature on in utero programming and NCDs highlighting potential medical strategies to prevent these diseases based upon this programming. We fully address the concept and mechanisms involved in this programming (anatomical disruptions, epigenetic modifications and microbiota alterations). We also examine the negative role of in utero programming on the increased predisposition of NCDs in the offspring, which introduces the passive medical approach that consists of avoiding adverse stimuli including an unhealthy diet and environmental chemicals. Finally, we extensively discuss active medical approaches that target the causes of NCDs and have the potential to significantly and rapidly reduce the incidence of NCDs. These approaches can be classified as direct in utero programming modifications and personalized lifestyle pregnancy programs; they could potentially provide transgenerational NCDs protection. Active strategies against NCDs constitute a promising tool for the reduction in NCDs.


Mitochondrial intermediate peptidase and the yeast frataxin homolog together maintain mitochondrial iron homeostasis in Saccharomyces cerevisiae.
Friedreich's ataxia (FRDA) is a neurodegenerative disease typically caused by a deficiency of frataxin, a mitochondrial protein of unknown function. In Saccharomyces cerevisiae, lack of the yeast frataxin homolog ( YFH1 gene, Yfh1p polypeptide) results in mitochondrial iron accumulation, suggesting that frataxin is required for mitochondrial iron homeostasis and that FRDA results from oxidative damage secondary to mitochondrial iron overload. This hypothesis implies that the effects of frataxin deficiency could be influenced by other proteins involved in mitochondrial iron usage. We show that Yfh1p interacts functionally with yeast mitochondrial intermediate peptidase ( OCT1 gene, YMIP polypeptide), a metalloprotease required for maturation of ferrochelatase and other iron-utilizing proteins. YMIP is activated by ferrous iron in vitro and loss of YMIP activity leads to mitochondrial iron depletion, suggesting that YMIP is part of a feedback loop in which iron stimulates maturation of YMIP substrates and this in turn promotes mitochondrial iron uptake. Accordingly, YMIP is active and promotes mitochondrial iron accumulation in a mutant lacking Yfh1p ( yfh1 [Delta]), while genetic inactivation of YMIP in this mutant ( yfh1 [Delta] oct1 [Delta]) leads to a 2-fold reduction in mitochondrial iron levels. Moreover, overexpression of Yfh1p restores mitochondrial iron homeostasis and YMIP activity in a conditional oct1 ts mutant, but does not affect iron levels in a mutant completely lacking YMIP ( oct1 [Delta]). Thus, we propose that Yfh1p maintains mitochondrial iron homeostasis both directly, by promoting iron export, and indirectly, by regulating iron levels and therefore YMIP activity, which promotes mitochondrial iron uptake. This suggests that human MIP may contribute to the functional effects of frataxin deficiency and the clinical manifestations of FRDA.


Local glucocorticoid production in the mouse lung is induced by immune cell stimulation.
Glucocorticoids (GC) are potent anti-inflammatory and immunosuppressive steroid hormones, mainly produced by the adrenal glands. However, increasing evidence supports the idea of additional extra-adrenal sources of bioactive GC. The lung epithelium is constantly exposed to a plethora of antigenic stimuli, and local GC synthesis could contribute to limit uncontrolled immune reactions and tissue damage. Expression of steroidogenic enzymes and GC synthesis in ex vivo organ cultures was studied in mouse lung tissue after in vivo stimulation of immune cells. Mouse lung tissue was found to express steroidogenic enzymes required for the synthesis of corticosterone from cholesterol and to synthesize corticosterone in large quantities after immune cell activation by anti-CD3 antibody, lipopolysaccharide, or TNFα. In marked contrast, ovalbumin-induced allergic airway inflammation failed to promote lung GC synthesis. Although the lung expresses all steroidogenic enzymes necessary for de novo synthesis of corticosterone from cholesterol, functional data indicated that inactive serum-derived dehydrocorticosterone is converted to active corticosterone by 11β-hydroxysteroid dehydrogenase 1. Our results support the notion that local GC synthesis represents a novel immunoregulatory mechanism to limit uncontrolled immune responses in the lung and indicate that defective local steroidogenesis may contribute to the pathogenesis of allergic airway inflammation.


Linking Particle Dynamics to Local Connectivity in Colloidal Gels.
Colloidal gels are a prototypical example of a heterogeneous network solid whose complex properties are governed by thermally activated dynamics. In this Letter we experimentally establish the connection between the intermittent dynamics of individual particles and their local connectivity. We interpret our experiments with a model that describes single-particle dynamics based on highly cooperative thermal debonding. The model, in quantitative agreement with experiments, provides a microscopic picture for the structural origin of dynamical heterogeneity in colloidal gels and sheds new light on the link between structure and the complex mechanics of these heterogeneous solids.


Somali immigrant women's perceptions of cesarean delivery and patient-provider communication surrounding female circumcision and childbirth in the USA.
To explore perceptions of cesarean delivery and patient-provider communication surrounding female circumcision and childbirth through interviews with Somali women residing in the USA. Semistructured in-depth interviews were conducted with 23 Somali immigrant women living in Boston who had given birth in the USA and Africa. Interviews asked about birth experiences in the USA and Africa, as well as norms and attitudes surrounding childbirth practices. Interview transcripts were coded and themes identified through an iterative process. Participants were aged 25-52 years and had been living in the USA for an average of 7 years. All women had experienced circumcision. Five women had undergone a cesarean delivery. Women feared having a cesarean because of their perception that it could result in death or disability. Women also highlighted that providers in the USA rarely discussed female circumcision or how it could affect childbirth experiences. Previous experiences and cultural beliefs can affect how Somali immigrant women understand labor and delivery practices in the USA and can explain why some women are wary of cesarean delivery. Educating providers and encouraging patient-provider communication about cesarean delivery and female circumcision can ease fears, increase trust, and improve birth experiences for Somali immigrant women in the USA.


A new isoform of human myosin phosphatase targeting/regulatory subunit (MYPT2): cDNA cloning, tissue expression, and chromosomal mapping.
Myosin phosphatase target subunit 1 (MYPT1), a subunit of myosin phosphatase, plays a pivotal role in the regulation of myosin phosphatase activity. Here we have cloned a novel isoform of MYPT1, termed MYPT2, from a human brain cDNA library screened with a cDNA fragment of rat MYPT1. Overlapping clones indicated an open reading frame of 3763 nucleotides and a predicted polypeptide of mass 110,398. Ankyrin repeats and leucine zipper motifs were identified for the sequences 57-316 and 956-982, respectively. Overall, the deduced amino acid sequence of MYPT2 was 61% identical to MYPT1. MYPT2 gene is transcribed abundantly in heart and skeletal muscle, while Western blots using an antibody specific for MYPT2 showed exclusive expression of MYPT2 in heart and brain. A recombinant of the N-terminal two-thirds of MYPT2 bound to the catalytic subunit of type 1 phosphatase (delta isoform) and increased activity toward phosphorylated myosin light chain. In situ hybridization localized the human MYPT2 gene on chromosome 1q32.1, compared to the chromosomal location 12q15-q21-2 for MYPT1. It is suggested that the products of the two gene families of myosin phosphatase target subunit may be localized differently among various tissues.


A multilayered valve leaflet promotes cell-laden collagen type I production and aortic valve hemodynamics.
Patients with aortic heart valve disease are limited to valve replacements that lack the ability to grow and remodel. This presents a major challenge for pediatric patients who require a valve capable of somatic growth and at a smaller size. A patient-specific heart valve capable of growth and remodeling while maintaining proper valve function would address this major issue. Here, we recreate the native valve leaflet structure composed of poly-ε-caprolactone (PCL) and cell-laden gelatin-methacrylate/poly (ethylene glycol) diacrylate (GelMA/PEGDA) hydrogels using 3D printing and molding, and then evaluate the ability of the multilayered scaffold to produce collagen matrix under physiological shear stress conditions. We also characterized the valve hemodynamics under aortic physiological flow conditions. The valve's fibrosa layer was replicated by 3D printing PCL in a circumferential direction similar to collagen alignment in the native leaflet, and GelMA/PEGDA sustained and promoted cell viability in the spongiosa/ventricularis layers. We found that collagen type I production can be increased in the multilayered scaffold when it is exposed to pulsatile shear stress conditions over static conditions. When the PCL component was mounted onto a valve ring and tested under physiological aortic valve conditions, the hemodynamics were comparable to commercially available valves. Our results demonstrate that a structurally representative valve leaflet can be generated using 3D printing and that the PCL layer of the leaflet can sustain proper valve function under physiological aortic valve conditions.


Oligomers matrix-assisted dispersion of high content of carbon nanotubes into monolithic column for online separation and enrichment of proteins from complex biological samples.
In this work, a new oligomer matrix-assisted dispersion (OMAD) method for the preparation of homogeneous dispersion of multi-walled carbon nanotubes (MWNTs) incorporated monolithic column was developed. Oligomers matrix as a scaffold could allow MWNTs to entangle with it instead of self-aggregation, so the MWNTs remain in the polymer network followed by in situ self-solidification. The OMAD method not only greatly enlarged the BET surface area of MWNTs incorporated monolithic column from 13.8 m(2) g(-1) to 85.5 m(2) g(-1) without a significant effect on the surface chemistry of the MWNTs, but also improved the dispersion of MWNTs making its content up to 5 wt% (with respect to monomers). The synthesized materials combine the favorable attributes of both high permeability and large surface area, making them excellent candidates for on-line separation and enrichment of proteins. The oligomer matrix-assisted dispersion MWNTs incorporated monolithic columns (OMAD-MMC) exhibited higher enrichment factors and the adsorption capacity is about 5-fold for basic proteins compared with MWNTs incorporated monolithic columns (MMC) prepared by the conventional in situ polymerization. The practical application of OMAD-MMC was proven by selective extraction of hemoglobin in human whole blood samples with SDS-PAGE. On the basis of the results, OMAD as a simple and effective method for dispersion high content MWNTs into monolithic columns shows great promise.


The natural history of acute hepatitis C: clinical presentation, laboratory findings and treatment outcomes.
Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. To establish natural history and complications of treatment of acute hepatitis C. Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4-8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. Among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Anti-viral treatment with a 24-week course of peginterferon and ribavirin was highly effective, but marked by frequent and severe side effects.


Antibiotics in early life: dysbiosis and the damage done.
Antibiotics are the most common type of medication prescribed to children, including infants, in the Western world. While use of antibiotics has transformed previously lethal infections into relatively minor diseases, antibiotic treatments can have adverse effects as well. It has been shown in children, adults and animal models that antibiotics dramatically alter the gut microbial composition. Since the gut microbiota plays crucial roles in immunity, metabolism and endocrinology, the effects of antibiotics on the microbiota may lead to further health complications. In this review, we present an overview of the effects of antibiotics on the microbiome in children, and correlate them to long-lasting complications of obesity, behavior, allergies, autoimmunity and other diseases.


Conical refraction as a tool for polarization metrology.
A method for polarization metrology based on the conical refraction (CR) phenomenon, occurring in biaxial crystals, is reported. CR transforms an input Gaussian beam into a light ring whose intensity distribution is linked to the incoming polarization. We present the design of a division-of-amplitude complete polarimeter composed of two biaxial crystals, whose measurement principle is based on the CR phenomenon. This design corresponds to a static polarimeter, that is, without mechanical movements or electrical signal addressing. Only one division-of-amplitude device is required, besides the two biaxial crystals, to completely characterize any state of polarization, including partially polarized and unpolarized states. In addition, a mathematical model describing the system is included. Experimental images of the intensity distribution related to different input polarization states are provided. These intensity patterns are compared with simulated values, proving the potential of polarimeters based on biaxial crystals.


Laparoscopic cryoablation of a metastatic carcinoid tumor.
Carcinoid tumors are rare, slow-growing neuroendocrine neoplasms that can cause a carcinoid syndrome. The majority of carcinoid syndromes are the result of multiple hepatic metastases and are usually unresectable. Medical therapy has not proven effective and often causes intolerable side effects. Cryoablation has emerged as a promising treatment for various hepatic lesions when resection is not an option and medical therapy has been exhausted. With the addition of laparoscopy, surgeons now possess a new technique to treat primary and various secondary liver lesions. We report for the first time laparoscopic cryoablation for the treatment of a carcinoid metastatic to the liver.


[Intra-uterine insemination with controlled ovarian hyperstimulation compared to an expectant management in couples with unexplained subfertility and an intermediate prognosis: a randomised study].
Intrauterine insemination (IUI) with controlled ovarian hyperstimulation (COH) is commonly used as treatment of first choice in couples with unexplained subfertility. This treatment should only be applied when there is a realistic increase in chance of pregnancy, particularly because it carries the increased risk of multiple pregnancies. We evaluated the effectiveness of IUI with COH relative to expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy. Multicentre randomised clinical study. 253 couples with unexplained subfertility and a probability of a spontaneous ongoing pregnancy of 30% to 40% within 12 months, were randomly assigned to IUI with COH for 6 months or expectant management for 6 months. The primary endpoint of our study was ongoing pregnancy within 6 months. Analysis was carried out according to the intention to treat principle. This study was registered with the Dutch Trial Register and has the International Standard Randomised Clinical Trial number ISRCTN72675518. Of the 253 couples included, 127 couples were allocated to IUI with COH and 126 to expectant management. In the intervention group, 42 women (33%) conceived, of which 29 pregnancies were ongoing (23%). In the expectant management group, 40 women (32%) conceived, of which 34 pregnancies were ongoing (27%) (relative risk: 0.85; 95% CI: 0.63-1.1). In the expectant management group one twin pregnancy occurred and in the intervention group one woman conceived twins and one a triplet. A substantial beneficial effect of IUI with COH in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for a period of 6 months therefore appears justified in these couples.


Assembling surface mounted components on ink-jet printed double sided paper circuit board.
Printed electronics is a rapidly developing field where many components can already be manufactured on flexible substrates by printing or by other high speed manufacturing methods. However, the functionality of even the most inexpensive microcontroller or other integrated circuit is, at the present time and for the foreseeable future, out of reach by means of fully printed components. Therefore, it is of interest to investigate hybrid printed electronics, where regular electrical components are mounted on flexible substrates to achieve high functionality at a low cost. Moreover, the use of paper as a substrate for printed electronics is of growing interest because it is an environmentally friendly and renewable material and is, additionally, the main material used for many packages in which electronics functionalities could be integrated. One of the challenges for such hybrid printed electronics is the mounting of the components and the interconnection between layers on flexible substrates with printed conductive tracks that should provide as low a resistance as possible while still being able to be used in a high speed manufacturing process. In this article, several conductive adhesives are evaluated as well as soldering for mounting surface mounted components on a paper circuit board with ink-jet printed tracks and, in addition, a double sided Arduino compatible circuit board is manufactured and programmed.


Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis.
Although myeloid-derived suppressor cells (MDSCs) have been linked to T cell tolerance, their role in autoimmune rheumatoid arthritis (RA) remains elusive. Here we investigate the potential association of MDSCs with the disease pathogenesis using a preclinical model of RA and specimen collected from patients with RA. The frequency of MDSCs in blood, lymphoid tissues, inflamed paws or synovial fluid and their association with disease severity, tissue inflammation and the levels of pathogenic T helper (Th) 17 cells were examined in arthritic mice or in patients with RA (n=35) and osteoarthritis (n=15). The MDSCs in arthritic mice were also characterised for their phenotype, inflammation status, T cell suppressive activity and their capacity of pro-Th17 cell differentiation. The involvement of MDSCs in the disease pathology and a Th17 response was examined by adoptive transfer or antibody depletion of MDSCs in arthritic mice or by coculturing mouse or human MDSCs with naïve CD4+ T cells under Th17-polarising conditions. MDSCs significantly expanded in arthritic mice and in patients with RA, which correlated positively with disease severity and an inflammatory Th17 response. While displaying T cell suppressive activity, MDSCs from arthritic mice produced high levels of inflammatory cytokines (eg, interleukin (IL)-1β, TNF-α). Mouse and human MDSCs promoted Th17 cell polarisation ex vivo. Transfer of MDSCs facilitated disease progression, whereas their elimination in arthritic mice ameliorated disease symptoms concomitant with reduction of IL-17A/Th17 cells. Our studies suggest that proinflammatory MDSCs with their capacity to drive Th17 cell differentiation may be a critical pathogenic factor in autoimmune arthritis.


Mixed methods evaluation research for a mental health screening and referral clinical pathway.
This study is an exemplar of mixed method evaluation research for development of a clinical pathway. To develop and evaluate an evidence-based, feasible mental health screening and referral clinical pathway for Department of Veterans' Affairs-funded community nursing care of war veterans and war widows in the Australian context. Mixed methods were applied to formulate and clinically evaluate an appropriate pathway. The pathway was applied at urban and rural sites for the nursing care of 97 war veteran and war widow clients. Evaluative data were collected from clients, their informal carers, community nurses, and general practitioners. Chart auditing and pre-post measures were undertaken. Collaboration occurred with an interdisciplinary design team. The final modified six-page pathway includes use of validated screening tools (Kessler Psychological Distress Scale [K10]) and Alcohol Use Disorder Identification Test, appropriate referral information, directions for support and health-promoting education, and evidence-based guidelines. The clinical pathway is a useful, tested, evidence-based guide for generalist community nurses to identify and suitably respond to common mental healthcare needs of war veterans and war widows. The pathway provides outcomes acceptable to clients and their carers, nurses and doctors. This study provides an evaluated clinical pathway for generalist community nurses to screen for mental health difficulties, make appropriate referrals as required and to support war veteran and war widow clients. However, the study also shows how research can be used to develop and evaluate practical, evidence-based clinical pathways.


CYFRA 21-1 as a tumour marker for bronchogenic carcinoma.
Despite extensive research, the role of the commonly employed tumour markers in the diagnosis of lung carcinoma is yet to be clarified. The utility of a new marker, CYFRA 21-1, in the preoperative evaluation of patients with bronchogenic carcinoma was investigated. CYFRA 21-1 was determined with a radiometric assay in serum of 280 patients with lung cancer and 208 patients with various nonmalignant lung diseases. The levels of the marker were significantly higher in lung cancer patients. Among benign lung diseases, elevated CYFRA 21-1 levels were found in pulmonary fibrosis. Using a cut-off of 3.2 ng.ml-1 (95th percentile of levels obtained in benign lung disease), the total sensitivity of the marker was 48%. The best sensitivity was obtained in squamous cell lung cancer (60%). The highest values of CYFRA 21-1 were found in metastatic lung cancer, and the marker sensitivity was more elevated in stage IIIb and IV. On the other hand, 40% of patients with surgically resectable lung cancer had CYFRA 21-1 levels above the cut-off. We conclude that CYFRA 21-1 may be satisfactorily employed in the differential diagnosis between malignant and benign lung diseases in association with other clinical and radiological data.


Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) and its complications are an expanding health problem associated with the metabolic syndrome. Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells localized at the interface between the blood derived from the gut and the adipose tissue on the one side, and other liver cells on the other side. In physiological conditions, LSECs are gatekeepers of liver homeostasis. LSECs display anti-inflammatory and anti-fibrogenic properties by preventing Kupffer cell and hepatic stellate cell activation and regulating intrahepatic vascular resistance and portal pressure. This review focusses on changes occurring in LSECs in NAFLD and on their consequences on NAFLD progression and complications. Capillarization, namely the loss of LSEC fenestrae, and LSEC dysfunction, namely the loss of the ability of LSECs to generate vasodilator agents in response to increased shear stress both occur early in NAFLD. These LSEC changes favour steatosis development and set the stage for NAFLD progression. At the stage of non-alcoholic steatohepatitis, altered LSECs release inflammatory mediators and contribute to the recruitment of inflammatory cells, thus promoting liver injury and inflammation. Altered LSECs also fail to maintain hepatic stellate cell quiescence and release fibrogenic mediators, including Hedgehog signalling molecules, promoting liver fibrosis. Liver angiogenesis is increased in NAFLD and contributes to liver inflammation and fibrosis, but also to hepatocellular carcinoma development. Thus, improving LSEC health appears to be a promising approach to prevent NAFLD progression and complications.


The Immunoreactive Platform of the Pancreatic Islets Influences the Development of Autoreactivity.
Tissue homeostasis is maintained through a finely tuned balance between the immune system and the organ-resident cells. Disruption of this process not only results in organ dysfunction but also may trigger detrimental autoimmune responses. The islet of Langerhans consists of the insulin-producing β-cells essential for proper control of body metabolism, but less appreciated is that these cells naturally interact with the immune system, forming a platform by which the β-cell products are sensed, processed, and responded to by the local immune cells, particularly the islet-resident macrophages. Although its physiological outcomes are not completely understood, this immunoreactive platform is crucial for precipitating islet autoreactivity in individuals carrying genetic risks, leading to the development of type 1 diabetes. In this Perspective, we summarize recent studies that examine the cross talk between the β-cells and various immune components, with a primary focus on discussing how antigenic information generated during normal β-cell catabolism can be delivered to the resident macrophage and further recognized by the adaptive CD4 T-cell system, a critical step to initiate autoimmune diabetes. The core nature of the islet immune platform can be extrapolated to other endocrine tissues and may represent a common mechanism underlying the development of autoimmune syndromes influencing multiple endocrine organs.


Depression and diabetes: the role and impact of models of health care systems.
Depression and diabetes often occur together and their comorbidity has a significant and detrimental impact on health outcomes. The aims of this paper are to review the existing international literature on approaches to health care for comorbid depression and diabetes and draw out the key conclusions for both research and future development in health care delivery. Narrative review of the literature with synthesis by an international team of authors. The synthesized findings are discussed under four main headings: specialty and generalist care; models for co-ordinating and integrating care; community approaches to service delivery; and the role of health policy. The review only included literature published in English. Translating basic and clinical research findings into improved treatment and outcomes of those with depression and diabetes remains a substantial challenge. There is little research on the difficulties of identifying and implementing best practice into routine health care. Systems need to be designed so that evidence-based interventions are provided in a timely way, with appropriate professional expertise where required.


Lymphoepitelioma-like hepatocellular carcinoma: a case report and a review of the literature.
Lymphoepitelioma is a particular form of undifferentiated carcinoma, characterized by a prominent lymphoid stroma, originally described in the nasopharynx. Lymphoid stroma-rich carcinomas arising in other organs have been termed lymphoepithelioma-like carcinoma (LELC). In the liver, primary LELCs are very rare, and the majority has been identified as cholangiocarcinomas. Here a rare case of lymphoepithelioma-like hepatocellular carcinoma (HCC) is described. A 47-year old woman presented with abdominal pain. Ultrasonography revealed a liver nodule, 2.2 cm in diameter, localized in the right lobe, adjacent to the gallbladder. Viral markers for hepatic B virus (HBV), hepatic C virus (HCV) and Epstein-Barr virus (EBV) were negative. The nodule was hypoechogenic. The patient underwent surgery, with resection of the nodule. Histology showed hepatocellular carcinoma, characterized by a prominent lymphoid infiltrate. At immunocytochemistry, tumor cells were reactive for Hep Par1 and glypican 3. Immunophenotyping of tumor infiltrating lymphocytes evidenced the predominance of CD8+ cytotoxic suppressor T cells. The postoperative clinical outcome was favorable and the patient was recurrence-free 15 mo after resection. This case, to the best of our knowledge, is the first reported non EBV and non cirrhosis-associated lymphoepithelioma-like hepatocellular carcinoma. The association between the lack of EBV infection, the absence of cirrhosis, a "cytotoxic profile" of the inflammatory infiltrate and a good prognosis could identify a variant of lymphoepithelioma-like HCC with a favorable clinical outcome.


Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies.
The effect of inhaled corticosteroids (ICS) on fracture risk in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to evaluate the association between ICS and fractures in COPD. MEDLINE, EMBASE, regulatory documents and company registries were searched up to August 2010. Randomised controlled trials (RCTs) of budesonide or fluticasone versus control treatment for COPD (≥24 weeks duration) and controlled observational studies reporting on fracture risk with ICS exposure vs no exposure in COPD were included. Peto OR meta-analysis was used for fracture risk from RCTs while ORs from observational studies were pooled using the fixed effect inverse variance method. Dose-response analysis was conducted using variance-weighted least squares regression in the observational studies. Heterogeneity was assessed using the I(2) statistic. Sixteen RCTs (14 fluticasone, 2 budesonide) with 17,513 participants, and seven observational studies (n=69,000 participants) were included in the meta-analysis. ICSs were associated with a significantly increased risk of fractures (Peto OR 1.27; 95% CI 1.01 to 1.58; p=0.04; I(2)=0%) in the RCTs. In the observational studies, ICS exposure was associated with a significantly increased risk of fractures (OR 1.21; 95% CI 1.12 to 1.32; p<0.001; I(2)=37%), with each 500 μg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p<0.001). Among patients with COPD, long-term exposure to fluticasone and budesonide is consistently associated with a modest but statistically significant increased likelihood of fractures.


Unplanned cigarette purchases and tobacco point of sale advertising: a potential barrier to smoking cessation.
In the USA, tobacco marketing expenditure is increasingly concentrated at the point of sale (POS). Previous studies have demonstrated an association between exposure to tobacco POS advertising and increased smoking initiation, but limited evidence is available on adult smokers' decisions and behaviours. An immediate post-cigarette purchase survey was administered to 301 cigarette purchasers outside of two grocery stores in Vermont to assess the prevalence of unplanned purchases and opinions about POS tobacco advertising and displays. In total, 11.3% of purchases were reported as unplanned. Certain groups were more likely to make unplanned purchases including: 18-24-year-olds (OR: 2.1, 95% CI 1.0 to 4.4), less than daily smokers (OR: 5.6, 95% CI 1.9 to 16.9), smokers who made 3+ quit attempts in the previous year (OR: 2.4, 95% CI 0.9 to 6.0), those who plan to quit in the next month (OR: 3.7, 95% CI 1.6 to 9.0), and those who agreed that tobacco POS advertising makes quitting smoking harder (OR: 2.3, 95% CI 1.1 to 4.8). Overall, 31.2% of participants agreed that tobacco POS advertising makes quitting smoking harder. Individuals who intended to quit within the next month, made 3+ quit attempts in the last year, or made an unplanned cigarette purchase were the most likely to agree. Young adults and individuals making multiple quit attempts or planning to quit in the next month are more likely to make unplanned cigarette purchases. Reducing unplanned purchases prompted by tobacco POS advertising could improve the likelihood of successful cessation among smokers.


Multisensory Information Facilitates the Categorization of Untrained Stimuli.
Although it has been demonstrated that multisensory information can facilitate object recognition and object memory, it remains unclear whether such facilitation effect exists in category learning. To address this issue, comparable car images and sounds were first selected by a discrimination task in Experiment 1. Then, those selected images and sounds were utilized in a prototype category learning task in Experiments 2 and 3, in which participants were trained with auditory, visual, and audiovisual stimuli, and were tested with trained or untrained stimuli within the same categories presented alone or accompanied with a congruent or incongruent stimulus in the other modality. In Experiment 2, when low-distortion stimuli (more similar to the prototypes) were trained, there was higher accuracy for audiovisual trials than visual trials, but no significant difference between audiovisual and auditory trials. During testing, accuracy was significantly higher for congruent trials than unisensory or incongruent trials, and the congruency effect was larger for untrained high-distortion stimuli than trained low-distortion stimuli. In Experiment 3, when high-distortion stimuli (less similar to the prototypes) were trained, there was higher accuracy for audiovisual trials than visual or auditory trials, and the congruency effect was larger for trained high-distortion stimuli than untrained low-distortion stimuli during testing. These findings demonstrated that higher degree of stimuli distortion resulted in more robust multisensory effect, and the categorization of not only trained but also untrained stimuli in one modality could be influenced by an accompanying stimulus in the other modality.


Truncated forms of Pax-6 disrupt lens morphology in transgenic mice.
Extensive literature shows that Pax-6 is critical for lens development and that Paxb mutations can result in aniridia in humans. In addition, it has been reported that truncated Pax-6 molecules can act as dominant-negative repressors of wild-type Pax-6 activity in cultured cells. This study was designed to determine whether Pax-6 molecules without either the activation domain (AD) or the homeodomain (HD) and the AD can function as dominant-negative repressors in vivo and alter the phenotype of the lens. Transgenic mice were created harboring the alphaA-crystallin promoter linked to a cDNA encoding either a truncated Pax-6 without the C terminus (paired domain [PD] + homeodomain) or Pax-6 consisting of only the PD. The phenotype of the resultant animals was investigated by light and electron microscopy as well as atomic absorption spectroscopy. Two lines of PD + HD mice and three lines of PD mice were generated, all of which exhibit posterior nuclear and/or cortical cataracts of variable severity. The lenses from mice transgenic for either Pax-6 truncation are smaller and more hydrated than normal. Morphologically, the mice expressing the PD + HD of Pax-6 have swollen lens fibers with attenuated ball-and-socket junctions. In contrast, the lenses from mice overexpressing the PD of Pax-6 have posterior nuclear cataracts composed of cell debris, whereas the remaining fiber cells appear generally normal. The presence of truncated Pax-6 protein in the lens is sufficient to induce cataract in a wild-type genetic background. The simplest explanation for this phenomenon is a dominant-negative effect; however, a number of other possible mechanisms are presented.


The prognostic importance of peritoneal involvement in colonic cancer: a prospective evaluation.
Prognostic parameters specific to the colon have been somewhat neglected compared with the rectum. This study was instituted to assess the influence of local peritoneal involvement (LPI) on pelvic and intraperitoneal recurrence and prognosis in an unselected, prospective series of colonic cancer resections. Meticulous examination of 412 resections included evaluation of the relation of the tumor to the peritoneal surface. Histological assessment was as follows: 1, peritoneal involvement absent (81 resections, 20%); 2, inflammatory reaction with tumor close but not present at the surface (89 resections, 22%); 3, peritoneal surface unequivocally infiltrated (112 resections, 27%); and 4, peritoneal involvement with ulceration and tumor cells lying apparently free in the peritoneum (130 resections, 32%). LPI showed strong independent prognostic influence in both curative surgery groups and in all patients. In multivariate analysis in curative surgery, LPI was the most powerful prognostic indicator. It was significantly associated with palliative surgery, extent of local spread, and mucinous subtype and predicted cases with subsequent intraperitoneal recurrence and/or persistence. LPI is a common event in colonic cancer and is a consistent predictor of subsequent intraperitoneal recurrence. It is an important independent pathological prognostic parameter and may supersede other parameters in current usage in colonic cancer prognosis.


Urine utilisation by microbial fuel cells; energy fuel for the future.
This communication reports for the first time the direct utilisation of urine in MFCs for the production of electricity. Different conversion efficiencies were recorded, depending on the amount treated. Elements such as N, P, K can be locked into new biomass, thus removed from solution, resulting in recycling without environmental pollution.


Understanding for whom, under what conditions, and how group-based physical activity interventions are successful: a realist review.
Participation in group-based physical activity (GBPA) interventions has been found to result in higher levels of exercise adherence and program compliance. However, previous reviews of GBPA programs have provided limited insight regarding 'for whom', 'under what conditions', and 'how' these interventions increase physical activity behavior. A realist review was conducted by following the seven recommended iterative and overlapping steps (J Health Serv Res Policy 10S1:21-34, 2005). The review was limited to group dynamics-based interventions for adults (>17 years of age). The search was conducted in PubMed, PsychInfo, and Web of Science search engines associated with the Science Citation Index Expanded, Social Sciences Citation Index, Arts & Humanities Citation Index, and MEDLINE. Using a realist review approach, data from 52 studies were synthesized. Of those, 92% (n = 48) reported significant increases in participant physical activity. The synthesis resulted in three main observations and recommendations. GBPA interventions have worked for a variety of populations, including those who are hard to reach; however, more research is needed on moderating factors to determine for whom different GBPA programs may be effective. Second, previous interventions have varied in the duration, frequency, and number of group-based strategies used, and comparative effectiveness research may be necessary to isolate the mechanisms of effect. Third, these interventions have been conducted in a diverse range of settings, using a variety of research designs and analytical approaches. Less information is known about the costs or sustainability of these programs in their intended settings. The results of this realist review have important implications for practice, refining trial designs, and replication across diverse populations and settings.


Multiple roles for acetylation in the interaction of p300 HAT with ATF-2.
The transcriptional coactivator paralogues p300 and CBP contain acetyltransferase domains (HAT) and catalyze the lysine acetylation of histones and other proteins as an important aspect of their functions. Prior studies revealed that the basic leucine zipper domain (b-ZIP) of transcription factor ATF-2 (also called CRE-BP1) can interact with the CBP HAT domain. In this study, we have examined the ATF-2 b-ZIP interaction with the p300 HAT domain and shown that p300 HAT autoacetylation can enhance the binding affinity. Pull-down assays revealed that hyperacetylated p300 HAT is more efficiently retained by immobilized ATF-2 b-ZIP than hypoacetylated p300 HAT. Loop deleted p300 HAT lacking autoacetylation was retained about as well as hyperacetylated p300 HAT, suggesting that the loop and ATF-2 compete for p300 HAT binding. While ATF-2 b-ZIP is a weak inhibitor of hypoacetylated p300 HAT acetylation of a histone H4 peptide, hyperacetylated p300 HAT is much more potently inhibited by ATF-2 b-ZIP. Moreover, we showed that ATF-2 b-ZIP could serve as an acetyltransferase substrate for p300 HAT. Using mass spectrometry, two p300 HAT lysine acetylation sites were mapped in ATF-2 b-ZIP. Immunoprecipitation-Western blot analysis with anti-acetyl-lysine antibody revealed that ATF-2 can undergo reversible acetylation in vivo. Mutational analysis of the two ATF-2 b-ZIP acetylation sites revealed their potential contributions to ATF-2-mediated transcriptional activation. Taken together, these studies suggest multiple roles for protein acetylation in the regulation of transcription by p300/CBP and ATF-2.


Genomewide analysis of phospholipid signaling genes in Phytophthora spp.: novelties and a missing link.
Phospholipids are cellular membrane components in eukaryotic cells that execute many important roles in signaling. Genes encoding enzymes required for phospholipid signaling and metabolism have been characterized in several organisms, but only a few have been described for oomycetes. In this study, the genome sequences of Phytophthora sojae and P. ramorum were explored to construct a comprehensive genomewide inventory of genes involved in the most universal phospholipid signaling pathways. Several genes and gene families were annotated, including those encoding phosphatidylinositol synthase (PIS), phosphatidylinositol (phosphate) kinase (PI[P]K), diacylglycerol kinase (DAG), and phospholipase D (PLD). The most obvious missing link is a gene encoding phospholipase C (PLC). In all eukaryotic genomes sequenced to date, PLC genes are annotated based on certain conserved features; however, these genes seem to be absent in Phytophthora spp. Analysis of the structural and regulatory domains and domain organization of the predicted isoforms of PIS, PIK, PIPK, DAG, and PLD revealed many novel features compared with characterized representatives in other eukaryotes. Examples are transmembrane proteins with a C-terminal catalytic PLD domain, secreted PLD-like proteins, and PIPKs that have an N-terminal G-protein-coupled receptor-transmembrane signature. Compared with other sequenced eukaryotes, the genus Phytophthora clearly has several exceptional features in its phospholipid-modifying enzymes.


Depot delivery of dexamethasone and cediranib for the treatment of brain tumor associated edema in an intracranial rat glioma model.
Treatments of brain tumor associated edema with systemically delivered dexamethasone, the standard of care, and cediranib, a novel anti-edema agent, are associated with systemic toxicities in brain tumor patients. A tunable, reservoir-based drug delivery device was developed to investigate the effects of delivering dexamethasone and cediranib locally in the brain in an intracranial 9L gliosarcoma rat model. Reproducible, sustained releases of both dexamethasone and solid dispersion of cediranib in polyvinylpyrrolidone (AZD/PVP) from these devices were achieved. The water-soluble AZD/PVP, which exhibited similar bioactivity as cediranib, was developed to enhance the release of cediranib from the device. Local and systemic administration of both dexamethasone and cediranib was equally efficacious in alleviating edema but had no effect on tumor growth. Edema reduction led to modest but significant improvement in survival. Local delivery of dexamethasone prevented dexamethasone-induced weight loss, an adverse effect seen in animals treated with systemic dexamethasone. Local deliveries of dexamethasone and cediranib via these devices used only 2.36% and 0.21% of the systemic doses respectively, but achieved similar efficacy as systemic drug deliveries without the side effects associated with systemic administration. Other therapeutic agents targeting brain tumor can be delivered locally in the brain to provide similar improved treatment outcomes.


Descemet membrane endothelial keratoplasty with a stromal rim (DMEK-S).
To describe a novel technique for the preparation and transplantation of posterior corneal lamellae consisting of endothelium and bare Descemet membrane with a stromal supporting rim. Posterior lamellar discs for Descemet membrane endothelial keratoplasty with a stromal rim (DMEK-S) were prepared manually immediately before surgery using the big bubble technique. The retrospective case series that underwent DMEK-S comprised 20 eyes of 18 patients with endothelial dysfunction. Best-corrected visual acuity (BCVA) and endothelial cell density (ECD) were measured preoperatively and 12-24 months after DMEK-S. At the end of the follow-up, 10 out of 18 eyes achieved a BCVA of 1.0 or better, and 17 reached 0.5 or better. Primary graft failure occurred in two eyes. The average ECD at 1 year was 1608 (+/-503) cells/mm(2), that is, a mean cell loss from preoperative values of 44%. Partial early postoperative graft detachment (12 of 20 eyes) was treated by injecting an air bubble into the anterior chamber in all cases. The loss of donor corneas during preparation decreased from approximately 10 to 5% as more experience was acquired with the procedure. Preliminary outcomes show that DMEK-S may be used in the treatment of corneal endothelial dysfunction. As this approach is entirely manual, and no special surgical equipment is needed, it has the potential to become widely adopted.


The impact of vitamin E supplementation on semen parameters and pregnancy rates after varicocelectomy: a randomised controlled study.
In this study, we aimed to investigate the impact of vitamin E supplementation on semen parameters and pregnancy after varicocelectomy. Forty-five infertile male patients who were diagnosed with varicocele and underwent subinguinal varicocelectomy were included in the study. After performing subinguinal varicocelectomy, the patients were randomised into two groups: 22 receiving vitamin E for 12 months, and 23 as the control group without receiving any supplementation. The pre-operative parameters of semen analyses and pregnancy rates of both groups were compared with those of post-operative parameters. There were no statistically significant differences between the groups in terms of sperm count and motile sperm percentage, in pre-operative, post-operative 3rd month, post-operative 6th month and post-operative 12th month periods. Repeated-measures anova was performed, and sperm count, percentage of change in sperm count, motile sperm count and percentage of change in motile sperm count of the groups were compared. The administration of vitamin E increased all of these parameters; however, they were not found to be statistically significant. In conclusion, vitamin E supplementation might improve the sperm parameters after varicocelectomy; however, further studies including larger number of samples are needed to make a proper decision on vitamin E supplementation after varicocelectomy.


Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy.
To identify biomarker candidates associated with early IgA nephropathy (IgAN) and thin basement membrane nephropathy (TBMN), the most common causes presenting isolated hematuria in childhood, a proteomic approach of urinary exosomes from early IgAN and TBMN patients was introduced. The proteomic results from the patients were compared with a normal group to understand the pathophysiological processes associated with these diseases at the protein level. The urinary exosomes, which reflect pathophysiological processes, collected from three groups of young adults (early IgAN, TBMN, and normal) were trypsin-digested using a gel-assisted protocol, and quantified by label-free LC-MS/MS, using an MS(E) mode. A total of 1877 urinary exosome proteins, including cytoplasmic, membrane, and vesicle trafficking proteins, were identified. Among the differentially expressed proteins, four proteins (aminopeptidase N, vasorin precursor, α-1-antitrypsin, and ceruloplasmin) were selected as biomarker candidates to differentiate early IgAN from TBMN. We confirmed the protein levels of the four biomarker candidates by semi-quantitative immunoblot analysis in urinary exosomes independently prepared from other patients, including older adult groups. Further clinical studies are needed to investigate the diagnostic and prognostic value of these urinary markers for early IgAN and TBMN. Taken together, this study showed the possibility of identifying biomarker candidates for human urinary diseases using urinary exosomes and might help to understand the pathophysiology of early IgAN and TBMN at the protein level.


Integrated management of ash from industrial and domestic combustion: a new sustainable approach for reducing greenhouse gas emissions from energy conversion.
This work supports, for the first time, the integrated management of waste materials arising from industrial processes (fly ash from municipal solid waste incineration and coal fly ash), agriculture (rice husk ash), and domestic activities (ash from wood biomass burning in domestic stoves). The main novelty of the paper is the reuse of wood pellet ash, an underestimated environmental problem, by the application of a new technology (COSMOS-RICE) that already involves the reuse of fly ashes from industrial and agricultural origins. The reaction mechanism involves carbonation: this occurs at room temperature and promotes permanent carbon dioxide sequestration. The obtained samples were characterized using XRD and TGA (coupled with mass spectroscopy). This allowed quantification of the mass loss attributed to different calcium carbonate phases. In particular, samples stabilized using wood pellet ash show a weight loss, attributed to the decomposition of carbonates greater than 20%. In view of these results, it is possible to conclude that there are several environmental benefits from wood pellet ash reuse in this way. In particular, using this technology, it is shown that for wood pellet biomass the carbon dioxide conversion can be considered negative.


Impact of financial incentives on alcohol intervention delivery in primary care: a mixed-methods study.
Local and national financial incentives were introduced in England between 2008 and 2015 to encourage screening and brief alcohol intervention delivery in primary care. We used routine Read Code data and interviews with General Practitioners (GPs) to assess their impact. A sequential explanatory mixed-methods study was conducted in 16 general practices representing 106,700 patients and 99 GPs across two areas in Northern England. Data were extracted on screening and brief alcohol intervention delivery for 2010-11 and rates were calculated by practice incentive status. Semi-structured interviews with 14 GPs explored which factors influence intervention delivery and recording in routine consultations. Screening and brief alcohol intervention rates were higher in financially incentivised compared to non-incentivised practices. However absolute rates were low across all practices. Rates of short screening test administration ranged from 0.05% (95% CI: 0.03-0.08) in non-incentivised practices to 3.92% (95% CI: 3.70-4.14) in nationally incentivised practices. For the full AUDIT, rates were also highest in nationally incentivised practices (3.68%, 95% CI: 3.47-3.90) and lowest in non-incentivised practices (0.17%, 95% CI: 0.13-0.22). Delivery of alcohol interventions was highest in practices signed up to the national incentive scheme (9.23%, 95% CI: 8.91-9.57) and lowest in non-incentivised practices (4.73%, 95% CI: 4.50-4.96). GP Interviews highlighted a range of influences on alcohol intervention delivery and subsequent recording including: the hierarchy of different financial incentive schemes; mixed belief in the efficacy of alcohol interventions; the difficulty of codifying complex conditions; and GPs' beliefs about patient-centred practice. Financial incentives have had some success in encouraging screening and brief alcohol interventions in England, but levels of recorded activity remain low. To improve performance, future policies must prioritise alcohol prevention work within the quality and outcomes framework, and address the values, attitudes and beliefs that shape how GPs' provide care.