Fundamentals of Scholarly Peer Review: A Workshop for Health Professions Educators on Practicing Scholarly Citizenship.
Education scholarship requires peer reviewers. For novice scholars, reviewing is an important developmental activity that cultivates deeper participation in the scholarship community. Yet getting started with reviewing is challenging for those not involved with the educational scholarship community. Beyond scientific expertise, reviewers must have a mentoring mindset, skills in providing constructive feedback, and knowledge of common ethical challenges associated with producing and evaluating scholarship. Our workshop introduced novice health professions educators to peer reviewing. It included four stimulus presentations about the peer reviewer's mindset and skills, followed by reinforcement activities. The workshop could be adapted to variously sized groups. An 8:1 ratio of participants to facilitators was ideal for activities. Topics covered included considerations before accepting an invitation, the review process, the good citizen approach to reviewing, and reviewer ethics. The session concluded with suggestions for continued development of peer reviewer competencies. The workshop was evaluated using a custom survey. Throughout 2019 and early 2020, 58 health professions educators and trainees participated in the workshop across varied venues. Evaluations were obtained from 33 participants (57%). Nearly all rated the workshop as high quality and valuable to peer reviewer preparation. Most (26 of 33; 75%) gained confidence about their qualifications to serve as reviewers. Eighty percent (28 of 33) believed they could recognize ethical dilemmas. This workshop provided a springboard for peer reviewing health professions education scholarship. Participants generally praised the experience for introducing them to the world of peer review and preparing them for it.


Template-free synthesis of phosphate-based spheres via modified supersaturated phosphate buffer solutions.
Modified supersaturated phosphate buffer solutions were used to synthesize phosphate-based spheres, including calcium phosphate (CaP), strontium phosphate (SrP) and barium phosphate (BaP). A series of ions concentrations in the modified phosphate buffer solutions were investigated in order to study their effects in precipitates morphologies. During synthesis, it was found that magnesium was the key factor in sphere formation. The morphologies of calcium phosphate, strontium phosphate and barium phosphate precipitates varied as the concentration of magnesium ions varied. When sufficient magnesium was provided, the precipitates appeared spherical, and the diameter was in range of 0.5-2 μm. The morphologies, compositions and structure of spheres were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and N2 adsorption analysis. Moreover, the application of magnesium substituted calcium phosphate spheres in dentin tubules occlusion was investigated.


Sulfonation Disposition of Acacetin: In Vitro and in Vivo.
Acacetin, an important component of acacia honey, exerts extensive therapeutic effects on many cancers. However, the sulfonation disposition of acacetin has rarely been reported. Therefore, this study aimed to investigate the sulfonation disposition of acacetin systematically. The results showed that acacetin-7-sulfate was the main metabolite mediated primarily by sulfotransferases (SULT) 1A1. Dog liver S9 presented the highest formation rate of acacetin-7-sulfate. Compared with that in wild-type Friend Virus B (FVB) mice, plasma exposure of acacetin-7-sulfate decreased significantly in multidrug resistance protein 1 knockout (Mrp1-/-) mice vut increased clearly in breast cancer resistance protein knockout (Bcrp-/-) mice. In Caco-2 monolayers, the efflux and clearance of acacetin-7-sulfate was reduced distinctly by the BCRP inhibitor Ko143 on the apical side and by the MRP1 inhibitor MK571 on the basolateral side. In conclusion, acacetin sulfonation was mediated mostly by SULT1A1. Acacetin-7-sulfate was found to be transported mainly by BCRP and MRP1. Hence, SULT1A1, BCRP, and MRP1 are responsible for acacetin-7-sulfate exposure in vivo.


Intrinsic Frequency Analysis and Fast Algorithms.
Intrinsic Frequency (IF) has recently been introduced as an ample signal processing method for analyzing carotid and aortic pulse pressure tracings. The IF method has also been introduced as an effective approach for the analysis of cardiovascular system dynamics. The physiological significance, convergence and accuracy of the IF algorithm has been established in prior works. In this paper, we show that the IF method could be derived by appropriate mathematical approximations from the Navier-Stokes and elasticity equations. We further introduce a fast algorithm for the IF method based on the mathematical analysis of this method. In particular, we demonstrate that the IF algorithm can be made faster, by a factor or more than 100 times, using a proper set of initial guesses based on the topology of the problem, fast analytical solution at each point iteration, and substituting the brute force algorithm with a pattern search method. Statistically, we observe that the algorithm presented in this article complies well with its brute-force counterpart. Furthermore, we will show that on a real dataset, the fast IF method can draw correlations between the extracted intrinsic frequency features and the infusion of certain drugs.


Review of MammoSite brachytherapy: advantages, disadvantages and clinical outcomes.
The MammoSite radiotherapy system is an alternative treatment option for patients with early-stage breast cancer to overcome the longer schedules associated with external beam radiation therapy. The device is placed inside the breast surgical cavity and inflated with a combination of saline and radiographic contrast to completely fill the cavity. The treatment schedule for the MammoSite monotherapy is 34 Gy delivered in 10 fractions at 1.0 cm from the balloon surface with a minimum of 6 hours between fractions on the same day. This review article presents the advantages, disadvantages, uncertainties and clinical outcomes associated with the MammoSite brachytherapy (MSB). Potential advantages of MSB are: high localised dose with rapid falloff for normal tissue sparing, minimum delay between surgery and RT, catheter moves with breast, improved local control, no exposure to staff, likely side-effects reduction and potential cost/time saving (e.g. for country patients). The optimal cosmetic results depend on the balloon-to-skin distance. Good-to-excellent cosmetic results are achieved for patients with balloon-skin spacing of > or =7 mm. There have been very few published data regarding the long term tumour control and cosmesis associated with the MSB. The available data on the local control achieved with the MSB were comparable with other accelerated partial breast irradiation techniques. The contrast medium inside the balloon causes dose reduction at the prescription point. Current brachytherapy treatment planning systems (BTPS) do not take into account the increased photon attenuation due to high Z of contrast. Some BTPS predicted up to 10% higher dose near the balloon surface compared with Monte Carlo calculations using various contrast concentrations (5-25%). Initial clinical results have shown that the MammoSite device could be used as a sole radiation treatment for selected patients with early stage breast cancer providing good local control, minimal complication rate and excellent cosmesis.


Patient selection and results of cardiac transplantation in patients with cardiomyopathy.
Cardiac transplantation for the treatment of end-stage congestive heart failure has been shown to be of benefit regardless of the etiology. With few exceptions, the evaluation of patients with end-stage heart failure is the same, regardless of the etiology. In those with cardiomyopathy not as a result of CAD, special attention must be given to exclude secondary causes of cardiomyopathy such as amyloidosis, hemochromatosis, and sarcoidosis, as well as generalized systemic illnesses that may also involve the heart, either secondary or hereditary, because special consideration must be given to these patients on a case-by-case basis to determine that there is no general systemic involvement of the illness that would preclude satisfactory rehabilitation after transplantation. Before cardiac transplantation becomes widely available, there must be a greater number of donor hearts, the lack of which now severely limits the number of transplants performed in comparison with the estimated need.66 Additionally, more effective and specific immunosuppressive agents must be identified in order to reduce the incidence of rejection, infection, and accelerated atherosclerosis that now limits the longevity of transplant recipients. Furthermore, the ideal immunosuppressive agent should be associated with fewer side effects than those currently available. The emotional and economic burdens placed on the patient, the family, and society must be balanced against the benefits generated by the procedure. Despite these limitations, cardiac transplantation continues to offer hope for the terminally ill patient, which must be tempered by an understanding of the real limitations of transplantation.


HGF/c-Met: A Key Promoter in Liver Regeneration.
Hepatocyte growth factor (HGF) is a peptide-containing multifunctional cytokine that acts on various epithelial cells to regulate cell growth, movement and morphogenesis, and tissue regeneration of injured organs. HGF is sequestered by heparin-like protein in its inactive form and is widespread in the extracellular matrix of most tissues. When the liver loses its average mass, volume, or physiological and biochemical functions due to various reasons, HGF binds to its specific receptor c-Met (cellular mesenchymal-epithelial transition) and transmits the signals into the cells, and triggers the intrinsic kinase activity of c-Met. The downstream cascades of HGF/c-Met include JAK/STAT3, PI3K/Akt/NF-κB, and Ras/Raf pathways, affecting cell proliferation, growth, and survival. HGF has important clinical significance for liver fibrosis, hepatocyte regeneration after inflammation, and liver regeneration after transplantation. And the development of HGF as a biological drug for regenerative therapy of diseases, that is, using recombinant human HGF protein to treat disorders in clinical trials, is underway. This review summarizes the recent findings of the HGF/c-Met signaling functions in liver regeneration.


Effect of subunit dissociation, denaturation, aggregation, coagulation, and decomposition on enzyme inactivation kinetics: II. Biphasic and grace period behavior.
A model previously developed to characterize enzymatic in activation behavior was used to explain the non-first-order biphasic and grace period phenomena that are often observed with oligomeric enzymes. Luciferase and urease were used as model enzyme such as luciferase, the oligomer initially dissociates reversibly into two native monomer species. These native monomers can then reversibly denature and irreversibly aggregate and coagulate. With the hexamer, urease, two trimers are formed that can subsequently aggregate to form an inactive hexamer. The dissociated monomer species of luciferase do not possess catalytic activity, so the inactivation mechanism, is biphasic; the first slope of a first-order kinetic plot is influenced by the reversible oligomer/monomer/denatured-monomer transition. Whereas the second slope is associated with either irreversible aggregation or coagulation. In contrast, the trimer of urease has the same activity as the hexamer; therefore, during the intitial hexamer-trimer transition, little activity loss occurs. However, as the trimer concentration increases, activity decreases as a result of trimer aggregation. As a result, grace period inactivation behavior is observed.


Concentration-dependent preferences of absorptive and excretive transport cause atypical intestinal absorption of cyclic phenylalanylserine: small intestine acts as an interface between the body and ingested compounds.
Intestinal absorption of cyclic phenylalanylserine (cyclo(Phe-Ser)), a precursor of gliotoxin, was studied in isolated rat small intestine as a model cyclic dipeptide. Absorption clearance (CLabs) decreased in the presence of glycylsarcosine, cephalexin or cephradine, substrates for H+/oligopeptide cotransporter (PEPT1). CLabs of cyclo(Phe-Ser) also decreased at 4 degrees C. These indicate that cyclo(Phe-Ser) is in part transported by PEPT1. However, Eadie-Hofstee plot of absorption revealed an atypical profile at lower concentrations of cyclo(Phe-Ser) (around 0.1 mM). Moreover, comparative experiments of absorptive and excretive transport showed that excretive transport from the serosal to mucosal side of isolated intestinal tissue at a 0.1 mM cyclo(Phe-Ser) was superior to absorptive transport from the mucosal side to the serosal side, and vise versa at a 1 mM cyclo(Phe-Ser). These results as well as the results of kinetic analysis indicate that intestinal absorption consists of passive transport, carrier-mediated absorptive transport by PEPT1 and carrier-mediated excretive transport, resulting in atypical absorption. Although cyclic dipeptides have potentials for drug, their intestinal absorption may be complex. The results of this study lead us conclude that absorptive and excretive transport by the small intestine acts as an interface between the body and ingested compounds.


Evaluation of efficacy and safety for bevacizumab in treating malignant pleural effusions caused by lung cancer through intrapleural injection.
Some clinical investigations have assessed the efficacy and safety of bevacizumab combined with platinum anti-cancer drugs versus platinum drugs alone in treating malignant pleural effusion (MPE) caused by lung cancer through intrapleural injection. This report is a meta-analysis of independent research conclusions. Eleven controlled trials with 769 MPE patients were included in this report. Pooled odds ratios and standardized mean difference with 95% confidence intervals were estimated using the fixed or random effects model of meta-analysis. For treating MPE through intrapleural injection, bevacizumab combined with platinum chemotherapy drugs increased the overall response rate (p = 0.003), decreased the incidence of chest pain (p < 0.001) and relieved the dyspnea of patients with MPE (p = 0.002), as compared with platinum chemotherapy drugs alone. In addition, intrapleural injection of bevacizumab participation decreased the expression of vascular endothelial growth factor in MPE (p < 0.001). The main adverse effects of two groups were myelotoxicity, hypertension, digestive reaction and damage of liver and kidney. However, the presence of bevacizumab did not show an extra influence on the incidence of adverse effects (p > 0.05). In summary, bevacizumab combined with platinum chemotherapy drugs for treating MPE caused by lung cancer through intrapleural injection has a better benefit of overall response rate and quality of life. And, the participation of bevacizumab did not increase adverse effects.


Catalytic dechlorination of chlorobenzene in water by Pd/Fe bimetallic system.
Catalytic reductive dechlorination of monochlorobenzene(MCB) was carried out in the palladium/iron system. With low Pd loading (0.005%), 45% dechlorination efficiency was achieved within 5 h. Pd as catalyst accelerated the reductive dechlorination reaction. Dechlorination mechanism and kinetics were discussed. The reaction took place on the bimetal surface in a pseudo-first-order reaction, with the rate constant being 0.0071 min(-1) (K(SA) = 8.0 x 10(-3) L/(m2 x h)). The reduction product for MCB was benzene.


A hypoxia-inducible gene expression system using erythropoietin 3' untranslated region for the gene therapy of rat spinal cord injury.
Many neurologic disorders are accompanied by ischemic injury during the pathologic process. To develop a controllable and injury-specific gene therapy system for the neurologic disorders, we constructed a hypoxia inducible plasmid with the erythropoietin (Epo) 3' untranslated region (UTR), which can enhance the stability of target mRNAs in response to hypoxia. The Epo 3' UTR was inserted at the 3' flanking region of luciferase gene in pSV-Luc, resulting in the construction of pSV-Luc-EpoUTR. In pEpo-SV-Luc-EpoUTR, the Epo enhancer was inserted into the upstream of the SV40 promoter to increase the hypoxia inducibility. The plasmids were evaluated in N2a mouse neuroblastoma cells under hypoxic conditions and in a rat spinal cord injury (SCI) model. The results showed that the Epo 3' UTR alone showed a three-fold increase in luciferase activity in hypoxic N2a cells as well as in the rat SCI model when compared to the sham control. In contrast, the Epo 3' UTR showed no effect on the luciferase activity in the presence of the Epo enhancer, probably because the Epo enhancer was more sensitive to hypoxia and showed a dominant effect. However, the Epo enhancer itself showed high level of luciferase activity even in normoxia (about five to eight-folds increase), while the Epo 3' UTR did not show enhanced background activity. Immunohistochemical staining showed expression of luciferase from pSV-Luc-EpoUTR both in neurons and astrocytes around the injured spinal cord of rat. These results suggest that the Epo 3' UTR could provide a specific and safe system for the hypoxia-inducible gene therapy of the neurologic disorders including SCI.


[Dermatology: science and art of sighting].
Art is beauty, reasoning, science and profession. Medicine is an art because it combines all these skills. But in the practice of medicine, experience is required and it can only be obtained through practice. Dermatology is also an art; it is learned through looking. To look is the act of perceiving the color and form of things through the eyes. The dermatologist utilizes art to learn, he uses observation, knowledge, reasoning to observe artwork. And through these acts he starts to observe figures, colors, and finally forms a pattern. After repeating this act, he establishes experience, and that is when the dermatologist learns the true art of dermatology, the art of seeing.


Distractive auditory stimuli reduce the unpleasantness of dyspnea during exercise in patients with COPD.
Dyspnea is the primary symptom limiting exercise in patients with COPD. Recent research has demonstrated that psychological factors can substantially influence the perception of dyspnea, but little is known about the modulation of perceived intensity or unpleasantness of dyspnea by attentional distraction. Therefore, we examined the impact of distractive auditory stimuli on the perception of exercise-induced dyspnea and the affective state in patients with COPD during 6-min walking tests (6MWTs). Twenty patients with mild-to-severe COPD (mean FEV1, 55.9% predicted) underwent two 6MWTs. Under one exercise condition, distractive auditory stimuli were presented with headphones, while the other condition was performed without auditory distraction. Lung function (FEV1), heart rate (HR), pulse oximetric saturation (SpO2), perceived intensity of dyspnea (ie, visual analog scale for perceived intensity of dyspnea [VAS-I]), and perceived unpleasantness of dyspnea (visual analog scale for perceived unpleasantness of dyspnea [VAS-U]) were measured before and after exercise. In addition, the global level of dyspnea (Borg score), positive affectivity (PA), and negative affectivity were assessed after both conditions. A similar exercise level during both conditions was confirmed by comparable results in FEV1, HR, SpO2, and distances walked. During auditory distraction, Borg scores and increases in VAS-U were smaller, while PA was higher compared to the nondistraction condition (p<0.05). VAS-I did not show differences across conditions. Distractive auditory stimuli decrease the global level of exercise-induced dyspnea in patients with COPD by reducing the perceived unpleasantness of dyspnea and lead to an additional increase in PA. Auditory distraction might therefore serve as an intervention for the reduction of dyspnea during exercise in this patient group.


Establishing a critical pathway for Korean medical management of lumbar disc herniation: A modified Delphi consensus process.
A modified Delphi method was used to establish a consensus. Stakeholders and experts were invited to participate in the expert panel. Best practice statements and decision-making questionnaires were distributed to the panel. Panel members were asked to mark "Strongly disagree" to "Strongly agree" after a series of statements over several rounds until either a consensus was reached or the decision-making method was deemed unsuitable for reaching a consensus.The most common cause of lumbar pain is intervertebral degeneration, which leads to degenerative disc disease and lumbar disc herniation. There is a lack of unanimity regarding appropriate patient protocols and rehabilitation expectations for Korean medical care. The long-term viability of Korean medical treatment, further adoption in the institutional setting, and specific patient outcomes are contingent on the existence of appropriate Korean medical programs.A Korean medical expert panel of 17 practitioners employed a modified Delphi method to achieve consensus on Korean medical care for lumbar disc herniation. The panel first reviewed the literature and guidelines relevant to Korean medical treatment for lumbar disc herniation. The panel members considered questionnaires intended to determine "standardized" Korean medical care recommendations for patients with a wide range of symptoms of lumbar disc herniation. Each panel member participated in a round of voting, which was followed by an opinion-collecting session online. Consensus was defined as a ≥75% agreement among the respondents.In the first round, 144 questionnaires across 5 domains were administered to the expert panels. After reviewing the responses and open-ended comments collected in the first round, the authors modified the questionnaires to 53 items and proceeded. In round 2, consensus was achieved in all 53 survey questions. The final treatment pathway comprised a standardized and comprehensive care approach for lumbar disc herniations in 4 types of medical institutions.This study identified a core set of evidence- and consensus-based principles that are essential to a comprehensive model of care, incorporating identification, referral, and management of patients with lumbar disc herniation.


Trochanteric fractures. Mobility, complications, and mortality in 607 cases treated with the sliding-screw technique.
Six hundred seven trochanteric fractures (563 patients) were treated with a sliding-screw technique and followed clinically and roentgenographically for at least one year. Of 351 patients admitted from their homes, 209 (60%) were discharged to their homes after an average of 18 days in the hospital. During the first year another 61 (17%) patients returned home after rehabilitation in a geriatric ward. Of 446 patients walking without support or with one cane before surgery, 360 (80%) had regained the same mobility after one year. The one-year mortality rate was 18%, while the ten-year rate was 74%. Compared with a control cohort, the mortality rate was increased during the first two years after fracture. The increase in mortality was influenced by advanced age, admission from long-term care institutions, male gender, and ambulatory or nonambulatory status before surgery. Forty-five (7.4%) were reoperated, 17 because of technical complications, three because of infection, and three because of nonunion. No further nonunions occurred. The deep infection rate was nine of 339 (2.7%) before and two of 268 (0.8%) after the introduction of antibiotic prophylaxis. Thromboembolic complications decreased from 4.1% to 1.2% after the introduction of dextran 70 as thromboembolic prophylaxis.


CD94/NKG2 inhibitory receptor complex modulates both anti-viral and anti-tumoral responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes.
Viral, bacterial, protozoal, and cancer-associated Ags elicit strong responses in human gammadelta T lymphocytes. The majority of these cells in the peripheral blood express the Vgamma9Vdelta2-encoded TCR and recognize nonpeptidic phosphoantigens without an apparent MHC restriction. We have shown that Vgamma9Vdelta2 T cells express the inhibitory CD94/NKG2 receptor for HLA class I molecules. The anti-CD94 mAb inhibits 1) the Vgamma9Vdelta2 T cell proliferation in response mycobacterial phosphoantigens and 2) the HIV-induced Vgamma9Vdelta2 T cell expansion. Vgamma9Vdelta2 T cells stimulated with nonpeptidic mycobacterial antigens produce IFN-gamma and TNF-alpha. Signaling through the CD94/NKG2 receptor interferes with the synthesis of these cytokines. The CD94/HLA class I interaction is also involved in the cytotoxic activity of Vgamma9Vdelta2 T cells. The Vgamma9Vdelta2 T cell regulation through the CD94 receptor may be important for the potentially dual function in innate immunity, i.e., 1) NK-like and 2) TCR ligand-induced cytolytic activities.


Spontaneous porto-systemic shunts in liver cirrhosis: Clinical and therapeutical aspects.
Spontaneous porto-systemic shunts (SPSS) are frequent in liver cirrhosis and their prevalence increases as liver function deteriorates, probably as a consequence of worsening portal hypertension, but without achieving an effective protection against cirrhosis' complications. Several types of SPSS have been described in the literature, each one associated with different clinical manifestations. In particular, recurrent or persistent hepatic encephalopathy is more frequent in patients with splenorenal shunt, while the presence of gastric varices and consequently the incidence of variceal bleeding is more common in gastrorenal shunt. In the advanced stage, the presence of large SPSS can lead to the so called "portosystemic shunt syndrome", characterized by a progressive deterioration of hepatic function, hepatic encephalopathy and, sometimes, portal vein thrombosis. The detection of SPSS in patients with liver cirrhosis is recommended in order to prevent or treat recurrent hepatic encephalopathy or variceal bleeding.


Normative pediatric brain data for spatial normalization and segmentation differs from standard adult data.
Spatial normalization and morphological studies of pediatric brain imaging data based on adult reference data may not be appropriate due to the developmental differences between the two populations. In this study, we set out to create pediatric templates and a priori brain tissue data from a large collection of normal, healthy children to compare it to standard adult data available within a widely used imaging software solution (SPM99, WDOCN, London, UK). Employing four different processing strategies, we found considerable differences between our pediatric data and the adult data. We conclude that caution should be used when analyzing pediatric brain data using adult a priori information. To assess the effects of using pediatric a priori brain information, the data obtained in this study is available to the scientific community from our website (www.irc.cchmc.org).


[Bioethics in Latin America: legal perspective].
The jurist's work is to detect the legal guiding principles, analize them and to anticipate what kind of acceptance they will have. The legislator must be prudent if the subject studied is changeable as it happens with the norms applied in Bioethics. This detection process is more delicate if the guiding principles that have to be detected are valid for such an extensive region, as it is Latin America, where the legislation of the different countries that form it would adopt them. The two problems that will be studied here are: a) if it is advisable or not to raise some Bioethic basic principles to the constitutional level. b) which are the main principles that have been adopted by the juridical legislations of Latin America and who, in some way, guide the legal regulation.


Interleukin 1 production by alveolar macrophages is decreased in smokers.
To evaluate the mechanism by which cigarette smoking suppresses pulmonary immune responses, we determined the capacity of alveolar macrophages (AM) to produce interleukin 1 (IL-1 in 32 normal subjects and in 40 patients with pulmonary sarcoidosis. The amount of IL-1 released from LPS-stimulated AM from smokers was significantly decreased compared with that in nonsmokers in both normal and sarcoid groups. The addition of indomethacin to the cultures in 18 normal subjects and in 22 patients with pulmonary sarcoidosis yielded similar results, thus excluding the possibility that this difference resulted from a difference in the amount of cyclooxygenase metabolites released in the culture supernatants. Similar results were obtained by enzyme-linked immunosolvent assay. Because IL-1 is thought to induce the accumulation of T cells at the site of disease and contribute to local cellular and humoral immunity of the lung, our data suggest that the reduced capacity of AM to release IL-1 in smokers affords partial protection against the initiation of immune responses in the lung and the development of granulomatous lung diseases.


[Insulin secretion and catecholamine content in the blood plasma in initial stages of cardiac insufficiency].
Test for glucose tolerance was performed in 28 patients with ischemic heart disease and stage IIA circulatory insufficiency and repeated in 17 of them after treatment with cardiac glycosides. The blood collected on an empty stomach, 60 and 120 min after oral administration of 50 g of glucose was tested for the sugar content and the plasma for the content of immunoreactive insulin. In some of these patients the plasma of blood collected on an empty stomach was tested for the contents of noradrenaline and adrenaline. No statistically reliable difference was revealed in the plasma immunoreactive insulin level in patients with ischemic heart disease and stage IIA circulatory insufficiency before and after treatment and also as compared to that in patients with ischemic heart disease but no clinical signs of circulatory insufficiency. In patients with circulatory insufficiency the content of noradrenaline and adrenaline in blood plasma was higher before treatment than after it, but the difference was statistically reliable only in the case of noradrenaline. The degree of intensification of the activity of the sympathicoadrenal system in patients with ischemic heart disease and initial stages of circulatory insufficiency is evidently not sufficient for inhibiting insulin secretion.


Hybridomas producing human monoclonal antibodies against varicella-zoster virus.
Hybridomas producing human monoclonal antibodies (mAb) against varicella-zoster virus (VZV) were generated by fusing human splenic lymphocytes with mouse myeloma cells. Before cell fusion, lymphocytes were stimulated in vitro with viral antigens and pokeweed mitogen. This combination synergistically increased the generation of VZV-specific hybridomas. Five established hybridomas have been stably producing mAb for at least 9 months. These mAb, designated V1, V2, V6, V8 and V9, were of the IgG1, lambda isotype. They bound to all 6 tested VZV strains but not to other herpes viruses, with the exception that V1 bound to herpes simplex virus (HSV) as well as VZV. Immunoprecipitation analysis showed that V1, V6 and V9 recognized glycoprotein gpII, whereas V2 and V8 recognized gpI. In addition, V1 reacted with the gB glycoprotein of HSV. All these mAb neutralized viral infectivity. The neutralizations by V2 and V8 were more effective and more complement dependent than those by V1, V6 and V9. Immunofluorescence tests revealed that all these mAb bound to the surface membrane of VZV-infected cells. These results suggest that cell fusion between in vitro stimulated lymphocytes and mouse myeloma cells is a reliable method for the generation of hybridomas capable of stable production of human mAb. The human mAb thus developed may provide a new means of passive immunization of humans against VZV infection.


Management of Entamoeba histolytica in the non-human primates at the Singapore Zoo.
Amebic dysentery caused by Entamoeba histolytica accounts for significant morbidity in the non-human primates (NHP) at the Singapore Zoo. This includes the animals in the collection as well as a sizeable free-roaming wild crab-eating macaque (Macaca fascicularis) population. The disease is of great concern because of its zoonotic potential. Passive surveillance, both ante and post-mortem, of NHP displaying clinical symptoms and active surveillance of NHP assessed to be at a higher risk of infection were carried out via fecal real-time polymerase chain reaction (PCR) testing for 4 years. Treatment of the disease with 25 mg/kg metronidazole BID for 10 days followed by 15 mg/kg paromomycin BID for 7 days achieved good clinical resolution in most cases that tested positive. Three diseased NHP with severe clinical signs of weight loss, lethargy, and diarrhea were anesthetized for veterinary diagnostic investigation. Mesenteric lymphadenopathy was consistently seen on ultrasound examination in these severe cases of entamoebiasis. Two animals eventually died of severe chronic enteritis due to the disease. The eradication of entamoebiasis in the NHP at the Singapore Zoo may be complicated by the maintenance of a disease reservoir in wildlife, but a combination of timely treatment and efforts at maintaining biosecurity can help manage the disease in the collection.


Diurnal changes in salivary amino acid concentrations.
It has been suggested that the features of saliva (e.g. fluidity, secretion and amino acid concentration) reflect physiological and psychological state of primates as well as subprimates, however, studies which revealed the relationship between the circadian rhythm and the concentrations of salivary amino acids have been limited. In order to better understand their physiological role, diurnal changes of salivary amino acids were investigated in three undergraduate students. Salivary amino acids were recovered after deproteinization with 5% trichloroacetic acid and determined by an amino acid analyzer. Most amino acids, except for methionine, cysteine and asparagine, were detected in the saliva. The intake of lunch or amino acid supplement transiently increased the salivary amino acids, and in the latter case, the amino acid levels returned to baseline within 10 minutes. Physical exercise also slightly elevated the salivary amino acid levels. During the university examination period, the secretion of saliva was slightly, but not significantly, increased, accompanied by the elevation of glycine, alanine, ornithine, histidine and threonine, and the decline of lysine, leucine, aspartic acid and hydroxyproline. Salivary amino acid levels may be useful to evaluate stressful conditions.


Customizable single-layer hydrogel robot with programmable NIR-triggered responsiveness.
Hydrogel robots are widely used in biomedical fields due to their excellent biocompatibility and response to external stimuli. However, traditional processing methods cannot rapidly fabricate complex structures, and smart response strategies often rely on double-layer structures fabricated from two materials with significantly different swelling properties. In this study, we present a single-layer hydrogel robot that can be fabricated in one step using a high-precision digital light processing (H-P DLP) 3D printing system. The robot has structural differences and the ability to maintain a repetitive response. Additionally, we fabricated several robot grippers to demonstrate their potential for customization and programming, as well as their potential applications in cargo delivery. Our work provides a new approach to achieve the formation and response of various irregular hydrogels, which is expected to advance the development of biomedical applications.


[Pheochromocytoma with reversal of tako-tsubo-like transient left ventricular dysfunction: a case report].
A 59-year-old male was admitted to the emergency department because of sustained chest oppression. Electrocardiography revealed J type ST depression and peaked T wave in leads II, III, aVF, and V4-V6. No stenosis was found in the coronary arteries by urgent coronary angiography. Left ventricular abnormal wall movement with akinesis in the base and hyperkinesis in the apical area was observed and improved on the 12th day. Myocardial scintigraphy with iodine-123-metaiodobenzylguanidine showed completely defective images and decreased accumulation in the base with combined thallium-201 and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid. Myocardial biopsy on the 12th day disclosed contraction band necrosis. The diagnosis was catecholamine-induced cardiomyopathy caused by pheochromocytoma.


Partial portal decompression for variceal hemorrhage.
To test the hypothesis that partial portal decompression in the treatment of variceal hemorrhage will diminish subsequent encephalopathy, 50 consecutive patients were studied after construction of a small-stoma (10 to 12 mm) side-to-side portacaval shunt, with the goal of a postoperative portacaval pressure gradient of 10 mm Hg. During follow-up averaging 26 months, six patients (12 percent) died. Four patients (8 percent) had episodes of rebleeding, only one from varices. All patients had patent shunts at subsequent angiography or ultrasonography. Despite consistent (100 percent) postoperative reversal or stagnation of portal flow on duplex scan, encephalopathy on clinical and psychometric grounds was observed in only three patients (6 percent). This study suggests that small-stoma portacaval shunt can be performed with reliably low rates of rebleeding and encephalopathy. That encephalopathy was rare despite loss of hepatic portal perfusion incriminates other factors besides portal flow in the genesis of postshunt hepatic failure.


Time- and radiation-dose dependent changes in the plasma proteome after total body irradiation of non-human primates: Implications for biomarker selection.
Acute radiation syndrome (ARS) is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI) in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy) with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure.


International Society of Urological Pathology (ISUP) Gleason Grade Groups stratify outcomes in the CHHiP Phase 3 prostate radiotherapy trial.
To compare the results of Gleason Grade Group (GGG) classification following central pathology review with previous local pathology assessment, and to examine the difference between using overall and worst GGG in a large patient cohort treated with radiotherapy and short-course hormone therapy. Patients with low- to high-risk localized prostate cancer were randomized into the multicentre CHHiP fractionation trial between 2002 and 2011. Patients received short-course hormone therapy (≤6 month) and radical intensity-modulated radiotherapy (IMRT). Of 2749 consented patients, 1875 had adequate diagnostic biopsy tissue for blinded central pathology review. The median follow-up was 9.3 years. Agreement between local pathology and central pathology-derived GGG and between central pathology-derived overall and worst GGG was assessed using kappa (κ) statistics. Multivariate Cox regression and Kaplan-Meier methods were used to compare the biochemical/clinical failure (BCF) and distant metastases (DM) outcomes of patients with GGG 1-5. There was poor agreement between local pathology- and central pathology-derived GGG (κ = 0.19) but good agreement between overall and worst GGG on central pathology review (κ = 0.89). Central pathology-derived GGG stratified BCF and DM outcomes better than local pathology, while overall and worst GGG on central pathology review performed similarly. GGG 3 segregated with GGG 4 for BCF, with BCF-free rates of 90%, 82%, 74%, 71% and 58% for GGGs 1-5, respectively, at 8 years when assessed using overall GGG. There was a progressive decrease in DM-free rates from 98%, 96%, 92%, 88% and 83% for GGGs 1-5, respectively, at 8 years with overall GGG. Patients (n = 57) who were upgraded from GGG 2-3 using worst GS had BCF-free and DM-free rates of 74% and 92% at 8 years. CHHiP eligibility criteria limit the interpretation of these results. Contemporary review of International Society of Urological Pathology GGG successfully stratified patients treated with short-course hormone therapy and IMRT with regard to both BCF-free and DM-free outcomes. Patients upgraded from GGG 2 to GGG 3 using worst biopsy GS segregate with GGG 3 on long-term follow-up. We recommend that both overall and worst GS be used to derive GGG.


Genomic insights into the diversity, virulence and resistance of Klebsiella pneumoniae extensively drug resistant clinical isolates.
Klebsiella pneumoniae has been implicated in wide-ranging nosocomial outbreaks, causing severe infections without effective treatments due to antibiotic resistance. Here, we performed genome sequencing of 70 extensively drug resistant clinical isolates, collected from Brasília's hospitals (Brazil) between 2010 and 2014. The majority of strains (60 out of 70) belonged to a single clonal complex (CC), CC258, which has become distributed worldwide in the last two decades. Of these CC258 strains, 44 strains were classified as sequence type 11 (ST11) and fell into two distinct clades, but no ST258 strains were found. These 70 strains had a pan-genome size of 10 366 genes, with a core-genome size of ~4476 genes found in 95 % of isolates. Analysis of sequences revealed diverse mechanisms of resistance, including production of multidrug efflux pumps, enzymes with the same target function but with reduced or no affinity to the drug, and proteins that protected the drug target or inactivated the drug. β-Lactamase production provided the most notable mechanism associated with K. pneumoniae. Each strain presented two or three different β-lactamase enzymes, including class A (SHV, CTX-M and KPC), class B and class C AmpC enzymes, although no class D β-lactamase was identified. Strains carrying the NDM enzyme involved three different ST types, suggesting that there was no common genetic origin.


Herpes simplex ocular disease.
The present epidemic of genital herpes has led to broad concern among both physicians and lay persons. For those who specialize in cornea and external disease, this new awareness provides a much needed opportunity to discuss ocular herpetic disease. Through ongoing medical education, great strides are being made toward early diagnosis and appropriate therapy. The primary care physician occupies a pivotal position in these efforts.


Development and comparison of four real-time polymerase chain reaction systems for specific detection and quantification of Zea mays L.
Four real-time polymerase chain reaction systems aiming at the specific detection and quantification of maize DNA are described. They have been developed in four independent laboratories targeting different maize sequences, i.e., alcohol dehydrogenase (Adh1), high mobility group protein (hmga), invertase A (ivr1), and zein, respectively. They were all fully specific, showing a very similar quantification accuracy along a number of distantly related maize cultivars and being either single or low copy number genes. They were highly sensitive and exhibited limits of quantification below 100 maize genomic copies. In consequence, they are considered suitable for use as maize specific endogenous reference genes in DNA analyses, including GMO quantitative tests.


Codependence of renal calcium and sodium transport.
Calcium and sodium absorption by the kidney normally proceed in parallel. However, a number of physiological, pharmacological, pathological, and genetic conditions dissociate this relation. In each instance, the dissociation can be traced to the distal convoluted tubule, where calcium and sodium transport are inversely related. Based on the identification of the relevant sodium transporters in these cells and on analysis of the mechanism of calcium transport, an explanation for this inverse relation can be developed. Apical membrane calcium entry is mediated by voltage-sensitive calcium channels that are activated upon membrane hyperpolarization. Basolateral calcium efflux is effected primarily by Na+/Ca2+ exchange. According to the model, inhibition of sodium entry through either the Na-Cl cotransporter or the Na+ channel hyperpolarizes the cell, as does parathyroid hormone, thereby activating the calcium entry channel and increasing the driving force for diffusional entry. Membrane hyperpolarization also increases the driving force of calcium efflux through the Na+/Ca2+ exchanger. Thus sodium-dependent changes of calcium transport are indirect and occur secondarily through effects on membrane voltage.


Controlling the Conformation of 2-Dimethylaminobiphenyls by Transient Intramolecular Hydrogen Bonding.
Temporal control of molecular motions is receiving increasing attention because it is central to the development of molecular switches and motors and nanoscopic materials with life-like properties. Inspired by previous studies, here, we report that acid 12 can be used to temporally control the conformational freedom around the C-C bond connecting the two aromatic rings of the ditopic bases 4 and 5. Consistent with NMR measurements and DFT calculations, before fuel addition, the conformational motion of the two aromatic rings of both 4 and 5 mainly consists of a large amplitude torsional oscillation spanning about 260° and passing for the anti conformation (the two nitrogen atoms at opposite sides). Immediately after the addition of 12, due to the protonation of one nitrogen and consequent formation of an N-H···N intramolecular hydrogen bond, the torsional oscillation in both 4H+ and 5H+ is not only restricted to a smaller range (about 100°) but explores the previously forbidden conformational space around the syn conformation (the two nitrogen atoms at the same side). However, the new state is an out-of-equilibrium state since decarboxylation of the conjugate base of 12 takes place and, at the end of the process, the system reverts to the more conformationally mobile state.


Structural and spectroscopic study of the linear proton-bound complex of PN with HNP+.
This work reports the results of high level ab initio calculations of the PN-HNP(+) complex and the corresponding hydrogen migration transition state. The geometries, rotational constants, harmonic vibrational frequencies, and energetics of each species involved in the complex are reported. A reduced dimensional 2D and 4D potential energy surface is constructed and used to obtain 2D and 4D vibrational states. The results of this study show excellent correlation to available experimental data for PN. The presented results can facilitate both laboratory and interstellar observations of this novel and strongly interacting linear proton-bound complex.


Vibrational and rotational dynamics of cyanoferrates in solution.
Ultrafast infrared spectroscopy has been used to measure vibrational energy relaxation (VER) and reorientation (Tr) times for the high frequency vibrational bands of potassium ferrocyanide and ferricyanide (CN stretches), and sodium nitroprusside (SNP, CN, and NO stretches) in water and several other solvents. Relatively short VER times (4-43 ps) are determined for the hexacyano species and for the NO band of SNP, but the CN band of SNP relaxes much more slowly (55-365 ps). The solvent dependence of the VER times is similar for all the solutes and resembles what has been previously observed for triatomic molecular ions [Li et al., J. Chem. Phys. 98, 5499 (1993)]. Anisotropy decay times are also measured from the polarization dependence of the transient absorptions. The Tr times determined for SNP are different for the different vibrational bands; for the nondegenerate NO mode of nitroprusside (SNP) they are much longer (>15 ps), correlate with solvent viscosity, and are attributed to overall molecular rotation. The short Tr (<10 ps) times for the CN band in SNP and for the hexacyanoferrates are due to dipole orientational relaxation in which the transition moment rapidly redistributes among the degenerate modes. There is no evidence of intramolecular vibrational relaxation (IVR) to other high frequency modes. VER times measured for hexacarbonyls and SNP in methanol are similar, which suggests that the generally faster VER for the latter is in part because they are soluble in more strongly interacting polar solvents. The results are compared to those for small ions and metal carbonyls and are discussed in terms of the importance of solute charge and symmetry on VER.


Inside and Beyond Color: Comparative Overview of Functional Quality of Tomato and Watermelon Fruits.
The quali-quantitative evaluation and the improvement of the levels of plant bioactive secondary metabolites are increasingly gaining consideration by growers, breeders and processors, particularly in those fruits and vegetables that, due to their supposed health promoting properties, are considered "functional." Worldwide, tomato and watermelon are among the main grown and consumed crops and represent important sources not only of dietary lycopene but also of other health beneficial bioactives. Tomato and watermelon synthesize and store lycopene as their major ripe fruit carotenoid responsible of their typical red color at full maturity. It is also the precursor of some characteristic aroma volatiles in both fruits playing, thus, an important visual and olfactory impact in consumer choice. While sharing the same main pigment, tomato and watermelon fruits show substantial biochemical and physiological differences during ripening. Tomato is climacteric while watermelon is non-climacteric; unripe tomato fruit is green, mainly contributed by chlorophylls and xanthophylls, while young watermelon fruit mesocarp is white and contains only traces of carotenoids. Various studies comparatively evaluated in vivo pigment development in ripening tomato and watermelon fruits. However, in most cases, other classes of compounds have not been considered. We believe this knowledge is fundamental for targeted breeding aimed at improving the functional quality of elite cultivars. Hence, in this paper, we critically review the recent understanding underlying the biosynthesis, accumulation and regulation of different bioactive compounds (carotenoids, phenolics, aroma volatiles, and vitamin C) during tomato and watermelon fruit ripening. We also highlight some concerns about possible harmful effects of excessive uptake of bioactive compound on human health. We found that a complex interweaving of anabolic, catabolic and recycling reactions, finely regulated at multiple levels and with temporal and spatial precision, ensures a certain homeostasis in the concentrations of carotenoids, phenolics, aroma volatiles and Vitamin C within the fruit tissues. Nevertheless, several exogenous factors including light and temperature conditions, pathogen attack, as well as pre- and post-harvest manipulations can drive their amounts far away from homeostasis. These adaptive responses allow crops to better cope with abiotic and biotic stresses but may severely affect the supposed functional quality of fruits.


Synergic effects of interferon and interferon inducer against ectromelia virus infection in mice.
Intraperitoneal injection of mouse brain interferon into mice 24 hr before inoculation of ectromelia virus, significantly reduced the mortality rate and prolonged the mean day of death (MDD). Intravenous injection of Newcastle disease virus (NDV) 24 hr before virus inoculation, also had significant beneficial effects. Furthermore, combined treatment with interferon and NDV had more protective effect against virus infection than either interferon or NDV treatment alone.


Mitigation in the toxicity of graphene oxide nanosheets towards Escherichia coli in the presence of humic acid.
GO nanosheets have been reported to show strong cytotoxicity towards Escherichia coli (E. coli) in aqueous solution. Natural organic matters (NOMs) in water may probably coat on the surface of GO nanosheets, which possibly influence its cytotoxicity. In this study, we illustrated how humic acid (HA), a ubiquitous NOM, mitigated the toxicity of GO nanosheets towards E. coli based on the cytotoxicity mechanism of GO nanosheets. Adsorption and cell viability tests proved that HA was adsorbed by GO nanosheets and decreased the toxicity of GO nanosheets towards E. coli. It was found that HA was adsorbed on the surface of GO nanosheets by polar groups, which prevented E. coli from contacting with GO nanosheets and weakened the toxicity of GO nanosheets. Besides, HA exerted an antioxidant role in maintaining the activity of the antioxidant enzyme and decreasing the ROS generation according to the results of oxidative stress experiments. The work revealed that HA relieved the toxicity of GO nanosheets and decreased the ecological risks induced by GO nanosheets.


[Efficacy of MR angiographic original images on surgery for posterior communicating artery aneurysms].
This study evaluated the usefulness of axial source images of magnetic resonance angiography (MRA) on preoperative depiction of surgical topography around posterior communicating artery aneurysms. Twenty patients with posterior communicating artery aneurysms, two ruptured and eighteen unruptured, underwent conventional angiography as well as axial source and projection images obtained by three-dimensional time-of-flight MRA techniques. By comparing the topography based on these angiograms to that confirmed during surgery, we evaluated useful information specific to the source images of MRA. Source images of MRA visualized the posterior communicating artery and the anterior choroidal artery in eighteen cases (90%) and five cases (25%), respectively. The posterior communicating artery was recognized at a higher rate by source images of MRA than by conventional angiography (65%), while the anterior choroidal artery was recognized at a lower rate than by combined angiography (75%). We realized some specific information to the source images of MRA including the topographical relations between the aneurysmal neck and the orifice of the posterior communicating artery, the relations between the aneurysmal dome and the oculomotor nerve and the aneurysmal dome buried into the temporal lobe. The information suggested a satisfactory direction of safe aneurysmal clipping so as not to occlude the posterior communicating artery. It was concluded that the source images of MRA provided additional useful information on surgical topography in 60% of the cases involving posterior communicating artery aneurysms. Although not essential in every case, the information would be beneficial in cases with the aneurysmal dome suspected to be in the temporal lobe or when the surrounding topography can not be clearly understood by angiography.


Necrotizing cutaneous infection caused by Curvularia brachyspora in an immunocompetent host.
A case of necrotizing cutaneous infection in an immunocompetent host caused by the dematiaceous fungus, Curvularia brachyspora is presented. A 58-year-old man was transferred to the Prince Henry Hospital for treatment of necrotizing cellulitis involving both thighs that developed following cryotherapy. The patient did not respond to antibacterial therapy and hyperbaric oxygen. He was empirically commenced on intravenous amphotericin B and began to respond even before the pathogen C. brachyspora was identified.


Variation in Practice Regarding Pretreatment With Dual Antiplatelet Therapy for Patients With Non-ST Elevation Myocardial Infarction.
Despite guideline recommendations, a significant number of patients with non-ST elevation myocardial infarction (NSTEMI) do not receive dual antiplatelet therapy (DAPT) before angiography "pretreatment." While there may be valid clinical reasons to not pretreat, such as concern for bleeding or multivessel disease warranting coronary artery bypass graft surgery, the degree of variability and factors associated with DAPT pretreatment are unknown. From the multicenter TRIUMPH registry, 1632 NSTEMI patients were not taking DAPT on admission and were included in the study cohort. Among the study patients, only 22% patients received DAPT pretreatment. A multivariable logistic regression model showed that race other than white or black (odds ratio [OR] 0.41, 95% CI 0.21-0.83), hemoglobin level (OR 1.18, 95% CI 1.08-1.29), patients' bleeding risk (assessed with NCDR CathPCI Bleeding Risk Score) (OR 0.85, 95% CI 0.74-0.99), and severe left ventricular dysfunction (OR 0.3, 95% CI 0.13-0.65) were the main predictors of pretreatment with DAPT, whereas likelihood of needing coronary artery bypass graft surgery (GRACE prediction model) was not (OR 1.09, 95% CI 0.88-1.35). Median ORs were calculated to assess variability of receiving DAPT pretreatment across sites after adjustment for patient characteristics. Receiving DAPT pretreatment varied substantially across sites (range 0-100%, mean OR 3.94, P<0.0001). While deviating from guideline-recommended DAPT pretreatment in patients with NSTEMI was associated with patient factors (eg, bleeding risk), marked variation was present across sites after accounting for patient-level characteristics. This suggests that site-level interventions are needed to improve concordance with current guidelines.


Thermoregulatory responses during thermal acclimation in pigs divergently selected for residual feed intake.
The objective of this study was to evaluate the performance and thermoregulatory responses during acclimation to high ambient temperature (Ta) of pigs from two lines selected for high (RFI(+)) or low (RFI(-)) residual feed intake with the hypothesis that RFI(-) pigs producing less heat would better tolerate high Ta. Pigs (50 kg initial body weight; 17 per line among which 10 of them were catheterized) were individually housed in a climatic-controlled room where Ta was maintained at 24.2 ± 0.4 °C during 7 days and thereafter at 30.4 ± 0.7 °C during 14 days. Irrespective of Ta, RFI(-) pigs had lower feed intake (ADFI) and similar average daily gain (ADG) than RFI(+) pigs. Whatever the line, ADFI, ADG, and feed efficiency decreased with increased Ta. Overall, the Ta increase resulted in an increase in rectal temperature (RT), skin temperature (ST), and respiratory rate (RR) within the first 24-48 h and, subsequently, in a decrease followed by stabilization. The RT decrease during acclimation occurred 24 h earlier in RFI(-) pigs than in RFI(+). Thyroid hormones and cortisol decreased at high Ta and it was similar in both lines. Based on performance and RT, ST, and RR responses, it seems that selection for low RFI tends to ameliorate pigs' tolerance to high Ta. Nevertheless, this selection does not induce significant differences between lines in endocrine and metabolite responses during thermal stress.


Models for recording age in 1692-1851 Canada: the political-cognitive functions of census statistics.
As a number of recent studies have emphasized, it is relevant to examine official statistics not just merely to assess the accuracy of historical data, but also in their own right, as political-cognitive devices which, by providing a standard to measure things, allow for an agreement regarding their objective existence and, therefore, the possibility to act upon them. In this paper, we focus on the different manners according to which, prior to the modern census era, ages of respondence were classified. Four different models emerge from this analysis, which in each case can be related to a specific political and social context.


Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha.
We studied IL-6 gene expression in human monocytes stimulated by muramyl dipeptide (MDP), a synthetic immunomodulator derived from mycobacterial cell walls. In control monocytes, two IL-6 transcripts of 3.4 kb and 1.6 kb were easily detected at 2.5 hr of culture and remained stable until 18 hr. In MDP-treated monocytes, three IL-6 RNA species displayed different kinetics of accumulation: a 3.4 kb RNA whose expression already reached its maximum after 2.5 hr exposure to MDP; a 1.6 kb RNA whose expression peaked at 5 hr; and a new RNA species of 1.4 kb which was transiently induced in early time of cell stimulation. TNF-alpha co-operated with MDP to increase IL-6 gene expression and secretion of biological active protein (measured by the hybridoma plasmacytoma growth factor assay). MDP exhibits a broad spectrum of immunomodulation properties such as adjuvant activity, enhancement of macrophage cytotoxicity against tumour and induction of non-specific resistance to intracellular agents. The results reported here suggest that these properties might be linked to the stimulation by MDP of genes coding for key cytokines such as IL-6, TNF and IL-1.


Congenital oesophageal stenosis due to fibromuscular thickening.
Three patients with fibromuscular oesophageal stenosis are reported. The onset was usually before 6 months of age; earlier than that of stenosis due to tracheobronchial remnants. The localization of the stenotic area varied from the distal to the mid-oesophagus. Extramucosal myotomy seemed to be the treatment of choice for this lesion, particularly in the mid-oesophagus involved diffusely, because of its good effectiveness, less invasiveness, and simplicity.


Comparison of acetylcholinesterase among employees based on job positions and personal protective equipment in fuel station.
The purpose of this study was to compare the levels of acetylcholinesterase (AChE) among employees based on job positions and the wearing of personal protective equipment (PPE) in fuel station areas. The sample group consisted of 200 people sorted into various groups, including (i) Inside fuel dispenser area (I-FDA) group consisting of 100 employees for refueling, cashier, and loading fuel into storage tanks, and (ii) Outside fuel dispenser area (O-FDA) group, consisting of 100 employees working in convenience stores, food stores, coffee shops, and offices, as well as general staff and car washers. Data were collected using interview questionnaires and blood samples were analyzed for AChE activity. The results showed that the I-FDA group had a significantly lower mean of serum AChE (7.38±1.73 U/ml) than the O-FDA group (7.85±1.49 U/ml) (p<0.05). The I-FDA group had a 2.43 times higher risk of abnormal serum AChE than the O-FDA group (OR=2.43, 95%CI=1.05-5.60). When considering the risk factors for job positions, it was found that refueling and cashier positions had lower AChE activity levels than those who did not (p<0.05). In the part, employees for food sales in a closed building and those wearing PPE masks had significantly higher AChE activity levels than those who did not or who wore them (p<0.05). Based on the aforementioned, employers at fuel stations should strictly determine the appropriate measures for wearing a PPE mask. Further, employees should be provided accommodation away from oil supply or enclosed buildings during breaks to reduce the effects on the neurotransmitter.


New insights in Cercopithecinae spermatozoa.
Sperm morphometric and morphologic data have been shown to represent useful tools for monitoring fertility, improving assisted reproduction techniques and conservation of genetic material as well as detecting inbreeding of endangered primates. We provide here for the first time sperm morphologic and morphometric data from Cercopithecus neglectus, Cercopithecus cephus, Papio papio and critically endangered Cercopithecus roloway, as well as comparative data from other Cercopithecinae species, i.e. Allochrocebus lhoesti, Mandrillus sphinx and Papio anubis. Following collection from the epididymis, spermatozoa were measured for each species for the following parameters: head length, head width, head perimeter, head area, midpiece length and total flagellum length, and the head volume, ellipticity, elongation, roughness and regularity were then calculated. Our data are consistent with both the general morphology and the morphometric proportions of Cercopithecinae sperm. Some specificities were observed, with C. cephus displaying a narrow head (width = 2.76 ± 0.26 µM) and C. roloway displaying a short midpiece (6.65 ± 0.61 µM). This data set represents an important contribution, especially for Cercopithecus roloway, one of the most endangered monkeys in the world, and further data on additional specimens coupled to data on mating systems and reproductive ecology should allow a better understanding of the mechanisms underlying these morphological differences across primate species.


Accounting for mediation in cyclist-vehicle crash models: A Bayesian mediation analysis approach.
Cyclist safety is affected by many factors on the zonal level. Previous studies have found associations between cyclist-vehicle crashes and vehicle and bike exposures, network configuration, land use, road facility, and the built environment. In addition, the network configuration, land use, and road facility were found to affect bike exposure levels. The association of zonal characteristics with both exposure and crashes may bias the development of macro-level bike safety models. This paper aims to explain these associations simultaneously using a form of Structural Equation Modelling approach. The analysis assesses the mediated effects that some variables have on crashes through their effects on bike exposure (by setting bike exposure as a mediator). Data from 134 traffic analysis zones (TAZ's) in the City of Vancouver, Canada is used as a case study. The indirect effect of network configuration, land use, and road facility on cyclist-vehicle crashes was assessed through Bayesian mediation analysis. Mediation analysis is an approach used to estimate how one variable transmits its effects to another variable through a certain mediator. These effects could be direct only, indirect only (through a certain mediator), or both direct and indirect. The results showed that the bike kilometers travelled (BKT) was a mediator of the relationship between network configuration, land use, and road facility and cyclist-vehicle crashes. The mediation analysis showed that some variables have different direct and indirect effect on cyclist-vehicle crashes. This indicates that while some variables may have negative direct association with crashes, their total crash effect can be positive after accounting for their effect through exposure. For example, bike network coverage and recreational density have negative direct association with cyclist-vehicle crashes, and positive indirect association leading to positive total effect on cyclist-vehicle crashes.


Solution conformation of an ET(B) selective agonist, ET-1[Cys(Acm)1,15,Ala3,Leu7,Aib11], in CD3OH/H2O by 1H NMR and molecular modelling.
To understand the basic structural requirements for the biological activity of endothelin peptides, the solution structure of an ETB selective agonist, ET-1[Cys-(Acm)1,15, Ala3,Leu7,Aib11, was investigated by 1H NMR spectroscopy and molecular modelling. The structure is characterised by an alpha-helical conformation between residues Ser5-His16 but is undefined at both the N and C termini. To date, neither the solution structures of linear modified peptides nor the effects of a methanol/water solvent system have been examined for endothelin or endothelin-like peptides. This structure plays an important role towards the design of endothelin receptor selective agonists and antagonists.


Electronic Cigarette Prevalence and Knowledge Among Medical Students in Saudi Arabia and Bahrain: A Cross-National Study.
Background Electronic cigarettes (e-cigarettes and vapour devices) are the most commonly used form of alternative tobacco products (ATPs). The use of these vapour devices has been dramatically increasing worldwide, especially among current and former traditional cigarette smokers. A strong influence that will affect patients' health attitudes and play a crucial role in tobacco control and smoking cessation are medical students, as they are future physicians. Therefore, in our study, we aimed to determine the prevalence rate of e-cigarettes and the level of knowledge among medical students in Saudi Arabia and Bahrain. Methods We conducted a cross-sectional study of medical students in Saudi Arabia and Bahrain using an online survey. This was distributed through social media platforms such as Twitter, WhatsApp, Telegram, and Facebook. Medical students of all years were included. The questionnaire was adapted from two previous studies. Results The study enrolled 1730 medical students. The majority of the participants did not recommend the use of e-cigarettes as a method for smoking cessation or believed that these types of ATPs lower the risk of cancer in comparison with traditional cigarettes. The data showed a strong association between gender and e-cigarette smoking, with the majority of current smokers being men (n = 184) and experimental smokers being women (n = 800). Moreover, an educational gap was discovered, as few of the students had received an education in their medical school's curriculum on the use of e-cigarettes. There was a significant association between receiving an education at a medical school and having adequate knowledge of e-cigarettes. Conclusion The increasing number of e-cigarette users among medical students is concerning. Our study showed that students are not receiving a decent education on the use of ATPs during medical school, which urges further adjustment of the curriculum. This will play a huge role in their behaviour and the provision of future treatment plans to patients as physicians.


[Effect of kontrikal on the activity of proteolytic enzymes and their inhibitors in blood, state of the bronchoalveolar secretion and the nature of the lung damage in dysenteric intoxication].
The development of dysenteric intoxication in rabbits led to an abrupt increase in the blood activity of proteolytic enzymes. This increase was accompanied by the reduced content of alpha 1-antitrypsin, and that of rapid and slow kallikrein inhibitor. Meanwhile there occurred a remarkable decrease in blood serum ability to bind chymotrypsin and kallikrein, and diminution of alpha 2-macroglobulin level. Trypsin, binding by blood serum did not undergo any substantial changes. In these conditions, the permeability of pulmonary vessels drastically rose and surface activity of the washing off dropped. The pathomorphological alterations in the lungs corresponded with the appearance of the "shock lung". Contrykal normalized the blood content of proteolytic enzymes and inhibitors, as well as that of the bronchoalveolar washing off, averted the development of gross pathomorphological alterations, exerting no appreciable effect on the surface activity of the bronchoalveolar washing off.


Spectral sensitivities of photoreceptors and their role in colour discrimination in the green-backed firecrown hummingbird (Sephanoides sephaniodes).
We studied the photopic spectral sensitivity in the green-backed firecrown, Sephanoides sephaniodes, a South American hummingbird, and its possible ecological relationship with preferred flowers and body colouration. Avian colour vision is in general tetrachromatic with at least four types of cones, which vary in sensitivity from the near ultraviolet (UV) to the red wavelength range. Hummingbirds represent an important family of birds, yet little is known about their eye sensitivity, especially about the role of photoreceptors and their oil droplet complements. The photopic electroretinogram shows a main sensitivity peak at 560 nm and a secondary peak in the UV, and may be explained by the presence of four single cones (lambda max at approximately 370, 440, 508 and 560 nm), and a double cone (lambda max at 560 nm) screened by oil droplets. The flowers preferred by the firecrown are those in which the red-green wavelength region predominates and have higher contrast than other flowers. The crown plumage of males is highly iridescent in the red wavelength range (peak at 650 nm) and UV; when plotted in a high-dimensional tetrachromatic space, it falls in a "red + UV" purple hue line, suggesting a potential significant communication signal for sexual differentiation.


Mapping brain development and aggression.
This article provides an overview of the basic principles guiding research on brain-behaviour relationships in general, and as applied to studies of aggression during human development in particular. Key literature on magnetic resonance imaging of the structure and function of a developing brain was reviewed. The article begins with a brief introduction to the methodology of techniques used to map the developing brain, with a special emphasis on magnetic resonance imaging (MRI). It then reviews briefly the current knowledge of structural maturation, assessed by MRI, of the human brain during childhood and adolescence. The last part describes some of the results of neuroimaging studies aimed at identifying neural circuits involved in various aspects of aggression and social cognition. The article concludes by discussing the potential and limitations of the neuroimaging approach in this field.


Altered profile of glycosylated proteins in serum samples obtained from patients with Hashimoto's thyroiditis following depletion of highly abundant proteins.
Hashimoto's thyroiditis (HT) is one of the most common autoimmune disorders; however, its underlying pathological mechanisms remain unclear. Although aberrant glycosylation has been implicated in the N-glycome of immunoglobulin G (IgG), changes in serum proteins have not been comprehensively characterized. This study aimed to investigate glycosylation profiles in serum samples depleted of highly abundant proteins from patients with HT and propose the potential functions of glycoproteins for further studies on the pathological mechanisms of HT. A lectin microarray containing 70 lectins was used to detect and analyze glycosylation of serum proteins using serum samples (N=27 HT; N=26 healthy control [HC]) depleted of abundant proteins. Significant differences in glycosylation status between HT patients and the HC group were verified using lectin blot analysis. A lectin-based pull-down assay combined with mass spectrometry was used to investigate potential glycoproteins combined with differentially present lectins, and an enzyme-linked immunosorbent assay (ELISA) was used to identify the expression of targeted glycoproteins in 131 patients with papillary thyroid carcinoma (PTC), 131 patients with benign thyroid nodules (BTN) patients, 130 patients with HT, and 128 HCs. Compared with the HC group, the majority of the lectin binding signals in HT group were weakened, while the Vicia villosa agglutinin (VVA) binding signal was increased. The difference in VVA binding signals verified by lectin blotting was consistent with the results of the lectin microarray. A total of 113 potential VVA-binding glycoproteins were identified by mass spectrometry and classified by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses. Using ELISA, we confirmed that lactoferrin (LTF) and mannan-binding lectin-associated serine protease 1 (MASP-1) levels were elevated in the serum of patients with HT and PTC. Following depletion of abundant proteins, remaining serum proteins in HT patients exhibited lower glycosylation levels than those observed in HCs. An increased level of potential VVA-binding glycoproteins may play an important role in HT development. LTF and MASP-1 expression was significantly higher in the serum of HT and PTC patients, providing novel insight into HT and PTC.


Effect of calcium on in vitro activity of LY146032 against Clostridium difficile.
The in vitro MICs of LY146032 against 63 isolates of Clostridium difficile tested in Wilkins-Chalgren broth ranged from 0.5 to greater than 32 micrograms/ml, with MICs of 4 and 8 micrograms/ml for 50 and 90% of the isolates, respectively. However, when the test medium was supplemented with physiologic concentrations of calcium, the MIC for 90% of the isolates was reduced to less than or equal to 0.12 microgram/ml.


Effect of socio-economic and biological variables on birth weight in Madhya Pradesh.
A study on a few selected socio-biological and demographic determinants of birth weight was conducted at a hospital in Sagar town, Madhya Pradesh. Records of 2,680 single live births over a period of one year (1st January to 31st December 2000) were analysed. It was found that male infants were 124 g heavier than female infants. Tabular representation of data showed that maternal age, education, ethnicity, father's income and occupation, infant's sex and parity were strongly associated with birth weight of infants. Regression analysis gave a comprehensive picture of such associations and confirmed the above findings. The study showed that the socio-economic and biological variables considered in the analysis have significant effect on birth weight.


[Successful treatment of primary small cell neuroendocrine carcinoma of the cervix].
Primary small cell neuroendocrine carcinoma of the cervix is a rare disease and associated with poor prognosis. Currently there are no guidelines regarding optimal treatment for this disease. This case report describes a successful approach with chemotherapy traditionally used for small cell lung cancer combined with intensity-modulated radiotherapy with concomitant chemotherapy followed by image-guided adaptive brachytherapy.


Regenerative Perspective in Modern Dentistry.
This review aims to trace the contour lines of regenerative dentistry, to offer an introductory overview on this emerging field to both dental students and practitioners. The crystallized depiction of the concept is a translational approach, connecting dental academics to scientific research and clinical utility. Therefore, this review begins by presenting the general features of regenerative medicine, and then gradually introduces the specific aspects of major dental subdomains, highlighting the progress achieved during the last years by scientific research and, in some cases, which has already been translated into clinical results. The distinct characteristics of stem cells and their microenvironment, together with their diversity in the oral cavity, are put into the context of research and clinical use. Examples of regenerative studies regarding endodontic and periodontal compartments, as well as hard (alveolar bone) and soft (salivary glands) related tissues, are presented to make the reader further acquainted with the topic. Instead of providing a conclusion, we will emphasize the importance for all dental community members, from young students to experienced dentists, of an early awareness rising regarding biomedical research progress in general and regenerative dentistry in particular.


Effects of ethanol infusion on serum hemoglobin and bile pigments.
Efforts to explain the apparent association between alcoholic liver disease and pigment gallstones have, to date, resulted in conflicting conclusions. While some clinical studies suggest hemolysis as the major pathogenetic factor other human and laboratory investigations describe increases in biliary pigment occurring in the absence of detectable hemolysis. In the present acute experiments various ethanol solutions ranging from 25 to 50% (v/v) were infused into miniswine to determine their effects on free hemoglobin in serum and total and unconjugated bilirubin in bile. Rapid and parallel increases in serum ethanol and serum hemoglobin levels were noted. Gradual and reversible increases in unconjugated and total bilirubin were observed after 1 hr. For unconjugated bilirubin the peak levels ranged from two times baseline levels at 25% (v/v) to 12 times baseline levels at 50%. When maximum values of hemoglobin and unconjugated bilirubin were compared in all experiments a strong positive correlation was confirmed. These findings suggest that the acute intravenous administration of ethanol causes intravascular hemolysis over a wide range of concentrations and results in the secretion of significant levels of bilirubin into bile. The role of this mechanism in pigment cholelithiasis remains to be determined.


Transport of albumin into the intestinal lumen of the rat.
The intestine is considered a major site for the breakdown and clearance of serum proteins. The mechanism of transport of macromolecules from the serosa into the lumen is unclear. The present study was designed to characterize the serosal to mucosal movement of albumin. Transport of bovine serum albumin (BSA) was assessed in short-circuited Ussing chambers, using stripped rat jejunum devoid of Peyer's patches. To define the kinetics of serosal to mucosal albumin transport the serosal surface was exposed to BSA at varying concentrations (0.5-5 mg.mL-1). Fluids from the mucosal compartment were sampled over time and assayed for immunologically intact BSA by ELISA. All subsequent experiments utilized a concentration of cold BSA (2 mg.mL-1) that produced maximal levels of intact BSA transport. To assess total BSA transport (intact BSA plus degraded BSA), 10 microCi (1 Ci = 37 GBq) 125I-labelled BSA was added to the serosal surface in addition to 2 mg.mL-1 cold BSA. To further characterize BSA transport tissues were treated with sodium fluoride (NaF) (metabolic inhibitor) or colchicine (an inhibitor of microtubule polymerization) or with the nerve blocker tetrodotoxin (TTX). All experiments using inhibitors were performed in paired tissues obtained from the same animal. Transport of intact BSA into the intestinal lumen was a saturable process, with a Vmax of 251 +/- 13 ng.cm-2.h-1 and a Km of 0.72 +/- 0.1 mg.mL-1, and represented 7% of the total BSA flux into the intestinal lumen. In the presence of NaF (2 x 10(-3) M), transport of both intact and total BSA was significantly inhibited (intact: control 374 +/- 80 vs. NaF 46 +/- 11, 88% inhibition; total: control 3288 +/- 296 vs. NaF 2550 +/- 235 ng.cm-2.h-1, 22% inhibition; p < 0.05). In addition, colchicine significantly inhibited intact BSA transport (control 339 +/- 15 vs. colchicine 206 +/- 13 ng.cm-2.h-1, 39% inhibition; p < 0.05). TTX had no effect on intact BSA flux. The findings suggest that transport of intact BSA from the serosa into the intestinal lumen is a saturable, energy-dependent process, which involves microtubules but is not under neural regulation.


Evaluation of health care workers' accuracy in recognising oral cancer and pre-cancer.
The aim of the study was to evaluate dental health care workers' ability to recognise oral cancer and pre-cancer from colour photographic slides. A set of 80 slides was prepared, 40 were negative (normal mucosa or lesions with no malignant potential) and 40 were positive (cancer or potentially malignant lesions). The slides were arranged in random order and projected in a standard format. The performance was evaluated in terms of mean sensitivity, specificity, mean correct score and likelihood ratio. There were no significant differences between the three groups of dentists (consultants, juniors hospital dentists and general dentists), all performed better than the auxiliaries. The chances of a consultant making a correct decision were 5.5 times better than for an auxiliary and 2.7 times better than for a junior hospital dentist. The slide show enables a comparison of health care workers to be made and may be useful for the evaluation, training and calibration of examiners for an oral cancer screening programme.


Acute kidney injury in acute Q fever.
Coxiella burnetii infection is not known to involve directly the kidneys. Kidney injury associated with Q fever usually manifests in the setting of chronic infection or endocarditis with development of immune complex deposition. Acute kidney injury (AKI) in the context of acute Q fever infection may be more pathologically heterogeneous. We describe two cases of severe AKI secondary to acute Q fever infection, each with marked differences in pathological characteristics, and clinical course.


Tumor necrosis factor-α alters integrins and metalloprotease ADAM12 levels and signaling in differentiating myoblasts.
The extracellular matrix (ECM) is important in the regulation of myogenesis. We hypothesized that tumor necrosis factor-α (TNF-α) modifies ECM during differentiation of mouse C2C12 myoblasts. Exogenous TNF-α (1 ng/ml) stimulated myoblast fusion on the 3rd day (by 160% vs control) but not on the 5th day of myogenesis. The level of integrin α5 was significantly augmented by TNF-α during 5 day-differentiation; however, integrin β1 was higher than control only on the 3rd day of cytokine treatment. Both the abundance of integrin α5 bound to actin and the level of integrin β1 complexed with integrin α5 increased in the presence of TNF-α, especially on the 3rd day of differentiation. Similarly, the stimulatory effects of TNF-α on integrin α3, metalloprotease ADAM12 and kinases related to integrins, FAK and ILK, were limited to the 3rd day of differentiation. We concluded that TNF-α-induced changes in ECM components in differentiating myogenic cells, i.e. i) increased expression of integrin α5, β1, α3, and metalloprotease ADAM12, ii) enhanced formation of α5β1 integrin receptors and interaction of integrin α5-cytoskeleton, and iii) increased expression of kinases associated with integrin signaling, FAK and ILK, were temporarily associated with the onset of myocyte fusion.


Prevalence of human papillomaviruses in the healthy oral mucosa of women with high-grade squamous intra-epithelial lesion and of their partners as compared to healthy controls.
Oral human papillomavirus (HPV) carriage rates were investigated in relation to genital HPV carriage in women with HPV-associated cervical lesions and male partner of such women, including several couples, in comparison with healthy individuals. Buccal and lingual mucosa of 60 males and 149 females with healthy oral mucosa and without known genital lesion, genital and oral mucosa of further 40 females with cervical high-grade squamous intraepithelial lesion (HSIL) and 34 male sexual partners of women with HSIL (including 20 couples) were sampled. HPV DNA was detected using MY/GP PCR. Genotype was determined by sequencing or restriction fragment length polymorphism. Virus copy numbers were determined by real-time PCR. Overall, oral HPV carriage rate was 5.7% (12/209) in healthy individuals; average copy number was 5.8 × 10(2) copies/1 μg DNA; male and female rates were comparable. Oral carriage in women with HSIL was significantly higher, 20.0% (8/40, P = 0.003); males with partners with HSIL showed a carriage rate of 17.6% (6/34), copy numbers were similar to the healthy controls. In contrast, genital carriage rate (52.9%, 18/34 vs. 82.5%, 33/40; P = 0.006) and average copy number were lower in males (5.0 × 10(5) vs. 7.8 × 10(5) copies/1 μg DNA; P = 0.01). Oral copy numbers in these groups and in healthy individuals were comparable. High-risk genotypes were dominant; couples usually had the same genotype in the genital sample. In conclusion, genital HPV carriage is a risk factor of oral carriage for the individual or for the sexual partner, but alone is not sufficient to produce an oral HPV infection in most cases.


A FOXO1-dependent transcription network is a targetable vulnerability of mantle cell lymphomas.
Targeting lineage-defined transcriptional dependencies has emerged as an effective therapeutic strategy in cancer treatment. Through screening for molecular vulnerabilities of mantle cell lymphoma (MCL), we identified a set of transcription factors (TFs) including FOXO1, EBF1, PAX5, and IRF4 that are essential for MCL propagation. Integrated chromatin immunoprecipitation and sequencing (ChIP-Seq) with transcriptional network reconstruction analysis revealed FOXO1 as a master regulator that acts upstream in the regulatory TF hierarchy. FOXO1 is both necessary and sufficient to drive MCL lineage commitment through supporting the lineage-specific transcription programs. We further show that FOXO1, but not its close paralog FOXO3, can reprogram myeloid leukemia cells and induce B-lineage gene expression. Finally, we demonstrate that cpd10, a small molecule identified from an enriched FOXO1 inhibitor library, induces a robust cytotoxic response in MCL cells in vitro and suppresses MCL progression in vivo. Our findings establish FOXO1 inhibition as a therapeutic strategy targeting lineage-driven transcriptional addiction in MCL.


Differential expression of two cathepsin Es during metamorphosis-associated remodeling of the larval to adult type epithelium in Xenopus stomach.
Cathepsin E (CE) was purified from the foregut of Xenopus laevis tadpoles as a mature dimeric form. The purified enzyme was a typical CE among aspartic proteinases with respect to pH dependence of proteolytic activity, susceptibility to pepstatin, and having N-linked high-mannose type oligosaccharide chains. We isolated two cDNAs for the CE (CE1 and CE2) from adult stomach. The amino acid sequence of the N-terminal region of the purified CE coincided with the corresponding sequence predicted from CE1. Northern blot analysis and in situ hybridization were performed. The CE1 mRNA was highly expressed in surface mucous cells and gland cells constituting the larval epithelium of the foregut of pro-metamorphic tadpoles. As metamorphosis began and progressed, CE1 mRNA drastically decreased in amount, and subsequently both CE1 and CE2 mRNAs gradually increased. The increase in CE2 mRNA was detected shortly after the increase in CE1 mRNA. The decrease in CE1 expression correlated with degeneration of the larval type epithelium, while the increases in both CE1 and CE2 expression correlated with formation of the adult type epithelium. Thus, cathepsin E gene expression was differentially regulated during metamorphosis-associated remodeling of the larval to adult type epithelium in stomach.


An Unusual Case of Dual Pancreatic Tumors.
We report a simultaneous occurrence of pancreatic adenocarcinoma and pancreatic neuroendocrine tumor. A 64-year-old woman presented with abdominal pain and weight loss. Abdominal computed tomography revealed a pancreatic head mass with a mesenteric artery encasement. Endoscopic ultrasound revealed a second mass in the tail of the pancreas. Pathology reported adenocarcinoma of the head of the pancreas and a neuroendocrine tumor in the tail of the pancreas. The neuroendocrine tumor was nonfunctional, with no symptoms or signs present on assessment. The patient had advanced unresectable carcinoma, so she was treated with chemotherapy.


The complement system of the duck.
Antibody (Ab)-dependent and-independent activation of the duck complement (C') system were studied. Ab-independent C' activity exhibited characteristics similar to those of the mammalian alternative C' pathway (ACP), including the selective lysis of rabbit erythrocytes (RRBC), a requirement for Mg2+, but not Ca2+, depletion of activity by zymosan, and lack of sensitivity to the mammalian C1 inhibitor carrageenan. Measurement of C' activity using antisera against sheep erythrocytes (SRBC) revealed that duck Abs activate C' by a pathway resembling the mammalian classical pathway (CCP) requiring both Ca2+ and Mg2+. Ab-dependent and-independent activities were further distinguishable by their kinetics of lysis and sensitivities to heat. Duck Abs were also found to activate C' in normal and carrageenan-treated serum by a mechanism that requires only Mg2+, and thus resembles the ACP. However, this Ab-dependent ACP-like activity exhibits patterns of ionic strength dependence and ontogeny which are clearly different from those of the conventional ACP and CCP. These findings indicate that duck C' can be activated by three mechanisms: Ab-mediated activation of the CCP, and Ab-mediated and Ab-independent activation of the ACP. Duck Ab responses to SRBC and RRBC were followed by direct agglutination, antiglobulin agglutination, and activation of the CCP and ACP. While the C'-activating abilities of duck anti-SRBC Abs persisted through a 3-month programme of inoculation, the anti-RRBC response lost its ability to activate C' after 2 weeks.


A dynamic model for anaerobic filter.
Anaerobic filters are frequently used to treat medium to high strength wastewater (2000-20000 mg/L COD), but have fewer applications to low strength wastewater (< 1000 mg/L COD). In order to understand the applicability of anaerobic treatment for low strength wastewater, such as domestic sewage, a dynamic mathematical model was developed. This Monod-type kinetic model, which predicts treatment efficiency and gas production, was used to describe literature observations and is offered as a predictive tool.


Identification of a lactoferrin-binding protein in Prevotella nigrescens.
A 40-kDa lactoferrin-binding protein was identified in a strain of Prevotella nigrescens isolated from a patient with periodontitis. The protein was purified by affinity column chromatography using a Sepharose-lactoferrin column and detergent-solubilized membranes. The N-terminal sequence revealed no apparent similarities with any other sequenced bacterial protein. The native conformation of the 40-kDa protein was a condition to bind either iron-free or iron-saturated lactoferrin. A possible function of this Lf-binding protein could be related with an iron acquisition mechanism in P. nigrescens.


[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].
To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC). This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed. The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001). ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.


Airborne microbial composition in a high-throughput poultry slaughtering facility.
A high-throughput chicken slaughtering facility in Beijing was systematically investigated for numbers of airborne microorganisms. Samples were assessed for counts of aerobic bacteria, Staphylococcus aureus, total coliforms, Escherichia coli, Pseudomonas aeruginosa, Listeria monocytogenes, Bacillus cereus, and Salmonella. During a 4-month period (September to December 2011), samples were collected for 10 min three times daily (preproduction, production, and postproduction). Samples were collected for three consecutive days of each month with an FA-1 sampler from six sampling sites: receiving-hanging, soaking-scalding and defeathering, evisceration, precooling, subdividing, and packing. Humidity, temperature, wind velocity, and airborne particulates also were recorded at each sampling site and time. The highest counts of microorganisms were recorded in the initial stages of processing, i.e., the receiving-hanging and defeathering areas, with a definite decline toward the evisceration, prechilling, subdividing, and packing areas; the prechilling area had the lowest microbial counts of 2.4 × 10(3) CFU/m(3). Mean total coliforms counts ranged from 8.4 × 10(3) to 140 CFU/m(3). Maximum E. coli counts were 6.1 × 10(3) CFU/m(3) in the soaking-scalding and defeathering area. B. cereus, P. aeruginosa, and S. aureus represented only a small proportion of the microbial population (1,900 to 20 CFU/m(3)). L. monocytogenes and Salmonella were rarely detected in evisceration, precooling, subdividing, and packing areas. Our study identified the levels of bioaerosols that may affect chicken product quality. This finding could be useful for improved control of microbial contamination to ensure product quality.