Secondary abdominal compartment syndrome is a highly lethal event.
Recent reports have described resuscitation-induced, "secondary" abdominal compartment syndrome (ACS) in trauma patients without intra-abdominal injuries. We have diagnosed secondary ACS in a variety of nontrauma as well as trauma patients. The purpose of this review is to characterize patients who develop secondary ACS. Our prospective ACS database was reviewed for cases of secondary ACS. Physiologic parameters and outcomes were recorded. Data are expressed as mean +/- SEM. Fourteen patients (13 male, aged 45 +/- 5 years) developed ACS 11.6 +/- 2.2 hours following resuscitation from shock. Eleven (79%) had required vasopressors; the worst base deficit was 14.1 +/- 1.9. Resuscitation included 16.7 +/- 3.0 L crystalloid and 13.3 +/- 2.9 red blood cell units. Decompressive laparotomy improved intra-abdominal, systolic, and peak airway pressures, as well as urine output; however, mortality was 38% among trauma and 100% among nontrauma patients. Secondary ACS may be encountered by general surgeons in a variety of clinical scenarios; resuscitation from severe shock appears to be the critical factor. Early identification and abdominal decompression are essential. Unfortunately, in our experience, this is a highly lethal event.


Regulation of angiogenesis by extracellular matrix.
During angiogenesis, endothelial cell growth, migration, and tube formation are regulated by pro- and anti-angiogenic factors, matrix-degrading proteases, and cell-extracellular matrix interactions. Temporal and spatial regulation of extracellular matrix remodeling events allows for local changes in net matrix deposition or degradation, which in turn contributes to control of cell growth, migration, and differentiation during different stages of angiogenesis. Remodeling of the extracellular matrix can have either pro- or anti-angiogenic effects. Extracellular matrix remodeling by proteases promotes cell migration, a critical event in the formation of new vessels. Matrix-bound growth factors released by proteases and/or by angiogenic factors promote angiogenesis by enhancing endothelial migration and growth. Extracellular matrix molecules, such as thrombospondin-1 and -2, and proteolytic fragments of matrix molecules, such as endostatin, can exert anti-angiogenic effects by inhibiting endothelial cell proliferation, migration and tube formation. In contrast, other matrix molecules promote endothelial cell growth and morphogenesis, and/or stabilize nascent blood vessels. Hence, extracellular matrix molecules and extracellular matrix remodelling events play a key role in regulating angiogenesis.


Association with actin mediates the EGTA-resistant binding of cytosolic phospholipase A2-alpha to the plasma membrane of activated platelets.
The association of cytosolic phospholipase A(2)-alpha (cPLA(2)alpha) with intracellular membranes is central to the generation of free arachidonic acid and thromboxane A(2) in activated platelets. Despite this, the site and nature of this membrane association has not been fully characterised upon platelet activation. High resolution imaging showed that cPLA(2)alpha was distributed in a partly structured manner throughout the resting platelet. Upon glass activation or thrombin stimulation, cPLA(2)alpha relocated to a peripheral region corresponding to the platelet plasma membrane. Upon thrombin stimulation of platelets a major pool of cPLA(2)alpha was associated with the plasma membrane in an EGTA-resistant manner. EGTA-resistant membrane binding was abolished upon de-polymerisation of actin filaments by DNase I and furthermore, cPLA(2)alpha co-immunoprecipitated with actin upon thrombin stimulation of platelets. Immunofluorescence microscopy studies revealed that, upon platelet activation, cPLA(2)alpha and actin co-localised at the plasma membrane. Thus we have identified a novel mechanism for the interaction of cPLA(2)alpha with its membrane substrate via interaction with actin.


Characterization of the temperate phage vB_RleM_PPF1 and its site-specific integration into the Rhizobium leguminosarum F1 genome.
Bacteriophages may play an important role in regulating population size and diversity of the root nodule symbiont Rhizobium leguminosarum, as well as participating in horizontal gene transfer. Although phages that infect this species have been isolated in the past, our knowledge of their molecular biology, and especially of genome composition, is extremely limited, and this lack of information impacts on the ability to assess phage population dynamics and limits potential agricultural applications of rhizobiophages. To help address this deficit in available sequence and biological information, the complete genome sequence of the Myoviridae temperate phage PPF1 that infects R. leguminosarum biovar viciae strain F1 was determined. The genome is 54,506 bp in length with an average G+C content of 61.9 %. The genome contains 94 putative open reading frames (ORFs) and 74.5 % of these predicted ORFs share homology at the protein level with previously reported sequences in the database. However, putative functions could only be assigned to 25.5 % (24 ORFs) of the predicted genes. PPF1 was capable of efficiently lysogenizing its rhizobial host R. leguminosarum F1. The site-specific recombination system of the phage targets an integration site that lies within a putative tRNA-Pro (CGG) gene in R. leguminosarum F1. Upon integration, the phage is capable of restoring the disrupted tRNA gene, owing to the 50 bp homologous sequence (att core region) it shares with its rhizobial host genome. Phage PPF1 is the first temperate phage infecting members of the genus Rhizobium for which a complete genome sequence, as well as other biological data such as the integration site, is available.


Characterization of a novel pyridinium bromide surface confined ionic liquid stationary phase for high-performance liquid chromatography under normal phase conditions via linear solvation energy relationships.
Utilizing linear solvation free energy relationship methodology, a novel pyridinium bromide surface confined ionic liquid (SCIL) stationary phase was characterized under normal phase high-performance liquid chromatographic conditions. A limited set of neutral aromatic probe solutes were utilized to rapidly assess the utility of the LSER model, using mobile phases of hexane modified with 2-propanol. The excellent correlation of the global fit across the mobile phase composition range used in this study for the experimental and calculated retention values (R(2)=0.994) indicates that the LSER model is an appropriate model of characterizing this polar bonded phase under normal phase conditions. For a limited subset of compounds, retention on the pyridinium bromide SCIL stationary phase is more highly correlated with that obtained on a cyano column than on a diol column under NP conditions.


Anti Inflammatory and Anti Arthritic Activity of Different Milk Based Formulation of Curcumin in Rat Model.
Inflammation is the key mediator for arthritis. Plant based products are most useful for treating various disorders, but at the same time drug absorption is utmost important for effective therapy. The present aim of our study was to find out the therapeutic concern in pharmacokinetic and pharmacodynamic parameters in an arthritis induced rat model. Carregenan and complete Freud's adjuvant, both were used for an arthritis induction as an animal model. Formulation of curcumin was prepared in different quality of milk brand, high fat milk with ghee and in an aqueous suspension. They were administered orally to the rats for 21 days continuously. Different pharmacodyanmic parameters were analyzed which include percentage inhibition of inflammation, cytokines (IL-6 and TNF-α), hematological levels, X-Rays and histology condition. Pharmacokinetics was also determined like Cmax, Tmax and Kel using HPLC method. The result concludes that, curcumin in full fat milk with ghee and full fat curcumin formulation treated group showed a higher statistical significant effect in the prevention of inflammation in both the models. The presence of curcumin in plasma was higher only in full fat with ghee formulation and full fat milk formulation treated group when compared to the other groups. Hence, it concludes that the presence of adjuvant act as an enhancer can increase the bioavailability of curcumin for achieving maximum effectiveness.


Rediscovery of Rhabdomastix (Rhabdomastix) incapax Starý, 2005 (Diptera, Limoniidae), a crane fly species flightless in both sexes and probably endemic to Sardinia.
Rediscovery of Rhabdomastix (Rhabdomastix) incapax Starý, 2005 in Sardinia made it possible to update the description of the male and to provide the first description of the female of this species. Notes on the wing reduction, ecology, and behaviour of this species are appended.


Depression Among Arab American and Arab Immigrant Women in the United States.
The difficult and tense political climate Arab populations are currently facing may be exacerbating mental health issues, reducing forms of social support in friend circles, and decreasing the desire to seek health care. There is room to better understand the mental health needs of Arab women residing in the United States and to develop policies and interventions that keep these women safe and in care. This column reviews two recent studies; the first examines barriers to reporting intimate partner violence and depression among Arab American women and the second highlights stressors and social support for Arab women immigrants throughout their immigration experience.


Malignant hematopoietic cell lines: in vitro models for the study of multiple myeloma and plasma cell leukemia.
Multiple myeloma (MM) is a neoplasm of a terminally differentiated B-cell. The disease is progressive and always lethal characterized by the slow proliferation of malignant plasma cells in the bone marrow. Much of our current understanding of the biology of MM has been obtained by studying MM-derived cell lines. Human myeloma cell lines were shown to be suitable model systems for use in various fields of the biological sciences. However, it has proved very difficult to establish cell lines from plasma cell dyscrasias. Most reported MM cell lines have been derived from patients with advanced disease and from extramedullary sites. Nevertheless, within the last 20 years more than 100 cell lines have been established. A significant portion of this panel is partially or well characterized with regard to their cell culture, clinical, immunophenotypic, cytogenetic and functional features. Distinct immunoprofiles could be assigned to MM cell lines. All MM cell lines display chromosomal aberrations; in more than 80% of the cell lines analyzed, chromosome 14 band q32 (immunoglobulin heavy chain locus) is affected; the various types of 14q+ chromosomes showed different distributions among the MM cell lines. A large percentage of MM cell lines is constitutively interleukin-6-dependent or responsive to various cytokines. It is important to realize that not every cell line established from a patient with myeloma is a neoplastic cell line. So-called 'myeloma cell lines' have been previously reported and are still widely used which are in reality Epstein-Barr virus (EBV)-positive B-lymphoblastoid cell lines. The presence of the EBV-genome in residual normal B-cells provides them with a selective growth advantage after explantation. In summary, a significant number of authentic and well-characterized MM cell lines has been established and described. The availability of these bona fide MM cell lines is of great importance for the study of the biology, etiology and treatment of the disease.


Inducing Pluripotency in Cattle.
Nuclear reprogramming technologies in general and induced pluripotent stem cells (iPSCs) in particular have opened the door to a vast number of practical applications in regenerative medicine and biotechnology. It also represents a possible alternative to the still evasive achievement of embryonic stem cells (ESCs) isolation from refractory species such as Bos. taurus. Herein, we described a protocol for bovine iPSCs (biPSCs) generation and characterization. The protocol is based on the overexpression of the exogenous transcription factors NANOG, OCT4, SOX2, KLF4 and c-MYC, using a pantropic retroviral system.


Micellar-enhanced ultrafiltration (MEUF) with mixed surfactants for removing Cu(II) ions.
A nonionic surfactant, polyoxyethylene Octyl phenyl ether (Triton-X), is added to a micellar-enhanced ultrafiltration process to lower the critical micellar concentration (CMC) of an anionic surfactant, sodium dodecyl sulfate (SDS). The effects of adding Triton-X on the copper removal efficiency, the permeate SDS concentration, the copper binding capacity of SDS micelles, and membrane fouling are investigated. Our results show that the addition of Triton-X at concentrations greater than its CMC can reduce the SDS dosage required for effective Cu removal, and at the same time, minimize the permeate SDS concentration. Although, no adverse effect on the copper binding capacity of SDS micelle is observed by the addition of Triton-X, the membrane fouling is worsen. Cleaning the membrane with DI water allowed restoring the membrane flux, indicating that the fouling caused by Triton-X was reversible.


Implication of intraoperative sentinel node imprint cytology for consent in the SNAC Trial.
Women randomized into the sentinel node biopsy-only arm of the Sentinel Node versus Axillary Clearance Trial require axillary clearance if the sentinel node is unable to be identified, or if the sentinel node contains metastases. The aim of the present study was to determine the likelihood of immediate and delayed axillary clearance in patients in the trial when nodes were subjected to intraoperative imprint cytology. A prospective database for 400 patients with operable breast cancer was analysed to determine the likelihood of lymph node involvement according to tumour size. The ability to successfully remove a sentinel node and the accuracy of intraoperative imprint cytology of sentinel nodes was investigated. These data were used to predict the likelihood of patients proceeding to immediate or delayed axillary clearance. The rate of lymph node involvement was 0%, 10%, 30%, and 53% in tumours measuring <5 mm, 6-10 mm, 11-20 mm and 21-30 mm, respectively. A sentinel node was identified in 95% of cases. In a series of 79 consecutive cases using intraoperative imprint cytology, 37% of sentinel nodes containing metastases were identified intraoperatively. The estimated likelihood of undergoing immediate axillary clearance therefore ranges from 5% for tumours <5 mm, up to 24% for tumours 21-30 mm. Similarly the likelihood of delayed clearance ranges from 0% to 32% depending on tumour size. It is possible to give detailed and accurate information to patients undergoing sentinel node biopsy about both the risk of lymph node involvement and the likelihood of requiring immediate or secondary axillary clearance.


Understanding equivalence and noninferiority testing.
Increasingly, the goal of many studies is to determine if new therapies have equivalent or noninferior efficacies to the ones currently in use. These studies are called equivalence/noninferiority studies, and the statistical methods for their analysis require only simple modifications to the traditional hypotheses testing framework. Nevertheless, important and subtle issues arise with the application of such methods. This article describes the concepts and statistical methods involved in testing equivalence/noninferiority. The aim is to enable the clinician to understand and critically assess the growing number of articles utilizing such methods.


Interleukin-6 is not involved in appetite regulation following moderate-intensity exercise in males with normal weight and obesity.
In obesogenic states and after exercise, interleukin (IL)-6 elevations are established, and IL-6 is speculated to be an appetite-regulating mechanism. This study examined the role of IL-6 on exercise-induced appetite regulation in sedentary normal weight (NW) males and those with obesity (OB). Nine NW participants and eight participants with OB completed one non-exercise control (CTRL) and one moderate-intensity continuous training (MICT; 60 minutes, 65% V̇O2max ) session. IL-6, acylated ghrelin, active peptide tyrosine-tyrosine3-36 , active glucagon-like peptide-1, and overall appetite perceptions were measured fasted, pre exercise, and 30, 90, and 150 minutes post exercise. Fasted IL-6 concentrations were elevated in OB (p = 0.005, η p 2 = 0.419); however, increases following exercise were similar between groups (p = 0.934, η p 2 = 0.000). Acylated ghrelin was lower in OB versus NW (p < 0.017, d > 0.84), and OB did not respond to MICT (p > 0.512, d < 0.44) although NW had a decrease versus CTRL (p < 0.034, d > 0.61). IL-6 did not moderate/mediate acylated ghrelin release after exercise (p > 0.251). There were no observable effects of MICT on tyrosine-tyrosine3-36 , glucagon-like peptide-1, or overall appetite (p > 0.334, η p 2 < 0.062). These results suggest that IL-6 is not involved in exercise-induced appetite suppression. Despite blunted appetite-regulatory peptide responses to MICT in participants with OB, NW participants exhibited decreased acylated ghrelin; however, no differences in appetite perceptions existed between CTRL and MICT or NW and OB.


Improved source localization in passive acoustic mapping using delay-multiply-and-sum beamforming with virtually augmented aperture.
High-intensity focused ultrasound (HIFU) is a promising non-invasive treatment method whose applications include tissue ablation, hemostasis, thrombolysis and blood-brain barrier opening etc. Its therapeutic effects come from the thermal necrosis and the mechanical destruction associated with acoustic cavitation. Passive acoustic mapping (PAM) is capable of simultaneous monitoring of HIFU-induced cavitation events using only receive beamforming. Nonetheless, conventional time exposure acoustics (TEA) algorithm has poor spatial resolution and suffers from the X-shaped artifacts. These factors lead to difficulties in precise localization of cavitation source. In this study, we proposed a novel adaptive PAM method which combines Delay-Multiply-and-Sum (DMAS) beamforming with virtual augmented aperture (VA) to overcome the problem. In DMAS-VA beamforming, the magnitude of each channel waveform is scaled by p-th root while the phase is multiplied by L. The p and L correspond respectively to the degree of signal coherence in DMAS beamforming and the augmentation factor of aperture size. After channel sum, p-th power is applied to restore the dimensionality of source strength and then the PAM image is reconstructed by accumulating the signal power over the observation time. Based on simulation and experimental results, the proposed DMAS-VA has better image resolution and image contrast compared with the conventional TEA. Moreover, since the VA method may introduce grating lobes into PAM because of the virtually augmented pitch size, DMAS coherent factor (DCF) is further developed to alleviate these image artifacts. Results indicate that, with DCF weighting, the PAM image of DMAS-VA beamforming could be constructed without detectable image artifacts from grating lobes and false main lobes.


Awareness and attitudes of the Lebanese population with regard to physician-pharmaceutical company interaction: a survey study.
To assess the awareness and attitudes of the general public in Lebanon regarding the interactions between physicians and pharmaceutical companies. Primary healthcare clinics and shopping malls in the Greater Beirut Area. 263 participants completed the questionnaire, of whom 62% were female and 38% were male. Eligible participants were Arabic-speaking or English-speaking adults (age≥18 years) residing in Lebanon for at least 5 years. Awareness, attitudes and beliefs of the general public. 263 out of 295 invited individuals (89% completion rate) completed the questionnaire. While the majority of participants were aware of pharmaceutical company presence (or absence) in physicians' offices (range of 71-76% across questions), smaller percentages were aware of gift-related practices of physicians (range of 26-69% across questions). 40% thought that the acceptance of small gifts or meals by physicians is wrong/unethical. The percentage of participants reporting lower trust in physicians due to their participation in various pharmaceutical company-related activities ranged from 12% to 45% (the highest percentage being for large gifts). Participants who reported receiving free medication samples were significantly more likely to consider physicians' acceptance of small gifts as 'not a problem' than 'unethical' (OR=1.53; p=0.044). Participants in our survey were generally more aware of pharmaceutical company presence (or absence) in physicians' offices than of gift-related practices of physicians. While the level of trust was not affected for the majority of participants for various types of interactions, it was affected the most for accepting large gifts.


Carbonyl formation on a copper-bound prion protein fragment, PrP23-98, associated with its dopamine oxidase activity.
The amino-terminal part of prion protein (PrP), containing a series of octapeptide repeats with the consensus sequence PHGGGWGQ, has been implicated in the binding of copper ion. This region possesses amino acid residues susceptible to oxidation, such as histidine, lysine, arginine and proline. In this study, we have investigated copper-catalyzed oxidation of an N-terminal part of human PrP, PrP23-98, that was prepared by the recombinant DNA technique. Carbonyl formations on copper-bound PrP23-98 induced by dopamine and L-ascorbate were analyzed kinetically, and it was found that the redox cycling of PrP23-98-bound copper, especially induced by dopamine, was coupled to the formation of carbonyls on the protein.


Lymphocytic interstitial pneumonitis: a cause of pulmonary gallium-67 uptake in a child with acquired immunodeficiency syndrome.
Lymphocytic interstitial pneumonitis (LIP) is currently recognized as a frequent pediatric manifestation of the acquired immunodeficiency syndrome (AIDS). We report the gallium scan findings in a 3-yr-old girl with this disorder and review its clinical, radiologic, and pathologic features. LIP must be a prime consideration in the differential diagnosis of diffuse pulmonary gallium uptake in pediatric AIDS patients. Further experience will afford greater perspective on the diagnostic role that nuclear medicine will ultimately play in this disease.


Short-course radiotherapy in elderly women with breast cancer: Comparison by age, comorbidity index and toxicity.
Breast cancer is the most common malignancy amongst elderly women. It represents the main cause of mortality for those women and it is steadily increasing. The primary therapeutic approach remains surgery, as in other age groups. The role of radiotherapy following surgery is still debated. The use of hypofractionated schedules is challenging the standard fractionation and has now been considered an advantageous option within this subgroup of patients. Results from randomized controlled trials have not been shown to be inferior to standard fractionation in terms of local recurrence, disease-free survival and overall survival. Acute and late side effects were not increased by hypofractionated regimens. 60 elderly women treated by hypofractionated radiotherapy after breast conserving surgery were stratified by age. Comorbidities associated compliance and toxicity correlation to age were the first endpoints of the study. Comorbidity associated compliance was calculated by Cumulative Illness Rating Scale Geriatric. At a median follow-up of 15 months overall survival was 100%, without severe late toxicity. No statistical significant differences were found between Cumulative Illness Rating Scale-Geriatric, systemic therapy and toxicity. In our experience hypofractioned regimens seem to be safe and reliable in the elderly setting, although longer follow up is needed.


Developing risk-based quality control plans: an overview of CLSI EP23-A.
What constitutes quality control (QC) in the clinical laboratory has expanded from being focused on the testing of QC samples to managing the risks of reporting incorrect patient results. To effectively implement this expanded vision of QC, the techniques of risk management are important tools. In 2011, the Clinical and Laboratory Standards Institute published EP23-A, Laboratory Quality Control Based on Risk Management, providing an introduction to risk management techniques and guidance on developing a risk-based QC plan. This article outlines the steps in developing and using a risk based QC plan based on the EP23 model.


ALLHAT says diuretics are better; ANBP2 says ACEs are better--can we resolve the differences?
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the second Australian National Blood Pressure Study (ANBP2) came to different conclusions about which class of drug to try first for treating high blood pressure: a diuretic or an angiotensin-converting enzyme (ACE) inhibitor. But when examined closely, the results may not be all that different after all.


Elucidation of a role for stromal steroid hormone receptors in mammary gland growth and development using tissue recombinants.
The use of tissue recombinants in conjunction with steroid receptor deficient mice is described as a tool to dissect the complex paracrine pathways of sex-hormone-regulated epithelial growth and ductal morphogenesis in the mammary gland and other hormone target organs. The basic methodology involves the construction of the four possible tissue recombinants composed of epithelium (E) and stroma (S) from wild-type (wt) and knock-out (KO) mice: wt-S + wt-S, wt-S + KO-E, KO-S + KO-E, and KO-S + wt-E. All tissue recombinants are grown as subrenal capsule grafts in nude mice. Following appropriate hormonal challenge epithelial growth can be studied in the four types of tissue recombinants. Such studies using estrogen receptor, androgen receptor and progesterone receptor knockout mice demonstrate that epithelial steroid receptors are neither necessary nor sufficient for hormonal regulation of epithelial proliferation. Instead, hormonal regulation of epithelial proliferation is a paracrine event mediated by hormone-receptor-positive stromal cells.


[Anti-HCV antibodies among blood donors in Cantabria. Incidence and relation to transaminase levels].
The incidence of anti-HCV antibodies found in 1,918 blood donors from Cantabria was 0.31%. Taking a level of 80 U/L ALT as a standpoint, 0.21% of samples with lower values correspond to anti-HCV positive cases, versus 6.25% of samples above that figure. Within those donors with ALT greater than 80 U/L, viral and non-viral profiles were established from biochemical criteria, their anti-VHC positivity frequencies being 22.22% and 0%, respectively. Non-viral profile donors represent 1% of the total number who might not be rejected.


Unexpected source of latex sensitization in a neonatal intensive care unit.
We report a term infant with gastroschisis who presented with a systemic allergic reaction at a specific time of each day coinciding with infusion from a new preparation of total parenteral nutrition and intravenous lipid emulsion. The source of latex was traced to the rubber stopper of the lipid emulsion. We present this case to highlight the possibility of allergy from this unexpected source in a neonate.


Distributions of eight bioactive components in rat tissues administered Marsdenia tenacissima extract orally detected through UPLC-MS/MS.
Marsdenia tenacissima (Roxb.) Wight et Arn. (M. tenacissima) is considered an anticancer medicine in traditional Chinese medicine, which is extensively used in clinical application since it has great therapeutic effects. Currently, although a number of articles have examined M. tenacissima in terms of its pharmacology and quality control, few have investigated the in vivo mechanism of M. tenacissima active ingredients. Previously, we have studied the pharmacokinetics of eight active ingredients after oral administration of M. tenacissima extracts in rat plasma. This study constructed a new scientific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach to simultaneously quantify the contents of tenacissosides B, G, H and I, cryptochlorogenic acid, chlorogenic acid, neochlorogenic acid and caffeic acid in rats orally administered M. tenacissima extract. The proposed approach was successfully used for investigating the distributions of those eight analytes in rat tissues, with digoxin being used as an internal control. The Eclipse Plus C18 RRHD column was used for determination at a column temperature of 30°C. The mobile phase system consisted of acetonitrile and water (supplemented with 0.1% formic acid) under optimal gradient elution conditions. Afterwards, this approach was validated according to the requirements for the analysis of biological samples developed by the US Food and Drug Administration, including precision, accuracy, stability and matrix effects. Based on tissue distribution analysis, those eight analytes showed rapid distribution within all the tested tissues. With regard to organic acid distribution, it followed the order stomach > liver > kidney > small intestine > lung > spleen > heart, whereas the four steroids followed the order stomach > lung > spleen > small intestine > liver > kidney > heart. The present study lays the theoretical foundation for the use and development of M. tenacissima in clinical practice.


Endoscopic large balloon sphincteroplasty is a useful, safe adjunct for difficult to treat choledocholithiasis.
The aim of this study was to assess the safety and efficacy of large balloon sphincteroplasty when used in conjunction with endoscopic biliary sphincterotomy during endoscopic retrograde cholangiopancreatography (ERCP) for therapy of choledocholithiasis. A retrospective audit of all ERCP's performed for choledocholithiasis between January 2012 and October 2013 at one institution was performed. Procedures that utilized large balloon sphincteroplasty were compared with those underwent standard endoscopic stone extraction. Outcomes including stone clearance rate for the individual procedure type, post-ERCP complications and need for surgical exploration of the bile duct were documented. A total of 346 procedures on 306 patients that met the inclusion criteria were identified. Fifty-four (15.6%) procedures included large balloon sphincteroplasty and were compared with 292 (84.4%) procedures that used standard balloon extraction techniques. Despite those patients in the large balloon sphincteroplasty group having a higher rate of previous ERCP (33.3% versus 19.5%, P = 0.031) and a larger proportion of patients with stones greater than 10 mm (40.3% versus 11.3%, P < 0.001), the overall initial clearance rate was similar at 83%. Ultimately, only 14 out of 306 (4.6%) of all patients required surgical intervention. There was no significant difference in the rate of post-ERCP pancreatitis between the two groups (5.6% versus 3.8%, P = 0.466). Large balloon sphincteroplasty of the sphincter of Oddi is a safe and effective adjunct to endoscopic biliary sphincterotomy in difficult to treat choledocholithiasis. The current study demonstrated large balloon sphincteroplasty did not result in more complications despite a tendency to being used for larger stones.


In situ nanopores enrichment of Mesh-like palladium nanoplates for bifunctional fuel cell reactions: A joint etching strategy.
Two-dimensional (2D) nanomaterials with nanopore display an enhancement effect on electrocatalysis behavior, whereas the nanopore engineering for 2D nanocatalysts remains an insurmountable challenge. We advance the synthesis of multilayer Pd nanoplates (Pd NPs) and two types of meshy nanoplates (Pd LMNPs/MNPs) with escalating nanopores from none and sparse to porous. Specially, an in situ nanopore enrichment on these Pd nanoplates hinges on a joint etching strategy with integrated manipulation of reaction kinetics. The optimized Pd MNPs exhibit exceptional oxygen reduction reaction performance, owing to the enhanced intermediates protonation on Pd site neighboring nanopore, which has been elucidated by density functional theory calculations. In addition, Pd MNPs also deliver excellent performances in fuel cell anodic reactions, including ethanol oxidation reaction and formic acid oxidation reaction. This study highlights a new strategy for in situ nanopores engineering, providing a prospect for designing superior nanocatalysts.


Genetic and immunopathological findings in a lymphoma family.
We have studied a remarkable family with seven cases of malignant lymphoma extending through three generations wherein five sisters and their mother had histopathologically documented non-Hodgkin's lymphoma, while a granddaughter had Hodgkin's disease. An immunological study of three lymphoma survivors, nine of their first degree relatives, and four spouse controls was undertaken. Significant findings consisted of a depressed serum IgG3 level in four of the nine first-degree relatives; in two of these four, lymphocyte stimulation by both pokeweed mitogen and concanavalin A were significantly depressed. The subtle immunological abnormalities present in this kindred may be associated with the pathogenesis of the lymphomas.


Evaluation of Multiparametric MRI Radiomics-Based Nomogram in Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer: A Two-Center study.
This study evaluated the performance of primary foci of breast cancer on multiparametric magnetic resonance imaging (MRI) contributing to establish and validate radiomics-based nomograms for predicting the different pathological outcome of breast cancer patients after neoadjuvant chemotherapy (NAC). Retrospectively collected 387 patients with locally advanced breast cancer, all treated with NAC and received breast dynamic contrast-enhanced MRI (DCE-MRI) before NAC. Radiomics signatures were extracted from region of interest (ROI) on multiparametric MRI to build rad score. Clinical-pathologic data and radiological features established the clinical model. The comprehensive model featured rad-score, predictive clinical-pathologic data and radiological features, which was ultimately displayed as a nomogram. Patients were grouped in 2 different ways in accordance with the Miller-Payne (MP) grading of surgical specimens. The first grouping method: 181 patients with pathological reaction grades Ⅳ∼Ⅴ were included in the significant remission group, while 206 patients with pathological reaction grades Ⅰ∼Ⅲ were included in the nonsignificant remission group. The second grouping method: 117 patients with pathological complete response (pCR) were assigned to the pCR group, and 270 patients who failed to meet pCR were assigned to in the non-pCR group. Two combined nomograms are created from 2 grouped data for predicting different pathological responses to NAC. The area under the curves (AUC) of the receiver operating characteristic curves (ROC) were used to evaluate the performance of each model. While decision curve analysis (DCA) and calibration curves were used for estimating the clinical application value of the nomogram. Two combined nomograms embodying rad score and clinical-pathologic data outperformed, showing good calibrations for predicting response to NAC. The combined nomogram predicting pCR showed the best performance with the AUC values of 0.97, 0.90 and 0.86 in the training, testing, and external validation cohorts respectively. The AUC values of another combined nomogram predicting significant remission: 0.98, 0.88 0.80 in the training, testing and external validation cohorts. DCA showed the comprehensive model nomogram obtained the most clinical benefit. The combined nomogram could preoperatively predict significant remission or even pCR to NAC in breast cancer based on multiparametric MRI and clinical-pathologic data.


Characterization of VOC sources in an urban area based on PTR-MS measurements and receptor modelling.
In this study, the concentrations of volatile organic compounds were measured by the use of proton transfer reaction mass spectrometry, together with NO x , NO, NO2, SO2, CO and PM10 and meteorological parameters in an urban area of Belgrade during winter 2014. The multivariate receptor model US EPA Unmix was applied to the obtained dataset resolving six source profiles, which can be attributed to traffic-related emissions, gasoline evaporation/oil refineries, petrochemical industry/biogenic emissions, aged plumes, solid-fuel burning and local laboratories. Besides the vehicle exhaust, accounting for 27.6 % of the total mixing ratios, industrial emissions, which are present in three out of six resolved profiles, exert a significant impact on air quality in the urban area. The major contribution of regional and long-range transport was determined for source profiles associated with petrochemical industry/biogenic emissions (40 %) and gasoline evaporation/oil refineries (29 %) using trajectory sector analysis. The concentration-weighted trajectory model was applied with the aim of resolving the spatial distribution of potential distant sources, and the results indicated that emission sources from neighbouring countries, as well as from Slovakia, Greece, Poland and Scandinavian countries, significantly contribute to the observed concentrations.


Immunoelectron microscopic localization of rabies virus antigen in central nervous system and peripheral tissue using low-temperature embedding and protein A-gold.
A protein A-gold technique was used in conjunction with low temperature embedding to visualize ultrastructurally mature virions and sites of viral replication in the brains of rabies virus-infected mice after peripheral inoculation of virus. The association of viral profiles and gold particles with synaptic membranes, microtubules and rough endoplasmic reticulum suggested a mechanism of rabies virus transport within the central nervous system. Early interactions of inflammatory cells with the virus inoculum were characterized by phagocytosis by non-degranulating neutrophils and mononuclear cells.


Learning Curve of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - an Analysis of Critical Perioperative and Surgical Outcomes among 155 Peritoneal Surface Malignancy Patients Treated at a Tertiary Care Cancer Centre.
Various factors can influence the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Initiating CRS and HIPEC programmes in low- and middle-income countries is challenging due to resource constraints and limited availability of expertise. We present our experience of CRS and HIPEC from a learning curve perspective among a cohort 155 peritoneal surface malignancy patients. Patients undergoing CRS and HIPEC between May 2015 and February 2019 were included in the study. Patients were divided into two consecutive cohorts: the first 73 cases comprised the learning phase, group 1; the subsequent cohort of 82 patients were considered as the implementation phase, group 2. A comparative analysis of clinical and surgical outcome parameters was carried out between the two groups. The clinical spectrum was comparable among group 1/group 2. Most were ovarian (56.8%), colorectal (13.5%) and appendiceal (11.0%) malignancies. Group 2 had a higher number of moderate to high peritoneal cancer index patients (34.1% versus 19.1%), total peritonectomies (48.8% versus 45.2%), multi-visceral resections (colonic 41.5% versus 27.4%, small bowel 25.6% versus 19.1%, diaphragmatic 8.5% versus 6.5% and hepatic resections 8.5% versus 2.7%) and completeness of cytoreduction 0/1 rates (97.6% versus 93.1%). A lower incidence of intraoperative urological injuries (2.6% versus 12.3%) was noticed in group 2 (P = 0.007). Non-significant improvements seen in group 2 included surgery duration (6.0 ± 1.3 h versus 6.4 ± 1.7 h), intensive care unit stay (1.3 ± 1.1 days versus 1.8 ± 1.5 days), overall hospital stay (8.1 ± 0.9 days versus 8.8 ± 1.4 days) and reduction in Clavien-Dindo grade 3-4 complications (25.4% versus 36.9%). The results of the current study indicate that by implementing standard protocols and mentoring by an experienced team, a learning curve of CRS and HIPEC can be achieved in fewer than 75 cases. The baseline expertise of the treating team can also influence the learning curve.


Novel taxa in the Fusarium fujikuroi species complex from Pinus spp.
The pitch canker pathogen Fusarium circinatum has caused devastation to Pinus spp. in natural forests and non-natives in commercially managed plantations. This has drawn attention to the potential importance of Fusarium species as pathogens of forest trees. In this study, we explored the diversity of Fusarium species associated with diseased Pinus patula, P. tecunumanii, P. kesiya and P. maximinoi in Colombian plantations and nurseries. Plants displaying symptoms associated with a F. circinatum-like infection (i.e., stem cankers and branch die-back on trees in plantations and root or collar rot of seedlings) were sampled. A total of 57 isolates were collected and characterised based on DNA sequence data for the translation elongation factor 1-α and β-tubulin gene regions. Phylogenetic analyses of these data allowed for the identification of more than 10 Fusarium species. These included F. circinatum, F. oxysporum, species within the Fusarium solani species complex and seven novel species in the Fusarium fujikuroi species complex (formerly the Gibberella fujikuroi species complex), five of which are described here as new. Selected isolates of the new species were tested for their pathogenicity on Pinus patula and compared with that of F. circinatum. Of these, F. marasasianum, F. parvisorum and F. sororula displayed levels of pathogenicity to P. patula that were comparable with that of F. circinatum. These apparently emerging pathogens thus pose a significant risk to forestry in Colombia and other parts of the world.


trans-Dichloridobis[dicyclo-hex-yl(4-isopropyl-phen-yl)phosphane-κP]platinum(II) acetone monosolvate.
The title compound, [PtCl(2)(C(21)H(33)P)(2)]·C(3)H(6)O, crystallizes with an accompanying acetone solvent mol-ecule. The metal atom shows a distorted square-planar coordination environment, with a P-Pt-P angle of 172.41 (3)° as the most prominent feature. Both isopropyl fragments were treated as disordered over two conformations with occupancy ratios of 0.55 (2):0.45 (2) and 0.58 (2):0.42 (2). The solvent mol-ecule was also disordered over two orientations in a 1:1 ratio. The crystal studied was a non-merohedral twin with a twin component of 32.4%.


An Infant with Respiratory Distress and Loose Stools.
We present the case of a 3-month-old girl who was admitted with complaints of loose stools and respiratory distress. She also had a history of rash and alopecia. Laboratory investigations revealed lymphopenia with reduced immunoglobulin G and immunoglobulin A. Lymphocyte subset analysis by flow cytometry revealed T-B+NK+ severe combined immunodeficiency (SCID). She died due to severe pneumonia, shock and pulmonary hemorrhage. Autopsy findings revealed disseminated cytomegalovirus infection in the lung, liver, adrenals and heart. Thymus was found to be dysplastic and showed characteristic histopathologic features of SCID.


Protection to testicular activity by a combination of 5-hydroxy L-tryptophan with a thiol compound in whole body gamma irradiated rats.
Radiation induced changes in testicular activity were studied by estimating sialic acid content in plasma and testis and 17-ketosteroids in 24 hr urine samples of male Sprague Dawley rats following 8 Gy whole body gamma ray exposure with and without pretreatment with 2-aminoethylisothiuronium bromide hydrobromide (AET) or with a combination of 5-hydroxy L-tryptophan (5-HTP) and AET. Combination of 5-HTP with AET or AET alone in optimum radioprotecting dose has significantly modified the radiation damage to the testis.


Diagnostic accuracy of 1p/19q codeletion tests in oligodendroglioma: A comprehensive meta-analysis based on a Cochrane systematic review.
Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for oligodendroglioma, IDH mutant and 1p/19q codeleted. 1p/19q codeletion is a diagnostic marker and allows prognostication and prediction of the best drug response within IDH-mutant tumours. We performed a Cochrane review and simple economic analysis to establish the most sensitive, specific and cost-effective techniques for determining 1p/19q codeletion status. Fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) test methods were considered as reference standard. Most techniques (FISH, chromogenic in situ hybridisation [CISH], PCR, real-time PCR, multiplex ligation-dependent probe amplification [MLPA], single nucleotide polymorphism [SNP] array, comparative genomic hybridisation [CGH], array CGH, next-generation sequencing [NGS], mass spectrometry and NanoString) showed good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma, irrespective of whether FISH or PCR-based LOH was used as the reference standard. Both NGS and SNP array had a high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. Our findings suggest that G banding is not a suitable test for 1p/19q analysis. Within these limits, considering cost per diagnosis and using FISH as a reference, MLPA was marginally more cost-effective than other tests, although these economic analyses were limited by the range of available parameters, time horizon and data from multiple healthcare organisations.


Combined therapy against murine-disseminated infection by Fusarium verticillioides.
Using a murine model of disseminated infection by two strains of Fusarium verticillioides, we have evaluated the efficacy of high doses of amphotericin B (AMB) (3 mg/kg of body weight/day), voriconazole (VRC) (60 mg/kg of body weight/day), posaconazole (PSC) (100 mg/kg of body weight/day), and the combinations of AMB plus VRC or PSC. In general, our results were very modest. Neither combination was superior to the respective monotherapies. VRC alone and in combination with AMB was able to prolong survival but not to reduce tissue burden, and AMB plus PSC was able to reduce fungal load in organs but not to prolong survival.


Percutaneous (endoscopic) decompression discectomy for non-extruded cervical herniated nucleus pulposus.
In 1838, Key described the pathological findings of two cases of cord compression by "intervertebral substance." In the 1800s and early 1900s many cases of chondromas of the cervical spine were reported. In 1928 Stookey, described the clinical symptoms and anatomic location of cervical disk herniation. In 1934, Mixter and Barr documented four cervical disc protrusions. Before 1950, the standard approach to discs in this region was posteriorly with laminectomy. In the 1950s Bailey, Badgley, Cloward, Smith and Robinson popularized the anterior approach with interbody fusion. Hirsch in 1960, then Robertson in 1973, recommended cervical discectomy without fusion. Similar results were noted.


Correlation between right ventricular Tei index by tissue Doppler imaging and pulsed Doppler imaging in fetuses.
The aim was to compare the right ventricular (RV) Tei index obtained by the tissue Doppler imaging (TDI) method with that obtained by the pulsed Doppler method in 29 fetuses aged 24-39 weeks (29.9 +/- 4.0 weeks). From pulsed Doppler recordings, the tricuspid closing-to-opening time (a) and RV ejection time (b) were measured. The Tei index determined by the pulsed Doppler method was calculated as (a - b)/b. From TDI recordings, the time interval during diastole (a') and the duration of the systole S-wave (b') were measured. The modified Tei index obtained by TDI was calculated as (a' - b')/b'. The time a' correlated strongly with a (r = 0.90, p < 0.0001). The mean difference between a' and a was 0.3 +/- 5.0 ms. There was also a strong correlation between b' and b (r = 0.94, p < 0.0001). The mean difference between b' and b was 0.5 +/- 3.3 ms. The TDI-Tei index correlated with the pulsed Doppler-Tei index (r = 0.83, p < 0.0001). The mean difference between the TDI-Tei index and the pulsed Doppler-Tei index was -0.003 +/- 0.04. This study demonstrated that the TDI-Tei index correlates well with the Tei index determined by pulsed Doppler in fetuses, suggesting that the TDI-Tei index is a feasible approach to assess global RV function in fetuses.


Hepoxilins and trioxilins in barnacles: an analysis of their potential roles in egg hatching and larval settlement.
The barnacle life cycle has two key stages at which eicosanoids are believed to be involved in cellular communication pathways, namely the hatching of nauplii and the settlement of cypris larvae. Barnacle egg-hatching activity has previously been reported to reside in a variety of eicosanoids, including 8-hydroxyeicosapentaenoic acid and a number of tri-hydroxylated polyunsaturated fatty acid derivatives, the trioxilins. The production of the eicosapentaenoic acid metabolite trioxilin A4 (8,11,12-trihydroxy-5,9,14,17-eicosatetraenoic acid) by the barnacles Balanus amphitrite and Elminius modestus was confirmed using a combination of high-performance liquid chromatography and gas chromatography, both linked to mass spectrometry. In addition, both species also generated trioxilin A3 (8,11,12-trihydroxy-5,9,14-eicosatrienoic acid; an arachidonic acid-derived product), 8,11,12-trihydroxy-9,14,17-eicosatrienoic acid (a omega3 analogue of trioxilin A3; derived from omega3 arachidonic acid) and 10,13,14-trihydroxy-4,7,11,16,19-docosapentaenoic acid (a docosahexaenoic acid-derived product). In contrast to earlier reports, trioxilin A3 had no E. modestus egg-hatching activity at any of the concentrations tested (10(-9)-10(-6) mol l(-1)). The unstable epoxide precursor hepoxilin A3, however, caused significant levels of hatching at 10(-6) mol l(-1). Furthermore, the stable hepoxilin B3 analogue PBT-3 stimulated hatching at 10(-7) mol l(-1). Neither trioxilin A3, hepoxilin A3 or PBT-3 at 0.25-30 micromol l(-1) served as settlement cues for B. amphitrite cypris larvae.


Maternal serum Down syndrome screening: free beta-protein is a more effective marker than human chorionic gonadotropin.
The use of quantitative human chorionic gonadotropin measurement in obstetrics has a long and successful history. Prior studies on the utility of human chorionic gonadotropin in Down syndrome screening have utilized assays that measure the intact human chorionic gonadotropin molecule. This study targeted a distinct marker, the human chorionic gonadotropin free beta-protein, which is present in second-trimester maternal serum at much lower concentrations than is intact human chorionic gonadotropin. Our study of 29 cases of trisomy 21 and 450 control samples shows 80% detection efficiency with maternal serum alpha-fetoprotein, the free beta-protein, and maternal age in pregnancies under 17 weeks' gestation. We conclude that the combination of maternal serum alpha-fetoprotein and the human chorionic gonadotropin free beta-protein will be useful in the prenatal detection of trisomy 21.


Congenital toxoplasmosis in Abyssinian cats.
Two of three litter-mate kittens born to an Abyssinian cat died of acute toxoplasmosis. Toxoplasma gondii was found in histologic sections of both kittens and this was confirmed by immunoperoxidase staining.


High-level disinfection, sterilization, and antisepsis: current issues in reprocessing medical and surgical instruments.
Technology is rapidly changing many aspects of health care. The intricate design of instruments, the configuration of instrument trays, and evidence-based practice have resulted in the need for complicated and specific reprocessing recommendations from instrument manufacturers. Patient safety depends on instruments that are appropriately cared for and adequately reprocessed. This article covers current issues that sterile processing and operating room professionals must deal with regarding reprocessing of medical and surgical instruments.


A Breast Cancer Polygenic Risk Score Is Feasible for Risk Stratification in the Norwegian Population.
Statistical associations of numerous single nucleotide polymorphisms with breast cancer (BC) have been identified in genome-wide association studies (GWAS). Recent evidence suggests that a Polygenic Risk Score (PRS) can be a useful risk stratification instrument for a BC screening strategy, and a PRS test has been developed for clinical use. The performance of the PRS is yet unknown in the Norwegian population. To evaluate the performance of PRS models for BC in a Norwegian dataset. We investigated a sample of 1053 BC cases and 7094 controls from different regions of Norway. PRS values were calculated using four PRS models, and their performance was evaluated by the area under the curve (AUC) and the odds ratio (OR). The effect of the PRS on the age of onset of BC was determined by a Cox regression model, and the lifetime absolute risk of developing BC was calculated using the iCare tool. The best performing PRS model included 3820 SNPs, which yielded an AUC = 0.625 and an OR = 1.567 per one standard deviation increase. The PRS values of the samples correlate with an increased risk of BC, with a hazard ratio of 1.494 per one standard deviation increase (95% confidence interval of 1.406-1.588). The individuals in the highest decile of the PRS have at least twice the risk of developing BC compared to the individuals with a median PRS. The results in this study with Norwegian samples are coherent with the findings in the study conducted using Estonian and UK Biobank samples. The previously validated PRS models have a similar observed accuracy in the Norwegian data as in the UK and Estonian populations. A PRS provides a meaningful association with the age of onset of BC and lifetime risk. Therefore, as suggested in Estonia, a PRS may also be integrated into the screening strategy for BC in Norway.


Implementation: The Next Giant Hurdle to Clinical Transformation With Digital Health.
Clinical implementation of digital health is a major hurdle to overcome in the coming years. Considering the role of the Journal of Medical Internet Research in the past 20 years and looking toward the journal's future, this viewpoint acknowledges the vision of medicine and the role that digital health plays in that vision. It also highlights barriers to implementation of digital health as an obstacle to achieving that vision. In particular, this paper focuses on how digital health research must start looking toward implementation as an area of inquiry and the role that the Journal of Medical Internet Research and its' sister journals from JMIR Publications can play in this process.


Clinical risk factors for obstructive sleep apnoea in children.
To identify the clinical factor(s) that identify obstructive sleep apnoea syndrome (OSAS) in children. A prospective study of children referred to the sleep clinic of the paediatric department was conducted in a public non-teaching regional hospital in Hong Kong. A standard questionnaire was administered and overnight sleep polysomnography was performed in a consecutive series of patients. Logistic regression analysis was performed to obtain significant risk factors for prediction of OSAS in this series of patients. Sixty-two children were enrolled into the study and 22 were diagnosed to have OSAS. Logistic regression analysis showed that, among all the answers, 'snoring every night' is the single most significant risk factor (p<0.0001) to predict OSAS. 'Snoring every night' has a sensitivity of 91% and specificity of 75% for OSAS patients. It also has a positive predictive value of 67% and negative predictive value of 94%. Snoring every night is an important risk factor in identifying OSAS in children. Priority for an overnight sleep polysomnogram should be given to those with this symptom.


Personality disorder traits evident by early adulthood and risk for eating and weight problems during middle adulthood.
The current article investigates the association of personality disorder (PD) with the subsequent development of eating and weight problems. Psychiatric interviews were administered to a community-based sample of 658 individuals at mean ages 14, 16, 22, and 33 years. Individuals with PD by age 22 were at an elevated risk for eating disorders at mean age 33 years. PDs were associated with risk for onset of binge eating, purging, daily dietary restriction, and obesity among individuals without a history of these problems. Borderline and histrionic PD symptoms were associated with recurrent binging and purging at mean age 33 years. Antisocial and schizotypal symptoms were associated with recurrent binging and obesity at mean age 33 years. Depressive PD symptoms were associated with recurrent binging and dietary restriction at mean age 33 years. PD symptoms, evident by early adulthood, may be associated with the risk for the development of eating and weight problems by middle adulthood.


Cross-dimensional magnitude interactions reflect statistical correlations among physical dimensions: Evidence from space-time interaction.
Magnitudes of different physical dimensions have been assumed to be processed by a common metric in order to account for interactions between different dimensions (e.g., space, time). This paper tested a different hypothesis, that these cross-dimensional interactions reflect people's experience of statistical correlations among physical dimensions. In the experiment, we manipulated the correlation between space (length) and time (duration). A stimulus consisting of two vertical bars that demarcated a variable stimulus length was presented for a variable stimulus duration; participants were to reproduce either the stimulus length or the stimulus duration. Critically, to reproduce a stimulus length, participants held down the spacebar to grow or shrink (in a blocked design) a length to the stimulus length such that space (i.e. reproduced length) positively or negatively co-varied with time. Reproduced lengths did not vary as a function of stimulus duration under positive space-time correlation but decreased as a function of stimulus duration under negative space-time correlation; reproduced durations increased as a function of stimulus length under positive space-time correlation but this space-on-time effect appeared to be attenuated under negative space-time correlation. These findings are consistent with a Bayesian inference account whereby cross-dimensional interactions reflect people's prior belief/knowledge of cross-dimensional statistical correlation, which itself tunes to recent input.


Geosmin disrupts energy metabolism and locomotor behavior of zebrafish in early life stages.
Geosmin has been commonly detected both in various aquatic environments and biota, but its exact toxicological mechanisms to organisms need further experimentation. In the present study, zebrafish embryos were exposed to geosmin at nominal concentrations of 50, 500 and 5000 ng/L for 120 h post-fertilization (hpf), followed by locomotor activity and biochemical parameter examination, and multi-omics investigation of the transcriptome and metabolome. The results showed that geosmin exposure significantly reduced the mitochondrial electron transport chain (ETC) complexes I-V, ATP content and mitochondrial respiration and suppressed the locomotor behavior of zebrafish larvae. Transcriptomics analysis revealed that the transcripts of genes involved in oxidative phosphorylation, glycolysis, and lipid metabolism were significantly affected, indicating that geosmin disrupts energy metabolism. Furthermore, metabolomics results showed that 3 classes of lipids, namely glycerophospholipids (GPs), sphingolipids (SLs) and fatty acyls (FAs) were significantly decreased after geosmin exposure. This study provides novel insight into the underlying mechanisms of geosmin-induced energy metabolism and highlights the need for concern about geosmin exposure.


Perforation of the colon by ingested chicken bone, leading to diagnosis of carcinoma of the sigmoid.
The patient described is the first reported case of a chicken bone perforating a tumorous narrowing of the lumen of the colon. Although unique, it illustrates one mechanism of foreign-body perforation of the bowel and underscores the advantage for prompt examination of all operative specimens.


Two analytical solutions for a model of pulsed arterial spin labeling with randomized blood arrival times.
A fairly general theoretical model for pulsed arterial spin labeling perfusion methods has been available for some time but analytical solutions were derived for only a small number of arterial blood input functions. These mostly assumed a sudden and simultaneous arrival of the tagged blood into the imaged region. More general cases had to be handled numerically. We present analytical solutions for two more realistic arterial input functions. They both allow the arrival times of the molecules of tagged arterial blood to be statistically distributed. We consider cases of (1) a uniform distribution on a finite time interval and (2) a normal distribution characterized by its mean and standard deviation. These models are physiologically meaningful because the statistical nature of the arrival times reflects the distribution of velocities and path lengths that the blood water molecules undertake from the tagging region to the imaged region. The model parameters can be estimated from the measured dependency of the perfusion signal on the tag inversion time.


Current clinical practice for familial adenomatous polyposis in Japan: A nationwide multicenter study.
In Japanese patients with familial adenomatous polyposis (FAP), colectomy tends to be postponed or avoided. This study aimed to clarify the current clinical practice from a Japanese multicenter cohort study database. We analyzed the records of 250 patients with non-dense FAP who did not require colorectal cancer removal. The clinical outcomes were compared between patients who received colectomy (n = 142) (Group A) and those who did not receive colectomy (n = 108) (Group B). The colectomy rate based on the age at the final follow-up examination was 46%, 60%, 54%, 65%, at ≤29, 30-39, 40-49, and ≥ 50 years, respectively (P = .11). The development of colorectal cancer did not differ between Groups A and B (25% vs 22% P = .67); however, colorectal cancer was diagnosed at the Tis stage in 88% of the patients with colorectal cancer in Group B, and 34% of the patients with colorectal cancer in Group A (P < .01). Regarding survival, all patients in Group B were alive at the final follow-up examination. In contrast, six patients in Group A died, including three patients with desmoid tumors and one with colon cancer. Over one-third of patients with non-dense FAP (polyps ≤ 1000) in Japan did not receive colectomy at >30 years of age, and patients who managed without colectomy showed acceptable survival with the early diagnosis of colorectal cancer, and a very low incidence of desmoid tumor development, indicating that this approach represents a potential option for the management of selected non-dense FAP patients.


Reverse vaccinology as an approach for developing Histophilus somni vaccine candidates.
Histophilosis of cattle is caused by the Gram negative bacterial pathogen Histophilus somni (H. somni) which is also associated with the bovine respiratory disease (BRD) complex. Existing vaccines for H. somni include either killed cells or bacteria-free outer membrane proteins from the organism which have proven to be moderately successful. In this study, reverse vaccinology was used to predict potential H. somni vaccine candidates from genome sequences. In turn, these may protect animals against new strains circulating in the field. Whole genome sequencing of six recent clinical H. somni isolates was performed using an Illumina MiSeq and compared to six genomes from the 1980's. De novo assembly of crude whole genomes was completed using Geneious 6.1.7. Protein coding regions was predicted using Glimmer3. Scores from multiple web-based programs were utilized to evaluate the antigenicity of these predicted proteins which were finally ranked based on their surface exposure scores. A single new strain was selected for future vaccine development based on conservation of the protein candidates among all 12 isolates. A positive signal with convalescent serum for these antigens in western blots indicates in vivo recognition. In order to test the protective capacity of these antigens bovine animal trials are ongoing.


Surface marker expression in adult acute myeloid leukaemia: correlations with initial characteristics, morphology and response to therapy.
The clinical significance of surface markers was investigated in 145 cases of acute myeloid (AML) or undifferentiated leukaemia (AUL), using a panel of six monoclonal antibodies directed to NHL-30.5 antigen (expressed on poorly differentiated myeloid cells), CD13, CD14, CD15, CD33 and CD34 antigens. Expression of CD14 was correlated with higher leucocyte count, higher serum lactate dehydrogenase level and presentation with extramedullary disease. There was no strict correlation with the French-American-British classification. However, the expression of CD14 was associated with monocytic subtypes. CD15 was mainly expressed in M2 and M3 subtypes, and NHL-30.5 and CD34 antigens in AUL and M1 leukaemias. All patients were treated with the same intensive induction treatment. Staining by three antibodies had a prognostic value. The complete remission (CR) rates were 38% (26/68) in NHL-30.5-positive versus 75% (62/77) in NHL-30.5-negative cases (P less than 10(-5), 50% (37/74) in CD34-positive versus 72% (51/71) in CD34-negative cases (P = 0.007) and 70% (77/110) in CD15-positive versus 31% (11/35) in CD15-negative cases (P less than 10(-4). Expression of NHL-30.5 and CD34 antigen was associated with shorter survival (P less than 10(-3) and P less than 10(-2) respectively), whereas survival was longer in CD15-positive cases (P less than 10(-3). In multivariate analysis, expression of NHL-30.5 antigen, absence of CD15, and high LDH level were associated with poor survival. CR duration was not influenced by any of the factors studied, including antigen expression. These results suggest that leukaemias with less differentiated phenotype have a lower response rate to induction treatment.


Does preserved kidney volume predict 1 year donor renal function after laparoscopic living donor nephrectomy?
The aim of the present study was to evaluate whether preserved kidney volume predicts donor renal function at 1-year post-surgery. Data of patients who underwent laparoscopic living donor nephrectomy between October 2006 and September 2010 were retrospectively reviewed. All patients underwent computed tomography scan with an estimation of kidney volume by using an automated segmentation algorithm. We also calculated kidney volume adjusted for donor body surface area and donor preserved kidney volume ratio (split volume). Estimated glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Predictors of the estimated glomerular filtration rate at 1 year were assessed by multiple linear regression. The 1-year estimated glomerular filtration rate was available in 140 patients. The median age was 40 years, and median adjusted preserved kidney volume was 160.5 cc/1.73 m(2) (interquartile range 143.7-177.9). Median estimated glomerular filtration rate was 92.4 (interquartile range 81.9-101.2) and 61.2 mL/min/1.73 m(2) (interquartile range 53.4-68.7), respectively, at baseline and at 1 year. Preserved kidney volume adjusted to body surface area (P = 0.02) with age (P = 0.002) and preoperative estimated glomerular filtration rate (P < 0.001) were independent predictors of estimated glomerular filtration rate at 1 year. However, split kidney volume was not statistically related to estimated glomerular filtration rate at 1 year (P = 0.47). In order to maximize preservation of donor renal function, the pre-donation kidney volume adjusted to body surface area might be a useful parameter to consider when deciding on living kidney donation.


Antihypertensive activity of recombinant peptide IYPR expressed in Escherichia coli as inclusion bodies.
To produce more angiotensin converting enzyme inhibitory peptides (ACEIP), we have established a high-efficiency Escherichia coli expression system. The DNA-coding sequence for the recombinant protein, which was subcloned into the vector pET-30a(+), has been expressed as inclusion bodies in E. coli BL21 (DE3). The influences of induction time and concentration of isopropyl-β-D-thiogalactopyranoside (IPTG) on the expression of recombinant protein were studied. The resulting expression level of the protein accounted for about 31% of cellular protein at a temperature of 37°C, IPTG concentration of 0.6mM and induction time of 7h. The inclusion bodies were washed, separated from the cells, and solubilized with urea. After purification by affinity chromatography, the recombinant protein was recovered with a high purity of about 90%. Molecular weight of the recombinant protein was measured using Tricine-SDS-PAGE. Peptide IYPR was obtained by cleavage of the recombinant protein with trypsin and the IC(50) value was 61 mg/L. The antihypertensive activity in spontaneously hypertensive rats (SHRs) was also investigated. Single oral administration of this peptide in 10-week old SHRs resulted in a significant reduction of systolic blood pressure to 50 mm Hg at 4 h. The data obtained provide a good reference for further development of peptide Ile-Tyr-Pro-Arg into an effective antihypertensive agent for prevention and treatment of hypertension.


Endothelial dysfunction, thrombophilia, and nailfold capillaroscopic features in livedoid vasculopathy.
Livedoid vasculopathy (LV) is a rare, disabling disease characterized by painful ulcers, livedo reticularis and atrophy blanche. Hypercoagulation, endothelial, and microcirculatory dysfunction are believed to be responsible for the pathogenesis of this difficult-to-treat disease. This study sought to investigate the frequency of endothelial dysfunction, hypercoagulability, and nailfold capillaroscopic features in LV patients to shed light on its etiology. This case-control study included 16 patients with LV, 24 with systemic sclerosis (SSc), and 23 control subjects. Serum markers of endothelial dysfunction soluble endoglin, endocan, endothelin-1, lipoprotein a, plasminogen activator inhibitor-1 (PAI-1), soluble thrombomodulin, and von Willebrand factor were measured using enzyme-linked immunosorbent assays. Flow-mediated dilation and carotid intima-media thickness were examined as markers of endothelial dysfunction, and microcirculation was assessed with nailfold capillaroscopy. Thrombophilia-related parameters, including gene polymorphisms of factor V Leiden, prothrombin, PAI-1 genes, methylenetetrahydrofolate reductase (MTHFR) and factor XIII mutation and serum levels of protein C, protein S, antithrombin, homocysteine, D-dimer and antiphospholipid antibodies were investigated in LV patients. Plasminogen activator inhibitor-1 and soluble thrombomodulin levels were significantly higher in LV patients compared to control subjects (2.3 [2.05-2.79] ng/ml vs. 1.89 [1.43-2.33] ng/ml, p = 0.007; 1.15 [0.88-1.4] ng/ml vs. 0.76 [0.56-0.9] ng/ml, p = 0.004, respectively). Flow-mediated dilation was 25.4 % lower in the LV patients compared to the control group (14.77 % [11.26-18.26] vs. 19.80 % [16.47-24.88], p = 0.034). Capillaroscopic features, including ramifications (75 % vs. 8.7 %, p < 0.001), avascular areas (25 % vs. 0 %, p = 0.011) and dilatations (33.2 % vs. 0 %, p = 0.016), were significantly higher in LV patients than in controls. LV patients had multiple biochemical or genetic abnormalities related to thrombophilia, including heterozygous factor V Leiden mutations (6.3 %), MTHFR (C677T) mutations (heterozygous 43.8 %, homozygous 18.8 %), MTHFR (A1298C) mutations (heterozygous 37.5 %, homozygous 12.5 %), factor XIII heterozygous mutation (12.5 %), antithrombin deficiency (31.3 %), protein S deficiency (12.5 %), hyperhomocysteinemia (31.3 %), D-dimer elevation (25 %), anti-β2-glycoprotein I (12.5 %), lupus anticoagulant antibodies (6.3 %), and anticardiolipin antibodies (6.3 %). In conclusion, LV patients were characterized by an increased presence of thrombophilia-related parameters, and also exhibited vascular endothelial and microcirculatory dysfunction, resembling SSc. These findings support the complex interaction of thrombophilia, endothelial dysfunction, and microcirculation dysregulation in the pathogenesis of LV. Thus, the treatment of LV patients should be individualized, based on the identification of the predominant pathological pathways.


Compliance with follow-up appointments generated in a pediatric emergency room.
We studied all follow-up visits generated by initial emergency room (ER) visits made over the course of one year by patients enrolled in a pediatric primary care clinic (PCC). A total of 2,552 ER visits were made by 714 patients, 960 (37.6 percent) of these resulting in a follow-up visit. Of the 960, (82.4 percent) resulted in appointments to the PCC, with a 53.9 percent compliance rate; and 169 (17.6 percent) resulted in appointments to the ER, with an 89.3 percent compliance rate (p less than .001). Factors found to be associated with greater compliance with follow-up appointments were (1) the appointment being made to the ER rather than to the clinic, (2) the child being less than 18 months of age, (3) the patient having private insurance, and (4) an initial ER diagnosis of trauma, seizure, or burn. Factors found to be unrelated to compliance with follow-up visits were the patient's sex (when corrected for trauma cases), race, having a chronic condition, having a telephone, length of time as a clinic enrollee, distance from home to hospital, and type of primary provider (physician versus nurse practitioner).


Analysis of dimycocerosates of glycosylphenolphthiocerols in the identification of some clinically significant mycobacteria.
Extracts of representative mycobacteria were examined by thin-layer chromatography for glycosylphenolphthiocerol dimycocerosates. The glycolipid typical of Mycobacterium bovis was also found in Mycobacterium africanum and Mycobacterium microti, but it was absent in Mycobacterium bovis AN 5. Mycobacterium gastri strains contained a glycolipid which was chromatographically similar to that in Mycobacterium kansasii. Representatives of Mycobacterium marinum produced a distinct glycolipid type, and one strain had major amounts of a more polar variant. The sugar moieties of purified lipids, including that from Mycobacterium leprae, were identified by thin-layer chromatography of methyl glycosides in acid methanolysates.


Gastrodia elata attenuates inflammatory response by inhibiting the NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes.
Gastrodia elata (GE), which belongs to the Orchidaceae family, was found to possess anti-inflammatory activity. However, the effect of GE on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) remains largely unknown. Thus, the aim of this study was to investigate the effects of GE on tumor necrosis factor-α (TNF-α)-induced inflammatory response in RA-FLS and the underlying molecular mechanism was also explored. Our results demonstrated that GE significantly attenuated TNF-α-induced IL-6 and IL-8 production in RA-FLS. GE also inhibited TNF-α-induced MMP-3 and MMP-13 expression in RA-FLS. Furthermore, pretreatment with GE significantly attenuated TNF-α-induced the expression of p-p65 and IκBα degradation in RA-FLS. In conclusion, this study demonstrated for the first time that GE attenuated inflammatory response by inhibiting the NF-κB pathway signaling in RA-FLS. Thus, GE might have a therapeutic potential towards the treatment of RA.


5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial.
Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results. A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of <-2.0 or fracture. The incidence of a 5% decrease in the total lumbar spine bone mineral density at 5 years was 10.2% in the upfront treatment arm versus 41.2% in the delayed treatment arm (P<.0001). A total of 41 patients in the delayed treatment arm were eventually started on ZA. With the exception of increased NCI Common Toxicity Criteria (CTC) grade 1/2 elevated creatinine and fever in the patients treated on the upfront arm and cerebrovascular ischemia among those in the delayed treatment arm, there were no significant differences observed between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront treatment arm (2 vs 8 cumulative cases), although this difference was not found to be statistically significant. Bone fractures occurred in 24 patients in the upfront treatment arm versus 25 patients in the delayed treatment arm. Immediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms.


[Corneal and conjunctival deposits in the eyes of patients treated with periodic haemodialysis. Study of 47 patients (author's transl)].
The study of 47 patients with terminal renal failure treated in the centre for haemodialysis of Geneva shows that 66% present corneo-conjunctival deposits. These deposits do not produce symptoms nor diminution of the vision. Their pathogenesis, linked to the important variations of calcaemia and phospho-calcic product, is not a function of duration of haemodialysis. Similarity seems evident between these deposits, other soft-tissue calcifications and experimentally induced topical calciphylaxis.


PRECIS-2 for retrospective assessment of RCTs in systematic reviews.
A randomized controlled trial (RCT) may be intended either to support real-world decisions on choice between alternative interventions or to help researchers understand mechanisms of action of an intervention. PRECIS-2 is widely used to help investigators match detailed design elements to their main intention for that RCT. PRECIS-2 is increasingly being used retrospectively for assessing RCTs within reviews. In this commentary, we counter arguments that RCTs with a placebo control group, masking/blinding of participants or providers, or conducted in a single center should be retrospectively assessed as completely explanatory, overriding a detailed PRECIS-2 assessment. We also counter arguments that a trial cannot be assessed using only the main peer-reviewed trial report. This is a commentary on the use of PRECIS-2 for systematic reviews. Although placebos are seldom openly prescribed in real-world care, knowing that an intervention achieves its impact via the placebo effect might change some clinical and policy decisions, which means that this feature does not always preclude decision-making use and so should not override a full PRECIS-2 assessment. A domain describing the comparator should be added to PRECIS-2. Conduct of an RCT in only a single centre should also not override PRECIS-2 as the decision support value of a single-centre RCT could be high for decision makers in that centre and others like it. Many journals require that submitted RCT reports meet CONSORT reporting guidelines, which standardizes the available information for all RCTs in systematic reviews; whereas information from registration and protocol documents is unstandardized and undermines comparison between RCTs and across reviews. Published RCT reports are thus more suitable for retrospective PRECIS-2 assessments, but PRECIS-2 domains with missing information should be scored as blank. Wider use of the CONSORT extension specific to pragmatic trials may reduce domains with missing data. PRECIS-2 can be used for retrospective assessments of trials in systematic reviews. The PRECIS-2 instrument should be expanded by including a domain describing the control group(s). Published RCT reports are suitable for retrospective PRECIS-2 assessments.


Lateral hypothalamus: food current intensity in maintaining self-stimulation of hunger.
Rats displaying stimulus-bound eating will press bars for currents slightly above eating threshold only when food is near the bar. At higher currents self-stimulation is maintained without food. Such currents may spread to activate consummatory feedback appropriate to the drive elicited; or, for more intensely stimulated drive mechanisms, wider ranges of sensory feedback may be reinforcing.


Data on German farmers risk preference, perception and management strategies.
The extent to which people are willing to take on risk, i.e. their risk preferences as well as subjective risk perception plays a major role in explaining their behavior. This is of particular relevance in agricultural production, which is inherently risky. The data presented here was collected amongst a total of 64 German farmers in 2015. It includes results of three different risk preference elicitation methods (multiple price list, business statements in four relevant domains and general self-assessment) as well as risk perception. Additionally, farm business characteristics (e.g. size, farm-level workforce, succession) and personal farmer characteristics (e.g. age, gender, risk literacy) are included.


Jealousy: interventions in couples therapy.
Jealousy is a ubiquitous phenomenon that often needs to be addressed in couples therapy. Eleven treatment interventions, with case examples, are discussed, ranging from traditional, direct, straightforward approaches to indirect, paradoxical solutions. Criteria are offered for determining which interventions to use.


Atopic dermatitis in Indian children: The influence of lower socioeconomic status.
Atopic dermatitis (AD) is a chronic inflammatory condition afflicting children and adults. In developing countries like India, the scenario is slightly different from its western counterparts, where the disease has been commonly described. Despite running a milder course, AD still has a significant negative impact on the quality of life. Environmental factors have a great influence on pathogenesis. While the diagnosis has remained clinical, variations in minor clinical features have been observed worldwide. Many indigenous and herbal agents are used for its treatment in India, in addition to conventional therapies. Treatment modalities in India emphasize less costly therapies and family education. This contribution reviews the epidemiologic issues and therapeutic differences in the Indian population with AD, highlighting important nuances in the care of the Indian patient.


Neighborhood physical disorder and common mental disorders in adolescence.
The aim of this study is to estimate the association between observed indicators of neighborhood physical disorder and common mental disorders in adolescents. The study population included 2506 adolescents from three Brazilian state capitals (Rio de Janeiro, Porto Alegre, and Fortaleza) who participated in the Cardiovascular Risk Study in Adolescents (ERICA), a cross-sectional school-based study conducted in 2013-2014. Common mental disorders were assessed using the 12-item General Health Questionnaire. Measures of neighborhood physical disorder were based on the 2010 Brazilian census data and were derived using principal component analysis. Although associations were found between some exposure components and CMD, there were no clear or consistent trends across exposure quartiles. Overall, there was no evidence of an association between observed indicators of neighborhood physical disorder and common mental disorders. Future studies should explore alternative tools for measuring neighborhood physical disorder to minimize the likelihood of exposure misclassification.


Functional brain network community structure in childhood: Unfinished territories and fuzzy boundaries.
Adult cortex is organized into distributed functional communities. Yet, little is known about community architecture of children's brains. Here, we uncovered the community structure of cortex in childhood using fMRI data from 670 children aged 9-11 years (48% female, replication sample n=544, 56% female) from the Adolescent Brain and Cognitive Development study. We first applied a data-driven community detection approach to cluster cortical regions into communities, then employed a generative model-based approach called the weighted stochastic block model to further probe community interactions. Children showed similar community structure to adults, as defined by Yeo and colleagues in 2011, in early-developing sensory and motor communities, but differences emerged in transmodal areas. Children have more cortical territory in the limbic community, which is involved in emotion processing, than adults. Regions in association cortex interact more flexibly across communities, creating uncertainty for the model-based assignment algorithm, and perhaps reflecting cortical boundaries that are not yet solidified. Uncertainty was highest for cingulo-opercular areas involved in flexible deployment of cognitive control. Activation and deactivation patterns during a working memory task showed that both the data-driven approach and a set of adult communities statistically capture functional organization in middle childhood. Collectively, our findings suggest that community boundaries are not solidified by middle childhood.


[PRODUCTION OF CERTAIN PRO- AND ANTI-INFLAMMATORY CYTOKINES DURING STIMULATION BY LIVE AND INACTIVATED LEPTOSPIRA PATHOGENS IN THE MODEL OF HUMAN WHOLE BLOOD].
Study of the ability of clinical isolates of leptospira to cause production of certain pro- and antiinflammatory cytokines in the model of human whole blood. Leptospira interrogans strain was taken for the experiment. Cytokine content was determined by a method based on xMAP technology using a standard panel, composed of 9 analytes: TNF-α, MCP-1, IL-8, IL-4, IL-6, IL-10, IL-IRa, IL- 12 (p70), IFN-γ. An optimal concentration of L. interrogans was selected for stimulation of human whole blood--1 x 10(6) leptospirae/ml. For the first time in the model of human whole blood it was determined, that at early stages of incubation IFN-γ, IL-12(p70), IL-4 and IL-1Ra are more actively produced; at later stages (6 hour incubation)--IL-8 and TNF-α. A differential pattern of cytokine production stimulation was shown in the model of human whole blood by live and inactivated leptospirae.


Effects of early low temperature exposure on the growth, glycolipid metabolism and growth hormone (gh) gene methylation in the late stage of Chinese perch (Siniperca chuatsi).
Temperature is an important factor affecting the early development, growth and physiology of fish, as well as on aspects of feeding and metabolism. Here, we investigated the impact of low temperature on the growth, glycolipid metabolism and growth hormone (gh) gene methylation in the late stage of Chinese perch (Siniperca chuatsi). Chinese perch larvae were exposed to temperatures with 21 °C (low temperature group (LT)) and 25 °C (control group) for 7 days, and then the LT group was slowly heated to 25 °C and raised at this temperature for two months. Results indicated that the LT group exhibited significantly lower growth rate and weight gain rate than the control group (p < 0.05), but no obvious food intake (FI) were detected yet between LT group and control group. The larvae exposed at 21 °C relative to the 25 °C group had significant decreased transcript levels of GH-IGF axis genes (gh, igf1 and igf2) in Chinese perch juvenile (p < 0.05). Further analysis of the DNA methylation levels of gh showed that the LT group had higher at the CpG sites of -3029 and - 3032 than the control group in larvae (p < 0.05), whereas the DNA methylation levels at CpG sites of -2982 and - 3039 of gh were significantly lower compared with the control group in juveniles (p < 0.05). In addition, the plasma glucose was significantly increased in the LT group (p < 0.05), suggesting the metabolism of blood glucose slowed at low temperature. In larvae, the expressions of glycolipid metabolism genes (ins-ra and ins-rb) in LT group were significantly up-regulated compared to control group in larvae (p < 0.05), while down-regulated in juveniles (p < 0.05). The expression level of ucp2 mRNA was continuously up-regulated under low temperature stress. All these data demonstrate that early exposure to low temperature affected the growth and glycolipid metabolism of Chinese perch.


Anderson Localization in Degenerate Spin-Orbit Coupled Fermi Gas with Disorder.
Competition between superconductivity and disorder plays an essential role in understanding the metal-insulator transition. Based on the Bogoliubov-de Gennes framework, we studied an 2D s-wave fermionic optical lattice system with both spin- orbit coupling and disorder are presented. We find that, with the increase of the strength of disorder, the mean superconducting order parameter will vanish while the energy gap will persist, which indicates that the system undergoes a transition from a superconducting state to a gapped insulating state. This can be confirmed by calculating the inverse participation ratio. We also find that, if the strength of disorder is small, the superconducting order parameter and the energy gap will decrease if we increase the strength of spin-orbit coupling and Zeeman field. In the large disorder limits, the increase of the strength of spin- orbit coupling will increase the mean superconducting order parameter. This phenomenon shows that the system is more insensitive to disorder if the spin-orbit coupling is presented. Numerical computing also shows that the whole system breaks up into several superconducting islands instead of being superconductive.


Frequent Gene Mutations and Their Possible Roles in the Pathogenesis, Treatment and Prognosis of Primary Central Nervous System Lymphoma.
Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma with poor prognosis. In recent years, the emergence of genetic subtypes of systematic diffuse large B-cell lymphoma has highlighted the importance of molecular genetics, but large-scale research on the molecular genetics of PCNSL is lacking. Herein, we summarize the frequent gene mutations and discuss the possible pathogenesis of PCNSL. Myeloid differentiation primary response gene 88 (MYD88) and CD79B mutations, which cause abnormal activation of noncanonical nuclear factor-κB, are prominent genetic abnormalities in PCNSL. They are considered to play a major role in the pathogenesis of PCNSL. Other genes, such as caspase recruitment domain family member 11 (CARD11), tumor necrosis factor alpha induced protein 3 (TNFAIP3), transducin (β)-like 1 X-linked receptor 1, cyclin dependent kinase inhibitor 2A, PR domain zinc finger protein 1, and proviral insertion in murine malignancies 1, are also frequently mutated. Notably, the pathogenesis of immune insufficiency-associated PCNSL is related to Epstein-Barr virus infection, and its progression may be affected by different signaling pathways. The different mutational patterns in different studies highlight the heterogeneity of PCNSL. However, existing research on the molecular genetics of PCNSL is still limited, and further research into PCNSL is required to clarify the genetic characteristics of PCNSL.


Renal angiomyolipoma: ultrastructural study.
An angiomyolipoma from a twenty-six-year-old woman was studied by electron microscopy. The tumor was composed of a mixture of mature smooth muscle cells, fat cells, and abnormal blood vessels. MAny of the smooth muscle cells showed excessive intracytoplasmic accumulation of glycogen, while the abnormal blood vessels lacked a normal media.


homothorax and iroquois-C genes are required for the establishment of territories within the developing eye disc.
In Drosophila the eye-antennal disc gives rise to most adult structures of the fly's head. Yet the molecular basis for its regionalization during development is poorly understood. Here we show that homothorax is required early during development for normal eye development and is necessary for the formation of the ventral head capsule. In the ventral region of the disc only, homothorax and wingless are involved in a positive feedback loop necessary to restrict eye formation. homothorax is able to prevent the initiation and progression of the morphogenetic furrow without inducing wingless, which points to homothorax as a key negative regulator of eye development. In addition, we show that the iroquois-complex genes are required for dorsal head development antagonizing the function of homothorax in this region of the disc.


Biotechnological potential of rhizobial metabolites to enhance the performance of Bradyrhizobium spp. and Azospirillum brasilense inoculants with soybean and maize.
Agricultural sustainability may represent the greatest encumbrance to increasing food production. On the other hand, as a component of sustainability, replacement of chemical fertilizers by bio-fertilizers has the potential to lower costs for farmers, to increase yields, and to mitigate greenhouse-gas emissions and pollution of water and soil. Rhizobia and plant-growth-promoting rhizobacteria (PGPR) have been broadly used in agriculture, and advances in our understanding of plant-bacteria interactions have been achieved; however, the use of signaling molecules to enhance crop performance is still modest. In this study, we evaluated the effects of concentrated metabolites (CM) from two strains of rhizobia-Bradyrhizobium diazoefficiens USDA 110(T) (BD1) and Rhizobium tropici CIAT 899(T) (RT1)-at two concentrations of active compounds (10(-8) and 10(-9) M)-on the performances of two major plant-microbe interactions, of Bradyrhizobium spp.-soybean (Glycine max (L.) Merr.) and Azospirillum brasilense-maize (Zea mays L.). For soybean, one greenhouse and two field experiments were performed and effects of addition of CM from the homologous and heterologous strains, and of the flavonoid genistein were investigated. For maize, three field experiments were performed to examine the effects of CM from RT1. For soybean, compared to the treatment inoculated exclusively with Bradyrhizobium, benefits were achieved with the addition of CM-BD1; at 10(-9) M, grain yield was increased by an average of 4.8%. For maize, the best result was obtained with the addition of CM-RT1, also at 10(-9) M, increasing grain yield by an average of 11.4%. These benefits might be related to a combination of effects attributed to secondary compounds produced by the rhizobial strains, including exopolysaccharides (EPSs), plant hormones and lipo-chitooligosaccharides (LCOs). The results emphasize the biotechnological potential of using secondary metabolites of rhizobia together with inoculants containing both rhizobia and PGPR to improve the growth and yield of grain crops.


Importance of dopaminergic neurotransmission for the RU 24969-induced locomotor activity of male and female rats during the preweanling period.
There is disagreement about whether the locomotor activity produced by serotonin (5-HT) 1A/1B receptor agonists is ultimately mediated through a dopaminergic mechanism or is independent of dopamine (DA) system functioning. Using a developing rat model, we examined whether DA neurotransmission is necessary for the locomotor activity produced by 5-HT1A/1B receptor stimulation. Depending on experiment, male and female preweanling rats were pretreated with vehicle, the monoamine-depleting agent reserpine, the 5-HT synthesis inhibitor 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), the DA synthesis inhibitor ∝-methyl-DL-p-tyrosine (AMPT), or the D1 and D2 receptor antagonists SCH 23390 and raclopride, respectively. After completing the pretreatment regimen, the behavioral effects of saline and the 5-HT1A/1B receptor agonist RU 24969 were assessed during a 2-h test session. Locomotor activity in the center and margin of the testing chamber was recorded. RU 24969's locomotor activating effects were sensitive to blockade of the D2 receptor, but not the D1 receptor. The DA synthesis inhibitor (AMPT) significantly attenuated the RU 24969-induced locomotor activity of preweanling rats, as did the 5-HT synthesis inhibitor PCPA. The latter result suggests that presynaptic 5-HT1A/1B receptors may have a role in mediating RU 24969-induced locomotion during the preweanling period. DA neurotransmission, especially involving D2 receptors, is necessary for the 5-HT1A/1B-mediated locomotor activity of preweanling rats. The actions of PCPA, reserpine, and SCH 23390 differ substantially between preweanling and adult rats, suggesting that the neural mechanisms underlying these DA/5-HT interactions vary across ontogeny.


[Congenital dermatofibrosarcoma of Darier and Ferrand: a pediatric case].
Dermatofibrosarcoma show an extremely aggressive tendency to invade surrounding tissue. It was first described in 1924. It usually occurs in young men. This type of tumor is exceptional in childhood. The authors report a case of congenital dermatofibrosarcoma diagnosed in a child. A two-year old female patient presented with a tumor of the vertex scalp since her birth. Biopsy revealed a dermatofibrosarcoma. The tumor was removed surgically with 3cm margins. The primary reconstruction was performed using a double temporoparietal flap (H). There was no recurrence at five years of follow-up. Congenital dermatofibrosarcoma is very rare. Only twenty cases have been reported.