Periapical status transitions in teeth with posts versus without posts: a retrospective longitudinal radiographic study.
The aim of this study was to compare periapical status transitions in teeth after post placement compared with other post-endodontic treatments in root-filled teeth. This retrospective longitudinal radiographic study included radiographs of 284 patients with root filled and restored teeth with composite fillings (Endo-fill group, n = 100), crown or fixed prosthesis (Endo-crown group, n = 82) or post and core restorations (Endo-post group, n = 102). All post and core restorations were made of gold alloy. The radiographs taken at the end of endodontic treatment, at the end of post-endodontic treatment and at least 8 months after post-endodontic treatment were evaluated. Post-operative periapical status was assessed according to the periapical index (PAI) and all teeth included in the study had no apical periodontitis preoperatively. Multi-state Markov analysis was used to assess periapical status transitions among the treatment groups. Of 284 root-filled teeth without apical periodontitis at baseline, 7.7% developed clear apical pathology within a minimum of 8 months observational period. In the Endo-post group 11 (10.78%) teeth transited from Healthy (PAI 1) to Disease (PAI 2-4) state compared with eight (9.75%) in the Endo-crown group and four (4%) in the Endo-fill group. The transition probabilities from Healthy (PAI 1) to Mild diseased (PAI 2) were 17.5% in the Endo-post group, 13.1% in the Endo-crown group and 5.3% in the Endo-fill group. Multivariate analysis showed that teeth in the Endo-fill group had 60% lower hazard to transit from Healthy (PAI 1) to Mild diseased (PAI 2) state [HR 0.40; 95% CI 0.12, 0.94]. A period exceeding 8 months between the end of the endodontic treatment and prosthetic treatment significantly increased the hazard of disease progression by three times compared with a period of ≤8 months [HR 3.16; 95% CI 1.06, 9.42]. Teeth without radiographic lesions at baseline and restored with posts had higher hazard to transit from healthy to diseased periapical status compared with teeth restored with composite restorations. Controlled clinical trials with longer follow-up periods are needed to validate these findings.


Emery-Dreifuss muscular dystrophy type 2 associated (?) with mild peripheral polyneuropathy.
In recent years numerous mutations in the LMNA gene encoding lamin A/C were shown to segregate with a wide spectrum of phenotypes. A recurrent p.R377H mutation in the LMNA gene was reported in patients with Emery-Dreifuss dystrophy (EDMD2) with various ethnic backgrounds. We present a patient with EDMD2 caused by a p.R377H mutation, associated with mild peripheral polyneuropathy. The analysis of peripheral myelin protein 22 (PMP22), ganglioside induced differentiation-associated protein 1 (GDAP1), gap junction β-1 protein (GJB1), and myelin protein zero (MPZ) genes did not reveal mutations; however, we identified a new sequence intronic variant in the mitofusin 2 (MFN2) gene of unknown pathogenic significance. A complex phenotype in the presented patient might depend either on single mutation in the LMNA gene or on bigenic defect; therefore, a wide genetic investigation is needed to elucidate the molecular background of EDMD2/polyneuropathy in this case.


Characterization of CalE10, the N-oxidase involved in calicheamicin hydroxyaminosugar formation.
As the first in vitro characterization of a sugar N-oxidase, this study establishes CalE10 as the key oxidase involved in calicheamicin hydroxylamino glycoside formation. This study confirms that oxidation occurs at the sugar nucleotide stage prior to glycosyltransfer, and substrate specificity studies reveal CalE10-catalyzed oxidation to be regiospecific and to present trace amounts of the corresponding nitrosugar in vitro. This work also sets a precedent for the future study of other N-oxidases involved in hydroxylamino-, nitroso-, and/or nitrosugar formation.


[Pulmonary emboli in sclerotherapy for peripheral vascular malformations under general anesthesia; a report of two cases].
Sclerotherapy with absolute ethanol and/or polidocanol is a well-established therapeutic modality for the treatment of peripheral vascular malformations, although systemic complications such as hemoglobinuria and pulmonary embolism could occur. We report two cases of pulmonary embolism associated with sclerotherapy for peripheral vascular malformations. Two patients, a 17-year-old man and a 17-year-old woman, undergoing absolute ethanol sclerotherapy for vascular malformations of the leg developed pulmonary embolism after injection of ethanol. Pulmonary embolism, suspected by the clinical symptoms such as hypoxia and hypocapnia, was confirmed by the pulmonary scintigraphy showing minimal pulmonary defects. Hemoglobinuria was also observed with injection of ethanol. Patients recovered rapidly with heparin and urokinase therapy. The review of perioperative complications with sclerotherapy for peripheral vascular malformations in our institution for past four years revealed that complications were observed in 18 out of 88 patients (20.5%), and in 32 out of 183 cases (17.5%). Major complications were hemoglobinuria, pulmonary embolism, shivering and delayed emergence from general anesthesia. We conclude that sclerotherapy for vascular malformations under general anesthesia is a risky procedure and this must be carefully managed with keen monitoring of Spo2 and Etco2.


Regression of advanced atherosclerosis in swine: chemical studies.
Advanced complicated atherosclerosis was produced in the abdominal aortas of swine by a combination of mechanical injury and of a four-month high-cholesterol, high-fat diet. After discontinuation of the atherogenic diet, the animals were given swine mash for 14 months; subsequent chemical studies showed that regression of lesions had occurred, as delineated by decreased levels of DNA and DNA synthesis, total and esterified cholesterol, and phospholipid but no change in the levels of free cholesterol and triglycerides. The rate of DNA synthesis, but not that of total protein synthesis, had decreased. Collagen content had increased. By all criteria studied, the regressed lesions did not differ greatly from the abdominal aortic tissue of animals that had received only a mash diet for 18 months after mechanical injury. These findings, if extrapolated to man, would make the prognosis for possible regression of atherosclerosis under strictly controlled dietary regimens excellent.


Examination of Associations Among Three Distinct Subjective Aging Constructs and Their Relevance for Predicting Developmental Correlates.
This study examined (a) the empirical associations among three subjective aging (SA) constructs: felt age, attitudes toward own aging (ATOA), and awareness of age-related change (AARC); (b) the moderating role of chronological age in these associations; and (c) the predictive relevance of the SA constructs with regard to two developmental correlates: functional health and satisfaction with life. Participants were 819 adults aged 40-98 years from the United States and Germany. Parallel multiple mediation, moderated mediation, and hierarchical regression analyses were used. As hypothesized, AARC mediated the association between the global measures of SA (felt age and ATOA) and the developmental correlates. Specifically, more negative global subjective aging predicted more AARC losses, which predicted poorer health and well-being. Furthermore, this mediation pathway was moderated by chronological age, such that, with increasing age, greater AARC was more strongly related to poorer functional health (but not well-being). The multidimensional measure, AARC, accounted for a significant amount of the variance in the developmental correlates over and above the unidimensional SA constructs. A consistent pattern emerged supporting the role of domain specificity and valence. These findings support the need for conceptualizing SA across different behavioral domains and for distinguishing between positive and negative SA.


Molecular pharmacology of the onco-TRP channel TRPV6.
TRPV6, a representative of the vanilloid subfamily of TRP channels, serves as the principal calcium uptake channel in the gut. Dysregulation of TRPV6 results in disturbed calcium homeostasis leading to a variety of human diseases, including many forms of cancer. Inhibitors of this oncochannel are therefore particularly needed. In this review, we provide an overview of recent advances in structural pharmacology that uncovered the molecular mechanisms of TRPV6 inhibition by a variety of small molecules, including synthetic and natural, plant-derived compounds as well as some prospective and clinically approved drugs.


An observational study of the securement of central venous access devices with a subcutaneous anchor device in a paediatric population at a tertiary level hospital.
Paediatric central venous access devices are associated with significant complications. Failure rates have been estimated to be as high as 25%, with securement failure a significant contributing factor. In this study, we evaluate the use of a subcutaneous securement device, securAcathTM, in minimising rates of central venous access device dislodgement and unintended early removal within a paediatric population. Data were collected on 52 consecutive paediatric patients, aged less than 18 years old, who required peripherally inserted central catheters and non-cuffed tunnelled centrally inserted central catheters. We found that the rate of securement failure with securAcathTM was 2.01 per 1000 catheter days. This compared to 2.58 in our previous practice without securAcathTM. With the use of securAcathTM, no securement failures were observed in our patients with non-cuffed tunnelled centrally inserted central catheters. There were three instances of securement failure in patients with peripherally inserted central catheters. We conclude that the use of a securAcathTM fixation device in central venous access devices is an effective method of securement, especially in use with non-cuffed tunneled centrally inserted central catheters. However, when significant tension is applied to the central venous access devices migration is still possible.


A Case of Adenomyosis with a High Titer of IgG Autoantibody to Calreticulin.
Background. High prevalence of autoantibodies to the calcium-binding, endoplasmic reticulum chaperone protein calreticulin has been reported in various autoimmune and parasitic diseases. It has been reported that adenomyosis is associated with the presence of autoantibodies, in particular to phospholipids; however, it is not known whether it is associated with autoimmunity to calreticulin. Results. A 35-year-old gravida 4 para 4 woman presented with a history of many years of intractable menorrhagia. Histopathological examination of a subsequent hysterectomy specimen revealed a bulky uterus, a poorly developed secretory endometrium with decidualization of the stroma and chronic endometritis, as well as the presence of adenomyosis uteri. IgG autoantibodies to calreticulin were measured in the plasma of this and 234 other patients. Nine (3.8%) patients tested positive. The titer of anticalreticulin IgG autoantibody in the sole case with adenomyosis was approximately 8 times the average of other positive-testing samples. Conclusions. The etiology of adenomyosis is unclear. The presence of a high titer, blocking anticalreticulin autoantibody may directly increase the risk that adenomyosis might develop. It is also possible that the expansion of endometrial glandular tissue, as well as elevated estrogens, during adenomyosis may lead to elevated calreticulin, which induces an autoimmune reaction to it. Further study is required to determine whether there is a significant association between adenomyosis and the prevalence of calreticulin autoantibodies.


A case report on accessory brachialis muscle.
Supernumerary heads or slips of brachialis (anticus) muscle is one among the most striking variations, described and encountered in the dissection routine. Very few studies are quoted in the list of its anomalies. We present a unique occurrence of an accessory brachialis muscle (acBr) that formed a fibro-muscular tunnel after blending with the medial intermuscular septum in the lower part of the arm. This tunnel contained the median nerve, the brachial artery and few additional twigs that innervated the neighboring muscles. Because of its intimate topographical relation with the neurovascular bundle, there is no doubt about its role, in the etiogenesis of various compression syndromes. Also, the brachial flexors received innervation from the median nerve, due to the absence of the musculo-cutaneous nerve. We discuss in this report the possible embryogenesis and the clinical application of this variation that can aid the physicians in their approach and required treatment.


The association of pretransplant native nephrectomy with decreased renal allograft rejection.
Analysis of 2808 first and 823 second or subsequent cadaveric renal allograft recipients transplanted between June 1977 and July 1982 as part of the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of pretransplant bilateral native nephrectomy (BNN) on graft and patient outcome. A highly significant increase in overall graft survival was associated with BNN in first transplant recipients (P less than 0.003) but not in regrafted patients. However, no increased graft survival was seen in patients receiving BNN at the time of the transplant operation. Interestingly, the improvement in graft survival associated with BNN appeared to be the result of a significant decrease in the incidence of graft loss caused by rejection--and especially accelerated acute rejection (P less than 0.007). Comparing actuarial graft survival for first graft recipients that had BNN prior to transplantation (n = 434) with those who had no nephrectomy (n = 2240) showed differences of 62% +/- 3 vs. 52% +/- 1 and 46% +/- 3 vs. 38% +/- 2 at one and three years, respectively. Analysis of first graft survival stratified for other factors known to influence outcome showed that the beneficial influence of BNN was independent of transfusion status or the number of transfusions given, use of antilymphocyte serum, pretransplant splenectomy, HLA match, or time on dialysis. The most striking increase in graft survival associated with BNN was seen in patients with evidence of presensitization as manifested by a positive panel reactive antibody (PRA) and in patients having delayed function (ATN) posttransplantation. The beneficial association of BNN was also found to be independent of the primary cause of renal failure or the specific indication leading to nephrectomy. These results suggest that patients receiving native bilateral nephrectomy prior to transplantation have a reduced incidence of graft loss from rejection by some as yet unexplained mechanism.


Effects of relaxation response training on attentional deficits in schizophrenics.
Four groups of six male patients each (12 = schizophrenic; 12 = antisocial personality) volunteered. One group from each diagnostic category were instructed in the Relaxation Response while the other two groups were instructed with a placebo exercise. After training, subjects were exposed to an attentional task involving manual responding to visual stimuli. Analyses of several dependent measures including mean correct responses yielded no significant group differences.


Intimate Partner Violence Victimization and Associated Factors among Male and Female University Students in 22 Countries in Africa, Asia and the Americas.
The study aimed at investigating the prevalence of intimate partner violence (IPV) and its associated factors among male and female university students in 22 countries in Africa, the Americas and Asia. In a cross-sectional questionnaire survey, data were collected from 16979 undergraduate university students, 49.3% male and 50.7% female, with an overall mean age of 21.8 years (SD=3.4). Of 7032 (41.9%) students who had been sexually active in the past 12 months, 16.3 % reported ever having experienced physical or sexual IPV, 15.4% among men and 17.2% among women, physical IPV was 11.3% among men and 10.4% among women, and the proportion of ever having experienced sexual IPV was 9.3% among men and 11.3% among women. In multivariate logistic regression analyses, among both men and women, sociodemographic factors (senior study year, living in a low or lower middle income country) and risk factors (history of childhood physical and sexual abuse, made someone pregnant or had been pregnant, having had two or more sexual partners in the past 12 months, current tobacco use and having PTSD symptoms) were associated with physical and/or sexual violence victimization. High burden of IPV was found and several factors identified that may help guide intervention efforts.


Rectangular collimation and radiographic efficacy in eight general dental practices in the West Midlands.
Rectangular collimation is recommended in order to reduce radiation doses to patients. However, anecdotal reports suggest that it may result in more retakes, with a possible net increase in patient dosage. To test this hypothesis, eight general dental practitioners were recruited to participate in a project. Each took 25 pairs of bitewing radiographs of patients before and 25 after fitting rectangular collimators to their x-ray machines. Double-pack films were used so that duplicates could be examined. These were assessed by a consultant oral radiologist according to the National Radiographic Protection Board (NRPB) grading system for positioning and general film quality. Initially, positioning quality was above the target level for six of the eight dentists; however, for all but one, this dropped after using rectangular collimation. General film quality was of a lower overall standard initially. Using rectangular collimation had an effect on general film quality but the direction and size of this varied among the dentists. It was concluded that amongst the participating dentists, although numbers of retakes increased by 7%, there would be a net reduction in dosage to patients following rectangular collimation.


Common principles underlying the control of rapid, single degree-of-freedom movements at different joints.
Studies of rapid, single degree-of-freedom movements have shown different changes in electromyographic patterns for movement tasks that appear very similar (e.g., movements over different ranges of distance). However, it is not clear whether these differences are a result of joint-specific control schemes or whether they are instead due to the limited range of task parameters studied relative to the mechanical constraints of each joint (e.g., short compared with long movements relative to the range of motion of a particular joint). In this study, we measured and compared the kinematic trajectories and electromyograms recorded during various movement tasks at the wrist, elbow, and ankle. Subjects performed movements over a wide range of distances "as fast as possible," "at a comfortable speed," and against two inertial loads (at the elbow only), and they performed movements over a fixed distance at three different speeds at the wrist and ankle. For fast movements we show that, in spite of some joint-specific differences, the basic pattern of electromyographic (EMG) modulation is similar at all three joints; for example, the agonist EMG burst transitions from a fixed duration to an increasing duration with increasing movement distance at all three joints. Moreover, the distance at which this transition occurs in one joint relative to the distance at which this transition occurs in the other two joints is consistent across subjects. The transition occurs at the shortest distance at the ankle and the longest distance at the wrist. In general we suggest that the data are consistent with a single set of control rules applied at all three joints, with the biomechanical constraints at each joint accounting for the differences in the EMG and kinematic patterns observed across joints.


Seasonal and spatial variations of heavy metals in two typical Chinese rivers: concentrations, environmental risks, and possible sources.
Ten metals were analyzed in samples collected in three seasons (the dry season, the early rainy season, and the late rainy season) from two rivers in China. No observed toxic effect concentrations were used to estimate the risks. The possible sources of the metals in each season, and the dominant source(s) at each site, were assessed using principal components analysis. The metal concentrations in the area studied were found, using t-tests, to vary both seasonally and spatially (P = 0.05). The potential risks in different seasons decreased in the order: early rainy season > dry season > late rainy season, and Cd was the dominant contributor to the total risks associated with heavy metal pollution in the two rivers. The high population and industrial site densities in the Taihu basin have had negative influences on the two rivers. The river that is used as a source of drinking water (the Taipu River) had a low average level of risks caused by the metals. Metals accumulated in environmental media were the main possible sources in the dry season, and emissions from mechanical manufacturing enterprises were the main possible sources in the rainy season. The river in the industrial area (the Wusong River) had a moderate level of risk caused by the metals, and the main sources were industrial emissions. The seasonal and spatial distributions of the heavy metals mean that risk prevention and mitigation measures should be targeted taking these variations into account.


Ethnic disparities in traumatic brain injury care referral in a Hispanic-majority population.
Functional outcomes after traumatic brain injury (TBI) can be significantly improved by discharge to posthospitalization care facilities. Many variables influence the discharge disposition of the TBI patient, including insurance status, patient condition, and patient prognosis. The literature has demonstrated an ethnic disparity in posthospitalization care referral, with Hispanics being discharged to rehabilitation and nursing facilities less often than non-Hispanics. However, this relationship has not been studied in a Hispanic-majority population, and thus, this study seeks to determine if differences in neurorehabilitation referrals exist among ethnic groups in a predominately Hispanic region. This study is a retrospective cohort that includes 1128 TBI patients who presented to University Medical Center El Paso, Texas, between the years 2005 and 2015. The patients' age, sex, race, residence, admission Glasgow Coma Scale (GCS), GCS motor, Injury Severity Score (ISS), hospital and intensive care unit length of stay (LOS), mechanism of injury, and discharge disposition were analyzed in univariate and multivariate models. Our study population had an insurance rate of 55.5%. Insurance status and markers of injury severity (hospital LOS, intensive care unit LOS, ISS, GCS, and GCS motor) were predictive of discharge disposition to rehabilitation facilities. The study population was 70% Hispanic, yet Hispanics were discharged to rehabilitation facilities (relative risk: 0.56, P: 0.001) and to long-term acute care/nursing facilities (relative risk: 0.35, P < 0.0001) less than non-Hispanics even after LOS, ISS, ethnicity, insurance status, and residence were adjusted for in multivariate analysis. This study suggests that patients of different ethnicities but comparable traumatic severity and insurance status receive different discharge dispositions post-TBI even in regions in which Hispanics are the demographic majority.


Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry.
During the development of new vasoactive agents, arterial blood pressure monitoring is crucial for evaluating the efficacy of the new proposed drugs. Indeed, research focusing on the discovery of new potential therapeutic targets using genetically altered mice requires a reliable, long-term assessment of the systemic arterial pressure variation. Currently, the gold standard for obtaining long-term measurements of blood pressure in ambulatory mice uses implantable radio-transmitters, which require artery cannulation. This technique eliminates the need for tethering, restraining, or anesthetizing the animals which introduce stress and artifacts during data sampling. However, arterial blood pressure monitoring in mice via catheterization can be rather challenging due to the small size of the arteries. Here we present a step-by-step guide to illustrate the crucial key passages for a successful subcutaneous implantation of radio-transmitters and carotid artery cannulation in mice. We also include examples of long-term blood pressure activity taken from freely moving mice after a period of post-surgery recovery. Following this procedure will allow reliable direct blood pressure recordings from multiple animals simultaneously.


[Effect of emodin on hepatocellular apoptosis following orthotopic liver transplantation in rats].
To evaluate the effect of emodin on hepatocellular apoptosis following orthotopic liver transplantation (OLT) in rats. The LEW --> BN OLT models were established. A total of 24 rats were divided randomly and equally into 4 groups. Group A was treated with normal saline at dose of 0.5 mL x d(-1) intraperitoneally from 1st day to 8 th day after operation. Group B, CsA at dose of 10.0 mg x kg(-1) x d(-1). Group C, emodin at dose of 50.0 mg x kg(-1) x d(-1). Group D, CsA at dose of 10.0 mg x kg(-1) x d(-1) and emodin at dose of 50.0 mg x kg(-1) x d(-1). Fifteen days after operation, rejection active index (RAI) and hepatocellular apoptosis index (AI) was confirmed after observing the pathologic change of transplanted liver in recipients. Respectively, the RAI of group A, B, C, D was 7.67 +/- 0.98, 5.17 +/- 0.40, 5.83 +/- 0.75, 3.83 +/- 0.75 and the AI of group A, B, C, D was 35.83 +/- 2.320, 15.83 +/- 1.33, 16.50 +/- 2.35, 11.50 +/- 1.05. The RAI and AI of group B, C, D was significantly lower than group A (P < 0.01) and group D was significantly lower than group B, C too (P < 0.05). There was no significant distinction between group B and C in RAI and AI. Emodin has the effect of reduce the hepatocellular apoptosis following OLT in rats and the effect can stronger by CsA.


Iron oxide-based nanoparticles with different mean sizes obtained by the laser pyrolysis: structural and magnetic properties.
Nano-sized iron oxide-based particles have been directly synthesized by the laser induced pyrolysis of a mixture containing iron pentacarbonyl/air (as oxidizer)/ethylene (as sensitizer). In this paper we further demonstrate the possibility to vary the chemical composition and the nanoparticle dimensions of the iron oxide-based materials by handling the oxidation procedure in the frame of the laser pyrolysis process. Thus, nanoparticles with major maghemite/magnetite content may change composition into mixtures with variable amounts of three components: major gamma-Fe2O3/Fe3O4 iron oxide, metallic Fe and cementite Fe3C. By X-ray diffraction (XRD) it is found that the relative proportion of these phases differs in function of the reaction temperature (laser power). As revealed by transmission electron microscopy (TEM), mean particle sizes between about 4 nm and 6 nm and between about 9 and 11 nm may be prepared by varying the oxidation procedure and the laser power, respectively. By the controlled heating of samples (maximum temperature 185 degrees C), increased crystallinity for the gamma-Fe2O3/Fe3O4 oxide phase was found as well as an increase of the mean particle diameters. The examination of the magnetization curves for samples obtained for different laser powers indicates notable differences in the magnetic behavior and parameters. The temperature dependent Mossbauer measurements confirm the formation of larger particles at higher laser power densities as well as the presence of inter-particle magnetic interactions. On this basis, the estimation of phase composition for the different representative samples is given.


Assessment of fetal-maternal haemorrhage in mothers with hereditary persistence of fetal haemoglobin.
Kleihauer examination of peripheral blood cannot be used reliably to detect transplacental fetal-maternal haemorrhage in mothers with hereditary persistence of fetal haemoglobin (HPFH). In Rh(D) negative pregnancies diagnostic confusion with a large fetal-maternal haemorrhage could result in the administration of inappropriately excessive amounts of anti-D immunoglobulin, and the inability to diagnose and quantify transplacental haemorrhage in maternal HPFH by current methods could result in insufficient anti-D administration and subsequent Rh(D) sensitisation. Accordingly, a method to detect and quantify fetal-Rh(D) positive maternal haemorrhage using erythrocyte fluorescent immunocytometry was developed. An indirect immunofluorescence method with IgG anti-D immunoglobulin as the primary antibody was used, combined with quantitative analysis on a fluorescence activated cell sorter. The method was accurate, specific, and sensitive and could detect a contaminating population of 0.1% Rh(D) positive cells in Rh(D) negative blood--a level of fetal-maternal haemorrhage well covered by a single dose of 500 IU of anti-D immunoglobulin.


Mayaro virus: imported cases of human infection in São Paulo State, Brazil.
Mayaro virus (MAYV) is an arbovirus (Togaviridae: Alphavirus) enzootic in tropical South America and maintained in a sylvan cycle involving wild vertebrates and Haemagogus mosquitoes. MAYV cases occur sporadically in persons with a history of recent activities inside or around forests. This paper reports three cases of MAYV fever detected in men infected in Camapuã, MS, Brazil. Serum samples collected at four days and two months after the onset of the symptoms and examined by hemagglutination inhibition test, revealed monotypic seroconversion to MAYV. Isolation of the virus was obtained from one of the samples by inoculation of the first blood samples into newborn mice. A suspension of the infected mouse brain was inoculated into C6/36 cells culture and the virus was identified by indirect immunofluorescent assay with alphavirus polyclonal antibodies. RT-PCR, performed with RNA extracted from the supernatant of C6/36 infected cells in the presence of alphavirus generic primers as well as specific MAYV primers, confirmed these results. The reported cases illustrate the importance of laboratory confirmation in establishing a correct diagnosis. Clinical symptoms are not always indicative of a disease caused by an arbovirus. Also MAYV causes febrile illness, which may be mistaken for dengue.


Enantiocomplementary enzymatic resolution of the chiral auxiliary: cis,cis-6-(2,2-dimethylpropanamido)spiro[4.4]nonan-1-ol and the molecular basis for the high enantioselectivity of subtilisin Carlsberg.
cis,cis-(+/-)-6-(2,2-Dimethylpropanamido)spiro[4.4]nonan-1-ol, 1, a chiral auxiliary for Diels-Alder additions, was resolved by enzyme-catalyzed hydrolysis of the corresponding butyrate and acrylate esters. Subtilisin Carlsberg protease and bovine cholesterol esterase both showed high enantioselectivity in this process, but favored opposite enantiomers. Subtilisin Carlsberg favored esters of (1S,5S,6S)-1, while bovine cholesterol esterase favored esters of (1R,5R,6R)-1, consistent with the approximately mirror-image arrangement of the active sites of subtilisins and lipases/esterases. A gram-scale resolution of 1-acrylate with subtilisin Carlsberg yielded (1S,5S,6S)-1 (1.1 g, 46 % yield, 99 % ee) and (1R,5R,6R)-1-acrylate (1.3 g, 44 % yield, 99 % ee) although the reaction was slow. The high enantioselectivity combined with the conformational rigidity of the substrate made this an ideal example to identify the molecular basis of the enantioselectivity of subtilisin Carlsberg toward secondary alcohols. When modeled, the favored (1S,5S,6S) enantiomer adopted a catalytically productive conformation with two longer-than-expected hydrogen bonds, consistent with the slow reaction rate. The unfavored (1R,5R,6R) enantiomer encountered severe steric interactions with catalytically essential residues in the model. It either distorted the catalytic histidine position or encountered severe steric strain with Asn155, an oxyanion-stabilizing residue.


Subset-specific, uniform activation among V gamma 6/V delta 1+ gamma delta T cells elicited by inflammation.
The V gamma 6/V delta 1(+) cells, the second murine gamma delta T cell subset to arise in the thymus, express a nearly invariant T cell receptor (TCR), colonize select tissues, and expand preferentially in other tissues during inflammation. These cells are thought to help in regulating the inflammatory response. Until now, V gamma 6/V delta 1(+) cells have only been detectable indirectly, by expression of V gamma 6-encoding mRNA. Here, we report that 17D1, a monoclonal antibody, which detects the related epidermis-associated V gamma 5/V delta 1(+) TCR, will also bind the V gamma 6/V delta 1(+) cells if their TCR is first complexed to an anti-C delta antibody. Features of this special condition for recognition suggest the possibility that an alternate structure exists for the V gamma 6/V delta 1 TCR, which is stabilized upon binding to the anti-C delta antibody. Using the 17D1 antibody as means to track this gamma delta T cell subset by flow cytometry, we discovered that the response of V gamma 6/V delta 1(+) cells during inflammation often far exceeds that of other subsets and that the responding V gamma 6/V delta 1(+) cells display a strikingly uniform activation/memory phenotype compared with other gamma delta T cell subsets.


Basis of bone metabolism around dental implants during osseointegration and peri-implant bone loss.
Despite the growing number of publications in the field of implant dentistry, there are limited studies to date investigating the biology and metabolism of bone healing around dental implants and their implications in peri-implant marginal bone loss. The aim of this review article is to provide a thorough understanding of the biological events taking place during osseointegration and the subsequent early and late phases of bone remodeling around dental implants. An update on the coupling mechanism occurring during bone resorption-bone remodeling is provided, focused on the relevance of the osteocytes, bone lining cells and immune cells during bone maintenance. An electronic and manual literature search was conducted by three independent reviewers in several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register databases for articles up to September 2016 with no language restriction. Local bone metabolism is subject to signals from systemic calcium-phosphate homeostasis and bone remodeling. Three areas of interest were reviewed due to recent reported compromises in bone healing including the putative effects of (1) cholesterol, (2) hyperlipidemia, and (3) low vitamin D intake. Moreover, the prominent influence of osteocytes and immune cells is discussed as being key regulators during dental implant osseointegration and maintenance. These cells are of crucial importance in the presence of biofilm accumulation and their associated byproducts that leads to hard and soft tissue breakdown; the so called peri-implantitis. Factors that could negatively impact osteoclastogenesis or osteal macrophage activation should be monitored in future research including implant placement/torque protocols, bone characteristics, as well as meticulous maintenance programs to favor osseointegration and future long-term stability and success of dental implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2075-2089, 2017.


Risperidone Induced Granulomatous Mastitis Secondary to Hyperprolactinemia in a Non-Pregnant Woman-A Rare Case Report in a Bipolar Disorder.
Idiopathic granulomatous lesion is a rare entity of the breast seen in young-middle aged women. Diagnosis and management of granulomatous lesions with known aetiology does not impose major clinical problems. However, most often these lesions are undetected or unnoticed due to lack of timely diagnosis and inappropriate management, as primarily it is idiopathic. Hyperprolactinemia have been proposed as one of the mechanisms underlying the development of granulomatous lesions of the breast. We report a case of hyperprolactinemia due to risperidone therapy for bipolar mood disorder in a woman who eventually developed granulomatous mastitis. Histologically, the diagnosis was confirmed by the presence of granulomatous lesion and by ruling out other potential causes. In this case, raised prolactin was possibly an important factor which was secondary to risperidone therapy. However, idiopathic granulomatous mastitis could not be completely ruled out.


Oviposition Preference and Larval Host Range of the Sugarbeet Root Maggot (Diptera: Ulidiidae).
The sugarbeet root maggot, Tetanops myopaeformis Röder (Diptera: Ulidiidae), is native to North America. However, its primary crop host, sugarbeet, Beta vulgaris L., was introduced to the continent from Europe in the late 19th century. This field and greenhouse research was conducted to compare the relative attractiveness of eight cultivated and wild plant species for oviposition by T. myopaeformis, and the suitability of these potential host plants for larval development to elucidate the potential native and current host range of this pest. Results indicated that females preferred ovipositing in soil immediately adjacent to or on the following plant species: sugarbeet; spinach, Spinacia olerocea L.; common lambsquarters, Chenopodium album L.; redroot pigweed, Amaranthus retroflexus L.; Palmer amaranth, Amaranthus palmeri S. Wats.; and to a lesser extent, spear saltbush, Atriplex patula L. Larval survival was greatest on spinach, sugarbeet, and spear saltbush, which all belong to the family Chenopodiaceae. Larval survival on these plants suggests that T. myopaeformis could have exploited wild chenopodiaceous plants or others within the order Caryophyllales before sugarbeet was introduced to North America. Low larval survival on common lambsquarters, redroot pigweed, and Palmer amaranth suggests that these species are suboptimal hosts, despite demonstrated attractiveness for oviposition. A general lack of oviposition preference by T. myopaeformis females was observed for sunflower, Helianthus annuus L., and common ragweed, Ambrosia artemisiifolia L. These results provide insights regarding the successful and somewhat rapid host preference shift by this insect to sugarbeet after cultivation of the crop began in the continent.


A prediction tool for nosocomial multi-drug Resistant Gram-Negative Bacilli infections in critically ill patients - prospective observational study.
The widespread use of empiric broad spectrum antibiotics has contributed to the global increase of Resistant Gram-Negative Bacilli (RGNB) infections in intensive care units (ICU). The aim of this study was to develop a tool to predict nosocomial RGNB infections among ICU patients for targeted therapy. We conducted a prospective observational study from August'07 to December'11. All adult patients who were admitted and stayed for more than 24 hours at the medical and surgical ICU's were included. All patients who developed nosocomial RGNB infections 48 hours after ICU admission were identified. A prediction score was formulated by using independent risk factors obtained from logistic regression analysis. This was prospectively validated with a subsequent cohort of patients admitted to the ICUs during the following time period of January-September 2012. Seventy-six patients with nosocomial RGNB Infection (31bacteremia) were compared with 1398 patients with Systemic Inflammatory Response Syndrome (SIRS) without any gram negative bacterial infection/colonization admitted to the ICUs during the study period. The following independent risk factors were obtained by a multivariable logistic regression analysis - prior isolation of Gram negative organism (coeff: 1.1, 95% CI 0.5-1.7); Surgery during current admission (coeff: 0.69, 95% CI 0.2-1.2); prior Dialysis with end stage renal disease (coeff: 0.7, 95% CI 0.1-1.1); prior use of Carbapenems (coeff: 1.3, 95% CI 0.3-2.3) and Stay in the ICU for more than 5 days (coeff: 2.4, 95% CI 1.6-3.2). It was validated prospectively in a subsequent cohort (n = 408) and the area-under-the-curve (AUC) of the GSDCS score for predicting nosocomial ICU acquired RGNB infection and bacteremia was 0.77 (95% CI 0.68-0.89 and 0.78 (95% CI 0.69-0.89) respectively. The GSDCS (0-4.3) score clearly differentiated the low (0-1.3), medium (1.4-2.3) and high (2.4-4.3) risk patients, both for RGNB infection (p:0.003) and bacteremia (p:0.009). GSDCS is a simple bedside clinical score which predicts RGNB infection and bacteremia with high predictive value and differentiates low versus high risk patients. This score will help clinicians to choose appropriate, timely targeted antibiotic therapy and avoid exposure to unnecessary treatment for patients at low risk of nosocomial RGNB infection. This will reduce the selection pressure and help to contain antibiotic resistance in ICUs.


Motor actions are spatially organized in motor and dorsal premotor cortex.
Frontal motor areas are central to controlling voluntary movements. In non-human primates, the motor areas contain independent, somatotopic, representations of the forelimb (i.e., motor maps). But are the neural codes for actions spatially organized within those forelimb representations? Addressing this question would provide insight into the poorly understood structure-function relationships of the cortical motor system. Here, we tackle the problem using high-resolution optical imaging and motor mapping in motor (M1) and dorsal premotor (PMd) cortex. Two macaque monkeys performed an instructed reach-to-grasp task while cortical activity was recorded with intrinsic signal optical imaging (ISOI). The spatial extent of activity in M1 and PMd was then quantified in relation to the forelimb motor maps, which we obtained from the same hemisphere with intracortical microstimulation. ISOI showed that task-related activity was concentrated in patches that collectively overlapped <40% of the M1 and PMd forelimb representations. The spatial organization of the patches was consistent across task conditions despite small variations in forelimb use. Nevertheless, the largest condition differences in forelimb use were reflected in the magnitude of cortical activity. Distinct time course profiles from patches in arm zones and patches in hand zones suggest functional differences within the forelimb representations. The results collectively support an organizational framework wherein the forelimb representations contain subzones enriched with neurons tuned for specific actions. Thus, the often-overlooked spatial dimension of neural activity appears to be an important organizing feature of the neural code in frontal motor areas.


Reduced Iron-Containing Clay Minerals as Antibacterial Agents.
Previous work documented the general antibacterial mechanism of iron containing clays that involved hydroxyl radical (•OH) production from soluble Fe2+, and attack of cell membrane and intracellular proteins. Here we explore the role of clay structural Fe(II) in •OH production at near neutral pH and identify a lipid involved in the antibacterial process. Structural Fe(III) in nontronite NAu-2 was reduced (rNAu-2) and E. coli, a model bacterium, was exposed to rNAu-2 in oxic suspension. The antibacterial activity of rNAu-2 was dependent on pH and Fe(II) concentration, where E. coli were completely killed at pH 6, but survived at pH 7 and 8. In the presence of a •OH scavenger or in anaerobic atmosphere, E. coli survived better, suggesting that cell death may be caused by •OH generated from oxidation of structural Fe(II) in rNAu-2. In-situ imaging revealed damage of a membrane lipid, cardiolipin, in the polar region of E. coli cells, where reactive oxygen species and redox-active labile Fe were enriched. Our results advance the previous antibacterial model by demonstrating that the structural Fe(II) is the primary source of •OH, which damages cardiolipin, triggers the influx of soluble Fe2+ into the cell, and ultimately leads to cell death.


Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors.
A role for the membrane/cytoskeleton interface in the development and progression of cancer is established, yet poorly understood. The neurofibromatosis type II (NF2) tumor suppressor gene encodes a member of the ezrin/radixin/moesin (ERM) family of membrane/cytoskeleton linker proteins thought to be important for cell adhesion and motility. We report that in contrast to the narrow spectrum of benign tumors in human NF2 patients, Nf2 heterozygous mice develop a variety of malignant tumors. Using the fact that Nf2 is linked to the p53 tumor suppressor locus in the mouse we have also investigated the effects of genetic linkage of cancer-predisposing mutations on tumorigenesis and examined the genetic pathway to tumor formation involving Nf2 loss. Importantly, we observed a very high rate of metastasis associated with Nf2 deficiency, with or without loss of p53 function, and we provide experimental evidence supporting a role for Nf2 loss in metastatic potential. Together, our results suggest an important role for the NF2 tumor suppressor, and perhaps the ERM family in tumor formation and metastasis.


Genome haploidisation with chromosome 7 retention in oncocytic follicular thyroid carcinoma.
Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20). Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways. All FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent). We demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research. MICROARRAYS: Data are made available at GEO (GSE31828).


Intraspecific variation in Heterobasidion annosum for mortality rate on Pinus sylvestris and Picea abies seedlings grown in pure culture.
One-month-old Scots pine (Pinus sylvestris) and Norway spruce (Picea abies) seedlings were inoculated in vitro with Heterobasidion annosum strains, four each of the P-, S- and F-intersterility groups. Variation among strains and between the IS groups in virulence, expressed in mortality rate, was detected during twelve months after inoculation. Most of the strains were more virulent on spruce than on pine, and mortality of spruce seedlings was significantly higher. The P strains displayed similar virulence on both hosts, while S strains caused higher mortality of spruce seedlings and significantly lower mortality of pine seedlings. Strains of the F group were less virulent, but killed significantly (P < 0.05) more spruce than pine seedlings. In the interspecific analyses with two hosts, the isolates and IS groups accounted for most of the explained variation in the host mortality.


Photogalvanic effect in monolayer black phosphorus.
We report a first-principles theoretical approach for analyzing linear and circular photogalvanic effects (PGEs) based on density functional theory within the nonequilibrium Green's function formalism. Using this approach we investigate the PGE phenomena in monolayer black phosphorus (MBP) doped with sulfur atoms. The impurity doping breaks the space inversion symmetry of pristine MBP, leading to a C s symmetry with a mirror reflection plane normal to the zigzag direction of the MBP lattice. Governed by this symmetry, a linear PGE is induced in both zigzag and armchair directions, and a circular PGE is induced along the zigzag direction. A robust broadband photoresponse is found from the near-infrared to the visible range for the MBP device. There is a strong anisotropy in PGE: photoresponse in the zigzag direction can be larger by an order of magnitude than that in the armchair direction. We identify the origin of the observed PGE as the inter-band transitions from the impurity and valence bands to the conduction bands, which involves a transfer of angular momentum from photons to electrons.


Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver.
To define the characteristics of the Italian patient presenting non-alcoholic fatty liver disease. A total of 305 patients with abnormally high plasma aminotransferase and/or gamma-glutamyl-transpeptidase levels for at least 12 months, with no known cause of chronic liver damage, were consecutively enrolled in the study. Clinical, routine biochemical and liver histology investigations were carried out in all patients. Also evaluated were: (a) oral glucose load; (b) insulinaemia and insulin-resistance using the HOMA test model; and (c) plasma endotoxaemia, total antioxidant plasma capability, tumour necrosis factor-alpha, plasma interleukin-6 and -10 levels. Malondialdehyde and 4-hydroxynonenal content were determined on liver samples from 120 patients. The majority of patients were young overweight or obese males, with dyslipidaemia (20-60%), diabetes (10.5%), hyperinsulinaemia (40%), hyperferritinaemia (35%). Endotoxaemia was negative in all patients and cytokines were only sporadically altered. Total antioxidant plasma capability was decreased in 38.4% of the patients. Eighty percent of the cases had histological steatosis with a mild degree of inflammation and fibrosis. Seven patients had cirrhosis. Lipid peroxidation markers were increased in 90% of the cases, inversely correlated with fibrosis. Even if at univariate analysis, age, ferritin and tissue 4-hydroxynonenal were independent factors of steatosis (P < 0.01), and insulin, HOMA and ferritin of inflammation and fibrosis (P < 0.01), at multivariate analysis no single factor was found to be an independent predictor of hepatic lesions. The typical Italian patient with non-alcoholic fatty liver disease is a young male, obese, not diabetic, with a variable incidence of dyslipidaemia and hyperinsulinaemia. Only liver biopsy may define the type of liver damage.


How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers.
It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated in this article, the reporting of ADRs via e-mail would cause real problems for the drug safety units. Finally, they consider that telephone call centres should be restricted to a specific communication problem such as crisis management or Dear Dr letters.


APP transgenic mice: their use and limitations.
Alzheimer's disease is the most widespread form of dementia. Its histopathological hallmarks include vascular and extracellular β-amyloid (Aβ) deposition and intraneuronal neurofibrillary tangles (NFTs). Gradual decline of cognitive functions linked to progressive synaptic loss makes patients unable to store new information in the earlier stages of the pathology, later becoming completely dependent because they are unable to do even elementary daily life actions. Although more than a hundred years have passed since Alois Alzheimer described the first case of AD, and despite many years of intense research, there are still many crucial points to be discovered in the neuropathological pathway. The development of transgenic mouse models engineered with overexpression of the amyloid precursor protein carrying familial AD mutations has been extremely useful. Transgenic mice present the hallmarks of the pathology, and histological and behavioural examination supports the amyloid hypothesis. As in human AD, extracellular Aβ deposits surrounded by activated astrocytes and microglia are typical features, together with synaptic and cognitive defects. Although animal models have been widely used, they are still being continuously developed in order to recapitulate some missing aspects of the disease. For instance, AD therapeutic agents tested in transgenic mice gave encouraging results which, however, were very disappointing in clinical trials. Neuronal cell death and NFTs typical of AD are much harder to replicate in these mice, which thus offer a fundamental but still imperfect tool for understanding and solving dementia pathology.


Histidine enhances carbamazepine action against seizures and improves spatial memory deficits induced by chronic transauricular kindling in rats.
To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and gamma-amino-butyric acid levels were measured by high performance liquid chromatography (HPLC). Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no ameliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures. Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.


Terminal Patients and the Right to Refuse Medical Treatment in Argentina.
The right to health has many dimensions. On the one hand, it entails positive duties for states to protect the health of individuals. On the other, it encompasses patient decision making regarding personal health, an idea which is closely linked to the right to autonomy and the right to free development of the individual-that is, to dignity.1 This is why the informed consent of the patient and her right to make a choice according to her own values should be honored, even when her decision may seem irrational or imprudent. When patients are incapable of providing informed consent-for example, if the patient is unconscious-the law can authorize certain persons to act as a proxy on their behalf. In Argentina, the Patients' Rights Act (2009) as amended by the Death with Dignity Act (2012) states that if a patient is unable to provide informed consent, consent may be provided on her behalf by her close relatives, affinal kin, or legal guardian, in this order of preference.2 The Patients' Rights Act also permits patients to set up advance directives regarding health decisions to be made if they become terminally ill. In 2015, the Argentine Supreme Court of Justice discussed the scope of patient autonomy in the case D., M.A. s/ declaración de incapacidad.3 This case presented a question that had yet to be explored by the court: how can we determine an unconscious patient's will if she does not have written advance directives concerning whether a life-sustaining medical treatment should be continued? This article examines the grounds of the Argentine Supreme Court's decision in D., M.A. First, we describe the case law that existed prior to D., M.A. Then, after explaining the facts of the case, we discuss the ruling and raise doubts about its scope.4.


Growth hormone replacement therapy improves hypopituitarism-associated hypoxemia in a patient after craniopharyngioma surgery: A case report.
There are some reports about hypoxemia related to hypopituitarism. However, little is known about the relationship between growth hormone deficiency (GHD) and hypoxemia. A 23-year-old female presented with severe hypoxemia after the operations of craniopharyngioma. Laboratory tests found that serum growth hormone (GH) levels were extremely low. She was diagnosed with growth hormone deficiency-related hypoxemia. In addition to oxygenation, low doses of GH replacement therapy was conducted for 3-month. After 3-month r-hGH replacement therapy, hypoxemia was improved significantly and the level of serum GH was elevated. We've already known that hypopituitarism may induce hypoxemia owing to multiple possible mechanisms according to previous literature. But little is known about growth hormone deficiency-related hypoxemia. Our case shows that GH replacement therapy is an effective treatment, and it's significant to examination the level of GH in serum for hypoxemia patients especially when the cause of hypoxemia is unknown.


Network pharmacology-based study of the protective mechanism of conciliatory anti-allergic decoction on asthma.
This study aimed to explore the underlying anti-asthma pharmacological mechanisms of conciliatory anti-allergic decoction (CAD) with a network pharmacology approach. Traditional Chinese medicine related databases were utilized to screen the active ingredients of CAD. Targets of CAD for asthma treatment were also identified based on related databases. The protein-protein interaction network, biological function and KEGG pathway enrichment analysis, and molecular docking of the targets were performed. Furthermore, an asthma mouse model experiment involving HE staining, AB-PAS staining, and ELISA was also performed to assess the anti-asthma effect of CAD. There were 77 active ingredients in CAD, including quercetin, kaempferol, stigmasterol, luteolin, cryptotanshinone, beta-sitosterol, acacetin, naringenin, baicalin, and 48 related targets for asthma treatment, mainly including TNF, IL4, IL5, IL10, IL13 and IFN-γ, were identified with ideal molecular docking binding scores by network pharmacology analysis. KEGG pathway analysis revealed that these targets were directly involved in the asthma pathway, Th1 and Th2 cell differentiation, and signaling pathways correlated with asthma (NF-κB, IL17, T cell receptor, TNF, JAK-STAT signaling pathways, etc.). Animal experiments also confirmed that CAD could attenuate inflammatory cell invasion, goblet cell hyperplasia and mucus secretion. The levels of the major targets TNF-α, IL4, IL5, and IL13 can also be regulated by CAD in an asthma mouse model. The anti-asthma mechanism of CAD possibly stemmed from the active ingredients targeting asthma-related targets, which are involved in the asthma pathway and signaling pathways to exhibit therapeutic effects.


Computational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanning.
Ribosome profiling (ribo-seq) provides experimental data on the density of elongating or initiating ribosomes at the whole transcriptome level that can be potentially used for estimating absolute levels of translation initiation at individual Translation Initiation Sites (TISs). These absolute levels depend on the mutual organisation of TISs within individual mRNAs. For example, according to the leaky scanning model of translation initiation in eukaryotes, a strong TIS downstream of another strong TIS is unlikely to be productive, since only a few scanning ribosomes would be able to reach the downstream TIS. In order to understand the dependence of translation initiation efficiency on the surrounding nucleotide context, it is important to estimate the strength of TISs independently of their mutual organisation, i.e. to estimate with what probability a ribosome would initiate at a particular TIS. We designed a simple computational approach for estimating the probabilities of ribosomes initiating at individual start codons using ribosome profiling data. The method is based on the widely accepted leaky scanning model of translation initiation in eukaryotes which postulates that scanning ribosomes may skip a start codon if the initiation context is unfavourable and continue on scanning. We tested our approach on three independent ribo-seq datasets obtained in mammalian cultured cells. Our results suggested that the method successfully discriminates between weak and strong TISs and that the majority of numerous non-AUG TISs reported recently are very weak. Therefore the high frequency of non-AUG TISs observed in ribosome profiling experiments is due to their proximity to mRNA 5'-ends rather than their strength. Detectable translation initiation at non-AUG codons downstream of AUG codons is comparatively infrequent. The leaky scanning method will be useful for the characterization of differences in start codon selection between tissues, developmental stages and in response to stress conditions.


Ultrasound-assisted extraction of soy isoflavones.
Efficiency in extracting four isoflavone derivatives (daidzin, glycitin, genistin and malonyl genistin) from freeze-dried ground soybeans was compared for mix-stirring extraction and ultrasound-assisted extraction, using different solvents and extraction temperatures with both. The efficiency of the extraction of soy isoflavones was improved by ultrasound but was dependent on the solvent employed. Optimization of the ratios of sample quantity to solvent volume and length of extraction time was also performed. Isoflavones can be quantitatively extracted from soybeans with 50% ethanol at 60 degrees C using ultrasound-assisted extraction in 20 min.


Improving the global identification of bipolar spectrum disorders: Meta-analysis of the diagnostic accuracy of checklists.
Shifting definitions and differences in the conceptualization of bipolar disorders have contributed to long diagnostic delays, poor reliability, and inconsistent findings. Rating scales are independent of clinical judgment and offer a reliable way to assess manic symptoms, making them good tools to improve both clinical and research diagnoses of bipolar disorder. However, there are dozens of candidates, with few obvious distinguishing characteristics, making it difficult to select one. Our goal was to metaanalyze the diagnostic accuracy of rating scales designed to identify [hypo]manic symptoms. Additionally, we explored potential moderator variables including global region, translation into a different language, and sample composition. Nearly 4000 articles were identified with searches in PubMed and PsycINFO, yielding 127 effect sizes from 103 studies that met the following inclusion criteria: (a) statistics reported by which a standardized effect size could be calculated, (b) participants age 18 + years, (c) reference diagnoses made by semistructured/structured diagnostic interview, (d) results published in English. Multivariate mixed regression models accounted for multiple effect sizes nested within sample. One hundred twenty-seven effect sizes across 14 rating scales were evaluated. There was significant heterogeneity across effect sizes; Cochran's Q(126 df) = 1622.08, p < .00005, and substantial variance components both within (σ2 = .057) and between samples (σ2 = .253). Four measures performed similarly well and significantly better than some competitors after controlling for design and reporting features. The best rating scales offer an inexpensive, efficient way to improve research and clinical diagnostic processes across diverse populations, and could also complement formal diagnoses for examining secular and cultural trends. (PsycINFO Database Record


[Surgical treatment of Hailey-Hailey disease or benign chronic familial pemphigus. Apropos of a case of submammary localization].
The authors report a case of Hailey-Hailey disease or familial benign chronic pemphigus and review the literature concerning the surgical treatments used for this disabling disease. The majority of authors recommend excision followed by split skin graft, while others prefer excision followed by directed healing or simple excision-suture. The case reported here is the first reported case of cure of Hailey-Hailey disease combined with mammaplasty in a single stage.


Identification of a novel glial cell line-derived neurotrophic factor-inducible gene required for renal branching morphogenesis.
In the developing kidney, activation of the rearrangement during transfection tyrosine kinase by glial cell line-derived neurotrophic factor (GDNF) is required for normal branching of the ureteric bud epithelium [corrected]. By differential display analysis we identified a novel GDNF-inducible gene (named GZF1) with a BTB/POZ (broad complex, tramtrack, and bric-a-brac)/(poxvirus and zinc finger) domain and 10 tandemly repeated zinc finger motifs. The up-regulation of the GZF1 gene showed two peaks at 1 h and 24-48 h after GDNF stimulation by Northern blotting. The late induction was also found at protein levels by Western blotting with anti-GZF1 antibody. As observed for other proteins with the BTB/POZ domain, the GZF1 protein had strong transcriptional repressive activity. Intriguingly, its expression was detected at high levels in branching ureteric buds and collecting ducts of mouse metanephric kidney in which RET was also expressed. Antisense phosphorothioated oligodeoxynucleotides of the GZF1 gene markedly impaired the ureteric bud branching in the metanephric organ culture, suggesting that the induction of GZF1 expression via the GDNF/RET signaling system is required for renal branching morphogenesis.


Evidence that the Vibrio vulnificus flagellar regulator FlhF is regulated by a quorum sensing master regulator SmcR.
A single polar flagellum and motility are potential virulence factors of Vibrio vulnificus, a foodborne pathogen. In the present study, the functions of FlhF and regulatory characteristics of the flhF expression of V. vulnificus were investigated. A deletion mutation in flhF abolished motility, flagella formation and flagellin synthesis, and introduction of flhF in trans complemented the defects. The flhF mutant revealed decreased expression of the class III and IV flagella genes, indicating that FlhF is a key regulator for the flagellar biogenesis of V. vulnificus. The influence of global regulatory proteins on the expression of flhF was examined and SmcR, a LuxR homologue, was found to downregulate flhF expression at the transcriptional level. SmcR represses flhF expression only in the stationary phase of growth and exerts its effects by directly binding to the flhF promoter region. Finally, an SmcR binding site, centred at 22.5 bp upstream of the transcription start site, was identified by a DNase I protection assay. The combined results demonstrate that a quorum sensing master regulator SmcR influences the motility and flagellar biogenesis of V. vulnificus through modulating the expression of FlhF in a growth-phase-dependent manner.


[The effect of NO, ET-1 on brain injury after hind limbs ischemia/reperfusion in rats].
To study the roles of nitric oxide (NO) and ET-1 in brain injury after hind limbs ischemia/reperfusion in rats and to investigate the effect of NO/ ET-1 balance on brain injury. On a model of the hind limbs ischemia/reperfusion (LI/R) of rats, we used L-Arg(L-arginine, L-Arg), one of the substrates in the process of nitric oxide, aminoguanidine (AG) which inhibits nitric oxide synthase(NOS) and ETA receptor antagonist BQ123, to observe the changes of NO, ET-1, MDA, XOD, SOD, LDH in plasma and tNOS, iNOS, cNOS, NO, ET-1, MDA, XOD, MPO, SOD in brain tissue. Compared with the control group, the content of MDA, XOD, LDH in plasma and MDA, XOD, MPO in brain tissue increased. The activity of SOD decreased (P < 0.01). The content of tNOS, iNOS in brain tissue increased, cNOS decreased (P < 0.01). The content of NO, ET-1 in I/R group in plasma and brain tissue increased, the ratio of NO/ET-1 decreased. The brain injury was deteriorated. After using L-Arg and BQ123, the ratio of NO/ET-1 in plasma and brain tissue increased, the brain injury lightened. Whereas after using AG, the ratio of NO/ET-1 decreased, brain injury became more serious. The NO/ET-1 ratio decreased after LI/R, brain injury became more serious.


An evaluation of the sling surgical method of the bulbar urethra in the treatment of men's stress urinary incontinence at Shohadaye Ashayer Teaching Hospital in 2008.
To evaluate the utility and efficacy of bulbar urethera sling in the management of sphincter insufficiency that usually occurs after prostate surgery or posterior urethral injuries and may lead to moderate to severe stress incontinence. A total of 30 patients underwent sling surgery with rectus fascia in a four-year period at the Shohadaye Ashayer Teaching Hospital in Iran. Urinary incontinence occurred in 8 patients after open prostatectomy, in 12 patients after prostatectomy through urethra, in 8 patients after radical prostatectomy. For the purpose of the study, 2 patients in whom incontinence occurred after pelvic fracture were excluded. The 28 patients were followed up for a one-year period after the operation. All patients had incontinence from one to six years. After hospitalisation, an 18 gauge Foley's catheter was introduced in the urethra in every patient. The perineum was incised longitudinally, and the bulbar urethra was freed and a 2x7 cm span of rectus fascia was separated and placed under the bulbar urethra. Treatment was defined as use of one or no pad per day and recovery, as a reduction of at least 50% in the number of the used pads after sling operation. After operation, all patients suffering from moderate to severe stress incontinence were treated with 0-1 pad per day. Four patients were unable to urinate; in 2 patients the sling was modified and loosened, and in two others dilatation resolved their problems. Bulbar urethra sling can be carried out in moderate to severe urinary incontinence treatment in any hospital at a modest cost with satisfactory results.


Ischemic conditioning prevents Na,K-ATPase dissociation from the cytoskeletal cellular fraction after repeat renal ischemia in rats.
Recent studies have suggested that heat shock proteins (HSPs) are involved in the restoration of the cytoskeletal anchorage of Na,K-ATPase after renal ischemia. To determine their role in ischemic conditioning, we investigated whether cytoskeletal Na,K-ATPase was stabilized during repeat ischemia concurrent with 25-kD and 70-kD HSPs induction. Anesthetized rats either underwent single unilateral renal ischemia or were conditioned with bilateral renal ischemia and, after 18 h of reflow, were then subjected to repeat unilateral renal ischemia. Renal cortex was harvested, and effects of single versus repeat ischemia were compared by Triton X-100 extraction, by immunohistochemistry, and by an in vitro assay of Na,K-ATPase association with isolated cytoskeletal fractions. In contrast to single ischemia, repeat ischemia did not result in increased Triton X-100 extractability of Na,K-ATPase. Levels of 25-kD and 70-kD HSPs were significantly induced by ischemic conditioning and redistributed into the cytoskeletal fraction after single and repeat ischemia. Immunohistochemistry also showed significant disruption of Na,K-ATPase within proximal tubules only after a single episode of ischemia, whereas repeat ischemia did not alter the pattern of restored Na,K-ATPase localization in conditioned renal cortex. The preserved association of Na,K-ATPase with the cytoskeletal fraction of conditioned renal cortex was effectively abolished in vitro by addition of antibodies against 25-kD or 70-kD HSP. These results suggest that 25-kD and 70-kD HSPs induced by ischemic conditioning stabilize the cytoskeletal anchorage of Na,K-ATPase during repeat renal ischemia.


Variability in anticardiolipin antibody detection: role of nonspecific IgG binding and different microtiter plates.
There are many studies that are available on the Internet that attempt to standardize the assay for anticardiolipin antibody evaluation because of the variability of results. The aim of this study was to evaluate simultaneously the role of different microplates and the importance of sample nonspecific binding in determining different results in anticardiolipin antibody detection. Sera from 8 patients with raised levels of IgG anticardiolipin antibodies and 10 control sera were assayed by enzyme-linked immunosorbent assay in the presence (specific binding) or in the absence of cardiolipin (sample blank) with four different microplates, that is, NUNC PolySorp, FALCON ProBIND, Greiner 655061 (high binding), and Greiner 655001 (medium binding). Results were expressed as optical densities or net-optical densities (following sample blank subtraction) as well as international IgG anticardiolipin units (GPL) or net-GPL. A wide interplate variability of optical densities was found. When results were expressed as GPL, significant differences were only found between Greiner 655061, FALCON ProBIND, and NUNC PolySorp (P < .05 and P < .001, respectively) whereas differences were not statistically significant if interplate variability was analyzed as net-GPL. Results expressed as categorical variables (ie, positive/negative, according to a GPL cut-off and net-GPL cut-off, obtained with sera from 100 apparently healthy blood donors) showed a good or excellent Cohen's kappa coefficient of concordance among plates when positivity was evaluated on net-GPL. Our data strongly suggest that quantification and subtraction of sample blank may improve both interlaboratory agreement and reliability of anticardiolipin assay and minimize false-positive results.


Intracavernous medication for treatment of premature ejaculation.
Sixteen men complained of premature ejaculation during a five-month period between May, 1987, and October, 1987. Eight patients entered this study using intracavernous vasoactive drugs as treatment for their problem. The patients, ages twenty-four through fifty-eight (average 42 years), were all physically healthy and taking no medications. Five patients had normal findings on nocturnal tumescence monitor, while 3 patients did not use the monitor. A mixture of phentolamine mesylate, 1.0 mg/mL, and papaverine hydrochloride, 30 mg/mL, was used. The dosage required was from 0.10 mL to 0.40 mL. All 8 patients responded successfully to this treatment. Three patients stated they were cured and stopped the treatment. The other 5 patients continued using the medication after fourteen months. The drug-induced erection lasted between two and four hours despite ejaculation. There have been no side effects through April, 1988. All patients report satisfaction with the results of this treatment. The study showed that intracavernous medication therapy can be successful in the treatment of premature ejaculation.


Phases in the early development of the human islet organ.
The study included morphometric examination and biochemical investigation of 41 human pancreata taken from 14th to 26th weeks of fetal development. 3 phases of development were observed. Phase I (weeks 14 to 16) is characterized by the presence of mainly islet buds. They were originated from the ducts and are vascularized during week 16. During phase II (17th to 20th weeks) the islet buds were detached from the ducts and they formed new mantled islets with the B cells in the centre. Non-B cells are situated on the periphery around the insulin producing cells. Phase III lasts from week 21 to week 26. During this phase B cells and non-B cells become more irregularly positioned within the islet, a cytology, which is similar approximating that of as also found in adult human islets. The changes of islet structure during pancreatic development are accompanied by other typical phenomena: Islet size increases during phases I and II, but decreases again during phase III. The proportion of isolated B cells outside of the islets varies during this stage of fetal development, but they generally account for about 15% of the total islet organ. This should be taken into account when assessing the islet function De Pablo et al. (1985) on a morphological basis.


Lipid parameters including Lp(a) in hemodialysis patients.
Chronic hemodialysis (CHD) patients have a high incidence and prevalence of atherosclerotic disease which may be related to numerous atherosclerotic risk factors. Among them dyslipidemia plays a significant role. Elevated Lp(a) levels, which are strongly associated with atherosclerosis, have been reported recently in uremic patients. The aim of our study was the determination of the levels of lipid parameters including Lp(a) in 151 CHD patients (76 male) aged 57 (12-81) years, who were on hemodialysis for a mean of 44.3 (range 1 to 189) months. Eighty-four normal individuals age and sex matched were used as controls. The median serum Lp(a) concentration in hemodialysis patients was 13 mg/dL compared with 6.5 mg/dL in healthy controls, p < 0.001 by distribution-free Mann-Whitney test. The prevalence of subjects with Lp(a) levels above 25 mg/dL was significantly higher in CHD patients compared to normal subjects (30% vs. 8%, p < 0.001). Even if CHD patients were matched for fasting lipid levels, they showed Lp(a) levels significantly higher than controls. No significant correlation was found between Lp(a) levels and either the age of the patients or the duration of hemodialysis. The etiology of primary renal disease did not influence the Lp(a) levels.


[Neisseria meningitidis invasive infections in children in Tunis: about 79 cases].
We conducted a retrospective study of meningococcal invasive diseases (MID) contracted in children in Tunis between January 1997 and January 2006. The purpose of this study is to specify the clinical, epidemiological, therapeutic and evolutionary features of these infections and to determine antimicrobial susceptibility and the antigenic formula of N. meningitidis isolates. During the study period, we have collected 79 cases of MID arising in children aged 3 days to 11 years. The majority of children's were less than of 4 years (57.3%). We note a frequency of the MID in winter and in spring. The most frequent clinical shape was meningitis (53%). Twenty one patients (26.6%) had a fulminant meningococcal disease. In our series, the rate of lethality was equal to 17.7%. Among the 46 meningococcal isolates, the most frequent serogroup was the B (73%) followed by C and A. A high heterogeneousness of the antigenic formulae was observed The most frequent phenotype was NT: NST for the group B isolates and 4:P1.13 for the group C ones. N meningitidis with reduced susceptibility to penicillin and to amoxicillin account for 54% and 10% of all isolates respectively. The cefotaxim and the rifampin were uniformly active.


Career satisfaction and work-life balance of specialist orthodontists within the UK/ROI.
Objectives To investigate factors affecting career satisfaction and work-life balance in specialist orthodontists in the UK/ROI.Design and setting Prospective questionnaire-based study.Subjects and methods The questionnaire was sent to specialist orthodontists who were members of the British Orthodontic Society.Results Orthodontists reported high levels of career satisfaction (median score 90/100). Career satisfaction was significantly higher in those who exhibited: i) satisfaction with working hours; ii) satisfaction with the level of control over their working day; iii) ability to manage unexpected home events; and iv) confidence in how readily they managed patient expectations. The work-life balance score was lower than the career satisfaction score but the median score was 75/100. Work-life balance scores were significantly affected by the same four factors, but additionally were higher in those who worked part-time.Conclusions Orthodontists in this study were highly satisfied with their career and the majority responded that they would choose orthodontics again. Work-life balance scores were lower than career satisfaction scores but still relatively high. It is important for the profession to consider ways of maintaining, or improving, career satisfaction and work-life balance; including maintaining flexibility of working hours and ensuring that all clinicians have ready access to appropriate training courses throughout their careers (for example, management of patient expectations).


Intermittent Hypoxia Conditioning: A Potential Multi-Organ Protective Therapeutic Strategy.
Severe hypoxia can induce a range of systemic disorders; however, surprising resilience can be obtained through sublethal adaptation to hypoxia, a process termed as hypoxic conditioning. A particular form of this strategy, known as intermittent hypoxia conditioning hormesis, alternates exposure to hypoxic and normoxic conditions, facilitating adaptation to reduced oxygen availability. This technique, originally employed in sports and high-altitude medicine, has shown promise in multiple pathologies when applied with calibrated mild to moderate hypoxia and appropriate hypoxic cycles. Recent studies have extensively investigated the protective role of intermittent hypoxia conditioning and its underlying mechanisms using animal models, demonstrating its potential in organ protection. This involves a range of processes such as reduction of oxidative stress, inflammation, and apoptosis, along with enhancement of hypoxic gene expression, among others. Given that intermittent hypoxia conditioning fosters beneficial physiological responses across multiple organs and systems, this review presents a comprehensive analysis of existing studies on intermittent hypoxia and its potential advantages in various organs. It aims to draw attention to the possibility of clinically applying intermittent hypoxia conditioning as a multi-organ protective strategy. This review comprehensively discusses the protective effects of intermittent hypoxia across multiple systems, outlines potential procedures for implementing intermittent hypoxia, and provides a brief overview of the potential protective mechanisms of intermittent hypoxia.


Fat embolism syndrome.
Fat embolism syndrome (FES) was first described in 1862, but its frequency today is still unclear. A diagnosis of FES is often missed because of a subclinical illness or coexisting confusing injuries or disease. Fat embolism syndrome develops most commonly after orthopedic injuries, but it has also been reported after other forms of trauma such as severe burns, liver injury, closed-chest cardiac massage, bone marrow transplantation, and liposuction. Although FES usually presents as a multisystem disorder, the most seriously affected organs are the lung, brain, cardiovascular system, and skin. Fat embolism syndrome is a self-limiting disease and treatment should be mainly supportive. Many drugs have been used to treat FES, but the results are inconclusive.


Thermoelectric quantum oscillations in ZrSiS.
Topological semimetals are systems in which conduction and valence bands cross each other and the crossings are protected by topological constraints. These materials provide intriguing tests for fundamental theories, while their unique physical properties promise a wide range of possible applications in low-power spintronics, optoelectronics, quantum computing and green energy harvesting. Here we report our study of the thermoelectric power of single-crystalline ZrSiS that is believed to be a topological nodal-line semimetal. We show that the thermoelectric power is an extremely sensitive probe of multiple quantum oscillations that are visible in ZrSiS at temperatures as high as 100 K. Two of these oscillations are shown to arise from three- and two-dimensional electronic bands, each with linear dispersion and the additional Berry phase predicted theoretically for materials with non-trivial topology. Our work not only provides further information on ZrSiS but also suggests a different route for studying other topological semimetals.


[Safety and efficacy analysis on modified FOLFOXIRI as first-line treatment for advanced colorectal cancer in China-single center experience].
To evaluate the safety and preliminary efficacy of modified FOLFOXIRI (combination of reducing dosage irinotecan, oxaliplatin and fluorouracil) in first-line treatment for patients with metastatic colorectal cancer. A total of 53 patients with advanced colorectal cancer receiving modified FOLFOXIRI regimen were recruited continuously from January 2010 to January 2014. Safety profile was recorded based on NCI Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Objective response was evaluated by Response Evaluation Criteria in Solid Tumors version1.1 (RECIST 1.1) after administration of at least 4 cycles chemotherapy. Kras and Braf gene sequencing was tested by dideoxy chain-termination method. Relation between efficacy and two genes was examined. Among 53 patients, no treatment-related mortality was presented. The rate of grade 3 to 4 adverse event was 32.1% (17/53), including neutropenia 13.2%(7/53), anemia 11.3% (6/53) and fatigue 9.4% (5/53). Overall response rate (ORR) and disease control rate (DCR) were respectively 65.9% (29/44) and 90.0% (40/44). Radical resection rate (R0) was 29.5% (13/44). Efficacy of mFOLFOXIRI regimen plus targeting therapy was assessed in 44 patients. mFOLFOXIRI regimen plus targeting therapy achieved an ORR of 72.7% (8/11), which was higher than the ORR 65.9% (21/33) of triplet regimen alone, but the difference was not statistically significant (P=0.198). Paraffin specimens of 48 colorectal cancer cases were tested. Twenty-one cases were Kras mutant (43.75%), 3 cases were Braf mutant (6.25%). There were no significant differences between two groups (P>0.05). Reducing dosage mFOLFOXIRI can be safely used in advanced colorectal cancer and can achieve promising results in terms of short term efficacy.


[An epizootiologic study of an outbreak of equine influenza in the Czech Republic in the fall of 1995].
A mild outbreak of acute respiratory infection was reported in racing horses in the fall of 1995. Four studs were investigated for the sources and routes of infection. In five horses from two herds, virus isolates were obtained which, in preliminary typing experiments, were identified as the influenza A/equi 2 virus. The presence of this illness in all the examined herds was confirmed by a rise in specific antibody titres. The affected animals included both older vaccinated horses and young horses not yet vaccinated. Epidemiological studies suggested that the spread of infection occurred in situations where infected and non-infected horses were together, most frequently at races. Newly infected horses brought the infection back to their studs where further animals became infected. Some of them, still being in the incubation period without any clinical signs, may have taken part in another race and passed the infection onto healthy animals from other studs. Since the races usually took place in 7-day intervals, the epidemiological chain remained continuous. The causes of the outbreak of infection in vaccinated horses are analysed. The length of post-vaccination immunity, the antigenic composition of vaccines and their completion with new strains of the influenza virus are discussed.


Commentary: Regulation and the Nursing Profession: A Personal Reflection.
Against the backdrop of Ontario's "Inquiry into the Safety and Security of Residents in the Long-Term Care Homes System," this commentary offers personal reflections about nursing regulation and the profession. The evolution of the three pillars of nursing is briefly described, and emerging changes in regulatory structures and professional associations are identified. The nature of the relationship between the regulator and the registrant is commented on, and the lived experiences of regulation from the perspective of an employer and a chief nursing executive are discussed. In the context of the examples shared in the commentary and the proceedings of the Inquiry, the author calls upon each pillar of the profession to work together more effectively to protect the public and optimize the contributions of our profession as a whole.


Trace mineral source influences digestion, ruminal fermentation, and ruminal copper, zinc, and manganese distribution in steers fed a diet suitable for lactating dairy cows.
High solubility of certain trace minerals (TM) in the rumen can alter nutrient digestibility and fermentation. The objectives of the present studies were to determine the effects of TM source on 1) nutrient digestibility and ruminal fermentation, 2) concentrations of soluble Cu, Zn, and Mn in the rumen following a pulse dose of TM, and 3) Cu, Zn, and Mn binding strength on ruminal digesta using dialysis against a chelating agent in steers fed a diet formulated to meet the requirements of a high producing dairy cow. Twelve Angus steers fitted with ruminal cannulae were adapted to a diet balanced with nutrient concentrations similar to a diet for a high producing lactating dairy cow for 21 d. Steers were then randomly assigned to dietary treatments consisting of 10 mg Cu, 40 mg Mn, and 60 mg Zn/kg DM from either sulfate (STM), hydroxychloride (HTM) or complexed trace minerals (CTM). The experimental design did not include a negative control (no supplemental Cu, Mn, or Zn) because the basal diet did not meet the National Research Council requirement for Cu and Zn. Copper, Mn, and Zn are also generally supplemented to lactating dairy cow diets at concentrations approximating those supplied in the present study. Following a 14-d adaptation period, total fecal output was collected for 5-d. Following the fecal collection period, rumen fluid was collected for Volatile fatty acid (VFA) parameters. On the following day, the same diet was provided for 14 d, without supplemental Cu, Zn, and Mn. This period served as a wash-out period. A pulse dose of 100, 400, and 600 mg of Cu, Zn, Mn, respectively, from either STM, HTM, or CTM, was administered via ruminal cannulae to the steers on day 15. Over a 24-h period ruminal samples were obtained every 2-h. Following centrifugation, the supernatant was analyzed for Cu, Mn, and Zn. Ruminal solid digesta samples from times 0, 12, and 24 h after bolus dosing were exposed to dialysis against Tris-EDTA. Digestibility of NDF and ADF were lesser in STM vs. HTM and vs. CTM supplemented steers. Steers receiving HTM and CTM had greater total VFA concentrations than STM, and molar proportions of individual VFA were not affected by treatment. Ruminal soluble Cu and Zn concentrations were greater post dosing in STM and CTM supplemented steers at 2, 4, and 6 h for Cu and 4, 6, 8, 10 and 12 h for Zn when compared to HTM supplemented steers. The release of Cu and Zn from ruminal solid digesta following dialysis against Tris-EDTA at 12 and 24 h postdosing was greater for steers receiving HTM compared to those receiving STM or CTM. Results indicate trace mineral source impacts: 1) how tightly bound Cu and Zn are to ruminal solid digesta; 2) fiber digestion; 3) and ruminal total VFA concentrations.


Electromagnetic energy and food processing.
The use of electromagnetic energy in food processing is reviewed with respect to food safety, nutritional quality, and organoleptic quality. The effects of nonionizing radiation sources such as microwave and radio-frequency energy and ionizing radiation sources, e.g. radioactive cobalt-60 and caesium-137, on the inactivation of microbes and nutrients are compared with those of conventional heating processes both in terms of their kinetic behavior and their mechanisms of interaction with foods. The kinetics of microwave and conventional thermal inactivation are considered for a generalized nth-order model based on time and temperature conditions. However, thermal inactivation effects are often modeled by 1st-order kinetics. Microbial and nutrient inactivation by ionizing sources are considered for a 1st-order model based on radiation dose. Both thermal and radiation resistance concepts are reviewed and some typical values of radiation resistance are given for sensitive vegetative bacterial cells, yeasts, and molds and for resistant bacterial spores and viruses. Nonionizing microwave energy sources are increasingly used in home and industrial food processing and are well-accepted by the American public. But, despite recent Food and Drug Administration approval of low and intermediate ionizing radiation dose levels for grains and other plants products and the fact that irradiated foods are sold in more than 20 countries of the world, public fears in the U.S. about nuclear energy may limit the role of ionizing radiation in food processing and preservation and may also limit the use of nuclear fuels as an alternate source of electrical energy.


The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: A systematic review and meta-analysis of randomized, placebo-controlled trials.
The efficacy and safety of testosterone replacement therapy (TRT) in hypogonadal men remain incompletely understood. To conduct a systematic review and meta-analysis of randomized clinical trials (RCT) to determine the effects of TRT on patient-important outcomes and adverse events in hypogonadal men. We searched Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus from inception to March 2th, 2017. RCTs that assessed the efficacy and adverse events of TRT of at least 12 weeks compared with placebo in adult men with hypogonadism, defined by morning testosterone ≤300 ng/dL and at least one symptom or sign of hypogonadism. Reviewers working independently and in duplicate assessed the quality of the trials and collected data on patient characteristics, interventions, and outcomes. We found 11 publications, reporting on 4 eligible trials (including 1,779 patients) at low risk of bias. Compared to placebo, TRT was associated with a small but significant increase in sexual desire or libido [standardized mean difference (SMD): 0.17, 95% CI 0.01, 0.34] (n=1383), erectile function [SMD: 0.16, 95% CI 0.06, 0.27] (n=1344), and sexual satisfaction [SMD: 0.16, 95% CI 0.01, 0.31] (n=676), but had no effect on energy or mood. TRT was associated with an increased risk of developing erythrocytosis [relative risk: 8.14, 95% CI: 1.87, 35.40] (n=1579) compared to placebo, but had no significant effect on lower urinary tract symptoms (LUTS). In hypogonadal men TRT improves sexual desire, erectile function, and sexual satisfaction, however it increases the risk of erythrocytosis.