Cell-mediated immune response of ragweed-sensitive patients to ragweed antigen E. In vitro lymphocyte transformation and elaboration of lymphocyte mediators.
The in vivo and in vitro responses to ragweed antigen E were evaluated in 28 untreated atopic patients with ragweed hayfever. The methods employed included direct skin testing, measurement of total serum IgE, measurement of specific IgE anti-ragweed antibodies, leukocyte histamine release, lymphocyte transformation, and release of lymphocyte mediators (migration inhibitory factor and mitogenic factor). The patients could be divided into sensitive and insensitive groups on the basis of their in vitro reactivity to antigen E. 20 patients in the sensitive group had statistically higher levels of total serum IgE, higher levels of specific IgE anti-ragweed antibodies, and greater leukocyte sensitivity as measured by antigen-induced histamine release than did eight patients in the insensitive group. Lymphocytes from sensitive patients produced greater amounts of migration inhibitory factor and mitogenic factor when challenged by antigen E than did lymphocytes from insensitive patients. A possible role for the lymphocyte in this allergic disease is discussed. The results of this study indicate that the immune response to ragweed antigen is complex and involves components of both immediate and delayed hypersensitivity.


Nivolumab for the treatment of hepatocellular carcinoma.
T-cell checkpoint inhibition as a cancer treatment approach has been the main breakthrough in cancer treatment during the last years. Since the approval of the first commercial CTLA-4 antibody ipilimumab in 2011 for the treatment of melanoma, research and drug development in this field has accelerated massively. In 2014, the US Food and Drug Administration (FDA) approved the first PD-1 targeting agent, namely pembrolizumab, shortly followed by nivolumab. Areas covered: Nivolumab is a fully human immunoglobulin G4 anti-PD-1 monoclonal antibody which is approved for multiple advanced malignancies, including melanoma, non-small cell lung cancer, renal cell cancer, Hodgkin's lymphoma, squamous head and neck cancer, and urothelial carcinoma. In September 2017, nivolumab was approved by the FDA for liver cancer as a second line treatment after failure of sorafenib based on the data of the multi-cohort phase 1/2 trial CheckMate-040. This article reviews the concept of immunotherapy in liver cancer with focus on nivolumab. Expert commentary: Immunotherapy in hepatocellular carcinoma is safe and is a new treatment option for patients with advanced stage disease besides sorafenib and regorafenib in the US. Randomized phase III trials of nivolumab, pembrolizumab, atezolizumab, durvalumab and tislelizumab as mono- or combination-therapy are ongoing.


Identification of odorant-binding and chemosensory protein genes and the ligand affinity of two of the encoded proteins suggest a complex olfactory perception system in Periplaneta americana.
The American cockroach (Periplaneta americana) is an urban pest with a precise chemosensory system that helps it achieve complex physiological behaviours, including locating food and mating. However, its chemosensory mechanisms have not been well studied. Here, we identified 71 putative odorant carrier protein genes in P. americana, including 57 new odorant-binding proteins (OBPs) and 11 chemosensory proteins (CSPs). To identify their physiological functions, we investigated their tissue expression patterns in antennae, mouthparts, legs, and the remainder of the body of both sexes, and determined that most of these genes were expressed in chemosensory organs. A phylogenetic tree showed that the putative pheromone-binding proteins of P. americana were in different clades from those of moths. Two genes, PameOBP24 and PameCSP7, were expressed equally in antennae of both sexes and highly expressed amongst the OBPs and CSPs. These genes were expressed in Escherichia coli and the resultant proteins were purified. The binding affinities of 74 common odorant compounds were tested with recombinant PameOBP24 and PameCSP7. Both proteins bound a variety of ligands. Our findings provide a foundation for future research into the chemosensory mechanisms of P. americana and help in identifying potential target genes for managing this pest.


Polyarticular tuberculosis in a young boy: a rare presentation.
Polyarticular tuberculosis involving bilateral hip and bilateral knee joints without obvious pulmonary or disseminated form of tuberculosis in a young boy is presented along with literature review.


Dynamically generating T32 training documents using structured data.
The US National Institutes of Health (NIH) funds academic institutions for training doctoral (PhD) students and postdoctoral fellows. These training grants, known as T32 grants, require schools to create, in a particular format, seven or eight Word documents describing the program and its participants. Weill Cornell Medicine aimed to use structured name and citation data to dynamically generate tables, thus saving administrators time. The author's team collected identity and publication metadata from existing systems of record, including our student information system and previous T32 submissions. These data were fed into our ReCiter author disambiguation engine. Well-structured bibliographic metadata, including the rank of the target author, were output and stored in a MySQL database. We then ran a database query that output a Word extensible markup (XML) document according to NIH's specifications. We generated the T32 training document using a query that ties faculty listed on a grant submission with publications that they and their mentees authored, bolding author names as required. Because our source data are well-structured and well-defined, the only parameter needed in the query is a single identifier for the grant itself. The open source code for producing this document is at http://dx.doi.org/10.5281/zenodo.2593545. Manually writing a table for T32 grant submissions is a substantial administrative burden; some documents generated in this manner exceed 150 pages. Provided they have a source for structured identity and publication data, administrators can use the T32 Table Generator to readily output a table.


Redefining the role of psr in beta-lactam resistance and cell autolysis of Enterococcus hirae.
The contribution of penicillin-binding protein 5 (PBP5) and the PBP5 synthesis repressor (Psr) to the beta-lactam resistance, growth, and cell autolysis of wild-type strain ATCC 9790 and resistant strain R40 of Enterococcus hirae was investigated by disruption or substitution of the corresponding pbp5 and psr genes by Campbell-type recombination. The resulting modifications were confirmed by hybridization and PCR. The low susceptibility of E. hirae to beta-lactams was confirmed to be largely dependent on the presence of PBP5. However, against all expectations, inactivation of psr in ATCC 9790 or complementation of R40 cells with psr did not modify the susceptibility to benzylpenicillin or the growth and cell autolysis rates. These results indicated that the psr gene does not seem to be involved in the regulation of PBP5 synthesis and consequently in beta-lactam resistance or in the regulation of cell autolysis in E. hirae.


Significance of ultrasound vaginal cervicometry in predicting preterm delivery.
The objective of the study was to verify whether ultrasound vaginal cervicometry, performed in the 18th-20th week of gestation, can effectively predict preterm delivery. 279 singleton pregnancies were prospectively studied from the middle of gestation until delivery. In the 18th-20th week of gestation we performed ultrasound vaginal cervicometry, which we used to determine the length of the cervix, judge the shape of the internal os, and evaluate the cervicometry as normal or abnormal on the basis of these parameters. With the aid of one-dimensional and multi-dimensional analysis, we tested the dependence of completed weeks of gestation and preterm delivery on the results of ultrasound cervicometry. 247 women completed the study. Cervicometry was evaluated as abnormal in 53 women (21.46%). We proved a significant dependence of delivery prior to the 34th week of gestation on cervical length (p<0.01), abnormal shape of the internal os (p<0.0001; RR=10.35), and abnormal cervicometric result (p<0.0001; RR=29.28). Delivery prior to the 37th week was also significantly dependent on all observed parameters. Of the individual cervicometric parameters, cervical length had the most significant impact on the completed weeks of gestation. The implementation of ultrasound vaginal cervicometry in the prenatal screening program can lead to effective and early selection of women with a significantly increased risk of preterm delivery.


Descriptions of Lutzomyia (Evandromyia) georgii n. sp. and a synopsis of the series infraspinosa (Diptera: Psychodidae).
Lutzomyia georgii n. sp. and the female of L. tarapacaensis in the Series infraspinosa of the subgenus Evandromyia are described, from specimens collected in rainforest in the north of the State of Pará, Brazil. The new species was taken together with five other Evandromyia species including L. infraspinosa (sensu strictu) in the same locality. L. georgii has previously been confused with both L. begonae and L. infraspinosa, whereas L. tarapacaensis would run to L. infraspinosa in recent taxonomic keys. The fact that both L. georgii and L. tarapacaensis are locally sympatric with L. infraspinosa helps to clarify the taxonomic limits of the latter species. New keys to the subgenus Evandromyia are provided.


Active ion transport pathways in the bovine retinal pigment epithelium.
1. Radioactive tracer flux measurements demonstrate that active ion transport across the isolated bovine retinal pigment epithelium (RPE)-choroid preparation can be maintained for hours after the eye is enucleated and the tissue removed from the eye. 2. It has been shown that 86Rb tracer fluxes can be used to monitor potassium (K+) transport across bull-frog RPE. In bovine RPE, net 86Rb (K+) absorption is zero. Apical barium (Ba2+) elevated active K+ absorption from zero to approximately 0.3 mu equiv cm-2 h-1. This Ba2(+)-induced increase in active K+ absorption was inhibited either by ouabain or bumetanide in the apical bath. 3. In control Ringer solution, buffered with bicarbonate and CO2, the RPE-choroid actively absorbs chloride (Cl-) at a rate of approximately 0.5 mu equiv cm-2 h-1. In contrast, sodium (Na+) is secreted at a rate of approximately 0.5 mu equiv cm-2 h-1. Chloride absorption was inhibited by apical bumetanide, and Na+ secretion was inhibited by apical ouabain. These drugs were only effective when placed in the solution bathing the apical or retinal side of the tissue. 4. Net Cl- absorption requires an exit mechanism at the basolateral membrane. DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) in the basal bath completely inhibited net Cl- absorption in bicarbonate-free Ringer solution. 5. These experiments show that the chloride transport pathway contains at least two components: (1) a bumetanide-sensitive uptake mechanism at the apical membrane; and (2) an efflux mechanism at the basolateral membrane that is blocked by DIDS. 6. Three apical membrane mechanisms were identified that could help modulate [K+]o in the subretinal or extracellular space that separates the distal retina and the RPE apical membrane. They are: (1) an ouabain-sensitive Na(+)-K+ pump; (2) a bumetanide-sensitive mechanism, the putative Na(+)-K(+)-Cl- co-transporter; (3) a barium-sensitive K+ channel that recycles, to the apical bath, most or all of the potassium that is actively taken up by the Na(+)-K+ pump and the co-transporter. 7. These data suggest that light-induced alterations in subretinal potassium that occur in vivo can activate the chloride transport pathway and help modulate RPE intracellular Cl- during transitions between the light and dark.


One-stage aortic replacement for type A aortic dissection: using a Vasoring and a conventional elephant trunk graft.
We used a vascular ring connector (Vasoring) and a conventional elephant trunk graft for complete repair in open surgery for type A aortic dissection. This report described the immediate and mid-term results of this new technique. We used a rigid titanic ring as a stent in the vascular graft for rapid sutureless anastomosis in the reconstruction of type A aortic dissection. A total of 65 consecutive patients with Stanford type A aortic dissection underwent open surgery performed by a single surgeon from November 2007 to February 2017. All patients underwent aortic reconstruction with vascular grafts and Vasorings (21 patients in the ascending aorta and 44 patients in the total aortic arch). For total aortic arch replacement, we implanted the conventional vascular graft in the proximal descending thoracic aorta as an elephant trunk graft. Concomitant procedures included the Bentall procedure (9 patients), the David operation (6 patients), coronary artery bypass grafting (9 patients), heart transplantation (1 patient), mitral valve replacement (2 patients) and endovascular aortic repair (1 patient). The mean duration of postoperative endotracheal intubation was 17.0 ± 11.8 h. The average blood loss was 520 ± 743 ml, and 25% of patients required no blood transfusion. The in-hospital mortality rate was 6%. The combined use of the vascular ring connector and the conventional elephant trunk graft may reduce bleeding and pump time, stop the blood flow in the false lumen and allow the 1-stage total arch replacement to be performed safely. The conventional elephant trunk graft is free from stent graft-induced new entry.


Ligand-Induced Luminescence Transformation in AgInS2 Nanoparticles: From Defect Emission to Band-Edge Emission.
I-III-VI2 semiconductor nanoparticles are strong candidates for fluorescent materials composed of nontoxic elements substituting highly fluorescent CdSe nanoparticles. Photoluminescence of I-III-VI2 nanoparticles essentially arise due to defect emission characterized by a broad spectral feature. Band-edge emission exhibits radiation with high monochromaticity, which can drastically expand its application range. Hence, numerous studies were conducted to realize band-edge emission. A successful observation of the band-edge emission was reported only when fabricating GaSx or InSx shells around AgInS2 nanoparticles via surface trap site passivation. This study demonstrates a much easier method of providing band-edge emission from AgInS2 nanoparticles using organic ligands of trioctylphosphine (TOP). Along with the TOP ligand formation around AgInS2 nanoparticles, the defect emission increases once and then decreases in conjunction with the appearance of the band-edge emission. Therefore, TOP ligands can passivate carrier trapping sites for radiative recombination as well as fluorescence quenching sites.


Interdependence of Inhibitor Recognition in HIV-1 Protease.
Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency. All-atom molecular dynamics simulations starting from these structures were performed and systematically analyzed in terms of atomic fluctuations, intermolecular interactions, and water structure. These analyses reveal that the S1' subsite highly influences other subsites: the extension of the hydrophobic P1' moiety results in 1) reduced van der Waals contacts in the P2' subsite, 2) more variability in the hydrogen bond frequencies with catalytic residues and the flap water, and 3) changes in the occupancy of conserved water sites both proximal and distal to the active site. In addition, one of the monomers in this homodimeric enzyme has atomic fluctuations more highly correlated with DRV than the other monomer. These relationships intricately link the HIV-1 protease subsites and are critical to understanding molecular recognition and inhibitor binding. More broadly, the interdependency of subsite recognition within an active site requires consideration in the selection of chemical moieties in drug design; this strategy is in contrast to what is traditionally done with independent optimization of chemical moieties of an inhibitor.


An increase in plasma adiponectin multimeric complexes follows hypocaloric diet-induced weight loss in obese and overweight pre-menopausal women.
Adiponectin is involved in the regulation of glucose and fatty acid metabolism, influences whole-body insulin sensitivity and protects arterial walls against the development of atherosclerosis. Plasma adiponectin is decreased in obese, insulin-resistant and Type 2 diabetic patients. Adiponectin circulates in plasma as high-, medium- and low-molecular-weight ('mass') forms (HMW, MMW and LMW respectively). The HMW form is believed to be closely associated with insulin sensitivity. The aim of the present study was to investigate whether diet-induced changes in body weight and insulin sensitivity were associated with changes in the quantity of adiponectin multimeric complexes. A total of 20 overweight or obese women (age, 39.4+/-9.5 years; body mass index, 32.2+/-6.4 kg/m(2)) underwent 12 weeks of low caloric diet (600 kcal/day less than energy requirements; where 1 kcal is approximately 4.184 kJ). Plasma samples were drawn before and after the study for biochemical analysis and Western blot detection of adiponectin multimeric complexes. The hypocaloric diet resulted in a weight reduction (89.8+/-16.4 kg compared with 83.1+/-15.6 kg; P<0.001) and an improvement in whole-body insulin sensitivity, as measured by HOMA (homoeostasis model assessment index; 1.9+/-0.8 compared with 1.5+/-0.7; P=0.013). Increases in the quantities of the HMW, MMW and LMW forms by 5.5, 8.5 and 18.1% respectively, were observed (P<0.05 for all of the forms). Total plasma adiponectin was increased by 36% with borderline significance (P=0.08). No correlations between changes in adiponectin complexes and changes in indices of insulin sensitivity were observed. In conclusion, diet-induced weight loss improved insulin sensitivity as well as increased the amount of HMW, MMW and LMW adiponectin complexes in plasma.


Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases.
Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and non-native polyketide substrates. Reactions pairing wildtype PKS modules with non-native substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing non-cognate TE domains was severely reduced. In contrast, non-native substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.


Causes of gas exchange impairment during general anaesthesia.
This review describes the distribution of ventilation and blood flow in the anaesthetized subject, during spontaneous breathing and after muscle paralysis. Within minutes after induction of anaesthesia, the diaphragm is shifted cranially (supine position), functional residual capacity is reduced and collapse of dependent lung regions can be seen by means of computed tomography. These changes occur whether anaesthesia is intravenous (barbiturate) or inhalational (halothane) and whether ventilation is spontaneous or mechanical. Ventilation is subsequently reduced in dependent lung regions, whereas blood flow is preferentially distributed to the lower lung regions. This causes a ventilation/perfusion mismatch, the hall-mark of which is shunt. Additional factors such as airway closure and release of hypoxic pulmonary vasoconstriction may contribute to the gas exchange disturbance. The major features of the lung function impairment are already present during spontaneous breathing in the anaesthetized subject, and muscle paralysis adds only little to the disturbance.


Unusual cause of lower extremity wounds: Cobb syndrome.
Cobb syndrome (Cutaneomeningospinal Angiomatosis) is a rare segmental neurocutaneous syndrome associated with metameric cutaneous and spinal cord arteriovenous malformations (AVMs). In this syndrome, capillary malformation or angiokeratoma-like lesions are formed in a dermatomal distribution, with an AVM in the corresponding segment of the spinal cord. The spinal cord lesions can cause neurological disorder and paraplegia, which typically develop during young adulthood. We report a 32-year-old male with the Cobb syndrome associated with lower extremity painful wounds and acute-onset paraplegia due to metameric vascular malformations.


Backbone 1H, 15N, and 13C resonance assignments of the Helicobacter pylori acyl carrier protein.
One of the small proteins from Helicobacter pylori, acyl carrier protein (ACP), was investigated by NMR. ACP is related to various cellular processes, especially with the biosynthesis of fatty acid. The basic NMR resonance assignment is a prerequisite for the validation of a heterologous protein interaction with ACP in H. pylori. Here, the results of the backbone (1)H, (15)N, and (13)C resonance assignments of the H. pylori ACP are reported using double- and triple-resonance techniques. About 97% of all of the (1)HN, (15)N, (13)CO, (13)Calpha, and (13)Cbeta resonances that cover 76 of the 78 non-proline residues are clarified through sequential- and specific- assignments. In addition, four helical regions were clearly identified on the basis of the resonance assignments.


Views of relatives, carers and staff on end of life care pathways.
More people die in hospital than at home (Department of Health (DH) 2008). Yet, many people do not want to die in hospital, which can be an inappropriate environment for end of life care. The government's end of life care strategy (DH 2008) and the NHS (2009) end of life care programme (EOLCP) state that people should be able to choose where they die. This article reports on the findings of a study on end of life care of decisions by patients, relatives and care professionals, and their perceptions of care pathways in the last 48 hours of life. It also highlights the challenges that must be overcome in acute and community settings for the aims of the EOLCP to be met.


Understanding the Rationale for Immunotherapy in Non-Small Cell Lung Cancer.
Although immunotherapy has been used for decades in immunogenic tumor types, such as melanoma and renal cell carcinoma, historically immunotherapeutic approaches in other tumor types, including non-small cell lung cancer (NSCLC), have met with failure. Nonetheless, evidence exists supporting the role of the immune system in tumor suppression, even in tumor types believed to be non-immunogenic. In NSCLC, immune checkpoint molecules have recently proven to be successful targets, with nivolumab, the first immune checkpoint inhibitor indicated for NSCLC, approved by the US Food and Drug Administration in March 2015. Several other immune checkpoint inhibitors are currently in phase III development in NSCLC.


Production of mevalonic acid by fermentation.
The purpose of this investigation was to select microorganisms that produce substantial quantities of mevalonic acid and to develop an economic fermentation process. To screen for mevalonic acid-producing microorganisms, it was necessary to improve the method for the quantitative determination of this acid. The biological assay was modified by shortening the incubation time and simplifying the procedure. The principle of the assay is based on the essential mevalonic acid requirement of the organism Lactobacillus heterohiochii for growth. Screening was carried out by selecting high mevalonic acid-producing organisms from various type cultures. Endomycopsis fibuliger was chosen for medium development studies, and 939 mug of mevalonic acid per ml was produced in the culture filtrate after modifications of medium and fermentation conditions.


A sequence of basic residues in the porcine circovirus type 2 capsid protein is crucial for its co-expression and co-localization with the replication protein.
Porcine circovirus type 2 (PCV2) encodes two major proteins: the replication protein (Rep) and the capsid protein (Cap). Cap displays a conserved stretch of basic residues situated on the inside of the capsid, whose role is so far unknown. We used a reverse-genetics approach to investigate its function and found that mutations in these amino acids hindered Cap mRNA translation and hampered Cap/Rep co-localization, yielding unfit viruses. Intriguingly, co-transfection with a WT PCV2 of a different genotype partially rescued mutant Cap expression, showing the importance of this basic pattern for efficient translation of Cap mRNA into protein. Our results show that Cap and Rep are expressed independently of each other, and that this amino acid sequence of Cap is vital for virus propagation. This study provides a method for studying unfit PCV2 virions and offers new insights into the intracellular modus vivendi of PCV2.


Infrared scattering: a method for evaluating the mass and size of bacteria.
In the realm of biophysics and biochemistry, light scattering is used extensively to evaluate the molecular weight and size of macromolecules and particles in suspension. Bacteria scatter strongly but are too large for the conventional procedures. By extending the wavelength lambda of the incident radiation into the infrared, we show that the effective size of the bacteria (relative to lambda) is reduced, and the usual Zimm plot measurements and procedure can be applied to evaluate the molecular weight and size. Details of the apparatus, its alignment, calibration and use are given along with data for aqueous suspensions of the three species Serratia marcescens, Escherichia coli and Thiobacillus ferrooxidans. The method has the advantages of being suitable for rod-like or ellipsoid-like bacteria as well as spheres, for polydisperse samples and for monitoring the effects of environment, antibodies and chemical therapeutic agents on the bacteria.


Correlations between the spread of ventricular activation and map patterns of measured and difference maps.
Three kinds of torso surface isopotential maps (measured, simulated, and difference maps) were delineated at every 1.5 (or 3) msec. during the QRS duration from the 85 unipolar lead ECG's led from the surface of a cylindrical torso model filled with perfusate and containing a canine heart undergoing Langendorff's perfusion. These three maps were compared as to the propagation process of ventricular activation obtained from the same heart and close correlations were found between the spread of ventricular activation and the map patterns of measured and difference maps. The difference map mainly reflected the proximity potential at each instant of ventricular activation in QRS duration and, when used in combination with the measured map, it was useful to estimate the spread of ventricular activation, especially around the stage of epicardial breakthrough of the activation front. It was confirmed that the interpretation of the difference map expressed in the present paper would not be misleading even if applied to a difference map obtained in a human torso model experiment.


Left ventricular function in patients with ankylosing spondylitis and Reiter's disease.
We have studied left ventricular function by non-invasive methods in 28 patients with ankylosing spondylitis and 14 with Reiter's disease and compared them with 42 normal subjects. A dilated and poorly contracting left ventricle with abnormal systolic time intervals were found in five (18%) of those with ankylosing spondylitis and two (14%) with Reiter's disease. Our results suggest that the high cardiovascular morbidity and mortality in these diseases may be due to abnormality of the myocardium in the absence of valve disease.


Differing effects of anesthetics on splanchnic arterial blood flow during hemorrhagic shock.
The effect of anesthesia on splanchnic blood flow was examined during hemorrhagic shock and resuscitation. Sprague-Dawley rats were anesthetized with the inhalation anesthetic, methoxyflurane, or pentobarbital (65 mg/kg). Transonic Doppler flow probes were placed around the superior mesenteric artery (SMA) and the abdominal aorta, and the animals were subjected to acute hemorrhage (or sham) to 30 mmHg for 90 min followed by 30 min of resuscitation with shed blood (n = 6/group). At 90, 105, and 120 min, sham animals in both anesthetic groups showed comparable blood pressures with a 50% decrease in SMA and aortic blood flow. Acute hemorrhage decreased SMA blood flow by 94.5 +/- 0.01 and 86.0 +/- 2.8%, respectively, in the pentobarbital and methoxyflurane groups, with similar changes occurring in aortic blood flow. During resuscitation, arterial pressure remained significantly depressed and SMA blood flow decreased by 65% in the pentobarbital group, whereas blood pressure returned to control levels and SMA blood flow increased to 56% of control values (P < 0.001) in the methoxyflurane group. The findings indicate that the choice of anesthetic agent may significantly impact splanchnic blood flow and needs to be taken into account when designing experiments examining effects of hemorrhagic shock.


Direct 3D cell-printing of human skin with functional transwell system.
Three-dimensional (3D) cell-printing has been emerging as a promising technology with which to build up human skin models by enabling rapid and versatile design. Despite the technological advances, challenges remain in the development of fully functional models that recapitulate complexities in the native tissue. Moreover, although several approaches have been explored for the development of biomimetic human skin models, the present skin models based on multistep fabrication methods using polydimethylsiloxane chips and commercial transwell inserts could be tackled by leveraging 3D cell-printing technology. In this paper, we present a new 3D cell-printing strategy for engineering a 3D human skin model with a functional transwell system in a single-step process. A hybrid 3D cell-printing system was developed, allowing for the use of extrusion and inkjet modules at the same time. We began by revealing the significance of each module in engineering human skin models; by using the extrusion-dispensing module, we engineered a collagen-based construct with polycaprolactone (PCL) mesh that prevented the contraction of collagen during tissue maturation; the inkjet-based dispensing module was used to uniformly distribute keratinocytes. Taking these features together, we engineered a human skin model with a functional transwell system; the transwell system and fibroblast-populated dermis were consecutively fabricated by using the extrusion modules. Following this process, keratinocytes were uniformly distributed onto the engineered dermis by the inkjet module. Our transwell system indicates a supportive 3D construct composed of PCL, enabling the maturation of a skin model without the aid of commercial transwell inserts. This skin model revealed favorable biological characteristics that included a stabilized fibroblast-stretched dermis and stratified epidermis layers after 14 days. It was also observed that a 50 times reduction in cost was achieved and 10 times less medium was used than in a conventional culture. Collectively, because this single-step process opens up chances for versatile designs, we envision that our cell-printing strategy could provide an attractive platform in engineering various human skin models.


Effectiveness of After-School Physical Activity Intervention on Body Mass Index and Waist Circumference/Height Ratio among Overweight Adolescents in Selected Schools at Puducherry, India: A Randomized Controlled Trial.
Globally, the prevalence of overweight and obesity has dramatically increased in the recent years. In India, more than 10% of schoolchildren are overweight or obese. Schools play a major role in the modification of behavior. The aim of this study was to assess the effectiveness of after-school physical activity intervention on body mass index (BMI) and waist circumference/height ratio as primary outcomes. A randomized controlled trial was adopted where the schools were randomized. Each group, i.e., study and control groups, had 140 overweight adolescents. BMI and waist circumference/height ratio were measured. After-school physical activity intervention was carried out for a period of 9 months by the study group. The posttests were carried out at an interval of 3 months up till 9 months. There was a statistically significant difference in BMI between the study and control groups during the 6th and 9th months (t = 1.256, P < 0.001 and t = 0.920, P < 0.001), respectively. The repeated measures analysis of variance did not show a significant reduction in BMI and waist circumference/height ratio over a period of time. School-based physical activity interventions are effective in prevention of childhood overweight/obesity and are a very cost-effective measure that can be easily implemented in schools.


Health planning: structure, processes, and social work involvement.
Health planning can be a significant influence on the delivery of social services. It has been increasingly characterized by regulation and restriction and, as such, presents both threats and possibilities to social work values and service ideals. Health planning priorities are consonant with social work values and service ideals. Its effect on health facilities and their responses to it, however, could pose threats to social work. On the other hand, health planning can be used to enhance social services as well as better integration of health and social services. The structure and processes of local health planning are described, and areas of social work involvement are suggested.


cAMP and calcium in generation of slow waves in cat colon.
Rhythmic oscillations in interactions between cAMP and calcium have been proposed to account for a variety of rhythmic phenomena in cells. This idea was investigated in relation to the rhythmic signals (electrical slow waves) found in the electromyogram of the cat colon. A longitudinal strip of muscularis propria from cat colon was studied in a superfusion bath that allowed recording of the electromyogram from eight sites that were 2 cm apart. The effect of increasing cAMP (by exposure of the tissue to cAMP, dibutyryl cAMP, isobutylmethylxanthine, theophylline, caffeine, and papaverine) was to reduce frequency and amplitude of slow waves and duration of migrating spike bursts. All these maneuvers raised tissue cAMP levels. Dibutyryl cGMP and cGMP had no effect. THe changes in slow waves, but not migrating spike bursts, seen with raised cAMP levels were partly reversed by raising the calcium concentration in the extracellular fluid. Raising the extracellular sodium and potassium concentrations had no effect. The results are consistent with the hypothesis that interactions between cAMP and calcium are involved in slow-wave generation in colon muscle.


Beta Palmitate Improves Bone Length and Quality during Catch-Up Growth in Young Rats.
Palmitic acid (PA) is the most abundant saturated fatty acid in human milk, where it is heavily concentrated in the sn-2-position (termed beta palmitate, BPA) and as such is conserved in all women, regardless of their diet or ethnicity, indicating its physiological and metabolic importance. We hypothesized that BPA improves the efficiency of nutrition-induced catch up growth as compared to sn-1,3 PA, which is present in vegetable oil. Pre-pubertal male rats were subjected to a 17 days food restriction followed by re-feeding for nine days with 1,3 PA or BPA-containing diets. We measured bone length, epiphyseal growth plate height (EGP, histology), bone quality (micro-CT and 3-point bending assay), and gene expression (Affymetrix). The BPA-containing diet improved most growth parameters: humeri length and EGP height were greater in the BPA-fed animals. Further analysis of the EGP revealed that the hypertrophic zone was significantly higher in the BPA group. In addition, Affymetrix analysis revealed that the diet affected the expression of several genes in the liver and EGP. Despite the very subtle difference between the diets and the short re-feeding period, we found a small but significant improvement in most growth parameters in the BPA-fed rats. This pre-clinical study may have important implications, especially for children with growth disorders and children with special nutritional needs.


Sex differences in hospital risk-adjusted mortality rates for Medicare beneficiaries undergoing CABG surgery.
The primary purpose of this study was to rank US hospitals performing coronary artery bypass graft (CABG) surgery on Medicare beneficiaries into 4 performance tiers and determine if there were overall and sex-specific differences in the risk-adjusted mortality rates across performance tiers. A retrospective analysis was done using a Medicare Provider Analysis and Review (MEDPAR) file of all Medicare beneficiaries who underwent CABG surgery without valve repair or replacement during fiscal years 2003 and 2004. Logistic regression models controlling for demographic characteristics, comorbidities, and cardiac risk factors were used to predict the probability of in-hospital mortality. Hospitals performing at least 52 CABG surgeries during a fiscal year (at least 17 female patients) were ranked into 4 tiers. Rankings were based on the number of lives saved, calculated as the expected number of risk-adjusted deaths minus the actual number of deaths in the hospital during each fiscal year. Average risk-adjusted mortality rate was stable and declining over the 2 years: 3.68% in 2003 and 3.61% in 2004. In 2004, the average risk-adjusted mortality rate ranged from 1.39% in tier 1 hospitals to 6.40% in tier 4 hospitals. The sex-specific mortality rate was consistently higher for women in all tiers, with the differential smallest (0.68%) in tier 1 hospitals and greatest (2.67%) in tier 4 hospitals. The sex differential increases from top- to bottom-tier hospitals, suggesting female beneficiaries could benefit from having CABG performed at tier 1 hospitals.


Preliminary antigenic characterization of an avian pneumovirus isolated from commercial turkeys in Colorado, USA.
An avian pneumovirus (APV) isolated from turkeys showing respiratory disease in Colorado, USA, shared some characteristics with earlier subgroup A and B APV strains. This virus, designated the Colorado isolate (Colorado), when used after either seven passages in chick embryo fibroblasts (CEF), or seven passages in CEF followed by six turkey passages, induced clinical signs in turkeys that were similar to those caused by earlier APV strains. Although it induced an antibody response in specific pathogen free chickens, clinical signs were not seen. Unlike subgroups A or B, Colorado did not cause ciliostasis in tracheal organ cultures, but produced a cytopathic effect in chick embryo fibroblasts typical of that seen with other APV strains. Monospecific antisera to A or B strains did not neutralize Colorado and vice versa; nor did monoclonal antibodies, which neutralize subgroup A or B strains, neutralize Colorado. However, it was partially neutralized by a subgroup A hyperimmune serum. A homologous enzyme-linked immunosorbent assay (ELISA) antigen was essential for the detection of Colorado antibodies, since ELISAs in which subgroup A or B strains were used detected antibody to Colorado very poorly. Subgroup A and B vaccines protected turkeys against challenge with Colorado. However, while Colorado protected turkeys, and to some extent chickens, against subgroup A strains, protection against a subgroup B challenge was less good in both species. These results indicate that Colorado should be classified as an APV, but the antigenic differences suggest that it does not belong to subgroups A or B, and represents a separate subgroup (subgroup C) or possibly a separate serotype.


Prospective evaluation of three rapid diagnostic tests for diagnosis of human leptospirosis.
Diagnosis of leptospirosis by the microscopic agglutination test (MAT) or by culture is confined to specialized laboratories. Although ELISA techniques are more common, they still require laboratory facilities. Rapid Diagnostic Tests (RDTs) can be used for easy point-of-care diagnosis. This study aims to evaluate the diagnostic performance of the RDTs LeptoTek Dri Dot, LeptoTek Lateral Flow, and Leptocheck-WB, prospectively. During 2001 to 2012, one or two of the RDTs at the same time have been applied prior to routine diagnostics (MAT, ELISA and culture) on serum specimens from participants sent in for leptospirosis diagnosis. The case definition was based on MAT, ELISA and culture results. Participants not fulfilling the case definition were considered not to have leptospirosis. The diagnostic accuracy was determined based on the 1(st) submitted sample and paired samples, either in an overall analysis or stratified according to days post onset of illness. The overall sensitivity and specificity for the LeptoTek Dri Dot was 75% respectively 96%, for the LeptoTek Lateral Flow 78% respectively 95%, and for the Leptocheck-WB 78% respectively 98%. Based on the 1(st) submitted sample the sensitivity was low (51% for LeptoTek Dri Dot, 69% for LeptoTek Lateral Flow, and 55% for Leptocheck-WB), but substantially increased when the results of paired samples were combined, although accompanied by a lower specificity (82% respectively 91% for LeptoTek Dri Dot, 86% respectively 84% for LeptoTek Lateral Flow, and 80% respectively 93% for Leptocheck-WB). All three tests present antibody tests contributing to the diagnosis of leptospirosis, thus supporting clinical suspicion and contributing to awareness. Since the overall sensitivity of the tested RDTs did not exceed 80%, one should be cautious to rely only on an RDT result, and confirmation by reference tests is strongly recommended.


Dupilumab and COVID-19: What should we expect?
Coronavirus disease 2019 (COVID-19) is a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. There are very limited data on the interference of immunomodulating drugs on the risk of infection and on the course of the disease. In particular, there are no current clinical data about the interference exerted by dupilumab, a biologic drugs blocking IL-4 and IL-13, used for adult atopic dermatitis. The pathogenesis of COVID-19 is complex, characterized by an immune response mainly Th1/Th17. The hyper-activation of these cells may cause the release of pro-inflammatory cytokines that may result in lung impairment. IL-4 and IL-13 are Th2 cytokines, thus being part of a pathway not considered implicated in host defense mechanism against viral infections. Indeed, viral infections, including respiratory infections, have not been reported as a significant adverse event in clinical trials. Furthermore, dupilumab has been proved to be efficacious also in exacerbations of asthma, and it is known that viral infections can worsen asthma. Therefore, the current data seem to suggest that treatment with dupilumab should not be stopped during COVID-19 pandemic. Obviously, a careful assessment is mandatory for each individual patient and further studies are necessary to characterize the immunologic responses in COVID-19.


Oesophageal Doppler guided goal-directed haemodynamic therapy in thoracic surgery - a single centre randomized parallel-arm trial.
Postoperative pulmonary and renal complications are frequent in patients undergoing lung surgery. Hyper- and hypovolaemia may contribute to these complications. We hypothesized that goal-directed haemodynamic management based on oesophageal Doppler monitoring would reduce postoperative pulmonary complications in a randomized clinical parallel-arm trial. One hundred patients scheduled for thoracic surgery were randomly assigned to either standard haemodynamic management (control group) or goal-directed therapy (GDT group) guided by an oesophageal Doppler monitoring-based algorithm. The primary endpoint was postoperative pulmonary complications, including spirometry. Secondary endpoints included haemodynamic variables, renal, cardiac, and neurological complications, and length of hospital stay. The investigator assessing outcomes was blinded to group assignment. Forty-eight subjects of each group were analysed. Compared to the control group, fewer subjects in the GDT group developed postoperative pulmonary complications (6 vs. 15 patients; P = 0.047), while spirometry did not differ between groups. Compared to the control group, patients of the GDT group showed higher cardiac index (2.9 vs. 2.1 [l min - 1 m - 2 ]; P < 0.001) and stroke volume index (43 vs. 34 [ml m 2 ]; P < 0.001) during surgery. Renal, cardiac and neurological complications did not differ between groups. Length of hospital stay was shorter in the GDT compared to the control group (9 vs. 11 days; P = 0.005). Compared to standard haemodynamic management, oesophageal Doppler monitor-guided GDT was associated with fewer postoperative pulmonary complications and a shorter hospital stay. The study was registered in the German Clinical Trials Register (DRKS 00006961). https://drks-neu.uniklinik-freiburg.de/drks_web/.


Angiotensin II acting on brain AT1 receptors induces adrenaline secretion and pressor responses in the rat.
Angiotensin II (AngII) plays important roles in the regulation of cardiovascular function. Both peripheral and central actions of AngII are involved in this regulation, but mechanisms of the latter actions as a neurotransmitter/neuromodulator within the brain are still unclear. Here we show that (1) intracerebroventricularly (i.c.v.) administered AngII in urethane-anesthetized male rats elevates plasma adrenaline derived from the adrenal medulla but not noradrenaline with valsartan- (AT1 receptor blocker) sensitive brain mechanisms, (2) peripheral AT1 receptors are not involved in the AngII-induced elevation of plasma adrenaline, although AngII induces both noradrenaline and adrenaline secretion from bovine adrenal medulla cells, and (3) i.c.v. administered AngII elevates blood pressure but not heart rate with the valsartan-sensitive mechanisms. From these results, i.c.v. administered AngII acts on brain AT1 receptors, thereby inducing the secretion of adrenaline and pressor responses. We propose that the central angiotensinergic system can activate central adrenomedullary outflow and modulate blood pressure.


Gastrointestinal transport of calcium and glucose in lactating ewes.
During lactation, mineral and nutrient requirements increase dramatically, particularly those for Ca and glucose. In contrast to monogastric species, in ruminants, it is rather unclear to which extend this physiological change due to increased demand for milk production is accompanied by functional adaptations of the gastrointestinal tract (GIT). Therefore, we investigated potential modulations of Ca and glucose transport mechanisms in the GIT of lactating and dried-off sheep. Ussing-chamber technique was applied to determine the ruminal and jejunal Ca flux rates. In the jejunum, electrophysiological properties in response to glucose were recorded. Jejunal brush-border membrane vesicles (BBMV) served to characterize glucose uptake via sodium-linked glucose transporter 1 (SGLT1), and RNA and protein expression levels of Ca and glucose transporting systems were determined. Ruminal Ca flux rate data showed a trend for higher absorption in lactating sheep. In the jejunum, small Ca absorption could only be observed in lactating ewes. From the results, it may be assumed that lactating ewes compensate for the Ca loss by increasing bone mobilization rather than by increasing supply through absorption from the GIT Presence of SGLT1 in the jejunum of both groups was shown by RNA and protein identification, but glucose uptake into BBMV could only be detected in lactating sheep. This, however, could not be attributed to electrogenic glucose absorption in lactating sheep under Ussing-chamber conditions, providing evidence that changes in jejunal glucose uptake may include additional factors, that is, posttranslational modifications such as phosphorylation.


A History of Previous Severe Injury and Health-Related Quality of Life Among Former Collegiate Athletes.
Empirical evidence supports the idea that previous severe injuries in former collegiate athletes may adversely affect their ability to participate in daily activities later in life, which may then decrease their health-related quality of life (HRQOL). To assess the influences of previous severe injuries on the HRQOL of former National Collegiate Athletic Association (NCAA) athletes. Cross-sectional study. Online survey. A total of 171 former NCAA collegiate athletes (69 men, 102 women; age = 29.7 ± 3.9 years, height = 171.5 ± 10.4 cm, mass = 76.4 ± 12.9 kg) participated. All individuals completed a demographics questionnaire and the Short Form-36 version 2 (SF-36v2) Health Survey via Qualtrics. The dependent variables were the physical composite and mental composite summary scores and the 8 subscales of the SF-36v2. The independent variable was the presence of previous severe injury (history of a severe injury or no history of a severe injury during collegiate athletics). Two multivariate analyses of variance were conducted. The first multivariate analysis of variance was conducted for the 8 SF-36v2 subscales and the second for the 2 summary scores. For the summary scores and all 8 SF-36v2 subscales, the responses were worse for the 103 former collegiate athletes who sustained a previous severe injury compared with the 68 who did not sustain a severe injury. The largest difference between groups was for the physical composite score, with a mean difference of 15.8 points (1.5 standard deviations worse than the US population); the physical functioning subscale demonstrated a mean difference of 12.9 points (1.3 standard deviations worse than the US population). A majority of the athletes in our sample had experienced a severe injury. Based on these data, previous severe injuries had a negative influence on the HRQOL of former NCAA collegiate athletes.


Polymeric Coatings for Magnesium Alloys for Biodegradable Implant Application: A Review.
Magnesium (Mg) alloys are a very attractive material of construction for biodegradable temporary implants. However, Mg alloys suffer unacceptably rapid corrosion rates in aqueous environments, including physiological fluid, that may cause premature mechanical failure of the implant. This necessitates a biodegradable surface barrier coating that should delay the corrosion of the implant until the fractured/damaged bone has healed. This review takes a brief account of the merits and demerits of various existing coating methodologies for the mitigation of Mg alloy corrosion. Since among the different coating approaches investigated, no single coating recipe seems to address the degradation control and functionality entirely, this review argues the need for polymer-based and biodegradable composite coatings.


An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.
The inhibitory signaling of natural killer (NK) cells is crucial in the regulation of innate immune responses. Here we show that the association of KIR2DL1, an inhibitory receptor of NK cells, with beta-arrestin 2 mediated recruitment of the tyrosine phosphatases SHP-1 and SHP-2 to KIR2DL1 and facilitated 'downstream' inhibitory signaling. Consequently, the cytotoxicity of NK cells was higher in beta-arrestin 2-deficient mice but was inhibited in beta-arrestin 2-transgenic mice. Moreover, beta-arrestin 2-deficient mice were less susceptible than wild-type mice to mouse cytomegalovirus infection, an effect that was abolished by depletion of NK cells. Our findings identify a previously unknown mechanism by which the inhibitory signaling in NK cells is regulated.


Anthropometric and Physical Qualities of Elite Male Youth Rugby League Players.
Rugby league is a collision team sport played at junior and senior levels worldwide, whereby players require highly developed anthropometric and physical qualities (i.e. speed, change-of-direction speed, aerobic capacity, muscular strength and power). Within junior levels, professional clubs and national governing bodies implement talent identification and development programmes to support the development of youth (i.e. 13-20 years) rugby league players into professional athletes. This review presents and critically appraises the anthropometric and physical qualities of elite male youth rugby league players aged between 13 and 20 years, by age category, playing standard and playing position. Height, body mass, body composition, linear speed, change-of-direction speed, aerobic capacity, muscular strength and power characteristics are presented and demonstrate that qualities develop with age and differentiate between playing standard and playing position. This highlights the importance of anthropometric and physical qualities for the identification and development of youth rugby league players. However, factors such as maturity status, variability in development, longitudinal monitoring and career attainment should be considered to help understand, identify and develop the physical qualities of youth players. Further extensive research is required into the anthropometric and physical qualities of youth rugby league players, specifically considering national standardised testing batteries, links between physical qualities and match performance, together with intervention studies, to inform the physical development of youth rugby league players for talent identification and development purposes.


The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy.
In a mouse model of oxygen induced retinopathy (OIR), beta adrenergic receptor (BAR) blockade has been shown to recover hypoxia-associated retinal damages. Although the adrenergic signaling is an important regulator of apoptotic and autophagic processes, the role of BARs in retinal cell death remains to be elucidated. The present study was aimed at investigating whether ameliorative effects of BAR blockers may occur through their coordinated action on apoptosis and autophagy. To this aim, retinas from control and OIR mice untreated or treated with propranolol, a non-selective BAR1/2 blocker, were characterized in terms of expression and localization of apoptosis and autophagy markers. The effects of propranolol on autophagy signaling were also evaluated and specific autophagy modulators were used to get functional information on the autophagic effects of BAR antagonism. Finally, propranolol effects on neurodegenerative processes were associated to an electrophysiological investigation of retinal function by recording electroretinogram (ERG). We found that retinas of OIR mice are characterized by increased apoptosis and decreased autophagy, while propranolol reduces apoptosis and stimulates autophagy. In particular, propranolol triggers autophagosome formation in bipolar, amacrine and ganglion cells that are committed to die by apoptosis in response to hypoxia. Also our data argue that propranolol, through the inhibition of the Akt-mammalian target of rapamycin pathway, activates autophagy which decreases retinal cell death. At the functional level, propranolol recovers dysfunctional ERG by recovering the amplitude of a- and b-waves, and oscillatory potentials, thus indicating an efficient restoring of retinal transduction. Overall, our results demonstrate that BAR1/2 are key regulators of retinal apoptosis/autophagy, and that BAR1/2 blockade leads to autophagy-mediated neuroprotection. Reinstating the balance between apoptotic and autophagic machines may therefore be viewed as a future goal in the treatment of retinopathies.


Cystic duct stones in postcholecystectomy Mirizzi syndrome - A novel endoscopic treatment.
Mirizzi syndrome is a rare type of cholelithiasis, and the main treatment is still surgery. The development of endoscopic technology has made surgeons more active in the management of rare diseases of the biliary tract and pancreas. Here we report that our center applied the new endoscopic method to treat a Mirizzi patient with residual cystic neck duct stones after laparoscopic cholecystectomy.


Oncostatin M-induced effects on EMT in human proximal tubular cells: differential role of ERK signaling.
Growing evidence suggests that a proportion of interstitial myofibroblasts detected during renal tubulointerstitial fibrosis originates from tubular epithelial cells by a process called epithelial-mesenchymal transition (EMT). The IL-6-type cytokine oncostatin M (OSM) has been recently implicated in the induction of EMT. We investigated OSM effects on the expression of both cell-cell contact proteins and mesenchymal markers and studied OSM-induced intracellular signaling mechanisms associated with these events in human proximal tubular cells. Human recombinant OSM attenuated the expression of N-cadherin, E-cadherin, and claudin-2 in human kidney-2 (HK-2) cells associated with the induction of HK-2 cell scattering in 3D collagen matrices. Conversely, expression of collagen type I, vimentin, and S100A4 was induced by OSM. OSM-stimulated cell scattering was inhibited by antibodies against gp130. Besides inducing phosphorylation of Stat1 and Stat3, OSM led to a strong concentration- and time-dependent phosphorylation of the mitogen-activated protein kinases ERK1, ERK2, and ERK5. MEK1/2 inhibitor U0126 (10 muM) blocked basal and OSM-induced ERK1/2 phosphorylation but not phosphorylation of either ERK5 or Stat1/3. Both synthetic MEK1/2 inhibitors U0126 and Cl-1040, when used at concentrations which inhibit ERK1/2 phosphorylation but not ERK5 phosphorylation, restored N-cadherin expression in the presence of OSM, inhibited basal claudin-2 expression, but did not affect either basal or OSM-inhibited E-cadherin expression or OSM-induced expression of collagen type I and vimentin. These results suggest that in human proximal tubular cells ERK1/2 signaling represents an important component of OSM's inhibitory effect on N-cadherin expression. Furthermore, functional ERK1/2 signaling is necessary for basal claudin-2 expression.


[Contrast-enhanced ultrasonography in diagnosis of inflammatory pseudotumor of liver].
To evaluate the application of contrast-enhanced ultrasonography (CEUS) in diagnosis of inflammatory pseudotumor of liver (IPL). The contrast-enhanced untrasonography was performed in 32 cases of IPL and the results were retrospectively analyzed. Among total 32 cases, 21 had absent contrast enhancement (type I); 6 had rimlike or stringlike enhancement during arterial phase and presented hypoechoic lesions during the late phase (type II); 2 had diffuse and homogeneous enhancement during early arterial phase,persisting hyperechoic during the late phase (type III); 3 had enhancement during arterial phases and washed out more quickly than liver parenchymal (type IV). The perfusion pattern of IPL with CEUS varies, the predominant type is no contrast enhancement; type IV may be confused with atypical hepatic carcinoma, in that case the needle biopsy is necessary.


Audio-visual navigation reduces treatment time in deep-inspiration breath hold radiotherapy.
The purpose of this study was to compare the treatment times for deep-inspiration breath hold with and without audio-visual (A-V) navigation. We measured the real treatment time in 60 patients with breast cancer undergoing postoperative radiotherapy. Thirty consecutive patients were treated without deep-inspiration breath hold (DIBH) and another 30 patients using deep-inspiration breath hold (10 patients with DIBH only, 10 patients with DIBH using visual feedback and 10 patients with DIBH using visual feedback following breath training). The treatment time was relativized to number of fields and 100 monitor units (MU). The independent t-test was used to analyse differences between cohorts. The mean treatment time for patients without DIBH was 46.5 seconds per field and 90.9 seconds per 100 MU, for DIBH only 92.3 and 170.2 seconds, for DIBH with audio-visual navigation 68.1 and 133.8 seconds, and for DIBH with A-V feedback including breath training 66.1 and 132.5 seconds. The treatment times for patients treated using DIBH with visual navigation were significantly shorter in comparison with patients without visual feedback. We were not able to prove any significant benefit for breath training in terms of reducing the treatment time. Audio-visual navigation enables to significantly reduce the treatment time in comparison with DIBH without A-V feedback.


Neuromuscular ultrasound in leprosy: A scanning protocol.
The diagnosis of leprosy neuropathies has been traditionally based on clinical findings and electrodiagnostic studies, but ultrasound has emerged as a new tool for use in clinical practice. We conducted a literature search on the subject and developed a pragmatic ultrasound scanning protocol for patients with confirmed or suspected leprosy neuropathy. We suggest scanning the ulnar, median, superficial radial, common fibular and sural nerves at specific sites and assessing cross-sectional area, vascularity, and epineural thickness. Our protocol is potentially useful in differentiating leprosy neuropathies from other demyelinating neuropathies, but its applicability and accuracy must be evaluated in different centers.


Use of asthma control indicators in measuring inhaled corticosteroid effectiveness in asthmatic smokers: a systematic review.
The objective of this review is to explore how current research measures the effectiveness of inhaled corticosteroids (ICS) in smokers with asthma. PubMed, CINAHL and PsycINFO databases were searched for combinations of terms relating to asthma, tobacco use and ICS effectiveness. The search was limited to articles published between 2004 and 2015, in English language. Studies met inclusion criteria if reporting the use of guideline-based asthma control indicators to measure the therapeutic effects of ICS or ICS combination therapies. This review did not exclude articles based on study design. Data were extracted and summarized to describe how indicators were measured across studies in order to characterize and describe the effects of ICS in smokers. Thirteen studies were included in this review. Six of these 13 studies used only one indicator to measure asthma control in smokers and ICS was found to improve asthma in only one of six of these studies. Of studies evaluating combination therapy, three of four studies reported a therapeutic benefit to smokers. In these studies of combination therapy multiple indicators of control were measured to assess drug effects. To assess the therapeutic benefit of ICS drugs in smokers, multiple indicators should be measured to determine if current therapy is improving asthma control. Asthma therapy should then be adjusted based on the patient's current asthma status. The development of clinical treatment guidelines for asthmatic smokers may help clinicians make best-practice, evidence-based recommendations in order to optimize care for these patients.


Interpretation of generalized grating imaging: further analysis and numerical calculation.
The generalized grating imaging based on the equations derived in a previous paper [J. Opt. Soc. Am. A25, 2244 (2008)] is described. There the fundamental order imaging was interpreted for gratings with real diffraction coefficients. Here the equations for higher-order imaging are derived and discussed for more general gratings with complex diffraction coefficients. Based on the derived equations the contrast of the grating image is calculated for two examples. A discussion of the effect of the spectrum width of the light source is made and applied to the examples.


Trichlortriethylamine (TS-160 Spofa) in combination chemotherapy of malignant lymphomas.
Thirteen patients with disseminated malignant lymphomas were treated with combination chemotherapy which included trichlortriethyl amine (TS-160), vincristine (Oncovin), procarbazine hydrochloride (Natulan) and prednisone. All patients but two received some form of chemotherapy and/or radiotherapy prior to being started on four-drug regimen. Good response to the combination chemotherapy was recorded in 84% of patients, while complete remission was achieved in 23% of cases. Drug toxicity has not proved to be a major problem in the combination used. Nausea and vomiting were the side effects the most frequently observed.


Effects of phonological length on the attentional blink for words.
The authors tested whether the attentional blink (AB), a deficit in the ability to report a second target appearing within half a second of a first target, may reflect limitations for consolidating visual stimuli into working memory and awareness. Previous research has shown that people are severely limited in the rate that they can identify and report visual events presented in rapid succession. Word length was examined, a variable known to affect verbal working memory. Experiment 1 showed that the AB was modulated by the phonological length of the first target. Phonologically longer pseudowords triggered larger blink deficits. Experiment 2 also demonstrated the word-length effect on the AB using real-world stimuli, anagrams, that controlled for low-level visual differences between conditions. These data support proposals that the AB reflects a difficulty in consolidating information into working memory.


Perfluorocarbon Nanocapsules Improve Hypoxic Microenvironment for the Tumor Ultrasound Diagnosis and Photodynamic Therapy.
Amelioration of hypoxia is an important factor increasing the effects of anti-tumor therapies. In the present experiments, nanocapsules of poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide (PFOB)/photosensitizers (IR780) have been developed to increase oxygen concentration inside the tumor and improve the outcome of photodynamic therapy (PDT). PFOB has high oxygen solubility, and IR780 is a photosensitizer particularly suited for a highly effective photodynamic therapy under the 808-nm laser irradiation. Thus, PFOB provides sufficient oxygen for the reaction with the photosensitizer, producing more singlet oxygen to induce cell apoptosis. The photodynamic effect of nanocapsules was confirmed to be enhanced after addition of PFOB through simulation experiments in vitro in the hypoxic microenvironment. The results have demonstrated that due to the addition of PFOB the nanocapsules can provide a contrast-enhanced ultrasound diagnosis and ensure more notable inhibition of the growth of lung tumors following the 808 nm laser irradiation. Furthermore, the nanocapsules allowed the photosensitizers to achieve sufficient therapeutic potential, which was optimal under the conditions of modest hypoxia with about 5% oxygen concentration.


Combining ZHENG Theory and High-Throughput Expression Data to Predict New Effects of Chinese Herbal Formulae.
ZHENG is the key theory in traditional Chinese medicine (TCM) and it is very important to find the molecular pharmacology of traditional Chinese herbal formulae. One ZHENG is related to many diseases and the herbal formulae are aiming to ZHENG. Therefore, many herbal formulae whose effects on a certain disease have been confirmed might also treat other diseases with the same ZHENG. In this study, the microarrays collected from patients with QiXuXueYu ZHENG (Qi-deficiency and Blood-stasis syndrome) before treatment and after being treated with Fuzheng Huayu Capsule were analyzed by a high-throughput gene microarrays-based drug similarity comparison method, which could find the small molecules which had similar effects with Fuzheng Huayu Capsule. Besides getting the results of anti-inflammatory and anti-fibrosis drugs which embody the known effect of Fuzheng Huayu Capsule, many other small molecules were screened out and could reflect other types of effects of this formula in treating QiXuXueYu ZHENG, including anti-hyperglycemic, anti-hyperlipidemic, hyposenstive effect. Then we integrated this information to display the effect of Fuzheng Huayu Capsule and its potential multiple-target molecular pharmacology. Moreover, through using clinical blood-tested data to verify our prediction, Fuzheng Huayu Capsule was proved to have effects on diabetes and dyslipidemia.


Natural and pyrogenic humic acids at goethite and natural oxide surfaces interacting with phosphate.
Fulvic and humic acids have a large variability in binding to metal (hydr) oxide surfaces and interact differently with oxyanions, as examined here experimentally. Pyrogenic humic acid has been included in our study since it will be released to the environment in the case of large-scale application of biochar, potentially creating Darks Earths or Terra Preta soils. A surface complexation approach has been developed that aims to describe the competitive behavior of natural organic matter (NOM) in soil as well as model systems. Modeling points unexpectedly to a strong change of the molecular conformation of humic acid (HA) with a predominant adsorption in the Stern layer domain at low NOM loading. In soil, mineral oxide surfaces remain efficiently loaded by mineral-protected organic carbon (OC), equivalent with a layer thickness of ≥ ~0.5 nm that represents at least 0.1-1.0% OC, while surface-associated OC may be even three times higher. In natural systems, surface complexation modeling should account for this pervasive NOM coverage. With our charge distribution model for NOM (NOM-CD), the pH-dependent oxyanion competition of the organo-mineral oxide fraction can be described. For pyrogenic HA, a more than 10-fold increase in dissolved phosphate is predicted at long-term applications of biochar or black carbon.


Recent advances in the field of doping detection.
Patterns of doping in Britain have on the whole changed from the use of CNS stimulants and depressants to therapeutic substances, or to accidental doping by feeding contaminated food or food supplements. Progress in detection and identification is largely a result of improvements in separation and isolation, especially by gas chromatography, together with the introduction of mass spectrometry. Radiommunoassay and high performance liquid chromatography promise to be important techniques in the future, especially in detection of anabolic steroids and corticosteroids.


[Renal preservation: comparative effectiveness of 2 simple perfusion technics].
The authors compare the efficacy of two perfusates, Collins' solution and Perfudex, for conservation of kidneys for short periods by perfusion and hypothermic immersion. 22 dog kidneys, removed by lombotomy, were preserved for 24 hours with one or other of these solutions and then re-implanted into their host. Radio-isotopic renography, the uptake of Hg 197 Cl3 and a hippuran renogram, used to assess the function of the transplants, suggested the functional superiority of kidneys preserved with Collins solutions. Histological controls carried out beyond the 10 th post-operative week, confirmed these results. The correlations observed between these various findings also assessed the reliability of radio-isotope examinations in the exploration of renal function.


Methicillin-resistant-Staphylococcus aureus colonization and infection in a rehabilitation facility.
Methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in a rehabilitation hospital (Rancho Los Amigos Hospital [RLAH]) were studied from October 1977 to May 1980. Eighty-four episodes of MRSA colonization or infection were observed in 81 patients (attack rate, 0.44 per 100 admissions). The MRSA was considered to have been acquired at RLAH in 65% of the episodes and from transferring hospitals in 34%. The infection rate was 35% among MRSA-colonized patients, and only one death was attributed to MRSA infection. Colonization for more than 100 days occurred most frequently in wounds and anterior nares. All but two of the MRSA isolates were resistant to aminoglycosides, and 80% of those typed belonged to phage type 83A. The patients were allowed to continue participation in rehabilitation programs. Spread of the MRSA occurred in wards where intensive medical and nursing care was being practiced. There was no evidence of MRSA spread in the services with less intense medical and nursing care and where physical and occupational therapy was continued. Patients in a rehabilitation hospital with MRSA colonization may receive intensive physical and occupational therapy as long as special precautions are observed to prevent MRSA spread.


Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal of paclitaxel resistance in human ovarian cancer cells.
Ovarian cancer is currently the most lethal gynecologic malignancy in developed countries, and paclitaxel is a cornerstone in the treatment of this malignancy. Unfortunately, the efficacy of paclitaxel is limited by the development of drug resistance. Clinical paclitaxel resistance is often associated with ABCB1 (MDR1) overexpression, and in vitro paclitaxel resistance typically demonstrates overexpression of the ABCB1 gene. In this study, we demonstrate that paclitaxel-resistant cell lines overexpress both ABCB1 and ABCB4 (MDR3). To evaluate the role of these transporters in paclitaxel-resistant ovarian cancer cells, small interference RNAs (siRNAs) were used to target ABCB1 and ABCB4 RNA in the paclitaxel-resistant SKOV-3TR and OVCAR8TR ovarian cancer cell lines. Treatment of these lines with either chemically synthesized siRNAs or transfection with specific vectors that express targeted siRNAs demonstrated decreased mRNA and protein levels of ABCB1 or ABCB4. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of siRNA-treated cells demonstrated 7- to 12.4-fold reduction of paclitaxel resistance in the lines treated with the synthesized siRNA of ABCB1 and 4.7- to 7.3-fold reduction of paclitaxel resistance in the cell lines transfected with siRNA of ABCB1 expressing vectors. ABCB4 siRNA-treated cell lines showed minor reduction in paclitaxel resistance. These results indicate that siRNA targeted to ABCB1 can sensitize paclitaxel-resistant ovarian cancer cells in vitro and suggest that siRNA treatment may represent a new approach for the treatment of ABCB1-mediated drug resistance.


Epidemiological profile of public servants absent from work due to mental disorders from 2010 to 2013.
Describe the epidemiological profile of mental and behavior disorders (MBD) of public servants in the State of Santa Catarina, which resulted in workers providing medical certificates, between 2010 and 2013. A descriptive cross-sectional study with a quantitative approach, performed from data provided by the State Secretary of Administration. All medical certificates classified as in Chapter V of ICD-10 - Group "F" - Mental and Behavioral Disorders (MBD) were considered for analysis in the period. The study included 71 state agencies, primarily the State Secretary of Education, which corresponds to about 46% of all workers. Considering all the pathologies, 79,306 medical certificates were registered, among which, 40.14% were for MDB. Of the 8,765 workers with medical certificated for MBD, significant differences were found in the prevalence of work absence between gender (more women, in general, with the exception of MBD caused by psychoactive substance use), levels of education, city of the working place, government agency of work, and workers job position.


Anatomic characterization of pulmonary accessory fissures in canine cadavers.
Accessory fissures in the lungs are well described in humans, considered a normal finding, being identified in 60% of autopsied lungs, and more prevalent in the right lung (Gesase, ; Nene, Gajendra, & Sarma, 2011). In dogs, interlobar fissures are well recognized, but there is the lack of anatomic characterization for accessory fissures in the accessible literature. The purpose of this descriptive study was to identify the prevalence and to describe the anatomic localization of accessory fissures. The lungs from 87 dog cadavers used to teach veterinary gross anatomy were collected. Accessory fissures were characterized for each lung lobe, specific lung lobe location, orientation, length and the number of accessory fissures per lobe. Accessory fissures were recognized in 48/87 (55%) of canine lungs, all located in the periphery of the individual lobes. We found a significant association between the presence of accessory fissures and the costal surface of the lung (p < 0.0001), the right lung (p < 0.004), the right cranial lung lobe (p < 0.002) and the left cranial lung lobe (p < 0.04). Histologic results showed normal alveolar and respiratory bronchioles to the level of the accessory fissures. Our results show that accessory fissures are a common finding and should be considered a normal variant. They are more prevalent in the right lung, in the costal surface, and in the right and left cranial lung lobes. An anatomic nomenclature for accessory fissures based on the current Nomina Anatomica Veterinaria and the human literature is proposed. Further studies include a comparison among anatomical accessory fissures, and radiographic and computed tomographic images.


Health professionals' detection of depression and anxiety in their patients with diabetes: The influence of patient, illness and psychological factors.
This study examines how often depression and anxiety, in patients with diabetes, are detected by health professionals; and whether detection is influenced by patient characteristics (age, gender), illness factors (duration of illness, diabetes control), and self-reported levels of depression and anxiety. Prevalence rates of clinically significant depression and anxiety were high (57% and 36%, respectively); however, of those identified, only 44 and 36 per cent, respectively, were detected by staff as depressed or anxious. The only significant predictors of detection were severity of depressive and anxious symptoms. Patient and illness characteristics did not influence whether professionals identified emotional problems in their patients.


Quality measures for anticoagulation care.
To systematically identify and assess current quality measures for anticoagulation in atrial fibrillation (AF), venous thromboembolism (VTE) treatment and surgical VTE prophylaxis. Fifteen quality measure websites were searched as were bibliographic databases (January 2000-February 2016). Quality measures were included if developed in the United States and incorporating an aspect of anticoagulation for the aforementioned indications or if applicable but not indication specific (non-disease specific measure). Two reviewers independently extracted data regarding the characteristics of each quality measure. Thirty-five measures were identified, mostly in VTE treatment (48.6%), followed by non-disease specific measures (25.7%), AF (17.6%) and surgical VTE prophylaxis (8.8%). Process measures predominated (82.9%). A majority of quality measures (65.7%) were focused on parenteral anticoagulants or warfarin and not applicable to novel oral anticoagulants (NOACs). Ten (28.6%) measures are used by the Centers for Medicare and Medicaid Services or as a core measure of The Joint Commission. Limitations include the inability to statistically pool data and possible publication bias given the nature of databases for quality measures. Quality measures are recognized in anticoagulation care. Areas for improvement include expanding beyond process measures and capturing adverse events and the advantages offered by NOACs.


Charge asymmetry of the purple membrane measured by uranyl quenching of dansyl fluorescence.
Purple membrane was covalently labeled with 5-(dimethylamino) naphthalene-1-sulfonyl hydrazine (dansyl hydrazine) by carbodiimide coupling to the cytoplasmic surface (carboxyl-terminal tail: 0.7 mol/mol bacteriorhodopsin) or by periodate oxidation and dimethylaminoborane reduction at the extracellular surface (glycolipids: 1 mol/mol). In 2 mM acetate buffer, pH 5.6, micromolar concentrations of UO2 +(2) were found to quench the dansyl groups on the cytoplasmic surface (maximum = 26%), while little quenching was observed at the extracellular surface (maximum = 4%). Uranyl ion quenched dansyl hydrazine in free solution at much higher concentrations. Uranyl also bound tightly to unmodified purple membrane, (apparent dissociation constant = 0.8 microM) as measured by a centrifugation assay. The maximum stoichiometry was 10 mol/mol of bacteriorhodopsin, which is close to the amount of phospholipid phosphorus in purple membrane. The results were analyzed on the assumptions that UO2 +(2) binds in a 1:1 complex with phospholipid phosphate and that the dansyl distribution and quenching mechanisms are the same at both surfaces. This indicates a 9:1 ratio of phosphate between the cytoplasmic and extracellular surfaces. Thus, the surface change density of the cytoplasmic side of the membrane is more negative than -0.010 charges/A2.


Therapeutic efficacy of macrolides, minocycline, and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae pneumonia in pediatric patients.
The importance of macrolide-resistant (MR) Mycoplasma pneumoniae has become much more apparent in the past decade. We investigated differences in the therapeutic efficacies of macrolides, minocycline, and tosufloxacin against MR M. pneumoniae. A total of 188 children with M. pneumoniae pneumonia confirmed by culture and PCR were analyzed. Of these, 150 patients had a strain with an MR gene and 134 had one with an A-to-G mutation at position 2063 of M. pneumoniae 23S rRNA domain V. Azithromycin (n = 27), clarithromycin (n = 23), tosufloxacin (n = 62), or minocycline (n = 38) was used for definitive treatment of patients with MR M. pneumoniae. Defervescence within 48 h after the initiation of antibiotic therapy was observed in 41% of the patients in the azithromycin group, 48% of those in the clarithromycin group, 69% of those in the tosufloxacin group, and 87% of those in the minocycline group. The average number of days of fever after the administration of antibiotic treatment was lower in the minocycline and tosufloxacin groups than in the macrolide groups. The decrease in the M. pneumoniae burden, as estimated by the number of DNA copies, after 48 to 96 h of treatment was more rapid in patients receiving minocycline (P = 0.016) than in those receiving tosufloxacin (P = 0.049), azithromycin (P = 0.273), or clarithromycin (P = 0.107). We found that the clinical and bacteriological efficacies of macrolides against MR M. pneumoniae pneumonia was low. Our results indicated that minocycline rather than tosufloxacin can be considered the first-choice drug for the treatment of M. pneumoniae pneumonia in children aged ≥ 8 years.


Signet ring cell lymphoma of T cell type.
A rare variant of non-Hodgkin's lymphoma, signet ring lymphoma of T cell phenotype (only the fourth to be reported) in a 75 year old man was studied by light microscopy, immunohistochemistry, electron microscopy and gene rearrangement studies. Ultrastructurally, a wider spectrum of cell size and nuclear shape was observed in this case than in the previously recorded cases. The morphology of the signet ring vacuoles was identical to that found in the commoner B cell signet ring lymphoma of clear vacuole type, and it is suggested that the vacuoles derive from multivesicular bodies. The four cases reported so far have all presented with skin disease, and the limited evidence available suggests that the prognosis may be good.


Facile preparation of graphene@polyaniline nanofiber network/oxidized carbon cloth composites for high-performance flexible solid-state supercapacitors.
The complicated preparation process and low energy density of polyaniline (PANI)-based electrodes limit their wide applications in flexible energy storage devices. In this work, a reduced graphene (rGO)-wrapped polyaniline nanofiber network (PANI-NFN)/oxidized carbon cloth (OCC) (rGO@PANI-NFN/OCC) composite was prepared by a facile impregnation method using reactive templates of MnO2 on the surface of OCC. The as-prepared rGO@PANI-NFN/OCC composite exhibited a high area specific capacitance of 4438 mF cm-2 and maintained an initial capacitance of 88.2% after 3000 GCD cycles. It can be used as an independent electrode to construct flexible solid-state supercapacitors (FSSCs), and the FSSCs based on rGO@PANI-NFN/OCC also exhibit a high energy density of 117.9 μW h cm-2 and 88.39% retention after 500 bending cycles, which shows a great prospect for flexible energy storage device applications. The enhanced performance of rGO@PANI-NFN/OCC composites is mainly attributed to the synergistic effect of PANI-NFN structures with a large specific surface area and a rGO wrap layer to reduce the swelling and shrinking of PANI.


Nonspecific esterase released from thymic macrophages accumulates in the apoptotic thymocytes: an indication for this enzyme participating in the clearance of apoptotic thymocytes.
In the mouse thymus, a large number of developing thymocytes die through apoptosis each day. It has been proposed that thymic macrophages are responsible for clearance of the massive number of thymocytes that die through apoptosis. The detailed clearance mechanism by which macrophages remove the apoptotic cells is not clear. Our in vitro studies in this report show that nonspecific esterase (NSE), a cytochemical marker enzyme of macrophages, was secreted from thymic macrophages as a consequence of stimulation by interaction with thymocytes, and the esterase accumulated in these macrophage-binding thymocytes (MBT). TUNEL staining demonstrated that these MBT were undergoing apoptosis. The inability to exclude eosin Y and the presence of pores on the plasma membrane were further evidence for the disintegration of these MBT. In vivo, the release of NSE was evident by the presence of NSE activity in the extracellular space between the macrophages and apoptotic thymocytes under the transmission electron microscope after dexamethasone injection, which causes massive apoptosis of thymocytes. Inhibition study showed that the inhibition of NSE delayed the MBT progressing to the late apoptotic phase. These results suggest that the NSE released from macrophages is involved in the clearance of apoptotic thymocytes.


Cardiac structure and function in cyclists and runners. Comparative echocardiographic study.
Twelve cyclists and 12 long distance runners matched for age, height, and weight with two control groups of 12 non-athletes were studied echocardiographically to evaluate cardiac structure and function. Runners weighed 8 kg less than cyclists, but age and height were similar. Peak oxygen uptake per kg body weight was higher in athletes than in the control subjects but was similar in the cyclists and in the runners. The athletes' hearts had a larger end diastolic left ventricular internal diameter, mean wall thickness, and cross sectional area of the left ventricular wall than those of the respective control subjects. Nevertheless, whereas the left ventricular internal diameter was not different between the cyclists and runners, mean wall thickness and cross sectional area of the left ventricular wall were greater in the cyclists even after adjustment for weight. The ratio of wall thickness to left ventricular internal radius was significantly larger in cyclists than in their control group, but the ratio was similar in runners and their control group. The echocardiographic indices of left ventricular function were similar in the athletes and the control groups. Systolic left ventricular meridional wall stress was lower in the cyclists than in the runners. The data suggest that runners develop an increase in left ventricular wall thickness which is proportionate to the internal diameter but that in cyclists the increase is disproportionate because of the isometric work of the upper part of the body during cycling.


Comparison of central corneal thickness measurements in corneal edema using ultrasound pachymetry, Visante anterior-segment optical coherence tomography, Cirrus optical coherence tomography, and Pentacam Scheimpflug camera tomography.
To compare the central corneal thickness (CCT) measurements in subjects with corneal edema using ultrasound pachymetry, Visante anterior-segment optical coherence tomography (OCT), Cirrus OCT, and Pentacam Scheimpflug camera tomography. This prospective cross-sectional study included 46 eyes of 33 patients with corneal edema and a CCT exceeding 550 μm evaluated by ultrasound pachymetry, Visante OCT, Cirrus OCT, and Pentacam. Two observers measured each eye twice. Intraobserver and interobserver reproducibility were determined and agreement among the devices calculated. CCT was measured in 40 eyes of 29 patients. Regardless of the CCT, the measurements obtained using Visante OCT, Cirrus CCT, and ultrasound pachymetry were well correlated. Interobserver and intraobserver reproducibility were high among the three devices. Pentacam overestimated the results compared with the other devices, and ultrasound pachymetry was unmeasurable in six (13%) eyes with very thick and opaque corneas. In eyes with mild corneal edema (CCT 551-650 μm), measurements from the four devices were comparable. All devices reliably measured the CCT <650 μm. In eyes with edema exceeding 650 μm, CCT measurements from the Visante OCT, Cirrus OCT, and ultrasound pachymetry devices showed good reproducibility and were well correlated, while the Pentacam overestimated the values compared to the other devices. Pentacam and ultrasound pachymetry should not be used in eyes with extreme corneal edema and opacity.


Convenient and Simple Esterification in Continuous-Flow Systems using g-DMAP.
The utility and applicability of polyethylene-g-polyacrylic acid-immobilized dimethylaminopyridine (g-DMAP) as a catalyst in a continuous-flow system were investigated for decarboxylative esterification. High catalytic activity toward acylation was provided by g-DMAP containing a flexible grafted-polymer structure. During decarboxylation, carboxylic acids and alcohols were converted cleanly using di-tert-butyl dicarbonate (Boc2O) as a coupling reagent, which reduced by-products. In addition, the use of Boc2O resulted in the formation of tert-butyl esters. These esterifications dramatically reduced the reaction time under continuous-flow conditions, with a residence time of approximately 2 min. This highly efficient esterification procedure will provide more practical industrial applications.


Mononuclear Ni(III) complexes [NiIII(L)(P(C6H3-3-SiMe3-2-S)3)]0/1- (L = thiolate, selenolate, CH2CN, Cl, PPh3): relevance to the nickel site of [NiFe] hydrogenases.
The stable mononuclear Ni(III)-thiolate complexes [NiIII(L)(P(C6H3-3-SiMe3-2-S)3)]- (L = SePh (2), Cl (3), SEt (4), 2-S-C4H3S (5), CH2CN (7)) were isolated and characterized by UV-vis, EPR, IR, SQUID, CV, 1H NMR, and single-crystal X-ray diffraction. The increased basicity (electronic density) of the nickel center of complexes [NiIII(L)(P(C6H3-3-SiMe3-2-S)3)]- modulated by the monodentate ligand L and the substituted groups of the phenylthiolate rings promotes the stability and reactivity. In contrast to the irreversible reduction at -1.17 V (vs Cp2Fe/Cp2Fe+) for complex 3, the cyclic voltammograms of complexes [NiIII(SePh)(P(o-C6H4S)3)]-, 2, 4, and 7 display reversible NiIII/II redox processes with E(1/2) = -1.20, -1.26, -1.32, and -1.34 V (vs Cp2Fe/Cp2Fe+), respectively. Compared to complex 2 containing a phenylselenolate-coordinated ligand, complex 4 with a stronger electron-donating ethylthiolate coordinated to the Ni(III) promotes dechlorination of CH2Cl2 to yield complex 3 (kobs = (6.01 +/- 0.03) x 10-4 s-1 for conversion of complex 4 into 3 vs kobs = (4.78 +/- 0.02) x 10-5 s-1 for conversion of complex 2 into 3). Interestingly, addition of CH3CN into complex 3 in the presence of sodium hydride yielded the stable Ni(III)-cyanomethanide complex 7 with a NiIII-CH2CN bond distance of 2.037(3) A. The NiIII-SEt bond length of 2.273(1) A in complex 4 is at the upper end of the 2.12-2.28 A range for the NiIII-S bond lengths of the oxidized-form [NiFe] hydrogenases. In contrast to the inertness of complexes 3 and 7 under CO atmosphere, carbon monoxide triggers the reductive elimination of the monodentate chalcogenolate ligand of complexes 2, 4, and 5 to produce the trigonal bipyramidal complex [NiII(CO)(P(C6H3-3-SiMe3-2-S)3]- (6).


Selective inhibition of the epidermal growth factor receptor tyrosine kinase by BIBX1382BS and the improvement of growth delay, but not local control, after fractionated irradiation in human FaDu squamous cell carcinoma in the nude mouse.
To investigate the effect of BIBX1382BS, an inhibitor of the epidermal growth factor receptor tyrosine kinase, on proliferation and clonogenic cell survival of FaDu human squamous cell carcinoma in vitro, and on tumour growth and local tumour control after fractionated irradiation over 6 weeks in nude mice. FaDu human squamous cell carcinoma is epidermal growth factor receptor positive and significant repopulation during fractionated irradiation was demonstrated in previous experiments. Receptor status, receptor phosphorylation, cell cycle distribution, cell proliferation and clonogenic cell survival after irradiation were assayed with and without BIBX1382BS (5 microM) in vitro. Tumour volume doubling time, BrdUrd and Ki67 labelling indices and apoptosis were investigated in unirradiated tumours growing in NMRI nude mice treated daily with BIBX1382BS (50 mg kg(-1) body weight orally) or carrier. Tumour growth delay and dose-response curves for local tumour control were determined after irradiation with 30 fractions within 6 weeks. BIBX1382BS blocked radiation-induced phosphorylation of the epidermal growth factor receptor and reduced the doubling time of FaDu cells growing in vitro by a factor of 4.9 (p=0.008). Radiosensitivity in vitro remained unchanged after incubation with BIBX1382BS for 3 days and decreased moderately after 6 days (p=0.001). BIBX1382BS significantly reduced the volume doubling time of established FaDu tumours in nude mice by factors of 2.6 when given over 15 days (p<0.001) and 3.7 when applied over 6 weeks (p<0.001). When given simultaneously to fractionated irradiation, growth delay was significantly prolonged by an average of 33 days (p=0.003). Local tumour control was not improved by BIBX1382BS. The radiation doses necessary to control 50% of the tumours locally were 63.6 Gy (95% confidence interval 55; 73) for irradiation alone and 67.8 Gy (60; 77) for the combined treatment (p=0.5). Despite clear antiproliferative activity in rapidly repopulating FaDu human squamous cell carcinoma and significantly increased tumour growth delay when combined with fractionated irradiation, local tumour control was not improved by BIBX1382BS. The results do not disprove that epidermal growth factor receptor inhibition might enhance the results of radiotherapy. However, the results imply that further preclinical investigations using relevant treatment schedules and appropriate endpoints are necessary to explore the mechanisms of action and efficacy of such combinations.


Erratum.
[This corrects the article doi: 10.5935/abc.20180086] [This corrects the article doi: 10.5935/abc.20180190] [This corrects the article doi: 10.5935/abc.20180153] [This corrects the article doi: 10.5935/abc.20180154].


Waldenstrom's Macroglobulinemia and Ascites: A Case Report.
Waldenstrom's disease is characterized by the presence of pathological changes in the B lymphocytes that are in the last stages of maturation. One characteristic of WM is the production of an abnormal high amount of IgM and hyper viscosity syndrome. The MW gets worse, symptoms such as fatigue, weight loss, night sweats, fever, recurrent infections and swollen lymph nodes develop in patients who have a known history of MGUS. In this clinical case, our patient without history of MGUS, presents for the first time for medical observation only for ascites and the presence of an interportocaval lymph node package. An atypical presentation of the disease that makes us reflect on the difficulty of making a diagnosis in the elderly patient and on pathogenetic hypotheses of ascites not yet explored. Seventy-three-year-old patient, hospitalized for the onset of ascites with sloping edema, diffuse left pulmonary opacification. At the ultrasound check, cava and portal vessels patent and of regular caliber, however with inversion of flow in correspondence with the right branch and of the door to the hilum, with a subdiaphragmatic retrocaval focus with a maximum diameter of about 3 cm, which cannot be better viewed. CT scan of the abdomen with confirmation of the presence of an interportocaval lymph node package. After evidence of the electrophoretic protein picture of a double component, probably monoclonal with positive urinary immunofixation for free K chains. IgM dosage equal to 2190 mg. Serum immunofixation practice that confirms the diagnosis of type B lymphoproliferative syndrome as per Waldenstrom's disease, confirmed by bone marrow aspiration with morphological and flow cytometric study. Immediately begin chemotherapy with Bendamustine 120 mg. After 4 weeks of therapy with the reduction of IgM values, the patient no longer presented ascites. This case has an unusual presentation of this disease and we could shed a new light on the possible pathogenesis of portal hypertension in Waldenstrom'disease.