Clinical and biochemical approach of a circulating Na+-pump inhibitor.
Inhibition of the activity of semipurified renal Na+, K+-ATPase and of 3H-Ouabain binding to erythrocytes was used to titrate the level of a plasmatic endogenous inhibitor of the Na+, K+-pump. The inhibition effect of plasma extracts was specific and unrelated to vanadate, calcium and products of proteolysis. Similar results were obtained with the two procedures. An endogenous pump inhibitor could be detected in 28 plasmas of the 42 normotensives investigated so far. In 18 out of 21 normotensives born of hypertensive parent(s) the level was found to be higher than that observed in normotensive controls devoid of hypertensive heredity. 13 untreated essential hypertensives out of 21 also exhibited higher levels of the sodium-potassium pump inhibitor. Plasma levels of the inhibitor appear stable during several months in male subjects. No clear relationship could be established either in normotensives or hypertensives between the pump inhibitor level, the urinary output of Na+, and blood pressure. Neither could any relationship be established between the inhibitor and the intraerythrocytic Na+ concentration. The accuracy of the methodology allows a large scale clinical investigation. It can also be used in the purification of the substance, and preliminary results precised that its molecular weight was inferior to 1 000 daltons and that it was anionic. Purified fractions were obtained after gel filtration, ion exchange chromatography, and high pressure liquid chromatography. Preliminary results suggest that the purified fraction may interfere with the mechanisms of hypertension. They inhibited the Na+-dependent serotonin uptake by human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)


[Technic and indications for cytodiagnosis for the early detection of cancer].
It is possible to detach cells from the surface of mucous membranes for cytodiagnostic purposes. The method is simple and does not involve discomfort to the patient. It can be repeated at any time and many times. The method should be used when observing changes in the mucous membranes during examination in order to detect precancerous formations and for tumor diagnosis.


Central IT-Structures for Integrated Medical Research and Health Care of Viral Hepatitis--Hep-Net.
Hep-Net is a German medical research and health care network dedicated to viral hepatitis. Its many activities include basic and clinical research, training and public awareness, and rely on modern information technology and the Internet. One major component is a central registry for medical data, serum and tissue samples. In order to build this registry, important legal and technological issues needed to be addressed. Specifically, commercially available electronic data capture systems for clinical trials are generally ill suited for this purpose. The framework of the solution described here may be the basis for similar networks dedicated to specific disease entities or other phenomena.


Management of Yellowmargined Leaf Beetle Microtheca ochroloma (Coleoptera: Chrysomelidae) Using Turnip as a Trap Crop.
The yellowmargined leaf beetle, Microtheca ochroloma Stål, is a major pest of cruciferous vegetable crops in organic production systems. Very few organically acceptable management options are currently available for this pest. Field studies were conducted at a research station in Alabama and at a commercial organic vegetable farm in Florida to investigate the effectiveness of turnip, Brassica rapa rapa, as a trap crop for M. ochroloma. In the research station trial with cabbage planted as the cash crop, perimeter planting of turnip as a trap crop effectively reduced beetle numbers and crop damage below levels recorded in the control. During the first season of our on-farm trial, with napa cabbage and mustard as the cash crops, using turnip as a trap crop effectively reduced both beetle numbers and cash crop damage below levels found in the control plots, but economic damage was still high. In the second season, beetle populations were too low for significant differences in damage levels to occur between the trap crop and control plots. Together, these results suggest that turnip planted as a trap crop can be an effective control tactic for cruciferous crops, like cabbage, that are much less attractive to M. ochroloma than turnip. In crops, like mustard and napa cabbage, that are equally or only slightly less attractive than turnip, planting turnip as a trap crop would have to be used in combination with other tactics to manage M. ochroloma.


Meta-analysis of glue versus sutured mesh fixation for Lichtenstein inguinal hernia repair.
Chronic pain remains a frequent complication after Lichtenstein inguinal hernia repair. As a consequence, mesh fixation using glue instead of sutures has become popular. This meta-analysis aimed to clarify which fixation technique is to be preferred for elective Lichtenstein inguinal hernia repair. A meta-analysis was conducted according to the PRISMA guidelines. Articles published between January 1990 and April 2012 were searched for in MEDLINE, Embase and the Cochrane Library. Randomized controlled trials (RCTs) comparing glue and sutured mesh fixation in elective Lichtenstein repair for unilateral inguinal hernia were included. The quality of the RCTs and the potential risk of bias were assessed using the Cochrane risk of bias tool. Of 254 papers found in the initial search, a meta-analysis was conducted of seven RCTs comprising 1185 patients. With the use of glue mesh fixation, the duration of operation was shorter (mean difference -2·57 (95 per cent confidence interval (c.i.) -4·88 to -0·26) min; P = 0·03), patients had lower visual analogue scores for postoperative pain (mean difference -0·75 (-1·18 to -0·33); P = 0·001), early chronic pain occurred less often (risk ratio 0·52, 95 per cent c.i. 0·31 to 0·87; P = 0·01), and time to return to daily activities was shorter (mean difference -1·17 (-2·30 to -0·03) days; P = 0·04). The hernia recurrence rate did not differ significantly. Elective Lichtenstein repair for inguinal hernia using glue mesh fixation compared with sutures is faster and less painful, with comparable hernia recurrence rates.


[Advances in the physiopathology of epileptogenesis: molecular aspects].
We review the molecular basis of epileptogenesis and the new perspectives in the treatment of epilepsy. Epileptogenesis are the molecular and cellular events producing the disordered firing of a subpopulation of neurons resulting in periodic seizures. Epilepsies may be due to genetic and acquired factors. Some idiopathic epilepsies are due to mutant genes coding voltage gated sodium and potassium channels, GABAA receptor chloride channels and nicotinic acetylcholine receptor sodium channels. Genetic defects also produce epilepsy secondary to either neuronal developmental or metabolic abnormalities, and may contribute to acquired epilepsy. Events observed in both animal and human acquired epilepsies are an increase in glutamate levels and NMDA receptor sensitivity, selective lost of pyramidal neurons, mossy fibre sprouting and neosinaptogenesis. There is also a reduction in inhibitory control due to lost of GABAergic interneurons, and a decrease in GABA levels and GABAA receptor sensitivity. Hyperexcitability may be also due to reduction in glial ATPasa activity, increase in astrocytes gap junctions, and decrease in extracellular calcium. Chandelier GABAergic interneuron microlesions and an hyperexcitable thalamus are key in spread of partial seizures. Absences may be caused by cortex hyperexcitability and genetic abnormalities in thalamic voltage gated T calcium channels. Brain stem is key in convulsive seizures. The role of voltage gated potassium, sodium and calcium channels, and GABAergic and glutamatergic neurotransmission in epileptogenesis and treatment of epilepsies are revised. The role of other neurotransmitters and neuromodulators, second messengers, and immediate early genes and neurotrophins are also commented. Understanding the molecular basis of epileptogenesis should lead to the rational design of drugs both to prevent the development of epilepsy, and minimize hyperexcitability which may be the result of a genetic or acquired disorder.


The role of weight teasing and weight bias internalization in psychological functioning: a prospective study among school-aged children.
Weight-related teasing is a widespread phenomenon in childhood, and might foster the internalization of weight bias. The goal of this study was to examine the role of weight teasing and weight bias internalization as mediators between weight status and negative psychological sequelae, such as restrained eating and emotional and conduct problems in childhood. Participants included 546 female (52%) and 501 (48%) male children aged 7-11 and their parents, who completed surveys assessing weight teasing, weight bias internalization, restrained eating behaviors, and emotional and conduct problems at two points of measurement, approximately 2 years apart. To examine the hypothesized mediation, a prospective design using structural equation modeling was applied. As expected, the experience of weight teasing and the internalization of weight bias were mediators in the relationship between weight status and psychosocial problems. This pattern was observed independently of gender or weight status. Our findings suggest that the experience of weight teasing and internalization of weight bias is more important than weight status in explaining psychological functioning among children and indicate a need for appropriate prevention and intervention approaches.


[Comparative quality measurements part 1: run charts].
Quality assessment may be based on data of quality indicators. There are two main approaches for comparative quality measurements: comparison of data of the same service at different points over time or comparison of data of different services at the same time. Risk adjustment and standardisation must be performed and random variation must be adequately taken into account. In Statistical Process Control (SPC) theory common cause and special cause variation are distinguished. Processes in statistical control are stable and predictable. If processes exhibit special cause variation the management should investigate the reasons for this and manage the causes. Run charts as simple tools to display and analyse data of processes and outcomes over time are discussed in this article. They can be used for self-comparison. The following two parts of this three-part series explain control charts and funnel plots.


Keratoacanthoma centrifugum marginatum accompanied by extensive granulomatous foreign body reaction.
We describe a 58-year-old woman with a 4-year history of papular lesions with a partly verruciform appearance on the eyelids and the adjacent areas of the nose. The lesions progressed slowly but constantly into the surrounding areas with central scarring. Histopathology showed epidermal endophytic proliferations under a pronounced hyperparakeratosis. In the adjacent dermis a lymphohistiocytic infiltrate with giant cells of the foreign-body-reaction type was seen in close contact to extracellular keratin deposits. Although some cytopathological signs typical for viropathic effects were observed, no human papilloma virus-DNA was detected within the lesions by polymerase chain reaction. According to the histological picture and the clinical course we diagnosed a keratoacanthoma centrifugum marginatum. We present this case because of the strong granulomatous foreign body reaction which might complicate the diagnosis and has not been described for this keratoacanthoma variant so far.


[Psychometric properties of a grammatical comprehension test].
The Grammatical Structures Comprehension Test (CEG) has been designed to evaluate the language alterations of both Spanish speaking children and adults (specific language impairment, aphasia, craneoencephalic traumatism...) in a rapid and simple way. To study the psychometric properties of the CEG (reliability, validity and discrimination rates). The test was carried out on a sample of 1,404 children. The criteria validity was done with 181 children, whom various tests other than CEG were applied to. The discrimination rate in the 27% of the subjects with the highest scores in the CEG and the 27% of those that had the worst scores show that more than the half of the test elements produce a rate higher than 0.3 between children with good and bad scores. Out of the 20 blocks of the CEG, 15 of them present a discrimination rate between 0.5 and 1. Finally, the discrimination rate data obtained for each age group reveal that the easiest and the most difficult elements and blocks are coherently those with a lower discrimination power. This trend can be noticed in each age group. CEG is a reliable and valid measure to evaluate the grammatical comprehension, being very useful in clinics.


An M protein with a single C repeat prevents phagocytosis of Streptococcus pyogenes: use of a temperature-sensitive shuttle vector to deliver homologous sequences to the chromosome of S. pyogenes.
The major virulence factor of the important human pathogen Streptococcus pyogenes is the M protein, which prevents phagocytosis of the bacterium. In different strains of streptococci, there are over 80 serologically different M proteins and there are additional M-like proteins, some of which bind immunoglobulins. Although the sequence of the M molecules differs among different S. pyogenes strains, all M proteins, and some of the immunoglobulin-binding molecules, have at least two copies of the C repeat region. We describe construction of a deletion mutation in S. pyogenes, which has only one C repeat copy, and show that the mutant strain is still resistant to phagocytosis. The mutation was constructed in vitro and used to replace the resident emm allele in an S. pyogenes strain. To facilitate homologous recombination into the streptococcal chromosome, we adapted a shuttle vector which is temperature sensitive for replication in Gram-positive bacteria but not in Gram-negative hosts. This new method for delivery of a homologous DNA fragment to the S. pyogenes chromosome is efficient and reproducible and should be of general use.


Inhibition of Escherichia coli serotype O157:H7 by bromthymol blue.
Bromthymol blue, at a concentration of 0.1% in tryptose-glucose broth, inhibited growth of 98.4% of Escherichia coli serotype O157:H7 isolates but only 0.8% of E. coli non-O157:H7 isolates after an overnight incubation at 44.5 degrees C, but not 35 degrees C. The inhibition was dependent on temperature, density of inoculum, bromthymol blue concentration, time of incubation, and composition of the medium. Compared with serologic typing, the inhibition had sensitivity, specificity, predictive values of the positive and negative tests, and overall agreement between the two tests of 98.4, 99.2, 98.4, 99.2, and 98.9%, respectively. The inhibition could be useful as a presumptive test to identify E. coli isolates of serotype O157:H7, especially in laboratories that do not have serotyping capabilities.


The emergence of a suburban penalty during the 1918/19 influenza pandemic in Malta: The role of a marketplace, railway, and measles.
The Malta 1918/19 influenza experience adds to our understanding of the pandemic by illustrating the importance of suburban populations, their vulnerabilities, and elevated mortality rates. Studies on the socio-geographical variation in the 1918/19 influenza mortality has largely overlooked the suburban experience, and thus the often-hidden heterogeneity of the disease experience is missing. A comparison of mortality rates across the three settlement types (urban, suburban, and rural) for the second wave of the pandemic revealed that there were significant differences across the settlement types (x2 = 22.67, 2df, p <0.0001). There was a statistically significant divide between suburban settlement type versus urban and rural communities. Further, the geographical division of the central suburban region had the highest mortality rate at 4.28 per 1000 living of all suburban regions. A closer examination of the central suburban communities revealed that the town of Birchicara was the driving force behind the elevated influenza mortality, with a rate of 5.28 per 1000 living. The exceedingly high rate of influenza mortality in Birchicara was significantly different from the other suburban communities (Z = 2.915, p = 0.004). Birchicara was notable as both a transmission and burden hotspot for influenza infection because of a unique conflation of factors not observed elsewhere on the island. Foremost, was the pitkali market, which was a produce wholesale distributing centre; second, was the fact that the train station was a central hub especially for Maltese labourers; third, was that the measles epidemic in 1916/17 contributed to elevated childhood influenza deaths because the presence of military personnel and their families. We argue that the interaction of the three factors, and in particular, the measles epidemic with childhood influenza, amounted to a syndemic. Factors associated with urbanization and high rates of infectious diseases, such as overcrowding and infant mortality, did not play a primary role in the syndemic.


The Ethics of Conscientious Objection to Teaching Physician-Assisted Death.
The literature on the ethics of conscientious objection focuses on objections to participating in morally contested practices. This literature emphasizes the potential for participation to undermine objecting clinicians' moral integrity. Significantly less attention has been given to conscientious objection to teaching morally contested practices. Thus, it is unclear whether teaching morally contested practices has the potential to undermine objecting educators' moral integrity, and to the extent that it does, what steps can be taken to address this concern. We accordingly examine the ethics of conscientious objection to teaching morally contested practices, with a focus on teaching physician-assisted death (PAD) to trainees in US palliative care programs. We focus on three primary components of teaching PAD: (1) teaching the history and context of PAD; (2) teaching trainees how to understand and respond to requests for PAD; and (3) teaching trainees how to provide PAD. We argue that teaching components one and two has little potential to undermine objecting educators' moral integrity. Moreover, permitting objecting educators to opt out of teaching components one and two might undermine the education of trainees. In contrast, allowing objecting educators to opt out of teaching how to provide PAD may be important to preserving their moral integrity, and is unlikely to undermine trainees' education. We argue that educators should be permitted to opt out of teaching trainees how to provide PAD and describe policies that training programs can adopt to implement this approach.


Fate and Characterization Factors of Nanoparticles in Seventeen Subcontinental Freshwaters: A Case Study on Copper Nanoparticles.
The lack of characterization factors (CFs) for engineered nanoparticles (ENPs) hampers the application of life cycle assessment (LCA) methodology in evaluating the potential environmental impacts of nanomaterials. Here, the framework of the USEtox model has been selected to solve this problem. On the basis of colloid science, a fate model for ENPs has been developed to calculate the freshwater fate factor (FF) of ENPs. We also give the recommendations for using the hydrological data from the USEtox model. The functionality of our fate model is proved by comparing our computed results with the reported scenarios in North America, Switzerland, and Europe. As a case study, a literature survey of the nano-Cu toxicology values has been performed to calculate the effect factor (EF). Seventeen freshwater CFs of nano-Cu are proposed as recommended values for subcontinental regions. Depending on the regions and the properties of the ENPs, the region most likely to be affected by nano-Cu is Africa (CF of 11.11 × 10(3) CTUe, comparative toxic units) and the least likely is north Australia (CF of 3.87 × 10(3) CTUe). Furthermore, from the sensitivity analysis of the fate model, 13 input parameters (such as depth of freshwater, radius of ENPs) show vastly different degrees of influence on the outcomes. The characterization of suspended particles in freshwater and the dissolution rate of ENPs are two significant factors.


Induction of apoptosis by FFJ-5, a novel naphthoquinone compound, occurs via downregulation of PKM2 in A549 and HepG2 cells.
Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor biomarker and as a potential target for cancer therapy. In this study, F§FJ-5, a characterized naphthoquinone modifier of mollugin, was synthesized in order to investigate its anticancer activity and the potential mechanisms. It was observed that FFJ-5 inhibited the cell growth of human lung adenocarcinoma cells A549 and human hepatoma cells HepG2 by MTT assays. FFJ-5 arrested cell cycle at the G2/M phase. Further analyses demonstrated that FFJ-5 attenuated the expression of PKM2 and reduced the production of adenosine triphosphate (ATP). Reduced expression and activity of epidermal growth factor receptor (EGFR) and Akt were observed in A549 and HepG2 cells exposed to FFJ-5. FFJ-5 exposure also resulted in cell apoptosis, in association with decreased intracellular pH level and mitochondrial membrane potential. In addition, FFJ-5 activated the caspase-3 cascade. In conclusion, FFJ-5 inhibited cancer cell growth via the blocking the EGFR-Akt-PKM2 pathway or through the synergistic action of EGFR, Akt and PKM2 proteins, alongside a decrease in ATP production. In addition, FFJ-5 induced cancer cell apoptosis by decreasing the intracellular pH level and the mitochondrial apoptosis pathway. The present results suggest a potential role of FFJ-5 on the therapy of human cancer.


[Do beta-blockers prevent coronary events in hypertensive patients?].
Beta-blockers have been considered for decades as effective agents in preventing coronary events in hypertensive patients. Actually, the scrutiny of the available data arises some doubts over the real value of this pharmacological class. In primary prevention, the clinical benefits of beta-blockers are poorly documented: the studies conducted against placebo (MRC, IPPPSH...) did not show any significant differences regarding the rate of coronary events (except within non smokers); moreover, the beneficial effect of propranolol in preventing sudden deaths and silent myocardial infarctions has been reported byjust one retrospective analysis. Likewise in HAPPHY study, the comparison with diuretics did not emphasize a clear superiority of one of both classes; the better effect of metoprolol regarding overall mortality and fatal coronary events was shown in the pecular subset MAPHY, only. Furthermore, in elderly people, HEP, MRC OA and STOP studies did not find any significant effect of beta-blockers in preventing coronary events, as compared with placebo. However, SHEP study, which involved patients older than 60 years with isolated systolic hypertension receiving first a diuretic, then a beta-blocker(atenolol) in 1/4 of the cases, demonstrated a significant reduction versus placebo both in strokes and in coronary events. Finally, in UKPDS, CAPP, LIFE and CONVINCE studies, atenolol turned out to have a similar efficacy as captopril, losartan and verapamil, in preventing ischemic heart disease. Among the numerous published meta-analyses, that of Psaty pointed out the absence of a primary cardioprotective effect by beta-blockers; more recently, that of Carlberg, emphasized atenolol given alone as the first-line drug to fail in significantly reducing coronary events and strokes. In secondary prevention, some more convincing data may be found in the literature, regarding post myocardial infarction patients (meta-analyses of Staessen, 1982, Yusuf, 1985 and Soriano, 1997), as well as those with stable angina (BIP study in diabetics) or silent ischemia (ASIST study: significant reduction in number and duration of ischemic events by atenolol). Moreover, INVEST study recently showed atenolol and verapamil to have an equivalent efficacy in the hypertensive patients with stable coronary artery disease. Last, hypertension should be reminded as resulting in many cases of heart failure, a pathology where beta-blockers have clearly demonstrated their beneficial effects.


Prediction of miRNA-Disease Associations by Cascade Forest Model Based on Stacked Autoencoder.
Numerous pieces of evidence have indicated that microRNA (miRNA) plays a crucial role in a series of significant biological processes and is closely related to complex disease. However, the traditional biological experimental methods used to verify disease-related miRNAs are inefficient and expensive. Thus, it is necessary to design some excellent approaches to improve efficiency. In this work, a novel method (CFSAEMDA) is proposed for the prediction of unknown miRNA-disease associations (MDAs). Specifically, we first capture the interactive features of miRNA and disease by integrating multi-source information. Then, the stacked autoencoder is applied for obtaining the underlying feature representation. Finally, the modified cascade forest model is employed to complete the final prediction. The experimental results present that the AUC value obtained by our method is 97.67%. The performance of CFSAEMDA is superior to several of the latest methods. In addition, case studies conducted on lung neoplasms, breast neoplasms and hepatocellular carcinoma further show that the CFSAEMDA method may be regarded as a utility approach to infer unknown disease-miRNA relationships.


Adhesion of exogenous human microglia and THP-1 cells to amyloid plaques of postmortem Alzheimer's disease brain.
Microglial phagocytosis of amyloid-beta (Abeta) deposits is involved in Abeta clearance in vivo. To explore the ability of microglia to phagocytose beta, we cultured human microglia or human monocytic THP-1 cells directly on unfixed frontal cortex sections of an Alzheimer disease (AD) case. We found that when these cells were activated by lipopolysaccharide (LPS) plus interferon (IFN)-gamma, they developed ameboid morphology and formed clusters around and attaching to amyloid plaques in the tissue. Some cells adhering to these plaques internalized Abeta and some appeared to be degraded. Nevertheless, no significant reduction of the overall Abeta burden was observed. If the cells were not stimulated, they adhered poorly to the sections. We quantified THP-1 cell adhesion to an AD brain section compared with a normal brain section and found it to be significantly increased. If a brain section was rinsed with phosphate buffered saline containing 0.1% Triton X-100, most LPS/IFN-gamma-activated THP-1 cells failed to adhere. However, in co-culture with human astrocytes, the number of adherent THP-1 cells was significantly increased. These results suggest that human microglial cells are capable of adhering to and phagocytosing post mortem AD plaque material but activation may be necessary. Astrocytes may further enhance the process.


Tocilizumab-Associated Reversible Cerebral Vasoconstriction: A Case Report.
To report a case of reversible cerebral vasoconstriction syndrome (RCVS) possibly precipitated by tocilizumab. Immunosuppressant drugs are a rare cause of reversible cerebral vasoconstriction, a syndrome characterized by segmental vasospasm. However, although it is considered a reversible process that resolves within 3 months, the cerebral vasoconstriction over time may lead to severe complications such as strokes. We describe a 53-year-old woman who presented with a reversible vasoconstriction syndrome possibly associated with tocilizumab, an inhibitor of IL-6 receptor used in inflammatory diseases such as rheumatoid arthritis. The patient developed a cerebellar infarction as the major complication of the vasoconstriction syndrome. Tocilizumab could be a trigger of RCVS. It is important to bear in mind the role of tocilizumab as a possible precipitating factor in order to remove it and reduce complications such as strokes. It is, to our knowledge, the first reversible vasoconstriction syndrome possibly precipitated by tocilizumab published to date.


Weiskotten survey, class of 1960: a profile of physician location and specialty choice.
This survey is the eighth in a series which has included every fifth American medical school graduating class, starting with the class of 1915. The questionnaire design differed from previous Weiskotten studies and emphasized attitudes towards location information not contained in the American Medical Association Physician Masterfile. Traditional tabular comparisons are focused on contemporary locational policy needs. The findings and methodology of this study are generally similar to those of many earlier studies of both physician location and, in a very limited way, of specialty choice. The paper contains findings on certain characteristics of physicians who move their practice and those who do not. These characteristics have not been contrasted previously in this series.


Inter-simple sequence repeat (ISSR) markers for the Ns resistance gene in potato (Solanum tuberosum L.).
Inter-simple sequence repeat (ISSR) polymorphism was used for finding markers linked to the Ns gene, responsible for a resistance of potato (Solanum tuberosum L.) to potato virus S (PVS). The ISSR markers UBC811(660) and UBC811(950) were found to be linked to Ns. Linkage distances were estimated to be 2.6 cM and 6.6 cM, respectively. UBC811(660) showed high accuracy for detection of PVS resistance in diploid potato clones. In tetraploids, among seventeen studied genotypes containing the resistance gene, this marker was revealed in eleven. UBC811(660) can be a powerful tool for detection of genotypes carrying the Ns gene in diploid potato breeding programmes.


Lipopolysaccharide-induced up-regulation of triggering receptor expressed on myeloid cells-1 expression on macrophages is regulated by endogenous prostaglandin E2.
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface molecule that is expressed by neutrophils and monocytes. TREM-1 expression is modulated by various ligands for TLRs in vitro and in vivo. However, the influence of PGE(2), a potential mediator of inflammation, on TREM-1 expression has not been elucidated. In this study, we examined the effects of PGE(2) on LPS-induced TREM-1 expression by resident murine peritoneal macrophages (RPM) and human PBMC. PGE(2) significantly induced murine TREM-1 (mTREM-1) expression by RPM. Up-regulation of TREM-1 expression was specific to PGE(2) among arachidonic acid metabolites, while ligands for chemoattractant receptor-homologous molecule expressed on Th2 cells and the thomboxane-like prostanoid receptor failed to induce mTREM-1 expression. PGE(2) also increased expression of the soluble form of TREM-1 by PBMC. LPS-induced TREM-1 expression was regulated by endogenous PGE(2) especially in late phase (>2 h after stimulation), because cyclooxygenase-1 and -2 inhibitors abolished this effect at that points. A synthetic EP4 agonist and 8-Br-cAMP also enhanced mTREM-1 expression by RPM. Furthermore, protein kinase A, PI3K, and p38 MAPK inhibitors prevented PGE(2)-induced mTREM-1 expression by RPM. Activation of TREM-1 expressed on PGE(2)-pretreated PBMC by an agonistic TREM-1 mAb significantly enhanced the production of IL-8 and TNF-alpha. These findings indicate that LPS-induced TREM-1 expression on macrophages is mediated, at least partly, by endogenous PGE(2) followed by EP4 and cAMP, protein kinase A, p38 MAPK, and PI3K-mediated signaling. Regulation of TREM-1 and the soluble form of TREM-1 expression by PGE(2) may modulate the inflammatory response to microbial pathogens.


Temporal lobe epilepsy surgery in childhood: rationale for greater use.
Anterior temporal resection may effectively relieve therapy-resistant seizures in children and give social, psychological and economic benefits. Epidemiological and prognostic data demonstrate that this is an under-utilised procedure: although an estimated 677 Ontario children per year would be candidates for anterior temporal resection, only 18 were performed in a 12 month period.


Technology selection and comparative performance of source-separating wastewater management systems in Sweden and The Netherlands.
The research described in this paper has evaluated five demonstration projects with source-separating sanitation at neighbourhood scale, 10 years or more after their establishment. It presents the results of two systems with local grey water treatment in The Netherlands and three sites with urine separation in Sweden. The study has focused on (1) the drivers and barriers of the stakeholders that were responsible for project implementation and (2) the comparative performance of the source separation systems after their establishment. In The Netherlands the main drivers were water use reduction, combating sewer overflows and reduction of emissions. For the Swedish cases the main drivers of the involved actors were nutrient recycling, emission reduction and an active policy of the local government. The main barriers in all cases were higher investment costs and low experience with new sanitation approaches systems compared with the conventional system. Three of the sites showed a lower performance with respect to public health because effluent monitoring protocols for the grey water treatment systems were not in place or people could have direct contact with faeces. Lack of operation and maintenance is a cause of occasional failure for the grey water treatment systems, while the dominant failure reason for the urine separation systems was pipe clogging. The inventory showed that source-separating sanitation systems have a high potential to save or recover resources (water and nutrients).


Diagnostic accuracy and cost analysis of the Alere™ i Influenza A&B near-patient test using throat swabs.
Clinical diagnostic sensitivity alone is inadequate in the diagnosis of influenza. Polymerase chain reaction (PCR) testing is sensitive but the inherent delays in result availability potentially prolong time to isolation and treatment. Until recently no near-patient test (NPT) has demonstrated adequate sensitivity for routine clinical use. To evaluate diagnostic accuracy, time to result availability, clinical impact, and cost consequences of Alere™ i Influenza A&B NPT (Alere Inc., Waltham, MA, USA) using off-label throat swabs. Prospective, multi-centre [four UK National Health Service (NHS) hospitals], diagnostic accuracy cohort study with cost modelling. Throat swab samples from suspected influenza patients were tested for influenza using the reference standard of PCR; a second throat swab was tested using NPT. A total of 827 participants were recruited; 589 were suitable for analysis: sensitivity was 75.8% [95% confidence interval (CI): 67.0-84.6]; specificity was 96.8% (95% CI: 95.2-98.3). Sensitivity varied between Sheffield (Northern General Hospital: 82.1%; Royal Hallamshire Hospital: 83.3%) and other sites (Doncaster Royal Infirmary: 71.4%; Newcastle's Royal Victoria Infirmary: 50.0%) whereas specificity was high (92-100%). Positive predictive value (PPV) was 81.2% (95% CI: 72.9-89.5) with negative predictive value 95.6% (95% CI: 93.9-97.4) with observed prevalence of 15.4%. Median time to result for PCR was 1.1 days (on-site laboratories) and 5.2 days (remote laboratories). Isolation findings: 75% influenza positive not isolated; 69% of isolated participants did not have influenza. For a cohort of 1000 participants, annual estimated non-diagnostic cost savings with NPT are £215,040. This first prospective study of the Alere i NPT using throat swabs demonstrates high specificity, high PPV during seasonal epidemics, and rapid result availability which could lead to substantial cost savings.


Brachial artery disruption following closed posterior elbow dislocation in a child--assessment with intravenous digital angiography. A case report with review of the literature.
An 11-year-old boy sustained complete brachial artery disruption following closed posterior elbow dislocation. This is the first documentation in the English-language literature of this type of arterial transection following closed elbow dislocation in a child. It is also the first report of surgical repair of the brachial artery following elbow dislocation in a child. The patient's radial pulse was absent the day following the injury, and on Doppler examination blood flow was audible over the radial artery. Hand perfusion, however, remained excellent. Intravenous digital angiography demonstrated complete disruption of the brachial artery. This procedure is relatively painless compared with conventional angiography with percutaneous arterial puncture. The procedure provides the treating physician with an objective method for assessing brachial artery integrity. Arterial repair may decrease the potential risks of delayed complications, e.g., cold intolerance, potential growth disturbance, and possible delayed neurovascular residues associated with localized ischemia to the forearm and hand.


Next-Generation Sequencing to Guide Clinical Trials.
Rapidly accruing knowledge of the mutational landscape of malignant neoplasms, the increasing facility of massively parallel genomic sequencing, and the availability of drugs targeting many "driver" molecular abnormalities have spurred the oncologic community to consider how to use these new tools to improve cancer treatment. In order to assure that assignment of patients to a particular targeted treatment is likely to be beneficial to the patient, it will be necessary to conduct appropriate clinical research. It is clear that clinical (histology and stage) eligibility criteria are not sufficient for most clinical trials using agents that target mutations that are present in only a minority of patients. Recently, several clinical trial designs have been suggested to test the benefit of targeted treatment in molecular and/or clinical subgroups of patients. However, challenges remain in the implementation of such trials, including choice of assay, levels of evidence regarding gene variants, tumor heterogeneity, identifying resistance mechanisms, the necessity of screening large numbers of patients, infrastructure needs, and collaboration of investigators and industry. This article reviews current trial designs and discusses some of the considerations, advantages, and drawbacks of designing clinical trials that depend on particular molecular variants as eligibility criteria.


Genetic Gains for Yield and Virus Disease Resistance of Cassava Varieties Developed Over the Last Eight Decades in Uganda.
Achieving food security for an ever-increasing human population requires faster development of improved varieties. To this end, assessment of genetic gain for key traits is important to inform breeding processes. Despite the improvements made to increase production and productivity of cassava in Uganda at research level, there has been limited effort to quantify associated genetic gains. Accordingly, a study was conducted in Uganda to assess whether or not genetic improvement was evident in selected cassava traits using cassava varieties that were released from 1940 to 2019. Thirty-two varieties developed during this period, were evaluated simultaneously in three major cassava production zones; central (Namulonge), eastern (Serere), and northern (Loro). Best linear unbiased predictors (BLUPs) of the genotypic value for each clone were obtained across environments and regressed on order of release year to estimate annual genetic gains. We observed that genetic trends were mostly quadratic. On average, cassava mosaic disease (CMD) resistance increased by 1.9% per year, while annual genetic improvements in harvest index (0.0%) and fresh root yield (-5 kg per ha or -0.03% per ha) were non-substantial. For cassava brown streak disease (CBSD) resistance breeding which was only initiated in 2003, average annual genetic gains for CBSD foliar and CBSD root necrosis resistances were 2.3% and 1.5%, respectively. It's evident that cassava breeding has largely focused on protecting yield against diseases. This underpins the need for simultaneous improvement of cassava for disease resistance and high yield for the crop to meet its current and futuristic demands for food and industry.


The Arabidopsis SIAMESE-RELATED cyclin-dependent kinase inhibitors SMR5 and SMR7 regulate the DNA damage checkpoint in response to reactive oxygen species.
Whereas our knowledge about the diverse pathways aiding DNA repair upon genome damage is steadily increasing, little is known about the molecular players that adjust the plant cell cycle in response to DNA stress. By a meta-analysis of DNA stress microarray data sets, three family members of the SIAMESE/SIAMESE-RELATED (SIM/SMR) class of cyclin-dependent kinase inhibitors were discovered that react strongly to genotoxicity. Transcriptional reporter constructs corroborated specific and strong activation of the three SIM/SMR genes in the meristems upon DNA stress, whereas overexpression analysis confirmed their cell cycle inhibitory potential. In agreement with being checkpoint regulators, SMR5 and SMR7 knockout plants displayed an impaired checkpoint in leaf cells upon treatment with the replication inhibitory drug hydroxyurea (HU). Surprisingly, HU-induced SMR5/SMR7 expression depends on ATAXIA TELANGIECTASIA MUTATED (ATM) and SUPPRESSOR OF GAMMA RESPONSE1, rather than on the anticipated replication stress-activated ATM AND RAD3-RELATED kinase. This apparent discrepancy was explained by demonstrating that, in addition to its effect on replication, HU triggers the formation of reactive oxygen species (ROS). ROS-dependent transcriptional activation of the SMR genes was confirmed by different ROS-inducing conditions, including high-light treatment. We conclude that the identified SMR genes are part of a signaling cascade that induces a cell cycle checkpoint in response to ROS-induced DNA damage.


Personalized and Regenerative Medicine for Liver Diseases.
Regeneration of diseased organ is a ubiquitous clinical need. The clinical utilities of adult stem cells and microRNA have become a promising strategy for treatment of a number disease. This review aims to highlight the current clinical evidence of personalized and regenerative therapy for diseases like liver which could revolutionize patient care in the near future at a global scale. Herein, we explain the importance of personalized and regenerative medicine for bedside (intraoperative) in situ and In vivo regeneration of damaged organ/ tissues that is now being transferred to a larger field of clinical applications in a novel translational approach.


Effect of acute hyperinsulinaemia with and without angiotensin II type 1 receptor blockade on resistin and adiponectin concentrations and expressions in healthy subjects.
The potential insulin-sensitizing function of angiotensin II type 1 receptor blockade (ARB) with regard to selected adipokines is not fully explained so far. Our study aimed to explore the influence of acute hyperinsulinaemia and acutely induced ARB on resistin and adiponectin concentrations and expressions in healthy subjects. Plasma adipokines were measured: 1) at 0, 30 and 240 min of hyperinsulinaemic (1 mU/kg per min) euglycaemic (5 mmol/l) clamp (HEC), and 2) during HEC after acute ARB (losartan 200 mg; AT-HEC) using the same protocol, in eight healthy subjects. Needle biopsy of abdominal s.c. fat was performed at 0, 30 and 240 min of both clamps to assess the adipokines' expressions. Comparing the glucose disposals of HEC and AT-HEC, no difference in insulin sensitivity was found. Plasma resistin increased equally during HEC and AT-HEC (P < 0.05). The expression of resistin in s.c. fat increased during HEC (P < 0.05), while no significant changes in expression were observed during AT-HEC. Plasma levels of adiponectin did not change during both clamps. Adiponectin expression increased during HEC (P < 0.05), while it did not change during AT-HEC. In healthy subjects, acute hyperinsulinaemia is associated with an increase in plasma resistin independently of ARB, while plasma adiponectin is not influenced by insulin or ARB. The expressions of both resistin and adiponectin in s.c. adipose tissue are stimulated by acute hyperinsulinaemia, whereas losartan attenuates their insulin-stimulated expressions. This suggests a potential effect of losartanon adipokines' expression.


Pilot study of a primary care internet-based depression prevention intervention for late adolescents.
There is currently no depression prevention intervention available to adolescents in primary care. Fourteen late adolescents evaluated the acceptability (performance and ratings), potential adverse effects (negative emotions), and benefits (pre/post measures of three risk factors for depression) of a combined primary care Internet-based depression prevention intervention. Nearly all participants engaged the website (13/14) and 8/14 completed the entire intervention. Completers reported high levels of readability and ease of understanding and low levels of negative emotions. Completers showed favorable trends for the targeted risk factors: depressive symptoms, dysfunctional thinking, and low social support. A primary care/prevention intervention may be acceptable and favorably impact risk factors for depression.


NOS1 upregulates ABCG2 expression contributing to DDP chemoresistance in ovarian cancer cells.
Nitric oxide synthase 1 (NOS1) has been reported to promote various cancer processes including chemoresistance. However, the role of NOS1 in chemoresistance has remained unclear. ATP-binding cassette, subfamily G, member 2 (ABCG2) has been identified as a molecular cause of multidrug resistance in a number of cancer types, including ovarian cancer. The present study observed that in ovarian cancer cells, the expression of ABCG2 was significantly upregulated in response to cis-diamminedichloroplatinum (cisplatin/DDP) treatment, in addition the expression of NOS1 exhibited an increasing trend. Additionally, the levels of NOS1 and ABCG2 in chemoresistant ovarian cancer profiles in Gene Expression Omnibus datasets (GSE26712 and GSE51373) were higher than in chemosensitive profiles. Furthermore, overexpression of NOS1 could upregulate ABCG2 expression, and expression of ABCG2 was inhibited by NOS1 selective inhibitor (N-PLA). In assays of cell survival, NOS1 appeared to increase the potential for DDP resistance, and this effect was reversed by addition of ABCG2 inhibitor (verapamil). The present study indicated that NOS1-induced chemoresistance was partly mediated by the upregulation of ABCG2 expression. This result suggests a link between the expression of NOS1 and the ABCG2-associated chemoresistance in ovarian cancer.


Achieving the HbA1c Target Requires Longer Time in Range in Pregnant Women With Type 1 Diabetes.
Continuous glucose monitoring (CGM) overcomes the limitations of glycated hemoglobin (HbA1c). This study aimed to investigate the relationship between CGM metrics and laboratory HbA1c in pregnant women with type 1 diabetes. An observational study enrolled pregnant women with type 1 diabetes who wore CGM devices during pregnancy and postpartum from 11 hospitals in China from January 2015 to June 2019. CGM data were collected to calculate time in range (TIR), time above range (TAR), time below range (TBR), and glycemic variability parameters. Relationships between the CGM metrics and HbA1c were explored. Linear and curvilinear regressions were conducted to investigate the best-fitting model to clarify the influence of HbA1c on the TIR-HbA1c relationship during pregnancy. A total of 272 CGM data and corresponding HbA1c from 98 pregnant women with type 1 diabetes and their clinical characteristics were analyzed in this study. Mean HbA1c and TIR were 6.49 ± 1.29% and 76.16 ± 17.97% during pregnancy, respectively. HbA1c was moderately correlated with TIR3.5-7.8(R = -0.429, P = .001), mean glucose (R = 0.405, P = .001) and TAR7.8 (R = 0.435, P = .001), but was weakly correlated with TBR3.5 (R = 0.034, P = .001) during pregnancy. On average, a 1% (11 mmol/mol) decrease in HbA1c corresponded to an 8.5% increase in TIR3.5-7.8. During pregnancy, HbA1c of 6.0%, 6.5%, and 7.0% were equivalent to a TIR3.5-7.8 of 78%, 74%, and 69%, respectively. We found there was a moderate correlation between HbA1c and TIR3.5-7.8 during pregnancy. To achieve the HbA1c target of less than 6.0%, pregnant women with type 1 diabetes should strive for a TIR3.5-7.8 of greater than 78% (18 hours 43 minutes) during pregnancy.


Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study.
Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD50). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.


Arthur Benton and a bunch of Dutch flowers.
This paper shows how Arthur Benton's excellent research in the field of neuropsychological topics like hemispheric specialization, Gerstmann syndrome, aphasia, prosopagnosia and visuospatial deficits has influenced the development of the field of neuropsychology in The Netherlands. Also, his outstanding methodological knowledge and clinical experience have had an enormously significant impact on neuropsychological assessment in this country. Benton's knowledge about the different topics in neuropsychology was tremendous, while at the same time he was always critical and aware of findings he was not able to understand.


A van der Waals Heterostructure with an Electronically Textured Moiré Pattern: PtSe2/PtTe2.
The interlayer interaction in Pt-dichalcogenides strongly affects their electronic structures. The modulations of the interlayer atom-coordination in vertical heterostructures based on these materials are expected to laterally modify these interlayer interactions and thus provide an opportunity to texture the electronic structure. To determine the effects of local variation of the interlayer atom coordination on the electronic structure of PtSe2, van der Waals heterostructures of PtSe2 and PtTe2 have been synthesized by molecular beam epitaxy. The heterostructure forms a coincidence lattice with 13 unit cells of PtSe2 matching 12 unit cells of PtTe2, forming a moiré superstructure. The interaction with PtTe2 reduces the band gap of PtSe2 monolayers from 1.8 eV to 0.5 eV. While the band gap is uniform across the moiré unit cell, scanning tunneling spectroscopy and dI/dV mapping identify gap states that are localized within certain regions of the moiré unit cell. Deep states associated with chalcogen pz-orbitals at binding energies of ∼ -2 eV also exhibit lateral variation within the moiré unit cell, indicative of varying interlayer chalcogen interactions. Density functional theory calculations indicate that local variations in atom coordination in the moiré unit cell cause variations in the charge transfer from PtTe2 to PtSe2, thus affecting the value of the interface dipole. Experimentally this is confirmed by measuring the local work function by field emission resonance spectroscopy, which reveals a large work function modulation of ∼0.5 eV within the moiré structure. These results show that the local coordination variation of the chalcogen atoms in the PtSe2/PtTe2 van der Waals heterostructure induces a nanoscale electronic structure texture in PtSe2.


Long-term follow-up of patients after intraarterial thrombolytic therapy of acute vertebrobasilar artery occlusion.
Local thrombolysis may reduce mortality after acute vertebrobasilar artery occlusion. We focused on variables affecting recanalization, outcome and long-term prognosis. Thirty-six patients with vertebrobasilar artery occlusion were treated with local intraarterial thrombolytic therapy. Four of the survivors were among the 16 patients without recanalization. Recanalization was associated with a higher survival rate. Top-of-the-basilar-type occlusions have the highest recanalization rate. The thrombolytic medication used did not influence the recanalization frequency. One patient died due to an intracerebral bleed after thrombolysis. There was no association between the time interval (greater or less than 6 h) between the onset of symptoms and therapy initiation and survival. Relapses during follow-up (mean follow-up 3.7 years) did not occur. MRI/MRA and ultrasound studies during follow-up showed unchanged results in these patients. All survivors at the time of follow-up lived at home.


Neuroanatomical characteristics of deep and superficial needling using LI11 as an example.
To compare the neuroanatomical characteristics of the deep and superficial tissues at acupuncture point LI11 using a neural tracing technique, in order to examine the neural basis of potential differences between deep and superficial needling techniques. In order to mimic the situations of the deep and superficial needling, the retrograde neural tracer Alexa Fluor 488 conjugate of cholera toxin subunit B (AF488-CTB) was injected into the muscle or subcutaneous tissue, respectively, at acupuncture point LI11 in eight rats (n=4 each). Three days following injection, the distribution of motor and sensory neurons labelled with AF488-CTB was examined in the spinal cord and dorsal root ganglia (DRG) under a fluorescent microscope. For both types of injection, labelled motor and sensory neurons were distributed on the side ipsilateral to the injection in the spinal cord and DRG between spinal levels C5 and T1. The number of labelled motor neurons following intramuscular injection was significantly higher than subcutaneous injection. By contrast, the number of labelled sensory neurons following subcutaneous injection was significantly higher in number and extended over a greater number of spinal segments compared to intramuscular injection. These data indicate that the motor and sensory innervation of muscle and subcutaneous tissue beneath LI11 differ, and suggest that acupuncture signals induced by deep and superficial needling stimulation may be transmitted through different neural pathways.


Hyperepiphyllous, perianthicolous hypocreales--highly specialized ascomycetes of the phyllosphere.
Five species of perithecial ascomycetes obligately infect the developing sporophytes of epiphyllous hepatics (Marchantiophyta, Porellales, Lejeuneaceae and Radulales, Radulaceae) while they are still enclosed by the calyptra and the perianth. These ascomycetes belong to the Hypocreales, which are especially well represented among the hyperepiphyllous fungi. The small and mostly brightly colored ascomata arise within the perianths and perforate its walls to discharge the ascospores. Conidiomata may be present as well. Colonization of the perianths prevents normal sporophyte development, sometimes causing deformities, while the foliose gametophyte remains unaltered. The fungus simultaneously can behave biotrophically toward the gametophyte and necrotrophically toward the sporophyte. Host fertility may be considerably reduced. Anthonectria mammispora is described as a new unispecific genus and Ticonectria testudinea as a new species. Ticonectria testudinea and presumably other species attack the region of the gametophyte-sporophyte junction including the transfer cells. The perianth-inhabiting fungi occupy one of the most distinct and nutrient-rich microniches in bryophytes. They are sex- and organ-specific and seem to be restricted to certain hosts but are not poor in characters as are many bryophilous fungi. These species increase the complexity of the phyllosphere.


The mechanism of detergent solubilization of lipid bilayers.
Multiple data are available on the self-assembly of mixtures of bilayer-forming amphiphiles, particularly phospholipids and micelle-forming amphiphiles, commonly denoted detergents. The structure of such mixed assemblies has been thoroughly investigated, described in phase diagrams, and theoretically rationalized in terms of the balance between the large spontaneous curvature of the curvophilic detergent and the curvophobic phospholipids. In this critical review, we discuss the mechanism of this process and try to explain the actual mechanism involved in solubilization. Interestingly, membrane solubilization by some detergents is relatively slow and the common attribute of these detergents is that their trans-bilayer movement, commonly denoted flip-flop, is very slow. Only detergents that can flip into the inner monolayer cause relatively rapid solubilization of detergent-saturated bilayers. This occurs via the following sequence of events: 1), relatively rapid penetration of detergent monomers into the outer monolayer; 2), trans-membrane equilibration of detergent monomers between the two monolayers; 3), saturation of the bilayer by detergents and consequent permeabilization of the membrane; and 4), transition of the whole bilayer to thread-like mixed micelles. When the detergent cannot flip to the inner monolayer, the outer monolayer becomes unstable due to mass imbalance between the monolayers and inclusion of the curvophilic detergent molecules in a flat surface. Consequently, the outer monolayer forms mixed micellar structures within the outer monolayer. Shedding of these micelles into the aqueous solution results in partial solubilization. The consequent leakage of detergent into the liposome results in trans-membrane equilibration of detergent and subsequent micellization through the rapid bilayer-saturation mechanism.


Differentiation of pluripotent stem cells into hypothalamic and pituitary cells.
The hypothalamic-pituitary system is essential to maintain life and control systemic homeostasis, but it is negatively affected by various diseases, leading to serious symptoms. Embryonic stem (ES) cells differentiate into neuroectodermal progenitors when cultured as floating aggregates under serum-free conditions. Recently, our colleagues have shown that strict removal of exogenous patterning factors during early differentiation steps induced efficient generation of rostral hypothalamic-like progenitors from mouse ES cell-derived neuroectodermal cells. The use of growth factor-free chemically defined medium was critical for this induction. The ES cell-derived hypothalamic-like progenitors generated rostral-dorsal hypothalamic neurons, especially magnocellular vasopressinergic neurons that release the hormone upon stimulation. Subsequently, we reported efficient self-formation of 3-dimensional adenohypophysis tissues in aggregate cultures of mouse ES cells. The ES cells were stimulated to differentiate into nonneural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate and then treated with hedgehog. Self-organization of Rathke's pouch-like structures occurred at the interface of the two epithelia, as observed in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotropin-releasing hormone. Furthermore, when engrafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Our present research aims are to prepare hypothalamic and pituitary tissues from human induced pluripotent stem cells and establish effective transplantation techniques with clinical applications. To replicate the complex and precise control of the hypothalamic-pituitary system, regenerative medicine using pluripotent cells may be a hopeful option.


Complement components C3b and C4b as potential reliable site-specific diagnostic biomarkers for periodontitis.
This study aimed to investigate the correlation between the expression levels of C3b and C4b in human gingival tissue (GT) and gingival crevicular fluid (GCF) and disease severity in human periodontitis and to determine whether C3b and C4b are significant site-specific complementary diagnostic markers for periodontitis. A variety of biomarkers that have potential for informing diagnoses of periodontitis have been proposed. The complement components C3b and C4b were found to be positively correlated with disease severity. The therapeutic effect of targeting C3b and C4b on inflammatory bone loss in experimental periodontitis models has been studied. However, studies on the diagnostic potential of the gingival C3b and C4b expression levels for periodontitis are scarce. The expression levels of C3b and C4b in the GT and GCF were investigated via immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The correlation between the expression levels of C3b and C4b and disease severity with probing depth as well as the clinical attachment level were determined. To evaluate the diagnostic accuracy of the C3b and C4b expression levels at the periodontitis sites, the receiver operating characteristic (ROC) curve, cut-off point, area under the ROC curve, sensitivity, and specificity were analyzed. The expression levels of C3b and C4b in human GT and GCF were significantly positively correlated with periodontitis severity. The expression levels of combined C3b + C4b in the GT can significantly differentiate the disease status at the tissue level (p < .0001). Similarly, the expression levels of C3b + C4b in GCF can statistically distinguish periodontitis sites from healthy ones (p < .0001). Locally deposited C3b and C4b were positively correlated with periodontitis severity and recognized as site-specific diagnostic biomarkers for clinicopathological features in periodontitis. The association between the C3b and C4b network and periodontitis may be further understood and provide a basis for the development of novel screening as well as diagnostic and therapeutic strategies for periodontitis.


Ethical issues in discharge planning for vulnerable infants and children.
Discharge planning for vulnerable infants and children is a collaborative, interdisciplinary, decision-making activity that is grounded in the ethical complexities of clinical practice. Although it is a psychosocial intervention that frequently causes moral distress for professionals and has the potential to inflict harm on children and their families, the process has received little attention from ethicists. An ongoing study of the transition of technology-dependent children from hospital to home suggests that the ethical issues embedded in the discharge-planning process may be concealed by dominant cultural values, institutional policies, clinical standards, historical precedents, and legal regulations.


Life threatening bleeding from duodenal ulcer after Roux-en-Y gastric bypass: Case report and review of the literature.
Acute upper gastrointestinal bleeding is a rare, but serious complication of gastric bypass surgery. The inaccessibility of the excluded stomach restrains postoperative examination and treatment of the gastric remnant and duodenum, and represents a major challenge, especially in the emergency setting. A 59-year-old patient with previous history of peptic ulcer disease had an upper gastrointestinal bleeding from a duodenal ulcer two years after having a gastric bypass procedure for morbid obesity. After negative upper endoscopy finding, he was urgently evaluated for gastrointestinal bleeding. At emergency laparotomy, the bleeding duodenal ulcer was identified by intraoperative endoscopy through gastrotomy. The patient recovered well after surgical hemostasis, excision of the duodenal ulcer and completion of the remnant gastrectomy. Every general practitioner, gastroenterologist and general surgeon should be aware of growing incidence of bariatric operations and coherently possible complications after such procedures, which modify patient's anatomy and physiology.


Oligomerization of PcrV and LcrV, protective antigens of Pseudomonas aeruginosa and Yersinia pestis.
Protective antigens of Pseudomonas aeruginosa (PcrV) and Yersinia pestis (LcrV) are key elements of specialized machinery, the type III secretion system (T3SS), which enables the injection of effector molecules into eukaryotic cells. Being positioned at the injectisome extremity, V proteins participate in the translocation process across the host cell plasma membrane. In this study, we demonstrate the assembly of V proteins into oligomeric doughnut-like complexes upon controlled refolding of the proteins in vitro. The oligomeric nature of refolded PcrV was revealed by size exclusion chromatography, native gel electrophoresis, and native mass spectrometry, which ascertain the capacity of the protein to multimerize into higher-order species. Furthermore, transmission electron microscopy performed on oligomers of both PcrV and LcrV revealed the presence of distinct structures with approximate internal and external diameters of 3-4 and 8-10 nm, respectively. The C-terminal helix, alpha12, of PcrV and notably the hydrophobic residues Val(255), Leu(262), and Leu(276) located within this helix, were shown to be crucial for oligomerization. Moreover, the corresponding mutant proteins produced in P. aeruginosa were found to be non-functional in in vivo type III-dependent cytotoxicity assays by directly affecting the correct assembly of PopB/D translocon within the host cell membranes. The detailed understanding of structure-function relationships of T3SS needle tip proteins will be of value in further developments of new vaccines and antimicrobials.


The role of steroid hormones, prolactin and placental lactogen on mammary gland development in ewes and heifers.
In the first part of the investigations the interaction between oestradiol-17 beta, progesterone and prolactin on the formation of the lobuloalveolar structure of the mammary gland was studied in 21 nulliparous intact postpubertal ewes. Tissue specimens of the mammary gland were evaluated by light microscopical examination and prolactin was measured in blood samples. Combined treatment with oestradiol and progesterone induced physiological development of the lobuloalveolar structure of the mammary gland in the presence of prolactin. Suppression of prolactin by bromocriptine prevented this effect. Treatment with progesterone alone was not effective and revealed histological structures comparable to the controls. The interaction of oestradiol-17 beta with prolactin appears to be a main trigger for mammary gland development. In the second part of the investigations the effect of bromocriptine treatment during pregnancy on mammary gland development was studied in primigravid ewes and heifers. Mammary gland specimens were obtained for light and electron microscopical evaluation in ewes and heifers 5 and 10 days respectively before the expected date of parturition. Concentrations of prolactin and ovine placental lactogen were determined by radioimmunoassay. Bromocriptine treatment suppressed prolactin concentrations in ewes to minimal values but did not affect ovine placental lactogen concentrations. The histological evaluation revealed almost comparable stages of mammogenesis in both ewes and heifers. This effect can be attributed, at least in ewes, to the action of placental lactogen on mammogenesis. Placental lactogen might therefore be of physiological relevance during mammogenesis.


Emerging concepts of epigenetic dysregulation in hematological malignancies.
The past decade brought a revolution in understanding of the structure, topology and disease-inducing lesions of RNA and DNA, fueled by unprecedented progress in next-generation sequencing. This technological revolution has also affected understanding of the epigenome and has provided unique opportunities for the analysis of DNA and histone modifications, as well as the first map of the non-protein-coding genome and three-dimensional (3D) chromosomal interactions. Overall, these advances have facilitated studies that combine genetic, transcriptomics and epigenomics data to address a wide range of issues ranging from understanding the role of the epigenome in development to targeting the transcription of noncoding genes in human cancer. Here we describe recent insights into epigenetic dysregulation characteristic of the malignant differentiation of blood stem cells based on studies of alterations that affect epigenetic complexes, enhancers, chromatin, long noncoding RNAs (lncRNAs), RNA splicing, nuclear topology and the 3D conformation of chromatin.


Strain and electric field induced electronic property modifications in two-dimensional Janus SZrAZ2 (A = Si, Ge; Z = P, As) monolayers.
Recently, significant attention has been directed towards two-dimensional Janus materials owing to their unique structure and novel properties. In this work, we have introduced novel two-dimensional Janus monolayers, SZrAZ2 (A = Si, Ge; Z = P, As), through first principles. Our primary focus was the investigation of the controllable electronic properties exhibited by the Janus SZrAZ2 structures under the influence of strain and an external electric field. Our research findings indicate the dynamic and thermodynamic stability of Janus SZrAZ2 (A = Si, Ge; Z = P, As) monolayers. In the equilibrium state, these monolayers exhibit properties of an indirect band gap semiconductor. When subjected to biaxial strain and an external electric field, we observed that the dependency of SZrSiAs2 and SZrGeAs2 monolayers on an external electric field is very weak. Their electronic properties can only be modulated by applying biaxial strain. For SZrSiP2 and SZrGeP2 monolayers, their electronic properties can be modulated under biaxial strain and an external electric field, resulting in a transition from semiconducting to metallic behavior. Finally, we calculated the carrier mobility of these four structures and observed that the SZrGeAs2 monolayer exhibits a hole mobility of up to 597.52 cm2 s-1 V-1 in the x-direction, whereas the SZrSiP2 monolayer demonstrates an electron mobility of up to 479.30 cm2 s-1 V-1 in the y-direction. In the x-direction, the electron mobility of SZrSiAs2 and SZrGeP2 monolayers was measured to be 189.88 and 528.44 cm2 s-1 V-1, respectively. These values are greater than or equivalent to that of experimentally synthesized MoS2 (∼200 cm2 s-1 V-1). Our research lays the foundation for utilizing two-dimensional Janus materials in electronic devices.


Inverse relationship between blood volume and blood pressure.
The outcome objectives for EG were met. In order for her blood pressure to improve, cardiac output had to improve. In her case, this could only be accomplished by reducing the vascular volume through aggressive ultrafiltration. Starling's Law and Laplace's Theorem provide the key to understanding this concept, namely that an increase or decrease in cardiac output will result in a corresponding increase or increase or decrease in mean arterial pressure (Smith & Kampine, 1990, p. 93). Thus, there is an inverse relationship between blood volume and blood pressure. In this case ultrafiltration treated the cause of hypotension. Discontinuing the ultrafiltration and/or giving a saline bolus would have been an incorrect attempt to treat the effects of hypotension.


Mechanisms of resistance against cancer therapeutic drugs.
Cancer is the manifestation of multiple dysregulated cellular pathways. Treatment protocols engaged in treating these diseases involve mainly the cell cycle regulating genes/proteins, DNA synthesis and repair, protein synthetic machinery, apoptotic and proliferation activity and cytoskeletal framework. Some of the traditional therapeutic strategies have over the years developed resistance making cure difficult to achieve. This paper analyzes the mechanisms employed by various cancers that render them resistant against therapeutic drugs.


Fortification of staple foods with calcium: a novel costing tool to inform decision making.
Low calcium intake and its impact on maternal and child health are a major concern in low- and middle-income countries. Given the low calcium in diet, as well as the low adherence and acceptability of calcium pills in those settings, the discussion about policies to increase calcium intake has moved toward staple food fortification strategies. Nevertheless, there is scarce information on the economic feasibility of implementing these strategies. We aimed to design and propose a novel costing tool to estimate the cost of the flour fortification with calcium by carrying out a literature review about costing studies for staple food fortification programs and costing tools previously developed. A deliberative meeting with stakeholders was held to discuss and face-validate the conceptual framework proposed. We showed the costing tool application for the case of Costa Rica (a country with a population with low calcium intake), including the absolute cost of the staple food fortification production process, the incremental cost of fortification according to the public/private sector, and the incremental cost by target population. This open-source and publicly available costing tool can be useful to inform policymaking in countries considering the implementation of staple food fortification programs.


Local and Bulk Probe of Vanadium-Substituted α-Manganese Oxide (α-KxVyMn8-yO16) Lithium Electrochemistry.
A series of V-substituted α-MnO2 (KxMn8-yVyO16·nH2O, y = 0, 0.2, 0.34, 0.75) samples were successfully synthesized without crystalline or amorphous impurities, as evidenced by X-ray diffraction (XRD) and Raman spectroscopy. Transmission electron microscopy (TEM) revealed a morphological evolution from nanorods to nanoplatelets as V-substitution increased, while electron-energy loss spectroscopy (EELS) confirmed uniform distribution of vanadium within the materials. Rietveld refinement of synchrotron XRD showed an increase in bond lengths and a larger range of bond angles with increasing V-substitution. X-ray absorption spectroscopy (XAS) of the as-prepared materials revealed the V valence to be >4+ and the Mn valence to decrease with increasing V content. Upon electrochemical lithiation, increasing amounts of V were found to preserve the Mn-Mnedge relationship at higher depths of discharge, indicating enhanced structural stability. Electrochemical testing showed the y = 0.75 V-substituted sample to deliver the highest capacity and capacity retention after 50 cycles. The experimental findings were consistent with the predictions of density functional theory (DFT), where the V centers impart structural stability to the manganese oxide framework upon lithiation. The enhanced electrochemistry of the y = 0.75 V-substituted sample is also attributed to its smaller crystallite size in the form of a nanoplatelet morphology, which promotes facile ion access via reduced Li-ion diffusion path lengths.


Characterization of paint samples used in drinking water reservoirs: identification of endocrine disruptor compounds.
Several migration tests are performed from various epoxy paint samples that, according to the regulation, can be used in food reservoirs such as drinking water reservoirs. The level of the organic compounds capable of producing migrations to water with special attention to endocrine disruptor compounds (EDCs) are identified and estimated by closed loop-stripping analysis (CLSA) and liquid-liquid extraction (LLE) methods coupled with gas chromatography (GC)-mass spectrometry (MS). Bisphenol A, a strong endocrine disruptor, is found in all migration experiments. Its concentration level reaches between 0.02 and 0.03 mg/cm2. The higher concentration corresponds with benzylic alcohol, which is used as a solvent and curing agent in epoxy paint. Other EDCs identified in the migration tests are phthalates, 4-nonylphenol, and t-butylphenol. The main non-EDCs identified are solvents, antioxidants, and rubber-like compounds. No great differences are found in the use of metallic plates or concrete slabs for migration experiments; only additional compounds related with the pretreatment of the concrete wall have been identified, too. In the study of a drinking water sample the same organic compounds identified in the migration test is not seen. This is probably because of the dynamic situation in a drinking water reservoir. Finally, a GC profile of a direct epoxy paint analysis is shown. The main peak identified is bisphenol A diglycidyl ether, monomer, and an active principle of the polymerization of epoxy resins based on bisphenol A. In addition, we report the recoveries of a selected group of EDCs using CLSA and LLE methods coupled with GC-MS.


Kinetics of tert-butyl hydroperoxide decomposition in erythrocyte suspension.
The kinetics of tert-butyl hydroperoxide (t-BHP) decomposition was examined in erythrocyte suspension from C57B1/6 mice by the chemiluminescence method. The reaction with horseradish peroxidase, t-BHP (20 nmol/ml), and luminol was accompanied by a rapid chemiluminescence increase. The integral value of the chemiluminescence signal correlated with the t-BHP concentration at every moment of time. In the erythrocyte suspension, the half-life of t-BHP decomposition was 23.8 s. The decomposition rate significantly decreased after pretreatment of the erythrocytes with o-phenanthroline (0.1 mM), EDTA (1 mM), benzohydroxamic acid (0.1 mM) or adriamycin (30 microM). These effects were not associated with the changes in the glutathione peroxidase activity and, more likely, could be related to the modification of the membrane iron-binding sites. The influence of iron chelators on the kinetics of t-BHP decomposition suggests the existence of various Fe-binding sites, that can decompose organic hydroperoxides upon their interaction with cell plasma membranes.


Mobile velocity-controlled respirometer: description and performance capabilities.
An apparatus modeled after the Scram respirometer designed by Corcoran is described in terms of design, specifications and performance capabilities. The results with the use of this apparatus in a study of 14 able-bodied adults of five controlled walking speeds are compared to those of a similar study previously reported by Corcoran and Brengelmann. Oxygen consumption (ml O2/kg body wt/min) increases proportionately to the square of the velocity of walking. Results of the two investigations are parallel, although the present report demonstrates a greater male-female difference at all speeds. Uses and limitations of the apparatus are considered.


Determinative and confirmatory method for residues of tetracyclines in honey by LC-MS/MS.
A limited number of substances are authorised for the treatment of bees. Maximum residue limits (MRLs) are set for tetracyclines in several matrices, but not for honey. Nevertheless, tetracycline antibiotics may be used in order to prevent bacterial diseases and the loss of honey bee populations. In this study, a sensitive multi-residue LC-MS/MS method was developed and optimised for the quantitative and qualitative determination of tetracycline residues in honey. Homogenisation of samples under acidic conditions was performed and solid-phase extraction was carried out. The eluate was evaporated under nitrogen and dissolved in an aqueous methanol solution prior to filtration. A mobile phase composed of acetic acid-water and acetic acid-acetonitrile was used. Separation of tetracycline, oxytetracycline, chlortetracycline and doxytetracycline was achieved by using gradient elution on a C18 chromatography column. The analytical method was validated according to Commission Decision 2002/657/EC by the analysis of spiked samples around the recommended concentration of 20 μg kg(-1) by EURL Guidance Paper, December 2007. A matrix effect was observed, so quantification was based on an external matrix calibration curve. Calculated decision limits (CCα) were lower than 10 μg kg(-1) for all tetracyclines. Good linearity, repeatability and within-laboratory reproducibility were achieved.


Correlation between phylogroups and intracellular proteomes of Propionibacterium acnes and differences in the protein expression profiles between anaerobically and aerobically grown cells.
Propionibacterium acnes is one of the dominant commensals on the human skin and also an opportunistic pathogen in relation to acne, sarcoidosis, prostate cancer, and various infections. Recent investigations using housekeeping and virulence genes have revealed that the species consists of three major evolutionary clades (types I, II, and III). In order to investigate protein expression differences between these phylogroups, proteomic profiles of 21 strains of P. acnes were investigated. The proteins extracted from cells cultured under anaerobic and aerobic conditions were analysed using a SELDI-TOF mass spectrometer, high-resolution capillary gel electrophoresis, and LC-MS/ MS. The SELDI spectral profiles were visualised as a heat map and a dendrogram, which resulted in four proteomic groups. Strains belonging to type I were represented in the proteome Group A, while Group B contained type III strains. Groups C and D contained mixtures of types I and II. Each of these groups was not influenced by differences in culture conditions. Under anoxic growth conditions, a type IB strain yielded high expressions of some proteins, such as methylmalonyl-CoA epimerase and the Christie-Atkins-Munch-Petersen (CAMP) factor. The present study revealed good congruence between genomic and proteomic data suggesting that the microenvironment of each subtype may influence protein expression.


Robotic Assistance Confers Ambidexterity to Laparoscopic Surgeons.
To examine whether a robotic surgical platform can complement the fine motor skills of the nondominant hand, compensating for the innate difference in dexterity between surgeon's hands, thereby conferring virtual ambidexterity. Crossover intervention study (Canadian Task Force classification II-1). Centers for medical simulation in 2 tertiary care hospitals of Harvard Medical School. Three groups of subjects were included: (1) surgical novices (medical graduates with no robotic/laparoscopic experience); (2) surgeons in training (postgraduate year 3-4 residents and fellows with intermediate robotic and laparoscopic experience); and (3) advanced surgeons (attending surgeons with extensive robotic and laparoscopic experience). Each study group completed 3 dry laboratory exercises based on exercises included in the Fundamentals of Laparoscopic Surgery (FLS) curriculum. Each exercise was completed 4 times: using the dominant and nondominant hands, on a standard laparoscopic FLS box trainer, and in a robotic dry laboratory setup. Participants were randomized to the handedness and setting order in which they tackled the tasks. Performance was primarily measured as time to completion, with adjustments based on errors. Means of performance for the dominant versus nondominant hand for each task were calculated and compared using repeated-measures analysis of variance. A total of 36 subjects were enrolled (12 per group). In the laparoscopic setting, the mean overall time to completion of all 3 tasks with the dominant hand differed significantly from that with the nondominant hand (439.4 seconds vs 568.4 seconds; p = .0008). The between-hand performance difference was nullified with the robotic system (374.4 seconds vs 399.7 seconds; p = .48). The evaluation of performance for each individual task also revealed a statistically significant disparate performance between hands for all 3 tasks when the laparoscopic approach was used (p = .003, .02, and .01, respectively); however, no between-hand difference was observed when the tasks were performed robotically. On analysis across the 3 surgeon experience groups, the performance advantage of robotic technology remained significant for the surgical novice and intermediate-level experience groups. Robot-assisted laparoscopy may eliminate the operative handedness observed in conventional laparoscopy, allowing for virtual ambidexterity. This ergonomic advantage is particularly evident in surgical trainees. Virtual ambidexterity may represent an additional aspect of surgical robotics that facilitates mastery of minimally invasive skills.


Transmission of mutans streptococci to infants following short term application of an iodine-NaF solution to mothers' dentition.
In a randomized clinical trial, six applications of an I2-NaF or a placebo solution were administered to the mothers' dentition at the time of tooth emergence of her infant, to evaluate its effect on transmission of mutans streptococci (MS) to the infant. MS and other bacterial levels were periodically monitored in 48 mother-infant pairs until the child's third birthday. There were significant reductions in maternal salivary MS (P = 0.04), lactobacilli (P = 0.04), total streptococci (P = 0.002), and total cultivable organisms (P = 0.004) immediately following treatment. In children, 3-yr incidence of MS colonization and the time of acquisition of MS or the caries experience did not differ significantly between the two groups. We conclude that short-term application of I2-NaF to the maternal dentition of predentate infants significantly lowers MS, lactobacilli, total streptococci, and total cultivable bacteria in mothers' saliva, but does not influence the incidence and the time of acquisition of MS or the caries experience in children.


An OFF-ON-OFF type fluorescent probe based on a naphthalene derivative for Al3+ and F- ions and its biological application.
A novel fluorescent probe-based naphthalene Schiff, 1-(C2-glucosyl-ylimino-methyl)-naphthalene-2-ol (L) was synthesized by coupling d-glucosamine hydrochloride with 2-hydroxy-1-naphthaldehyde. It exhibited excellent selectivity and highly sensitivity for Al3+ in ethanol with a strong fluorescence response, while other common metal ions such as Pb2+ , Mg2+ , Cu2+ , Co2+ , Ni2+ , Cd2+ , Fe2+ , Mn2+ , Hg2+ , Li+ , Na+ , K+ , Fe3+ , Cr3+ , Zn2+ , Ag+ , Ba2+ and Ca2+ did not cause the same fluorescence response. The probe selectively bound Al3+ with a binding constant (Ka ) of 5.748 × 103 M-1 and a lowest detection limit (LOD) of 4.08 nM. Moreover, the study found that the fluorescence of the L - Al3+ complex could be quenched after addition of F- in the same medium, while other anions, including Cl- , Br- , I- , NO2- , NO3- , ClO4- , CO32- , HCO3- , SO42- , HSO4- , CH3 COO- , PO43- , HPO42- , S2- and S2 O32- had nearly no influence on probe behaviour. Binding of the [L - Al3+ ] complex to a F- anion was established by different fluorescence titration studies, with a detection limit of 3.2 nM in ethanol. The fluorescent probe was also successfully applied in the imaging detection of Al3+ and F- in living cells.


[Atypical presentation of a giant prolactinoma in a 15-year-old boy].
Giant prolactinomas are rare pituitary adenomas characterized by their great local invasion. In this paper, we report a 15-year-old male with left retro-ocular pain and ipsilateral exophthalmos of 4 months of evolution, secondary to a tumour in the base of the skull that invaded the orbit. Hormonal studies revealed serum prolactin of 6913,7 ng/ml (normal value < 20), confirming the diagnosis of giant prolactinoma. The patient started treatment with the dopaminergic agonist cabergoline in increasing doses. After 7 months of follow-up the prolactin had decreased to 349.8 ng/ml and the tumor volume was reduced by 70%, without presenting adverse effects to the treatment. The patient was asymptomatic and had restarted puberty. The rapid remission of symptoms without the need for invasive treatments underlines the importance of considering the diagnosis of prolactinoma among the possible differential diagnoses of tumor of the skull base.


New heteroleptic magnesium complexes for MgO thin film application.
Novel heteroleptic magnesium complexes, [Mg(dmamp)(acac)]2 (), [Mg(dmamp)(tmhd)]2 (), [Mg(dmamp)(tfac)]2 (), and [Mg(dmamp)(hfac)]2 (), were successfully synthesized using dmamp and β-diketonate as ligands. The thermogravimetric analyses and volatile studies of the complexes showed that the complexes and display high volatility and thermal stability. The single crystal X-ray study of the complexes reveals that both the complexes and were crystalized in the triclinic space group and as dimers, where magnesium atoms are in the pentacoordinate state with distorted trigonal bipyramidal geometry.


Physiology of epithelial chloride and fluid secretion.
Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epithelial anion and fluid secretion, their regulation, and how these processes are altered in CF disease to account for organ-specific secretory phenotypes.


Precipitating antibodies to epizootic hemorrhagic disease and bluetongue viruses in white-tailed deer in the southeastern United States.
From 1981 to 1989, sera were collected from 3,077 white-tailed deer (Odocoileus virginianus) in Georgia and from 1,749 deer from 12 additional states in the southeastern United States. In Georgia, prevalence of precipitating antibodies to epizootic hemorrhagic disease virus (EHDV) and bluetongue virus (BTV), as determined by agar gel immunodiffusion tests, was dependent on physiographic region, age, and year. Overall prevalence of antibodies to EHDV and/or BTV was 11, 33, 48, and 14% for the Mountain, Piedmont, Coastal Plain, and Barrier Island regions, respectively. Results suggested varying patterns of EHDV and BTV activity throughout the state. Serologic results from other southeastern states were consistent with the Georgia sample; prevalence estimates (EHDV and/or BTV) for corresponding physiographic regions deviated by less than 10%. Over this larger geographical area, antibody prevalence in deer appeared to increase with decreasing latitude.


Regulation of MHC class II expression in human T-cell malignancies.
Expression of major histocompatibility complex (MHC) class II molecules in human activated T cells is under normal circumstances regulated exclusively by the CIITA-PIII subtype of the class II transactivator (CIITA). In this study, we show that the absence of MHC class II expression in leukemic T cells was due to a lack of expression of CIITA, whereas in T-lymphoma cells, expression of CIITA correlated with expression of MHC class II. Interestingly, activation of a CIITA-promoter (P)III-reporter construct was not affected in leukemic T cells. This revealed that the absence of endogenous CIITA expression was not caused by a lack of transcription factors critical for CIITA-PIII activation but suggests the involvement of an epigenetic silencing mechanism. Subsequent analysis showed that the lack of human leukocyte antigen-DR (HLA-DR) expression correlated with hypermethylation of CIITA-PIII in leukemic T-cell lines and in primary T-cell acute lymphoblastic leukemia (T-ALL) and a T-cell prolymphocytic leukemia (T-PLL). Treatment of leukemic T-cell lines with a demethylation agent showed re-expression of CIITA-PIII and HLA-DRA. Furthermore, in vitro methylation of CIITA-PIII and subsequent assessment of CIITA-PIII activity in Jurkat leukemic T cells resulted in reduction of constitutive and CREB-1 (cyclic adenosine monophosphate [cAMP]-response element binding protein 1)-induced promoter activity. Together, these results argue for an important role of DNA hyper-methylation in the control of CIITA expression in leukemic T cells.


Natural killer-like T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus.
A 42-year-old man with acquired immunodeficiency syndrome developed a mass of the right parotid gland and multiple hepatic masses. Hematoxylin-eosin-stained sections of the parotid lesion showed a diffuse infiltrate of large mononuclear cells with vesicular nuclei and prominent nucleoli, consistent with a non-Hodgkin lymphoma. Immunohistochemical stains demonstrated expression of the T-cell markers CD3 and UCHL-1, as well as latent membrane protein 1 and T-cell intracellular antigen 1. Flow cytometry showed surface expression of CD2, CD3, CD7 (dim), CD8, and CD56. CD5 was not expressed. Molecular evaluation by polymerase chain reaction demonstrated monoclonal rearrangement of the T-cell receptor gamma gene. Epstein-Barr virus early RNA and human immunodeficiency virus RNA were demonstrated by in situ hybridization. To our knowledge, this is the first reported case of T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus. After 2 separate chemotherapy regimens, the patient achieved clinical remission for 1(1/2) years; he then developed progressive pulmonary lesions and died.


A novel prognostic indicator for in-hospital and 4-year outcomes in patients with pulmonary embolism: TIMI risk index.
Thrombolysis in Myocardial Infarction (TIMI) risk index (TRI) was recently evaluated in patients with acute myocardial infarction and found as an important prognostic index. In the current study, we evaluated the prognostic value of TRI in patients with moderate-high and high risk pulmonary embolism (PE) who were treated with thrombolytic agents. We retrospectively evaluated the in-hospital and long-term (4-year) prognostic impact of TRI in a total number of 456 patients with moderate-high and high risk PE. Patients were stratified by quartiles (Q) of admission TRI. In-hospital analysis revealed significantly higher rates of in-hospital death for patients with TRI in Q4. After adjustment for confounding baseline variables, TRI in Q4 was associated with 2.8-fold hazard of in-hospital death. Upon multivariate analysis, admission TRI in Q4 vs. Q1-3 was associated with 3.1 fold hazard of 4-year mortality rate. TRI in Q4, as compared to Q1-3, was significantly predictive of short term and long-term outcomes in PE patients who treated with thrombolytic agents. Our data suggest TRI to be an independent, feasible, and cost-effective tool for rapid risk stratification in moderate-high and high risk PE patients who treated with thrombolytic agents.


Effects of lactate concentration on hybridoma culture in lactate-controlled fed-batch operation.
To investigate the effects of lactate on cell growth and antibody production, a new method of maintaining the lactate concentration constant in a fed-batch culture is described. When the pH was initially adjusted by sodium hydroxide, the specific growth rate decreased and specific death rate increased with an increase of lactate concentration. To investigate whether the inhibition was due to the lactate concentration itself or to the osmotic pressure, the effect of the osmotic pressure adjusted by sodium chloride was compared with that of sodium lactate. When the osmotic pressure was adjusted to same condition as that of sodium lactate using sodium chloride, the specific growth data showed the same degree of growth inhibition. It was thus evident that the inhibition to cell growth was mainly due to osmotic pressure while lactate production from glucose was found to be inhibited by the lactate itself compared with sodium chloride. The specific antibody production rate had a maximum value within a certain range of lactate concentration. Moreover, specific antibody production rate had a unified relationship with the kinetic parameter mu, in spite of the different causes of inhibition by lithium lactate and sodium lactate. A certain "trade-off" relationship between growth and antibody production existed at higher growth rates.