Personality Traits in Obesity Associated with Binge Eating and/or Night Eating.
Specific personality traits, as assessed by the Temperament and Character Inventory (TCI), have been identified in individuals with obesity, but their association with binge and/or night eating has scarcely been reported. Indeed, our systematic search of Medline (1987 to 2013) yielded only five studies on the issue. Taken together, they suggest that personality traits do not have any significant role in determining body mass index, and therefore obesity class. However, obese individuals, in comparison with normal weight individuals, do seem to have a distinctive personality profile, characterized by low self-directedness and cooperativeness, and obese individuals with binge eating show lower self-directedness than those without. Moreover obese individuals with binge eating and/or night eating share a temperament profile characterized by high novelty-seeking and harm-avoidance, two traits also observed in other eating disorder categories and in clinical depression. Future longitudinal studies are needed to investigate the role of personality traits in the onset of binge eating and night eating in obese individuals, and to clarify their influence, if any, on treatment outcomes. Such information will enable us to determine whether the evaluation of personality traits should be included in the comprehensive assessment of obese individuals.


Concise review: current trends on applications of stem cells in diabetic nephropathy.
Diabetic nephropathy, with high prevalence, is the main cause of renal failure in diabetic patients. The strategies for treating DN are limited with not only high cost but an unsatisfied effect. Therefore, the effective treatment of DN needs to be explored urgently. In recent years, due to their self-renewal ability and multi-directional differentiation potential, stem cells have exerted therapeutic effects in many diseases, such as graft-versus-host disease, autoimmune diseases, pancreatic diseases, and even acute kidney injury. With the development of stem cell technology, stem cell-based regenerative medicine has been tried to be applied to the treatment of DN. Related stem cells include embryonic stem cells, induced pluripotent stem cells, mesenchymal cells, and endothelial progenitor cells. Undoubtedly, stem cell transplantation has achieved certain results in the treatment of DN animal models. However, stem cell therapy still remains certain thorny issues during treatment. For instance, poor engraftment and limited differentiation of stem cells caused by the diabetic microenvironment, differentiation into unwanted cell lineages, and malignant transformation or genetic aberrations of stem cells. At present, various researches on the therapeutic effects of stem cells in DN with different opinions are reported and the specific mechanism of stem cells is still unclear. We review here the potential mechanism of stem cells as new therapeutic agents in the treatment of DN. Also, we review recent findings and updated information about not only the utilization of stem cells on DN in both preclinical and clinical trials but limitations and future expectations of stem cell-based therapy for DN.


Metabolic flux analysis of HEK-293 cells in perfusion cultures for the production of adenoviral vectors.
To meet increasing needs of adenovirus vectors for gene therapy programs, development of efficient and reproducible production processes is required. Perfusion cultures were employed to allow infection at greater cell concentrations. In an effort to define culture conditions resulting in enhanced productivities, experiments performed at different feed rates and infected at various cell densities were compared using metabolic flux analysis. The highest specific product yields were achieved in experiments performed at high perfusion rates and/or low cell concentrations. The intracellular flux analysis revealed that these experiments exhibited greater glycolytic fluxes, slightly higher TCA fluxes, and greater ATP production rates at the time of infection. In contrast, cultures infected at high cell density and/or low medium renewal rates were characterized by a more efficient utilization of glucose at the time of infection, but the specific product yields achieved were lower. The intracellular flux analysis provided a rational basis for the implementation of a feeding strategy that allowed successful infection at a density of 5x10(6)cells/ml.


Excision of gamma-ray induced thymine lesions by preparations from ataxia telangiectasia fibroblasts.
The capacity of whole cell sonicates of skin fibroblasts of normal individuals and patients with the autosomal recessive disease Ataxia telangiectasia (AT) to remove aerobic gamma-ray products of the 5,6-dihydroxydihydrothymine type (tgamma02) from exogenous DNA substrates was investigated. All four AT strains (AT CRL 1312, AT CRL 1343, AT GM 367, AT 4BI) possessed normal capabilities to excise tgamma02 from irradiated bacteriophage DNA and irradiated chromatin isolated from normal and AT-skin fibroblasts.


Protection of respiration of a crude mitochondrial preparation in cerebral ischaemia by control of blood glucose.
There is evidence that systemic hyperglycaemia influences the evolution of cerebral ischaemia adversely, through enhancement of brain lactic acidosis. A potential protective regimen based on induction of mild hypoglycaemia with insulin was therefore studied. Respiratory control in brain mitochondria prepared from the ischaemic hemisphere of rats subjected to unilateral common carotid artery occlusion for one hour was abolished, but was partially preserved in insulin-treated rats (p = 0.01).


Human recognition memory and conflict control: An event-related potential study.
The relationship between recognition memory and cognitive control is an important research topic. The current study investigated how conflict control influences an individual's emotional memory. During the encoding phase, participants were required to judge the affective valence of a Chinese Chengyu word (either positive or negative) in a modified Simon paradigm and to remember the word. Half of the words were presented in the congruent condition and the other half were displayed in the incongruent condition. During the retrieval phase, participants were instructed to make an 'old/new judgment' and decide whether the word had been presented previously. Electrophysiological responses were recorded using the event-related potential (ERP) technique. The behavioral results of retrieval processes showed that participants remembered more positive than negative words when they were encoded in the congruent condition. The electrophysiological results revealed that the retrieval of words encoded in the incongruent condition elicited less negative frontal negativity (FN) and early posterior negativity (EPN) amplitudes than those encoded in the congruent condition. The retrieval of words encoded in the incongruent condition induced greater late positive complex (LPC) amplitudes, relative to those encoded in the congruent condition on the left hemisphere. It was also observed that the recognition of positive words induced faster LPC responses than negative words when they were encoded in the incongruent condition. The present electrophysiological study illustrates that emotional memory processes may be affected by conflict control.


Q Fever Osteoarticular Infection in Children.
Q fever osteoarticular infection in children is an underestimated disease. We report 3 cases of Q fever osteomyelitis in children and review all cases reported in the literature through March 2018. A high index of suspicion is encouraged in cases of an unusual manifestation, prolonged course, relapsing symptoms, nonresolving or slowly resolving osteomyelitis, culture-negative osteomyelitis, or bone histopathology demonstrating granulomatous changes. Urban residence or lack of direct exposure to animals does not rule out infection. Diagnosis usually requires use of newer diagnostic modalities. Optimal antimicrobial therapy has not been well established; some case-patients may improve spontaneously or during treatment with a β-lactam. The etiology of treatment failure and relapse is not well understood, and tools for follow-up are lacking. Clinicians should be aware of these infections in children to guide optimal treatment, including choice of antimicrobial drugs, duration of therapy, and methods of monitoring response to treatment..


The Relationship between Bone Remodeling and the Clockwise Rotation of the Facial Skeleton: A Computed Tomographic Imaging-Based Evaluation.
Information on the onset and gender differences of midfacial skeletal changes, including the complete understanding of the theory behind the clockwise rotational theory, remains elusive. One hundred fifty-seven Caucasian individuals (10 men and 10 women aged 20 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, 60 to 69 years, 70 to 79 years, and 80 to 89 years, and eight men and nine women aged 90 to 98 years) were investigated. Multiplanar computed tomographic scans with standardized angle and distance measurements in all three anatomical axes and in alignment to the sella-nasion (horizontal) line were conducted. Both men and women displayed an increase in orbital floor angle (p < 0.001, maximum at 60 to 69 years), decrease in maxillary angle (p = 0.035, 40 to 49 years), increase in palate angle (p < 0.001, 50 to 59 years), increase in vomer angle (p = 0.022, 30 to 39 years), but a decrease in the pterygoid angle (p = 0.002, 80 to 89 years). Orbital width decreased (p < 0.001, 60 to 69 years), pyriform aperture width increased (p = 0.015, 60 to 69 years), and midfacial height decreased with aging (p < 0.001, 60 to 69 years). Age-related changes of the midfacial skeleton occurred independently of gender, but at various time points in different locations. The observed changes seem to be driven by a bone resorption center located in the posterior maxilla, rather than by a rotational movement of the facial skeleton.


A novel technique to determine the cell type specific response within an in vitro co-culture model via multi-colour flow cytometry.
Determination of the cell type specific response is essential towards understanding the cellular mechanisms associated with disease states as well as assessing cell-based targeting of effective therapeutic agents. Recently, there have been increased calls for advanced in vitro multi-cellular models that provide reliable and valuable tools correlative to in vivo. In this pursuit the ability to assess the cell type specific response is imperative. Herein, we report a novel approach towards resolving each specific cell type of a multi-cellular model representing the human lung epithelial tissue barrier via multi-colour flow cytometry (FACS). We proved via ≤ five-colour FACS that the manipulation of this in vitro model allowed each cell type to be resolved with no impact upon cell viability. Subsequently, four-colour FACS verified the ability to determine the biochemical effect (e.g. oxidative stress) of each specific cell type. This technique will be vital in gaining information upon cellular mechanics when using next-level, multi-cellular in vitro strategies.


Inactivation of Salmonella enterica serovar Typhimurium and Escherichia coli O157:H7 in peanut butter cracker sandwiches by radio-frequency heating.
A multistate outbreak of Salmonella enterica serovar Typhimurium recently occurred in the USA, which was traced back to various food products made with contaminated peanut butter. This study was conducted to investigate the efficacy of radio-frequency (RF) heating to inactivate S. Typhimurium and Escherichia coli O157:H7 in peanut butter cracker sandwiches using creamy and chunky commercial peanut butter and to determine the effect on quality by measuring color changes and sensory evaluation. Samples were treated for a maximum time of 90 s in a 27.12 MHz RF heating system. Samples were prepared in the form of peanut butter cracker sandwiches and placed in the middle of two parallel-plate electrodes. After 90 s of RF treatment, the log reductions of S. Typhimurium and E. coli O157:H7 were 4.29 and 4.39 log CFU/g, respectively, in creamy peanut butter. RF treatment of chunky peanut butter for 90 s also significantly (P < 0.05) reduced levels of S. Typhimurium and E. coli O157:H7 by 4.55 log CFU/g and 5.32 log CFU/g. Color values and sensory characteristics of the RF treated peanut butter and crackers were not significantly (P > 0.05) different from the control. These results suggest that RF heating can be applied to control pathogens in peanut butter products without affecting quality.


Impact of transposable elements on the evolution of complex living systems and their epigenetic control.
Transposable elements (TEs) contribute to genomic innovations, as well as genome instability, across a wide variety of species. Popular designations such as 'selfish DNA' and 'junk DNA,' common in the 1980s, may be either inaccurate or misleading, while a more enlightened view of the TE-host relationship covers a range from parasitism to mutualism. Both plant and animal hosts have evolved epigenetic mechanisms to reduce the impact of TEs, both by directly silencing them and by reducing their ability to transpose in the genome. However, TEs have also been co-opted by both plant and animal genomes to perform a variety of physiological functions, ranging from TE-derived proteins acting directly in normal biological functions to innovations in transcription factor activity and also influencing gene expression. Their presence, in fact, can affect a range of features at genome, phenotype, and population levels. The impact TEs have had on evolution is multifaceted, and many aspects still remain unexplored. In this review, the epigenetic control of TEs is contextualized according to the evolution of complex living systems.


Rapid detection of mussels contaminated by heavy metals using near-infrared reflectance spectroscopy and a constrained difference extreme learning machine.
The consumption of mussels contaminated with heavy metals can cause toxicity in humans. To realize quick, accurate, and non-destructive detection of heavy metals in mussels, a new method based on near-infrared reflection spectroscopy was developed in this study. Spectral data from 900 nm to 1700 nm of non-contaminated mussels and mussels contaminated with Cd, Zn, Pb, and Cu were collected using a near-infrared spectrometer. After pre-processing spectral data with multiplicative scatter correction, wavelength selection algorithms based on consistency measures of neighborhood rough sets were used to extract wavelengths for distinguishing non-contaminated and contaminated mussels. A constrained difference extreme learning machine was established as a classification model to detect contaminated mussels. In the proposed model, the weight and bias of the hidden layers are calculated by the difference vectors of samples between classes instead of being randomly selected. The results indicate that the proposed model performs significantly well in differentiating between non-contaminated and contaminated mussels. The average classification accuracy of 50 randomly generated test datasets reaches 97.53%, 95.67%, 99.00%, and 98.80% for the detection of Zn, Pb, Cd, and Cu contamination, respectively. This study demonstrates that near-infrared spectroscopy coupled with a constrained difference extreme learning can be used to rapidly and accurately detect mussels contaminated with heavy metals. This is of great significance for the evaluation of the quality and safety of mussels.


A model of the synchronic self.
The phenomenology of the self includes the sense of control over one's body and mind, of being bounded in body and mind, of having perspective from within one's body and mind and of being extended in time. I argue that this phenomenology is to be accounted for by a set of five dissociable cognitive capacities that compose the self. The focus of this paper is on the four capacities that compose the synchronic self: the agentive(B) self, which underlies the sense of control over one's body; the boundary(B) self, which underlies the sense of being bounded within one's body; the agentive(M) self which underlies the sense of control over one's thoughts; and the boundary(M) self which underlies the sense of being bounded within one's mind. I model the agentive(B) and agentive(M) selves as parts of the motor control system and the boundary(B) self as the capacity to form and integrated map of the body. I point to the delusion of thought broadcast as a possible source of evidence for future research on the boundary(M) self.


[Histochemical analysis of phenoloxidase in leukocytes and lymphocytes isolated from human blood].
Among the cells containing phenoloxidase (POZ) of the human blood there was an evidence of cell forms being morphologically similar to macrophages. Lymphocytes represented no uniform cell fraction. There is a variety of large cells with a different enzyme distribution and activity. All POZ cells can develop a cell form which can be considered as an eye cell. Hypothetically it is connected with the cell generation.


Immunochemical characterization of Klebsiella antigens which specifically modify an HLA-B27-associated cell-surface component.
Culture filtrates of some Klebsiella isolates contain a factor(s) capable of specifically modifying the HLA-B27-positive lymphocytes of normal individuals, resulting in a phenotypic change similar to that seen on lymphocytes from patients with ankylosing spondylitis (AS). To further delineate the nature of the interaction between HLA-B27 and some Klebsiella products we have undertaken a chemical characterization of B27+AS+-cross-reactive Klebsiella antigens from the culture filtrate and the bacterial cell-membrane. Biogel P-100 chromatography of the Klebsiella K43-derived modifying factor from the culture filtrate and from an NP-40-solubilized membrane extract gave a molecular weight of 26,000-30,000. Isoelectric focusing revealed that the modifying factor had an isoelectric point of approximately 5.4. Membrane-associated modifying factor activity was found only in outer-membrane preparations indicating that the cross-reactivity between Klebsiella K43 and B27+AS+ cells is defined, at least in part, by outer-membrane antigens. These studies demonstrate that membrane components of Klebsiella K43 share antigenic determinants with a modifying factor, which is released into the culture medium, and that these components are capable of specifically altering the HLA-B27 antigen or an associated cell-surface structure. Such a modification occurring in vivo following exposure to Klebsiella, or to antigenically related organisms, could explain the triggering of the B27-associated arthropathies such as AS.


Blood pressure control and perceived health status in African Americans with subclinical hypertensive heart disease.
The role of antihypertensive therapy in reducing the risk of cardiovascular complications such as heart failure is well established, but the effects of different blood pressure goals on patient-perceived health status has not been well defined. We sought to determine if adverse effects on perceived health status will occur with lower blood pressure goals or more intensive antihypertensive therapy. Data were prospectively collected as a part of a single center, randomized controlled trial designed to evaluate standard (Seventh Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure-compliant) versus intense (<120/80 mm Hg) blood pressure goals for patients with uncontrolled hypertension and subclinical hypertensive heart disease. Blood pressure management was open label, and health status was measured at 3-month intervals over 1 year of follow-up using the short-form (SF)-36. Mixed linear models were constructed for each of the SF-36 summary scores. One hundred twenty-three (mean age 49.4 ± 8.2; 65% female; 95.1% African American) patients were randomized, 88 of whom completed the protocol. With the exception of a decrease in perceived health transition, health status did not change significantly on repeat measurement. Lower blood pressure goals and more intensive antihypertensive therapy appear to be well tolerated with limited effects on patients' perception of health status.


Aflatoxin production on the pits (seeds) of the date palm (Phoenix dactylifera L.).
Pits -a by-product of the utilization of date fruits, are widely used as components of animal feeds, but an incident of aflatoxicosis in camels fed rations containing date pits has caused concern in the Gulf Region. This present study has shown that date pits can support aflatoxin production when inoculated withAspergillus parasiticus (IMI 91019b) and that variety and/or stages of maturation within a given variety can affect the final level of aflatoxin in the material. In one variety, Lulu, aflatoxin production was 44.5,38.7 and 21.0 [Symbol: see text]g/g in pits taken from the first three stages of ripening namelyKimri, Khalal andRutab, but no significant aflatoxin production was noted at the fully-ripeTamr stage. Moisture content was considered to be the most important factor with respect to the capacity of the mould to synthesise aflatoxin in date pits.


New records of Rhyparochromidae (Hemiptera: Heteroptera: Lygaeoidea) from Colombia.
Five species in the tribes Lethaeini, Cistalia neotropicalis Slater & Baranowski and Paragonatas divergens Distant, and Ozophorini, Balboa variabilis Distant, Lygofuscanellus ozophoroides Slater, and Pamozophora englemani Ashlock & Slater, are recorded for the first time from Colombia. They are also the first generic record for this country. Photographs of all five species are included.


Effect of the Timing of Anterior Cruciate Ligament Reconstruction on Clinical and Stability Outcomes: A Systematic Review and Meta-analysis.
The purpose of this systematic review and meta-analysis was to evaluate the effect of the timing of anterior cruciate ligament (ACL) reconstruction on clinical and stability outcomes by analyzing high-quality studies that assessed timing as a primary objective. The MEDLINE, EMBASE, and Cochrane database were systematically searched. The inclusion criteria were as follows: (1) English articles, (2) noncomparative study or relevant study reporting clinical and/or stability results, and (3) timing of the ACL reconstruction as a primary objective. Study type, level of evidence, randomization method, exclusion criteria, number of cases, age, sex, timing of ACL reconstruction, follow-up, clinical outcomes, stability outcomes, and other relevant findings were recorded. Statistical analysis of the Lysholm scores and KT-1000 arthrometer measurements after early and delayed ACL reconstruction was performed using R version 3.3.1. Seven articles were included in the final analysis. There were 6 randomized controlled trials and 1 Level II study. Pooled analysis was performed using only Level I studies. All studies assessed the timing of ACL reconstruction as a primary objective. The definition of early ranged broadly from 9 days to 5 months and delayed ranged from 10 weeks to >24 months, and there was an overlap of the time intervals between some studies. The standard timing of the delayed reconstruction was around 10 weeks from injury in the pooled analysis. After pooling of data, clinical result was not statistically different between groups (I2: 47%, moderate level of heterogeneity). No statistically significant difference was observed in the KT-1000 arthrometer measurements between groups (I2: 76.2%, high level of heterogeneity) either. This systematic review and meta-analysis performed using currently available high-quality literature provides relatively strong evidence that early ACL reconstruction results in good clinical and stability outcomes. Early ACL reconstruction results in comparable clinical and stability outcomes compared with delayed ACL reconstruction. Level II, a systematic review and meta-analysis of Level I and II studies.


Cardiac Mass, Aortic Intramural Hematoma, and IgG4-related Disease: A Case Report.
As a designated entity within medicine, immunoglobulin G4 (IgG4)-related disease is relatively new. It is immune-mediated origin, characterized by a tendency for formation of tumefactive lesions, the infiltration of IgG4-positive plasma cells, and frequent but not invariable elevations of IgG4 levels in the serum. IgG4-related cardiac mass accompanying aortic intramural hematoma is an extremely rare clinical presentation. Herein we present the case of a patient who was admitted to our department complaining of severe chest pain. Computed tomographic angiography examination revealed a cardiac mass accompanying an aortic intramural hematoma. He underwent a surgical resection of the cardiac mass and a replacement of the ascending aorta with Hemashield Platinum graft and made an uneventful recovery. A diagnosis of an IgG4-related disease was made based on laboratory results and pathological examination. Corticosteroids were administered postoperatively. This case shows that the heart itself can also be a potential site for IgG4-related disease.


Right Ventricular Ejection Fraction Assessed by Three-Dimensional Echocardiography Is Associated with Long-Term Adverse Clinical Cardiac Events in Patients with Anthracycline-Induced Cardiotoxicity.
Patients with cancer treated with chemotherapy are at risk for cardiovascular toxicity. Global longitudinal strain has been reported to play important roles in predicting cardiovascular adverse events (CAEs) in patients treated with anthracycline. In addition to various left ventricular indicators, the authors hypothesized that right ventricular (RV) parameters might be associated with CAEs related to anthracycline treatment. In this retrospective study, 96 patients diagnosed with diffuse large B-cell lymphoma who received chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) were studied using three-dimensional transthoracic echocardiography. Baseline demographic data and oncologic and echocardiographic parameters were analyzed. The main outcome was the proportion of patients with grade 3 to 5 CAEs. The association of all three-dimensional transthoracic echocardiographic parameters with long-term CAEs was analyzed using Cox proportional-hazard analysis. Over a median follow-up period of 6.1 years (range, 4.9-7.6 years) after the completion of anthracycline chemotherapy, 18 of 96 patients (19%) experienced CAEs. Percentage changes (%Δ) in left ventricular global longitudinal strain (LVGLS), global circumferential strain, RV ejection fraction (RVEF), and RV end-systolic volume were associated with CAEs (P < .05). A relative reduction of RVEF (hazard ratio, 0.847; 95% CI, 0.785-0.915; P < .001) was the strongest associated factor for CAEs. An increase in CAEs was also observed in patients with impaired %ΔLVGLS > 15% and impaired %ΔRVEF > 12.7% compared with those with impaired %ΔLVGLS > 15% and impaired %ΔRVEF < 12.7% (P = .032). Three-dimensional echocardiography-based assessments of %ΔRVEF and %Δ in RV end-systolic volume were significantly associated with CAEs in patients with lymphoma treated with anthracycline chemotherapy.


Mechanisms and models of immune tolerance breakdown in the ovary.
Ovarian autoimmunity is increasingly implicated in the etiology of primary ovarian insufficiency (POI), previously termed PREMATURE OVARIAN FAILURE or PREMATURE MENOPAUSE. Links to autoimmunity in human POI have long been noted due to the close association of POI with several autoimmune diseases and syndromes such as Addison's disease and Autoimmune polyglandular syndrome 1. However, diagnosis of autoimmune-mediated POI (aPOI) remains challenging because of the lack of sensitive or specific markers of disease. Autoimmunity can arise from the breakdown of immunological tolerance in several ways. How then may we discern what constitutes a relevant target and what represents a downstream phenomenon? The answer lies in the study of pathogenic mechanisms in translational models of disease. From examples in humans and mice, we see that ovarian autoimmunity likely arises from a limited number of antigens targeted in the ovary that are organ specific. These antigens may be conserved but not limited to those seen in animal models of autoimmune ovarian disease. Recent advances in these areas have begun to define the relevant antigens and mechanisms of immune tolerance breakdown in the ovary. Work in translational models continues to provide insight into mechanisms of disease pathogenesis that will allow more accurate diagnosis and, ultimately, improved interventions for women with aPOI.


Detection of subclinical microvascular changes in systemic lupus erythematous using optical coherence tomography angiography: A systematic review and meta-analysis.
Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune connective tissue disease that affects several vascular territories. We sought to assess the role of optical coherence tomography angiography in detecting subclinical microvascular alterations in SLE patients. PubMed, Scopus, and Web of Science databases were systematically searched until January 21, 2023. Studies using optical coherence tomography angiography as a primary diagnostic method to evaluate the macular microvasculature of SLE patients versus healthy controls were included. Primary outcomes were macular vessel density and foveal zone parameters. A meta-analysis was performed using a random-effects model. Of 301 screened abstracts, 15 were found eligible, enrolling 1,246 eyes from 1,013 patients. SLE patients presented a reduction of macular vessel density at both plexuses in all zones (whole scan, fovea, parafovea, and perifovea), and of foveal density compared with healthy controls. No differences were found at foveal avascular zone parameters. SLE patients presented a reduction of macular vessel density without signs or symptoms of SLE ocular involvement. Optical coherence tomography angiography application for the assessment of subclinical microvascular changes needs to be elucidated with longitudinal studies.


A computational model of cardiomyocyte metabolism predicts unique reperfusion protocols capable of reducing cell damage during ischemia/reperfusion.
If a coronary blood vessel is occluded and the neighboring cardiomyocytes deprived of oxygen, subsequent reperfusion of the ischemic tissue can lead to oxidative damage due to excessive generation of reactive oxygen species. Cardiomyocytes and their mitochondria are the main energy producers and consumers of the heart, and their metabolic changes during ischemia seem to be a key driver of reperfusion injury. Here, we hypothesized that tracking changes in cardiomyocyte metabolism, such as oxygen and ATP concentrations, would help in identifying points of metabolic failure during ischemia and reperfusion. To track some of these changes continuously from the onset of ischemia through reperfusion, we developed a system of differential equations representing the chemical reactions involved in the production and consumption of 67 molecular species. This model was validated and used to identify conditions present during periods of critical transition in ischemia and reperfusion that could lead to oxidative damage. These simulations identified a range of oxygen concentrations that lead to reverse mitochondrial electron transport at complex I of the respiratory chain and a spike in mitochondrial membrane potential, which are key suspects in the generation of reactive oxygen species at the onset of reperfusion. Our model predicts that a short initial reperfusion treatment with reduced oxygen content (5% of physiological levels) could reduce the cellular damage from both of these mechanisms. This model should serve as an open-source platform to test ideas for treatment of the ischemia reperfusion process by following the temporal evolution of molecular concentrations in the cardiomyocyte.


Hypotensive effect in the rat after oral prostacyclin (PGI2).
PGI2 dose dependently lowers mean systemic arterial pressure in conscious normotensive and spontaneously hypertensive rats after oral administration. The ED30 was respectively 0.79 and 0.63 mg/kg. Heart rate was not significantly modified. The hypotensive effect appears to be due to PGI2 itself and not to its metabolite 6-keto-PGF1 alpha which, administered at 2 mg/kg p.o., did not modify blood pressure.


Outpatient Parenteral Antimicrobial Therapy Practices Among Pediatric Infectious Diseases Consultants: Results of an Emerging Infections Network Survey.
We conducted a survey of pediatric members of the Emerging Infections Network regarding outpatient parenteral antimicrobial therapy (OPAT) practices and clinical decision making about OPAT initiation. We identified substantial variation in characteristics and resources of pediatric OPAT practices. Opportunities to improve oversight of OPAT in children should be explored.


Acute permethrin neurotoxicity: Variable presentations, high index of suspicion.
Permethrin is a synthetic Type I pyrethroidal neurotoxic pesticide that has been responsible for accidental animal deaths. Despite its widespread use, there are no published case reports on pediatric intensive care unit admissions due to permethrin exposure. We report the unusual and varied presentations of permethrin toxicity in three siblings presenting to a tertiary care pediatric intensive care unit (PICU). While there is no standard clinical diagnostic test for permethrin, accurate diagnosis was obtained by rapidly analyzing the offending agent. In the absence of a known antidote for permethrin, supportive management was initiated and resulted in a favorable outcome for all three siblings.


Characterization of immobilized artificial membrane (IAM) and XTerra columns by means of chromatographic models.
Immobilized artificial membranes (IAMs) prepared from phosphatidylcholine analogs are used as stationary phases in liquid chromatography systems to model drug partitioning between an aqueous phase (mobile phase) and a cell membrane (IAM column). Two different chromatographic models, which describe retention as a function of solute and column-mobile phase properties, have been applied to characterization of an IAM and two reversed phase C18 columns (Waters XTerra MSC18 and XTerra RP18) with acetonitrile-water mobile phases. The comparison of the results shows that the phosphatidylcholine group makes IAM column more polar than both XTerra columns, specially in terms of hydrogen-bond acceptor ability. XTerra RP18 is slightly more polar than XTerra MSC18 because of the presence of the embedded carbamate polar group.


Essential oil yield estimation by Gas chromatography-mass spectrometry (GC-MS) after Methyl jasmonate (MeJA) elicitation in in vitro cultivated tissues of Coriandrum sativum L.
Coriandrum sativum is an important spice plant known for its unique fragrance. Coriander oil is also one of the major essential oils in world global market. The oil yield varies with different coriander varieties; and the content and quality of oil is governed by several factors. In recent times, a variety of technologies have been exploited to improve phyto-compounds including essential oils. In this present study, Methyl jasmonate (MeJA) was amended in medium and the yield of essential oil was measured and compared in different cultivating tissues. The cultured tissues were nonembryogenic callus and embryogenic tissues (induction, proliferation and maturation stages of embryos). MeJA acts as a signaling molecule in accumulating secondary metabolites. Four different MeJA treatments i.e. T1 = 50, T2 = 100, T3 = 150 and T4 = 200 μM, along with a control (T0) were used and the yield of coriander essential oil was estimated in different in vitro cultivating tissues by using Gas chromatography-mass spectrometry (GC-MS). The addition of MEJA enriched essential oil yield, maximum oil being in maturation stage of embryos at T3 (150 μM). Other added treatments also had varied stimulatory role. The addition of MeJA induced stress as the stress marker enzymes like superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) content were high compared to non treated tissue (T0). In T4, the CAT activity was maximum i.e. 5.83 and 6.28 mg-1 protein min-1 in Co-1 and RS respectively in matured somatic embryos. The SOD activity was also high at maturation stage of embryos at T4 (5.3 mg-1 protein min-1 in RS). The APX activity on the other, was high (3.32 mg-1 protein min-1) in induction stage of embryogenesis at T3. The comparative biochemical (sugar, protein and proline) analyses of tissues were performed and presented that had high and low essential oil. MeJA induced stress may help in accumulating essential oils in C. sativum.


Analysis of the enzymatic formation of citral in the glands of sweet basil.
Basil glands of the Sweet Dani cultivar contain high levels of citral, a mixture of geranial and its cis-isomer neral, as well as low levels of geraniol and nerol. We have previously reported the identification of a cDNA from Sweet Dani that encodes an enzyme responsible for the formation of geraniol from geranyl diphosphate in the glands, and that these glands cannot synthesize nerol directly from geranyl diphosphate. Here, we report the identification of two basil cDNAs encoding NADP+-dependent dehydrogenases that can use geraniol as the substrate. One cDNA, designated CAD1, represents a gene whose expression is highly specific to gland cells of all three basil cultivars examined, regardless of their citral content, and encodes an enzyme with high sequence similarity to known cinnamyl alcohol dehydrogenases (CADs). The enzyme encoded by CAD1 reversibly oxidizes geraniol to produce geranial (which reversibly isomerizes to neral via keto-enol tautomerization) at half the efficiency compared with its activity with cinnamyl alcohol. CAD1 does not use nerol and neral as substrates. A second cDNA, designated GEDH1, encodes an enzyme with sequence similarity to CAD1 that is capable of reversibly oxidizing geraniol and nerol in equal efficiency, and prolonged incubation of geraniol with GEDH1 in vitro produces not only geranial and neral, but also nerol. GEDH1 is also active, although at a lower efficiency, with cinnamyl alcohol. However, GEDH1 is expressed at low levels in glands of all cultivars compared with its expression in leaves. These and additional data presented indicate that basil glands may contain additional dehydrogenases capable of oxidizing geraniol.


The role of minimally invasive surgery in multifocal renal cell carcinoma.
Surgical excision remains the reference standard for treatment of localized renal cell carcinoma (RCC). Laparoscopic and robotic minimally invasive extirpative approaches are being increasingly employed in current urologic practice. Multiple tumors in the same kidney present a unique set of challenges for minimally invasive surgeons. As such, we review recent literature regarding minimally invasive nephron-sparing surgery in patients with synchronous, ipsilateral, multifocal renal tumors. As the experience with these complex operations grows, perioperative, short-term functional and oncologic outcomes appear comparable to traditional open nephron-sparing surgery. Data on surgical approaches to patients with synchronous, ipsilateral, multifocal RCC are emerging. Short-term results suggest minimally invasive nephron-sparing surgery is safe, feasible, and should be considered as a potential treatment option for patients who present with multiple tumors in the same renal unit.


Effects of a choline-deficient diet and a hypolipidemic agent on single glutathione S-transferase placental form-positive hepatocytes in rat liver.
Using the placental form of glutathione S-transferase (GST-P) as a marker of carcinogen-initiated hepatocytes, we investigated how a choline-deficient (CD) diet and BR931, a carcinogenic hypolipidemic agent, modify populations of single GST-P-positive hepatocytes. The liver of male Fischer rats (6-7 weeks old) fed a CS or basal diet contained mostly single or double GST-P-positive hepatocytes. Feeding a CD diet for 2-4 weeks led to increases in the number of aggregates of two and three GST-P-positive hepatocytes. By 8-12 weeks, there was an emergence of discrete foci of GST-P-positive hepatocytes consisting of more than 20 hepatocytes. Feeding a BR931 diet for 4-8 weeks resulted in no significant change in the number of single GST-P-positive hepatocytes in the liver as compared to feeding a basal diet. It is suggested that single GST-P-positive hepatocytes in the liver of relatively young rats maintained on a commercial diet may represent endogenously initiated cells. A CD diet promotes endogenously initiated cells to form larger aggregates or foci of GST-P-positive cells.


A flow-batch analyzer using a low cost aquarium pump for classification of citrus juice with respect to brand.
This paper proposes a novel flow-batch analyzer (FBA), which employs a compact, low-cost aquarium air pump as an alternative to a peristaltic pump. The feasibility of using this simple propulsion device is demonstrated in a case study involving the classification of citrus juice samples with respect to brand. For this purpose, UV-vis spectra and SIMCA (soft independent modelling of class analogies), PLS-DA (Partial Least Squares for Discriminant Analysis) and SPA-LDA (Linear Discriminant Analysis with variables selected by the Successive Projections Algorithm) are employed. Good classification results were obtained, thus indicating that the proposed FBA system is a viable alternative to the use of more costly peristaltic pumps. In addition, the smaller size and weight of the aquarium pump are useful features for the construction of portable FBAs to be deployed in field applications.


First-principles study of the structural, optoelectronic and thermophysical properties of the π-SnSe for thermoelectric applications.
Tin selenide (SnSe) has thermoelectric (TE) and photovoltaic (PV) applications due to its exceptional advantages, such as the remarkable figure of merit (ZT ≈ 2.6 at 923 K) and excellent optoelectronic properties. In addition, SnSe is nontoxic, inexpensive, and relatively abundant. These aspects make SnSe of great practical importance for the next generation of thermoelectric devices. Here, we report structural, optoelectronic, thermodynamic, and thermoelectric properties of the recently experimentally identified binary phase of tin monoselenide (π-SnSe) by using the density functional theory (DFT). Our DFT calculations reveal that π-SnSe features an optical bandgap of 1.41 eV and has an exceptionally large lattice constant (12.2 Å, P213). We report several thermodynamic, optical, and thermoelectric properties of this π-SnSe phase for the first time. Our finding shows that the π-SnSe alloy is exceptionally promising for the next generation of photovoltaic and thermoelectric devices at room and high temperatures.


Microwave oven-related injuries treated in hospital EDs in the United States, 1990 to 2010.
The widespread availability of microwave ovens has sparked interest in injuries resulting from their use. Using a retrospective cohort design, the objective of this study is to investigate the epidemiology of microwave oven-related injuries treated in United States emergency departments (EDs) from 1990 through 2010 by analyzing data from the National Electronic Injury Surveillance System. An estimated 155959 (95% confidence interval [CI], 133515-178402) individuals with microwave oven-related injuries were treated in US hospital EDs from 1990 through 2010, which equals an average of 21 individuals per day; 60.7% were female; 63.3% were adults (≥18 years); 98.1% of injury events occurred at home; and 3.9% of patients were hospitalized. During the 21-year study period, the number and rate of microwave oven-related injuries increased significantly by 93.3% and 50.0%, respectively. The most common mechanism of injury was a spill (31.3%), and the most common body region injured was the hand and fingers (32.4%). Patients younger than 18 years were more likely to sustain an injury to their head and neck (relative risk: 1.65; 95% CI, 1.39-1.96) than adults. To our knowledge, this is the first study to investigate microwave oven-related injuries on a national scale. Microwave ovens are an important source of injury in the home in the United States. The large increases in the number and rate of these injuries underscore the need for increased prevention efforts, especially among young children.


Examining diagnostic variability among pediatric subspecialists using case examples of infant head injury.
Although there is research regarding the diagnosis and timing of abusive head trauma, there remains practice variation among pediatric subspecialists. To examine diagnostic variability among pediatric subspecialists using case examples of infant head injury. Secondary objectives were timing variability among subspecialists, and diagnostic and timing variability among Child Abuse Pediatricians (CAPs). Pediatric subspecialists were recruited from Child Abuse Pediatrics, Hospital Medicine, Emergency Medicine, Critical Care, and Neurosurgery to complete a research instrument. Participants qualified for the study if they evaluated at least 1 case of possible abusive head trauma during their career. This multi-institutional, mixed-methods study used a research instrument with 4 case examples of infant head injury: severe retinal hemorrhages (RH), mass-effect subdural hemorrhage (SDH), SDH membrane formation, and sepsis. The response selected by most CAPs was reference and compared across subspecialties and among CAPs using Chi-square or Fisher's exact tests. A Bonferroni correction (p < 0.01) was used for subspecialty comparisons. There were 288 participants who completed at least 1 case example. Diagnostic variability was observed in all case examples. Significantly fewer Hospital Medicine (34.9 % vs. 57.9 %, p < 0.01), Emergency Medicine (28.0 % vs. 57.9 %, p < 0.0001), and Neurosurgery (24.0 % vs. 57.9 %, p < 0.01) participants selected the reference response for the mass-effect SDH case example. Timing variability was statistically significant for all case examples (p < 0.01). Significantly fewer CAPs aged 44-64 years selected the reference response for timing (p < 0.01) for the severe RH case example. Additional peer review processes and consensus guidelines for challenging issues in abusive head trauma may be beneficial.


Prothrombin fragments in cardiovascular disease.
Prothrombin fragment 1+2 (F1+2), which comes from in vivo cleavage of prothrombin by factor Xa, is considered to be useful for diagnosis of thrombosis. Recognition of the central role of thrombosis in the pathogenesis ofcardiovascular disease has prompted growing interest in the association o F1+2 with cardiovascular clinical syndromes. Increased F1+2 levels have reported in venous thromboembolism, inflammation, cancer, sepsis, acute coronary syndromes, stroke, peripheral arterial disease, atrial fibrillation and during the postoperative period. However, a clear relationship with the appearance of thrombosis has not always been consistently demonstrated. Besides its potential prognostic and diagnostic value, it could also be usefu in assessing the impact of various therapies. However, it should be kept in mind that measurement of hemostasis activation markers has several important biological and methodological disadvantages. Activation markers reflect the presence of thrombosis in any vascular bed, so they are not specific. Furthermore, elevations occur not only in the presence of overt thrombosis but also during the hypercoagulable state. The cutoff level to be used for the definition of elevations is still largely unknown due to the use of different analytical methods, none of which have been standardized until know. Finally, the prognostic value of F1+2 and other markers of coagulation activation remains to be fully defined in future studies.


Identification of phytochemicals and antioxidant activity of Premna microphylla Turcz. stem through UPLC-LTQ-Orbitrap-MS.
Premna microphylla Turcz. is a commonly used traditional Chinese medicine totreatdysentery and appendicitis. Present study is focused to explore antioxidants and other compounds in the Premna microphylla Turcz. stem. Assessment of chemical composition was done with high sensitivity UPLC-LTQ-Orbitrap-MS and for Separation Thermo Hypersil Gold (100 mm × 2.1 mm, 1.9 µm) was used while electrospray ionization (ESI) was used for the mass spectrometry. 18 compounds were identified including Vitexin (1), Schaftoside (2), Vicenin-2 (3), Apigenin-6, 8-di-C-arabinoside (4), Apigenin-7-O-β-d-glucoside (5), Carnosic acid (6), Apigenin-8-C-β-d-xylopyranoside (7), Prostratin (8), Aurantio-obtusin-β-d-glucoside (9), Royleanone (10), 5-hydroxy-7,3',4'-Trimethoxy flavonols (11), 6-Hydroxy-5,6-dehydrosugiol (12), 14-deoxycoleon (13), Arucadiol (14), Obtusinone-B (15), Trehalose (16), Citric acid (17) and Betaine (18). Among these, 6 compounds including (6), (8), (9), (16), (17) and (18) were identified first time within this genus and plant. Study highlights the importance of Premna microphylla Turcz. stem extract for strong therapeutic potential against oxidation-related diseases.


Acid-resistant calcium silicate-based composite implants with high-strength as load-bearing bone graft substitutes and fracture fixation devices.
To achieve the excellent mechanical properties of biodegradable materials used for cortical bone graft substitutes and fracture fixation devices remains a challenge. To this end, the biomimetic calcium silicate/gelatin/chitosan oligosaccharide composite implants were developed, with an aim of achieving high strength, controlled degradation, and superior osteogenic activity. The work focused on the effect of gelatin on mechanical properties of the composites under four different kinds of mechanical stresses including compression, tensile, bending, and impact. The evaluation of in vitro degradability and fatigue at two simulated body fluid (SBF) of pH 7.4 and 5.0 was also performed, in which the pH 5.0 condition simulated clinical conditions caused by bacterial induced local metabolic acidosis or tissue inflammation. In addition, human mesenchymal stem cells (hMSCs) were sued to examine osteogenic activity. Experimental results showed that the appropriate amount of gelatin positively contributed to failure enhancement in compressive and impact modes. The 10wt% gelatin-containing composite exhibits the maximum value of the compressive strength (166.1MPa), which is within the reported compressive strength for cortical bone. The stability of the bone implants was apparently affected by the in vitro fatigue, but not by the initial pH environments (7.4 or 5.0). The gelatin not only greatly enhanced the degradation of the composite when soaked in the dynamic SBF solution, but effectively promoted attachment, proliferation, differentiation, and formation of mineralization of hMSCs. The 10wt%-gelatin composite with high initial strength may be a potential implant candidate for cortical bone repair and fracture fixation applications.


Primary chemoprevention of endometrial hyperplasia with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone in the PTEN heterozygote murine model.
PTEN mutations have been implicated in the development of endometrial hyperplasia and subsequent cancer. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists have demonstrated antineoplastic and chemopreventive effects. The purpose of this study was to evaluate the effects of the PPAR-gamma agonist rosiglitazone on both PTEN wild type and PTEN null cell lines and in the PTEN heterozygote((+/-)) murine model. Hec-1-A (PTEN wild type) and Ishikawa (PTEN null) cells were treated with rosiglitazone. Thirty-five female PTEN(+/-) mice were genotyped and placed into one of four groups for treatment for 18 weeks: A) PTEN wild type with 4 mg/kg rosiglitazone, B) PTEN(+/-) mice with vehicle, C) PTEN(+/-) mice with 4 mg/kg rosiglitazone, and D) PTEN(+/-) mice with 8 mg/kg rosiglitazone. Proliferation and apoptosis were measured by bromodeoxyuridine (BrdU) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of DNA fragmentation sites assay. Rosiglitazone caused cell growth inhibition in both Hec-1-A and Ishikawa in a dose-dependent manner (P < 0.02 and P < 0.03, respectively). Rosiglitazone also induced apoptosis in both Hec-1-A (P < .001) and Ishikawa (P < .001) cells in a dose-dependent manner. In the murine model, rosiglitazone decreased proliferation of the endometrial hyperplastic lesions (B vs C; 39.7% vs 9.3% and B vs D; 39.7% vs 4.2%; P < 0.0001) and increased apoptosis of glandular endometrial epithelial cells (B vs C; 2.8% vs 22.4%; P < 0.0001 and B vs D; 2.8% vs 30.2%; P = 0.003). PPAR-gamma agonist rosiglitazone inhibits proliferation and induces apoptosis in both PTEN intact and PTEN null cancer cell lines and in hyperplastic endometrial lesions in the PTEN(+/)(-)murine model.


Sporadic worldwide "clusters" of feed driven Zilpaterol identifications in racing horses: a review and analysis.
Zilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary "identifications" of Zilpaterol. These "identifications" occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presents in horse urine, yielding clusters of feed related Zilpaterol identifications in racehorses. The first cluster, April 2013, involved 48 racehorses in California; the second cluster, July 2013, involved 15 to 80 racehorses in Hong Kong. The third cluster, March 2019, involved 24 racehorses in Mauritius; this cluster traced to South African feedstuffs, triggering an alert concerning possible Zilpaterol feed contamination in South African racing. The fourth cluster, September/October 2020 involved 18 or so identifications in French racing, reported by the French Laboratories des Courses Hippiques, (LCH), and in July 2021, a fifth cluster of 10 Zilpaterol identifications in South Africa.The regulatory approach to these identifications has been to alert horsemen and feed companies and penalties against horsemen are generally not implemented. Additionally, given their minimal exposure to Zilpaterol, there is little likelihood of Zilpaterol effects on racing performance or adverse health effects for exposed horses.The driving factor in these events is that Zilpaterol is dissolved in molasses for incorporation into cattle feed. Inadvertent incorporation of Zilpaterol containing molasses into horse feed was the source of the California and Hong Kong Zilpaterol identifications. A second factor in the 2019 Mauritius and 2020 French identifications was the sensitivity of testing for Zilpaterol in Mauritius and France, with the French laboratory reportedly testing at a "more sensitive level for Zilpaterol". As of January 1st, 2021, the new FEI Atypical Finding (ATF) policy specifies Zilpaterol as a substance to be treated as an Atypical Finding (ATF), allowing consideration of inadvertent feed contamination in the regulatory evaluation of Zilpaterol identifications.


Surgical management of the patient with bilateral internal carotid artery occlusion.
The patient with bilateral internal carotid artery occlusion is at high risk for development of stroke. Medical management and extracranial-intracranial bypass do not appear to offer these patients any protection from symptoms of cerebrovascular insufficiency. Our initial treatment in 11 of 12 patients who had this pattern of extracranial arterial occlusion has been external carotid artery revascularization. Nineteen procedures were performed for symptomatic lesions in all cases except one. There were no perioperative strokes or deaths. During a mean follow-up of 44.7 months, no new strokes occurred. Among 10 patients undergoing external carotid artery revascularization alone, only one transient ischemic attack occurred in follow-up. Seven of the eight surviving patients are presently asymptomatic. External carotid artery revascularization may be an effective and durable treatment for the patient with bilateral internal carotid artery occlusion.


Simple calculation for compounds lost by gas stripping in a two-phase liquid system involving dilute substances.
Compounds lost by gas stripping from a two-phase liquid system can be deduced from the slope of the logarithmic plot of the residual concentration in a given layer against time. This results in straight lines even when thermodynamic equilibrium is not reached, provided all phases belong to the diluted region. Partition coefficients were calculated during 2-heptanone reduction to 2-heptanol by Saccharomyces cerevisiae.


Scena propylea (Druce) (Lepidoptera: Erebidae) an endemic species of Mexico.
A revision of the bibliography, as well as an analysis on the data from the specimen labels of Scena propylea (Druce) (Erebidae: Arctiinae: Euchromiina) deposited in different scientific collections, was carried out and included information from 1894 to 2010. Its geographical distribution is restricted to the Trans-Mexican Volcanic Belt which determines this species as endemic. Data are provided on the biogeography, ecology and biology for this species. Its food plant is Thenardia floribunda (Apocynaceae) which is also endemic to Mexico. From this analysis, we propose the inclusion of both species in the document known as the Norma Oficial Mexicana 059 which encompasses the environmental protection of wild flora and fauna species native to Mexico and their risk categories, as well as the specifications for their inclusion, exclusion or change and a list of all species at risk.


Effect and cost-effectiveness of national gastric cancer screening in Japan: a microsimulation modeling study.
A national endoscopic screening program for gastric cancer was rolled out in Japan in 2015. We used a microsimulation model to estimate the cost-effectiveness of current screening guidelines and alternative screening strategies in Japan. We developed a microsimulation model that simulated a virtual population corresponding to the Japanese population in risk factor profile and life expectancy. We evaluated 15 endoscopic screening scenarios with various starting ages, stopping ages, and screening intervals. The primary outcomes were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio. Cost-effective screening strategies were determined using a willingness-to-pay threshold of $50,000 per QALY gained. One-way sensitivity and probabilistic sensitivity analyses were done to explore model uncertainty. Using the threshold of $50,000 per QALY, a triennial screening program for individuals aged 50 to 75 years was the cost-effective strategy, with an incremental cost-effectiveness ratio of $45,665. Compared with no endoscopic screening, this strategy is predicted to prevent 63% of gastric cancer mortality and confer 27.2 QALYs gained per 1000 individuals over a lifetime period. Current screening guidelines were not on the cost-effectiveness efficient frontier. The results were robust on one-way sensitivity analyses and probabilistic sensitivity analysis. This modeling study suggests that the endoscopic screening program in Japan would be cost-effective when implemented between age 50 and 75 years, with the screening repeated every 3 years. These findings underscore the need for further evaluation of the current gastric cancer screening recommendations.


Mutations in genes encoding cardiac ion channels previously associated with sudden infant death syndrome (SIDS) are present with high frequency in new exome data.
Sudden infant death syndrome (SIDS) is the leading cause of death in the first 6 months after birth in the industrialized world. The genetic contribution to SIDS has been investigated intensively and to date, 14 cardiac channelopathy genes have been associated with SIDS. Newly published data from National Heart, Lung, and Blood Institute Grand Opportunity (NHLBI GO) Exome Sequencing Project (ESP) provided important knowledge on genetic variation in the background population. Our aim was to identify all variants previously associated with SIDS in ESP to improve the discrimination between plausible disease-causing mutations and variants most likely to be false-positive. The PubMed database was searched to identify SIDS-associated channelopathy variants and the prevalence of these in the ESP population (6500 individuals) were obtained. In silico prediction tools were applied to variants present in ESP and 6 SIDS-associated variants (CAV3 p.C72W, p.T78M; KCNH2 p.R148W, and SCN5A p.S216L, p.V1951L, p.F2004L) were genotyped in our own control population. Nineteen different missense variants previously associated with SIDS were identified in ESP affecting 225 of 6424 alleles. This corresponds to 1:29 individuals in the ESP population being carriers of a SIDS-associated variant. Genotyping of 6 SIDS-associated variants in our own controls revealed frequencies comparable with those found in ESP. A very high prevalence of previously SIDS-associated variants was identified in exome data from population studies. Our findings indicate that the suggested disease-causing role of some of these variants is questionable. A cautious interpretation of these variants must be made when found in SIDS victims.


Structure and dynamics of the nucleocapsid-binding domain of the Sendai virus phosphoprotein in solution.
The RNA-dependent RNA polymerase of the Sendai virus (SeV) consists of the large protein (L) and the phosphoprotein (P). P plays a crucial role in the enzyme by positioning L (which carries the polymerase activity) onto the matrix for transcription and replication formed by the RNA and the nucleoprotein, the N-RNA. P has a modular structure with distinct functional domains: an N-terminal domain involved in binding to N degrees (N that is not yet bound to RNA) and a C-terminal domain that carries the oligomerisation domain, the N-RNA binding domain and the L binding domain and that, combined with L, is active in transcription. Structural data have previously been obtained on the N-terminal domain and on the oligomerisation domain of P, but not yet on its N-RNA binding domain (also-called the X protein). Here we present an NMR and a small angle neutron scattering study of the SeV X protein. We show that this molecule presents two subdomains linked by an 11-residue linker, with the N-subdomain lacking a well-defined conformation. The 3D structure of the C-subdomain consists of three alpha-helices revealing an asymmetric charge distribution that may be important for binding to RNA-bound nucleoprotein. The structure of the entire C-terminal domain of P is modelled from its constituent parts in combination with small angle scattering data on this domain.


Destruction of the Kondo effect in the cubic heavy-fermion compound Ce3Pd20Si6.
How ground states of quantum matter transform between one another reveals deep insights into the mechanisms stabilizing them. Correspondingly, quantum phase transitions are explored in numerous materials classes, with heavy-fermion compounds being among the most prominent ones. Recent studies in an anisotropic heavy-fermion compound have shown that different types of transitions are induced by variations of chemical or external pressure, raising the question of the extent to which heavy-fermion quantum criticality is universal. To make progress, it is essential to broaden both the materials basis and the microscopic parameter variety. Here, we identify a cubic heavy-fermion material as exhibiting a field-induced quantum phase transition, and show how the material can be used to explore one extreme of the dimensionality axis. The transition between two different ordered phases is accompanied by an abrupt change of Fermi surface, reminiscent of what happens across the field-induced antiferromagnetic to paramagnetic transition in the anisotropic YbRh2Si2. This finding leads to a materials-based global phase diagram--a precondition for a unified theoretical description.


Superoxide dismutase and catalase failed to improve neurologic outcome after complete cerebral ischemia in the dog.
Superoxide dismutase (SOD) and catalase, natural scavengers of free oxygen radicals, or saline were administered as a continuous systemic infusion to 12 dogs, in a blind randomized fashion, starting 10 min prior to a 10-min episode of complete cerebral ischemia, and continued thereafter for 60 min. Reversible complete cerebral ischemia was achieved by simultaneously occluding the ascending aorta and venae cavae. There were no significant differences in physiological variables (arterial blood gases, hemoglobin, mean arterial blood pressure, heart rate, and temperature) between the two groups, either pre-ischemia or post-ischemia. There was no significant difference in neurologic outcome when evaluated at 48 h post-ischemia. It has previously been reported that the same dose of SOD and catalase as used in the current study could reduce infarct size by 50% when given systemically before reperfusion following coronary ischemia in dogs. The lack of a measurable effect on neurologic outcome in our cerebral ischemic model might be because of the failure of the free oxygen radical scavengers to reach the ischemic cells in sufficient amounts, or because free oxygen radicals do not contribute to brain injury following complete cerebral ischemia.


Adjuvant chemotherapy benefits on patients with elevated carcinoembryonic antigen in stage IIA colon cancer: a SEER-based analysis.
Indications for adjuvant chemotherapy in stage IIA (T3N0M0) colon cancer are still controversial. The purpose of this study was to evaluate the prognostic value of elevated carcinoembryonic antigen (CEA) levels for cancer-specific survival (CSS) and overall survival (OS) in patients with stage IIA colon cancer. We aimed to examine the impact of adjuvant chemotherapy on OS in stage IIA colon cancer patients with elevated CEA levels. Patients with stage IIA colon cancer (N = 3477) diagnosed between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier and Cox proportional hazards regression models were used to assess the prognostic effect of CEA on CSS and OS. Cox regression analysis demonstrated that CEA was an independent risk factor for CSS and OS in patients with stage IIA colon cancer (CSS: HR = 2.001, 95% CI 1.603-2.499, P < 0.001; OS: HR = 1.530, 95% CI 1.335-1.752, P < 0.001). In the subgroup with elevated CEA, patients received adjuvant chemotherapy had a better OS compared with those did not (χ2 = 10.585, p = 0.001). CEA was an independent risk factor for CSS and OS in patients with stage IIA colon cancer. Patients with stage IIA colon cancer with an elevated CEA level might benefit from adjuvant chemotherapy.


Recombinant group B Streptococcus alpha-like protein 3 is an effective immunogen and carrier protein.
Conjugate vaccines against pathogens of multiple serotypes are optimized when all components induce functional antibody, resulting in broadened coverage. While most clinical studies of vaccines against group B Streptococcus (GBS) have evaluated conjugates composed of capsular polysaccharide (CPS) coupled to tetanus toxoid, conjugates prepared with GBS proteins as carriers have also been efficacious in animals. Here, we report that recombinant GBS alpha-like protein 3 (rAlp3) is both a strong immunogen and a viable carrier protein for type III CPS. The type III CPS-specific immunoglobulin G (IgG) titer rose from <100 to 64,000 among mice that received type III CPS coupled to rAlp3 (III-rAlp3) compared with an absence of a specific response among mice that received an uncoupled mixture. Most (94%) newborn pups born to III-rAlp-vaccinated dams survived challenge with viable type III GBS, compared with 43% survival among those born to dams that received the uncoupled mixture (P < 0.0001). A tricomponent conjugate of type III CPS, rAlp3, and a GBS recombinant beta C protein lacking its IgA binding site (III-rAlp3-rBCP(DeltaIgA)) provided protection against a serotype III strain and a serotype Ia strain bearing beta C protein. High-titered anti-rAlp3 rabbit serum opsonized Alp3-containing strains of two GBS serotypes (types V and VIII) and invasive type III strains bearing the cross-reactive Rib protein for in vitro killing by human peripheral blood leukocytes. Thus, the potential exists for the inclusion of rAlp3 in a GBS vaccine formulated to provide multiserotype coverage.


Chemical Tailoring of β-Cyclodextrin-Graphene Oxide for Enhanced Per- and Polyfluoroalkyl Substances (PFAS) Adsorption from Drinking Water.
We report on the synthesis of β-cyclodextrin (βCD) modified graphene oxide (GO) nanosheets, having different sized alkyl linkers (GO-Cn -βCD) and their exploitation as sorbent of per- and polyfluoroalkyl substances (PFAS) from drinking water. βCD were functionalized with a pending amino group, and the resulting precursors grafted to GO nanosheets by epoxide ring opening reaction. Loading of βCD units in the range 12 %-36 % was estimated by combined XPS and elemental analysis. Adsorption tests on perfluorobutanoic acid (PFBA), a particularly persistent PFAS selected as case study, revealed a strong influence of the alkyl linker length on the adsorption efficiency, with the hexyl linker derivative GO-C6 -βCD outperforming both pristine GO and granular activated carbon (GAC), the standard sorbent benchmark. Molecular dynamic simulations ascribed this evidence to the favorable orientation of the βCD unit on the surface of GO which enables a strong contaminant molecules retention.


Postoperative hyponatremia predicts an increase in mortality and in-hospital complications after cardiac surgery.
The association between postoperative hyponatremia (Na < 135 mEq/L) and outcomes after cardiac surgery has not been established. We studied the prevalence of postoperative hyponatremia and its effects on outcomes after cardiac surgery. We studied 4,850 patients who underwent cardiac surgery from 2002 to 2008. We used multivariable logistic and Cox regression analysis to study the association between postoperative hyponatremia and mortality, length of hospital stay (LOS), and complications. Postoperative hyponatremia was present in 59%. Hyponatremic patients were older (mean ± SD, 62 ± 13 vs 61 ± 14 years, p = 0.001), had lower left ventricle ejection fraction (mean ± SD, 44% ± 16% vs 48% ± 13%, p < 0.001), higher mean pulmonary artery pressures (mean ± SD, 30 ± 11 vs 27 ± 9 mmHg, p < 0.001), lower glomerular filtration rate (mean ± SD, 72 ± 29 vs 74 ± 27 mg/min/1.73 m(2), p = 0.01), higher EuroSCORE (median, 15% vs 6%, p < 0.001), higher New York Heart Association class IV (31% vs 26%, p = 0.002), prevalence of COPD (23% vs 14%, p < 0.001), and peripheral vascular disease (16% vs 12%, p < 0.001). Hyponatremia increased overall (24% vs 18.2%, p < 0.001) and late mortality (18.6% vs 13.9%, p < 0.001) and length of stay (LOS; 11 vs 7 days, p < 0.001). Mortality increased with the severity of the hyponatremia. After adjusting for baseline and procedure variables, postoperative hyponatremia was associated with increase in mortality (hazard ratio 1.22, 95% CI 1.06-1.4, p = 0.004), LOS (multiplier 1.34, 95% CI 1.22-1.49, p < 0.001), infectious (odds ratio [OR] 2.32, 95% CI 1.48-3.62, p < 0.001), pulmonary (OR 1.82, 95% CI 1.49-2.21, p < 0.001), and renal failure complications (OR 2.46, 95% CI 1.58-3.81, p < 0.001) and need for dialysis (OR 3.66, 95% CI 1.72-7.79, p = 0.001). Hyponatremia is common after cardiac surgery and is an independent predictor of increased mortality, length of hospital stay, and postoperative complications.


A new radiopharmaceutical for gallbladder studies: 99mTc-Sn-LIDA complex.
A simple method for the preparation of 99mTc-Sn-LIDA complex is described. Organ distribution and blood clearance studies in animals are reported. This complex has also been used successfully in more than 50 patients for assessing gallbladder function.


Magnitude of dental caries, missing and filled teeth in Malawi: National Oral Health Survey.
Oral health problems are significant cause of morbidity particularly in sub-Saharan Africa. In Malawi, routine health management information system data over the years showed that oral health problems were one of the top ten reasons for outpatient attendance. However, to date, no national oral survey has been carried out to determine the prevalence of oral health problems. A national population-based cross-sectional survey was conducted in 2013. A total of 130 enumeration areas (EAs) were randomly selected and from each EA, 40 participants were randomly selected as per WHO STEPS survey protocol. Eligible participants were 12, 15, 35-44 and 65-74 year old. A multi-stage sampling design was used to obtain a national representative sample of these age groups. Oral examination was based on WHO diagnostic criteria (2010). A total of 5400 participants were enrolled in the survey. Of these: 3304 (61.3 %) were females, 2090 (38.7 %) were males; 327 (6.9 %) were from urban and 4386 (93.1 %) from rural areas; 1115 (20.6 %), 993 (17.3 %), 2306 (42.7 %) and 683 (12.6 %) were aged 12, 15, 35-44, 65-74 years respectively. Among 12 year-old, 15 year-old, 35-44 and 65-74 year age groups, prevalence of dental caries was 19.1, 21.9, 49.0 and 49.2 % respectively, overall 37.4 %. Prevalence of missing teeth was 2.7, 5.2, 47.7 and 79.9 %, overall 35.2 %. Prevalence of filled teeth was 0.2 %, 1.3 %, 8.7 %, 12.7 %, overall 6.5 %. Prevalence of bleeding gums was 13.0, 11.8, 30.8 and 36.1 %, overall 23.5 %. Toothache, dental caries and missing teeth were more common in females than males; 46.5 % vs 37.9 %, 40.5 % vs 32.4 %, 37.7 % vs 30.1 % respectively, all p < 0.05. Prevalence of dental caries and missing teeth in urban areas were as high as in the rural areas; 33.3 % vs 37.4 % and 30.9 % vs 33.7 % respectively, all p > 0.05. The mean number of decayed, missing and filled teeth (DMFT) in 12, 15, 35-44, 65-74 year old was 0.67, 0.71, 3.11 and 6.87 respectively. Self- reported brushing of teeth was poor with only 35.2 % of people brushed their teeth twice a day and tobacco smoking was high, particularly among adult males where one in five (22.9 %) was a smoker. This study demonstrated that oral health problems are major public health problems in Malawi. One in five (21 %) adolescents aged 12-15 years and half (49 %) of adults aged 35 years or more had dental caries, half (48 %) and 80 % of the population aged 35-44, 65-74 years had missing teeth respectively. Toothache, dental caries and missing teeth were more prevalent in females than males and prevalence in urban was as high as in rural areas. Oral hygiene was poor with less than 40 % of the population brush their teeth twice a day and tobacco smoking was high, particularly in men where prevalence was 23 %. These findings could be used to develop evidence-informed national policy, action and resource mobilization plan and community based interventions to reduce the prevalence of oral health problems in Malawi.


Effects of particulate matter exposure during pregnancy on birth weight: A retrospective cohort study in Suzhou, China.
Recent studies have identified that exposure to particulate matter during pregnancy could result in adverse birth outcomes, but the effects of exposure at trimester-specific intervals are inconsistent. Our primary goal was to investigate whether particulate matter exposure during pregnancy could affect birth weight and gestational age of neonates. A retrospective cohort study was conducted to examine the relationship between maternal particulate matter exposure and neonatal birth weight. We collected 14,455 births records linked to hospital admission records (delivery and antenatal) from January 2013 to December 2015 in Suzhou Municipal Hospital. Air monitoring data in the same timeframe were also collected from Suzhou Environmental Protection Agency. The risk of low birth weight due to the exposure to PM2.5 (with median aerodynamic diameter≤2.5μm) and PM10 (with median aerodynamic diameter≤10μm) at each trimester and throughout the entire pregnancy were assessed. Linear regression models were applied and potential confounding factors were adjusted for data analysis. Gestational age, which was another important birth outcome, and its association with maternal particulate matter exposure were also studied. The final analysis included 10,915 singleton live births. Using multiple linear regression models, we found that gestational exposure to PM2.5 and PM10 at 10μg/m3 increments in the second trimester led to decreases in birth weight of 4.94g (95% confidence interval: -9.828, -0.046) and 5.65g (95% confidence interval: -10.110, -1.188), respectively. However, gestational age was not significantly associated with maternal particulate matter exposure in term neonates. These findings indicate that pregnant women might be more susceptible to particulate matter during the second trimester which may lead to decreased neonatal birth weight.


fMRI functional connectivity as an indicator of interictal epileptic discharges.
To explore the relationship between functional connectivity and presence of interictal epileptic discharges (IEDs) in different brain regions in intracranial EEG (iEEG). We studied 38 focal epilepsy patients who underwent simultaneous EEG/fMRI scanning and subsequent intracerebral stereo-EEG investigation. In EEG/fMRI analysis, IEDs with different spatial distributions were considered independent studies and IED-related maximal BOLD responses were evaluated. Studies with iEEG electrodes inside the maximal responses were selected and divided into three groups: Studies with 1. distinct maximal BOLD highly concordant with seizure-onset-zone (SOZ); 2. Moderate maximal BOLD concordant with SOZ; 3. maximal BOLD discordant with SOZ. Using maximal BOLD as seed, its functionally connected zone (FCZ) was determined. IED rates in iEEG channels inside and outside the FCZ were compared in the three groups. The effect of laterality and distance between channels and maximal BOLD, and correlation between functional connectivity values and IED rates were analyzed. Thirty-six studies in 25 patients were included. IED rates of intracranial EEG channels inside the FCZ were significantly higher than outside in Group 1 (p = 2.6×10-6) and Group 2 (p = 1.2×10-3) and the inside-outside difference remained after regressing distance and laterality factors. In Group 1, connectivity values were significantly correlated with IED rates in channels inside the FCZ (p < 0.05). Our results indicate a higher probability of finding intracranial IEDs in the FCZ of SOZ-concordant maximal BOLD responses than in other regions, regardless of distance and laterality. In studies with distinct maximal BOLD, connectivity values can partially predict IED rates in intracranial EEG. It is thus feasible to non-invasively delineate brain regions that are likely to have high IED rates.


Direct generation of a 10 GHz 816 fs pulse train from an erbium-fiber soliton laser with asynchronous phase modulation.
By employing the technique of asynchronous mode locking, we have successfully demonstrated direct generation of stable 10 GHz 816 fs pulse trains with a supermode-suppression ratio >70 dB from a hybrid mode-locked Er-fiber laser. When the modulation frequency deviates from the cavity harmonic frequency by 15-40 kHz, stable femtosecond soliton pulses are formed. Our results demonstrate that asynchronous mode locking can act as an effective mechanism for achieving a shorter pulse width and for stabilizing high-repetition-rate pulse trains in soliton fiber lasers.


ARDS after accidental inhalation of zinc chloride smoke.
Five soldiers were injured by inhalation of hexite smoke (ZnCl2) during military training. Two soldiers, not wearing gas masks breathed hexite for 1 or 2 min, they slowly developed severe adult respiratory distress syndrome (ARDS) over the ensuing 2 weeks. This slow, progressive clinical course has not been previously described. In both patients, an increased plasma zinc concentration was measured 3 weeks after the incident. Intravenous and nebulized acetylcysteine increased the urinary excretion of zinc, and briefly decreased the plasma levels. In an attempt to arrest collagen deposition in the lungs, L-3,4 dehydroproline was administered. Both patients died of severe respiratory failure (25 and 32 days after inhalation). At autopsy diffuse microvascular obliteration, widespread occlusion of the pulmonary arteries and extensive interstitial and intra-alveolar fibrosis was observed. Three soldiers wearing ill fitting gas masks, immediately developed severe coughing and dyspnea. They improved, and 12 months after exposure their lung function tests were nearly normal, but they still had slight dyspnea on exercise.


Purification and analysis of variant and modified histones using 2D PAGE.
Two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) systems employing combinations of acetic acid/urea (AU), acetic acid/urea/Triton X-100 (AUT) and sodium dodecyl sulfate (SDS) gel formulations are uniquely effective for resolution of histone variants and their modified derivatives. Coupled with Western transfer methods using modification-specific antibodies and recent advances in mass spectrometry, 2D PAGE emerges as a versatile tool for histone purification and analysis. This chapter describes 2D PAGE gel systems appropriate for histone proteins, including detailed procedures for designing, running, and staining gels. Methods for electrophoretic transfer of histones from AUTxSDS and AUTxAU 2D gels are described and evaluated. Alternatively, methods are provided for obtaining highly purified protein samples from fixed and stained gels via electroelution of proteins from specific gel spots.


Spirostane-type saponins from Dracaena fragrans "Yellow Coast".
Three steroidal glycosides were isolated from the bark of Dracaena fragrans (L.) Ker Gawl. "Yellow Coast", and a fourth from the roots and the leaves. Their structures were characterized on the basis of extensive 1D and 2D NMR experiments and mass spectrometry, and by comparison with NMR data of the literature. These saponins have the spirostane-type skeleton and are reported in this species for the first time.


Understanding of blood pressure and behavioural risk factors amongst British adolescents.
To survey students aged 16-18 years in secondary education establishments in one school district in the south of England in order to: assess knowledge about the importance of blood pressure (BP) for health; investigate associations between knowledge and health-related behaviours; and explore home, school and health service influences on knowledge. Observational. Self-reported data from a structured questionnaire administered to convenience samples of students in schools were analysed by Chi-squared tests and multiple linear regression. The questionnaire assessed knowledge about BP risks, symptoms, consequences and measurement, and collected information on BP-related instruction, health behaviours (smoking, exercise, alcohol and nutrition) and family background. A cross-section of 569 students completed questionnaires, representing 19.6% of the total age cohort. Most students recognized the major behavioural risks and consequences of high BP, but 104 (18.3%) could not describe how BP is measured, and 401 (88.1%) had no idea what a normal BP reading should be. In multivariate analysis, BP knowledge was associated with previous academic attainment, having received advice or instruction about BP, and having BP measured in the last 2 years. Family experience was not significant. Many students reported unhealthy behaviours: current smoker (n = 87, 15.3%); less than three exercise sessions per week (n = 172, 30.2%); and two portions or less of fruit/vegetables per day (n = 223, 39.2%). BP knowledge was significantly associated with regular exercise but not with other health-promoting behaviours. One hundred and twenty-one (21.3%) students acknowledged having received instruction about BP, mainly from doctors/nurses (32%) and schools (28%). Gaps in adolescents' knowledge about BP were identified. Greater awareness was associated with having received formal advice and instruction, so health services and schools could play an important part in improving BP knowledge among adolescents. More understanding of cumulative risks may encourage fuller engagement in health-promoting activities.


The Effects of Amniotic Membrane Transplantation on Vocal Fold Regeneration.
Vocal fold (VF) scar and sulcus cause severe vocal problems, but optimal methods have not been established. Total replacement of the mucosa is required particularly for cases in which the whole lamina propria is occupied by severe fibrosis and vibratory function is totally lost. The amniotic membrane (AM) has been proven to have regenerative potential, as it contains stem cells and growth factors. The current study investigated the biocompatibility and effects of AM for regeneration of the VF mucosa. In vitro and in vivo studies. Vocal fold fibroblasts (VFFs) from 13 Sprague-Dawley rats were seeded on AM and subjected to histology and immunohistochemistry, and gene expressions in the VFFs on AM were examined in in vitro study. Twelve New Zealand White rabbits were used in in vivo study. VFs were stripped down and were reconstructed with AM. The regenerative effects were examined 3 months later by histological examination. In vitro study indicated VFFs survived on AM and stained positively for Ki67, vimentin, and fibronectin. Gene expressions of Has1, Has2, and Hgf were significantly increased in the VFFs on AM compared with the other groups. The in vivo study indicated AM-transplanted VFs showed a significantly higher density of hyaluronic acid and lower density of collagen compared with sham VFs. The current preliminary study suggests biocompatibility and possible regenerative effects of AM for VFs. NA Laryngoscope, 132:2017-2025, 2022.


The effect of graded doses of secretin on serum trypsin, serum pancreatic amylase, serum insulin, plasma somatostatin, and plasma pancreatic polypeptide in man.
Six healthy men were studied with intravenous infusions of 0.3, 1.0, and 3.0 CU/kg-h of pure porcine secretin on separate days. The secretin elimination followed a first-order kinetics. Low pharmacological doses of secretin had no significant effects on blood levels of trypsin, pancreatic amylase, insulin, somatostatin, or pancreatic polypeptide (PP), whereas high pharmacological doses significantly elevated the blood levels of trypsin, pancreatic amylase, insulin, and somatostatin but were without effect on PP.


Monitoring healthy metabolic trajectories with nutritional metabonomics.
Metabonomics is a well established analytical approach for the analysis of physiological regulatory processes via the metabolic profiling of biofluids and tissues in living organisms. Its potential is fully exploited in the field of "nutrimetabonomics" that aims at assessing the metabolic effects of active ingredients and foods in individuals. Yet, one of the greatest challenges in nutrition research is to decipher the critical interactions between mammalian organisms and environmental factors, including the gut microbiota. "Nutrimetabonomics" is today foreseen as a powerful approach for future nutritional programs tailored at health maintenance and disease prevention.


Determination of thyreostat residues from bovine matrices using high-performance liquid chromatography.
High-performance liquid chromatography (HPLC) methodologies were evaluated for the detection and quantification of thyreostatic drug residues in cattle serum and thyroid tissue. The paper details a protocol, using a simple ethyl acetate extraction for the determination of thiouracil, tapazole, methyl thiouracil, propyl thiouracil and phenyl thiouracil in thyroid tissue. Using two sequential HPLC injections, and quantitative analysis, in two steps, all five thyreostats were detectable at concentrations greater than 2.45-4.52 ng/g. Modifications to a published method for detection of thyreostatic residues in serum involving the addition of mercaptoethanol and a freezing step are described. The modifications improved sensitivity and allowed detection of the five thyreostats at levels greater than 16.98-35.25 ng/ml. Young bulls were treated with thyreostats to demonstrate the validity of the methodologies described. Administered thyreostats were not absorbed equally by the test animals and the compounds were not all detected in the serum samples removed at 7 days following drug withdrawal. These experiments indicate the necessity to be able to detect thyreostat residues in a variety of matrices.


Professionals' perceptions of the establishment of a specialized brief therapy unit in a district psychiatric centre - a qualitative study.
Increasing mental health problems and scarce treatment resources put pressure on mental health services to make innovations in service provision, such as developing differentiated services adapted to different needs. One innovation in differentiated service provision is brief or short-term treatment to patients with moderate mental health problems. Implementing a new unit in an organization usually faces many potential barriers and facilitators, and knowledge on how the professionals providing the services perceive the implementation of innovative approaches in mental health services is scarce. The aim of this study was therefore to explore the professionals' perceptions of how the establishment of a specialized brief therapy unit had affected the organization, especially the everyday work in the outpatient clinics. Eleven professionals, five men and six women, took part in individual interviews. All participants were between 40 and 60 years old and had leading or coordinating positions in the organization. Their professional backgrounds were within psychology, nursing and medicine, most of them specialists in their field. Data was analyzed according to Systematic text condensation. The professionals' experiences represented four main themes: (1) The brief therapy unit was perceived as successful and celebrated. (2) The general outpatient clinics, on the other hand, were described as "forgotten". (3) The establishment process had elucidated different views on treatment in the outpatient clinics - and had set off (4) a discussion regarding the criteria for prioritizing in mental health services. Providing targeted treatment to patients with moderate mental health problems, while having a concurrent aim to solve broader problems in mental health services, entails a discussion regarding resource use and the appropriate level of treatment provision. Professionals should be more involved when innovative efforts are implemented, and the criteria for success must be conceptualized and evaluated. Longitudinal research on the implementation of innovative efforts in the services should include professionals' and service users' perspectives.


Molecular modeling and dynamics studies of cytidylate kinase from Mycobacterium tuberculosis H37Rv.
Bacterial cytidylate kinase or cytidine monophosphate kinase (CMP kinase) catalyses the phosphoryl transfer from ATP to CMP and dCMP, resulting in the formation nucleoside diphosphates. In eukaryotes, CMP/UMP kinase catalyses the conversion of UMP and CMP to, respectively, UDP and CDP with high efficiency. This work describes for the first time a model of bacterial cytidylate kinase or cytidine monophosphate kinase (CMP kinase) from mycobacterium tuberculosis (MtCMPK). We modeled MtPCMPK in apo form and in complex with cytidine 5'-monophosphate (CMP) to try to determine the structural basis for specificity. Comparative analysis of the model of MtCMPK allowed identification of structural features responsible for ligand affinities. Analysis of the molecular dynamics simulations of these two systems indicates the structural features responsible for the stability of the structure, and may help in the identification of new inhibitors for this enzyme.


Regulation of the release of cholecystokinin by bile salts in dogs and humans.
The objective of these studies was to investigate the role of bile salts in the regulation of release of cholecystokinin in response to nutrients in dogs and humans. In dogs, the intraduodenal administration of a bile salt sequestrant, cholestyramine (2, 4, or 8 g/h), resulted in a dose-related enhancement of the release of cholecystokinin-33/39 and pancreatic protein secretion in response to intraduodenal administration of amino acids. Intraduodenal administration of cholestyramine alone did not affect basal levels of cholecystokinin-33/39 or pancreatic protein secretion. Total diversion of bile also significantly increased the release of cholecystokinin and pancreatic protein secretion in response to intraduodenal administration of amino acids. Replacement of the bile salt pool by intraduodenal administration of taurocholate completely reversed the enhancement effect of both cholestyramine and bile diversion. In humans, oral ingestion of cholestyramine (12 g) significantly increased the release of cholecystokinin-33/39 and gallbladder contraction in response to the oral ingestion of either a triglyceride or amino acids. These results support a physiologic role of bile salts in the negative feedback regulation of release of cholecystokinin in response to luminal nutrients.


Sitagliptin ameliorates busulfan-induced pulmonary and testicular injury in rats through antioxidant, anti-inflammatory, antifibrotic, and antiapoptotic effects.
Busulfan (BUS) is an anticancer agent with serious adverse effects on various body organs, including the lung and testis. Sitagliptin was proven to have antioxidant, anti-inflammatory, antifibrotic, and antiapoptotic effects. This study aims to evaluate whether sitagliptin, a DPP4I, ameliorates BUS-induced pulmonary and testicular injury in rats. Male Wistar rats were split into control, sitagliptin (10 mg/kg), BUS (30 mg/kg), and sitagliptin + BUS groups. Weight change, lung and testis indices, serum testosterone, sperm parameters, markers of oxidative stress [malondialdehyde (MDA) and reduced glutathione (GSH)], inflammation [tumor necrosis factor-alpha (TNF-α)], and relative expression of sirtuin1 (SIRT1) and forkhead box protein type O1 (FOXO1) genes were estimated. Histopathological examination of lung and testicular tissues was done to detect architectural changes [Hematoxylin & Eosin (H&E)], fibrosis (Masson's trichrome), and apoptosis (caspase-3). Sitagliptin treatment reduced body weight loss, lung index, lung and testis MDA, serum TNF-α and sperm abnormal morphology, and increased testis index, lung and testis GSH, serum testosterone, sperm count, viability and motility. SIRT1/FOXO1 balance was restored. Also, sitagliptin attenuated fibrosis and apoptosis in lung and testicular tissues via reducing collagen deposition and caspase-3 expression. Accordingly, sitagliptin ameliorated BUS-induced pulmonary and testicular damage in rats via attenuating oxidative stress, inflammation, fibrosis, and apoptosis.


Biologically Active Compounds from Goji (Lycium Barbarum L.) Leaves Aqueous Extracts: Purification and Concentration by Membrane Processes.
Goji (Lycium barbarum L.) leaves and fruits have been described as a valuable source of bioactive compounds with a great potential for the development of health-promoting formulations. The present study aimed to evaluate the potential of a sustainable process for the recovery of phenolic compounds from Goji leaves through a combination of aqueous extraction and membrane-based operations. Water was used as a safe, cheap, and non-hazardous extraction solvent, and parameters of extraction of dried Goji leaves were optimized in order to maximize the yield of polyphenols, total soluble solids (TSS), and total antioxidants simultaneously. The aqueous extract was clarified by ultrafiltration and then processed with three flat-sheet polyethersulphone (PES) membranes with molecular weight cut-off (MWCO) values in the range of 0.3-4.0 kDa, in order to remove sugar compounds from polyphenols and improve the antioxidant activity of the produced fractions. Among the selected membranes, a 1 kDa membrane exhibited the best performance in terms of purification of polyphenols from the clarified aqueous extract. The rejection by this membrane of TSS and total carbohydrates was in the range of 15.8-25.3%, and was decreased by increasing the volume reduction factor (VRF). On the other hand, the retention values for total polyphenols and total antioxidant activity (TAA) were in the range of 73-80%, and were increased by increasing the VRF.


The role of lignin as a defence against the spruce bark beetle Dendroctonus micans: effect on larvae and adults.
The role of lignin as a physical defence against Dendroctonus micans was investigated in laboratory feeding experiments. The effect of lignin is dose-dependent, reducing larval survival, growth rate, and weight, as well as affecting gallery construction. Adults lay fewer eggs in lignified bark and also tend to construct abnormal galleries. The distribution of lignin in trees suggests a role in defence against bark beetles that feed in the thicker bark on the lower bole.