Evidence for a complex formation between CYP2J5 and mEH in living cells by FRET analysis of membrane protein interaction in the endoplasmic reticulum (FAMPIR).
The potential complex formation between microsomal epoxide hydrolase (mEH) and cytochrome P450-dependent monooxygenase (CYP) has been a subject of research for many decades. Such an association would enable efficient substrate channeling between CYP and mEH and as such represent an attractive strategy to prevent deleterious accumulation of harmful metabolic by-products such as CYP-generated epoxide intermediates. However, such complex formation is experimentally difficult to prove, because CYP and mEH are membrane-bound proteins that are prone to unspecific aggregation after solubilization. Here, we report the development of a FRET-based procedure to analyze the mEH-CYP interaction in living cells by fluorescence-activated cell sorting. With this non-invasive procedure, we demonstrate that CYP2J5 and mEH associate in the endoplasmic reticulum of recombinant HEK293 cells to the same extent as do CYP2J5 and its indispensible redox partner cytochrome P450 reductase. This presents final proof for a very close proximity of CYP and mEH in the endoplasmic reticulum, compatible with and indicative of their physical interaction. In addition, we provide with FAMPIR a robust and easy-to-implement general method for analyzing the interaction of ER membrane-resident proteins that share a type I topology.


[Factors associated with birthweight of Terena indigenous children living in the urban area of Campo Grande, Mato Grosso do Sul State, Brazil].
The study aimed to verify the association between birthweight of Terena children living in the urban area of Campo Grande, Mato Grosso do Sul State, Brazil, and demographic, socioeconomic, and health variables and to describe the prevalence of low birthweight. Data were collective through home visits with a form completed with the mothers and based on records from the prenatal and neonatal cards. The sample included all the Terena women who gave birth to liveborn children from June 1, 2017, to July 31, 2018, and living in the Água Bonita, Darcy Ribeiro, Marçal de Souza, and Tarsila do Amaral villages. Birthweight was the outcome, and demographic, socioeconomic, and health characteristics were the exposure variables. A total of 43 mothers participated with their children. Low birthweight prevalence was 2.3%. In the final model, children living in households with makeshift cesspools showed lower birthweight when compared to those living in households connected to the public sewage disposal system, and daughters of mothers who were obese prior to the pregnancy presented higher birthweight than those born to normal weight mothers, according to pregestational body mass index. The data seek to contribute to discussions on the health and nutrition of this important share of the indigenous population that lives in urban areas.


Effects of Testosterone Administration on Strategic Gambling in Poker Play.
Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone's primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players' bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one's reputation by revealing deceptive intent, and secondly, not calling the other players' bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous.


Blockade of β2-adrenoceptor, rather than β1-adrenoceptor, deteriorates cardiac anaphylaxis in isolated blood-perfused rat hearts.
Cardiac anaphylaxis is one of the features of anaphylactic hypotension. Patients treated with propranolol, a nonselective β-adrenoceptor (AR) antagonist, develop severe anaphylaxis, but the mechanism remains unknown. Under examination were the effects of β1- and β2-AR antagonist on anaphylaxis-induced coronary vasoconstriction and cardiac dysfunction in isolated blood-perfused rat hearts. Isolated hearts from ovalbumin-sensitized Wistar rats were subjected to coronary perfusion with blood at a constant pressure and measurements were made of coronary blood flow and left ventricu-lar (LV) pressure. Following pretreatment with selective β2-AR antagonist ICI118,551 or selective β1-AR antagonist atenolol, cardiac anaphylaxis was induced by intracoronary injections of ovalbumin antigen. LV contractility was evaluated by the maximum increasing rate of systolic LV pressure (dP/dtmax). In response to antigen administrations, ICI118,551 pretreated hearts showed a greater de-crease in coronary blood flow and consequently a greater increase in coronary vascular resistance than the atenolol pretreated hearts. Pretreatment with ICI118,551 caused a greater decrease in dP/dtmax than those with atenolol. Cardiac anaphylaxis-induced contractile dysfunction and coronary spasm are severe in b2-, rather than β1-AR antagonist, pretreated isolated blood-perfused rat hearts.


N,N-Dimethyl-3-phenyl-isoxazole-5-carbox-amide.
In the title compound, C12H12N2O2, synthesized by ammonolysis of 3-phenyl-isoxazole-5-carbonyl chloride in di-chloro-methane, the dihedral angle between the isoxazole ring and the phenyl ring is 14.05 (7)°. In the crystal, centrosym-metrically related mol-ecules are linked into dimers by pairs of C-H⋯O hydrogen bonds, generating rings of graph-set motif R 2 (2)(10).


Secondary Metabolites of Onygenales Fungi Exemplified by Aioliomyces pyridodomos.
Fungi from the order Onygenales include human pathogens. Although secondary metabolites are critical for pathogenic interactions, relatively little is known about Onygenales compounds. Here, we use chemical and genetic methods on Aioliomyces pyridodomos, the first representative of a candidate new family within Onygenales. We isolated 14 new bioactive metabolites, nine of which are first disclosed here. Thirty-two specialized metabolite biosynthetic gene clusters (BGCs) were identified. BGCs were correlated to some of the new compounds by heterologous expression of biosynthetic genes. Some of the compounds were found after one year of fermentation. By comparing BGCs from A. pyridodomos with those from 68 previously sequenced Onygenales fungi, we delineate a large biosynthetic potential. Most of these biosynthetic pathways are specific to Onygenales fungi and have not been found elsewhere. Family level specificity and conservation of biosynthetic gene content are evident within Onygenales. Identification of these compounds may be important to understanding pathogenic interactions.


Effect of low-temperature oxidation and heat treatment under vacuum on the Al-Be interdiffusion process.
The oxidation of the Be/Al and Al/Be bilayer thin film systems deposited by magnetron sputtering have been studied by photoelectron spectroscopy and transmission electron microscopy. Both systems are oxidized according to the Cabrera-Mott model in the air. A Be/BeO/Al/Al2O3 structure is formed, with aluminium represented as localized nanocrystals. The thickness of the beryllium in the Al/Be system and the formed beryllium oxide is not enough to prevent the diffusion of aluminium ions under the influence of the Mott potential, and as a result, the surface layer is a mixture of beryllium and aluminium oxides. The effect of oxidation processes on the intermixing of non-interacting metals in a bilayer nanostructure has been shown for the first time. Annealing of the Be/Al bilayer leads to beryllium diffusion to the surface and the reduction of aluminium oxide, which leads to the destruction of the bilayer structure. In the Al/Be system in the range up to 200 °C, additional beryllium oxide is formed with increasing temperature, and the rest of the metallic beryllium diffuses into the aluminium layer. Based on studies, we conclude that multilayer Al/Be nanostructures have potentially low thermal stability, which requires the use of barrier layer techniques to limit interdiffusion.


Eupatorin Suppressed Tumor Progression and Enhanced Immunity in a 4T1 Murine Breast Cancer Model.
Eupatorin is a polymethoxy flavone extracted from Orthosiphon stamineus and was reported to exhibit cytotoxic effects on several cancer cell lines. However, its effect as an anti-breast cancer agent in vivo has yet to be determined. This study aims to elucidate the potential of eupatorin as an anti-breast cancer agent in vivo using 4T1 challenged BALB/c mice model. In this article, BALB/c mice (20-22 g) challenged with 4T1 cells were treated with 5 mg/kg or 20 mg/kg eupatorin, while the untreated and healthy mice were fed with olive oil (vehicle) via oral gavage. After 28 days of experiment, the mice were sacrificed and blood was collected for serum cytokine assay, while tumors were harvested to extract RNA and protein for gene expression assay and hematoxylin-eosin staining. Organs such as spleen and lung were harvested for immune suppression and clonogenic assay, respectively. Eupatorin (20 mg/kg) was effective in delaying the tumor development and reducing metastasis to the lung compared with the untreated mice. Eupatorin (20 mg/kg) also enhanced the immunity as the population of NK1.1+ and CD8+ in the splenocytes and the serum interferon-γ were increased. Concurrently, eupatorin treatment also has downregulated the expression of pro-inflammatory and metastatic related genes (IL-1β. MMP9, TNF-α, and NF-κB). Thus, this study demonstrated that eupatorin at the highest dosage of 20 mg/kg body weight was effective in delaying the 4T1-induced breast tumor growth in the animal model.


Pentastomiasis: case report of an acute abdominal emergency.
A 34-year-old native women presented as an acute abdominal emergency at the Surgery Department, Missionary Hospital "Ad Lucem" in Banka-Bafang, Cameroon. She complained of colicky, epigastric abdominal pain, nausea, vomiting, constipation, and retention of flatus. At laparotomy, numerous small cystic nodules (3-8 mm in diameter) were noted in the mesentery and under the intestinal and parietal peritoneum. Histological examination of two of them revealed slightly enlarged mesenteric lymph nodes containing several parasitic pseudocysts. The parasites were diagnosed as well-preserved, encysted, Armillifer armillatus nymphs. Neither degenerative nor inflammatory granulomatous reactions were observed in the adjacent tissue. Two and a half years later, a similar attack of acute abdominal symptoms recurred. A radiological examination revealed several C-shaped or circular, dense opacities characteristic of calcified pentastomid nymphs. At laparotomy, local findings similar to those at the previous surgical examination were noted. Additionally, a few firm, whitish, calcified nodules were found in the mesentery and under the fibrous capsule of the liver.


[How to minimize weight gain associated with insulin treatment].
Insulin treatment is associated with two important and frequent side effects: hypoglycemia and weight gain. Weight gain is in contradiction with the physiological central effect of insulin which leads to decreased food intake like leptin. However, decreased urinary caloric loss due to better glycemic control, prevention and correction of hypoglycemia, the anabolic effect of insulin and the possible central resistance to insulin explain the observed weight gain. Insulin is often necessary when oral antidiabetic treatment fails; the physician and the patient need to remain alert to minimize the side effects through adequate insulin regimen and life style.


Overexpression of GmPHR1 Promotes Soybean Yield through Global Regulation of Nutrient Acquisition and Root Development.
MYB-CC transcription factors (TFs) are essential for plant growth and development. Members of the MYB-CC subfamily with long N terminal domains, such as phosphate starvation response 1 (PHR1) or PHR1-like TFs, have well documented functions, while those with short N terminal domains remain less understood. In this study, we identified a nodule specific MYB-CC transcription factor 1 (GmPHR1) in soybean that is different from other canonical PHR family genes in that GmPHR1 harbors a short N terminal ahead of its MYB-CC domain and was highly induced by rhizobium infection. The overexpression of GmPHR1 dramatically increased the ratio of deformed root hairs, enhanced subsequent soybean nodulation, and promoted soybean growth in pot experiments. The growth promotion effects of GmPHR1 overexpression were further demonstrated in field trails in which two GmPHR1-OE lines yielded 10.78% and 8.19% more than the wild type line. Transcriptome analysis suggested that GmPHR1 overexpression led to global reprogramming, with 749 genes upregulated and 279 genes downregulated, especially for genes involved in MYB transcription factor activities, root growth, and nutrient acquisition. Taken together, we conclude that GmPHR1 is a key gene involved in the global regulation of nodulation, root growth, and nutrient acquisition in soybeans, and is thus a promising candidate gene to target for soybean yield enhancement.


Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing.
The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well as other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. The intestinal mucosa is covered by mucin, which contains antimicrobial peptides and secretory IgA and prevents luminal bacteria, fungi, and viruses from stimulating intestinal immune responses. Conversely, the transport of luminal microorganisms-mediated by M, dendritic, and goblet cells-into intestinal tissues facilitates the harmonization of active and quiescent mucosal immune responses. The bacterial population within gut-associated lymphoid tissues creates the intratissue cohabitations for harmonized mucosal immunity. Intermolecular and intercellular communication among epithelial, immune, and mesenchymal cells creates an environment conducive for epithelial regeneration and mucosal healing. This review summarizes the so-called intestinal mucosal ecological network-the complex but vital molecular and cellular interactions of epithelial mesenchymal cells, immune cells, and commensal microbiota that achieve intestinal homeostasis, regeneration, and healing.


Complete Genome Sequence of Staphylococcus aureus Myophage Maine.
Multidrug-resistant strains of Staphylococcus aureus cause serious human disease worldwide. Bacteriophages offer a promising alternative to traditional antibiotics. Here, we announce the 141,712-bp genome of S. aureus phage Maine. A myophage with 9,019-bp predicted terminal repeats and high similarity to other Staphylococcus phages, Maine falls into the Twort-like group.


Diagnosis of osteoporosis.
Early diagnosis is the key to the prevention and treatment of osteoporosis. A healthy skeleton has intrinsic properties that confer strength to resist fracture under ordinary stress. Some of the properties that confer strength and fracture resistance include: bone mass or density and bone quality determined by skeletal composition, fine structure and spatial organization, geometric properties, and rate of remodeling. The current approach to early diagnosis of osteoporosis is based on the measurement of bone mass or bone mineral density (BMD). Low bone mass is the single most accurate predictor of increased fracture risk. BMD accounts for 70% to 80% of the future fracture risk in older white women and is a far better predictor of osteoporosis than hypertension is for stroke or total cholesterol is for cardiovascular events in men. Perhaps in the future a better understanding and quantification of bone quality will help refine our ability to identify patients at risk. BMD can be measured at a variety of skeletal sites using several different methods that have been approved by the FDA. The basic attributes of each method will be addressed in this paper, with particular attention given to the method that is currently considered the gold standard, dual energy x-ray absorptiometry. The indications for BMD testing, clinical utility of BMD, frequency of follow-up testing, correlation between the available densitometry methods, problems and pitfalls in interpretation, and features of a satisfactory densitometry report of results will all be addressed. The current role of biochemical markers of bone turnover in the diagnosis and monitoring of treatment will be discussed briefly.


Robust quantification of the SMN gene copy number by real-time TaqMan PCR.
Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutation or deletion of the survival motor neuron gene 1 (SMN1). The highly homologous gene, SMN2, is present in all patients, but it cannot compensate for loss of SMN1. SMN2 differs from SMN1 by a few nucleotide changes, but a C --> T transition in exon 7 leads to exon skipping. As a result, most transcripts from the SMN2 gene lack exon 7. Although SMN1 is the disease-determining gene, the number of SMN2 copies appears to modulate SMA clinical phenotypes. Thus, determining the SMN copy number is important for clinical diagnosis and prognosis. We have developed a quantitative real-time TaqMan polymerase chain reaction assay for both the SMN1 and SMN2 genes, in which reliable copy number determination was possible on deoxyribonucleic acid samples obtained by two different isolation methods and from two different sources (human blood and skin fibroblasts). For SMN1, allele specificity was attained solely by addition of an allele-specific forward primer and, for SMN2, by addition of a specific forward primer and a nonextending oligonucleotide (SMN1 blocker) that reduced nonspecific amplification from SMN1 to a negligible level. We validated the reliability of this real-time polymerase chain reaction approach and found that the coefficient of variation for all the gene copy number measurements was below 10%. Quantitative analysis of the SMN copy number in SMA fibroblasts by this approach showed deletion of SMN1 and an inverse correlation between the SMN2 copy number and severity of the disease.


Aspirin failure in patients presenting with acute cerebrovascular ischaemia.
Aspirin is the most commonly used antiplatelet drug for prevention of ischaemic stroke. In order to determine the prevalence and nature of aspirin failure, we studied 51 adults admitted with suspected ischaemic stroke and already prescribed daily aspirin. Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet aggregation, activation and aspirin response by a range of methods. All tests were then repeated on a second sample taken 24 h after witnessed administration of 75 mg or 150 mg aspirin. At entry to the study, incomplete response to aspirin, measured by arachidonic acid (AA)-stimulated platelet aggregation, was found in 43% of patients. Following in-hospital aspirin administration, there was a significant decrease in AA-aggregation (p=0.001) suggesting poor adherence to therapy prior to admission. However, residual aggregation (10-15%) persisted in 11 subjects - suggesting alternative causes. In incomplete responders on admission, platelet aggregation with adenosine diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there were no significant differences in collagen aggregation, platelet fibrinogen binding or P-selectin expression, plasma von Willebrand factor, fibrinogen, high-sensitivity C-reactive protein, or the urinary metabolite, 11-dehydro-TxB2. Incomplete platelet inhibition is common around the time of acute cerebrovascular ischaemic events in patients prescribed aspirin. Up to 50% of these observations appear due to incomplete adherence to aspirin therapy. Intervention studies are required to determine the clinical relevance of measured platelet response to aspirin in terms of outcome, and the effectiveness of improved pharmacotherapy for stroke prevention.


Old Drugs and New Targets as an Outlook for the Treatment of Tuberculosis.
Despite of the globally positive trends in the epidemiology of tuberculosis, the increasing rates of drug-resistant strains are urging to introduce new antituberculars into clinical practice. Development of a new chemical entity from hit to marketed drug is an extremely time and resources consuming process with uncertain outcome. Repurposing of clinically used drugs can be a cheaper alternative to develop new drugs effective in the treatment of tuberculosis. To extract the latest information on new mechanisms of action described or proposed for clinically used antitubercular drugs. To identify drugs from various pharmacodynamic groups as candidates for repurposing to become effective in combatting tuberculosis. Attention will be paid to elucidate the connection between repurposed drugs and new antituberculars in clinical practice or in clinical trials. Scientific databases were searched for the keywords. We reviewed the latest aspects of usage and new mechanisms of action for both first-line and second-line antitubercular drugs in clinical practice. Further, we found that surprisingly large number of clinically used drugs from various pharmacodynamic groups have potential to be used in the treatment of tuberculosis, including antimicrobial drugs not typically used against tuberculosis, statins, CNS drugs (tricyclic phenothiazines, antidepressants, anticonvulsants), non-steroidal anti-inflammatory drugs, kinase inhibitors, and others (metformin, disulfiram, verapamil, lansoprazole). Repurposed drugs may become effective antituberculars, acting either by direct effects on mycobacteria or as adjunct, host-directed therapy. In this review, we showed that proper research of old drugs is a very efficient tool to develop new antituberculars.


Prevalence, frequency, and disability of migraine headaches and tension headaches among the general population in the Eastern Region of Saudi Arabia.
A tension-type headache (TTH) is a recurrent headache that is mild to moderate in intensity, unlike migraine (MH), which is accompanied by crippling effects of nausea, vomiting, photophobia, or phonophobia. TTH is more frequent than migraine, but it is less likely to cause severe pain and physical dysfunction. TTHs account for more lost workdays due to their prevalence. The study aimed to evaluate the prevalence, frequency, and disability of MHs and TTHs among the general population in the Eastern Region of Saudi Arabia. A cross-sectional study was employed using a validated questionnaire. The questionnaire implemented the HARDSHIP algorithm to diagnose MH and TTH and questions to correlate their prevalence to socio-demographic data, measurement of the level of disability, headache management, and treatment effectiveness using the chi-square test. The study reviewed 877 subjects (46.6% males vs. 53.4% females). 52.9% of the participants experienced headaches during the previous three months, and 35.6% experienced headaches recently. The most common type of headache was a probable MH (32.1%), followed by a TTH (26.9%), probable TTH (19.5%), and MH (15%). It was reported that some disability was attributed to 47% of MHs and 26% of TTHs. The most commonly used headache medication was paracetamol (53.5%). This study revealed that TTH and MH are common illnesses in Saudi Arabia's Eastern Region. TTH and MH are correlated with significant individual and social burdens, particularly for MH. Headache sufferers mostly manage their headaches using conventional over-the-counter methods.


Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells.
Influenza A virus (IAV) poses global threats to human health. Acute respiratory distress syndrome and multi-organ dysfunction are major complications in patients with severe influenza infection. This may be explained by the recent studies which highlighted the role of the pulmonary endothelium as the center of innate immune cells recruitment and excessive pro-inflammatory cytokines production. In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3'-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3'-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs). Infection of H9N2 on HPMECs induced a high level of chemokines and cytokines production including IP-10, RANTES, IL-6, IFN-β and IFN-γ1. Post-treatment of E804 or E231 could significantly suppress the production of these cytokines. H9N2 infection rapidly triggered the activation of innate immunity through phosphorylation of signaling molecules including mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT) proteins. Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways. These results underscore the immunomodulatory effects of indirubin derivatives on pulmonary endothelium and its therapeutic potential on IAV-infection.


A Case of Generalized Xerotic Eczema in a Patient with Congenital Insensitivity to Pain with Anhidrosis.
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare disease characterized by insensitivity to pain, anhidrosis, and intellectual disability. CIPA is caused by a genetic mutation in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene on chromosome 1. The anhidrosis leads to cutaneous changes such as skin dryness, lichenification, and impetiginization. Moreover, patients with CIPA may experience repeated trauma and recalcitrant eczema due to excessive scratching of wounds on their skin, because they do not feel any pain. Severe whole-body eczema in a patient with CIPA may be overlooked, leading these patients to be frequently diagnosed with atopic dermatitis and common eczema. Indeed, in patients with treatment-resistant or atypically distributed eczema and underlying anhidrosis, CIPA should be considered as a potential causative disease. Increased awareness of CIPA among dermatologists is necessary to ensure that patients receive an appropriate diagnosis. Herein, we report a rare case of generalized xerotic eczema in a patient with CIPA.


Effectiveness of Vigna unguiculata seed extracts in preventing colorectal cancer.
Colorectal cancer (CRC) is one of the most common types of cancer, especially in Western countries, and its incidence rate is increasing every year. In this study, for the first time Vigna unguiculata L. Walp. (cowpea) water boiled seed extracts were found to reduce the viability of different colorectal cancer (CRC) cell lines, such as E705, DiFi and SW480 and the proliferation of Caco-2 line too, without affecting CCD841 healthy cell line. Furthermore, the extracts showed the ability to reduce the level of Epidermal Growth Factor Receptor (EGFR) phosphorylation in E705, DiFi and SW480 cell lines and to lower the EC50 of a CRC common drug, cetuximab, on E705 and DiFi lines from 161.7 ng mL-1 to 0.06 ng mL-1 and from 49.5 ng mL-1 to 0.2 ng mL-1 respectively. The extract was characterized in its protein and metabolite profiles by tandem mass spectrometry and 1H-NMR analyses. A Bowman-Birk protease inhibitor was identified within the protein fraction and was supposed to be the main active component. These findings confirm the importance of a legume-based diet to prevent the outbreak of many CRC and to reduce the amount of drug administered during a therapeutic cycle.


Objective Assessment of Physiologic Alterations Associated With Hemodynamically Significant Patent Ductus Arteriosus in Extremely Premature Neonates.
Delay in closure of ductus arteriosus in postnatal life may lead to serious consequences and complications in an extremely premature neonate secondary to hemodynamic alterations in regional blood flow pattern in various organs. Despite the widespread recognition amongst neonatologists to identify a hemodynamically significant patent ductus arteriosus (hsPDA) early in the postnatal course, there is lack of consensus in its definition and thus the threshold to initiate treatment. Echocardiographic assessment of PDA shunt size and volume combined with neonatologists' impression of clinical significance is most frequently used to determine the need for treatment of PDA. Common clinical signs of hsPDA utilized as surrogate for decreased tissue perfusion may lag behind early echocardiographic signs. Although echocardiogram allows direct assessment of PDA shunt and hemodynamic alterations in the heart, it is limited by dependence on pediatric cardiologist availability, interobserver variation and isolated time point assessment. Electrical cardiometry (EC) is a non-invasive continuous real time measurement of cardiac output by applying changes in thoracic electrical impedance. EC has been validated in preterm newborns by concomitant transthoracic echocardiogram assessments and may be beneficial in studying changes in cardiac output in premature newborns with hsPDA. Alterations in perfusion index derived from continuous pulse oximetry monitoring has been used to study changes in cardiac performance and tissue perfusion in infants with PDA. Near infrared spectroscopy (NIRS) has been used to objectively and continuously assess variations in renal, mesenteric, and cerebral oxygen saturation and thus perfusion changes due to diastolic vascular steal from hsPDA in preterm neonates. Doppler ultrasound studies measuring resistive indices in cerebral circulation indicate disturbance in cerebral perfusion secondary to ductal steal. With recent trends of change in practice toward less intervention in care of preterm newborn, treatment strategy needs to be targeted for select preterm population most vulnerable to adverse hemodynamic effects of PDA. Integration of these novel ways of hemodynamic and tissue perfusion assessment in routine clinical care may help mitigate the challenges in defining and targeting treatment of hsPDA thereby improving outcomes in extremely premature neonates.


Evidence for hidden order in a nonlinear model elastic system.
Hidden order may arise in strongly correlated systems even if there is an apparent lack of long-range order as measured by local order parameters. This phenomenon has been essentially associated with topological order in quantum systems. Here, we demonstrate the emergence of hidden order in a 1D non-linear classical mechanical system that supports rotational degrees of freedom. The potential energy of the model system creates a bistable system for which hidden order emerges with the introduction of a biquadratic term. To our surprise, we discover that varying the strength of the biquadratic term leads to four distinct phases quantified by the behaviors of the Néel and string order parameters. Three of these phases are locally disordered. Hidden order is identified by a string order parameter that shows correlations with significantly longer range than the Néel order parameter. The hidden order correlation length diverges as the kinetic energy of the system is lowered with a critical exponent ~0.5. The observation of hidden order in a mechanical system reveals that instability and non-linearity may play critical roles in the generation of nonlocal long-range correlations in apparently locally disordered systems.


The role of the extracellular matrix in neoplastic glial invasion of the nervous system.
Intrinsic tumours of the central nervous system (CNS) are generally derived from the glial cells: the astrocytes, oligodendrocytes and ependymal cells. Although such tumours rarely metastasize to distant organs, they show a marked propensity for local invasion of the surrounding nervous tissue. Sub-populations of neoplastic glia may migrate several millimetres away from main tumour mass into the contiguous CNS parenchyma, resulting in poor demarcation of the tumour. These migratory, so-called "guerrilla" cells give rise to recurrent tumours following surgical debulking and adjuvant radio- and chemo-therapeutic intervention. As in other organs, tumour cell invasion is, in part, facilitated by interaction with the extracellular matrix (ECM); however, apart from the vascular basal lamina and the glia limitans externa, the CNS lacks a well-defined ECM. Invading neoplastic cells must, therefore, provide their own ECM, a process which may be stimulated by such agents as gangliosides or growth factors. Glioma cell-derived laminin and hyaluronic acid may provide the most important substrates for invasion, cell adhesion to these substrates being achieved largely through integrin receptors (the function of which may be determined by interaction with cell surface gangliosides) and CD44, respectively. Modulation of these ECM components is facilitated by a variety of proteinases including the matrix metalloproteinases and hyaluronidase, the activity of which is also thought to stimulate angiogenesis. Interference with the mechanisms which promote glioma cell adhesive properties may provide suitable targets for novel anti-invasive therapies. These might include ECM components, growth factors, gangliosides, integrin receptors and proteases and their inhibitors.


Comparison of ThinPrep and conventional smears in detecting carcinoma in bile duct brushings.
Bile duct brushing cytology is a common procedure for the exclusion of adenocarcinoma in the bile duct. The authors evaluated the use of ThinPrep (TP) to determine whether the information obtained is equivalent to that found with conventional smear cytology (CS). Thirty-eight prospectively collected endoscope retrograde cholangiopancreatography-guided bile duct brushing samples were split in the following manner. First, two to four CS were prepared and immediately spray-fixed or wet-fixed. Second, the remaining sample was rinsed in PreservCyt (Cytyc Corp., Boxborough, MA). In the laboratory, one TP slide was prepared from each sample. TP and CS were stained by routine Papanicolaou stain. For the current study, TP and CS were reviewed independently by two cytopathologists. The diagnoses made by the two methods were compared with the final histology. The cytologic diagnoses for both TP and CS were categorized into five main groups: 1) unsatisfactory, 2) negative, 3) reactive, 4) suspicious for malignancy, and 5) malignant. The diagnoses on the 38 TP bile duct brushings and CS were categorized as follows: 1) unsatisfactory-2, 4; 2) negative-7, 4; 3) reactive-10, 14; 4) suspicious for malignancy-9, 9; and 5) malignant-10, 7, respectively. Histologic follow-up was available in 14 cases (reactive-4, suspicious for malignancy-1, and malignant-9). The sensitivity was 77% for TP and 66% for CS. The specificity was 100% for both methods. The two methods described in the current study detected equivalent disease on bile duct brushings. TP was found to provide better preservation and cytologic detail. However, the diagnostic criteria may require modification.


Fluorescence probe for real-time malonaldehyde detection in epilepsy model.
Oxidative stress, a condition involving an imbalance between reactive oxygen species (ROS) and antioxidants, is closely linked to epilepsy, contributing to abnormal neuronal excitability. This study introduces a novel fluorescent probe, the MDP probe, designed for the efficient detection of malondialdehyde (MDA), a critical biomarker associated with oxidative stress. The MDP probe offers several key advantages, including high sensitivity with a low detection limit of 0.08 μM for MDA, excellent selectivity for MDA even in the presence of interfering substances, and biocompatibility, making it suitable for cell-based experiments. The probe allows for real-time monitoring of MDA levels, enabling dynamic studies of oxidative stress. In vivo experiments in mice demonstrate its potential for monitoring MDA levels, particularly in epilepsy models, which could have implications for disease research and diagnosis. Overall, the MDP probe represents a promising tool for studying oxidative stress, offering sensitivity and specificity in cellular and in vivo settings. Its development opens new avenues for exploring the role of oxidative stress in various biological processes and diseases, contributing to advancements in healthcare and biomedical research.


Elevated body mass index as a causal risk factor for symptomatic gallstone disease: a Mendelian randomization study.
Elevated body mass index (BMI) is associated with an increased risk of gallstone disease. Whether this reflects a causal association is unknown. Using a Mendelian randomization approach, we studied 77,679 individuals from the general population. Of these, 4,106 developed symptomatic gallstone disease during up to 34 years of follow-up. Subjects were genotyped for three common variants known to associate with BMI: FTO(rs9939609); MC4R(rs17782313); and TMEM18(rs6548238). The number of BMI-increasing alleles was calculated for each participant. In observational analyses, mean baseline BMI was 55% (11.6 kg/m(2) ) increased in individuals in the fifth quintile versus the first quintile, similar in women and men. The corresponding multifactorially adjusted hazard ratio (HR) for symptomatic gallstone disease was 2.84 (95% confidence interval [CI]: 2.32-3.46) overall, 3.36 (95% CI: 2.62-4.31) in women, and 1.51 (95% CI: 1.09-2.11) in men (P trend: 0.001 to <0.001; P interaction: BMI*sex on risk = 0.01). In genetic analyses, carrying 6 versus 0-1 BMI-increasing alleles was associated with a 5.2% (1.3 kg/m(2) ) increase in BMI overall and with increases of 4.3% in women and 6.1% in men (all P trend: <0.001). Corresponding HRs for symptomatic gallstone disease were 1.43 (95% CI: 0.99-2.05) overall, 1.54 (95% CI: 1.00-2.35) in women, and 1.19 (95% CI: 0.60-2.38) in men (P trend = 0.007, 0.02, and 0.26, respectively; P interaction allele score*sex on risk = 0.49). The estimated causal odds ratio (OR) for symptomatic gallstone disease, by instrumental variable analysis for a 1 kg/m(2) increase in genetically determined BMI, was 1.17 (95% CI: 0.99-1.37) overall and 1.20 (95% CI: 1.00-1.44) and 1.02 (95% CI: 0.90-1.16) in women and men, respectively. Corresponding observational HRs were 1.07 (95% CI: 1.06-1.08), 1.08 (95% CI: 1.07-1.10), and 1.04 (95% CI: 1.02-1.07), respectively. These results are compatible with a causal association between elevated BMI and increased risk of symptomatic gallstone disease, which is most pronounced in women.


Initial Experiments for Pharmacovigilance Analysis in Social Media Using Summaries of Product Characteristics.
We report initial experiments for analyzing social media through an NLP annotation tool on web posts about medications of current interests (baclofen, levothyroxine and vaccines) and summaries of product characteristics (SPCs). We conducted supervised experiments on a subset of messages annotated by experts according to positive or negative misuse; results ranged from 0.62 to 0.91 of F-score. We also annotated both SPCs and another set of posts to compare MedDRA annotations in each source. A pharmacovigilance expert checked the output and confirmed that entities not found in SCPs might express drug misuse or unknown ADRs.


Replantation in the mutilated hand.
With the evolution of surgical techniques and scientific technology, replantation has become more refined, establishing specific indications for replantation, rituals for preparation, efficient techniques to ultimately minimize ischemia times, improved survival rates, guidelines for postoperative care, strategies for treating complications, and goals for outcomes. Patient satisfaction hinges on their level of expectation as defined and explained in the preoperative discussion and informed consent. Studies have demonstrated patients can be expected to achieve 50% function and 50% sensation of the replanted part. Initially all that was amputated was replanted, as surgeons adopted the philosophy of George C. Ross (1843-1892): "Any fool can cut off an arm or leg but it takes a surgeon to save one." Forty years after the first replant (1962-2002), however, we recognize the ultimate goal: not merely to preserve all living tissue through nonselective replantation, but rather to preserve one's quality of life by improving their function and appearance. This objective to care for the patient with the intent to optimize function and appearance is important not only to the replantation of amputations but to all mutilated hand injuries.


Interventions for central retinal vein occlusion: an evidence-based systematic review.
To assess the evidence for the effectiveness of interventions to improve visual acuity (VA) and prevent or treat neovascularization secondary to central retinal vein occlusion (CRVO). Central retinal vein occlusion is a common cause of visual morbidity and blindness. Many different interventions have been advocated, but the evidence justifying their use remains unclear. English and non-English language articles were retrieved using a keyword search of Medline (1966 onwards), Embase, the Cochrane Collaboration, the National Institutes of Health Clinical Trials database, and the Association for Research in Vision and Ophthalmology (2003-2005). This was supplemented by manually searching references of review articles. Two investigators independently identified all randomized clinical trials (RCTs) on interventions in CRVO with more than 3 months' follow-up. Of 4133 citations retrieved, 17 RCTs comparing intervention with a control group were identified. There were 4 RCTs on laser photocoagulation. Grid macular laser photocoagulation did not improve VA in CRVO with macular edema. Prophylactic panretinal photocoagulation did not prevent angle and iris neovascularization in ischemic CRVO, but resulted in regression of angle and iris neovascularization and reduced progression to neovascular glaucoma. There were 4 RCTs that reported improvement in VA with inpatient hemodilution, 2 RCTs with no significant improvement, and 1 RCT showing deterioration in VA after outpatient hemodilution. Randomized clinical trials evaluating ticlodipine, troxerutin, and streptokinase showed a limited or no benefit. This review found limited level I evidence for any intervention to improve VA in patients with CRVO. Panretinal photocoagulation resulted in regression of neovascularization. Hemodilution may improve vision in some patients, but the data conflict. More robust randomized controlled trials evaluating current treatments for CRVO are needed. The results of ongoing RCTs on intravitreal triamcinolone, anti-vascular endothelial growth factor agents, and chorioretinal anastomosis are awaited with interest.


Intracellular localization of the Menkes and Wilson's disease proteins and their role in intracellular copper transport.
Copper is a heavy metal ion essential for the activity of a variety of enzymes in the body. In excess, copper is a very toxic ion and therefore efficient regulation of its metabolism is required. This is dramatically illustrated by the genetic disorders X-linked Menkes disease and autosomal recessive Wilson's disease. In 1993, both the Menkes and Wilson's genes were isolated and it was found that these genes encode homologous cation copper transporting P-type ATPase proteins. The Menkes protein (ATP7A) is expressed in most tissues, except liver. In contrast, the Wilson's protein (ATP7B) is abundantly expressed in liver. Intracellular localization of those proteins was investigated. Both ATP7A and ATP7B are localized in the trans-Golgi network and post-Golgi vesicular compartment (PGVC) in the cell. This intracellular localization was altered by the copper content present in the cell. This result may support the hypothesis that ATP7A and ATP7B are involved in cellular copper transport and those proteins could be suitable models for elucidating intracellular copper metabolism.


Chronic Gastrointestinal and Joint-Related Sequelae Associated with Common Foodborne Illnesses: A Scoping Review.
To strengthen the burden estimates for chronic sequelae of foodborne illness, we conducted a scoping review of the current literature for common foodborne pathogens and their associated sequelae. We aim to describe the current literature and gaps in knowledge of chronic sequelae associated with common foodborne illnesses. A comprehensive search was conducted in PubMed, EMBASE, and Web of Science for peer-reviewed articles published January 1, 2000 to April 1, 2018. Articles available in English, of any epidemiological study design, for 10 common foodborne pathogens (Campylobacter, Salmonella, Escherichia coli, Listeria, Shigella, Cryptosporidium, Cyclospora, Giardia, Yersinia, and norovirus) and their associated gastrointestinal (GI)- and joint-related sequelae were included. Of the 6348 titles screened for inclusion, 380 articles underwent full-text review; of those 380, 129 were included for data extraction. Of the bacterial pathogens included in the search terms, the most commonly reported were Salmonella (n = 104) and Campylobacter (n = 99); E. coli (n = 55), Shigella (n = 49), Yersinia (n = 49), and Listeria (n = 15) all had fewer results. Norovirus was the only virus included in our search, with 28 article that reported mostly GI-related sequelae and reactive arthritis (ReA) reported once. For parasitic diseases, Giardia (n = 26) and Cryptosporidium (n = 18) had the most articles, and no results were found for Cyclospora. The most commonly reported GI outcomes were irritable bowel syndrome (IBS; n = 119) and inflammatory bowel disease (n = 29), and ReA (n = 122) or "joint pain" (n = 19) for joint-related sequelae. Salmonella and Campylobacter were most often associated with a variety of outcomes, with ReA (n = 34 and n = 27) and IBS (n = 17 and n = 20) reported most often. This scoping review shows there are still a relatively small number of studies being conducted to understand specific pathogen/outcome relationships. It also shows where important gaps in the impact of chronic sequelae from common foodborne illnesses still exist and where more focused research would best be implemented.


Lifelong intake of flaxseed or menhaden oil to provide varying n-6 to n-3 PUFA ratios modulate bone microarchitecture during growth, but not after OVX in Sprague-Dawley rats.
Skeletal health is a lifelong process impacted by environmental factors, including nutrient intake. The n-3 source and PUFA ratio affect bone health in growing rats, or following ovariectomy (OVX), but no study has investigated the longitudinal effect of PUFA-supplementation throughout these periods of bone development. One-month-old, Sprague-Dawley rats (n = 98) were randomized to receive one of four diets from 1 through 6 months of age. Diets were modified from AIN-93G to contain a varying amount and source of n-3 (flaxseed versus menhaden oil) to provide an n-6 to n-3 ratio of 10:1 or 5:1. At 3 (prior to SHAM or OVX) and 6 months of age, bone microarchitecture of the tibia was quantified using in vivo micro-computed tomography (SkyScan 1176, Bruker microCT). Providing 5:1 (flaxseed) resulted in lower trabecular thickness and medullary area and greater cortical area fraction during growth compared to diets with a 10:1 PUFA ratio, but many of these differences were not apparent following OVX. PUFA-supplementation at levels attainable in human diet modulates some bone structure outcomes during periods of growth, but is not an adequate strategy for the prevention of OVX-induced bone loss in rats.


SO(2)-induced neurotoxicity is mediated by cyclooxygenases-2-derived prostaglandin E(2) and its downstream signaling pathway in rat hippocampal neurons.
Sulfur dioxide (SO(2)) pollution in atmospheric environment is involved in neurotoxicity and increased risk for hospitalization and mortality of many brain disorders; however, our understanding of the mechanisms by which SO(2) caused harmful insults on neurons remains elusive. Here, we show that SO(2) exposure produced a neuronal insult, and the neurotoxic effect was likely via stimulating cyclooxygenase-2 (COX-2) elevation by activation of nuclear factor-κB (NF-κB) activity and its acting on the promoter-distal NF-κB-binding site of COX-2 promoter. The action of SO(2) on elevating COX-2 ultimately appeared to be dependent on the increased production of arachidonic acid-derived prostaglandins, mainly prostaglandin E(2) (PGE(2)), and functioning of its EP2/4 receptors. Also, the molecular modulating process might be triggered by free radical attack from SO(2) metabolism in vivo and followed by activating cyclic adenosine monophosphate/protein kinase A pathway and enhancing probability of the release of glutamate, upregulating N-methyl-D-aspartic acid receptor expression and causing neuronal apoptosis. Our results reveal a mechanistic basis for exploring an association between SO(2) inhalation and increased risk for neurological disorders and opening up therapeutic approaches of treating, ameliorating, or preventing brain injuries resulting from SO(2) exposure in atmospheric polluting environment.


Focusing ion funnel-assisted ambient electrospray enables high-density and uniform deposition of non-spherical gold nanoparticles for highly sensitive surface-enhanced Raman scattering.
Surface-enhanced Raman scattering (SERS) is a powerful technique for detecting trace amounts of analytes. However, the performance of SERS substrates depends on many variables including the enhancement factor, morphology, consistency, and interaction with target analytes. In this study, we investigated, for the first time, the use of electrospray deposition (ESD) combined with a novel ambient focusing DC ion funnel to deposit a high density of gold nanoparticles (AuNPs) to generate large-area, uniform substrates for highly sensitive SERS analysis. We found that the combination of ambient ion focusing with ESD facilitated high-density and intact deposition of non-spherical NPs. This also allowed us to take advantage of a polydisperse colloidal solution of AuNPs (consisting of nanospheres and nanorods), as confirmed by finite-difference time domain (FDTD) simulations. Our SERS substrate exhibited excellent capture capacity for model analyte molecules, namely 4-aminothiophenol (4-ATP) and Rhodamine 6G (R6G), with detection limits in the region of 10-11 M and a relative standard deviation of <6% over a large area (∼500 × 500 μm2). Additionally, we assessed the quantitative performance of our SERS substrate using the R6G probe molecule. The results demonstrated excellent linearity (R2 > 0.99) over a wide concentration range (10-4 M to 10-10 M) with a detection limit of 80 pM.


Contingency is not enough: Social context guides third-party attributions of intentional agency.
Four experiments investigated whether infants and adults infer that a novel entity that interacts in a contingent, communicative fashion with an experimenter is itself an intentional agent. The experiments contrasted the hypothesis that such an inference follows from amodal representations of the contingent interaction alone with the hypothesis that features of the experimenter's behavior might also influence intentional attribution. Twelve- to 13-month-old infants and adults observed a novel entity respond contingently to a confederate experimenter, the form of whose actions varied across conditions. For infants, intentionality attribution was assessed by the extent to which they subsequently followed the faceless entity's implied attentional focus. For adults, intentionality attribution was assessed from their use of psychological terms when later describing the entity's behavior. In both groups, construal of the entity as an intentional agent was limited to a subset of contingent interaction conditions. At both ages, the pattern of responses across conditions suggests that whether an observed contingent interaction can be seen as a social interaction influences the attribution of intentional agency. These results further indicate that the agent detection mechanism responding to third-party contingent interactions, as a context-sensitive process, is distinct from the mechanism responding to directly experienced contingent interactions, suggested by prior developmental work to be based solely on amodal representations of an entity's contingent reaction to behaviors of an infant.


Interchain disulphide bridges of mouse immunoglobulin M.
Mouse IgM (immunoglobulin M) was selectively and partially reduced and treated with iodo[2-14C]acetate to label the interchain disulphide bridges. The carboxymethylation was studied in some detail. The labelled peptides were purified, sequenced and positioned by homology with human IgM. Only peptides originating from three interchain disulphide bridges were labelled, in contrast with the four labelled bridges obtained in human IgM under the same conditions. These peptides are homologous to human bridge peptides forming the heavy-light bridge and two inter-heavy bridges, one present in the CMU2 region and the other in the C-terminal region. The inter-heavy bridge in the Cmu2 region was alone cleaved and radioactively labelled in selectively reduced IgM held together as a pentamer by non-covalen interactions. The same bridge was the only one to be totally cleaved in subunits released after more extensive, though still selective, reduction. In the light of these results a possible arrangement of the disulphide bridges of the mouse IgM.


RACE to protect brains.
Rapid-access carotid endarterectomy (RACE) is an evidence-based treatment for symptomatic carotid stenosis. Our vascular centre aims to provide this service within 48 h of symptoms in appropriate patients. This study audits safety and efficacy of the first year of RACE. A clear trust protocol was publicised for the RACE pathway. A prospective database was established for all carotid endarterectomies (CEAs) performed. Outcomes were compared between elective (ECE) and rapid-access operations. In 1 year, 96 patients received CE; 20 were performed urgently. There were no significant differences in age or gender between ECE and RACE groups. Twenty-three (30%) of ECE were for asymptomatic stenoses; no other significant differences in surgical indication were seen. Of symptomatic ECE, 43% were for completed stroke versus 55% for RACE. Median delay between diagnosis and surgery was 113 days for elective and 2 days for RACE patients. There was one death following ECE (1.3%) and one stroke after RACE (5%), all not significant. Anaesthetic method did not influence outcome. The main reasons for delaying surgery in RACE patients were optimisation of patient fitness and availability of theatre time. The RACE pathway dramatically reduces delay without compromising patient safety. In the first year of service, we have treated 50% of suitable patients within 48 h. Further education of patients and colleagues should reduce delay and improve outcomes for symptomatic carotid disease.


Characteristics of long-term survivors after treatment for inoperable carcinoma of the lung.
Between January, 1971 and August, 1978, 410 patients with histologically or cytologically confirmed inoperable or unresectable carcinoma of the lung of all cell types were treated with curative intent. Forty-five patients lived a minimum of 3 years and 32 patients lived 5 or more years. The 3-year survival rate increased from 7.6% (15/197) between January, 1971 and June, 1975 to 14.1% (30/213) for the interval from July, 1975 to August, 1978 (p less than 0.01). Factors associated with long-term survival were performance status (p less than 0.01), early stage (p less than 0.001), high total dose of radiation (p less than 0.02), large cell carcinoma (p less than 0.01), inoperable for medical reasons (p less than 0.001), and thoracotomy to determine unresectability (p less than 0.04). The difference in survival rates between the two time periods was not related to different patient factors. Survival rates were most improved in the second time period for patients with Stage II or Stage III carcinoma of the lung. Eight patients died from cancer between 36 and 54 months of initial treatment. Five patients died of intercurrent disease without evidence of cancer of the lung after 3 years. An increasing proportion of long-term survivors of inoperable carcinoma of the lung can be expected to result from a better understanding of these diseases, more technically sophisticated external irradiation, and the use of combination chemotherapy for small cell carcinoma.


Mediators of Socioeconomic Inequity in Living-donor Kidney Transplantation: Results From a UK Multicenter Case-Control Study.
There is evidence of socioeconomic inequity in access to living-donor kidney transplantation, but limited evidence as to why. We investigated possible mediators of the inequity. This questionnaire-based case-control study included 14 UK hospitals. Participants were adults transplanted between April 1, 2013 and March 31, 2017. Living-donor kidney transplant (LDKT) recipients (cases) were compared with deceased-donor kidney transplant recipients (controls). We collected data on mediators identified in earlier qualitative work: perceived social support (Interpersonal Support Evaluation List shortened version-12), patient activation (Patient Activation Measure 13), and LDKT knowledge (Rotterdam Renal Replacement Knowledge Test). We performed mediation analyses to investigate what proportion of the effect of socioeconomic position (education and income) on case-control status was mediated by these variables. One thousand two-hundred and forty questionnaires were returned (40% response). Receipt of an LDKT over a deceased-donor kidney transplant was associated with higher socioeconomic position [adjusted odds ratio (aOR) university degree versus no degree aOR = 1.48 (95% confidence interval [CI], 1.18-1.84), P = 0.001 and aOR per +£1000 increase in monthly household income after tax 1.14 (95% CI, 1.11-1.17), P < 0.001] higher perceived social support (aOR per +1-point Interpersonal Support Evaluation List shortened version-12 score = 1.05 (95% CI, 1.03-1.08), P < 0.001), higher levels of patient activation (aOR per +1 patient activation measure level = 1.35 (95% CI, 1.24-1.48), P < 0.001), and greater LDKT knowledge (aOR per + 1-point Rotterdam Renal Replacement Knowledge Test score = 1.59 (95% CI, 1.49-1.69), P < 0.001). Mediation analyses revealed that perceived social support, patient activation, and LDKT knowledge together mediate 48.5% (95% CI, 12.7-84.3, P = 0.008) of the association between university education and LDKT status, and 46.0% (95% CI, 28.7-63.4, P < 0.001) of the association between income and LDKT status. LDKT knowledge, perceived social support, and patient activation are associated with the socioeconomic position of people with kidney disease, and mediate approximately 50% of the association between the socioeconomic position and receipt of an LDKT. Interventions that target these factors may redress observed socioeconomic inequity.


Cloning, sequencing, and overexpression of the Anaerobiospirillum succiniciproducens phosphoenolpyruvate carboxykinase (pckA) gene.
The phosphoenolpyruvate (PEP) carboxykinase-encoding gene from the anaerobic, CO2-fixing, succinate-producing bacterium Anaerobiospirillum succiniciproducens was cloned, sequenced, and expressed in Escherichia coli. The gene encoded a 532-residue polypeptide with a calculated molecular mass of 58.7 kDa. The sequence of the A. succiniciproducens PEP carboxykinase was similar to those of all known ATP/ADP-dependent PEP carboxykinases. In particular, the A. succiniciproducens enzyme was 67.3% identical and 79.2% similar to the E. coli enzyme. The A. succiniciproducens pckA transcription start site was determined, and putative promoter regions were identified. The recombinant enzyme was overexpressed in E. coli. The purified enzyme was indiscernible from the native enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and had the same activity as the native enzyme.


Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons.
Reelin, an extracellular glycoprotein secreted in embryonic and adult brain, participates in neuronal migration and neuronal plasticity. Extensive evidence shows that reelin via activation of the ApoER2 and VLDLR receptors promotes dendrite and spine formation during early development. Further evidence suggests that reelin signaling is needed to maintain a stable architecture in mature neurons, but, direct evidence is lacking. During activity-dependent maturation of the neuronal circuitry, the synaptic protein PSD95 is inserted into the postsynaptic membrane to induce structural refinement and stability of spines and dendrites. Given that ApoER2 interacts with PSD95, we tested if reelin signaling interference in adult neurons reactivates the dendritic architecture. Unlike findings in developing cultures, the presently obtained in vitro and in vivo data show, for the first time, that reelin signaling interference robustly increase dendritogenesis and reduce spine density in mature hippocampal neurons. In particular, the expression of a mutant ApoER2 form (ApoER2-tailless), which is unable to interact with PSD95 and hence cannot transduce reelin signaling, resulted in robust dendritogenesis in mature hippocampal neurons in vitro. These results indicate that reelin/ApoER2/PSD95 signaling is important for neuronal structure maintenance in mature neurons. Mechanistically, obtained immunofluorescent data indicate that reelin signaling impairment reduced synaptic PSD95 levels, consequently leading to synaptic re-insertion of NR2B-NMDARs. Our findings underscore the importance of reelin in maintaining adult network stability and reveal a new mode for reactivating dendritogenesis in neurological disorders where dendritic arbor complexity is limited, such as in depression, Alzheimer's disease, and stroke. J. Cell. Physiol. 232: 1187-1199, 2017. © 2016 Wiley Periodicals, Inc.


Tendency for interlaboratory precision in the GMO analysis method based on real-time PCR.
The Horwitz curve estimates interlaboratory precision as a function only of concentration, and is frequently used as a method performance criterion in food analysis with chemical methods. The quantitative biochemical methods based on real-time PCR require an analogous criterion to progressively promote method validation. We analyzed the tendency of precision using a simplex real-time PCR technique in 53 collaborative studies of seven genetically modified (GM) crops. Reproducibility standard deviation (SR) and repeatability standard deviation (Sr) of the genetically modified organism (GMO) amount (%) was more or less independent of GM crops (i.e., maize, soybean, cotton, oilseed rape, potato, sugar beet, and rice) and evaluation procedure steps. Some studies evaluated whole steps consisting of DNA extraction and PCR quantitation, whereas others focused only on the PCR quantitation step by using DNA extraction solutions. Therefore, SR and Sr for GMO amount (%) are functions only of concentration similar to the Horwitz curve. We proposed S(R) = 0.1971C 0.8685 and S(r) = 0.1478C 0.8424, where C is the GMO amount (%). We also proposed a method performance index in GMO quantitative methods that is analogous to the Horwitz Ratio.


Proliferative, structural and molecular features of the Mdx mouse prostate.
The prostate is fundamental to the male reproductive process, and the stroma-epithelium interaction has an important role in prostate maintenance. Studies suggest that dystroglycan (DG) plays a role in cancer development in various organs. Thus, the aims of this work were to characterize morphological and proliferative features of the prostatic stroma and epithelium of mdx mice; to verify the immunolocalization of the α and β DG, IGF-1 and laminin α3 receptors; and to relate those structural and molecular events to prostate pathogenesis and to verify the viability of this experimental model in prostate studies. Thirty male mice (mdx and C57BL10/Uni) were divided into control and mdx groups. Samples from the ventral prostate were collected for immunological, Western Blotting, transmission electron microscopy and morphometric analyses. Oestradiol and testosterone measurements were verified. The results showed diminished testosterone and increased oestradiol levels in the mdx group. Atrophied cells and hypertrophied stroma were seen in the mdx mice. Weak α and β DG and laminin α3 immunolocalization was demonstrated in the mdx group. Intense insulin-like growth factor receptor α-1 (IGFRα-1) localization was identified in the mdx animals. Thus, mdx animals showed changes in molecular and structural integrity and proliferation signals, leading to glandular homoeostasis imbalance, and compromise of prostate function. Also, the steroid hormone imbalance and the increased IGF-1 receptor level detected in mdx mice could be considered as a crucial factor in the pathogenesis of prostatic disorders.


Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion.
A neurochemical target at which cannabinoids interact to have global effects on behavior is brain noradrenergic circuitry. Acute and repeated administration of a cannabinoid receptor synthetic agonist is capable of increasing multiple indices of noradrenergic activity. This includes cannabinoid-induced 1) increases in norepinephrine (NE) release in the medial prefrontal cortex (mPFC); 2) desensitization of cortical α2-adrenoceptor-mediated effects; 3) activation of c-Fos in brainstem locus coeruleus (LC) noradrenergic neurons; and 4) increases in anxiety-like behaviors. In the present study, we sought to examine adaptations in adrenoceptor expression and function under conditions of cannabinoid receptor type 1 (CB1r) deletion using knockout (KO) mice and compare these to wild type (WT) controls. Electrophysiological analysis of α2-adrenoceptor-mediated responses in mPFC slices in WT mice showed a clonidine-induced α2-adrenoceptor-mediated increase in mPFC cell excitability coupled with an increase in input resistance. In contrast, CB1r KO mice showed an α2-adrenoceptor-mediated decrease in mPFC cell excitability. We then examined protein expression levels of α2- and β1-adrenoceptor subtypes in the mPFC as well as TH expression in the locus coeruleus (LC) of mice deficient in CB1r. Both α2- and β1-adrenoceptors exhibited a significant decrease in expression levels in CB1r KO mice when compared to WT in the mPFC, while a significant increase in TH was observed in the LC. To better define whether the same cortical neurons express α2A-adrenoceptor and CB1r in mPFC, we utilized high-resolution immunoelectron microscopy. We localized α2A-adrenoceptors in a knock-in mouse that expressed a hemoagglutinin (HA) tag downstream of the α2A-adrenoceptor promoter. Although the α2A-adrenoceptor was often identified pre-synaptically, we observed co-localization of CB1r with α2-adrenoceptors post-synaptically in the same mPFC neurons. Finally, using receptor binding, we confirmed prior results showing that α2A-adrenoceptor is unchanged in mPFC following acute or chronic exposure to the synthetic cannabinoid receptor agonist, WIN 55,212-2, but is increased, following chronic treatment followed by a period of abstinence. Taken together, these data provide convergent lines of evidence indicating cannabinoid regulation of the cortical adrenergic system.


Learning the Languages of the Chloroplast: Retrograde Signaling and Beyond.
The chloroplast can act as an environmental sensor, communicating with the cell during biogenesis and operation to change the expression of thousands of proteins. This process, termed retrograde signaling, regulates expression in response to developmental cues and stresses that affect photosynthesis and yield. Recent advances have identified many signals and pathways-including carotenoid derivatives, isoprenes, phosphoadenosines, tetrapyrroles, and heme, together with reactive oxygen species and proteins-that build a communication network to regulate gene expression, RNA turnover, and splicing. However, retrograde signaling pathways have been viewed largely as a means of bilateral communication between organelles and nuclei, ignoring their potential to interact with hormone signaling and the cell as a whole to regulate plant form and function. Here, we discuss new findings on the processes by which organelle communication is initiated, transmitted, and perceived, not only to regulate chloroplastic processes but also to intersect with cellular signaling and alter physiological responses.


Regional Variation in Neonatal Intensive Care Admissions and the Relationship to Bed Supply.
To characterize geographic variation in neonatal intensive care unit (NICU) admission rates across the entire birth cohort and evaluate the relationship between regional bed supply and NICU admission rates. This was a population-based, cross-sectional study. 2013 US birth certificate and 2012 American Hospital Association data were used to assign newborns and NICU beds to neonatal intensive care regions. Descriptive statistics of admission rates were calculated across neonatal intensive care regions. Multilevel logistic regression was used to examine the relationship between bed supply and individual odds of admission, with adjustment for maternal and newborn characteristics. Among 3 304 364 study newborns, the NICU admission rate was 7.2 per 100 births and varied across regions for all birth weight categories. IQRs in admission rates were 84.5-93.2 per 100 births for 500-1499 g, 35.3-46.1 for 1500-2499 g, and 3.5-5.5 for ≥2500 g. Adjusted odds of admission for newborns of very low birth weight were unrelated to regional bed supply; however, newborns ≥2500 g in regions with the highest NICU bed supply were significantly more likely to be admitted to a NICU than those in regions with the lowest (aOR 1.20 [1.03-1.40]). There is persistent underuse of NICU care for newborns of very low birth weight that is not associated with regional bed supply. Among larger newborns, we find evidence of supply-sensitive care, raising concerns about the potential overuse of expensive and unnecessary care. Rather than improving access to needed care, NICU expansion may instead further deregionalize neonatal care, exacerbating underuse.


Lifetime selection on adult body size and components of body size in a waterstrider: opposing selection and maintenance of sexual size dimorphism.
Sexual size dimorphism (SSD), the difference in body size between males and females, is common in almost all taxa of animals and is generally assumed to be adaptive. Although sexual selection and fecundity selection alone have often been invoked to explain the evolution of SSD, more recent views indicate that the sexes must experience different lifetime selection pressures for SSD to evolve and be maintained. We estimated selection acting on male and female adult body size (total length) and components of body size in the waterstrider Aquarius remigis during three phases of life history. Opposing selection pressures for overall body size occurred in separate episodes of fitness for females in both years and for males in one year. Specific components of body size were often the targets of the selection on overall body size. When net adult fitness was estimated by combining each individual's fitnesses from all episodes, we found stabilizing selection in both sexes. In addition, the net optimum overall body size of males was smaller than that of females. However, even when components of body size had experienced opposing selection pressures in individual episodes, no components appeared to be under lifetime stabilizing selection. This is the first evidence that contemporary selection in a natural population acts to maintain female size larger than male size, the most common pattern of SSD in nature.


[Temporal changes in the epidemiology of diabetes mellitus in Turkey: A systematic review and meta-analysis].
Diabetes mellitus (DM) is a serious public health problem. Despite various epidemiological studies reporting prevalence of DM in Turkey, there is no meta-analysis or systematic review evaluating these studies as a whole and assessing temporal changes in the prevalence of DM. In this meta-analysis, the studies that have been conducted in the last 15 years and which provide information on the prevalence of DM in our country are examined. Epidemiological studies on cardiovascular risk factors in adult Turkish population that had been conducted within the last 15 years and having the capacity of either representating or potentially representing the country, were searched through Ovid, Medline and Web of Science Core Collection the Turkish Academic Network and Information Center (ULAKBIM) databases. Additionally, websites of Ministry of Health and related societies were investigated for additional studies. Random effects model was used in meta-analysis of low bias risk studies. Meta-regression was performed to evaluate the temporal change in DM prevalence. There were 8 studies which provided information with regard to DM prevalence (n=84656). Four of these studies (n=56853) had low bias risk and four had high bias risk (n=27803). When compared with low bias risk studies, those with high bias risk had very large variation of DM prevalence (between 4% to 15%). Meta-analysis of the low bias risk group yielded a crude DM prevalence of 13.5% (95% CI: 11.6-15.5%) in the whole group, 14.2% (95% CI: 12.3-16.2%) in females, 12.6% (95% CI: 10.5-14.9%) in males. In meta-regression analysis of low bias risk group, mean age difference among the studies and the time period in which the study was undertaken were partially able to explain the inter-study heterogeneity (R2 values were 52% and 78%). This meta-analysis shows that DM is a highly prevalent public health problem in our country. Contrary to studies, which compare the recent studies with previous ones and report an increasing prevalence of DM, the present meta-analysis-despite its limitations-provides findings that the temporal increase of DM prevalence is at least paused over time. This situation underlines the need for new studies.


A new antibiotic with potent activity targets MscL.
The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery is declining, with most of the recently approved antibiotics corresponding to new uses for old antibiotics or structurally similar derivatives of known antibiotics. We used an in silico approach to design a new class of nontoxic antimicrobials for the bacteria-specific mechanosensitive ion channel of large conductance, MscL. One antimicrobial of this class, compound 10, is effective against methicillin-resistant Staphylococcus aureus with no cytotoxicity in human cell lines at the therapeutic concentrations. As predicted from in silico modeling, we show that the mechanism of action of compound 10 is at least partly dependent on interactions with MscL. Moreover we show that compound 10 cured a methicillin-resistant S. aureus infection in the model nematode Caenorhabditis elegans. Our work shows that compound 10, and other drugs that target MscL, are potentially important therapeutics against antibiotic-resistant bacterial infections.


Basal and stress-induced corticosterone levels in olive ridley sea turtles (Lepidochelys olivacea) in relation to their mass nesting behavior.
Adrenocortical responsiveness to turning stress was examined in wild, reproductively-active olive ridley sea turtles (Lepidochelys olivacea) in relation to their mass nesting (arribada) behavior. We hypothesized that the high sensitivity threshold (HST) observed in ovipositing sea turtles is associated with a diminished sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to stressful stimuli in arribada females. We tested this hypothesis by determining whether arribada females exhibited an increased activation threshold of the HPA axis to an imposed stressor (turning stress). Mean basal corticosterone (B) and glucose levels were below 1.0 ng/ml and 60 mg/dl, respectively. Basal B remained unchanged throughout a 24-hr period in basking females. Most animals responded to turning stress with elevated mean B levels (up to 6.5 ng/ml after 6 hr) and no increase in circulating glucose. Nearly 50% of females (and none of the males) were refractory to the stimulation. Males exhibited the most rapid response, with B levels significantly elevated by 20 min over basal levels. Among females, arribada and solitary nesters exhibited a slower rate of response than basking, non-nesting animals. These results demonstrate that olive ridleys exhibit stress-induced changes in circulating B which are slower than those observed in most reptilian and in mammalian, avian, and piscine species. Furthermore, the presence of refractory females and the relatively slower increase in B in arribada and solitary nesters indicate a hyporesponsiveness of the HPA axis to turning stress in nesting olive ridleys. The hyporesponsiveness may be part of a mechanism to facilitate arribada nesting. J. Exp. Zool. 284:652-662, 1999.


A Systematic Review of the Clinical Presentation, Diagnosis, and Treatment of Small Bowel Obstruction.
This study aimed to systematically review small bowel obstruction (SBO), focusing on recent changes in diagnosis/therapy. SBO incidence is about 350,000/annum in the USA. Etiologies include adhesions (65%), hernias (10%), neoplasms (5%), Crohn's disease (5%), and other (15%). Bowel dilatation occurs proximal to obstruction primarily from swallowed air and secondarily from intraluminal fluid accumulation. Dilatation increases mural tension, decreases mucosal perfusion, causes bacterial proliferation, and decreases mural tensile strength that increases bowel perforation risks. Classical clinical tetrad is abdominal pain, nausea and emesis, abdominal distention, and constipation-to-obstipation. Physical exam may reveal restlessness, acute illness, and signs of dehydration and sepsis, including tachycardia, pyrexia, dry mucous membranes, hypotension/orthostasis, abdominal distention, and hypoactive bowel sounds. Severe direct tenderness, involuntary guarding, abdominal rigidity, and rebound tenderness suggest advanced SBO, as do marked leukocytosis, neutrophilia, bandemia, and lactic acidosis. Differential diagnosis includes postoperative ileus, narcotic bowel, colonic pseudo-obstruction, mesenteric ischemia, and large bowel obstruction. Medical resuscitation includes intravenous hydration, correcting electrolyte abnormalities, intravenous antibiotics, nil per os, and nasoenteral suction. Abdominal CT with oral and intravenous gastrografin contrast is highly sensitive and specific in detecting/characterizing SBO. SBO usually resolves with medical therapy but requires surgery, preferentially by laparoscopy, for unremitting total obstruction, bowel perforation, severe ischemia, or clinical deterioration with medical therapy. Overall mortality is 10% but increases to 30% with bowel necrosis/perforation. Key point in SBO is early diagnosis, emphasizing abdominal CT; aggressive medical therapy including rehydration, antibiotics, and nil per os; and surgery for failed medical therapy.


FARSB Facilitates Hepatocellular Carcinoma Progression by Activating the mTORC1 Signaling Pathway.
Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality. Human phenylalanine tRNA synthetase (PheRS) comprises two α catalytic subunits encoded by the FARSA gene and two β regulatory subunits encoded by the FARSB gene. FARSB is a potential oncogene, but no experimental data show the relationship between FARSB and HCC progression. We found that the high expression of FARSB in liver cancer is closely related to patients' low survival and poor prognosis. In liver cancer cells, the mRNA and protein expression levels of FARSB are increased and promote cell proliferation and migration. Mechanistically, FARSB activates the mTOR complex 1 (mTORC1) signaling pathway by binding to the component Raptor of the mTORC1 complex to play a role in promoting cancer. In addition, we found that FARSB can inhibit erastin-induced ferroptosis by regulating the mTOR signaling pathway, which may be another mechanism by which FARSB promotes HCC progression. In summary, FARSB promotes HCC progression and is associated with the poor prognosis of patients. FARSB is expected to be a biomarker for early screening and treatment of HCC.


Two-Phase, Generalized Case-Control Designs for the Study of Quantitative Longitudinal Outcomes.
We propose a general class of 2-phase epidemiologic study designs for quantitative, longitudinal data that are useful when phase 1 longitudinal outcome and covariate data are available but data on the exposure (e.g., a biomarker) can only be collected on a subset of subjects during phase 2. To conduct a study using a design in the class, one first summarizes the longitudinal outcomes by fitting a simple linear regression of the response on a time-varying covariate for each subject. Sampling strata are defined by splitting the estimated regression intercept or slope distributions into distinct (low, medium, and high) regions. Stratified sampling is then conducted from strata defined by the intercepts, by the slopes, or from a mixture. In general, samples selected with extreme intercept values will yield low variances for associations of time-fixed exposures with the outcome and samples enriched with extreme slope values will yield low variances for associations of time-varying exposures with the outcome (including interactions with time-varying exposures). We describe ascertainment-corrected maximum likelihood and multiple-imputation estimation procedures that permit valid and efficient inferences. We embed all methodological developments within the framework of conducting a substudy that seeks to examine genetic associations with lung function among continuous smokers in the Lung Health Study (United States and Canada, 1986-1994).


The effects of alcohol and drug abuse on the skin.
Skin changes associated with alcohol and drug abuse can be the earliest clinical manifestation of these disorders. The signs associated with these conditions may be distinctive and easily recognizable. Alcohol abuse can present with jaundice, pruritus, hyperpigmentation, and urticaria. Commonly associated vascular changes include spider telangiectasias, angiomas, caput medusas, flushing, and palmar erythema. Disease states related to alcohol abuse include psoriasis, porphyria cutanea tarda, and nutritional deficiencies. Alcohol abuse may predispose to the development of carcinomas of the skin, oropharynx, liver, pancreas, and breast. Cutaneous signs of drug abuse include skin granulomas, ulcerations, and recurrent infections. Specifically, oral disease and tooth decay are examples of stigmata often associated with methamphetamine abuse, a popular and inexpensive drug now on the scene. By being cognizant of these cutaneous markers of alcohol and drug abuse, dermatologists are often in the unique position of being able to recognize these changes, prompting early diagnosis and intervention, hopefully resulting in a better clinical outcome for these troubled patients and their families.


Triton WR-1339 injected into rats enters renal renin granules.
To test directly the possibility that substances in extracellular fluid can gain access to renin storage granules in renal juxtaglomerular cells, rats were injected with Triton WR-1339, which binds to plasma proteins. A heavy granule fraction was prepared, and isopycnic sucrose density gradient centrifugation was performed. The renin granule peak was found to be altered from a mean equilibrium density of 1.202 g/ml in control rats to 1.196 g/ml for rats injected with Triton WR-1339 (P less than 0.005). The distribution of angiotensinogen, which is bound in kidney granules having a different buoyant density, was also examined and found to be unaltered. After injection, Triton WR-1339 binds to circulating plasma proteins. The results for renin support the possibility of pinocytotic uptake of protein-Triton WR-1339 complexes by the juxtaglomerular cells with subsequent fusion of the endocytotic lysosomal vacuoles with renin granules accounting for the translocation of ingested substances into the granule matrix. If so, the potential would therefore exist for interaction(s) of ingested extracellular substances with renin or other components in the granules. The present study has therefore demonstrated directly that endogenous extracellular substances may enter renin granules.


The complement system in pediatric systemic lupus erythematosus, atypical hemolytic uremic syndrome, and complocentric membranoglomerulopathies.
This review summarizes the recent advances in complement biology and the evolving understanding of these contributions to the pathophysiology and treatment of predominantly pediatric disease syndromes. Identification of lupus patients with complete deficiencies of one of the plasma complement proteins enabled the field to move beyond the notion of complement as a laboratory curiosity. Clinical investigation of the manifestations observed in deficient patients has further defined the biology of the system in normal individuals. Definition of the assembly of the C3 convertases, particularly that of the alternative pathway and its regulation, has led to the appreciation that the complement system includes membrane inhibitors that are every bit as important as those in plasma. The exploration of disease states in which significant complement deposition occurs has moved the field away from consideration of this finding as a bystander effect. Dissection of these syndromes has led to the unanticipated finding of a central role for function-altering mutations in the complement proteins that form or regulate the alternative pathway C3 convertase and has opened the door to new therapeutic approaches. The disease states discussed in the review - pediatric systemic lupus erythematosus, atypical hemolytic uremic syndrome, and the complocentric membranoglomerulopathies - illustrate this evolutionary history of complement biology. This review emphasizes that both the lack of classical pathway complement activation and excessive activation of the alternative pathway contribute to distinct disease pathogenesis, and emphasizes the critical importance of homeostatic regulation, in both plasma and in tissues, of the system as a whole.


The Integrated Effect of Microbial Inoculants and Biochar Types on Soil Biological Properties, and Plant Growth of Lettuce (Lactuca sativa L.).
Numerous reports confirm the positive effect of biochar application on soil properties and plant development. However, the interaction between root-associated beneficial microbes and different types of biochar is not well understood. The objective of this study was to evaluate the plant growth of lettuce after the application of three types of biochar in loamy, sandy soil individually and in combination with plant-beneficial microbes. Furthermore, total microbial activity in rhizosphere soil of lettuce was measured by means of fluorescein diacetate (FDA) hydrolase and enzyme activities linked to carbon, nitrogen, and phosphorus cycling. We used three types of biochar: (i) pyrolysis char from cherry wood (CWBC), (ii) pyrolysis char from wood (WBC), and (iii) pyrolysis char from maize (MBC) at 2% concentration. Our results showed that pyrolysis biochars positively affected plant interaction with microbial inoculants. Plant dry biomass grown on soil amended with MBC in combination with Klebsiella sp. BS13 and Klebsiella sp. BS13 + Talaromyces purpureogenus BS16aPP inoculants was significantly increased by 5.8% and 18%, respectively, compared to the control plants. Comprehensively, interaction analysis showed that the biochar effect on soil enzyme activities involved in N and P cycling depends on the type of microbial inoculant. Microbial strains exhibited plant growth-promoting traits, including the production of indole 3-acetic-acid and hydrogen cyanide and phosphate-solubilizing ability. The effect of microbial inoculant also depends on the biochar type. In summary, these findings provide new insights into the understanding of the interactions between biochar and microbial inoculants, which may affect lettuce growth and development.


Neutral-pion photoproduction off protons in the energy range 0.3 GeV<E(gamma)<3 GeV.
Single pi(0) photoproduction has been studied with the CB-ELSA experiment at Bonn using tagged photon energies between 0.3 and 3.0 GeV. The experimental setup covers a very large solid angle of approximately 98% of 4pi. Differential cross sections dsigma/dOmega have been measured. Complicated structures in the angular distributions indicate a variety of different resonances being produced in the s channel intermediate state gammap-->N(*)(Delta(*))-->ppi(0). A combined analysis including the data presented in this letter along with other data sets reveals contributions from known resonances and evidence for a new resonance N(2070)D15.


Effectiveness and patient safety of platelet aggregation inhibitors in the prevention of cardiovascular disease and ischemic stroke in older adults - a systematic review.
Platelet aggregation inhibitors (PAI) are among the most frequently prescribed drugs in older people, though evidence about risks and benefits of their use in older adults is scarce. The objectives of this systematic review are firstly to identify the risks and benefits of their use in the prevention and treatment of vascular events in older adults, and secondly to develop recommendations on discontinuing PAI in this population if risks outweigh benefits. Staged systematic review consisting of three searches. Searches 1 and 2 identified systematic reviews and meta-analyses. Search 3 included controlled intervention and observational studies from review-articles not included in searches 1 and 2. All articles were assessed by two independent reviewers regarding the type of study, age of participants, type of intervention, and clinically relevant outcomes. After data extraction and quality appraisal we developed recommendations to stop the prescribing of specific drugs in older adults following the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Overall, 2385 records were screened leading to an inclusion of 35 articles reporting on 22 systematic reviews and meta-analyses, 11 randomised controlled trials, and two observational studies. Mean ages ranged from 57.0 to 84.6 years. Ten studies included a subgroup analysis by age. Overall, based on the evaluated evidence, three recommendations were formulated. First, the use of acetylsalicylic acid (ASA) for primary prevention of cardiovascular disease (CVD) in older people cannot be recommended due to an uncertainty in the risk-benefit ratio (weak recommendation; low quality of evidence). Secondly, the combination of ASA and clopidogrel in patients without specific indications should be avoided (strong recommendation; moderate quality of evidence). Lastly, to improve the effectiveness and reduce the risks of stroke prevention therapy in older people with atrial fibrillation (AF) and a CHA2DS2-VASc score of ≥ 2, the use of ASA for the primary prevention of stroke should be discontinued in preference for the use of oral anticoagulants (weak recommendation; low quality of evidence). The use of ASA for the primary prevention of CVD and the combination therapy of ASA and clopidogrel for the secondary prevention of vascular events in older people may not be justified. The use of oral anticoagulants instead of ASA in older people with atrial fibrillation may be recommended. Further high quality studies with older adults are needed.


Tracheal compression in pupae of the beetle Zophobas morio.
Insects that are small or exhibit low metabolic rates are considered to not require active ventilation to augment diffusive gas exchange. Some pupae with low metabolic rates exhibit abdominal pumping, a behaviour that is known to drive tracheal ventilation in the adults of many species. However, previous work on pupae suggests that abdominal pumping may serve a non-respiratory role. To study the role of abdominal pumping in pupa of the beetle Zophobas morio, we visualized tracheal dynamics with X-rays while simultaneously measuring haemolymph pressure, abdominal movement, and CO2 emission. Pupae exhibited frequent tracheal compressions that were coincident with both abdominal pumping and pulsation of pressure in the haemolymph. However, more than 63% of abdominal pumping events occurred without any tracheal collapse and hence ventilation, suggesting that the major function of the abdominal pump is not respiratory. In addition, this study shows that the kinematics of abdominal pumping can be used to infer the status of the spiracles and internal behaviour of the tracheal system.


A systematic study of the synthesis of cesium lead halide nanocrystals: does Cs4PbBr6 or CsPbBr3 form?
Cs4PbBr6 nanocrystals (NCs) have been recently studied as they can enhance the light emitting efficiency and stability of CsPbBr3 NCs. However, the synthesis of Cs4PbBr6 NCs is often accompanied by the generation of CsPbBr3 NCs, and less attention has been paid to how to exactly control their formation. Here, we investigated the key factors in deciding the final products in the hot-injection synthesis by a modified amine-free method. We found that the molarity ratio of Cs/Pb dominated the final products, while the amount of bromine had a relatively small effect. In addition, introducing a certain amount of oleylamine into the amine-free reaction leads to the formation of Cs4PbBr6, instead of CsPbBr3 NCs. This clearly shows that the protection ligand oleylamine also plays an important role in the formation of Cs4PbBr6 NCs. This well understood and fine control of the synthesis may inspire a new CsPbBr3@Cs4PbBr6 core-shell structure, with the same chemical elements but a different crystal phase in the core and the shell. This nanostructure would open a new avenue for enhancing the stability of perovskite nanocrystals.


[Nature, classification and nursing interventions for patients with mediastinitis].
This is a descriptive and retrospective study that aimed at analyzing the nature and classification of nursing interventions for patients with mediastinitis following cardiac surgery. The results obtained from the surgical wards show an incidence of mediastinitis of 3%. The subjects studies were primarily male, all of whom suffer from diabetes. The nursing problems were categorized according to Horta and the interventions according to the NIC. Among the problems found, 76.5% were of psychobiological needs and 23.5% were psychosocial. Fifty-three (53) nursing interventions were implemented: 84.9% were physiological in nature, 11.3% behavioral and 3.8% family related. The relationship between the problems identified and the interventions developed were adjusted principally to address the psychobiological needs. Educational interventions were used frequently to attend to the psychosocial needs of the patients.


Interaction between the posterior pituitary and LHRH in the control of LH secretion.
We have recently reported that the posterior lobe of the pituitary differentially inhibits the secretion of prolactin (PRL) and luteinizing hormone (LH), but not follicle stimulating hormone (FSH) throughout the estrous cycle. Removal of the posterior pituitary (posterior pituitary lobectomy) results in elevations of plasma LH on all days of the cycle except on diestrus-day-2. In the present study we examined: whether the control of LH release involves an interaction between the posterior pituitary and hypothalamic luteinizing hormone-releasing hormone (LHRH), and whether the elevation of LH seen following posterior lobectomy is due to the removal of a posterior pituitary substance(s) which alters anterior pituitary sensitivity to LHRH. In order to block the action of hypothalamic LHRH, a potent LHRH inhibitory analog (50 micrograms) was injected SC two hours prior to removal of the posterior pituitary in estrous rats. Administration of the inhibitory analog completely eliminated the elevation of plasma LH seen following posterior lobectomy, but did not alter the posterior lobectomy-induced rise of plasma PRL, or plasma FSH concentrations. In order to test whether anterior pituitary sensitivity to LHRH is altered by posterior lobectomy, a moderate dose of LHRH (15 ng) was administered to both posterior lobectomized and sham lobectomized estrous rats. The time-course and magnitude of the LH response to LHRH was similar in both groups. The results are consistent with the hypothesis that LH secretion is controlled by an interaction between hypothalamic LHRH and the posterior lobe of the pituitary, but this interaction does not appear to involve lobectomy-induced changes in anterior pituitary responsiveness to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)